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Introduction: The circadian timing system regulates diurnal sleep-wake rhythm. Previously, we showed that, in patients undergoing elective surgery, sleep-wake timing is altered and post-operative sleep quality is reduced. However, how the timing of the surgical procedure affects the disturbance and what other factors affect this disturbance remain unknown., Methods: Single-centre prospective observational study investigating the influence of surgery timing on post-operative sleep in adult patients (≥18 years) undergoing elective surgery. Sleep-wake timing was measured from three nights before until seven nights after surgery with a daily sleeping log. Primary outcome was post-operative midpoint of sleep shift between patients undergoing morning and afternoon surgeries. Secondary outcomes included factors affecting sleep timing disturbance and changes in subjective sleep quality., Results: We included 259 patients: 144 patients underwent morning procedures (08:00 h-12:00 h) and 115 underwent afternoon procedures (12:00 h-17:00 h). Both groups had significant phase advance of midpoint of sleep on the night after surgery when compared with three nights before surgery (mean - 00:41 h, 95% CI -00:27 h to -00:54 h, p < .001, for morning surgery and mean - 00:28 h, 95% CI -00:09 h to -00:46 h, p = .003, for afternoon surgery). However, there was no between-group difference (mean - 00:13 h, 95% CI -00:35 h-00:09 h, p = .25). Reduction of sleep quality was also similar. Phase advance was larger for patients with an evening chronotype or with lower pre-operative sleep quality. Decline of sleep quality after surgery was larger for patients with an evening chronotype, longer procedures or better pre-operative sleep quality., Conclusion: Our results suggest that the timing of surgery between 08:00 h and 17:00 h does not modulate the effect of anaesthesia and surgery on phase of the sleep-wake rhythm in patients undergoing elective surgery with a low pre-operative risk of delirium., Editorial Comment: Timing of surgery may impact post-operative sleep. However, in this prospective cohort study of elective surgical patients, sleep-wake timing and post-operative sleep quality did not differ between those undergoing morning versus afternoon surgery., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Nitrous oxide (N 2 O) is a common adjuvant to general anaesthesia. It is also a potent greenhouse gas and causes ozone depletion. We sought to quantify the influence of N 2 O as an adjuvant to general anaesthesia on postoperative patient outcomes., Methods: We searched Medline, EMBASE, and Cochrane Central for works published from inception to July 6, 2023. RCTs comparing general anaesthesia with or without N 2 O were included. Risk ratios (RRs) and standardised mean differences (SMDs) were calculated, along with 95% confidence intervals (CIs), using a random-effects model. Outcomes were derived from the Standardised Endpoints for Perioperative Medicine (StEP) outcome set. Primary outcomes were mortality and organ-related morbidity, and secondary outcomes were anaesthetic and surgical morbidity., Results: Of 3305 records, 179 full-text articles were assessed, and 71 RCTs, totalling 22 147 patients, were included in the meta-analysis. Addition of N 2 O to general anaesthesia did not influence postoperative mortality or most morbidity outcomes. N 2 O increased the incidence of atelectasis (RR 1.62, 95% CI 1.24 to 2.12) and postoperative nausea and vomiting (RR 1.27, 95% CI 1.15 to 1.40), and decreased intraoperative opioid consumption (SMD -0.19, 95% CI -0.35 to -0.04) and time to extubation (MD -2.17 min, 95% CI -3.32 to -1.03 min)., Conclusions: N 2 O did not influence postoperative mortality or most morbidity outcomes. Considering the environmental effects of N 2 O, these findings confirm that current policy recommendations to limit its use do not affect patient safety., Systematic Review Protocol: PROSPERO CRD42023443287., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The timing of elective surgery could affect clinical outcome because of diurnal rhythms of patient physiology as well as surgical team performance. Waiting times for elective surgery are increasing in many countries, leading to increasing interest in undertaking elective surgery in the evening or at night. We aimed to systematically review the literature on the effect of the timing of elective (but not urgent or emergency) surgery on mortality, morbidity and other clinical outcomes., Methods: We searched databases for relevant studies combining the terms 'circadian rhythm' and 'anaesthesia/surgery'. Additional relevant articles were found by hand-searching the references. All studies were screened for bias. Included studies examined daytime vs. evening/night-time surgery, morning vs. afternoon surgery, multiple timeslots or used time as a continuous variable., Results: Nineteen retrospective cohort studies, one prospective cohort study and one randomised controlled trial were included (n = 798,914). Evening/night-time elective surgery was associated with a higher risk of mortality when compared with daytime procedures in three studies (n = 611,230), with odds ratios (95%CI) for mortality ranging from 1.35 (1.16-1.56) to 3.98 (1.54-10.30), while no differences were found in three other studies (n = 142,355). No differences were found for morning vs. afternoon surgery (four studies, n = 3277). However, most studies had a low quality of evidence due to their retrospective nature and because not all studies corrected for patient characteristics. Moreover, the studies were heterogeneous in terms of the reported time slots and clinical outcomes., Conclusions: We found that evening/night-time elective surgery is associated with a higher risk of mortality compared with daytime surgery. However, the quality of evidence was graded as low, and thus, future prospective research should publish individual patient data and standardise outcome measures to allow firm conclusions and facilitate interventions., (© 2024 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Objective: To compare quality of recovery in patients receiving epidural or paravertebral analgesia for minimally invasive esophagectomy (MIE)., Summary Background Data: Paravertebral analgesia may be a promising alternative to epidural analgesia, avoiding potential side effects and improving postoperative recovery., Methods: This randomized controlled superiority trial was conducted across four Dutch centers with esophageal cancer patients scheduled for transthoracic MIE with intrathoracic anastomosis, randomizing patients to receive either epidural or paravertebral analgesia. The primary outcome was Quality of Recovery (QoR-40) on the third postoperative day (POD). Secondary outcomes included quality of life, postoperative pain, opioid consumption, inotropic/vasopressor medication use, hospital stay, complications, readmission, and mortality., Results: From December 2019 to February 2023, 192 patients were included: 94 received epidural and 98 paravertebral analgesia. QoR-40 score on POD3 was not different between groups (mean difference 3.7, 95%CI -2.3 to 9.7; P=0.268). Epidural patients had significant higher QoR-40 scores on POD1 and 2 (mean difference 7.7, 95%CI 2.3-13.1; P=0.018 and mean difference 7.3, 95%CI 1.9-12.7; P=0.020) and lower pain scores (median 1 versus 2; P=<0.001 and median 1 versus 2; P=0.033). More epidural patients required vasopressor medication on POD1 (38.3% versus 13.3%; P<0.001). Urinary catheters were removed earlier in the paravertebral group (median POD3 versus 4; P=<0.001). No significant differences were found in postoperative complications or hospital/Intensive Care Unit stay., Conclusions: This randomized controlled trial did not demonstrate superiority of paravertebral over epidural analgesia regarding quality of recovery on POD3 after MIE. Both techniques are effective and can be offered in clinical practice., Competing Interests: Declaration of interests Prof. dr. Ruurda reported serving an advisory or consulting