Comparing the haemodynamic effects of high- and low-dose opioid anaesthesia: a secondary analysis of a randomised controlled trial.

Post-induction hypotension (MAP < 65 mmHg) occurs frequently and is usually caused by the cardiovascular adverse effects of the anaesthetic induction drugs used. We hypothesize that a clinically significant difference in the incidence and severity of hypotension will be found when different doses of propofol and remifentanil are used for induction of anaesthesia. METHODS: This is a secondary analysis of a randomised controlled trial wherein four groups (A-D) of patients received one out of four different combinations of propofol and remifentanil, titrated to a predicted equipotency in probability of tolerance to laryngoscopy (PTOL) according to the Bouillon interaction model. In group A, a high dose of propofol and a low dose of remifentanil was administered, and across the groups this ratio was gradually changed until it was reversed in group D. Mean and systolic arterial blood pressure (MAP, SAP) were compared at four time points (Tbaseline, Tpost-bolus, T3min, Tnadir) within and between groups Heart rate, bispectral index (BIS) and the incidence of hypotension were compared. RESULTS: Data from 76 patients was used. At Tpost-bolus a statistically significant lower MAP and SAP was found in group A versus D (p = 0.011 and p = 0.002). A significant higher heart rate was found at T3min and Tnadir between groups A and B when compared to groups C and D (p = < 0.001 and p = 0.002). A significant difference in BIS value was found over all groups at T3min and Tnadir (both p < 0.001). All other outcomes did not differ significantly between groups. CONCLUSION: Induction of anaesthesia with different predicted equipotent combinations of propofol and remifentanil did result in statistically different but clinically irrelevant differences in haemodynamic endpoints during induction of anaesthesia. Our study could not identify preferable drug combinations that decrease the risk for hypotension after induction, although they all yield a similar predicted PTOL.

Feasibility and optimal choice of stimulation parameters for supramaximal stimulation of motor evoked potentials.

PURPOSE: The aim was to investigate the feasibility and optimal stimulation parameters for supramaximal stimulation of muscle recorded transcranial electrical stimulation motor evoked potentials (mTc-MEP). METHODS: Forty-seven consecutive patients that underwent scoliosis surgery were included. First, the feasibility of supramaximal stimulation was assessed for two settings (setting 1: pulse duration 0.075ms, interstimulus interval (ISI) 1.5ms; setting 2: pulse duration 0.300ms, ISI 3ms). Thereafter, three mTc-MEP parameters were considered for both settings; (1) elicitability, (2) amplitude, and (3) if supramaximal stimulation was achieved with ≥ 20 V below maximum output. Finally, ISIs (1ms-4ms) were optimized for setting 1. RESULTS: Nine patients (19.15%) were excluded. Of the remaining patients, supramaximal stimulation was achieved in all patients for setting 1, and in 26 (68.42%) for setting 2. In one patient, mTc-MEPs were elicitable in more muscles for setting (1) Amplitudes were not significantly different. Stimulation voltage could be increased ≥ 20 V in all 38 patients for setting 1 and in 10 (38.46%) for setting (2) Optimal ISI's differed widely. CONCLUSION: We recommend using setting 1 when monitoring mTc-MEPs with supramaximal stimulation, after which an individualized ISI optimization can be performed. Moreover, when using supramaximal stimulation, short ISI's (i.e. 1ms or 1.5ms) can be the optimal ISI for obtaining the highest mTc-MEP amplitude.

The influence of depth of anesthesia and blood pressure on muscle recorded motor evoked potentials in spinal surgery. A prospective observational study protocol.

For high-risk spinal surgeries, intraoperative neurophysiological monitoring (IONM) is used to detect and prevent intraoperative neurological injury. The motor tracts are monitored by recording and analyzing muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs). A mTc-MEP amplitude decrease of 50-80% is the most common warning criterion for possible neurological injury. However, these warning criteria often result in false positive warnings. False positives may be caused by inadequate depth of anesthesia and blood pressure on mTc-MEP amplitudes. The aim of this paper is to validate the study protocol in which the goal is to investigate the effects of depth of anesthesia (part 1) and blood pressure (part 2) on mTc-MEPs. Per part, 25 patients will be included. In order to investigate the effects of depth of anesthesia, a processed electroencephalogram (pEEG) monitor will be used. At pEEG values of 30, 40 and 50, mTc-MEP measurements will be performed. To examine the effect of blood pressure on mTc-MEPs the mean arterial pressure will be elevated from 60 to 100 mmHg during which mTc-MEP measurements will be performed. We hypothesize that by understanding the effects of depth of anesthesia and blood pressure on mTc-MEPs, the mTc-MEP monitoring can be interpreted more reliably. This may contribute to fewer false positive warnings. By performing this study after induction and prior to incision, this protocol provides a unique opportunity to study the effects of depths of anesthesia and blood pressure on mTc-MEPs alone with as little confounders as possible. Trial registration number NL7772.

