BRIEF CLINICAL OBSERVATIONS

shape of the tablets. The patient s tar ted to complain of feeling chilled and tired, and became poorly responsive the night prior to her admission. In the emergency room, physical examination re- vealed a semi-comatose thin young woman with a diffuse conjun.ctival erythema of the right eye. The pa- tient did not show response to an injection of naloxone, but regained consciousness after intravenous administration of 75 ml of 50 per- cent dextrose solution. A venous plasma glucose measurement ob- tained on arrival was 2.5 retool/li- ter with a simultaneous serum in- sulin concentration (SmithKline Bio-Sc|ence Laboratories) of 87 #U/ml (normal: 4 to 24 #U/ml). Six hours after admission to the emer- gency room, the patient had recur- rent hypoglycemia. She showed an immedia~ response to another in- travenous injection of 75 ml of 50 percent dextrose solution. Eugly- cemia was maintained by an infu- sion of 10 percent dextrose solution for the subsequent 36 hours. A plasma C-peptide concentration (SmithKline Bio-Science Labora- tories) obtained during the infu- sion of 10 percent dextrose was 7.4 ng/ml (normal: 0.5 to 3 ng/ml); si- multaneous serum insulin and ve- nous plasma glucose concentra- tions were 129 #U/ml and 4.9 mmol/liter, respectively. Examina- tion of the patient's medications and identification of the tablets by the poison center revealed that the bottle labeled acetazolamide con- tained chlorpropamide.

Seventeen cases of erroneous dispensing of sulfonylureas in place of another medication have been reported during the past de- cade [1-10]. As in the present case, eight cases involved acetazolamide (Diamox) [1-5]. Chlorpropamide (Diabinese) was the most frequent inadvertently substituted sulfonyl- urea (nine of 17 cases) [3-6,8-10], and acetohexamide (Dymelor) was the most frequently mistaken with acetazolamide (four of eight cases) [1,2]. Dispensing errors were most commonly attributed to the prox- imity of the drugs on the pharma- cy's shelves. This was the cause of the dispensing error in our patient; chlorpropamide tablets were mis- placed in the acetazolamide con- tainer on the pharmacy's shelf. Most of the patients described have had prolonged hypoglycemia and needed infusion of dextrose for

six hours to three weeks to main- tain euglycemia. In the present case, the prolonged duration of ac- tion of chlorpropamide and the use of ophthalmic timolol may have contributed to the prolonged hypo- glycemia.

The possibility of inadvertent ingestion of oral sulfonylureas due to dispensing errors should be con- sidered in all patients with unex- plained hypoglycemia. All medica- tions should be carefully examined and identified and prolonged dex- trose infusions should be adminis- tered. Inadvertent use of sulfony- lureas may be indistinguishable from insulinoma, since insulin and C-peptide concentrations are ele- vated, and should be considered in all patients with fasting hypoglyce- mia.

MICHELE R. GORDON, M.D. DAVID FLOCKHART, M.D., Ph.D.

JOANNA K. ZA WADZKI, M.D. TERRY TAYLOR, M.D.

JAMES N. RAMEY, M.D. RICHARD C. EASTMAN, M.D.

Georgetown University Hospital Washington, D.C. 20007

1. Hargett NA, Ritch R, Mardirossian J, Kass MA, Po- dos SM: Inadvertent substitution of acetohexarnide for acetazolarnide. Am J Ophthalrno11977; 84: 580- 583. 2. Rabb EL: Substitution of acetohexamide for acet- azolarnide (letter). Am J Ophthalrno11979; 87: 848- 849. 3. Aderka D, Pinkhas J: Inadvertently induced hypo- glycemia (letter). JAMA 1978: 240: 1140. 4. Crowson TW, Kriel RL: Hypoglycemia from the in- advertent use of oral hypoglycernic agents. Ann In- tern Med 1980; 92: 134. 5. Ludrnan P, Mason P, Joplin GF: Dangerous misuse of sulfonylureas. Br Med J 1986; 293: 1287-1288, 6. Scala-Barnett DM, Donoghue ER: Dispensing error causing fatal chlorproparnide intoxication in a non dia- betic. J Forensic Sci 1986: 31: 293-295. 7. Ahlquist DA, Nelson RL, Callaway CW: Pseudoinsu- linoma syndrome from inadvertent tolazamide inges- tion. Ann Intern Med 1980; 93: 281-282. 8. Heifetz S, Day D, Ipp E: Inadvertent chlorprop- arnide hypoglycernia--no longer once in a blue moon (letter)? N Engl J Meal 1987; 316: 223. 9. Hunter JH, Jordan RM: Diabinese and Dialurne (let-

i ter). Ann Intern Med 1982; 97: 285. 10. Cohen D J, Saltzrnan M, AppeTGB: Diabinese and Dialume (letter). Ann Intern Med 1982; 97: 285-286.

