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JANUARY

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SERVING THE MEDICAL PROFESSION OF MINNESOTA, NORTH DAKOTA, SOUTH DAKOTA AND MONTANA

Femoral Shortening for Equalization of Leg Length

i GEORGE M. HART, M.D.

Minot, North Dakota

EQUALIZATION OF DISCREPANCIES ill leg length has long been considered an important prob- lem in orthopedic practice. Compensation for minor differences can readily be made by simply applying a lift to the sole and heel of the shoe on the short side. As the difference in length of the limbs increases, however, the elevated shoe be- comes not only more unsightly but more difficult and unwieldy for the patient. It is natural, there- fore, that reports of surgical measures to resolve the problem appear earlv in the literature of orthopedic surgery.

In general, two methods of approach have been considered: (1) shortening of the long leg and ( 2 ) lengthening of the short leg. Shortening of the long leg may be accomplished bv one of two methods— arrestment of longitudinal growth by cancellation of epiphysial growth, as first ad- vocated bv Phemister1 in 1933, or by actual short- ening of one of the bones of the extremity by segmental resection. It is with the latter method that this article is concerned.

Steindler2 noted that femoral shortening was first carried out in 1847 by Rizzoli, whose claim of priority has not, however, found much recog- nition. His method was osteotomy with overrid- ing of the bone fragments. Two other authors

george m. hart is consultant in orthopedic surgery at Veterans Hospital , Minot; on the staffs of Trinity Ho.spital and the Northwest Clinic, both in Minot; and surgeon for the Soo Line Railroad.

used similar technics, Mayer in 1850 and Sayre in 1863. In 1908, Glaessner3 reported 2 cases and Deutschlander4 described fixing the fragments with an aluminum plate and screws. Shands5 recorded 3 cases in 1917, using wire sutures for fixation of the bone ends. Fassett9 in 1918 des- cribed fixation of the fragments with a Lane plate in 3 cases. In another case, he used a tongue and groove osteotomy. Royle,7 in 1923, described 5 cases, 4 of which were fixed with in- tramedullary pegs and 1 with a Lane plate.

In 1935, White8 described a method of femoral shortening which has since been widely accept- ed. He performed a transverse osteotomy of the mid-third of the femur. The bone fragments were allowed to override the correct amount and were fixed by obliquely placed, removable pins. A plaster hip spica cast was applied from the toes to the ribs with the hip slightlv flexed and abducted. The knee was similarly flexed, and the pins were incorporated in the cast. Eonr weeks postoperatively the pins were removed. The cast was maintained for an additional month and then removed if x-ray examination revealed sufficient callus formation.

In 1940, Harmon,9 in discussing the surgical treatment of unequal leg length, noted that either the tibia or femur could be shortened as much as 3 in. He felt that femoral shortening was usually more applicable. The site elected for this procedure was at the junction of the middle and lower thirds of the femur. The author

used a Gigli saw to sever the bone transversely and then removed the desired excess bone with a hand saw. The excised bone was split into several fragments, one of which was constructed to fit snugly as an intramedullary graft. The re- maining pieces of bone were placed across the osteotomy site as onlay grafts. Bronze aluminum wire was used in a number of cases to prevent separation of the bone ends. The author con- cluded that although epiphysial arrest was the most conservative surgical method of equalizing leg length, it was limited to the seventh to twelfth years in girls and the seventh to fifteenth years in boys. He stated that the most exact universally applicable method of equalization of leg length was operative shortening of the sound extremity.

Howorth,10 in 1942, described his operation for femoral shortening. An osteotomy was carried out in the mid-shaft of the femur by making drill holes to step-cut the bone. Separation was com- pleted with an osteotome. The required amount of bone was removed, and a bone plate was applied to the shaft of the femur securing the fragments. A double hip spica cast was worn three months postoperatively, depending on heal- ing.

Blount,11 in 1943, in discussing the use of his blade-plate for internal fixation of high femoral osteotomies, mentioned use of the plate for in- ternal fixation after femoral shortening. A Blount plate with a single angle was placed in the neck of the femur, and a screw was inserted through the proximal hole of the plate into the sub- trochanteric region of the bone. Osteotomy was performed distally to the screw, and the required length of bone was removed from the femoral shaft. The bone ends were approximated and additional screws placed through the plate for fixation.

In 1947, Moore12 described a method of short- ening through the supracondylar region of the femur. He noted that, in published reports, the usual site of election for this procedure was the diaphysis. He felt that the maximum correction advisable was about 3 in. and that shortening in excess of this amount tended to produce per- manent quadriceps weakness. Moore used a lateral approach to the distal end of the femur and sectioned the bone with a Gigli saw just above the condyles. The shaft of the femur was displaced outwardly, and a proximal osteotomy with a Gigli saw was carried out, removing the required length of bone. The resected segment was divided longitudinally into several parts with a motor saw, and one fragment was used as an intramedullary graft between the femoral cond-

yles and the shaft. The graft was inserted first into the proximal shaft of the bone and secured with a single transfixion screw passing through both cortices and the graft. The protruding end of the graft was then introduced into the meta- physis and likewise secured with a transfixion screw. The remaining bone segments were used as onlay grafts across the osteotomy site. Post- operative immobilization was maintained in a single hip spica cast. The author noted that the longest period of postoperative immobilization required was sixteen and one-half weeks in his series of 15 cases. The average period of im- mobilization was ten weeks, and weightbearing with support was begun in the cast six to eight weeks after operation. In all of his patients, quadriceps power returned to normal soon after removal of the cast, and no permanent quadri- ceps weakness occurred.

Thornton,13 in 1949, described a method of subtrochanteric femoral shortening. The upper third of the shaft of the femur and the trochanter were exposed by a lateral incision, and a Smith- Petersen nail was placed in the neck and head of the bone. Osteotomy was performed in the sub- trochanteric region. A flange of bone was left extending down along the medial cortex of the proximal fragment. The required length of bone was then removed from the distal fragment, the fragments of bone were brought into apposition, and a plate was attached to the Smith-Petersen nail. This was fastened to the femoral shaft be- low the osteotomy with screws penetrating both cortices. No external fixation was used postoper- atively.

White, in discussing Thornton’s procedure, made a plea for shortening the middle third of the femur, noting that in 5 of 6 subtrochanteric shortenings which he had performed, 2 resulted in delayed union and 1 in nonunion. When he performed femoral shortening in the middle third of the bone, no delayed unions or nonunions oc- curred. J. Albert Key stated, “I have used the subtrochanteric method and I do not like it very well.”

In 1951, Eyre-Brook14 described his operative technic, which was essentially the same as that described by White except that transfixion screws instead of metal pins were placed transversely through the overriding fragments. He noted that in one of his patients, the leg was shortened 4 in. and normal quadriceps power maintained.

In 1954. Thompson and associates15 compared results and complications of femoral shortening by means of oblique osteotomy with screw fixa- tion and transverse osteotomy with intramedull- arv nail fixation. The former consisted of placing

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a long osteotomy obliquely through the mid-third of the femoral shaft. The line of osteotomy was marked with numerous drill holes, and the oper- ation was completed with an osteotome. The distal and proximal spikes were then overlapped to produce the desired amount of shortening, and the protruding ends were removed. A fracture clamp was used to hold the bone ends in apposi- tion, while 4 transverse screws were placed in staggered relationship to each other for fixation. Postoperatively, a single hip spica cast was ap- plied or the extremity was suspended in a Thomas splint.

In shortening the femur by transverse osteo- tomy, Thompson removed the required segment of bone by making 2 transverse cuts through the mid-shaft. A Kuntscher nail was then placed in- tramedullarly to secure the fragments. A staple was driven across the osteotomy site in several cases to prevent distraction of the fragments. The fragment of bone removed during the osteo- tomy was cut into longitudinal segments and placed across the osteotomy site as a bone graft. Thompson concluded from a study of his 2 series of cases that secure internal fixation was not provided by intramedullary Kuntscher nail fix- ation alone. He suggested the use of staples across the bone ends to prevent distraction of the fragments. He felt that transverse osteotomv of the femur with intramedullary fixation was not a simple procedure and one often attended by serious complications. As oblique osteotomy with screw fixation was uniformly successful in his hands, he preferred this method.

In 1955, Jones"5 described a method of femoral shortening by “oblique-step” osteotomv and in- tramedullary fixation. With this operation, the author attempted to avoid one of the complica- tions noted by Thompson— distraction of the frag- ments after osteotomy and intramedullary nail- ing. He shaped an oblique-step osteotomv so that the distal end of the proximal fragment and the proximal end of the distal fragment were wider than the radius of the shaft of the femur. The plane of each step then inclined away from the midline proximally on the proximal fragment and distallv on the distal fragment to become slightly less in width than the radius of the shaft. The two projecting segments locked with each other when placed together and were held by an intramedullary femoral nail. No screws were used, and distraction was prevented by the inter- locking of the oblique-step projections.

INDICATIONS FOB FEMORAL SHORTENING

Surgical shortening of an extremity is not con- sidered unless the discrepancy in length is great-

er than 1 in. By tilting the pelvis, a person of average stature can compensate for shortening of /2 or of an inch. Inequalities of 1 or 1)1 in. can readily be corrected by lifting the heel of one shoe and dropping the opposite heel. Minor shoe corrections such as these are not readily noticeable either to the patient or to others. When the discrepancy in length approaches 1/2 in., however, the patient frequently prefers sur- gical shortening to a shoe with a built-up sole and heel of an inch or more.

There are many causes of unequal leg lengths. Fractures occasionally heal with overriding of the fragments, producing shortening, or the epi- physial line may be involved, creating an arrest of growth. Bone infections, including pyogenic osteomyelitis, tuberculosis, variola, or syphilis may produce either relative lengthening of the involved bone or shortening of the extremity. Bone tumors may be responsible for differentials in extremity growth. Neurofibromatosis is fre- quently attended by enlargement in breadth and increase in length of an extremity. Congenital abnormalities, including arteriovenous aneurysms and congenital absence or malformations of bone, contribute to variations in leg length. Residuals of poliomyelitis frequently produce a differential in the rate of growth of the lower extremities. Prolonged cast immobilization in growing child- ren may contribute to a slowing of the growth of the immobilized extremity.

An inequality of 2 in. or more prevents the patient from standing with the legs together un- less the hip and knee are flexed on the long side and interferes considerably with normal activi- ties, such as walking, running, sports, and danc- ing. Howorth noted that his patients desired leg shortening because of limp, the necessity of wearing a raised shoe and the associated asym- metric and undesirable appearance of the foot and leg. Pain was an unimportant factor. Par- tial disability in walking, running, working and playing was present in most of his patients. He noted that the long leg was usually completely sound except for occasional minor involvement in patients whose opposite leg was short as a result of poliomyelitis.

OPERATIVE LENGTHENING VERSUS SHORTENING

When studying the problem of equalization of leg length, the first inclination is to correct the deformity by lengthening the short extremity. By doing so, the involved rather than the normal extremity is operated upon, and the patient re- tains his height. However, because of numerous complications following leg lengthening proced- ures, the trend at present is to approach the

JANUARY 1958

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problem by the less dramatic but safer procedure of femoral shortening. As noted by White, in patients with lower extremities differing enough in length to necessitate an operative procedure, the short limb is almost invariably sufficiently involved with atrophic muscles so that further stretching by a lengthening procedure would result in inadequate function. Complications of lengthening include nonunion, postoperative in- fection, and traction damage to nerves, vessels, and museles which frequently residt in postoper- ative deformities of the extremity.

Abbott and Saunders,17 who worked extensive- ly with the problem of bone lengthening, wrote in 1939: “We emphasize that the procedure of bone lengthening is, and in all probability always will be, a major operation with the possibility of serious complications.”

A well-founded criticism of femoral shortening is the fact that the well leg is jeopardized. Be- side the aesthetic reaction against reducing height, the possibility of surgical sepsis exists. However, if this fear on the part of the surgeon is great, as pointed out by White, shortening of the long leg should not be attempted.

COMPLICATIONS

Thompson has discussed in detail the complica- tions following operative shortening of the femur with intramedullary nail fixation. In his series of 11 patients, 5 operative complications occurred. In 3 of the patients, the nail was too tight, while in 2, it was too loose. Fragmentation of the osteotomy site occurred in 1 patient. This was regarded as unfortunate because of the possibil- ity of shortening the leg more than anticipated. In 2 patients, difficulty was experienced in plac- ing the intramedullary nail. In 1 instance, the nail became wedged in the distal fragment of the femur leaving an excessively long portion of nail protruding above the greater trochanter. In another instance, the nail impacted and broke above the greater trochanter when continued attempts were made to drive it against resistance.

In 2 patients, the Kuntscher nail fit too looselv in the medullary canal. Staples were used to bridge the osteotomy site in 1 of them, and union occurred without complication. However, in the other, distraction of the femur occurred, re- quiring a secondary stapling operation three weeks later.

Fourteen postoperative complications occurred in the 11 femoral shortenings performed by Thompson. These included painful irritation produced by the proximal tip of the nail at the greater trochanter; severe and disabling gluteal pain with sciatica, which was relieved by removal

of the Kuntscher nail; angular deformity caused bv bending of the nail one month postoperative- ly; and fracture of the nail.

Genu recurvatum occurred in 4 of Thompson’s patients after Kuntscher nail fixation. In 3 of these patients, the femur had been shortened 5 cm. or more. The genu recurvatum persisted in 3 patients from one to five months and in the fourth for two years. Thompson noted that this complication had not occurred in patients in whom femoral shortening had been carried out by oblique osteotomy and felt that the deformity was produced by temporary partial loss of muscle tone in the thigh.

Thompson also noted that secure healing as demonstrated by x-ray examination seemed to be obtained more rapidly in patients treated bv oblique osteotomy than in those in whom fixation was accomplished by means of an intramedullarv nail. Although abundant peripheral callus ap- peared early in patients treated by transverse osteotomy and Kuntscher nailing, obliteration of the osteotomy site did not occur until eight to ten months postoperatively. In patients in whom oblique osteotomy was performed, union usually was complete by the end of the fourth month.

TECHNIC

The desired length of bone to be removed is determined by clinical measurement of the lower extremities between the anterior superior iliac spines and the medial malleoli. The patient is placed upon the operating table in the supine position, and the limb is draped to expose the thigh and the region of the greater trochanter. Using Henry’s18 technic, an anterolateral incision is made. The rectus femoris muscle is retracted medially and the vastus lateralis laterally to ex- pose the vastus intermedins, which is split longi- tudinally and reflected subperiosteally from the femoral shaft. A series of longitudinal drill holes are made through the mid-shaft of the femur, passing in an anteroposterior direction through the anterior and posterior cortices of the bone. These holes are placed in a Z-shaped configura- tion to outline a step-cut osteotomv. The longi- tudinal length of the osteotomv is twice the length of the desired amount of bone to be re- moved. The drill holes are then connected bv means of a sharp osteotome, using care to avoid splintering or splitting the femoral shaft. The desired length of bone is then removed from each of the proximal and distal fragments with a motor saw.

A Kuntscher cloverleaf nail is used for intra- medullary fixation of the bone. A guide pin is first introduced into the medullary canal of the

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j proximal fragment and directed proximad to emerge above the greater trochanter through the skin of the buttock. The thigh is adducted and flexed at the hip during introduction of the guide pin in order to place the point of emergence on the buttock as close to the greater trochanter laterally as possible. The proper length of nail i is determined preoperatively by clinical measure- ment of the extremity, and the diameter of the pin is determined during the operative procedure by introducing nails of various sizes into the med- ullary canal of the femur. The nail should fit snugly within the medullary canal but should not be so great in diameter that the femoral shaft is split during its insertion. The proper diameter can be judged by striking the nail with a mallet and noting its progress into the bone. A nail of proper diameter will advance 3 to 4 mm. with each mallet stroke. After the proper sized nail has been chosen, it is introduced along the guide pin into the proximal fragment of the femur so that it is just visible at the osteotomy site. The femur fragments are then reduced and held with a bone clamp while the nail is driven into the distal fragment. X-rays are made on the operat- ing table in both the anteroposterior and lateral planes. Films of sufficient size are used so that the knee joint is visualized to determine the posi- tion of the distal end of the intramedullary nail. Two metal screws are then placed transversely across the step-cut osteotomy to prevent distrac- tion of the bone fragments. In preparing the drill holes for the screws, the intramedullary nail must be missed with the drill point. Sufficient cortex is present, however, to provide secure fixation of the fragments with the screws.

Postoperatively, the patient is kept at bed rest until quadriceps strength is sufficient for active straight leg raising. He is then allowed to be- come ambulatory on crutches and instructed to walk in normal fashion, placing approximately the weight of the shortened extremity on the floor. Two to three months postoperatively, if x-ray examination reveals sufficient callus for- mation, the crutch on the operated side is dis- carded. The intramedullary nail is removed in one and one-half to two years, when the osteo- tomy site is shown to be completely crossed by normal bone trabeculae on x-ray examination.

CASE REPORT

J.L.R., age 6, was examined at a crippled children’s clinic May 8, 1948, by another orthopedist. Examina- tion revealed a waddling gait, a bilateral positive Tren- delenburg test, and limited abduction of both hips. A roentgenogram of the pelvis disclosed bilateral congenital dislocation of the hips.

She was admitted to Trinity Hospital June 28, 1948,

where Kirschner wires were placed through the supra- condylar regions of both femurs, and skeletal traction was applied until August 10, 1948, when the right hip was exposed through a Smith-Petersen incision. The capsule of the joint was found to be markedly thickened and the neck of the femur shortened and anteverted. The head of the bone was somewhat flattened and the acetabulum was shallow and filled with fibrous tissue which was excised. The ligamentum teres appeared rudimentary. The head of the femur was reduced into the acetabulum and a rim of bone turned down with a curved chisel from the ilium, including the upper aceta- bular rim. Bone was removed from the wing of the ilium and placed as a wedge above the shelf. A hip spica cast was applied postoperatively. Skeletal traction was continued on the left lower extremity until Septem- ber 30, 1948, when the left hip was operated upon. The head of the femur was found to lie above the acetabulum, which was also filled with fibrous and fatty tissue and excised. The hip was then easily reduced and was moderately stable. A shelf was turned down from above the acetabulum, including the acetabular rim, and bone was taken from the ilium above to form a wedge above the shelf. A bilateral subcutaneous adductor tenotomy was also done. A single hip spica cast was applied post- operatively. The patient was discharged from the hospit- al December 21, 1948, on crutches.

On February 25, 1949, she was readmitted to the hospital for physiotherapy and instruction in gait. She was able to walk fairly well when discharged April 18, 1949. She had a negative Trendelenburg test bilaterally, but some internal rotation of both lower extremities and adduction of the right thigh were present. She re- turned to the hospital July 15, 1949, for a supracondylar rotation osteotomy of the left femur.

Examination November 1, 1949, demonstrated that she walked with both feet pointing forward, had negative Trendelenburg tests bilaterally, and the hips felt stable.

The patient was seen about once yearly bv various

Fig. 1. Roentgenogram of pelvis June 19, 1956, eight years after bilateral open reduction and shelf operations for congenital dislocated hips. Shelf on the left has ab- sorbed, but both hips remain in acetabula and range of motion is excellent.

JANUARY 1958

5

Fig. 2. Roentgeno- gram of left femur August 5 , 1957, seven weeks after shortening and fix- ation with intra- medullary nail. Transverse screws prevent distraction.

orthopedists at crippled children’s clinics from 1949 to 1957. During this time, a gradual relative discrepancy between the length of the lower extremities was noted. WHen examined June 19, 1956, leg length was found to be 3154 in. on the right and 3354 in. on the left. It was further noted that she walked with a slight right hip limp and that the Trendelenburg test was negative on the left but slightly positive on the right. Motion in both hips was excellent. An x-ray of the pelvis ( figure 1 ) revealed that the hips were seated within the aeeta- bula. A good shelf was present on the right. The head of the right femur was somewhat flattened, and the neck was somewhat shortened. The shelf on the left had absorbed. She was advised to wear a 1-in. lift on her right sole and heel, and the possibility of shortening the left femur was discussed.

She was next seen May 1, 1957, at a crippled chil- dren’s clinic by another orthopedist. He noted that the right lower extremity remained 2 in. short and discussed femoral shortening with the family as the patient was not wearing a shoe lift for “social reasons.”

The girl returned to the Northwest Clinic, June 17. 1957, at the age of 15 years. Leg length now was 3154

in. on the right and 3354 in. on the. left. On June 18, 1957, she was admitted to the hospital for shortening o. the left femur. A step-cut osteotomy was made in the mid-shaft of the femur using a motor drill and an osteo- tome. The length of the longitudinal limb of the osteo- tomy was 3 in. to produce 1 54 in. of shortening. One and one-half inches were removed from both the proximal and distal fragments of the femur, and the bone fragments were reduced and held with a bone clamp while a Kunt- scher cloverleaf intramedullary nail was inserted. Two metal screws were placed transversely across the tongues of the osteotomy. Postoperative reeoverv was unevent- ful. Physiotherapy was started postoperatively and by July 10 she was able to actively lift her left leg when lying in the supine position, and ambulation on crutches was begun. She was discharged from the hospital July 14.

She was last seen in the office August 5, 1957, walking well with two crutches. Leg length measured from the anteriorsuperior spine to the medial malleolus was 31 in. on the right and 3154 in. on the left. Measurements from the anterior spine to the upper pole of the patella were 15 in. on the right and 1554 in. on the left. A roentgeno- gram of the left femur (figure 2) revealed that the frac- ture fragments and the metal fixation had remained in satisfactory position and alignment with good callus formation. She was advised to place about 25 per cent of her weight on her left leg and to discontinue the left crutch in about six weeks.

SUMMARY

Femoral shortening is an accepted method of equalization of leg length after the individual is past the age when epiphysial arrest is effective. The advantages of intramedullary fixation can be utilized if proper selection of nail size is made and distraction is prevented by internal fixation.

A case report is presented in which step-cut osteotomy and intramedullary nailing are com- bined with simple screw transfixion for fixation and prevention of distraction. The literature of femoral shortening is reviewed.

REFERENCES

1. Phemistfr, D. B.: Operative arrestment of longitudinal

growth of hones in treatment of deformities. T- Bone & Joint Surg. 15:1, 1933.

