Showing papers in "Anesthesiology in 2008"

Stop questionnaire: a tool to screen patients for obstructive sleep apnea

Abstract: Background Obstructive sleep apnea (OSA) is a major risk factor for perioperative adverse events. However, no screening tool for OSA has been validated in surgical patients. This study was conducted to develop and validate a concise and easy-to-use questionnaire for OSA screening in surgical patients. Methods After hospital ethics approval, preoperative patients aged 18 yr or older and without previously diagnosed OSA were recruited. After a factor analysis, reliability check, and pilot study; four yes/no questions were used to develop this screening tool. The four questions were respectively related to snoring, tiredness during daytime, observed apnea, and high blood pressure (STOP). For validation, the score from the STOP questionnaire was evaluated versus the apnea-hypopnea index from monitored polysomnography. Results The STOP questionnaire was given to 2,467 patients, 27.5% classified as being at high risk of OSA. Two hundred eleven patients underwent polysomnography, 34 for the pilot test and 177 for validation. In the validation group, the apnea-hypopnea index was 20 +/- 6. The sensitivities of the STOP questionnaire with apnea-hypopnea index greater than 5, greater than 15, and greater than 30 as cutoffs were 65.6, 74.3, and 79.5%, respectively. When incorporating body mass index, age, neck circumference, and gender into the STOP questionnaire, sensitivities were increased to 83.6, 92.9, and 100% with the same apnea-hypopnea index cutoffs. Conclusions The STOP questionnaire is a concise and easy-to-use screening tool for OSA. It has been developed and validated in surgical patients at preoperative clinics. Combined with body mass index, age, neck size, and gender, it had a high sensitivity, especially for patients with moderate to severe OSA.

Predictors of Cognitive Dysfunction after Major Noncardiac Surgery

Abstract: This article and its accompanying editorial have been selected for the ANESTHESIOLOGYCME Program. After reading both articles, go to http://www.asahq.org/journal-cme to take the test and apply for Category 1 credit. Complete instructions may be found in the CME section at the back of this issue. Background: The authors designed a prospective longitudinal study to investigate the hypothesis that advancing age is a risk factor for postoperative cognitive dysfunction (POCD) after major noncardiac surgery and the impact of POCD on mortality in the first year after surgery. Methods: One thousand sixty-four patients aged 18 yr or older completed neuropsychological tests before surgery, at hospital discharge, and 3 months after surgery. Patients were categorized as young (18‐39 yr), middle-aged (40‐59 yr), or elderly (60 yr or older). At 1 yr after surgery, patients were contacted to determine their survival status. Results: At hospital discharge, POCD was present in 117 (36.6%) young, 112 (30.4%) middle-aged, and 138 (41.4%) elderly patients. There was a significant difference between all age groups and the age-matched control subjects (P < 0.001). At 3 months after surgery, POCD was present in 16 (5.7%) young, 19 (5.6%) middle-aged, and 39 (12.7%) elderly patients. At this time point, the prevalence of cognitive dysfunction was similar between age-matched controls and young and middle-aged patients but significantly higher in elderly patients compared to elderly control subjects (P < 0.001). The independent risk factors for POCD at 3 months after surgery were increasing age, lower educational level, a history of previous cerebral vascular accident with no residual impairment, and POCD at hospital discharge. Patients with POCD at hospital discharge were more likely to die in the first 3 months after surgery (P 0.02). Likewise, patients who had POCD at both hospital discharge and 3 months after surgery were more likely to die in the first year after surgery (P 0.02). Conclusions: Cognitive dysfunction is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 yr or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery. POSTOPERATIVE cognitive dysfunction (POCD) is often associated with cardiac surgery, but less is known about the prevalence of this problem after other types of surgery. 1,2 In 1998, the International Study of Postoperative Cognitive Dysfunction (ISPOCD1) evaluated cognitive decline in 1,218 elderly patients, aged 60 yr or older, who had undergone major noncardiac surgery, and found that cognitive dysfunction was present in 26% of older patients 1 week after surgery and in 10% 3 months after surgery. 3 However, this study had significant differences in the incidence of early POCD at the 13 participating hospitals, placing this finding in question. Research evaluating cognitive decline after cardiac and noncardiac surgery has primarily focused on older patients, who might have an increased vulnerability to neurologic deterioration. 1,3,4 However, the cognitive effects of surgery and anesthesia in younger adults are poorly understood, making it difficult to determine whether advancing age is the primary risk factor for this complication. Studies on normal aging have shown that abrupt declines in cognitive function in older adults are associated with early death. 5,6 The relation between POCD and mortality has not been reported. To investigate the hypothesis that advancing age is a risk factor for POCD, we designed a prospective cohort study evaluating the incidence of early (hospital discharge) and late (3 months after surgery) cognitive dysfunction in adults of all ages undergoing elective, major noncardiac surgery. This study used the same neuropsychological methodology as the ISPOCD1 study in an attempt to replicate its results at a single institution. 3 Patients were also followed to determine the impact of POCD on survival in the first year after major surgery. A companion article analyzes the type and severity of cognitive impairment in the elderly patients in this study. 7

A rational approach to perioperative fluid management.

