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.

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 posttetanic count [PTC] of 1 to 2) and how to implement it has not been reached. The European Society of Anaesthesiology and Intensive Care 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 total intravenous anesthesia (n = 424) were 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 in which the algorithm was not used (n = 180). RESULTS: The mean rocuronium dose based on actual bodyweight for PTC 1 to 2 was (mean ± SD) 1.0 ± 0.27 mg · kg-1 ·h-1 in the trials, in which mean duration of surgery was 116 min. An induction dose of 0.6 mg ·kg-1 led to a PTC of 1 to 5 in a quarter of patients after a mean of 11 min. The remaining patients were equally divided over too shallow (additional bolus and direct start of continuous infusion) or too deep; a 15-min wait after PTC of 0 for return of PTC to 1 or higher. Using the proposed algorithm, a mean 76% of all 5-min measurements throughout surgery were on target PTC 1 to 2 in the validation cohort. The algorithm performed significantly better than anesthesiology residents without the algorithm, even after a learning curve from 0 to 20 patients (42% on target, P ≤ 0.001, Cohen's d = 1.4 [95% CI, 0.9 to 1.8]) to 81 to 100 patients (61% on target, P ≤ 0.05, Cohen's d = 0.7 [95% CI, 0.1 to 1.2]). CONCLUSIONS: This study proposes a dosing algorithm for deep NMB with rocuronium in patients receiving total intravenous anesthesia.

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.

Residual neuromuscular block in the postanaesthesia care unit: a single-centre prospective observational study and systematic review.

BACKGROUND: Concerns regarding residual neuromuscular block (RNMB) have persisted since the introduction of neuromuscular blocking agents, with reported incidences in the 21st century up to 50%. Advances in neuromuscular transmission (NMT) monitoring and the introduction of sugammadex have addressed this issue, but the impact of these developments remains unclear. METHODS: This prospective observational study evaluated RNMB in 500 surgical patients in a large Dutch teaching hospital with readily available quantitative NMT monitoring and reversal agents. The anaesthetic technique and intraoperative NMT monitoring were independently chosen by the attending anaesthesiologist. Acceleromyography was performed upon arrival in the PACU for patients who received nondepolarising neuromuscular blocking agents. RNMB was defined as a train-of-four ratio (TOFR) <0.9. A systematic review was conducted to analyse trends in RNMB in contemporary practice. RESULTS: Out of 500 patients, 11 (2.2%) had a TOFR <0.9. Intraoperative NMT monitoring was performed in 77.6% of patients, and sugammadex was administered to 38% of patients. No patient received neostigmine. The only difference was an automatically recorded TOFR ≥0.9 at the end of surgery in 61.1% in the non-RNMB group compared with 18.2% in the RNMB group (P=0.009). Our systematic review identified incidences ranging from 3.5% to 53.3% since 2000, with a decreasing trend in Europe and North America. CONCLUSIONS: The incidence of residual neuromuscular block in the PACU was 2.2%. This suggests significant improvement in the prevention of residual neuromuscular block and stresses the importance of rigorous neuromuscular transmission monitoring and adequate use of reversal agents.

Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial.