role for Intuitive Surgical and Medtronic. Prof. dr. Luyer reported receiving research grants from Medtronic outside the submitted work. Dr. Nieuwenhuijzen reported serving a consulting or advisory role for Medtronic. Dr. Buise reported serving a consulting or advisory role for Medtronic. Dr. van Det reported serving a consulting or advisory role for Intuitive Surgical. Dr. Kouwenhoven reported serving a consulting or advisory role for Intuitive Surgical. Prof. dr. Hollmann reported serving roles as Executive Section Editor Pharmacology with Anesthesia & Analgesia, Section Editor Anesthesiology with J Clin Med, Editor with Front Physiol, and research support and honorarium for consultancy by PAION, Medical Developments & IDD Pharma. Prof. dr. van Berge Henegouwen reported serving a consulting or advisory roles for Viatris, Johnson & Johnson, BBraun, Stryker and Medtronic, all fees paid to the institution. Prof. dr. van Hillegersberg reported serving a consulting or advisory role for Intuitive Surgical, Medtronic and Olympus. The other authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The objectives of the current research were to evaluate the accuracy and reliability of continuous glucose monitoring (CGM) in patients undergoing cardiac surgery and assess the impact of preoperative liraglutide administration on perioperative glucose control as captured by CGM., Design: This was a prospective, single-center, prespecified analysis of the GLOBE trial, a randomized controlled trial comparing preoperative liraglutide treatment to placebo in patients undergoing cardiac surgery., Setting: The work took place at a single-center academic hospital in the Netherlands., Participants: Twenty-five patients undergoing cardiac surgery were recruited from the hospital's cardiac surgery department., Interventions: Participants received the Dexcom G5 CGM system from the day before surgery until discharge from the intensive care unit after surgery. Additionally, participants were randomized to receive either preoperative liraglutide or placebo., Measurements and Main Results: Arterial blood gas (ABG) glucose measurements were collected as a reference and matched to CGM readings to assess accuracy and reliability. In 240 paired CGM-ABG glucose measurements, the mean absolute relative difference was 14.4 ± 12.5%. Temporary sensor interruption occurred mainly intraoperatively (92% of patients). The median duration of intraoperative sensor interruption was 65 (48-95) minutes. Liraglutide increased glycemic time in range 72% versus 47% in the control group (absolute difference 25%, 95% confidence interval -41.4 to -8.9, p = .004)., Conclusions: Despite intraoperative sensor interruption, CGM seems an accurate method for semi-invasive, real-time assessment of blood glucose levels. CGM can provide a detailed observation of the pre- and postoperative glycemic trajectory, demonstrating increased time in range following perioperative liraglutide treatment compared with placebo., Competing Interests: Declaration of competing interest M. J. P. Oosterom-Eijmael, I. W. K. Kouw, and J. H. DeVries have no conflicts of interest to declare. D. H van Raalte has acted as a consultant and received honoraria from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Merck, and Sanofi, and received research operating funding from AstraZeneca, Boehringer Ingelheim, Eli Lilly Diabetes Alliance, and Merck. A. H. Hulst and J. Hermanides received a grant from the European Society of Anesthesiology. The study's funder, Novo Nordisk, had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and final responsibility for the decision to submit., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract: Developments in human cellular reprogramming now allow for the generation of human neurons for in vitro disease modelling. This technique has since been used for chemotherapy-induced peripheral neuropathy (CIPN) research, resulting in the description of numerous CIPN models constructed from human neurons. This systematic review provides a critical analysis of available models and their methodological considerations (ie, used cell type and source, CIPN induction strategy, and validation method) for prospective researchers aiming to incorporate human in vitro models of CIPN in their research. The search strategy was developed with assistance from a clinical librarian and conducted in MEDLINE (PubMed) and Embase (Ovid) on September 26, 2023. Twenty-six peer-reviewed experimental studies presenting original data about human reprogrammed nonmotor neuron cell culture systems and relevant market available chemotherapeutics drugs were included. Virtually, all recent reports modeled CIPN using nociceptive dorsal root ganglion neurons. Drugs known to cause the highest incidence of CIPN were most used. Furthermore, treatment effects were almost exclusively validated by the acute effects of chemotherapeutics on neurite dynamics and cytotoxicity parameters, enabling the extrapolation of the half-maximal inhibitory concentration for the 4 most used chemotherapeutics. Overall, substantial heterogeneity was observed in the way studies applied chemotherapy and reported their findings. We therefore propose 6 suggestions to improve the clinical relevance and appropriateness of human cellular reprogramming-derived CIPN models., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Study Objective: Management of pain after foot and ankle surgery remains a concern for patients and healthcare professionals. This study determined the effectiveness of ambulatory continuous popliteal sciatic nerve blockade, compared to standard of care, on overall benefit of analgesia score (OBAS) in patients undergoing foot or ankle surgery. We hypothesized that usage of ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care., Design: Single center, randomized, non-inferiority trial., Setting: Tertiary hospital in the Netherlands., Patients: Patients were enrolled if ≥18 years and scheduled for elective inpatient foot or ankle surgery., Intervention: Patients were randomized to ambulatory continuous popliteal sciatic nerve blockade or standard of care., Measurements: The primary outcome was the difference in OBAS, which includes pain, side effects of analgesics, and patient satisfaction, measured daily from the first to the third day after surgery. A non-inferiority margin of 2 was set as the upper limit for the 90% confidence interval of the difference in OBAS score. Mixed-effects modeling was employed to analyze differences in OBAS scores over time. Secondary outcome was the difference in opioid consumption., Main Results: Patients were randomized to standard of care (n = 22), or ambulatory continuous popliteal sciatic nerve blockade (n = 22). Analyzing the first three postoperative days, the OBAS was significantly lower over time in the ambulatory continuous popliteal sciatic nerve blockade group compared to standard of care, demonstrating non-inferiority (-1.9 points, 90% CI -3.1 to -0.7). During the first five postoperative days, patients with ambulatory continuous popliteal sciatic nerve blockade consumed significantly fewer opioids over time compared to standard of care (-8.7 oral morphine milligram equivalents; 95% CI -16.1 to -1.4)., Conclusions: Ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care with single shot popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia., Competing Interests: Declaration of competing interest The authors declare no conflict of interest regarding the submitted work. Outside the submitted manuscript, MWH serves as Executive Section Editor Pharmacology with Anesthesia and Analgesia and Section Editor Anesthesiology with the Journal of Clinical Medicine, Editor with Frontiers in Physiology and he served as consultant for PAION, IDD & Medical Developments Pharma., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI., Methods: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8)., Results: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes., Conclusion: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology., (© 2024. The Author(s).)

