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 Comparative Study Clinical TrialA comparison of the laryngeal mask airway ProSeal and the laryngeal tube airway in paralyzed anesthetized adult patients undergoing pressure-controlled ventilation.
We compared the laryngeal mask airway ProSeal (PLMA) and the laryngeal tube airway (LTA), two new extraglottic airway devices, with respect to: 1) insertion success rates and times, 2) efficacy of seal, 3) ventilatory variables during pressure-controlled ventilation, 4) tidal volume in different head/neck positions, and 5) airway interventional requirements. One-hundred-twenty paralyzed anesthetized ASA physical status I and II adult patients were randomly allocated to the PLMA or LTA for airway management. A standardized anesthesia protocol was followed by two anesthesiologists experienced with both devices. The criteria for an effective airway included a minimal expired tidal volume of 6 mL/kg during pressure-controlled ventilation at 17 cm H(2)O with no oropharyngeal leak or gastric insufflation. First attempt success rates at achieving an effective airway were similar (PLMA: 85%; LTA: 87%), but after 3 attempts, success was more frequent for the PLMA (100% versus 92%, P = 0.02). Effective airway time was similar. Oropharyngeal leak pressure was larger for PLMA at 50% maximal recommended cuff volume (29 +/- 7 versus 21 +/- 6 cm H(2)O, P < 0.0001), but was similar at the maximal recommended cuff volume (33 +/- 7 versus 31 +/- 8 cm H(2)O). Tidal volumes (614 +/- 173 versus 456 +/- 207 mL, P < 0.0001) were larger and ETCO(2) (33 +/- 9 versus 40 +/- 11 mm Hg, P = 0.0001) lower for the PLMA. The number of airway interventions was significantly less frequent for the PLMA. Airway obstruction was more common with the LTA. When comparing mean tidal volumes in different head/neck positions, the quality of airway was unchanged in 56 of 60 patients (93%) with the PLMA and 42 of 55 (76%) with the LTA (P = 0.01). The PLMA offers advantages over the LTA in most technical aspects of airway management in paralyzed patients undergoing pressure-controlled ventilation. ⋯ The laryngeal mask airway ProSeal offers advantages over the laryngeal tube airway in most technical aspects of airway management in paralyzed patients undergoing pressure-controlled ventilation.
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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 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.