BACKGROUND: Colorectal surgery is associated with moderate-to-severe postoperative complications in over 25% of patients, predominantly infections. Monocyte epigenetic alterations leading to immune tolerance could explain postoperative increased susceptibility to infections. This research explores whether changes in monocyte DNA accessibility contribute to postoperative innate immune dysregulation. METHODS: Damage-associated molecular patterns (DAMPs) and ex vivo cytokine production capacity were measured in a randomized controlled trial (n = 100) in colorectal surgery patients, with additional exploratory subgroup proteomic (proximity extension assay; Olink) and epigenomic analyses (Assay for Transposase-Accessible Chromatin [ATAC sequencing]). Monocytes of healthy volunteers were used to study the effect of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70) on cytokine production capacity in vitro. RESULTS: Plasma DAMPs were increased after surgery. HMGB1 showed a mean 235% increase from before- (preop) to the end of surgery (95% confidence interval [CI] [166 - 305], P < .0001) and 90% increase (95% CI [63-118], P = .0004) preop to postoperative day 1 (POD1). HSP70 increased by a mean 12% from preop to the end of surgery (95% CI [3-21], not significant) and 30% to POD1 (95% CI [18-41], P < .0001). Nuclear deoxyribonucleic acid (nDNA) increases by 66% (95% CI [40-92], P < .0001) at the end of surgery and 94% on POD1 (95% CI [60-127], P < .0001). Mitochondrial DNA (mtDNA) increases by 370% at the end of surgery (95% CI [225-515], P < .0001) and by 503% on POD1 (95% CI [332-673], P < .0001). In vitro incubation of monocytes with HSP70 decreased cytokine production capacity of tumor necrosis factor (TNF) by 46% (95% CI [29-64], P < .0001), IL-6 by 22% (95% CI [12-32], P = .0004) and IL-10 by 19% (95% CI [12-26], P = .0015). In vitro incubation with HMGB1 decreased cytokine production capacity of TNF by 34% (95% CI [3-65], P = .0003), interleukin 1ß (IL-1ß) by 24% (95% CI [16-32], P < .0001), and IL-10 by 40% (95% CI [21-58], P = .0009). Analysis of the inflammatory proteome alongside epigenetic shifts in monocytes indicated significant changes in gene accessibility, particularly in inflammatory markers such as CXCL8 (IL-8), IL-6, and interferon-gamma (IFN-γ). A significant enrichment of interferon regulatory factors (IRFs) was found in loci exhibiting decreased accessibility, whereas enrichment of activating protein-1 (AP-1) family motifs was found in loci with increased accessibility. CONCLUSIONS: These findings illuminate the complex epigenetic modulation influencing monocytes' response to surgical stress, shedding light on potential biomarkers for immune dysregulation. Our results advocate for further research into the role of anesthesia in these molecular pathways and the development of personalized interventions to mitigate immune dysfunction after surgery.

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.

Reamputation rate, mortality and the incidence of risk factors for ipsilateral reamputation among patients with dysvascular major lower limb amputation.

INTRODUCTION: A major lower-limb amputation (LLA) for dysvascular disease carries the risk of disturbed wound healing necessitating reamputation at a higher level. A reamputation causes a delay in prosthetic fitting and recovery of walking ability. The combination of a prolonged open wound and inability to walk can worsen of the physical and psychological situation. Prevention of reamputation seems therefore important. This study aims to identify risk factors for reamputation, and to evaluate a possible altered mortality rate after a dysvascular major LLA. These issues are crucial for shared decision-making prior to surgery. METHODS: Retrospective study investigating a Dutch regional cohort of patients with a dysvascular below-knee, through-knee, or above-knee LLA. RESULTS: 516 Dysvascular major LLAs were included (2014-2018). One hundred reamputations were performed within 1 year after initial amputation (19.4%). Risk factors for ipsilateral reamputation were diabetes mellitus, lipid-lowering drugs usage, and lower level of amputation (respectively P = < 0.01, 0.037, and < 0.01). The 30-day mortality rates were 1% and 12% for the reamputation group and the non-reamputation group respectively (P = < 0.01). The 1-year mortality rates were 23% and 27% for the reamputation group and the non-reamputation group respectively (P = 0.423). CONCLUSIONS: Ipsilateral reamputation within one year after initial amputation is common. Several risk factors for reamputation were identified. The 30-day and 1-year mortality rate is high, but not significantly different after one year. A clinical decision tool for dysvascular patients needs to be developed to improve shared decision-making, reduce reamputation rates, and improve survival.

Treatment of Renal Artery Aneurysm by ex situ Repair and Autotransplantation: A Nationwide Cohort Study.