Submitted April 11, 1988, and accepted in revised form June 3, 1988

EVALUATING DISCHARGES IN THE MEDICAL INTENSIVE CARE UNIT To the Editor: The a r t i c le by Rubins and Moskowitz (Am J Med 1988; 84: 863-869) on discharge decision- making in a medical intensive care unit is an excellent description of a difficult clinical problem. It is sur- prising how similar their prospec- tive data are to our data gathered

more than five years before [1]. A decade of work in this area permits several observations that might form a basis for future study and prospective validation:

(1) It is of note that the authors selected the same time interval, 72 hours, that we did to characterize early readmissions. In the great majority of cases, patients who die (excluding patients in whom a des- ignation of "do not resuscitate" has been made) or who are readmitted within three days of discharge from the intensive care unit (ICU) have been discharged too early. Once this time interval has been exceed- ed, such conclusions are less firm due to the number of variables af- fecting the patient's course.

(2) The authors note a difficulty in devising predictive instruments to identify negative outcomes. This is as much a function of the tools as it is the problem. Readmissions are common to certain diseases seen in the medical ICU and this may not be directly related to pat ients ' physiologic scores. Patients with chronic obstructive lung disease (especially those receiving ste- roids), cirrhosis, and sepsis may be more prone to negative outcomes than other patients who have com- parable or higher physiologic scores. Scoring systems such as APACHE are limited in this re- spect since they are not disease- specific. Clearly, much remains to be learned about the natural histo- ry of ICU diseases.

(3) The notion that readmis- sions, or other negative outcomes, are not related to bed census must be called into question. The article by Strauss et al [2] proposing this concept had a selection bias com- mon to ICU research [3]. If Rubins and Moskowitz had analyzed their data with a significantly smaller medical ICU available to them, then ei ther admission cr i ter ia would have had to be altered so that fewer patients would be ad- mitted or discharge criteria would have had to be changed so that pa- tients would have shorter ICU stays. In either case, if and when the census approached 100 per- cent, then negative outcomes (non- ICU deaths, post-discharge deaths, and/or readmissions) outside the ICU would ultimately increase. The obvious question this raises, yet to be answered, is "when does increasing the number of ICU beds reach the point of diminishing r e -

272 August 1988 The American Journal of Medicine Volume 85

BRIEF CLINICAL OBSERVATIONS

turn (i.e., little or no reduction in negative outcomes)?"

(4) Finally, measuring standard management variables such as re- admission rates and post-discharge deaths is a promising area of re- search and comparison between different ICUs. Because of the rela- tively uniform definitions, these data can promote analysis of differ- ent types of ICUs and similar ICUs in different hospitals. Obviously, conclusions are limited by diagno- sis and severity of illness, but when case mix and severity scoring are used, these standard management variables can provide valuable in- fo rmat ion abou t how d i f fe ren t ICUs function. The work by Ru- bins and Moskowitz is a promising initial venture in this field.

CORY FRANKLIN, M.D. Cook County Hospital

1835 West Harrison Street Chicago, Illinois 60612.

1. Franklin C, Jackson D: Discharge decision-making in a medical intensive care unit: characteristics of unexpected readmissions. Crit Care Med 1983; 11: 61-66. 2. StPauss M J, LoGerfo JP, Yelatzie JA, et al: Ration- ing of intensive care unit services: an everyday occur- rence. JAMA 1986; 255: 1143-1146. 3. Franklin C, Mamdani B, Burke G: The allocation and rationing of high cost services. JAMA 1986; 256: 350.

Submitted May 24, 1988, and accepted May 31, 1988

SEVERE P R I A P I S M AS A C O M P L I C A T I O N OF T E S T O S T E R O N E S U B S T I T U T I O N T H E R A P Y

The treatment of male hypogonad- ism with the long-acting ester of testosterone, testosterone enanth- ate,. given as intramuscular injec- tions at two- to three-week inter- vals, is widely considered to be ap- propriate and safe [1]. Serious side effects of this therapy in men are not reported in a recent edition of a well-known textbook of endocri- nology [2]. We herein describe the occurrence of severe priapism as a complication of testosterone sub- stitution therapy in a hypogonadal man.

