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Kingston, ON, Canada London, ON, Canada
Correspondence to: Charles F. Bolton, MD, FRCP, Queen’s University, 94 Stuart St, Kingston, K7L 3N6, ON, Canada; e-mail: CB41{at}post.queensu.ca
Sepsis and multiple organ failure (critical illness, systemic inflammatory response syndrome) develop in the majority of patients receiving mechanical ventilation for 
1 week in major medical and surgical ICUs, and the majority are nervous system complications of septic encephalopathy,12 critical illness polyneuropathy (CIP),3 and critical illness myopathy (CIM).4 These complications appear as stupor or coma, difficulty weaning from mechanical ventilation, and limb weakness. As intensivists struggle to overcome the complex problems of sepsis and multiple organ failure, these nervous system complications are either overlooked or misdiagnosed. Stupor is attributed to sedation, weaning difficulties to diaphragmatic fatigue, and limb weakness to catabolic myopathy. With successful weaning, the patient is discharged to a general ward, where the patient experiences impaired cognition; difficulty dressing, eating, and rising from the bed or toilet seat; difficulty standing and walking; shortness of breath; and fatigue. A prolonged stay in a rehabilitation center may be necessary. Unless further investigated, the nature of these symptoms remains unexplained and a puzzle to the patient, family, and caregivers.
Comprehensive neurologic assessment during ICU stay will identify these nervous system complications.5 CT head scans and cerebrospinal fluid examination are unremarkable in septic encephalopathy, but the EEG shows abnormalities consistent with a diffuse encephalopathy. Electromyography (EMG) and nerve conduction studies of the limbs, measurement of creatine kinase, and at times muscle biopsy will disclose the presence and severity of CIP, CIM or, as is often the case, a combination of both conditions. The knowledge gained will aid management: determining the need and type of sedation, adjustments in weaning procedures tailored to neuromuscular respiratory insufficiency, and early rehabilitation.
Intensivists are now beginning to realize the importance of these nervous system complications. The "least-sedation" method of briefly discontinuing sedation each day and determining the level of alertness is now used as a guide to managing sedation in some ICUs.67 In this issue of CHEST (see page 1541), Schweickert and Hall8 provide a comprehensive review of what they term ICU-acquired weakness (ICU-AW), and they propose that it be assessed in conjunction with the least-sedation method to assess muscle strength. When the patient becomes alert enough, limb strength can be tested through voluntary activation with grading according to the Medical Research Council scale (see Table 1 in Schweickert and Hall8). The method has proved reasonably accurate in patients with Guillain-Barré syndrome.9 In a prospective study by De Jonghe et al,10 utilization of this method identified 28% of patients who had sepsis and multiple organ failure as having CIP and CIM, demonstrated by subsequent electrophysiologic studies and muscle biopsy. The weak patients had a longer duration of weaning and mechanical ventilation than patients who were not weak.
An early sign of CIP or CIM is observed when testing the level of consciousness in a patient who is stuporous or comatose; nail bed pressure will evoke weak or absent limb movements but obvious facial grimacing. Another early sign is loss of tendon reflexes that were previously present.5 These early signs could be added to the above protocol. All signs could be readily taught to ICU nurses.
Schweickert and Hall8 propose that once ICU-AW is identified, if there is improvement, no further studies are needed. However, if there is deterioration, further nervous system tests including CT head scan, electrophysiologic studies (EEG, EMG), and possibly muscle biopsy are performed. Earlier identification of the problem, noting its course, possibly its exact nature, may aid further management: problems with sedation, the use of neuromuscular blocking agents and steroids (which are thought to predispose to CIM), and early rehabilitation.
This proposal is welcome, and we recommend it be adopted in all major medical and surgical ICUs. It must however be realized that only a quarter of those with CIP and CIM would be identified by clinical examination alone. A further quarter or more would be identified by electrophysiologic studies. Not only do electrophysiologic studies help establish the diagnosis of CIP and CIM, they are invaluable in eliminating other conditions. For example, myasthenia gravis, Lambert-Eaton myasthenic syndrome, and amyotrophic lateral sclerosis may present, for the first time, as acute respiratory insufficiency requiring mechanical ventilation and admission to an ICU.5 Thus, patients with long-term neuromuscular disability and those "stuck on a ventilator" who are managed in chronic care respiratory facilities remain undiagnosed.
In the future, electrophysiologic monitoring may become feasible. For example, EEG monitoring would disclose the varying effects of sedation, septic encephalopathy, or the combination of both.11 The simple measurement of the compound muscle action potential of the thenar muscle by stimulation of the median nerve at the wrist would detect a drop in amplitude as an early sign of CIP and CIM.5 Park et al12 have shown that an increase in the duration of the compound muscle action potential in addition to the drop in amplitude is specific for CIM. For research purposes, these methods would be sensitive to changes induced by interventions designed to alleviate sepsis and its nervous system complications.
Footnotes
Dr. Bolton is affiliated with Queen’s University, and Dr. Young is Professor, University of Western Ontario.
The authors have no conflicts of interest to disclose.
References
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