tClinical associate professor, Department of Psychiatry, Uni- versity of British Columbia, Vancouver. jClinical director, emergency psychiatry, Vancouver General.
Psychosis due to transdermally administered scopolamine G. William MacEwan,* MD Ronald A. Remick,t MD, FRCPC Joseph A. Noone,4 LRCPI, LRCSI, FRCPC
oxic psychosis after oral
or subcutaneadministration of scopolamine or other cholinergic blocking agents is well documented.' Symptoms include
ous
confusion, agitation, hallucinations and
insomnia.' Other side effects of anticholinergics are
mydriasis, drowsiness, dryness of the mouth,
urinary retention, tachycardia and impairment of
visual accommodation. Since 1981 a transdermal preparation of scopolamine, Transderm-V (CIBA Pharmaceuticals, Mississauga, Ont.), has been marketed as an antiemetic. The delivery system is a 0.2-mm-thick plastic disc with an adhesive side that adheres to the skin, usually behind the ear. The disc contains 1.5 mg of scopolamine and delivers 0.5 mg/d at a constant rate for 3 days. With this preparation tachycardia, impairment of accommodation and hallucinations are rare.3 Over 7 million transdermal scopolamine patches have been sold, and there are few reports in the American literature of toxic psychosis associated with the product.4-7 This is the first Canadian report of such a toxic state. Case report A 62-year-old woman was transferred to a hospital emergency department from a cruise ship infirmary with a 3-day history of agitation, aggressive behaviour, confusion, disorientation, incoherent speech and repetitive picking at the air. As the ship left port after she was admitted to hospital, no further pertinent history could be obtained. At the time of admission her temperature was 37.50C, heart rate 100 beats/min, blood pressure 135/90 mm Hg and respiratory rate 21/min. The levels of serum potassium, sodium, chloride, bicar*Resident, Department of Psychiatry, University of British Columbia, Vancouver tClinical associate professor, Department of Psychiatry, University of British Columbia, Vancouver jClinical director, emergency psychiatry, Vancouver General Hospital Reprint requests to: Dr. Ronald A. Remick, Department of Psychiatry, Shaughnessy Hospital, 4500 Oak St., Vancouver, BC V6H 3N1
bonate, urea, creatinine and glucose were within normal limits. The hemoglobin concentration was 119 g/L and the leukocyte count 8.4 X 109/L, with a normal differential count. Screening for amphetamines, barbiturates, alcohol and hallucinogens gave negative results. When examined the patient was incontinent of urine, scratched at her arms, causing bleeding, and talked incoherently. Her pupils were moderately dilated and reacted slowly; horizontal nystagmus was also present. The remainder of the examination gave normal results. Collateral information was obtained from the patient's husband by telephone. The woman was not taking any medications. However, after repeated questioning he remembered that she had been intending to use Transderm-V. Re-examination of the patient revealed no patch behind either ear. Physostigmine, 1 mg given intramuscularly, was administered immediately and 1 hour later. Within 11/2 hours after she received the first dose the patient was less confused, and within 3 hours she was oriented, alert and acting appropriately. She confirmed that she had been using Transderm-V on her voyage. The patient was discharged the next morning. Comments
This case illustrates several of the problems associated with diagnosing toxic psychosis due to transdermally administered scopolamine. First, many of the signs of anticholinergic poisoning (e.g., widely dilated pupils, urinary retention and fever) may be absent, whereas some of those present (e.g., moderate tachycardia) are seen in almost every agitated patient. Second, a patch behind the ear often may not be reported as medication unless the patient is specifically questioned about it. Third, since patients using this medication are often travelling away from home, important collateral information may be difficult to obtain. There are two approaches to the treatment of scopolamine-induced psychosis. A test dose of physostigmine, usually 0.5 or 1 mg administered intramuscularly, subcutaneously or intravenously, may be given and the patient observed.8-10 The patient's vital signs should be monitored because of the possibility of arrhythmias or hypotension. Relative contraindications to physostigmine administration, such as renal hypertension, hyperthyroidism, diabetes and coronary artery disease, CAN MED ASSOC J, VOL. 133, SEPTEMBER 1,1985
431