Aims and Scope: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management., Methods: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements., Results: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology., Conclusions: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting., (© 2024. The Author(s).)

Background: General anaesthesia is provided to more than 300 million surgical patients worldwide, every year. It is administered either through total intravenous anaesthesia, using only intravenous agents, or through inhalational anaesthesia, using volatile anaesthetic agents. The debate on how this affects postoperative patient outcome is ongoing, despite an abundance of published trials. The relevance of this topic has grown by the increasing concern about the contribution of anaesthetic gases to the environmental impact of surgery. We aimed to summarise all available evidence on relevant patient outcomes with total intravenous anaesthesia versus inhalational anaesthesia., Methods: In this systematic review and meta-analysis, we searched PubMed/Medline, Embase and Cochrane Central Register of Controlled trials for works published from January 1, 1985 to August 1, 2023 for randomised controlled trials comparing total intravenous anaesthesia using propofol versus inhalational anaesthesia using the volatile anaesthetics sevoflurane, desflurane or isoflurane. Two reviewers independently screened titles, abstracts and full text articles, and assessed risk of bias using the Cochrane Collaboration tool. Outcomes were derived from a recent series of publications on consensus definitions for Standardised Endpoints for Perioperative trials (StEP). Primary outcomes covered mortality and organ-related morbidity. Secondary outcomes were related to anaesthetic and surgical morbidity. This study is registered with PROSPERO (CRD42023430492)., Findings: We included 317 randomised controlled trials, comprising 51,107 patients. No difference between total intravenous and inhalational anaesthesia was seen in the primary outcomes of in-hospital mortality (RR 1.05, 95% CI 0.67-1.66, 27 trials, 3846 patients), 30-day mortality (RR 0.97, 95% CI 0.70-1.36, 23 trials, 9667 patients) and one-year mortality (RR 1.14, 95% CI 0.88-1.48, 13 trials, 9317 patients). Organ-related morbidity was similar between groups except for the subgroup of elderly patients, in which total intravenous anaesthesia was associated with a lower incidence of postoperative cognitive dysfunction (RR 0.62, 95% CI 0.40-0.97, 11 trials, 3834 patients) and a better score on postoperative cognitive dysfunction tests (standardised mean difference 1.68, 95% CI 0.47-2.88, 9 trials, 4917 patients). In the secondary outcomes, total intravenous anaesthesia resulted in a lower incidence of postoperative nausea and vomiting (RR 0.61, 95% CI 0.56-0.67, 145 trials, 23,172 patients), less emergence delirium (RR 0.40, 95% CI 0.29-0.56, 32 trials, 4203 patients) and a higher quality of recovery score (QoR-40 mean difference 6.45, 95% CI 3.64-9.25, 17 trials, 1835 patients)., Interpretation: The results indicate that postoperative mortality and organ-related morbidity was similar for intravenous and inhalational anaesthesia. Total intravenous anaesthesia offered advantages in postoperative recovery., Funding: Dutch Society for Anaesthesiology (NVA)., Competing Interests: NSW and SR are both frequent speakers at public and private events on sustainability in healthcare, for which they have received travel reimbursements, but never any other financial payment. NSW chairs the Sustainability Taskforce of the Dutch Society for Anaesthesiology and is a member of the Sustainability Committee of the European Society for Anaesthesiology and Intensive Care (ESAIC). He is a section editor (anaesthesiology and intensive care) for the Amsterdam Medical Student Journal (AMSj). SR is a member of the advisory committee about sustainability at the University of Amsterdam. MH is section editor for Anaesthesia & Analgesia, Journal of Clinical Medicine and Frontiers of Physiology, and has received research support and honorariums from BBraun, Fresenius, IDD Pharma and PAION. The other authors declare no relationships or activities that could appear to have influenced the submitted work., (© 2024 The Author(s).)

Introduction: Low and high volume mid-thigh (ie, distal femoral triangle) and distal adductor canal block approaches are frequently applied for knee surgical procedures. Although these techniques aim to contain the injectate within the adductor canal, spillage into the popliteal fossa has been reported. While in theory this could improve analgesia, it might also result in motor blockade due to coverage of motor branches of the sciatic nerve. This radiological cadaveric study, therefore, investigated the incidence of coverage of sciatic nerve divisions after various adductor canal block techniques., Methods: Eighteen fresh, unfrozen and unembalmed human cadavers were randomized to receive ultrasound-guided distal femoral triangle or distal adductor canal injections, with 2 mL or 30 mL injectate volume, on both sides (36 blocks in total). The injectate was a 1:10 dilution of contrast medium in local anesthetic. Injectate spread was assessed using whole-body CT with reconstructions in axial, sagittal and coronal planes., Results: No coverage of the sciatic nerve or its main divisions was found. The contrast mixture spread to the popliteal fossa in three of 36 nerve blocks. Contrast reached the saphenous nerve after all injections, whereas the femoral nerve was always spared., Conclusions: Adductor canal block techniques are unlikely, even when using larger volumes, to block the sciatic nerve, or its main branches. Furthermore, injectate reached the popliteal fossa in a small minority of cases, yet if a clinical analgesic effect is achieved by this mechanism is still unknown., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood-brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI.

More than 25% of older adults in Europe have diabetes mellitus. It is estimated that 45% of patients with diabetes are currently undiagnosed, which is a known risk factor for perioperative morbidity. We investigated whether routine HbA1c screening in older adult patients undergoing surgery would identify patients with undiagnosed diabetes. We included patients aged ≥65 years without a diagnosis of diabetes who visited the preoperative assessment clinic at the Amsterdam University Medical Center and underwent HbA1c screening within three months before surgery. Patients undergoing cardiac surgery were excluded. We assessed the prevalence of undiagnosed diabetes (defined as HbA1c ≥ 48 mmol·mol -1 ) and prediabetes (HbA1c 39-47 mmol·mol -1 ). Using a multivariate regression model, we analysed the ability of HbA1c to predict days alive and at home within 30 days after surgery. From January to December 2019, we screened 2015 patients ≥65 years at our clinic. Of these, 697 patients without a diagnosis of diabetes underwent HbA1c screening. The prevalence of undiagnosed diabetes and prediabetes was 3.7% (95%CI 2.5-5.4%) and 42.9% (95%CI 39.2-46.7%), respectively. Preoperative HbA1c was not associated with days alive and at home within 30 days after surgery. In conclusion, we identified a small number of patients with undiagnosed diabetes and a high prevalence of prediabetes based on preoperative HbA1c screening in a cohort of older adults undergoing non-cardiac surgery. The relevance of prediabetes in the perioperative setting is unclear. Screening for HbA1c in older adult patients undergoing non-cardiac surgery does not appear to help predict postoperative outcome.

