A Massive Venlafaxine Intoxication: Evolution of Cardiac Toxicity with Venlafaxine and O-Desmethylvenlafaxine Elimination Kinetics: A Grand Round.

BACKGROUND: This study presents the case of a 19-year-old woman who attempted suicide by ingesting 11.25 g of venlafaxine (V). She was admitted to the hospital with severe biventricular dysfunction, progressing to cardiac arrest requiring extracorporeal circulatory life support for 11 days. The pharmacokinetics of venlafaxine during impaired cardiac output and the effect of its active metabolite, the O-desmethylvenlafaxine (ODV), are currently not very well understood. METHODS AND RESULTS: Serum concentrations of V and ODV were monitored twice daily for 3 weeks. The maximum concentrations of venlafaxine and ODV were at 14 hours after ingestion, with 29,180 mcg/L for V and 5399 mcg/L for ODV. Half-lives increased, requiring 2 weeks to eliminate the drug. The left ventricular ejection fraction significantly improved when V + ODV was below 1000 mcg/L and remained altered until the ODV concentrations were lower than 400 mcg/L. CONCLUSIONS: This report, with complete elimination kinetic of V and ODV in a monodrug intoxication, provides information about the modification of pharmacokinetics in the case of an overdose managed by extracorporeal circulatory life support, the cardiac toxicity of ODV, and the value of the toxic threshold for the active moiety.

Clues of incomplete reversal of heparin in cardiac surgery.

OBJECTIVES: In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing. METHODS: In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1 month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added. RESULTS: Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 (p < .0001) and 0.95 (p = .0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58-97] and a specificity of 85% [58-97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30-94] and a specificity of 100% [18-100]. CONCLUSION: The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin.

Cardiac index assessment: validation of a new non-invasive very low current thoracic bioimpedance device by thermodilution.

INTRODUCTION: The accuracy of impedance cardiography for cardiac index assessment is matter of debate, with available studies reporting inconsistent results. Our study aimed at evaluating the agreement between measurements of cardiac index provided by a new-generation thoracic electrical bioimpedance device (Hotman System) and an invasive approach based on thermodilution in humans. METHODS: Cardiac index was assessed simultaneously with thoracic electrical bioimpedance and conventional thermodilution through comparison of five consecutive measurements in 51 cardiac patients, hospitalized in an intensive care unit (mean± SD age: 60 ± 11 years; 68% males). The agreement between cardiac index values measured by both methods was assessed by the Bland-Altman approach, adjusted for repeated measures. The repeatability coefficient and the intraclass correlation coefficient were used to assess reproducibility of replicates. RESULTS: Average (± SD) cardiac index was 3.05 ± 0.91 l/min/m(2) with Hotman System and 3.14 ± 1.12 l/min/m(2) with thermodilution. The bias of precision was -0.09 ± 0.41. The coefficients of repeatability and intraclass correlation coefficients were high and similar for the two techniques (0.95 l/min/m(2) and 0.91 for Hotman System vs 0.78 l/min/m(2) and 0.90 for thermodilution). CONCLUSIONS: Cardiac index values yielded by Hotman system compares favorably with that obtained with thermodilution in cardiac patients.