2. Steindler, A.: A Textbook of Operative Orthopedics. New York: D. Appleton & Co., 1925, p. 174.

3. Glaessner, P.: Die Kontinnitatsresektion der langen Rohren- knochen zur Ausgleichung von Verkurzungen. Ztschr. Orthop. 30:39, 1908.

4. Deutschlander, K.: Die funktionelle Bedeutung des Langeu- ausgleiches nach Heine. Ztschr. Orthop. 51:64, 1929.

5. Shands, A. R.: Shortening the long leg. Internat. 1. Surg. 30:273, 1917.

6. Fassett, F. L.: Inquiry into the practicability of equalizing

unequal legs by operation. Am. J. Orthop. Surg. 16:277, 1918.

7. Royle, N. D.: Treatment of inequality of length in lower

limbs. M. J. Australia 1:716, 1923.

8. White, J. W.: Femoral shortening for equalization of leg length. J. Bone & Joint Surg. 17:597, 1935.

9. Harmon, P. H., and Krigsten, W. M.: Surgical treatment

of unequal leg length. Surg., Gynec. & Obst. 71:482, 1940.

10. Howorth, M. B.: Leg shortening operation for equalizing

leg length. Arch. Surg. 44:543-555, March, 1942.

11. Blount, W. P.: Blade-plate internal fixation for high femoral osteotomies. J. Bone & Joint Surg. 25:319, 1943.

12. Moore, R. D.: Supracondylar shortening of femur for leg length inequality. Surg., Gynec. & Obst. 84:1087, 1947.

13. Thornton, L.: Method of subtrochanteric limb shortening. J. Bone & Joint Surg. 31A:81, 1949.

14. Eyre-Brook, A. L.: Bone-shortening for inequality of leg lengths. Brit. M. J. 1:222, 1951.

15. Thompson, T. C., Straub, L. R.. and Campbell. R. D.: Evaluation of femoral shortening with intramedullary nailing. J. Bone & Joint Surg. 36A:43, 1954.

16. Jones, K. G.: Femoral shortening by “oblique-step” osteotomy and intramedullary fixation. J. Bone & Joint Surg. 37 A: 575, 1955.

17. Abbott, L. C., and Saunders, J. B. deC. M.: Operative lengthening of tibia and fibula; preliminary report on further development of principle and technic. Ann. Surg. 110:961, 1939.

18. Henry, A. K.: Extensile Exposure Applied to Limb Surgery. Baltimore: Williams & Wilkens Co., 1954.

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Angina Pectoris Treated by Relaxation and Automatic Attentive Respiration

AARON FRIEDELL, M.D.

Minneapolis, Minnesota

Twenty-one patients in whom angina pec- toris developed after severe coronary dis- ease and/or eoronarv thrombosis were followed carefully between the years 1925 and 1955. Sat- isfactory results were obtained by teaching them simple methods of relaxation, mild light physical exercises, and, most important, automatic at- tentive diaphragmatic breathing at stated rest periods three to four times daily with a natural pause between the respiratory functions.

Of these 21 patients, 12 are living and are comfortably well. Two died from coronary thrombosis, and 7 died from other than cardiac causes. But, all of them were free from pain at least for more than two years after they learned the technic of automatic relaxed diaphragmatic breathing. One was under care for over thirtv years, and he was presented before several medi- cal groups to demonstrate the method and ration- ale of breathing. His death was caused by an accident after the Christmas holidays in 1955.

This case of H. R. was reported before in 1948. 1 To briefly summarize it, this patient had an acute myocardial infarction in 1924. He came under medical care one year later in September of 1925 with symptoms of angina pectoris, from which he had obtained relief bv taking nitro- glvcerin sublingually.

He was taught the method of relaxation and automatic attentive breathing. He gradually showed improvement and was symptom-free and normally active until the day of his sudden death. He had not needed nitroglycerin nor had he been confined with any major ailment for twentv-eight years. His electrocardiograms were always ab- normal ( figure 1 ) .

The pathologist. Dr. S. T. Nerenberg, stated in H.R.’s autopsy report: “The main left coronary artery and descending branch show severe in- timal arteriosclerosis. The circumflex branch and right coronary vessels show only mild to moder- ate intimal arteriosclerosis. On opening into the cardiac chambers, the left side of the heart is

aaron friedell is on the staffs of Mount Sinai and Asbunj Methodist hospitals, Minneapolis.

seen to be moderately dilated. The left ventri- cular wall is hypertrophied. The heart weighs 500 gm. The valves are all grossly normal in appearance. The right side is not remarkable.”

During the last thirty years of his life, this patient had spent ten minutes or more two to three times a day performing this relaxation and breathing exercise, apparently with good results.

This presentation will not analyze the age and sex of the 21 patients nor will etiology be dis- cussed. Two subjects will be presented: (1) the technic that was used and ( 2 ) the rationale most likely to produce satisfactory results.

TECHNIC

If an angina pectoris patient was on any medica- tion when we started our training, he was ad- vised to continue temporarily. However, the chief aim has been to reduce the physical and mental tension and effort. The patient was told to: “Put yourself at ease at the first appearance of pain. Bring to mind some pleasant thought and then relax your entire body. Keep the lips closed but teeth slightly apart, and, if necessary, put the tongue somewhat between the teeth so as to keep them apart, which helps to keep the jaw and facial muscles relaxed. Then, with the rest of the body in a state of relaxation, turn the attention to slow diaphragmatic breathing. Slow down the breathing without effort, make breath- ing effortless. Bring the breathing rate down to 6 per minute or less and at ease.”

Some of these patients could breathe at a rate of only 2 per minute ( figure 2 ) for ten to fifteen minutes or longer and then feel completely re- laxed.

Patients were instructed to cultivate effortless breathing with a pause after inhalation and after exhalation. The pauses between respirations were extremely important to our observations, and that phase will be discussed later.

RATIONALE FOR TREATMENT

1. When the body musculature is at ease, the oxygen demand is greatly reduced.

Krogh2 called attention in his book, Anatomy

JANUARY 1958

7

Fig. 1. Abnormal electrocardiogram and yet patient folly active and comfortable.

and Physiology of Capillaries, that at rest the body musculature needs only 1/15, and could be as low as 1/30, of the oxygen that is required during marked activity.

Best and Taylor5 showed that slow deep breathing affords a better oxygen supply than fast shallow breathing. Thus relaxation and auto- matic attentive breathing afford a reduced de- mand and increased supply of oxygen.

2. Slow diaphragmatic breathing reduces card- iac effort. During inhalation, the lungs widen and lengthen. According to Macklin,4 the pul- monary vasculature both lengthens and widens. So, while blood accumulates in the pulmonary vessels during inhalation, less blood is returned to the left side of the heart. Then, too, during a deep inhalation as the lungs are distended, the superior vena cava and the subclavian veins are compressed between the distended upper lobes of the lungs and the first ribs.5 These vessels are

compressed, and blood is not returned to the right heart during the latter half of a deep in- halation. Similarly, the inferior vena cava is verv easilv compressed between the diaphragm and the posterior edge of the liver.6 After all, the pressure in the veins, both superior and inferior vena cava, is very low— only about 8 to 15 mm. of Hg. The veins are soft as compared to the arter- ies, and not much pressure is required to shut off the return of blood to the right heart. Thus, during deep inhalation, less blood is returned both to the left heart and to the right heart. And. the heart gets a reduced work load after about the third pulse beat.6

Bearing in mind that the pulsations during the time of deep inspiration mean less work for the left heart, we can simplify the explanation for the benefits derived by taking for an example person A with a pulse rate of 80 per minute and a res- pirators' rate of 20 and compare him with person

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Fig. 2. Respiration chart il- lustrating an automatic res- piratory rate of less than 3 per minute.

B, whose pulse rate is 80 but whose respiratory rate is only 4. Then, of course, person A would have 20 inspirations and 20 expirations which means 40 actions during that minute of 80 pulse beats. Dividing 80 by 40 gives us 2 pulse beats during an inspiration. However, if person B breathes only 4 times per minute, that means he has 8 actions— 4 inspirations and 4 expirations— and dividing 80 bv 8 gives us 10 pulse beats per minute or 7 pulsations for reduced left heart effort. That could mean a reduced oxygen de- mand for the cardiac musculature.

a 80 0 „ 80 1A

A- 40 8 ~ 1

3. Breathing affects the acid-alkaline relation- ship in the blood and in the other body fluids and tissues as well.7 Normally, the pH of the blood is about 7.4 but it shifts with respiration, 7.35 on inhalation and 7.45 on exhalation. That shift takes place at the usual respiratory rate of 16 to 20 per minute. However, if the respiratoiy rate is markedly slowed up, the pH shift will be greater, since, during inspiration, C02 is retained and increases the hvdrogen ion concentration in the blood.7 And, since the hydrogen ion has a very rapid diffusion rate, it affects all other tis- sues as well.3 So, a definitelv slowed-up respira- tory rate may well affect the body, possibly through the Krebs cycle,8 wherever it functions in the body tissues.

4. I woidd also like to call attention to the action of the hemoglobin-oxygen pump.9 For, as the blood flows through the capillaries in the alveoli of the lungs, the carbon dioxide is de- livered and flows into the alveolus. On the other hand, the oxvgen that is present in the alveolus is

absorbed by the hemoglobin and is carried into the circulations. The carbon dioxide comes into the alveolus where, if the alveolus is contracting and ventilating, it is only pushed upward. Other- wise, since the COL. molecule is heavier than the 02 molecule, it remains and is accumulated in the alveolus and also in the terminal bronchus,10 and its concentration increases with the increas- ing pause following an inhalation and exhalation. While the carbon dioxide content in the air is only .04 per cent, in the alveoli, it is a little better than 4 per cent, depending upon the rate of res- piration. If respiration is slow with a lengthened pause, then the concentration of 0O2 in the al- veoli and terminal bronchi is much greater. If respiration is very slow, the concentration of C02 may be better than 8 per cent.10 A concen- tration of COL. of 8 per cent or more has anesthe- tic qualities and contributes valuably to the acetvlcholine cycle.11

Gesell and associates11 have shown that the acetylcholine production in the lungs can be in- creased fivefold or more with an increase of C02, since C02 checks the action of cholinesterase which destroys acetylcholine. So, if respiration is slowed up to 6 per minute or less, the amount of C02 in the alveoli and terminal bronchi is increased and the acetylcholine function is im- proved. Acetylcholine also has a very marked permeability rate and even though it is short lived due to the ubiquitous cholinesterase of the tissue, in the presence of an increased CO_> con- centration, its life cycle is longer.1 That, too, very likely improves the function of the coronary blood flow by its vasodilator action. Therefore, slow, automatic, deep diaphragmatic breathing

JANUARY 1958

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at a rate of 6 per minute or less with a pause be- tween both inhalation and exhalation can be a valuable adjunct in the treatment of angina pec- toris.

5. One may speculate also that with a breath- ing rate reduced to 6 or less per minute and with a lengthened and more effective inhalation per- iod, the diastoles, which take place during such inhalations, afford a greater gradient of systemic pressure12-15 in the right auricle than in the left

REFERENCES

1. Friedell, A.: Automatic attentive breathing in angina pec-

toris. Minnesota Med. 31:875, 1948.

2. Krogh, A.: The Anatomy and Physiology of Capillaries. New Haven: Yale University Press, 1930, p. 57 and 158-159.

3. Best, C. H., and Taylor, N. B.: Physiological Basis of Med- ical Practice, ed. 3. Baltimore: Williams and Wilkins Co., 1945, p. 527.

4. Macklin, C. C.: Evidences of increase in capacity of pul-

monary arteries and veins of cats, dogs, and rabbits during inflation of freshly excised lungs. Rev. Canad. de biol. 5:199, 1946.

5. Candel, S., and Ehrlich, D. E.: Venous blood flow during valsalva experiment including some clinical applications. Am. J. Med. 15:307, 1953.

6. Edholm, O. G.: Peripheral circulation. Ann. Rev. Physiol.

12:311, 1950.

7. VanSlyke, D. D.: Acidosis and alkalosis. Bull. New York

Acad. Med. 10:103-137, 1934.

8. Soskin, S., and Rachmiel, L.: Carbohydrate Metabolism,

revised edition. Chicago: University of Chicago Press, 1952, P. 57.

ventricle. Since during diastole, the pressure in the left ventricle is supposed to be zero, diastole at a very slow breathing rate may well provide an opportunity to call the thebesian and luminal vasculature into play and, perhaps, improve the collateral coronary circulation.13,16

In summary, an additional report is made on automatic attentive breathing and relaxation as a valuable adjunct in the treatment of angina pectoris.

9. Draper, W. B., and Whitehead, R. W.: Phenomenon of

diffusion respiration. 28:307, 1949.

10. DuBois, A. B., Fenn, W. O., Fowler, R. C., and Soffer,

A.: Alveolar COo measured by expiration into the rapid in-

frared gas analyzer. J. Appl. Physiol. 4:526, 1952.

11. Gesell, R., Mason, A., and Brassfield, C. R.: Acid hu-

moral control of heart beat. Am. J. Physiol. 141:312, 1944.

12. Gregg, D. E.: Coronary circulation. Physiol. Rev. 26:28,

1946.

13. Lauson, H. D., Bloomfield, R. A., and Cournand, A.: Influence of respiration on circulation in man. Am. J. Med. 1:315, 1946.

14. MacCanon, D. M., and Horvath, S. M.: Influence of res-

piration on arterial, and right and left ventricular pressures. Am. J. Physiol. 168:612, 1952.

15. Seely, R. D.: Dynamic effect of inspiration on simultaneous

stroke volumes of right and left ventricles. Am. J. Physiol. 154:273, 1948.

16. Mautz, F. R., and Gregg, D. E.: Dynamics of collateral

circulation following chronic occlusion of coronary arteries. Proc. Soc. Exper. Biol. & Med. 36:797, 1937.

Hematemesis, melena, or shock is often the first manifestation of acute ulcer- ation of the gastrointestinal tract which may occur as a result of stress after cardiac surgerv. These lesions often arise without previous ulceration and without premonitory symptoms; hemorrhage, perforation, and death mav ensue. Patients who have responded abnormally to stress in the past appear prone to stress ulcers. However, this complication cannot be predicted with accuracy.

The abdomen, as well as the heart and lungs, should be examined frequently after cardiac operations. Sometimes, rectal examination may be advisable to detect melena. The physician should be alert to the possibility of acute ulcer- ation in any patient whose progress is not normal after an operation on the heart.

Immediate transfusion and earlv surgery may he lifesaving. Abdominal ex- ploration should not he deferred simply because the patient has recently had a cardiac operation.

Of 7 patients with acute peptic ulceration after cardiac surgery, 4 died and 1 had emergency gastric resection.

Donald Berkowitz, M. D., Bernard M. Wagner, M.D., and Joseph F. Uricchio, M.D., Hahnemann Medical College and Bailey Thoracic Clinic, Philadelphia. Ann. Int. Med. 46:1015- 1023, 1957.

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The Diagnostic Value of Various Ocular Symptoms

ROBERT W. HOLLENHORST, M.D. Rochester, Minnesota

Many ocular symptoms are so characteristic that diagnosis may be made solely from the history. Others are sufficiently suggestive to per- mit a minimum of delay in proving the diagnosis. Still other symptoms of organic ocular disease enable the alert physician to make the correct diagnosis even though the eyes may be normal at the time of examination. The discussion that follows concerns, for the most part, such char- acteristic complaints and omits those of lesser diagnostic value.

As the eye is primarily an organ of sight, it is plain that the major, most frequent, and most varied complaints are those pertaining to distur- bances of vision which may occur in one or both eyes. This paper will center chiefly around var- ious disturbances of sight and pain, as nearly all other ocular symptoms are accompanied by rath- er obvious signs.

DISTURBANCES OF VISION

Complaints due to errors of refraction include the following.

1. Blurring of distant vision only is usually due to myopia. It is common among children, although they are almost never aware of this visual defect unless the school nurse or teacher discovers it. Such children often unconsciouslv but efficaciously better their vision by narrowing the palpebral fissures. In so doing, they wrinkle up their noses and their eyelids, a characteristic gesture. Early nuclear cataracts and uncontroll- ed diabetes often cause progressive myopia, and, thus, they produce blurred distant vision without notable decrease of near vision.

2. Blurring of near vision only is due to just one thing — inadequate accommodation. It is found: (a) among hyperopes whose far-sighted- ness is either undercorrected or inadequately corrected; (b) among patients of the third and

robert w. hollenhorst is with the Section of Ophthalmology at the Mayo Clinic and assistant professor of ophthalmology in the Mayo Foundation.

Read at the meeting of the North Dakota State Medical Association. Fargo, North Dakota, May 27 and 28, 1957.

fourth decades of life who have subnormal ac- commodative power or premature presbyopia; (c) among patients in the fifth or older decades whose presbyopia has become manifest; ( d ) among patients who have developed a temporary subnormal accommodation while under treat- ment for hypertension with the ganglion-block- ing agents; and (e) among patients who have had atropine, homatropine, cyclopentolate ( Cy- clogyl), or other cycloplegics instilled into their eyes or who may be using systemically excessive amounts of atropine, belladonna, trihexyphenidyl ( Artane), or other antispasmodic agents. Patients who have internal ophthalmoplegia as a result of palsy of the third cranial nerve are usually so disturbed by the resultant diplopia that they do not complain of being unable to read with the affected eye.

3. Blurring of both distant and near vision re- quires complete ophthalmologic examination, as it may be due to a variety of causes, such as uncorrected refractive errors, cataract, glaucoma, or disease of the cornea, vitreous, retina, optic nerves, or the higher visual pathways.

Intermittent blurring of vision of both eyes lasting several hours to a day or more may be caused by diabetes, for fluctuations in the blood - sugar level cause changes in the density of the lens and, therefore, produce variations in the refractive power of the eyes. Sometimes there may be a difference of as much as 2 or 3 diopters on successive days. Intermittent loss of vision of one or both eyes is a very common symptom of insufficiency of the basilar or carotid artery and is usually of four or five minutes’ duration. This svmptom also accompanies the choked disks of increased intracranial pressure.

An instantaneous loss of vision in one eye unaccompanied by pain or other symptoms is probably due to occlusion of the central artery of the retina. This is especially true if the patient awakens in the morning with a sightless eye. If the individual is more than 60 years old, tempo- ral arteritis should be considered and ruled out as soon as possible. Half of such patients go blind in the remaining eye during the next few

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hours or days. Patients with temporal arteritis often complain of transient diplopia or amaurosis fugax several hours prior to the actual permanent visual loss. The ophthalmoscope may show a swollen, hazily seen optic disk and, perhaps, several cotton wool patches in the retina. The patient may have had tender scalp arteries, an influenza-like syndrome, and temporal headaches for the previous several weeks. He frequently has an ervthrocvte sedimentation rate of more than 100 mm. in one hour (Westergren method). Biopsy of the temporal artery usually corrob- orates the diagnosis. Very high doses of corti- sone are a specific treatment for temporal arter- itis and prevent further loss of vision. There is no good treatment for occlusion of the central artery, although oxygen and anticoagulant ther- apy should he started if the patient is seen dur- ing the first twelve hours.

A moderateh/ rapid loss of vision in one eye occurring over a few hours to a day is usually due to one of the following: (1) occlusion of the central vein, which causes red vision if the hemorrhage extends anterior to the retina into the vitreous; (2) acute glaucoma when the visual loss is accompanied by seeing rainbows around lights, severe pain, cloudiness of the cornea, dilatation of the pupil, and redness and hard- ness of the eye; (3) acute iritis, with moderate pain, miosis, cloudiness of the aqueous and red- ness of the eye; and (4) optic neuritis, which causes pain on moving the eye, more rapid loss of vision, diminished pupillary reflex, and papil- ledema. The same symptoms occur with retrobul- bar neuritis, but the disk then looks normal at first.

Loss of vision in both eyes, whether rapid or slow, is caused by bilateral intraocular disease, lesions of both optic nerves, a lesion of the optic chiasm, or a lesion of the higher visual pathways in the cerebrum. Immediate further ophthalmo- logic and neurologic investigation is indicated.

In addition to losses of vision, such as those previously described, a host of interesting entop- tic visual disturbances may bring the patient to the physician for examination. The patient's de- scription of most of these disturbances is sufficient for making the diagnosis on the basis of the history alone.

The most common disturbances, of course, are represented by the so-called floaters, spots, or muscae volitantes. Almost everyone can see against the background of blue skies, snow, and bright ceilings the small cobwebby or stringy threads which always float away when one tries to look directly at them. These are small rem- nants of the fetal vascular system or condensa-

tions ol the vitreous and have no pathologic sig- nificance. Often, a patient who complains of these disturbances and comes for advice is in an anxiety state or has another, more severe psychiatric problem. Such patients frequently complain also of other entoptic phenomena. They may be alarmed by the dancing lights that are seen when the lids are closed over the eyes. Thev fearfully observe the after-images that are always present after gazing at bright objects. They often have learned to prolong the duration of these images by blinking their eyes slightly from time to time. Thus, instead of disappearing in a few seconds, these after-images may persist five min- utes and longer. Some patients observe the very interesting entoptic phenomenon in which if a bright surface, such as the sky, is observed, they may see a great number of small dancing spots like electric sparks which shoot up suddenly along a curved short path and then disappear as abruptly as they appeared. These are prob- ably red blood cells going through tiny capil- laries in the macular portion of the retina.

Another interesting but pathologic visual phe- nomenon is called “ Moore’s lightning streaks.” These are seen more frequently by persons in their fifties, sixties, and seventies but may appear at any age. They come as sudden, bright, light- ning flashes in one eye, almost invariably in the far temporal field. Turning the eyes rapidly, shaking the head, or, often, merely walking down a stairway will produce the phenomenon. The cause is a degenerative shrinkage of the vitreous of the eye. In attempting to separate from the contiguous retina, a strand of vitreous tugs and pulls on the retina and causes the lightning streaks. The vitreous continues to shrink and eventually separates completely from the internal limiting membrane of the retina. When this oc- curs, the patient notes the advent of several large floaters in his field of vision, but the light- ning streaks will have gone and will not return. During the period in which the lightning streaks are seen, there is danger the retina may be pulled oil, especially if a strand of the vitreous tugs on a cvstic space in the retina. Therefore, such patients should have a thorough ophthalmoscopic examination through a widely dilated pupil, us- ing 2 per cent solution of homatropine hvdrobro- mide and 10 per cent solution of phenylephrine ( Neo-Synephrine) hydrochloride, to rule out in- cipient retinal detachment. Sometimes, a small hole is found without detachment of the retina. This is, of course, the ideal time to surgically close such a hole. After the streaks are gone and the floaters appear, the danger of retinal detach- ment is probably over.

