Anesthesia and analgesia
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialThe effect of clonidine on the minimum local analgesic concentration of epidural ropivacaine during labor.
On the basis of the determination of minimum local analgesic concentration (MLAC), ropivacaine has been demonstrated to be less potent than bupivacaine during the first stage of labor. In this study we assessed the effect of clonidine on the MLAC of ropivacaine. Seventy-seven parturients of mixed parity requesting epidural analgesia for labor (cervical dilation, 3-7 cm) were included in the study. They received an epidural bolus of either ropivacaine (n = 30), ropivacaine plus clonidine 30 microg (n = 28), or ropivacaine plus clonidine 60 microg (n = 19) in the second part of the study. The concentration of the ropivacaine solution was determined by the response of the previous parturient in that group by using an up-down sequential allocation. A visual analog pain score of < or =10 mm within 30 min after the epidural bolus (20 mL) was considered an effective response. An effective result directed a 0.01% wt/vol decrement for the next patient. An ineffective result directed a 0.01% wt/vol increment. The MLAC of ropivacaine was 0.097% wt/vol (95% confidence interval, 0.085%-0.108%). It was unaffected by a 30-microg dose of epidural clonidine (0.081% [0.045%-0.117%]) but was significantly decreased by a 60-microg clonidine dose (0.035% [0.024%-0.046%]) (P < 0.001). This study documents a decrease in the MLAC of ropivacaine by clonidine, significant for a 60- microg dose. ⋯ Epidural ropivacaine potency in labor can be increased by the addition of epidural clonidine. This study demonstrates that 60 microg of epidural clonidine significantly decreases the minimum local analgesic concentration of ropivacaine during the first stage of labor but is associated with sedation.
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialClinical application of acoustic reflectometry in predicting the difficult airway.
Acoustic reflectometry, a noninvasive test that produces a length versus cross-sectional area map of the airway, has been used to identify difficult-to-tracheally intubate patients in a small retrospective case-control study. A critical airway volume of 40.2 mL separated those patients whose tracheas were impossible to intubate from those who were easily intubated. To determine if this technology was applicable for prospectively predicting difficult intubation and difficult ventilation in routine clinical practice, we performed a double-blinded, prospective cohort study. Our a priori hypothesis was that small airway volumes in adults (<40.2 mL) would predict absolute inability to intubate. We conclude that by use of acoustic reflectometry, there was no relationship between inability to intubate, poor glottic visualization, and multiple laryngoscopies with airway volume. ⋯ Acoustic reflectometry, a noninvasive test that uses sound to produce a length versus cross-sectional area map of the airway, was not able to predict inability to intubate, poor glottic visualization, and multiple laryngoscopies.
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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 TrialIntrathecal magnesium prolongs fentanyl analgesia: a prospective, randomized, controlled trial.
Magnesium is a noncompetitive, N-methyl-D-aspartate receptor antagonist that does not effectively cross the blood-brain barrier when given IV. Intrathecal magnesium potentiates opioid antinociception in rats, and the safety of intrathecal magnesium has been demonstrated in animals. This is the first prospective human study evaluating whether intrathecal magnesium could prolong spinal opioid analgesia. Fifty-two patients requesting analgesia for labor were randomized to receive either intrathecal fentanyl 25 micro g plus saline or fentanyl 25 micro g plus magnesium sulfate 50 mg as part of a combined spinal-epidural technique. The duration of analgesia of the intrathecal drug combination was defined by the time of patient request for additional analgesia. There was significant prolongation in the median duration of analgesia (75 min) in the magnesium plus fentanyl group compared with the fentanyl alone group (60 min). There was no associated increase in adverse events in the group that received intrathecal magnesium. Larger doses of intrathecal magnesium were not studied in this group of patients because of the limitations on cephalad spread when hyperbaric solutions are injected in the sitting position. Our data indicate that intrathecal magnesium prolongs spinal opioid analgesia in humans and suggest that the availability of an intrathecal N-methyl-D-aspartate antagonist could be of clinical importance for pain management. ⋯ Magnesium occurs naturally in the spinal cord and blocks the NMDA glutamate channel. In animal studies, intrathecal magnesium sulfate improves spinal morphine analgesia. For patients receiving spinal analgesia for labor, the addition of magnesium sulfate to the opioid fentanyl prolonged analgesia with no increase of side effects.