Functional constipation in the pediatric population is a prevalent issue that is usually well managed. However, in rare cases, conservative treatment fails, and surgical intervention is necessary. This retrospective cohort study aimed to describe and compare different perioperative analgesic techniques in children undergoing major abdominal surgery for intractable constipation. Conducted between 2011 and 2021, this study enrolled patients under 18 years old who underwent initial major abdominal surgery for intractable constipation (i.e., creation of ostomy or subtotal colectomy). Patients were categorized according to the perioperative analgesic technique (i.e., systemic, neuraxial, or truncal block). Of 65 patients, 46 (70.8%) were female, and the median age was 13.5 [8.8-16.1] years during initial major abdominal surgery. Systemic analgesia was used in 43 (66.2%), neuraxial in 17 (26.2%), and truncal blocks in 5 (7.7%) of the surgeries. Patients with neuraxial analgesia reported less postoperative pain (median [interquartile range] numeric rating scale (NRS) 2.0 [0-4.0]), compared to systemic analgesia (5.0 [2.0-7.0], p < 0.001) and to truncal blocks (5.0 [3.0-6.5], p < 0.001). In this preliminary investigation, neuraxial analgesia appears to be the most effective approach to reducing acute postoperative pain in pediatric patients undergoing major abdominal surgery for intractable functional constipation. However, well-designed studies are warranted.

Study Objective: Poorly controlled acute postsurgical pain is associated with delayed recovery, chronic postsurgical pain (CPSP), chronic opioid use and impaired functioning in daily activities. The aim was to determine the effectiveness of a transitional pain service (TPS) to improve quality of recovery for patients at risk of CPSP. We hypothesized that a TPS improves the quality of recovery in patients at risk of CPSP., Design: Single-center, pragmatic, randomized, superiority trial., Setting: Tertiary hospital in the Netherlands., Patients: Assessed for eligibility if ≥18 years of age, undergoing elective surgery, and had an increased risk of developing CPSP. After being stratified for sex, 176 patients were included., Intervention: Patients were randomized to receive TPS or standard of care (SOC). TPS was a multidisciplinary intervention providing a patient-tailored perioperative pain management plan, throughout all phases of surgery., Measurements: The primary outcome was the difference in quality of recovery on the third postoperative day, measured by the Quality of Recovery (QoR)-15 questionnaire. Secondary outcomes include the between group differences in opioid consumption., Main Results: The primary outcome was available in 169 (96.0%) patients. No difference between groups was found in QoR-15 on the third postoperative day (mean difference 2.0, 95% CI -5.5 to 9.4, p = 0.607). A decrease in opioid usage (compared to baseline) was observed in chronic opioid users, the median [IQR] reduction in total daily oral morphine milligram equivalents (MME) for TPS was -30 [-60, 0] at three and - 29.3 [-65.6, 0] at six months, whereas SOC had a median reduction of 0 [-56, 0] at three, and 0 [-60, 7.5] at six months., Conclusions: TPS did not significantly affect short-term quality of recovery but might improve long-term outcomes, such as the incidence of chronic pain, opioid consumption, and functioning in daily life. However, sample size in the present study was too small to provide solid evidence for this positive signal., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding the submitted work. Outside the submitted manuscript, MWH serves as Executive Section Editor Pharmacology with Anesthesia and Analgesia and Section Editor Anesthesiology with the Journal of Clinical Medicine, Editor with Frontiers in Physiology and he received speakers fees from PAION and IDD Pharma., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objective: To evaluate all available evidence thus far on opioid based versus opioid-free anesthesia and its effect on acute and chronic postoperative pain., Design: Systematic review and meta-analysis of randomized clinical trials., Setting: Operating room, postoperative recovery room and ward., Patients: Patients undergoing general anesthesia., Interventions: After consulting MEDLINE, EMBASE and Cochrane database, studies which compared opioid free anesthesia (OFA) with opioid based anesthesia (OBA) were included (last search April 15th 2022)., Measurements: Primary outcomes were acute and chronic pain scores in NRS or VAS. Secondary outcomes were quality of recovery and postoperative opioid consumption. Risk of bias was assessed using the RoB2 tool and a random effects model for the meta-analysis was conducted., Main Results: We identified 1245 citations, of which 38 studies met our inclusion criteria. There is moderate quality evidence showing no clinically relevant difference of Numeric Rating Scale (NRS) scores or opioid consumption in the postoperative period (pooled mean difference of 0.39 points with a CI of 0.19-0.59 and 4.02 MME with a CI of 1.73-6.30). We found only one small-sized study reporting no effect of opioid-free anesthesia on chronic pain. The quality of recovery was superior in patients with opioid-free anesthesia (mean difference of 8.26 points), however, this pooled analysis was comprised of only two studies. Postoperative nausea and vomiting (PONV) occurred less in opioid-free anesthesia, but bradycardia was more frequent., Conclusions: We concluded that we cannot recommend one strategy over the other. Future studies could focus on quality of recovery as outcome measure and adequately powered studies on the effects of opioid-free anesthesia on chronic pain are eagerly awaited., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Globally, life expectancy is increasing, leading to more surgeries being performed in older patients. Postoperative pain is associated with complications after surgery. The aim of this study is to explore potential age-related risk factors for acute postoperative pain in older patients undergoing surgery. This was a prospective, single-center study. Patients ≥65 years, with and without disability, as defined by the WHO Disability Assessment Schedule 2.0, undergoing elective surgery, were compared. Primary outcome was the postoperative pain (ie, numeric rating scale (NRS) score) on the first postoperative day. Secondary outcomes were postoperative pain and pain trajectories in patients with and without mild cognitive impairment (MCI), frailty, preoperative opioid use, and new-onset disability after surgery. Between February 2019 and July 2020, 155 patients were enrolled. On the first day after surgery, postoperative pain did not differ between patients with and without disability. NRS scores differed between patients with-, and without MCI on the first (P = .01), and second postoperative day (P < .01). Patients who used opioids before surgery reported higher median NRS score on the first (P < .001) and second (P < .01) postoperative day. Out of a total of 1816 NRS scores, 2 pain clusters were identified. Acute postoperative pain did not differ between patients with or without preoperative disability and frailty in older patients undergoing surgery. Reduced postoperative pain in older patients with MCI warrants further investigation. The PIANO study (Comparison of Postoperative NeurocognitiveFunction in Older Adult Patients with and without Diabetes Mellitus) was registered with www.clinicaltrialregister.nl (search term: Which can predict memory problems after surgery better; blood sugar levels or memory before surgery?). PERSPECTIVE: This study explored risk factors for acute postoperative pain in older patients. No differences in postoperative pain were observed in patients with or without preexistent disability or frailty, however, patients with mild cognitive impairment experienced reduced pain. We suggest to simplify pain assessment in this group and take functional recovery into account., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Optimal pain management for esophagectomy facilitates prevention of postoperative complications such as pneumonia, but also chronic pain. Historically, multimodal intravenous analgesia was employed. In the last decades, regional anesthesia including epidural and paravertebral analgesia is frequently used. In this narrative review, we provide a comprehensive overview of the available evidence for the different