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A similar but quite different visual phenomenon is sometimes described as a “lightning streak.” This is the peculiar and characteristic scintil- lating scotoma of migraine which takes many forms. However, careful questioning ordinarily leaves no doubt as to the diagnosis. The visual symptoms appear during the aura, supposedly during the period of vasoconstriction of the cere- bral vessels. The patient may suddenly see a bright spot of light a little to one side of the axis of his vision. The spot begins to expand and then he notes a loss of part of the letters of words he tries to read, or he may see only the right half or the left half of objects he regards with either eye or with both eyes. The bright area begins to expand further, and it pulsates at a rapid rate (computed to be about 10 beats per second, comparable to the rate of the alpha rhythm in the electroencephalogram). It may expand to fill either the same quadrant in each eye or a whole homonymous half-field, and it may be brightlv colored. At its maximum, the whole phenomenon suddenly disappears in a maelstrom of light. The episode usually lasts at least ten minutes and sometimes as long as thirty minutes. Shortly after the aura is over, the head- ache develops. It usually affects the side of the head opposite to the visual aura and, therefore, corresponds to the part of the brain from which the aura emanated. Sometimes, the visual phe- nomena may be so-called “fortifications.” These are figures which look like the top of an ancient battlement. Other patients may merely see snow- flakes or dancing twinkling lights or experience a sensation as of heat waves. Some patients have a homonymous hemianopsia without scintillating lights, which may last ten to thirty minutes. Those who have this phenomenon must be eval- uated carefullv to be sure an intracranial lesion is not overlooked. Intermittent insufficiency of an internal carotid artery or of the vertebral or basilar arteries may produce a transient homonv- mous hemianopsia, but never, or almost never, such scintillating scotomas. Many patients who have the tvpical visual aura of migraine are spared the headaches and suffer only the terrify- ing visual symptoms.

Patients with tumors of the temporal or occipi- tal lobe sometimes see images or scenes of vari- ous types. These are quite different from the phe- nomena that are described by patients who have ocular migraine, although these phenomena too may appear for short periods. They may occur with increasing frequency several times a week or even daily, in contrast to migraine equivalents which usually have occurred for years and, ordi- narily, only once or twice a month.

Patients who have tumors in the parietal lobes are sometimes bothered by peculiar visual disturbances which come periodically. These rare phenomena consist of a confusion of right and left and, sometimes, of an inversion of the envi- ronment. Such patients may note that people seem to be walking on the walls of the room in a horizontal position rather than on the Hoor.

Micropsia is the term applied to the visual phenomenon in which objects appear smaller than they really are. This is commonly due to spasm of the accommodation and is observed among patients whose accommodation is partial- ly paralyzed as in early presbyopia. Voluntary convergence and concomitant accommodation produce micropsia. It is sometimes the present- ing complaint in psychiatric patients. Patients who have edema of the macula may have this symptom, although more often they, have meta- morphopsia.

Macropsia, in which images seem larger than normal, occurs when there are scars in the retina and is rarely observed.

Metamorphopsia, the condition in which the shape of objects is distorted so that a square looks asymmetric or a circle looks oval or a straight line appears bent, usually results from a disturbance of the macula by edema, hemor- rhage, choroiditis, detachment of the retina, or other lesions. A hole in the fovea may cause a straight line to be seen as a bisected or bent line. Improperly corrected astigmatism may distort the entire environment so that objects appear twisted or closer or farther away than they really are.

Colored vision, so-called chromatopsia, is al- ways indicative of some type of pathologic proc- ess. Rainbows seen around artificial lights are caused by edema of the cornea, as in acute con- gestiye glaucoma, and sometimes by nuclear cataracts. Rainbows caused by cataracts are constant, while those due to glaucoma appear with a rise of intraocular pressure and disappear when the pressure becomes normal. Red vision occurs among patients who have preretinal hemorrhages or hemorrhage into the vitreous. Exposure to snow or bright lights, aphakia, iri- dectomy, or prolonged dilatation of the pupil may also lead to red vision. Yellow vision mav be associated with jaundice, santonin poisoning, or carbon monoxide poisoning. White or blue vision may be caused by digitalis intoxication; sometimes objects may appear to be covered by snow.

Photophobia is a common complaint. Organic lesions of the eyes cause severe photophobia. These lesions are always easilv discovered bv

JANUARY 1958

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examination and consist of albinism, lesions of the cornea, and inflammatory involvement of the internal eye. Most people are more comfortable in bright light if they wear colored glasses. How- ever, photophobia is often a symptom of severe psychoneurosis; such individuals seem to find security behind dark glasses and wear them even indoors, a form of purdah.

Oscillopsia is an interesting manifestation of cerebellar or pontine dysfunction. There may be no visible disturbance of eye movements, al- though sometimes there is nystagmus. The patient complains of inability to recognize people unless he and the person he is attempting to recognize are stationary. One woman complain- ed that whenever she walked into a room, she could not identify any of her friends sitting or standing until she herself had come to a stand- still. This phenomenon is usually due to multiple sclerosis but sometimes to other lesions of the pons. It has been observed as a toxic effect of streptomycin on the vestibular nerves. The symp- toms result from ataxia of the ocular movements so that the eyes cannot move smoothly from one point of fixation to another.

Double vision requires complete ophthalmo- logic and neurologic examination. It indicates serious intracranial disease as a rule, since it is due to paresis of one of the extraocular muscles.

Triple or quadruple vision is caused by abnor- malities in the cornea, lens, or vitreous of one or both eyes. Diplopia in one eye may have the same etiologic basis.

Night blindness, in which the individual has trouble seeing in dim light, is the result of loss of function of the rod cells in the retina and is most frequently due to degeneration of the ret- ina as in retinitis pigmentosa or, more rarelv, to deficiency of vitamin A.

PAIN

Pain in and about the eyes may come from a multitude of causes, some due to ocular disease and others not in any way related to the eyes. Pain may be unilateral or bilateral. It may be aching, boring, sharp and stabbing, scratchy, burning, or itching in character.

A sharp stabbing pain results from a lesion of the epithelium of the cornea and is often followed by a scratchy sensation. It is the characteristic pain of a foreign body on the cornea or lodged under the upper lid scratching the cornea. The scratchy sharp pain is accompanied by profuse laerimation and severe photophobia.

A patient, usually a young married woman, frequently complains that she is awakened every night between 2 and 3 a.m. by a sharp, very

severe knife-like pain in one eye. The pain lasts ten to fifteen minutes and during this time the eye also feels scratchy. When the pain is gone, she falls asleep again and has no trouble the rast of the night. The next morning when she has the eye examined, the physician finds nothing to ac- count for her symptoms and passes the episode off as of no consequence. Such patients some- times go from physician to physician until finally one recognizes this sequence of events as the characteristic symptomatology of recurrent ero- sion of the cornea. Usually, some weeks or months before, the eye may have been scratched by a baby’s fingernail or other foreign body. The abrasion probably healed promptly. However, such abraded areas may remain roughened and the epithelium may not grow securely to the basement membrane. Thus, when the lids are closed in sleep, the epithelium of the lid and that of the cornea may grow together. A slight movement of the lid in sleep then rips off the piece of cornea, thus producing the characteristic chain of events. Duration of the pain is only ten to fifteen minutes because the wound heals rapidly. Simply instilling boric acid eye oint- ment liberally at bedtime for several consecutive days heals this lesion. Tetracaine (Pontocaine) drops instilled during the height of the pain pro- duce immediate relief. Recurrent corneal blebs may produce similar symptoms.

The so-called ether burn of the cornea, occur- ring when a patient wakes up from general anesthesia with a severely painful, scratchy, photophobic eye, is not an ether burn at all but an abrasion of the cornea caused bv brushing the cornea inadvertently or else by allowing the lids to remain partially open and thus drying and macerating the cornea. Use of tetracaine (Pon- tocaine) and a patch relieves pain until the cor- nea is healed.

Burning of the eyes, aggravated by tobacco smoke in the air and sometimes accompanied bv scratchiness and photophobia, is usuallv due to dry eyes (keratitis sicca). This condition is often associated with a dry cottony mouth, sour stomach, constipation, and, usually, with arthri- tis. It is caused by a systemic alteration in the production of glandular fluids on the serous sur- faces of the body. Tear secretion, as tested by Schirmer’s method of inserting a strip of filter paper over the lower punctum, will be absent or minimal in a five-minute test period. Fluores- cein will stain innumerable minute areas of epithelial erosion of the corneas, which are vis- ible only by biomicroscopic examination. The medication used is artificial tears, an isotonic solution of methyl cellulose ( Isopto-Alkaline ) ,

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which is effective in 98 per cent of patients. The other 2 per cent may be helped by using a prep- aration of their own blood serum made under sterile conditions.

Itching of the eyes almost invariably denotes an allergic condition of the eyelids or conjunc- tivae. Pollens, cosmetics, house dust, and animal dandruff are the most common causes. Two diseases of the eylids cause itching: (1) angular conjunctivitis and (2) vernal conjunctivitis. The former, an infection of the lids and conjunc- tivae caused by a diplobacillus, frequently occurs in aged people and is manifested by a distressing itching of the lids accompanied by Assuring at the outer canthi. It responds well to 1/3 per cent zinc sulfate drops administered four times daily for about a month. People with vernal conjunc- tivitis have a well-known way of rubbing their itching eyes by grinding the heel of the hand into the orbit. If the examiner everts the upper lids, he will see large cauliflower-like vegetations of venial catarrh. Treatment with hydrocortisone or prednisone drops is effective.

The severe pain of acute glaucoma has been mentioned. Chronic simple glaucoma does not usually cause pain in the eyes. The pain of iritis is much less severe. A patient who has optic neuritis or retrobulbar neuritis often complains of pain when the eyes are moved. Scleritis causes a severe, deep, orbital pain which is aggravated by turning the eyes. This disease not infre- quently accompanies rheumatoid arthritis and may develop in a very severe form in arthritic patients who have been treated with steroids for a long time and who have had the hormone withdrawn too rapidly. The treatment consists of

either systemic or subconjunctival administration of steroids.

A patient may periodically experience very severe pain deep in one orbit, which lasts one to two hours. These attacks usually occur in the spring and fall and cause excruciating pain which is generally at its worst during the night. Each pain rises rapidly to peak intensity and is accompanied by redness of the eye, lacrimation, stuffiness of the corresponding side of the nose, and, sometimes, by constriction of the homo- lateral pupil. Such a patient, of course, has his- taminic cephalgia or so-called cluster headaches.

Other types of pain which may be in the vicinity of the eyes include the scalp pain of temporal arteritis, the characteristic burning pain of herpes zoster, and the electric-shock pains of trigeminal neuralgia. Patients with an intracranial aneurysm may have severe pains above one eye accompanied by Horner’s syn- drome on the same side.

Finally, there is a little known unilateral orbital pain some people experience when the nasal mucosa at the ostia of the nasal sinuses is congested or when the turbinates lie in con- tact with congested mucosa. Such pain is often present on awakening, may be aggravated by consumption of alcohol the night before, and can be prevented by lying at night with the painful side of the head turned up. Nasal decon- gestants often relieve this headache promptly.

Milder forms of pain are occasionally the re- sult of uncorrected refractive errors and, some- times, of uncorrected muscle imbalance of a mild degree. Large amounts of muscle imbal- ance do not usually cause ocular pain.

Hypoglycemia, with extensor rigidity of the extremities, coma, and acidosis, can occur as a result of intoxication with Solox, a paint solvent.

Solox, consists principally of methanol and ethvl alcohol and is often ingested by chronic alcoholics in the southern states. Many persons drink this fluid re- peatedly with no ill effects. However, occasional patients are hospitalized be- cause of coma, blurred vision, cramping abdominal pain, or burning of the eyes.

Physical findings include foul breath and chest rales like those of hydrocar- bon or aspiration pneumonitis. Mania, convulsions, widely dilated pupils, generalized flaccidity, decreased gag and cough reflexes, loss of deep tendon reflexes, or extensor rigidity of hvpoglvcemia may be noted.

The carbon dioxide combining power and blood sugar concentration are low; blood ketones and lactate are increased.

Treatment includes: (1) correction of acidosis by intravenous administration of 2 per cent sodium bicarbonate solution; (2) reversal of hypoglycemia by intravenous infusion of hypertonic dextrose at four- to six-hour intervals for the first twenty-four hours; and (3) supportive care, including antibiotic ther- apy if aspiration has occurred. Pressor agents may be needed to combat shock.

William J. Hammack, M.D., Veterans Administration Hospital, Birmingham, Alabama. J.A.M.A. 165:24-27, 1957.

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15

Care of the Patient with a Colostomy

WILLIAM C. BERNSTEIN, M.D.

St. Paul, Minnesota

There is much misunderstanding and mis- information relative to the status of the pa- tient with a colostomy, and I hesitate to admit that much of this misinformation originates with physicians. Far too many doctors feel that a colostomy is a dreadful contraption that must not be considered for a patient except as a last resort. The truth of the matter is that a well- functioning colostomy is a wonderful device that makes it possible for people with serious illnesses and malignant tumors to be restored to health. These people can live relatively normal lives and can be economically independent and socially acceptable. Experience in caring for a large number of patients for many years has convinced me that an intelligent and cooperative patient does not feel that his colostomy is much of a handicap. However, we cannot expect all pa- tients to be intelligent and cooperative, but we should expect every doctor who assumes respons- ibility for the care of patients who need this type of surgery to equip himself with the necessary information on the subject. Unfortunately for the patients, too few physicians have shown enough interest in colostomy problems in the past. A surgeon may perform an excellent bowel resection and provide the patient with a good anatomic colostomy, but, if that patient is not given proper instructions regarding the care and function of the colostomy, he soon is in trouble. He becomes miserable until an attempt is made to help him adjust to his new way of life. By that time, some patients have become depressed and quite unable to cope with the problems involved. A planned method of approach by the physician before surgery, during the period of hospitaliza- tion, and during the period of convalescence usually pays big dividends in helping the patient adjust to his new situation and to become reha- bilitated in his family and outside environments.

When a patient learns that he has a veiy ser- ious illness which often is due to a cancerous tumor, the blow is hard to take, Add to this trauma the knowledge that a colostomy must be

WILLIAM C. BERNSTEIN US' clinica 1 USSOCWte pwfeSSOr

of proctology in the Department of S urgert/ at the University of Minnesota.

performed and that he will have to accept a com- plete change in his bowel elimination and the shock is often overpowering. At times, the effect on the patient is so serious that he may refuse surgery altogether. In other cases, the patient may become depressed and feel that his future will be dark and dismal. It is at this point that an understanding and well-informed physician can do a tremendous amount of good. The choice of words used in describing a colostomy is very important. A colostomy should never be referred to as “an opening in the side.” This ex- pression came into use about 1800 when the first lumbar colostomy was performed by Callisen1 in Copenhagen. To my knowledge, no one has performed a “side” colostomy since the 1890’s. A few minutes devoted to an explanation of how a colostomy works and how it can be regu- lated, augmented by a few well-chosen case histories of persons who are completely rehabili- tated, does much to restore the patient’s equilib- rium and implant a feeling of hope and confi- dence. Merely to tell a patient that the rectum must be removed and that an artificial opening will be made on the abdomen is, to my mind, a cruel approach and must produce frightening thoughts in patients.

Much has been written in recent years on this subject. Lay persons as well as physicians have become aware of the gravity of this problem and have taken an active part in the educational pro- gram for physicians and patients. In some cities, clubs have been formed to help in the rehabili- tation of colostomy patients. These organizations have done much to lessen the load of the physi- cians and to improve the mental attitude of the patients. They have also made available much information concerning newer technics and ap- pliances which may be of use to colostomv patients.

Each doctor must approach this problem in his own way. However, since the ultimate goal is the same in each case, namely, a well-adjusted and rehabilitated patient, certain basic principles must be observed. I will attempt to describe our approach in the handling of these patients, since we feel that the end results have been uni- formly good. When we diagnose cancer of the

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rectum or any other disease requiring a perma- nent colostomy, we explain that the surgery will entail construction of a new opening, which will serve very satisfactorily and with little inconven- ience to the patient. We assume a very optimis- tic attitude and try never to instill a feeling of doubt or fear in the patient’s mind. We are quite positive in our approach and, if the patient mani- fests some real anxiety, we suggest that we will he glad to bring in a patient who has a colostomy and who is happy with it. We try to forewarn the nurses on the hospital floor where the patient is to be admitted so that they will assume an op- timistic attitude toward the patient and his ill- ness. A thoughtless nurse can destroy all of the confidence the physician has built up in the patient. We have had several bitter experiences resulting from tactless remarks about those “aw- ful” colostomies. Some nurses offer unsolicited sympathy to these patients without realizing the damage they are doing.

After surgery, these patients are prone to be apprehensive and fearful of their new status. We make every attempt to bolster their morale and, on the day that the colostomv is opened, we explain that the first few times the colostomy functions we are unable to predict whether the stool will be well-formed, soft, or watery. We state that if a waterv stool should occur and soil the bedclothes, it is not cause for alarm or fear that this condition will continue. We ask the nurses to be extraordinarily helpful in keeping these patients clean in order to avoid unneces- sary embarrassments. Usually, the first move- ment will be well-formed or soft. With the advance warning we have given, the patient is happily surprised and becomes quite satisfied with his colostomy. After several days our pa- tients are told that it would be well to start car- ing for the colostomy themselves, since they will want to be independent when they go home. It is interesting to see how well most patients ac- cept this assignment soon after surgery. We like to impress upon our patients the fact that they should not expect to have others care for their colostomy when they are at home.

I must admit that there are healthy differences of opinion concerning the patient’s care from this point on. Breidenbach and Secor,2 in an excel- lent paper published in the American Journal of Surgery in January of this year, state that a patient should be taught to irrigate his colostomy about the tenth day after surgery. In this pro- gram, we do not concur. We feel that a patient will be in a much better position to irrigate and to appreciate the value of irrigation after he has learned more about the functioning of and care

of the colostomy before irrigations are started. When our patients leave the hospital, they are given a supply of dressings and are told exactly how to take care of the colostomy. They are advised to take tub baths and are told that a soft wash cloth can be used directly on the stoma. They are given a prescription for pare- goric in case the bowels move too often and are given some insight into the dietary regime. This I will discuss subsequently. The patients are told to report to the office at the end of two weeks. At that time, they are interrogated in detail as to the behavior of the colostomy. Not infrequently, we have a patient who states that his colostomy has given him very little trouble. The bowel moves once a day, usually on arising in the moring or just after breakfast. These patients need very little further instruction. Ir- rigation would serve only to complicate the life of the patient and is totally unnecessary. The other patients whose bowels move several times a day or at erratic intervals are taught a very simple method of irrigation. An Asepto syringe, a catheter, and lubricant are all that are needed in the way of equipment. We demonstrate var- ious types of irrigating appliances, but most of our patients are well satisfied with the simple procedure. 1 am not surprised that many doctors state that a certain method of irrigation, and that alone, is the proper procedure. Nor am I sur- prised when many patients come to me with their ideas of the proper way to irrigate a colos- tomy. The truth of the matter is that there are many ways of doing it, some of which work well for one patient while results are not the same for others. If a patient can irrigate and empty his colon in a period of thirty to forty-five minutes and if he can remain clean for twenty-four to forty-eight hours, this function is being per- formed satisfactorily. The important point is that the surgeon who performs the operation should supervise the education of the patient.

There are many appliances on the market for patients who have colostomies. We do not feel that an appliance is necessary for an intelligent and cooperative patient. If the bowel is emptied well, with or without irrigation, a small piece of gauze under an elastic abdominal support should be all that is required. When a patient wears a bag or a plastic pouch, it is quite obvious that he is not doing well in emptying his bowel at stated intervals. We have a few patients who, in spite of good colostomy care, absolutely insist on wearing a ring and plastic cover for their own self-assurance. We do not feel that the point is worth arguing. We discourage use of colostomv belts, bags, domes, and other bulky appliances.

JANUARY 1958

17

The subject of diet is extremely important for the patient with a colostomy. It is very easy for such a patient to become a dietary cripple. We do everything possible to prevent this occur- rence. Our patients are told that they will be able to eat essentially the same foods as they ate before surgery. We sincerely believe that there are verv few foods which influence the function of the large bowel. We believe that the trans- portation of feces in the colon is influenced more by the neuromuscular mechanism, which de- pends on bulk and fluid, and by the emotional status of the patient than by any other factors. Our patients are told to eat everything, but we explain that they may find that one or more foods will cause some trouble. If a patient decides that his colon is functioning improperly because of a certain food, it is well to omit that particular item from the diet. In our experience, most colostomy patients have one or two foods from which they abstain, but, for the most part, the diet is extremely liberal and all inclusive. It is true that some foods, such as beans, cauliflower, and cabbage produce more gas than others. This is just as true in patients without colostomies. Common sense should dictate that these foods be avoided as much as possible. Highly spiced foods may produce an increased amount of gas. Each patient must decide whether this is true in his particular case. The importance of restrict-

REFERENCES

1. Dinnick, T.: Origins and evolution of colostomy. Brit. J.

Surg. 22:142-154, 1934-35.

ing the diet in patients with colostomies has been unnecessarily overemphasized in the past. It is high time that this practice be discontinued. The patient with a colostomy has been penalized enough without being unnecessarily burdened with a restricted diet.

