A 60-Year-Old Man with a 34-Year History of Chronic Exertional Compartment Syndrome and 3 Previous Surgical Fasciotomies, Successfully Treated with Injection of Botulinum Toxin.

BACKGROUND Patients with post-fasciotomy CECS recurrence can experience significant mobility issues at baseline that limit independent living. For these patients, a repeat fasciotomy is not ideal because they are older and post-surgical scar tissue will make the fasciotomy technically challenging. Therefore, post-fasciotomy patients with CECS recurrence require new, non-surgical treatment options. Recent studies show botulinum toxin injections can be effective for the initial management of chronic exertional compartment syndrome (CECS) prior to surgery, especially in young patients primarily experiencing pain on exertion with minimal lower-extremity symptoms at rest. However, the ability to treat CECS recurrence status after fasciotomy with botulinum toxin injections of the legs has not been studied. CASE REPORT We present the first case where botulinum toxin was applied to this patient population. Our patient was a 60-year-old man with a 34-year history of CECS who, 8 years after his third bilateral fasciotomy, progressively developed rest pain in his calves bilaterally, paresthesias, and difficulties when walking or descending stairs, with multiple near-falls due to his toes catching on stair steps. OnabotulinumtoxinA (BTX-A) injections into the posterior and lateral compartments resolved baseline symptoms: within 2 weeks, he was able to walk, negotiate stairs symptom-free, and enjoy an overseas vacation without complications. CONCLUSIONS Symptoms related to recurrent CECS status after multiple fasciotomies can successfully be treated with BTX-A injections. Our patient's baseline mobility issues resolved within 2 weeks after the injection and remained that way for over 31 months. However, his exertional symptoms and rest pain recurred at 9 months, suggesting that BTX-A injections are not completely curative.

Botulinum Toxin A for Chronic Exertional Compartment Syndrome Evaluated With Shear Wave Elastography: A Case Report.

ABSTRACT: This case presentation offers supportive evidence that shear wave elastography may provide an alternative method of diagnosis of chronic exertional compartment syndrome (CECS). A 39-year-old female runner presented with bilateral anterior shin pain on exertion. She initially underwent compartmental pressure testing confirming the diagnosis of CECS but declined fasciotomy. When her symptoms recurred, she was referred for botulinum toxin therapy. Shear wave muscle elastography was performed in the bilateral anterior and lateral compartments following symptom provocation treadmill testing and compared with 2 control subjects. At 6 weeks and 7 months after onabotulinumtoxinA injections, she was asymptomatic, and elastography measurements revealed a reduction in muscle stiffness from initial treadmill testing.

Use of Recombinant Factor VIIa for Bleeding Control in Treatment of Acute Extremity Compartment Syndrome Secondary to Primary Myelofibrosis: A Case Report.

CASE: A 40-year-old man was admitted to our emergency department with a painful and swollen calf. There was no history of significant trauma, and the physical examination revealed a pulseless, swollen left lower leg. Clinical history revealed a diagnosis of primary myelofibrosis, and magnetic resonance imaging showed a rupture of the gastrocnemius medial head. The diagnosis of spontaneous acute extremity compartment syndrome (AECS) secondary to myelofibrosis was established. An open fasciotomy procedure was performed, and recombinant factor VIIa treatment was applied to control bleeding. Postoperatively, fasciotomy wounds were closed with skin grafts. CONCLUSION: AECS may develop in patients with bleeding disorders, and recombinant factor VII may help control bleeding.

Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

N-Acetyl-L-Cysteine Reduces Fibrosis and Improves Muscle Function After Acute Compartment Syndrome Injury.

