Early postoperative pain and 30-day complications following major abdominal surgery: a retrospective cohort study.

BACKGROUND: Increasing evidence supports a positive relationship between the intensity of early postoperative pain, and the risk of 30-day postoperative complications. Higher pain levels may hamper recovery and contribute to immunosuppression after surgery. This leaves patients at risk of postoperative complications. METHODS: One thousand patients who underwent major abdominal surgery (cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, esophageal, liver, or pancreas surgery) at the Radboud university medical center were randomly selected from eligible patients between 2014 and 2020. Pain scores on day 1, the independent variable of interest, were extracted from the electronic patient files. Outcome measures were 30-day postoperative complications (infectious, non-infectious, total complications and classification according to Clavien-Dindo). RESULTS: Seven hundred ninety complications occurred in 572 patients within 30 days after surgery, of which 289 (36.7%) were of infectious origin, and 501 (63.4%) complications were non-infectious. The mean duration from the end of surgery to the occurrence of infectious complications was 6.5 days (SD 5.6) and 4.1 days (SD 4.7) for non-infectious complications (p<0.001). Logistic regression analysis revealed that pain scores on postoperative day 1 (POD1) were significantly positively associated with 30-day total complications after surgery (OR=1.132, 95% CI (1.076 to 1.190)), Clavien-Dindo classification (OR=1.131, 95% CI (1.071 to 1.193)), infectious complications (OR=1.126, 95% CI (1.059 to 1.196)), and non-infectious complications (OR=1.079, 95% CI (1.022 to 1.140)). CONCLUSIONS: After major abdominal surgery, higher postoperative pain scores on day 1 are associated with an increased risk of 30-day postoperative complications. Further studies should pursue whether optimization of perioperative analgesia can improve immune homeostasis, reduce complications after surgery and enhance postoperative recovery.

A Practical Dosing Algorithm for Deep Neuromuscular Blockade During Total Intravenous Anesthesia: ROCURITHM.

BACKGROUND: The number of trials investigating the effects of deep neuromuscular blockade (NMB) on surgical conditions and patient outcomes is steadily increasing. Consensus on which surgical procedures benefit from deep NMB (a post tetanic count of 1-2) and how to implement it has not been reached. The ESAIC does not advise routine application but recommends use of deep NMB to improve surgical conditions on indication. This study investigates the optimal dosing strategy to reach and maintain adequate deep NMB during total intravenous anesthesia. METHODS: Data from three trials investigating deep NMB during laparoscopic surgery with TIVA (n=424) was pooled to analyze the required rocuronium dose, when to start continuous infusion and how to adjust. The resulting algorithm was validated (n=32) and compared to the success rate in ongoing studies where the algorithm was not used (n=180). RESULTS: The mean rocuronium dose based on actual bodyweight for PTC 1-2 was 1.0 ± 0.27 mg.kg -1.h -1 in the trials where mean duration of surgery was ±2 hours (116 minutes). An induction dose of 0.6 mg.kg -1 lead to a PTC of 1-5 in a quarter of patients after a mean of 11 minutes. The remaining patients were equally divided over too shallow (additional bolus and direct start of continuous infusion) or too deep; a ±15-minute wait after PTC 0 for return of PTC to ≥1. Using the proposed algorithm, a mean 76% of all 5-minute measurements throughout surgery were on target PTC 1-2 in the validation cohort. The algorithm performed significantly better than anesthesiology residents without the algorithm, even after a learning curve from 0-20 patients (42% on target, P≤.001, Cohen's d=1.4 [95% CI 0.9, 1.8]) to 81-100 patients (61% on target, P≤.05, Cohen's d=0.7 [95% CI 0.1, 1.2]). CONCLUSIONS: We propose a dosing algorithm for deep NMB with rocuronium in patients receiving TIVA.

