Background The soft tissue of the limb is divided into various compartments confined by the fascia and skeletal system. In compartment syndrome, an increase in tissue pressure in a closed, nonelastic fascial compartment compromises the circulation to the neurovascular bundle and affects their function. Acute compartment syndrome (ACS) is a rare complication of certain fractures and surgeries and constitutes a serious medical emergency. The key to managing patients with ACS is its early detection and treatment. Its onset can be fast and lead to permanent tissue damage within no time. So, any delay in the diagnosis may be devastating to the patient as an emergent fasciotomy within six hours is crucial to prevent sequelae and the risk of complications such as loss of function in the limb or amputation due to muscle necrosis, delayed fracture union, Volkmann ischemic contraction, neurological deficits, cardiac arrhythmias, myoglobinuria, renal failure, and potentially death increases as time of tissue anoxia is prolonged.

Diagnosis of ACS The diagnosis of ACS is mainly based on clinical symptoms and one needs to have a high index of suspicion. The cardinal symptoms of ACS include pain, pallor, paraesthesias, pulselessness, and paralysis. The initial and most consistent indicator and a sign of impending compartment syndrome is pain that increases on passive muscle stretch in the concerned compartment. Pain on a passive stretch of the affected compartment is associated with a 68% chance of compartment syndrome. Particularly, if a patient experiences progressive pain not relieved by opioids and increases disproportionately on examination and passive motion, one should be worried and consider the likelihood of ACS. Change in sensation and weakness of muscle may also occur but it is not confirmatory of ACS.

Regional anesthesia (RA) is often considered to relieve pain in patients with trauma to limb. However, the increased use of RA may lead to delayed diagnosis of ACS and may increase subsequent morbidity. The increasing use of RA in the management of orthopedic and trauma patients, specifically on tibial fractures, does raise concern regarding a possible delayed diagnosis of ACS by ‘‘masking’’ important initial symptoms and signs, therefore delaying the diagnosis.

Various case reports have highlighted the role of RA in possible delay in the diagnosis and treatment of ACS. The invasive measurement of intramuscular pressure (IMP) is the only objective measurement method to monitor ACS and has been advocated in high-risk patients. Proper risk stratification and monitoring protocols are essential for the safe use of RA in patients at risk of ACS.

Causes and risk factors A fracture causes up to 75% of ACS cases. The most common cause is a fracture of the shaft of the tibia due to injury in up to 36% of all ACS, followed by 9% due to a fracture of the forearm. In open fractures, there is an added space for expansion of compartment tissue, which reduces the risk of ACS. The ACS is more common in males than females(up to ten times), perhaps due to a elevated mass of muscle. The risk factors for ACS include males less than 35 years old with fractures of the tibia (specifically ballistic injury to tibial diaphysis). The large injuries to tissue and vessels that require intramedullary rod and vessel repair also increase the risk.

Mechanism of ACS Injury dilates the arterioles, collapses small vessels, and increases the extravasation of fluid which raises interstitial fluid pressure. Thus, an increase in pressure in the compartment decreases perfusion to tissues and leads to hypoxia, increased oxidative stress, and f hypoglycemia. This leads to cell edema as ATPase channels, which manage osmotic balance at the cellular level close. In early ACS, a microvascular dysfunction leads to decreased capillary perfusion and increased cell injury. The compromised microcirculation due to elevated pressure reduces oxygen and nutrient delivery, resulting in tissue anoxia and myonecrosis. The loss of cell-membrane potential leads to chloride ions influx, further increasing tissue swelling and deteriorating hypoxic state. Prolonged ischemia can lead to a ‘no-reflow phenomenon’ due to occlusion of capillaries by swelling of endothelial and clogged capillaries with red and white blood cells, further increasing compartment pressure. Subsequent reperfusion releases derivatives of cell necrosis and ischemia in blood, like potassium, creatine kinase, organic acids, phosphate, myoglobin, and thromboplastin. This may result in metabolic acidosis, hyperphosphatemia, hyperkalemia, and myoglobinuria. This may result in an acute kidney injury and disseminated intravascular coagulation.

