Nalbuphine
Nalbuphine is an agonist-antagonist opioid that is structurally
related to oxymorphone and naloxone. Nalbuphine binds to μ-receptors as well
as to κ- and δ-receptors.[481]
Nalbuphine
acts as an antagonist at the μ-receptor and an agonist at the κ-receptor.
Activation of supraspinal and spinal κ-receptors results in limited analgesia,
respiratory depression, and sedation.[481]
Nalbuphine,
like other agonist-antagonist compounds, interferes with the analgesia produced by
pure μ-receptor agonists. In rats, coadministration of nalbuphine with morphine
dose-dependently blocked the development of morphine tolerance and dependence, without
attenuation of the antinociceptive effect of morphine.[482]
Nalbuphine is only available for parenteral use. The onset of effect is rapid (5
to 10 minutes), and its duration is long (3 to 6 hours) because of a long plasma
elimination half-life (5 hours).
Premedication with nalbuphine (0.1 mg/kg) in patients scheduled
for cardiac surgery results in sedation, relief of anxiety, and respiratory depression
similar to morphine (0.1 mg/kg), but it causes no significant hemodynamic changes.
Nalbuphine (10 mg) caused no significant changes in systemic, pulmonary arterial,
and pulmonary capillary wedge pressures in patients experiencing myocardial infarction.
Nalbuphine has been administered as an analgesic supplement for
conscious sedation or balanced anesthesia and as an analgesic for postoperative and
chronic pain problems. Conscious sedation during monitored anesthesia care has been
recommended with a combination of nalbuphine (0.05–0.2 mg/kg) and midazolam
(0.05 mg/kg).[483]
Balanced anesthesia with nalbuphine
as an IV analgesic
supplement is effective for surgical procedures not associated with severe pain.
[484]
Postoperative sedation, dreaming, anxiety,
and a longer recovery room stay are more common when nalbuphine (0.3 to 0.5 mg/kg)
is used with N2
O for laparoscopy than when fentanyl (1.5 µg/kg)
is employed as the opioid.[484]
For postoperative
patient-controlled epidural analgesia, the combination of hydromorphone (0.075 mg/mL)
and nalbuphine (0.04 mg/mL) resulted in lower incidence of nausea and decreased need
of bladder catheterization compared with hydromorphone alone.[485]
The inability to decrease the MAC of potent inhaled anesthetics by nalbuphine (maximum
10% to 30%) suggests it has little or no role as a sole or primary anesthetic.[486]
Nalbuphine has been extensively evaluated for preservation of
analgesia following reversal of opioid-induced respiratory depression. Nalbuphine
(0.21 mg/kg) does not reverse and may actually increase respiratory depression after
morphine (0.21 mg/kg) ( Fig. 11-32
).
[487]
Nalbuphine (20 mg IV) adequately reversed
respiratory depression but not analgesia in patients who had received 7 µg/kg
of fentanyl and N2
O for general surgery.[488]
Unfortunately, other investigators have documented the occurrence of significant
pain, hypertension, and tachycardia (often requiring pharmacologic intervention)
following opioid reversal with nalbuphine.[489]
[490]
[491]
Restoration
of spontaneous ventilation using small titrated doses of nalbuphine (2.5 mg IV every
2 to 3 minutes) results in less pain than naloxone (0.08 mg IV every 2 to 3 minutes)
after fentanyl (mean dose 25 µg/kg), isoflurane, and N2
O anesthesia.
[492]
Figure 11-32
Resting end-tidal CO2
(PETCO2
)
at baseline; 5 minutes and 30 minutes after morphine (0.21 mg/kg IV); and after nalbuphine
(0.21 mg/kg IV), naloxone (0.014 mg/kg IV) and saline given 55 minutes after morphine.
(From Bailey PL, Clark NJ, Pace NL, et al: Failure of nalbuphine to antagonize
morphine: A double-blind comparison with naloxone. Anesth Analg 65:605–611,
1986.)
