Session VII - Tibia

·*Use of Tissue Ultrafiltration for Treatment of Compartment Syndrome

Rick Odland, MD (a,d-Twin Star Medical; (NIH); Andrew H. Schmidt, MD (a,b,d,e-Twin Star Medical; (NIH); Brian Hunter, BS; Louis S. Kidder, PhD (a,e-Twin Star Medical; (NIH); Joan E. Bechtold, PhD (a,d,e-Twin Star Medical; (NIH); Robert A. Pedowitz, MD (e-Twin Star Medical; (NIH); Alan R. Hargens, PhD, Minneapolis Medical Research Foundation, Minneapolis, MN

Purpose: This is a report of the application of a new technology to the diagnosis, prevention and treatment of compartment syndrome (CS). Currently, decision making regarding treatment of CS relies on clinical findings and leaves little room for error. Measurements of compartment pressure are unreliable, since the significance of elevated intramuscular pressure varies depending on the nature of the injury, the duration of the increased pressure, and the patient's vital signs. Failure to do fasciotomy is a frequent cause of malpractice judgments, but performing a fasciotomy commits the patient to a hospital stay, skin grafting, scarring, and possible venous insufficiency. After open reduction of tibial fractures, fasciotomy can lead to exposure of bone or plating hardware. A less invasive treatment for compartment syndrome would alleviate this clinical dilemma. Tissue ultrafiltration (TUF) is a minimally traumatic method allowing sampling and removal of interstitial tissue fluid. This treatment is accomplished by percutaneous insertion of a 1-mm diameter catheter into the muscle compartment, which is then connected to down-regulated wallsuction. TUF has been used in skin flaps and after traumatic brain injury to reduce tissue edema. The purpose of this study is to demonstrate the efficacy of TUF for the treatment of CS in an animal model.

Methods: TUF was tested in a porcine model of compartment syndrome (CS). CS was created by infusion of saline to elevate intracompartmental pressure to 30 mm Hg above mean arterial pressure, which was maintained for 8 hours. After 2 hours of reperfusion, TUF catheters were placed in both limbs. In the control limb, the catheters were not connected. In the experimental limb, treatment was accomplished by maintaining the catheters at negative 500-mmHg pressure for 9.5 hours. Intramuscular pressure, mean arterial pressure, and rate of fluid recovery were recorded. Serum levels and ultrafiltrate levels of metabolic markers were analyzed. At the completion of the study period, muscle samples were taken and analyzed for necrosis. Histologic analysis was done on specimens in a blinded fashion by 2 methods. Tissue samples were coded and placed in random order. The transverse cell diameter and interstitial distance were measured using a computer-assisted digitizer. To assess the degree of tissue damage, the percent of the cross-sectional area of the specimen that showed tissue injury was measured. The entire slide was examined, and areas of the muscle section containing necrotic cells (large, round cells with increased dye uptake and loss of intracellular structure) were marked and digitized. Statistical analysis was done using standard tests for paired continuous data.

Results: The intramuscular pressure (IMP) was lower on the treated side at the end of the treatment period (treated leg: 9.3 ± 4.0 mmHg [± Standard Error]), control leg:19.3 ± 1.4 mm Hg; P = .03, df = 2, one-tailed t test). One criterion for the diagnosis of CS is when the perfusion pressure (DP = MAP-IMP) < 45 mm Hg. Prior to the initiation of treatment, both limbs were within CS range (DP of 36.0 ± 6.1 mm Hg and 37.7 ± 3.4 mm Hg, for control and treatment limbs, respectively). After completion of the treatment period, the control side mean still met the criterion of CS (DP of 41.7 ± 7.7 mm Hg), whereas the treated limb was within normal limits (DP of 51.7 ± 7.8 mm Hg).

Analysis of ultrafiltrate fluid showed that levels of creatine kinase and lactate dehydrogenase were elevated compared to serum levels. Creatine kinase levels in serum were measured at 4,150 U/l, whereas ultrafiltrate levels of creatine kinase were 28,714 ± 17,700 U/l (SE), P = .1). Lactate dehydrogenase was measured at 1,947 U/l in serum but markedly elevated in ultrafiltrate (159,838 ± 76,981 U/l, (SE), P = .05).

Histologic analysis found the transverse cell diameter to be slightly smaller in the treated side (22.03 ± 1.4 u) compared to the control side (22.79 ± 1.3 u, not significant). Measurement of interstitial distance showed the treated limb maintained extracellular pathways (4.37 ± .4 m versus 4.09 ± .6 m, not significant). Quantification of the degree of necrosis revealed 6.1 ± 2.7% necrosis in the treated limb compared to 11.3 ± 1.6% necrosis in the control group. This difference was significant at P = .02 (df = 2, one tailed paired t test).

Discussion: TUF reduced intramuscular pressure levels. We also observed a trend towards decreased tissue necrosis in treated limbs in this model of compartment syndrome. Histologic analysis showed that this was a severe model in which necrosis and cellular swelling was extensive. A 5- to 80-fold increase in levels of metabolic markers was observed in the limbs undergoing TUF, but some of the elevation may have been due to injury >from placement of the catheters. However, we think that interstitial fluid sampling with measurement of such markers of injury may allow earlier, more sensitive, and more specific diagnosis of compartment syndrome. Further study will be necessary to determine the specificity and sensitivity of interstitial fluid sampling in diagnosing CS. Clinical studies have shown that CS is rare if a perfusion pressure (DP) of at least 45 mm Hg can be maintained. The finding that we were able to reduce intramuscular pressure enough to allow an adequate perfusion pressure may mean that this technique can reduce the need for fasciotomy. The finding of less muscle necrosis in the treated limbs suggests that functional outcome may be improved with TUF use. Further clinical studies are warranted.

Conclusion: With low morbidity of treatment, TUF can be used prophylactically for patients at risk of CS. Sampling of interstitial fluid and frequent measurement of intramuscular pressure may allow earlier diagnosis of CS, and the reduction of tissue pressure by TUF may prevent CS from occurring. TUF will not hinder the ability of clinicians to use the clinical examination as the gold standard for diagnosis of CS. The use of TUF may allow earlier treatment of CS, without the morbidity of fasciotomy, and save thousands of dollars per patient in costs.

· The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an "off label" use). For full information refer to page 444.