Anesthesia and analgesia
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Anesthesia and analgesia · Sep 1997
Randomized Controlled Trial Comparative Study Clinical TrialIntracranial pressure, middle cerebral artery flow velocity, and plasma inorganic fluoride concentrations in neurosurgical patients receiving sevoflurane or isoflurane.
This study examined the concentration-related effects of sevoflurane and isoflurane on cerebral physiology and plasma inorganic fluoride concentrations. Middle cerebral artery flow velocity (Vmca), intracranial pressure (ICP), electroencephalogram (EEG) activity, and jugular bulb venous oxygen saturation were measured, and cerebral perfusion pressure (CPP) and estimated cerebral vascular resistance (CVRe) were calculated at baseline and at 0.5, 1.0, and 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane (n = 8) or isoflurane (n = 6). Mannitol 0.5-0.75 g/kg was given before dural incision, and blood was sampled for plasma inorganic fluoride during surgery and for up to 72 h postoperatively. Both sevoflurane and isoflurane decreased Vmca (to 31 +/- 12 - 36 +/- 14 cm/s, mean +/- SD), did not significantly alter ICP (13 +/- 9 - 15 +/- 11 mm Hg), and did not cause epileptiform EEG activity. With sevoflurane, decreased Vmca was accompanied by decreased CPP and unchanged CVRe at 0.5 MAC, and unchanged CPP and increased CVRe at 1.0 and 1.5 MAC. Plasma inorganic fluoride was 39.0 +/- 12.9 microM at the end of anesthesia (3.2 +/- 2.0 MAC hours) with sevoflurane, similar to the value (36.2 +/- 3.9 microM) for 3.7 +/- 0.1 MAC hours sevoflurane in patients not receiving mannitol. Decreased Vmca during sevoflurane presumably results from decreased cerebral metabolic rate, with CVRe changing secondarily in accord with CPP. Plasma inorganic fluoride does not seem to be altered by mannitol-induced diuresis. ⋯ In neurosurgical patients, sevoflurane decreased middle cerebral artery flow velocity and caused no epileptiform electroencephalogram activity and no increase of intracranial pressure or plasma inorganic fluoride. These effects are suitable for neurosurgery. Two other possible effects of sevoflurane, i.e., increased cerebrospinal fluid volume and/or intracranial elastance, may not be suitable for neurosurgery and warrant further study.
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Anesthesia and analgesia · Sep 1997
Randomized Controlled Trial Multicenter Study Clinical TrialTreatment of postoperative nausea and vomiting with single intravenous doses of dolasetron mesylate: a multicenter trial. Dolasetron Mesylate PONV Treatment Study Group.
This study was conducted to determine the efficacy and safety of four intravenous (I.V.) doses of dolasetron, an investigational 5-HT3 receptor antagonist, for the treatment of postoperative nausea and/or vomiting (PONV) after outpatient surgery under general anesthesia. This multicenter, randomized, double-blind trial compared the antiemetic efficacy of 12.5, 25, 50, or 100 mg I.V. dolasetron with placebo over 24 h using complete response (no emetic episodes and no rescue medication), time to first emetic episode or rescue medication, and patient nausea and satisfaction with antiemetic therapy as rated by visual analog scale (VAS). Of 1557 patients enrolled, 620 patients were eligible for treatment. Complete response rates for all dolasetron doses--12.5 mg (35%), 25 mg (28%), 50 mg (29%), and 100 mg (29%)--were significantly more effective than placebo (11%, P < 0.05). There was a significant gender interaction for complete response (P < 0.01). Of the patients in the 25-mg and 100-mg dose groups, 12% and 13%, respectively, experienced no nausea (VAS score < 5 mm) versus 5% in the placebo group (P < 0.05). There were no clinically relevant changes in vital signs or laboratory values and no trends with dose for adverse events. Dolasetron is effective for treating PONV and has an adverse event profile similar to that of placebo. The 12.5-mg dose was as effective as larger doses for complete response. ⋯ Nausea and vomiting are common problems for postsurgical patients. In this study of 620 patients undergoing surgery, a 12.5-mg dose of intravenous dolasetron, a new serotonin-receptor blocker, was significantly more effective than placebo in treating established postoperative nausea and vomiting. Dolasetron 12.5 mg was as safe as placebo.
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Anesthesia and analgesia · Sep 1997
Randomized Controlled Trial Clinical TrialPostcesarean analgesia with both epidural morphine and intravenous patient-controlled analgesia: neurobehavioral outcomes among nursing neonates.