INTRODUCTION: Upon injury, skeletal muscle undergoes a multiphase process beginning with degeneration of the damaged tissue, which is accompanied by inflammation and finally regeneration. One consequence of an injured microenvironment is excessive production of reactive oxygen species, which results in attenuated regeneration and recovery of function ultimately leading to fibrosis and disability. The objective of this research was to test the potential of the antioxidant, N-Acetyl-L-Cysteine (NAC), as a mediator of reactive oxygen species damage that results from traumatic muscle injury in order to support repair and regeneration of wounded muscle tissue and improve function recovery. MATERIALS AND METHODS: Adult female Lewis rats were subjected to compartment syndrome injury as previously published by our group. Rats received intramuscular injections of NAC or vehicle at 24, 48, and 72 hours postinjury. Muscle function, tissue fibrosis, and the expression of myogenic and angiogenic markers were measured. RESULTS: Muscle function was significantly improved, and tissue fibrosis was significantly decreased in NAC-treated muscles. CONCLUSIONS: These results suggest that NAC treatment of skeletal muscle after injury may be a viable option for the prevention of long-term fibrosis and scar formation, facilitating recovery of muscle function.

Botulinum Toxin as a Novel Treatment for Chronic Exertional Compartment Syndrome in the U.S. Military.

Chronic exertional compartment syndrome (CECS) is a debilitating condition that is not uncommon in athletes and military service members. The only curative treatment for this condition, surgical fascial release, was first described in 1956. In the ensuing 62 years, this has remained the standard therapy despite symptom recurrence in 45% of military service members who underwent surgery. In 2013, a case series introduced intracompartmental injections of botulinum toxin A as a non-surgical treatment option for CECS, which proved effective in 15 out of 16 patients. In this case report, we present the case of a U.S. military service member treated with BoNT-A for bilateral lower leg CECS. This patient remains pain free at 11 months after initial treatment. This case, coupled with previously published cases series, demonstrates the potential of this novel treatment as a long-term, non-surgical alternative for CECS in the U.S. military population.

Systemic Administration of Carbon Monoxide-Releasing Molecule-3 Protects the Skeletal Muscle in Porcine Model of Compartment Syndrome.

OBJECTIVES: Acute limb compartment syndrome, a complication of musculoskeletal trauma, results in muscle necrosis and cell death. Carbon monoxide, liberated from the carbon monoxide-releasing molecule-3, has been shown protective in a rat model of compartment syndrome. The purpose of this study was to test the effect of carbon monoxide-releasing molecule-3 in a preclinical large animal model of compartment syndrome, with the ultimate goal of developing a pharmacologic adjunct treatment for compartment syndrome. DESIGN: Animal research study. SETTING: Basic research laboratory in a hospital setting. SUBJECTS: Male Yorkshire-Landrace pigs (50-60 kg). INTERVENTIONS: Pigs underwent 6 hours of intracompartmental pressure elevation by infusing fluid into the anterior compartment of the right hind limb. Carbon monoxide-releasing molecule-3 was administered systemically (2 mg/kg, IV) at fasciotomy, followed by 3-hour reperfusion. MEASUREMENTS AND MAIN RESULTS: Muscle perfusion, inflammation, injury, and apoptosis were assessed in the skeletal muscle. Systemic leukocyte activation was assessed during compartment syndrome and reperfusion. Elevation of hind limb intracompartmental pressure resulted in significant microvascular perfusion deficits (44% ± 1% continuously perfused capillaries in compartment syndrome vs 76% ± 4% in sham; p < 0.001), increased tissue injury (ethidium bromide/bisbenzimide of 0.31 ± 0.07 in compartment syndrome vs 0.17 ± 0.03 in sham; p < 0.05), apoptosis (fluorescence in vivo/bisbenzimide of 0.26 ± 0.06 in compartment syndrome vs 0.13 ± 0.03 in sham; p < 0.05), and systemic leukocyte activation (14.7 relative luminescence units/10 polymorphonuclear leukocytes in compartment syndrome vs 1.0 ± 0.1 in baseline; p < 0.001). Systemic application of carbon monoxide-releasing molecule-3 at fasciotomy increased the number of continuously perfused capillaries (68% ± 3%; p < 0.001), diminished tissue injury (ethidium bromide/bisbenzimide of 0.13 ± 0.04; p < 0.05), apoptosis (fluorescence in vivo/bisbenzimide of 0.12 ± 0.03; p < 0.05), and blocked systemic leukocyte activation (3.9 ± 0.3 relative luminescence unit/10 polymorphonuclear leukocytes; p < 0.001). CONCLUSIONS: Administration of carbon monoxide-releasing molecule-3 at fasciotomy offered protection against compartment syndrome-induced microvascular perfusion deficit, tissue injury, and systemic leukocyte activation. The data suggest the potential therapeutic application of carbon monoxide-releasing molecule-3 to patients at risk of developing compartment syndrome.

