Page 254 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

158 PART 2: General Management of the Patient

A variety of metabolic and endocrine processes are regulated by sleep CIRCADIAN RHYTHMICITY
and by circadian processes. For instance, prolactin secretion increases IN THE CRITICALLY ILL PATIENT
dramatically during sleep and declines acutely with awakenings. The
secretion of growth hormone is similarly enhanced by sleep, while Organisms have acquired during evolution a variety of adaptations
cortisol and thyrotropin secretion are inhibited. Several compelling to their external environment that promote survival. One of the most
lines of evidence link sleep deprivation, including chronic partial sleep conspicuous characteristics of the external environment on Earth is the
deprivation experienced by a significant segment of modern society to presence of a roughly 24-hour light-dark cycle. Organisms throughout
insulin resistance and weight gain. The study of the effects of disrupted nature therefore developed the ability to synchronize their activities
15
sleep and circadian rhythmicity on endocrine processes in critical illness to the light-dark cycle through an endogenously driven timekeeping
constitutes an exciting avenue of future research. mechanism that is periodically “reset” to solar time. In mammals, the
Of course, the restorative processes conferred by sleep that have long hypothalamic suprachiasmatic nucleus (SCN) is the central pacemaker
been most obvious are those conferred on the brain. Sleep restores alert- for these circadian (derived from the Latin terms circa, around, and
ness and vigilance and enhances memory consolidation; while sleep diem, day) rhythms. Circadian rhythms can be found in a host of physi-
deprivation worsens mood, vigilance, reaction time, and cognitive and ological and behavioral processes ranging from somatotropic functions
task performance. 2 to temperature regulation to endothelial function and to countless other
■ POTENTIAL ADVERSE EFFECTS OF SLEEP DISRUPTION processes. The central pacemaker is synchronized (ie, “reset”) to the
external environment daily chiefly through photic cues transmitted
IN CRITICALLY ILL PATIENTS through the retinohypothalamic tract to neurons in the SCN. 18,19 This
In a series of experiments performed by Alan Rechtschaffen, rats sub- process of modifying an organism’s intrinsic rhythm in order to align it
with the external environment is called entrainment. Although there are
jected to total sleep deprivation died within several weeks. While no
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similar such experiment has been performed in humans, disrupted sleep other Zeitgebers (“timegivers”) including food, social interactions, and
ambient temperature, these are less potent than light.
and circadian rhythmicity have been linked to a host of basic physiologic
Neurons from the SCN project to the pineal gland, which secretes
processes and to a variety of adverse health outcomes. While it is surely melatonin in a rhythmic pattern that is primarily determined by the SCN
true that “Sleep is of the brain, by the brain, and for the brain,” it is
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increasingly clear that sleep is for the whole body as well. and its circadian rhythm. Melatonin thus serves as a practical “hand of
the clock,” allowing investigators to determine the circadian rhythm
Currently, there are no data demonstrating that the sleep or circadian
rhythms of critically ill patients influences either their short-term or of the central pacemaker by analyzing the 24-hour secretion pattern of
melatonin. Normally, serum melatonin levels are high during the sub-
long-term outcomes. It is also worth noting, however, that the absence
of an effect has not been shown. Based on extrapolation from other jective night and lower during the subjective day, and a similar pattern
is seen in the urinary metabolite of melatonin, 6-sulfatoxymelatonin.
20
populations, sleep disruption could have a myriad of adverse effects
on the critically ill patient (Table 23-2). Consider the following hypo- Bright light during the subjective night acutely suppresses melatonin
production, an effect that is independent from light’s phase-shifting
thetical scenario for a patient admitted to the ICU. In the acute setting,
severe sleep deprivation causes the patient to be lethargic and encepha- effects. Melatonin itself has a variety of pharmacologic properties and
has receptors throughout the brain and in a variety of peripheral tissues.
lopathic with increased sensitivity to sedatives and narcotics and a 21
depressed ventilatory response to CO , frustrating physician attempts The physiological functions of melatonin itself are still being clarified.
Circadian clocks are also present in a variety of peripheral tissues, and
2
to liberate him or her from the ventilator. Subsequently, sleep depriva- 22
tion reduces insulin sensitivity and glycemic control and impairs the the study of the role of clock genes in human disease is exploding. An
interesting study performed by Haimovich and colleagues found that the
immune response, predisposing the patient to infection. After discharge,
the profound sleep debt incurred by the patient during critical illness injection of intravenous endotoxin dramatically altered the expression
of circadian clock genes in peripheral blood leukocytes, and that this
persists as a result of physical illness, anxiety, and medication effect. 23
This sleep deprivation worsens her mood and motivation, reduces her activity may have been uncoupled from the activity of the central clock.
Further study is needed to clarify the role of the central and peripheral
energy expenditure and physical activity, impairs her executive func-
tion and memory consolidation, and leads to long-term psychological clocks in modulating the immune response, endothelial function, and a
host of other processes relevant to critical illness. At a minimum, disor-
distress and neurocognitive dysfunction. This hypothetical example is
biologically plausible based on extrapolations from basic investigations dered circadian timing in the critically ill patient may disrupt sleep in a
manner similar to the effects of jet lag or shift work; the considerations
and from studies in other patient populations but awaits confirmation
in the critically ill patient. mentioned above suggest that much more derangement of the circadian
rhythm may yet be discovered.
There are certain challenges to studying circadian rhythms in criti-
TABLE 23-2 Potential Harm From Sleep and Circadian Disruption During cal illness. For instance, while core body temperature is a fairly reliable
and After Critical Illness marker of circadian rhythm in health, its validity as a phase marker of
circadian rhythmicity is less certain in patients with critical illness, many
Excessive sleepiness of whom exhibit altered thermoregulation due to infection, age, and the
Acute brain dysfunction/delirium effects of medications. Clinically recorded temperatures may also not be
Reduced ventilatory and arousal response to CO and to hypoxia measured sufficiently frequently or at sites that closely approximate core
2
Increased upper airway collapsibility body temperature. Analysis of the temporal profiles of serum melatonin
Exacerbation of preexisting or latent sleep disordered breathing and of urinary 6-sulfatoxymelatonin is a useful method for analyzing
Postextubation obstructive sleep apnea circadian rhythmicity in this population but may still be confounded
Increased sensitivity to medications, particularly sedatives and narcotics by the effects of various medications or by abnormalities in liver or
Dysregulated immune response renal function. 24
Impaired glucose tolerance Notwithstanding these challenges, the available evidence suggests that
Reduced motivation and drive the circadian rhythms of critically ill patients are frequently disturbed.
Long-term neuropsychiatric effects Mundigler et al demonstrated striking abnormalities in the 6-sulfat-
Neurocognitive dysfunction oxymelatonin excretion patterns of sedated critically ill patients with
Psychiatric illness (depression, anxiety, posttraumatic stress disorder) sepsis. Paul et al similarly demonstrated a disturbed pattern of melato-
25
Reduced health-related quality of life nin secretion in 24 critically ill sedated patients, along with abnormalities

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