This discussion would not be complete without further comments on the value of colostomy clubs. We are all cognizant of the value of group therapy in emotional and other psychiatric disturbances. The colostomy club acts as a group therapy class. Patients with common problems get together for discussion and to learn how best to handle their individual problems. When a person with a new colostomy sees other people who are entirely rehabilitated and who are lead- ing normal lives, it cannot help but raise his morale. In St. Paul, we have a colostomy and ileostomy club which has performed outstanding service in visiting patients both pre- and post- operatively and in helping during the period of readjustment. I heartily recommend the forma- tion of these clubs in all medical centers in the country. The life of a patient with a colostomy need not be a restricted and unhappy one. With proper education and with the help of an under- standing physician, these patients can lead rela- tively normal lives. One need only to attend a meeting of a colostomy club to appreciate the accuracy of this statement.

2. Breidenbach, L., and Secor, S. M.: Proper handling of the colostomy patient. Am. J. Surg. 93:50-56, 1957.

After abdominal hysterectomy, early feeding decreases the need for in- travenously administered fluids but increases nausea, vomiting, distention, and gas pains. Onlv 0.39 liters of intravenous fluids were given on the third post- operative day to 38 patients fed a solid, high-protein diet immediately after total abdominal hysterectomy, whereas administration of 0.89 liters was neces- sary in 41 patients managed in the usual manner. Nausea and vomiting oc- curred in 18 of the women fed the special diet but in only 8 of the controls. Moderate or severe abdominal distention was observed in 3 of the control group and 5 of the special diet group. Onlv 10 control subjects had moderate or severe gas pains, whereas 15 patients fed immediately after operation had such distress. More thorough preoperative explanation of the regimen to the subjects might have led to better results, since some opposition to early feeding expressed bv relatives and some of the nursing staff may have dismayed the patients.

Joseph H. Pratt, Jr., M.D., and Glenn Cantrell, M.D., Mayo Clinic and Foundation, Roches- ter, Minnesota. S. Clin. North America 37:1091-1099, 1957.

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Comparative Clinical Pharmacodynamic Evaluation of Newer Hypotensive Drugs

RUDOLPH E. FREMONT, M.D., F.A.C.P., F.A.C.C. Brooklyn, New York

Although the cause of hypertension cannot be established in the great majority of patients with this malady, they all have in com- mon an abnormal increase of the peripheral vas- cular resistance at the arteriolar level. This is the only one of the factors known to influence the level of arterial blood pressure that is consistently abnormal. Other factors— blood volume, cardiac output, arterial elasticity, and blood viscosity- become abnormal but not consistently and onlv in complicated and advanced forms of hypertension.

There is considerable controversy concerning the importance of humoral and neurogenic fac- tors in relation to the increased peripheral vas- cular resistance present in hypertension. So far. however, onlv the neurogenic factor, manifested by an excessive increase of the sympathetic tone, can be modified sufficiently by therapeutic means to lead to reversibility of the hypertension or postponement of the organic sequelae.

Until recently, chemotherapy directed against the excess activity of the sympathetic nervous system was greatlv handicapped by the inade- quacy and nonspecificity of the drugs available. The dissatisfaction with the results of medical therapy led, therefore, to rapid and widespread acceptance of surgical therapy when sympa- thectomy was shown to be effective in reducing hypertension and in abolishing secondary symp- toms and sequelae.

When eventually large statistics of surgically treated patients became available, their compari- son with adequate control observations revealed, however, to quote Page, “a few brilliant succes- ses, some patients definitely . . . benefited and some not at all.”

A renewed chemotherapeutic attack upon hy- pertension has been under way since the end of the last war due to the discovery of a number of drugs of sufficient potency and specificity to

rudolph e. fremont is chief of the Cardiovascular j Section at Veterans Administration Hospital , Brook- lyn, New York and clinical assistant professor of medicine at the State University of New York, Down State Medical School.

affect the hypertensive state both as produced experimentally and as encountered in man. The ever increasing number of these drugs, their pronounced variation in chemical structure, pharmacodynamic activity, and potency of both specific and nonspecific character have brought with them a similarly high variation in clinical applicability. This often confusing and poten- tially hazardous situation requires a critical ap- praisal at frequent intervals. This is the reason for the following review, which attempts a com- parative clinical pharmacodynamic evaluation of the most important antihypertensive drugs.

DEFINITION AND CLASSIFICATION

Hypotensive agents can be classified in a general manner into those that influence the peripheral resistance bv: (1) direct inhibition of the vaso- motor center, ( 2 ) blocking of autonomic ganglia, and (3) adrenergic blocking at peripheral sym- pathetic nerve endings. Such classification is however, misleading unless it is understood to reflect merely the predominant action of a par- ticular hypotensive agent. Many act simultane- ously at different sites within the sympathetic nervous system ( table 1 ) . Another matter of terminology and inherent implication of action deserves discussion. Much has been made until verv recently of the differentiation between the “sympatholytic” and the “adrenolytic” effects of some of these hypotensive agents. The first sup- posedly indicates a blocking of sympathetic nerve activity, the last a blocking or neutralization of circulating adrenergic substances, such as epi- nephrine and norepinephrine. It has been dem- onstrated conclusively that such differentiation is artificial and that it merely reflects the predom- inating activity of a hypotensive drug which, al- most without exception, can be shown to have complex activity. In general, the sympatholytic action is less marked than the adrenolytic.

The broader term “adrenergic blockade” was, therefore, recommended by Nickerson for the description of the activity of these agents, and it has found general acceptance. It is, however, often used to describe the action of hypotensive

JANUARY 1958

19

TABLE 1

SITE AND DEGREE OF EFFECT OF HYPOTENSIVE AGENTS

Drug	Ganglionic	“ Sympatholytic ”	“Adrenolytic”	CNS	Humoral	Other
1 . Dibenamine	0	+	+ +	+ +	0
2. Piperoxan	0	0	+ +	+	0
3. DHE alkaloids	0	+ +	+	+	0
4a. Priscoline	0	+ +	+	+	0
b. Regitine	0	+	+ ( + )	( + )	0
5. Hydralazine	0	++	+	+	+
6a. TEA	+
b. C5	+ +	0	0	0	0
C. Co	+ + +
7. Thiophanium derivative	( + )	+	+	+	0
8. Veratrum alkaloids	0	0	0	p	0	Card?
9. Rauwolfia	0	0	0	+	0

drugs that decrease peripheral resistance bv mechanisms other than adrenergic blockade. Obviously, such terminology is again misleading and should be abandoned in favor of the general term of “hypotensive action.”

SITE OF EFFECT AND CHEMICAL STRUCTURE

Table 1 demonstrates the site of action of the hypotensive drugs to be presently discussed. Their degree of activity is characterized by the use of symbols. A consideration of the chemical structure and its relation to the pharmacologic activity reveals striking differences both in chem- ical structure and pharmacodynamic activity of the drugs under consideration.

Dibenamine, one of the most potent and most highly specific adrenergic blocking agents, is a /3-haloalkvlamine related to the nitrogen mus- tards. Related to it are its benzyl-methyl phe- noxyethyl derivative ( Dibenzyline ) and piper- oxan (Benodaine). The adrenergic blocking ac- tivity of these drugs depends on the basic chemi- cal structure /3-phenylethylamine (figure 1) which they have in common. The specific adrenergic blocking activity of these and related tertiary amines presupposes a particular chemical reac- tivity with the formation of highly active inter- mediate compounds.

The next group of agents showing adrenergic blocking action is made up of structurally com- plex substances. They are obtained bv hydro- genation of the three alkaloids contained in ergo- toxine: namely, ergocornine, ergocristine and ergokrvptine. This process of reduction increases the adrenergic blocking effect of these alkaloids

and decreases at the same time their ability to stimulate smooth muscle. These three alkaloids, referred to subsequently as DHE alkaloids, have in common a dimethylpyruvic acid, an amino group, and proline as the protein molecule. Their difference in adrenergic blocking activity appears to be related to the difference in the type of amino acid present in their structure.

However, this group, available for clinical use under the name of Hydergine, does not exhibit as exclusively an adrenergic blocking activity as Dibenamine, since it shows also direct central effect. This additional action was overlooked for some time but is now well recognized as being responsible to a considerable degree for the so- called sympatholytic effect. The duration of ac- tivity of these agents is moderate.

Another group of chemically related hypoten- sive agents, consisting of Priscoline and Regitine, exhibits mixed adrenergic blocking and central activity. The chemical structure is basically that of imidazoline and as such is related to histamine (figure 2). This relationship is considered a possible explanation for the many histamine-like effects of Priscoline and Regitine.

There is some controversy as to whether Prisco- line is more strongly sympatholytic or adrenoly- tic. Species differences may account for the dis- crepant data obtained in animal experiments. In man, the direct depression of sympathetic nerve activity appears more pronounced than the ad- renolytic effect. In addition, a direct central in- fluence is also often evident. The duration of activity of Priscoline is quite short, though slight- ly longer than that of piperoxan. Regitine dis-

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plays a more pronounced adrenolytic action than Priscoline and one of longer duration than piper- oxan.

The next hypotensive agent of importance is hydralazine, an abbreviation for 1-hydrazinoph- thalozine, available clinically under the name of Apresoline (figure 3). This drug shows mixed activity with only very slight adrenolytic and moderate sympatholytic activity. The main site of its effect lies centrally, probably at the hypo-

H

N— ch

HC

HISTAMINE

N— CH-CH2-CH2-NH2

H,C

CH2— C

H

N-CHZ

n-ch2

N— C

H

, N — C H2

N — C H2

PRISCOLINE

REGITINE

Fig. 2. Chemical relationship of Priscoline and Regitine to histamine.

0 - PHENYLETHYLAMINE RADICAL

0 1 BEN AM I N E

Fig. 1. Chemical struc- ture of Dibenamine, Di- benzvline, and piperoxan shown to be basically the same as /3-phenvlethyla- mine.

DIBENZYL I NE

PIPEROXAN (933 F)

thalamic level. It appears further to be the onlv hypotensive agent available which, according to early and as yet inadequately confirmed reports, blocks pherentasin, a humoral vasopressor sub- stance demonstrated in cerebral extracts.

We come next to the ganglionic blocking group of quaternary ammonium compounds, tetractlujl- ammonium (TEA), pentamethonium (C5) and hexamethonium (C6). Chemically, all three show a striking relation to acetylcholine (figure 4).

It is suggested that the pharmacologic effect of these agents which block both sympathetic and parasympathetic activity at the ganglionic level is due to interference with acetylcholine activity. They are highly potent hypotensive drugs, with potency weakest in TEA and most marked in C6. Newer related compounds such as pendiomid and pentolinium ( pentapyrrolidin- ium) have been introduced recently into clinical usage. The most promising is pentolinium tar- trate marketed as Ansolvsen. This whole group of agents will be referred to subsequently as the methonium group.

Of entirely different chemical constitution is Arfonad, a Thiophanium derivative. Pharmaco- dynamically, it resembles TEA with its gangli- onic blocking effect but differs from it by the additional possession of moderate adrenergic- blocking and central activity.

The next important group of hypotensive

JANUARY 1958

21

NH— NH2- HCL

Fig. 3. Chem- ical structure of hydralazine.

HYDRALAZINE

agents is derived from Veratrum viride. Several alkaloids have been extracted, some in fairly purified form. These alkaloids and even their crystalline fractions are very complex com- pounds. Chemically, some of them are esters, others alkamines. The latter have been foun 1 to have sterol structures. Veriloid and protover- atrines A and B, the latter under the name of Veralba, are the two most extensively studied fractions and have come into general clinical use.

Although Veratrum is an almost ancient drug, the mechanism of its hypotensive action has been elucidated only very recently. Because of the bradycardia appearing in association with the hypotension and because of the lack of any demonstrable effect upon any part of the intact sympathetic nervous system, it was thought for a long time that the hypotensive activity of Vera- trum alkaloids was in some manner tied up with the Bezold reflex, whose afferent fibers arise in the myocardium of the left ventricle. However, cross circulation experiments in dogs in whom head and body circulation were completely sep- arated except for intact nervous communication have shown that hypotension in the body can be obtained when Veriloid or Protoveratrine is in- jected into the head circulation alone and is then not accompanied by bradycardia. Since in man these agents similarly cause hypotension without significant bradycardia, it seems reasonable to assume a central (hypothalamic) site of action in man. More recently, experimental work has yielded data suggesting that the hypotensive effect may be mediated via the carotid sinus.

Another hypotensive agent has recently been introduced into clinical use and has become established quickly as one of the most widely applicable drugs for the treatment of hyperten- sion. It is a mixture of alkaloids extracted from the Indian plant Rauwolfia serpentina. They

have been broken down into several purified fractions, of which reserpine was found to be one of the most active. The site of action of this agent appears to be limited to the hypothalamic region. It does not block ganglia nor is it adrenolytic or sympatholytic. The basic chemical structure of reserpine alkaloids as well as many of the phar- macodynamic effects resemble those of yohim- bine, an ancient “sympatholytic” drug.

PHARMACODYNAMIC MANIFESTATIONS OF HYPOTENSIVE ACTIVITY IN MAN

When pharmacologic and pharmacodynamic data obtained with hypotensive agents in animal ex- periments are applied to man, considerable diffi- culties may be encountered. Most important are those related to species differences. These are a familiar phenomenon to the experimental phar- macologist but tend to escape the attention of the clinician who is too eager to translate phar- macologic findings into clinical usage. These considerations must prevail as long as basic ex- perimental work in animals is required for the study of drugs. In the instance of hypotensive agents, this means the use of common carotid occlusion, central vagal stimulation, stimulation of the superior cervical ganglion of the cat, and the nictitating membrane. However, certain pro- cedures, such as cold exposure, the Valsalva ma- neuver, tiltback and orthostatic maneuvers, and the digital inspiratory constrictor response, allow even in the moderately ill patient the observation of vasopressor stimulation and the antagonism by hypotensive drugs. Even the blocking effects upon the action of adrenergic drugs, such as epinephrine and norepinephrine, and of the cho- linergic substances can be studied in man with safety. Furthermore, newer methods of renal clearance, cardiac and coronary sinus catheteri- zation, and cerebral blood flow studies permit the observation of the effect of hypotensive drugs on the most vital compartments of the circula- tion in man.

Thus, while data obtained with these methods are not able to pinpoint all of the effects of hypo- tensive agents in man, considerable information is gained regarding the nature of the desired specific action and any undesirable side effects of these drugs.

There are, however, some fallacies inherent in

C2 h5

C2 H5

N— CL

CH3 / ch3

CH3 — ^N-(CH2)6-N^— CH3

ch3 ch3

Fig. 4. Chemical relation- ship of TEA and hexa- methoniuni to acetylcholine.

ACETYLCHOLINE TEA(ETAMON) C6 (HEXAMETHONIUM)

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TABLE 2

COMPARATIVE VASOMOTOR RESPONSE TO HYPOTENSIVE AGENTS

Drug	Rate	Blood Nor- mals	pressure of Hyper- tensives	Orthostatic hypotension	Cold Valsalva Tilthack pressure overshoot overshoot	At BP	tercn-l PR	Epinephrine BP PR
1. Dihenamine	A	zb	y	+ + +	TOTAL BLOCK	y	0	y	0
2. Piperoxan	A	zb	OA	0	0	y	A	y	zb
3. DHE alkaloids	V	oy	y	+	PARTIAL BLOCK	0	0	0	o
4. Priscolinc	A	zb	A	+	PARTIAL BLOCK	0	0	0	0
5. Hydralazine	A	y	y	+(+)	NEAR TOTAL BLOCK	y	A	y	0
6a. TEA			y	+
b. C5	A	y	y	+(+)	PARTIAL BLOCK	A	0	A	0
c. Cfi			y	+ +
7. Thiophanium	A	y	y	+(+)	Block	y	0	y	0
derivative
8. Veratrum	y	zb		+(+)	0 0 0	y	0	y	0
alkaloids
9. Rauwolfia	y	zb	y	0	0 0 0	0	-	0	-

testing the efficacy of these drugs in man. These must be kept in mind when pharmacodynamic data are used as a basis for therapeutic applica- tion. First, the response of a given patient to a drug administered intravenously in the course of an acute experiment is not necessarily the same as during a period of prolonged maintenance. Developing tolerance on one side and cumula- tive action and inherent side effects on the other side may cause decisive differences that can negate all predictability of a therapeutic res- ponse based on preliminary testing. Second, even in the acute experiment, the observed results of vasomotor and general hemodynamic responses to drugs that affect the sympathetic nervous sys- tem are notoriously variable. This may be due in any given instance to the degree of initial sym- pathetic constrictor tone, the degree of organic vascular disease present, the extent of blockade achieved, and the resultant blood pressure re- duction. It is with these limitations in mind that we present in the following tables a survey of the comparative vasomotor response to these hy- potensive agents (table 2), their effect on renal dynamics (table 3), and their over-all effect on the circulation through various vascular compart- ments ( table 4 ) .

It appears superfluous to elaborate on all the data assembled and presented in these tables. Most of them are self-explanatory. However, those germane to a discussion of criteria for the most desirable hypotensive drug deserve emphasis.

CRITERIA FOR DRUG SELECTION

The criteria to be fulfilled by the ideal hypoten- sive drug may be listed as follows:

1. High specificity.

2. Blocking of strong vasopressor stimuli.

3. Significant reduction of blood pressure.

4. Favorable effect upon symptoms and signs of hypertension.

5. No undue increase of pulse rate.

6. No impairment of circulation through kid- ney, brain, and coronary arteries.

7. Easy, preferably oral, administration.

8. High therapeutic index.

In regard to specificity, if, under this term, exclusive influence upon the sympathetic nervous system with resultant reduction of the blood pressure is understood, then no drug presently available can be said to possess this character-

TABLE 3

COMPARATIVE EFFECT OF HYPOTENSIVE AGENTS ON RENAL FUNCTION

Drug	Glomerular Renal filtration blood flow	Filtration factor	Urine volume
1. Dihenamine	initiaiy initial	y	variable	-
2. DHE alkaloids	initiaiy initial	y	0	y
3a. Priscolinc b. Regitine	y	y
4. Hydralazine	yy	A	y	A
5a. TEA b. C5 c. Cfi	y	oy	variable	y
6. Thiophanium derivative	y	y	—	y
7. Veratrum alkaloids	y	y	—	y
8. Rauwolfia	zbD	zb	zb	-

D lor dog

JANUARY 1958

23

TABLE 4

COMPARATIVE OVER-ALL EFFECT OF HYPOTENSIVE AGENTS

	ON	CIRCULATION THROUGH	VARIOUS VASCULAR	AREAS
Drug	Peripheral	Coronary	Renal	Cerebral	Splanchnic
1. Dibenamine	A	0	A	A
				NH
2. DHE alkaloids	A	A	A	aa	A
3. Priscoline	A	A D OA	A	A	-
4. Hydralazine	A	A	A	—
5a. TEA	A		OA	NH
b. C5	A	OA	OA	AO	A
c. Ce	A		A
6. Thiophanium	A	—	A	±N	_
derivative
7. Veratrum	0	0	A		A
alkaloids
8. Rauwolfia	-	0	0	-	-

D for dog

N for normotensive man H for hypertensive man

istic, with the possible exception of the Veratrum and Ranwolfia groups.

The blocking of strong vasopressor stimuli and significant reduction of the blood pressure are interrelated. Table 2 demonstrates that those drugs that, in a potent manner, block pressor stimuli from which one likes to protect the over- reacting hypertensive patient, usually cause mod- erate to severe orthostatic hypotension. This effect is not limited to the ganglionic blocking agents hut holds for all drugs that show moder- ate to marked hypotensive effects. It is so exces- sive in the case of Dibenamine that this drug cannot be used for the treatment of hypertension and so pronounced in the case of the methonium group that treatment must be administered with utmost caution.

An attempt to select a drug that possesses the desirable property of slowing rather than acceler- ating the pulse rate yields only a few, the DHE, Veratrum, and Rauwolfia alkaloids. In mean, this effect is considerable only with the Rauwolfia group and minimal and inconstant with the other two. Fortunately, those hypotensive drugs in clinical use that accelerate the heart rate do so only rarely to an excessive degree.

Since of all circulatory compartments, the renal circulation maintains the most intimate and in- terdependent relationship to hypertension, there is ample reason for careful evaluation of the effect of hypotensive agents upon the dynamics of the renal circulation. The ideal effect would be one of increased renal blood flow regardless of whether renal involvement plays a primary or secondary role in hypertension. As evident from

table 3, only one drug, hydralazine, has been demonstrated to possess this effect. All the other potent hypotensive drugs tend to depress renal function, all the more so the higher the initial blood pressure and the more severely disturbed the renal function is prior to treatment. This is most pronounced in the malignant phase of hy- pertension with uremia and least striking when hypertension is moderate and renal function only slightly disturbed.

Observations involving the prolonged use of hydralazine have, however, shown that the in- itially increased renal blood flow may eventually return to normal levels. Similarly, the initial re- duction of the renal blood flow produced by the methonium group and protoveratrines tends also to disappear with prolonged use. This may ex- plain the occasional increase in urinarv output and drop of blood urea nitrogen observed clini- cally.

As regards the effect upon the other circula- tory compartments, table 4 reveals no undue di- rect effect of any of the hypotensive agents under discussion upon the coronartj circulation. A few have been shown in animals or man to be act- ually able to increase coronary blood flow to a slight degree. This is hardly of any clinical sig- nificance. The effect upon the cardiac output has i been studied in the case of several hypotensive drugs. Some, like the DHE alkaloids and hydra- lazine, tend to increase the cardiac output, the first mainly by a centrally mediated increase of the rate, the latter both by this means and poss- ible direct stimulation of the myocardium. The clinical significance of this is demonstrated by

24

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the not infrequent occurrence of angina pectoris with or without preceding tachycardia and even of myocardial infarction in hypertensive patients with coronary disease treated with hydralazine.

Other hypotensive drugs, such as the Veratrum and the methonium groups, tend to decrease the cardiac output. It is not certain whether this is accomplished by direct depressive action upon the myocardium, as has been held for a long time in the case of Veratrum, or via splanchnic pooling and resultant decrease of venous return, as appears more recently documented for both the methonium and Veratrum group. This effect has actually proved of benefit to hypertensive patients in acute left ventricular failure.

