Microsynt: Exploring the syntax of EEG microstates.

Microstates represent electroencephalographic (EEG) activity as a sequence of switching, transient, metastable states. Growing evidence suggests the useful information on brain states is to be found in the higher-order temporal structure of these sequences. Instead of focusing on transition probabilities, here we propose "Microsynt", a method designed to highlight higher-order interactions that form a preliminary step towards understanding the syntax of microstate sequences of any length and complexity. Microsynt extracts an optimal vocabulary of "words" based on the length and complexity of the full sequence of microstates. Words are then sorted into classes of entropy and their representativeness within each class is statistically compared with surrogate and theoretical vocabularies. We applied the method on EEG data previously collected from healthy subjects undergoing propofol anesthesia, and compared their "fully awake" (BASE) and "fully unconscious" (DEEP) conditions. Results show that microstate sequences, even at rest, are not random but tend to behave in a more predictable way, favoring simpler sub-sequences, or "words". Contrary to high-entropy words, lowest-entropy binary microstate loops are prominent and favored on average 10 times more than what is theoretically expected. Progressing from BASE to DEEP, the representation of low-entropy words increases while that of high-entropy words decreases. During the awake state, sequences of microstates tend to be attracted towards "A - B - C" microstate hubs, and most prominently A - B binary loops. Conversely, with full unconsciousness, sequences of microstates are attracted towards "C - D - E" hubs, and most prominently C - E binary loops, confirming the putative relation of microstates A and B to externally-oriented cognitive processes and microstate C and E to internally-generated mental activity. Microsynt can form a syntactic signature of microstate sequences that can be used to reliably differentiate two or more conditions.

EEG microstate dynamics indicate a U-shaped path to propofol-induced loss of consciousness.

Evidence suggests that the stream of consciousness is parsed into transient brain states manifesting themselves as discrete spatiotemporal patterns of global neuronal activity. Electroencephalographical (EEG) microstates are proposed as the neurophysiological correlates of these transiently stable brain states that last for fractions of seconds. To further understand the link between EEG microstate dynamics and consciousness, we continuously recorded high-density EEG in 23 surgical patients from their awake state to unconsciousness, induced by step-wise increasing concentrations of the intravenous anesthetic propofol. Besides the conventional parameters of microstate dynamics, we introduce a new implementation of a method to estimate the complexity of microstate sequences. The brain activity under the surgical anesthesia showed a decreased sequence complexity of the stereotypical microstates, which became sparser and longer-lasting. However, we observed an initial increase in microstates' temporal dynamics and complexity with increasing depth of sedation leading to a distinctive "U-shape" that may be linked to the paradoxical excitation induced by moderate levels of propofol. Our results support the idea that the brain is in a metastable state under normal conditions, balancing between order and chaos in order to flexibly switch from one state to another. The temporal dynamics of EEG microstates indicate changes of this critical balance between stability and transition that lead to altered states of consciousness.

Language Monitoring in Brain Surgery Under General Anesthesia.

BACKGROUND: Awake surgeries for cerebral lesion resection have several limitations including patient fear, discomfort, or pain. This study aimed to determine whether components of language function could be measured under general anesthesia. In this study, the occurrence of mismatch negativity (MMN) was searched in evoked potentials for phonological sounds. MATERIALS AND METHODS: Five normal hearing, French native speaker, awake volunteers participated in evaluating the phonological task (4 females and 1 male). Eleven normal-hearing, French native speaker patients (6 left and 5 right hemisphere lesions) participated at the time of their tumor neurosurgery (3 females and 8 males). Repetitions of the standard syllable /pa/ with the insertion of 1 deviant /po/ were presented through earphones. The difference between averaged epochs of standards and deviants syllables determined the MMN. During surgery, total intravenous anesthesia was performed with propofol and synthetic opioid sufentanil. The bispectral index was targeted (40 to 60). RESULTS: The MMN was found in all awake volunteers and validated by an N250 component. In the patient group, the electroencephalogram analysis was not possible in 4 of 11 patients because of anesthesia being too deep, burst suppression, or a high level of noise (>40 µV). Significant N250 response was obtained in 5 of 7 (71.4%) patients under general anesthesia. The 2 other patients also showed MMN which did not reach significance. CONCLUSIONS: To our knowledge, this is the first demonstration that phonological processing can be measured during brain surgery under general anesthesia, suggesting that some language processing persists under the condition of unconsciousness. These results encourage further study of language processing under general anesthesia with the goal of making intraoperative neuromonitoring.

