Anesthesia and analgesia
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialThe influence of parecoxib, a parenteral cyclooxygenase-2 specific inhibitor, on the pharmacokinetics and clinical effects of midazolam.
Parecoxib, a parenteral cyclooxygenase-2 inhibitor, is undergoing clinical development as an analgesic/antiinflammatory drug for perioperative use. Parecoxib, an inactive prodrug, is hydrolyzed in vivo to valdecoxib, a substrate for hepatic cytochrome P450 (CYP) 3A4. Thus, potential exists for interactions with other CYP3A4 substrates. In this investigation, we determined the influence of parecoxib on the pharmacokinetics and clinical effects of midazolam, a CYP3A4 substrate, in volunteers. This was a randomized, balanced crossover, placebo-controlled, double-blinded clinical investigation. Twelve healthy subjects aged 23-41 yr were studied after providing IRB-approved informed consent. Midazolam 0.07 mg/kg IV infusion was administered 1 h after placebo (control) or parecoxib 40 mg IV. Venous midazolam concentrations were determined by using liquid chromatography-mass spectrometry/mass spectrometry assay. Pharmacokinetic variables were determined by noncompartmental analysis. Pharmacodynamic measurements included clinical end-points, cognitive function (memory; digit symbol substitution tests), subjective self-assessment of recovery (visual analog scales), and bispectral index. Midazolam plasma concentrations were similar between placebo and parecoxib-treated subjects. No differences were found in midazolam pharmacokinetics (maximal observed plasma concentration, clearance, elimination half-life, volume of distribution) or pharmacodynamics (clinical end-points, digit symbol substitution tests, memory, visual analog scales, bispectral index). Single-bolus parecoxib does not alter the pharmacokinetics or pharmacodynamics of midazolam infusion. Parecoxib did not affect CYP3A4 activity as assessed using midazolam clearance as the in vivo probe. ⋯ Parecoxib, a parenteral cyclooxygenase-2 inhibitor intended for perioperative use as an analgesic/antiinflammatory drug, is a substrate for hepatic cytochrome P450 3A4. The potential for a drug interaction with midazolam, an in vivo CYP3A4 probe, was tested in healthy volunteers. Single-bolus parecoxib does not alter the pharmacokinetics or pharmacodynamics of midazolam.
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialA randomized controlled trial examining the effect of naproxen on analgesia during the second day after cesarean delivery.
Whereas nonsteroidal antiinflammatory drugs augment spinal morphine on Day l, the analgesia gained by simply combining these drugs with conventional "on request" oral regimens on Day 2 is less clear. In this trial, we randomized 80 women undergoing elective cesarean delivery with spinal morphine (0.2 mg) to receive naproxen (500 mg) or placebo every 12 h after surgery. Both groups received conventional therapy with acetaminophen with codeine (on request) and rescue IM opioids. Incision pain on sitting (IPS), incision pain at rest, uterine cramping, and gas pain were evaluated with visual analog scales (0-100). Worst interval pain (0-10), analgesic use, and side effects were measured over 72 h. At 36 h (primary outcome), naproxen use was associated with reductions in IPS (38.2 +/- 26.0 versus 51.4 +/- 25.7; P = 0.05), incision pain at rest, uterine cramping, and worst interval pain scores. Clinically modest, statistically significant reductions in IPS (P = 0.0001) and opioid use were found over time (P < 0.0l). Reductions in the incidence of inadequate analgesia and improvements in overall pain relief (P = 0.0006) on Day l did not persist on Day 2 (overall pain relief, P = 0.057; inadequate analgesia, 24% naproxen versus 27% controls; P = 1.00). The addition of regular doses of naproxen to conventional oral pain therapy after cesarean delivery leads to reductions in IPS at 36 h and pain over Day 2 but does not reduce the incidence of inadequate analgesia. ⋯ This randomized trial suggests that adding regular doses of naproxen to conventional "on request" acetaminophen and codeine therapy provides small reductions in pain on the second day after cesarean delivery. The greatest effects occur at 36 h, when pain peaks.
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialThe analgesic efficacy of bilateral combined superficial and deep cervical plexus block administered before thyroid surgery under general anesthesia.
In this study we evaluated the analgesic efficacy of combined deep and superficial cervical plexus block in patients undergoing thyroidectomy under general anesthesia. For this purpose, 39 patients undergoing elective thyroid surgery were randomized to receive a bilateral combined deep and superficial cervical block (14 mL per side) with saline (Group 1; n = 13), ropivacaine 0.5% (Group 2; n = 13), or ropivacaine 0.5% plus clonidine 7.5 microg/mL (Group 3; n = 13). Deep cervical plexus block was performed with a single injection (8 mL) at the C3 level. Superficial cervical plexus block consisted of a subcutaneous injection (6 mL) behind the lateral border of the sternocleidomastoid muscle. During surgery, the number of additional alfentanil boluses was significantly reduced in Groups 2 and 3 compared with Group 1 (1.3 +/- 1.0 and 1.1 +/- 1.0 vs 2.6 +/- 1.0; P < 0.05). After surgery, the opioid and non-opioid analgesic requirements were also significantly reduced in Groups 2 and 3 (P < 0.05) during the first 24 h. Except for one patient in Group 3, who experienced transient anesthesia of the brachial plexus, no side effect was noted in any group. We conclude that combined deep and superficial cervical plexus block is an effective technique to alleviate pain during and immediately after thyroidectomy. ⋯ Combined deep and superficial cervical plexus block is an effective technique to reduce opioid requirements during and after thyroid surgery.
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialPropofol-sufentanil anesthesia for thyroid surgery: optimal concentrations for hemodynamic and electroencephalogram stability, and recovery features.
Hypnotics and opioids interact synergistically to block responses to surgery and different dose combinations may be used to provide adequate anesthesia. In this study, we sought to determine the optimal concentrations of propofol and sufentanil, given by target-controlled infusions, to ensure hemodynamic stability, adequate hypnosis (assessed by electroencephalogram bispectral index), and fast recovery for a moderately painful operation. Forty-five patients, ASA physical status I or II, undergoing thyroidectomy, were randomly assigned to a sufentanil target concentration (STC) that was maintained throughout surgery (0.1, 0.2, or 0.3 ng/mL). The propofol target concentration was adjusted to keep mean arterial blood pressure within 30% of a reference value, and bispectral index between 40 and 60. Adequate anesthesia was obtained in all groups. Hypertension and clinically dangerous movements were more frequent with the small STC, and hypotension requiring treatment was more frequent with the large STC. Propofol target concentration during surgery decreased significantly with increasing STC (median at thyroid removal 5.0, 4.0, and 2.5 microg/mL, respectively) as well as the propofol consumption (740, 668, 474 mg/h). The 0.3 ng/mL STC significantly delayed the return of spontaneous breathing. ⋯ Given as a target-controlled infusion for thyroid surgery, sufentanil 0.3 ng/mL for intubation and 0.2 ng/mL during surgery, combined with propofol 4 microg/mL (corresponding to a maintenance infusion rate of approximately 7-10 mg. kg(-1). h(-1)), is recommended to ensure both optimal intraoperative stability and fast recovery.
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialThe use of magnesium sulfate to prevent pain on injection of propofol.
Magnesium sulfate, 2.48 mmol, injected 20 s before the administration of propofol significantly reduced the incidence of pain caused by a propofol injection and may be useful in minimizing this common side effect.