Risk Factors for Surgical Site Infection after Lower Limb Revascularisation Surgery: a Systematic Review and Meta-Analysis of Prognostic Studies.

OBJECTIVE: To systematically review and meta-analyse adjusted risk factors for surgical site infection (SSI) after lower limb revascularisation surgery. DATA SOURCES: MEDLINE, Embase, Evidence Based Medicine Reviews, and the Cochrane Central Register of Controlled Trials (inception to 28 April 2022). REVIEW METHODS: Systematic review and meta-analysis conducted according to PRISMA guidelines. After protocol registration, databases were searched. Studies reporting adjusted risk factors for SSI in adults who underwent lower limb revascularisation surgery for peripheral artery disease were included. Adjusted odds ratios (ORs) were pooled using random effects models. GRADE was used to assess certainty. RESULTS: Among 6 377 citations identified, 50 studies (n = 271 125 patients) were included. The cumulative incidence of SSI was 12 (95% confidence interval [CI] 10 - 13) per 100 patients. Studies reported 139 potential SSI risk factors adjusted for a median of 12 (range 1 - 69) potential confounding factors. Risk factors that increased the pooled adjusted odds of SSI included: female sex (pooled OR 1.41, 95% CI 1.20 - 1.64; high certainty); dependent functional status (pooled OR 1.18, 95% CI 1.03 - 1.35; low certainty); being overweight (pooled OR 1.82, 95% CI 1.29 - 2.56; moderate certainty), obese (pooled OR 2.20, 95% CI 1.44 - 3.36; high certainty), or morbidly obese (pooled OR 1.65, 95% CI 1.08 - 2.52; moderate certainty); chronic obstructive pulmonary disease (pooled OR 1.42, 95% CI 1.17 - 1.71; high certainty); chronic limb threatening ischaemia (pooled OR 1.67, 95% CI 1.22 - 2.29; moderate certainty); chronic kidney disease (pooled OR 2.13, 95% CI 1.18 - 3.83; moderate certainty); intra-operative (pooled OR 1.23, 95% CI 1.02 - 1.49), peri-operative (pooled OR 1.92, 95% CI 1.27 - 2.90), or post-operative (pooled OR 2.21, 95% CI 1.44 - 3.39) blood transfusion (moderate certainty for all); urgent or emergency surgery (pooled OR 2.12, 95% CI 1.22 - 3.70; moderate certainty); vein bypass and or patch instead of endarterectomy alone (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty); an operation lasting ≥ 3 hours (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty) or ≥ 5 hours (pooled OR 1.60, 95% CI 1.18 - 2.17; moderate certainty); and early or unplanned re-operation (pooled OR 4.50, 95% CI 2.18 - 9.32; low certainty). CONCLUSION: This systematic review identified evidence informed SSI risk factors following lower limb revascularisation surgery. These may be used to develop improved SSI risk prediction tools and to identify patients who may benefit from evidence informed SSI prevention strategies.

Prediction Models for Forecasting Risk of Development of Surgical Site Infection after Lower Limb Revascularization Surgery: A Systematic Review.

BACKGROUND: Surgical site infections (SSIs) are a common and potentially preventable complication of lower limb revascularization surgery associated with increased healthcare resource utilization and patient morbidity. We conducted a systematic review to evaluate multivariable prediction models designed to forecast risk of SSI development after these procedures. METHODS: After protocol registration (CRD42022331292), we searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies describing multivariable prediction models designed to forecast risk of SSI in adults after lower limb revascularization surgery. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risk of bias. A narrative synthesis was performed to summarize predictors included in the models and their calibration and discrimination, validation status, and clinical applicability. RESULTS: Among the 6,671 citations identified, we included 5 studies (n = 23,063 patients). The included studies described 5 unique multivariable prediction models generated through forward selection, backward selection, or Akaike Information Criterion-based methods. Two models were designed to predict any SSI and 3 Szyilagyi grade II (extending into subcutaneous tissue) SSI. Across the 5 models, 18 adjusted predictors (10 of which were preoperative, 3 intraoperative, and 5 postoperative) significantly predicted any SSI and 14 adjusted predictors significantly predict Szilagyi grade II SSI. Female sex, obesity, and chronic obstructive pulmonary disease significantly predicted SSI in more than one model. All models had a "good fit" according to the Hosmer-Lemeshow test (P > 0.05). Model discrimination was quantified using the area under the curve, which ranged from 0.66 to 0.75 across models. Two models were internally validated using non-exhaustive twofold cross-validation and bootstrap resampling. No model was externally validated. Three studies had a high overall risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). CONCLUSIONS: Five multivariable prediction models with moderate discrimination have been developed to forecast risk of SSI development after lower limb revascularization surgery. Given the frequency and consequences of SSI after these procedures, development and external validation of novel prediction models and comparison of these models to the existing models evaluated in this systematic review is warranted.

