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Background: Risk prediction models are used for many purposes in emergency surgery, including critical care triage and benchmarking. Several risk prediction models have been developed, and some are used for purposes other than those for which they were developed. We aim to provide an overview of the existing literature on risk prediction models used in emergency surgery and highlight knowledge gaps., Methods: We will conduct a scoping review on risk prediction models used for patients undergoing emergency surgery in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We will search Medline, EMBASE, and the Cochrane Library and include all study designs. We aim to answer the following questions: (1) What risk prediction models are used in emergency surgery? (2) Which variables are used in these models? (3) Which surgical specialties are the models used for? (4) Have the models been externally validated? (5) Where have the models been externally validated? (6) What purposes were the models developed for? (7) What are the strengths and limitations of the included models? We will summarize the results descriptively. The certainty of evidence will be evaluated using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Conclusion: The outlined scoping review will summarize the existing literature on risk prediction models used in emergency surgery and highlight knowledge gaps., (© 2024 Acta Anaesthesiologica Scandinavica Foundation.)

Risk prediction models are frequently used to identify high-risk patients undergoing emergency laparotomy. The National Emergency Laparotomy Audit (NELA) developed a risk prediction model specifically for emergency laparotomy patients, which was recently updated. In this study, we validated the updated NELA model in an external population. Furthermore, we compared it with three other risk prediction models: the original NELA model, the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) model, and the American Society of Anesthesiologists Physical Status (ASA-PS). We included adult patients undergoing emergency laparotomy at Zealand University Hospital, from March 2017 to January 2019, and Herlev Hospital, from November 2017 to January 2020. Variables included in the risk prediction models were collected retrospectively from the electronic patient records. Discrimination of the risk prediction models was evaluated with area under the curve (AUC) statistics, and calibration was assessed with Cox calibration regression. The primary outcome was 30-day mortality. Out of 1226 included patients, 146 patients (11.9%) died within 30 days. AUC (95% confidence interval) for 30-day mortality was 0.85 (0.82-0.88) for the updated NELA model, 0.84 (0.81-0.87) for the original NELA model, 0.81 (0.77-0.84) for the P-POSSUM model, and 0.76 (0.72-0.79) for the ASA-PS model. Calibration showed underestimation of mortality risk for both the updated NELA, original NELA and P-POSSUM models. The updated NELA risk prediction model performs well in this external validation study and may be used in similar settings. However, the model should only be used to discriminate between low- and high-risk patients, and not for prediction of individual risk due to underestimation of mortality., (© 2023 Acta Anaesthesiologica Scandinavica Foundation.)

Background: Hyperoxia and oxidative stress may be associated with increased risk of myocardial injury. The authors hypothesized that a perioperative inspiratory oxygen fraction of 0.80 versus 0.30 would increase the degree of myocardial injury within the first 3 days of surgery, and that an antioxidant intervention would reduce degree of myocardial injury versus placebo., Methods: A 2 × 2 factorial, randomized, blinded, multicenter trial enrolled patients older than 45 yr who had cardiovascular risk factors undergoing major noncardiac surgery. Factorial randomization allocated patients to one of two oxygen interventions from intubation and at 2 h after surgery, as well as antioxidant intervention or matching placebo. Antioxidants were 3 g IV vitamin C and 100 mg/kg N-acetylcysteine. The primary outcome was the degree of myocardial injury assessed by the area under the curve for high-sensitive troponin within the first 3 postoperative days., Results: The authors randomized 600 participants from April 2018 to January 2020 and analyzed 576 patients for the primary outcome. Baseline and intraoperative characteristics did not differ between groups. The primary outcome was 35 ng · day/l (19 to 58) in the 80% oxygen group; 35 ng · day/l (17 to 56) in the 30% oxygen group; 35 ng · day/l (19 to 54) in the antioxidants group; and 33 ng · day/l (18 to 57) in the placebo group. The median difference between oxygen groups was 1.5 ng · day/l (95% CI, -2.5 to 5.3; P = 0.202) and -0.5 ng · day/l (95% CI, -4.5 to 3.0; P = 0.228) between antioxidant groups. Mortality at 30 days occurred in 9 of 576 