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Neurologists working in the hospital are often called to evaluate patients with severe muscle weakness. Some of these patients can develop ventilatory compromise and require admission to the intensive care unit (ICU). This article reviews the general evaluation of neuromuscular respiratory failure, discusses its differential diagnosis, and provides practical advice on the management of its most common causes.Determining the cause of acute neuromuscular respiratory failure is crucial because functional prognosis is poor in patients for whom the cause cannot be defined. The differential diagnosis is extensive, but the first step is to discriminate between cases related to a primary neurologic disease (primary neuromuscular respiratory failure) and those provoked by systemic disease, most often critical illness from sepsis and multiorgan failure (secondary neuromuscular respiratory failure). Guillain-Barré syndrome (GBS) and myasthenic crisis are the two most frequent causes of primary neuromuscular respiratory failure. Although they are both autoimmune conditions that benefit from the administration of plasma exchange or IV immunoglobulin (IVIg), they are otherwise very different disorders with unique features and distinct complications. Optimal strategies for mechanical ventilation also differ between these two conditions; while myasthenic crisis is ideally managed with noninvasive bilevel positive airway pressure (BiPAP) ventilation, GBS demands early intubation.Prompt recognition of neuromuscular respiratory failure can be lifesaving, and identification of its cause has substantial prognostic implications. Adequate management of these patients requires a multidisciplinary team with the neurologist at its center, not only to guide the diagnostic evaluation but often also to prescribe the optimal management.