Comparison of haemodynamic- and electroencephalographic-monitored effects evoked by four combinations of effect-site concentrations of propofol and remifentanil, yielding a predicted tolerance to laryngoscopy of 90.

This prospective study evaluates haemodynamic and electroencephalographic effects observed when administering four combinations of effect-site concentrations of propofol (CePROP) and remifentanil (CeREMI), all yielding a single predicted probability of tolerance of laryngoscopy of 90% (PTOL = 90%) according to the Bouillon interaction model. We aimed to identify combinations of CePROP and CeREMI along a single isobole of PTOL that result in favourable hypnotic and haemodynamic conditions. This knowledge could be of advantage in the development of drug advisory monitoring technology. 80 patients (18-90 years of age, ASA I-III) were randomized into four groups and titrated towards CePROP (Schnider model, ug⋅ml-1) and CeREMI (Minto model, ng⋅ml-1) of respectively 8.6 and 1, 5.9 and 2, 3.6 and 4 and 2.0 and 8. After eleven minutes of equilibration, baseline measurements of haemodynamic endpoints and bispectral index were compared with three minutes of responsiveness measurements after laryngoscopy. Before laryngoscopy, bispectral index differed significantly (p < 0.0001) between groups in concordance with CePROP. Heart rate decreased with increasing CeREMI (p = 0.001). The haemodynamic and arousal responses evoked by laryngoscopy were not significantly different between groups, but CePROP = 3.6 µg⋅ml-1 and CeREMI = 4 ng⋅ml-1 evoked the lowest median value for ∆HR and ∆SAP after laryngoscopy. This study provides clinical insight on the haemodynamic and hypnotic consequences, when a model based predicted PTOL is used as a target for combined effect-site controlled target- controlled infusion of propofol and remifentanil. Heart rate and bispectral index were significantly different between groups despite a theoretical equipotency for PTOL, suggesting that each component of the anaesthetic state (immobility, analgesia, and hypnotic drug effect) should be considered as independent neurophysiological and pharmacological phenomena. However, claims of (in)accuracy of the predicted PTOL must be considered preliminary because larger numbers of observations are required for that goal.

Comparison of predicted and real propofol and remifentanil concentrations in plasma and brain tissue during target-controlled infusion: a prospective observational study.

Target-controlled infusion systems are increasingly used to administer intravenous anaesthetic drugs to achieve a user-specified plasma or effect-site target concentration. While several studies have investigated the ability of the underlying pharmacokinetic-dynamic models to predict plasma concentrations, there are no data on their performance in predicting drug concentrations in the human brain. We assessed the predictive performance of the Marsh propofol model and Minto remifentanil model for plasma and brain tissue concentrations. Plasma samples were obtained during neurosurgery from 38 patients, and brain tissue samples from nine patients. Propofol and remifentanil concentrations were measured using gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry. Data were analysed from the nine patients in whom both plasma and brain samples were simultaneously obtained. For the Minto model (five patients), the median performance error was 72% for plasma and -14% for brain tissue concentration predictions. The model tended to underestimate plasma remifentanil concentrations, and to overestimate brain tissue remifentanil concentrations. For the Marsh model (five patients), the median prediction errors for plasma and brain tissue concentrations were 12% and 81%, respectively. However, when the data from all blood propofol assays (36 patients) were analysed, the median prediction error was 11%, with overprediction in 15 (42%) patients and underprediction in 21 (58%). These findings confirm earlier reports demonstrating inaccuracy for commonly used pharmacokinetic-dynamic models for plasma concentrations and extend these findings to the prediction of effect-site concentrations.

Intraoperative neurophysiological monitoring during scoliosis surgery in patients with Duchenne muscular dystrophy.

