Factors associated with myonecrosis at time of fasciotomy in acute leg compartment syndrome.

INTRODUCTION: The objective of this study is to determine factors associated with myonecrosis at the time of fasciotomy in patients with acute leg compartment syndrome. METHODS: A retrospective cohort study was conducted of 546 patients with acute leg compartment syndrome treated with fasciotomies from January 2000 to June 2015 at two tertiary trauma centers. The main outcome measurement was clinical myonecrosis diagnosed by the treating surgeon at the time of fasciotomy. RESULTS: Eighty-two patients (15.0%) with acute leg compartment syndrome had myonecrosis at time of fasciotomy. Multivariable logistic regression analyses showed that younger age (p = 0.004) and diabetes mellitus (p < 0.001) were associated with myonecrosis at time of fasciotomy in acute leg compartment syndrome. Serum creatine kinase at presentation greater than 2405 U/L was found to be associated with myonecrosis at time of fasciotomy in post hoc analysis (p < 0.001). CONCLUSIONS: Myonecrosis is associated with patient-related factors. Younger age by 10 years is associated with a 1.3 times increase and diabetes mellitus with a 3-time increase in the odds of myonecrosis. Serum creatine kinase at presentation greater than 2405 U/L denotes an almost 3 times increase in odds of myonecrosis and may be useful for preoperative counseling.

Low compartment pressure and myoglobin levels in tibial fractures with suspected acute compartment syndrome.

BACKGROUND: The intense ischemic pain of acute compartment syndrome can be difficult to discriminate from the pain related to an associated fracture. Lacking objective measures, the decision to perform fasciotomy is often only based on clinical findings and performed at a low threshold. Biomarkers of muscle cell damage might help to identify and monitor patients at risk. In patients with fractures, however, markers of muscle cell damage could be elevated because of other reasons associated with the trauma, which would make interpretation difficult. In a review of all patients who underwent emergency fasciotomy in our health care district we aimed to investigate the decision-making process and specifically the use of biomarkers in patients with and without fractures. METHODS: In the southeast health care region of Sweden 79 patients (60 men) with fractures (median age 26 years) and 42 patients (34 men) without associated fractures (median age 44 years) were treated with emergency fasciotomy of the lower leg between 2007 and 2016. Differences in clinical findings, p-myoglobin and p-creatine phosphokinase as well as pressure measurements were investigated. RESULTS: P-myoglobin was analyzed preoperatively in 20% of all cases and p-creatine phosphokinase in 8%. Preoperative levels of p-myoglobin were lower in patients with fractures (median 1065 µg/L, range 200-3700 µg/L) compared with those without fractures (median 7450 µg/L, range 29-31,000 µg/L), p < 0.05. Preoperative intracompartmental pressure was lower in the fracture group (median 45 mmHg, range 25-90 mmHg) compared with those without fractures (median 83 mmHg, range 18-130 mmHg), p < 0.05. CONCLUSIONS: Biomarkers are seldom used in the context of acute fasciotomy of the lower leg. Contrary to our expectations, preoperative levels of p-myoglobin and intracompartmental pressures were lower in fracture patients. These findings support differences in the underlying pathomechanism between the groups and indicate that biomarkers of muscle cell necrosis might play a more important role in the diagnosis of acute compartment syndrome than previously thought.

Prediction of compartment syndrome based on analysis of biochemical parameters.

BACKGROUND: The possibility of predicting severe compartment syndrome using simple biochemical parameters was evaluated in a single-center study of 55 patients who presented with acute femoral embolism and who were treated with open surgical embolectomy. METHODS: Parameters related to tissue damage and oxidative metabolism (i.e., lactate, bilirubin, myoglobin, uric acid, glucose, and fibrinogen) were monitored in ipsilateral femoral vein blood. RESULTS: Several statistically significant predictors of relevant compartment syndrome after surgical reperfusion were found, including lactate, uric acid, transcutaneous oxygen pressure, bilirubin, intrafascial pressure, and serum myoglobin. Glycemia and serum albumin did not significantly change over time. CONCLUSIONS: The lactate concentration in femoral vein blood sampled during surgical embolectomy can be used for the stratification of additional postoperative risk of clinically significant compartment syndrome complicating reperfusion after acute embolism of the femoral artery.

