Clinical PotpourriCorticosteroids and neuromuscular blockers in development of critical illness neuromuscular abnormalities: A historical review
Introduction
Weakness is common in critically ill patients [1], associated with prolonged mechanical ventilation, increased intensive care unit (ICU) length of stay, and extended rehabilitation, as well as increased mortality [2]. Prevention of ICU-acquired complications, such as weakness, while still providing lifesaving therapies is a fundamental goal of critical care. Some critical care treatments, including corticosteroids and neuromuscular blockade (NMB) administration, have been implicated as etiologies of acquired weakness in the ICU. Historically, corticosteroids were administered in much higher doses than typically used today [3], [4], [5], [6], [7], [8], [9], with some patients receiving more than a gram of hydrocortisone a day [10]. Neuromuscular blockade was used more commonly in mechanically ventilated patients, with continuous infusions of 6 days or longer, for larger cumulative doses [6], [7], [8], [11], [12]. Although, recently, corticosteroids are prescribed less often and at lower doses, and NMB is no longer used routinely [13], steroids and NMB are still indicated in selected critically ill patients, such as the administration of NMB in severe acute respiratory distress syndrome (ARDS) [14], [15], [16], [17].
Although many authors and clinicians remain concerned about steroids, NMB, and the development of weakness [18], [19], the data implicating steroids, and especially NMB, in ICU acquired weakness are older and are of lower quality than more recent findings. Furthermore, the association between weakness and consequences of critical illness, such as hyperglycemia and prolonged mechanical ventilation, traditionally has been underappreciated [2]. Understanding the evidence base behind the purported risk factors for weakness is key to weighing options for appropriate ICU treatments. The purpose of this narrative review is to appraise the historical and more recent data regarding the risk of neuromuscular pathology related to corticosteroids and NMB, as well as to consider other confounding factors associated with weakness, such as sepsis, mechanical ventilation, and hyperglycemia.
Section snippets
Definitions of weakness in critical illness
The existing literature uses several terms to refer to neuromuscular pathology acquired during critical illness. The main clinical feature of these neuromuscular abnormalities is weakness. Critical illness myopathy classically involves the proximal muscles of the limbs and the respiratory muscles, and is associated with increases in creatinine kinase (CK) in about 50% of cases [20]. A hallmark of isolated myopathy is weakness with preserved sensation [21]. Critical illness polyneuropathy is
Data regarding steroids and neuromuscular blockers in weakness
The NMB appraised in this review are those most commonly found in the literature. Pancuronium bromide, an aminosteroid NMB, was first introduced in 1967 [24] and is the oldest NMB still in clinical use [25]. Vecuronium bromide, a derivative of pancuronium, was brought into clinical use in 1980 [26]. Atracurium besylate, introduced in 1981 [27], another intermediate acting, nondepolarizing NMB, is a benzylisoquinoline NMB rather than an aminosteroid. Aminosteroid NMB undergo deacetylation in the
Other etiologies of weakness in critical illness
Assessing the contribution of steroids and NMB to ICU-acquired weakness is challenging, as there are many confounding factors, including sepsis, hyperglycemia, and mechanical ventilation itself.
Conclusion
The existing data support that critically ill patients are at risk for developing CINMA, with sepsis being an associated risk factor. The historical literature since the 1970s is replete with numerous case reports and small case series of patients with weakness after receiving high-dose corticosteroids, prolonged NMB, or both. Several risk factors appear thematically in the early literature including the dose and duration of NMB, large dosing of steroids, hyperglycemia, and the duration of
Acknowledgments
The author would like to thank Jeremy B. Richards, MD, for his editorial assistance in reviewing the manuscript.
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