Recovery and immune function after low pressure pneumoperitoneum during robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To compare the effectiveness of low intra-abdominal pressure (IAP) facilitated by deep neuromuscular block (NMB) to standard practice in improving the quality of recovery, preserving immune function, and enhancing parietal perfusion during robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: In this blinded, randomised controlled trial, 96 patients were randomised to the experimental group with low IAP (8 mmHg) facilitated by deep NMB (post-tetanic count 1-2) or the control group with standard IAP (14 mmHg) and moderate NMB (train-of-four 1-2). Recovery was measured using the 40-item Quality of Recovery questionnaire and 36-item Short-Form Health survey. Immune function was evaluated by plasma damage-associated molecular patterns, cytokines, and ex vivo lipopolysaccharide-stimulated cytokine production. Parietal peritoneum perfusion was measured by analysing the recordings of indocyanine-green injection. RESULTS: Quality of recovery was not superior in the experimental group (n = 46) compared to the control group (n = 50). All clinical outcomes, including pain scores, postoperative nausea and vomiting, and hospital stay were similar. There were no significant differences in postoperative plasma concentrations of damage-associated molecular patterns, cytokines, and ex vivo cytokine production capacity. The use of low IAP resulted in better parietal peritoneum perfusion. CONCLUSION: Despite better perfusion of the parietal peritoneum, low IAP facilitated by deep NMB did not improve the quality of recovery or preserve immune function compared to standard practice in patients undergoing RARP.

Trends in the use of neuromuscular blocking agents, reversal agents and neuromuscular transmission monitoring: a single-centre retrospective cohort study.

BACKGROUND: Residual neuromuscular blockade (rNMB) remains a persistent and preventable problem, with serious risks. METHODS: Our objective was to describe and assess patterns in the use of neuromuscular blocking agents (NMBAs), neuromuscular transmission (NMT) monitoring, and factors associated with the use of sugammadex. We performed a retrospective, observational cohort study based on electronic medical records in a large teaching hospital in the Netherlands that introduced an integrated NMT monitoring module with automatic recording in 2017. A total of 22,000 cases were randomly selected from all surgeries between January 2015 and December 2019 that required endotracheal intubation with the use of an NMBA. A total of 14,592 cases fulfilled all the inclusion criteria for complete analyses. RESULTS: Relative NMBA usage remained the same over time. For rocuronium, spontaneous reversal decreased from 86 to 81%, sugammadex reversal increased from 12 to 18%. There was a decline in patients extubated in the operating room (OR) with neither documented NMT monitoring nor sugammadex-mediated reversal from 46 to 31%. The percentage of patients extubated in the OR without a documented train-of-four ratio ≥ 0.9, decreased from 77 to 56%. Several factors were independently associated with the use of sugammadex, including BMI > 30 kg/m2 (odds ratio: 1.41; 95% CI: 1.24-1.60), ASA class 3 or 4 (1.20; 1.07-1.34), age > 60 years (1.37; 1.23-1.53), duration of surgery < 120 min (3.01; 2.68-3.38), emergency surgery (1.83; 1.60-2.09), laparoscopic surgery (2.01; 1.71-2.36), open abdominal/thoracic surgery (1.56; 1.38-1.78), NMT monitoring used (5.31; 4.63-6.08), total dose of rocuronium (1.99; 1.76-2.25), and (inversely) use of inhalational anaesthetics (0.88; 0.79-0.99). CONCLUSION: Our data demonstrate that the implementation of NMT monitoring with automatic recording coincides with a gradual increase in the (documented) use of NMT monitoring and an increased use of sugammadex with a more precise dose. Factors associated with sugammadex use include higher age, ASA score, BMI, abdominal and thoracic surgery, higher rocuronium doses, emergency surgery and the use of NMT monitoring. Trial registration N/A. KEY POINTS: • Introduction of NMT monitoring with automatic recording coincides with an increase in (documented) use of NMT monitoring. • Sugammadex is more frequently used in patients with a presumed higher a priori risk of pulmonary complications. • Despite increased NMT monitoring and use of sugammadex a significant percentage of patients remain at potential risk of rNMB.

The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study.

