Impaired Consciousness in the Traumatic Brain Injury Patient

Acute disturbances in cognition and consciousness are widely prevalent in neurologic intensive care units and have been associated with worse outcomes. Studies of critically ill patients with traumatic brain injuries have found that delirium developed in up to 60% of cases for a median duration of 4 days. Selection of analgesics and sedating agents for these patients can be challenging and management strategies should include consideration of altered cerebral physiology that commonly occurs after TBI in order to optimize recovery times and long term cognitive funciton.

Key points

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Delirium is a broad term that encompasses any acute change in attention and arousal, while encephalopathy is a discrete pathobiological process in the brain.
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Use of benzodiazepines and neuroleptic medications should be minimized whenever possible, as these can slow recovery after brain injury and negatively affect cognition.
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Daily interruption of sedation (with resumption at 50% dose) in eligible patients is important and may reduce ventilator days and the need for neuro-imaging.
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Connectivity between the medial prefrontal cortex and precuneus is correlated with preserved consciousness after neurotrauma. Disruptions to this pathway may be reversible; and early evaluation is consequential.

Abbreviations

BIS	Bispectral Index
CAM-ICU	Confusion Assessment Method for the intensive care unit
CPOT	Critical Care Pain Observation Tool
CT	computed tomography
FOUR	Full Outline of UnResponsiveness
GCS	Glasgow Coma Score
HIE	hypoxic-ischemic
ICU	intensive care unit
PRES	posterior reversible encephalopathy
PRIS	propofol-related infusion syndrome
RASS	Richmond Agitation Sedation Scale
SAT	spontaneous awakening trial

“Delirium,” “encephalopathy,” “altered mental status,” and “acute confusional state” are the terms used (often interchangeably) to describe a patient whose cognition is affected in the setting of acute illness or injury. Acute disturbances in cognition and consciousness are widely prevalent in neurologic intensive care units (ICUs) and have been associated with worse outcomes in terms of mortality, length of ICU admission, and long-term cognitive impairment. This section aims to define and distinguish these terms, as well as provide clinical and diagnostic tools for identifying and managing patients who show signs of cognitive dysfunction after a traumatic brain injury.

Delirium

Delirium, as outlined in the DSM-V, (Diagnositic and Statistical Manual of Mental Disorders Fifth Edition) is a broad term that refers to any acute change in both attention and arousal that develops over a short period of time and tends to fluctuate in severity over the course of a day; it can present as a hyperactive, hypoactive, or mixed state. By contrast, coma refers to “a clinical state of severely depressed responsiveness” based on a diagnostic system, for example, the Glasgow Coma Score (GCS) or the Full Outline of UnResponsiveness (FOUR) score.

There are several diagnostic tools that have been used to identify delirium in an ICU setting. The most widely accepted among them is the Confusion Assessment Method for the ICU (CAM-ICU) which is preferred for its rapid administration and the fact that it does not necessitate verbal communication from the patient, which is often a challenge with critically ill patients who are intubated and/or sedated. Using CAM-ICU, a diagnosis of delirium is made based on the presence of 2 major criteria (acute or fluctuating onset plus lack of attention) and at least 1 minor criteria (disorganized thinking or altered consciousness level). Electroencephalogram (EEG) has also been used to diagnose delirium by identifying a slow wave pattern as a marker for cerebral metabolic damage. However, while highly sensitive, this method lacks specificity and, therefore, is not considered practical in the assessment of critically ill patients.

As mentioned previously, delirium is widely prevalent in the ICU setting; in fact, a large retrospective cohort study of critically ill trauma patients with TBI found that delirium developed in 60% of the patients for a median duration of 4 days. Risk factors for developing delirium as well as increased delirium duration in this population included increased age, severe initial injury, intracranial hemorrhage, and reduced GCS motor score. Female sex, higher minimum glucose, and higher minimum hemoglobin levels on hospital day 1 appeared to be protective against delirium.

