buprenorphine and Heart-Arrest

To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, corrected QT interval (QTc) prolongation or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone.. Retrospective pharmacoepidemiological study.. Adverse drug events reported spontaneously to the FDA between 1969 and June 2011 originating in 196 countries (71% events from the United States).. Adverse event cases mentioning methadone (n = 14 915) or buprenorphine (n = 7283) were evaluated against all other adverse event cases (n = 4 796 017).. The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR > 2, χ(2) error > 4, with ≥ 3 cases.. There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.10, 95%, confidence interval (0.93-1.31, χ(2)  = 1.2) or QTc prolongation/torsade de pointes (1.03, 95% CI = 0.66-1.62, χ(2)  = 0.01), but were for methadone (7.20, 95% CI = 6.88-7.52, χ(2)  = 8027; 10.7, 95% CI = 9.66-11.8, χ(2)  = 1538, respectively).. In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed and disproportionality analysis cannot quantify absolute risk per treatment episode. Population-based studies to definitively quantify differential incidence rates are warranted.

Topics: Adult; Arrhythmias, Cardiac; Buprenorphine; Female; Heart Arrest; Humans; Long QT Syndrome; Male; Methadone; Narcotic Antagonists; Retrospective Studies; Torsades de Pointes; United States; United States Food and Drug Administration

Extensive loss of neurons occurs from the middle region of the thalamic reticular nucleus (RT) in rats resuscitated after 10 min of cardiac arrest. Administration of the partial mu opiate agonist buprenorphine 45 min after resuscitation produces a small but significant increase in spared neurons along the medial and lateral margins of the middle RT, regions where mu receptors have been localized. Systemic administration of mu agonists may augment endogenous opiate mechanisms that contribute to the relative ischemic resistance of subpopulations of RT neurons.

Topics: Animals; Buprenorphine; Cell Death; Heart Arrest; Immunohistochemistry; Male; Neurons; Rats; Receptors, Opioid, mu; Retina; Thalamic Nuclei