In general, however, any precipitous drop of the blood pressure, particularly when associated with an increase of the pulse rate, may precipi- tate myocardial ischemia and even infarction. Thus, where concern for the integrity of coronary circulation is paramount, the use of drugs, such as hydralazine, the methonium group, and Vera- trum alkaloids, must be particularly circumspect. The use of reserpine in combination with such agents should prove particularly advantageous in these circumstances by virtue of its ability to slow the rate and also to decrease the need for larger doses of the more potent hypotensive drugs.

Regarding the cerebral circulation ( table 4 ) ,

fortunately, none of the drugs under discussion decreases cerebral flow. Many decrease cerebral resistance in line with the drop of the systemic blood pressure, but, again, as in the case of the hypertensive patient with coronary disease, the one with cerebrovascular involvement must not be subjected to precipitous reduction of the blood pressure, since this is bound to lead to severe decrease of cerebral blood flow.

Limited documentation is available regarding the effect of hypotensive drugs upon the splanch- nic circulation. Undoubtedly, it participates with skin and muscle circulation to a considerable degree in the general relaxation of the peripheral vascular resistance, which is responsible for the reduction of the blood pressure.

As regards administration, table 5 summarizes data based, in addition to the basic pharmacody- namic properties, also on such factors as the speed of onset of activity, feasible route of ad- ministration, speed of excretion, duration of ac- tivity, cumulative effects, and development of tolerance. Extensive and carefully conducted clinical studies have shown that most of the hy- potensive drugs now available leave much to be desired in terms of ease of administration.

The clinical applicability is further compli- cated by a variable incidence and degree of side effects (table 6).

The latter are not limited to systemic toxicity

TABLE 5

CRITERIA FOR DESIRABLE CHARACTERISTICS OF HYPOTENSIVE DRUGS AND RELATIVE STANDING OF THOSE NOW IN USE

				Improvement	Slowing	Unimpaired blood	Easy	High
		Blocking of		of symptoms	of heart		flow		administration	tlxera-
	Sped-	vasomotor	Reduction	and of	rate		Coro-	Cere-	Paren-		peutic
Drug	flcity	stimuli	of BP	hypertension		Renal	nary	hral	teral	Oral	index
1. Dibenamine	No	Marked	Marked	—	No	No	Yes	—	No	No	No
2. Dibenzyl ine	No	Slight	Slight		No					Yes	Fair
n tv	No	No			No		No2
4. DHE alkaloids No	Slight	Minimal	Minimal	Occas.	No	Yes	Yes	Yes	Yes	Yes
5. Priscoline	No	Slight	Minimal		No	Yes	Yes	Yes	Yes	Yes	Yes
r n	No				No
7. Hydralazine	No	Marked	Mod.	Yes	No	Incr.	Usually	Yes	Yes	Yes	Yes
8. Methonium
group	No	Marked	Marked	Yes	No	No	Yes'	Yes'	Yes	Fair	Fair
9. Arfonad	No	Mod	Mod.		No	No	—	—	Yes	No	Fair
10. Veratrum
alkaloids	Yes?	Slight	Mod.	Yes	Occas.	No	Yes1	Yes1	No	No	No
1 1 . Reserpine	Yes?	No	Slight	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes

1Except with precipitous drop of blood pressure.

^Associated with hypertensive crisis occasionally induced by piperoxan.

JANUARY 1958

25

TABLE 6

	CLINICAL	APPLICABILITY AND	SIDE EFFECTS OF	HYPOTENSIVE AGENTS
		Peripheral	Hypertensive	Pheochromo-	Side effects
	Drug	vascular disease	vascular disease	cytoma	Degree	Incidence
la.	Dibenamine	+	+	+ +	Severe	Freq.
b.	Dibenzyline	+ +	+ +	0	Mod.	Freq.
2.	Piperoxan	0	0	+ + +	Mod.	Freq.
3.	DHE alkaloids	+ +	+	0	Mild	Freq.
4a.	Priscoline	+ + +	0		Mod.	Freq.
b.	Regitine	+ ( + )	0	+++	Mild	Freq.
5.	Hydralazine	( + )	++	0	Mod. Severe	Freq. Occas.
6a.	TEA	( + )	(+)	+	Mod.
b.	C5	+	++	—	Mod.	Freq.
c.	C«	+ ( + )	+ H — h	—	Severe
7.	Thiophanium derivative	( + )	(+)	—	0	—
8.	Veratrum alkaloids	0	++	0	Mod. Severe	Freq. Occas.
9.	Rauwolfia	0	+(+)	0	Minimal	Occas.

but also frequently involve excesses of the in- herent pharmacodynamic activity. Examples of the first type are the occurrence of a lupus erythematosus-like syndrome produced by the prolonged use of large doses of hydralazine and gastrointestinal intolerance observed with Dibenzyline and Priscoline. Examples of the second type are the unpredictable and, at times, unavoidable peripheral vascular collapse follow- ing the use of Veratrum drugs; the excessive cen- tral stimulation by Dibenamine, resulting in de- lirium and convulsion; unpleasant tremulousness after use of DHE alkaloids; severe depression occasionally seen with Rauwolfia; and accom- modation paralysis noted with the methonium group.

These side effects do not affect the clinical applicability of these drugs in terms of their use- fulness in peripheral vascular disease, hyperten- sive cardiovascular disease, and hypertension due to pheochromocytoma (table 6). Their re- spective place in the management of these con- ditions depends primarily on their site and de- gree of pharmacodynamic activity as seen in table 1. Thus, those drugs with markedly pre- dominant adrenolytic action are best suited for the diagnostic and therapeutic management of crises due to a pheochromocytoma. Those with relatively strong, if not exclusive, sympatholytic action are most useful as peripheral vasodilators, while the ganglionic blockers tend to be useful only as hypotensive agents. Their predominant effect upon the blood pressure makes their use

for the treatment of peripheral vascular disease impracticable and often impossible even in nor- motensive patients. They can be employed, how- ever, on a short term basis for the diagnostic evaluation of peripheral vascular conditions, such as the presence or absence of peripheral vascular spasm.

CONCLUSIONS

Evaluation of available hypotensive drugs in the light of the pharmacodynamic and clinical ob- servations makes it obvious that no single hypo- tensive agent has yet been found able to fulfill all criteria of desirability. A careful selection of a combination of hypotensive drugs and the fre- quent addition of drugs counteracting their side effects are at present the best and only working solutions for the management of all but the mild- est forms of hypertension. Such a selective order of hypotensive drugs is offered in table 7.

The choice is based on the consideration of all basic pharmacodynamic data in animal and man and the likely clinical response of patients in various phases of hvpertensive vascular disease. It is recommended as a systematic approach to the medical management of hvpertension and, as such, has proved of great practical usefulness in our experience. It may well be modified as better hypotensive drugs become available.

ADDENDUM

Since completion of this review, two new hvpo- tensive drugs have become available, Ecolid

26

THE JOURNAL-LANCET

TABLE 7

SELECTION OK HYPOTENSIVE DRUGS FOR TREATMENT OF HYPERTENSION

Hypertensive state	Initial Drug It	1	Additional drugs in order of choice 2 3
1. Mild, symptomatic	Reserpine	Usually	not	required
2. Mod., with grade 3 fundi	Reserpinc	Apresoline	Ansolysen	Protoveratrine
3. Moil, or severe, with a. Card, failure or	Reserpine	Ansolysen	Protoveratrine	Apresoline
h. Coronary insuff. c. Renal insuff.	Reserpinc	Apresoline	Protoveratrine	Ansolysen
d. Cerebrovascular insufficiency	Reserpine	Apresoline	Ansolysen	or Protoveratrine
4. Acute hypertensive encephalopathy	i.v. Protoveratrine	or Ansolysen	or Apresoline	or Reserpine
5. Malignant phase a. Incipient	Reserpine	Protoveratrine Ansolysen	Apresoline
b. Established 1 . renal insuff.	Reserpine	Apresoline	Protoveratrine	Ansolysen
2. card, insuff.	Reserpine	Ansolysen	Protoveratrine	Apresoline

( chlorisondamine dimethochloride ) and meca- mvlamine, marketed as Inversine, a secondary amine ( 3-methylaminoisocamphane hydrochlor- ide). Both are potent ganglionic blocking agents and, according to experimental and limited clini-

BIBLIOGRAPHY

GENERAL

1. Smithwick, R. H.: Surgical treatment of hypertension. Am.

J. Med. 4:744, 1948.

2. Fishberg, A. M.: Sympathectomy for essential hypertension.

J.A.M.A. 137:670, 1948.

3. Perera, G. A.: Diagnosis and natural history of hyperten-

sive vascular disease. Am. J. Med. 4:416, 1948.

4. Palmer, R. S., Loofbourow, D. G., and Doering, C. R.: Prognosis in essential hypertension; 8-year follow-up study of 430 patients on conventional medical treatment. New Eng- land J. Med. 239:990, 1948.

5. Grimson, K. S., and others: Results of treatment of patients with hypertension by total thoracic and partial to total lumbar sympathectomy, splanchnicectomy and celiac ganglionectomy. Ann. Surg. 129:850, 1949.

6. Evans, J. A., and Bartels, C. C.: Results of high dorsolum- bar sympathectomy for hypertension. Ann. Int. Med. 30: 307, 1949.

7. Evelyn, K. A., Alexander, F., and Cooper, S. R.: Effect

of sympathectomy on blood pressure in hypertension. J.A.M.A. 140:592, 1949. '

8. Hammarstrom, S., and Bechgaard, P.: Prognosis in arterial hypertension. Comparison between 251 patients after sym- pathectomy and a selected series of 435 non-operated pa- tients. Am. J. Med. 8:53, 1950.

9. White, P. D., Dimond, E. G., and Williams, A.: Follow-

up study of 100 private hypertensive patients with cardiovas- cular complications. J.A.M.A. 143:1311, 1950.

10. Smithwick, R. H.: Hypertensive cardiovascular disease.

J.A.M.A. 147:1611, 1951.'

11. Hoobler, S. W., and others: Effects of splanchnicectomy on blood pressure in hypertension. Circulation 4:173, 1951.

12. Page, I. H.: Treatment of essential and malignant hyperten- sion. J.A.M.A. 147:1311, 1951.

13. Palmer, R. S.: Medical progress; essential hypertension: se-

lected review and commentary. New England J. Med. 252: 940, 1955.

14. Nickerson, M.: Pharmacology of adrenergic blockade. J.

Pharmacol. & Exper. Therap. 95:28, 1949.

cal reports, behave much like the methonium group. Both have the suggested advantage of more complete absorption and Mecamvlamine has, in addition, that of leaving renal blood flow undisturbed.

DIB ENA MINE

15. Nickerson, M., and Goodman, L. S.: Pharmacology of series of new sympatholytic agents. Proc. Am. Federation Clin. Re- search 2:1092, 1945.

16. Nickerson, M., Nomaguchi, G., and Goodman, L. S.: Rela- tion of structure to activity in new series of sympatholytic agents. Federation Proc. 5:195, 1946.

17. Hecht, H. H., and Anderson, R. B.: Influence of Dibena-

mine on certain functions of sympathetic nervous system in man. Am. J. Med. 3:3, 1947.

18. Haimovici, H., and Medinets, H. E.: Effect of Dibenamine

on blood pressure in normotensive and hypertensive subjects. Proc. Soc. Exper. Biol. & Med. 67:163, 1948.

Dl HYDROERGOT ALKALOIDS

19. Hartman, M., and Isler, H.: Chemische Konstitution und

pharmakologische Wirksamkeit von in 2- Stellung substituier- ten Imidazoline. Arch, exper. Path. u. Pharmakol. 192:141, 1939.

20. Stoll, A., and Hoffman, A.: Die Alkaloide der Ergotoxin-

gmppe: Ergocristin, Ergokrvptin und Ergocormin. Helvet.

chem. acta 26:1570, 1943.

21. Rothlin, E.: Zur Pharmakologie der hydrierten naturlichen

Mutterkomalkaloide. Helvet. med. acta 2:48, 1944.

22. Bluntschli, H. J., and Goetz, R. H.: Effect of ergot deriva- tives on circulation in man with special reference to 2 new hydrogenated compounds. Am. Heart J. 35:873, 1948.

23. Bancroft, H., Konzett, H., and Swan, H. J. C.: Observa- tions on action of hydrogenated alkaloids of ergotoxine group on circulation in man. J. Physiol. 112:273, 1951.

PRJSCOLINE

24. Grimson, K. S., Reardon, M. J., Marzoni, F. A., and Hen- drix, J. P. : Effects of Priscoline on peripheral vascular dis-

eases, hypertension and circulation in patients. Ann. Surg. 127:968, 1948.

25. Ahlquist, R. P., Huggins, R. A., and Woodbury, R. A.: Pharmacology of benzylimidazoline (Priscol). J. Pharmacol. & Exper. Therap. 89:271, 1947.

PIPEROXAN

26. Vleeschhouwer, G. R. de: Au sujet de Faction du diethyl-

JANUARY 1958

27

aminomethvl-3-benzodioxane ( F 883 ) et du piperido-methyl- 3-benzodioxane ( F 933 ) sur le systeme circulatoire. Arch, internat. pharmacodyn. 50:251, 1935.

27. Bovet, D., and Simon, A.: Recherches sur l’activite sympa- tholytique des derives de l’aminomethylbenzodioxane. Arch, internat. pharmacodyn. 55:15, 1937.

28. Goldenberg, M., Snyder, C. H., and Aranow, H., Jr.: New test for hypertension due to circulating epinephrine. J.A.M.A. 135:971, '1947.

REGITLNE

29. Grimson, K. S., Longino, F. H., Kernodle, C. E., and O’Rear, H. B.: Treatment of patient with pheochromocytoma; use of adrenolytic drug before and during operation. J.A.M.A. 140:1273, 1949.

30. Emlet, J. R., Grimson, K. S., Bell, D. M., and Orgain,

E. S.: Use of piperoxan and Regitine as routine tests in pa-

tients with hypertension. J.A.M.A. 146:1383, 1951.

hydralazine

31. Reubi, F.: Influence de quelques vasodilatateurs peripheriques sur le flux sanguin renal. Helvet. med. acta 16:297, 1949.

32. Schroeder, 11. A.: Effect of 1-hvdrazinophthalozine in hyper- tension. Circulation 5:28, 1949.

33. Gross, F., Druey, J., and Meier, R.: Eine neue Gruppe

Blutdrucksenkender Substanzen von besonderem Wirkungs- charakter. Experientia, 6:19, 1950.

34. Freis, E. D., and Finnerty, F. A., Jr.: Suppression of vaso- motor reflexes in man following 1-hydrazinophthalozine (C- 5968). Proc. Soc. Exper. Biol. & Med. 75:23, 1950.

35. Grimson, K. S., Cittum, J. R., and Metcalf, B. H.: Action of 1-hydrazinophthalozine (C-5968) on vasomotor reflexes and hypertension in dog and man. Federation Proc. 9:279, 1950. '

36. Taylor, R. D., Page, I. H., and Corcoran, A. C.: Hor-

monal neurogenic vasopressor mechanism. Arch. Int. Med. 88:1, 1951.

37. Taylor, R. D., Dustan, H. P., Corcoran, A. C., and Page,

I. H.: Evaluation of 1-hydrazinophthalozine ( “Apresoline” )

in treatment of hypertensive disease. Arch. Int. Med. 90: 734, 1952.

38. Moyer, J. H., Huggins, R. A., and Handley, C. A.: Fur-

ther cardiovascular and renal hemodynamic studies following the administration of hydralazine and effect of ganglionic blockade with hexamethonium on these responses. J. Phar- macol. & Exper. Therap. 109:175, 1953.

39. Perry, H. M., Jr., and Schroeder, H. A.: Syndrome simu- lating collagen disease caused by hydralazine (Apresoline).

J. A.M.A. 154:670, 1954.

METHONIUM GROUP

40. Lyons, R. H., and others: Effects of blockade of autonomic

ganglia in man with tetraethylammonium; preliminary obser- vations on its clinical application. Am. J. Med. Sc. 213:315, 1947.

41. Moe, G. K., and others: Evaluation of vasomotor tone in ani- mal and man bv means of tetraethylammonium. J. Lab. & Clin. Med. 32:311, 1947.

42. Arnold, P., Goetz, R. H., and Rosenheim, M. L.: Effect of pentamethonium on peripheral circulation. Lancet 2:408, 1949.

43. Burt, C. C., and Graham, A. J. P.: Pentamethonium and

hexamethonium iodide in investigation of peripheral vascular disease and hypertension. Brit. M. J. 1:455, 1950.

44. Moe, G. K., and Freyburger, W. A.: Ganglionic blocking

agents. Pharmacol. Rev. 2:61, 1950.

45. Finnerty, F. A., Jr., and Freis, C. D.: Experimental and

clinical evaluation in man of hexamethonium (C6), a new ganglionic agent. Circulation 2:828, 1950.

46. Smirk, F. H., and Alstad, K. S.: Treatment of arterial hy- pertension by penta- and hexamethonium salts. Brit. Med. J. 1:1217, 1951.

47. Paton, W. D. M., and Zaimis, E. J.: Methonium compounds. Pharmacol. Rev. 4:219, 1952.

48. Moyer, J. H., Huggins, R. A., Handley, C. A., and Mills,

L. C.: Effects of hexamethonium chloride on cardiovascular

and renal hemodynamics and on electrolyte excretion. J. Pharmacol. & Exper. Therap. 106:157, 1952.

49. Rein, H. J., and Meier, R.: Phannakologische Untersuchun-

gen iiber Pendiomid, eine neuartige Substanz mit ganglien- blockierender Wirkung. Schweiz, med. Wchnschr. 81:446, 1951.

50. Smirk. F. H.: Action of a new methonium compound in ar- terial hypertension. Lancet 1:457, 1953.

51. Wien, R., and Mason, D. F. J.: Pharmacology of M&B

2050. Lancet 1:454, 1953.

52. Freis, E. D., Partenope, E. A., and Rose, J. C.: Penta-

pyrrolidinium (M&B 2050) in treatment of severe hyperten- sion. Circulation 8:448, 1953.

53. Crumpton, C. W., Rowe, E. G., O’Brien, E., and Murphy, O. R., Jr.: Effect of hexamethonium bromide upon coronary flow, cardiac work and cardiac efficiency in nonnotensive and renal hypertensive dogs. Circ. Res. 2:79, 1954.

54. Com insky , B., Prudy, J. R. K., Wheeler, H. O., Hays, R. M., and Bradley, S. E.: “Splanchnic pooling’’ during hypo- tensive action of hexamethonium bromide in dog. J. Clin. Investigation 33:924, 1954.

55. Freis, E. D., Partenope, E. A., Lilienfeld, L. S., and

Rose, J. C.: Clinical appraisal of pentapyrrolidinium (M&

B 2050 ) in hypertensive patients. Circulation 9:540, 1954.

56. Maxwell, R. D. H., and Campbell, A. J. M.: New sym-

pathicolytic agents. Lancet 1:455, 1953.

57. Agrest, A., and Hoobler, S. W.: Long-term management

of hypertension with pentolinium tartrate (Ansolysen). J.A.M.A. 157:999, 1955.

58. Smith, J. R., Agrest, A., and Hoobler, S. W.: Effect of

acute and chronic administration of pentolinium tartrate on the blood pressure and cardiac output in hypertensive pa- tients. Circulation 12:777, 1955.

ARFONAD

59. Sarnoff, S. J., Goodale, W. T., and Sarnoff, L. C.: Graded reduction of arterial pressure in man by means of a thiophanium derivative ( Ro 2-2222 ) ; preliminary observa- tions of its effect in acute pulmonary edema. Circulation 6: 63, 1952.

VERATRUM ALKALOID

60. Krayer, O., and Acheson, G. H.: Pharmacology of veratrum alkaloids. Physiol. Rev. 26:383, 1946.

61. Meilman, E., and Krayer, O.: Clinical studies on veratrum alkaloids; action of protoveratrine and veratridine in hyper- tension. Circulation 204, 1950.

62. Swiss, E. D., and Maison, G. L.: Site of cardiovascular ac- tion of veratrum derivatives. J. Pharmacol. & Exper. Therap. 105:87, 1952.

63. Currens, J. H., Meyers, G. S., and White, P. D.: Use of

protoveratrine in treatment of hypertensive vascular disease. Am. Heart J. 46:576, 1953.

RAUWOLFIA

64. Chopra, R. N., Gupta, J. C., and Mikherjee, B.: Pharma- cological action of an alkaloid obtained from Rauwolfia serpen- tina. Benth: preliminary note. Indian J. M. Research 21:261, 1933.

65. Wilkins, R. W.: New drug therapies in arterial hyperten-

sion. Ann. Int. Med. 37, 1144, 1952.

66. Wilkins, R. W., and Judson, W. E.: Lise of Rauwolfia ser- pentina in hypertensive patients. New England J. Med. 248: 48, 1953.

67. Hughes, W. M., Moyer, J. H., and Daeschner, C. W.: Parenteral reserpine in treatment of hypertensive emergencies. Arch. Int. Med. 95:563, 1955.

ECOLID

68. Plummer, A. J., Trapold, J. H., Earl, A. E., and Max- well, R. A.: Ganglionic blockade in a new bisquatemary

series including Ecolid ( chlorisondamine dimethochloride (SU 3088). J. Pharmacol. & Exper. Therap. (cited bv Grimson, K. S. J.A.M.A. 158:359, 1955.

69. Smirk, F. H., and Hamilton, M.: Action of Ecolid in man. Brit. M. J. 1:319, 1956.

MEC AMYL AMINE

70. Moyer, J. H., and others: Drug therapy of hypertension; pre- liminary observations on clinical use of mecamylamine, a ganglionic block agent. Med. Rec. & Ann. 49:390, 1955.

71. Moyer, J. H., and others: Drug therapy (mecamylamine) of hypertension; results with mecamylamine, completely absorbed ganglionic blocking agent. Arch. Int. Med. 98:187, 1956.

28

THE JOURNAL-LANCET

Section on PAIN

Comments concerning this Section, criticisms, or suggestions for papers will he most welcome. Physicians are cordially invited to submit articles pertaining to pain for consideration. All inquiries and manuscripts should be sent to Dr. John S. Lundy, 102 Second Avenue Southwest, Rochester, Minnesota, or to the Editorial Depart- ment, The Journal-Lancet, 84 South Tenth Street, Minneapolis, Minnesota.

