Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2005
The gamma-subunit governs the susceptibility of recombinant gamma-aminobutyric acid type A receptors to block by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N).
To identify anesthetic effects that produce the different components of the complex anesthetic state, the so-called nonanesthetics/nonimmobilizer classes of compounds have been introduced. Because ionotropic gamma-aminobutyric acid type A (GABA(A)) receptors play an important role in the mediation of the central nervous system (CNS) effects of general anesthetics, and their susceptibility to modulation by various drugs depends on subunit composition, we have compared the effect of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) on GABA(A) receptors expressed in human embryonic kidney 293 cells transfected with alpha1beta2 versus alpha1beta2gamma2s subunits. Using rapid perfusion and whole-cell recording techniques, we found that, like isoflurane, F6 blocked GABA-induced currents through alpha1beta2 receptors but, unlike isoflurane, the presence of the gamma2s subunit conferred complete resistance to block by F6. Also, in contrast to isoflurane, F6 had no effect on deactivation kinetics of GABA-induced currents in either type of receptor. We conclude that modulation of alphabetagamma receptors plays little or no role in the actions of F6, but the block of alphabeta receptors may contribute to its effects on the CNS. ⋯ Gamma-aminobutyric acidA receptors are the target of numerous drugs affecting the central nervous system. The subunit composition of the GABAA receptors governs their interaction with many drugs. We investigated whether the gamma-subunit influences the interaction with the nonimmobilizer F6.
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Anesthesia and analgesia · Aug 2005
Randomized Controlled Trial Comparative Study Clinical TrialA double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia.
We assessed the efficacy and safety of ondansetron (0.1 mg/kg IV) prophylactically administered before surgery for prevention of postoperative vomiting (POV) in a double-blind, placebo-controlled study of 670 pediatric patients, 1- to 24-mo-old, undergoing elective surgery under general anesthesia. The study enrolled 335 children in each treatment group (ondansetron versus placebo). Significantly fewer children treated with ondansetron exhibited emesis or discontinued the study prematurely after surgery (ondansetron, 11%; placebo, 28%; odds ratio = 0.33; P < 0.0001). The number required to treat prophylactically with ondansetron to prevent POV was approximately six. Ondansetron treatment also resulted in fewer patients requiring rescue medication or assumed to have had rescue upon early discontinuation from the study during the postoperative period (ondansetron, 5%; placebo, 10%) and less emesis (0 of 6) after rescue medication when compared with placebo (7 of 21). The incidence of POV and other antiemetic effects of ondansetron were similar in children aged 1-12 mo and 13-24 mo and in children prospectively expected or not expected to require opioids as part of their anesthetic or analgesic management. Ondansetron was well tolerated; the incidence of adverse events considered possibly related to study drug was similar between treatment groups (ondansetron, 1.8%; placebo, 1.5%). ⋯ This prospective, randomized, double-blind, placebo-controlled study establishes the efficacy and tolerability of IV ondansetron (0.1 mg/kg) in the prevention of postoperative emesis in 1- to 24-mo-old pediatric patients undergoing elective surgery under general anesthesia.
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Anesthesia and analgesia · Aug 2005
Randomized Controlled Trial Comparative Study Clinical TrialThe short-lasting analgesia and long-term antihyperalgesic effect of intrathecal clonidine in patients undergoing colonic surgery.
In this study, we investigated the antihyperalgesic effect of clonidine after surgery. Sixty patients undergoing right colic resection were studied. Patients were randomized to receive prior to general anesthesia a 2-mL intrathecal (IT) injection of 300 microg of clonidine or saline, or 10 mg of bupivacaine. General anesthesia was achieved using a target concentration propofol infusion and monitored using bispectral index. Postoperative analgesia was provided by morphine IV given through a patient-controlled analgesia device. Postoperative analgesia was assessed by morphine requirements and visual analog scale pain scores at rest, cough, and movement during the first 72 h. Mechanical hyperalgesia was measured by von Frey filaments. Patients were questioned regarding residual pain at 2 wk,1, 6, and 12 mo. The patient-controlled analgesia morphine requirements were significantly smaller in the IT clonidine group (31.5 +/- 12 versus 91 +/- 25.5 and 43 +/- 15 mg, respectively, in groups clonidine, saline, and bupivacaine: P < 0.05 at 72 postoperative hours). The area of hyperalgesia at 72 h was 3 +/- 5 cm(2) in the clonidine group versus 90 +/- 30 and 35 +/- 20 cm(2) in the saline and bupivacaine groups (P < 0.05). At 6 mo, fewer patients in the clonidine group experienced residual pain than in the saline group (0 of 20 versus 6 of 20, P < 0.05). We conclude that both intraoperative spinal clonidine and bupivacaine improve immediate postoperative analgesia. IT clonidine was, however, more potent than IT bupivacaine to reduce postoperative secondary hyperalgesia. ⋯ Spinal clonidine contributes to the reduction of secondary hyperalgesia in patients recovering from abdominal surgery.
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Anesthesia and analgesia · Aug 2005
Randomized Controlled Trial Clinical TrialDigital skin blood flow as an indicator for intravascular injection of epinephrine-containing simulated epidural test dose in sevoflurane-anesthetized adults.
I designed this study to determine the efficacy of heart rate (HR), systolic blood pressure (SBP), and digital skin blood flow (DSBF) in detecting intravascular injection after a simulated epidural test dose containing 15 mug of epinephrine in sevoflurane-anesthetized adults. In addition, the testing threshold using DSBF was derived. Eighty patients were randomized to receive either 0.5 minimum alveolar anesthetic concentration (MAC) sevoflurane or 1.0 MAC sevoflurane and nitrous oxide in oxygen (n = 40 for each sevoflurane concentration). Each group of patients was further randomized to receive either 3 mL of 1.5% lidocaine containing 15 mug of epinephrine IV or 3 mL of saline IV (n = 20 each). HR, SBP, and DSBF were monitored for 5 min after injection. By using the HR (positive if >or=10 bpm increase) and SBP (positive if >or=15 mm Hg increase) criteria, a positive response rate to epinephrine was 95% for both variables during 0.5 MAC and 90% during 1.0 MAC sevoflurane anesthesia. Injection of the test dose resulted in peak DSBF decrease by 87% +/- 8% and 81% +/- 12% at 52 +/- 10 and 53 +/- 13 s in the sevoflurane 0.5 and 1.0 MAC groups, respectively. Positive DSBF criterion, as determined from peak increases during saline administration, was a decrease in DSBF >or=15%. Using this value, the sensitivity, specificity, positive predictive value, and negative predictive value were 100% in both sevoflurane groups. In conclusion, DSBF was superior to conventional hemodynamic criteria for detection of an intravascular injection of epidural test dose. ⋯ This study examined the efficacy of digital skin blood flow to detect an intravascular injection of an epinephrine-containing epidural test dose. This new variable when measured with a laser Doppler flowmeter was superior to conventional hemodynamic criteria during sevoflurane anesthesia.