Emmanuel Samain

Prolongation of QTc Interval after Postoperative Nausea and Vomiting Treatment by Droperidol or Ondansetron

Background:At dosages above 0.1 mg/kg, droperidol inducesa dose-dependent QTc interval prolongation. Although subject to controversy, low-dose droperidol has recently been suspected to induce cardiac arrhythmias. Hence, 5-hydroxytryptamine type 3 antagonists have become the first-line drug for management of postoperative nausea and vomiting. These drugs are also known to prolong the QTc interval at high dosages. This study describes QTc interval changes associated with postoperative nausea and vomiting treatment by droperidol or ondansetron at low doses. Methods:Eighty-five patients with postoperative nausea and vomiting were included in this prospective, single-blind study. Patients received either 0.75 mg intravenous droperidol (n = 43) or 4 mg intravenous ondansetron (n = 42). Electrocardiographic recordings were obtained before administration of antiemetic drug and then 1, 2, 3, 5, 10, and 15 min after. Electrocardiographic monitoring was maintained for 3 h in eight patients in each group. Results:The QTc interval was prolonged (> 450 ms in men, > 470 ms in women) in 21% of the patients before antiemetic drug administration. This was significantly correlated with lower body temperature and longer duration of anesthesia. Compared with predrug QTc measurement, both antiemetics were associated with a significant QTc interval prolongation (P < 0.0001). The mean maximal QTc interval prolongation was 17 ± 9 ms after droperidol occurring at the second minute and 20 ± 13 ms after ondansetron at the third minute (both P < 0.0001). Compared with predrug measurement, the QTc interval was significantly lower after the 90th minute in both groups. Conclusions:Droperidol and ondansetron induced similar clinically relevant QTc interval prolongations. When used in treatment of postoperative nausea and vomiting, a situation where prolongation of the QTc interval seems to occur, the safety of 5-hydroxytryptamine type 3 antagonists may not be superior to that of low-dose droperidol.

In Vivo RNA Interference Analysis Reveals an Unexpected Role for GNBP1 in the Defense against Gram-positive Bacterial Infection in Drosophila Adults*

The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions via the selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi, whereas the Imd pathway is required to resist Gram-negative bacterial infection. Microbial recognition is achieved through peptidoglycan recognition proteins (PGRPs); Gram-positive bacteria activate the Toll pathway through a circulating PGRP (PGRP-SA), and Gram-negative bacteria activate the Imd pathway via PGRP-LC, a putative transmembrane receptor, and PGRP-LE. Gram-negative binding proteins (GNBPs) were originally identified in Bombyx mori for their capacity to bind various microbial compounds. Three GNBPs and two related proteins are encoded in the Drosophila genome, but their function is not known. Using inducible expression of GNBP1 double-stranded RNA, we now demonstrate that GNBP1 is required for Toll activation in response to Gram-positive bacterial infection; GNBP1 double-stranded RNA expression renders flies susceptible to Gram-positive bacterial infection and reduces the induction of the antifungal peptide encoding gene Drosomycin after infection by Gram-positive bacteria but not after fungal infection. This phenotype induced by GNBP1 inactivation is identical to a loss-of-function mutation in PGRP-SA, and our genetic studies suggest that GNBP1 acts upstream of the Toll ligand Spätzle. Altogether, our results demonstrate that the detection of Gram-positive bacteria in Drosophila requires two putative pattern recognition receptors, PGRP-SA and GNBP1.

Closed-loop Coadministration of Propofol and Remifentanil Guided by Bispectral Index: A Randomized Multicenter Study

BACKGROUND:We have developed a proportional-integral-derivative controller allowing the closed-loop coadministration of propofol and remifentanil, guided by a Bispectral Index (BIS) monitor, during induction and maintenance of general anesthesia. The controller was compared with manual target-controlled infusion. METHODS:In a multicenter study, 196 surgical patients were randomly assigned to dual closed-loop or manual administration of propofol and remifentanil. Comparison between groups was evaluated by calculating a global score that characterized the overall performance of the controller including the percentage of adequate anesthesia, defined as BIS between 40 and 60, the median absolute performance error, and wobble. Secondary outcomes included occurrence of burst suppression ratio, time to tracheal extubation, and drug consumption. RESULTS:Eighty-three patients assigned to dual-loop control and 84 patients assigned to manual control completed the study. The global score and the percentage of time with BIS between 40 and 60 were better in the dual-loop group (26 ± 11 vs 43 ± 40, P < 0.0001; 82% ± 12% vs 71% ± 19%, P < 0.0001). Overshoot (BIS <40), undershoot (BIS >60), and burst suppression ratio were all significantly less common in the dual-loop group. Modifications to the propofol and remifentanil infusions were more frequent, and adjustments smaller in the dual-loop group. Remifentanil consumption was greater (0.22 ± 0.07 vs 0.16 ± 0.07 &mgr;g · kg−1 · min−1; P < 0.0001) and the speed to tracheal extubation was shorter (10 ± 4 vs 11 ± 5 minutes; P = 0.02) in the dual-loop group. CONCLUSION:The controller allows the automated delivery of propofol and remifentanil and maintains BIS values in predetermined boundaries during general anesthesia better than manual administration.