Abstract: Replacement of assumed preoperative deficits, in addition to generous substitution of an unsubstantiated increased insensible perspiration and third space loss, plays an important role in current perioperative fluid regimens. The consequence is a positive fluid balance and weight gain of up to 10 kg, which may be related to severe complications. Because the intravascular blood volume remains unchanged and insensible perspiration is negligible, the fluid must accumulate inside the body. This concept brings into question common liberal infusion regimens. Blood volume after fasting is normal, and a fluid-consuming third space has never been reliably shown. Crystalloids physiologically load the interstitial space, whereas colloidal volume loading deteriorates a vital part of the vascular barrier. The endothelial glycocalyx plays a key role and is destroyed not only by ischemia and surgery, but also by acute hypervolemia. Therefore, undifferentiated fluid handling may increase the shift toward the interstitial space. Using the right kind of fluid in appropriate amounts at the right time might improve patient outcome.

The effects of mild perioperative hypothermia on blood loss and transfusion requirement

Abstract: Background: Anesthetic-induced hypothermia is known to reduce platelet function and impair enzymes of the coagulation cascade. The objective of this meta-analysis and systematic review was to evaluate the hypothesis that mild perioperative hypothermia increases surgical blood loss and transfusion requirement. Methods: The authors conducted a systematic search of published randomized trials that compared blood loss and/or transfusion requirements in normothermic and mildly hypothermic (34 –36°C) surgical patients. Results are expressed as a ratio of the means or relative risks and 95% confidence intervals (CI); P < 0.05 was considered statistically significant. Results: Fourteen studies were included in analysis of blood loss, and 10 in the transfusion analysis. The median (quartiles) temperature difference between the normothermic and hypothermic patients among studies was 0.85°C (0.60°C versus 1.1°C). The ratio of geometric means of total blood loss in the normothermic and hypothermic patients was 0.84 (0.74 versus 0.96), P 0.009. Normothermia also reduced transfusion requirement, with an overall estimated relative risk of 0.78 (95% CI 0.63, 0.97), P 0.027. Conclusion: Even mild hypothermia (<1°C) significantly increases blood loss by approximately 16% (4 –26%) and increases the relative risk for transfusion by approximately 22% (3–37%). Maintaining perioperative normothermia reduces blood loss and transfusion requirement by clinically important amounts.

Temperature monitoring and perioperative thermoregulation.

Abstract: Most clinically available thermometers accurately report the temperature of whatever tissue is being measured. The difficulty is that no reliably core-temperature measuring sites are completely non-invasive and easy to use — especially in patients not having general anesthesia. Nonetheless, temperature can be reliably measured in most patients. Body temperature should be measured in patients having general anesthesia exceeding 30 minutes in duration, and in patients having major operations under neuraxial anesthesia. Core body temperature is normally tightly regulated. All general anesthetics produce a profound dose-dependent reduction in the core temperature triggering cold defenses including arterio-venous shunt vasoconstriction and shivering. Anesthetic-induced impairment of normal thermoregulatory control, and the resulting core-to-peripheral redistribution of body heat, is the primary cause of hypothermia in most patients. Neuraxial anesthesia also impairs thermoregulatory control, although to a lesser extant than general anesthesia. Prolonged epidural analgesia is associated with hyperthermia whose cause remains unknown.

Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis

Abstract: Background Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. Methods In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. Results After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Conclusions Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.

Validation of the Berlin questionnaire and American Society of Anesthesiologists checklist as screening tools for obstructive sleep apnea in surgical patients.

Abstract: Background: Because of the high prevalence of obstructive sleep apnea (OSA) and its adverse impact on perioperative outcome, a practical screening tool for surgical patients is required. This study was conducted to validate the Berlin questionnaire and the American Society of Anesthesiologists (ASA) checklist in surgical patients and to compare them with the STOP questionnaire. Methods: After hospital ethics approval, preoperative patients aged 18 yr or older and without previously diagnosed OSA were recruited. The scores from the Berlin questionnaire, ASA checklist, and STOP questionnaire were evaluated versus the apnea– hypopnea index from in-laboratory polysomnography. The perioperative data were collected through chart review. Results: Of 2,467 screened patients, 33, 27, and 28% were respectively classified as being at high risk of OSA by the Berlin questionnaire, ASA checklist, and STOP questionnaire. The performance of the screening tools was evaluated in 177 patients who underwent polysomnography. The sensitivities of the Berlin questionnaire, ASA checklist, and STOP questionnaire were 68.9 – 87.2, 72.1– 87.2, and 65.6 –79.5% at different apnea– hypopnea index cutoffs. There was no significant difference between the three screening tools in the predictive parameters. The patients with an apnea– hypopnea index greater than 5 and the patients identified as being at high risk of OSA by the STOP questionnaire or ASA checklist had a significantly increased incidence of postoperative complications. Conclusions: Similar to the STOP questionnaire, the Berlin questionnaire and ASA checklist demonstrated a moderately high level of sensitivity for OSA screening. The STOP questionnaire and the ASA checklist were able to identify the patients who were likely to develop postoperative complications.

