Cardiac Complications in Amitriptyline Poisoning: Successful Treatment With Physostigmine

1. Sathmary MN: Bacillus subtilis septicemia and generalized aspergillosis in a patient with acute myeloblastic leukemia. NY State J Med 58:1870-1876, 1958. 2. Coonrod JD, Leadley PJ, Eickhoff TC: Bacillus cereus pneumonia and bacteremia. Am Rev Respir Dis 103:711-714, 1971. 3. Ihde DC, Armstrong D: Clinical spectrum of infection due to Bacillus species. Am J Med 55:839-845, 1973. 4. Sickles EA, Young VM, Greene WH, et al: Pneumonia in acute leukemia. Ann Intern Med 79:528-534, 1973. 5. Bonventre PF, Eckert NJ: The biologic activities of Bacillus anthracis and Bacillus cereus culture filtrates. Am J Pathol 43:201-211, 1963.

79:528-534, 1973. 5. Bonventre PF, Eckert NJ: The biologic ac- tivities of Bacillus anthracis and Bacillus cereus culture filtrates.Am J Pathol 43:201-211, 1963.Cardiac Complications in Amitriptyline Poisoning Successful Treatment With Physostigmine Jonathan Tobis, MD, Bodh N. Das, MD THE USE of tricyclic antidepressant medications is increasing as a form of self-poisoning.There have been a number of reports of the anti- cholinergic effects of amitriptyline hydrochloride and imipramine hydrochloride.1Although many cases of cardiotoxicity have been reported,2 there is little information concerning the treatment of the serious cardiac complications.Physostigmine salicylate has been used successfully to treat the central effects of tricyclic antidepressants, such as agitation, seizures, and coma, as well as their peripheral effects, such as tachycardia.1 We have used this drug in treat- ing a young woman who had a cardiac arrest subsequent to an amitriptyline overdose.To our knowledge, this is the first reported case of amitriptyline poisoning in which malignant arrhythmias and conduction defects were successfully treated with physostigmine.
Report of a Case A 22-year-old woman ingested an esti- mated 750 to 1,000 mg of amitriptyline hydrochloride (Elavil) on March 25, 1975.She was brought to the Lincoln Hospital emer- gency room two hours later in a severely agitated state, and she became progres¬ sively obtunded.An electrocardiogram showed a wide QRS complex with a rate of -125 to 135 beats per minute (Fig 1, A). Physostigmine salicylate was given intrave¬ nously in three successive 2-mg doses.Each injection produced only minimal re¬ sponses in level of consciousness, diminu¬ tion of pupil size, and decrease of the tachycardia.
The patient was transferred to the in¬ tensive care unit where an ECG showed sinus tachycardia (115 beats per minute) with some variation of PR interval, right bundle-branch block with left axis devia- Fig 1 .-A,Initial cardiogram (March 25, 1975, 3 pm) (lead II) shows supraventricular tachycardia with wide QRS complex.B, Lead II rhythm strip taken six days after inges¬ tion of amitriptyline (April 1, 1575) shows sinus rhythm with frequent atrial premature contractions.C, Lead V, rhythm strip taken seven days after overdose (April 2, 1975, 2 pm) shows atrioventricular dissociation with junctional rhythm and premature contrac¬ tions.D, Lead II rhythm strip shows restoration of normal sinus rhythm following 2 mg of physostigmine given intravenously (April 2, 1975, 2:20 pm).
From the University of California at Irvine (Dr Tobis), and Lincoln Hospital, Bronx, NY (Dr Das).
Reprints not available.tion (-120°), and a QRS complex of 0.16 sec (Fig 2).The rate increased to 140 beats per minute and soon thereafter the monitor showed a ventricular tachycardia, and the pulse became unobtainable.External car¬ diac massage was begun.Lidocaine, 100 mg given intravenously, suppressed the ventricular focus, and treatment with physostigmine was reattempted.The QRS complex began to narrow, and the rate slowed.A total of 22 mg of physostigmine salicylate was given over the following 48 hours to maintain the heart rate under 110 beats per minute.The patient was alert by the morning of March 26; an ECG demon¬ strated a narrow QRS complex with an axis of +60°and an incomplete right bundle-branch block (Fig 3).
On April 1, six days after the ingestion of amitriptyline, an ECG showed frequent atrial premature contractions, for which she was not treated (Fig 1, B), and she was discharged.On the following day, she com¬ plained of dizziness and returned to the emergency room.An ECG disclosed atrioventricular dissociation with frequent junctional premature contractions (Fig 1,  C).One mg of physostigmine salicylate was given intravenously, with no response after five minutes.A repeat dose of 1 mg of physostigmine salicylate given intrave¬ nously induced a general tonic-clonic sei¬ zure, during which time her ECG con¬ verted to normal sinus rhythm (Fig 1, D).She subsequently remained in good health.

