Calcium Channel Blocker Overdose Research Articles

SURVIVING AMLODIPINE OVERDOSE WITH ECMO SUPPORT

Amlodipine toxicity is commonly reported medication involved in overdose. Its management involves early action with aggressive measures. We describe such a case managed successfully. 64-year-old female was admitted to hospital with severe hypotension and junctional rhythm 36 hours following

Methylene blue in the management of severe distributive shock in calcium channel blocker overdose

Introduction: Deliberate polypharmacy overdose is associated with an increasing proportion of admissions to the intensive care unit. Overdose on hemodynamic active substances such as calcium channel blockers can be fatal as it is associated with severe distributive shock. Methylene blue has drawn attention in critical care medicine for its use in the management of distributive shock, particularly in cases of anaphylaxis, septic shock, and shock following cardiac bypass surgery. We describe the use of methylene blue in the management of refractory shock due to calcium channel blocker (CCB) overdose. Case Report: We present a case of benzothiazepine type CCB overdose which leads to admission to the intensive care unit for the management of severe distributive shock. Conventional treatments including vasopressors and high dose insulin therapy were instituted, but despite these treatments the patient remained hypotensive. The decision was made to administer methylene blue following which the patient achieved hemodynamic stability and was successfully weaned off all vasopressors. Conclusion: This case report specifically focuses on the use of methylene blue in distributive shock secondary to CCB overdose. Currently there are no randomized control trials to support its use, and evidence is limited to observational studies including single case reports. In this case report we describe the mechanism of action of methylene blue and why we believe it makes for the perfect adjunct therapy in calcium channel blocker overdose.

Non-Cardiogenic Pulmonary Edema With Refractory Hypotension in a Child From Amlodipine Overdoses

Intoxications from calcium blockers are not common in daily pediatric practice, but often they can be life-threatening and result fatal for children. Non-cardiogenic edema in children as a result of overdose from amlodipine is rare. In this article, we want to present a case of an intentional intoxication from overdose of amlodipine in a teen girl who suffered complications with refractory hypotension and non-cardiogenic pulmonary edema after 2 days from ingestion. This article wants to highlight the reporting of this rare life-threatening complication because of overdose. It will also focus on the successful supportive treatment with liquids, salt of calcium, vasopressors, glucagon, intra-lipids, mechanical ventilation and the superiority of using high-dose insulin-euglycemia in the concomitant refractory hypotension. Int J Clin Pediatr. 2020;9(4):120-124 doi: https://doi.org/10.14740/ijcp398

Amlodipine poisoning management

Amlodipine is a commonly used calcium-channel blocker (CCB) used in the treatment of hypertension. Severe CCB toxicity is highly lethal, as a result of cardiovascular collapse. Amlodipine overdose can lead to prolonged hypotension and potent vasodilatation which can result in fatality. Early identification of CCB overdose can save lives and reduce the risk of complications. The management of CCB intoxication will be reviewed.

Nifedipine toxicity is exacerbated by acetyl l-carnitine but alleviated by low-dose ketamine in zebrafish in vivo.

Calcium channel blocker (CCB) poisoning is a common and sometimes life-threatening emergency. Our previous studies have shown that acetyl l-carnitine (ALCAR) prevents cardiotoxicity and developmental toxicity induced by verapamil, a CCB used to treat patients with hypertension. Here, we tested whether toxicities of nifedipine, a dihydropyridine CCB used to treat hypertension, can also be mitigated by co-treatment with ALCAR. In the zebrafish embryos at three different developmental stages, nifedipine induced developmental toxicity with pericardial sac edema in a dose-dependent manner, which were surprisingly exacerbated with ALCAR co-treatment. Even with low-dose nifedipine (5μm), when the pericardial sac looked normal, ALCAR co-treatment showed pericardial sac edema. We hypothesized that toxicity by nifedipine, a vasodilator, may be prevented by ketamine, a known vasoconstrictor. Nifedipine toxicity in the embryos was effectively prevented by co-treatment with low (subanesthetic) doses (25-100μm added to the water) of ketamine, although a high dose of ketamine (2mm added to the water) partially prevented the toxicity.As expected of a CCB, nifedipine either in the presence or absence of ketamine-reduced metabolic reactive oxygen species (ROS), a downstream product of calcium signaling, in the rapidly developing digestive system. However, nifedipine induced ROS in the trunk region that showed significantly stunted growth indicating that the tissues under stress potentially produced pathologic ROS. To the best of our knowledge, these studies for the first time show that nifedipine and the dietary supplement ALCAR together induce adverse effects while providing evidence on the therapeutic efficacy of subanesthetic doses of ketamine against nifedipine toxicity in vivo.