Venous function and central venous pressure: a physiologic story.

Abstract: The veins contain approximately 70% of total blood volume and are 30 times more compliant than arteries; therefore, changes in blood volume within the veins are associated with relatively small changes in venous pressure. The terms venous capacity, compliance, and stressed and unstressed volumes are defined. Decreases in flow into a vein are associated with decreases in intravenous pressure and volume, and vice versa. Changes in resistance in the small arteries and arterioles may affect venous return in opposite directions; this is explained by a two-compartment model: compliant (mainly splanchnic veins) and noncompliant (nonsplanchnic veins). Effects of intrathoracic and intraabdominal pressures on venous return and central venous pressure as well as the value of central venous pressure as a diagnostic variable are discussed.

Utility of the photoplethysmogram in circulatory monitoring.

Abstract: The photoplethysmogram is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is displayed by many pulse oximeters and bedside monitors, along with the computed arterial oxygen saturation. The photoplethysmogram is similar in appearance to an arterial blood pressure waveform. Because the former is noninvasive and nearly ubiquitous in hospitals whereas the latter requires invasive measurement, the extraction of circulatory information from the photoplethysmogram has been a popular subject of contemporary research. The photoplethysmogram is a function of the underlying circulation, but the relation is complicated by optical, biomechanical, and physiologic covariates that affect the appearance of the photoplethysmogram. Overall, the photoplethysmogram provides a wealth of circulatory information, but its complex etiology may be a limitation in some novel applications.

Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine.

Abstract: BACKGROUND Traditionally, reversal of nondepolarizing neuromuscular blocking agents was achieved using acetylcholinesterase inhibitors, but these are unable to adequately reverse profound blockade. Sugammadex is a novel reversal agent, reversing the effects of rocuronium by encapsulation. This study assessed the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced neuromuscular blockade. METHODS This phase III, randomized study enrolled surgical patients, aged 18 yr or older with American Society of Anesthesiologists physical status I-IV. Patients were randomized to receive sugammadex (4.0 mg/kg) or neostigmine (70 microg/kg) plus glycopyrrolate (14 microg/kg). Anesthetized patients received an intubating dose of rocuronium (0.6 mg/kg), with maintenance doses (0.15 mg/kg) as required. Neuromuscular monitoring was performed by acceleromyography. Sugammadex or neostigmine was administered at reappearance of 1-2 posttetanic counts (profound neuromuscular blockade). The primary efficacy parameter was the time from sugammadex or neostigmine-glycopyrrolate administration to return of the train-of-four ratio to 0.9. RESULTS In the intent-to-treat population (n = 37 in each group), geometric mean time to recovery to a train-of-four ratio of 0.9 with sugammadex was 2.9 min versus 50.4 min with neostigmine-glycopyrrolate (P < 0.0001) (median, 2.7 min vs. 49.0 min). Most sugammadex patients (97%) recovered to a train-of-four ratio of 0.9 within 5 min after administration. In contrast, most neostigmine patients (73%) recovered between 30 and 60 min after administration, with 23% requiring more than 60 min to recover to a train-of-four ratio of 0.9. CONCLUSIONS Recovery from profound rocuronium-induced neuromuscular blockade was significantly faster with sugammadex versus with neostigmine, suggesting that sugammadex has a unique ability to rapidly reverse profound rocuronium neuromuscular blockade.

Perineural Administration of Dexmedetomidine in Combination with Bupivacaine Enhances Sensory and Motor Blockade in Sciatic Nerve Block without Inducing Neurotoxicity in Rat

Abstract: Background The present study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage.

Randomized placebo-controlled study evaluating lateral branch radiofrequency denervation for sacroiliac joint pain.

Abstract: Background Sacroiliac joint pain is a challenging condition accounting for approximately 20% of cases of chronic low back pain. Currently, there are no effective long-term treatment options for sacroiliac joint pain.

Intraoperative acceleromyographic monitoring reduces the risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit.

