Intravenous buspirone for the prevention of postoperative nausea and vomiting

Rationale: Buspirone, a partial 5HT1A agonist and D2 and D3 antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown. Objective: To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV. Methods: A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable). Results: A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0% (90% confidence interval [CI] 37.5-60.5%). With buspirone, that incidence ranged from a mean of 40.8% (29.3-52.4%) in the 1mg arm to 58.0% (46.5-69.5%) in the 0.3mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures. Conclusion: We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PON

Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery.

Fluorescence-based enhanced reality (FLER) is a technique to evaluate intestinal perfusion based on the elaboration of the Indocyanine Green fluorescence signal. The aim of the study was to assess FLER's performances in evaluating perfusion in an animal model of long-lasting intestinal ischemia. An ischemic segment was created in 18 small bowel loops in 6 pigs. After 2 h (n = 6), 4 h (n = 6), and 6 h (n = 6), loops were evaluated clinically and by FLER to delineate five regions of interest (ROIs): ischemic zone (ROI 1), presumed viable margins (ROI 2a-2b), and vascularized areas (3a-3b). Capillary lactates were measured to compare clinical vs. FLER assessment. Basal (V 0 ) and maximal (V max) mitochondrial respiration rates were determined according to FLER. Lactates (mmol/L) at clinically identified resection lines were significantly higher when compared to those identified by FLER (2.43 ± 0.95 vs. 1.55 ± 0.33 p = 0.02) after 4 h of ischemia. Lactates at 2 h at ROI 1 were 5.45 ± 2.44 vs. 1.9 ± 0.6 (2a-2b; p < 0.0001) vs. 1.2 ± 0.3 (3a-3b; p < 0.0001). At 4 h, lactates were 4.36 ± 1.32 (ROI 1) vs. 1.83 ± 0.81 (2a-2b; p < 0.0001) vs. 1.35 ± 0.67 (3a-3b; p < 0.0001). At 6 h, lactates were 4.16 ± 2.55 vs. 1.8 ± 1.2 vs. 1.45 ± 0.83 at ROI 1 vs. 2a--2b (p = 0.013) vs. 3a-3b (p = 0.0035). Mean V 0 and V max (pmolO2/second/mg of tissue) were significantly impaired after 4 and 6 h at ROI 1 (V 0 (4h) = 34.83 ± 10.39; V max (4h) = 76.6 ± 29.09; V 0 (6h) = 44.1 ± 12.37 and V max (6h) = 116.1 ± 40.1) when compared to 2a--2b (V 0 (4h) = 67.1 ± 17.47 p = 0.00039; V max (4h) = 146.8 ± 55.47 p = 0.0054; V 0 (6h) = 63.9 ± 28.99 p = 0.03; V max (6h) = 167.2 ± 56.96 p = 0.01). V 0 and V max were significantly higher at 3a-3b. FLER may identify the future anastomotic site even after repetitive assessments and long-standing bowel ischemia

Treatment of established postoperative nausea and vomiting: a quantitative systematic review

BACKGROUND: The relative efficacy of antiemetics for the treatment of postoperative nausea and vomiting (PONV) is poorly understood. METHODS: Systematic search (MEDLINE, Embase, Cochrane Library, bibliographies, any language, to 8.2000) for randomised comparisons of antiemetics with any comparator for the treatment of established PONV. Dichotomous data on prevention of further nausea and vomiting, and on side effects were combined using a fixed effect model. RESULTS: In seven trials (1,267 patients), 11 different antiemetics were tested without placebos; these data were not further analysed. Eighteen trials (3,809) had placebo controls. Dolasetron 12.5–100 mg, granisetron 0.1–3 mg, tropisetron 0.5–5 mg, and ondansetron 1–8 mg prevented further vomiting with little evidence of dose-responsiveness; with all regimens, absolute risk reductions compared with placebo were 20%–30%. The anti-nausea effect was less pronounced. Headache was dose-dependent. Results on propofol were contradictory. The NK(1) antagonist GR205171, isopropyl alcohol vapor, metoclopramide, domperidone, and midazolam were tested in one trial each with a limited number of patients. CONCLUSIONS: Of 100 vomiting surgical patients receiving a 5-HT(3) receptor antagonist, 20 to 30 will stop vomiting who would not have done so had they received a placebo; less will profit from the anti-nausea effect. There is a lack of evidence for a clinically relevant dose-response; minimal effective doses may be used. There is a discrepancy between the plethora of trials on prevention of PONV and the paucity of trials on treatment of established symptoms. Valid data on the therapeutic efficacy of classic antiemetics, which have been used for decades, are needed

Nausea: Current knowledge of mechanisms, measurement and clinical impact

AbstractNausea is a subjective sensation, which often acts as a signal that emesis is imminent. It is a widespread problem that occurs as a clinical sign of disease or as an adverse effect of a drug therapy or surgical procedure. The mechanisms of nausea are complex and the neural pathways are currently poorly understood. This review summarises the current knowledge of nausea mechanisms, the available animal models for nausea research and the anti-nausea properties of commercially available anti-emetic drugs. The review also presents subjective assessment and scoring of nausea. A better understanding of the underlying mechanisms of nausea might reveal potential clinically useful biomarkers for objective measurement of nausea in species of veterinary interest