Showing papers in "Anesthesiology in 2011"

Molecular mechanisms of opioid receptor-dependent signaling and behavior.

Abstract: Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled and activate inhibitory G proteins. These receptors form homo- and heterodimeric complexes and signal to kinase cascades and scaffold a variety of proteins.The authors discuss classic mechanisms and developments in understanding opioid tolerance and opioid receptor signaling and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. The authors put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, the authors conclude there is a continued need for more translational work on opioid receptors in vivo.

Perioperative Single Dose Systemic Dexamethasone for Postoperative Pain: A Meta-analysis of Randomized Controlled Trials

Abstract: Background Dexamethasone is frequently administered in the perioperative period to reduce postoperative nausea and vomiting. In contrast, the analgesic effects of dexamethasone are not well defined. The authors performed a meta-analysis to evaluate the dose-dependent analgesic effects of perioperative dexamethasone. Methods We followed the PRISMA statement guidelines. A wide search was performed to identify randomized controlled trials that evaluated the effects of a single dose systemic dexamethasone on postoperative pain and opioid consumption. Meta-analysis was performed using a random-effect model. Effects of dexamethasone dose were evaluated by pooling studies into three dosage groups: low (less than 0.1 mg/kg), intermediate (0.11-0.2 mg/kg) and high (≥ 0.21 mg/kg). Results Twenty-four randomized clinical trials with 2,751 subjects were included. The mean (95% CI) combined effects favored dexamethasone over placebo for pain at rest (≤ 4 h, -0.32 [0.47 to -0.18], 24 h, -0.49 [-0.67 to -0.31]) and with movement (≤ 4 h, -0.64 [-0.86 to -0.41], 24 h, -0.47 [-0.71 to -0.24]). Opioid consumption was decreased to a similar extent with moderate -0.82 (-1.30 to -0.42) and high -0.85 (-1.24 to -0.46) dexamethasone, but not decreased with low-dose dexamethasone -0.18 (-0.39-0.03). No increase in analgesic effectiveness or reduction in opioid use could be demonstrated between the high- and intermediate-dose dexamethasone. Preoperative administration of dexamethasone appears to produce a more consistent analgesic effect compared with intraoperative administration. Conclusion Dexamethasone at doses more than 0.1 mg/kg is an effective adjunct in multimodal strategies to reduce postoperative pain and opioid consumption after surgery. The preoperative administration of the drug produces less variation of effects on pain outcomes.

Association between Intraoperative Blood Transfusion and Mortality and Morbidity in Patients Undergoing Noncardiac Surgery

Abstract: Background: The impact of intraoperative erythrocyte transfusiononoutcomesofanemicpatientsundergoingnoncardiacsurgeryhasnotbeenwellcharacterized.Theobjective of this study was to examine the association between blood transfusion and mortality and morbidity in patients with severeanemia(hematocritlessthan30%)whoareexposedto one or two units of erythrocytes intraoperatively. Methods: Thiswasaretrospectiveanalysisoftheassociationof blood transfusion and 30-day mortality and 30-day morbidity in 10,100 patients undergoing general, vascular, or orthopedic surgery. We estimated separate multivariate logistic regression models for 30-day mortality and for 30-day complications. Results: Intraoperative blood transfusion was associated with an increased risk of death (odds ratio [OR], 1.29; 95% CI, 1.03–1.62). Patients receiving an intraoperative transfusion were more likely to have pulmonary, septic, wound, or thromboembolic complications, compared with patients not receiving an intraoperative transfusion. Compared with patients who were not transfused, patients receiving one or two units of erythrocytes were more likely to have pulmonary complications (OR, 1.76; 95% CI, 1.48–2.09), sepsis (OR, 1.43; 95% CI, 1.21–1.68), thromboembolic complications (OR, 1.77; 95% CI, 1.32–2.38), and wound complications (OR, 1.87; 95% CI, 1.47–2.37). Conclusions: Intraoperative blood transfusion is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia. It is unknown whether this association is due to the adverse effects of blood transfusion or is, instead, the result of increased blood loss in the patients receiving blood.

Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach

Abstract: BACKGROUND: Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. METHODS: The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. RESULTS: The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.92) for PPV, compared with 0.57 (95% CI: 0.54-0.59) for central venous pressure (P < 10). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. CONCLUSION: Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia.