FAILURE OF HYPERINSULINEMIC-EUGLYCEMIA IN CALCIUM CHANNEL BLOCKER OVERDOSE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: There is a growing body of evidence to support hyperinsulinemic-euglycemia for calcium-channel blocker overdose. However, when given in lower doses than the recommended protocol, hyperinsulinemic-euglycemia was shown to be ineffective in maintaining adequate blood pressure. CASE PRESENTATION: 56-year-old female with hypertension, depression, and a previous suicide attempt admitted to the ICU for an intentional drug overdose with 105 mg of amlodipine. She was hypotensive in the ED despite fluid resuscitation and required pressor support with norepinephrine and phenylephrine. Poison Control recommended starting hyperinsulinemic-euglycemia. She was started on only 0.5u/kg short-acting insulin bolus, followed by a short-acting insulin drip starting at 0.5u/kg/hr. She required multiple doses of glucose and potassium supplementation, showed no marked increase in BP, and continued to require pressor support for the next 48 hours which is approximately the half-life of amlodipine. DISCUSSION: There has been a growing evidence supporting hyperinsulinemic-euglycemia for calcium-channel blocker overdose with improved survival compared to epinephrine [1]. Evidence has been mostly noted in case reports and animal models [2]. The mechanism by which hyperinsulinemic-euglycemia works is still poorly understood, although there is a theory that calcium-channel blockers cause insulin-resistance in the myocardium that is overcome by high-doses insulin [3]. The recommended dose of high-dose insulin therapy by poison control, and in literature, is 1u/kg bolus followed by 0.5u/kg/hr drip to be titrated up to a max of 10u/kg/hr with an end-goal of improvement of hypotension [1]. In the case of our patient, concern over hypoglycemia and hypokalemia, the patient was started with only 0.5u/kg bolus, followed by 0.5u/kg/hr drip that was only titrated up to 0.7u/kg/hr. At this rate, high dose insulin therapy was ineffective in maintaining adequate BP in our patient. CONCLUSIONS: As proven by previous studies, a full 1u/kg bolus must be given to calcium channel blocker overdose patients in order to show any measurable effect on blood pressure. Concern for hypoglycemia and hypokalemia should not prevent clinicians from administering the full dose. Reference #1: Boyer EW, Shannon M. Treatment of calcium-channel-blocker intoxication with insulin infusion. N Engl J Med. 2001 May 31;344(22):1721-2. PubMed PMID: 11386285. Reference #2: Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM. Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther. 1993 Nov;267(2):744-50. PubMed PMID: 8246150. Reference #3: Kline JA, Raymond RM, Schroeder JD, Watts JA. The diabetogenic effects of acute verapamil poisoning. Toxicol Appl Pharmacol. 1997 Aug;145(2):357-62. PubMed PMID: 9266809. DISCLOSURES: No relevant relationships by Charles Hildebrand, source=Web Response No relevant relationships by Samer Ibrahim, source=Web Response No relevant relationships by Howard Sklarek, source=Web Response

