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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 83 - 83
1 Dec 2022
Van Meirhaeghe J Vicente M Leighton R Backstein D Nousiainen M Sanders DW Dehghan N Cullinan C Stone T Schemitsch C Nauth A
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The management of periprosthetic distal femur fractures is an issue of increasing importance for orthopaedic surgeons. Because of the expanding indications for total knee arthroplasty (TKA) and an aging population with increasingly active lifestyles there has been a corresponding increase in the prevalence of these injuries. The management of these fractures is often complex because of issues with obtaining fixation around implants and dealing with osteopenic bone or compromised bone stock. In addition, these injuries frequently occur in frail, elderly patients, and the early restoration of function and ambulation is critical in these patients. There remains substantial controversy with respect to the optimal treatment of periprosthetic distal femur fractures, with some advocating for Locked Plating (LP), others Retrograde Intramedullary Nailing (RIMN) and finally those who advocate for Distal Femoral Replacement (DFR). The literature comparing these treatments, has been infrequent, and commonly restricted to single-center studies. The purpose of this study was to retrospectively evaluate a large series of operatively treated periprosthetic distal femur fractures from multiple centers and compare treatment strategies.

Patients who were treated operatively for a periprosthetic distal femur fracture at 8 centers across North America between 2003 and 2018 were retrospectively identified. Baseline characteristics, surgical details and post-operative clinical outcomes were collected from patients meeting inclusion criteria. Inclusion criteria were patients aged 18 and older, any displaced operatively treated periprosthetic femur fracture and documented 1 year follow-up. Patients with other major lower extremity trauma or ipsilateral total hip replacement were excluded. Patients were divided into 3 groups depending on the type of fixation received: Locked Plating, Retrograde Intramedullary Nailing and Distal Femoral Replacement. Documented clinical follow-up was reviewed at 2 weeks, 3 months, 6 months and 1 year following surgery. Outcome and covariate measures were assessed using basic descriptive statistics. Categorical variables, including the rate of re-operation, were compared across the three treatment groups using Fisher Exact Test.

In total, 121 patients (male: 21% / female: 79%) from 8 centers were included in our analysis. Sixty-seven patients were treated with Locked Plating, 15 with Retrograde Intramedullary Nailing, and 39 were treated with Distal Femoral Replacement. At 1 year, 64% of LP patients showed radiographic union compared to 77% in the RIMN group (p=0.747). Between the 3 groups, we did not find any significant differences in ambulation, return to work and complication rates at 6 months and 1 year (Table 1). Reoperation rates at 1 year were 27% in the LP group (17 reoperations), 16% in the DFR group (6 reoperations) and 0% in the RIMN group. These differences were not statistically significant (p=0.058).

We evaluated a large multicenter series of operatively treated periprosthetic distal femur fractures in this study. We did not find any statistically significant differences at 1 year between treatment groups in this study. There was a trend towards a lower rate of reoperation in the Retrograde Intramedullary Nailing group that should be evaluated further with prospective studies.

For any figures or tables, please contact the authors directly.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 31 - 31
1 Aug 2020
Nowak L DiGiovanni R Walker R Sanders DW Lawendy A MacNevin M McKee MD Schemitsch EH
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Delayed management of high energy femoral shaft fractures is associated with increased complication rates. It has been suggested that there is less urgency to stabilize lower energy femoral shaft fractures. The purpose of this study was to evaluate the effect of surgical delay on 30-day complications following fixation of lower energy femoral shaft fractures.

Patients ≥ 18 years who underwent either plate or nail fixation of low energy (falls from standing or up to three steps' height) femoral shaft fractures from 2005 – 2016 were identified from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) via procedural codes. Patients with pathologic fractures, fractures of the distal femur or femoral neck were excluded. Patients were categorized into early (< 2 4 hours) or delayed surgery (2–30 days) groups. Bivariate analyses were used to compare demographics and unadjusted rates of complications between groups. A multivariable logistic regression was used to compare the rate of major and minor complications between groups, while adjusting for relevant covariables. Head injury patients and polytrauma patients are not included in the NSQIP database.

