Gert Jan Scheffer

Early warning system (EWS) scores are implemented on surgical wards to identify patients at high risk of postoperative clinical deterioration, but its predictive value in older patients is unclear. This study assessed the prognostic value of EWS scores to predict severe postoperative complications in older patients compared to younger patients. This study utilized data from the TRACE study. EWS scores were routinely measured on postoperative days one (POD1) and three (POD3). The cohort was divided by age: < 70 years and ≥ 70 years. Performance measures of EWS scores on POD1 and POD3 were assessed to predict severe postoperative complications. Missed event rates (proportion of events not detected by the EWS threshold) and nonevent rates (proportion of EWS values above the threshold without an adverse event) were calculated. Among 4866 patients, 39.3% were ≥ 70 years old. Severe complications occurred in 6.1% of older compared to 5.8% of younger patients (P = 0.658). EWS scores on POD1 and POD3 did not differ between age groups. For severe complications, EWS showed moderate discrimination in both older (POD1: C-statistic 0.65 (95%CI 0.59–0.70); POD3: 0.63 (95%CI 0.57–0.69)) and younger patients (POD1: 0.68 (95%CI 0.65–0.72); POD3: 0.65 (95%CI 0.61–0.70)). Overall, calibration was good. For EWS score ≥ 3, the missed event rate was at least 69% and nonevent rate 75%. Predicted performance of the EWS score was moderate among older and younger patients. A limitation of the EWS score is the high rate of missed events and nonevents.

Background: Guidelines do not provide clear recommendations with regard to the use of low intra-abdominal pressure (IAP) during laparoscopic surgery. The aim of this meta-analysis is to assess the influence of low versus standard IAP during laparoscopic surgery on the key-outcomes in perioperative medicine as defined by the StEP-COMPAC consensus group. Materials and methods: We searched the Cochrane Library, PubMed, and EMBASE for randomized controlled trials comparing low IAP (<10 mmHg) with standard IAP (10 mmHg or higher) during laparoscopic surgery without time, language, or blinding restrictions. According to the PRISMA guidelines, two review authors independently identified trials and extracted data. Risk ratio (RR), and mean difference (MD), with 95% CIs were calculated using random-effects models with RevMan5. Main outcomes were based on StEP-COMPAC recommendations, and included postoperative complications, postoperative pain, postoperative nausea and vomiting (PONV) scores, and length of hospital stay. Results: Eighty-five studies in a wide range of laparoscopic procedures (7349 patients) were included in this meta-analysis. The available evidence indicates that the use of low IAP (<10 mmHg) leads to a lower incidence of mild (Clavien–Dindo grade 1–2) postoperative complications (RR=0.68, 95% CI: 0.53–0.86), lower pain scores (MD=−0.68, 95% CI: −0.82 to 0.54) and PONV incidence (RR=0.67, 95% CI: 0.51–0.88), and a reduced length of hospital stay (MD=−0.29, 95% CI: −0.46 to 0.11). Low IAP did not increase the risk of intraoperative complications (RR=1.15, 95% CI: 0.77–1.73). Conclusions: Given the established safety and the reduced incidence of mild postoperative complications, lower pain scores, reduced incidence of PONV, and shorter length of stay, the available evidence supports a moderate to strong recommendation (1a level of evidence) in favor of low IAP during laparoscopic surgery.

Background: Standardized risk assessment tools can be used to identify patients at higher risk for postoperative complications and death. In this study, we validate the PreOperative Score to predict Post-Operative Mortality (POSPOM) for in-hospital mortality in a large cohort of non-cardiac surgery patients. In addition, the performance of POSPOM to predict postoperative complications was studied. Methods: Data from the control cohort of the TRACE (routine posTsuRgical Anesthesia visit to improve patient outComE) study was analysed. POSPOM scores for each patient were calculated post-hoc. Observed in-hospital mortality was compared with predicted mortality according to POSPOM. Discrimination was assessed by receiver operating characteristic curves with C-statistics for in-hospital mortality and postoperative complications. To describe the performance of POSPOM sensitivity, specificity, negative predictive values, and positive predictive values were calculated. For in-hospital mortality, calibration was assessed by a calibration plot. Results: In 2490 patients, the observed in-hospital mortality was 0.5%, compared to 1.3% as predicted by POSPOM. 27.1% of patients had at least one postoperative complication of which 22.4% had a major complication. For in-hospital mortality, POSPOM showed strong discrimination with a C-statistic of 0.86 (95% CI, 0.78–0.93). For the prediction of complications, the discrimination was poor to fair depending on the severity of the complication. The calibration plot showed poor calibration of POSPOM with an overestimation of in-hospital mortality. Conclusion: Despite the strong discriminatory performance, POSPOM showed poor calibration with an overestimation of in-hospital mortality. Performance of POSPOM for the prediction of any postoperative complication was poor but improved according to severity.