INTRODUCTION: Renal artery aneurysm (RAA) is a rare vascular disease with a mortality rate of up to 80% upon rupture. This study aimed to investigate the safety and efficacy of ex situ repair and autotransplantation for endovascularly untreatable RAA. METHODS: A retrospective nationwide cohort study was conducted in RAA patients undergoing ex situ repair and autotransplantation in the Netherlands. Surgical techniques, postoperative complications, and graft outcomes were assessed. RESULTS: Ex situ repair was performed in 9 patients with 11 RAAs. Eight RAAs were located at the first bifurcation, one on the main trunk, one on the first branch, and one on the second branch. Nephrectomy was performed via laparoscopy (n = 7), robotic-assisted laparoscopy (n = 1), and laparotomy (n = 1). Postoperative complications were recorded in 4 patients, including bowel obstruction, delirium, pneumonia, and hydronephrosis due to double-J dislocation. The median estimated glomerular filtration rate was 83 mL/min/1.73 m2 pretransplant and 88 mL/min/1.73 m2 posttransplant. By an average follow-up of 32 months, 2 patients had died due to lung adenocarcinoma and stroke, while all autotransplanted kidneys had good patency and remained functional. CONCLUSIONS: Ex situ repair and autotransplantation are safe and feasible for endovascularly untreatable RAA cases. Larger cohorts with longer follow-up periods are necessary to further evaluate the role of this surgical approach.

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.

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.

Current State of MRI-Guided Endovascular Arterial Interventions: A Systematic Review of Preclinical and Clinical Studies.

BACKGROUND: MRI guidance of arterial endovascular interventions could be beneficial as it does not require radiation exposure, allows intrinsic blood-tissue contrast, and enables three-dimensional and functional imaging, however, clinical applications are still limited. PURPOSE: To review the current state of MRI-guided arterial endovascular interventions and to identify the most commonly reported challenges. STUDY TYPE: Systematic review. POPULATION: Pubmed, Embase, Web of Science, and The Cochrane Library were systematically searched to find relevant articles. The search strategy combined synonyms for vascular pathology, endovascular therapy, and real-time MRI guidance. FIELD STRENGTH/SEQUENCE: No field strength or sequence restrictions were applied. ASSESSMENT: Two reviewers independently identified and reviewed the original articles and extracted relevant data. STATISTICAL TESTS: Results of the included original articles are reported. RESULTS: A total of 24,809 studies were identified for screening. Eighty-eight studies were assessed for eligibility, after which data were extracted from 43 articles (6 phantom, 33 animal, and 4 human studies). Reported technical success rates for animal and human studies ranged between 42% to 100%, and the average complication rate was 5.8% (animal studies) and 8.8% (human studies). Main identified challenges were related to spatial and temporal resolution as well as safety, design, and scarcity of current MRI-compatible endovascular devices. DATA CONCLUSION: MRI guidance of endovascular arterial interventions seems feasible, however, included articles included mostly small single-center case series. Several hurdles remain to be overcome before larger trials can be undertaken. Main areas of research should focus on adequate imaging protocols with integrated tracking of dedicated endovascular devices.

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.

The relation between physical fitness, frailty and all-cause mortality after elective endovascular abdominal aortic aneurysm repair.

