Fosaprepitant for postoperative nausea and vomiting in patients undergoing laparoscopic gastrointestinal surgery: a randomised trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3 receptor antagonist, the incidence is still high in many at-risk patients. Fosaprepitant, a neurokinin-1 receptor antagonist, is an effective antiemetic, but its efficacy and safety in combination antiemetic therapy for preventing PONV remain unclear. METHODS: In this randomised, controlled, double-blind trial, 1154 participants at high risk of PONV and undergoing laparoscopic gastrointestinal surgery were randomly assigned to either a fosaprepitant group (n=577) receiving fosaprepitant 150 mg i.v. dissolved in 0.9% saline 150 ml, or a placebo group (n=577) receiving 0.9% saline 150 ml before anaesthesia induction. Dexamethasone 5 mg i.v. and palonosetron 0.075 i.v. mg were each administered in both groups. The primary outcome was the incidence of PONV (defined as nausea, retching, or vomiting) during the first 24 postoperative hours. RESULTS: The incidence of PONV during the first 24 postoperative hours was lower in the fosaprepitant group (32.4% vs 48.7%; adjusted risk difference -16.9% [95% confidence interval: -22.4 to -11.4%]; adjusted risk ratio 0.65 [95% CI: 0.57 to 0.76]; P<0.001). There were no differences in severe adverse events between groups, but the incidence of intraoperative hypotension was higher (38.0% vs 31.7%, P=0.026) and intraoperative hypertension (40.6% vs 49.2%, P=0.003) was lower in the fosaprepitant group. CONCLUSIONS: Fosaprepitant added to dexamethasone and palonosetron reduced the incidence of PONV in patients at high risk of PONV undergoing laparoscopic gastrointestinal surgery. Notably, it increased the incidence of intraoperative hypotension. CLINICAL TRIAL REGISTRATION: NCT04853147.

DRP1 knockdown and atorvastatin alleviate ox-LDL-induced vascular endothelial cells injury: DRP1 is a potential target for preventing atherosclerosis.

Vascular endothelial cells (VECs) injury is the first step in the pathogenesis of atherosclerosis (AS). Mitochondrial dysfunction plays a significant role in VECs injury, but the underlying mechanisms are still unclear. Here, the human umbilical vein endothelial cells were exposed to 100 µg/mL oxidized low-density lipoprotein for 24 h to establish AS model in vitro. We reported that mitochondrial dynamics disorder is a prominent feature of VECs in AS models and associated with mitochondrial dysfunction. Moreover, the knockdown of dynamin-related protein 1 (DRP1) in AS model significantly alleviated the mitochondrial dynamics disorder and VECs injury. On the contrary, DRP1 overexpression significantly aggravated this injury. Interestingly, atorvastatin (ATV), a classical anti-atherosclerotic drug, prominently inhibited the expression of DRP1 in AS models and similarly alleviated the mitochondrial dynamics disorder and VECs injury in vitro and in vivo. At the same time, we found that ATV alleviated VECs damage but did not significantly reduce lipid concentration in vivo. Our findings provide a potential therapeutic target of AS and a new mechanism of the anti-atherosclerotic effect of ATV.

[Comparison of safe duration of apnea and intubation time in face mask ventilation with air versus 100% oxygen during induction of general anesthesia].

OBJECTIVE: To compare the safe duration of apnea and intubation time between face mask ventilation with air and 100% oxygen during induction of general anesthesia. METHODS: Eighty adult patients with ASA class I or II without predicted difficult airways were scheduled for elective surgery under general anesthesia. The patients were randomized to receive anesthesia induction with preoxygenation [Group 1, n=40, fraction of inspired oxygen (FiO2)=1] or without preoxygenation (Group2, n=40, FiO2=0.21). Two experienced anesthesiologists performed the mask ventilation and tracheal intubation during induction, and the assistants adjusted the oxygen concentration and recorded the pulse oxygen saturation (SpO2) and other variables. The cases where SpO2 decreased to below 90% before accomplishment of intubation were considered unsuccessful, and mask ventilation with 100% oxygen was given. After tracheal intubation, mechanical ventilation was not initiated until the SpO2 decreased to 90%. The number of unsuccessful cases, the safe duration of apnea and intubation time were recorded in the two groups. RESULTS: There was no unsuccessful case in either groups. The safe duration of apnea was 469.5∓143.0 s in Group 1 and 63.6∓20.0 s in Group 2, and the intubation time was 34.4∓12.6 s and 32.8∓9.6 s, respectively. The safe duration of apnea was significantly longer than the intubation time in both groups (P<0.01). The intubation time and the number of cases with SpO2≥90% before completion of tracheal intubation were similar between the two groups. The safe duration of apnea was significantly shorter in Group 2 than in Group 1 (P<0.01) and was correlated with the body mass index of the patients (P<0.05). CONCLUSION: Anesthesia induction without preoxygenation can provide sufficient time for experienced anesthesiologists to complete tracheal intubation.