Montelukast jest skutecznym lekiem w zapobieganiu zespołowi hiperstymulacji jajników: badania eksperymentalne

Objectives: To determine the efficacy of montelukast in comparison with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in rats. Material and methods: An experimental OHSS model was formed in 35 female Wistar rats. Rats (22 days old) were randomized into 5 groups, each containing 7 animals. The control group received no therapy; the mild OHSS group was administered pregnant mare serum gonadotropin (PMSG) 10 IU for 4 days, hCG 10 IU on the 5th day; the severe OHSS group received PMSG 10 IU for 4 days, hCG 30 IU on the 5th day. The montelukast group: received montelukast 10 mg/kg/day and the cabergoline group was administered cabergoline 100μg/kg/day via oral gavage for 6 days (days 22–27), in addition to those of severe OHSS. All groups were sacrificed on 28th day. Body weight, ovarian diameter and weight, vascular permeability, vascular endothelial growth factor (VEGF), semiquantitative VEGF receptor-1, and VEGF receptor-2 (VEGFR-2) immunohistochemistry were evaluated. Results: Ovarian diameter and VEGF expression were significantly lower in the montelukast and cabergoline groups than in the severe OHSS group. While montelukast was more effective in limiting vascular permeability in the severe OHSS, cabergoline was superior to montelukast with respect to the limiting effect on increased body weight and VEGFR-2 expression. Conclusions: The VEGF/VEGFR-2 interaction plays an important role in OHSS pathogenesis. Montelukast limits VEGF expression, and cabergoline reduces both VEGF and VEGFR-2 expressions; they are both effective therapies for the prevention of severe OHSS.Cel: Ocena skuteczności montelukastu w porównaniu z kabergoliną w zapobieganiu zespołowi hiperstymulacji jajników (OHSS) u szczurów. Materiał i metoda: Model doświadczalny OHSS stanowiło 35szczurów rasy Wistar, płci żeńskiej. Szczury (22 dniowe) podzielono na 5 grup, każda zawierająca 7 zwierząt. Grupa kontrolna nie otrzymała żadnej terapii. Grupa z łagodnym OHSS otrzymała gonadotropinę z surowicy ciężarnych klaczy (PMSG) w ilości 10IU przez 4 dni, hCG 10IU w 5 dniu, grupa z ciężkim OHSS otrzymała PMSG 10IU przez 4 dni, hCG 30IU w 5 dniu. Grupa z montelukastem otrzymała montelukast w dawce 10mg/kg/dzień a grupa z kabergoliną otrzymała kabergolinę 100μg/kg/dzień przez doustny zgłębnik przez 6 dni (dni 22-27). Wszystkie zwierzęta zabito w 28 dniu. Oceniono masę ciała, wymiar i wagę jajników, przepuszczalność naczyń, czynnik wzrostu śródbłonka naczyń (VEGF) oraz w immunohistochemii półilościowo receptor – 1 VEGF i receptor-2 VEGF. Wyniki: Wymiar jajnika oraz ekspresja VEGF były istotnie niższe w grupach z monelukastem i kabergoliną niż w grupie z ciężkim OHSS. Podczas gdy montelukast był bardziej skuteczny w ograniczaniu przepuszczalności śródbłonków w ciężkim OHSS, to kabergolina okazała się lepsza od montelukastu po uwzględnieniu ograniczającego efektu zwiększonej masy ciała i ekspresji VEGFR-2. Wnioski: Wzajemne oddziaływanie VEGF/VEGFR-2 odgrywa istotną role w patogenezie OHSS. Montelukast ogranicza ekspresję VEGF, a kabergolina zmniejsza zarówno ekspresję VEGF jak i VEGFR-2; obie terapie są skuteczne w zapobieganiu ciężkiemu OHSS

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - An observational study in 29 countries

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (V T) size was 500 ml, or 7 to 9 ml kg−1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P ˂ 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P ˂ 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high V T and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome.</p

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P &lt; 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P &lt; 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. Methods/design The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. Discussion To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. Trial registration ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1929-0) contains supplementary material, which is available to authorized users