BACKGROUND: Accurate determination of probable surgical outcomes is fundamental in decision-making regarding appropriate abdominal aortic aneurysm treatment. These outcomes depend, among other factors, on patient-related factors such as physical fitness. The primary aim of this study was to evaluate the correlation between physical fitness, measured by the metabolic equivalent of task (MET) score and the five-factor Modified Frailty Index (MFI-5), and all-cause mortality. METHODS: Four hundred twenty-nine patients undergoing elective endovascular treatment of an infrarenal aortic aneurysm (EVAR) from January 2011 to September 2018 were identified in an existing local abdominal aortic aneurysm database. Physical fitness was measured by the MFI-5 and the METs as registered during preoperative screening. The primary end point was 1-year all-cause mortality and secondary end points included 5-year all-cause mortality, freedom from aneurysm-related mortality and aneurysm-related reinterventions. Correlations were analyzed using Spearman's rho and survival was analyzed using Kaplan-Meier analyses. The effect of physical fitness on mortality was assessed by binary logistics regression analyses. RESULTS: There was a positive correlation between the MFI-5 and 1-year all-cause mortality (Rho = 0.163; P = .001), but not between the METs and 1-year all-cause mortality (Rho = -0.083; P = .124). A significant correlation between both MFI-5 and METs and 5-year all-cause mortality was observed (Rho = 0.255; P < .001 and Rho = -0.154; P = .004). When stratified by the MFI-5, the 1- and 5-year follow-up survival rates were 95.1% and 85.9%, respectively, in the group with the lowest MFI-5 and 74.5% and 33.1% in the group with the highest MFI-5 score (P = .007 and P < .001). When stratified by METs categories for 1-year follow-up, no significant differences in survival between the groups were observed (P = .090). The 5-year follow-up survival rate was 39.4% in the lowest METs category and 76.3% in the highest METs category (P = .039). Logistic regression analysis, assessing the impact of age, sex, METs, and the MFI-5 on the risk of all-cause mortality, showed that only age and the MFI-5 made a significant contribution. CONCLUSIONS: There is a significant positive association between the MFI-5 and both the 1- and 5-year all-cause mortality rates after EVAR; METs only correlated with the 5-year all-cause mortality. Only age and the MFI-5 contributed to predicting overall survival after EVAR; therefore, it could be recommended to add the MFI-5 for guidance in preoperative counselling.

Chronic pain following laparoscopic living-donor nephrectomy: Prevalence and impact on quality of life.

Chronic postsurgical pain (CPSP) following laparoscopic donor nephrectomy (LDN) is a disregarded topic. In this cross-sectional study, all consecutive patients who underwent an LDN at the Radboud University Medical Center (Radboudumc; 2003-2016) were approached for participation. Five hundred twelve living kidney donors were included and asked to complete two questionnaires, including the McGill Pain Questionnaire and the RAND Short Form-36 Health Status Inventory (RAND SF-36) regarding their health-related quality of life (HRQoL). The mean prevalence of CPSP following LDN was 5.7%, with a mean follow-up time of 6 years. Possible predictors of CPSP following LDN are severe early postoperative pain, previous abdominal surgery, and preexisting backache. The RAND SF-36 revealed an impaired HRQoL in patients with CPSP when compared to patients without CPSP. In conclusion, this study revealed that the prevalence of CPSP following LDN is substantial. Given the possible association between the presence of CPSP and impaired HRQoL scores, living kidney donors should be well informed in the preoperative phase about the risk of CPSP.

Carotid Artery Reactivity Predicts Events in Peripheral Arterial Disease Patients.

OBJECTIVE: Patients with peripheral arterial disease (PAD) have increased risk on future cerebro- and cardiovascular events. Our aim was to examine whether carotid artery reactivity (CAR; a novel, simple procedure to examine endothelial function) predicts cardiovascular events in PAD patients. BACKGROUND: Increased risk for future cardiovascular events in PAD patients is likely related to endothelial dysfunction, highlighting the necessity for simple assessment of endothelial function. METHODS: A total of 172 PAD patients (68 ±â€Š10 years, 67% male) underwent the CAR, which involves ultrasound measurement of carotid artery diameter during sympathetic stimulation produced by 90-second hand immersion in 4°C ice-water (ie, cold pressor test). CAR-responses were dichotomized into carotid constriction or dilation. We recorded cardiac and cerebrovascular events, mortality, and clinical progression to percutaneous transluminal angioplasty or loss of patency during 12-month follow-up. RESULTS: Eighty-two PAD patients demonstrated carotid constriction and 90 patients demonstrated dilation. PAD patients with carotid constriction showed more cardiovascular events compared to patients with dilation (Kaplan-Meier Log rank; P < 0.05). Cox proportional hazard models showed that patients with carotid constriction continued to show higher risk for cardiovascular events [hazard ratio: 4.1; 95% confidence interval (CI), 1.3-12.5] and clinical progression (hazard ratio: 2.0; 95% CI, 1.2-3.3), even after adjustment for other risk factors. Ankle brachial pressure index and carotid intima-medial thickness alone did not predict (cardiovascular) event or improve risk assessment beyond that provided by CAR. CONCLUSION: Carotid vasoconstriction identifies PAD patients with a 4-fold increased risk for future cardiovascular events and 2-fold increased risk for clinical deterioration. CAR provides a simple, novel strategy to predict cardiovascular events and progression in PAD patients. CLINICAL TRIAL REGISTRATION: www.trialregister.nl/trialreg/index.asp, NTR-4117.