Efficacy of Strategies Intended to Prevent Surgical Site Infection After Lower Limb Revascularization Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The objective of this study is to evaluate the efficacy of strategies intended to prevent surgical site infection (SSI) after lower limb revascularization surgery. BACKGROUND: SSIs are common, costly complications of lower limb revascularization surgery associated with significant morbidity and mortality. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 28, 2022). Two investigators independently screened abstracts and full-text articles, extracted data, and assessed the risk of bias. We included randomized controlled trials (RCTs) that evaluated strategies intended to prevent SSI after lower limb revascularization surgery for peripheral artery disease. We used random-effects models to pool data and GRADE to assess certainty. RESULTS: Among 6258 identified citations, we included 26 RCTs (n=4752 patients) that evaluated 12 strategies to prevent SSI. Preincision antibiotics [risk ratio (RR)=0.25; 95% CI, 0.11-0.57; n=4 studies; I2 statistic=7.1%; high certainty] and incisional negative-pressure wound therapy (iNPWT) (RR=0.54; 95% CI, 0.38-0.78; n=5 studies; I2 statistic=7.2%; high certainty) reduced pooled risk of early (≤30 days) SSI. iNPWT also reduced the risk of longer-term (>30 days) SSI (pooled-RR=0.44; 95% CI, 0.26-0.73; n=2 studies; I2 =0%; low certainty). Strategies with uncertain effects on risk of SSI included preincision ultrasound vein mapping (RR=0.58; 95% CI, 0.33-1.01; n=1 study); transverse groin incisions (RR=0.33; 95% CI, 0.097-1.15; n=1 study), antibiotic-bonded prosthetic bypass grafts (RR=0.74; 95% CI, 0.44-1.25; n=1 study; n=257 patients), and postoperative oxygen administration (RR=0.66; 95% CI, 0.42-1.03; n=1 study) (low certainty for all). CONCLUSIONS: Preincision antibiotics and iNPWT reduce the risk of early SSI after lower limb revascularization surgery. Confirmatory trials are required to determine whether other promising strategies also reduce SSI risk.

Outcomes After Neuraxial or Regional Anaesthesia Instead of General Anaesthesia for Lower Limb Revascularisation Surgery: A Systematic Review and Meta-Analysis of Randomised and Non-Randomised Studies.

OBJECTIVE: To determine whether receipt of neuraxial or regional anaesthesia instead of general anaesthesia for lower limb revascularisation surgery affects patient outcomes. DATA SOURCES: MEDLINE, EMBASE, Evidence Based Medicine Reviews, and Google Scholar. REVIEW METHODS: After protocol registration, the data sources were searched for randomised and non-randomised studies comparing neuraxial or regional anaesthesia with general anaesthesia for lower limb revascularisation surgery in adults. Two investigators independently selected articles, extracted data, and assessed risks of bias. Data were pooled using random effects models. GRADE was used to assess certainty in cumulative evidence. RESULTS: From 10 755 citations identified, five randomised (n = 970) and 13 non-randomised (n = 96 800) studies were included. Use of neuraxial instead of general anaesthesia for lower limb revascularisation surgery was associated with no statistically significant reduction in short term (in hospital or 30 day) mortality in randomised studies (pooled odds ratio [OR] 0.77; 95% confidence interval [CI] 0.33 - 1.81; low certainty) and a statistically significant reduction in adjusted short term mortality in non-randomised studies (pooled OR 0.67; 95% CI 0.56 - 0.81; low certainty). Adults allocated to neuraxial anaesthesia in randomised studies had fewer pulmonary complications (pooled OR 0.35; 95% CI 0.16 - 0.76; low certainty). In non-randomised studies, neuraxial instead of general anaesthesia was associated with a lower adjusted odds of any morbidity (pooled OR 0.66; 95% CI 0.52 - 0.84), cardiac complications (pooled OR 0.68; 95% CI 0.58 - 0.79), pneumonia (pooled OR 0.81; 95% CI 0.64 - 1.02), prolonged mechanical ventilation (OR 0.09; 95% CI 0.002 - 0.55), and bypass graft thrombosis (OR 0.70; 95% CI 0.59 - 0.85), as well as a shorter operative duration (low certainty for all). Use of a nerve block instead of general anaesthesia was associated with a lower adjusted odds of delirium (OR 0.16; 95% CI 0.06 - 0.42) and a shorter operative duration (low certainty for both). CONCLUSION: Randomised and non-randomised data suggest that neuraxial anaesthesia for lower limb revascularisation surgery reduces morbidity and possibly mortality. Until randomised trials with a low risk of bias become available, this study supports use of neuraxial anaesthesia for these procedures where appropriate.

A Meta-Analysis to Derive Population-Based Quality Benchmarks of the Incidence of Surgical Site Infection after Lower Limb Revascularization Surgery.

