Respiratory Depression

Drug-induced respiratory disease has a low incidence but is associated with a high mortality when manifest. Patients with COPD, reduced hepatic and renal function, and the elderly are particularly at risk. Additionally, patients receiving combination therapies with other respiratory depressants and/or oxygen supplementation are at even greater risk.

Alcohol is particularly important when consumed in combination with other respiratory depressants, and patients should be counseled to avoid alcohol or alcohol-containing products.

Opioid analgesics are highly associated with respiratory depression, but tolerance develops over time. Additionally, in the non-COPD patient the drug level for pain relief is below the level for respiratory depression. However, pharmacists must be aware that COPD patients may have a much smaller therapeutic range and opioids should be initiated at lower doses and the dosage titrated slowly. Furthermore, complete cross-tolerance from one opioid analgesic to another cannot be assumed, and a 25% (normal patient) to 50% (COPD patient) decrease in initial conversion dose should be sought. Finally, naloxone and nalmefene can reverse the respiratory depression associated with narcotics, but should be dosed until the desired effect is achieved while avoiding precipitation of an acute return of pain.

Tramadol is a reasonable alternative agent to narcotics for the patient at risk. Unfortunately, care must be taken to avoid overdose and/or concomitant use of other respiratory depressants since the respiratory depression that can result is not fully reversible with naloxone or nalmefene. Also, concurrent use of tramadol with phenelzine or tranylcypromine is contraindicated.