Transcranial Doppler in the Diagnosis of Cerebral Vasospasm: An Updated Meta-Analysis.

OBJECTIVES: To evaluate the performance of transcranial Doppler and transcranial color-coded duplex Doppler in patients with cerebral vasospasm due to aneurysm rupture. Angiography was considered as the gold standard comparator. DATA SOURCES: Search in MEDLINE, Embase, and Central from January 2001 to October 2017, without language restriction. Bibliographies of retrieved articles were screened for additional studies. STUDY SELECTION: Randomized studies comparing transcranial Doppler or transcranial color-coded duplex Doppler with angiography in adults. DATA EXTRACTION: Data were extracted independently by several investigators. Sensitivity and specificity were combined across studies using a bivariate model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used for reporting and Quality Assessment of Diagnostic Accuracy Studies-2 for quality assessment. DATA SYNTHESIS: We included 18 studies. Fifteen tested transcranial Doppler. For the middle cerebral artery (10 studies, 1,408 tests), the pooled sensitivity was 66.7% (95% CI, 55.9-75.9) and specificity was 89.5% (80.3-94.7). Three studies (278 tests) tested transcranial color-coded duplex Doppler for the middle cerebral artery. The pooled sensitivity was 81.5% (66.0-90.0), and specificity was 96.6% (93.0-98.0). For an arbitrarily chosen prevalence of vasospasm of 70%, positive and negative predictive values were 93.7% (88.9-96.6) and 53.4% (46.7-60.9) for transcranial Doppler and 98.2% (96.4-99.1) and 69.1% (56.1-80.9) for transcranial color-coded duplex Doppler. CONCLUSIONS: Assuming a high prevalence of vasospasm of the middle cerebral artery, both transcranial Doppler and transcranial color-coded duplex Doppler are likely to detect it, but neither is useful to exclude it. There is no convincing evidence that the accuracy of transcranial color-coded duplex Doppler is any better than that of transcranial Doppler. For arteries other than middle cerebral artery, there is a lack of evidence of the usefulness of transcranial Doppler.

Contraction response to muscle percussion: A reappraisal of the mechanism of this bedside test.

OBJECTIVE: To study whether the contraction evoked by muscle percussion stems from the excitation of the muscle or of the nerve and to discuss the changes of this response in neuromuscular disorders. METHODS: In 30 neurologically healthy patients undergoing surgery (for ear, nose, or throat problems unrelated to the study) under general anesthesia with propofol and sufentanil we measured with an electrogoniometer the maximal dorsiflexion of the ankle evoked by reflex hammer percussion of the tibialis anterior muscle before and under neuromuscular junction blockade with rocuronium bromide. In 3 additional healthy volunteers we searched for F-waves to disclose whether percussion excites axons within the muscle. RESULTS: Responses from 28 neurologically healthy patients (15 women) were analyzed after exclusion of 2 due to technical problems. Mean age (SD) was 28 (9) years. Maximal dorsiflexion of the ankle was not significantly modified by neuromuscular junction blockade (mean difference 0.01 mV [95%CI, -0.07 to 0.08], p=0.879). Muscle percussion evoked F-waves in the 3 healthy volunteers tested. CONCLUSIONS: Maximal contraction response to muscle percussion has a muscular rather than a neural origin. However, percussion also excites axons within the muscle. SIGNIFICANCE: These findings may provide clues to understand the changes observed in neuromuscular disorders.

Continuous Intraoperative Monitoring of Temporal Lobe Epilepsy Surgery.

BACKGROUND/AIMS: The monitoring of interictal epileptiform discharge rates (IEDRs) all along anterior temporal lobe resections (ATLRs) has never been reported. Here the effect of ATLR on continuous IEDR monitoring is described. METHODS: IEDRs computed automatically during entire interventions were recorded in 34 patients (38.2%, 13/34 depth; 61.8%, 21/34 scalp electrodes only). Monitorings were invalidated when burst suppression occurred or if initial IEDRs were <5. RESULTS: Monitoring was successful for 69.2% (9/13) of the patients with depth recordings and for 4.8% (1/21) of the patients with scalp recordings. Burst suppressions precluded it in 30.8% (4/13) of the depth and in 57.1% (12/21) of the scalp recordings. Initial IEDRs were <5 for 38.1% (8/21) of the scalp recordings. Significant IEDR decreases were observed in 8/10 patients with successful monitoring. These decreases started with resection of the superior temporal gyrus. IEDRs decreased further with amygdalohippocampectomy in 3/5 patients. At the 12-month follow-up, all patients with IEDR decreases remained seizure free; both patients without did not. CONCLUSION: IEDR monitoring was possible with depth, but not with scalp electrodes. IEDR decreases started with resection of the superior temporal gyrus. A larger patient cohort is necessary to confirm the high predictive values of IEDR monitoring that could become a tool for surgery customization.

