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      Treatment for calcium channel blocker poisoning: A systematic review

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          Abstract

          Context

          Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion.

          Objective

          To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations.

          Methods

          Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types.

          Results

          The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5–2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue.

          Conclusions

          The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.

          Related collections

          Most cited references 333

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          2011 Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 29th Annual Report.

          This is the 29th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 July 2011, 57 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 8.43 [6.29, 13.7] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system. We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 38 medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death. In 2011, 3,624,063 closed encounters were logged by NPDS: 2,334,004 human exposures, 80,266 animal exposures, 1,203,282 information calls, 6,243 human confirmed nonexposures, and 268 animal confirmed nonexposures. Total encounters showed an 8.3% decline from 2010, while health care facility exposure calls increased by 4.8%. Human exposures with less serious outcomes decreased by 3.4% while those with more serious outcomes (moderate, major or death) increased by 6.8%. All information calls decreased by 17.9% and health care facility (HCF) information calls decreased by 2.9%, Medication identification requests (Drug ID) decreased by 24.1%, and human exposures reported to US poison centers decreased by 2.2%. The top 5 substance classes most frequently involved in all human exposures were analgesics (11.7%), cosmetics/personal care products (8.0%), household cleaning substances (7.0%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%). Analgesic exposures as a class increased most rapidly (10,134 calls/year) over the last 11 years. The top 5 most common exposures in children aged 5 years or less were cosmetics/personal care products (14.0%), analgesics (9.9%), household cleaning substances (9.2%), foreign bodies/toys/miscellaneous (6.9%), and topical preparations (6.6%). Drug identification requests comprised 59.5% of all information calls. NPDS documented 2,765 human exposures resulting in death with 1,995 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). These data support the continued value of poison center expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response and situational awareness tracking. NPDS is a model system for the nation and global public health.
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            Distinguishing case series from cohort studies.

            Case series are a commonly reported study design, but the label "case series" is used inconsistently and sometimes incorrectly. Mislabeling impairs the appropriate indexing and sorting of evidence. This article tries to clarify the concept of case series and proposes a way to distinguish them from cohort studies. In a cohort study, patients are sampled on the basis of exposure and are followed over time, and the occurrence of outcomes is assessed. A cohort study may include a comparison group, although this is not a necessary feature. A case series may be a study that samples patients with both a specific outcome and a specific exposure, or one that samples patients with a specific outcome and includes patients regardless of whether they have specific exposures. Whereas a cohort study, in principle, enables the calculation of an absolute risk or a rate for the outcome, such a calculation is not possible in a case series.
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              Emergency feasibility in medical intensive care unit of extracorporeal life support for refractory cardiac arrest.

              To report the feasibility, complications, and outcomes of emergency extracorporeal life support (ECLS) in refractory cardiac arrests in medical intensive care unit (ICU). Prospective cohort study in the medical ICU in a university hospital in collaboration with the cardiosurgical team of a neighboring hospital. Seventeen patients (poisonings: 12/17) admitted over a 2-year period for cardiac arrest unresponsive to cardiopulmonary resuscitation (CPR) and advanced cardiac life support, without return of spontaneous circulation. ECLS femoral implantation under continuous cardiac massage, using a centrifugal pump connected to a hollow-fiber membrane oxygenator. Stable ECLS was achieved in 14 of 17 patients. Early complications included massive transfusions (n=8) and the need for surgical revision at the cannulation site for bleeding (n=1). Four patients (24%) survived at medical ICU discharge. Deaths resulted from multiorgan failure (n=8), thoracic bleeding(n=2), severe sepsis (n=2), and brain death (n=1). Massive hemorrhagic pulmonary edema during CPR (n=5) and major capillary leak syndrome (n=6) were observed. Three cardiotoxic-poisoned patients (18%, CPR duration: 30, 100, and 180 min) were alive at 1-year follow-up without sequelae. Two of these patients survived despite elevated plasma lactate concentrations before cannulation (39.0 and 20.0 mmol/l). ECLS was associated with a significantly lower ICU mortality rate than that expected from the Simplified Acute Physiology Score II (91.9%) and lower than the maximum Sequential Organ Failure Assessment score (>90%). Emergency ECLS is feasible in medical ICU and should be considered as a resuscitative tool for selected patients suffering from refractory cardiac arrest.
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                Author and article information

                Journal
                Clin Toxicol (Phila)
                Clin Toxicol (Phila)
                CTX
                Clinical Toxicology (Philadelphia, Pa.)
                Informa Healthcare
                1556-3650
                1556-9519
                November 2014
                06 October 2014
                : 52
                : 9
                : 926-944
                Affiliations
                1Ontario and Manitoba Poison Centre , Toronto, ON, Canada
                2Institute of Medical Science, University of Toronto , Toronto, ON, Canada
                3Department of Clinical Pharmacology and Toxicology, University of Toronto , Toronto, ON, Canada
                4Direction of Environmental Health and Toxicology, Institut national de santé publique du Québec , Québec, QC, Canada
                5Centre Hospitalier Universitaire de Québec , Québec, QC, Canada
                6Faculty of Pharmacy, Université Laval , Québec, QC, Canada
                7Centre antipoison du Québec , Québec, QC, Canada
                8Department of Medicine, McGill University , Montréal, QC, Canada
                9Toxicology Consulting Service, McGill University Health Centre , Montréal, QC, Canada
                10Centre Hospitalier Universitaire de Québec , Québec, QC, Canada
                11Centre de santé et services sociaux Alphonse-Desjardins (CHAU de Lévis) , Lévis, QC, Canada
                12Department of Family Medicine and Emergency Medicine, Université Laval , Québec, QC, Canada
                13Division de soins intensifs, Université Laval , Québec, QC, Canada
                14Populations Health and Optimal Health Practices, Centre Hospitalier Universitaire de Québec Research Centre , Québec, QC, Canada
                15Hôpital du Sacré-Coeur de Montréal , Montréal, QC, Canada
                16Department of Family and Emergency Medicine, University of Montreal , Montréal, QC, Canada
                17Faculty of Pharmacy, University of Montreal , Montréal, QC, Canada
                18Pharmacy Department, Centre de santé et services sociaux Alphonse-Desjardins (CHAU de Lévis) , Lévis, QC, Canada
                19Institut universitaire de Cardiologie et de Pneumologie de Québec , Québec, QC, Canada
                20Sunnybrook Research Institute and Institute for Clinical Evaluative Sciences , Toronto, ON, Canada
                21Departments of Medicine and Pediatrics, University of Toronto , Toronto, ON, Canada
                Author notes
                Address correspondence to Maude St-Onge, Centre antipoison du Québec , 1270 Chemin Sainte-Foy, Québec (Qc), G1S 2M4, Canada. Tel: + 416-605-0387. E-mail: egnomie@ 123456hotmail.com
                Article
                10.3109/15563650.2014.965827
                4245158
                25283255
                © 2014 Informa Healthcare USA, Inc.

                This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.

                Product
                Categories
                Review Article

                Toxicology

                antidotes, calcium channel blockers, cardiotoxins, drug overdose, poisoning, toxicity, treatment

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