Sedation and analgesia strategies in the neuro intensive care unit

Table 1 Summary of drugs

Drug	MoA	Adult dosing1	Contraindications2	Pros	Cons	AEs
Morphine (IV)[105]	μ, δ, & κ opioid receptor agonist	2-10 mg (loading); 2-4 mg/1-2 hours or 4-8 mg/3-4 hours (maintenance)	Hypersensitivity; Epidural/intrathecal infusion site infection; Concomitant anticoagulant therapy; Uncontrolled bleeding; Upper airway obstruction	Widespread cortical, subcortical, and brainstem effects, making them potent enough to significantly modulate pain and sedation; Can be combined with NSAIDs to provide pain relief when not controlled by other methods; Often favored over sedatives in the ICU setting as it reduces the rate of drug-related adverse events, increases pain control, and reduces time on mechanical ventilation; Short half-lives allow for frequent reevaluations of neurological status	Limited ability to provide deep sedation and amnesic effects; Widespread list of more commonly experienced adverse effects compared to other sedatives or analgesics; Can complicate and prolong postoperative recovery times; The nature of these drugs’ effects can mask intracranial events; Can be challenging to manage in patients with acute brain injuries	Constipation and/or diarrhea; Neurotoxicity; Pruritus; Respiratory depression and/or apnea; Withdrawal; Profound drowsiness and/or dizziness; Headaches; Nausea and/or vomiting; Arthralgias; Peripheral edema; Dehydration; Hypokalemia; Abdominal pain and/or anorexia; Anemia; Insomnia; Asthenia and/or fatigue
Oxycodone (oral)[106]		5-10 mg/4-6 hours	Hypersensitivity; Respiratory depression; Hypercapnia; Bronchial asthma; GI obstruction
Hydromorphone (IV)[107]		0.5-2 mg/1 hour (initial); 0.25-4 mg/1 hour	Hypersensitivity; Respiratory depression; Hypercapnia; Bronchial asthma; GI obstruction
Fentanyl (IV)[108]		0.025-0.1 mg or 0.001-0.002 mg/kg (loading); 0.025-0.050 mg or 0.00035-0.0005 mg/kg/0.5-1 hour	Hypersensitivity; Respiratory depression; Bronchial asthma; GI obstruction; Patients requiring short-term therapy; Management of acute or intermittent pain, postoperative or mild pain; Patients who are not opioid tolerant
Remifentanil (IV)[109]		0.0015 mg/kg (loading); 0.0005-0.015 mg/kg/1 hour (maintenance)	Hypersensitivity Intrathecal or epidural administration
Lorazepam (IV)[110]	GABAA receptor agonist	0.02-0.04 mg/kg (initial); 0.02-0.06 mg/kg/2-6 h (maintenance)	Hypersensitivity; Acute narrow-angle glaucoma; Sleep apnea; Intra-arterial injection; Premature infants; Severe respiratory insufficiency	Lorazepam has high efficacy and longer duration of action; Midazolam has a rapid onset and versatility in route of administration; Diazepam has a shorter duration of action and can be used rectally; Useful in controlling seizures; Minimal cardiovascular effects	High-dose midazolam is only used to break seizures; Prolonged use (24-48 hours) can increase delirium, delay extubation, longer LOS, and long-term neuropsychiatric effects; Should not typically be used in hemodynamically unstable patients	Profound drowsiness; Nausea and/or vomiting; Respiratory depression and/or apnea; Anterograde amnesia; Paradoxical reactions (e.g., aggression); Propylene glycol toxicity; Withdrawal
Midazolam (IV)[111]		0.5-5 mg or 0.01-0.05 mg/kg/10-15 minutes	Hypersensitivity; Intrathecal or epidural injections; Premature infants; Acute narrow-angle glaucoma; Concurrent use with protease inhibitors; Concurrent use with fosamprenavir