PURPOSE: Little is known about the reliability and value of intraoperative neurophysiological monitoring (IONM) in patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction surgery. The aim of this study was to investigate the feasibility of IONM and the cortical excitability in these patients. METHODS: Fifteen patients with DMD and scoliosis and 15 patients with adolescent idiopathic scoliosis (AIS) underwent scoliosis correction surgery with the use of IONM. IONM consisted of transcranial electrical stimulation motor evoked potential (Tc-MEP) and somatosensory evoked potential (SSEP) monitoring. The highest Tc-MEP amplitudes were collected to test the feasibility. Preoperative compound muscle action potentials (CMAPs) and transcranial magnetic stimulation (TMS)-MEPs were recorded to test the cortical excitability. SSEPs were scored as elicitable or not elicitable. RESULTS: Tc-MEP amplitudes were significantly lower in the DMD group for both the gastrocnemius and tibialis anterior muscles. However, the abductor hallucis muscle had similar amplitudes in both the DMD as the AIS group. TMS/CMAP and Tc-MEP/CMAP ratios were similar in the DMD and AIS group (P = 0.126 and P = 0.792 respectively). CONCLUSIONS: Tc-MEP and SSEP monitoring is feasible, particularly when Tc-MEPs are recorded from the abductor hallucis muscle in patients with DMD. Similar TMS/CMAP and Tc-MEP/CMAP ratios show that there were no differences observed in cortical excitability between the groups. IONM seems a feasible and valuable neurophysiological tool to signal possible surgically induced damage to the spinal cord during scoliosis correction surgery in patients with DMD.

Guidelines for the safe practice of total intravenous anaesthesia (TIVA): Joint Guidelines from the Association of Anaesthetists and the Society for Intravenous Anaesthesia.

Guidelines are presented for safe practice in the use of intravenous drug infusions for general anaesthesia. When maintenance of general anaesthesia is by intravenous infusion, this is referred to as total intravenous anaesthesia. Although total intravenous anaesthesia has advantages for some patients, the commonest technique used for maintenance of anaesthesia in the UK and Ireland remains the administration of an inhaled volatile anaesthetic. However, the use of an inhalational technique is sometimes not possible, and in some situations, inhalational anaesthesia is contraindicated. Therefore, all anaesthetists should be able to deliver total intravenous anaesthesia competently and safely. For the purposes of simplicity, these guidelines will use the term total intravenous anaesthesia but also encompass techniques involving a combination of intravenous infusion and inhalational anaesthesia. This document is intended as a guideline for safe practice when total intravenous anaesthesia is being used, and not as a review of the pros and cons of total intravenous anaesthesia vs. inhalational anaesthesia in situations where both techniques are possible.

Systematic review of the effects of intensive-care-unit noise on sleep of healthy subjects and the critically ill.

Intensive-care-unit (ICU) patients exhibit disturbed sleeping patterns, often attributed to environmental noise, although the relative contribution of noise compared to other potentially disrupting factors is often debated. We therefore systematically reviewed studies of the effects of ICU noise on the quality of sleep to determine to what extent noise explains the observed sleep disruption, using the Cochrane Collaboration method for non-randomized studies. Searches in Scopus, PubMed, Embase, CINAHL, Web of Science, and the Cochrane Library were conducted until May 2017. Twenty papers from 18 studies assessing sleep of adult patients and healthy volunteers in the ICU environment, whilst recording sound levels, were included and independently reviewed by two reviewers. We found that the numbers of arousals between the baseline and the ICU noise condition in healthy subjects differed significantly (mean difference 9.59; 95% confidence interval 2.48-16.70). However, there was considerable heterogeneity between studies (I2 94%, P < 0.00001), and all studies suffered from a considerable risk of bias. The meta-analysis of results was hampered by widely varying definitions of sound parameters between studies and a general lack of detailed description of methods used. It is, therefore, currently impossible to quantify the extent to which noise contributes to sleep disruption among ICU patients, and thus, the potential benefit from noise reduction remains unclear. Regardless, the majority of the observed sleep disturbances remain unexplained. Future studies should, therefore, also focus on more intrinsic sleep-disrupting factors in the ICU environment.

Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation.

BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a desired target concentration in a central or effect-site compartment. Our aim was to develop a PK-PD model for propofol that can predict the bispectral index (BIS) for a broad population, suitable for TCI applications. METHODS: Propofol PK data were obtained from 30 previously published studies, five of which also contained BIS observations. A PK-PD model was developed using NONMEM. Weight, age, post-menstrual age (PMA), height, sex, BMI, and presence/absence of concomitant anaesthetic drugs were explored as covariates. The predictive performance was measured across young children, children, adults, elderly, and high-BMI individuals, and in simulated TCI applications. RESULTS: Overall, 15 433 propofol concentration and 28 639 BIS observations from 1033 individuals (672 males and 361 females) were analysed. The age range was from 27 weeks PMA to 88 yr, and the weight range was 0.68-160 kg. The final model uses age, PMA, weight, height, sex, and presence/absence of concomitant anaesthetic drugs as covariates. A 35-yr-old, 170 cm, 70 kg male (without concomitant anaesthetic drugs) has a V1, V2, V3, CL, Q2, Q3, and ke0 of 6.28, 25.5, 273 litres, 1.79, 1.75, 1.11 litres min-1, and 0.146 min-1, respectively. The propofol TCI administration using the model matches well with recommendations for all age groups considered for both anaesthesia and sedation. CONCLUSIONS: We developed a PK-PD model to predict the propofol concentrations and BIS for broad, diverse population. This should be useful for TCI in anaesthesia and sedation.

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

BACKGROUND: Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. METHODS: Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 µg kg-1 min-1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. RESULTS: No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. CONCLUSIONS: Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. CLINICAL TRIAL REGISTRATION: NTR4735.

Accidental awareness during general anaesthesia - a narrative review.

Unintended accidental awareness during general anaesthesia represents failure of successful anaesthesia, and so has been the subject of numerous studies during the past decades. As return to consciousness is both difficult to describe and identify, the reported incidence rates vary widely. Similarly, a wide range of techniques have been employed to identify cases of accidental awareness. Studies which have used the isolated forearm technique to identify responsiveness to command during intended anaesthesia have shown remarkably high incidences of awareness. For example, the ConsCIOUS-1 study showed an incidence of responsiveness around the time of laryngoscopy of 1:25. On the other hand, the 5th Royal College of Anaesthetists National Audit Project, which reported the largest ever cohort of patients who had experienced accidental awareness, used a system to identify patients who spontaneously self-reported accidental awareness. In this latter study, the incidence of accidental awareness was 1:19,600. In the recently published SNAP-1 observational study, in which structured postoperative interviews were performed, the incidence was 1:800. In almost all reported cases of intra-operative responsiveness, there was no subsequent explicit recall of intra-operative events. To date, there is no evidence that this occurrence has any psychological consequences. Among patients who experience accidental awareness and can later remember details of their experience, the consequences are better known. In particular, when awareness occurs in a patient who has been given neuromuscular blocking agents, it may result in serious sequelae such as symptoms of post-traumatic stress disorder and a permanent aversion to surgery and anaesthesia, and is feared by patients and anaesthetists. In this article, the published literature on the incidence, consequences and management of accidental awareness under general anaesthesia with subsequent recall will be reviewed.

Pharmacokinetics and pharmacodynamics of propofol: changes in patients with frontal brain tumours.

BACKGROUND: Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour influences propofol pharmacokinetics and pharmacodynamics and existing PK-PD model performance. METHODS: Twenty patients with a frontal brain tumour and 20 control patients received a propofol infusion to achieve an induction-emergence-induction anaesthetic sequence. Propofol plasma concentration was measured every 4 min and at each transition of the conscious state. Bispectral index (BIS) values were continuously recorded. We used non-linear mixed-effects modelling to analyse the effects of the presence of a brain tumour on the pharmacokinetics and pharmacodynamics of propofol. Subsequently we calculated the predictive performance of Marsh, Schnider, and Eleveld models in terms of median prediction error (MdPE) and median absolute prediction error (MdAPE). RESULTS: Patients with brain tumours showed 40% higher propofol clearance than control patients. Performance of the Schnider model (MdPEpk -20.0%, MdAPEpk 23.4%) and Eleveld volunteer model (MdPEpk -8.58%, MdAPEpk 21.6%) were good. The Marsh model performed less well (MdPEpk -14.3%, MdAPEpk 41.4%), as did the Eleveld patient model (MdPEpk -30.8%, MdAPEpk 32.1%). CONCLUSIONS: Brain tumours might alter the pharmacokinetics of propofol. Caution should be exerted when using propofol TCI in patients with frontal brain tumours due to higher clearance. TRIAL REGISTRY NUMBER: NCT01060631.

Dexmedetomidine pharmacokinetic-pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation.

BACKGROUND: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties. METHODS: In a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokinetic-pharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG. RESULTS: We found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise. CONCLUSIONS: The new pharmacokinetic-pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation. CLINICAL TRIAL REGISTRATION: NCT01879865.

