The neurointensivist should adopt an "analgesia first" or "A-1" approach to relieve the patient's pain before administration of sedation.1 This will avoid disinhibiting a patient whose agitation is due to pain, as discussed above. There is evidence that an A-1 approach decreases sedation requirements and time on the ventilator.2-6 ICU patients experience pain and discomfort with procedures such as tracheal intubation, endotracheal tube suctioning, and repositioning. Failure to treat pain exacerbates endogenous catecholamine activity, which predisposes to myocardial ischemia, hypercoagulability, hypermetabolic states, sleep deprivation, and delirium.7,8
Opioids are the mainstay of pain management in the ICU. Synthetic analgesics such as fentanyl and remifentanil are commonly used. These agents are administered as a bolus or as an infusion to manage pain and facilitate synchronous mechanical ventilation. Fentanyl, a short-acting opioid, has an intravenous onset time of less than 1 minute and duration of action of ½ to 1 hour. Duration of analgesia increases with prolonged infusions or repeated dosing. Fentanyl does not have an active metabolite and its pharmacokinetics is not altered by renal failure. However, uremia potentiates its pharmacodynamic effect, and sensitivity to sedation and respiratory depression is increased. Fentanyl has a high hepatic extraction ratio and its metabolism is slowed in patients with liver disease (eg, cirrhosis) or hepatic dysfunction (eg, congestive heart failure, shock).9
Remifentanil is an ultrashort-acting opioid and as such may be preferred for patients who require frequent neurologic evaluations. It is metabolized directly in the blood by plasma esterases and has an elimination half-life of 8 to 9 minutes. Described as a "forgiving opioid," remifentanil is characterized by a rapid onset and offset of action that is independent of liver or renal function.10,11 Infusion of remifentanil has an onset of action of 1 minute10 and rapidly achieves steady-state plasma levels. Its analgesic and sedative effects dissipate within 3 to 10 minutes of discontinuation of an infusion. Abrupt discontinuation of an infusion (eg, disconnect, empty bag) can precipitate the sudden return of severe pain and discomfort with hypertension and tachycardia.
In a randomized controlled trial comparing remifentanil infusion (0.15 mcg/kg per minute) with morphine, the duration of mechanical ventilation, time to tracheal extubation, and the interval between tracheal extubation and ICU discharge were significantly shorter with remifentanil.3 Nonetheless, because of its high cost and the risk of sudden discontinuation (see above), remifentanil is not widely used in the ICU in the United States.
Bradycardia, hypotension, respiratory depression, nausea, and skeletal muscle rigidity are potential adverse effects of opioids. Given this patient's chronic renal insufficiency, morphine and meperidine should not be prescribed because they have active metabolites that are eliminated by the kidneys. Although it does not accumulate in renal failure, hydromorphone has a half-life of 2 to 3 hours, which makes it difficult to titrate for frequent neurologic assessment.
Epidural analgesia effectively prevents chest wall splinting after rib fractures, but placement of an epidural catheter is contraindicated in patients who have received a dose of clopidogrel within 7 days.