Spontaneous and non-spontaneous bleeding complications in patients with oral vitamin K antagonist therapy.

PURPOSE: The aim of the study was to evaluate potential differences between patients with spontaneous and non-spontaneous bleeding episodes during treatment with vitamin K antagonists which mainly resulted in compartment syndromes. METHODS: The population in this study comprised 116 patients who suffered at least one bleeding complication which required surgical treatment during therapy with an oral vitamin K antagonist. The patients were treated between September 2001 and July 2008. RESULTS: Significant differences were observed between the two patient groups with regard to the presence of renal failure, arterial hypertension, and diabetes mellitus, which occurred more frequently in patients with spontaneous bleeding. Also, significantly more patients with spontaneous bleedings developed compartment syndrome that needed emergency operation. Overall mortality was 9.6 %, was associated with multiorgan failure in all patients, and was not different between the two patient groups. CONCLUSIONS: The identification of high-risk patients before treatment with an oral vitamin K antagonist is of major importance. The existence of over-anticoagulation syndrome and compartment syndrome is associated with significant mortality and morbidity and should not be underestimated.

Extremity compartment syndrome in pigs during hypobaric simulation of aeromedical evacuation.

INTRODUCTION: Extremity compartment syndrome (ECS) is diagnosed when the pressure within a muscle compartment increases to within 45 mmHg of mean arterial pressure. Increased pressure limits perfusion and eventually produces tissue necrosis. This can result in disability or loss of the affected limb. Hypobaric pressure during aeromedical evacuation (AE) has been hypothesized to increase the incidence of ECS. This was tested in a threshold model of ECS in swine. METHODS: Injury was induced by placing an angioplasty balloon between the tibia and the anterior muscle compartment and inflating the balloon to produce an intracompartmental pressure (ICP) 30 mmHg greater than mean arterial pressure for either 5 h or 6 h. Afterwards, animals were maintained either at ground level pressure or at a pressure equivalent to a simulated altitude of 2135 m above sea level for 8 h. ICP was monitored for signs of ECS development. At the end of the period the muscle was collected and evaluated for pathological changes and expression of various molecules associated with inflammation and tissue injury. RESULTS: Simulated altitude did not increase incidence of ECS, peak intracompartmental pressures, or time to onset of ECS. However, muscle degeneration and formation of microvascular thrombi were reduced by exposure to altitude. TNF, IL-1 b, IL-6, IGFBP5, and TGFB2 were increased (P < 0.05) by exposure to altitude, whereas FGF, IGF1, IGFBP4, BMP4, nitrotyrosine, and nitrate were unchanged (P > 0.05). DISCUSSION: Simulated altitude did not increase incidence of ECS. Inflammatory protein expression was increased in muscle, but some aspects of pathology were less severe following altitude exposure.

Use of Oxygen Tissue Monitoring in Patients With Compartment Syndrome: Two Clinical Cases and Literature Review.

Compartment syndrome is defined as the pathology caused by the increase of pressure within a muscular compartment to the point where the vascular perfusion necessary for the viability of the tissues included therein is reduced. The diagnosis is established by clinical exam and pressure measurement. Measurement of intracompartmental pressure is an invasive method with no option of easy continuous monitoring. Continuous tissue oximetry, using near-infrared light spectroscopy, can estimate soft-tissue oxygenation several centimeters below the sensor placement. This method of monitoring has been used successfully in the diagnosis of compartment syndrome, presenting itself as a non-invasive method of continuous measurement that can be a very useful alternative in complex situations or doubtful cases. We present two clinical cases of patients with acute compartment syndrome, in which the use of near-infrared light spectroscopy was determinant, both for the diagnosis and to verify the surgical treatment performed.

Acute lung injury and multiple organ dysfunction syndrome secondary to intra-abdominal hypertension and abdominal decompression in extensively burned patients.