Impact of Study Design on Reported Incidences of Acute Mountain Sickness: A Systematic Review.

AIMS: Published incidences of acute mountain sickness (AMS) vary widely. Reasons for this variation, and predictive factors of AMS, are not well understood. We aimed to identify predictive factors that are associated with the occurrence of AMS, and to test the hypothesis that study design is an independent predictive factor of AMS incidence. We did a systematic search (Medline, bibliographies) for relevant articles in English or French, up to April 28, 2013. Studies of any design reporting on AMS incidence in humans without prophylaxis were selected. Data on incidence and potential predictive factors were extracted by two reviewers and crosschecked by four reviewers. Associations between predictive factors and AMS incidence were sought through bivariate and multivariate analyses for different study designs separately. Association between AMS incidence and study design was assessed using multiple linear regression. RESULTS: We extracted data from 53,603 subjects from 34 randomized controlled trials, 44 cohort studies, and 33 cross-sectional studies. In randomized trials, the median of AMS incidences without prophylaxis was 60% (range, 16%-100%); mode of ascent and population were significantly associated with AMS incidence. In cohort studies, the median of AMS incidences was 51% (0%-100%); geographical location was significantly associated with AMS incidence. In cross-sectional studies, the median of AMS incidences was 32% (0%-68%); mode of ascent and maximum altitude were significantly associated with AMS incidence. In a multivariate analysis, study design (p=0.012), mode of ascent (p=0.003), maximum altitude (p<0.001), population (p=0.002), and geographical location (p<0.001) were significantly associated with AMS incidence. Age, sex, speed of ascent, duration of exposure, or history of AMS were inconsistently reported and therefore not further analyzed. CONCLUSIONS: Reported incidences and identifiable predictive factors of AMS depend on study design.

Erythromycin for Gastric Emptying in Patients Undergoing General Anesthesia for Emergency Surgery: A Randomized Clinical Trial.

IMPORTANCE: Patients undergoing emergency procedures under general anesthesia have impaired gastric emptying and are at high risk for aspiration of gastric contents. Erythromycin has strong gastric prokinetic properties. OBJECTIVE: To evaluate the efficacy of erythromycin lactobionate in gastric emptying in patients undergoing emergency surgery. DESIGN, SETTING, AND PARTICIPANTS: The Erythro-Emerge trial was a single-center, randomized, double-blinded, placebo-controlled clinical trial in patients undergoing emergency surgery under general anesthesia at Geneva University Hospitals. We included 132 patients from March 25, 2009, through April 10, 2013, and all patients completed the study. Randomization was stratified for trauma and nontrauma procedures. The randomization code was opened on April 23, 2013, and analyses were performed through July 26, 2013. We performed an intention-to-treat analysis. INTERVENTIONS: Patients were randomized to intravenous erythromycin lactobionate, 3 mg/kg, or placebo 15 minutes before tracheal intubation. Patients were followed up for 24 hours. MAIN OUTCOMES AND MEASURES: The primary outcome was a clear stomach, defined as less than 40 mL of liquids and no solids and identified through endoscopy immediately after intubation. The secondary outcome was the pH level of residual gastric content. RESULTS: A clear stomach was diagnosed in 42 of 66 patients (64%) receiving placebo compared with 53 of 66 patients (80%) receiving erythromycin (risk ratio, 1.26 [95% CI, 1.01-1.57]). In the population undergoing surgery for nontrauma, the association between receipt of erythromycin and having a clear stomach (adjusted odds ratio [95% CI]) was statistically significant (13.4 [1.49-120]; P = .02); in the population undergoing surgery for trauma, it was not (1.81 [0.64-5.16]; P = .26). Median (interquartile range) pH of the residual gastric liquid was 2 (1-4) in 36 patients receiving placebo and 6 (3-7) in 16 receiving erythromycin (P = .002). Patients receiving erythromycin had nausea (20 [30%] vs 4 [6%]) and stomach cramps (15 [23%] vs 2 [3%]) more often than those receiving placebo. One patient receiving erythromycin vomited before induction of anesthesia. CONCLUSIONS AND RELEVANCE: In patients undergoing general anesthesia for emergency procedures, erythromycin administration increased the proportion with a clear stomach and decreased the acidity of residual gastric liquid. Erythromycin was particularly efficacious in the nontrauma population. Adverse effects were minor. Further large-scale studies are warranted to confirm the potential of erythromycin to reduce the incidence of bronchoaspiration in patients undergoing emergency surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00827216.

