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CHAPTER 23: Sleep 155

acetylcholine from synaptic vesicles. In the absence of pharmacologic critically ill patients receiving mechanical ventilatory support: a
neuromuscular blockade, the fourth twitch of the adductor pollicis randomized clinical trial. JAMA. 2013;309(22):2335-2344.
muscle is as strong as the first. However, when neuromuscular recep-
tors are occupied by nondepolarizing NMBs, the strength of the fourth • Devabhakthuni S, Armahizer MJ, Dasta JF, et al. Analgosedation:
twitch is less than the first, until eventually the muscle does not twitch a paradigm shift in intensive care unit sedation practice. Ann
with the fourth stimulus. This phenomenon is known as fade. When Pharmacother. 2012;46(4):530-540.
85% to 90% of the neuromuscular receptors are occupied by NMBs, • Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired
only the first twitch in the train of four is visible. When 70% to 85% sedation and ventilator weaning protocol for mechanically ventilated
of the neuromuscular receptors are occupied by NMBs, between two patients in intensive care (Awakening and Breathing Controlled
and four twitches are visible. Typically, two or three of four twitches are trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134.
sought, and dosing of NMBs is titrated to this goal. Peripheral nerve • Kress JP, Pohlman AS, O’Connor MF, et al. Daily interruption of
stimulator use in the ICU has been shown to reduce the amount of drug sedative infusions in critically ill patients undergoing mechanical
used and shorten recovery of neuromuscular function and spontaneous ventilation. N Engl J Med. 2000;342(20):1471-1477.
ventilation. Another study showed a reduction in the incidence
93
of persistent neuromuscular weakness. However, in the largest study of • Papazian L, Forel JM, Gacouin A, et al. Neuromuscular block-
94
neuromuscular blockade in severe ARDS, peripheral nerve stimulator ers in early acute respiratory distress syndrome. N Engl J Med.
monitoring was not used. 91 2010;363(12):1107-1116.
■ COMPLICATIONS OF NEUROMUSCULAR BLOCKADE • Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs
midazolam for sedation of critically ill patients: a randomized trial.
Prolonged weakness after the use of NMBs is the most concerning com- JAMA. 2009;301(5):489-499.
plication of their use. Categorically, two separate conditions may arise • Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-
that lead to this problem. As mentioned earlier, accumulation of NMB Sedation Scale: validity and reliability in adult intensive care unit
parent drug or its metabolites is seen with several drugs, particularly patients. Am J Respir Crit Care Med. 2002;166(10):1338-1344.
with renal and/or hepatic insufficiency. This condition of prolonged • Shehabi Y, Bellomo R, Reade MC, et al. Early intensive care
recovery from NMBs is defined by an increase in the time to recovery sedation predicts long-term mortality in ventilated critically ill
of 50% to 100% longer than predicted by pharmacologic parameters patients. Am J Respir Crit Care Med. 2012;186(8):724-731.
after the drugs are stopped. The second cause of weakness associated • Strom T, Martinussen T, Toft P. A protocol of no sedation for criti-
95
with NMBs is acute quadriplegic myopathy syndrome. Patients with this cally ill patients receiving mechanical ventilation: a randomised
syndrome manifest acute paresis, myonecrosis with increased creatine trial. Lancet. 2010;375(9713):475-480.
phosphokinase (CPK) concentration, and abnormal electromyography
(EMG). Findings on EMG are consistent with denervation of skeletal
muscle (decreased compound motor action potential amplitudes). This REFERENCES
may progress to muscle atrophy and even necrosis.
Concerns over complications of NMBs have led to a dramatic decrease Complete references available online at www.mhprofessional.com/hall
in their use in the ICU. This is particularly noteworthy when cortico-
96
steroids are used in conjunction with NMBs. Several studies have sug-
gested that this combination is associated with a significant incidence of
myopathy. 97,98 However, there is a recent increased interest in NMB use CHAPTER Sleep
in severe ARDS following the study by Papazian and colleagues.
23 Brian K. Gehlbach
CONCLUSIONS Sairam Parthasarathy

Sedation is an important component of the treatment of critically ill
patients who require mechanical ventilation. Directing treatment to
specific and individualized goals will ensure that patient needs are met. KEY POINTS
All currently available sedatives for use in the ICU have limitations.
Rather than seeking an ideal drug, strategies of drug administration • Sleep is necessary for life, and disrupted sleep and circadian rhyth-
that focus attention on principles of sedative pharmacology in critical micity have been linked to a variety of adverse health outcomes.
illness should be used. Recognition of the goals of sedation in individual It is likely that critically ill patients are harmed by poor sleep,
patients will allow rational administration strategies to be implemented although evidence to support this contention does not yet exist.
in the care of these patients. The use of NMBs should be considered in • Until further research is conducted, recommendations for improv-
patients with severe ARDS. ing sleep in critically ill patients are drawn upon limited evidence
and extrapolations from other patient populations.
• Critically ill patients exhibit disordered circadian timing, which may
KEY REFERENCES contribute to poor sleep and adverse health outcomes. These abnor-
• Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines malities may reflect an inability of critically ill patients to synchronize
for the management of pain, agitation, and delirium in adult their internal clocks to the ICU environment, although it is likely that
patients in the intensive care unit. Crit Care Med. 2013;41(1): acute illness and medications also contribute to these abnormalities.
278-280. • Exposure to bright light during the day (particularly the morning)
• Brook AD, Ahrens TS, Schaiff R, et al. Effect of a nursing-imple- and avoidance of nocturnal light exposure may strengthen circa-
mented sedation protocol on the duration of mechanical ventila- dian rhythmicity and promote sleep.
tion. Crit Care Med. 1999;27(12):2609-2615. • Patients receiving continuous intravenous sedation are likely at
• Chlan LL, Weinert CR, Heiderscheit A, et al. Effects of patient- increased risk of disordered circadian rhythmicity due to low reti-
directed music intervention on anxiety and sedative exposure in nal light exposure from sedative-induced eye closure.

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