Massive diltiazem and metoprolol overdose rescued with extracorporeal life support

Chenoweth, James A.; Colby, Daniel; Sutter, Mark E.; Radke, Joshua B.; Ford, James S.; Young, J. Nilas; Richards, John R.

doi:10.1016/j.ajem.2017.07.023

Cited by 17 publications

(11 citation statements)

References 19 publications

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“…[ 7 ] There are also reports surrounding the use of ILE for reversing lipid soluble medication toxicity beyond local anesthetics (e.g. tricyclic antidepressants,[ 8 ] calcium channel blockers,[ 9 ] beta blockers[ 10 ]). Recommendations published recently by the American College of Medical Toxicology[ 3 ] and the American Heart Association[ 11 ] state that consideration of ILE use at the discretion of the responsible physician is reasonable and may be considered when the standards of care are failing.…”

Section: Introductionmentioning

confidence: 99%

Low dose Intralipid resuscitation improves survival compared to ClinOleic in propranolol overdose in rats

et al. 2018

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BackgroundMedication overdose is a prevalent issue and despite mixed reports of efficacy, the use of intravenous lipid emulsions, notably Intralipid®, for the management of toxicity from lipid-soluble drugs is becoming increasingly prevalent. Whether alternative lipid emulsion formulations have similar efficacy for resuscitation compared to Intralipid is not known. Here, we compared the efficacy of Intralipid and ClinOleic® for resuscitation following overdose with the lipid-soluble beta-adrenergic antagonist propranolol.MethodsMale Sprague-Dawley rats (age 3–4 months) were anesthetized with isoflurane and instrumented for direct hemodynamic assessments. In Study One, rats (n = 22) were pre-treated with Intralipid 20% (n = 12) or ClinOleic 20% (n = 10) to determine whether the hemodynamic effects of propranolol could be prevented. In Study Two, rats were randomly assigned to Intralipid 20% (1, 2, or 3 mL/kg IV, n = 21) or ClinOleic 20% (1, 2, or 3 mL/kg IV, n = 20) resuscitation groups following propranolol overdose (15 mg/kg IV). In Study Three the effect of Intralipid 20% (1 mL/kg IV, n = 3) and ClinOleic 20% (1 mL/kg IV, n = 3) in the absence of propranolol was investigated. The primary endpoint in all studies was survival time (up to a maximum of 120 minutes), and secondary endpoints were time to achieve 50%, 75%, and 90% of baseline hemodynamic parameters.ResultsIn Study One, pre-treatment with Intralipid prior to propranolol administration resulted in prolonged survival compared to pre-treatment with ClinOleic at low doses (1 mL/kg; P = 0.002), but provided no benefit at higher doses (3 mL/kg; P = 0.95). In Study Two, Intralipid conferred a survival advantage over ClinOleic, with 18/21 rats surviving 120 minutes in the Intralipid group and only 4/20 survivors in the ClinOleic group (P<0.0001). Median survival times (with interquartile ranges) for rats treated with Intralipid, and ClinOleic, and saline were 120 (80.5–120) min, 21.5 (3.25–74.5) min, and 1 (0.25–2.5) min respectively (P<0.001). Only 3/21 rats in the Intralipid group survived less than 30 minutes, whereas 12/20 ClinOleic treated rats had survival times of less than 30 minutes. The number of rats achieving 75%, and 90% of baseline mean arterial pressure was also greater in the Intralipid group (P<0.05 for both values). Treatment in Study Three did not alter survival times.ConclusionsLow-dose Intralipid (1, 2, or 3 mL/kg IV) confers a survival advantage up to 120 minutes post-propranolol overdose (the end-point of the experiment) and better hemodynamic recovery compared to ClinOleic (1, 2, or 3 mL/kg IV) in rats with propranolol overdose. As health care centres choose alternate intravenous lipid emulsions, limited availability of Intralipid could impact efficacy and success of overdose treatment for lipid-soluble drugs.