analgesia regimens for esophagectomy., Methods: A search was conducted in the PubMed/MEDLINE database in November 2022. Only reports in English or Dutch were included. Editorials or articles lacking full text were excluded. A review of different analgesia regimens after esophagectomy is provided., Key Content and Findings: Epidural analgesia (EA) was suggested to reduce postoperative pneumonia and prevent chronic postsurgical pain (CPSP) as compared to opioid-based systemic analgesia and was considered the gold standard of pain management for esophagectomy. In the last decades, the side-effects of EA became more evident. Next to mild or moderate side-effects such as hypotension and urinary retention, several reports emphasized the incidence of serious neurologic complications to be much higher than estimated before. In addition, minimally invasive surgery fostered that other regional analgesia (RA) techniques are potential alternatives for EA. Paravertebral catheter placement can be performed under videoscope view during the thoracic phase of esophagectomy, making it a safe and easily placed block. Evidence on the effectiveness of erector spinae plane block (ESPB) is limited in this context., Conclusions: Several analgesia regimens after esophagectomy are described. EA is most common, however paravertebral analgesia is a good alternative. Other techniques are also gaining ground but randomized clinical trials are lacking. Future studies should focus on the efficacy of paravertebral and erector spinae blocks for postoperative pain management for esophagectomy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-241/coif). MLF, JH and WJE report funding from ZonMW for the PEPMEN trial. MIvBH is consultant for Viatris, Johnson & Johnson, Alesi Surgical, Bbraun and Medtronic, and received unrestricted research grants from Stryker. He also received a research grant from ZonMWfor the PEPMEN trial. All fees paid to institution. MWH has no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

This study evaluated the effect of adductor canal block (ACB) versus femoral nerve block (FNB) on readiness for discharge in patients undergoing outpatient anterior cruciate ligament (ACL) reconstruction. We hypothesized that ACB would provide sufficient pain relief while maintaining motor strength and safety, thus allowing for earlier discharge. This was a randomized, multi-center, superiority trial. From March 2014 to July 2017, patients undergoing ACL reconstruction were enrolled. The primary outcome was the difference in readiness for discharge, defined as Post-Anesthetic Discharge Scoring System score ≥ 9. Twenty-six patients were allocated to FNB and twenty-seven to ACB. No difference in readiness for discharge was found (FNB median 1.8 (95% CI 1.0 to 3.5) vs. ACB 2.9 (1.5 to 4.7) hours, p = 0.3). Motor blocks and (near) falls were more frequently reported in patients with FNB vs. ACB (20 (76.9%) vs. 1 (3.7%), p < 0.001, and 7 (29.2%) vs. 1 (4.0%), p = 0.023. However, less opioids were consumed in the post-anesthesia care unit for FNB (median 3 [0, 21] vs. 15 [12, 42.5] oral morphine milligram equivalents, p = 0.004) for ACB. Between patients with FNB or ACB, no difference concerning readiness for discharge was found. Despite a slight reduction in opioid consumption immediately after surgery, FNB demonstrates a less favorable safety profile compared to ACB, with more motor blocks and (near) falls.

Objective: To study ICU trials published in the four highest-impact general medicine journals by comparing them with concurrently published non-ICU trials in the same journals., Data Sources: PubMed was searched for randomized controlled trials (RCTs) published between January 2014 and October 2021 in the New England Journal of Medicine , The Lancet , the Journal of the American Medical Association , and the British Medical Journal., Study Selection: Original RCT publications investigating any type of intervention in any patient population., Data Extraction: ICU RCTs were defined as RCTs exclusively including patients admitted to the ICU. Year and journal of publication, sample size, study design, funding source, study outcome, type of intervention, Fragility Index (FI), and Fragility Quotient were collected., Data Synthesis: A total of 2,770 publications were screened. Of 2,431 original RCTs, 132 (5.4%) were ICU RCTs, gradually rising from 4% in 2014 to 7.5% in 2021. ICU RCTs and non-ICU RCTs included a comparable number of patients (634 vs 584, p = 0.528). Notable differences for ICU RCTs were the low occurrence of commercial funding (5% vs 36%, p < 0.001), the low number of RCTs that reached statistical significance (29% vs 65%, p < 0.001), and the low FI when they did reach significance (3 vs 12, p = 0.008)., Conclusions: In the last 8 years, RCTs in ICU medicine made up a meaningful, and growing, portion of RCTs published in high-impact general medicine journals. In comparison with concurrently published RCTs in non-ICU disciplines, statistical significance was rare and often hinged on the outcome events of just a few patients. Increased attention should be paid to realistic expectations of treatment effects when designing ICU RCTs to detect differences in treatment effects that are reliable and clinically relevant., Competing Interests: Dr. Hollmann’s institution received funding from International Drug Development Pharma and Medical Development; he received funding as Executive Section Editor of Pharmacology with Anesthesia and Analgesia. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: Pain management during a vaso-occlusive crisis (VOC) for patients with sickle cell disease (SCD) remains a major challenge and strongly depends on opioids. We developed a multimodality pain protocol for rapid, opioid-sparing pain treatment of VOC and evaluated its feasibility., Methods: Patients were included for evaluation if they were ≥18 years, diagnosed with SCD and visited the emergency department (ED) because of VOC between July 2018 and December 2020. Primary evaluation outcome was the feasibility of multimodal pain analgesia (i.e., the use of at least two analgesics with different underlying mechanisms of action)., Results: A total of 131 SCD patients visited the ED because of VOC with a total of 550 ED presentations, of which 377 were eventually hospitalised. A total of 508 (92.4%) ED presentations and 374 (99.2%) hospital admissions received multimodal pain treatment. Time to first administration of an opioid was median [IQR] 34.0 [21.0-62.0] minutes., Conclusion: The implementation of a pain protocol using multimodal analgesia for VOC in patients with SCD appeared to be feasible and facilitated rapid administration of opioids. Controlled trials are needed to investigate the effectiveness of multimodal analgesia on pain and should focus on patient reported outcome measures., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: The appropriate management of a "difficult airway" remains a challenge for novices and experienced anaesthetists. With the current available airway technologies, e.g., video laryngoscopy, flexible bronchoscopy (fibreoptic intubation (FOI)) for endotracheal intubation is decreasing, likely diminishing caregiver skills. We investigated whether bronchoscopy simulator training improved FOI skills., Methods: 72 volunteers, consisting of anaesthetists, anaesthesia residents, and nurses, performed six exercises on a bronchoscopy simulator. At baseline and after 12 months, the six exercises included one serious game (to train agility), two basic airways, and three difficult airways. After a baseline assessment, subjects were randomly allocated to the intervention group (with) or control group without bronchoscopy simulator training every six weeks for 10 min using a preloaded serious game. The primary outcome was the difference in the time to reach the carina after 12 months, as measured objectively by the simulator. The level of stress and FOI confidence after 12 months were secondary outcomes., Results: The control and intervention groups had a similar time to reach the carina in difficult airway cases and the reported stress levels, at baseline and 12 months, showed no difference. In contrast, the intervention group's self-reported confidence in FOI skills improved more., Conclusions: Although participants rated higher in confidence, practicing FOI skills on an airway simulator with an agility game did not increase their performance in simulated challenging airway instances.