BACKGROUND: Secondary abdominal compartment syndrome (ACS) is a lethal complication after resuscitation from burn shock, even after abdominal decompression (AD) is performed. This study investigated increased susceptibility to multiple organ dysfunction syndrome (MODS) in extensively burned patients with ACS. METHODS: Patients admitted to our burn unit between 2002 and 2005 with burns affecting 40% or more of the total body surface area without severe inhalation injury were analyzed. Hemodynamic parameters, blood gas analysis, and intrabladder pressure as intra-abdominal pressure were recorded. Serum interleukin (IL)-8 and IL-6 concentrations were measured in 20 of these patients. Lung injury score and Sequential Organ Failure Assessment scores were serially determined. RESULTS: Fourteen of 38 patients developed intra-abdominal hypertension in 22.9 +/- 8.9 hours postburn. Hemodynamic parameters in these 14 patients, including peak intra-abdominal pressure (46.6 +/- 11.2 to 19.8 +/- 9.9 cm H2O), peak inspiratory pressure (51.4 +/- 10.5 to 31.8 +/- 7.0 cm H2O), and abdominal perfusion pressure (51.3 +/- 18.3 to 73.9 +/- 13.6 mm Hg), were improved immediately after AD. Despite AD, lung injury score and Sequential Organ Failure Assessment scores increased significantly 2 and 3 days postburn in patients who required AD. Plasma concentration of IL-8 was elevated in intra-abdominal hypertension patients 3 days postburn. CONCLUSION: Intra-abdominal hypertension induced acute lung injury and MODS with IL-8 elevation, even though AD improved hemodynamic parameters in extensively burned patients.

Spontaneous Compartment Syndrome in a Patient with McArdle Disease: A Case Report and Review of the Literature.

CASE: McArdle disease, a glycogen storage disorder, often manifests as exercise intolerance secondary to muscle ischemia. Few authors have reported on rhabdomyolysis or compartment syndrome following inciting events among patients with McArdle disease. We present the case of a 40-year-old woman who developed spontaneous compartment syndrome of the right forearm and subsequently underwent emergency fasciotomy. CONCLUSION: On the basis of the present case and our review of the current literature, we advocate a high level of suspicion for compartment syndrome in patients with a history of McArdle disease.

Hyperbaric oxygen as an adjunctive therapy for bilateral compartment syndrome, rhabdomyolysis and acute renal failure after heroin intake.

Heroin abuse causes various medical and surgical complications. We report a case of heroin-induced severe bilateral compartment syndrome complicated by rhabdomyolysis, acute renal failure and extremely elevated creatinine kinase. A 30-year-old male heroin addict presented to the emergency department of Mount Vernon Hospital, Mount Vernon, New York complaining of severe pain and burning sensation in both legs and feet 1 day after abusing intravenous heroin. He had severe swelling and tenderness of both legs and feet. Laboratory data revealed tremendous elevation of creatine kinase (236,000 IU/L) consistent with rhabdomyolysis. Acute renal failure developed over subsequent days. Treatment consisted of fasciotomy, hyperbaric oxygen therapy (HBO2) and supportive therapy. The condition gradually improved over 4 weeks and the patient did not require dialysis or amputation.

Elevated cytokine levels in peritoneal fluid from burned patients with intra-abdominal hypertension and abdominal compartment syndrome.

BACKGROUND: Burn patients with intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) undergo vigorous resuscitation and accumulate peritoneal fluid (PF) that is a plasma ultra-filtrate. This study compared antithrombin (AT) and cytokine levels in burn patient plasma and peritoneal fluid (PF). METHODS: Twenty-nine patients were studied: 22 developed IAH and 9 progressed to ACS. Burn + inhalation injury was present in 22 patients; 5 had burn only and 2 had inhalation only. Sixteen patients died: of these, 9 survived less than 48 h due to the severity of their injuries. Flow cytometry utilized the Cytometric Bead Array kit for Human Th1/Th2 cytokines. AT levels were determined by the Accucolor method spectrophotometrically. RESULTS: All cytokine levels were significantly elevated in burn plasma and PF compared to normal plasma, p < 0.001. AT plasma levels were decreased compared to normal. AT and cytokines were present in peritoneal fluid of burn patients with IAH and ACS. Patients who died had decreased plasma levels of AT and increased IFN-gamma, IL-10, IL-6, IL-4, IL-2 peritoneal fluid levels compared to survivors. CONCLUSIONS: Peritoneal fluid may be a reservoir for cytokines during initial resuscitation and contributes to homeostatic perturbations in burn patients.