Relationship Between Postoperative Pain and Overall 30-Day Complications in a Broad Surgical Population: An Observational Study.

OBJECTIVE: The aim of this study was to establish the relationship between postoperative pain and 30-day postoperative complications. BACKGROUND: Only scarce data are available on the association between postoperative pain and a broad range of postoperative complications in a large heterogeneous surgical population. METHODS: Having postoperative pain was assessed in 2 ways: the movement-evoked pain score on the Numerical Rating Scale (NRS-MEP) and the patients' opinion whether the pain was acceptable or not. Outcome was the presence of a complication within 30 days after surgery. We used binary logistic regression for the total population and homogeneous subgroups to control for case complexity. Results for homogeneous subgroups were summarized in a meta-analysis using inverse variance weighting. RESULTS: In 1014 patients, 55% experienced moderate-to-severe pain on the first postoperative day. The overall complication rate was 34%. The proportion of patients experiencing postoperative complications increased from 0.25 [95% confidence interval (CI) = 0.21-0.31] for NRS-MEP = 0 to 0.45 (95% CI = 0.36-0.55) for NRS-MEP = 10. Patients who found their pain unacceptable had more complications (adjusted odds ratio = 2.17 (95% CI = 1.51-3.10; P < 0.001)). Summary effect sizes obtained with homogeneous groups were similar to those obtained from the total population who underwent very different types of surgery. CONCLUSIONS: Higher actual postoperative pain scores and unacceptable pain, even on the first postoperative day, are associated with more postoperative complications. Our findings provide important support for the centrality of personalized analgesia in modern perioperative care.

Efficacy of profound versus moderate neuromuscular blockade in enhancing postoperative recovery after laparoscopic donor nephrectomy: A randomised controlled trial.

BACKGROUND: Profound neuromuscular blockade (NMB) during anaesthesia has been shown to reduce postoperative pain scores, when compared with a moderate block. We hypothesised that profound NMB during laparoscopic donor nephrectomy (LDN) could also improve the early quality of recovery after surgery. OBJECTIVES: To compare the effectiveness of profound versus moderate NMB during LDN in enhancing postoperative recovery. DESIGN: A phase IV, double-blinded, randomised controlled trial. SETTING: Multicentre trial, from November 2016 to December 2017. PATIENTS: A total of 101 living kidney donors scheduled for LDN were enrolled, and 96 patients were included in the analyses. INTERVENTIONS: Patients were randomised to receive profound (posttetanic count 1 to 3) or moderate (train-of-four count 1 to 3) neuromuscular block. MAIN OUTCOME MEASURES: The primary outcome was the early quality of recovery at postoperative day 1, measured by the Quality of Recovery-40 Questionnaire. Secondary outcomes were adverse events, postoperative pain, analgesic consumption and length-of-stay. RESULTS: The intention-to-treat analysis did not show a difference with regard to the quality of recovery, pain scores, analgesic consumption and length-of-stay. Less intra-operative adverse events occurred in patients allocated to profound NMB (1/48 versus 6/48). Five patients allocated to a profound NMB received a moderate block and in two patients neuromuscular monitoring failed. The as-treated analysis revealed that pain scores were significantly lower at 6, 24 and 48 h after surgery. Moreover, the quality of recovery was significantly better at postoperative day 2 in patients receiving a profound versus moderate block (179.5 ±â€Š13.6 versus 172.3 ±â€Š19.2). CONCLUSION: Secondary analysis indicates that an adequately maintained profound neuromuscular block improves postoperative pain scores and quality of recovery. As the intention-to-treat analysis did not reveal a difference regarding the primary endpoint, future studies should pursue whether a thoroughly maintained profound NMB during laparoscopy improves relevant patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02838134.

