Factors Affecting Opioid-Induced Respiratory Depression
Many factors affect the magnitude and duration of opioid-induced
respiratory depression ( Table 11-6
).
Older patients
are more sensitive to the anesthetic and respiratory-depressant effects of opioids.
[124]
Older patients experience higher plasma concentrations
of opioids administered on a weight basis. Older patients also have more frequent
apnea, periodic breathing, and upper airway obstruction after morphine than young
adults.[168]
Morphine alone produces greater respiratory
depression on a weight basis in neonates than in adults. In neonates and infants
with incomplete blood-brain barriers, morphine easily penetrates the brain.
The respiratory-depressant effects of opioids are increased and/or
prolonged when administered with other CNS depressants, including the potent inhaled
anesthetics, alcohol, barbiturates, benzodiazepines, and most of the intravenous
sedatives and hypotics.[162]
Exceptions are droperidol,
scopolamine, and clonidine, which do not enhance the respiratory-depressant effects
of fentanyl or other opioids.[169]
Pain, particularly surgically induced pain, is thought to counteract
the respiratory-depressant effects of opioids. However, some investigators have
suggested the contrary.[170]
Certain postoperative
breathing patterns are not predominantly determined by the level or mode of pain
relief.[171]
Although opioid action is usually dissipated by redistribution
and hepatic metabolism, rather than by urinary excretion, adequacy of renal function
may influence the duration of opioid activity. In renal insufficiency, the more
potent respiratory-depressant properties of the morphine metabolite morphine-6-glucuronide
(M6G) becomes evident as it is accumulated.[172]
One study indicates that M6G is a somewhat weaker respiratory depressant than morphine.
[173]
Hypocapnic hyperventilation has been shown to enhance and prolong
postoperative respiratory depression after fentanyl. Intraoperative hypercarbia
produces opposite effects. Possible explanations for these findings include increased
brain opioid penetration (increased un-ionized fentanyl with hypocarbia) and removal
(decreased CBF with hypocarbia). In patients who
hyperventilate because of anxiety and/or pain, even small doses of intravenous opioids
can result in transient apnea because of acute shifts in apneic thresholds.
Delayed or recurring respiratory depression has been reported
with most opioids. Explanations for this phenomenon are not clear. Numerous investigators
have noted the occurrence of significant secondary peaks and fluctuations in plasma
opioid levels during the elimination phase.[174]
The existence of large peripheral compartments (e.g., skeletal muscle) and the variability
in drug uptake from them contributes to and can augment this phenomenon. Mechanisms
for renarcotization may include augmented release of fentanyl or other opioids from
skeletal muscle into the systemic circulation on rewarming, shivering, motion, or
any other condition that enhances muscle perfusion.
