The dose-response pharmacology of intrathecal sufentanil in female volunteers.

The pharmacologic effects of intrathecal sufentanil (ITS) beyond what is clinically administered (10 microg) are not known. We observed 18 healthy, young, adult female volunteers who received 12.5, 25, or 50 microg of ITS in a randomized, double-blind fashion for 11 h. Analgesia was assessed by pressure algometry at the tibia. Respiratory function was assessed by pulse oximetry, respiratory rate, arterial blood gas, the ventilatory response to CO2, and a respiratory intervention score (RIS). The incidence and severity of side effects also were documented. Serum sufentanil levels were measured for 4 h after ITS administration. We found that ITS produced statistically significant changes in algometry, doubling the pressure required to produce moderate pain. However, doses of ITS greater than 12.5 microg failed to produce proportionate increases in the duration or intensity of analgesia. All doses of ITS produced significant respiratory depression, but only the RIS was significantly related to ITS dose. Neither respiratory rate nor sedation reliably predicted hypoxemia. Supplemental oxygen by nasal cannula consistently prevented pulse oximeter readings below 90%. Serum sufentanil concentrations were related to ITS dose in a statistically significant manner, reached clinically significant concentrations, and followed a time course similar to analgesia and measures of respiratory depression. However, there was no significant increase in measured analgesia associated with the increases in serum sufentanil concentrations. We conclude that in our volunteer model of lower extremity pain, administering ITS in doses larger than 12.5 microg does not improve the speed of onset, magnitude, or duration of analgesia and only causes dose-related increases in serum sufentanil concentrations, which may augment respiratory depression.

Comparison of methohexital and alfentanil on movement during placement of retrobulbar nerve block.

We compared the use of methohexital (0.5 mg/kg) with alfentanil (20 micrograms/kg) as a drug for limiting movement and pain during the placement of a retrobulbar block (RBB). Thirty patients (ASA class I-III) were randomly assigned to receive either methohexital or alfentanil (15 patients in each group). All but two patients (87%) treated with alfentanil were awake and responsive to command. All of the patients given methohexital were unresponsive at the time of block placement. However, less movement was observed when patients were treated with alfentanil compared to methohexital (P < 0.0002). None of the patients treated with alfentanil complained of pain during placement of the RBB. No difference was detected in the incidence of respiratory depression. However, one patient who received alfentanil had a prolonged period of apnea (approximately 30 s) with a significant decrease in oxygen saturation. The incidence of nausea and vomiting and the time to discharge from the outpatient department were similar in the two groups. The results of this study suggest that alfentanil may be used as a single drug to limit movement during placement of retrobulbar block for ophthalmic surgery.

Propofol anaesthesia in paediatric ambulatory patients: a comparison with thiopentone and halothane.

The purpose of this study was to evaluate the haemodynamic changes during induction, as well as the speed and quality of recovery when propofol (vs thiopentone and/or halothane) was used for induction and maintenance of anaesthesia in paediatric outpatients. One hundred unmedicated children, 3-12-yr-old, scheduled for ambulatory surgery were studied. The most common surgical procedures performed were eye muscle surgery (42%), plastic surgery (21%), dental restoration (15%), and urological procedures (15%). The children were randomized to an anaesthetic regimen for induction/maintenance as follows: propofol/propofol infusion; propofol/halothane; thiopentone/halothane; halothane for both induction and maintenance. Succinylcholine 1.5 mg.kg-1 was used to facilitate tracheal intubation and N2O/O2 were used as the carrier gases in each case. All maintenance drugs were titrated according to the clinical response of the patient to prevent movement and/or maintain BP +/- 20% of baseline. Two patients (4%) who received propofol expressed discomfort during injection. The mean propofol dose required to prevent movement was 267 +/- 83 micrograms.kg-1.min-1. The overall pattern of haemodynamic changes, as well as awakening (extubation) times were not different among the four groups. Children who received propofol recovered faster (22 vs 29-36 min) (P < 0.05), were discharged home sooner (101 vs 127-144 min) (P < 0.05), and had less postoperative vomiting (4 vs 24-48%) (P < 0.05) than all others.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypokalemia and anesthetic implications.