The ultimate solution to ACS is a surgical fasciotomy within a stipulated time. If fasciotomies are performed more than 8 hours after the onset of ACS, they are contraindicated as they were associated with a significantly higher risk of infection. It is better to do a fasciotomy, which may prove to be futile later, than to perform one late in a symptomatic patient.

Reperfusion after fasciotomy may cause local and systemic effects that may be life-threatening. An increase in muscle blood flow after restoring normal tissue pressure may lead to edema. Animal studies suggest cellular damage begins three hours after ischemic injury and is almost complete within six hours. The tolerance level varies in humans, and not all ischemic insults are complete.

Diagnosis Classically, ACS is characterized by the ‘five Ps’ (pain, pallor, pulselessness, paralysis, and paraesthesia). Swelling and tense tissue over a muscle compartment are some of the earliest signs of ACS and manifest as increased pressure. Pain is often portrayed as burning, deep-seated pain produced by stretching the muscles passively. Paralysis and pulselessness are rare and may occur if there is an injury to the artery. Physical signs include a firm, wood-like feeling on palpation and a reduction in the two-point sense of vibration sense in the early stages. A sensory deficit occurs in an advanced stage. Thus, combining palpation and clinical signs can help to establish a diagnosis of ACS with high specificity.

In many cases, an objective measurement method like direct intramuscular pressure (IMP) measurement would be beneficial when diagnosing ACS. The physiological value of IMP is 8 mm Hg at rest and up to 16 mm Hg in children, and it may be beneficial in patients who cannot give feedback to the physician. IMP should be measured in all patients with fractures who are at high risk of developing ACS. It may help detect the development of ACS before the symptom onset and reduce the waiting time for diagnosis and enable a timely intervention for a better prognosis. Though the thresholds of IMP for ACS vary from 30 mm Hg to 45 mm Hg, it depends on the blood pressure of the patient and should be compared with it. Perfusion pressure(PP) is difference between diastolic blood pressure and IMP, and any decrease in PP to less than 30 mm Hg is indicative of ACS.

Perfusion pressure has a high negative predictive value and is a better test to rule out ACS than to confirm it. Studies indicate that if PP is low for ACS diagnosis, it is usually not present. IMP measurement is an accurate method but not infallible. It may vary among compartments, where the anterior compartment may show higher values of IMP than other compartments. In patients with fractures, it also varies on the measurement distance from the fracture site, as maximum values occur within 5 cm of the fracture.

A simple, noninvasive method to measure IMP could allow reliable, continuous monitoring of patients at risk of developing ACS and enhance the quality of care. Various trials are validating near-infrared spectroscopy (NIRS) to measure the oxygenation of muscle compartments. Other methods include ultrasound, bioimpedance measurements, elastography using ultrasound, and measurement of quantitative tissue hardness.

What are regional anesthesia (RA) benefits in patients with limb fractures?In the surgical setting, the use of RA has produced enormous results for the perioperative pain management of patients. The ability to provide procedure-specific analgesia reduces the need for parenteral medications and their side effects. Multiple studies demonstrate the benefits of peripheral nerve blocks (PNB), including improved wound healing, reduced stress response, greater hemodynamic stability, and improved local blood flow, which may benefit trauma patients. Hence, PNB is considered a safe and effective modality for analgesia in patients after injury and surgery. PNB improves pain scores and decreases opioid requirement, associated side effects, duration of stay, and overall cost of health care. Enhanced recoveries after surgery (ERAS) protocols include RA as a part of a multimodal strategy. RA may provide added benefits in patients at risk for ACS by decreasing catecholamine release and stress response and enhancing blood flow through the extremity due to sympatholysis. So, RA should be combined to multimodal analgesia regimes in the at-risk ACS population also.