Of 2,716 lower energy femoral shaft fracture patients identified, 2,412 (89%) were treated within 1 day of hospital admission, while 304 (11.2%) were treated between 2 and 30 days post hospital admission. Patient age, American Society of Anesthesiologists (ASA) classification score, presence of diabetes, functional status, smoking status, and surgery type (nail vs. plate) were significantly different between groups (p After adjusting for all relevant covariables, delayed surgery significantly increased the odds of 30-day minor complications (p=0.02, OR = 1.48 95%CI 1.01–2.16), and 30-day mortality (p < 0 .001), OR = 1.31 (95%CI 1.03–2.14).

The delay of surgical fixation of femoral shaft fractures appears to significantly increase patients' risk of minor adverse events as well as increase mortality. With only 89% of patients being treated in the 24 hour timeframe that constitutes best practice for treatment of femoral shaft fractures, there remains room for improvement. These results suggest that early treatment of all femoral shaft fractures, even those with a lower energy mechanism of injury, leads to improved outcomes.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 34 - 34
1 Aug 2020
Nowak L MacNevin M McKee MD Sanders DW Lawendy A Schemitsch EH
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Distal radius fractures are the most common adult fractures, yet there remains some uncertainty surrounding optimal treatment modalities. Recently, the rate of operative treatment of these injuries has been increasing, however, predictors of outcomes in patients treated surgically remain poorly understood. The purpose of this study was to evaluate independent predictors of 30-day readmission and complications following internal fixation of distal radius fractures.

Patients ≥18 years who underwent surgical intervention for distal radius fractures between 2005 and 2016 were identified from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) using procedural codes. Patient demographics, as well as 30-day readmission, complication, and mortality rates were ascertained. Multivariable logistic regression was used to determine independent predictors of 30-day outcomes while adjusting for patient age, sex, American Society of Anaesthesiologists (ASA) class, functional status, smoking status, comorbidities, and Body Mass Index (BMI).

A total of 10,051 patients were identified (average age 58 ±16). All patients received open reduction and internal fixation with no cases of external fixation identified in the data set. Included fractures were 37% extraarticular and 63% intraarticular. Within 30-days of initial fixation 143 (1.42%) patients were readmitted to the hospital, 71 patients experienced a complication, and 18 (0.18%) patients died. After adjusting for relevant covariables, current smoking increased the odds of readmission by 1.73 (95%Confidence interval [95%CI] 1.15 – 2.50), ASA class III/IV vs. I/II increased the odds of readmission by 2.74 (95%CI 1.85 – 4.06), and inpatient surgery vs. outpatient surgery increased the odds of readmission by 2.10 (95%CI 1.46 – 3.03). Current smoking also increased the odds of complications by 2.26 (95%CI 1.32 – 3.87), while ASA class III/IV increased it by 2.78 (95%CI 1.60 – 4.85), inpatient surgery increased it by 2.26 (95%CI 1.37 – 3.74), and dependent functional status increased it by 2.55 (1.16 – 5.64).

In conclusion, patients with severe systemic disease, current smokers and patients undergoing inpatient surgery are at risk for 30-day readmissions and complications following operative treatment of distal radius fractures. In addition, patients with dependent functional statuses are more likely to experience a complication within 30-days.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 22 - 22
1 Jul 2020
Wong M Buckley R Duffy P Korley R Martin R Harrison T Sanders DW Schneider P Wiens C
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The syndesmosis ligament complex stabilizes the distal tibiofibular joint, while allowing for the subtle fibular motion that is essential for ankle congruity. Flexible fixation with anatomic syndesmosis reduction results in substantial improvements in functional outcomes. New dynamic CT technology allows real-time imaging, as the ankle moves through a range of motion. The aim of this study was to determine if dynamic CT analysis is a feasible method for evaluating syndesmosis reduction and motion following static and flexible syndesmosis fixation.

This is a subgroup analysis of a larger multicenter randomized clinical trial, in which patients with AO 44-C injuries were randomized to either Tightrope (one knotless Tightrope, Group T) or screw fixation (two 3.5-mm cortical screws, Group S). Surgical techniques and rehabilitation were standardized. Bilateral ankle CT scans were performed at one year post-injury, while patients moved from maximal dorsiflexion (DF) to maximal plantar flexion (PF). Three measurements were taken at one cm proximal to the ankle joint line in maximal DF and maximal PF: anterior, midpoint, and posterior tibiofibular distances. T-tests compared Group T and Group S, and injured and uninjured ankles in each group.

