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1.
ASAIO J ; 70(5): 404-408, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38165982

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) has had increasing prevalence and indications in the last decade. Calcium channel blocker overdose (CCBOD) can lead to significant cardiopulmonary dysfunction and has also increased in recent years. CCBOD results in cardiac depression, vasoplegia, and hyperglycemia. Expert consensus recommends treatment with calcium, high-dose insulin, inotropes, and vasopressors. Our systematic review evaluated when to initiate ECMO in the CCBOD population and the mortality rate associated with use. Electronic literature review identified all relevant studies for CCBOD and ECMO. PRISMA guidelines for systematic review were followed. Three independent authors reviewed abstracts and full texts, and only CCB ingestion without polypharmacy was included. Two authors independently collected data, which included demographics, current medical treatments, ECMO type, and survival. From 314 abstracts, 25 papers were included with a median publication year of 2019. Twenty-six patients were included with an average age of 32.7 years and 42%/58% male/female. Average time on ECMO 4.3 days. VA and VV ECMO use were 92.3% and 7.7%, respectively, and 84.6% of patients survived to hospital discharge. Before ECMO, most patients received 4-5 medical treatments (53.8%). Our systematic review demonstrates ECMO is a newly used, yet valuable therapy for CCBOD when medical treatment fails. Survival to discharge after ECMO for CCBOD is substantially higher than standard VV or VA ECMO. Medical management is still the mainstay therapy for CCBOD, but we show that a persistently unstable patient may benefit from prompt evaluation at an ECMO center for treatment.


Subject(s)
Calcium Channel Blockers , Drug Overdose , Extracorporeal Membrane Oxygenation , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/adverse effects , Humans , Calcium Channel Blockers/therapeutic use , Calcium Channel Blockers/poisoning , Drug Overdose/therapy , Female , Male , Adult
2.
Arch. argent. pediatr ; 119(6): e610-e615, dic. 2021. tab, ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1353045

ABSTRACT

La intoxicación por bloqueantes de los canales de calcio es un cuadro poco frecuente en la población pediátrica. Los signos y síntomas pueden progresar de forma rápida y llevar al colapso cardiovascular y muerte. El sostén hemodinámico con inotrópicos y vasopresores no suele ser efectivo. La terapia con insulina y glucosa es un complemento eficaz del tratamiento inicial, que está ampliamente estudiado, y se utiliza en diferentes patologías con compromiso hemodinámico. Se presenta el caso de una paciente pediátrica con antecedente de ingestión de dosis altas de amlodipina con fines suicidas, con descompensación hemodinámica refractaria al tratamiento de soporte inotrópico habitual. A partir del tratamiento con insulina y glucosa, se logró la estabilidad hemodinámica, con evolución favorable de la paciente.


Calcium channel blocker poisoning is a rare condition in the pediatric population. Signs and symptoms can be rapidly progressive and lead to cardiovascular collapse and death. Hemodynamic support with inotropics and vasopressors is usually not effective. The insulin/glucose therapy is an effective complement to the initial treatment, which is widely studied and used in different pathologies with hemodynamic compromise. The case of a pediatric patient with a history of high-dose ingestion of amlodipine for suicidal purposes, with hemodynamic decompensation refractory to usual inotropic support treatment, is presented. From the insulin/glucose treatment, hemodynamic stability was achieved with a favorable evolution


Subject(s)
Humans , Female , Adolescent , Suicide, Attempted , Calcium Channel Blockers/poisoning , Amlodipine/poisoning , Drug Overdose/therapy , Glucose/therapeutic use , Insulin/therapeutic use
3.
Clin Toxicol (Phila) ; 59(5): 361-375, 2021 May.
Article in English | MEDLINE | ID: mdl-33555964

ABSTRACT

BACKGROUND: Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning. METHODS: We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods. RESULTS: A total of 83 publications (6 in vitro and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR. CONCLUSIONS: Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.