Comment
Earlier reports of physostigmine in the treatment of anticholinergic poi¬ soning dealt predominantly with the neurologic complications or the more benign cardiac effects such as tachy¬ cardia.Our patient exemplifies some of the more severe cardiac compli¬ cations of amitriptyline, such as the abnormal conduction pathways, atrioventricular dissociation, and ventricular tachycardia.These abnor¬ malities were suppressed with con¬ version to sinus rhythm by physostig¬ mine salicylate, 22 mg given over 48 hours-a higher total dose than is usu¬ ally required to treat the central ner¬ vous system complications.Prolonged period and may respond to physostig¬ mine, but drug must be given cau¬ tiously to avoid inducing seizures.
It is believed that the tachycardia of amitriptyline poisoning occurs through competitive blockade of acetylcholine receptors, resulting in an increased sympathetic tone.It is unclear how the tricyclic anti- depressants induce the high degree of heart block and conduction abnormal¬ ities.Available experimental evi¬ dence indicates that amitriptyline may exert a direct myocardial toxic effect2 and that physostigmine may be effective in reversing the cardio- toxic properties.
Alan Ross, MD, Larry Klecatsky, MD, and the Lincoln Collective provided guidance.

Nonproprietary Names and
Trademarks of Drugs Amitriptyline hydrochloride-Biavii.
Physostigmine salicylate-iïsromioiiri. Pituitary Abscess Following General Sepsis in a Diabetic Patient Yiechul Jung, MD; Jae Dong Kim, MD; Rajagopal Chadaga, MD; Joseph Tandatnick, MD; Leonard P. Caccamo, MD SINCE Glinski1 and Simmonds2 in 1913 and 1914 described pituitary ab- scesses accompanying systemic bacte- rial infection there have been only two such reports in the world litera- ture.3,4 We now report the case of a patient with diabetes mellitus and fatal Es- cherichia coli septicemia in whom se- vere hypoglycemic reactions devel- oped.An abscess of the pituitary gland was found on postmortem ex- amination.

Report of a Case
A 47-year-old woman with a ten-year history of diabetes mellitus was admitted to the hospital because of agitation and disorientation.Her temperature was 38 C, pulse rate 120 beats per minute, and blood pressure 70/50 mm Hg.
She had been taking 40 units of isophane insulin suspension daily, with good control of diabetes and without any history of hypoglycemia or ketoacidosis.On admission, blood glucose level was 400 mg/100 ml with glycosuria (3+ ) and albuminuria (3+ ), as well as many white blood cells (WBC) per high power field.No acetone was detected in either urine or undiluted plasma.The hemoglobin concentration was 9.5 gm/100 ml and the WBC count 13,400/cu mm.Sev¬ eral microaneurysms were noted in the ocular fundi, and there was mild atrophy of the hand muscles.No other substantial abnormalities were found.
Initially, the patient was treated with 20 to 40 units of isophane insulin suspension daily and continuous intravenous infusions of 5% dextrose solution at 125 ml/hr.Cul¬ tures of both blood and urine yielded many E coli.One gram of ampicillin sodium ev¬ ery six hours and 80 mg of gentamicin sul¬ fate every eight hours were given intrave¬ nously.
The patient remained relatively com¬ fortable, though febrile, until the fourth day of hospitalization, when she lapsed into coma, with cold and clammy skin while 5% dextrose solution was running intravenously at 125 ml/hr.Her blood glu¬ cose level was 36 mg/100 ml.She re¬ sponded promptly to the parenteral adminis¬ tration of 50 ml of 50% dextrose solution.
Subsequently, there were eight additional episodes of a similar nature, with blood glucose concentrations ranging from 23 to 59 mg/100 ml while she was receiving 15 to 30 units of isophane insulin suspension a day as well as continuous infusions of 5% dextrose solution.At least two hypoglycé¬ mie reactions occurred without insulin and with glucose when needed for one week.Throughout the entire hospital course, con¬ trol of the sepsis was never achieved, despite the change of antibiotics to chlor- amphenicol, clindamycin hydrochloride hydrate, and cephalothin sodium, accord¬ ing to reports of sensitivity tests.
Pituitary integrity was tested by ad- renocortical function and growth-hormone responses.Plasma cortisol level on the sixth hospital day was 9.0/ig/100 ml and 7.4/jg/100 ml at 8 am and 4 pm, respectively.The 24-hour urine 17-hydroxycorticosteroid and 17-ketosteroid levels were 13.4 and 4.0 mg, respectively, on the seventh day, and 12.6 and 5.4 mg on the tenth day.On the 11th day, however, repeated plasma Corti¬ sol determinations were 3.6/ig/100 ml and 2.2fig/100 ml at 8 am and 4 pm, respectively.
Growth-hormone responses to 1 mg of glucagon were normal on the tenth day, and serial blood glucose levels were 358, 388, 420, 396, and 392 mg/100 ml.
The patient died on her 27th day in the hospital.Autopsy revealed widespread pi¬ tuitary necrosis with massive neutrophilic infiltration.In addition, there were acute and chronic pyelonephritis and multiple abscesses in the renal parenchyma.There was bronchopneumonia in both lower lobes, with multiple septic infarctions of the up¬ per lungs.The adrenal glands and pan¬ creas were normal.

Comment
The severity and frequency of hy¬ poglycémie reactions in this case are impressive.Pituitary functions in terms of growth-hormone responses and adrenocortical function were nor¬ mal initially.Subsequently, however, plasma cortisol levels were very low, indicating flagging pituitary func¬ tion, which ultimately ended in de¬ struction by overwhelming infection.The patient of Brenner3 had a similar course.