Management of Tic Douloureux

O

CHARLES M. POSER, M.D.

Kansas City, Kansas

Pitfalls beset the path of the medical practi- tioner in attempting to solve the problem of facial pain. One of the reasons is that the area which is usually affected is served by a number of different nerves. Among them are the trigem- inal, some of the upper cervical roots, the glos- sopharyngeal, the great occipital, and, possibly, some ill-understood contributions from the sym- pathetic pathways.

With the great number of neuroanatomic struc- tures possibly causing pain, go an even wider variety of etiologic agents. In 1940, Glaser1 sug- gested the following classification of the dis- orders comprising what he called “atypical facial neuralgia”:

1. Primary atypical facial neuralgia of un- known etiology.

2. Facial neuralgia secondary to such causes as herpes, abnormalities of the mandibular joints, convulsive disorders, nuchal myositis, and so on.

3. Atypical facial neuralgia produced by systemic diseases, such as allergy or psychoneu- rosis.

4. Atypical facial neuralgia secondary to in- fection or neoplasms in the region of the head and neck.

Unfortunately, many patients who have gen- uine atypical facial pain go from doctor to doc- tor forever undiagnosed and overtreated. Re-

charles m. poser is assistant professor of experi- mental neurology at the University of Kansas School of Medicine, Kansas City, Kansas.

Read, in part, at a Symposium on Pain under di- rection of the Department of Postgraduate Medical Education, University of Kansas Medical Center, and the University of Kansas City School of Dentistry, March 6, 1957.

cause ignorance of the pathophysiologic mech- anism of many painful syndromes still prevails, their real distress is labeled a “psychosomatic reaction.”

Nevertheless, among the host of painful con- ditions affecting the face and its surrounding structures, one syndrome is easily differentiated. It is called “tic douloureux” or “trigeminal neu- ralgia" and is manifested in the areas served by the trigeminal nerve. The description of the tics is so characteristic that the disease may be diag- nosed by this means alone. The presence of the tics coupled with a completely negative neuro- logic examination is incontrovertible evidence for true trigeminal neuralgia.

The distinguishing features of tic douloureux are recurrent paroxysms of sharp, stabbing, and, occasionally, burning or searing pain in the dis- tribution of one or more of the sensory branches of the trigeminal nerve. The single most out- standing peculiarity of this disease, which makes it easy to differentiate from other painful facial conditions, is the paroxysmal nature of the at- tacks. They are characterized by a lightning- like suddenness of onset, short duration (from a few seconds to a few minutes), rapid disappear- ance of the pain, and completely pain-free inter- vals between attacks. When the pain is in the ascendant, it is excruciating and almost unbear- able. In the colorful words of Harry Lee Parker,2 the sufferer from tic douloureux “looks miserable and haggard, and he has every reason to be so, for he has such a pain in his face that all the devils out of Hell might be tearing at it.”

Trigeminal neuralgia is a disease of unknown etiology, undetermined pathology, and unex- plained phvsiology. It occurs most commonly in

JANUARY 1958

29

Section on PAIN

middle or late life and is slightly more common in women. Usually, it is unilateral, but in 2 to 5 per cent of the cases, there is bilateral involve- ment.3 The second division of the trigeminal nerve is the most commonly involved; the first, the least often affected.

Because the pain is so severe, tearing of the eyes frequently accompanies it. The paroxysms of pain may occur every few minutes or the patient mav go for days, weeks, or months com- pletely pain free. The pain may prevent him from holding any job and even keep him from carrying out any of his normal daily activities. This is particularly true if so-called “trigger points” or “trigger zones" are present. These are areas of hypersensitivity, which, when touch- ed or affected by motion, set off painful parox- ysms. They are usually located on the face or inside the mouth. When they are part of the syndrome, it may be difficult or even impossible for the patient to wash, shave, speak, or eat. The face assumes a “masklike expression of . . . immobility. There is in this expression the hope of avoidance and the dread of recurrence.

Avicenna was the first to differentiate this dis- ease about 1000 A. D., but the first clear deline- ation of the syndrome is ascribed to Fehr and Schmidt in the latter part of the seventeenth cen- tury.4 Fothergill ' wrote a description of it in 1773 which remains unequalled to this day.

At times, tic douloureux affecting the third division of the trigeminal nerve is difficult to distinguish from glossopharyngeal neuralgia. This disease is probably identical in nature with tri- geminal neuralgia but affects the throat rather than the face.3 Trigeminal neuralgia may occur in combination with glossopharyngeal neuralgia3 as well as in combination with a tic-like neuralgia of the great occipital nerve.6

The nathology of tic douloureux has never been elicited, although theories abound. Its on- set in late middle life seems to offer evidence in favor of the theory that vasospastic ischemia of the gasserian ganglion accounts for the symp- toms in at least some cases. Since the disease is never fatal and surgical removal of the gasser- ian ganglion is not performed, histopathologic studies are scarce. In the few that have been done, no histologic changes have been shown that would account for the disease.

A few conditions may mimic the syndrome and must be distinguished from it. Most important among these are acoustic neurinomas, which occasionally produce tic douloureux. A history of hearing loss, tinnitus, and findings of the neu-

rologic examination should help establish the correct diagnosis and lead to the proper therapy. Neurinomas of the gasserian ganglion will also, on occasion, produce similar symptomatology, but the finding of objective sensory changes in the division of the trigeminal nerve should im- mediately suggest such a diagnosis.

Harris7 has pointed out that on rare occasions, sharp shooting pains in the face may occur following thrombosis of the posterior inferior cerebellar artery or of small perforating pontine branches of the basilar artery. Here again, the presence of objective neurologic signs should establish the fact that the disease is not true tic douloureux.

The pain of dental or periodontal disease is rarely confused with trigeminal neuralgia of the second or third division of the trigeminal nerve, while migraine equivalents seldom are limited to the anatomic distribution of the trigeminal nerve. The pain of Costen’s syndrome is so clear- ly related to movements of the jaw as to be un- mistakable. Postherpetic trigeminal neuralgia is easily diagnosed on the basis of previous herpetic infection, and, although it is associated with some paroxysmal pain, there is an almost con- stant “background” of pain. A syndrome identi- cal to tic douloureux occurs in multiple sclerosis, but rarely is it the first symptom of the disease. Therefore, here too the history, age of onset, and the neurologic findings should help in establish- ing the etiology of the manifestation.

From the preceding, it can be seen that in tic douloureux, the neurologic examination is always normal, and there are never objective signs in the sensory distribution of the trigeminal nerve. Should such signs be present, the diagnosis of true trigeminal neuralgia can no longer be enter- tained.

One of the few mitigating factors in this dis- ease is that long-term and, occasionally, per- manent remissions do occur. This, of course, complicates the evaluation of any medical ther- apy. Occasionally, if the history suggests that an episode in the disease usually lasts a few days or, perhaps, two or three weeks and then goes into remission for a considerable period, it is better to withhold therapy of any kind, provided the patient understands his illness and agrees with this decision.

The type of therapy to be employed must de- pend on bow severely the patient is incapacitat- ed, not only physically by the pain but also psychologically by his dread of the next parox- ysm. The physician may try purely medical

30

THE JOURNAL-LANCET

Section on PAIN

therapy if attacks are infrequent or simply inter- fere with household duties, whereas, if the pa- tient’s employment is in jeopardy, he may find injection or early operation necessary. The pa- tient’s attitude toward his illness as well as the extent, type, and success of previous therapeutic procedures are important considerations.

Little short of injecting the offending division can be done for the patient during the actual paroxysm of pain. However, the paroxysm is usually of such short duration as to make this procedure of questionable value. If possible, narcotics should not be used, since, in a disease such as this, with frequent recurrences and in which the fear of the recurrent attack is so prom- inent, the risks of iatrogenic addiction are serious. The inhalation of trichlorethylene every two or three hours may give transient relief of the acute attack.8 In attacks of moderate severity, aspirin and codeine may be of some help.

For longer term therapy, intramuscular injec- tions of cyanocobalamin (vitamin B^) have relieved paroxysmal attacks in 50 to 80 per cent of the patients.9 There are various ways of ad- ministering this treatment, a common way being the daily injection of 1 cc. of cyanocobalamin containing 1,000 /.ig. per cc. for a period of ten or twelve days. Needless to say, it is difficult to evaluate the actual value of the therapy against the possibility of a spontaneous remission. Evi- dence seems to suggest that these injections may indeed be helpful. Certainly, this simple, harm- less method of treatment should be made avail- able to all patients with tic douloureux.

The intravenous injection of stilbamidine ise- thionate lias also been recommended in the treat- ment of this condition.10 The potential toxicity of this drug, the long period necessary before eval- uation of results is possible, the difficulties in- herent in continuous and repeated intravenous therapy, and the large percentage of patients who complain of the burning paresthesia result- ing from the characteristic neuropathy of the trigeminal nerve make this type of therapy of doubtful value.

Oral administration of various vitamin prepar- ations, including cyanocobalamin has had no effect. Injection of the trigger zones with local anesthetics has been ineffective in most instances.

A different form of therapy consists of the in- jection of either local anesthetic agents, such as procaine, or of absolute alcohol into the gasserian . ganglion or into whichever sensory branch is | affected. Injection of alcohol into the ganglion was first proposed by Hartel11 in 1912. Harris12

reviewed his experience and reported extremely satisfactory results with this method in 1,433 cases. However, the occasional resultant devast- ating paralysis of cranial nerves has deterred most neurosurgeons from using this method. Jae- ger18 recently proposed injecting boiling water into the gasserian ganglion, claiming that it was effective in relieving tic douloureux in 98 per cent of his patients. It has none of the dangers of alcohol injection and is, as far as he has been able to determine from his follow-up studies, capable of producing complete cure.

A simpler and more popular form of therapy has been the injection of the different sensory branches of the trigeminal nerve at the periphery. The first division is easily accessible at the supra- orbital notch; the second, with some practice and experience, can be injected through the infra- orbital foramen; while the third division may be injected at the mandibular foramen. If relief and an anesthetic zone are obtained with procaine, the needle is left in place and absolute alcohol is then injected into the nerve. This, of course, results in an area of anesthesia corresponding to the area of distribution of the affected sensory branch.

Alcohol injection remains an eminently satis- factory means of managing tic douloureux even though the results are rarely permanent. Peet and Schneider14 reported that 74 per cent of their patients obtained relief for less than two months, and only 15 per cent were relieved for more than one year. The alcohol injection can be perform- ed as an office procedure and may naturally have to be repeated on several occasions.

Because of the close association and connec- tions with other nerves in the area, it has been suggested that relief may be obtained by injec- tion of other nerves. Thus, Wyburn-Mason1"’ ob- tained relief in 56 patients with tic douloureux by alcohol injection of the greater auricular nerve. Crue and his co-workers Ui reported good results by injecting alcohol into the great occipi- tal nerve.

The value of these different tvpes of injections must once more be viewed in relation to the possibility of spontaneous remission in this dis- ease. In addition, the possibility exists that al- most any procedure might be useful as long as the cycle of the paroxysmal attack is interrupted. This is known to take place in the treatment of migraine, which comes in cycles similar to those encountered in tic douloureux. Since some authors have postulated the establishment of “reverberating circuits” or “self-contained eir-

JANUARY 1958

31

Section oh PAI N

cuits' in the thalamus in cases of severe pain, such as tic douloureux, the interruption of such a circuit by a nonspecific procedure might ex- plain the temporary relief in the same manner as the fact that root section may not necessarily lead to permanent relief of the disease.

Surgical intervention is probably the best es- tablished type of therapy for this condition. It is almost predictable that the great majority of patients with tic douloureux eventually require surgery to achieve complete lasting relief.

A variety of surgical approaches to this prob- lem were used17 until Spiller and Frazier18 intro- duced the modern operation, which consisted of sectioning the sensory roots between the gang- lion and the pons. Later, this operation was further refined by the introduction of differen- tial root section, so that anesthesia would be restricted only to the affected area. The results of this type of operation are unfortunately not entirelv satisfactory. Even though the mortality varies between 0.5 and 1.6 per cent, postopera- tive complications include keratitis in 5 to 15 per cent, facial paralysis in 2 to 6 per cent, and residual paresthesia develops in approximately half of the patients.9 The latter complication frequently becomes the most objectionable, and many patients complain bitterly of the constant and painful “numbness” which has replaced the occasional attacks of pain. In one large series,14 severe trigeminal pain recurred in 14 per cent of patients upon whom operations were per- formed.

A more recent procedure, introduced by Taarn- liPj19 in 1952, consists of decompression of the posterior root by simply opening the dural sheath. This operation has the advantage of not producing unpleasant postoperative pares- thesia. Relief is obtained in a considerable num- ber of patients. An added advantage is that post- terior root section can always be resorted to if the trigeminal neuralgia recurs. This operation

REFERENCES

1. Glaser, M. A.: Atypical facial neuralgia. Arch. Int. Med. 65:340, 1940.

2. Parker, H. L.: Clinical Studies in Neurology. Springfield, Illinois: Charles C Thomas, 1956.

3. Brzustowicz, R. J.: Combined trigeminal and glossopharyn- geal neuralgia. Neurology 5:1, 1955.

4. Lewy, F. H.: First authentic case of major trigeminal neural- gia. Ann. M. Hist. N.S. 10:247, 1938.

5. Fothergill, J.: Cited by Crawford and Walker.17

6. Skillfrn, P. G.: Great occipital-trigeminus syndrome as re-

vealed bv induction of block. Arch. Neurol. & Psvchiat. 72: 335, 1954.

7. Harris, W.: Rare forms of paroxysmal trigeminal neuralgia and their relation to disseminated sclerosis. Brit. M. J. 2:1015, 1950.

8. Glaser, M. A.: Treatment of trigeminal neuralgia with tri- chloroethylene. J.A.M.A. 96:916, 1931.

has gained considerably in popularity in this country in recent years.

Trigeminal tractotomy in the brain stem, in- troduced by Sjoqvist20 in 1938, is a rather formid- able procedure. The results are not materially better than those gained in other procedures and do not justify the risks of this operation.

Compression rather than decompression of the gasserian ganglion proposed by Shelden,21 simple exposure of the ganglion with production of hy- peremia as practiced by Stender,22 electrocoagu- lation of the gasserian ganglion used by Kirsch- ner,23 and section of the greater auricular nerve advocated by Wybum-Mason15 have all been used to limited extent with various degrees of success and are still in the process of evaluation.

CONCLUSIONS

The proper management of the patient with trigeminal neuralgia depends upon the patient’s attitude towards his illness, the degree of severitv of the disease in terms of discomfort and disabil- ity, and the amount and extent of previous treat- ment.

It is advisable to suggest a course of medical therapy, that is, cyanocobalamin injections, to the patient whose tic occurs at infrequent inter- vals and does not materiallv interfere with his normal activities. Alcohol injections of the offend- ing branch should always precede surgical in- tervention, but endless repetitions of this pro- cedure rapidly reach the point of diminishing returns. Effective surgical therapv in a patient who has been adequately prepared for possible complications of the operation, suggested at the proper time in the course of the management, will result in complete rehabilitation of the great majority of severelv disabled patients.

There is no doubt that in most cases of tic douloureux, patients should be prepared for eventual surgical relief, since medical therapy is, in most instances, of onlv temporary value.

9. Farmer, T. W.: Treatment of disorders involving the cranial and peripheral nerves, in Modem Therapy in Neurology, edited bv F. M. Forster. St. Louis: C. V. Mosbv Co., 1957.

10. Smith, G. W., and Miller, J. M.: Relief of tic douloureux with stilbamidine. Ann. Int. Med. 38:335, 1953.

11. Hartel, F.: Die Leitungsaniisthesie und Injectionsbehandlung des Ganglion Gasseri und der Trigeminusstamme. Arch. klin. chir. 100:193, 1912.

12. Harris, W.: Analysis of 1,433 cases of paroxysmal trigeminal neuralgia (trigeminal tic) and the end result of gasserian alcohol injection. Brain 63:209, 1940.

13. Jaeger, R.: Permanent relief of tic douloureux by gasserian injection of hot water. Arch. Neurol. Psvchiat. 77:1, 1957.

14. Peet, M. M., and Schneider, R. C.: Trigeminal neuralgia, review of 689 ciises with follow-up study on 65 per cent of group. J. Neurosurg. 9:367, 1952.

15. Wyburn-Mason, R.: Nature of tic douloureux; treatment by

32

THE JOURNAL-LANCET

Section on PAIN

alcohol block or section of great auricular nerve. Brit. M. J. 2:119, 1953.

16. Crue, B. L., Shelden, C. II., Pudenz, R. H., and Fresh- water, D. B.: Observations on pain and trigger mechanism in trigeminal neuralgia. Neurology 6:196, 1956.

17. Crawford, J. V., and Walker, A. E.: Surgery for pain, in: A history of Neurological Surgery, edited by A. E. Walker. Baltimore: Williams & Wilkens, Co., 19.51.

18. Spiller, W. G., and Frazier, C. H.: Division of sensory root of trigeminus for relief of tic douloureux. Univ. Penn- sylvania. M. Bull. 1-1:342, 1901.

19. Taarnh0j, P.: Decompression of trigeminal root and poster-

ior part of ganglion as treatment in trigeminal neuralgia. J. Neurosurg. 9:288, 1952.

20. Sjoqvist, O.: Studies on pain conduction in trigeminal nerve; contribution to surgical treatment of facial pain. Acta psychiat. et neurol. (supp). 17:1, 1938.

21. Shelden, C. H., Pudenz, R. H., Freshwater, D. B., and

Crue, B. L.: Compression rather than decompression for

trigeminal neuralgia. J. Neurosurg. 12:123, 1955.

22. Stender, A.: “Gangliolysis” for surgical treatment of tri-

geminal neuralgia. J. Neurosurg. 11:333, 1954.

23. Kirschnf.r, M.: Die Punktionstechnik und die Elektrokoagu- lation des Ganglion Gasseri; liber “gezielte” Operationen. Arch. klin. Chir. 176:581, 1933.

Book Reviews on Pain

INTRODUCTION TO ANESTHESIA: THE PRIN-

CIPLES OF SAFE PRACTICE, by Robert D. Dripps, M.D., professor and chairman, department of anes- thesiology, Schools of Medicine, University of Penn- sylvania and anesthetist, Hospital of the University of Pennsylvania, Philadelphia; James E. Eckenhoff, M.D., professor of anesthesiology, Schools of Medi- cine, University of Pennsylvania and anesthetist, Hos- pital of the University of Pennsylvania, Philadelphia; and Leroy D. Vandam, M.D., clinical professor of anesthesia, Harvard Medical School and director of anesthesia, Peter Bent Brigham Hospital, Boston, 1957. Philadelphia and London: W. B. Saunders Co., 266 pages.

All the authors of this work are well known and are persons of authority in the field. What they have to say represents accepted sound opinion. They cover the field of anesthesia rather well, and they have included useful information on the management of narcotic poi- soning. They have made use of the most difficult but most commendable literary technic of saying much in few words, a technic which calls for a high degree of accuracy. This requirement they have successfully sat- isfied.

The book is printed on good paper, is easily read, and is fairly well indexed. It is pleasant to come upon a book as well done as this one. Anvone who is interested in anesthesia should acquire the book.

John S. Lundy, M.D.

•

ANATOMIES OF PAIN, by K. D. Keele, M.D., F.R.C.P., 1957. Springfield/ Illinois: Charles C

Thomas, 206 pages. $5.50.

This book should become a classic and very likely it will. Seldom does the reader experience such genuine pleasure and even excitement from a book as are pro- vided by this one. The work both stimulates thought and enlarges one’s understanding of the ancient problem of pain. The book would add greatly to the knowledge, practical and cultural, of anyone interested in the sub- ject of pain.

In his prefatory remarks, the author wisely observes, “There appears to exist a widespread conviction that, owing to the technical advances of the last century, nothing of value can have existed previously that can cast anv useful or revealing light on our present prob- lems. The result is that historical introductions rarely

press further into the past than to a vaguely defined ‘Victorian era;’ and often with imperfect comprehension even this far. A case in point occurs in a comprehensive current work on the subject of pain, which by attrib- uting the discovery of the spino-thalamic tract to Spiller in 1905, ignores some fifty years of significant previous work on this subject. To ignore the time dimension of any problem is to risk misunderstanding it. Particularly is this so if, as with regard to Pain, it involves neglect of the keenest and most brilliant thinkers the world has known.

“It is only of recent years that Pain itself has emerged as a problem in its own right. Yet it has received spe- cial attention as part of disease from the earliest dawn of civilization. It is the purpose of this book to show how the changing ideas on the anatomical and physio- logical basis of Pain have flowed as a continuous process from the most ancient medicine until the present day. To attempt this is not to attempt a complete history of the subject, but only to trace the growth of anatomy and physiological concepts which lie, often unconsciously, at the roots of our present ideas. To achieve such an in- tegration I have necessarily been selective of those writers whose works are for the most part well known, for their influence has been greatest. Though authorities have been omitted whose names rightly carry much honor in the history of medicine, I have included all those I have found who made significant contributions to the process of the evolution of the subject.

“It is my own conviction that ‘right thinking’ is an impersonal mode of mental activity in the Buddhist sense; and that thinkers like Aristotle or Leonardo da Vinci achieve exquisitely intimate interpretations of ob- served phenomena, outstripping humbler thinkers, when- ever they are born. However, one of the clearest lessons to be learned from such a survey is that it is not enough to have the right ideas; if they are to be fruitful of results, thev must be produced at the right time, when there is sufficient contextual background to support them. It was just this failure of the intellectual milieu of his dav that gave Leonardo’s right ideas such poor fruit, leaving him in so manv fields merely the ‘anticipator’ rather than the recognized ‘discoverer.’

“In this book there will be found a story of anticipa- tions needing firmer ground to raise them to discoveries. Some have achieved such status already; others await it.

( Continued on page 34 )

JANUARY 1958

33

Editorial

A COMMON PAIN AND AN UNCOMMON PROBLEM

Among the many common pains which may visit the head, tic douloureux is one of the most severe. This pain is so disabling that any- thing which can be done to alleviate it is emi- nently worth while. In fact, this type of pain is so stubborn that the subject itself never becomes old. It is treated in this issue by Dr. Charles M. Poser under the title of “The Management of Tic Douloureux.”

