Page 146 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

112 PART 1: An Overview of the Approach to and Organization of Critical Care

Hypoxemia The mechanisms of critical illness–induced brain injury are of delirium was 2 days in these 77 critically ill patients. Survivors had
unknown, but hypoxemia is undoubtedly implicated. 9,146 Hopkins et al a high rate of neurocognitive impairments at 3 and 12 months (~71%).
evaluated pulse oximetry in a prospective cohort of mechanically venti- A longer duration of delirium predicted worse neurocognitive impair-
lated ARDS survivors and studied the relationship between the duration ment at 3 and 12 months. The association between duration of delir-
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and severity of a mean oxygen saturation below 90 and neurocognitive ium and longer-term neurocognitive dysfunction was also confirmed in
outcome. The pulse oximetry was measured for a total of 31,665 hours, the Pandharipande study. 6
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excluding data without a good pulse waveform. Patients’ mean satura- Mechanisms of delirium are complex and thought to be related to
tions were below 90% for 122 ± 144 hours per patient. The degree of imbalances in synthesis, release, and inactivation of neurotransmitters.
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2
hypoxemia correlated significantly with neurocognitive sequelae (r = For example, dopamine excess or acetylcholine depletion can result in
0.25 to 0.45, all p < 0.01). The recent ICOS study also confirmed this as delirium. Serotonin imbalance and increased noradrenergic activity
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an important risk factor for the subsequent development of neurocogni- can also contribute to the development of delirium. Other mecha-
tive dysfunction. 88 nisms of delirium include endotoxin- and cytokine-induced inflam-
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Supportive evidence includes neuronal death in the CA1 subfield of matory abnormalities, inadequate cerebral perfusion, metabolic
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the hippocampus and increased S-100B protein serum levels in pigs derangements, and hypothalamic pituitary activation. 177
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with acute lung injury and associated hypoxemia. Hypoxia can cause
cortical atrophy, 148-150 and ventricular enlargement, a sensitive indica- Glucose Dysregulation Hyperglycemia (>110 mg/dL) is common in critically
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tor of structural damage. 149,150 Nonspecific neuronal cell loss results in ill patients, and contributes to morbidity and mortality. Hyperglycemia
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brain volume reduction manifest by reduced gyral volume, increased is associated with (a) increased mortality in acute ischemic stroke ;
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sulcal space, passive increase in ventricular volume (ie, hydrocephalus (b) impaired neurological recovery following ischemia, anoxia, and
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ex vacuo), and an increase in whole brain cerebral spinal fluid (CSF). traumatic brain injury ; (c) poor neurologic outcome following
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Neurocognitive impairments are frequent in patients with chronic stroke ; and (d) neurocognitive impairments in diabetic patients.
obstructive pulmonary disease (COPD), 152,153 cardiac and/or respiratory Hypoglycemia leads to neuronal death in the hippocampus, cerebral
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arrest, 148,154,155 obstructive sleep apnea syndrome (OSAS), and postop- cortex, and striatum due to increased extracellular glutamate concen-
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erative hypoxia following cardiac surgery. 156 tration, glutamate receptor activation and associated excitotoxicity.