The prevalence of diabetes is increasing, and patients with diabetes mellitus have both an increased likelihood of requiring surgery and of developing postoperative complications when they do. We summarise available evidence underpinning current guidelines on preoperative assessment and optimisation, perioperative management of prescribed insulin and oral hypoglycaemic medication, intraoperative glycaemic control, and postoperative patient care., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Whether the fascia iliaca compartment block (FICB) involves the obturator nerve (ON) remains controversial. Involvement may require that the injectate spreads deep in the cranial direction, and might thus depend on the site of injection. Therefore, the effect of suprainguinal needle insertion with five centimeters of hydrodissection-mediated needle advancement (S-FICB-H) on ON involvement and cranial injectate spread was studied in this radiological cadaveric study. Results were compared with suprainguinal FICB without additional hydrodissection-mediated needle advancement (S-FICB), infrainguinal FICB (I-FICB), and femoral nerve block (FNB). Seventeen human cadavers were randomized to receive ultrasound-guided nerve block with a 40 mL solution of local anesthetic and contrast medium, on both sides. Injectate spread was objectified using computed tomography. The femoral and lateral femoral cutaneous nerves were consistently covered when S-FICB-H, S-FICB or FNB was applied, while the ON was involved in only one of the 34 nerve blocks. I-FICB failed to provide the same consistency of nerve involvement as S-FICB-H, S-FICB or FNB. Injectate reached most cranial in specimens treated with S-FICB-H. Our results demonstrate that even the technique with the most extensive cranial spread (S-FICB-H) does not lead to ON involvement and as such, the ON seems unrelated to FICB. Separate ON block should be considered when clinically indicated., (© 2023. The Author(s).)

Diabetes mellitus is often treated as a uniform disease in the perioperative period. Type 2 diabetes is most commonly encountered, and only a minority of surgical patients have been diagnosed with another type of diabetes. Patients with a specific type of diabetes can be particularly prone to perioperative glycaemic dysregulation. In addition, certain type-related features and pitfalls should be taken into account in the operating theatre. In this narrative review, we discuss characteristics of types of diabetes other than type 2 diabetes relevant to the anaesthetist, based on available literature and data from our clinic., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert van Wilpe reports a relationship with European Society of Anaesthesiology that includes: funding grants. Abraham H. Hulst reports a relationship with Novo Nordisk that includes: funding grants. Abraham H. Hulst reports a relationship with European Society of Anaesthesiology that includes: funding grants. Abraham H. Hulst reports a relationship with Netherlands Organisation for Health Research and Development that includes: funding grants. Benedikt Preckel reports a relationship with GE Healthcare that includes: funding grants. Benedikt Preckel reports a relationship with Air Liquide SA that includes: funding grants. Benedikt Preckel reports a relationship with Novo Nordisk that includes: funding grants. Benedikt Preckel reports a relationship with Society of Cardiovascular Anesthesiologists that includes: funding grants. Benedikt Preckel reports a relationship with European Society of Anaesthesiology that includes: funding grants. Benedikt Preckel reports a relationship with Netherlands Organisation for Health Research and Development that includes: funding grants. Benedikt Preckel reports a relationship with Laboratoire Aguettant SAS that includes: board membership. Benedikt Preckel reports a relationship with Sensium Healthcare that includes: board membership. Jeroen Hermanides reports a relationship with Novo Nordisk Inc. that includes: funding grants. Jeroen Hermanides reports a relationship with European Society of Anaesthesiology that includes: funding grants. Jeroen Hermanides reports a relationship with Netherlands Organisation for Health Research and Development that includes: funding grants., (Copyright © 2022. Published by Elsevier Inc.)

Chronic postsurgical pain develops in 10% of patients undergoing surgery. Recently, multidisciplinary, patient-tailored interventions, such as a Transitional Pain Service (TPS) have been developed and implemented to improve perioperative pain management and thereby prevent chronic postsurgical pain. The purpose of this survey was to analyse health care providers satisfaction and learn from their experiences on the implementation of a TPS. In the TRUST study, a randomized controlled trial investigating the effectiveness of a TPS, 176 patients were enrolled. Afterwards, a satisfaction survey was internally developed, which consisted of eight items. Satisfaction was measured using a Likert scale with five response options from never (1 point) to always (5 points). Surveys were sent to all anaesthetists and anaesthesia residents in our department that were faced with the consequences of TPS implementation. In May 2022, 36 caregivers of the Department of Anaesthesiology returned the survey after four rounds of distribution, with a response rate of 82.3%. Thirty staff members (81.0%) strongly felt that patient care had improved with the introduction of a TPS and 33 (86.8%) would like to see the TPS to be continued in the future. Health care provider satisfaction improved after implementation of a TPS in our hospital.