BACKGROUND: Breast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival. METHODS: In this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20). RESULTS: Ex vivo cytokine production capacity of TNF, IL-6 and IL-1ß was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1ß after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1ß and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively). CONCLUSIONS: This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.

Deep neuromuscular blockade in adults undergoing an abdominal laparoscopic procedure.

BACKGROUND: Laparoscopic surgery is the preferred option for many procedures. To properly perform laparoscopic surgery, it is essential that sudden movements and abdominal contractions in patients are prevented, as it limits the surgeon's view. There has been a growing interest in the potential beneficial effect of deep neuromuscular blockade (NMB) in laparoscopic surgery. Deep NMB improves the surgical field by preventing abdominal contractions, and it is thought to decrease postoperative pain. However, it is uncertain if deep NMB improves intraoperative safety and thereby improves clinical outcomes. OBJECTIVES: To evaluate the benefits and harms of deep neuromuscular blockade versus no, shallow, or moderate neuromuscular blockade during laparoscopic intra- or transperitoneal procedures in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 July 2023. SELECTION CRITERIA: We included randomised clinical trials (irrespective of language, blinding, or publication status) in adults undergoing laparoscopic intra- or transperitoneal procedures comparing deep NMB to moderate, shallow, or no NMB. We excluded trials that did not report any of the primary or secondary outcomes of our review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. health-related quality of life, and 3. proportion of participants with serious adverse events. Our secondary outcomes were 4. proportion of participants with non-serious adverse events, 5. readmissions within three months, 6. short-term pain scores, 7. measurements of postoperative recovery, and 8. operating time. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 42 randomised clinical trials with 3898 participants. Most trials included participants undergoing intraperitoneal oncological resection surgery. We present the Peto fixed-effect model for most dichotomous outcomes as only sparse events were reported. Comparison 1: deep versus moderate NMB Thirty-eight trials compared deep versus moderate NMB. Deep NMB may have no effect on mortality, but the evidence is very uncertain (Peto odds ratio (OR) 7.22, 95% confidence interval (CI) 0.45 to 115.43; 12 trials, 1390 participants; very low-certainty evidence). Deep NMB likely results in little to no difference in health-related quality of life up to four days postoperative (mean difference (MD) 4.53 favouring deep NMB on the Quality of Recovery-40 score, 95% CI 0.96 to 8.09; 5 trials, 440 participants; moderate-certainty evidence; mean difference lower than the mean clinically important difference of 10 points). The evidence is very uncertain about the effect of deep NMB on intraoperatively serious adverse events (deep NMB 38/1150 versus moderate NMB 38/1076; Peto OR 0.95, 95% CI 0.59 to 1.52; 21 trials, 2231 participants; very low-certainty evidence), short-term serious adverse events (up to 60 days) (deep NMB 37/912 versus moderate NMB 42/852; Peto OR 0.90, 95% CI 0.56 to 1.42; 16 trials, 1764 participants; very low-certainty evidence), and short-term non-serious adverse events (Peto OR 0.94, 95% CI 0.65 to 1.35; 11 trials, 1232 participants; very low-certainty evidence). Deep NMB likely does not alter the duration of surgery (MD -0.51 minutes, 95% CI -3.35 to 2.32; 34 trials, 3143 participants; moderate-certainty evidence). The evidence is uncertain if deep NMB alters the length of hospital stay (MD -0.22 days, 95% CI -0.49 to 0.06; 19 trials, 2084 participants; low-certainty evidence) or pain scores one hour after surgery (MD -0.31 points on the numeric rating scale, 95% CI -0.59 to -0.03; 22 trials, 1823 participants; very low-certainty evidence; mean clinically important difference 1 point) and 24 hours after surgery (MD -0.60 points on the numeric rating scale, 95% CI -1.05 to -0.15; 16 trials, 1404 participants; very low-certainty evidence; mean clinically important difference 1 point). Comparison 2: deep versus shallow NMB Three trials compared deep versus shallow NMB. The trials did not report on mortality and health-related quality of life. The evidence is very uncertain about the effect of deep NMB compared to shallow NMB on the proportion of serious adverse events (RR 1.66, 95% CI 0.50 to 5.57; 2 trials, 158 participants; very low-certainty evidence). Comparison 3: deep versus no NMB One trial compared deep versus no NMB. There was no mortality in this trial, and health-related quality of life was not reported. The proportion of serious adverse events was 0/25 in the deep NMB group and 1/25 in the no NMB group. AUTHORS' CONCLUSIONS: There was insufficient evidence to draw conclusions about the effects of deep NMB compared to moderate NMB on all-cause mortality and serious adverse events. Deep NMB likely results in little to no difference in health-related quality of life and duration of surgery compared to moderate NMB, and it may have no effect on the length of hospital stay. Due to the very low-certainty evidence, we do not know what the effect is of deep NMB on non-serious adverse events, pain scores, or readmission rates. Randomised clinical trials with adequate reporting of all adverse events would reduce the current uncertainties. Due to the low number of identified trials and the very low certainty of evidence, we do not know what the effect of deep NMB on serious adverse events is compared to shallow NMB and no NMB. We found no trials evaluating mortality and health-related quality of life.