Efficacy of sugammadex for the reversal of moderate and deep rocuronium-induced neuromuscular block in patients pretreated with intravenous magnesium: a randomized controlled trial.

BACKGROUND: Magnesium enhances the effect of rocuronium. Sugammadex reverses rocuronium-induced neuromuscular block. The authors investigated whether magnesium decreased the efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular block. METHODS: Thirty-two male patients were randomized in a double-blinded manner to receive magnesium sulfate (MgSO4) 60 mg/kg or placebo intravenously before induction of anesthesia with propofol, sufentanil, and rocuronium 0.6 mg/kg. Neuromuscular transmission was monitored using TOF-Watch SX acceleromyography (Organon Ltd., Dublin, Ireland). In 16 patients, sugammadex 2 mg/kg was administered intravenously at reappearance of the second twitch of the train-of-four (moderate block). In 16 further patients, sugammadex 4 mg/kg was administered intravenously at posttetanic count 1 to 2 (deep block). Primary endpoint was recovery time from injection of sugammadex to normalized train-of-four ratio 0.9. Secondary endpoint was recovery time to final T1. RESULTS: Average time for reversal of moderate block was 1.69 min (SD, 0.81) in patients pretreated with MgSO4 and 1.76 min (1.13) in those pretreated with placebo (P = 0.897). Average time for reversal of deep block was 1.77 min (0.83) in patients pretreated with MgSO4 and 1.98 min (0.58) in those pretreated with placebo (P = 0.572). Times to final T1 were longer compared with times to normalized train-of-four ratio 0.9, without any difference between patients pretreated with MgSO4 or placebo. CONCLUSION: Pretreatment with a single intravenous dose of MgSO4 60 mg/kg does not decrease the efficacy of recommended doses of sugammadex for the reversal of a moderate and deep neuromuscular block induced by an intubation dose of rocuronium.

Effect of intraoperative high inspired oxygen fraction on surgical site infection, postoperative nausea and vomiting, and pulmonary function: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Intraoperative high inspired oxygen fraction (FIO2) is thought to reduce the incidence of surgical site infection (SSI) and postoperative nausea and vomiting, and to promote postoperative atelectasis. METHODS: The authors searched for randomized trials (till September 2012) comparing intraoperative high with normal FIO2 in adults undergoing surgery with general anesthesia and reporting on SSI, nausea or vomiting, or pulmonary outcomes. RESULTS: The authors included 22 trials (7,001 patients) published in 26 reports. High FIO2 ranged from 80 to 100% (median, 80%); normal FIO2 ranged from 30 to 40% (median, 30%). In nine trials (5,103 patients, most received prophylactic antibiotics), the incidence of SSI decreased from 14.1% with normal FIO2 to 11.4% with high FIO2; risk ratio, 0.77 (95% CI, 0.59-1.00). After colorectal surgery, the incidence of SSI decreased from 19.3 to 15.2%; risk ratio, 0.78 (95% CI, 0.60-1.02). In 11 trials (2,293 patients), the incidence of nausea decreased from 24.8% with normal FIO2 to 19.5% with high FIO2; risk ratio, 0.79 (95% CI, 0.66-0.93). In patients receiving inhalational anesthetics without prophylactic antiemetics, high FIO2 provided a significant protective effect against both nausea and vomiting. Nine trials (3,698 patients) reported on pulmonary outcomes. The risk of atelectasis was not increased with high FIO2. CONCLUSIONS: Intraoperative high FIO2 further decreases the risk of SSI in surgical patients receiving prophylactic antibiotics, has a weak beneficial effect on nausea, and does not increase the risk of postoperative atelectasis.