HIGH DOSE AMLODIPINE POISONING TREATED WITH HIGH INSULIN EUGLYCEMIC THERAPY

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Calcium channel blockers (CCB) are one of the most commonly prescribed anti-hypertensive medications. CCB poisoning is life-threatening due to myocardial suppression and severe refractory hypotension. To date, there are no specific recommendations on when to initiate high insulin euglycemic therapy (HIET). Management has been aimed at achieving adequate vasopressor support with epinephrine, norepinephrine, and dopamine. fluid resuscitation, and calcium are also provided. Recently, case series have reported successful outcomes in treating CCB poisoning with HIET. CASE PRESENTATION: A 72 year old female presented to the ED with lethargy and dizziness after attempting to commit suicide by ingesting 100 tablets of Amlodipine 5 mg twelve hours prior to presentation, per report of the patient and family. Patient had a past medical history of macular degeneration, depression, cataract and hypertension. Upon presentation the patient’s physical exam was significant for a blood pressure of 87/53 mmHg, a temperature of 98.4 °F, a heart rate of 98 and a respiratory rate of 18. The cardiovascular exam showed a regular rhythm and normal heart sounds. The remainder of the exam was unremarkable. Electrocardiogram showed normal sinus rhythm of 97 with no evidence of any conduction delays. Abnormal labs included a serum sodium of 134, ALT of 110 and AST of 88. Renal function and blood counts were normal. The patient’s blood pressure began to decrease dramatically, prompting the initiation of HIET, calcium gluconate infusion and vasopressor support within the first 4 hours after presentation. The patient required continuous infusion of insulin with D10, calcium gluconate infusion, and close monitoring of both calcium and glucose for three days after admission. On day 6, she became normotensive and no longer required vasopressor support. DISCUSSION: Dihydropyridine CCB’s block L-type calcium channels, which cause smooth muscle relaxation with no-to-minimal effect on the myocardium in usual doses. At higher and more toxic doses, it can block sodium channels in the myocardium causing myocardial suppression. CCB poisoning in high doses can be fatal. However, there are no clear guidelines outlining the time to initiate HIET in CCB poisoning. In this case HIET had a positive outcome, but it was started almost 16-18 hours after ingestion of the calcium channel blocker. This presents the question of whether or not timing of HIET initiation could decrease ICU stay and mortality.In addition, it is unclear wether HIET should be used concurrently with vasopressor support as a first-line therapy. CONCLUSIONS: Patients who present with CCB poisoning due to higher dose ingestions require more aggressive therapy in order to demonstrate clinical improvement. Data in past years have supported the use of HIET in these patients, but appropriate time of HIET initiation has not been established. Reference #1: St-Onge M, Dubé PA, Gosselin S. et.al. Treatment for calcium channel blocker poisoning: a systematic review. Clinical Toxicology. 2014.1;52(9):926-44. Reference #2: Kumar K, Biyyam M, Bajantri B, et.al. Critical Management of Severe Hypotension Caused by Amlodipine Toxicity Managed With Hyperinsulinemia/Euglycemia Therapy Supplemented With Calcium Gluconate, Intravenous Glucagon and Other Vasopressor Support: Review of Literature. Cardiology research. 2018;9(1):46. Reference #3: St-Onge M, Anseeuw K, Cantrell FL, et.al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Critical care medicine. 2017;45(3):e306. DISCLOSURES: No relevant relationships by ahmad alkhatatneh, source=Web Response No relevant relationships by Razan Elsayed, source=Web Response

Management of Calcium Channel Blocker Toxicity in the Pediatric Patient.

Calcium channel blockers (CCBs) are commonly prescribed cardiovascular medications used in several disease states including hypertension, coronary artery disease, and atrial fibrillation. Inadvertent exposure or intentional overdose of CCBs may result in hypotension, bradycardia, dysrhythmias, conduction disturbances, and hyperglycemia. In the most severe cases, CCB toxicity can lead to rapid cardiovascular collapse. Given the risk of significant morbidity and mortality associated with CCB toxicity, it is important that health care professionals are able to recognize and treat patients who present with a potentially toxic ingestion. Due to the paucity of literature in managing pediatric patients with severe CCB toxicity, treatment strategies for pediatric patients are mostly limited to case reports and extrapolation from expert consensus recommendations for adults. All pediatric patients with a potentially toxic CCB ingestion should be evaluated in the emergency department. Activated charcoal may be considered for asymptomatic patients presenting within an hour of ingestion. Symptomatic patients should be placed under cardiac monitoring and treatments to stabilize the patient's hemodynamics should not be delayed. Traditional first-line IV therapies include small boluses of fluids, calcium, and vasopressors. High-dose insulin has been proposed to independently increase inotropy and improve CCB-induced hypoinsulinemia and insulin resistance that results from CCB inhibition of insulin release from pancreatic β-islet cells. High-dose insulin is recommended as first-line therapy for adults and shows promising efficacy and safety in several pediatric case reports. Intravenous lipid emulsion may be considered in patients who are refractory to first-line therapies, although the data for pediatric patients are extremely limited.

Emergency management of calcium channel blocker overdose.

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.

Development and Feasibility of a Porcine Model of Amlodipine Toxicity.

Toxicity related to calcium-channel blockers remains a significant cause of morbidity and mortality. Amlodipine-induced shock is unique in that its mechanism of action is thought to occur in part via the release of nitric oxide (NO) in the peripheral vasculature. Specific therapeutic interventions, including methylene blue (an NO scavenger), have been suggested, but efficacy studies are severely limited. To facilitate a larger porcine study into the effect of various interventions on amlodipine toxicity, we undertook this model development and feasibility study. Intravenous amlodipine was prepared by dissolving commercially obtained amlodipine tablets in dimethylsulfoxide. The concentration of the drug was verified using ultraviolet spectroscopy. We administered this solution to three animals in order to determine a toxic dose, capable of facilitating a two-arm study of amlodipine toxicity. The first pig died rapidly after the bolus infusion. The second pig developed mild toxicity, but the dissolution of the plastic tubing by the solvent and subsequent leakage limited the interpretability of the result. The third animal developed expected toxicity with an infusion rate between 2.0 and 5.5mg/kg/h. This study demonstrates a potentially repeatable model of amlodipine-induced toxic shock using intravenous administration of amlodipine and several methodological considerations for researchers undertaking similar work.