Fifteen patients (six Group T [three male], nine Group S [eight male]) were included. There was no difference for mean age (T = 42.8 ± 14.1 years, S = 37 ± 12.6, P = 0.4) or time between injury and CT scan (T = 13 ± 1.8 months, S = 13.2 ± 1.8, P = 0.8). Of note in Group S, seven of nine patients had at least one broken screw and one additional patient had screws removed by the time of their dynamic CT. There was no significant difference between treatment groups for tibiofibular distance measurements in maximal PF or DF. Group T showed no significant difference between the injured and uninjured side for tibiofibular measurements in maximal PF and DF, suggesting anatomic reduction. For Group S, however, there was a significantly larger distance for all three measurements at maximal PF compared to the uninjured ankle (all P < 0 .05).

In all but one Group S patient, screws were broken or removed prior to their dynamic CT, allowing possible increased syndesmotic motion, similar to Group T. Despite this, dynamic CT analysis detected increased tibiofibular distance in Group S as ankles moved into maximal PF when compared with the uninjured ankle. Given the importance of anatomic syndesmosis reduction, dynamic ankle CT technology may provide valuable physiologic information warranting further investigation.


The Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1132 - 1137
1 Aug 2016
Lawendy A Bihari A Sanders DW Badhwar A Cepinskas G

Aims

Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs.

Methods

Using a rat model of compartment syndrome, its systemic effects on the viability of hepatocytes and on inflammation and circulation were directly visualised using intravital video microscopy.


The Bone & Joint Journal
Vol. 97-B, Issue 4 | Pages 539 - 543
1 Apr 2015
Lawendy A Bihari A Sanders DW McGarr G Badhwar A Cepinskas G

Compartment syndrome, a devastating consequence of limb trauma, is characterised by severe tissue injury and microvascular perfusion deficits. We hypothesised that leucopenia might provide significant protection against microvascular dysfunction and preserve tissue viability. Using our clinically relevant rat model of compartment syndrome, microvascular perfusion and tissue injury were directly visualised by intravital video microscopy in leucopenic animals. We found that while the tissue perfusion was similar in both groups (38.8% (standard error of the mean (sem) 7.1), 36.4% (sem 5.7), 32.0% (sem 1.7), and 30.5% (sem 5.35) continuously-perfused capillaries at 45, 90, 120 and 180 minutes compartment syndrome, respectively versus 39.2% (sem 8.6), 43.5% (sem 8.5), 36.6% (sem 1.4) and 50.8% (sem 4.8) at 45, 90, 120 and 180 minutes compartment syndrome, respectively in leucopenia), compartment syndrome-associated muscle injury was significantly decreased in leucopenic animals (7.0% (sem 2.0), 7.0%, (sem 1.0), 9.0% (sem 1.0) and 5.0% (sem 2.0) at 45, 90, 120 and 180 minutes of compartment syndrome, respectively in leucopenia group versus 18.0% (sem 4.0), 23.0% (sem 4.0), 32.0% (sem 7.0), and 20.0% (sem 5.0) at 45, 90, 120 and 180 minutes of compartment syndrome in control, p = 0.0005). This study demonstrates that the inflammatory process should be considered central to the understanding of the pathogenesis of cellular injury in compartment syndrome.

Cite this article: Bone Joint J 2015;97-B:539–43


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 70 - 70
1 Sep 2012
Schemitsch EH Investigators S Sanders DW
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Purpose

There is no clear definition of a critical sized defect of the tibia. We defined it as a fracture gap at least one centimeter in length and involving over 50% of the cortical diameter. We explored if the presence of a critical-sized defect predicted reoperation, and which other factors predict reoperation in patients with the critical defect. The patient based outcomes of these patients were compared to patients without a critical defect.

