Massive diltiazem overdose

and aortic insufficiencF5 - complicated by aortic dissection in 1 case5- consistently showed cystic degeneration and collagen disruption. From the clinical viewpoint, polycystic kidney disease has been associated with mitral valve prolapse, mild dilatation of the aortic root,’ occasional thoracic,4T5abdominal and cerebral aneurysms,6and a predisposition to valvular regurgitation; all theselesions are reminiscent of the Mat-fan syndrome,1,2which is the paradigm of connective tissue

disorder and frequently ends in the catastrophic complication of acute aortic dissection. This familiar clustering of aortic dissection in polycystic kidney disease is consistent with the hypothesized connective tissue disorder, may occur independently of mitral valve prolapse and arterial hypertension, and outlines another potentially treatablecauseof adverseoutcome in these patients.

1. HossackKF, Leddy CL, JohnsonAM, ScbrierRW, GaboawPA. Echccardiogmphicfindings in autosomal

Massive Diltiazem Overdose

dominant polycystic kidney disease.N Engi J h4ed 1988;3:907-909. 2. Leier CV, Baker PB, Kilman JW, Wooley CF. Car-

diovascularabnormalitiesassociatedwith adult polycystic kidney disease. Ann intern h4ed 1984;loo: 683688.

8. Wilson P, Schrier RW, Breckon RD, Gabow PA. A new method for studying human kidney disease epithelia in culture.Kidney Inr 1986;30:371-378. 4. Di Mattes J, Ficard R, Vachemn A, Bensaid J. Polykystoserenal associd B un syndromede Marfan fmste axec dilatation de l’aorte i&ale et insuftisance aortique.Sot Meld Hop Paris. 1965;118:1665-1673. 5. SelgasR, TemesJL, SobrinoJA, Viguer JM, Otto A, SanchezSicilia L. Enfennedadpoliquistica renal de1adult0asociada.con una forma incompletade sindromede Marfan. Med Chin (Bare) 1981;76:311-313. 8. ChapmanJR, Hison AJW. Polycystic kidneys and abdominal aortic aneurysms.Lancer 1980;1646 652.

morseful. He was discharged afrer I week on diltiazem (60 mg, 3 times daily) and remains well 9 months later.

Derek L. Connolly, MB, Mark A. Nettleton, MB, and Michael D. Bastow, MD

After oral administration of one he became asystolic, and cardiores60 mg diltiazem tablet, the onset of piratory resuscitation was com- action is 93% throughout this period. Urine from 4.0 to 10.2 hours, but in this entated, His pulse was 68 beatslmin and his blood pressure was 76140 output was initially poor. Renal case it was 12 hours, which is the dose intravenous dopamine (3 longest documented4;this is despite mm Hg. An electrocardiogram showed complete heart block, with a ,uglkglmin) was added, and urine normal liver function, as assessedby serum transaminase, albumin and junctional escape rhythm and infe- output increased. The patient gradurolateral 1 mm ST depression (mim- ally became more orientated and re- clotting studies. This case reallirms icking changes subsequently observed on exercise testing of the patient to stage IV of the Bruce TABLE I Diltiazem and Desacetyl-Diltiazem Levels Measured protocol). Shortly after admission,

iltiazem is a calcium antagonist used in the treatment of angina, hypertension and some tachyarrhythmias. It has negative chronotropic and dromotropic effectson the sinoatrial and atrioventricular nodes, and is negatively inotropic. It also reduces systemic vascular resistance by arterial smooth muscle relaxation. There is limited experience in the managementof a massive diltiazem overdose that can be fatal.‘” The present case, in which the patient survived, involves one of the largest diltiazem overdoses described.

D

Serially After Ingestion of the Diltiazem Overdose

From the Department of Medicine, Queen Elizabeth Hospital, Kings Lynn, Norfolk, United Kingdom. Dr. Connolly’s address is: Department of Cardiology, Papworth Hospital, Cambridge, United Kingdom CB3 8RE. Manuscript received October 29, 1992; revised manuscript received May 17, 1993, and accepted May 20. 742

THE AMERICAN JOURNAL OF CARDIOLOGY

Time (hours)

Diltiazem @/ml)

2.5 10.5

4,528 3,577 2,348 1,520 923

18.5 26.5 34.5

VOLUME 72

SEPTEMBER 15, 1993

Desacetyl-Diltiazem @/ml) 954 872 802 434 288

previous reports that the major features of massive diltiazem overdose are: (1) bradycardia with complete heart block and junctional escape; and (2) hypotension thought to be due to a combination of bradycardia, reduced systemic vascular resistance and negative inotropism.3 The patient survived with supportive measures. Calcium therapy has been reported to be ineffective in some reports, but beneficial in others.3-5In the present case, intravenous calcium gluconate restored the junctional rhythm and blood pressurerapidly after the developmentof asystole, such that atropine was not needed.Dobutamine and plasma expanders maintained and increased systemic blood pressures,and were associated with an increase in the rate of the junctional escaperhythm.

Although epinephrine, isoproterenol and dopamine have been used as inotropes in overdosage with calcium antagonists,there are few previous records of the use of dobutamine in this scenario.1,3Administration of dobutamine enabled the use of dopamine at a low dose to selectively improve renal blood flow and urine output.3 The presence of an external transthoracic cardiac pacing system avoided the need for temporary transvenous cardiac pacing and was available immediately. Delays in time to transvenouspacing have led to fatalities in similar cases.* Early gastric lavage and tablet recovery reduced the final peak serum concentrations of diltiazem. Oral administration of charcoal was not used, because reports suggestno benefit, although charcoal

hemoperfusion may be beneficial.4,6 The present case shows that a massive diltiazem overdosecan be tolerated with gastric lavage, intravenous calcium gluconate, inotropes and plasma expanders. 1. Jakubowski AT, MizgaJa HF. Effect of diltiazem overdose. Am J Cardiol 1987:60:932-933. 2. Beno JM, Nemeth DR. Diltiazem and metoclopramide overdose. J Anal Toxirol 1991; 15:2X5-287. 3. Erickson FC, Ling LJ, Grande GA, Anderson DL. Diltnran overdose: case report and review. .I Emer,q Med 1991;9:357-366. 4. Roberts D, Honchaik N, Sitar DS, Tenenbein M. Diltiazem overdose: pharmokinetics of diltiazem and its met&&es and effect of multiple dose charcoal, therapy. J Tmicol C/in Torim/ 1991:29:45-52. 6. Femer RE, Odemuyiwa 0, Field AB, Walker S, Volans GN, Bateman DN. Phannokinetics and toxic effect of diltiazem in ma..sive overdose. Hum Exp Tmicol 1989:X:497-499. 6. Anthony T, Jastremeski M, Elliot W, Morris G, Prasad H. Charcoal hemoperfusion for the treatment of a combined diltlazem and metoprolol overdose. Ann Emery Med 1986;15:1344-1348.

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