Book and Other Media Reviews

The fine line between emergency medicine and critical care has been blurred during the past decade. The causes are many. In the past, a critical patient was stabilized in the emergency department (ED) then transported quickly to the appropriate intensive care unit (ICU), now we board these patients in the ED because “there is no room in the inn.” Emergency physicians are becoming fellowship-trained and board-certified in critical care specialties. In my institution, my former residents are attending in all of the ICUs. Emergency physicians are now performing procedures formerly practiced by intensivists; extracorporeal membrane oxygenation (ECMO), fiberoptic intubations, resuscitative endovascular balloon occlusion of the aorta, continuous electroencephalography, and dialysis. The number of drugs and poisons that patients are exposed to seems to increase exponentially. Intentional overdoses, illegal drugs of abuse, over-the-counter medications, herbals, accidental ingestions, alternative therapies, and occupational exposures have complicated the diagnosis and management of the poisoned patient. It is not unusual to see a patient with a combination of β-blocker, calcium channel blocker, opioid, and antidepressant overdose who is comatose, hypotensive, hypoxic, and having seizures.

Abstract #435 Insulin A Potential Life –Saving Medication in a Noniabetic Patient: A Case of Calcium Channel Blocker Overdose

Abstract #435 Insulin A Potential Life –Saving Medication in a Noniabetic Patient: A Case of Calcium Channel Blocker Overdose

Comparative effectiveness of methylene blue versus intravenous lipid emulsion in a rodent model of amlodipine toxicity

Context: Calcium channel blocker (CCB) poisonings are the leading cause of death from cardiovascular medication-related overdoses. Current treatments (calcium salts, vasopressors, inotropes) are often insufficient. Intravenous lipid emulsion (ILE) and methylene blue (MB) show promise in treating CCB overdoses unresponsive to conventional therapy.Objective: To compare the effectiveness of MB versus ILE in a rodent model of amlodipine (AML) poisoning with survival as the primary outcome and hemodynamic parameters as secondary outcomes.Materials and methods: Sixty-four adult male albino rats were anesthetized and cannulated for non-invasive hemodynamic measurement. Rats received amlodipine intraperitoneally (42 mg/kg). We then divided the rats into four groups: AML only without antidote, AML followed by ILE (24.8 mL/kg over 10 min), AML followed by normal saline (an equivalent volume of ILE), and AML followed by IV MB (2 mg/kg over 5 min). They received study treatments at 5, 30, and 60 minutes from the start of the protocol and with observation for 2 hours.Results: Survival time in ILE group was greater than in the control and NS groups. Differences between ILE and MB and between MB and NS were not significant. Hemodynamic parameters significantly increased in ILE group compared to the MB group at the 30, 60 and 120 min assessments but not after induction of AML poisoning and at 5 min assessment.Conclusions: Survival was greatest in rats treated with ILE. Both MB and NS had little effect on survival when compared to control animals. Both ILE and MB improved hemodynamics.

A Case of Life-threatening Amlodipine and Atenolol Overdose

ABSTRACTTreating a patient of amlodipine-atenolol poisoning is nightmare for a physician. In high dose both the drugs individually cause severe bradycardia and hypotension. In combination they cause severe cardiovascular depression. Here we report a case of 66-year-old obese, hypertensive, depressed male, who presented to emergency 9 hours after consumption of 25 tablets of amlodipine-atenolol (5 mg+50 mg). On evaluation, he had refractory bradycardia, hypotension and acute kidney injury (AKI). Eventually he developed cardiac arrest. He was revived after 5 minutes of cardio-pulmonary resuscitation (CPR). He was successfully managed with gastric lavage, fluids, inotropes, atropine, isoprenaline and subsequently with calcium gluconate infusion, high-dose insulin euglycemia therapy (HIET) and lipid emulsion therapy. Glucagon infusion was also planned but it was not available. Patient hemodynamics improved and on 8th day he got the discharge. Our case exemplifies the importance of timely and aggressive management of lethal overdose of amlodipine-atenolol poisoning.How to cite this article: Tale S, Kumar M, Ghosh S, Bhalla A. A Case of Life-threatening Amlodipine and Atenolol Overdose. Indian J Crit Care Med 2019;23(6):281–283.