Method

Patients enrolled in the SPRINT trial with a critical sized defect were evaluated for secondary interventions to gain union. Other factors predicting the need for reoperation were studied. We also compared the patients with critical sized defects to the larger cohort of patients without a defect with respect to demographics, injury mechanism, fracture characteristics, and patient-based outcome.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 185 - 185
1 Sep 2012
Slobogean GP Marra C Sanders DW
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Purpose

A recent multicentre randomized control trial (RCT) failed to demonstrate superior quality of life at one year following open reduction and internal fixation (ORIF) compared to nonoperative treatment for unstable isolated fibular fractures. We sought to determine the cost-effectiveness of ORIF compared to non-operative management of unstable fibular fractures.

Method

A decision tree was used to model the results of a multicentre trial comparing ORIF versus nonoperative treatment for isolated fibular fractures. A single payer, governmental perspective was used for the analysis. Utilities (a measure of preference for a health state) were obtained from the subjects Short-Form-6D scores and used to calculated Quality Adjusted Life Years (QALYs). Probabilities for each strategy were taken from the one-year trial endpoint. Costs were obtained from the Ontario Case Costing Initiative. Sensitivity analysis was performed for all model variables to determine when ORIF is a cost-effective treatment (incremental cost per QALY gained < $75,000).


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 197 - 197
1 Sep 2012
Fraser BP Chant CB Lawendy AR Manjoo A Badhwar A Ang LC Bihari R Sanders DW
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Purpose

Compartment syndrome is a limb threatening condition. Prior research has been limited by an inability to assess functional and histologic changes in muscle over time. This study was designed to assess and quantify functional deficits and histologic changes following acute compartment syndrome of the lower limb in a novel rat model.

Method

Twenty-three male Wistar rats were trained to perform an incentive-based standard task on an optical gait tracking system. Animals were then randomized to three groups: Control (n=4), Sham (n=4) and Compartment Syndrome (CS, n=15). Control and sham animals had no elevation of intracompartmental pressure, while CS animals had elevated intracompartmental pressure to 30mmHg for 180 minutes in the anterior compartment of the left hind limb using a saline infusion technique. Following intervention, gait analysis was performed at 2hrs, 24hrs, 48hrs, 72hrs and 7days following injury. Several parameters for the injured hind limb were analyzed including: print area, print intensity, maximum contact timing, duty cycle and stance phase time. A 2-way ANOVA with Bonferroni post-hoc analysis was performed. The EDL muscle was harvested (n=17), fixed in formalin and prepared with an H&E stain. Mid-muscle sections were analyzed by a blinded senior pathologist for cell infiltration, necrosis and regeneration.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 130 - 130
1 Sep 2012
Desai SJ Sanders DW Wood K Bryant D
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Purpose

Blood transfusions cause morbidity and complications in hip fracture patients. This includes increased risk of bacterial infection, potentially increased mortality, and higher hospital costs. Factors such as delay from admission to surgery, fracture pattern, method of fixation, operating time, age, and gender, may affect transfusion requirements. The purpose of this study was to evaluate the effect of patient and operative factors on blood loss and transfusion requirements.

Method

A retrospective analysis of 631 hip fracture patients between October 2005 and February 2010 was performed. Patients were reviewed for demographics, fracture type, fixation method, delay from admission to surgery and operating time. Patients receiving post operative blood transfusions were recorded. A logistic regression analysis was performed to establish a relationship between all independent variables and transfusion requirements.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 50 - 50
1 Sep 2012
Mayich DJ McCormick W Tieszer C Lawendy AR Sanders DW
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Purpose

Educational handouts designed for patients are promoted as a tool to educate, increase satisfaction, and potentially improve outcome. However, the value of these educational handouts as an adjunct to standard surgical care has not been formally assessed after ankle fracture. The purpose of this study was to compare standard post-operative care following surgically treated rotational ankle fracture to care supplemented with the use of adjunctive educational handouts.