Diazepam (IV)[112]		5-10 mg (initial); 0.03-0.1 mg/kg/0.5-6 hour (maintenance)	Hypersensitivity; Acute narrow-angle glaucoma; Untreated open-angle glaucoma; Infants < 6 months; Myasthenia gravis; Severe respiratory impairment; Severe hepatic impairment; Sleep apnea
Pentobarbital (IV)[113]		10 mg/kg + 5 mg/kg/h × 3 (loading); 1-4 mg/kg/h (maintenance)	Hypersensitivity; Porphyria	Used for treatment of super-refractory status epilepticus (SRSE)	Third-line agent that carries many potential adverse effects with little utility in neuro ICU settings	Bradycardia and/or hypotension; Gastrointestinal upset and hepatotoxicity; Respiratory effects
Propofol (IV)[114]		0.005-0.050 mg/kg/min or 0.3-3 mg/kg/h	Hypersensitivity; Hypersensitivity to eggs, egg products, soybeans, or soy products	Widely used in critical care due to its rapid onset, short duration, and predictable recovery profile; Able to reduce cerebral metabolic rate and ICP; Allows for frequent neurologic reevaluation; Has anti-epileptic and anti-emetic properties	Should not typically be used in patients with hemodynamic instability; Lacks analgesic effects by itself and must be adjunctive with another drug for pain control; Risk for drug accumulation, especially in obese patients	Cardiac conduct disturbances (e.g., prolonged QT interval); Hypersensitivity reactions; Hypertriglyceridemia; Hypotension; Propofol-related infusion syndrome (PRIS)
Dexmedetomidine (IV)[115]	α-2 receptor agonist	0.0002-0.0015 mg/kg/h	Hypersensitivity	Can provide an arousable state without concerning respiratory effects; Neuroprotective, allowing for better neurological assessment	Hemodynamic effects can limit the patient population for its use	Bradycardia and/or hypotension; Hypertension; Tachyphylaxis; Tolerance and withdrawal
Clonidine (IV)[116]		0.05-0.15 mg/6-8 hours	Hypersensitivity; Epidural injection site infection; Concurrent anticoagulant therapy; Bleeding diathesis; Administration above the C4 dermatome	Many different routes of administration; Relatively safe and versatile drug	Sudden withdrawal can lead to rebound hypertension and hypertensive crisis	Bradycardia and/or hypotension; Withdrawal
Ketamine[117]	NMDA & glutamate receptor antagonist	0.1-0.5 mg/kg (initial); 0.2-0.5 mg/kg/h (maintenance)	Hypersensitivity; Increased blood pressure; Infants < 3 months; Known or suspected schizophrenia	Very rapid onset and short duration of action; Can be used for procedural sedation; Good option for patients at risk of bronchospasm, those refractory to opioid treatment, and those with conditions that cause chronic pain; Can be used for treatment-resistant status epilepticus; Prevents cortical spreading depolarization, making it a great drug for TBIs; Better hemodynamic stability than many other ICU drugs	Causes a profound dissociative state in patients; Can cause many somatosensory effects, even at small doses, having made it a popular drug of recreational abuse; Produces the highest rate of agitation and vomiting in patients who undergo procedural sedation with this drug	Laryngospasm; Cardiovascular instability; Dependence & tolerance; Prolonged emergence from anesthesia; Vivid dreams, hallucinations, and/or delirium; Genitourinary effects; Respiratory depression or apnea

¹Adult dosing is listed for ICU-level patients without evidence of kidney or liver disease.

²Based on United States labeling.

GI: Gastrointestinal; ICP: Intracranial pressure; ICU: Intensive care unit; IV: Intravenous; LOS: Length of stay; NSAIDs: Non-steroidal anti-inflammatory drugs; PRIS: Propofol-related infusion syndrome; SRSE: Super-refractory status epilepticus; TBI: Traumatic brain injury; NMDA: N-methyl-D-aspartate.