should be excluded before this approach is considered. The second, more conservative, approach is to remove the patch, wash the skin where it was applied and observe the patient. Psychosis secondary to scopolamine should resolve within 24 hours. This approach avoids the potential dangers of physostigmine as well as the need for intensive monitoring of vital signs. References 1. Gilman AG, Goodman LS, Gilman A (eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed, Macmillan, New York, 1980: 281-287 2. Dysken MW, Merry W, Davis JM: Anticholinergic psychosis. Psychiatr Ann 1978; 8: 452-456 3. Goldman P: Rate controlled drug delivery. N Engi J Med
1982; 307: 286-290
4. Steer RC: Transdermal scopolamine patches for prevention of motion sickness [C]. N Engi J Med 1984; 311: 7 5. Peterson L, Trappolini A: Transdermal scopolamine patches for prevention of motion sickness [C]. Ibid 6. Osterholm RK, Camoriano JK: Transdermal scopolamine psychosis [C]. JAMA 1982; 247: 3081 7. Rodysill KJ, Warren JB: Transdermal scopolamine and toxic psychosis [C]. Ann Intern Med 1983; 98: 561 8. Granacher RP, Baldessarini RJ: Physostigmine: its use in acute anticholinergic syndrome with antidepressant and antiparkinson drugs. Arch Gen Psychiatry 1975; 32: 375380
9. Johnson A, Hollister LE, Berger PA: Anticholinergic intoxication syndrome: diagnosis and treatment. i Clin Psychiatry 1981; 42: 313-317
10. Daunderer M: Physostigmine salicylate as an antidote. Int J Clin Pharmacol Ther Toxicol 1980; 18: 523-535
John Stewart's case of sudden death: a reassessment T.J. Murray,* MD, FRCPC, FACP I
n 1909 Dr. John Stewart (1848-1933), a student of Lister and, later, dean of Dalhousie University's medical school, briefly outlined the tragic, sudden death of a patient under his care whose collapse was so unexpected and dramatic that he put it forward to the medical profession for some explanation.' Although Dean Stewart is long dead, I think his honest and forthright search for an answer to his patient's death deserves a response. The pages of CMAJ seem appropriate because this journal was begun in 1911 as an amalgamation of the Maritime Medical News, which carried Stewart's communication, and the Montreal Medical Journal. Case report A 50-year-old male farmer was being treated by Stewart for a urethral stricture. Previous dilatations had been successful, but the stricture was becoming more difficult to dilate. In the office Stewart was unable to pass a dilator, and there was oozing of blood and small clots. He then injected
into the urethra a "drachum or two" of a solution "prepared by dissolving three grains of eucaine and three and one half ounces of normal saline and adding about eighteen drops of adrenalin solution". Another attempt to pass a bougie was unsuccessful, and arrangements were made for
*Professor of medicine and head, Division of Neurology, Dalhousie University, Halifax Reprint requests to: Dr. 1.1. Murray, Clinical Research Centre, 5849 University Ave., Halifax, NS B3H 4H7 432
CAN MED ASSOC J, VOL. 133, SEPTEMBER 1, 1985
admission and surgery at the Halifax Infirmary. The next day the patient looked rested, comfortable and cheerful. He had been able to pass urine, and Stewart decided to try again to pass the dilator so the farmer would not have to recuperate from an operation during a busy farming season. He injected the solution of eucaine and epinephrine and, "intending it should remain in the urethra for a few minutes, I was about to leave the room . . . when my patient, who had been conversing quietly, remarked 'It did not act this way before', at the same time raising his hand to his forehead". Asked it if caused pain, the man replied "No, but it seems to be going to my head." Stewart continued, "I was quickly at his side and felt his pulse. It was extremely rapid. I asked if he felt sick. There was no reply. His head and eyes turned to the right and there was a single slight convulsive movement and the pulse suddenly stopped. At the same moment, his face, which had been a natural colour, perhaps slightly flushed, became cyanosed and the veins became turgid. I at once began artificial respiration, but the enormously distended veins called for venesection, and I had no lancet or knife of any kind by me." Stewart called a nurse and another physician, and with a scalpel he opened the basilic vein, but very little blood came. He then opened the external jugular vein, and a few ounces of very dark blood appeared, and then the flow ceased. He kept up artificial respiration for over an hour and also used hypodermic injection of strychnine and rectal injections of hot black coffee, but all in vain. "There was not the slightest sign of life from the moment the pulse ceased so abruptly." There was no autopsy. Stewart pondered the cause of "this appallingly sudden death". "I was at