Reappraisal of acetazolamide for the prevention of acute mountain sickness: a systematic review and meta-analysis.

Acetazolamide is used to prevent acute mountain sickness (AMS). We assessed efficacy and harm of acetazolamide for the prevention of AMS, and tested for dose-responsiveness. We systematically searched electronic databases (until April 2011) for randomized trials comparing acetazolamide with placebo for the prevention of AMS. For each dose, risk ratios were aggregated using a Mantel-Haenszel fixed effect model. Numbers needed to treat (NNT) to benefit one subject with each dose were calculated for different baseline risks. Modes of ascent were taken as proxies of baseline risks. Twenty-four trials were included; 1011 subjects received acetazolamide 250, 500, or 750 mg day⁻¹; 854 received placebo. When climbing, median speed of ascent was 14 m/h, average AMS rate in controls was 34%, and NNT to prevent AMS with acetazolamide 250, 500, and 750 mg/day compared with placebo was 6.5, 5.9, and 5.3. When ascending by transport and subsequent climbing (speed of ascent 133 m/h) or by transport alone (491 m/h), average AMS rate in controls was 60%, and NNT with acetazolamide 250, 500, and 750 mg/day was 3.7, 3.3, and 3.0. In hypobaric chambers, median speed of ascent was 4438 m/h, average AMS rate in controls was 86%, and NNT with acetazolamide 250, 500, and 750 mg/day was 2.6, 2.3, and 2.1. The risk of paresthesia was increased with all doses. The risk of polyuria and taste disturbance was increased with 500 and 750 mg/day. The degree of efficacy of acetazolamide for the prevention of AMS is limited when the baseline risk is low, and there is some evidence of dose-responsiveness.

Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including hyperalgesia. METHODS: The authors searched for randomized placebo-controlled trials testing systemic α2 agonists administrated in surgical patients and reporting on postoperative cumulative opioid consumption and/or pain intensity. Meta-analyses were performed when data from 5 or more trials and/or 100 or more patients could be combined. RESULTS: Thirty studies (1,792 patients, 933 received clonidine or dexmedetomidine) were included. There was evidence of postoperative morphine-sparing at 24 h; the weighted mean difference was -4.1 mg (95% confidence interval, -6.0 to -2.2) with clonidine and -14.5 mg (-22.1 to -6.8) with dexmedetomidine. There was also evidence of a decrease in pain intensity at 24 h; the weighted mean difference was -0.7 cm (-1.2 to -0.1) on a 10-cm visual analog scale with clonidine and -0.6 cm (-0.9 to -0.2) with dexmedetomidine. The incidence of early nausea was decreased with both (number needed to treat, approximately nine). Clonidine increased the risk of intraoperative (number needed to harm, approximately nine) and postoperative hypotension (number needed to harm, 20). Dexmedetomidine increased the risk of postoperative bradycardia (number needed to harm, three). Recovery times were not prolonged. No trial reported on chronic pain or hyperalgesia. CONCLUSIONS: Perioperative systemic α2 agonists decrease postoperative opioid consumption, pain intensity, and nausea. Recovery times are not prolonged. Common adverse effects are bradycardia and arterial hypotension. The impact of α2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking.

Low-dose droperidol (≤1 mg or ≤15 µg kg-1) for the prevention of postoperative nausea and vomiting in adults: quantitative systematic review of randomised controlled trials.

CONTEXT: Droperidol is widely used for the prevention of postoperative nausea and vomiting (PONV) in European countries. It is unclear how efficacious low-dose droperidol is in the prevention of PONV. OBJECTIVES: To test the efficacy of low-dose droperidol in the prevention of PONV in adults and to test for dose-responsiveness. DESIGN: Systematic review of randomised controlled trials with meta-analyses. DATA SOURCES: Comprehensive search in electronic databases (Medline, Embase, Central) up to June 2011. Additional trials were obtained from bibliographies of retrieved reports. No language restriction was applied. ELIGIBILITY CRITERIA: Randomised trials testing prophylactic intravenous droperidol ≤1 mg or ≤15 µg kg compared with placebo (or no treatment) in adults undergoing general anaesthesia and reporting on PONV. RESULTS: We analysed 25 trials (2957 patients). Doses varied from 0.25 to 1.0 mg. For prevention of early nausea (within 6 h postoperatively), relative risk (RR) was 0.45 (95% CI, 0.35 to 0.58); number needed to treat (NNT) was 7, 4, and 2 for low, medium and high baseline risk (i.e. control event rate 25, 50, 75%). For prevention of early vomiting, RR was 0.65 (95% CI, 0.57 to 0.74), NNT 11, 6, and 4. For prevention of late nausea (within 24 h), RR was 0.74 (95% CI, 0.62 to 0.87), NNT 15, 8, and 5. For prevention of late vomiting, RR was 0.61 (95% CI, 0.47 to 0.80), NNT 10, 5, and 3. Droperidol decreased the risk of headache but increased the risk of restlessness. For these outcomes there was no evidence of dose-responsiveness. There were no differences in the incidences of sedation or dizziness. Two patients receiving droperidol 0.625 mg had extrapyramidal symptoms. Cardiac toxicity data were not reported. CONCLUSION: Prophylactic doses of droperidol of 1 mg or below are antiemetic. Because adverse drug reactions are likely to be dose-dependent, there is an argument to stop using doses of more than 1 mg.