BACKGROUND: The reported incidence of surgical site infection (SSI) after lower limb revascularization surgery varies. We conducted a systematic review and meta-analysis of population-based studies reporting the incidence of SSI in adults who underwent these surgeries in high-income countries to derive SSI quality benchmarks. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception-to-April 28th, 2022) for population-based studies estimating the cumulative incidence of SSI among adults who underwent lower limb revascularization surgery for peripheral artery disease (PAD) in high-income countries. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risks of bias. We used random-effects models to pool data and GRADE to assess certainty. RESULTS: Among 6,258 citations, we included 53 studies (n = 757,726 patients); 8 of which (n = 435,769 patients) reported nonoverlapping data that were meta-analyzed. The pooled cumulative incidence of any SSI was 6.0 in 100 patients [95% confidence interval (CI) = 4.3-8.0 in 100 patients; n = 8 studies; n = 435,769 patients; moderate certainty]. The cumulative incidence of Szilagyi grade I (cellulitis), grade II (subcutaneous tissue), and grade III (prosthetic graft) SSI was 6.5 in 100 patients (95% CI = 4.3-8.6 in 100 patients; n = 2 studies; n = 39,645 patients; low certainty), 2.1 in 100 patients (95% CI = 2.0-2.3 in 100 patients; n = 2 studies; low certainty), and 0.4 in 100 patients (95% CI = 0.4-0.4 in 100 patients; n = 1 study; n = 333,275 patients; low certainty), respectively. The pooled cumulative incidence of any early (in-hospital/≤30-days) and late (>30-days) SSI was 6.2 in 100 patients (95% CI = 4.4-8.0 in 100 patients; n = 7 studies; n = 431,273 patients; moderate certainty) and 3.7 in 100 patients (95% CI = 2.2-5.2 in 100 patients; n = 2 studies; n = 10,565 patients; low certainty), respectively. CONCLUSIONS: This systematic review derived population-based benchmarks of the incidence of any SSI; Szilagyi I, II, and III SSI; and early and late SSI after lower limb revascularization surgery. These may be used by practicing surgeons and healthcare leaders/administrators to guide quality improvement efforts in the United States and perhaps other countries.

Contraindications to use of neuraxial anesthesia for lower limb revascularization surgery in adults: a cross-sectional study.

PURPOSE: Nonrandomized and some randomized data suggest neuraxial anesthesia may improve outcomes after lower limb revascularization surgery. Nevertheless, the prevalence of contraindications to neuraxial anesthesia in vascular surgery patients is unknown. We aimed to identify the prevalence of patients with contraindications to neuraxial anesthesia, and to derive and validate a case ascertainment algorithm identifying individuals likely to have contraindications. METHODS: We conducted a historical cross-sectional study of open lower limb revascularization surgeries performed between 2019 and 2021 at The Ottawa Hospital. Medical records were reviewed for demographic data, admission, procedural characteristics, and presence of contraindications to neuraxial anesthesia. Case ascertainment algorithms to predict the presence of absolute contraindications to neuraxial anesthesia were derived and internally validated. RESULTS: We identified 340 cases. General anesthesia was used in 219 (64.4%) cases, isolated neuraxial (spinal and/or epidural) in 106 (31.2%) cases, and general plus neuraxial in 15 (4.4%) cases. Seventy-eight (22.9%; 95% confidence interval [CI], 18.8 to 27.7) patients had absolute contraindications to neuraxial anesthesia, primarily because of anticoagulation or antiplatelet medication (89.4%); 21 (6.2%; 95% CI, 4.1 to 9.3) had relative contraindications, primarily long anticipated duration of surgery (16/21, 76.2%). We derived and validated three nested case-ascertainment algorithms. Using admission and procedure variables, discrimination was moderate with moderately explained variance, and calibration was inadequate for reliable use. Patient comorbidity and laboratory data did not improve algorithm performance. CONCLUSION: Most patients undergoing lower limb revascularization surgery did not have absolute contraindications to neuraxial anesthesia. When present, contraindications typically related to anticoagulation. Admission, procedure, comorbidity, and laboratory data did not provide adequate accuracy to ascertain contraindication status.