The mechanisms by which hypoxia/hypoxemia damage the brain has Sustained glutamate receptor activation results in the production of
been elucidated over the last decade, in both in vivo and in vitro models peroxynitrate and other reactive oxygen species, leading to additional
and reviewed by Johnston et al Mechanisms include (1) decreased neuronal cell death. 185
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ATP production without decreasing ATP utilization, (2) lactic Hopkins and colleagues assessed relationships between blood
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acidosis, 159,160 (3) neurotoxicity of excitatory amino acid neurotransmit- glucose and neurocognitive function at 1-year posthospital dis-
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ters, 161,162 (4) increased calcium influx and intracellular accumulation of charge. The incidence of hypoglycemia (<60 mg/dL) was low
calcium due to ionic pump failure, 163,164 (5) reperfusion and/or reoxy- (<0.5%). Moderate hyperglycemia during ICU hospitalization was
genation injury, 165-167 (6) necrosis due to edema and rupture of the cell associated with poor neurocognitive outcomes at 1 year. Blood glucose
membrane, and (7) apoptosis or programmed cell death. 168,169 values greater than 153 mg/dL predicted adverse cognitive sequelae,
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but the effect did not worsen as blood glucose values increased above
Hypotension Hypotension may represent a more modest risk factor for that threshold. Greater duration of mechanical ventilation and longer
poor neurocognitive outcome. Continuous mean blood pressure data ICU stays also predicted neurocognitive sequelae. Blood glucose
were automatically collected through the GE-Marquette (Milwaukee, dysregulation—specifically moderate hyperglycemia—was associated
Wisconsin) bedside physiological monitoring system connected to a with adverse neurocognitive sequelae in critically ill ARDS survi-
computer during ventilatory support. Continuous blood pressure was vors. A recent study in surgical critically ill patients demonstrated
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measured from the arterial catheters and was sampled every 2 minutes that hypoglycemia, hyperglycemia, and fluctuations in blood glucose
and the median value for each 15-minute period recorded. The were associated with worse neurocognitive outcome. Further evi-
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duration of hypotension events was calculated by adding consecutive dence of the adverse neural effects comes from Dowdy and colleagues
measurements (each measurement represents a 15-minute interval) who found hypoglycemia was associated with a 3.6-fold increased risk
that were <60 and <50 mm Hg. The mean blood pressure <50 mm Hg of depression in ARDS patients. 188
correlated with memory scores at hospital discharge. There were no sig- Mechanisms of hyperglycemic-induced brain injury include increased
nificant correlations between neuropsychological test scores and mean lactic acid formation and impaired phosphorus metabolism, 189-191 free
blood pressure <50 mm Hg at 2 years. Thus, the duration of hypoten- radical production, increased calcium release, calcium overload of
sion modestly correlated with impaired memory at hospital discharge mitochondria, increased catecholamine release, 192-194 and neuronal death
and 1 year, but not at 2 years. 28 following anaerobic glycolysis. Hyperglycemia also leads to increased
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neutrophil accumulation that is associated with an increase in the
Delirium Another possible contributor to neurocognitive sequelae is size of the brain contusion or ischemic area due to microvascular
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delirium, a common condition among critically ill patients that occlusion, formation of oxygen radicals, cytolytic proteases, and pro-
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is associated with adverse neurologic outcomes in wide-ranging hos- inflammatory cytokines. 198,199 Hyperglycemia decreases cerebral blood
pital populations. A recent review of the association between delirium flow, 200,201 damages the vascular endothelium, 202,203 increases blood-brain
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and development of long-term neurocognitive function found four barrier permeability, and increases release of excitatory neurotrans-
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studies with greater decline on neurocognitive measures at follow-up mitters resulting in neuronal death. 205
among patients experiencing delirium during hospitalization and four
studies found higher incidence of dementia at long-term follow-up in Sedatives or Analgesics The role of certain medications such as sedatives, nar-
elderly patients. The only study that assessed delirium and neurocog- cotics, and paralytics in the development of delirium are well known ;
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nitive outcomes in critically ill patients found long-term neurocognitive however, less is known regarding their impact on long-term neurocogni-
impairment in one in three patients with delirium at 6-month follow- tive function. Although data on the impact of anesthetics and sedatives
up. A trend toward a longer duration of delirium (number of days on long-term neurocognitive functioning are conflicting, reports suggest
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of delirium) was found for patients with neurocognitive impairment they may have neurotoxic effects particularly for high-risk groups such
compared to patients without neurocognitive impairment, but it did not as the very old (>75 years) and/or those with a recent history of neuro-
reach statistical significance. cognitive impairment. 207,208 Reducing sedation reduces time on mechani-
A recent study compared long-term neurocognitive outcomes in cal ventilation and ICU length of stay. One study assessed long-term
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critically ill mechanically ventilated patients. The median duration neurocognitive outcomes in patients treated with spontaneous breathing
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