Subject(s)
Calcium Channel Blockers/poisoning , Drug-Related Side Effects and Adverse Reactions/nursing , Extracorporeal Membrane Oxygenation/standards , Pharmaceutical Preparations , Poisoning/therapy , Practice Guidelines as Topic , Renal Dialysis/standards , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged
4.
Emerg Med Pract ; 22(Suppl 9): 1-42, 2020 09 15.
Article in English | MEDLINE | ID: mdl-33136356

ABSTRACT

While relatively uncommon, an overdose of calcium channel blockers, beta blockers, or digoxin can result in significant morbidity and mortality, and management can be complex. An acute overdose will require different management strategies than chronic toxicity while on therapeutic dosing. Toxicity from these agents must be considered in bradycardic and hypotensive patients. This supplement provides an evidence-based overview of emergency department management of calcium channel blocker overdose, beta blocker overdose, and digoxin toxicity, and focuses on the caveats of treatment for each.


Subject(s)
Adrenergic beta-Antagonists/poisoning , Calcium Channel Blockers/poisoning , Digoxin/poisoning , Drug Overdose/diagnosis , Drug Overdose/therapy , Advanced Cardiac Life Support , Diagnosis, Differential , Emergency Service, Hospital , Evidence-Based Medicine , Humans
5.
J Med Toxicol ; 16(4): 465-469, 2020 10.
Article in English | MEDLINE | ID: mdl-32656624

ABSTRACT

INTRODUCTION: Overdoses of beta-adrenergic antagonists and calcium channel antagonists represent an uncommonly encountered but highly morbid clinical presentation. Potential therapies include fluids, calcium salts, vasopressors, intravenous lipid emulsion, methylene blue, and high-dose insulin. Although high-dose insulin is commonly used, the kinetics of insulin under these conditions are unknown. CASE REPORT: We present a case of a 51-year-old male who sustained a life-threatening overdose after ingesting approximately 40 tablets of a mixture of amlodipine 5 mg and metoprolol tartrate 25 mg. Due to severe bradycardia and hypotension, he was started on high-dose insulin (HDI) therapy; this was augmented with epinephrine. Despite the degree of his initial shock state, he ultimately recovered, and HDI was discontinued. Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter. CONCLUSION: The kinetics of insulin following discontinuation of high-dose insulin therapy are largely unknown, but supraphysiologic insulin levels persist for some time following therapy; this may allow for simple discontinuation rather than titration of insulin at the end of therapy. Dextrose replacement is frequently needed; although the duration is often difficult to predict, prolonged infusions may not be necessary.


Subject(s)
Adrenergic beta-1 Receptor Antagonists/poisoning , Amlodipine/poisoning , Bradycardia/drug therapy , Calcium Channel Blockers/poisoning , Hyperinsulinism/chemically induced , Hypoglycemic Agents/administration & dosage , Hypotension/drug therapy , Insulin/administration & dosage , Metoprolol/poisoning , Bradycardia/chemically induced , Bradycardia/diagnosis , Bradycardia/physiopathology , Drug Administration Schedule , Drug Overdose , Humans , Hyperinsulinism/blood , Hyperinsulinism/diagnosis , Hypoglycemic Agents/blood , Hypoglycemic Agents/pharmacokinetics , Hypotension/chemically induced , Hypotension/diagnosis , Hypotension/physiopathology , Infusions, Intravenous , Insulin/blood , Insulin/pharmacokinetics , Male , Middle Aged , Suicide, Attempted
6.
Dtsch Med Wochenschr ; 145(3): 161-165, 2020 02.
Article in German | MEDLINE | ID: mdl-32018289

ABSTRACT

While monitoring and symptomatic care is sufficient for most intoxicated patients, some develop life threatening symptoms. We present recent changes in the recommendations of the treatment in patients with calcium channel blocker, beta blocker and high dose paracetamol intoxications. Additionally, new insights in the efficacy and safety of the use of physostigmine in anticholinergic patients and beta blockers in cocaine intoxication are discussed as well as the specific considerations in the resuscitation of intoxicated patients.