First-line Therapy with Coagulation Factor Concentrates Combined with Point-of-Care Coagulation Testing Is Associated with Decreased Allogeneic Blood Transfusion in Cardiovascular Surgery A Retrospective, Single-center Cohort Study

Abstract: INTRODUCTION Blood transfusion is associated with increased morbidity and mortality. We developed and implemented an algorithm for coagulation management in cardiovascular surgery based on first-line administration of coagulation factor concentrates combined with point-of-care thromboelastometry/impedance aggregometry. METHODS In a retrospective cohort study including 3,865 patients, we analyzed the incidence of intraoperative allogeneic blood transfusions (primary endpoints) before and after algorithm implementation. RESULTS Following algorithm implementation, the incidence of any allogeneic blood transfusion (52.5 vs. 42.2%; P < 0.0001), packed red blood cells (49.7 vs. 40.4%; P < 0.0001), and fresh frozen plasma (19.4 vs. 1.1%; P < 0.0001) decreased, whereas platelet transfusion increased (10.1 vs. 13.0%; P = 0.0041). Yearly transfusion of packed red blood cells (3,276 vs. 2,959 units; P < 0.0001) and fresh frozen plasma (1986 vs. 102 units; P < 0.0001) decreased, as did the median number of packed red blood cells and fresh frozen plasma per patient. The incidence of fibrinogen concentrate (3.73 vs. 10.01%; P < 0.0001) and prothrombin complex concentrate administration (4.42 vs. 8.9%; P < 0.0001) increased, as did their amount administered per year (179 vs. 702 g; P = 0.0008 and 162 × 10³ U vs. 388 × 10³ U; P = 0.0184, respectively). Despite a switch from aprotinin to tranexamic acid, an increase in use of dual antiplatelet therapy (2.7 vs. 13.7%; P < 0.0001), patients' age, proportion of females, emergency cases, and more complex surgery, the incidence of massive transfusion [(≥10 units packed red blood cells), (2.5 vs. 1.26%; P = 0.0057)] and unplanned reexploration (4.19 vs. 2.24%; P = 0.0007) decreased. Composite thrombotic/thromboembolic events (3.19 vs. 1.77%; P = 0.0115) decreased, but in-hospital mortality did not change (5.24 vs. 5.22%; P = 0.98). CONCLUSIONS First-line administration of coagulation factor concentrates combined with point-of-care testing was associated with decreased incidence of blood transfusion and thrombotic/thromboembolic events.

Routine clinical practice effectiveness of the Glidescope in difficult airway management: an analysis of 2,004 Glidescope intubations, complications, and failures from two institutions.

Abstract: Introduction: The Glidescope video laryngoscope has been shown to be a useful tool to improve laryngeal view. However, its role in the daily routine of airway management remains poorly characterized. Methods: This investigation evaluated the use of the Glidescope at two academic medical centers. Electronic records from 71,570 intubations were reviewed, and 2,004 cases were indentified where the Glidescope was used for airway management. WeanalyzedthesuccessrateofGlidescopeintubationinvarious intubationscenarios.Inaddition,theincidenceandcharacterof complications associated with Glidescope use were recorded. PredictorsofGlidescopeintubationfailureweredeterminedus

3,423 emergency tracheal intubations at a university hospital: airway outcomes and complications.

Abstract: Background There are limited outcome data regarding emergent nonoperative intubation. The current study was undertaken with a large observational dataset to evaluate the incidence of difficult intubation and complication rates and to determine predictors of complications in this setting. Methods Adult nonoperating room emergent intubations at our tertiary care institution from December 5, 2001 to July 6, 2009 were reviewed. Prospectively defined data points included time of day, location, attending physician presence, number of attempts, direct laryngoscopy view, adjuvant use, medications, and complications. At our institution, a senior resident with at least 24 months of anesthesia training is the first responder for all emergent airway requests. The primary outcome was a composite airway complication variable that included aspiration, esophageal intubation, dental injury, or pneumothorax. Results A total of 3,423 emergent nonoperating room airway management cases were identified. The incidence of difficult intubation was 10.3%. Complications occurred in 4.2%: aspiration, 2.8%; esophageal intubation, 1.3%; dental injury, 0.2%; and pneumothorax, 0.1%. A bougie introducer was used in 12.4% of cases. Among 2,284 intubations performed by residents, independent predictors of the composite complication outcome were as follows: three or more intubation attempts (odds ratio, 6.7; 95% CI, 3.2-14.2), grade III or IV view (odds ratio, 1.9; 95% CI, 1.1-3.5), general care floor location (odds ratio, 1.9; 95% CI, 1.2-3.0), and emergency department location (odds ratio, 4.7; 95% CI, 1.1-20.4). Conclusions During emergent nonoperative intubation, specific clinical situations are associated with an increased risk of airway complication and may provide a starting point for allocation of experienced first responders.

Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study.

Abstract: Background Although animal studies have indicated that general anesthetics may result in widespread apoptotic neurodegeneration and neurocognitive impairment in the developing brain, results from human studies are scarce. We investigated the association between exposure to surgery and anesthesia for inguinal hernia repair in infancy and subsequent academic performance. Methods Using Danish birth cohorts from 1986-1990, we compared the academic performance of all children who had undergone inguinal hernia repair in infancy to a randomly selected, age-matched 5% population sample. Primary analysis compared average test scores at ninth grade adjusting for sex, birth weight, and paternal and maternal age and education. Secondary analysis compared the proportions of children not attaining test scores between the two groups. Results From 1986-1990 in Denmark, 2,689 children underwent inguinal hernia repair in infancy. A randomly selected, age-matched 5% population sample consists of 14,575 individuals. Although the exposure group performed worse than the control group (average score 0.26 lower; 95% CI, 0.21-0.31), after adjusting for known confounders, no statistically significant difference (-0.04; 95% CI, -0.09 to 0.01) between the exposure and control groups could be demonstrated. However, the odds ratio for test score nonattainment associated with inguinal hernia repair was 1.18 (95% CI, 1.04-1.35). Excluding from analyses children with other congenital malformations, the difference in mean test scores remained nearly unchanged (0.05; 95% CI, 0.00-0.11). In addition, the increased proportion of test score nonattainment within the exposure group was attenuated (odds ratio = 1.13; 95% CI, 0.98-1.31). Conclusion In the ethnically and socioeconomically homogeneous Danish population, we found no evidence that a single, relatively brief anesthetic exposure in connection with hernia repair in infancy reduced academic performance at age 15 or 16 yr after adjusting for known confounding factors. However, the higher test score nonattainment rate among the hernia group could suggest that a subgroup of these children are developmentally disadvantaged compared with the background population.

Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

Abstract: Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However, in the adult NGF has been found to play an important role in nociceptor sensitization after tissue injury. The authors outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. The authors also document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events and how humans may change their behavior and use of the injured/degenerating tissue after significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF.

Smoking and perioperative outcomes

Abstract: Background Patients are often concerned about the effects of smoking on perioperative risk. However, effective advice may be limited by the paucity of information about smoking and perioperative risk. Thus, our goal was to determine the effect of smoking on 30-day postoperative outcomes in noncardiac surgical patients. Methods We evaluated 635,265 patients from the American College of Surgeons National Surgical Quality Improvement Program database; 520,242 patients met our inclusion criteria. Of these patients, 103,795 were current smokers; 82,304 of the current smokers were propensity matched with 82,304 never-smoker controls. Matched current smokers and never-smokers were compared on major and minor composite morbidity outcomes and respective individual outcomes. Results Current smokers were 1.38 (95% CI, 1.11-1.72) times more likely to die than never smokers. Current smokers also had significantly greater odds of pneumonia (odds ratio [OR], 2.09; 95% CI, 1.80-2.43), unplanned intubation (OR, 1.87; 95% CI, 1.58-2.21), and mechanical ventilation (OR, 1.53; 95% CI, 1.31-1.79). Current smokers were significantly more likely to experience a cardiac arrest (OR, 1.57; 95% CI, 1.10-2.25), myocardial infarction (OR, 1.80; 95% CI, 1.11-2.92), and stroke (OR, 1.73; 95% CI, 1.18-2.53). Current smokers also had significantly higher odds of having superficial (OR, 1.30; 95% CI, 1.20-1.42) and deep (OR, 1.42; 95% CI, 1.21-1.68) incisional infections, sepsis (OR, 1.30; 95% CI, 1.15-1.46), organ space infections (OR, 1.38; 95% CI, 1.20-1.60), and septic shock (OR, 1.55; 95% CI, 1.29-1.87). Conclusion Our analysis indicates that smoking is associated with a higher likelihood of 30-day mortality and serious postoperative complications. Quantification of increased likelihood of 30-day mortality and a broad range of serious smoking-related complications may enhance the clinician's ability to motivate smoking cessation in surgical patients.

Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery

Abstract: Background: The current study was designed to determine the relation between preoperative cerebral oxygen saturation (ScO2), variables of cardiopulmonary function, mortality, and morbidityinaheterogeneouscohortofcardiacsurgerypatients. Methods: In this study, 1,178 consecutive patients scheduled for on-pump surgery were prospectively studied. Preoperative ScO2, demographics, N-terminal pro-B-type natriuretic peptide, high-sensitive troponin T, clinical outcomes, and 30-day and 1-yr mortality were recorded. Results: MedianadditiveEuroSCOREwas5(range:0–19). Thirty-day and 1-yr mortality and major morbidity (at least twomajorcomplicationsand/orahigh-dependencyunitstay of at least 10 days) were 3.5%, 7.7%, and 13.3%, respectively. Median minimal preoperative oxygen supplemented ScO2 (ScO2min-ox) was 64% (range: 15–92%). ScO2min-ox was correlated (all: P value 0.0001) with N-terminal pro-Btype natriuretic peptide (: 0.35), high-sensitive troponin T(:0.28),hematocrit(:0.34),glomerularfiltrationrate (: 0.19), EuroSCORE (: 0.20), and left ventricular ejection fraction class (: 0.12). Thirty-day nonsurvivors had a lower ScO 2min-ox than survivors (median 58% [95% CI, 50.7–62%] vs. 64% [95% CI, 64–65%]; P 0.0001). Receiver-operating curve analysis of ScO 2min-ox and 30-day mortality revealed an area-under-the-curve of 0.71 (95% CI, 0.68–0.73%; P 0.0001) in the total cohort and an areaunder-the-curve of 0.77 (95% CI, 0.69–0.86%; P 0.0001) in patients with a EuroSCORE more than 10. Logistic regression based on different EuroSCORE categories (0–2; 3–5, 6–10, 10), ScO 2min-ox , and duration of cardiopulmonary bypass showed that a ScO 2min-ox equal or less than 50% is an independent risk factor for 30-day and 1-yr mortality. Conclusions: Preoperative ScO 2 levels are reflective of the severity of cardiopulmonary dysfunction, associated with shortand long-term mortality and morbidity, and may add to preoperative risk stratification in patients undergoing cardiac surgery.

Efficacy of tranexamic acid in pediatric craniosynostosis surgery: a double-blind, placebo-controlled trial.

Abstract: Background: Extensive blood loss is common in pediatric craniosynostosis reconstruction surgery. Tranexamic acid (TXA) is increasingly used to reduce perioperative blood loss in various settings, but data on its efficacy are limited in children. The purpose of this randomized, double-blind, placebo-controlled, parallel trial was to evaluate the efficacy of TXA in pediatric craniosynostosis correction surgery. The primary and secondary outcome variables were reduction in perioperative blood loss and reduction in blood transfusion, respectively. Methods: Forty-three children, ages 2 months to 6 yr, received either placebo or TXA in a loading dose of 50 mg·kg ―1 , followed by an infusion of 5 mg·kg ―1 ·h ―1 during surgery. TXA plasma concentrations were measured. Results: The TXA group had significantly lower perioperative mean blood loss (65 vs. 119 ml·kg ―1 , P < 0.001) and lower perioperative mean blood transfusion (33 vs. 56 ml· kg ―1 , P = 0.006) compared to the placebo group. The mean difference between the TXA and placebo groups for total blood loss was 54 ml·kg ―1 (95% CI for the difference, 23-84 ml·kg ―1 ) and for packed erythrocytes transfused was 23 ml·kg ―1 (95% CI for the difference, 7-39 ml·kg ―1 ). TXA administration also significantly diminished (by two thirds) the perioperative exposure of patients to transfused blood (median, 1 unit vs. 3 units; P < 0.001). TXA plasma concentrations were maintained above the in vitro thresholds reported for inhibition of fibrinolysis (10 μg·ml ―1 ) and plasmin-induced platelet activation (16 μg·ml ―1 ) throughout the infusion. Conclusions: TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.

Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids.