Reductions in serum potassium influence myocardial cell excitability by increasing membrane potential, diastolic depolarization, duration of refractory period and action potential, and decreasing conduction velocity. Disturbances in electrolyte balance typically involve alterations in two or more cations whose effects can be additive or antagonist. Serum magnesium and calcium have been demonstrated to influence the electrophysiologic effects of potassium imbalances. The arrhythmogenic potential of hypokalemia is thought to result from electrical inhomogeneity, alterations in conduction, changes in automaticity and disturbances in sodium pump kinetics. Potassium balance is maintained by two separate, yet interrelated, systems: distribution and the balance between intake and excretion. Cell wall integrity, osmolality, hormones and acid-base balance influence the relative concentrations of potassium between the intracellular and extracellular compartments. Renal excretion is the major route of elimination and is affected by acid-base balance, potassium and sodium intake, urinary flow rates and mineralocorticoid states. Serum potassium is not an accurate reflection of total body potassium stores. Acute hypokalemia differs from chronic, for the former results in a change in only the serum potassium concentration, whereas the latter is accompanied by a reduction in both the total body stores and serum levels. The importance of intracellular and extracellular concentrations lies in their determination of the resting membrane potential and, therefore, membrane excitability. Although experimental studies have demonstrated an association between ventricular ectopy and hypokalemia, the clinical studies to date have reported conflicting results. The arrhythmogenic role of hypokalemia has been examined in ambulatory hypertensive patients with acute myocardial infarctions and those with magnesium deficiencies, the results of which have been difficult to interpret because of differences in study design, durations, and characteristics of study population. During general anesthesia, both experimental and clinical studies have failed to demonstrate an increase in the incidence of ventricular ectopy in hypokalemic patients. The common practice of acute repletion therapy or cancellation is not warranted based on the studies to date. Repletion therapy is neither inexpensive nor benign. In one study of 4921 hospitalized patients, the frequency of dangerous complications of oral and/or intravenous potassium therapy was approximately 1 in 175. Certain patients are susceptible to hyperkalemia, so commonly prescribed medication can promote elevations in serum potassium including indomethacin, amiloride, beta-adrenergic blocking agents, and angiotensin-converting enzyme inhibitors. Evaluation of hypokalemia should include identification of the etiology precipitating the electrolyte imbalance. Examinations should include the duration and severity of the depletion, history of past and present illness, current medications, and the presence of concurrent electrolyte disturbances.(ABSTRACT TRUNCATED AT 400 WORDS)

Dose-response pharmacology of intrathecal morphine in human volunteers.

BACKGROUND: Intrathecal morphine sulfate (ITMS) administration was introduced into clinical practice in 1979. Inadequate information exists delineating ITMS respiratory effects in the dosage range most frequently employed today. This study evaluated 0.2, 0.4, and 0.6 mg ITMS in male volunteers. METHODS: Twenty healthy, young, adult male volunteers received 0.0, 0.2, 0.4, or 0.6 mg preservative-free ITMS in an isobaric solution administered at the L3-L4 interspace in a double-blind randomized fashion. Respiratory function was assessed by finger pulse oximetry (SpO2), respiratory rate, and arterial blood gas analysis via an indwelling arterial catheter and the slope of the ventilatory response to carbon dioxide (VE/CO2). Analgesia was assessed by the effect of ITMS on moderate pain produced by pressure algometry at the tibia. The need for supplemental oxygen, 2 L/min via nasal cannulae, was determined by the failure of verbal and tactile prompts to maintain subjects' SpO2 > or = 85% on more than two occasions. Heart rate, arterial blood pressure, sedation level, pupil size, and the incidence of adverse effects also were documented. All the above measurements were made before and 30 min after ITMS, hourly for 11 h, and then every 2 h for 12 more h. RESULTS: ITMS produced significant dose-related decreases in SpO2. Mild desaturations (SpO2 > or = 85 and < 90%) occurred in 2 of 5, 3 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. Moderate to severe desaturations (SpO2 < 85%) occurred in 0 of 5, 2 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. The need for supplemental oxygen also was significantly related to ITMS dose, with 0 of 5, 1 of 5, and 4 of 5 subjects requiring oxygen after 0.2, 0.4, and 0.6 mg ITMS, respectively. Nasal oxygen administration consistently alleviated hypoxemia. Increases in arterial carbon dioxide tension (PaCO2) and decreases in pH were significantly related to ITMS dose. Peak mean PaCO2s were 42.4, 44.9, and 50.7 mmHg in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These peaks occurred 6.5-7.5 h after ITMS injection. ITMS produced significant dose-related depression of VE/CO2. Maximum mean depressions of VE/CO2 were to 61%, 63%, and 32% of baseline in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These nadirs occurred 3.5-7.5 h after ITMS injection. Some subjects receiving 0.6 mg ITMS experienced profound (< 20% of baseline) and prolonged (< 50% of baseline for up to 20 h) VE/CO2 depression. Magnitude and duration of analgesia after ITMS were dose-related. Changes in heart rate, systolic blood pressure, and respiratory rate were not significantly related to ITMS dose. Hypoxemia was not related to respiratory rate. Although ITMS produced statistically significant dose-related increases in sedation and decreases in pupil size, these changes were small and did not coincide with hypoxemia. ITMS caused dose-related increases in emesis, but the severity of pruritus and urinary retention was unrelated to dose. CONCLUSION: ITMS produced dose-related analgesia and respiratory depression in nonsurgical healthy, young, adult male volunteers. Respiratory depression was significant after 0.2 or 0.4 mg and profound and prolonged after 0.6 mg. No clinical signs or symptoms, including respiratory rate, reliably indicated hypoxemia. Pulse oximetry reliably detected hypoxemia after ITMS, and supplemental nasal oxygen (2 L/min) effectively corrected this hypoxemia.