Quality of Recovery After Low-Pressure Laparoscopic Donor Nephrectomy Facilitated by Deep Neuromuscular Blockade: A Randomized Controlled Study.

BACKGROUND: The use of low intra-abdominal pressure (<10 mmHg) reduces postoperative pain scores after laparoscopic surgery. OBJECTIVE: To investigate whether low-pressure pneumoperitoneum with deep neuromuscular blockade improves the quality of recovery after laparoscopic donor nephrectomy (LDN). DESIGN, SETTING AND PARTICIPANTS: In a single-center randomized controlled trial, 64 live kidney donors were randomly assigned to 6 or 12 mmHg insufflation pressure. A deep neuromuscular block was used in both groups. Surgical conditions were rated by the five-point Leiden-surgical rating scale (L-SRS), ranging from 5 (optimal) to 1 (extremely poor) conditions. If the L-SRS was insufficient, the pressure was increased stepwise. MAIN OUTCOME MEASURE: The primary outcome measure was the overall score on the quality of recovery-40 (QOR-40) questionnaire at postoperative day 1. RESULTS: The difference in the QOR-40 scores on day 1 between the low- and standard-pressure group was not significant (p = .06). Also the overall pain scores and analgesic consumption did not differ. Eight procedures (24%), initially started with low pressure, were converted to a standard pressure (≥10 mmHg). A L-SRS score of 5 was significantly more prevalent in the standard pressure as compared to the low-pressure group at 30 min after insufflation (p < .01). CONCLUSIONS: Low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade during LDN does not reduce postoperative pain scores nor improve the quality of recovery in the early postoperative phase. The question whether the use of deep neuromuscular blockade during laparoscopic surgery reduces postoperative pain scores independent of the intra-abdominal pressure should be pursued in future studies. TRIAL REGISTRATION: The trial was registered at clinicaltrial.gov before the start of the trial (NCT02146417).

Ischaemic preconditioning for the reduction of renal ischaemia reperfusion injury.

