Anesthesia and analgesia
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialThe median effective dose of nefopam and morphine administered intravenously for postoperative pain after minor surgery: a prospective randomized double-blinded isobolographic study of their analgesic action.
The aim of this study was to characterize the nature of analgesic interaction between nefopam and morphine administered i.v. for postoperative pain after minor surgery. To do so, we defined the median effective analgesic dose (ED(50)) for each drug and also the median ED(50) of their combination and compared them using the isobolographic method. Determination of median effective doses was performed by the up-and-down sequential drug administration in a two-stage study. First, in a prospective, randomized, double-blinded study, we enrolled 60 patients with mild to moderate pain after minor surgery; this was followed by an open study enrolling 30 patients. The end-point was a pain score less than 3 on a Numerical Pain Scale (0-10). Initial doses were 16 mg in group N, 5 mg in group M, and 7.5 mg of N combined with 2.5 mg of M in group N+M. The testing interval was 2 mg in group N, 1 mg in group M, and 1.5 mg of N combined with 0.5 mg of M in group N+M. ED(50) (95% confidence interval) was 5 mg (4-6 mg) for morphine, 18 mg (16-18 mg) for nefopam, and 4 mg (3.5-4.5 mg) with 12 mg (10.5-13.5 mg) for the combination of morphine and nefopam administered at a 3:1 dose ratio. Isobolographic analysis demonstrated a significant infra-additive interaction. The incidence of side effects did not differ significantly among morphine, nefopam, and their combination. These findings suggest that the combination of nefopam and morphine does not offer any advantage compared to each drug administered i.v. or alone after minor surgery. This study is the first to define the ED(50) of nefopam and morphine in postoperative patients. In conclusion, the addition of nefopam has a morphine-sparing effect, but the combination is infra-additive. ⋯ Pharmacologic interaction between nefopam and morphine shows infra-additivity but their combination may be clinically useful as morphine consumption is decreased in postoperative patients.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialReducing venipuncture pain by a cough trick: a randomized crossover volunteer study.
We tested the effectiveness of the cough trick (CT) as a method of pain relief during peripheral venipuncture (VP) in a crossover study. Twenty healthy volunteers were punctured twice in the same hand vein within an interval of 3 wk, once with the CT procedure and once without it. The intensity of pain, hand withdrawal, palm sweating, blood pressure, heart rate, and serum glucose concentration were recorded. The intensity of pain during VP with the CT procedure was less than without it, whereas the other variables changed insignificantly. The easily performed CT was effective in pain reduction during VP, although the mechanism remains unclear. ⋯ The effectiveness of a cough trick for pain reduction during peripheral venipuncture was tested in a volunteer study in which each subject served as his own control. The easily performed cough-trick procedure was effective for pain reduction, although the mechanism remains unclear.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialIntravenous administration of flurbiprofen does not affect cerebral blood flow velocity and cerebral oxygenation under isoflurane and propofol anesthesia.
Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been used to treat rheumatic and osteoarthritic pain and to reduce postoperative pain. Although other NSAIDs, such as indomethacin, reduce cerebral blood flow (CBF), the effect of flurbiprofen on CBF is unknown. In the present study, we investigated the effects of flurbiprofen on cerebral blood flow velocity (CBFV) and cerebral oxygenation under isoflurane or propofol anesthesia. Forty-eight patients undergoing orthopedic or abdominal surgery were enrolled. Patients were randomly allocated to receive either propofol (target control infusion: target site effect concentration 3 microg/mL) or isoflurane (1 MAC) for maintenance of anesthesia. In each group (n = 12), 1 mg/kg of flurbiprofen (PROP-F and ISO-F groups) or 0.1 mL/kg saline (PROP-S and ISO-S groups) was administered i.v. for 5 min. During and after the administration of flurbiprofen or saline, cerebral oxygenation variables (tissue oxygen index [TOI], total hemoglobin change [Delta cHb], oxygenated hemoglobin changes [Delta O(2)Hb], and deoxygenated hemoglobin changes [Delta HHb]), and middle cerebral artery flow velocity (Vmca) were measured using a cerebral oximeter (NIRO 300) and transcranial Doppler, respectively, from 5 min before study drug administration to 60 min post-administration. Before the administration of flurbiprofen, control values of TOI in the ISO-S and ISO-F groups were significantly higher than those in the PROP-S and PROP-F groups, respectively (ISO-S versus PROP-S, 67% +/- 4% versus 60% +/- 7%; IOS-F versus PROP-F, 69% +/- 4% versus 63% +/- 8%; P < 0.05). However, values of TOI, Delta cHb, Delta O(2)Hb, Delta HHb, and Vmca did not change significantly during and after the administration of flurbiprofen under propofol or isoflurane anesthesia, and these values were similar to those during and after the administration of saline in the same anesthesia group. These data indicate that flurbiprofen does not affect CBFV and cerebral oxygenation under propofol or isoflurane anesthesia. ⋯ Indomethacin, a nonsteroidal antiinflammatory drug (NSAID), has been demonstrated to reduce cerebral blood flow (CBF). The CBF effects of flurbiprofen, another NSAID, are unknown. We investigated cerebral blood flow velocity (CBFV) and cerebral oxygenation during and after the administration of flurbiprofen under isoflurane and propofol anesthesia. We found that flurbiprofen had no effect on CBFV and cerebral oxygenation.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Multicenter Study Clinical TrialThe safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial.