Institutional Variability in Transfusion Practice for Liver Transplantation

We prospectively evaluated the institutional variability in perioperative transfusion therapy in orthotopic liver transplantation (OLT). Adult OLTs completed during a 12-mo period were studied until the 48th postoperative hour at 8 centers. A multivariate analysis using mixed-effects logistic regression included variables predisposing to blood loss and a center random effect. In addition, the influence of the calculated perioperative hemoglobin (Hb) loss on the individual probability of receiving red blood cells (RBCs), fresh frozen plasma (FFP), and platelets in excess of the overall median were explored. The analysis was performed on 301 cases. The overall median numbers transfused were 5 RBC units, 6 FFP units, and the median platelet dose was 5.1011, with significant intercentric differences in the proportions of cases given more than the overall median. Intercentric differences remained significant after adjustment for factors independently associated with a large blood component use. Intercentric differences in RBCs, FFP, and platelet use decreased but persisted after adjustment for the perioperative Hb loss. Intercentric differences in RBC use disappeared after adjustment for the postoperative Hb concentration. The significant heterogeneity in transfusion therapy mandates reassessment of the rational use of blood products in OLT.

A French Multicenter Clinical Trial of SPARC for Stress Urinary Incontinence

OBJECTIVE To evaluate the safety and efficacy of the SPARC procedure in women with genuine stress urinary incontinence. METHODS We conducted a prospective multicenter trial of a suprapubic approach to suburethral polypropylene (SPARC) taping for the treatment of genuine stress urinary incontinence. Between June 2001 and June 2002, 104 consecutive women (mean age 58.7 years) underwent SPARC in three centers. All the women had urethral hypermobility preoperatively. Detrusor instability was ruled out by cystometry. The women were evaluated 1, 3, 6 and 12 months postoperatively. The objective cure rate was evaluated by clinical and urodynamic examination, and the subjective cure rate was assessed using the Kings and Bristol questionnaire. RESULTS The mean follow-up time was 11.9+/-1.9 months (range 8 to 20 months). The mean operating time was 30 min (25-50 min). Most of the patients received general anesthesia (48%). The overall complication rate was 44.2% (46/104). The perioperative complication rate was 10.5%, including 11 bladder injuries. A significant difference in the bladder injury rate was observed between women with and without previous incontinence surgery (respectively 4/11, 36.3% versus 7/93, 7.5%; p<0.001). No hemorrhaging occurred. The early postoperative complication rate was 22.1%. The main complication was voiding disorders (11 patients), which necessitated intermittent self-catheterization for less than 15 days (1.3+/-1.1 days, range 1 to 10 days). The late postoperative complication rate was 11.5%, including de novo urge symptoms in 12 women. The objective cure rate was 90.4%. No difference was found between patients with genuine stress incontinence and those with mixed incontinence. The subjective cure rate was 72%. The objective and subjective cure rates differed significantly (p<0.05). The subjective cure rate among patients with de novo urge symptoms was 58%. CONCLUSION The SPARC procedure is a safe and effective treatment for women with stress urinary incontinence, despite a high incidence of de novo urge symptoms.

QT interval measurement: evaluation of automatic QTc measurement and new simple method to calculate and interpret corrected QT interval.

Background:Assessment of repolarization duration is often recommended to avoid administration of QT-prolonging drugs in patients with prolonged QTc interval, a frequent situation in the postoperative period. Bazett QT correction inappropriately increases QTc when heart rate is increased, and the use of the Fridericia formula may avoid a falsely prolonged QTc interval. The authors assessed automatic QT interval measurement to detect prolonged QTc interval (women >450 ms; men >440 ms) in the postoperative setting. Methods:Automatic and manual electrocardiograms were performed in 108 patients after anesthesia. Automatic electrocardiographic measurement used the Bazett formula. Manual measurements were made from each electrocardiogram and used as the reference. Agreement between the two methods was analyzed. Bazett and Fridericia QT corrections were compared in this population. Results:Agreement between automatic and manual measurements was low. The Fridericia correction, but not the Bazett correction, was independent from heart rate and allowed adequate QT correction. Sensitivity of automatic measurements to detect prolonged QTc-Bazett interval was 54%. Automatic QTc-Bazett interval less than 430 ms ruled out a manual prolonged QTc interval. When automatic QTc-Bazett was greater than 430 ms, this value was converted according to Fridericia. Automatic QTc-Fridericia greater than 430 ms identified all patients with prolonged manual QTc with a negative predictive error of 0% (95% confidence interval, 0–7%). QTc-Fridericia can be approximated by respectively adding or subtracting 5% to the uncorrected QT for each increase or decrease by 10 beats/min in heart rate from 60 beats/min. Conclusions:Automatic QTc-Bazett measurement, if abnormal, associated with calculation of QTc-Fridericia reliably identifies patients in whom manual QTc measurement must be performed to confirm postoperative prolonged QTc interval.

