β-Blocker and Calcium Channel Blocker Poisoning: High-Dose Insulin/Glucose Therapy

2016 ◽  
Vol 36 (2) ◽  
pp. 45-50 ◽  
Author(s):  
Dana Bartlett

Overdoses of β-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.

Author(s):  
Rachel F Schult ◽  
Nicholas Nacca ◽  
Tori L Grannell ◽  
Rachel M Jorgensen ◽  
Nicole M Acquisto

Abstract Purpose High-dose insulin/euglycemia (HDIE) is targeted therapy for β-blocker and calcium channel blocker overdose. A guideline using concentrated insulin infusions (20 units/mL), aggressive monitoring, and supportive recommendations was implemented. We sought to evaluate safety before and after HDIE guideline implementation and describe the patient population, insulin doses, supplemental dextrose, vasopressor use, hospital and intensive care unit (ICU) lengths of stay, and mortality. Methods Retrospective review was performed of patients receiving HDIE before and after guideline implementation at an academic medical center and community hospital from March 2011 through December 2019. Information on patient and overdose demographics, ingestion data, vital signs, interventions, adverse events, and disposition was collected. Data are presented descriptively with comparisons using Mann-Whitney U analysis and Fisher’s exact tests. Results During the study period, 27 patients were treated with HDIE, 10 before guideline implementation (37%; mean [SD] initial insulin dose, 0.49 [0.35] units/kg/h; mean [SD] maximum insulin dose, 2.25 [3.29] units/kg/h; median [interquartile range] duration, 10 [5.5-18.75] hours) and 17 after guideline implementation (63%; mean [SD] initial insulin dose, 1.01 [0.34] units/kg/h; mean [SD] maximum insulin dose, 2.99 [5.05] unit/kg/h; median [interquartile range] duration, 16 [11.5-37] hours). Hypoglycemia, hypokalemia, and volume overload occurred in 80% vs 29% (P = 0.018), 40% vs 53% (P = 0.69), and 50% vs 65% (P = 0.69) of patients in the preguideline vs postguideline group, respectively. Most patients received an initial insulin bolus (85%; mean [SD], 70.3 [21.8] units, 0.9 [0.26] units/kg) and vasopressor infusion (85%). More postguideline patients received a dextrose infusion with a concentration of 20% or higher (93% vs 50%, P = 0.015). There were no differences in cardiac arrest, in-hospital mortality, or hospital or ICU length of stay between the groups. Conclusion Hypoglycemia was reduced using an HDIE guideline and concentrated insulin.


2019 ◽  
Vol 24 (5) ◽  
pp. 378-389 ◽  
Author(s):  
Jenna W. Bartlett ◽  
Pamela L. Walker

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.


2008 ◽  
Vol 7 (1) ◽  
pp. 39-42
Author(s):  
Harpreet Lota ◽  
◽  
Natalie Powell ◽  
Rupert Negus ◽  
Richard Leonard ◽  
...  

A 54 year gentleman was admitted to hospital within four hours of taking an overdose of modified release felodipine tablets, with a total dose of approximately 250 mg. The initial management comprised fluid resuscitation, calcium chloride and glucagon. He remained hypotensive and was commenced on hyperinsulinaemia-euglycaemic therapy. Hypotension persisted with the development of progressive metabolic acidosis despite increasing inotropic support, haemofiltration and high dose insulin-dextrose infusions. The patient died 60 hours post overdose. The case highlights the profound, refractory circulatory collapse and lethal consequences of significant calcium channel blocker overdose and also reviews potential management strategies to attempt to reverse these changes. Despite the lack of evidence of whole bowel irrigation in overdose per se, its role in the removal of modified release compounds has not been studied. We would strongly urge emergency departments to consider this therapeutic modality, especially in overdoses involving delayed release preparations of calcium channel blockers, which are extremely toxic in overdose and are associated with very high mortality.