Abstract: Background: Exercise is often prescribed as a therapy for chronic pain. Short-term exercise briefly increases the production of endogenous analgesics, leading to transient antinociception. In limited studies, exercise produced sustained increases in endogenous opioids, sustained analgesia, or diminished measures of chronic pain. This study tests the hypothesis that regular aerobic exercise leads to sustained reversal of neuropathic pain by activating endogenous opioid-mediated pain modulatory systems. Methods: After baseline measurements, the L5 and L6 spinal nerves of male Sprague–Dawley rats were tightly ligated. Animals were randomized to sedentary or 5-week treadmill exercise–trained groups. Thermal and tactile sensitivities were assessed 23 h after exercise, using paw withdrawal thresholds to von Frey filaments and withdrawal latencies to noxious heat. Opioidreceptorantagonistswereadministeredbysubcutaneous,intrathecal, or intracerebroventricular injection. Opioid peptides were quantified using immunohistochemistry with densitometry. Results: Exercise training ameliorated thermal and tactile hypersensitivity in spinal nerve–ligated animals within 3 weeks. Sensory hypersensitivity returned 5 days after discontinuation of exercise training. The effects of exercise were reversed by using systemically or intracerebroventricularly administered opioid receptor antagonists and prevented by continuous infusion of naltrexone. Exercise increased -endorphin and met-enkephalin content in the rostral ventromedial medulla and the mid-brain periaqueductal gray area. Conclusions: Regularmoderateaerobicexercisereversedsigns of neuropathic pain and increased endogenous opioid content in brainstem regions important in pain modulation. Exercise effects were reversed by opioid receptor antagonists. These results suggest that exercise-induced reversal of neuropathic pain results from an up-regulation of endogenous opioids.

Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice.

Abstract: Background: Volatileanestheticsfacilitatesurgicalprocedures andimagingstudiesinmillionsofchildreneveryyear.Neuronal cell death after prolonged exposure to isoflurane in developing animals has raised serious concerns regarding its safe use in children. Although sevoflurane and desflurane are becoming more popular for pediatric anesthesia, their cytotoxic effects have not been compared with those of isoflurane. Accordingly, using newborn mice, the current study established the respective potencies of desflurane, isoflurane, and sevoflurane and then compared equipotent doses of these anesthetics regarding their effects on cortical neuroapoptosis. Methods: Minimumalveolarconcentrationsweredetermined in littermates (aged 7–8 days, n 42) using tail-clamp stimulationinabracketingstudydesign.Byusingequipotentdosesof approximately 0.6 minimum alveolar concentration, another group of littermates was randomly assigned to receive desflurane, isoflurane, or sevoflurane or to fast in room air for 6 h. After exposure, animals (n 47) were euthanized, neocortical apoptotic neuronal cell death was quantified, and caspase 3 activity was compared between the four groups. Results: The minimum alveolar concentration was determined to be 12.2% for desflurane, 2.7% for isoflurane, and 5.4% for sevoflurane. After a 6-h exposure to approximately

Perioperative Stroke and Associated Mortality after Noncardiac, Nonneurologic Surgery

Abstract: Background: Stroke is a leading cause of morbidity and mortality in the United States and occurs in the perioperative period. The authors studied the incidence, predictors, and outcomes of perioperative stroke using the American College of Surgeons National Surgical Quality Improvement Program. Methods: Data on 523,059 noncardiac, nonneurologic patientsintheAmericanCollegeofSurgeonsNationalSurgical Quality Improvement Program database were analyzed for the current study. The incidence of perioperative stroke was identified. Logistic regression was applied to a derivation cohort of 350,031 patients to generate independent predictors of stroke and develop a risk model. The risk model was subsequently applied to a validation cohort of 173,028 patients. The role of perioperative stroke in 30-day mortality was also assessed. Results: The incidence of perioperative stroke in both the derivation and validation cohorts was 0.1%. Multivariate analysis revealed the following independent predictors of stroke in the derivation cohort: age 62 yr, history of myocardialinfarctionwithin6monthsbeforesurgery,acuterenal failure, history of stroke, dialysis, hypertension, history of transient ischemic attack, chronic obstructive pulmonary disease, current tobacco use, and body mass index 35–40 kg/m 2 (protective). These risk factors were confirmed in the validation cohort. Surgical procedure also influenced the incidence of stroke. Perioperative stroke was associated with an 8-fold increase in perioperative mortality within 30 days (95% CI, 4.6–12.6). Conclusions: Noncardiac, nonneurologic surgery carries a risk of perioperative stroke, which is associated with higher mortality. The models developed in this study may be informative for clinicians and patients regarding risk and prevention of this complication.

Clinical and molecular pharmacology of etomidate.