Deep versus moderate neuromuscular blockade during total hip arthroplasty to improve postoperative quality of recovery and immune function: protocol for a randomised controlled study.

INTRODUCTION: There is accumulating evidence that deep neuromuscular blockade (NMB) improves intraoperative surgical conditions during laparoscopic surgery. Studies investigating the effects of deep NMB in open surgery are scarce. In theory, by limiting surgical damage through deeper muscle relaxation, postoperative inflammation and concomitant immune suppression can be reduced. Therefore, this study will investigate the effects of deep NMB during total hip arthroplasty, which demands a relatively large exposure of the hip joint through and in between muscles. METHODS AND ANALYSIS: This study is a monocentre blinded randomised controlled trial in 100 patients undergoing total hip arthroplasty under general anaesthesia. Patients will be randomised in a 1:1 fashion to an intervention group of intraoperative deep NMB (a post-tetanic count of 1-2) or a control group receiving moderate NMB (a train-of-four count of 1-2). NMB will be achieved by continuous or bolus administration of rocuronium, respectively. The primary endpoint is the quality of recovery at postoperative day 1 measured by the Quality of Recovery-40 Questionnaire, analysed by Analysis of Variance. The secondary endpoint is postoperative innate immune function, measured by ex vivo production capacity of tumour necrosis factor and interleukin-1ß on endotoxin stimulation of whole blood. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Ethics Committee 'METC Oost-Nederland' (reference number 2022-15754). Informed consent will be obtained prior to study participation. Study results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov Registry (NCT05562999) and EudraCT Registry (2022-002451-19).

MRI measurement of the effects of moderate and deep neuromuscular blockade on the abdominal working space during laparoscopic surgery, a clinical study.

BACKGROUND: Conflicting data exist regarding the effects of deep neuromuscular blockade (NMB) on abdominal dimensions during laparoscopic procedures. We performed a clinical study to establish the influence of moderate and deep neuromuscular blockade (NMB) on the abdominal working space, measured by Magnetic Resonance Imaging (MRI), during laparoscopic donor nephrectomy with standard pressure (12 mmHg) pneumoperitoneum under sevoflurane anaesthesia. METHODS: Ten patients were intraoperatively scanned three times in the lateral decubitus position, with pneumoperitoneum maintained by a mobile insufflator. The first scan without NMB (T1) was followed by scans with moderate (T2) and deep NMB (T3). The skin-sacral promontory (S-SP) distance was measured, and 3D pneumoperitoneum volumes were reconstructed. RESULTS: The mean difference in the S-SP distance was -0.32 cm between T2 and T3 (95% CI -1.06 - 0.42 cm; p = 0.344) and + 2.1 cm between T1 and T2 (95% CI 0.81 - 3.39 cm; p = 0.006). The mean differences in pneumoperitoneum volume were 166 mL between T2 and T3 (95% CI, 5 - 327 mL; p = 0.044) and 108 mL between T1 and T2 (95% CI, -273 - 488 mL; p = 0.525). The pneumoperitoneum volume showed high inter-individual variability and no increase in three patients with a high volume at T1. CONCLUSIONS: During laparoscopic surgery in the lateral decubitus position with standard pressure under sevoflurane anaesthesia, deep NMB did not increase the S-SP distance compared to moderate NMB. Moderate NMB increased the S-SP distance by a mean of 2.1 cm (15.2%) compared with no NMB. The mean pneumoperitoneum volume increased slightly from moderate to deep NMB, with high inter-individual variability. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03287388.