Background: Cerebral autoregulation (CA) continuously adjusts cerebrovascular resistance to maintain cerebral blood flow (CBF) constant despite changes in blood pressure. Also, CBF is proportional to changes in arterial carbon dioxide (CO 2 ) (cerebrovascular CO 2 reactivity). Hypercapnia elicits cerebral vasodilation that attenuates CA efficacy, while hypocapnia produces cerebral vasoconstriction that enhances CA efficacy. In this study, we quantified the influence of sevoflurane anesthesia on CO 2 reactivity and the CA-CO 2 relationship., Methods: We studied patients with type 2 diabetes mellitus (DM), prone to cerebrovascular disease, and compared them to control subjects. In 33 patients (19 DM, 14 control), end-tidal CO 2 , blood pressure, and CBF velocity were monitored awake and during sevoflurane-based anesthesia. CA, calculated with transfer function analysis assessing phase lead (degrees) between low-frequency oscillations in CBF velocity and mean arterial blood pressure, was quantified during hypocapnia, normocapnia, and hypercapnia., Results: In both control and DM patients, awake CO 2 reactivity was smaller (2.8%/mm Hg CO 2 ) than during sevoflurane anesthesia (3.9%/mm Hg; P <0.005). Hyperventilation increased CA efficacy more (3 deg./mm Hg CO 2 ) in controls than in DM patients (1.8 deg./mm Hg CO 2 ; P <0.001) in both awake and sevoflurane-anesthetized states., Conclusions: The CA-CO 2 relationship is impaired in awake patients with type 2 DM. Sevoflurane-based anesthesia does not further impair this relationship. In patients with DM, hypocapnia induces cerebral vasoconstriction, but CA efficacy does not improve as observed in healthy subjects., Competing Interests: B.J.P.v.d.S. is supported by an educational grant from Edwards Lifesciences (2010B0797). J.H. has received an investigator-initiated study grant from Novo Nordisk, a project grant from the European Society of Anaesthesiology , and a MarieCurie individual fellowship grant from H2020 EU programme. M.W.H. is Executive Section Editor Pharmacology with Anaesthesia & Analgesia and has provided consultancy for BBraun, Baxter, Fresenius, CSL Behring, Eurocept, ECHO Pharmaceuticals, and MSD. B.P. has received research funding from GE Healthcare, Edwards Lifesciences, Air Liquide France, and Novo Nordisk Netherlands. He is part of an advisory board for Laboratoire Aguettant, France, and has received lecture fees from Abbvie, The Netherlands and Orion Pharma BVBA, The Netherlands, as well as research grants from SCA, ESA, and ZonMW. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Delayed neurocognitive recovery (DNR; neurocognitive disorder up to 30 days postoperative) and postoperative neurocognitive disorders (POCD; neurocognitive disorder 1-12 months postoperative) occur frequently after surgery, with diabetes mellitus (DM) suggested to contribute to this. This was a single-center prospective cohort study. The main aim of this study was to investigate the role of DM and preoperative hemoglobin A1c (HbA1c) in the development of POCDs after noncardiac surgery., Methods: Older adult patients ≥65 years of age scheduled for elective surgery were recruited. The Modified Telephone Interview for Cognitive Status questionnaire (TICS-M), a test of global cognitive functioning, was administered to determine cognition. Preoperative, 30-day postoperative, and 6-month postoperative cognition were compared for patients with and without DM. Cognitive decline was subdivided into mild (1 to 2 standard deviations below controls) and major (≥2 standard deviations below controls) DNR or POCD. Preoperative HbA1c levels were correlated with TICS-M scores., Results: We analyzed 102 patients [median (IQR [range]) age 72.0 (5 [68-74])]), who were divided into patients with DM (80 patients [78%]) and patients without DM (22 patients [22%]). Baseline cognitive function was similar for both groups. Repeated measures ANOVA showed that mean DM patient TICS-M scores decreased 30 days postoperative (F(2, 200) = 4.0, p = 0.02), with subsequent recovery 6-month postoperative, compared to stable TICS-M scores in non-DM patients. There were significantly more DM patients with DNR than non-DM patients (n = 11 [50%] vs. n = 14 [17.5%]; p = 0.031). There were no between-group differences in mild or major POCD. Higher preoperative HbA1c levels were significantly correlated with decreased 30-day Δcognition scores (F(1, 54) = 9.4, p = 0.003) with an R2 of 0.149 (β -0.45, 95% confidence interval: -0.735 to -0.154)., Conclusions: Older adult patients with DM undergoing surgery have an increased risk of DNR compared to older adult non-DM patients, but no increased risk of POCD. In DM patients, higher preoperative HbA1c levels were associated with an increased risk of DNR., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Study Objective: Rising patient numbers, with increasing complexity, challenge the sustainability of the current preoperative process. We evaluated whether an electronic screening application can distinguish patients that need a preoperative consultation from low-risk patients that can be first seen on the day of surgery., Design: Prospective cohort study., Setting: Preoperative clinic of a tertiary academic hospital., Patients: 1395 adult patients scheduled for surgery or procedural sedation., Interventions: We assessed a novel electronic preoperative screening application which consists of a questionnaire with a maximum of 185 questions regarding the patient's medical history and current state of health. The application provides an extensive health report, including an American Society of Anesthesiologists physical status (ASA-PS) classification and a recommendation for either consultation by an anesthesiologist at the preoperative clinic or approval for screening on the day of surgery., Measurements: The recommendation of the electronic screening system was compared with the regular preoperative assessment using measures of diagnostic accuracy and agreement. Secondary outcomes included ASA-PS classification, patient satisfaction, and the anesthesiologists' opinion on the completeness and quality of the screening report., Results: Sensitivity to detect patients who needed additional consultation was 97.5% (95%CI 91.2-99.7) and the negative likelihood ratio was 0.08 (95%CI 0.02-0.32). 407 (29.2%) patients were approved for surgery by both electronic screening and anesthesiologist. In 909 (65.2%) cases, the electronic screening system recommended further consultation while the anesthesiologist approved the patient (specificity 30.9% (95%CI 28.4-33.5); poor level of agreement (ĸ = 0.04)). Agreement regarding ASA-PS classification scores was weak (ĸ = 0.48). The majority of patients (78.0%) felt positive about electronic screening replacing the regular preoperative assessment., Conclusions: Electronic screening can reliably identify patients who can have their first contact with an anesthesiologist on the day of surgery, potentially allowing a major proportion of patients to safely bypass the preoperative clinic., Competing Interests: Declaration of Competing Interest The authors declare no conflicting interests. E-POS® software was provided free of charge by Novacair (Leiden, the Netherlands), and the CEO of Novacair is staff anesthesiologist in the same institution as the authors. Novacair had no role in the design, conduct, analysis, and interpretation of the study, or the decision to publish., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine whether the statistical fragility of randomized controlled trials (RCTs) in high-impact journals has improved in the last decade and to perform an umbrella review of all published data on the Fragility Index (FI) across medical specialties., Study Design and Setting: The FI was calculated for all eligible RCTs published from 2014-2021 in the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, the British Medical Journal, and the Annals of Internal Medicine. Trials reporting dichotomous, statistically significant, superiority results were eligible. All previously published systematic reviews on the FI were included in the umbrella review and analyzed by medical (sub) specialty., Results: Of 2,544 screened RCTs, 643 were eligible for the FI analysis. These had a median sample size of 625 (interquartile range [IQR]: 265-2,056), a median FI of 12 (IQR: 3-28), and a median Fragility Quotient of 0.015 (IQR: 0.004-0.045). This is an improvement compared with the median FI of 8 (IQR: 3-18) of RCTs published a decade earlier in the same five journals (P < 0.001). The umbrella review included 57 publications across 15 different medical specialties, with a total of between 10 and 692 RCTs for each specialty. The median FI ranged between two and four for all disciplines., Conclusion: In the last decade, the median statistical robustness of RCTs published in high-impact journals has improved, yet the unchanged lower bound of the interquartile range reveals