Abstract: This review focuses on the unique clinical and molecular pharmacologic features of etomidate. Among general anesthesia induction drugs, etomidate is the only imidazole, and it has the most favorable therapeutic index for single-bolus administration. It also produces a unique toxicity among anesthetic drugs: inhibition of adrenal steroid synthesis that far outlasts its hypnotic action and that may reduce survival of critically ill patients. The major molecular targets mediating anesthetic effects of etomidate in the central nervous system are specific γ-aminobutyric acid type A receptor subtypes. Amino acids forming etomidate binding sites have been identified in transmembrane domains of these proteins. Etomidate binding site structure models for the main enzyme mediating etomidate adrenotoxicity have also been developed. Based on this deepening understanding of molecular targets and actions, new etomidate derivatives are being investigated as potentially improved sedative-hypnotics or for use as highly selective inhibitors of adrenal steroid synthesis.

Clinical Assessment of the Ultrasonographic Measurement of Antral Area for Estimating Preoperative Gastric Content and Volume

Abstract: Background: This prospective observational study aimed to assess the feasibility and performance of the ultrasonographic measurementofantralcross-sectionalarea(CSA)forthepreoperative assessment of gastric contents and volume in adult patients and for the diagnosis of risk stomach (defined by the presence of solid particles and/or gastric fluid volume 0.8 ml/kg). Methods: A preoperative ultrasonographic measurement of theantralCSAwasperformedforeachpatientbyaphysician (L.B.)blindedtothehistoryofthepatient.Immediatelyafter tracheal intubation, an 18-French multiorifice Salem tube was inserted and gastric contents were aspirated in five different patient positions; during this time, the patient’s epigastrium was massaged and the tube was moved backward and forward in the stomach. The relationship between the antral area and the volume of aspirated gastric contents was analyzed, as was the performance of ultrasonographic measurement of antral area for the diagnosis of risk stomach. Results: The measurement of antral CSA was performed on 180 of 183 patients. A significant positive relationship between antral CSA and aspirated fluid volume was found. The cutoff value of antral CSA of 340 mm 2 for the diagnosis of risk stomach was associated with a sensitivity of 91% and a specificity of 71%. The area under the receiver operating characteristic curve for the diagnosis of risk stomach was 90%. Conclusions: The ultrasonographic measurement of antral CSA could be an important help for the anesthesiologist in minimizing the risk of pulmonary aspiration of gastric contents due to general anesthesia.

An increase in aortic blood flow after an infusion of 100 ml colloid over 1 minute can predict fluid responsiveness: the mini-fluid challenge study.

Abstract: Background: Predicting fluid responsiveness remains a difficult question in hemodynamically unstable patients. The author’s objective was to test whether noninvasive assessment by transthoracic echocardiography of subaortic velocity time index (VTI) variation after a low volume of fluid infusion (100 ml hydroxyethyl starch) can predict fluid responsiveness.

Perineural Dexmedetomidine Added to Ropivacaine for Sciatic Nerve Block in Rats Prolongs the Duration of Analgesia by Blocking the Hyperpolarization-activated Cation Current

Abstract: Background The present study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (Ih)current.

Developmental Stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial prefrontal cortex.

Abstract: Recent observations demonstrate that anesthetics rapidly impair synaptogenesis during neuronal circuitry development. Whether these effects are lasting and depend on the developmental stage at which these drugs are administered remains, however, to be explored.

Ultrasonography of the Adult Thoracic and Lumbar Spine for Central Neuraxial Blockade

Abstract: The role of ultrasound in central neuraxial blockade has been underappreciated, partly because of the relative efficacy of the landmark-guided technique and partly because of the perceived difficulty in imaging through the narrow acoustic windows produced by the bony framework of the spine However, this also is the basis for the utility of ultrasound: an interlaminar window that permits passage of sound waves into the vertebral canal also will permit passage of a needle In addition, ultrasound aids in identification of intervertebral levels, estimation of the depth to epidural and intrathecal spaces, and location of important landmarks, including the midline and interlaminar spaces This can facilitate neuraxial blockade, particularly in patients with difficult surface anatomic landmarks In this review article, the authors summarize the current literature, describe the key ultrasonographic views, and propose a systematic approach to ultrasound imaging for the performance of spinal and epidural anesthesia in the adult patient

Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis.

Abstract: There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery.