Emergency management for orbital compartment syndrome-is decompression mandatory?

Current guidelines for the urgent management of patients with orbital compartment syndrome include immediate lateral canthotomy and cantholysis, followed by surgical decompression. Medical treatment is also advocated to 'buy time' while preparing the patient for theatre. This consists of high-dose steroids, mannitol, and acetazolamide diuretics to reduce swelling and orbital pressure. It is generally recognized that late or delayed intervention is associated with poor outcomes including blindness. With early presentation, given the potential risk to sight, there is generally a low threshold for treating suspected cases. However, whether or not to treat late cases is more controversial, partly because clinicians could face accusations of medical negligence if they do nothing. The case of a patient who sustained an orbital trauma to his only seeing eye, which resulted in acute proptosis and loss of vision, is presented here. He received no treatment at all for what appeared to be an orbital compartment syndrome secondary to retrobulbar haemorrhage, but surprisingly made a full recovery of vision within 48h. In contrast to the current literature in favour of urgent treatment, this case would appear to cast some doubt over the concept of 'always' treating orbital compartment syndrome and our understanding of the condition.

Efficacy of Intravenous Mannitol in the Management of Orbital Compartment Syndrome: A Nonhuman Primate Model.

PURPOSE: To report the efficacy of intravenous mannitol in the treatment of orbital compartment syndrome. METHODS: An experimental study was conducted on 4 nonhuman primates (8 orbits). Orbital compartment syndrome was simulated by injecting autologous blood into both orbits of each nonhuman primate until a pressure of 80 mm Hg was reached (time 0). After 10 minutes, nonhuman primates were randomized to receive an infusion of either mannitol or saline, given over 15 minutes. Five minutes after the infusion was complete, lateral canthotomy and cantholysis was performed on both orbits in isolated steps every 5 minutes. During the study protocol, orbital and intraocular pressures were recorded every 5 minutes, with a final set of measurements at 60 minutes. The primary outcome measures were the mean change in pressure from time 0 to 60 minutes, as well as the mean change in pressure during the infusion period. RESULTS: There was no statistically significant difference in the mean changes in orbital or intraocular pressure from time 0 to 60 minutes of the protocol. However, during the infusion period there was significantly greater decrease in both orbital and intraocular pressure in the mannitol compared with saline group (-34.0 vs. -9.3 mm Hg for orbital pressure [p = 0.03]; -34.8 vs. -9.7 mm Hg for intraocular pressure [p = 0.04]). CONCLUSIONS: While the definitive treatment of orbital compartment syndrome is lateral canthotomy and cantholysis, mannitol results in a rapid and clinically meaningful drop in orbital and intraocular pressure. The authors believe that their data support the routine use of mannitol in orbital compartment syndrome, especially when there is a delay in timely surgical management.

Non-Necrotizing Streptococcal Cellulitis as a Cause of Acute, Atraumatic Compartment Syndrome of the Foot: A Case Report.