Abstract: BACKGROUND Incomplete recovery from neuromuscular blockade in the postanesthesia care unit (PACU) may contribute to adverse postoperative respiratory events. This study determined the incidence and degree of residual neuromuscular blockade in patients randomized to conventional qualitative train-of-four (TOF) monitoring or quantitative acceleromyographic monitoring. The incidence of adverse respiratory events in the PACU was also evaluated. METHODS One hundred eighty-five patients were randomized to intraoperative acceleromyographic monitoring (acceleromyography group) or qualitative TOF monitoring (TOF group). Anesthetic management was standardized. TOF patients were extubated when standard criteria were met and no fade was observed during TOF stimulation. Acceleromyography patients had a TOF ratio of greater than 0.80 as an additional extubation criterion. Upon arrival in the PACU, TOF ratios of both groups were measured with acceleromyography. Adverse respiratory events during transport to the PACU and during the first 30 min of PACU admission were also recorded. RESULTS A lower frequency of residual neuromuscular blockade in the PACU (TOF ratio < or = 0.9) was observed in the acceleromyography group (4.5%) compared with the conventional TOF group (30.0%; P < 0.0001). During transport to the PACU, fewer acceleromyography patients developed arterial oxygen saturation values, measured by pulse oximetry, of less than 90% (0%) or airway obstruction (0%) compared with TOF patients (21.1% and 11.1%, respectively; P < 0.002). The incidence, severity, and duration of hypoxemic events during the first 30 min of PACU admission were less in the acceleromyography group (all P < 0.0001). CONCLUSIONS Incomplete neuromuscular recovery can be minimized with acceleromyographic monitoring. The risk of adverse respiratory events during early recovery from anesthesia can be reduced by intraoperative acceleromyography use.

Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury.

Abstract: Background Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury. Methods Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes. Results Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P Conclusion The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.

Biologic effects of nitrous oxide: a mechanistic and toxicologic review

Abstract: Nitrous oxide is the longest serving member of the anesthesiologist’s pharmacologic armamentarium but remains a source of controversy because of fears over its adverse effects. Recently, the Evaluation of Nitrous oxide In a Gas Mixture for Anaesthesia (ENIGMA) trial reported that nitrous oxide use increases postoperative complications; further preclinical reports have suggested that nitrous oxide may contribute to neurocognitive dysfunction in the young and elderly. Therefore, nitrous oxide’s longevity in anesthetic practice is under threat. In this article, the authors discuss the evidence for the putative toxicity of nitrous oxide, from either patient or occupational exposure, within the context of the mechanism of nitrous oxide’s action. Although it would seem prudent to avoid nitrous oxide in certain vulnerable populations, current evidence in support of a more widespread proscription from clinical practice is unconvincing. NITROUS oxide has been used in clinical anesthetic practice for more than 150 yr, and its longevity should be considered within the context of all the major advances in anesthetic practice over that time. Fifty years ago, concerns were expressed about nitrous oxide’s toxicity after anesthesia. 1 This report was followed 10 yr later with concerns

Impact of heart failure on patients undergoing major noncardiac surgery.

Abstract: This article and its accompanying editorial have been selected for the ANESTHESIOLOGYCME Program. After reading both articles, go to http://www.asahq.org/journal-cme to take the test and apply for Category 1 credit. Complete instructions may be found in the CME section at the back of this issue. Background: Changes in the demographics and epidemiology of patients with cardiovascular comorbidities who undergo major noncardiac surgery require an updated assessment of which patients are at greater risk of mortality or readmission. The authors evaluated short-term outcomes among patients with heart failure, coronary artery disease (CAD), or neither who underwent major noncardiac surgery. Methods: Patients were aged 65 and older, had Medicare fee-for-service coverage, and underwent 1 of 13 major noncardiac procedures from 2000 through 2004, excluding patients with end-stage renal disease and patients who did not have at least 1 yr of Medicare fee-for-service eligibility before surgery. Main outcome measures were operative mortality and 30-day all-cause readmission. Results: Of 159,327 procedures, 18% were performed in patients with heart failure and 34% were performed in patients with CAD. Adjusted hazard ratios of mortality and readmission for patients with heart failure, compared with patients with neither heart failure nor CAD, were 1.63 (95% confidence interval, 1.52‐1.74) and 1.51 (95% confidence interval, 1.45‐1.58), respectively. Adjusted hazard ratios of mortality and readmission for patients with CAD, compared with patients with neither heart failure nor CAD, were 1.08 (95% confidence interval, 1.01‐1.16) and 1.16 (95% confidence interval, 1.12‐1.20), respectively. These effects were statistically significant. Patients with heart failure were at significantly higher risk for both outcomes compared with patients with CAD. Conclusions: Elderly patients with heart failure who undergo major surgical procedures have substantially higher risks of operative mortality and hospital readmission than other patients, including those with coronary disease, admitted for the same procedures. Improvements in perioperative care are needed for the growing population of patients with heart failure undergoing major noncardiac surgery.