RéSUMé: OBJECTIF: Les données non randomisées et certaines données randomisées suggèrent que l'anesthésie neuraxiale pourrait améliorer les devenirs après une chirurgie de revascularisation des membres inférieurs. Néanmoins, la prévalence de contre-indications à l'anesthésie neuraxiale chez la patientèle de chirurgie vasculaire est inconnue. Notre objectif était d'identifier la prévalence de la patientèle présentant des contre-indications à l'anesthésie neuraxiale, et de dériver et valider un algorithme de détermination des cas identifiant les personnes susceptibles de présenter des contre-indications. MéTHODE: Nous avons mené une étude transversale historique sur les chirurgies ouvertes de revascularisation des membres inférieurs réalisées entre 2019 et 2021 à l'Hôpital d'Ottawa. Les dossiers médicaux ont été passés en revue pour en tirer les données démographiques, les détails d'admission, les caractéristiques procédurales et la présence de contre-indications à l'anesthésie neuraxiale. Des algorithmes de détermination des cas pour prédire la présence de contre-indications absolues à l'anesthésie neuraxiale ont été dérivés et validés en interne. RéSULTATS: Nous avons identifié 340 cas. L'anesthésie générale a été utilisée dans 219 cas (64,4 %), une anesthésie neuraxiale isolée (rachidienne et/ou péridurale) dans 106 cas (31,2 %) et une anesthésie générale plus neuraxiale dans 15 cas (4,4 %). Soixante-dix-huit (22,9 %; intervalle de confiance [IC] à 95 %, 18,8 à 27,7) patient·es présentaient des contre-indications absolues à l'anesthésie neuraxiale, principalement en raison d'une anticoagulation ou de médicaments antiplaquettaires (89,4 %); 21 (6,2 %; IC 95 %, 4,1 à 9,3) présentaient des contre-indications relatives, principalement une longue durée anticipée de chirurgie (16/21, 76,2 %). Nous avons dérivé et validé trois algorithmes imbriqués de détermination des cas. En utilisant les variables d'admission et de procédure, la discrimination était modérée, avec une variance modérément expliquée, et l'étalonnage était inadéquat pour une utilisation fiable. Les données portant sur les comorbidités des patient·es et de laboratoire n'ont pas amélioré les performances de l'algorithme. CONCLUSION: La plupart des patient·es bénéficiant d'une chirurgie de revascularisation des membres inférieurs n'avaient pas de contre-indications absolues à l'anesthésie neuraxiale. Les contre-indications, lorsque présentes, étaient généralement liées à l'anticoagulation. Les données d'admission, d'intervention, de comorbidité et de laboratoire n'ont pas fourni de précisions suffisantes pour confirmer un statut de contre-indication.

Hospital-, Anesthesiologist-, Surgeon-, and Patient-Level Variations in Neuraxial Anesthesia Use for Lower Limb Revascularization Surgery: A Population-Based Cross-Sectional Study.

BACKGROUND: Although neuraxial anesthesia may promote improved outcomes for patients undergoing lower limb revascularization surgery, its use is decreasing over time. Our objective was to estimate variation in neuraxial (versus general) anesthesia use for lower limb revascularization at the hospital, anesthesiologist, surgeon, and patient levels, which could inform strategies to increase uptake. METHODS: Following protocol registration, we conducted a historical cross-sectional analysis of population-based linked health administrative data in Ontario, Canada. All adults undergoing lower limb revascularization surgery between 2009 and 2018 were identified. Generalized linear models with binomial response distributions, logit links and random intercepts for hospitals, anesthesiologists, and surgeons were used to estimate the variation in neuraxial anesthesia use at the hospital, anesthesiologist, surgeon, and patient levels using variance partition coefficients and median odds ratios. Patient- and hospital-level predictors of neuraxial anesthesia use were identified. RESULTS: We identified 11,849 patients; 3489 (29.4%) received neuraxial anesthesia. The largest proportion of variation was attributable to the hospital level (50.3%), followed by the patient level (35.7%); anesthesiologists and surgeons had small attributable variation (11.3% and 2.8%, respectively). Mean odds ratio estimates suggested that 2 similar patients would experience a 5.7-fold difference in their odds of receiving a neuraxial anesthetic were they randomly sent to 2 different hospitals. Results were consistent in sensitivity analyses, including limiting analysis to patients with diagnosed peripheral artery disease and separately to those aged >66 years with complete prescription anticoagulant and antiplatelet usage data. CONCLUSIONS: Neuraxial anesthesia use primarily varies at the hospital level. Efforts to promote use of neuraxial anesthesia for lower limb revascularization should likely focus on the hospital context.

Structure, processes, and initial outcomes of The Ottawa Hospital Multi-Specialist Limb-Preservation Clinic and Programme: A unique-in-Canada quality improvement initiative.

In 2017, The Ottawa Hospital initiated a unique-in-Canada quality improvement initiative by opening a novel, multi-specialist limb-preservation clinic. We sought to describe the structure, processes, and initial outcomes of the clinic and evaluate whether it is achieving its mandate of providing high-quality wound clinical care, education, and research. We conducted a descriptive prospective cohort study alongside a nested study of 162 clinic patients requiring serial assessments. There have been 1623 visits, mostly (72.2%) from outpatients. During 17.8% of visits, patients were evaluated by >1 specialist. Therapies provided most often included negative-pressure wound therapy (32.7%), biological wound dressings (21.6%), and total contact casting (18.5%). Furthermore, 1.2% underwent toe/ray amputations or skin grafting in clinic and 22.8% were initiated on antimicrobials. Mixed-effects models suggested that mean wound volumes for those requiring serial assessments decreased by 1.6 (95% confidence interval = -0.86 to -2.27) cm3 between visits. The clinic provided seven rotations to vascular surgery, infectious diseases, dermatology, and palliative care physicians; three nursing preceptorships; and two educational workshops. It also initiated provincial and national vascular health and wound care research initiatives. This study may be used to guide development of other limb-preservation clinics and programmes. Findings support that our programme is achieving its mandate.

Angiotensin-Converting Enzyme Inhibitor/Receptor Blocker, Diuretic, or Nonsteroidal Anti-inflammatory Drug Use After Major Surgery and Acute Kidney Injury: A Case-Control Study.