Acute compartment syndrome is widely accepted as a surgical emergency. Most cases of acute compartment syndrome occur after high-energy trauma, especially crush injuries. We present a unique case of acute, atraumatic compartment syndrome of the foot associated with infectious cellulitis. A 53-year-old male, with a medical history significant for human immunodeficiency virus, presented to the emergency department secondary to an insidious onset of intense foot pain, swelling, and an inability to bear weight on the affected extremity. He had no history of recent trauma. He was admitted to the hospital because of a suspected infection and subsequently was given intravenous antibiotics. During the admission, he developed a severe infection, and blood cultures demonstrated growth of group A streptococcus. No abscess or hematoma was identified on magnetic resonance imaging or during exploratory surgery. The findings from intraoperative cultures were negative. Despite proper medical care for his infection, the lower extremity pain worsened; therefore, compartmental pressures were obtained at the bedside. Multiple compartment pressures were measured and were >40 mm Hg. Compartment syndrome was diagnosed, and the patient was taken to the operating room for emergent fasciotomies. Surgical release of the medial, lateral, interosseous, and adductor compartments revealed copious amounts of serosanguinous drainage. Again, no definitive hematoma or purulence was identified. The patient's symptoms resolved after the fasciotomies, and he healed uneventfully. Our case highlights the need to consider acute compartment syndrome in the differential diagnosis for pain out of proportion to the clinical situation, even when a traditional etiology is absent.

The severity of microvascular dysfunction due to compartment syndrome is diminished by the systemic application of CO-releasing molecule-3.

OBJECTIVES: To examine the protective effects of carbon monoxide (CO), liberated from a novel CO-releasing molecule (CORM-3), on the function of compartment syndrome (CS)-challenged muscle in a rodent model, thus providing for a potential development of a pharmacologic adjunctive treatment for CS. METHODS: Wistar rats were randomized into 4 groups: sham (no CS), CS, CS with inactive CORM-3 (iCORM-3), and CS + CORM-3 (10 mg/kg intraperitoneally). CS was induced by elevation of intracompartmental pressure to 30 mm Hg through an infusion of isotonic saline into the anterior compartment of the hind limb for 2 hours. Both CORM-3 and iCORM-3 were injected immediately after fasciotomy. Microvascular perfusion, cellular tissue injury, and inflammatory response within the extensor digitorum longus muscle were assessed using intravital video microscopy 45 minutes after fasciotomy. Systemic levels of tumor necrosis factor alpha (TNF-α) were also measured. RESULTS: Elevation of intracompartmental pressure resulted in significant microvascular perfusion deficits (23% ± 2% continuously perfused capillaries in CS vs. 76% ± 4% in sham, P < 0.0001; 55% ± 2% nonperfused capillaries in CS vs. 13% ± 2% in sham, P < 0.0001), significant increase in tissue injury (ethidium bromide/bisbenzimide of 0.31 ± 0.05 in CS vs. 0.05 ± 0.03 in sham, P < 0.0001) and adherent leukocytes (13.7 ± 0.9 in CS vs. 1.8 ± 0.5 in sham, P < 0.0001), and a progressive rise in systemic TNF-α. CORM-3 (but not iCORM-3) treatment restored the number of continuously perfused capillaries (57% ± 5%, P < 0.001), diminished tissue injury (ethidium bromide/bisbenzimide of 0.07 ± 0.01, P < 0.001), reversed the CS-associated rise in TNF-α, and decreased leukocyte adherence (0.6 ± 0.3, P < 0.001). CONCLUSIONS: CORM-3 displays a potent protective/anti-inflammatory action in an experimental model of CS, suggesting a potential therapeutic application to patients at risk of developing CS.

Acute pain control challenges with buprenorphine/naloxone therapy in a patient with compartment syndrome secondary to McArdle's disease: a case report and review.

