A Prospective Randomized Equivalence Trial of the GlideScope Cobalt® Video Laryngoscope to Traditional Direct Laryngoscopy in Neonates and Infants.
Anesthesiology. 2012 Jan 20;
Authors: Fiadjoe JE, Gurnaney H, Dalesio N, Sussman E, Zhao H, Zhang X, Stricker PA
Abstract
BACKGROUND:: Intubation in children is increasingly performed using video laryngoscopes. Many pediatric studies examine novice laryngoscopists or describe single patient experiences. This prospective randomized nonblinded equivalence trial compares intubation time for the GlideScope Cobalt® video laryngoscope (GCV, Verathon Medical, Bothell, WA) with direct laryngoscopy with a Miller blade (DL, Heine, Dover, NH) in anatomically normal neonates and infants. The primary hypothesis was that intubation times with GCV would be noninferior to DL. METHODS:: Sixty subjects presenting for elective surgery were randomly assigned to intubation using GCV or DL. Intubation time, time to best view, percentage of glottic opening score, and intubation success were documented. We defined an intubation time difference of less than 10 s as clinically insignificant. RESULTS:: There was no difference in intubation time between the groups (GCV median = 22.6 s; DL median = 21.4 s; P = 0.24). The 95% one-sided CI for mean difference between the groups was less than 8.3 s. GCV yielded faster time to best view (median = 8.1 s; DL 9.9 s; P = 0.03). Endotracheal tube passage time was longer for GCV (median = 14.3 s; DL 8.5 s; P = 0.007). The percentage of glottic opening score was improved with GCV (median 100; DL 80; P < 0.0001). CONCLUSIONS:: Similar intubation times and success rates were achieved in anatomically normal neonates and infants with the GCV as with DL. The GCV yielded faster time to best view and better views but longer tube passage times than DL.
PMID: 22270505 [PubMed - as supplied by publisher]
Prevalence of Survivor Bias in Observational Studies on Fresh Frozen Plasma: Erythrocyte Ratios in Trauma Requiring Massive Transfusion.
Anesthesiology. 2012 Jan 20;
Authors: Ho AM, Dion PW, Yeung JH, Holcomb JB, Critchley LA, Ng CS, Karmakar MK, Cheung CW, Rainer TH
Abstract
Observational studies on transfusion in trauma comparing high versus low plasma:erythrocyte ratio were prone to survivor bias because plasma administration typically started later than erythrocytes. Therefore, early deaths were categorized in the low plasma:erythrocyte group, whereas early survivors had a higher chance of receiving a higher ratio. When early deaths were excluded, however, a bias against higher ratio can be created. Survivor bias could be reduced by performing before-and-after studies or treating the plasma:erythrocyte ratio as a time-dependent covariate.We reviewed 26 studies on blood ratios in trauma. Fifteen of the studies were survivor bias-unlikely or biased against higher ratio; among them, 10 showed an association between higher ratio and improved survival, and five did not. Eleven studies that were judged survivor bias-prone favoring higher ratio suggested that a higher ratio was superior.Without randomized controlled trials controlling for survivor bias, the current available evidence supporting higher plasma:erythrocyte resuscitation is inconclusive.
PMID: 22270506 [PubMed - as supplied by publisher]
A Mixed (Long- and Medium-chain) Triglyceride Lipid Emulsion Extracts Local Anesthetic from Human Serum In Vitro More Effectively than a Long-chain Emulsion.
Anesthesiology. 2012 Feb;116(2):334-339
Authors: Ruan W, French D, Wong A, Drasner K, Wu AH
Abstract
BACKGROUND:: Lipid emulsion infusion reverses cardiac toxicity of local anesthetics. The predominant effect is likely creation of a “lipid sink.” This in vitro study determined the extent to which Intralipid® (Fresenius Kabi, Uppsala, Sweden) and Lipofundin® (B. Braun Melsungen AG, Melsungen, Germany) sequester anesthetics from serum, and whether it varies with pH. METHODS:: Bupivacaine, ropivacaine, and mepivacaine were added to human drug-free serum (pH 7.4) at 10 μg/ml. The lipid emulsions were added, and the mixture shaken and incubated at 37°C. Lipid was removed by ultracentrifugation and drug remaining in the serum measured. Additional experiments were performed using 100 μg/ml bupivacaine and at pH 6.9. RESULTS:: Lipofundin® extracted all three anesthetics to a greater extent than Intralipid® (34.7% vs..22.3% for bupivacaine, 25.8% vs..16.5% for ropivacaine, and 7.3% vs..4.7% for mepivacaine). By increasing either concentration of bupivacaine or lipid, there was an increase in drug extraction from serum. Adjusting the pH to 6.9 had no statistically significant effect on the percentage of bupivacaine sequestered. CONCLUSIONS:: Bupivacaine, ropivacaine, and mepivacaine were sequestered to an extent consistent with their octanol:water partition constants (logP). In contrast with previous studies of extraction of lipids from buffer solutions, an emulsion containing 50% each of medium- and long-chain triglycerides extracted local anesthetics to a greater extent from human serum than one containing exclusively long-chain triglycerides, calling into question recent advanced cardiac life support guidelines for resuscitation from anesthetic toxicity that specify use of a long-chain triglyceride. The current data also do not support recent recommendations to delay administration until pH is normalized.