Transcutaneous nicotine does not prevent postoperative nausea and vomiting: a randomized controlled trial.

AIMS: There is empirical evidence that smokers are less likely to suffer from postoperative nausea and vomiting (PONV). We sought to investigate whether transcutaneus nicotine prevents PONV. METHODS: Non-smokers receiving general anaesthesia for surgery were randomly allocated to Nicotinell Patch 10cm(2) (TTS 10), containing 17.5mg of nicotine (average delivery rate, 7mg 24h(-1) ) or matching placebo patch. Patches were applied 1h before surgery and were left in situ until 24h after surgery (or until the first PONV symptoms occurred). RESULTS: We randomized 90 patients (45 nicotine, 45 placebo). In the post-anaesthetic care unit, the incidence of nausea was 22.2% with nicotine and 24.4% with placebo (P= 0.80), and the incidence of vomiting was 20.0% with nicotine and 17.8% with placebo (P= 0.78). Cumulative 24h incidence of nausea was 42.2% with nicotine and 40.0% with placebo (P= 0.83), and of vomiting was 31.1% with nicotine and 28.9% with placebo (P= 0.81). PONV episodes tended to occur earlier in the nicotine group. Postoperative headache occurred in 17.8% of patients treated with nicotine and in 15.6% with placebo (P= 0.49). More patients receiving nicotine reported a low quality of sleep during the first postoperative night (26.7% vs. 6.8% with placebo; P= 0.01). CONCLUSIONS: Non-smokers receiving a prophylactic nicotine patch had a similar incidence of PONV during the first 24h and tended to develop PONV symptoms earlier compared with controls. They had a significantly increased risk of insomnia during the first postoperative night.

Dexamethasone and risk of nausea and vomiting and postoperative bleeding after tonsillectomy in children: a randomized trial.

CONTEXT: Dexamethasone is widely used to prevent postoperative nausea and vomiting (PONV) in pediatric tonsillectomy. OBJECTIVE: To assess whether dexamethasone dose-dependently reduces the risk of PONV at 24 hours after tonsillectomy. DESIGN, SETTING, AND PATIENTS: Randomized placebo-controlled trial conducted among 215 children undergoing elective tonsillectomy at a major public teaching hospital in Switzerland from February 2005 to December 2007. INTERVENTIONS: Children were randomly assigned to receive dexamethasone (0.05, 0.15, or 0.5 mg/kg) or placebo intravenously after induction of anesthesia. Acetaminophen-codeine and ibuprofen were given as postoperative analgesia. Follow-up continued until the 10th postoperative day. MAIN OUTCOME MEASURES: The primary end point was prevention of PONV at 24 hours; secondary end points were decrease in the need for ibuprofen at 24 hours and evaluation of adverse effects. RESULTS: At 24 hours, 24 of 54 participants who received placebo (44%; 95% confidence interval [CI], 31%-59%) had experienced PONV compared with 20 of 53 (38%; 95% CI, 25%-52%), 13 of 54 (24%; 95% CI, 13%-38%), and 6 of 52 (12%; 95% CI, 4%-23%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P<.001 for linear trend). Children who received dexamethasone received significantly less ibuprofen. There were 26 postoperative bleeding episodes in 22 children. Two of 53 (4%; 95% CI, 0.5%-13%) children who received placebo had bleeding compared with 6 of 53 (11%; 95% CI, 4%-23%), 2 of 51 (4%; 95% CI, 0.5%-13%), and 12 of 50 (24%; 95% CI, 13%-38%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P = .003). Dexamethasone, 0.5 mg/kg, was associated with the highest bleeding risk (adjusted relative risk, 6.80; 95% CI, 1.77-16.5). Eight children had to undergo emergency reoperation because of bleeding, all of whom had received dexamethasone. The trial was stopped early for safety reasons. CONCLUSION: In this study of children undergoing tonsillectomy, dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00403806.