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Section: Introductionmentioning

confidence: 99%

Low dose Intralipid resuscitation improves survival compared to ClinOleic in propranolol overdose in rats

et al. 2018

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“…Although cases of HIET for BB/CCB overdose are often subject to reporting bias, there are some reported cases of novel therapies used when HIET and other treatment modalities failed. For example, one case reported a 26‐year‐old female patient who had ingested ~2400 mg diltiazem and an unknown amount of metoprolol . The patient deteriorated despite interventions with IV fluids, calcium, ILE, and HIET and was placed on extracorporeal membrane oxygenation .…”

Section: Current Literaturementioning

confidence: 99%

“…37 The patient deteriorated despite interventions with IV fluids, calcium, ILE, and HIET and was placed on extracorporeal membrane oxygenation. 37 It is important to note that this patient's maximum insulin infusion only reached a rate of 1 unit/kg/hour. This case highlights that the condition of some patients may still deteriorate despite HIET or other therapies.…”

Section: Hyperinsulinemic-euglycemic Therapy Failurementioning

confidence: 99%

“…For example, one case reported a 26‐year‐old female patient who had ingested ~2400 mg diltiazem and an unknown amount of metoprolol . The patient deteriorated despite interventions with IV fluids, calcium, ILE, and HIET and was placed on extracorporeal membrane oxygenation . It is important to note that this patient's maximum insulin infusion only reached a rate of 1 unit/kg/hour.…”

Section: Current Literaturementioning

confidence: 99%

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An Overview of Hyperinsulinemic‐Euglycemic Therapy in Calcium Channel Blocker and β‐blocker Overdose

Krenz

Kaakeh

2018

Pharmacotherapy

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Both calcium channel blockers (CCBs) and β blockers (BBs) are associated with fatal substance exposures within the United States. Cases of overdose with these agents have the potential to be both complex and difficult to manage. A variety of pharmacologic treatment options are available for clinicians to use to help mitigate harm from these poisonings. Hyperinsulinemic-euglycemic therapy (HIET) was once regarded as a last-ditch effort to treat patients in highly refractory cases. In recent years, this therapy has become a routine therapy in the treatment of CCB/BB overdose. This article provides a literature review regarding HIET in cases of overdose with CCB and BB agents. Relevant literature articles from 1997-2018 were identified and reviewed using the PubMed and Embase databases. The following search terms were used to identify potential articles: "hyperinsulinemic-euglycemic therapy," "overdose," "calcium channel blocker," "beta blocker," and "insulin." Articles published in the English language were included in this review. A manual search of reference lists was also conducted. Much of the literature is limited to case reports, series, retrospective chart reviews, and small prospective studies. The success rate observed in published case series ranged from 80.4-100%. Regular insulin is most commonly dosed at an initial bolus of 1 unit/kg followed by a regular insulin infusion of 0.5-1 unit/kg/hour. Euglycemia is often maintained using intravenous fluids containing dextrose. Hyperinsulinemic-euglycemic therapy exhibited a promising safety profile, provided close monitoring is conducted. More research is needed to determine optimal strategies for maintaining euglycemia, ideal monitoring parameters, and consistent efficacy goals.

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“…The reluctance to initiate ECLS may be related to the high complication rate or the huge resources needed. [16][17][18] Late initiation of ECLS often means increased stress during insertion of the vascular cannulas. Resuscitation scenarios have been shown to be associated with a higher failure rate of cannula insertion.…”

Section: Early Initiation Of Extracorporeal Life Supportmentioning

confidence: 99%

Extracorporeal life support: The final ‘antidote’ for massive propranolol overdose

Chen

Mao

Chen

2018

Hong Kong Journal of Emergency Medicine

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Massive propranolol overdose may result in severe cardiotoxicity. A 48-year-old female had consumed more than 5000 mg of propranolol. Despite high-dose insulin, intravenous sodium bicarbonate, glucagon and inotropic support, she became hypotensive and subsequently arrested. Following cardiopulmonary resuscitation, she had a return of spontaneous circulation but continued to experience refractory hypotension. Resuscitation continued with venoarterial extracorporeal life support. Therapeutic plasma exchange was initiated to shorten time on extracorporeal life support. Extracorporeal life support was weaned off within 67 h, and she survived without neurological deficits. This records the largest propranolol overdose in recent years. When traditional antidotes are insufficient to prevent collapse, extracorporeal life support is a salvage therapy to maintain perfusion and reduce vasopressor requirements. As drug clearance is significantly prolonged, therapeutic plasma exchange can enhance removal of propranolol and reduce the time to extracorporeal life support removal. With increasing expertise and availability, extracorporeal life support should be considered early in patients who have overdosed with significant cardiotoxicity.

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Massive diltiazem and metoprolol overdose rescued with extracorporeal life support

Cited by 17 publications

References 19 publications

Low dose Intralipid resuscitation improves survival compared to ClinOleic in propranolol overdose in rats

Low dose Intralipid resuscitation improves survival compared to ClinOleic in propranolol overdose in rats

An Overview of Hyperinsulinemic‐Euglycemic Therapy in Calcium Channel Blocker and β‐blocker Overdose

Extracorporeal life support: The final ‘antidote’ for massive propranolol overdose

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