Method

Fifty-one patients who sustained a rotational ankle fracture requiring open reduction and internal fixation were randomized to receive either standard care (group S) for an ankle fracture, or to additionally receive the AAOS handout on ankle fractures and a handout describing appropriate mobilization exercises (group H). Standard care included follow up visits at 2, 6, and 12 weeks postoperatively in a busy orthopaedic fracture clinic, including brief instructions on mobilization exercises. A bulky plaster-reinforced dressing was used for immobilization for the first two weeks following surgery, followed by a removable boot. Range of motion exercises were encouraged after the first two weeks and weight bearing was encouraged six weeks after surgery. Surgeons and outcome assessors were blinded to treatment group.

Patients completed functional outcome assessment (Olerud-Molander ankle score), objective measurement of ankle motion, and visual analog scale questions related to satisfaction at 6 and 12 weeks after surgery.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 190 - 190
1 Sep 2012
Assini J Lawendy AR Manjoo A Paul R Sanders DW
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Purpose

The anterior inferior tibiofibular ligament (AiTFL) is the primary lateral ligamentous stabilizer of the ankle syndesmosis. Current syndesmosis repair techniques traverse the tibia and fibula, but do not anatomically reconstruct the AiTFL. We compared a novel AiTFL anatomic repair technique (ART) to rigid syndesmosis screw fixation (SCREW).

Method

Twelve cadaveric below knee specimens were compared radiographically and using a biomechanical testing protocol. All specimens underwent a CT scan of the ankle joint prior to testing. Next, the AiTFL, interosseous membrane and deltoid ligament were sectioned, and the posterior malleolus osteotomized, to recreate a trimalleolar-equivalent ankle fracture. The posterior malleolus was repaired with the posterior ligamentous insertions intact and functional (PMALL). Ankles were examined under fluoroscopy with an external rotation stress exam and the medial clear space (MCS) measured. Specimens were then randomized to receive either a conventional syndesmosis screw (SCREW), or the novel anatomic repair technique (ART). External rotation stress fluoroscopy was repeated. A second CT was completed and the fibular position compared to the pre-injury CT. Each specimen was then loaded in external rotation until failure using a custom biomechanical jig.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 184 - 184
1 Sep 2012
Steyn C Sanders DW
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Purpose

Operative treatment of Lisfranc joint injuries typically includes reduction and stabilization of the medial and middle columns of the midfoot. Mobility of the lateral column is preserved where possible, such that indications for lateral column stabilization rely upon the surgeons assessment of instability. In this case series, the indication for lateral column stabilization was defined by the results of an intra-operative stress test. The purpose of this study was to determine whether an intra-operative fluoroscopic stress test of the lateral column was sufficient to determine the need for internal fixation of the lateral column in Lisfranc joint injuries.

Method

35 adult patients with Lisfranc injuries operated in our centre by a single surgeon from 2005–2009 were reviewed. All patients had unstable midfoot fracture dislocations, treated by reduction and internal fixation including an intra-operative stress examination to determine the need for lateral column fixation. Patients were contacted for clinical and radiographic review at a mean of 31 months post injury. Functional outcome was assessed using general and joint-specific outcome tools (AOFAS midfoot score and LEM). Radiographic review included analysis of joint displacement and arthritic changes in preoperative, postoperative, and most recent radiographs.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 582 - 582
1 Nov 2011
Sanders DW Desai S Ferreira LM Giles JW Johnson J
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Purpose: Blocking screws placed adjacent to intramedullary nails supplement fixation in long bone fractures with a short proximal or distal segment. Clinically, blocking screws are placed using fluoroscopy, resulting in variability in screw placement. The clinical significance of the accuracy of screw placement is unknown. Recently, a targeted blocking screw device was developed, enabling precise placement of screws adjacent to the nail. The purpose of this study was to evaluate the mechanical effects of locking screws (LS) and targeted (TBS) and non-targeted blocking screws (NBS) in distal femur fractures.

Method: Sawbone® femurs were used to create a fracture model. Femoral sawbone specimens were osteotomized eight cm proximal to the knee joint and a two cm gap was created. Intramedullary nails were used for stabilization, including one proximal locking screw and varying the distal screw configuration for study purposes. Targeted blocking screws were inserted directly adjacent to the intramedullary device using the commercially-available targeting device. Non-targeted screws were inserted one screw diameter medial or lateral to the “ideal” position. Four study groups were created; group one consisted of TBS and two distal LS. Group two had TBS and one LS. Group three had NBS and two LS, and group four consisted of NBS and one LS. Specimens were subjected to a cyclic compression protocol along the mechanical axis of the femur. Applied load varied from 100 to 700 N in 100 N incremental staircase loading protocol. Load-displacement curves recorded construct stiffness. Fracture gap motion was measured with electronic calipers.