Subject(s)
Critical Care , Poisoning/drug therapy , Acetaminophen/poisoning , Adrenergic beta-Antagonists/poisoning , Calcium Channel Blockers/poisoning , Carbon/therapeutic use , Humans , Physostigmine/adverse effects , Physostigmine/therapeutic use
7.
S Afr Med J ; 109(9): 635-638, 2019 Aug 28.
Article in English | MEDLINE | ID: mdl-31635586

ABSTRACT

Calcium channel blockers (CCBs) are commonly used in South Africa (SA) in the management of hypertension and other cardiovascular disease. Their ubiquitous availability makes them a common agent in drug overdose (OD), whether through accidental ingestion or deliberate self-harm. It is essential that medical practitioners know how to recognise and manage CCB OD, as severe CCB OD is often fatal. As there is a lack of local literature in SA, we highlight the general principles of management of CCB OD, as well as complications and problems that may be encountered during treatment. This narrative review is based on existing clinical guidelines, retrospective studies and systematic reviews on the emergency management of CCB OD. High-dose insulin euglycaemic therapy has become the mainstay of treatment in severe CCB OD. The rationale, the recommended protocol for its use and its adverse effects are described.


Subject(s)
Calcium Channel Blockers/poisoning , Drug Overdose/therapy , Emergency Treatment/methods , Calcium Channel Blockers/administration & dosage , Cardiovascular Diseases/drug therapy , Humans , Hypertension/drug therapy , Insulin/administration & dosage , Practice Guidelines as Topic , South Africa
8.
Pharmacotherapy ; 38(11): 1130-1142, 2018 11.
Article in English | MEDLINE | ID: mdl-30141827

ABSTRACT

Both calcium channel blockers (CCBs) and ß 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.


Subject(s)
Adrenergic beta-Antagonists/poisoning , Blood Glucose , Calcium Channel Blockers/poisoning , Drug Overdose/drug therapy , Hyperinsulinism , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Humans , Treatment Outcome
9.
BMJ Case Rep ; 20182018 Aug 27.
Article in English | MEDLINE | ID: mdl-30150339

ABSTRACT

Cardiovascular instability associated with calcium channel blocker toxicity comprises a small percentage of overdose presentations, yet they are associated with a high mortality rate. We detail the management of a 64-year-old man who took an intentional overdose of 840 mg nimodipine. We include the treatment he received and highlight the scarcity of evidence behind the use of gastric decontamination, calcium, glucagon, intravenous lipid emulsion, high-dose insulin therapy, sodium bicarbonate, vasopressors and methylene blue in calcium channel blocker toxicity. Additionally, the article explores the use of electrical pacing and venoarterial extracorporeal membrane oxygenation (VA-ECMO). Following successful weaning of VA-ECMO, the patient was successfully extubated but remained neurologically impaired due to hypoxic-ischaemic brain injury, critical care polyneuropathy and renal failure requiring dialysis. He has cerebral performance category 3; he has mild cognitive impairment but able to perform some activities of daily living independently and communicate his thoughts and needs. He requires no respiratory or cardiovascular support.


Subject(s)
Calcium Channel Blockers/poisoning , Drug Overdose/therapy , Nimodipine/poisoning , Acute Kidney Injury/chemically induced , Combined Modality Therapy , Extracorporeal Membrane Oxygenation , Fat Emulsions, Intravenous/administration & dosage , Humans , Hypoxia-Ischemia, Brain/chemically induced , Male , Middle Aged , Polyneuropathies/chemically induced , Suicide, Attempted , Treatment Outcome
10.
Am J Emerg Med ; 36(10): 1817-1824, 2018 10.
Article in English | MEDLINE | ID: mdl-29452919

ABSTRACT

BACKGROUND/OBJECTIVES: High dose insulin (HDI) is a standard therapy for beta-blocker (BB) and calcium channel-blocker (CCB) poisoning, however human case experience is rare. Our poison center routinely recommends HDI for shock from BBs or CCBs started at 1U/kg/h and titrated to 10U/kg/h. The study objective was to describe clinical characteristics and adverse events associated with HDI. METHODS: This was a structured chart review of patients receiving HDI for BB or CCB poisoning with HDI defined as insulin infusion of ≥0.5U/kg/h. RESULTS: In total 199 patients met final inclusion criteria. Median age was 48years (range 14-89); 50% were male. Eighty-eight patients (44%) were poisoned by BBs, 66 (33%) by CCBs, and 45 (23%) by both. Median nadir pulse was 54 beats/min (range 12-121); median nadir systolic blood pressure was 70mmHg (range, 30-167). Forty-one patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus was 1U/kg (range, 0.5-10). Median starting insulin infusion was 1U/kg/h (range 0.22-10); median peak infusion was 8U/kg/h (range 0.5-18). Hypokalemia occurred in 29% of patients. Hypoglycemia occurred in 31% of patients; 50% (29/50) experienced hypoglycemia when dextrose infusion concentration ≤10%, and 30% (31/105) experienced hypoglycemia when dextrose infusion concentration ≥20%. CONCLUSIONS: HDI, initiated by emergency physicians in consultation with a poison center, was feasible and safe in this large series. Metabolic abnormalities were common, highlighting the need for close monitoring. Hypoglycemia was more common when less concentrated dextrose maintenance infusions were utilized.


