Pathophysiology of Compartment Syndrome

Acute limb compartment syndrome (CS), a potentially devastating complication of musculoskeletal trauma, is characterized by increased pressure within a closed osseofascial compartment, resulting in muscle-threatening and ultimately limb-threatening ischemia. Urgent fasciotomy remains the only effective treatment and a current gold-standard surgical therapy. Despite a large body of literature dedicated to understanding the pathophysiology of CS, the mechanisms of CS-induced tissue damage are rather poorly understood. The established view is that increasing compartmental pressure compromises microcirculatory perfusion, restricting oxygen and nutrient delivery to vital tissues, resulting in cellular anoxia and severe tissue necrosis. However, unlike complete ischemia, CS causes myonecrosis in the face of patent vessels. The purpose of this thesis was to investigate the mechanisms that contribute to the pathophysiology of CS. We developed a reproducible small-animal model of CS, utilizing saline infusion into the hind limb of the rat as the means of raising (and controlling) the compartment pressure. The microcirculatory parameters (capillary perfusion, tissue injury and leukocyte behaviour) were then assessed using intravital video microscopy (IVVM). A severe acute inflammatory component was detected in CS; the role of inflammation in muscle damage in compartment syndrome is unknown. This study provides evidence of the relationship between limb compartment syndrome, systemic inflammation and remote organ dysfunction, presumably through the release of pro-inflammatory cytokines (primarily TNF-α). The ultimate goal is to lay the groundwork for the development of rational therapeutic interventions that would, at least, extend the surgical window for fasciotomy, if not prevent the development of this condition completely

Factors affecting transfusion requirement after hip fracture: Can we reduce the need for blood?

© 2014 Association médicale canadienne. Background: Hip fractures are common injuries that result in blood loss and frequently require the transfusion of blood products. We sought to identify risk factors leading to increased blood transfusion in patients presenting with hip fractures, especially those factors that are modifiable. Methods: We retrospectively reviewed the cases of all patients who had fixation of their hip fractures between October 2005 and February 2010. The need for transfusion was correlated with potential risk factors, including age, sex, preoperative hemoglobin, fracture type, fixation method and more. Results: A total of 835 patients had fixation of their hip fractures during the study period; 631 met the inclusion criteria and 249 of them (39.5%) were transfused. We found an association between need for blood transfusion and female sex (p = 0.018), lower preoperative hemoglobin (p \u3c 0.001), fracture type (p \u3c 0.001) and fixation method (p \u3c 0.001). Compared with femoral neck fractures, there was a 2.37 times greater risk of blood transfusion in patients with intertrochanteric fractures (p \u3c 0.001) and a 4.03 times greater risk in those with subtrochanteric fractures (p \u3c 0.001). Dynamic hip screw (DHS) fixation decreased the risk of transfusion by about half compared with intramedullary nail or hemiarthroplasty. We found no association with age, delay to operation (p = 0.17) or duration of surgery (p = 0.30). Conclusion: The only modifiable risk factor identified was fixation method. When considering blood transfusion requirements in isolation, we suggest a potential benefit in using a DHS for intertrochanteric and femoral neck fractures amenable to DHS fixation

Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

© 2017 Elsevier Ltd Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0·83, 95% CI 0·63–1·09; p=0·18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1·91, 1·06–3·44; p=0·0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0·82; appendix); these events included pulmonary embolism (two patients [\u3c1%] vs four [1%] patients; p=0·41) and sepsis (seven [1%] vs six [1%]; p=0·79). Interpretation In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. Funding National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians\u27 Services Incorporated

Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p\u3c0·0001). 140 (9%) patients assigned to accelerated surgery and 154 (10%) assigned to standard care died, with a hazard ratio (HR) of 0·91 (95% CI 0·72 to 1·14) and absolute risk reduction (ARR) of 1% (−1 to 3; p=0·40). Major complications occurred in 321 (22%) patients assigned to accelerated surgery and 331 (22%) assigned to standard care, with an HR of 0·97 (0·83 to 1·13) and an ARR of 1% (−2 to 4; p=0·71). Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared with standard care. Funding: Canadian Institutes of Health Research

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Carbon monoxide-releasing molecule-3 (CORM-3) offers protection in an in vitro model of compartment syndrome