Comparison of NIRS, serum biomarkers, and muscle damage in a porcine balloon compression model of acute compartment syndrome.

BACKGROUND: Near-infrared spectroscopy (NIRS) has been shown to aid in the diagnosis of extremity acute compartment syndrome (ACS), offering continuous real-time capability to monitor perfusion in extremities. Porcine models of ACS have been developed to attempt to aid in the understanding of the development of ACS and provide better methods of diagnosing ACS. The objective of the present study was to assess and correlate NIRS, tibial intracompartmental pressure (TICP), tibial intracompartmental perfusion pressure (TIPP), serum markers of inflammation and muscle injury in a balloon compression model of ACS. METHODS: Six swine were used. Balloon catheters were inflated below the cranial tibial muscle. Systolic, diastolic, and mean arterial pressures; compartmental pressures; and oximetry were measured before, during, and after balloon inflation/deflation. Cranial tibial muscle was collected for muscle damage scoring. Serum creatine kinase, myoglobin, tumor necrosis factor α, IL-1ß, and IL-6 were measured. Data analysis included comparing differences in TICP, NIRS, and TIPP measurements as well as creatine kinase, myoglobin, tumor necrosis factor α, IL-1ß, and IL-6 levels between time points. Pearson correlations were calculated for muscle degeneration and edema and NIRS. RESULTS: Increases in TICP and decreases in TIPP were found. Near-infrared spectroscopy detected significant changes in tissue oxygenation at all the same time points. Myoglobin significantly increased from 45.7 ± 13.0 ng/mL (baseline) to 219.5 ± 57.3-ng/mL (balloon deflation) and continued to increase over the duration of the study. Creatine kinase significantly increased 2 hours after balloon deflation. Cranial tibial muscle degeneration, necrosis, and edema scores were higher in the test than the control legs. CONCLUSIONS: Near-infrared spectroscopy of the compartment provided a reliable, sensitive measure of both an increase and decrease in TICP and TIPP in this porcine balloon model of ACS. Creatine kinase and myoglobin significantly increased following balloon removal. Significant correlations between muscle degeneration, edema, hemorrhage, and NIRS were found.

Intestinal fatty acid binding protein as a marker for intra-abdominal pressure-related complications in patients admitted to the intensive care unit; study protocol for a prospective cohort study (I-Fabulous study).

BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have detrimental effects on all organ systems and are associated with increased morbidity and mortality in critically ill patients admitted to an intensive care unit. Intra-bladder measurement of the intra-abdominal pressure (IAP) is currently the gold standard. However, IAH is not always indicative of intestinal ischemia, which is an early and rapidly developing complication. Sensitive biomarkers for intestinal ischemia are needed to be able to intervene before damage becomes irreversible. Gut wall integrity loss, including epithelial cell disruption and tight junctions breakdown, is an early event in intestinal damage. Intestinal Fatty Acid Binding Protein (I-FABP) is excreted in urine and blood specifically from damaged intestinal epithelial cells. Claudin-3 is a specific protein which is excreted in urine following disruption of intercellular tight junctions. This study aims to investigate if I-FABP and Claudin-3 can be used as a diagnostic tool for identifying patients at risk for IAP-related complications. METHODS/DESIGN: In a multicenter, prospective cohort study 200 adult patients admitted to the intensive care unit with at least two risk factors for IAH as defined by the World Society of the Abdominal Compartment Syndrome (WSACS) will be included. Patients in whom an intra-bladder IAP measurement is contra-indicated or impossible and patients with inflammatory bowel diseases that may affect I-FABP levels will be excluded. The IAP will be measured using an intra-bladder technique. During the subsequent 72 hours, the IAP measurement will be repeated every six hours. At these time points, a urine and serum sample will be collected for measurement of I-FABP and Claudin-3 levels. Clinical outcome of patients during their stay at the intensive care unit will be monitored using the Sequential Organ Failure Assessment (SOFA) score. DISCUSSION: Successful completion of this trial will provide evidence on the eventual role of the biomarkers I-FABP and Claudin-3 in predicting the risk of IAP-associated adverse outcome. This may aid early (surgical) intervention. TRIAL REGISTRATION: The trial is registered at the Netherlands Trial Register (NTR4638).

