Rationale: Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard. Objective: We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimulation test, and the prevalence of sepsis-associated adrenal insufficiency. Methods: This was an inception cohort study. Measurements and Results: In two consecutive septic cohorts (n = 61 and n = 40), in 44 patients without sepsis and in 32 healthy volunteers, we measured (1) serum cortisol before and after cosyntropin stimulation, albumin, and corticosteroid-binding globulin levels, and (2) serum corticotropin, cortisol, and 11β-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11β-deoxycortisol levels below 7 μg/dl. More patients with sepsis (31/61 [59% of original cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p < 0.001 for both comparisons). Baseline cortisol (< 10 μg/dl), Δ cortisol (< 9 μg/dl), and free cortisol (< 2 μg/dl) had a positive likelihood ratio equal to infinity, 8.46 (95% confidence interval, 1.19–60.25), and 9.50 (95% confidence interval, 1.05–9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol of 10 μg/dl or less or Δ cortisol of less than 9 μg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 μg/dl or greater and Δ cortisol of 16.8 μg/dl or greater. Conclusions: In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 μg/dl or delta cortisol is less than 9 μg/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 μg/dl or greater or Δ cortisol is 16.8 μg/dl or greater.

A new rapid and sensitive high-performance liquid chromatography method has been developed for the screening and determination in human plasma of the 11 most commonly prescribed nontricyclic antidepressants and two metabolites: fluoxetine, norfluoxetine, sertraline, paroxetine, citalopram, fluvoxamine, moclobemide, mirtazapine, milnacipram, toloxatone, venlafaxine, desmethyl venlafaxine, and viloxazine. It involves liquid-liquid extraction procedures followed by liquid chromatography coupled to photodiode-array UV detection with three fixed wavelengths (220, 240, and 290 nm). Compounds were separated on a 5-μm Hypurity C18 (ThermoHypersil) analytic column (250 × 4.6 mm i.d.) using a gradient of acetonitrilephosphate buffer pH 3.8 at a flow rate of 1.0 mL/min. The total analysis time was only 18 min per sample. Extraction recoveries were in the 74-109% range for 11 compounds but were of only 59% for moclobemide and less than 10% for toloxatone. Calibration curves were linear in the 25 to 1000 ng/mL range for all compounds, all of them with coefficients of determination (r2 values) ≥ 0.999. Limits of detection (LODs) ranged from 2.5 to 5 ng/mL except for toloxatone (10 ng/mL). Intraassay and interassay precision and accuracy were studied at two concentration levels (50 and 500 ng/mL). The intraassay coefficients of variation (CVs) for all compounds were ≤ 7.6%, and all interassay CVs were below 11.5% except for milnacipram (14.8%). The intraassay and interassay accuracies for all compounds were found to be within 88.4% and 105.9% at 50 ng/mL and within 87.2% and 100.5% at 500 ng/mL. The performance of the method allows the therapeutic drug monitoring of the most prescribed nontricyclic antidepressant drugs as well as its use in toxicologic screening.

DROPERIDOL and 5-hydroxytryptamine type 3 receptor antagonists belong to the most effective antiemetics for prevention or treatment of postoperative nausea and vomiting.1 In 2001, the US Food and Drug Administration issued a “black box” warning regarding the potential for proarrhythmic events related to QT interval prolongation with droperidol use.1As a consequence, 5-hydroxytryptamine type 3 antagonists became the most used antiemetics, in particular in the United States.2 However, setrons share with droperidol the property to block the human ether-a-go-go–related gene (HERG) cardiac potassium channel underlying their theoretical proarrhythmic potential.3,4 Electrocardiographic data from patients in clinical studies are conflicting.5–8 In previous reports, White et al. 7 failed to demonstrate a statistically significant QT interval prolongation with 1.25 mg droperidol. In a study that was not placebo controlled, we found significant QT interval prolongation with 0.75 mg droperidol but also after 4 mg ondansetron.8 Despite the weak evidence for cardiac arrhythmic events in the clinical experience accumulated so far with these antiemetics, a new QT study was deemed to be important for a definitive assessment of the effects of these agents on the QT interval. Such a study was requested by the Food and Drug Administration but was stopped because of adverse neurologic effects induced by droperidol.2

Background: The analgesic effect of perioperative low doses of intravenous lidocaine has been demonstrated after abdominal surgery. This study aimed to evaluate whether a continuous intravenous low-dose lidocaine infusion reduced postoperative pain and modified nociceptive pain threshold after total hip arthroplasty. Methods: Sixty patients participated in this randomized double-blinded study. Patients received lidocaine 1% (lidocaine group) with a 1.5 mg/kg intravenous bolus in 10 min followed by a 1.5 mg . kg . h intravenous infusion or saline (control group). These regimens were started 30 min before surgical incision and stopped 1h after skin closure. Lidocaine blood concentrations were measured at the end of administration. In both groups, postoperative analgesia was provided exclusively by patient-controlled intravenous morphine. Pain scores, morphine consumption, and operative hip flexion were recorded over 48 h. In addition, pressure pain thresholds and the extent of hyperalgesia around surgical incision were systematically measured at 24 and 48 h. Results: In comparison with the placebo, lidocaine did not induce any opioid-sparing effect during the first 24 h (median [25-75% interquartile range]; 17 mg [9-28] vs. 15 mg [8-23]; P = 0.54). There was no significant difference regarding the effects of lidocaine and placebo on pain score, pressure pain thresholds, extent in the area of hyperalgesia, and maximal degree of active hip flexion tolerated. Mean plasma lidocaine concentration was 2.1 +/- 0.4 mug/ml. Conclusion: Low dose perioperative intravenous lidocaine after total hip arthroplasty offers no beneficial effect on postoperative analgesia and does not modify pressure and tactile pain thresholds.