A noninvasive method of delivery of parenteral opioids for management of acute pain may offer logistic advantages for patients and nursing staff. A patient-controlled transdermal system (PCTS) under development consists of a preprogrammed, self-contained drug-delivery system that uses electrotransport technology (E-TRANS, ALZA Corp, Mountain View, CA) to deliver 40 micro g of fentanyl HCl over 10 min per on-demand dose for patient-controlled analgesia (PCA). In this randomized, double-blinded, placebo-controlled trial we compared the efficacy and safety of on-demand fentanyl HCl PCTS 40 microg against placebo for postoperative pain up to 24 h after major abdominal, orthopedic, or thoracic surgery in 205 patients. The primary efficacy measurement was the percentage of patients withdrawn from the study because of inadequate analgesia after completing at least 3 h of treatment. Secondary efficacy measures included mean pain intensity (using visual analog scales), patient global assessments, and investigator global assessments. Of 189 patients considered evaluable for efficacy, 25% of patients in the fentanyl HCl PCTS 40 microg group withdrew because of inadequate analgesia, compared with 40.4% of the placebo group (P < 0.05). Use of fentanyl HCl PCTS 40 micro g was associated with lower VAS scores and higher mean patient and investigator global assessment scores compared with placebo. No patient experienced clinically relevant respiratory depression. This study showed that a fentanyl HCl PCTS 40 microg for PCA was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. ⋯ This multicenter, randomized, double-blinded, placebo-controlled trial showed that an on-demand fentanyl HCl patient-controlled transdermal system (PCTS) was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. This fentanyl HCl PCTS is a preprogrammed, needle free, self-contained drug-delivery system that uses electrotransport technology (iontophoresis) to deliver 40 microg of fentanyl per on-demand dose.
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Anesthesia and analgesia · Feb 2004
Meta AnalysisA dose-response meta-analysis of prophylactic intravenous ephedrine for the prevention of hypotension during spinal anesthesia for elective cesarean delivery.
We systematically reviewed available studies to determine the dose-response characteristics of prophylactic i.v. ephedrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. We searched for randomized controlled trials (RCTs) or cohort studies-obtained through MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and reference lists of published articles-in which two or more different doses of prophylactic i.v. ephedrine were used to prevent hypotension during spinal anesthesia for cesarean delivery. Four RCTs and one cohort study were found (total n = 390). There was a significant dose-response relationship in the RCTs pooled for hypotension (slope = -0.0128; 95% confidence interval [CI], -0.0213 to -0.0044), hypertension (slope = 0.0563; 95% CI, 0.0235 to 0.0892), and umbilical arterial pH (slope = -0.03; 95% CI, -0.05 to 0.00). The efficacy of ephedrine for preventing hypotension was small. At 14 mg, the number-needed-to-treat was only 7.6 (95% CI, 4.8-21.1), and this was the same as the number-needed-to-harm (7.6; 95% CI, 3.7-23.4). At larger doses, the likelihood of causing hypertension was actually more than that of preventing hypotension, and there was also a minor decrease in umbilical arterial pH. ⋯ The authors performed a systematic review of dose-response studies of i.v. bolus ephedrine for preventing hypotension during spinal anesthesia for cesarean delivery. Prophylactic ephedrine cannot be recommended. The efficacy is poor at smaller doses, whereas at larger doses, the likelihood of causing hypertension is actually more than that of preventing hypotension.