Low intra-abdominal pressure in laparoscopic surgery: a systematic review and meta-analysis.

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.

[The impact of shift work: did hard work ever kill anyone?] / De impact van werken in diensten.

An increasing body of evidence suggests that complaints of fatigue among healthcare staff is widespread and rising, owing to a combination of high work intensity, understaffed workplace and nightshift working. This has been linked to poorer outcomes for patients and to increased risks of injuries for practitioners. Fatiguedecreases performance andphysicalandmentalwellbeing. Moreover, it can lead to sickness absence. What lies behind this culture, behaviour and what are possible solutions to this? A committee called I'm Safe, assigned by the Dutch Association of Anaesthesiology, will address these issues, raise awareness and inform physicians about the impact of shift working. Its aim is to provide tools on where changes can be made in order to create a healthier work environment.

Quality of Recovery and Innate Immune Homeostasis in Patients Undergoing Low-pressure Versus Standard-pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery (RECOVER): A Randomized Controlled Trial.

OBJECTIVE: To study the effects of intra-abdominal pressure on the quality of recovery and innate cytokine production capacity after laparoscopic colorectal surgery within the enhanced recovery after surgery program. BACKGROUND: There is increasing evidence for the safety and advantages of low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade (NMB). Nonetheless, there is a weak understanding of the relationship between clinical outcomes, surgical injury, postoperative immune dysfunction, and infectious complications. METHODS: Randomized controlled trial of 178 patients treated at standard-pressure pneumoperitoneum (12 mm Hg) with moderate NMB (train-of-four 1-2) or low pressure (8 mm Hg) facilitated by deep NMB (posttetanic count 1-2). The primary outcome was the quality of recovery (Quality of Recovery 40 questionnaire) on a postoperative day 1 (POD1). The primary outcome of the immune substudy (n=100) was ex vivo tumor necrosis factor α production capacity upon endotoxin stimulation on POD1. RESULTS: Quality of Recovery 40 score on POD1 was significantly higher at 167 versus 159 [mean difference (MD): 8.3 points; 95% confidence interval (CI): 2.5, 14.1; P =0.005] and the decline in cytokine production capacity was significantly less for tumor necrosis factor α and interleukin-6 (MD: -172 pg/mL; 95% CI: -316, -27; P =0.021 and MD: -1282 pg/mL; 95% CI: -2505, -59; P =0.040, respectively) for patients operated at low pressure. Low pressure was associated with reduced surgical site hypoxia and inflammation markers and circulating damage-associated molecular patterns, with a less impaired early postoperative ex vivo cytokine production capacity. At low pressure, patients reported lower acute pain scores and developed significantly less 30-day infectious complications. CONCLUSIONS: Low intra-abdominal pressure during laparoscopic colorectal surgery is safe, improves the postoperative quality of recovery and preserves innate immune homeostasis, and forms a valuable addition to future enhanced recovery after surgery programs.

Chronic postsurgical pain after minimally invasive adrenalectomy: prevalence and impact on quality of life.