patients (1.6%; odds ratio, 2.01 [95% CI, 0.50 to 8.1]; P = 0.329 for the 80% vs. 30% oxygen groups; and odds ratio, 0.79 [95% CI, 0.214 to 2.99]; P = 0.732 for the antioxidants vs. placebo groups)., Conclusions: Perioperative interventions with high inspiratory oxygen fraction and antioxidants did not change the degree of myocardial injury within the first 3 days of surgery. This implies safety with 80% oxygen and no cardiovascular benefits of vitamin C and N-acetylcysteine in major noncardiac surgery., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Purpose: The optimal timing for laparoscopic cholecystectomy for acute cholecystitis (AC) has not been resolved. In the revised Tokyo Guidelines from 2018 (TG18), early laparoscopic cholecystectomy (ELC) is recommended regardless of the duration of symptoms. The aim of this study was to evaluate the safety of ELC compared with delayed laparoscopic cholecystectomy (DLC) for AC. In addition, we assessed the perioperative outcomes after ELC based on duration of symptoms., Methods: A retrospective cohort study of patients operated for acute calculous cholecystitis from January 1, 2017, to June 30, 2018, at Copenhagen University Hospital, Herlev. ELC was divided into three subgroups based on the duration of symptoms from onset to operation, ≤ 72 h, > 72-120 h, > 120 h., Results: Two hundred twenty-two patients underwent ELC and 26 (10.5%) patients underwent DLC. We found no difference in mortality, morbidity, conversion rate, or bile duct injuries between DLC and ELC or in the subgroups based on duration of symptoms. We found significantly longer total hospital length of stay for patients with symptoms > 72 h (4.1-5.6 days) compared to ≤ 72 h (3.1 days) and the longest in DLC (9.9 days). Twenty-three percent of DLC needed an emergency operation in the waiting period with a high conversion rate (1/3)., Conclusion: ELC for AC even beyond 5 days of symptoms is safe and not associated with increased complications. The duration of symptoms in AC is not an independent predictor and should not influence the surgeonsmsdecision to perform an ELC. Delaying cholecystectomy has a high failure rate., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacokinetics, and pharmacodynamics of LKYN in humans have not been previously investigated. In an open-label, single ascending dose study, six participants received an intravenous infusion of 50, 100, and 150 µg/kg LKYN and new six participants received an intravenous infusion of 0.3, 0.5, 1, and 5 mg/kg LKYN. To compare the pharmacological effects between species, we investigated in vivo the vascular effects of LKYN in rats. In humans, LKYN was safe and well-tolerated at all dose levels examined. After infusion, LKYN plasma concentration increased significantly over time 3.23 ± 1.12 µg/mL (after 50 µg/kg), 4.04 ± 1.1 µg/mL (after 100 µg/kg), and 5.25 ± 1.01 µg/mL (after 150 µg/kg) (p ≤ 0.001). We observed no vascular changes after infusion compared with baseline. In rats, LKYN had no effect on HR and MAP and caused no dilation of dural and pial arteries. This first-in-human study of LKYN showed that LKYN was safe and well-tolerated after intravenous infusion up to 5 mg/kg over 20 minutes. The lack of change in LKYN metabolites in plasma suggests a relatively slow metabolism of LKYN and no or little feed-back effect of LKYN on its synthesis. The therapeutic potential of LKYN in stroke and epilepsy should be explored in future studies in humans., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Background: The Transient Receptor Potential Ankyrin 1 (TRPA1) channel might play a role in migraine. However, different mechanisms for this have been suggested. The purpose of our study was to investigate the localization and significance of TRPA1 channels in rat pial and dural arteries., Methods: Immunofluorescence microscopy was used to localize TRPA1 channels in dural arteries, pial arteries, dura mater and trigeminal ganglion. The genuine closed cranial window model was used to examine the effect of Na 2 S, a donor of the TRPA1 channel opener H 2 S, on the diameter of pial and dural arteries. Further, we performed blocking experiments with TRPA1 antagonist HC-030031, calcitonin gene-related peptide (CGRP) receptor antagonist olcegepant and K Ca 3.1 channel blocker TRAM-34., Results: TRPA1 channels were localized to the endothelium of both dural and pial arteries and in nerve fibers in dura mater. Further, we found TRPA1 expression in the membrane of trigeminal ganglia neuronal cells, some of them also staining for CGRP. Na 2 S caused dilation of both dural and pial arteries. In dural arteries, this was inhibited by HC-030031 and olcegepant. In pial arteries, the dilation was inhibited by TRAM-34, suggesting involvement of the K Ca 3.1 channel., Conclusion: Na 2 S causes a TRPA1- and CGRP-dependent dilation of dural arteries and a K Ca 3.1 channel-dependent dilation of pial arteries in rats.

