False positive amphetamines and 3,4-methylenedioxymethamphetamine immunoassays in the presence of metoprolol-two cases reported in clinical toxicology.

Amphetamines, frequently used recreational drugs with high risk of toxicity, are commonly included in urine drug screens. This screening is based on enzyme immunoassay, which is a quick and easy-to-perform technique, but may lack specificity resulting from cross-reactivity with other compounds, causing false positive results. We present two cases of presumed false positive MULTIGENT® amphetamine/methamphetamine and MULTIGENT® ecstasy (Abbott®) immunoassays with the beta-blocker metoprolol. Both metoprolol-poisoned patients presented positive urine screening despite no history of drug abuse. No confirmation for amphetamine molecular structures was found with gas chromatography-mass spectrometry. The cross-reactivity was further investigated by doping urine samples with metoprolol and its two major phase-I metabolites. Metoprolol showed positive results for both amphetamine and MDMA tests at low concentrations (200 and 150 µg/mL, respectively). Metoprolol metabolites cross-reacted with the amphetamines immunoassay only, but at higher concentrations (i.e., 2000 µg/mL for α-hydroxymetoprolol and 750 µg/mL for O-demethylmetoprolol). In conclusion, false positive results in amphetamines and MDMA immunoassays are possible in the presence of metoprolol. Toxicologists should be aware of frequent analytical interferences with immunoassays and a detailed medication history should be taken into consideration for interpretation. In vitro investigation of suspected cross-reactivity should include not only the parent drug but also its related metabolites.

Predictors of mortality in verapamil overdose: usefulness of serum verapamil concentrations.

Verapamil poisoning may result in life-threatening cardiovascular morbidities and fatalities. To date, prognosticators of mortality have been poorly investigated and the use of serum verapamil concentration for prognosis remains unclear. We aimed to evaluate the ability of usual clinical and laboratory parameters including serum verapamil concentrations measured on admission to predict outcome (survival versus death) in verapamil poisoning. We reviewed the medical records of all intentional and symptomatic verapamil poisonings admitted over 8 years to two medical intensive care units. Clinical and laboratory parameters were measured in 65 patients, and final outcomes of survival or death recorded. A multivariable analysis was conducted to evaluate the prognostic values of recorded parameters. Life-threatening complications of verapamil poisonings included shock (62%), atrioventricular blocks (24%), sinoatrial blocks (20%), acute respiratory distress syndrome (19%) and cardiac arrest (11%) resulting in death (8%). Verapamil concentration measured on intensive care unit admission was the only independent factor associated with mortality (p = 0.01). The optimal verapamil cut-off point was 5.0 µM (100% sensitivity, 91% specificity), which conferred a 2.76-times increase in odds of fatality. In conclusion, cardiovascular monitoring and assessment of organ failure are vital in symptomatic verapamil poisonings. The serum verapamil concentration has excellent prognostic ability for predicting fatality in verapamil overdose.

Reduction of paracetamol metabolism after hepatic resection.

INTRODUCTION: Paracetamol is often used as an analgesic following hepatic resection. During liver resection, vascular clamping is carried out to reduce blood loss. Previous studies have described transient postoperative rises in serum aminotransferase levels and decreases in prothrombin time and factor V levels. We have examined paracetamol metabolism after liver resection. METHODS: A prospective observational study was performed. All patients undergoing liver resection were included. Propacetamol was given every 6 h. Blood samples for plasma paracetamol concentrations were collected before, 1 h after the end of the first injection (T1), just before the second injection (6 h: T6), and just before the fifth injection (24 h: T24). RESULTS: 37 patients were recruited. 13 had hepatic vascular exclusion (HVE group), 13 had portal triad clamping (PTC group) and 11 had abdominal surgery with no liver resection (NLR group: control group). At T6, the plasma paracetamol concentration in the HVE group was significantly higher than in the NLR groups; at T24, this concentration was significantly higher in the HVE group than in the NLR and PTC groups, and was higher in the PTC group than in the NLR group. Prothrombin time and factor V was significantly lower in the HVE group than in the PTC group on the first postoperative day. DISCUSSION: This study showed a reduction of paracetamol metabolism in the liver resection group with significantly increased paracetamol levels. However, the maximum mean plasma concentration reached was not clinically or toxicologically significant. For these reasons, we cannot suggest that paracetamol should or should not be avoided in patients undergoing liver resection.