BACKGROUND: Acute kidney injury (AKI) is common after surgery and associated with increased mortality, costs, and lengths of hospitalization. We examined associations between angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), diuretic, or nonsteroidal anti-inflammatory drug (NSAID) use after major surgery and AKI. MATERIALS AND METHODS: We conducted a nested case-control study of patients who underwent major cardiac, thoracic, general, or vascular surgery in Calgary, Alberta, Canada. Cases with AKI were matched on age, gender, and surgery type with up to five controls without AKI within 30-d after surgery. Adjusted odds ratios (ORs) for AKI were determined based on postoperative administration of ACEIs/ARBs, diuretics, or NSAIDs. RESULTS: Among 33,648 patients in the cohort, 2911 cases with AKI were matched to 9309 controls without AKI. Postoperative diuretic [OR = 1.96; 95% confidence interval (CI) = 1.68-2.29], but not ACEI/ARB (OR = 0.83; 95% CI = 0.72-0.95) or NSAID (OR = 1.12; 95% CI = 0.96-1.31), use was independently associated with higher odds of AKI (including stages 1 and 2/3 AKI) after all types of major surgery. There were increased adjusted odds of AKI 1 to 5 d after first exposure to diuretics and 1 d after first exposure to NSAIDs (but not after later exposures). Relationships between ACEI/ARB use and AKI varied by surgery type (p-interaction = 0.004), with lower odds of AKI observed among ACEI/ARB use after cardiac surgery (OR = 0.70; 95% CI = 0.57-0.81), but no difference after other major surgeries. CONCLUSIONS: Postoperative administration of diuretics and NSAIDs was associated with increased odds of AKI after major surgery. These findings characterize potentially modifiable medication exposures associated with AKI after surgery.

S100B as a biomarker of blood-brain barrier disruption after thoracoabdominal aortic aneurysm repair: a secondary analysis from a prospective cohort study.

PURPOSE: The objective of this study was to determine whether the magnitude of the peripheral inflammatory response to cardiovascular surgery is associated with increases in blood-brain barrier (BBB) permeability as reflected by changes in cerebrospinal fluid (CSF)/plasma S100B concentrations. METHODS: We conducted a secondary analysis from a prospective cohort study of 35 patients undergoing elective thoracoabdominal aortic aneurysm repair with (n = 17) or without (n = 18) cardiopulmonary bypass (CPB). Plasma and CSF S100B, interleukin-6 (IL-6), and albumin concentrations were measured at baseline (C0) and serially for up to five days. RESULTS: Following CPB, the median [interquartile range] plasma S100B concentration increased from 58 [32-88] pg·mL-1 at C0 to a maximum concentration (Cmax) of 1,131 [655-1,875] pg·mL-1 over a median time (tmax) of 6.3 [5.9-7.0] hr. In the non-CPB group, the median plasma S100B increased to a lesser extent. There was a delayed increase in CSF S100B to a median Cmax of 436 [406-922] pg·mL-1 in the CPB group at a tmax of 23.7 [18.5-40.2] hr. In the non-CPB group, the CSF concentrations were similar at all time points. In the CPB group, we did not detect significant correlations between plasma and CSF S100B with plasma IL-6 [r = 0.52 (95% confidence interval [CI], -0.061 to 0.84)] and CSF IL-6 [r = 0.53 (95% CI, -0.073 to 0.85)] concentrations, respectively. Correlations of plasma or CSF S100B levels with BBB permeability were not significant. CONCLUSION: The lack of parallel increases in plasma and CSF S100B following CPB indicates that S100B may not be a reliable biomarker for BBB disruption after thoracoabdominal aortic aneurysm repair employing CPB. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00878371); registered 7 April 2009.

RéSUMé: OBJECTIF: L'objectif de cette étude était de déterminer si l'intensité de la réponse inflammatoire périphérique à la chirurgie cardiovasculaire était associée à une augmentation de la perméabilité de la barrière hémato-encéphalique (BHE), telle que reflétée par des changements dans les concentrations de S100B dans le liquide céphalorachidien (LCR) et le plasma. MéTHODE: Nous avons mené une analyse secondaire à partir d'une étude de cohorte prospective portant sur 35 patients bénéficiant d'une réparation élective d'un anévrisme aortique thoraco-abdominal avec (n = 17) ou sans (n = 18) circulation extracorporelle (CEC). Les concentrations plasmatiques et dans le LCR de S100B, d'interleukine-6 (IL-6) et d'albumine ont été mesurées au départ (C0) et en série jusqu'à cinq jours. RéSULTATS: Après la CEC, la concentration médiane [écart interquartile] plasmatique de S100B est passée de 58 [32­88] pg·mL-1 au départ (C0) à une concentration maximale (Cmax) de 1131 [655­1875] pg·mL-1 sur une période médiane (tmax) de 6,3 [5,9­7,0] h. Dans le groupe sans CEC, la concentration plasmatique médiane de S100B a augmenté dans une moindre mesure. Il y a eu une augmentation retardée de S100B dans le LCR à une Cmax médiane de 436 [406­922] pg·mL-1 dans le groupe CEC à une tmax de 23,7 [18,5­40,2] h. Dans le groupe sans CEC, les concentrations dans le LCR étaient similaires à tous les moments. Dans le groupe CEC, nous n'avons pas détecté de corrélations significatives entre la concentration de S100B dans le plasma et le LCR avec les concentrations plasmatiques d'IL-6 [r = 0,52 (intervalle de confiance [IC] à 95 %, -0,061 à 0,84)] et d'IL-6 dans le LCR [r = 0,53 (IC 95 %, -0,073 à 0,85)], respectivement. Les corrélations entre les taux plasmatiques ou dans le LCR de S100B et la perméabilité de la BHE n'étaient pas significatives. CONCLUSION: L'absence d'augmentations parallèles de la concentration de S100B dans le plasma et le LCR après la CEC indique que la S100B pourrait ne pas être un biomarqueur fiable de la perturbation de la BHE après une réparation d'anévrisme aortique thoraco-abdominal sous CEC. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT00878371); enregistrée le 7 avril 2009.