Author(s):  
Geoffrey Isbister ◽  
Colin Page

β‎-blocker and calcium channel-blockers can cause life-threatening toxicity due to cardiogenic shock. Both β‎-blockers and calcium channel-blockers are heterogenous groups of drugs and particular drugs, such as propranolol, diltiazem, and verapamil are far more toxic than the others in their class. The most important investigations in β‎-blocker and calcium channel-blocker overdose are an electrocardiogram, blood glucose measurement, and electrolytes. Like most overdoses, supportive treatment is the most important, with emphasis on the primary pathophysiology. Early decontamination should be considered based on the severity of the poisoning. Treatment of β‎-blockers and calcium channel-blockers poisoning, using absolute blood pressure as an endpoint can be misleading and measuring cardiac output can be more informative in gauging response to treatment. There are no specific antidotes, although β‎-agonists may be effective in β‎-blocker overdose and calcium has been shown to be effective in calcium channel-blocker overdose. The choice of inotropes and/or vasopressors will differ for β‎-blockers and calcium channel-blockers. These include isoprenaline, high dose insulin euglycaemia, phosphodiesterase inhibitors, and other catecholaminergic inotropes for β‎-blocker poisoning and adrenaline, high dose insulin euglycaemia and vasopressors for calcium channel-blocker poisoning.


2005 ◽  
Vol 39 (5) ◽  
pp. 923-930 ◽  
Author(s):  
Greene Shepherd ◽  
Wendy Klein-Schwartz

OBJECTIVE: To evaluate the evidence for using high-dose insulin therapy with supplemental dextrose and potassium in calcium-channel blocker (CCB) overdose. DATA SOURCES: Evidence of efficacy for high-dose insulin therapy with supplemental dextrose and potassium was sought by performing a search of MEDLINE and Toxline between 1966 and July 2004 using combinations of the terms calcium-channel blocker, overdose, poisoning, antidote, and insulin. Abstracts from the North American Congress of Clinical Toxicology for the years 1996–2003 were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Identified articles, including animal studies, case reports, and case series, were evaluated for this review. No clinical trials were available. DATA SYNTHESIS: Animal models of CCB overdose demonstrate that high-dose insulin with supplemental dextrose and potassium was a more effective therapy than calcium, glucagon, or catecholamines. High-dose insulin appears to enhance cardiac carbohydrate metabolism and has direct inotropic effects. Published clinical experience is limited to 13 case reports where insulin was used after other therapies were failing; 12 of these patients survived. High-dose insulin therapy was beneficial for CCB-induced hypotension, hyperglycemia, and metabolic acidosis. Bradycardia and heart block resolved in some patients, but persisted in others. CONCLUSIONS: Based on animal data and limited human experience, as well as the inadequacies of available alternatives for patients with significant poisoning, high-dose insulin therapy warrants further study and judicious use in patients with life-threatening CCB poisoning.


2020 ◽  
Vol 16 ◽  
Author(s):  
Seiji Umemoto ◽  
Toshio Ogihara ◽  
Masunori Matsuzaki ◽  
Hiromi Rakugi ◽  
Kazuyuki Shimada ◽  
...  

Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events) three benidipine (a calcium channel blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional angiotensin receptor blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events p=0.92 renal events p=0.16 log-rank test. Conclusions: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there is no enough these events to compare the difference in the three treatment groups.


2019 ◽  
Vol 15 (3) ◽  
pp. 207-218 ◽  
Author(s):  
Fatma Ağın

Background:Calcium Channel Blockers (CCBs) are widely used in the treatment of cardiovascular and ischemic heart diseases in recent years. They treat arrhythmias by reducing cardiac cycle contraction and also benefit ischemic heart diseases. Electroanalytical methods are very powerful analytical methods used in the pharmaceutical industry because of the determination of therapeutic agents and/or their metabolites in clinical samples at extremely low concentrations (10-50 ng/ml). The purpose of this review is to gather electroanalytical methods used for the determination of calcium channel blocker drugs in pharmaceutical dosage forms and biological media selected mainly from current articles.Methods:This review mainly includes recent determination studies of calcium channel blockers by electroanalytical methods from pharmaceutical dosage forms and biological samples. The studies of calcium channel blockers electroanalytical determination in the literature were reviewed and interpreted.Results:There are a lot of studies on amlodipine and nifedipine, but the number of studies on benidipine, cilnidipine, felodipine, isradipine, lercanidipine, lacidipine, levamlodipine, manidipine, nicardipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, diltiazem, and verapamil are limited in the literature. In these studies, DPV and SWV are the most used methods. The other methods were used less for the determination of calcium channel blocker drugs.Conclusion:Electroanalytical methods especially voltammetric methods supply reproducible and reliable results for the analysis of the analyte. These methods are simple, more sensitive, rapid and inexpensive compared to the usually used spectroscopic and chromatographic methods.