HIGH DOSE INSULIN AND VA ECMO FOR POISON-INDUCED CARDIOGENIC SHOCK

SESSION TITLE: Critical Care 2 SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/09/2018 05:00 PM - 06:00 PM INTRODUCTION: High dose insulin therapy (HDI) is an emerging and increasingly well described intervention for poison-induced cardiogenic shock (PICS). PICS due to beta-blocker or calcium channel blocker overdose is both frequent and life-threatening [1]. When traditional therapies such as fluid resuscitation, cardiac pacing, atropine, calcium, glucagon, vasopressors and inotropes fail to provide hemodynamic stability, HDI can be effective [2-7]. While the current literature is limited to case series and animal models [2-7], we present a case of successful HDI in a patient with beta-blocker toxicity. CASE PRESENTATION: We report a 36-year-old female who presented in cardiogenic shock secondary to polypharmacy overdose, including significant amounts of propranolol. She suffered cardiopulmonary arrest shortly after arrival to the hospital. Despite aggressive resuscitation, she required emergent venoarterial extracorporeal membrane oxygenation (VA ECMO) support to achieve hemodynamic stability. HDI was subsequently initiated by assessing hemodynamic responsiveness to progressively increased bolus doses, starting with 1 unit per kilogram. HDI was continued with an insulin infusion at 15 units/kilogram/hour. She demonstrated an excellent response, and was successfully transitioned off VA ECMO support and all vasoactive medications. The following day, the insulin drip was carefully weaned to avoid large potassium shifts. The patient was eventually discharged to home, neurologically intact with normal biventricular function by echocardiogram. DISCUSSION: This patient demonstrated a rapid and robust response to HDI in the setting of profound cardiogenic shock. Despite requiring escalation of care to VA ECMO, HDI allowed for rapid discontinuation of this salvage therapy. Several mechanisms of action have been postulated for HDI, including a direct positive inotropic effect and multiple favorable metabolic properties [3,5,8-12]. HDI also induces vasodilation, which improves both microcirculation and systemic perfusion [5,11]. While evidence for specific dosing regimens remains limited, the doses used in this case are consistent with previously described values including bolus doses of 1 unit per kilogram and infusions of 10 units/kilogram/hour or more [13-15]. CONCLUSIONS: In patients with PICS due to either calcium channel blockers or beta-blockers, HDI can be a definitive and life-saving treatment. While large clinical trials are lacking, sufficient evidence exists to consider this therapy in patients with PICS refractory to traditional treatment [16]. Note: All sixteen references available in uploaded document Reference #1: DeWitt CR, et al. Pharmacology, pathophysiology and management of calcium channel blocker and beta blocker toxicity. Toxicol Rev 2004, 23:223-38 Reference #2: Yuan TH, Kerns WP, Tomaszewski CA, Ford MD, Kline JA. Insulin-glucose as adjunctive therapy of severe calcium channel antagonist poisoning. J Toxicol Clin Toxicol 1999, 37:463-74 Reference #3: Megarbane B, et al. The role of insulin and glucose (hyperinsulinemia/euglycemia) therapy in acute calcium channel antagonist and beta-blocker poisoning. Toxicol Rev 2004, 23:215-22 DISCLOSURES: No relevant relationships by Benjamin Abrams, source=Web Response No relevant relationships by David Douin, source=Web Response No relevant relationships by Scott Wolf, source=Web Response

Barriers and Facilitators of Intensivists' Adherence to Hyperinsulinemia-Euglycemia Therapy in the Treatment of Calcium Channel Blocker Poisoning.