A118G Single Nucleotide Polymorphism of Human μ-Opioid Receptor Gene Influences Pain Perception and Patient-controlled Intravenous Morphine Consumption after Intrathecal Morphine for Postcesarean Analgesia

Abstract: Background Previous studies have shown that genetic variability at position 118 of the human mu-opioid receptor gene altered patients' response to intravenous morphine. The purpose of this study was to investigate whether this polymorphism contributes to the variability in response to morphine for postcesarean analgesia. Methods After investigators obtained informed consent, 588 healthy women received 0.1 mg intrathecal morphine for postcesarean analgesia. Their blood samples were genotyped for the A118G polymorphism-A118 homozygous (AA), heterozygous (AG), or homozygous for the G allele (GG). Pain scores, the severity of nausea and vomiting, the incidence of pruritus, and the total self-administered intravenous morphine were recorded for the first 24 postoperative hours. Results Two hundred seventy women (46%) were AA, 234 (40%) were AG, and 82 (14%) were GG. The 24-h self-administered intravenous morphine consumption was lowest in the AA group (P = 0.001; mean, 5.9; 95% confidence interval, 5.1-6.8) versus the AG (8.0; 6.9-9.1) and GG groups (9.4; 7.3-11.5). Pain scores were lowest in the AA group and highest in the GG group, with a statistically significant difference detected between AA, AG, and GG (P = 0.049). Total morphine consumption was also influenced by patients' age and paying status. AA group was associated with the highest incidence of nausea (26 of 272 [9.6%]; P = 0.02) versus the other two groups (13 of 234 [5.6%] and 1 of 82 [1.2%] for AG and GG, respectively). Conclusion Genetic variation at position 118 of the mu-opioid receptor is associated with interindividual differences in pain scores, self-administered intravenous morphine, and the incidence of nausea postoperatively.

Cardiac risk of noncardiac surgery after percutaneous coronary intervention with drug-eluting stents.

Abstract: Background: The American College of Cardiology released a scientific advisory that included a recommendation to delay elective of noncardiac surgery (NCS) for 1 yr after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods: This single-center, retrospective study examined the risk for complications of NCS performed within 2 yr after DES placement and examined whether this risk changed based on the time between procedures. The primary endpoint was major adverse cardiac events (MACEs) during the hospitalization for NCS. Bleeding events were analyzed as a secondary endpoint. Results: From April 22, 2003, to December 31, 2006, a total of 520 patients underwent NCS within 2 yr after PCI with a DES at Mayo Clinic. The majority, 84%, of the DES placed were Cypher stents. The frequency of MACE was not found to be significantly associated with the time between PCI and NCS (rate of MACEs 6.4, 5.7, 5.9, and 3.3% at 0-90, 91-180, 181-365, and 366-730 days after PCI with DES, respectively; P = 0.727 for comparison across groups). Characteristics found to be associated with MACEs in univariate analysis were advanced age (P = 0.031), emergent NCS (P = 0.006), shock at time of PCI (P = 0.035), previous history of myocardial infarction (P = 0.046), and continuation of a thienopyridine (ticlopidine or clopidogrel) into the preoperative period (P = 0.040). The rate of transfusion did not seem to be associated with antiplatelet therapy use. Conclusions: The risk of MACEs with NCS after DES placement was not significantly associated with time from stenting to surgery, but observed rates of MACEs were lowest after 1 yr.

Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial.

Abstract: Background Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated. Methods A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography. Results Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min. Conclusion Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.

Type and severity of cognitive decline in older adults after noncardiac surgery.

Abstract: Background: The authors investigated type and severity of cognitive decline in older adults immediately and 3 months after noncardiac surgery. Changes in instrumental activities of daily living were examined relative to type of cognitive decline. Methods: Of the initial 417 older adults enrolled in the study, 337 surgery patients and 60 controls completed baseline, discharge, and/or 3-month postoperative cognitive and instrumental activities of daily living measures. Reliable change methods were used to examine three types of cognitive decline: memory, executive function, and combined executive function/ memory. SD cutoffs were used to grade severity of change as mild, moderate or severe. Results: At discharge, 186 (56%) patients experienced cognitive decline, with an equal distribution in type and severity. At 3 months after surgery, 231 patients (75.1%) experienced no cognitive decline, 42 (13.6%) showed only memory decline, 26 (8.4%) showed only executive function decline, and 9 (2.9%) showed decline in both executive and memory domains. Of those with cognitive decline, 36 (46.8%) had mild, 25 (32.5%) had moderate, and 16 (20.8%) had severe decline. The combined group had more severe impairment. Executive function or combined (memory and executive) deficits involved greater levels of functional (i.e., instrumental activities of daily living) impairment. The combined group was less educated than the unimpaired and memory groups. Conclusion: Postsurgical cognitive presentation varies with time of testing. At 3 months after surgery, more older adults experienced memory decline, but only those with executive or combined cognitive decline had functional limitations. The findings have relevance for patients and caregivers. Future research should examine how perioperative factors influence neuronal systems.