Accuracy of Published Indications for Predicting Use of Damage Control During Laparotomy for Trauma.

BACKGROUND: Although studies have identified published indications that experts and practicing surgeons agree indicate use of damage control (DC) laparotomy, it is unknown whether these indications predict use of the procedure in practice. MATERIALS AND METHODS: We conducted a diagnostic performance study of the accuracy of a set of published appropriateness indications for predicting use of DC laparotomy. We included consecutive adults that underwent emergent laparotomy for trauma (2011-2016) at Memorial Hermann Hospital. RESULTS: We included 1141 injured adults. Two published preoperative appropriateness indications [a systolic blood pressure (BP) persistently <90 mmHg or core body temperature <34°C] produced moderate shifts in the pretest probability of conducting DC instead of definitive laparotomy. Five published intraoperative appropriateness indications produced large and often conclusive changes in the pretest probability of conducting DC during emergent laparotomy. These included the finding of a devascularized or completely disrupted pancreas, duodenum, or pancreaticoduodenal complex; an estimated intraoperative blood loss >4 L; administration of >10 U of packed red blood cells (PRBCs); and a systolic BP persistently <90 mmHg or arterial pH persistently <7.2 during operation. Most indications that produced large changes in the pretest probability of conducting DC laparotomy had an incidence of 2% or less. CONCLUSIONS: This study suggests that published appropriateness indications accurately predict use of DC laparotomy in practice. Intraoperative variables exert greater influence on the decision to conduct DC laparotomy than preoperative variables, and those indications that produce large shifts in the pretest probability of conducting DC laparotomy are uncommonly encountered.

Challenges and potential solutions to the evaluation, monitoring, and regulation of surgical innovations.

BACKGROUND: As it may be argued that many surgical interventions provide obvious patient benefits, formal, staged assessment of the efficacy and safety of surgical procedures has historically been and remains uncommon. The majority of innovative surgical procedures have therefore often been developed based on anatomical and pathophysiological principles in an attempt to better manage clinical problems. MAIN BODY: In this manuscript, we sought to review and contrast the models for pharmaceutical and surgical innovation in North America, including their stages of development and methods of evaluation, monitoring, and regulation. We also aimed to review the present structure of academic surgery, the role of methodological experts and funding in conducting surgical research, and the current system of regulation of innovative surgical procedures. Finally, we highlight the influence that evidence and surgical history, education, training, and culture have on elective and emergency surgical decision-making. The above discussion is used to support the argument that the model used for assessment of innovative pharmaceuticals cannot be applied to that for evaluating surgical innovations. It is also used to support our position that although the evaluation and monitoring of innovative surgical procedures requires a rigorous, fit-for-purpose, and formal system of assessment to protect patient safety and prevent unexpected adverse health outcomes, it will only succeed if it is supported and championed by surgical practice leaders and respects surgical history, education, training, and culture. CONCLUSION: We conclude the above debate by providing a recommended approach to the evaluation, monitoring, and regulation of surgical innovations, which we hope may be used as a guide for all stakeholders involved in interpreting and/or conducting future surgical research.

Weekend Surgical Care and Postoperative Mortality: A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: An association between weekend health care delivery and poor outcomes has become known as the "weekend effect." Evidence for such an association among surgery patients has not previously been synthesized. OBJECTIVE: To systematically review associations between weekend surgical care and postoperative mortality. METHODS: We searched PubMed, EMBASE, and references of relevant articles for studies that compared postoperative mortality either; (1) according to the day of the week of surgery for elective operations, or (2) according to weekend versus weekday admission for urgent/emergent operations. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for postoperative mortality (≤90 d or inpatient mortality) were pooled using random-effects models. RESULTS: Among 4027 citations identified, 10 elective surgery studies and 19 urgent/emergent surgery studies with a total of >6,685,970 and >1,424,316 patients, respectively, met the inclusion criteria. Pooled odds of mortality following elective surgery rose in a graded manner as the day of the week of surgery approached the weekend [Monday OR=1 (reference); Tuesday OR=1.04 (95% CI=0.97-1.11); Wednesday OR=1.08 (95% CI=0.98-1.19); Thursday OR=1.12 (95% CI=1.03-1.22); Friday OR=1.24 (95% CI=1.10-1.38)]. Mortality was also higher among patients who underwent urgent/emergent surgery after admission on the weekend relative to admission on weekdays (OR=1.27; 95% CI=1.08-1.49). CONCLUSIONS: Postoperative mortality rises as the day of the week of elective surgery approaches the weekend, and is higher after admission for urgent/emergent surgery on the weekend compared with weekdays. Future research should focus on clarifying underlying causes of this association and potentially mitigating its impact.