Subject(s)
Adrenergic beta-Antagonists/poisoning , Calcium Channel Blockers/poisoning , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Poison Control Centers/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Emergency Service, Hospital/statistics & numerical data , Female , Heart Arrest/chemically induced , Heart Arrest/mortality , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Male , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Young Adult
11.
Cardiovasc Toxicol ; 18(3): 290-293, 2018 06.
Article in English | MEDLINE | ID: mdl-29383633

ABSTRACT

Using calcium salts in management of amlodipine overdose is challenging. A 25-year-old male with known history of adult polycystic kidney disease presented with hypotension, tachycardia, and intact neurological status after ingestion of 450 mg of amlodipine. Immediately, normal saline infusion and norepinephrine were initiated. Two grams of calcium gluconate was injected, followed by intravenous infusion of 1.16 mg/kg/h. The patient was put on insulin-glucose protocol to maintain euglycemia and hyperinsulinemia. Electrocardiography demonstrated junctional rhythm. Serum creatinine was 2.5 mg/dL with metabolic acidosis. By the end of 24 h post-admission, his consciousness, blood pressure, and urine output were normal. Almost 32 h post-admission, he became disoriented and his oxygen saturation decreased and therefore was mechanically ventilated. Second chest X-ray showed pulmonary edema. Serum calcium level increased to 26.1 mg/dL. Calcium was discontinued, and furosemide infusion and calcitonin were intravenously administrated. Urine output increased and hemodialysis improved pulmonary edema and serum calcium level with no change in consciousness. Three days after admission, the patient became anuric and developed multi-organ failure and died 5 days post-admission. To avoid the consequences of excessive infusion of calcium in renal failure patients, the minimum calcium dose with close monitoring is recommended.


Subject(s)
Amlodipine/poisoning , Calcium Channel Blockers/poisoning , Calcium Gluconate/adverse effects , Hypercalcemia/chemically induced , Hypotension/drug therapy , Iatrogenic Disease , Tachycardia/drug therapy , Adult , Amlodipine/administration & dosage , Calcium Channel Blockers/administration & dosage , Calcium Gluconate/administration & dosage , Electrocardiography , Fatal Outcome , Humans , Hypercalcemia/blood , Hypercalcemia/diagnosis , Hypercalcemia/physiopathology , Hypotension/chemically induced , Hypotension/diagnosis , Hypotension/physiopathology , Kidney/physiopathology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/physiopathology , Male , Multiple Organ Failure/chemically induced , Risk Factors , Suicide , Tachycardia/chemically induced , Tachycardia/diagnosis , Tachycardia/physiopathology
12.
Am J Emerg Med ; 36(4): 736.e5-736.e6, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29331270

ABSTRACT

A 54-year-old female presented after taking an overdose of an unknown amount of hydrochlorothiazide, doxazocin, atenolol and amlodipine. She was initially refractory to treatment with conventional therapy (intravenous fluids, activated charcoal, glucagon 5 mg followed with glucagon drip, calcium gluconate 10%, and atropine). Furthermore, insulin at 4 U/kg was not effective in improving her hemodynamics. Shortly after high dose insulin was achieved with 10 U/kg, there was dramatic improvement in hemodynamics resulting in three of five vasopressors being weaned off in 8 h. She was subsequently off all vasopressors after six additional hours. The role of high dose insulin has been documented in prior cases, however it is generally recommended after other conventional therapies have failed. However, there are other reports that suggest it as initial therapy. Our patient failed conventional therapies and responded well only with maximum dose of insulin. Physicians should consider high dose insulin early in severe beta blocker or calcium channel blocker overdose for improvement in hemodynamics. This leads to early discontinuation of vasopressors. It is important that emergency physicians be aware of the beneficial effects of high dose insulin when initiated early as opposed to waiting for conventional therapy to fail; as these patients often present first to the emergency department. Early initiation in the emergency department can be beneficial in these patients.