BACKGROUND: Ischaemia reperfusion injury can lead to kidney dysfunction or failure. Ischaemic preconditioning is a short period of deprivation of blood supply to particular organs or tissue, followed by a period of reperfusion. It has the potential to protect kidneys from ischaemia reperfusion injury. OBJECTIVES: This review aimed to look at the benefits and harms of local and remote ischaemic preconditioning to reduce ischaemia and reperfusion injury among people with renal ischaemia reperfusion injury. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 5 August 2016 through contact with the Information Specialist using search terms relevant to this review. SELECTION CRITERIA: We included all randomised controlled trials measuring kidney function and the role of ischaemic preconditioning in patients undergoing a surgical intervention that induces kidney injury. Kidney transplantation studies were excluded. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality; data were extracted by two independent authors. We collected basic study characteristics: type of surgery, remote ischaemic preconditioning protocol, type of anaesthesia. We collected primary outcome measurements: serum creatinine and adverse effects to remote ischaemic preconditioning and secondary outcome measurements: acute kidney injury, need for dialysis, neutrophil gelatinase-associated lipocalin, hospital stay and mortality. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. MAIN RESULTS: We included 28 studies which randomised a total of 6851 patients. Risk of bias assessment indicated unclear to low risk of bias for most studies. For consistency regarding the direction of effects, continuous outcomes with negative values, and dichotomous outcomes with values less than one favour remote ischaemic preconditioning. Based on high quality evidence, remote ischaemic preconditioning made little or no difference to the reduction of serum creatinine levels at postoperative days one (14 studies, 1022 participants: MD -0.02 mg/dL, 95% CI -0.05 to 0.02; I2 = 21%), two (9 studies, 770 participants: MD -0.04 mg/dL, 95% CI -0.09 to 0.02; I2 = 31%), and three (6 studies, 417 participants: MD -0.05 mg/dL, 95% CI -0.19 to 0.10; I2 = 68%) compared to control.Serious adverse events occurred in four patients receiving remote ischaemic preconditioning by iliac clamping. It is uncertain whether remote ischaemic preconditioning by cuff inflation leads to increased adverse effects compared to control because the certainty of the evidence is low (15 studies, 3993 participants: RR 3.47, 95% CI 0.55 to 21.76; I2 = 0%); only two of 15 studies reported any adverse effects (6/1999 in the remote ischaemic preconditioning group and 1/1994 in the control group), the remaining 13 studies stated no adverse effects were observed in either group.Compared to control, remote ischaemic preconditioning made little or no difference to the need for dialysis (13 studies, 2417 participants: RR 0.85, 95% CI 0.37 to 1.94; I2 = 60%; moderate quality evidence), length of hospital stay (8 studies, 920 participants: MD 0.17 days, 95% CI -0.46 to 0.80; I2 = 49%, high quality evidence), or all-cause mortality (24 studies, 4931 participants: RR 0.86, 95% CI 0.54 to 1.37; I2 = 0%, high quality evidence).Remote ischaemic preconditioning may have slightly improved the incidence of acute kidney injury using either the AKIN (8 studies, 2364 participants: RR 0.76, 95% CI 0.57 to 1.00; I2 = 61%, high quality evidence) or RIFLE criteria (3 studies, 1586 participants: RR 0.91, 95% CI 0.75 to 1.12; I2 = 0%, moderate quality evidence). AUTHORS' CONCLUSIONS: Remote ischaemic preconditioning by cuff inflation appears to be a safe method, and probably leads to little or no difference in serum creatinine, adverse effects, need for dialysis, length of hospital stay, death and in the incidence of acute kidney injury. Overall we had moderate-high certainty evidence however the available data does not confirm the efficacy of remote ischaemic preconditioning in reducing renal ischaemia reperfusion injury in patients undergoing major cardiac and vascular surgery in which renal ischaemia reperfusion injury may occur.

Repeated remote ischemic preconditioning and isoflurane anesthesia in an experimental model of renal ischemia-reperfusion injury.

BACKGROUND: In animal studies, remote ischemic preconditioning (RIPC) and anesthetic preconditioning are successful in reducing renal ischemia reperfusion injury (IRI), however the protective effect of RIPC may be improved by repeating the RIPC stimulus. METHODS: Sprague-Dawley rats underwent unilateral nephrectomy followed by 30 min of renal pedicle clamping. Animals were allocated into six groups: sham, control (IRI), RepISO (daily isoflurane anesthesia), RIPC (single dose isoflurane anesthesia and single dose RIPC), RepISO + RIPC (7-day isoflurane anesthesia and single dose RIPC) and RepISO + RepRIPC (7-day isoflurane anesthesia with 7-day RIPC). RIPC was applied by 3×5 min of cuff inflation on both thighs. Serum creatinine and urea levels were measured and histology was obtained at day two. RESULTS: RepISO diminished renal IRI, as reflected by a significant reduction in serum creatinine levels as compared to the control group, 170 ± 74 resp. 107 ± 29 µmol/L. The other preconditioning protocols showed similar reduction in serum creatinine levels as compared to the control group. No significant differences were observed between the different preconditioning protocols. For urea levels, only RepISO + RIPC resulted in significantly lower levels as compared to the control group, 14 ± 4 resp. 22 ± 7 mmol/L (p = 0.010). In the preconditioning groups only RepISO showed less histological damage as compared to controls 1.73 ± 1.19 resp. 2.91 ± 1.22 (p = 0.032). CONCLUSIONS: In this study no additional protective effect of repeated ischemic preconditioning was observed as compared to single dose RIPC. Repeated administration of isoflurane provided stronger protection against renal IRI as compared to single dose isoflurane.