Among nursing parturients after cesarean delivery, intravenous patient-controlled analgesia (PCA) with meperidine is associated with significantly more neonatal neurobehavioral depression than PCA with morphine. A single dose of epidural morphine (4 mg) decreases postcesarean opioid analgesic requirements and may reduce or prevent neonatal neurobehavioral depression associated with PCA meperidine. Prospectively, 102 term parturients underwent cesarean delivery with epidural anesthesia, 2% lidocaine and epinephrine 1:200,000. After umbilical cord clamping, each patient received epidural morphine 4 mg and was randomly allocated to receive either PCA meperidine or PCA morphine. Initial neonatal characteristics, included gestational age, Apgar scores, weight, and umbilical cord gas partial pressures. Brazelton Neonatal Behavioral Assessment Scale (NBAS) examinations were performed on each of the first 4 days of life. Nursing infants (n = 47) were grouped according to maternal PCA opioid in breast milk (meperidine [n = 24] or morphine [n = 23]); bottle-fed infants (n = 56) served as the control group. The three infant groups were equivalent with respect to initial characteristics and NBAS scores on the first 2 days of life. On the third day of life, infants in the morphine group were significantly more alert and oriented to animate human cues compared with infants in the meperidine or control group. On the fourth day of life, infants in the morphine group remained significantly more alert and oriented to animate human auditory cues than infants in the meperidine group. Average PCA opioid consumption through 48 h postpartum was equivalent (0.54 mg/kg morphine and 4.7 mg/kg meperidine); however, even with these small doses, meperidine was associated with significantly poorer neonatal alertness and orientation than morphine. Morphine is the PCA opioid of choice for postcesarean analgesia among nursing parturients. ⋯ Among nursing parturients after cesarean delivery, intravenous patient-controlled analgesia with meperidine is associated with more neonatal neurobehavioral depression than patient-controlled analgesia with morphine. In this study, we found that nursing infants exposed to morphine were more alert and oriented to animate human cues than those exposed to meperidine.
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Anesthesia and analgesia · Sep 1997
Randomized Controlled Trial Clinical TrialThe influence of three L-type calcium channel blockers on morphine effects in healthy volunteers.
Numerous animal studies and several clinical studies have shown that calcium channel blockers (CCBs) augment opioid analgesia. We sought to determine whether three CCBs from three L-type subgroups (i.e., L-CCBs) enhanced morphine analgesic effects in healthy volunteers, and whether other effects of morphine (e.g., mood-altering effects) were altered by the CCB pretreatment. We examined the effects of three L-CCBs--diltiazem (30 mg, per os [P.O.]), nimodipine (60 mg, P.O.), and verapamil (80 mg, P.O.)--on morphine (10 mg/70 kg, intravenously) effects in nine healthy volunteers. Subjects first ingested the oral drug or placebo and 120 min later were injected with morphine or saline. Dependent measures included pain ratings measured during a cold-pressor test and subjective, psychomotor, and physiological effects. The L-CCBs alone had no effect on any of the dependent measures. Morphine alone and in combination with the L-CCBs reduced pain ratings, but there were no statistically significant differences in the pain measures between the morphine alone and the L-CCB/morphine conditions. Pretreatment with the L-CCBs in most cases neither potentiated nor attenuated the other effects of morphine. L-CCBs as well as the N-type CCBs currently under drug development should continue to be investigated to determine their potential as analgesic adjuvants. ⋯ This study is important because the results are at odds with numerous animal studies and several clinical studies, which indicate that calcium channel blockers of the L-type increase the amount of analgesia produced by morphine. Using clinically relevant doses of L-type blockers, we could find no potentiation of morphine analgesia.
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Anesthesia and analgesia · Sep 1997
Randomized Controlled Trial Clinical TrialUse of alfentanil and propofol for outpatient monitored anesthesia care: determining the optimal dosing regimen.
Propofol and alfentanil are both rapid and short-acting drugs that can be used for sedation and analgesia during monitored anesthesia care (MAC). This study was designed to determine the optimal infusion rates of propofol and alfentanil when administered during local anesthesia. In this randomized, double-blind study, we evaluated the effects of different propofol infusion rates on the alfentanil requirement, level of sedation, intraoperative recall, respiratory and cardiovascular variables, and recovery. Seventy-two consenting ASA physical status I or II female outpatients undergoing breast biopsy procedures with local anesthesia were randomly assigned to one of four treatment groups. All patients received midazolam, 2 mg intravenously (I.V.) for premedication. Propofol was infused at 0, 25, 50, or 75 microg x kg(-1) x min(-1) during the operation. Sedation was evaluated using the Observer's Assessment of Alertness/Sedation (OAA/S) scale at 5-min intervals by a blinded observer. Two minutes before the infiltration of the local anesthetic solution, a bolus of alfentanil, 2.5 microg/kg I.V., was administered, followed by a maintenance infusion of 0.5 microg x kg(-1) x min(-1). The alfentanil infusion rate was subsequently varied to maintain patient comfort and stable cardiovascular and respiratory function. Pictures were shown at the start of the propofol infusion, upon initiating the alfentanil infusion, and at 45 min after the skin incision to evaluate recall of intraoperative events. Propofol produced dose-dependent increases in the level of sedation (with median OAA/S scores of 2-4, P < 0.05). Higher infusion rates of propofol (50-75 microg x kg(-1) x min(-1)) produced significant amnesia, opioid-sparing effects (alfentanil 0.3 +/- 0.2 vs 0.6 +/- 0.2 microg x kg(-1) x min(-1)), and less postoperative nausea and vomiting (P < 0.05). However, episodes of transient hemoglobin oxygen desaturation were more common in the deeply sedated patients. Thus, in healthy outpatients premedicated with midazolam, 2 mg I.V., a propofol infusion of 25-50 microg x kg(-1) x min(-1) in combination with an alfentanil infusion of 0.2-0.4 microg x kg(-1) x min(-1) is recommended for sedation and analgesia during MAC in the ambulatory setting. ⋯ Sedation is often given during local anesthesia. This study demonstrated that administration of an intravenous anesthetic, propofol, in combination with an opioid infusion (i.e., alfentanil) to provide sedation analgesia and amnesia with a low incidence of side effects, such as nausea and vomiting and respiratory depression in outpatients premedicated with midazolam.