Subject(s)
Adrenergic beta-Antagonists/poisoning , Calcium Channel Blockers/poisoning , Cardiotonic Agents/administration & dosage , Drug Overdose/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Vasodilator Agents/administration & dosage , Combined Modality Therapy , Dialysis , Drug Overdose/complications , Drug Overdose/physiopathology , Emergency Service, Hospital , Female , Fluid Therapy , Hemodynamics/drug effects , Humans , Middle Aged , Pulmonary Edema/etiology , Pulmonary Edema/therapy , Suicide, Attempted , Vasoconstrictor Agents/therapeutic use
13.
Lakartidningen ; 1142017 10 09.
Article in Swedish | MEDLINE | ID: mdl-28994852

ABSTRACT

High dose insulin euglycemia therapy - an important addition to the treatment arsenal in severe toxic myocardial depression Fifty-nine patients who developed hemodynamic symptoms necessitating treatment with vasopressors or inotropes after poisoning with calcium channel blockers (CCB) and beta blockers (BB) between January 2010 and August 2016 were identified by a search of the Poisons Information Centre database. In-hospital circulatory arrest occurred in 16/59 (27 %) and the mortality rate was 7/59 (12 %). Two cases of analytically confirmed combined BB and CCB poisoning were treated with high dose insulin therapy (HIE) and are presented in detail. The outcome in both cases was good. They were the only cases in the study population treated with HIE, although signs of cardiac dysfunction was present in 55/59 (93%) and in all cases of circulatory arrest. Animal studies and international clinical cases indicate that HIE is a safe and effective method to improve cardiac function in CCB and BB poisoning, and its implementation in Sweden may improve the outcome for this at risk population.


Subject(s)
Adrenergic beta-Antagonists/poisoning , Calcium Channel Blockers/poisoning , Glucose , Insulin , Shock , Female , Glucose/administration & dosage , Glucose/therapeutic use , Humans , Insulin/administration & dosage , Insulin/therapeutic use , Middle Aged , Practice Guidelines as Topic , Shock/chemically induced , Shock/drug therapy
14.
Basic Clin Pharmacol Toxicol ; 121(5): 447-449, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28503840

ABSTRACT

The morbidity and mortality of a severe calcium channel blocker intoxication is high due to serious toxic cardiac effects. Its treatment is supported by low-quality evidence from the heterogeneous literature. We describe a case of a severe diltiazem intoxication and critically appraise the efficacy and role of high-dose calcium and glucagon infusions. A 53-year-old woman was admitted to the emergency department with a cardiogenic shock with complete AV block, not responding to atropine, isoprenaline and an external pacemaker. Later on, it became clear that she had a severe diltiazem intoxication which was successfully treated with isotone fluids, inotropes, vasopressors and continuous infusion of high-dose calcium and glucagon. The patient developed, however, an acute, necrotizing pancreatitis, probably related to iatrogenic high calcium levels. This case demonstrates lack of consensus regarding target levels of serum calcium for treatment of a severe diltiazem intoxication. Goal-directed tapering of calcium should prevent side effects of iatrogenic hypercalcaemia. The contribution of glucagon infusions is doubtful due to the instability of solubilized glucagon. This might explain why the effect of glucagon is variable in the literature.


Subject(s)
Calcium Channel Blockers/poisoning , Calcium/administration & dosage , Diltiazem/poisoning , Glucagon/administration & dosage , Atrioventricular Block/chemically induced , Atrioventricular Block/drug therapy , Calcium/blood , Drug Overdose , Emergency Service, Hospital , Female , Humans , Middle Aged , Shock, Cardiogenic/chemically induced , Shock, Cardiogenic/drug therapy
15.
Crit Care Med ; 45(3): e306-e315, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27749343

ABSTRACT

OBJECTIVE: To provide a management approach for adults with calcium channel blocker poisoning. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. DATA SYNTHESIS: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). CONCLUSION: We offer recommendations for the stepwise management of calcium channel blocker toxicity. For all interventions, the level of evidence was very low.