BACKGROUND: Minimally invasive adrenalectomy is the standard of care for small adrenal tumours. Both the transperitoneal lateral approach and posterior retroperitoneal approach are widely used and have been proven to be safe and effective. However, the prevalence of chronic postsurgical pain has not been specifically investigated in previous studies. The primary goal of this study was to identify the prevalence of chronic postsurgical pain after minimally invasive adrenalectomy. METHODS: A cross-sectional study was performed among all consecutive patients who had undergone minimally invasive adrenalectomy in a single university medical centre. The primary outcome was the prevalence of chronic postsurgical pain. Secondary outcomes were the prevalence of localized hypoesthesia, risk factors for the development of chronic postsurgical pain, and the Health-Related Quality of Life. Three questionnaires were used to measure the prevalence and severity of chronic postsurgical pain, hypoesthesia, and Health-Related Quality of Life. Logistic regression analysis was performed to determine risk factors for development of chronic postsurgical pain. RESULTS: Six hundred two patients underwent minimally invasive adrenalectomy between January 2007 and September 2019, of whom 328 signed informed consent. The prevalence of chronic postsurgical pain was 14.9%. In the group of patients with chronic postsurgical pain, 33% reported hypoesthesia as well. Young age was a significant predictor for developing chronic postsurgical pain. The prevalence of localized hypoesthesia was 15.2%. In patients with chronic postsurgical pain, Health-Related Quality of Life was significantly lower, compared to patients without pain. CONCLUSIONS: The prevalence of chronic postsurgical pain following minimally invasive adrenalectomy is considerable. Furthermore, the presence of chronic postsurgical pain was correlated with a significant and clinically relevant lower Health-Related Quality of Life. These findings should be included in the preoperative counselling of the patient. In the absence of evidence for effective treatment in established chronic pain, prevention should be the key strategy and topic of future research.

Deep neuromuscular block reduces the incidence of intra-operative complications during laparoscopic donor nephrectomy: a pooled analysis of randomized controlled trials.

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 (<10 mmHg) intra-abdominal pressure. MEASUREMENTS: The primary endpoint is the number of intra-operative surgical complications defined as any deviation from the ideal intra-operative course occurring between skin incision and closure with five severity grades, according to ClassIntra. Multiple logistic regression analyses were used to identify predictors of intra- and postoperative complications. MAIN RESULTS: In 53/556 (9.5%) patients, an intra-operative complication with ClassIntra grade ≥ 2 occurred. Multiple logistic regression analyses showed standard intra-abdominal pressure (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 ).

Positive end-expiratory pressure affects geometry and function of the human diaphragm.

Positive end-expiratory pressure (PEEP) is routinely applied in mechanically ventilated patients to improve gas exchange and respiratory mechanics by increasing end-expiratory lung volume (EELV). In a recent experimental study in rats, we demonstrated that prolonged application of PEEP causes diaphragm remodeling, especially longitudinal muscle fiber atrophy. This is of potential clinical importance, as the acute withdrawal of PEEP during ventilator weaning decreases EELV and thereby stretches the adapted, longitudinally atrophied diaphragm fibers to excessive sarcomere lengths, having a detrimental effect on force generation. Whether this series of events occurs in the human diaphragm is unknown. In the current study, we investigated if short-term application of PEEP affects diaphragm geometry and function, which are prerequisites for the development of longitudinal atrophy with prolonged PEEP application. Nineteen healthy volunteers were noninvasively ventilated with PEEP levels of 2, 5, 10, and 15 cmH2O. Magnetic resonance imaging was performed to investigate PEEP-induced changes in diaphragm geometry. Subjects were instrumented with nasogastric catheters to measure diaphragm neuromechanical efficiency (i.e., diaphragm pressure normalized to its electrical activity) during tidal breathing with different PEEP levels. We found that increasing PEEP from 2 to 15 cmH2O resulted in a caudal diaphragm displacement (19 [14-26] mm, P < 0.001), muscle shortening in the zones of apposition (20.6% anterior and 32.7% posterior, P < 0.001), increase in diaphragm thickness (36.4% [0.9%-44.1%], P < 0.001) and reduction in neuromechanical efficiency (48% [37.6%-56.6%], P < 0.001). These findings demonstrate that conditions required to develop longitudinal atrophy in the human diaphragm are present with the application of PEEP.NEW & NOTEWORTHY We demonstrate that PEEP causes changes in diaphragm geometry, especially muscle shortening, and decreases in vivo diaphragm contractile function. Thus, prerequisites for the development of diaphragm longitudinal muscle atrophy are present with the acute application of PEEP. Once confirmed in ventilated critically ill patients, this could provide a new mechanism for ventilator-induced diaphragm dysfunction and ventilator weaning failure in the intensive care unit (ICU).

