Analgesic Dosage Precautions and Comorbidity

The key principle for safe and effective use of opioids is to titrate the dose against the desired effect—pain relief—and minimize unwanted effects. Opioids in larger doses than necessary to control pain, or when given to patients who are not in pain, can result in respiratory depression and hypotension. Relative potency estimates provide a rational basis for selecting the appropriate dose (see Table.3.2:5.). In the setting of comorbid conditions that include underlying neurologic deficits, altered mental status, hemodynamic instability, respiratory dysfunction, or multisystem trauma, systemic narcotics should be used cautiously.

Patients at the extremes of age are at risk for both inadequate analgesia and pharmacotherapy complications. For the comprehensive management of pediatric pain, age-appropriate assessment techniques and medication dosages and developmentally specific nonpharmacologic adjuncts are essential (see chapter..1,30). Elderly patients may have more than one source of pain and comorbidity and are at increased risk for drug-drug as well as drug-disease interactions. The elderly, especially opioid-naive patients, are more sensitive to the analgesic effects of opioid drugs as they experience a higher peak and longer duration of pain relief. Moreover, they are more sensitive to sedation and respiratory depression and cognitive and neuropsychiatric dysfunction. Some patients may have concerns about physiologic or psychological dependence and should be informed that this is extremely unlikely after short-term use for acute pain. -I4!5

As most analgesics are metabolized by the liver or kidney, caution is essential when using opioids in patients with altered hepatic or renal function. Renal excretion is a major route of elimination for such pharmacologically active opioid metabolites as norpropoxyphene, normeperidine, morphine-6-glucuronide, and dihydrocodeine. Mild renal failure can impede excretion of the metabolites of many opioids, resulting in clinically significant narcosis and respiratory depression.

Patients with respiratory insufficiency and those with chronic obstructive pulmonary disease, cystic fibrosis, and neuromuscular disorders affecting respiratory effort (e.g., muscular dystrophy, myasthenia gravis) are particularly vulnerable to the respiratory depressant effects of opioids and nitrous oxide. Appropriate monitoring of respiratory rate and effort and adequacy of gas exchange is necessary.

Opioids may have adverse synergistic sedative effects in patients with psychiatric illnesses taking anxiolytics or other psychoactive drugs. The use of MAOIs with meperidine has been associated with severe adverse reactions, including death through mechanisms that mimic malignant hyperthermia. The tricyclic antidepressants clomipramine and amitriptyline may increase morphine levels.

Patients in shock, as well as those with trauma and burns, and hemodynamic or respiratory instability mandate judicious use of narcotics. Cautious titration, in consideration of cardiovascular and respiratory stability, of an intravenous short-acting opioid analgesic such as fentanyl 16 and maximal use of regional analgesia are recommended.1 The intramuscular route has poor and variable absorption and bioavailability in this setting and should be avoided. Additionally, in the trauma patient there is potential for masking occult trauma with excessive use of systemic narcotics. Use of analgesic therapy also must allow for continuous monitoring of neurologic status after a head injury and neurovascular status after limb injury. In the setting of closed head injury or multiple injuries, maximal use of regional and nonpharmacologic modalities minimizes the use of systemic analgesics. While of value in the patient with minor trauma, the use of NSAIDs in the major trauma patient remains controversial. The risk of excessive bleeding from platelet dysfunction, gastric stress ulcers, and potential for acute renal failure in the volume-depleted patient minimize their utility for this patient group.

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