Author(s):  
Bagas Mukti

Hipertensi merupakan suatu manifestasi dari gangguan hemodinamik kardiovaskular yang penyebabnya multifactor. Prevalensi penderita hipertensi di Indonesia sendiri pada tahun 2018 meningkatkan dari tahun 2013 dan peningkatan tersebut sebesar 8,3 %. Seseorang dikatakan hipertensi jika tekanan darah diatas atau sama dengan 140/90 mmHg dan harus persisten. Hipertensi sendiri masih menjadi penyebab kematian tertinggi dan dapat menyebabkan komplikasi yang serius seperti stroke, penyakit jantung iskemik, gagal ginjal, retinopati dan sebagainya. Ada banyak guidelines yang menjelaskan bagaimana manajemen terapi untuk mengurangi tekanan darah tinggi. Ada dua cara untuk mentatalaksana penderita hipertensi, yaitu dengan terapi farmakologis (Diuretik, β-blocker, ACE Inhibitor, Angiotensin Receptor Blockers (ARB), Calcium-channel blocker (CCB) dan sebagainya) dan terapi non farmakologi dengan memodifikasi gaya hidup seperti olahraga teratur, mengurangi konsumsi alcohol, menghentikan rokok, serta menurunkan berat badan, mengurangi konsumsi garam dengan cara mengadaptasi diet DASH (Dietary Approaches to Stop Hypertension). Diet DASH menerapkan pola makan yang kaya akan sayuran, buah-buahan, susu dan produk-produk susu tanpa lemak atau rendah lemak, biji-bijian, ikan, unggas, kacang-kacangan dan diet ini juga mengandung sedikit natrium, makanan manis, gula, lemak, dan daging merah. Pada penelitian meta-analisis dan sistematik review dari randomized controlled trials (RCTs), mengungkapkan bahwa penerapan diet DASH pada pasien hipertensi dapat menurunkan tekanan darah sistolik sebesar 6,74 mmHg dan tekanan darah diastolic sebesar 3,54 mmHg. Studi meta-analisis lain dari RCTs membuktikan bahwa dengan penerapan diet ini dapat menurunkan berat badan pada pasien yang mengalami obesitas sebesar 1,42 kg dalam waktu 8-24 minggu. Sehingga diet DASH ini sangat bermanfaat untuk diterapkan pada pasien hipertensi.


2021 ◽  
Author(s):  
Anmol Kumar ◽  
Stefan Mutter ◽  
Erika Parente ◽  
Valma Harjutsalo ◽  
Raija Lithovius ◽  
...  

Objective: Vascular endothelial growth factor (VEGF) plays a key role in diabetic retinopathy (DR). L-type calcium channel blockers (LTCCBs) have been widely used as antihypertensive medication (AHM), but their association with VEGF and DR is still unclear. Therefore, we explored the effect of LTCCBs compared to other AHMs on VEGF concentrations in retinal cells and human serum. Furthermore, we evaluated the association between the use of LTCCBs and the risk of severe diabetic eye disease (SDED). Research design and methods: Muller cells (MIO-M1) were cultured as per recommended protocol and treated with LTCCBs and other AHMs. VEGF secreted from cells were collected at 24 hours intervals. In an interventional study, 39 individuals received LTCCBs or other AHM for four weeks with a four-week wash-out placebo period between treatments. VEGF was measured during the medication and placebo periods. Finally, we evaluated the risk of SDED associated with LTCCB usage in 192 individuals from the FinnDiane Study in an oberservational setting. Results: In the cell cultures, medium VEGF concentration increased time-dependently after amlodipine (p<0.01) treatment, but not after losartan (p>0.01), or lisinopril (p>0.01). Amlodipine, but no other AHM, increased serum VEGF concentration (p<0.05) during the interventional clinical study. The usage of LTCCB was not associated with the risk of SDED in the observational study. Conclusions: LTCCB increases VEGF concentrations in retinal cells and human serum. However, the usage of LTCCBs does not appear to be associated with SDED in adults with type 1 diabetes.


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