Subject(s)
Calcium Channel Blockers/poisoning , Drug Overdose/therapy , Consensus , Hospitalization , Humans
16.
Cardiovasc Toxicol ; 17(2): 223-225, 2017 04.
Article in English | MEDLINE | ID: mdl-26913719

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) use in poisoned patients is increasing, but is rare post cardiac arrest. We report a case of ECMO use with complete recovery in a patient who arrested twice after a cardiotoxicant overdose. A 17-year-old male presented after an unknown overdose. He rapidly became hypotensive and bradycardic and received aggressive supportive care without improvement. He was transferred to our institution and suffered a cardiac arrest shortly after arrival. Six minutes of advanced cardiac life support resulted in return of spontaneous circulation. High-dose insulin, lipid emulsion, and ECMO were initiated. While awaiting ECMO deployment, he again became pulseless. Compressions resumed, and after 30 min, ROSC was achieved, and he was cannulated for veno-arterial ECMO. Within 48 h, he was decannulated, and then weaned off epinephrine 2 days later. Upon extubation, he was neurologically intact. Amlodipine and metoprolol were later confirmed in serum. Adolescent poisoned patients represent an ideal population for ECMO due to lack of comorbidities. As experience with ECMO in overdose increases, additional research is needed to determine appropriate indications and timing for its use. ECMO is an option for patients poisoned with a cardiotoxicant drug, even following witnessed cardiac arrest.


Subject(s)
Adrenergic beta-1 Receptor Antagonists/poisoning , Amlodipine/poisoning , Calcium Channel Blockers/poisoning , Extracorporeal Membrane Oxygenation , Heart Arrest/therapy , Metoprolol/poisoning , Adolescent , Drug Overdose , Heart Arrest/chemically induced , Heart Arrest/diagnosis , Heart Arrest/physiopathology , Humans , Male , Suicide, Attempted , Treatment Outcome
17.
J Med Toxicol ; 12(4): 380-385, 2016 12.
Article in English | MEDLINE | ID: mdl-27501853

ABSTRACT

Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre- and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05 significant). Nifedipine toxicity was characterized by vasodilatory hypotension, impaired vascular contractility, and tachycardia with terminal bradycardia. The median time to imminent cardiac arrest from start of nifedipine infusion was 218 min. Lipid treatment did not improve hemodynamics or restore circulation in any animal. There was no benefit from lipid rescue in this model of nifedipine toxicity. Further study of ILE for dihydropyridine toxicity is warranted but initial animal model results are not promising.


Subject(s)
Calcium Channel Blockers/poisoning , Fat Emulsions, Intravenous/therapeutic use , Nifedipine/poisoning , Shock/chemically induced , Shock/therapy , Animals , Blood Glucose/analysis , Blood Glucose/drug effects , Blood Pressure/drug effects , Bradycardia/etiology , Calcium Channel Blockers/administration & dosage , Dihydropyridines/administration & dosage , Dihydropyridines/poisoning , Disease Models, Animal , Female , Heart Arrest, Induced , Humans , Metabolome/drug effects , Myocardial Contraction/drug effects , Nifedipine/administration & dosage , Pilot Projects , Swine , Tachycardia/etiology
18.
Clin Toxicol (Phila) ; 54(9): 829-832, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27432286

ABSTRACT

CONTEXT: High-dose insulin has become a first-line therapy for treating severe calcium channel blocker and beta blocker toxicity. Insulin infusions used to treat other conditions (e.g., diabetic ketoacidosis) may be used, but this may lead to pulmonary compromise due to fluid volume overload. An obvious solution would be to use a more concentrated insulin infusion; however, data describing the stability of insulin in polyvinyl chloride bags at concentrations >1 unit/mL are not readily available. OBJECTIVE: To determine the stability of insulin at 16 units/mL in 0.9% saline solution. MATERIALS AND METHODS: Eight-hundred units of regular insulin (8 mL from a stock vial containing 100 units/mL) were added to 42 mL of 0.9% saline solution in a polyvinyl chloride bag to make a final concentration of 16 units/mL. Two bags were stored at 4 °C (refrigerated) and two at 25 °C (room temperature). Samples were withdrawn and tested for insulin concentration periodically over 14 days. RESULTS: Concentrated regular insulin in a polyvinyl chloride bag remained within 90% of equilibrium concentration at all time points, indicating the 16 units/mL concentration was sufficiently stable both refrigerated and at room temperature for 14 days. DISCUSSION: Administration of high-dose insulin can cause fluid volume overload when using traditional insulin formulations. The 16 units/mL concentration allows for the treatment of a patient with severe calcium channel blocker or beta blocker toxicity for a reasonable period of time without administering excessive fluid. CONCLUSION: Insulin at a concentration of 16 units/mL is stable for 14 days, the maximum timeframe currently allowed under US Pharmacopeia rules for compounding of sterile preparations. This stability data will allow institutions to issue beyond-use dating for intravenous fluids containing concentrated insulin and used for treating beta blocker and calcium channel blocker toxicity.


