Butorphanol kinetics were studied in 8 young (23-34 years of age) and 9 elderly (65-79 years of age) healthy male subjects following a single, intravenous 2-mg dose of butorphanol tartrate. Plasma and blood concentrations collected over 24 h were analyzed by a second antibody radioimmunoassay for unchanged drug. Systemic blood clearance (21.29 +/- 7.18 ml/min/kg), apparent steady-state volume of distribution (9.02 +/- 2.40 liters/kg), distribution half-life (7.67 +/- 4.66 min), and the blood/plasma concentration ratio (1.21 +/- 0.36) in the elderly did not differ from those in the younger subjects. However, the terminal elimination half-life was significantly prolonged in the elderly (5.51 +/- 2.49 versus 3.67 +/- 0.52 h, p less than 0.05). Positive correlations between age and terminal elimination half-life and volume of distribution were noted. Our data suggest that young and old subjects attain similar plasma concentrations after single doses; however, longer dosing intervals may be necessary for multiple dosing in the elderly. The appropriate dosing interval for butorphanol needs to be assessed in elderly patients.
Third molar surgery in the oral and maxillofacial surgery office has been a predictable model for evaluating the efficacy of sedatives and analgesics. In this setting, butorphanol plus diazepam and fentanyl plus diazepam were compared for surgical effectiveness and postoperative recovery. The comparison of butorphanol to a known sedative combination was clinically very satisfactory. It appears from this data that butorphanol has a pharmacologic place in outpatient conscious sedation.
Patient-controlled analgesia (PCA) has been studied extensively for the treatment of postoperative pain using narcotic analgesics. Butorphanol, a nonnarcotic injectable analgesic, has not previously been investigated using this drug delivery mechanism. Twenty-five patients undergoing general abdominal surgery and general anesthesia used a PCA device with butorphanol as the analgesic agent. Most patients (84%) were able to obtain excellent postoperative pain relief. The role of butorphanol in the management of postoperative pain should be expanded to include patient-controlled drug delivery.
The analgesic efficacy and safety of butorphanol tartrate are discussed in 2 groups of patients who underwent urological procedures. The first group of 83 patients is presented as a retrospective review of the postoperative use of butorphanol. The second group of patients was involved in a double-blind, randomized comparative trial of butorphanol (2 or 4 mg) and meperidine (80 mg) for the relief of moderate to severe pain due to renal colic. Eighty-three patients with documented upper urinary tract calculi were evaluated for efficacy; 120 patients were evaluated for safety. Butorphanol 4 mg (i.m.) was more effective than butorphanol 2 mg (i.m.) and equivalent to meperidine 80 mg (i.m.). There were no statistically significant differences among the three treatment groups in regard to side effects. Overall, in the urology patients studied, butorphanol was found to be an effective and well tolerated agent that possesses important safety advantages when compared with the narcotic analgesics.
In this study, the patient-controlled analgesia (PCA) technique was used to compare the suitability of butorphanol with that of morphine in relieving postoperative pain. Twelve patients, 19-77 years old, who had abdominal surgery, used the PCA device through the first 24-hour postoperative period. Results showed that all patients expressed satisfaction with the PCA technique. Analysis of the degree of discomfort according to the verbal description scale, recordings of respiratory rate, and assessment of sedation status showed no significant differences between patients who received butorphanol and those who received morphine. Patients were able to maintain acceptable analgesia with minimal sedation. There were no adverse side effects reported with butorphanol.
Intraspinal epidural or intrathecal injection of opiates can provide outstanding analgesia in obstetric patients. Epidural and intrathecal opiates may afford more prolonged analgesia without interference of neuromuscular function or depression of the sympathetic nervous system that can occur with other anesthetic regimens. However, certain precautions are recommended to minimize potential side effects.
A variety of drugs have been used to antagonize the respiratory depression caused by narcotics. Some of these drugs, such as nalorphine, naloxone, butorphanol, and nalbuphine, are opiates, which interact directly with opiate receptors. Others, such as physostigmine, doxapram, and aminophylline, probably act indirectly by stimulating neuronal pathways involved in the regulation of ventilation. None of these drugs is ideal, and all have adverse side effects. Cardiovascular instability and eradication of analgesia have been troublesome, especially with the use of naloxone. The newer mixed agonist-antagonist agents, butorphanol and nalbuphine, may have significant advantages compared with naloxone. The purpose of this review is to summarize the pharmacology of the common narcotic antagonists, with an emphasis on obtaining acceptable results while avoiding adverse side effects.
Premedication that provides sedation and analgesia is commonly used for patients undergoing endoscopic procedures. We studied the efficacy and safety of butorphanol and diazepam as preprocedure medications for patients having upper gastrointestinal endoscopy. To achieve an adequate level of sedation, patients receiving diazepam required a mean (+/- SEM) dose of 12.0 +/- 1.0 mg, whereas those receiving butorphanol required a mean dose of 4.8 +/- 0.4 mg. There were no differences between treatment groups in the overall assessment of sedation, the ease of performance of the endoscopic procedure, or vital signs during or following the procedure. Fifty-four percent of butorphanol patients and 48% of diazepam patients experienced at least one minor adverse event. Butorphanol in small doses can produce satisfactory sedation and analgesia for patients undergoing gastrointestinal endoscopic procedures.
In summary, we believe that the osmotic difference between the brain cell and the extracellular fluid is the critical parameter in determining therapy. A gradient of 30 mosm/kg or more produces significant shifts of intracellular water and cell damage. Seizure and coma are the neurologic signs associated with acute life-threatening osmotic imbalance between swelling brain cells and the extracellular space. Treatment is designed to decrease this osmotic gradient to less than 30 mosm/kg to prevent this cell swelling. Thus in acute symptomatic hyponatremia, treatment (fluid restriction alone if urine osmolality is less than 100 mosm/kg or 3% saline if needed or both) is needed to decrease this osmotic gradient. If hyponatremia is chronic and brain osmotic adaptations have already taken place, increased extracellular osmolality would cause brain cells to undergo water loss, which may result in cell shrinkage and neurologic damage (for example, central pontine myelinosis). Unfortunately, there is as yet no clinically available tool to rapidly assess intracellular brain osmolality. Clinical judgment is therefore mandatory in trying to estimate the osmotic gradient between the intracellular and extracellular environment. Appropriate treatment must be initiated to prevent excessive changes in cell volume.
I have reviewed the identifiable hemodynamic effects of selected inotropic and vasoactive agents in the context of several clinical patient subsets. Knowledge of relative hemodynamic effects of various agents permits the selection of those that are best in specific clinical circumstances. Combining drugs may only occasionally be advisable to supplement a desired effect or to attenuate an unwanted one.
Recent studies showed that the patient work of breathing may be unexpectedly high during mechanical ventilation. During assisted mechanical ventilation and synchronous intermittent mechanical ventilation particularly, attention must be paid to the patient work if the respiratory muscles are to be rested. Clinicians should observe chest wall movements to recognize inspiratory efforts and incoordination. Monitoring the profile of inspiratory airway pressure over time is also helpful, with irregular and only partially positive pressures indicating inspiratory effort by patients.