What is the concern about the use of RA in patients at risk for ACS?It has been a widely prevalent belief that PNB in this cohort is dangerous as dense analgesia via PNB blocks pain, may alter the baseline values of nerve examination and mask diagnosis of early ACS. However, this assumption is flawed because in the absence of PNB in extremity trauma, one has to use opioids and other multimodal drugs for analgesia, which is no better and case reports have suggested a missed ACS due to systemic opioids.

What is the evidence in favour of RA in patients at risk of ACS?Several case reports have shown severe pain despite an intact dense PNB. Kucera and Boezaart purported that ischemic pain provoked by ACS may be transferred via a pathway distinct from the common sensory-motor pathway blocked by PNB. This pathway in perivascular sympathetic fibres may be unaffected by PNB, ensuring that one can detect ischemic pain. A decent knowledge of ischemic pain transmission may ensure a targeted PNB without masking ACS.

So, the argument that PNB masking an impending ACS is based on several outdated published literature. Moreover, an alternative to providing opioid-based analgesia is no more protective. It is paramount that large registries should be evaluated to compare the actual risk of ACS by using different analgesia options. A systematic review by Driscoll et al. on the use of PNB in patients requiring orthopedic extremity procedures documented that in 75% of the cases, RA does not delay ACS diagnosis.

What strategies will optimize adequate analgesia without jeopardizing patient safety with the use of RA in these patients?The fear of RA masking an early ACS is based on the assumption that RA leads to dense motor and sensory blockade for an extended duration. However, advancements in PNB allow for suitable analgesia without compromising timely neurological examinations. The use of diluted local anesthetics, continuous infusions which can be that can be intermittently stopped, and direct targeting of sensory nerves provide adequate analgesia without affecting appropriate nerve function. So, a developing breakthrough pain due to ACS may easily detected. However, due to assumptions without evidence, patients with minimal to no risk of ACS are often denied PNB. Moreover, patients in high-risk groups often require prophylactic fasciotomy and are ideal candidates for PNB. Nathanson et al. suggested a validated ACS risk stratification scoring system that allows for PNB in low-risk patients and careful consideration in high-risk patients. So, dedicated RA and acute pain service (APS) must be done based on case-specific risk.

APS clinicians should also know risk stratification and be experienced with modifications in PNB based on ACS risk. The APS team should empower nurses, patients, and their families regarding the earliest signs and symptoms of ACS.

Opposition to PNB in these patients should be based on the maintenance of the patient’s ability to voice deterioration in pain as the ACS worsens. However, one cannot rely only on subjective complaints in patients with trauma as they may have an altered sensorium due to various reasons which may hinder their capability to report pain or respond appropriately to demonstrate an accurate neurological examination. PNB in these patients offers better analgesia without altering objective assessments of the extremity, which include pulse check, capillary refill, and compartment pressure. Bae et al. reported that around 10% of ACS cases in pediatric patients with isolated injury to extremity present without pain. Moreover, disproportionate pain is nonspecific, with most patients experiencing increased pain without other signs of compartment syndrome. PNB may prevent the escalation of nociceptive trauma pain to a level that may necessitate a negative decompressive fasciotomy. Also, patients may better tolerate repeated invasive intracompartmental pressure checks in presence of PNB.

Conclusion ACS is a rare entity and can be detected early and permanent sequelae prevented with emergent surgical fasciotomies. Though traditional teaching dictates avoiding RA in patients at risk for compartment syndrome, recent literature and new understanding on the topic, however, highlight the safety and benefits of PNB in these patients provided adequate precautions are in place to enable early detection of ACS. We perceive the urgent need for guidelines focusing on the role of RA in patients with fracture of lower limb, to reduce morbidity due to the delays in t ACS diagnosis with multidisciplinary drive of education on the techniques of early diagnosis of acute compartment syndrome. Further, there is a need for more research endeavours directed towards outlining the best analgesia protocol in this cohort, which preserves safety and optimal analgesia in tandem.

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