Ultrasound assessment of gastric volumes of thick fluids: Validating a prediction model.

BACKGROUND: Enteral nutrition is essential in the treatment of critically ill patients. Current methods to monitor enteral nutrition such as aspiration of residual volume may be inaccurate. Gastric ultrasonography estimates total gastric fluid volume using the Perlas model, but this model is validated for clear fluids only, and its accuracy for measuring thick fluids is unknown. OBJECTIVES: The primary aim of this study was to evaluate the Perlas model for gastric volume estimation of enteral nutrition, a thick fluid product. DESIGN: A single-centre, single blinded, randomised controlled study. SETTING: Single university hospital, from May to July 2019. PARTICIPANTS: Seventy-two healthy fasted volunteers were randomly allocated to different fluid volume groups. INTERVENTION: Participants randomly ingested predetermined volumes between 50 and 400 ml of a feeding-drink (Nutricia Nutridrink). Following a standardised gastric ultrasound scanning protocol, a blinded sonographer measured the antral cross-sectional area in the supine and right-lateral decubitus positions. MAIN OUTCOME MEASURES: Measurements were performed at baseline, 5 min postingestion and 20 min postingestion. Gastric volumes were predicted using the previously established Perlas model and compared with total gastric fluid volumes after ingestion of the study drink. RESULTS: The Perlas model underestimated the volume of thick gastric fluid and yielded a suboptimal fit for our data. However, antral cross-sectional area and total gastric thick fluid volumes were significantly correlated (Pearson's correlation coefficient 0.73, P < 0.01). A new model was fitted to predict gastric volumes of thick fluids, using the antral cross-sectional area (cm2) in the right-lateral decubitus position: Volume (ml) = 79.38 + 13.32 x right-lateral cross-sectional area. CONCLUSION: The Perlas model for clear gastric fluid volume estimation is suboptimal for thick fluid volume assessment and an alternative model is presented. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register Trial NL7677, Registration date: 16 April 2019; https://www.trialregister.nl/trial/7677.

Early postoperative pain after laparoscopic donor nephrectomy predicts 30-day postoperative infectious complications: a pooled analysis of randomized controlled trials.

Our research group recently published a positive association between early postoperative pain and 30-day postoperative complications in a broad surgical population. To investigate whether heterogeneity of the population and surgical procedures influenced these results, we explored this association in a homogenous surgical population. A secondary analysis of the LEOPARD-2 (clinicaltrials.gov NCT02146417) and RELAX-1 study (NCT02838134) in laparoscopic donor nephrectomy patients (n = 160) was performed. Pain scores on the postanesthesia care unit and postoperative day (POD) 1 and 2 were compared between patients with infectious, noninfectious, and no complications 30 days after surgery. Patients who developed infectious complications had significantly higher pain scores on POD1 and 2 (6.7 ± 2.1 and 6.4 ± 2.8) than patients without complications (4.9 ± 2.2 and 4.1 ± 1.9), respectively (P = 0.006 and P = 0.000). Unacceptable pain (numeric rating scale [NRS] ≥ 6) on POD1 was reported by 72% of patients who developed infectious complications, compared to 38% with noninfectious complications and 30% without complications (P = 0.018). This difference was still present on POD2 at 67% with infectious complications, 21% with noninfectious, and 40% without complications (P = 0.000). Multiple regression analysis identified unacceptable pain (numeric rating scale ≥6) on POD2 as a significant predictor for 30-day infectious complications (odds ratio 6.09, P = 0.001). Results confirm the association between early postoperative pain and 30-day infectious complications in a separate, homogenous surgical population. Further clinical trials should focus on finetuning of postoperative analgesia to elucidate the effects on the endocrine and immune response, preserve immune homeostasis, and prevent postoperative infectious complications.