Administrator Perspectives on ICU-to-Ward Transfers and Content Contained in Existing Transfer Tools: a Cross-sectional Survey.

BACKGROUND: The transfer of critically ill patients from the intensive care unit (ICU) to hospital ward is challenging. Shortcomings in the delivery of care for patients transferred from the ICU have been associated with higher healthcare costs and poor satisfaction with care. Little is known about how hospital ward providers, who accept care of these patients, perceive current transfer practices nor which aspects of transfer they perceive as needing improvement. OBJECTIVE: To compare ICU and ward administrator perspectives regarding ICU-to-ward transfer practices and evaluate the content of transfer tools. DESIGN: Cross-sectional survey design. PARTICIPANTS: We administered a survey to 128 medical and/or surgical ICU and 256 ward administrators to obtain institutional perspectives on ICU transfer practices. We performed qualitative content analysis on ICU transfer tools received from respondents. KEY RESULTS: In total, 108 (77%) ICU and 160 (63%) ward administrators responded to the survey. The ICU attending physician was reported to be "primarily responsible" for the safety (93% vs. 91%; p = 0.515) of patient transfers. ICU administrators more commonly perceived discharge summaries to be routinely included in patient transfers than ward administrators (81% vs. 60%; p = 0.006). Both groups identified information provided to patients/families, patient/family participation during transfer, and ICU-ward collaboration as opportunities for improvement. A minority of hospitals used ICU-to-ward transfer tools (11%) of which most (n = 21 unique) were designed to communicate patient information between providers (71%) and comprised six categories of information: demographics, patient clinical course, corrective aids, mobility at discharge, review of systems, and documentation of transfer procedures. CONCLUSION: ICU and ward administrators have similar perspectives of transfer practices and identified patient/family engagement and communication as priorities for improvement. Key information categories exist.

One thousand consecutive in-hospital deaths following severe injury: Has the etiology of traumatic inpatient death changed in Canada?

SUMMARY: A wide range of factors have traditionally led to early in-hospital death following severe injury. The primary goal of this commentary was to evaluate the causes of early posttraumatic inpatient deaths over an extended period. Although early posttraumatic in-hospital death remains multifactorial, severe traumatic brain injuries are the dominant cause and have increased in proportion over time. Other traditional causes of death have also decreased owing to improved clinical care.

History of the Innovation of Damage Control for Management of Trauma Patients: 1902-2016.

OBJECTIVE: To review the history of the innovation of damage control (DC) for management of trauma patients. BACKGROUND: DC is an important development in trauma care that provides a valuable case study in surgical innovation. METHODS: We searched bibliographic databases (1950-2015), conference abstracts (2009-2013), Web sites, textbooks, and bibliographies for articles relating to trauma DC. The innovation of DC was then classified according to the Innovation, Development, Exploration, Assessment, and Long-term study model of surgical innovation. RESULTS: The "innovation" of DC originated from the use of therapeutic liver packing, a practice that had previously been abandoned after World War II because of adverse events. It then "developed" into abbreviated laparotomy using "rapid conservative operative techniques." Subsequent "exploration" resulted in the application of DC to increasingly complex abdominal injuries and thoracic, peripheral vascular, and orthopedic injuries. Increasing use of DC laparotomy was followed by growing reports of postinjury abdominal compartment syndrome and prophylactic use of the open abdomen to prevent intra-abdominal hypertension after DC laparotomy. By the year 2000, DC surgery had been widely adopted and was recommended for use in surgical journals, textbooks, and teaching courses ("assessment" stage of innovation). "Long-term study" of DC is raising questions about whether the procedure should be used more selectively in the context of improving resuscitation practices. CONCLUSIONS: The history of the innovation of DC illustrates how a previously abandoned surgical technique was adapted and readopted in response to an increased understanding of trauma patient physiology and changing injury patterns and trauma resuscitation practices.

An observational study examining the effects of a surgically induced inflammatory response on the distribution of morphine and its metabolites into cerebrospinal fluid.