Delirium prevention

No intervention has been shown to reverse delirium; however, measures can be taken to reduce the risk of its development. The use of opioids, access to a television, and number of hours mobilized per day have been associated with significantly reduced risk of delirium. Current guidelines recommend use of anticonvulsants for the first 7 days following injury to reduce the incidence of post-traumatic seizures; however, routine use after 7 days is not recommended, in part due to sedating effects. The use of benzodiazepines and neuroleptic medications in general should be minimized whenever possible, as these can slow recovery after brain injury and have a negative effect on cognition. While not a treatment for delirium, amantadine has been used to enhance arousal, consciousness, and accelerate short-term functional recovery in patients who are in a minimally responsive state after a TBI.

Sedation and analgesia

Sedation of the neurocritically ill patient is challenging and must provide a balance of comfort and safety with the need for frequent neurologic checks and a thorough neurologic examination. Goals are similar to other critically ill patients and include pain control, ventilator synchrony, management or prevention of alcohol or benzodiazepine withdrawal, patient and nursing safety, and the ability to perform bedside procedures. Patients with neurologic illnesses who have concomitant intracranial pressure elevation, status epilepticus, paroxysmal hyperactivity, or shivering may have different goals and require alternative agents for management. In the case of status epilepticus, for example, sedative agents such as propofol and midazolam may be used at higher doses without spontaneous awakening trials (SATs), resulting in deeper sedation and longer time to awakening upon discontinuation of the agent. Additionally, patients who require neurosurgical or other procedures or surgeries will receive anesthetics in the operating room and may experience prolonged effects even after returning to the ICU. It is important to note that accumulation affects the half-lives of these medications and should be considered prior to considering a brain death examination.

Reversible causes of pain and agitation should be explored prior to initiating pharmacotherapy. These can include discomfort, noise, sleep disturbances (sometimes caused by middle of the night blood draws and frequent neurologic checks), disorientation to person, place, or time, catheter, line, or device placement, overstimulation, or medication side effects (eg, agitation associated with levetiracetam). Whenever possible, the need for invasive treatments should be assessed and reduced to help address these issues.

Analgesia

Analgosedation is recommended to reduce overall sedative use and ensure that pain is treated first. Preferentially using opioid analgesics to treat pain may avoid the need for other sedatives. A numerical scale (0–10) for communicative patients or the Critical Care Pain Observation Tool (CPOT, goal <3) for nonverbal patients should be used to assess and titrate opioid infusions. The 3 most commonly used opioid infusions in the ICU are fentanyl, hydromorphone, and morphine ( Table 1 ). Fentanyl is the most lipophilic of these agents with a fast onset and short duration of action and is commonly preferred in neurocritically ill patients. However, it can accumulate with prolonged use or in obese patients. Hydromorphone has a longer duration of action and may be a good option for patients transitioning from infusion to scheduled, intermittent dosing. Morphine is less commonly used as it has 2 active metabolites (morphine-3-glucuronide and morphine-6-glucuronide) which are renally eliminated and can cause neurotoxicity and oversedation, respectively. In addition, morphine causes histamine release which can lead to hemodynamic instability.

Table 1

Commonly used analgesics and sedatives

Data from Adams, 2020.

Drug	Bolus Dose	Common Infusion Dose	Onset	Half-Life	Active Metabolites	Considerations
Opioid Analgesics
Fentanyl	25–100 mcg	25–400 mcg/h	2 min	2–4 h	N	Chest wall rigidity, accumulation in obesity, respiratory depression
Hydromorphone	0.25–1 mg	0.5–2 mg/h	15 min	2–3 h	N	Respiratory depression
Morphine	0.5–10 mg	1–10 mg/h	15 min	3–4 h	Y	Neurotoxicity from morphine-3-glucuronide active metabolite, hypotension (histamine release), respiratory depression
Sedatives
Lorazepam	0.5–1 mg	0.5–10 mg/h	5–20 min	8–15 h	N	Propylene glycol toxicity/acidosis
Midazolam	0.5–3 mg	1–10 mg/h	2–5 min	3–11 h	Y	Accumulation of active metabolite
Propofol	10–20 mg ^a	5–80 mcg/kg/min	1 min	3–12 h	N	PRIS, hypertriglyceridemia, hypotension
Dexmedetomidine	0.5–1 mcg/kg ^a	0.2–1.5 mcg/kg/h	30 min	2–5 h	N	Bradycardia, hypotension
Ketamine	0.1–0.3 mg/kg	1–5 mcg/kg/min	5–15 min	2–3 h	Y	Hypertension, increased salivation