Subject(s)
Adrenergic beta-Antagonists/poisoning , Calcium Channel Blockers/poisoning , Hypoglycemic Agents/chemistry , Insulin/chemistry , Drug Overdose , Drug Packaging , Drug Stability , Drug Storage , Humans , Hypoglycemic Agents/administration & dosage , Infusions, Intravenous , Insulin/administration & dosage , Polyvinyl Chloride/chemistry , Refrigeration , Sodium Chloride/chemistry , Temperature , Time Factors
19.
Crit Care Nurse ; 36(2): 45-50, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27037338

ABSTRACT

Overdoses of ß-blockers and calcium channel blockers can produce significant morbidity and mortality, and conventional therapies often do not work as treatments for these poisonings. High-dose insulin/glucose therapy has been successful in reversing the cardiotoxic effects of these drugs in cases where the standard therapies have failed, and it appears to be relatively safe. Many successes have been well documented, but the clinical experience consists of case reports, the mechanisms of action are not completely understood, and guidelines for use of the therapy are empirically derived and not standardized. Regardless of these limitations, high-dose insulin/glucose therapy can be effective, it is often recommended by clinical toxicologists and poison control centers, and critical care nurses should be familiar with when and how the therapy is used.


Subject(s)
Adrenergic beta-Antagonists/poisoning , Calcium Channel Blockers/poisoning , Cardiotoxins/adverse effects , Critical Care Nursing/methods , Glucose/therapeutic use , Insulin/therapeutic use , Poisoning/drug therapy , Adrenergic beta-Antagonists/adverse effects , Adult , Aged , Aged, 80 and over , Calcium Channel Blockers/adverse effects , Dose-Response Relationship, Drug , Education, Nursing, Continuing , Female , Humans , Male , Middle Aged
20.
Neth J Med ; 74(2): 60-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26951350

ABSTRACT

Calcium channel antagonists (CCAs) are widely used for different cardiovascular disorders. At therapeutic doses, CCAs have a favourable side effect profile. However, in overdose, CCAs can cause serious complications, such as severe hypotension and bradycardia. Patients in whom a moderate to severe intoxication is anticipated should be observed in a monitored setting for at least 12 hours if an immediate-release formulation is ingested, and at least 24 hours when a sustained-release formulation (or amlodipine) is involved, even if the patient is asymptomatic. Initial treatment is aimed at gastrointestinal decontamination and general supportive care, i.e., fluid resuscitation and correction of metabolic acidosis and electrolyte disturbances. In moderate to severe CCA poisoning, a combined medical strategy might be indispensable, such as administration of vasopressors, intravenous calcium and hyperinsulinaemia/euglycaemia therapy. Especially hyperinsulinaemia/euglycaemia therapy is an important first-line treatment in CCA-overdosed patients in whom a large ingestion is suspected. High-dose insulin, in combination with glucose, seems to be most effective when used early in the intoxication phase, even when the patient shows hardly any haemodynamic instability. Intravenous lipid emulsion therapy should only be considered in patients with life-threatening cardiovascular toxicity, such as refractory shock, which is unresponsive to conventional therapies. When supportive and specific pharmacological measures fail to adequately reverse refractory conditions in CCA overdose, the use of extracorporeal life support should be considered. The efficacy of these pharmacological and non-pharmacological interventions generally advocated in CCA poisoning needs further in-depth mechanistic foundation, in order to improve individualised treatment of CCA-overdosed patients.


Subject(s)
Calcium Channel Blockers/poisoning , Drug Overdose/prevention & control , Practice Guidelines as Topic , Humans
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