OBJECTIVE: We report the first case of non-iatrogentic exertional rhabdomyolysis leading to acute compartment syndrome in a patient with McArdle's disease. We describe considerations of concurrent buprenorphine/naloxone therapy during episodes of severe acute pain. DESIGN: Case report. CASE PRESENTATION: A 50-year-old male with a history of McArdle's disease, taking buprenorphine/naloxone for chronic pain and opioid dependence, presented to the Emergency Department with severe bilateral anterior thigh pain. Over the following 8 hours, he was given a total of 12 mg of intravenous hydromorphone with minimal pain relief. The decision was made to initiate patient-controlled analgesia (PCA) with hydromorphone started at 0.5 mg as needed with a 15-minute lockout. Subsequently, the patient's anterior thighs were found to be extremely tense. His creatine kinase level rose to 198,688 units/L and compartment pressures were greater than 90 mm Hg bilaterally. The patient was taken for emergent bilateral fasciotomies. The hydromorphone PCA was increased to 0.8 mg as needed with a 15-minute lockout and a basal rate of 0.5 mg/h. The patient's reported pain plateaued at 3/10 intensity 2 days after surgery, and he was transitioned to oxycodone and hydrocodone/acetaminophen. He followed up with his pain management physician 2 months later who restarted suboxone and a buphrenorphine transdermal patch. DISCUSSION: Buprenorphine/naloxone is being prescribed off-label with increasing frequency for pain management in patients with or without a history of opioid abuse. Severe acute pain is more difficult to control with opioid analgesics in patients taking buprenorphine/naloxone, requiring higher than usual doses. If buprenorphine/naloxone is discontinued to better treat acute pain with other opioids, monitoring for overdose must take place for at least 72 hours.

VEGF improves skeletal muscle regeneration after acute trauma and reconstruction of the limb in a rabbit model.

BACKGROUND: Complicated tibial fractures with severe soft tissue trauma are challenging to treat. Frequently associated acute compartment syndrome can result in scarring of muscles with impaired function. Several studies have shown a relationship between angiogenesis and more effective muscle regeneration. Vascular endothelial growth factor (VEGF) is associated with angiogenesis but it is not clear whether it would restore muscle force, reduce scarring, and aid in muscle regeneration after acute musculoskeletal trauma. QUESTIONS/PURPOSES: Therefore, we asked whether local application of VEGF (1) restores muscle force, (2) reduces scar tissue formation, and (3) regenerates muscle tissue. METHODS: We generated acute soft tissue trauma with increased compartment pressure in 22 rabbits and shortened the limbs to simulate fracture débridement. In the test group (n = 11), a VEGF-coated collagen matrix was applied locally around the osteotomy site. After 10 days of limb shortening, gradual distraction of 0.5 mm per 12 hours was performed to restore the original length. Muscle force was measured before trauma and on every fifth day after trauma. Forty days after shortening we euthanized the animals and histologically determined the percentage of connective and muscle tissue. RESULTS: Recovery of preinjury muscle strength was greater in the VEGF group (2.4 N; 73%) when compared with the control (1.8 N; 53%) with less connective and more muscle tissue in the VEGF group. The recovery of force was related to the percentage of connective tissue versus muscle fibers. CONCLUSIONS: Local application of VEGF may improve restoration of muscle force by reducing connective tissue and increasing the relative amount of muscle fibers. CLINICAL RELEVANCE: VEGF may be useful to improve skeletal muscle repair by modulating muscle tissue regeneration and fibrosis reduction after acute trauma.

Beneficial effects of theophylline infusions in surgical patients with intra-abdominal hypertension.

BACKGROUND: Intra-abdominal hypertension (IAH) can cause high mortality. Recently, we found that IAH was associated with increased serum levels of adenosine and interleukin 10. Our present "hypothesis-generated study" was based on the above mentioned results. MATERIALS AND METHODS: In this uncontrolled clinical trial, a total of 78 patients with IAH were enrolled representing a 13-20 mmHg range of intra-abdominal pressure (IAP). Patients requiring surgical abdominal decompression were excluded. Patients were treated with the following protocols: standard supportive therapy (ST, n = 38) or ST plus infusion with the adenosine receptor antagonist theophylline (T, n = 40). Over the 5-day measurement period, IAP was monitored continuously and serum adenosine concentration and other clinical and laboratory measurements were monitored daily. Mortality was followed for the first 30 days following the diagnosis of IAH. RESULTS: Mortality of ST patients was 55%, which is compatible to other studies. Serum adenosine concentration was found to be directly proportional to IAP. Of the 40 patients receiving T treatment, survival was 100%. An increased survival related to theophylline infusion correlated with improving serum concentrations of IL-10, urea, and creatinine, as well as 24-h urine output, fluid balance, mean arterial pressure, and O(2)Sat. CONCLUSIONS: Adenosine receptor antagonism with T following IAH diagnosis resulted in markedly reduced mortality in patients with moderated IAH (<20 mmHg). Theophylline-associated mortality reduction may be related to improved renal perfusion and improved MAP, presumably caused by adenosine receptor blockade. Because this study was not a randomized controlled study, these compelling observations require further multicentric clinical confirmation.