In a 20 -yea r -o ld , o the rw i se healthy man, the diagnosis of idio- pathic hypogonadotropic hypogo- nadism was made (serum testoster- one level, 0.90 nmol/liter [normal, 9 to 35]; luteinizing hormone and fol- licle-stimulating hormone values, both 1 IU/liter) and treatment was insti tuted with testosterone en- anti]ate 250 mg by intramuscular

injection every two weeks. Follow- ing the first two injections, the pa- tient experienced em increase in frequency and duration of erec- tions for some days, but these al- ways subsided spontaneously and were not inconvenient. Three days after the third injection, the pa- tient had an erection that was un- accompanied by sexual stimulation and became more and more pain- ful. It failed to subside spontane- ously, and finally, four days later, he was admitted to the hospital. On examination, there was severe pria- pism with strong congestion of the corpora cavernosa and flaccid cor- pus spongiosum. Physical exami- nation and laboratory investiga- tions revealed no underlying dis- ease. Conservative treatment (local cooling with ice, systemic heparin- ization, among others) was insti- tuted at once. Despite these mea- sures, priapism failed to subside and a cavernosum-spongiosum shunt with extensive irrigation of the corpora cavernosa with heparin was performed. Despite initial de- tumescence, recurrent rigidity of the penis was observed one day lat- er and a second shunt operation was necessary. Unfortunately, in- tracavernous thrombosis was pre- sent at this time. This second oper- ation eventually resulted in com- plete and definitive detumescence.

Priapism is a persistent, usually painful, erection of the penis unre- lated to sexual stimulation , and in- volving only the corpora cavernosa, whereas the corpus spongiosum re- mains flaccid. The goal of treat- ment is detumescence of the penis with preservation of erectile func- tion. The earlier therapy is started, the better the chances for preserv- ing potency, and in general it may be assumed that late fibrosis of the corpora cavernosa ensues af ter more than 72 hours of persistent erection [3]. The most frequent causes of priapism are sickle cell anemia, leukemia, and malignan- cies. Drugs have also been incrimi- nated, albeit rarely [4]. The World Health Organization (WHO) Col- laborating Centre for International Drug Monitoring (Uppsala, Swe- den) received in the past years (1968 up to 1987) 122 reports of priapism, comprising 138 suspect- ed drugs, but testosterone was not included in this list. In our patient, priapism was very probably caused by testosterone enanthate, consid- ering the temporal relat ionship

and the absence of any underlying disease. The relationship between the administration of testosterone in hFpogonadal men and the in- creasing frequency and duration of penile erections is well known in clinical prac t ice and has been shown in several experiments [5]. The contrary is true for'priapism, of which the occurrence during tes- tosterone treatment appears to be extremely rare considering the vir- tual lack of case reports in the world literature and in the WHO data base. In 1940, Finkler [6] re- ported the case of a 24-year-old hy- pogonadal man in whom priapism of 17 days' duration developed fol- lowing the administration of 100 mg of testosterone propionate in divided doses over a period of sev- en days. Another case of priapism in a patient with thyrotoxicosis and exophtha lmus who was t rea ted with a high dose of testosterone and estrogens together with para- sympathomimetic drugs was re- ported by Recordier et al [7].

The mechanism by which testos- terone administration may cause priapism is not clear. Considering the observation that genital over- st imulation by excessively pro- longed sexual behavior can lead to priapism [4], it is conceivable that in susceptible persons, the increase in frequency and duration of erec- tions after testosterone adminis- tration might induce hitherto un- known pathologic changes eventu- ally resulting in priapism. Also, the sudden increase in local testoster- one concentration following treat- ment in a patient with a low thresh- old for arousal could be a pathoge- netic factor. Notwithstanding the fact that priapism is rare, we be- lieve it might be wise to instruct tes tos terone- t rea ted pat ients to seek medical help in due time if priapism occurs, in order to dimin- ish the chance of irreversible erec- tile dysfunction.

PIERRE M.J. ZELISSEN, M.D. BRUNO H.eh. STRICKER, M.B., Ph.D.

University Hospital Utrecht, The Netherlands

and The Netherlands Centre for Monitoring of Adverse Reactions

to Drugs Rijswijk, The Netherlands

1. Snyder P J, Lawrence DA: Treatment of male hypo- gonadism with testosterone enanthate. J Clin Endo- crinol Metab 1980; 51: 1335-1339. 2. Griffin JE, Wilson JD: Disorders of the testes and male reproductive tract. In: Wilson JD, Foster DW. williams textbook of endocrinology, 7th ed. Philadel- phia: WB Saunders, 1985; 259-311.

August 1988 The American Journal of Medicine Volume 85 273 ~.