Study objective: To assess whether different intensities of intra-abdominal pressure and deep neuromuscular blockade influence the risk of intra-operative surgical complications during laparoscopic donor nephrectomy. Design: A pooled analysis of ten previously performed prospective randomized controlled trials. Setting: Laparoscopic donor nephrectomy performed in four academic hospitals in the Netherlands: Radboudumc, Leiden UMC, Erasmus MC Rotterdam, and Amsterdam UMC. Patients: Five hundred fifty-six patients undergoing a transperitoneal, fully laparoscopic donor nephrectomy enrolled in ten prospective, randomized controlled trials conducted in the Netherlands from 2001 to 2017. Interventions: Moderate (tetanic count of four > 1) versus deep (post-tetanic count 1–5) neuromuscular blockade and standard (≥10 mmHg) versus low (OR 0.318, 95% CI 0.118–0.862; p = 0.024) as a predictor of less intra-operative complications and moderate neuromuscular blockade (OR 3.518, 95% CI 1.244–9.948; p = 0.018) as a predictor of more intra-operative complications. Postoperative complications occurred in 31/556 (6.8%), without significant predictors in multiple logistic regression analyses. Conclusions: Our data indicate that the use of deep neuromuscular blockade could increase safety during laparoscopic donor nephrectomy. Future randomized clinical trials should be performed to confirm this and to pursue whether it also applies to other types of laparoscopic surgery. Trial registration: Clinicaltrials.gov LEOPARD-2 (NCT02146417), LEOPARD-3 trial (NCT02602964), and RELAX-1 study (NCT02838134), Klop et al. (NTR 3096), Dols et al. 2014 (NTR1433).

Diaphragm dysfunction develops frequently in ventilated intensive care unit (ICU) patients. Both disuse atrophy (ventilator over-assist) and high respiratory muscle effort (ventilator under-assist) seem to be involved. A strong rationale exists to monitor diaphragm effort and titrate support to maintain respiratory muscle activity within physiological limits. Diaphragm electromyography is used to quantify breathing effort and has been correlated with transdiaphragmatic pressure and esophageal pressure. The neuromuscular efficiency index (NME) can be used to estimate inspiratory effort, however its repeatability has not been investigated yet. Our goal is to evaluate NME repeatability during an end-expiratory occlusion (NMEoccl) and its use to estimate the pressure generated by the inspiratory muscles (Pmus). This is a prospective cohort study, performed in a medical-surgical ICU. A total of 31 adult patients were included, all ventilated in neurally adjusted ventilator assist (NAVA) mode with an electrical activity of the diaphragm (EAdi) catheter in situ. At four time points within 72 h five repeated end-expiratory occlusion maneuvers were performed. NMEoccl was calculated by delta airway pressure (ΔPaw)/ΔEAdi and was used to estimate Pmus. The repeatability coefficient (RC) was calculated to investigate the NMEoccl variability. A total number of 459 maneuvers were obtained. At time T = 0 mean NMEoccl was 1.22 ± 0.86 cmH2O/μV with a RC of 82.6%. This implies that when NMEoccl is 1.22 cmH2O/μV, it is expected with a probability of 95% that the subsequent measured NMEoccl will be between 2.22 and 0.22 cmH2O/μV. Additional EAdi waveform analysis to correct for non-physiological appearing waveforms, did not improve NMEoccl variability. Selecting three out of five occlusions with the lowest variability reduced the RC to 29.8%. Repeated measurements of NMEoccl exhibit high variability, limiting the ability of a single NMEoccl maneuver to estimate neuromuscular efficiency and therefore the pressure generated by the inspiratory muscles based on EAdi.