PMID: 22273855 [PubMed - as supplied by publisher]
Lack of Indinavir Effects on Methadone Disposition Despite Inhibition of Hepatic and Intestinal Cytochrome P4503A (CYP3A).
Anesthesiology. 2012 Feb;116(2):432-47
Authors: Kharasch ED, Bedynek PS, Hoffer C, Walker A, Whittington D
Abstract
BACKGROUND: : Methadone disposition and pharmacodynamics are highly susceptible to interactions with antiretroviral drugs. Methadone clearance and drug interactions have been attributed to cytochrome P4503A4 (CYP3A4), but actual mechanisms are unknown. Drug interactions can be clinically and mechanistically informative. This investigation assessed effects of the protease inhibitor indinavir on methadone pharmacokinetics and pharmacodynamics, hepatic and intestinal CYP3A4/5 activity (using alfentanil), and intestinal transporter activity (using fexofenadine).
METHODS: : Twelve healthy volunteers underwent a sequential crossover. On three consecutive days they received oral alfentanil plus fexofenadine, intravenous alfentanil, and intravenous plus oral (deuterium-labeled) methadone. This was repeated after 2 weeks of indinavir. Plasma and urine analytes were measured by mass spectrometry. Opioid effects were measured by miosis.
RESULTS: : Indinavir significantly inhibited hepatic and first-pass CYP3A activity. Intravenous alfentanil systemic clearance and hepatic extraction were reduced to 40-50% of control, apparent oral clearance to 30% of control, and intestinal extraction decreased by half, indicating 50% and 70% inhibition of hepatic and first-pass CYP3A activity. Indinavir increased fexofenadine area under the plasma concentration-time curve 3-fold, suggesting significant P-glycoprotein inhibition. Indinavir had no significant effects on methadone plasma concentrations, methadone N-demethylation, systemic or apparent oral clearance, renal clearance, hepatic extraction or clearance, or bioavailability. Methadone plasma concentration-effect relationships were unaffected by indinavir.
CONCLUSIONS: : Despite significant inhibition of hepatic and intestinal CYP3A activity, indinavir had no effect on methadone N-demethylation and clearance, suggesting little or no role for CYP3A in clinical disposition of single-dose methadone. Inhibition of gastrointestinal transporter activity had no influence of methadone bioavailability.
Impaired nociception and peripheral opioid antinociception in mice lacking both kinin b1 and b2 receptors.
Anesthesiology. 2012 Feb;116(2):448-57
Authors: Cayla C, Labuz D, Machelska H, Bader M, Schäfer M, Stein C
Abstract
BACKGROUND: : Kinins (e.g., bradykinin) acting through the constitutively expressed B2 and the injury-induced B1 receptors are involved in pain and hyperalgesia, as previously shown by use of receptor-selective antagonists and single-receptor knockout models. Because the overall contribution of kinins to painful processes remains unclear, the aim of this study was to analyze pain-related behaviors of mice unable to respond to kinins because of a lack of both B1 and B2 receptors.
METHODS: : In knockout mice lacking both B1 and B2 receptors and in wild-type mice (n = 8-21 per group) the authors assessed nociceptive thresholds to mechanical and heat stimuli (von Frey and Hargreaves tests, respectively) in healthy animals and after induction of inflammatory and neuropathic pain, acid-induced visceral nociception, and modulation of nociceptive responses by peripherally administered opioid agonists.
RESULTS: : In knockout mice lacking both B1 and B2 receptors baseline nociceptive responses to heat were unaltered, nocifensive responses to bradykinin were abolished, acute acetic acid-induced visceral nociception was reduced by approximately 70% (mean difference: 19.5 writhes/30 min) and heat hypersensitivity in carrageenan-induced paw inflammation was decreased 48 h after injection (mean difference 2.88 s), hypersensitivities in chronic complete Freund’s adjuvant-induced paw inflammation or after chronic constriction injury of the sciatic nerve were unchanged, and peripheral μ- and δ-opioid-induced analgesia after chronic constriction injury was reduced by 30-35% (mean differences: μ-agonist: 0.495 g, δ-agonist: 0.555 g).
CONCLUSIONS: : These data suggest that kinins are important for nociception associated with acute short-lasting inflammation but are less essential in chronic stages of pain. The results also highlight a new protective function of kinins via interactions with the opioid system.
