Fatal diltiazem overdose: report of four cases and review of the literature

Roper, T. A.; Sykes, R.; Gray, Cecil

doi:10.1136/pgmj.69.812.474

Cited by 24 publications

(11 citation statements)

References 6 publications

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“…The LD50 of diltiazem in animals is 10 -100 times the therapeutic dose; thus, the potential for toxic sequelae after ingestion of only 1-2 pills may be much lower than for a medication with a smaller toxic-to-therapeutic ratio. This is corroborated by the finding that in adults, mortality has been associated with blood concentrations in excess of 1500 g/mL, many times the therapeutic blood concentrations of 100 -200 g/mL (71). However, LD50 varies significantly between species (Table 2) and extrapolation of animal data to humans is difficult.…”

Section: Discussionmentioning

confidence: 63%

Are One or Two Dangerous? Calcium Channel Blocker Exposure in Toddlers

Ranniger

Roche

2007

The Journal of Emergency Medicine

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Section: Discussionmentioning

confidence: 63%

Are One or Two Dangerous? Calcium Channel Blocker Exposure in Toddlers

Ranniger

Roche

2007

The Journal of Emergency Medicine

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“…Improvement in heart rate and cardiac output was observed with glucagon (IV bolus of 3 mg, followed by an infusion of 3 mg/h) in two of three animal studies, 86 , 87 but in only one 88 of the three human case series. 48 53 , 84 Cardiac output was not measured in case series. Hyperglycemia and vomiting were side effects observed in six case reports.…”

Section: Resultsmentioning

confidence: 99%

“…Based on human case series, only calcium 48–50 , 56 and dopamine 27 , 49 , 84 were associated with reduced mortality. Most human studies did not report a survival benefit with atropine, 45 , 50 , 53 glucagon, 39 , 53 pacemaker, 117 levosimendan, 108 or plasma exchange. 126 Animal studies did not report any survival benefit either with atropine in a rat model, 45 glucagon in a dog model, 39 or levosimendan in a rat model.…”

Section: Resultsmentioning

confidence: 99%

Treatment for calcium channel blocker poisoning: A systematic review

St‐Onge

Dubé

Gosselin

et al. 2014

Clinical Toxicology

159

135

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ContextCalcium channel blocker poisoning is a common and sometimes life-threatening ingestion.ObjectiveTo evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations.MethodsMedline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types.ResultsThe only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5–2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was assoc...

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“…1). Further, the doseresponse relationship for diltiazem (even at therapeutic doses) is poor [3,6,28,35,36] so a decrease in plasma concentration may not produce a rapid improvement in clinical toxicity.…”

Section: Discussionmentioning

confidence: 99%

Lessons learnt in the pharmacokinetic analysis of the effect of haemoperfusion for acute overdose with sustained‐release diltiazem

Roberts

Mason

et al. 2008

Anaesthesia

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SummaryThe effect of charcoal haemoperfusion on the pharmacokinetics of diltiazem is described in a patient with severe clinical toxicity following acute overdose. The patient presented within 3 h following acute ingestion of multiple medications including sustained-release diltiazem. Routine resuscitation and supportive care were administered, but hypotension did not resolve despite intravenous fluids and infusions of calcium, adrenaline, noradrenaline and vasopressin. Multipledoses of activated charcoal, haemodialysis and charcoal haemoperfusion were prescribed to expedite the elimination of diltiazem. The maximum diltiazem concentration (577 lg.l )1 ) was recorded 7 h post ingestion which was followed by an erratic and prolonged elimination phase.The maximum clearance of diltiazem due to haemoperfusion was calculated to be 19.4 and 15.1 ml.min )1 at different times, equating to removal of approximately 1.5 mg diltiazem during 4 h of haemoperfusion. Haemoperfusion did not appear to remove sufficient diltiazem to recommend its routine use in the treatment of patients with acute diltiazem overdose. Severe cardiovascular depression and death is reported from self-poisoning with diltiazem. In overdose these effects manifest as bradycardia and hypotension which relates more to decreased systemic vascular resistance than cardiac contractility [1]. Standard and sustained-release formulations of diltiazem differ in their pharmacokinetic profile. Acute poisoning with the standard formulation usually leads to a rapid onset of toxicity which largely resolves within 12 h. This differs from the more frequently used sustainedrelease formulation where toxicity is delayed in onset and prolonged [1,2]. For example, in two recent cases only mild hypotension preceded the development of a cardiac arrest more than 13 and 18 h post ingestion [3,4]. The variable time-course of toxicity relates to unpredictable changes in the concentration of diltiazem. This may reflect erratic absorption from an aggregate of sustainedrelease tablets [2], or dose-related factors such as ileus [5][6][7] or changes in clearance due to enzyme saturation or hepatic hypoperfusion with marked hypotension [1,8].The initial management of acute diltiazem poisoning includes gastrointestinal decontamination and the administration of intravenous fluids and calcium. Unfortunately, many cases are refractory to these first-line treatments, requiring other interventions, including atropine, glucagon, vasopressors, temporary pacing, balloon pump,

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Fatal diltiazem overdose: report of four cases and review of the literature

Abstract: As the use and risk of abuse of diltiazem increases, these reports serve to highlight the possible hazards and to alert physicians to what must be regarded as a dangerous and potentially lethal drug in overdosage.

Cited by 24 publications

References 6 publications

Are One or Two Dangerous? Calcium Channel Blocker Exposure in Toddlers

Are One or Two Dangerous? Calcium Channel Blocker Exposure in Toddlers

Treatment for calcium channel blocker poisoning: A systematic review

Lessons learnt in the pharmacokinetic analysis of the effect of haemoperfusion for acute overdose with sustained‐release diltiazem

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