Prehospital point-of-care ultrasound used by nonradiologists in emergency medicine is gaining ground. It is feasible on-scene and during aeromedical transport and allows health-care professionals to detect or rule out potential harmful conditions. Consequently, it impacts decision-making in prioritizing care, selecting the best treatment, and the most suitable transport mode and destination. This increasing relevance of prehospital ultrasonography is due to advancements in ultrasound devices and related technology, and to a growing number of applications. This narrative review aims to present an overview of prehospital ultrasonography literature. The focus is on civilian emergency (trauma and non-trauma) setting. Current and potential future applications are discussed, structured according to the airway, breathing, circulation, disability, and environment/exposure (ABCDE) approach. Aside from diagnostic implementation and specific protocols, procedural guidance, therapeutic ultrasound, and challenges are reviewed.

Postoperative recovery after live donor nephrectomy is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade has been shown to reduce postoperative pain scores after laparoscopic surgery. In this study, we will investigate whether deep neuromuscular blockade also improves the early quality of recovery after live donor nephrectomy. The RELAX-study is a phase IV, multicenter, double-blinded, randomized controlled trial, in which 96 patients, scheduled for living donor nephrectomy, will be randomized into two groups: one with deep and one with moderate neuromuscular blockade. Deep neuromuscular blockade is defined as a post-tetanic count of 1–2. Our primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 24 h after extubation. This study is, to our knowledge, the first randomized study to assess the effectiveness of deep neuromuscular blockade during laparoscopic donor nephrectomy in enhancing postoperative recovery. The study findings may also be applicable for other laparoscopic procedures. clinicaltrials.gov, NCT02838134 . Registered on 29 June 2016.

Introduction: Controlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to possess anti-oxidative and anti-inflammatory properties. The aim of the present study was to investigate the effects of levosimendan on markers for diaphragm nitrosative and oxidative stress, inflammation and proteolysis in a mouse model of endotoxemia and mechanical ventilation. Methods: Three groups were studied: (1) unventilated mice (CON, n =8), (2) mechanically ventilated endotoxemic mice (MV LPS, n =17) and (3) mechanically ventilated endotoxemic mice treated with levosimendan (MV LPS + L, n =17). Immediately after anesthesia (CON) or after 8 hours of mechanical ventilation, blood and diaphragm muscle were harvested for biochemical analysis. Results: Mechanical ventilation and endotoxemia increased expression of inducible nitric oxide synthase (iNOS) mRNA and cytokine levels of interleukin (IL)-1β, IL-6 and keratinocyte-derived chemokine, and decreased IL-10, in the diaphragm; however, they had no effect on protein nitrosylation and 4-hydroxy-2-nonenal protein concentrations. Levosimendan decreased nitrosylated proteins by 10% (P P P <0.05). Levosimendan did not affect the inflammatory response in the diaphragm induced by mechanical ventilation and endotoxemia. Conclusions: Mechanical ventilation in combination with endotoxemia results in systemic and diaphragmatic inflammation. Levosimendan partly decreased markers of nitrosative and oxidative stress, but did not affect the inflammatory response.

Since technique modifications of laparoscopic donor nephrectomy, e.g. retroperitoneoscopic donor nephrectomy or hand-assistance, have not shown significant benefit regarding safety or improvement of recovery, further research should focus on improving postoperative recovery. The use of low pressure pneumoperitoneum has shown to significantly reduce postoperative pain after laparoscopy. To facilitate the use of low pressure pneumoperitoneum, deep neuromuscular block will be used. This trial is a phase IV, single center, double-blind, randomized controlled clinical trial in which 64 patients will be randomized to: low pressure pneumoperitoneum (6 mmHg) and deep neuromuscular block or normal pressure pneumoperitoneum (12 mmHg) and deep neuromuscular block. Deep neuromuscular block is defined as post tetanic count < 5. Primary outcome measurement will be Quality of Recovery-40 questionnaire (overall score) on day 1. This study is the first randomized study to assess the combination of low pressure pneumoperitoneum in combination with deep neuromuscular block from a patients’ perspective. The study findings may also be applicable for other laparoscopic procedures. The trial was registered at trials.gov ( NCT02146417 ) in July 2014.