Background: Patients undergoing emergency abdominal surgery are at high risk of post-operative complications. Although post-operative treatment at an intermediate care unit may improve early outcome, there is a lack of studies on the long-term effects of such therapy. The aim of this study was to assess the long-term effect of intermediate care versus standard surgical ward care on mortality in the Intermediate Care After Emergency Abdominal Surgery (InCare) trial., Methods: We included adult patients undergoing emergency major laparoscopy or laparotomy with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 10 or more, who participated in the InCare trial from October 2010 to November 2012. In the InCare trial, patients were randomized to either post-operative intermediate care or standard surgical ward care. The primary outcome was time to death within 6 years after surgery. We assessed mortality with Coxregression analysis., Results: A total of 286 patients were included. The all-cause 6-year landmark mortality was 52.8% (76 of 144 patients) in the intermediate care group and 47.9% (68 of 142 patients) in the ward care group. There was no statistically significant difference in mortality risk between the two groups (hazard ratio 1.06 (95% confidence interval 0.76-1.47), P = .73)., Conclusion: We found no statistically significant difference in 6-year mortality between patients randomized to post-operative intermediate care or ward care after emergency abdominal surgery. However, we detected an absolute mortality risk reduction of 5% in favour of ward care, possibly due to random error., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Patients undergoing emergency abdominal surgery are at high risk of morbidity and mortality. Accurate identification of high-risk patients is important. The Acute Physiology and Chronic Health Evaluation (APACHE) II score needs to be validated in a larger heterogeneous population before implementation. We aimed to assess the predictive value of the APACHE II score in emergency abdominal surgical patients. Furthermore, we compared the APACHE II score with the American Society of Anesthesiologists (ASA) physical status score and the Charlson Comorbidity Index (CCI)., Methods: We included adult patients undergoing emergency abdominal surgery screened for enrolment in the InCare trial from October 2010 to November 2012. The APACHE II score was evaluated with area under the receiver operating characteristics curve (AUROC) statistics. The primary outcome was 30-day mortality. Secondary outcomes included 90-day mortality and admission to the intensive care unit., Results: We included a total of 885 patients. All-cause 30-day mortality was 5.0%, 90-day mortality was 8.9%, and a total of 7.9% of the patients were admitted to the intensive care unit. The AUROC (95% confidence interval) of the APACHE II score was 0.72 (0.65-0.80) for 30-day mortality, 0.70 (0.64-0.76) for 90-day mortality and 0.65 (0.59-0.71) for admission to the intensive care unit. The CCI performed better in prediction of 90-day mortality (P = .04). All other results for the ASA score and CCI were comparable with the APACHE II score., Conclusion: The APACHE II score predicted mortality moderately and admission to intensive care unit poorly in emergency abdominal surgical patients., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Transient receptor potential ankyrin 1 (TRPA1) channels may have a role in migraine as some substances known to cause headache activate the channel. In the craniovascular system such activation causes a calcitonin gene-related peptide (CGRP)-dependent increase in meningeal blood flow. TRPA1 channels in the endothelium of cerebral arteries cause vasodilation when activated. The headache preventive substance feverfew inhibits activation of TRPA1 channels. In this study we aim to compare and characterize the effect of the TRPA1 agonist allyl isothiocyanate (AITC) on the diameter of rat dural and pial arteries in vivo., Methods: The genuine closed-cranial window technique in rats was used to examine changes in dural and pial artery diameter and mean arterial blood pressure (MABP) after intracarotid infusion of AITC. Blockade experiments were performed by intravenous infusion of olcegepant, HC-030031, sumatriptan or capsazepine immediately after infusion of AITC, in four different groups of rats., Results: AITC caused a significant dilation of dural arteries, which was inhibited by HC-030031, olcegepant and sumatriptan, but not by capsazepine. In pial arteries AITC caused a significant dilation, which was not inhibited by any of the pre-treatments, suggesting a poor penetration of the blood-brain barrier or autoregulation due to dimethyl sulfoxide (DMSO) mediated decrease in MABP during HC-030031 infusion. AITC did not cause a significant change in MABP., Conclusion: AITC causes dilation of dural arteries via a mechanism dependent on CGRP and TRPA1 that is sensitive to sumatriptan. AITC causes a small but significant dilation of pial arteries., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)