that statistical significance in 25% of trials is still dependent on three or less events. The umbrella review revealed that statistical fragility is prevalent across all medical specialties. The FI is an easy-to-understand metric that can be used to supplement reported P values and help readers look beyond merely reaching statistical significance., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Early oral postoperative nutrition is a proven beneficial element of postoperative care, resulting in improvement in quality of life and a shorter hospital stay. Guidelines state that postoperative oral nutrition can safely be started within the first hours after surgery. However, oral nutrition is mainly investigated starting from postoperative day one (POD1). This pragmatic study assessed whether a food service in the Post Anaesthesia Care Unit (PACU) may reduce postoperative fasting times on postoperative day zero (POD0) early after surgery on this high care unit. The primary outcome was postoperative fasting time in the PACU. Secondary outcomes were postoperative patient experiences and nutritional tolerance., Methods: This pragmatic prospective before-after study, included adult patients with a planned overnight stay in the PACU, and without anticipated postoperative dietary restrictions. A food service was developed, allowing re-uptake of oral nutrition early after surgery, already at POD0. Postoperative fasting time in the PACU was defined as the duration of time between the moment of arrival at the PACU, until first postoperative intake or until 9 a.m. on POD1, when most patients were discharged to the surgical ward. Secondary outcomes such as postoperative patient experiences and nutritional tolerance were scored on POD0 at 8 p.m. and on POD1 at 8 a.m., Results: A total of 235 patients were included, 119 in the pre-implementation (control) and 116 in the post-implementation (intervention) group. Mean postoperative fasting time was reduced by a mean of 6.0 h (95% CI 4.8-7.4, p-value ≤ .001), from 17.5 h in controls to 11.5 h in the intervention group. In the intervention group, 45% of patients had nutritional intake on POD0 (8 p.m.), increasing to 80% of patients on POD1 (8 a.m.), compared to no intake at both time-points in the control group. In the intervention group, average patient satisfaction increased over time. Flatus frequency was higher in the intervention group on POD1 (45% vs. 22%, p-value ≤ .001), while postoperative nausea and/or vomiting, and usage of anti-emetic medication were not different between groups., Conclusions: In a heterogeneous group of adult post-surgical patients with a planned overnight stay in the PACU, implementation of a food service resulted in a significant and clinically relevant reduction of postoperative fasting time, and increased patient satisfaction without compromising nutritional tolerance. Registered at www.isrctn.org with study ID ISRCTN17976930., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Dysglycaemia complicates most critical care admissions and is associated with harm, yet glucose targets, particularly in those with preexisting diabetes, remain controversial. This review will summarise advances in the literature regarding personalised glucose targets in the critically ill., Recent Findings: Observational data suggest that the degree of chronic hyperglycaemia in critically ill patients with diabetes attenuates the relationship between mortality and several metrics of dysglycaemia, including blood glucose on admission, and mean blood glucose, glycaemic variability and hypoglycaemia in the intensive care unit. The interaction between acute and chronic hyperglycaemia has recently been quantified with novel metrics of relative glycaemia including the glycaemic gap and stress hyperglycaemia ratio. Small pilot studies provided preliminary data that higher blood glucose thresholds in critically ill patients with chronic hyperglycaemia may reduce complications of intravenous insulin therapy as assessed with biomakers. Although personalising glycaemic targets based on preexisting metabolic state is an appealing concept, the recently published CONTROLLING trial did not identify a mortality benefit with individualised glucose targets, and the effect of personalised glucose targets on patient-centred outcomes remains unknown., Summary: There is inadequate data to support adoption of personalised glucose targets into care of critically ill patients. However, there is a strong rationale empowering future trials utilising such an approach for patients with chronic hyperglycaemia., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Sodium glucose co-transporter 2 inhibitors (SGLT-2is) improve cardiovascular outcomes in both diabetic and non-diabetic patients. Preclinical studies suggest that SGLT-2is directly affect endothelial function in a glucose-independent manner. The effects of SGLT-2is include decreased oxidative stress and inflammatory reactions in endothelial cells. Furthermore, SGLT2is restore endothelium-related vasodilation and regulate angiogenesis. The favourable cardiovascular effects of SGLT-2is could be mediated via a number of pathways: (1) inhibition of the overactive sodium-hydrogen exchanger; (2) decreased expression of nicotinamide adenine dinucleotide phosphate oxidases; (3) alleviation of mitochondrial injury; (4) suppression of inflammation-related signalling pathways (e.g., by affecting NF-κB); (5) modulation of glycolysis; and (6) recovery of impaired NO bioavailability. This review focuses on the most recent progress and existing gaps in preclinical investigations concerning the direct effects of SGLT-2is on endothelial dysfunction and the mechanisms underlying such effects., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aims/hypothesis: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations., Methods: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels., Results: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels., Conclusions/interpretation: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities., (© 2022. The Author(s).)

Inflammation causing oxidative stress in endothelial cells contributes to heart failure development. Sodium/glucose cotransporter 2 inhibitors (SGLT2i's) were shown to reduce heart failure hospitalization and oxidative stress. However, how inflammation causes oxidative stress in endothelial cells, and how SGLT2i's can reduce this is unknown. Here we hypothesized that 1) TNF-α activates the Na + /H + exchanger (NHE) and raises cytoplasmatic Na + ([Na + ] c ), 2) increased [Na + ] c causes reactive oxygen species (ROS) production, and 3) empagliflozin (EMPA) reduces inflammation-induced ROS through NHE inhibition and lowering of [Na + ] c in human endothelial cells. Human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) were incubated with vehicle (V), 10 ng/ml TNF-α, 1 µM EMPA or the NHE inhibitor Cariporide (CARI, 10 µM) and NHE activity, intracellular [Na + ] c and ROS were analyzed. TNF-α enhanced NHE activity in HCAECs and HUVECs by 92% (p < 0.01) and 51% (p < 0.05), respectively, and increased [Na + ] c from 8.2 ± 1.6 to 11.2 ± 0.1 mM (p < 0.05) in HCAECs. Increasing [Na + ] c by ouabain elevated ROS generation in both HCAECs and HUVECs. EMPA inhibited NHE activity in HCAECs and in HUVECs. EMPA concomitantly lowered [Na + ] c in both cell types. In both cell types, TNF α-induced ROS was lowered by EMPA or CARI, with no further ROS lowering by EMPA in the presence of CARI, indicating EMPA attenuated ROS through NHE inhibition. In conclusion, inflammation induces oxidative stress in human endothelial cells through NHE activation causing elevations in [Na + ] c , a process that is inhibited by EMPA through NHE inhibition., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and 18F-FDG transport into the brain (K1) and its phosphorylation (k3). We calculated oxygen metabolism, 18F-FDG influx rate constant (Ki), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k3 hotspot regions were compared with plasma and microdialysis glucose in patients. Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined 18F-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2-5, and Days 6-12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent 18F-FDG PET. Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K1 were decreased in the vicinity of lesions, and closely related when blood flow was <25 ml/100 ml/min. Within normal-appearing brain, K1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P < 0.001). k3 was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k3 hotspots were found distant from lesions, with k3 increases associated with lower plasma glucose (Rho -0.33, P < 0.001) and microdialysis glucose (Rho -0.73, P = 0.02). k3 hotspots showed similar K1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P < 0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon. We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)