In the October 1957 issue of the Section of Pain, I pointed out that I had been able, by means of the combined use of several new agents, to develop a plan to assist those who are doing cardiac catheterization in children too young to cooperate. Mv experience at that time was not very broad. It still is not too extensive, but I did describe in more detail in the November 1957 issue of the Journal of American Association of Nurse Anesthetists' how this was managed. Much more detailed instructions having to do with this problem will appear soon, I hope, in the Journal of the American Medical Associa- tion.-

The present editorial was written on Decem- ber 11, 1957. To that date I had carried out the

REFERENCES

1. Lundy, J. S.: New Methods for the conquest of pain through use of antagonists and a new management of analgesia- amnesia for cardiac catheterization in children too young to cooperate. J. Am. A. Nurse Anesthetists. 25:221, 1957.

procedure for 34 patients, and, in general, the method has been very satisfactory. I am in the process of making it easier to measure the dose of the drugs required. One drug, alphaprodine hydrochloride (Nisentil hydrochloride) was sup- plied by the manufacturer in the proportion of 60 mg. to the cubic centimeter of solution, a pro- portion which made it almost impossible to mea- sure a dose that would be minute enough to ad- minister to a small baby. The proportion of this agent to its solution will be corrected in the fu- ture, I am sure.

As for the procedure itself, I have also used it for two or three patients who were to under- go examination of the eyes. It permitted ex- amination adequate for arrival at a diagnosis- something which has been difficult heretofore.

I think it is worth repeating that sometimes better results can be obtained with drugs which produce only analgesia and amnesia than with drugs used in a dose large enough to produce anesthesia. Cyanotic patients who have under- gone cardiac catheterization have ranged from 15 months to 14 years and from 15 to 90 lb. There may be other uses for this particular method, but thus far we have not tried others. The editor would appreciate comment about other methods of managing these small children during the diagnostic maneuver concerned.

John S. Lundy, M.D.

2. Lundy, J. S.: Method of producing amnesia-analgesia for

management of children too young to co-operate undergoing cardiac catheterization and other procedures. J.A.M.A. (In press. )

BOOK REVIEWS

( Continued from page 33 )

Perhaps one of the most topical of such anticipations is the concept of the sensorium commune, which, far from being an idea of our Victorian ancestors (as stated in a current medical journal), is traceable back to the most ancient thinkers on the nature of sensation, and now ap- pears due for rebirth.

“It is my hope that present-day workers on Pain will find in these Anatomies of Pain a useful background to the problem, and possibly some still fertile seeds from the past worthy of germination.

“To avoid the manifest risk of errors inherent in para- phrasing views of ancient authorities, 1 have freely quoted from their works. This however does not obviate the erroneous significance which may be attached, for example, to Aristotle’s often quoted description of pain as a ‘passion of the soul,’ which words cannot be intel- ligible without some background of Aristotelian physi-

ology. I have therefore endeavored to introduce each authority’s views on pain with a sketch of his concept of the basis of sensation sufficient to render the quotations comprehensible.

“It has been my endeavor to render these accounts as objective as possible in all chapters, with the exception of the last, in which I have allowed myself to express a more personal interpretation of the present anatomy of pain.”

It is fascinating indeed to be taken back oxer the years on a scientific Pegasus in a sort of guided tour of the various anatomic and physiologic monuments to signifi- cant thought in the understanding of pain mechanisms.

The book is printed on good paper and can be easily read. It contains two indices — one on subjects and one on personal names. Each chapter is well documented with a bibliography. In sum, this book is a magnificent contribution to the literature on pain.

John S. Lundy, M.D.

34

THE JOURNAL-LANCET

Section on PAIN

Current Literature on Pain

ANALGESICS AND THEIR ANTAGONISTS: SOME STERIC AND CHEMICAL CONSIDERATIONS. PART III. THE INFLUENCE OF THE BASIC CROUP ON THE BIOLOGICAL RESPONSE, by A. H. Beckett, A. F. Casy, and N. J. Harper: j. Pharm. & Pharmacol. 8:874-884, 1956.

“Elsewhere the thesis was advanced that the basic group of the molecule influenced analgesic activity and evidence , was adduced in support. In morphine-type compounds, a gradual transition from analgesic to anti-analgesic activ- ity occurred as the group was changed from N-mcthyl to N-ethyl, N-n-propyl and N-allyl .... It seems rea- sonable to assume that the mechanism of action of an ! analgesic antagonist involves competition with an anal- 1 gesic for the ‘analgesic receptor site,’ but ‘fit’ at the re- ceptor surface does not of necessity mediate an analgesic response ....

“The hypothesis is advanced that analgesics and their j antagonists undergo a similar chemical reaction subse- quent to adsorption, the rate constant for the former be- ing very much greater than that for the latter. Oxidative dealkylation to produce nor-compounds is presumed to be the first step in the reaction sequence leading to anal- gesia. Nor-morphine has been shown to have a greater I analgesic activity than morphine upon intracisternal in- j jection into mice.”

jl From John S. Lundy and Fi.orence A. McQuillen: Anesthesia 1 Abstracts. Minneapolis: Burgess Publishing Company, 1957, vol. 45, page 19. Copyright by John S. Lundy.

FATALITIES FOLLOWING TOPICAL APPLICATION OF LOCAL ANESTHETICS TO MUCOUS MEM- BRANES, by J. Adriani and D. Campbell: |.A.M.A.

162:1527-1530, 1956.

j “It is surprising that many physicians are unaware of the hazards of local anesthesia. The pioneers in this field recognized and emphasized the pitfalls that residt from the misuse of local anesthetic drugs .... Accurate statistics on the frequency of untoward reactions and j fatalities due to local anesthetics are not available, be- cause few such mishaps are reported. We are familiar with 10 unreported fatalities in a 15-year period in this institution [Charity Hospital, New Orleans] caused by the topical application of tetracaine to mucous surfaces | for endoscopic procedures ....

“It is the intent of this report to emphasize the extreme potency and relative frecpiency of toxic effects from tet- racaine and not to incriminate the drug as a lethal sub- stance that should be discarded .... The major dis- tinction between reactions due to tetracaine and those of the other aforementioned drugs has been the absence of convulsions and the abrupt opset of syncope. The inter- val between the onset of symptoms and the moment of the fatal termination was brief .... The incidence of l reactions with use of tetracaine by other routes has been considerably less than with the topical route ....

“Rapid absorption has been presumed as the cause, but data in support of this contention have not been available. Studies of blood levels of tetracaine indicate that this occurs and at a more rapid rate than has been supposed. A quantity of drug that results in no detect- j able blood level when infiltrated subcutaneously gives j levels when applied topically that are equal to one-third to one-half of those after intravenous injection. The un-

toward responses are due to the rapid passage of the drug from the site of application into the systemic circu- lation. The absorption from mucous membranes is far more rapid than clinicians have realized and simulates intravenous administration. Study of the fatalities that have occurred indicates that the cause of death is over- dosage from rapid absorption.”

From John S. Lundy and Florence A. McQuillen: Anesthesia

Abstracts. Minneapolis: Burgess Publishing Company, 1957, vol. 45, page 4. Copyright by John S. Lundy.

CORTISONE AND ANESTHESIA, by S. W. Corens:

J. Am. A. Nurse Anesthetists 24:259-264, 1956.

“Evidence exists to indicate that with more prolonged administration of cortisone, suppression of adrenal cor- tical function may persist for as long as 3 to 6 months after the use of the hormone is discontinued .... The patient may show evidences of adrenal insufficiency at induction of anesthesia .... during the course of sur- gery or in the immediate postoperative period. The first and possibly only evidence of acute adrenal insufficiency is otherwsie unexplainable cardiovascular collapse with shock, tachycardia, pallor, etc

“The pituitary-adrenal interrelationship .... is al- tered by the exogenous administration of cortisone so that as a result you may get adrenal atrophy and insuf- ficiency. That with the stress of anesthesia and surgery, adrenal response may be inadequate and you may get collapse, shock and death. In view of the ever increasing number of individuals who are and will be receiving cortisone and may have potential adrenal insufficiency, it is important that anesthesiologists and surgeons be aware of the dangers and be prepared to handle any emergency situation that may arise in this regard.”

From Lundy, John S., and McQuillen, Florence A: Anesthesia Abstracts. Minneapolis: Burgess Publishing Company, 1957, vol. 45, page 73. Copyright by John S. Lundy.

•

THE ASSESSMENT OF THE CARDIAC PATIENT

FOR ANAESTHESIA, by A. J. W. Beard and J. F.

Goodwin: Brit. J. Anaesth. 28:557-568, 1956.

“Patients with cardiac disorders present the anaesthetist with three main problems which are related to ( 1 ) the operation itself, (2) the ability of the patient to with- stand operation or any of its complications, and (3) the selection of the anaesthetic agent and technique .... A close rapport between anaesthetist and surgeon, and their joint understanding of the physiopathologv of heart disease makes for greater safety ....

“The cardiovascular state may be such that even an urgent condition such as an operable neoplasm must re- main untreated, but this is unusual, as, given time for treatment of such conditions as congestive heart failure or for the healing of a recent cardiac infarction, surgery can often be carried through with little increased risk. The control of cardiac rhythm and rate, the correction of sodium and water retention, the treatment of anaemia, the prevention of pulmonary infections, and weight re- duction in obesity can so change the picture as to allow the completion of even radical surgery ....

“Hvpoxia is the greatest danger to which the cardiac patient is exposed during surgical operation. It is often associated with other pathological conditions, such as heart failure or hypotension, either as cause or effect.

JANUARY 1958

35

Section on PAIN

Hypoxia must therefore be considered in relation to such states rather than as an isolated condition ....

“Ordinarily hypoxia is associated with carbon dioxide retention which in moderate excess causes tachycardia; gross carbon dioxide excess, however, impairs the con- duction in the bundle of His, producing heart block and slow ventricular rate. Furthermore, carbon dioxide re- tention increases cardiac irritability and, especially in the presence of cyclopropane or chloroform, cardiac irregu- larity may be so gross as to impair the circulation ....

“Hypoxia may also result from anaemia. The danger of circulatory overloading is well recognized, especially in heart conditions associated with left ventricular failure, mitral stenosis, or pulmonary heart failure. Any trans- fusion to remedy the anaemia must be given slowly, and the use of packed red blood cells is advisable. The use of iron, perhaps given intramuscularly, may sometimes make transfusion unnecessary ....

“In order to reduce the oxygen consumption of the tissues, hypothermia may be used, but it carries a greater liability to ventricular fibrillation with increasing age and in the presence of heart disease .... On the other hand, the avoidance of hyperthermia, or even permitting a few degrees of cooling, is of considerable benefit ....

“The blood pressure is maintained by the cardiac out- put and the total peripheral resistance. The total periph- eral resistance depends on the state of constriction or dilatation of the arterioles. If these are dilated the blood pressure will fall .... There is not yet agreement as to the circulatory effects of the generally accepted anaes- thetic sequences .... While there are difficulties in assessing the haemodynamics of anaesthetic agents in experimental animals and in healthy men, there is, for obvious reasons, very little precise information from pa- tients with cardiac disease ....

“The risk of anaesthesia often depends as much upon the experience and skill of the anaesthetist and the pre- operative degree of cardiac efficiency as upon the type of heart disease .... In general, the risks to which the patient with cardiac disease is exposed depend on the nature of the proposed operation and its possible com- plications and on the general cardiovascular status of the patient. The type of anaesthetic, provided it is com- petently administered and conforms to basic principles, together with the specific nature of the cardiac disability is usually of lesser importance. Nothing overrides the truth that techniques and disease processes which impair the oxygen supply to the heart are always a threat to life.”

From John S. Lundy and Florence A. McQuillen: Anesthesia Abstracts. Minneapolis: Burgess Publishing Company, 1957, vol. 45, pages 16-18. Copyright by John S. Lundy.

•

PEDIATRIC ANESTHESIA, by L. D. Bridenbauch, Jr.: J. Am. A. Nurse Anesthetists 24:155-163, 1956. “Anesthetists who have had limited experience in admin- istering anesthesia to children are still proceeding on the theory that children are ‘just small adults,’ and that if an anesthetic agent is appropriate for an adult, it is also appropriate for a child. However, certain anatomical and physiological characteristics peculiar to the child must be recognized and, accordingly, the amount of anesthetic agent and the technique of administering it must be suit- ably altered ....

“Variations between the respiratory system of the child and that of the adult are of the utmost importance to the anesthetist. These include — Resilience of the bony part

of the thoracic cage, .... Incomplete development of

the lung tissue, Increased respiratory rate .... |

and Small tidal volume ....

“Peculiarities of the child’s cardiovascular system, im- portant to the anesthetist, include — Inherent automatici- ty, . . . . Increased heart rate, .... (and) Low blood pressure, .... Blood loss during surgery is tolerated poorly by infants because they have a small blood volume : ( roughly 80 cc. per Kg. ) and are naturally hypotensive, i “The central nervous system of the infant also presents variations from that of the adult. Most of them are due I to the immaturity of the nervous tissue and result in — Decreased sensation, .... and Increased incidence of convulsions, . . . .The heat regulating centers of the in- >1 fant are immature ....

“The anesthetist should check to see that the patient to be anesthetized has an empty stomach. Aspiration of vomitus is as serious a complication in the child as it is in the adult .... During the course of anesthesia an infant frequently develops an acute distention of the stomach. The cause for this is unknown .... The child’s kidney is much less capable of dealing adequately witli excess amounts of saline than is the adult’s kidney.

“A plea is made for those administering children’s anesthesia to use the drugs and techniques with which they are most familiar and to use them cautiously. If this is done, pediatric anesthesia will truly be ‘anesthesia without tears’ — on the part of both child and parents.”

From John S. Lundy' and Florence A. McQuillen: Anesthesia I Abstracts. Minneapolis: Burgess Publishing Company, 1957, vol. 45, pages 28-29. Copyright by John S. Lundy*.

•

CONTRIBUTION TO THE THERAPY OF MYOCAR- DIAL DEPRESSION CAUSED BY THIOPENTONE SODIUM (STUDIED BY HIGH FREQUENCY CAR- DIOMYOGRAPHY), bv A. Fronek and Z. Pisa: J. Anaesth. 28:366-372, 1956.

“A fall in blood pressure occasionally occurs during intravenous anaesthesia with various barbiturate prepa- rations .... In the studies to be reported, there have been analysed more closely the factors causing lowering of the blood pressure during intravenous anaesthesia with sodium thiopentone and we have attempted to influence this decrease in pressure therapeutically. The effect of this therapeutic intervention on the depth and duration of anaesthesia has also been investigated .... Experi- ments were carried out in a total of 15 dogs ....

“A weakening of ventricular contraction during intra- venous administration of thiopentone has been demon- strated with high frequency cardiomyography. A direct depressant action on myocardial muscle by this drug has also been demonstrated following its intracoronary ad- ministration. It has been found that falls in blood pres- sure caused by thiopentone are immediately reversible by the intravenous administration of 5 to 10 ml. of 10 per cent CaCL.

“The intravenous administration of CaCL affects nei- ther the duration nor the depth of anaesthesia in rabbits.

It has been emphasized that these findings may be of some importance by increasing the safety of intravenous barbiturate anaesthesia: (1) in patients with latent or manifest ischaemic myocardial diseases; (b) in patients in shock; (c) in cases of accidental overdosage or when more toxic preparations are used.”

From John S. Lundy and Florence A. McQuillen: Anesthesia Abstracts. Minneapolis: Burgess Publishing Company, 1957, vol. 45, page 67. Copyright by John S. Lundy-.

36

THE JOURNAL-LANCET

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The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence, by Lawson Wilkins, M.D., ed. 2, 1957.

Springfield, Illinois: Charles C

Thomas. $17.50.

This is a thorough revision of the first edition of Dr. Wilkins’ excel- lent textbook. In addition, the text and illustrations have been expand- ed considerably. The author has done an excellent job in bringing this book up-to-date at a time when progress in this field has been very rapid. Although not intended to be a thorough treatise of every endo- crine disorder in children, it is without doubt the best available source from which to start complete coverage of any facet of endocrinol- ogy in childhood. The notable ex- ception is that diabetes in children is not included. Now included is the latest information on the steroid physiology and clinical aspects of diagnosis and treatment of the ad- renogenital syndrome. The author and his co-workers have been lead- ers in this field, and their very val- uable experience is documented in a clear-cut, easily read section. In addition, a new section is devoted to the newer knowledge regarding the “goiterous cretins.” An entire new chapter has been included to

REVIEWS

familiarize the practitioner with new diagnostic laboratory hormone de- terminations. The purpose of this chapter appears to be to familiarize the clinician with the intelligent use of these tests rather than to serve as a laboratory manual. Such a pur- pose is quite well fulfilled.

Each chapter of this book is writ- ten in essentially the same form as the first edition, although most chapters have not only been revised and brought up-to-date but also en- larged. Very little material is in- cluded that is not essential to the understanding of the conditions dis- cussed. The style creates a logical sequence of written presentation and is accompanied by fine illustrations. The number of illustrations also have been increased and are repro- duced in excellent quality. The use of schematic diagrams as well as

pertinent summaries of the illus- trated pictures gives one the im- pression of having worked with the patient himself.

This book cannot be recommend- ed too highly to any physician who deals with children, including those in the sub-specialties. It is also recommended to owners of the first edition, because so much new ma- terial essential to understanding the rapid advances which have been made has been added since this book was first published.

Robert Ulstrom, M.D.

•

Regulation and Mode of Action of Thyroid Hormones, Ciba Founda- tion Colloquia on Endocrinology, Vol. 10, edited by G. E. W. Wolstenholme and Elaine C. P. Millar, 1957. Boston: Little, Brown and Co., 303 pages. $8.50.

This volume should be brought to the attention of all those especially interested in the mode of action of thyroid hormones, which was made possible through conferences spon- sored by the Ciba Foundation and supported by Ciba Ltd., of Switzer- land. Scientists from various coun- tries participated in this colloquia presenting chiefly physiologic as- pects as shown in well-illustrated scientific articles. Each contains ( Continued on page 26A )

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pertinent bibliography followed by free discussion from the participants. The clinical reader should appro- priate stimulating items of interest from such perusal. The Ciba Foun- dation, its editors, and the support- ing industry are to be praised for their sponsorship.

C. A. McKinlay, M.D.

•

The Surgical Management of Pul- monary Tuberculosis, edited bv John D. Steele, 1957. Spring- field, Illinois: Charles C Thomas, 213 pages. $9.50.

This monograph is the first of a series concerned with various phases of thoracic surgery and dedicated to Dr. John Alexander. It is fitting that this initial volume should be con- cerned with a subject to which Dr. Alexander contributed so greatly, and most of the participants are his former residents. It is a reasonably short but complete presentation of current concepts regarding the sur- gical treatment of pulmonary tuber- culosis. The initial chapters trace the development of surgical pro- cedures for the treatment of pulmo- nary tuberculosis. Ensuing chap-

ters outline the indications for vari- ous types of resections and give morbidity and mortality figures. Combined collapse and resection therapy is discussed, as is plombage and the treatment of pleural tuber- culosis. An interesting chapter on thoracoplasty indicates the general trend away from such a procedure as an isolated form of surgical ther- apy, although its use as an adjunct either before or after resection is common. Good results with decorti- cation and cavernostomy in certain cases are pointed out, and such pro- cedures appear to have considerable usefulness in the treatment of per- sistent pleural spaces and cavities. There is an interesting chapter on the surgical management of tuber- culous psychotic patients. A final chapter is devoted to the chemo- therapy of tuberculosis and includes historic, bacteriologic, and clinical material. The volume is well-writ- ten, extremely readable, and the ref- erences following each chapter are remarkably up-to-date, considering the number of contributors. It should find wide favor with all those interested in this important subject.

Richard H. Egdahl, M.D.

Urology and Industry, by Leonard Paul Wershub, 1956. Spring- field, Illinois: Charles C Thomas, 151 pages, 3 parts. $5.00.

The purpose of this book, as stated by the author in the preface, “to serve as a practical guide to the in- dustrial physician and the urologist in the medico-legal problems aris- ing from industrial accidents and illnesses,” is achieved satisfactorily.

The evolution of industrial medi- cine and Workmen’s Compensation Acts is discussed briefly. The second part of this book is concerned with the legal and medical evaluation of liability. In the third part, 100 in- dustrial urologic cases and their le- gal connotations are adequately pre- sented. Three typographical errors are noted: on page 56, vesicle should be vesical; on page 86, prostatis should be prostatic; and on page 94, diverticuli should be diverticula.

The text is well written and con- cerned with a subject with which most physicians are unfamiliar. The inadequacies in the teaching of fo- rensic medicine in most medical schools are emphasized. It is a val- uable addition to the library of the industrial physician and urologist. The bibliography is adequate.

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The Treatment of Diabetic Acidosis

EDMUND B. FLINK, M.D., and THOMAS K. OLWIN, M.D. Minneapolis, Minnesota

A brief review of the pathogenesis of diabetic ketosis will be made in order to outline a rational basis for therapy. The reader is referred to the most recent Medical Progress review of diabetes mellitus by Beaser.1

Diagnosis requires a clear definition of diabetic acidosis and coma and adherence to strict cri- teria. A state of coma, that is, a profound state of unconsciousness, may occur in a diabetic patient, as in any other person, without being related to diabetic acidosis. The other most im- portant cause of a comatose state in diabetic patients is hypoglycemia. Many tragedies have resulted from confusing hypoglycemia with dia- betic acidosis, since the former is one of the most i serious medical emergencies and must be treated immediately. Other causes include head trauma, cerebrovascular occlusions, meningitis, encepha- litis, and brain tumor. Any of these conditions could also be the precipitating factor in acidosis.