Results: Targeted constructs were stiffer at all load levels, and 10% stiffer overall. Differences were statistically significant at moderate load levels (Group one vs three, 400N and 500N, p< 0.05).

Conclusion: Targeted constructs were stiffer at all load levels despite Sawbones® undergoing significant deformation at the proximal femur, masking the relatively smaller differences in motion at the fracture site. A difference in sagittal motion was found between groups with one and two LS, independent of the position of blocking screws. In conclusion, targeted blocking screw constructs were stiffer at all load levels compared to non-targeted constructs. The number of LS was a factor in sagittal plane stability. This study suggests that using targeted blocking screws in distal femur fractures may reduce fracture motion and decrease post operative malalignment.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 280 - 280
1 Jul 2011
Sanders DW Chan G Badhwar A
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Purpose: Compartment syndrome is a limb-threatening condition. Treatment is urgent decompression by fas-ciotomy. However, orthopedic surgeons are often confronted by a limb at risk for compartment syndrome, in which treatments to preserve tissue might be considered. Hypothermia has shown promise as a technique of maintaining tissue viability in transplant surgery, replant surgery and soft tissue injury. Cooling reduces microvascular dysfunction, inflammation and edema. This study was designed to determine whether tissue cooling might reduce muscle damage in the setting of elevated intracompartmental pressure. Purpose This study investigated the effect of hypothermia on tissue perfusion, viability and the inflammatory response in an animal model of elevated intracompartmental pressure. We hypothesize that hypothermia will preserve muscle tissue viability in an animal model of elevated intracom-partmental pressure.

Method: Twenty Wistar rats were randomized. Five animals had elevated intracompartmental pressure for 2 hours (CS). Five had elevated pressure and hindlimb cooling to 25oC (CS-HY). Five had hindlimb cooling to 25oC (HY) and 5 were control animals (C). All animals were anaesthesized for study. Core temperature was maintained over 30oC. Elevated ICP was maintained (30mmHg) using a saline infusion technique (groups CS and CS-HY). After 2 hours, fasciotomies were completed and intravital microscopy was used to measure tissue viability, microvascular perfusion and inflammation.

Results: The use of hypothermia reduced tissue damage by approximately 50% in the CS-HY group (8.2% injured cells) compared with the CS group (16.5% injured cells). There was no difference in capillary perfusion comparing the CS and CS-HY groups (p> 0.05). The number of adherent inflammatory cells was fewer comparing the CS-HY with the CS groups, but this did not reach statistical significance with the numbers available for study.

Conclusion: Hypothermia preserved tissue viability in an animal model of elevated intracompartmental pressure. Fasciotomy remains the gold standard treatment for established compartment syndrome. However cooling may be useful to preserve tissue viability in extremities that are at risk of developing compartment syndrome. The clinical utility of hypothermia for compartment syndrome requires further study.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 244 - 244
1 Jul 2011
McGarr GW Sanders DW Badhwar A
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Purpose: Compartment syndrome is a severe complication of skeletal trauma. Intravital microscopy (IVVM) has demonstrated an inflammatory response to compartment syndrome (CS). The molecular mechanisms underlying this inflammatory response are unknown. The purpose of this study was threefold. First, a broad inflammatory cytokine profile was examined to determine the molecules responsible for white cell recruitment. As well, skeletal muscle expression of white cell adhesion molecules including P-Selectin, E-Selectin, Mac-1 and ICAM-1 were examined to assess the extent of white cell activation in target tissues. Finally, skeletal muscle apoptosis was measured to determine the magnitude of cell death.