Human Alzheimer and Inflammation Biomarkers after Anesthesia and Surgery

Abstract: Background The prevalence of post-operative cognitive disturbance, coupled with growing in vitro, cell and animal evidence suggesting anesthetic effects on neurodegeneration, calls for further study of the interaction between surgical care and Alzheimer neuropathology. Here, we study human cerebral spinal fluid (CSF) biomarkers perioperatively.

Ultrasound imaging facilitates spinal anesthesia in adults with difficult surface anatomic landmarks.

Abstract: Background: Poor surface anatomic landmarks are highly predictive of technical difficulty in neuraxial blockade. The authors examined the use of ultrasound imaging to reduce this difficulty. Methods: The authors recruited 120 orthopedic patients with one of the following: body mass index more than 35 kg/m 2 and poorly palpable spinous processes; moderate to severe lumbar scoliosis; or previous lumbar spine surgery. Patients were randomized to receive spinal anesthetic by the conventional surface landmark-guided technique (group LM) or by an ultrasound-guided technique (group US). Patients in group US had a preprocedural ultrasound scan to locate and mark a suitable needle insertion point. The primary outcome was the rate of successful dural puncture on the first needle insertion attempt. Normally distributed data were summarized as mean ± SD and nonnormally distributed data were summarized as median [interquartile range]. Results: The first-attempt success rate was twice as high in group US than in group LM (65% vs. 32%; P < 0.001). There was a twofold difference between groups in the number of needle insertion attempts (group US, 1 [1―2] vs. group LM, 2 [1―4]; P < 0.001) and number of needle passes (group US, 6 [1―10] vs. group LM, 13 [5―21]; P = 0.003). More time was required to establish landmarks in group US (6.7 ± 3.1; group LM, 0.6 ± 0.5 min; P < 0.001), but this was partially offset by a shorter spinal anesthesia performance time (group US, 5.0 ± 4.9 vs. group LM, 7.3 ± 7.6 min; P = 0.038). Similar results were seen in subgroup analyses of patients with body mass index more than 35 kg/m 2 and patients with poorly palpable landmarks. Conclusion: Preprocedural ultrasound imaging facilitates the performance of spinal anesthesia in the nonobstetric patient population with difficult anatomic landmarks.

Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study.

Abstract: Background: Surgical correction of craniosynostosis in children is associated with substantial intraoperative bleeding. Tranexamic acid (TXA) decreases intraoperative blood loss during cardiac or orthopedic surgery in children. We hypothesized that intraoperative TXA would reduce blood transfusion relative to placebo in patients pretreated with erythropoietin. Methods: Forty consecutive children, American Society of Anesthesiologists status 1 or 2, scheduled to undergo surgical correction of craniosynostosis were randomly assigned to receive either intravenous TXA or saline, 0.9%, intraoperatively. All children received preoperative erythropoietin (600 U/kg once a week for 3 weeks before surgery). Perioperative blood loss, number and volume of transfusions, percentage of children who underwent transfusion, and side effects were noted after surgery and at the end of the study. Surgeon satisfaction and cost of treatment were also recorded. Results: There was no significant difference between groups in demographic or surgical data. In the TXA group, the volume of packed erythrocytes transfused was significantly reduced by 85% (from 11 to 1.6 ml/kg) intraoperatively and by 57% (from 16.6 to 7.2 ml/kg) throughout the study period (P < 0.05). Compared with the placebo group, the percentage of children requiring blood transfusion was lower in the TXA group during surgery (9 [45%] of 20 vs. 2 [11%] of 19 children; P < 0.05) and during the whole study period (14 [70%] of 20 vs. 7 [37%] of 19; P < 0.05). Preoperative and postoperative hematologic parameters were comparable in both groups. There were no adverse events. Conclusion: In children undergoing surgical correction of craniosynostosis and pretreated with erythropoietin, intraoperative TXA reduces the transfusion requirement.

Magnesium--essentials for anesthesiologists.