The effect of glutamine on oxidative damage in an experimental abdominal compartment syndrome model in rats.

BACKGROUND: The aim was to investigate whether or not glutamine, an antioxidant effective amino acid, improves the reperfusion-induced oxidative injury of abdominal hypertension. METHODS: Wistar Albino rats were used. Group 1: Abdominal compartment syndrome alone: With the rats under anesthesia, intraabdominal pressure was obtained. Three days later, the rats were sacrificed, and intestine, lung and liver samples were removed for determination of tissue malondialdehyde (MDA) and glutathione (GSH) levels as oxidative injury parameters and of myeloperoxidase (MPO) activity as an inflammatory parameter. Trunk blood was analyzed for the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Group 2: Abdominal compartment syndrome and glutamine: intragastric glutamine was given for seven days before and three days following establishment of the abdominal compartment syndrome model. The same examination procedure was then performed. Group 3: Glutamine administration alone. Group 4: Control group. RESULTS: Intraabdominal pressure significantly increased the intestine, lung and liver MDA levels and MPO activities in comparison to the control group. Glutamine was associated with decreased MDA levels and MPO activities and increased GSH levels. CONCLUSION: Glutamine appears to have protective effects against reperfusion-induced oxidative damage via its anti-inflammatory and antioxidant effect.

Pretreatment of vitamin D3 ameliorates lung and muscle injury induced by reperfusion of bilateral femoral vessels in a rat model.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a challenge in peripheral vascular disease. Clinical observations show reperfusion of occluded vessels may cause compartment syndrome or remote organ injury. Less well known is the role of vitamin D3 in tissue injury; therefore, we attempted to determine whether vitamin D3 could alleviate local and remote organ injury induced by reperfusion of occluded vessels in animal models. METHODS: Twenty-four male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, vitamin D3 + sham, and vitamin D3 + I/R group. After pretreatment for 5 d, the animals designed to I/R injury were subjected to 3 h of ischemia induced by bilateral femoral arteries clamp, followed by reperfusion of the vessels for 3 h on d 6. Left lung and left anterior tibial muscle tissue were harvested for wet/dry weight ratio and histopathologic analysis. Blood was collected for analysis of urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), ionized calcium levels, and heme oxygenase-1 (HO-1). RESULTS: Compared with the saline + sham group, there was a significant increase in plasma IL-6 level in both saline + I/R and vitamin D3 + I/R groups and muscle, lung wet/dry weight ratio in the saline + I/R group (P < 0.05). Compared with the saline + I/R group, there was a significant decrease in plasma IL-6 level, muscle and lung wet/dry weight ratio in both vitamin D3 + sham and vitamin D3 + I/R groups, and leukocyte HO-1 expression in vitamin D3 + sham group (P < 0.05). Compared with the vitamin D3 + sham group, there was a significant increase in plasma IL-6 levels in the vitamin D3 + I/R group, and leukocyte HO-1 expression in vitamin D3 + sham group (P < 0.05). BUN, Cr, AST, ALT, TNF-α, ionized calcium levels did not differ significantly among the groups. CONCLUSIONS: Pretreatment of vitamin D3 ameliorates the systemic IL-6 levels, lung and muscle injury induced by ischemia followed by reperfusion of bilateral occluded vessels in a rat model.