Method: Normal and neutropenic rats were randomised to either compartment syndrome or control groups. CS Animals were treated with 45 minutes of elevated intra-compartmental pressure (EICP) of the hindlimb. Fasciotomy was then performed, followed by 60 minutes of reperfusion. Control animals experienced no EICP. Blood was collected from carotid arterial lines used for pressure monitoring. Skeletal muscle tissue samples were collected from the EDL following reperfusion. Blood samples were obtained from carotid arterial lines and skeletal muscle was collected following reperfusion. A Multiplex assay was used to examine serum levels of 24 proinflammatory cytokines/chemokines. Skeletal muscle mRNA levels of P-Selectin, E-Selectin, Mac-1 and ICAM-1 were evaluated using real-time PCR. Finally, skeletal muscle apoptosis was measured by DNA laddering and a caspase-3 assay.

Results: Neutropenic CS animals demonstrated a continuous increase in TNF-alpha levels, peaking at 700+/−350pg/ml by 60 minutes of reperfusion. TNF-alpha values for other groups did not increase. A 104-fold increase in ICAM-1 mRNA levels was observed in neutropenic CS rats while other groups showed no significant increase. There was no significant increase in any group for P-Selectin, E-Selectin, or Mac-1.

Conclusion: This study is the first to attempt to describe the molecular inflammatory response in CS. Neutropenic CS animals demonstrated an upregulation in TNF-alpha and ICAM-1 mRNA levels. This likely represents an attempt to generate an inflammatory response in the neutropenic animals. Additional data at incremental timepoints is necessary to further characterize the molecular mechanisms. However, both TNF-alpha and ICAM-1 appear to be important in the mechanism of inflammatory activation in compartment syndrome.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 280 - 280
1 Jul 2011
Lawendy A McGarr G Phillips J Sanders DW Bihari A Badhwar A
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Purpose: Severe compartment syndrome is associated with renal failure, end organ damage, and systemic inflammatory response syndrome (SIRS). Intravital videomicroscopy (IVVM) is a useful tool to study capillary perfusion and inflammation in end organs such as the liver and lungs. In this study, the systemic effect of hindlimb compartment syndrome was studied using hepatic IVVM. The purpose was to measure the effect of increased hindlimb intracompartmental pressure on hepatocyte viability, inflammation, and blood flow in a rodent model.

Method: Ten Wistar rats were randomised into control (C) and Compartment Syndrome (CS) groups. Animals were anaesthetized with 5 % isoflurane. Mean arterial pressure was monitored using a carotid artery catheter. Elevated intracompartmental pressure (EICP) was induced by saline infusion into the anterior compartment of the hind limb and maintained for 2 hours between 30–40mmHg in the CS group. Two hours following fasciotomy, the liver was analyzed using IVVM to quantify capillary perfusion as a measure of microvascular dysfunction. The numbers of adherent and rolling leukocytes in venules and sinusoids were quantified to measure the inflammatory response. Irreversible hepatocyte injury was measured using a fluorescent vital dye which labels the nuclei of severely injured cells.

Results: Hepatocellular injury was significantly higher in the CS group (325±103 PI labeled cells/10-1 mm2) compared to controls (30±12 PI labeled cells/10-1 mm2)(p=0.0087). The number of adherent venular white blood cells (WBC) was significantly higher for the CS group (5±2/hpf) than controls (0.2±0.2)(p=0.0099). Volumetric blood flow was not significantly different between CS and controls.

Conclusion: After only 2 hours of compartment syndrome in this animal model, the number of activated white blood cells increased 25-fold and liver cellular injury increased 10-fold compared to controls. Marked systemic inflammation and hepatocellular damage was detected in response to isolated limb compartment syndrome. Compartment syndrome is a low-flow ischemia/reperfusion injury with a profound inflammatory response. Further research into the severe end-organ damage associated with compartment syndrome is required.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 243 - 243
1 Jul 2011
Lawendy A Sanders DW Bihari A Badhwar A
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Purpose: Compartment syndrome is a limb-threatening complication of skeletal trauma. Both ischemia and inflammation may be responsible for tissue necrosis in compartment syndrome (CS). In this study, normal rodents were compared with neutropenic animals to determine the importance of inflammation as a mechanism of cellular damage using techniques of intravital videomicroscopy (IVVM) and histochemical staining.