Are Blood Transfusions Associated with Greater Mortality Rates? : Results of the Sepsis Occurrence in Acutely Ill Patients Study

Abstract: P < 0.001) and a higher ICU mortality rate (23.0 vs. 16.3%; P < 0.001) but were also more severely ill on admission (Simplified Acute Physiology Score II, 40.2 vs. 34.7; P < 0.001; Sequential Organ Failure Assessment score, 6.5 vs. 4.5; P < 0.001). There was a direct relation between the number of blood transfusions and the mortality rate, but in multivariate analysis, blood transfusion was not significantly associated with a worse mortality rate. Moreover, in 821 pairs matched according to a propensity score, there was a higher 30-day survival rate in the transfusion group than in the other patients (P 0.004). Conclusion: This observational study does not support the view that blood transfusions are associated with increased mortality rates in acutely ill patients.

Using permutation entropy to measure the electroencephalographic effects of sevoflurane.

Abstract: Background Approximate entropy (AE) has been proposed as a measure of anesthetic drug effect in electroencephalographic data. Recently, a new method called permutation entropy (PE) based on symbolic dynamics was also proposed to measure the complexity in an electroencephalographic series. In this study, the AE and PE were applied to electroencephalographic recordings for revealing the effect of sevoflurane on brain activity. The dose-response relation of PE during sevoflurane anesthesia was compared with that of AE. Methods Nineteen patients' electroencephalographic data were collected during the induction of general anesthesia with sevoflurane. PE and AE were applied to the electroencephalographic recordings, and the performance of both measures was assessed by pharmacokinetic-pharmacodynamic modeling and prediction probability. To ensure an accurate complexity measure of electroencephalographic recordings, a wavelet-based preprocessor was built in advance. Results Both PE and AE could distinguish between the awake and anesthetized states and were highly correlated to each other (r = 0.8, P = 0.004). The pharmacokinetic-pharmacodynamic model adequately described the dose-response relation between PE and AE and sevoflurane effect site concentration. The coefficient R between PE and effect site concentration was 0.89 +/- 0.07 for all patients, compared with 0.60 +/- 0.14 for AE. Prediction probabilities of 0.86 +/- 0.04 and 0.79 +/- 0.09 for PE and AE showed that PE has a stronger ability to differentiate between the awake and anesthetic states. Conclusion The results show that PE can estimate the sevoflurane drug effect more effectively than AE. This method could be applied to design a new electroencephalographic monitoring system to estimate sevoflurane anesthetic drug effect.

Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion.

Abstract: Background: Prevention of hemodynamic instability during cesarean delivery during spinal anesthesia has been the aim of several studies. Noninvasive monitoring has been used in all previous studies. This is the first study in healthy pregnant women with continuous invasive recording of arterial blood pressure, cardiac output, and systemic vascular resistance. The aim of this randomized trial was to compare the effects of two different intrathecal doses of bupivacaine, with or without intravenous phenylephrine infusion, on cardiac output and systolic blood pressure. Methods: In this double-blinded study, 80 healthy women scheduled to undergo elective cesarean delivery were randomly assigned to one of four different groups receiving 7 mg spinal bupivacaine with or without a concomitant low-dose infusion of phenylephrine (0.25 g·k g 1 · min 1 ) or 10 mg spinal bupivacaine with or without phenylephrine infusion. All patients had 4 g sufentanil added to the spinal solution and had cohydration with 750 ml saline, 0.9%. Results: The low-dose spinal bupivacaine group with intravenous phenylephrine infusion was the most stable group regarding all hemodynamic variables. The authors found significant differences between this group and the group that was given the high dose of bupivacaine with intravenous placebo infusion regarding cardiac output (P 0.005), systemic vascular resistance (P < 0.0001), and systolic blood pressure (P 0.012). Conclusions: This study shows that low-dose bupivacaine (with sufentanil), combined with a low-dose infusion of phenylephrine and moderate cohydration, gives the best hemodynamic stability during spinal anesthesia for cesarean delivery.

Obesity-induced insulin resistance and hyperglycemia: etiologic factors and molecular mechanisms.

Abstract: Obesity is a major cause of type 2 diabetes, clinically evidenced as hyperglycemia. The altered glucose homeostasis is caused by faulty signal transduction via the insulin signaling proteins, which results in decreased glucose uptake by the muscle, altered lipogenesis, and increased glucose output by the liver. The etiology of this derangement in insulin signaling is related to a chronic inflammatory state, leading to the induction of inducible nitric oxide synthase and release of high levels of nitric oxide and reactive nitrogen species, which together cause posttranslational modifications in the signaling proteins. There are substantial differences in the molecular mechanisms of insulin resistance in muscle versus liver. Hormones and cytokines from adipocytes can enhance or inhibit both glycemic sensing and insulin signaling. The role of the central nervous system in glucose homeostasis also has been established. Multipronged therapies aimed at rectifying obesity-induced anomalies in both central nervous system and peripheral tissues may prove to be beneficial.