Abstract: Magnesium plays a fundamental role in many cellular functions, and thus there is increasing interest in its role in clinical medicine Although numerous experimental studies indicate positive effects of magnesium in a variety of disease states, large clinical trials often give conflicting results However, there is clear evidence for magnesium to benefit patients with eclampsia or torsades de pointes arrhythmias In addition, magnesium seems to have antinociceptive and anesthetic as well as neuroprotective effects, yet well-designed large clinical trials are required to determine its actual efficacy in pain management or in the state of stroke or subarachnoid hemorrhage The current review aims to provide an overview of current knowledge and available evidence with respect to physiologic aspects of magnesium and proposed indications and recommendations for its use in the clinical setting

Effects of Volatile and Intravenous Anesthesia on the Alveolar and Systemic Inflammatory Response in Thoracic Surgical Patients

Abstract: Background: One-lung ventilation (OLV) results in alveolar proinflammatory effects, whereas their extent may depend on administration of anesthetic drugs. The current study evaluates the effects of different volatile anesthetics compared with an intravenous anesthetic and the relationship between pulmonary and systemic inflammation in patients undergoing open thoracic surgery. Methods: Sixty-three patients scheduled for elective open thoracic surgery were randomized to receive anesthesia with 4 mg · kg ―1 · h ―1 propofol (n = 21), 1 minimum alveolar concentration desflurane (n = 21), or 1 minimum alveolar concentration sevoflurane (n = 21). Analgesia was provided by remifentanil (0.25 μg · kg ―1 · min ―1 ). After intubation, all patients received pressure-controlled mechanical ventilation with a tidal volume of approximately 7 ml · kg ―1 ideal body weight, a peak airway pressure lower than 30 cm H 2 O, a respiratory rate adjusted to a Paco 2 of 40 mmHg, and a fraction of inspired oxygen lower than 0.8 during OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed immediately after intubation and after surgery. The expression of inflammatory cytokines was determined in the lavage fluids and serum samples by multiplexed bead-based immunoassays. Results: Proinflammatory cytokines increased in the ventilated lung after OLV. Mediator release was more enhanced during propofol anesthesia compared with desflurane or sevoflurane administration. For tumor necrosis factor-α, the values were as follows: propofol, 5.7 (8.6); desflurane, 1.6 (0.6); and sevoflurane, 1.6 (0.7). For interleukin-8, the values were as follows: propofol, 924 (1680); desflurane, 390 (813); and sevoflurane, 412 (410). (Values are given as median [interquartile range] pg · ml ―1 ). Interleukin-1β was similarly reduced during volatile anesthesia. The postoperative serum interleukin-6 concentration was increased in all patients, whereas the systemic proinflammatory response was negligible. Conclusions: OLV increases the alveolar concentrations of proinflammatory mediators in the ventilated lung. Both desflurane and sevoflurane suppress the local alveolar, but not the systemic, inflammatory responses to OLV and thoracic surgery.

Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during and after intubation of morbidly obese patients: a randomized controlled study.

Abstract: Background: Morbid obesity predisposes patients to lung collapse and hypoxemia during induction of anesthesia. The aim of this prospective study was to determine whether noninvasive positive pressure ventilation (NPPV) improves arterial oxygenation and end-expiratory lung volume (EELV) compared with conventional preoxygenation, and whether NPPV followed by early recruitment maneuver (RM) after endotracheal intubation (ETI) further improves oxygenation and respiratory function compared with NPPV alone. Methods: Sixty-six consecutive patients (body mass index, 46 6 kg/m 2 ) were randomized to receive 5 min of either

Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory.

Abstract: BACKGROUND: In animal models, neonatal exposure to volatile anesthetics induces neuroapoptosis, leading to memory deficits in adulthood. However, effects of neonatal exposure to desflurane are largely unknown. METHODS: Six-day-old C57BL/6 mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp method as a function of anesthesia duration. Apoptosis was evaluated by immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze, and fear conditioning tests were performed to evaluate general activity, anxiety-related behavior, working memory, and long-term memory, respectively. RESULTS: Minimum alveolar concentrations at 1 h were determined to be 11.5% for desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in 6-day-old mice. Neonatal exposure to desflurane (8%) induced neuroapoptosis with an anatomic pattern similar to that of sevoflurane or isoflurane; however, desflurane induced significantly greater levels of neuroapoptosis than almost equivalent doses of sevoflurane (3%) or isoflurane (2%). In adulthood, mice treated with these anesthetics had impaired long-term memory, whereas no significant anomalies were detected in the open-field and the elevated plus-maze tests. Although performance in a working memory task was normal in mice exposed neonatally to sevoflurane or isoflurane, mice exposed to desflurane had significantly impaired working memory. CONCLUSIONS: In an animal model, neonatal desflurane exposure induced more neuroapoptosis than did sevoflurane or isoflurane and impaired working memory, suggesting that desflurane is more neurotoxic than sevoflurane or isoflurane.