Adherence to poison center (PC) recommendations for the management of calcium channel blocker (CCB) poisoning is inconsistent. This study aimed to identify behaviors that determine adherence to hyperinsulinemia-euglycemia therapy (HIET) for CCB poisoning. Semistructured interviews were conducted involving a convenience sample of 18 intensivists. Interview responses were analyzed using the theoretical domains framework (TDF) to identify relevant domains influencing physician adherence to HIET. Two independent reviewers performed qualitative content analysis of the interview transcripts to identify beliefs influencing decisions to initiate HIET. Initially, beliefs were classified and frequencies reported as being likely to facilitate, likely to decrease, or unlikely to affect adherence. Subsequently, beliefs were linked to a domain within the TDF. Based on the potential impact on physician behavior and frequency of reported behavior, we selected the most relevant domains likely to influence physician adherence to HIET for CCB poisoning. Positive beliefs were identified in the following domains: "behavioral regulation" (e.g., algorithm for adjustment of perfusions), "belief about capabilities" (e.g., confidence about being able to manage HIET), "belief about consequences" (e.g., fear of clinical deterioration), and "reinforcement" (e.g., clinical instability). Negative beliefs were identified in the following domains as "nature of behavior" (e.g., preference for vasopressors over HIET) and "environmental context and resources" (e.g., accessing dextrose 50% and increased nurse workload). This qualitative study identified potential behavioral targets for future implementation strategies to address to improve adherence to HIET.

The Effect of Intravenous Lipid Emulsion in a Rat Model of Verapamil Toxicity

Purpose: Intravenous lipid emulsion (ILE) has been shown to have significant therapeutic effects on calcium channel blocker overdose in animal studies and clinical cases. In this preliminary experiment, we investigated the hemodynamic changes and survival in a rat model of verapamil intoxication. Methods: Fourteen male Sprague-Dawley rats were sedated and treated with ILE or normal saline (control), followed by continuous intravenous infusion of verapamil (20 mg/kg/h). Mean arterial pressure and heart rate of rats were monitored during the infusion. In addition, the total dose of infused verapamil and the duration of survival were measured. Results: Survival was prolonged in the ILE group ($32.43{pm}5.8min$) relative to the control group ($24.14{pm}4.3min$) (p=0.01). The cumulative mean lethal dose of verapamil was higher in the ILE group ($4.3{pm}0.7mg/kg$) than in the control group ($3.2{pm}0.5mg/kg$; p=0.017). Conclusion: ILE pretreatment prolonged survival and increased the lethal dose in a rat model of verapamil poisoning.

Non-Fatal Amlodipine and Insulin Overdose in an Elderly Person

Background:Amlodipine belongs to the dihydropyridine class of calcium channel blockers (CCB). We present a patient who concomitantly overdosed on amlodipine and subcutaneous insulin. Case Presentation:An elderly man presented within 2 hours to the Emergency department after ingesting 140mg of amlodipine and self-injected 2 cartridges of NovoMix 30/70(600 units) in a suicidal attempt. He developed mild hypotension and had multiple episodes of hypoglycemia but was otherwise asymptomatic. He was managed with activated charcoal, low dose noradrenaline and multiple doses of dextrose for his hypoglycaemia. He was discharged well after 3 days. Discussion:The clinical manifestations of dihydropyridine toxicity are hypotension, hyperglycaemia and metabolic acidosis. Our patient was elderly with multiple medical problems but he was alert and haemodynamically stable on presentation. Activated charcoal is the recommended form of decontamination when the patient presents early. He also developed initial hyperglycemia, which correlates with the degree of the calcium channel blocker overdose. The early coadministration of insulin would correct the patient’s hyperglycemia, acidosis, myocardial function and even provide inotropic support. It may be possible that the subcutaneous route of administering high dose insulin has similar effects as those of intravenous HIET. Our patient’s hypoglycaemia occurred about 12 hours of the overdose, which is expected after an insulin overdose. He required many boluses of dextrose infusions before his blood sugar level stabilised. Conclusion:It is postulated that self-administration of insulin and early decontamination could have resulted in patient’s good outcome despite having ingested a potentially fatal dose of amlodipine.

High dose insulin for beta-blocker and calcium channel-blocker poisoning

Background/objectivesHigh 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. MethodsThis 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. ResultsIn 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%. ConclusionsHDI, 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.

Intoxication with Calcium Channel Blockers and Other Highly Protein-Bound Drugs: Why Use MARS? Two Clinical Case Reports

Overdose with calcium channel blockers is often a life-threating condition that is frequently exacerbated by the availability of extended-release preparations with slow drug clearances. In the annual report of the American Association of Poison Control Centers, calcium channel inhibitor overdose is one of the most deadly poisonings. In addition, calcium channel blockers are highly bound to proteins, making them difficult to remove using standard dialysis techniques. We describe two cases of amlodipine overdose that presented with profound circulatory shock and were treated with the Molecular Adsorbent Recirculating System™ (MARS™). In this regard, the authors reviewed other cases reported in the literature to discuss the rationale for using albumin dialysis techniques in the setting of highly protein-bound drug intoxication.