Because of these considerations, a diagnosis of diabetic acidosis should not be made and in- tensive treatment should not be given unless the following criteria are present: ketonemia and hyperglycemia (and, usually, ketonuria and gly- cosuria), decrease of carbon dioxide content or capacity to less than 15 mEq./l., and clinical evidence of acidosis and dehydration. Milder ketosis than this needs prompt treatment with

edmund b. flink is chief of the Medical Service at Veterans Administration Hospital, Minneapolis. thomas k. olwin is with the Department of Medi- \cine at Veterans Administration Hospital.

insulin and other measures but doesn’t require the heroic treatment which will be discussed in detail. Obviously, prevention of severe acidosis by the early treatment of ketosis is better than the best later management of severe acidosis.

PATHOLOGIC PHYSIOLOGY OF DIABETES ACIDOSIS

Lack of insulin is of prime importance and re- sults in impaired glycogenesis, increased glvco- genolysis, and failure of the glycolytic cycle. This causes insufficient pyruvic acid production and disturbance of metabolic equilibrium with keto- nemia and ketonuria (acetone, aceto-acetic acid, beta-hydroxybutyric acid). The ketonemia and ketonuria, the hyperglycemia and glucosuria, in turn, result in polyuria, cellular and extracellu- lar dehydration, loss of electrolytes, and acidosis. These processes develop as a chain reaction and can be reversed only by adequate insulin and replacement of fluids and electrolytes which have been lost. The lack of insulin may be due simply to failure to administer it, an increased demand due to infection, stress, and so forth, or to previously unrecognized diabetes. It is important to ascertain immediately the precipi- tating factor in each instance.

Three studies have defined clearly the very large fluid and electrolyte deficits which occur in diabetic acidosis.3-5 Two of these studies re- cord the cumulative negative balances during production of acidosis by insulin withdrawal, and the third records balance studies of a group of 5 patients during recovery from acidosis. Table 1 summarizes the findings of these studies.

TABLE 1

	Atchley	Butler	Nabarro
Body size	58 kg.	68 kg.	1.73 sq.m.
Water, liters	3.8	6.6	5.5
Sodium and
magnesium, mEq.	216.
Sodium, mEq.		322.	428.
Magnesium, mEq.		50.	40.
Potassium, mEq.	362.	388.	339.
Chloride, mEq.	42.	272.	390.
Phosphorus, gm.	4.6	5.	1.13

Severe enough acidosis developed on the fourth day in the patient of Atchley and associ- ates3 so that the experiment was stopped at a time when the C02 was 14.6 mEq./l. The data recorded in table 1 were actually observed. The observations of Butler and associates4 are part- ially derived data in that theoretic losses from severe acidosis are added to those actually ob- served and are included, since the acidosis was not permitted to progress to a serious point. The data of Nabarro and associates5 are the actual cumulative balances from 5 patients being treat- ed for diabetic acidosis. These latter data, there- fore, are the most representative, but the close similarity of all 3 studies is very impressive. It is noteworthy that the extracellular losses repre- sent from 20 to 25 per cent of the total extracellu- lar volume and that the potassium loss repre- sents 8 to 9 per cent of body stores.

If one uses 70 kg. as the weight of a 1.73 square meter person (Nabarro study), the aver- age losses in Butler s and in Nabarro ’s studies can be expressed as follows on a per kg. basis.

	Butler	Nabarro
Water, ml. /kg.	100.	80.
Sodium, mEq. /kg.	5.	6.
Chloride, mEq. /kg.	4.	5.5
Potassium, mEq. /kg.	6.	5.
Magnesium, mEq. /kg.	0.8	0.6
Phosphorus, mg. /kg.	70.	15.

It is evident from Nabarro's detailed data that there is quite a bit of variability in certain items, particularly in nitrogen and phosphorus. It is also clear that mild acidosis of short duration

is associated with much smaller cellular ion losses but often nearly maximum extracellular fluid losses. The importance of these studies can- not be overestimated, for they permit us to make a reasonable calculation of the requirements of a patient with diabetic acidosis. The studies em- phasize the fact that large quantities of both intracellular and extracellular ions are lost.

The recognition of fatal respiratory paralysis due to hypopotassemia during the course of treatment of diabetic acidosis6 marked a mile- stone in the understanding of potassium metabol- ism. Many cases have been reported since then of serious hypopotassemia. In spite of their con- certed effort to prevent hypopotassemia, Smith and Martin” found that the largest single cause of death in their series was hypopotassemia, since inadequate amounts of potassium were adminis- tered in some cases. “Some” potassium is not sufficient, hut at least 1/3 and preferably 1/2 of the theoretic deficit is necessary in the first twelve to sixteen hours.

A brief case report bears out the need for vigorous therapy. This patient, age 23, had class- ical symptoms of diabetes mellitus for three weeks and then acidosis developed. His treat- ment for the first forty-eight hours at another hospital and for the next forty-eight hours at this hospital is outlined in table 2.

He was admitted to the Minneapolis Veterans Hospital because of progressive weakness to the point of severe generalized paresis. Some cloud- ing of sensorium and typical electrocardiographic changes of hypopotassemia were noted on ad- mission. Unnecessarily large amounts of sodium salts were administered during the second fortv- eight-honr period. The ready-made solution used in this instance had an inadequate concentration of potassium for the treatment of a known potas- sium deficit. Such solutions are adequate only for daily maintenance unless an ampule of po- tassium salt is added.

Nabarro and co-workers5 emphasize the fact that bowel function and a feeling of well-being were brought to normal more rapidly when ade- quate potassium was supplied early in treatment. The transfer of sodium into cells when potassium

TABLE 2

J.T.W., 23	Insulin	Water	Na.	Cl.	Lactate	K.	Mg.	HPOi
Rx. first 48 hours Paralysis Serum K. 1.9	1,200	7,000	481	460	75	75	18	37
Rx. second 48 hours Strength good Serum K. 3.2		6,000	579	745	50	230	12	25

38

THE JOURNAL-LANCET

was not used can be prevented to a large extent by use of potassium. They emphasize the fact that potassium (and probably also magnesium and phosphate) are indicated for general meta- bolic functions of cells and not simply for pre- vention of an occasional instance of cardiac arrhythmia or respiratory paralysis.

THERAPY

General measures. Diabetic acidosis must be re- garded as a major medical emergency. A physi- cian should be in attendance all the time. Local infections of the skin, ears, respiratory or urin- ary tract, and systemic infections should be look- ed for and treated adequately with antibiotics. A detailed history of the diabetes from an in- formant, if necessary, should include information about insulin dosage and sensitivity, other epi- sodes of coma, precipitating episodes, and so forth.

A chart of the important clinical and chemical data is imperative. This chart should include: pulse, blood pressure, state of consciousness, urine volume, urine sugar, urine acetone and di- acetic acid, blood glucose, carbon dioxide ca- pacity, sodium, potassium, plasma acetone, blood urea nitrogen; therapy: insulin, fluid volume, sodium, potassium, chloride, lactate (or bicar- bonate), phosphate, magnesium, glucose; and space for comment on associated illnesses. It is important to keep this chart current.

Each chart must be individualized, but a few generalizations can be made. Some data, such as vital signs, should be cheeked every half hour and oftener if shock exists, of course. Urinalysis should be recorded hourly. Plasma acetone and blood glucose can profitably be checked every two hours until recovery is well under way. The carbon dioxide combining power could be check- ed at six hours, but, if the course is favorable clinically, it need not be determined again. In order to detect hvpopotassemia, serum shoidd be obtained six to twelve hours after starting insulin for optimum results.

When the initial serum potassium is normal in a patient with severe acidosis and, especially, when the blood urea nitrogen is elevated, the

need for potassium is greater, and therapy must be started earlier and given more vigorously. Serial electrocardiograms from the start of ther- apy are particularly valuable as an aid to potas- sium administration, since the information is immediately available. A single lead, such as V:!, is all that is needed for these comparative pur- poses and should be obtained every hour or two.

A severity index8 may be calculated from the data charted to roughly determine the prognosis, but it is more important to alert the physician to the need for vigorous therapy because of un- favorable signs. Such an index, furthermore, has the real advantage of calling attention to the most important unfavorable variables, some of which are often ignored in routine management. Zieve and Hill8 concluded their study as follows: “considered individually, the order of effective- ness of the significant prognostic variables was age, blood pressure (i.e. hypotension), associated conditions, blood urea nitrogen, degree of un- consciousness, and duration of coma.” The need for individualizing treatment according to sever- ity of illness is strongly suggested by the statisti- cal study of Zieve and Hill.9 They found no significant differences in treatment in spite of great differences in severity of illness. As shall be apparent later, there appears to be a particu- lar need for individualizing the dose of insulin. The score can easily be calculated from table 3. 8

Zero is the dividing line between those who have a poor prognosis (negative score) and those who have a better prognosis (positive score). The quantitative value of term I is obtained di- rectly from table 4.

Insulin. The insulin dose used is the subject of considerable controversy. Smith and Martin7 found that there was no significant difference in response of patients given 80 units, 160 units, or 240 units initially and every two hours thereafter until hyperglycemia decreased significantly. To the contrary, however, others believe that an in- crease in insulin dosage has been responsible for great improvement in morbidity and mortal- ity. 10-1 - The following doses were used in a large group of patients who were treated at the Joslin Clinic (table 5).

TABLE 3

SUMMARY OK INFORMATION NEEDED TO CALCULATE SEVERITY SCORE

Severity score = 1 + 11 — III

I = ( 14 AC + 7 DU) AC = associated condition

DU = degree of unconsciousness

II = (0.3 BP + 0. 1 BS) BP = mean blood pressure (S + D)/2

BS = blood sugar, mg./ 100 cc.

Ill = (DC + BUN + 44) DC = duration of coma/hr.

BL^N = blood urea nitrogen. mg./lOO cc.

FEBRUARY 1958

39

TABLE 4

			RATING OF AC
	0	i	2	3 4	5
§ 0	27.9	14.5	7.6	2.0 —4.6	—15.6
fc 1	21.4	8.1	1.1	—4.4 —11.0	—22.0
o 2	15.6	2.2	—4.7	—10.2 —16.9	—27.9
2 Q H °	10.2	—3.2	—10.1	—15.6 —22,3	—33.3
2 4	4.2	—9.2	—16.1	—21.6 —28.3	—39,3
Rating scheme of AC			Rating scheme of DU
0 None				0 Conscious and alert
1 Very mild				1 Drowsy
2 Mild				2 Semiconscious
3 Moderately	severe			3 Unconscious but responds to pain
4 Severe				4 Unconscious and unresponsive
5 Very severe
			TABLE 5
BLOOD SUGAR	LEVEL CORRELATED WITH INSULIN DOSE IN 153 COMA CASES
Blood sugar				Average insulin	Average insulin
on admission				in first 3 hours.	in first 24 hours.
mg. per 100 cc.		Cases		units	units
1,300-1,600		2		800	1,775
1,000-1,300		12		490	826
600-1,000		51		317	482
400-600		46		224	370
200-400		40		110	155
100-200°		2		56	123

•Low values due to administration of insulin on way to hospital

Duncan12 recommends the following initial doses of insulin according to the severity of the acidosis as measured by plasma acetone reaction:

Initial insulin dose	Plasma acetone test
100 units	4+ undiluted
200 units	4-f 1-2 diluted
300 units	4-f 1-4 diluted
400 units	4-f 1-8 diluted

Following the initial doses, as much as 100 units is given every half hour until plasma acetone is less than 4-f in undiluted plasma.

In a review of 25 instances of diabetic acidosis studied at this hospital, the average doses used were:

	Initial blood sugar	Average insulin dosage Total 6 hours 24 hours
1	1,136	475	725
1	660	100	160
12	400-600	255	374
10	296-400	195	248
1	396	780	1,030
Total 25	296-1,136	262	355

The group of patients treated is too small to draw many conclusions from the study. Review- I ing the charts individually indicated inadequate early insulin dosage in some. One patient singled out for attention had a blood sugar of 396. He I received invert sugar in large amounts almost from the start of therapy with the result that hyperglycemia was prolonged, and he received what would otherwise have been an unnecessar- I ily large dose of insulin.

The initial dose of insulin should be large and can be given intravenously or half intravenously and half subcutaneously. Unless there is a his- i tory of marked insulin sensitivity, the initial dose should be 100 units. If the blood glucose is over 700-mg. per cent, the initial dose should be 200 units, and if the blood glucose is over 1,000 mg./ per cent, it should be 300 units. Depending on the severity of the acidosis, a dose of 50 to 100 units should be repeated every half hour for two hours. The most important consideration is the close observation of the glucose response to in- sulin in the first four hours. Failure to respond in this time calls for increase in insulin dose.

Fluid and electroh/tes. The following fluid re- placement therapy for an average sized adult is

40

THE JOURNAL-LANCET

TABLE 6

Fluid

Electrolytes to be added

1. 1,000 cc. distilled water

2. 1,000 cc. distilled water

3. 1,000 cc. 5% glucose

4. 1,000 cc. 5% glucose

5. 1,000 cc. 5% glucose

Two 44 mEq. (3.75 gm.) ampules NaHCCL and one 50 mEq. (2.92 gm. ) vial NaCl. One ampule NaIICO;, and two vials NaCl.

One ampule NaCl. and one 40 mEq. (2.98 gm.) ampule KCL.

One ampule NaCl., 40 mEq. ampule KJIPO,, and 2 gm. MgSO, (17 mEq. Mg.++). One ampule K-HPO., one 20 mEq. ampule KCL, and 2 gm. MgSO,.

TABLE 7

	Water	Na.	Cl.	HCOs	K.	HPOn	Mg.	Glucose
1.	1,000 cc.	139	50	89
2.	1,000 cc.	144	100	44
3.	1,000 cc.	50	90		40			50 gm.
4.	1,000 cc.	50	50		40	40	17	50 gm.
5.	1,000 cc.		20		60	40	17	50 gm.
	Total mEq.	383	310	133	140	80	34

based on knowledge of average losses. Of course, this therapy has to be individualized. Concen- trated ion solutions can be added to a liter of water to make up the solutions as shown in table 6. These solutions will provide the elements shown in table 7.

Appropriate adjustments of these amounts can easily be made for smaller adults and for child- ren. Children require relatively more water, and this can be accomplished by giving somewhat more dilute solutions. Usually, the patient is able to begin oral feeding, including potassium, after this amount of fluid has been given, hut some patients require continued parenteral fluid. Potassium chloride (40 mEq.) should be added to the sixth liter, and potassium phosphate (40 mEq.) should be added to the seventh liter of 5 per cent glucose solution. If symptoms or signs of hypopotassemia (weakness, respiratory par- alysis, and electrocardiographic changes) super- vene in spite of the aforementioned potassium therapy, the concentration can be increased to 80 mEq./l.

It is possible to use commerciallv available

solutions to accomplish approximately the same, results (table 8). One can substitute half-strength lactated Ringer’s solution to which is added 40 mEq. of potassium phosphate to 1 liter and 40 mEq. of potassium chloride to the other. Butler’s solution can also be used. Still other solutions with this approximate composition can be sub- stituted.

On admission, shock or borderline shock may be corrected by the rapid infusion of the first 2 liters of fluid, since simple hypovolemia may be the cause. However, not all patients with shock will respond, and, particularly, those with pro- found shock will require a plasma expander, such as 6 per cent dextran solution or whole blood or plasma. In some instances, noradrenalin (or other vasopressor substances ) may be needed to maintain blood pressure if plasma expanders in reasonable amount fail to do so.

Potassium should be started about four hours after starting insulin. In general, potassium should not be administered unless urine flow is adequate. However, if respiratory symptoms or grave electrocardiographic abnormalities occur.

TABLE 8

	Volume	Na.	Cl.	Lactate	K.	HPO,	Mg.
Ringer’s lactate	1,000	130	107	28	4
Ringer’s lactate	1,000	130	107	28	4
“Electrolyte No. 2	1,000	57	70	25	45	12.5	6
“Electrolyte No. 2	1,000	57	50	25	45	32.5	6
Glucose 5 % with KC1.	1,000		20		60	40.
	5,000	374	354	106	158	85.	12

“Plus 20 mEq. potassium chloride to 1 liter and 20 mEq. potassium phosphate to the other.

FEBRUARY 1958

41

a small amount of potassium (40 mEq.) should be given. Extremely careful observation is neces- sary under these circumstances. Some initial potassium deficit would be an advantage during the treatment of prolonged anuria, but hvpopo- tassemia could also aggravate the renal damage or cause death from arrhythmia or paralysis.

In the presence of congestive heart failure or alter acute myocardial infarction, the fluid pro- gram has to be greatly modified. When edema exists in heart failure, the extra fluid stores will be called on, and the primary and, often, only therapy is adequate insulin administration. Since the electrocardiogram becomes useless to detect hypopotassemia in many cardiac patients, po- tassium determinations are needed to decide whether to administer potassium.

A review of the course of treatment of 25 patients with diabetic acidosis treated at this hospital from 1952 to 1955 was made to deter- mine how the general principles mentioned before were actually put into practice. Some records showed many defects, whereas others approached ideal management. There were no deaths, but onlv 3 patients were actually coma- tose and the severity in general was not as great as in many reported series.

The following records the average fluid and electrolyte therapy of 25 instances of diabetic acidosis (in 17 patients) during the first twenty- four hours.

REFERENCES

1. Beaser, S. B.: Diabetes mellitus (medical progress review). New England J. Med. 255:173, and 223, 1956.

2. Field, J. B., Stetten, DeWitt, Jr.: Observations on causes and mechanism of insulin resistance during diabetic acidosis. J. Clin. Investigation. 35:703, 1956.

3. Atchley, D. W., and others: On diabetic acidosis; detailed study of electrolyte balances following withdrawal and re- establishment of insulin therapy. J. Clin. Investigation. 12: 297, 1933.

4. Butler, A. M., and others: Metabolic studies in diabetic coma. Tr. Assoc. Am. Physicians. 60:102, 1947.

5. Nabarro, J. D. N., Spencer, A. G., and Stowers, J. M.: Metabolic studies in severe diabetic ketosis. Quart. J. Med. 21:225, 1952.

6. Holler, J. W.: Potassium deficiency occurring during treat- ment of diabetic acidosis. J.A.M.A. 131:1186, 1946.

Water, cc. 5,700

Sodium, niEtj. 525

Potassium, mEq. (20°) 105

Chloride, mEq. 454

Bicarbonate, mEq. (18®) 150

Phosphate, mEq. (7®) 77

“Number of instances where the ion was administered.

Since the figures shown are average, some patients received inadequate amounts and some excessive amounts. The extremes were 155 mEq. of NaCl. in 1 patient to 1,065 mEq. of sodium, 783 mEq. of chloride, and 332 mEq. of bicarbo- nate in another. Potassium therapy was inade- quate in many instances. These figures do not take into account electrolytes and fluid lost in the urine. Rapid control of hyperglycemia and ketonemia minimize such losses.

SUMMARY

An attempt has been made to present a form of therapy for diabetic acidosis which is based on knowledge of deficits which occur during the development phase of acidosis. Major emphasis has been placed on a correct diagnosis, large doses of insulin given early, treatment of allied and precipitating conditions, early and repeated determinations of desired progress of glucose and ketone levels, and a reasonable approach to replacement of deficits of fluid and electrolytes known to exist in diabetic acidosis.

7. Smith K., and Martin, H. E.: Response of diabetic coma to various insulin dosages. Diabetes 3:287, 1954.

8. Zieve, L., and Hill, E.: Prognosis in moderate or severe diabetic acidosis. Arch. Int. Med. 92:63, 1953.

9. Zieve, L., and Hill, E.: Comparative importance of severity, and therapeutic effort in determining outcome of diabetic acidosis as observed in a representative group of patients. J. Lab. & Clin. Med. 43:107, 1954.

10. Harwood, R.: Diabetic acidosis. New England J. Med. 245: 1, 1951.

11. Joslin, E. P., Root, H. F.. White, P., and Marble, A.: The Treatment of Diabetes Mellitus, ed. 9. Philadelphia: Lea & Febiger, 1952, p. 371-373.

12. Duncan, G. G.: Diabetic coma — therapeutic problem. Ann.

Int. Med. 37:1188, 1952.

42

THE JOURNAL-LANCET

Trauma and Thrombophlebitis

JOHN FARR, M.D., F.R.C.S.(C.) (Edin.) Winnipeg, Manitoba

Thrombophlebitis in the lower extremities is sometimes a late complication of severe injury elsewhere than in the legs. It may de- velop days or weeks after such an injury. After a fracture of the spine or the femur, patients are usually at rest in bed and, in addition, have suf- fered trauma to their soft tissues. The mechan- ism of thrombosis in such patients is thus very similar to that of thrombophlebitis occurring after surgical procedures, and the later effects of the thrombophlebitis are usually recognized and treated because the acute phase has been recognized.

There is another group of cases of great im- portance, namely, direct injuries to the leg, which may or may not result in fracture. Re- cause the swelling may be thought to be due to simple trauma or because the limb is hidden in a cast, the resultant thrombophlebitis is fre- quently not recognized. The high incidence of this condition is evidently not appreciated and, therefore, it is frequently not treated early or with the vigorous postphlebitic management that such a case should have. Reviewing the litera- ture for the last ten years fails to reveal one article on thrombophlebitis directly related to trauma. The absence of literature on the subject indicates either a lack of awareness or indiffer- ence to this condition. Recause of the consid- erable disability that results when the postphle- bitic changes have progressed to a stage where the patient is unable to work, despite his recov- ery from the original Tin jury, careful evaluation and recognition of this condition is important. Dr. D. J. Fraser has kindly provided me with some data on such patients taken from the Work- men's Compensation Board’s files here. They are not statistical samplings but illustrate how im- portant the disability in certain cases may be. A few illustrative examples follow.

A 28-year-old male had a fractured calcaneus and ischium in 1952. He did not work for approximately a year. In May 1956, four years later, lie was receiving a 5 per cent disability for thrombophlebitis. There was a 4-cm. difference in the circumference of the leg.

A 39-year-old male fractured his tibia and femur in

john farr is a lecturer in surgery at the University of Manitoba and a surgeon at the Winnipeg Clinic.

1943. This patient suffered mostly from postphlebitic edema, and permanent disability was 30 per cent. He would have received 40 per cent if he had had an am- putation.

A 50-year-old male, who suffered bruises and swelling of both legs and thighs in December 1946, was dis- charged from the hospital in February 1947 and returned to work in Ap