Plasma concentrations of brain-derived neurotrophic factor in patients undergoing minor surgery: a randomized controlled trial.

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15 min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24 h postoperatively. Data from 26 patients (13 in each group) were analyzed. At each time point, BDNF plasma concentrations showed large variability. At baseline, concentrations were 631 +/- 337 (mean +/- SD) pg ml(-1) in the propofol group and were 549 +/- 512 pg ml(-1) in the thiopental-isoflurane group (P = 0.31). At 15 min, concentrations significantly decreased in the propofol group (247 +/- 219 pg ml(-1), P = 0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597 +/- 471 pg ml(-1), P = 0.798 compared with baseline). At skin closure and in the post-anesthetic care unit, concentrations were not different from baseline in both groups. At 24 h, concentrations significantly decreased below baseline in both groups (propofol: 232 +/- 129 pg ml(-1), P = 0.0015; thiopental-isoflurane: 253 +/- 250 pg ml(-1), P = 0.016). In the propofol group, there was a weak but statistically significant positive correlation (R2 = 0.38, P = 0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surgery.

Magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials.

BACKGROUND: Randomized trials have reached different conclusions as to whether magnesium is a useful adjuvant to postoperative analgesia. METHODS: We performed a comprehensive search (electronic databases, bibliographies, all languages, to 4.2006) for randomized comparisons of magnesium and placebo in the surgical setting. Information on postoperative pain intensity and analgesic requirements was extracted from the trials and compared qualitatively. Dichotomous data on adverse effects were combined using classic methods of meta-analysis. RESULTS: Fourteen randomized trials (778 patients, 404 received magnesium) tested magnesium laevulinate, gluconate or sulfate. With magnesium, postoperative pain intensity was significantly decreased in four (29%) trials, was no different from placebo in seven (50%), and was increased in one (7%); two trials (14%) did not report on pain intensity. With magnesium, postoperative analgesic requirements were significantly reduced in eight (57%) trials, were no different from placebo in five (36%), and were increased in one (7%). Magnesium-treated patients had less postoperative shivering (relative risk 0.38, 95% confidence interval 0.17-0.88, number-needed-to-treat 14). Seven trials reported on magnesium serum levels. In all, serum levels were increased in patients who received magnesium; in six, serum levels were decreased in those who received placebo. CONCLUSIONS: These trials do not provide convincing evidence that perioperative magnesium may have favorable effects on postoperative pain intensity and analgesic requirements. Perioperative magnesium supplementation prevents postoperative hypomagnesemia and decreases the incidence of postoperative shivering. It may be worthwhile to further study the role of magnesium as a supplement to postoperative analgesia, since this relatively harmless molecule is inexpensive, and the biological basis for its potential antinociceptive effect is promising.

Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials.

The authors analyzed data from 52 randomized placebo-controlled trials (4,893 adults) testing acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors given in conjunction with morphine after surgery. The median of the average 24-h morphine consumption in controls was 49 mg (range, 15-117 mg); it was significantly decreased with all regimens by 15-55%. There was evidence of a reduction in pain intensity at 24 h (1 cm on the 0- to 10-cm visual analog scale) only with nonsteroidal antiinflammatory drugs. Nonsteroidal antiinflammatory drugs also significantly reduced the incidence of nausea/vomiting from 28.8% to 22.0% (number needed to treat, 15) and of sedation from 15.4% to 12.7% (number needed to treat, 37) but increased the risk of severe bleeding from 0% to 1.7% (number needed to harm, 59). Selective cyclooxygenase-2 inhibitors increased the risk of renal failure in cardiac patients from 0% to 1.4% (number needed to harm, 73). A decrease in morphine consumption is not a good indicator of the usefulness of a supplemental analgesic. There is evidence that the combination of nonsteroidal antiinflammatory drugs with patient-controlled analgesia morphine offers some advantages over morphine alone.