An acquired factor VIII inhibitor responsive to high-dose gamma globulin.

A 55-year-old previously well woman noted easy bruising and developed a swollen, painful leg after minimal trauma. A compartment syndrome was diagnosed, and medial and lateral fasciotomies were performed with evacuation of a massive hematoma. However, blood rapidly reaccumulated in the wound. The VII:C level was 2%, and 4 Bethesda units of factor VIII inhibitor were detected. After initial treatment with clotting factor concentrates and corticosteroids failed to control bleeding or reduce inhibitor titers, gamma globulin, 25 g daily for 5 days, was administered. The inhibitor became undetectable, VIII:C levels rose, and bleeding stopped. However, 5 days later VIII:C levels were again low and bleeding recurred. A second course of gamma globulin, 50 g daily for 2 days, was accompanied by a prompt increase in VIII:C, and uneventful recovery. In conclusion, in this patient with an autoantibody to VIII:C, a response to gamma globulin was observed on two occasions, and the second response came when steroids were being tapered and the patient was on no other medication.

Patients with impending abdominal compartment syndrome do not respond to early volume loading.

BACKGROUND: It is recommended that patients with impending abdominal compartment syndrome (ACS) should be volume loaded to insure the adequate preload. We evaluated our prospective resuscitation database to determine how patients who developed ACS differ from non-ACS patients in response to early volume loading. METHODS: Over 36 months, 152 consecutive high-risk patients were resuscitated by a standard intensive care unit (ICU) protocol that escalates interventions in nonresponders. Interventions, responses, and outcomes are prospectively collected and the characteristics of ACS and non-ACS patients were compared. RESULTS: Twenty-three patients (15%) developed ACS and were decompressed 8 +/- 1 hours after ICU admission. The ACS and non-ACS patients had similar demographics and injury severity. The severity of pre-ICU shock tended to be greater in the ACS patients. During the first 8 hours of ICU resuscitation, patients who developed ACS received more blood transfusions (11 +/- 2 versus 2 +/- 0.2 units; P<0.05) and crystalloids (13 +/- 2 versus 4 +/- 0.3 L; P<0.05). As a result, pulmonary capillary wedge pressure increased more in the ACS patients (20 +/- 1.5 versus 15 +/- 0.5 mm Hg; P<0.05), but comparatively the cardiac index did not (3.2 +/- 0.2 versus 4.2 +/- 0.1 L/min/m(2); P<0.05) and the ACS patients developed pathologic elevations of gastric regional CO(2) pressures (70 +/- 7 versus 48 +/- 1 mm Hg P<0.05). CONCLUSIONS: Conventional preload directed resuscitation to enhance cardiac function is not effective in patients with impending ACS, and this traditional resuscitation strategy is detrimental in this subgroup of patients.

[Assessment of regional and systemic toxicity of isolated hyperthermic extremity perfusion with tumor necrosis factor-alpha and melphalan]. / Erfassung regionaler und systemischer Toxizität der isolierten, hyperthermen Extremitätenperfusion mit Tumor-Nekrose-Faktor alpha und Melphalan.

Following isolated limb perfusion (ILP) with TNF alpha and melphalan the damage to muscle tissue and its systemic consequences in terms of myoglobinemia and myoglobinuria as well as the activation of the cytokine cascade were investigated. We measured the compartmental pressure of the limb during and after perfusion and determined the serum changes of myoglobin, creatine kinase (CK), interleukin (IL)-6, IL-1, s-IL-2-receptor, TNF-receptor, and ICAM-1 levels. The compartmental pressure rose significantly during ILP and decreased after reperfusion. Following its course, the decision whether to perform a fasciotomy or not can be more reliably made. Serum myoglobin levels exceeded 200 times normal values and the increase occurred significantly earlier than that of CK, thus enabling judgement of the risk of renal failure (crush kidney syndrome). The elevation of serum IL-1 and IL-6 values correlated with the frequency of cardiopulmonary problems (hyperdynamic shock) and facilitated counter-maneuvers. Our data, although obtained from ILP with TNF alpha, could be used to monitor toxicity also when other drug regimens are administered.