Method: Forty Wistar rats were randomised. Twenty animals served as a control (group C). Twenty rats were rendered neutropenic using cyclophosphamide (250mg/kg) (group N). Animals were anaesthetised with 5 % isoflurane. Elevated intracompartmental pressure was induced by saline infusion into the anterior hindlimb compartment and maintained at 30–40 mmHg for 0, 15, 45 or 90 minute time intervals. Following fasciotomy, the EDL muscle was analyzed using IVVM to quantify tissue injury, capillary perfusion, and inflammatory response.

Results: The proportion of injured cells decreased in group N compared to group C at all time intervals of EICP (p< 0.05). The proportion of injured cells in group N was 8 % after 0 minutes EICP, and 12, 15, and 10 % at 15, 45, and 90 min of EICP. In group C injured cells increased from 8 % to 20, 22, and 21 % at 15, 45, and 90 minutes EICP respectively. Groups N and C both demonstrated a time-dependent reduction in capillary perfusion. In group N continuously-perfused capillaries decreased from 79±4/mm with 0 min of EICP, to 48±11/mm (15min), 36±7/mm (45min), and 24±10/mm (90min) (p < 0.05). Overall, There was no difference between groups N and C with regards to perfusion (p> 0.05).

Conclusion: This study demonstrates the importance of inflammation as a cause of injury in compartment syndrome. There was a 50% decrease in injury in neutropenic animals compared to controls after 90 minutes of elevated intracompartmental pressure. Microvascular perfusion analysis demonstrated a time-dependent decrease in capillary perfusion in both neutropenic and control animals. Blocking of the inflammatory response via neutropenia was protective against tissue injury. These results provide evidence toward a potential therapeutic benefit for anti-inflammatory treatment of elevated intra-compartmental pressure.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 252 - 253
1 Jul 2011
Sanders DW Manjoo A Lawendy A Badhwar A Gladwell MS
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Purpose: Indomethacin may preserve tissue viability in compartment syndrome. The mechanism of improved tissue viability is unclear, but the anti-inflammatory effects may alter the relative contribution of tissue necrosis versus apoptosis to cellular injury. Existing studies have only considered indomethacin administration prior to induction of compartment syndrome. The purpose of this study was to determine the effect of timing of indomethacin administration on muscle damage in compartment syndrome, and to assess apoptosis as a cause of tissue demise.

Method: Twenty-four Wistar rats were randomized to elevated intracompartmental pressure (EICP) for either 45 or 90 minutes (30mm Hg). In the 45 min group, indomethacin was withheld (group 1), given prior to induction of EICP (group 2) or given 15 min prior to fasciotomy (group 3). In the 90 min group, indomethacin was withheld (group 4) or provided 30 or 60 minutes prior to fasciotomy (groups 5 and 6). Intravital microscopy and histochemical staining assessed capillary perfusion, cell damage and inflammatory activation within EDL muscle. Apoptosis was assessed using ELISA staining for caspase-3. Groups were compared with one-way ANOVA (p< 0.05).

Results: Perfusion improved in indomethacin-treated groups. Nonperfused capillaries decreased from group 1 (50.1±2.5), to groups 2 (38.4±1.8) and 3 (14.13±1.73)(p< 0.0001). Similarly, groups 5 and 6 had 25% fewer non-perfused capillaries compared to group 4 (p< 0.0001). Tissue viability improved in indo-methacin-treated groups. Groups 2 and 3 showed fewer damaged cells (1±0.5% and 8.7±2%) compared to group 1 (20±14%)(p< 0.0001). Groups 5 and 6 showed decreased cell damage (13±1% and 11±1%) compared to group 4 (18±1%) (p< 0.01). Apoptotic activity was present in compartment syndrome. At 30 minutes there were elevated caspase levels in EICP groups (0.47±0.08) compared to controls (0.19±0.02). However, indomethacin treated groups did not differ from controls with regards to caspase levels (p> 0.05).

Conclusion: Indomethacin decreased cell damage and improved perfusion in compartment syndrome. The benefits of indomethacin were partially time dependent; some improvement in tissue viability occurred regardless of timing of administration. Although apoptosis was common in compartment syndrome, the protective effect of indomethacin does not appear to be related to apoptosis.