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Trauma, surgery, and infection represent a common source of stress in critically ill patients admitted in intensive care units (ICUs). Although the consequences of stress response in critical illness are still debated and not well understood, many neural and hormonal responses have been recognized to activate homeostatic mechanisms aimed at favoring survival and healing. These responses develop toward three different phases: the first immediate and short (24 h) phase, termed ebb, is directed to immediate survival; the second longer phase (6–7 days), termed flow, is characterized by an increase in total body oxygen consumption and carbon dioxide production with hypermetabolism; the third phase, termed chronic, may last some months and identifies the post-stress period of critical illness. Although the effects of sedatives (analgesics and hypnotics) on tissue metabolic demand of critically ill patient remain difficult to be adequately defined, these drugs commonly delivered in intensive care units actually influence the stress response by decreasing neurohumoral reactions, involving the sympathetic system, and affecting the inflammatory mechanisms. After the neuroendocrine activation, uncontrolled metabolic reactions, characterized by catabolism and the resistance to anabolic signals as insulin, develop. Secondary negative effects (infections, muscle atrophy and weakness, respiratory insufficiency, delayed wound healing) can occur as direct consequences of metabolic phenomena that are clearly difficult to monitor. Finally, sedatives administered to control stress response clearly have detrimental effects (hemodynamic alterations, immunosuppression, delirium) that should be carefully evaluated in the context of a balance between benefits and damages.

Over the last 50 years, botulinum toxin (BoNT) has been transformed from a cause of life-threatening disease to an effective therapy, mainly for muscle spasticity, blepharospasm, and bladder overactivity. Certainly the use of intradetrusor BoNT for the treatment of DO has revolutionized the care of patients with neurogenic bladder and iOAB, largely improving their quality of life. A recent growing body of evidence suggests that intradetrusor injection of BoNT may have beneficial effects in patients with refractory detrusor overactivity (DO) for conservative and/or medical treatments, and it is a new minimally invasive alternative to bladder augmentation in patients with severe overactive bladder (OAB) symptoms and/or untreatable neurogenic bladder.