Exertional compartment syndrome in covert mild hemophilia. A case report.

A 37-year-old white male experienced unexpected postoperative bleeding after fasciotomy and decompression for left pronator and compartment syndromes of the forearm. He was subsequently diagnosed with a mild form of hemophilia A. One year later, surgery was required for right pronator and compartment syndromes. Pre- and postoperative cryoprecipitate infusions controlled bleeding following the second operation until the patient discontinued his infusions, resulting in a wound hematoma. Covert mild hemophilia is implicated in the pathogenesis of his compartment syndromes.

Acute compartment syndrome in haemophilia.

Acute compartment syndrome (ACS) is characterized by an increase in pressure (intramuscular pressure) within a muscle compartment, which reduces capillary perfusion threatening tissue survival. Persistence of this increased pressure for a few hours will result in necrosis of muscle and nerve tissue, with contracture in the affected limb and permanent loss of function. For that reason, early treatment and diagnosis of ACS is fundamental. Diagnosis should be based on physical examination (pain on stretching the involved muscles) and on an objective measurement of the limb perfusion pressure (DBP minus intramuscular pressure) within the affected compartment. To obtain a reliable clinical diagnosis, the patient must be evaluated every 1-2  h. In children and in unconscious patients, where the level of pain cannot be appropriately determined, an accurate clinical diagnosis is unfeasible, hence the importance of measuring compartment pressure. A fasciotomy should be performed when the limb perfusion pressure is less than 30  mmHg when averaged over a 12-h period (monitored every 1-2  h). Only 16 studies have been published on haemophilic patients with ACS, which report on a total of 34 cases. If symptoms or pressure measurements are suggestive of ACS, an extensive fasciotomy will be required. Unfortunately, fasciotomy is not exempt from complications such as the need of subsequent surgery because of a delay in wound healing, the need of a skin graft, pain, cosmetic problems, nerve injury, permanent muscle weakness and chronic venous insufficiency. Overlooked compartment syndrome remains one of most common causes of malpractice lawsuits. In haemophilia, adequate substitution of coagulation factor must be the first step. The main principle of surgical treatment is an extensive fasciotomy.

Serum creatine kinase levels are associated with extremity compartment syndrome.

BACKGROUND: Limb compartment syndrome (CS) is a difficult diagnosis. Accurate measurement of compartment pressure is user dependent, and there is no consensus on values to define CS. Given the prevalence of extremity CS, difficulty in timely diagnosis, and ramifications of a delay in diagnosis, a precise and reliable means for early diagnosis is needed. The purpose of our study was to determine if a threshold serum creatinine kinase (CK) level is associated with the development of CS. METHODS: All patients with isolated tibial/fibula fractures or extremity CS admitted to a three-hospital consortium from July 1, 2001, to June 30, 2011, were identified retrospectively using coded data. Age, basic metabolic panel, lactic acid, CK, and troponin I levels were abstracted. Univariate and multivariate regression analysis was undertaken using maximum and minimum values for each laboratory test to evaluate the association between the test and CS versus tibia/fibula fracture. RESULTS: Of the 97 patients in the study, 39 had CS. Tests most strongly associated with CS were maximum CK, minimum calcium, minimum blood urea nitrogen (BUN), maximum chloride, maximum lactate, and minimum HCO3. On univariate analysis, only maximum CK had adequate correlation with CS. Optimal cut points were maximum CK of greater than 4,000 U/L. Using the model CK level of greater than 4,000 U/L, chloride level of greater than 104 mg/dL, and BUN level of less than 10 mg/dL, 0 of 6 patients had CS when all three variables were absent. When one, two, or three variables were present, the percentage of patients with CS was 36%, 80%, and 100%, respectively. Using a cut point of two or more of these three variables being positive produced sensitivity, specificity, positive and negative prediction values, and total accuracy of 0.85, 0.87, 0.76, 0.92, and 0.86, respectively. CONCLUSION: CK level greater than 4,000 U/L is associated with CS. A model combining maximal CK level greater than 4,000 U/L, maximal chloride level greater than 104 mg/dL, and minimal BUN level less than 10 mg/dL has a 100% association with CS. LEVEL OF EVIDENCE: Diagnostic study, level III.