Ambulatory Continuous Femoral Nerve Blocks Decrease Time to Discharge Readiness after Tricompartment Total Knee Arthroplasty: A Randomized, Triple-masked, Placebo-controlled Study

Abstract: Background The authors tested the hypotheses that, compared with an overnight continuous femoral nerve block (cFNB), a 4-day ambulatory cFNB increases ambulation distance and decreases the time until three specific readiness-for-discharge criteria are met after tricompartment total knee arthroplasty.

Airway Changes during Labor and Delivery

Abstract: Background: There are no prospective studies that evaluated airway changes during labor. The purpose of this study was to evaluate airway changes in women undergoing labor and delivery. Methods: Two studies were undertaken to evaluate airway changes during labor. The first study used the conventional Samsoon modification of the Mallampati airway class. The airway was photographed at the onset and the end of labor. Women with class 4 airways were excluded from initial participation. In the second study, upper airway volumes were measured using acoustic reflectometry at the onset and the conclusion of labor. Acoustic reflectometry software computed the values for the components of upper airway, oral volume, and pharyngeal volume. Results: In study 1 (n 61), there was a significant increase in airway class from prelabor to postlabor (P < 0.001). The airway increased one grade higher in 20 (33%) and two grades higher in 3 (5%) after labor. At the end of labor, there were 8 parturients with airway class 4 (P < 0.01) and 30 parturients with airway class 3 or class 4 (P < 0.001). In study 2 (n 21), there were significant decreases in oral volume (n 21; P < 0.05), and pharyngeal area (P < 0.05) and volume (P < 0.001) after labor and delivery. No correlation was observed between airway changes during labor and duration of labor, or fluids administered during labor in either study. Conclusion: Airways can change during labor. Therefore, a careful airway evaluation is essential just before administering anesthesia during labor rather than obtaining this information from prelabor data. THE incidence of failed tracheal intubation in the pregnant population is perhaps eight times higher than in the nonpregnant population. 1 Difficult or failed intubation after induction of general anesthesia for cesarean delivery remains the major contributing factor to anesthesiarelated maternal complications. 2,3 The first national study of anesthesia-related maternal mortality in the United States revealed that 52% of the deaths resulted from complications of general anesthesia predominantly related to airway management problems. 4 Despite decreases in the number of obstetric general anesthetics and better awareness of obstetric airway difficulties, a recent survey has shown that the incidence of difficult intubation and subsequent complications have not diminished with time. 5 Furthermore, a critical evaluation of anesthesia-related maternal deaths in Michigan, 1985– 2003, showed that airway obstruction or hypoventilation during emergence and extubation were the cause of five maternal deaths. 6 Obvious factors such as enlarged

Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose.

Abstract: Background: Lipid emulsion infusion reverses cardiovascular compromise due to local anesthetic overdose in laboratory and clinical settings. The authors compared resuscitation with lipid, epinephrine, and saline control in a rat model of bupivacaine-induced cardiac toxicity to determine whether lipid provides a benefit over epinephrine. Methods: Bupivacaine, 20 mg/kg, was infused in rats anesthetized with isoflurane, producing asystole in all subjects. Ventilation with 100% oxygen and chest compressions were begun immediately, along with intravenous treatment with 30% lipid emulsion or saline (5-ml/kg bolus plus continuous infusion at 0.5 ml kg -1 ·min -1 ) or epinephrine (30 μg/kg). Chest compressions were continued and boluses were repeated at 2.5 and 5 min until the native rate-pressure product was greater than 20% baseline. Electrocardiogram and arterial pressure were monitored continuously and at 10 min, arterial blood gas, central venous oxygen saturation, and blood lactate were measured. Effect size (Cohen d) was determined for comparisons at 10 min. Results: Lipid infusion resulted in higher rate-pressure product (P < 0.001, d = 3.84), pH (P < 0.01, d = 3.78), arterial oxygen tension (P < 0.05, d = 2.8), and central venous oxygen saturation (P < 0.001, d = 4.9) at 10 min than did epinephrine. Epinephrine treatment caused higher lactate (P < 0.01, d = 1.48), persistent ventricular ectopy in all subjects, pulmonary edema in four of five rats, hypoxemia, and a mixed metabolic and respiratory acidosis by 10 min. Conclusions: Hemodynamic and metabolic metrics during resuscitation with lipid surpassed those with epinephrine, which were no better than those seen in the saline control group. Further studies are required to optimize the clinical management of systemic local anesthetic toxicity.

Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention

Abstract: Background: The duration of time that elective noncardiac surgery (NCS) should be delayed after percutaneous coronary intervention (PCI) with bare metal stents (BMSs) is unknown. Methods: This large, single-center, retrospective study examined the relation between complication rate in patients with BMSs undergoing NCS and the duration of time between PCI and NCS. Primary endpoints included in-hospital major adverse cardiac events (death, myocardial infarction, stent thrombosis, or repeat revascularization with either coronary artery bypass grafting or PCI of the target vessel) and bleeding events. The relation between the events and the timing of noncardiac surgery after PCI with BMS was assessed using univariate analysis and multiple logistic regression. Results: From January 1, 1990, to January 1, 2005, a total of 899 patients were identified. The frequency of major adverse cardiac events was 10.5% when NCS was performed less than 30 days after PCI with BMS, 3.8% when NCS was performed between 31 and 90 days after PCI with BMS, and 2.8% when NCS was performed more than 90 days after PCI with BMS. In univariate and multivariate analyses, a shorter time interval between PCI with BMS and noncardiac surgery was significantly associated with increased incidence of major adverse cardiac events (univariate: P < 0.001; odds ratio 4.0; 95% confidence interval, 2.0‐8.3; multivariate: P 0.006; odds ratio 3.2; 95% confidence interval, 1.5‐6.9). Bleeding events were not associated with time between PCI with BMS and NCS or with the use of antiplatelet therapy in the week before NCS. Conclusions: The incidence of major adverse cardiac events is lowest when NCS is performed at least 90 days after PCI with BMS. PERCUTANEOUS coronary intervention (PCI) with stenting 1 is the most common method of myocardial revascularization. Coronary stents have been shown to provide better short- and long-term outcome when compared with balloon angioplasty alone. 2 Both bare-metal stents (BMSs) and drug-eluting stents are used in clinical practice, the former for more than 10 yr, whereas drugeluting stents have been commercially available since 2003 in the United States. 3 Although drug-eluting stents are now used in the majority of procedures, BMSs are still indicated for a variety of patients based on individual clinical situations. 4 Thrombosis of a stent is associated with major morbidity and mortality. 5 Antiplatelet therapy is routinely administered to prevent stent thrombosis after PCI with BMS. 6 Current oral pharmacotherapy includes aspirin and clopidogrel. Bare metal stent thrombosis with this regimen occurs in less than 0.5% of patients at 30 days after PCI with BMS. 7

Role of CYP2B6 in Stereoselective Human Methadone Metabolism

Abstract: Background Metabolism and clearance of racemic methadone are stereoselective and highly variable, yet the mechanism remains largely unknown. Initial in vitro studies attributed methadone metabolism to cytochrome P4503A4 (CYP3A4). CYP3A4 was also assumed responsible for methadone clearance in vivo. Nevertheless, recent clinical data do not support a primary role for CYP3A4 and suggest that CYP2B6 may mediate methadone clearance. Expressed CYP2B6 and also CYP2C19 N-demethylate methadone in vitro. This investigation tested the hypothesis that CYPs 2B6, 3A4, and/or 2C19 are responsible for stereoselective methadone metabolism in human liver microsomes and in vivo. Methods N-demethylation of racemic methadone and individual enantiomers by expressed CYPs 2B6, 2C19, and 3A4 was evaluated. Stereoselective microsomal methadone metabolism was quantified, compared with CYP 2B6 and 3A4 content, and probed using CYP isoform-selective inhibitors. A crossover clinical investigation (control, CYP2B6 and CYP3A4 induction by rifampin, CYP3A inhibition by troleandomycin and grapefruit juice) evaluated stereoselective methadone disposition. Results At clinical concentrations, methadone enantiomer N-demethylation by recombinant CYPs 2B6, 3A4, and 2C19 was S > R, S = R, and S R) occurred in livers expressing high levels of CYP2B6 compared with CYP3A4. Clopidogrel, troleandomycin, and (+)-N-3-benzyl-nirvanol, selective inhibitors of CYPs 2B6, 3A4, and 2C19, respectively, inhibited microsomal methadone metabolism by 50-60%, 20-30%, and less than 10%. Only inhibition by clopidogrel was stereoselective. Clinically, rifampin diminished both R- and S-methadone plasma concentrations, but troleandomycin and grapefruit juice altered neither R- nor S-methadone concentrations. Plasma R/S-methadone ratios were increased by rifampin but unchanged by CYP3A inhibition. Conclusions These results suggest a significant role for CYP2B6, but not CYP3A, in stereoselective human methadone metabolism and disposition.

Addiction and Substance Abuse in Anesthesiology

Abstract: Despite substantial advances in our understanding of addiction and the technology and therapeutic approaches used to fight this disease, addiction still remains a major issue in the anesthesia workplace, and outcomes have not appreciably changed. Although alcoholism and other forms of impairment, such as addiction to other substances and mental illness, impact anesthesiologists at rates similar to those in other professions, as recently as 2005, the drug of choice for anesthesiologists entering treatment was still an opioid. There exists a considerable association between chemical dependence and other psychopathology, and successful treatment for addiction is less likely when comorbid psychopathology is not treated. Individuals under evaluation or treatment for substance abuse should have an evaluation with subsequent management of comorbid psychiatric conditions. Participation in self-help groups is still considered a vital component in the therapy of the impaired physician, along with regular monitoring if the anesthesiologist wishes to attempt reentry into clinical practice.