Monitoring patient-ventilator breath contribution in the critically ill during neurally adjusted ventilatory assist: reliability and improved algorithms for bedside use.

The patient-ventilator breath contribution (PVBC) index estimates the relative contribution of the patient to total tidal volume (Vtinsp) during mechanical ventilation in neurally adjusted ventilator assist mode and has been used to titrate ventilator support. The reliability of this index in ventilated patients is unknown and was investigated in this study. PVBC was calculated by comparing tidal volume (Vtinsp) and diaphragm electrical activity (EAdi) during assisted breaths (Vtinsp/EAdi)assist and during unassisted breaths (Vtinsp/EAdi)no-assist. Vtinsp was normalized to peak EAdi (EAdipeak) using 1) one assisted breath, 2) five consecutive assisted breaths, or 3) five assisted breaths with matching EAdi preceding the unassisted breath (N1PVBC2, X5PVBC2, and PX5VBCEAdi-matching2 , respectively). In addition, PVBC was calculated by comparing only Vtinsp for breaths with matching EAdi (PVBCß2). Test-retest reliability of the different PVBC calculation methods was evaluated with the intraclass correlation coefficient (ICC) using five repeated PVBC maneuvers performed with a 1-min interval. In total, 125 PVBC maneuvers were analyzed in 25 patients. ICC [95% confidence interval] values were 0.46 [0.23-0.66], 0.51 [0.33-0.70], and 0.42 [0.14-0.69] for N1PVBC2, X5PVBC2, PX5VBCEAdi-matching2 , respectively. Complex waveform analyses showed that insufficient EAdi filtering by the ventilator software affects reliability of PVBC calculation. With our new EAdi-matching techniques reliability improved (PVBCß2 ICC: 0.78 [0.60-0.90]). We conclude that current techniques to calculate PVBC exhibit low reliability and that our newly developed criteria and estimation of PVBC-using Vtinsp of assisted breaths and unassisted breaths with matching EAdi-improves reliability. This may help implementation of PVBC in clinical practice. NEW & NOTEWORTHY The patient-ventilator breath contribution (PVBC) index estimates the relative contribution of the patient to tidal volume generated by the patient and the mechanical ventilator during mechanical ventilation in neurally adjusted ventilator assist mode. It could be used to titrate ventilator support and thus to limit development of diaphragm dysfunction in intensive care unit patients. Currently available methods for bedside assessment of PVBC are unreliable. Our newly developed criteria and estimation of PVBC largely improve reliability and help to quantify patient contribution to total inspiratory effort.

The teacher, the physician and the person: how faculty's teaching performance influences their role modelling.

OBJECTIVE: Previous studies identified different typologies of role models (as teacher/supervisor, physician and person) and explored which of faculty's characteristics could distinguish good role models. The aim of this study was to explore how and to which extent clinical faculty's teaching performance influences residents' evaluations of faculty's different role modelling statuses, especially across different specialties. METHODS: In a prospective multicenter multispecialty study of faculty's teaching performance, we used web-based questionnaires to gather empirical data from residents. The main outcome measures were the different typologies of role modelling. The predictors were faculty's overall teaching performance and faculty's teaching performance on specific domains of teaching. The data were analyzed using multilevel regression equations. RESULTS: In total 219 (69% response rate) residents filled out 2111 questionnaires about 423 (96% response rate) faculty. Faculty's overall teaching performance influenced all role model typologies (OR: from 8.0 to 166.2). For the specific domains of teaching, overall, all three role model typologies were strongly associated with "professional attitude towards residents" (OR: 3.28 for teacher/supervisor, 2.72 for physician and 7.20 for the person role). Further, the teacher/supervisor role was strongly associated with "feedback" and "learning climate" (OR: 3.23 and 2.70). However, the associations of the specific domains of teaching with faculty's role modelling varied widely across specialties. CONCLUSION: This study suggests that faculty can substantially enhance their role modelling by improving their teaching performance. The amount of influence that the specific domains of teaching have on role modelling differs across specialties.