PURPOSE: Morphine is administered intravenously for pain management in the perioperative period. The effect of the inflammatory response to surgery on morphine distribution across the blood-brain barrier (BBB) in humans was investigated. We hypothesized that a graded surgically induced, systemic inflammatory response alters cerebrospinal fluid (CSF) levels of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a temporary reduction in BBB drug efflux transporter function. METHODS: We conducted a prospective pharmacokinetic study of the plasma and CSF distribution of the P-glycoprotein (PGP) substrate morphine in 33 patients undergoing open thoracic (n = 18) or endovascular (n = 15) aortic aneurysm repair. Morphine was administered with induction of anesthesia and in the intensive care unit. Plasma and CSF concentrations of interleukin (IL)-6, morphine, M3G, M6G, and albumin were measured prior to surgery (baseline), during surgery, and postoperatively every six hours until removal of the CSF drain. The area under the curve (AUC) was determined for plasma and CSF IL-6, morphine, M3G, and M6G concentrations vs time. The primary endpoint measures were the correlations between the morphine, M6G, and M3G AUC CSF/plasma ratios and systemic inflammation as quantified by the time-normalized IL-6 exposure, which was calculated for each individual by dividing the total exposure (AUC) by time (t). A Bonferroni corrected P < 0.017 indicated a significant correlation. RESULTS: Plasma and CSF IL-6 concentrations increased postoperatively. The median [interquartile range] IL-6 exposures were significantly higher in the open vs endovascular surgical group for plasma (105 [40-256] pg·mL-1 vs 29 [16-70] pg·mL-1, respectively; P = 0.013) and CSF (79 [26-133] pg·mL-1 vs 16 [9-80] pg·mL-1, respectively; P = 0.013). For the primary endpoint, the plasma IL-6 AUC/t did not correlate with the CSF accumulation of morphine (r = -0.009; P = 0.96) or M3G (r = 0.37; P = 0.04) when corrected for surgical procedure, age, and sex. There were insufficient data on CSF concentration to complete the primary analysis for M6G. CONCLUSION: Morphine distribution into the CSF was not significantly altered in patients undergoing thoracic aortic aneurysm repair. This suggests that BBB PGP function may not be affected by the perioperative inflammatory response. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT 00878371. Registered 7 April 2009.

High Mobility Group Box-1 Protein and Outcomes in Critically Ill Surgical Patients Requiring Open Abdominal Management.

Background. Previous studies assessing various cytokines in the critically ill/injured have been uninformative in terms of translating to clinical care management. Animal abdominal sepsis work suggests that enhanced intraperitoneal (IP) clearance of Damage-Associated Molecular Patterns (DAMPs) improves outcome. Thus measuring the responses of DAMPs offers alternate potential insights and a representative DAMP, High Mobility Group Box-1 protein (HMGB-1), was considered. While IP biomediators are being recognized in critical illness/trauma, HMGB-1 behaviour has not been examined in open abdomen (OA) management. Methods. A modified protocol for HMGB-1 detection was used to examine plasma/IP fluid samples from 44 critically ill/injured OA patients enrolled in a randomized controlled trial comparing two negative pressure peritoneal therapies (NPPT): Active NPPT (ANPPT) and Barker's Vacuum Pack NPPT (BVP). Samples were collected and analyzed at the time of laparotomy and at 24 and 48 hours after. Results. There were no statistically significant differences in survivor versus nonsurvivor HMGB-1 plasma or IP concentrations at baseline, 24 hours, or 48 hours. However, plasma HMGB-1 levels tended to increase continuously in the BVP cohort. Conclusions. HMGB-1 appeared to behave differently between NPPT cohorts. Further studies are needed to elucidate the relationship of HMGB-1 and outcomes in septic/injured patients.

Indications for Use of Damage Control Surgery in Civilian Trauma Patients: A Content Analysis and Expert Appropriateness Rating Study.

OBJECTIVES: To characterize and evaluate indications for use of damage control (DC) surgery in civilian trauma patients. BACKGROUND: Although DC surgery may improve survival in select, severely injured patients, the procedure is associated with significant morbidity, suggesting that it should be used only when appropriately indicated. METHODS: Two investigators used an abbreviated grounded theory method to synthesize indications for DC surgery reported in peer-reviewed articles between 1983 and 2014 into a reduced number of named, content-characteristic codes representing unique indications. An international panel of trauma surgery experts (n = 9) then rated the appropriateness (expected benefit-to-harm ratio) of the coded indications for use in surgical practice. RESULTS: The 1107 indications identified in the literature were synthesized into 123 unique pre- (n = 36) and intraoperative (n = 87) indications. The panel assessed 101 (82.1%) of these indications to be appropriate. The indications most commonly reported and assessed to be appropriate included pre- and intraoperative hypothermia (median temperature <34°C), acidosis (median pH <7.2), and/or coagulopathy. Others included 5 different injury patterns, inability to control bleeding by conventional methods, administration of a large volume of packed red blood cells (median >10 units), inability to close the abdominal wall without tension, development of abdominal compartment syndrome during attempted abdominal wall closure, and need to reassess extent of bowel viability. CONCLUSIONS: This study identified a comprehensive list of candidate indications for use of DC surgery. These indications provide a practical foundation to guide surgical practice while studies are conducted to evaluate their impact on patient care and outcomes.

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.

BACKGROUND: Although serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. RESULTS: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. CONCLUSIONS: Most 5-HT3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting. TRIAL REGISTRATION: This study was registered at PROSPERO: ( CRD42013003564 ).