Pain control is an important aspect of critical care medicine and the use of opiate medications has typically been an important method of achieving control in the intensive care unit (ICU) setting.

The brain has four opiate receptors that include the mu, kappa, delta, and sigma receptors. Currently used opioid analgesics bind to the mu receptor and initiate the pharmacological effects of analgesia, miosis, respiratory depression, euphoria, and physical dependence.

The route of opiate administration is often intravenous, with bolus administration for mild to moderate pain, continuous infusion for moderate to severe pain, and patient-controlled analgesia for the post-surgical patient who can participate in his or her care.

Like other ICU interventions where benefits must be balanced against risks, adequate analgesia must carefully be balanced with the side effects of opiate therapy, particularly in the critically ill patient. These include respiratory depression, hypotension, emesis, flushing, bronchospasm, and constipation.

What to Do

The three most commonly prescribed opiate analgesics in the ICU are morphine, hydromorphone, and fentanyl. While morphine is widely used in the ICU setting, fentanyl has additional benefits for the critically ill patient because of its increased potency, lipid solubility, and hemodynamic stability.

Morphine dosing usually begins at 2 mg and is then titrated up by 1 mg to 2 mg every few hours if given in intermittent bolus form and 1 mg/hour if given continuously. Morphine metabolism occurs in the liver with excretion occurring in the kidney. Therefore, the dose should be reduced if the patient has a glomerular filtration rate less than 30 mL/min in order to prevent accumulation of its active metabolite.

Hydromorphone, a semisynthetic opiate agonist, is markedly more potent and quicker in onset than morphine. Dosing begins at 0.2 to 0.6 mg with repeated doses every 2 to 3 hours. This dose may need to be increased in patients who have had marked exposure to opiates in the past.

In addition, if given as an intravenous continuous infusion, the dose should be 0.5 to 1 mg per hour after the bolus dose. Like morphine, hydromorphone is metabolized by the liver. In contrast to morphine, however, the metabolites are all inactive. Therefore, dose adjustment should be considered for hepatic failure.

Fentanyl is a synthetic opiate agonist and is 100 times more potent than morphine. Many ICUs have increasingly used fentanyl as the analgesic of choice because of its rapid onset and potency. When administered in intermittent boluses, the dose is usually 25 to 75 mcg every hour.

However, it is more effectively used to prevent pain if given continuously at a rate of 25 to 50 mcg/hour after the bolus dose. Fentanyl accumulates in adipose tissue and if administered for longer than 5 days may have prolonged sedation effects upon its discontinuation. Fentanyl is metabolized to inactive compounds by the liver and excreted by the kidneys; thus the dose may need to be adjusted for liver failure, but not renal failure.

Physical dependence can occur with any of these medications and will result in withdrawal if stopped abruptly. In addition, many patients develop tolerance to the opiates and require increasing dosages to achieve the same level of pain control.

One method of overcoming opiate tolerance is to use adjuvant therapies that enhance the effect of opiates. For example, the concomitant use of benzodiazepines will assist with anxiolysis and improve the response to analgesia. However, it will also contribute to the side effect of respiratory depression already seen with opiate medications.


Hamill-Ruth RJ. Evaluation of pain in the intensive care unit. Crit Care Clin 1999;15

Joranson DE, Ryan KM, Gilson AM, et al. Trends in medical use and abuse of opioid analgesics. JAMA 2000;283:1710.

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