Can steel heal a compartment syndrome caused by rattlesnake venom?☆☆☆

Compartment syndrome is a feared complication of a rattlesnake bite. It is often followed by severe compartmental muscle necrosis, resulting in dysfunction of an extremity. Other types of compartment syndromes appear to be the result of increased compartment pressure. If the pressure is relieved promptly, the detrimental effects are reduced. Because fasciotomy is a common treatment for other causes of compartment syndrome, it is reasonable to consider it for the management of compartment syndrome induced by snake venom. Indeed, some practitioners have advocated for early fasciotomy in nearly all victims of rattlesnake envenomation.1

Few published studies have addressed the issue of increased compartment pressure induced by snake venom. The few reports (all retrospective) in human beings have reported good outcomes after surgical or nonsurgical approaches.2., 3., 4. Animal studies have yielded mixed results. Grace and Omer5 injected Western diamondback (Crotalus atrox) venom into the hind leg of rabbits. Unfortunately, this did not produce an increase in compartment pressure. They reported that extremity swelling was reduced in rabbits treated with antivenom alone, antivenom plus steroids, or fasciotomy alone. Histologic sections showed severe muscular necrosis in all groups. Stewart et al6 performed a similar experiment with C atrox venom in rabbits, but also tested long-term muscle function. Experimental groups included venom alone, venom plus antivenom, venom plus fasciotomy, venom plus antivenom and fasciotomy, and controls. The mean compartment pressure for all animals increased after venom injection from 3 mm Hg to 30 mm Hg. Nine weeks after envenomation, they found that the limb muscles had reduced ability to generate tension in all groups that received venom when compared with a nonenvenomated group; however, the group treated with antivenom alone was statistically superior to all other groups injected with venom. The fasciotomy technique used by Stewart et al involved both decompression and the debridement of “clinically nonviable tissue,” the usual technique reported for venom-induced compartment syndromes.1 Therefore, the reduced muscle performance could theoretically be caused by necrosis or the debridement of potentially viable tissue.

Garfin et al7., 8. studied the hind limb in a dog model using southern Pacific rattlesnake (C viridis helleri) venom. Venom injected into the anterolateral compartment increased the intracompartmental pressure from a mean of 4 mm Hg to 44 mm Hg at 4 hours and 80 mm Hg at 24 hours after injection. They reported that a small dose of antivenom failed to reduce compartment pressure, but a large dose successfully reduced compartment pressure.7 Using the same model, Garfin et al8 found that fasciotomy performed before venom injection successfully reduced the intracompartmental pressure, but did not reduce muscle necrosis.

The results of Tanen et al9., 10. extend these animal studies substantially. First, they performed their study using the established methodology of a clinical trial. In many animal trials, the principles developed for clinical trials are not applied.11 Tanen et al9 randomized animals to an experimental group, and the investigators were blinded to the use of antivenom. They were unable to blind the use of fasciotomy, but the pathologist evaluating the biopsies was blinded. These techniques allow bias to be distributed evenly among groups, unlike the many reports where animals are tested in groups.9

Tanen et al9., 10. were able to demonstrate that venom injection produced intracompartmental pressures above 30 mm Hg. The first report from Tanen et al9 found that injection of C atrox venom into the anterior compartment reduced the compartmental perfusion pressure from about 54 mm Hg to 32 mm Hg. The administration of antivenom 1 hour after venom injection into the anterior leg compartment improved perfusion pressure substantially. In this issue of Annals, Tanen et al10 report that immediate fasciotomy prevented an increase in compartment pressure, as expected. However, the reduction in pressure was not associated with improved histologic appearance of the muscle. In fact, the extent of myonecrosis appeared worse in the animals that received fasciotomy. This finding is similar to that of Grace and Omer,5 as well as that of Garfin et al.8 If compartment pressure is an important component of the pathogenesis of this injury, early fasciotomy should eliminate this factor.

In short, the data available indicate that surgical steel is not likely to improve the outcome of venom-induced compartment syndrome. For compartment syndrome following trauma and related conditions, the pathophysiology appears to hinge on increased pressure. For venom-induced compartment syndrome, the central factor is likely to be direct venom effects on the tissue and not solely the resulting increase in compartment pressure. In animals, neither prevention of increased compartment pressure nor relief of established compartment syndrome with fasciotomy has been demonstrated to improve muscle injury in animals.6., 8., 10. Proponents of fasciotomy must demonstrate improved functional outcome using appropriate research design in the study of venom-induced compartment syndrome.

In their 2 reports, Tanen et al9., 10. have found that the administration of antivenom improved perfusion pressure within the compartment, but failed to improve histologic appearance. This creates the discouraging possibility that injury caused by venom inside of a compartment is not amenable to either surgical or antivenom treatment. However, Tanen et al9., 10. did not attempt to address functional outcome. Two studies in other animal models have suggested that the relatively early administration of antivenom does improve functional outcome.6., 8. Thus, the jury is still out on the efficacy of antivenom in the treatment of venom-induced compartment syndrome. Antivenom is often used in victims of rattlesnake envenomation. The patient with compartment syndrome from snake venom is almost certain to require antivenom for other manifestations of the venom. It remains unknown whether additional doses of antivenom specifically for increased compartment pressure are useful. This practice is supported currently only by animal data and case reports.6., 7., 9.

Given the remaining uncertainties and the dismal prospects for a patient with elevated compartment pressure after snakebite, many physicians have adopted the “kitchen sink” approach of attempting several treatments in a last ditch effort to reduce injury. One approach involves (1) rapid infusion of additional antivenom, (2) attempting to decrease the fluid in the compartment by administering mannitol, and (3) performing fasciotomy if the intracompartmental pressure remains elevated (Figure). In several cases over a 15-year period, I have witnessed the intracompartmental pressure decrease from 45 or 50 mm Hg to below 30 mm Hg after the combined use of antivenom and mannitol. Fasciotomy was averted in a few cases, but we have no idea whether these patients had improved outcomes. In contrast, another patient developed an anterior leg compartment pressure of 110 mm Hg after a C atrox bite, which decreased only to 90 mm Hg after this treatment. Future evaluations of venom-induced compartment syndrome must emphasize outcome. Although such research is difficult to accomplish because of variability in clinical severity and difficulty in the assessment of functional outcome, it is the only information that will answer the question.

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Figure. Management of suspected compartment syndrome in victims of crotaline snakebite.