Assessment of topographic brachial plexus nerves variations at the axilla using ultrasonography

BACKGROUND The aim of this study was to describe topographic variations in the arrangement of the four main brachial plexus nerves at the junction of the axilla and the upper part of the arm. METHODS In 153 patients undergoing upper arm surgery using axillary block, we studied nerve arrangements with a three-step approach, combining: (A) cross-sectional ultrasound imaging using a 12 MHz linear ultrasound probe; (B) distal shift of the ultrasound scanhead from the axilla to the elbow joint following the paths of individual nerves; and (C) identifying the distal motor response to electrical nerve stimulation of each nerve. These results were then converted into a 12-section pie chart with the axillary artery (AA) as the axis. RESULTS The order of the nerves around the AA was median, ulnar, radial, and musculocutaneous in all cases. The most frequent arrangement was observed in 65% of the patients. Five less frequent variations were observed in 4-20% of the patients, with four other variations seen in <2% of the patients. In 78% of the cases, the four nerves were seen separately using static ultrasound imaging. The musculocutaneous nerve was close to the artery in 18% of the patients. CONCLUSIONS Topographic variations of the four main nerves at the axilla were found to be numerous, the most frequent arrangement being seen in less than two-thirds of the patients. Four separate nerves were seen on static ultrasound imaging at this sectional level of the axilla in only 78% of the cases.

QT interval prolongation after oxytocin bolus during surgical induced abortion.

Although oxytocin, a uterotonic agent, may cause short‐term vasodilation that results in severe hypotension, it is still routinely given as an intravenous bolus injection during surgical suction curettage. Two reported cases of ventricular tachycardia after oxytocin bolus in patients with long QT interval syndrome led us to assess the effect of oxytocin on QT interval.

The Effect of Propofol on Angiotensin Ii-induced Ca2+ Mobilization in Aortic Smooth Muscle Cells from Normotensive and Hypertensive Rats

We studied the effect of propofol (5.6–560 &mgr;mol/L; 1–100 &mgr;g/mL) on the mechanisms involved in Ca2+ mobilization elicited by angiotensin II (AngII) in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We studied the variations in intracellular Ca2+ ([Ca2+]i) concentrations in cultured aortic vascular smooth muscle cells (VSMCs) isolated from 6-wk-old WKY and SHR rats loaded with the Ca2+-sensitive fluorescent dye, Fura-2, using fluorescent imaging microscopy. In the absence of external Ca2+, AngII (1 &mgr;mol/L) induced a transient [Ca2+]i mobilization from internal stores that was larger in SHR than in WKY rats. Ca2+ influx was assessed after external Ca2+ (1 mmol/L) reintroduction. Propofol (1–100 &mgr;g/mL) added 5 min before the experiments did not alter AngII-induced Ca2+ release from internal stores in either strain. By contrast, Ca2+ influx elicited by AngII was significantly decreased by propofol. This effect occurred at a smaller concentration of propofol in the SHR than in the WKY rats. When Ca2+ stores were depleted by exposure of cells to thapsigargin, an inhibitor of the sarcoendoplasmic reticulum Ca2+-ATPase, reintroduction of Ca2+ to the medium induced a capacitative Ca2+ influx of similar magnitude than that elicited by AngII. This influx was also significantly decreased by propofol at 100 &mgr;g/mL ( WKY: 27 ± 3% of control values, n = 107; SHR: 16 ± 3%, n = 47;P < 0.001). In conclusion, propofol decreased AngII-induced Ca2+ influx through voltage-independent channels, without altering Ca2+ release from internal stores in aortic VSMCs. The hypertensive rats were found to be more sensitive to the effect of propofol than the normotensive rats. This suggests that the response of VSMCs to AngII may be altered by propofol. Implications: In rat aortic vascular smooth muscle cells, propofol reduced angiotensin II-elicited Ca2+ entry through capacitative Ca2+ channels without altering Ca2+ release from intracellular stores. Spontaneously hypertensive rats were more sensitive to these effects of propofol than normotensive rats. The response of vascular smooth muscle cells to angiotensin II may be altered by propofol.

Vaginal hysterectomy for benign disorders in obese women: a prospective study.

Objective  To compare the morbidity of vaginal hysterectomy in obese and non‐obese women in a single institution.