© 2019 John Wiley & Sons Ltd Objective: Limb compartment syndrome (CS), a complication of trauma, results in muscle necrosis and cell death; ischemia and inflammation contribute to microvascular dysfunction and parenchymal injury. Carbon monoxide-releasing molecule-3 (CORM-3) has been shown to protect microvascular perfusion and reduce inflammation in animal models of CS. The purpose of the study was to test the effect of CORM-3 in human in vitro CS model, allowing exploration of the mechanism(s) of CO protection and potential development of pharmacologic treatment. Methods: Confluent human vascular endothelial cells (HUVECs) were stimulated for 6 h with serum isolated from patients with CS. Intracellular oxidative stress (production of reactive oxygen species (ROS)) apoptosis, transendothelial resistance (TEER), polymorphonuclear leukocyte (PMN) activation and transmigration across the monolayer in response to the CS stimulus were assessed. All experiments were performed in the presence of CORM-3 (100 μM) or its inactive form, iCORM-3. Results: CS serum induced a significant increase in ROS, apoptosis and endothelial monolayer breakdown; it also increased PMN superoxide production, leukocyte rolling and adhesion/transmigration. CORM-3 completely prevented CS-induced ROS production, apoptosis, PMN adhesion, rolling and transmigration, while improving monolayer integrity. Conclusion: CORM-3 offers potent anti-oxidant and anti-inflammatory effects, and may have a potential application to patients at risk of developing CS

Early post-operative outcomes of plate versus nail fixation for humeral shaft fractures

© 2019 Elsevier Ltd Introduction: This study was designed to measure early postoperative outcomes of plate vs. nail fixation for humeral shaft fractures. Patients and methods: Patients ≥18 years who underwent plate or nail fixation for low-energy humeral shaft fractures between 2005–2016 were identified from the National Surgical Quality Improvement Program (NSQIP). Multivariable regression was used to compare postoperative outcomes using propensity score adjustment to account for differences between fixation groups. Variables included in the propensity score were age, American Society of Anesthesiologists (ASA) class, hypertension, steroid use, cancer, functional status, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and sex. Results: Plate fixation was used in 1418 patients (70.6%), while nail fixation was used in 591 (29.4%). Patients undergoing nail fixation were more likely to be older, have a higher American Society of Anesthesiologists (ASA) class, and have comorbidities. Mean operative time was statistically longer in the plate fixation group (130 +/−62 min vs. 102 +/−54 min). After propensity score adjustment, type of fixation was not a significant predictor of major or minor complications, length of stay, or readmission. However, nail fixation was a significant predictor of mortality following propensity score adjustment (OR 3.15, 95% Confidence interval 1.26–7.85). Conclusion: Patients undergoing intramedullary nail fixation tended to be older patients with more comorbidities, suggesting that surgeons are selecting nail fixation in patients who may not be ideal surgical candidates. Although LOS, complications, and readmission rates were higher in the nail group, this difference was not statistically significant following propensity score adjustment. However, nail fixation remained an independent predictor of 30-day mortality following adjustment. This suggests that nail fixation may not be a safer surgical option in patients with multiple medical co-morbidities and low-energy humeral shaft fractures

Factors Predictive of Early Complications Following Total Ankle Arthroplasty

Background: The safety of outpatient total ankle arthroplasty (TAA), and factors predictive of early complications are poorly understood. The objective of this study was to determine the frequency of early complications in patients undergoing outpatient TAA compared to a matched inpatient TAA cohort. Factors predictive of early complications following TAA are elucidated. Methods: A retrospective review of prospectively collected data from the 2011-2018 American College of Surgeons–National Surgical Quality Improvement Program (ACS-NSQIP) database was performed. An unadjusted analysis comparing complication rates in outpatient, and inpatient TAA was performed followed by a propensity score–matched cohort analysis. A multivariate logistic regression model was then used to identify significant independent predictors for complications, reoperation, and readmission following TAA. Results: A total of 1487 patients (198 outpatient, 1289 inpatient) undergoing TAA were included in the study. Inpatient TAA was associated with increased 30-day readmission compared with outpatient TAA (3.54% vs 0.51%, P = .032) in a matched cohort analysis. Thirty-eight (2.6%) patients had a minor complication, with 16 (1.1%) patients having a major complication after TAR. Nineteen (1.3%) patients underwent reoperation, and 42 (2.8%) patients were readmitted within 30 days of the index TAR. Multivariate analysis identified factors predictive of early complications to include length of stay (LOS) >2 days, smoking, hypertension, bleeding disorders, and diabetes mellitus. Conclusion: From this relatively limited data set, outpatient TAA appears to be safe for management of end-stage ankle arthritis in select patients. Inpatient status was associated with an increased rate of 30-day readmission following TAA. Postoperative length of stay >2 days, smoking, hypertension, bleeding disorders, and diabetes mellitus were identified to be associated with early postoperative complications following TAA in this cohort. Level of Evidence Level III, retrospective cohort study