Dexmedetomidine pharmacodynamics in healthy volunteers: 2. Haemodynamic profile.

BACKGROUND: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate. METHODS: Dexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM. RESULTS: Our model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal E max model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion. CONCLUSIONS: The present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects. CLINICAL TRIAL REGISTRATION: NCT01879865.

Pharmacokinetic and pharmacodynamic interactions in anaesthesia. A review of current knowledge and how it can be used to optimize anaesthetic drug administration.

This review describes the basics of pharmacokinetic and pharmacodynamic drug interactions and methodological points of particular interest when designing drug interaction studies. It also provides an overview of the available literature concerning interactions, with emphasis on graphic representation of interactions using isoboles and response surface models. It gives examples on how to transform this knowledge into clinically and educationally applicable (bedside) tools.

Influence of Bayesian optimization on the performance of propofol target-controlled infusion.

BACKGROUND: Target controlled infusion (TCI) systems use population-based pharmacokinetic (PK) models that do not take into account inter-individual residual variation. This study compares the bias and inaccuracy of a population-based vs a personalized TCI propofol titration using Bayesian adaptation. Haemodynamic and hypnotic stability, and the prediction probability of alternative PK models, was studied. METHODS: A double-blinded, prospective randomized controlled trial of 120 subjects undergoing cardiac surgery was conducted. Blood samples were obtained at 10, 35, 50, 65, 75 and 120 min and analysed using a point-of-care propofol blood analyser. Bayesian adaptation of the PK model was applied at 60 min in the intervention group. Median (Absolute) Performance Error (Md(A)PE) was used to evaluate the difference between bias and inaccuracy of the models. Haemodynamic (mean arterial pressure [MAP], heart rate) and hypnotic (bispectral index [BIS]) stability was studied. The predictive performance of four alternative propofol PK models was studied. RESULTS: MdPE and MdAPE did not differ between groups during the pre-adjustment period (control group: 6.3% and 16%; intervention group: 5.4% and 18%). MdPE differed in the post-adjustment period (12% vs. -0.3%), but MdAPE did not (18% vs. 15%). No difference in heart rate, MAP or BIS was found. Compared with the other models, the Eleveld propofol PK model (patients) showed the best prediction performance. CONCLUSIONS: When an accurate population-based PK model was used for propofol TCI, Bayesian adaption of the model improved bias but not precision. CLINICAL TRIAL REGISTRATION: Dutch Trial Registry NTR4518.

Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery.

Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein ß, as well as plasma-free haemoglobin concentration as a measure of haemolysis, could be used to predict the risk of long-term cognitive decline after coronary artery bypass grafting with or without cardiopulmonary bypass. We assessed cognitive function using the CogState brief computerised cognitive test battery at 3 months and at 15 months after surgery. Blood samples were obtained pre-operatively, after sternal closure, and at 6 h and 24 h postoperatively. We found signs of cognitive decline at 3 months in 15 of 57 patients (26%), and in 13 of 48 patients (27%) at 15 months. Brain fatty acid-binding protein was already significantly higher before surgery in patients with postoperative cognitive dysfunction at 15 months, with pre-operative plasma levels of 22.8 (8.3-33.0 [0-44.6]) pg.ml-1 compared with 9.7 (3.9-17.3 [0-49.0]) pg.ml-1 in patients without cognitive dysfunction. This biomarker remained significantly higher in patients with cognitive decline throughout the entire postoperative period. At 3 months after surgery, high levels of plasma-free haemoglobin at sternal closure were associated with a negative influence on cognitive performance, as were high baseline scores on neuropsychological tests, whereas a higher level of education proved to beneficially influence cognitive outcome. We found that postoperative cognitive dysfunction at 3 months was associated with cognitive decline at 15 months after surgery, and served as a valuable prognostic factor for declines in individual cognitive performance one year later. Classical neuronal injury-related biomarkers were of no clear prognostic value.

Bispectral index values and propofol concentrations at loss and return of consciousness in patients with frontal brain tumours and control patients.

BACKGROUND: The influence of frontal brain tumours on bispectral index (BIS) measurements and propofol requirements is unknown. The primary aim of our study was to determine whether BIS values recorded at loss and return of consciousness (LOC and ROC, respectively) differ between patients with unilateral frontal brain tumours and control patients. Secondary goals were to compare propofol requirements for LOC and to determine whether there were significant inter-hemispheric differences between BIS values in tumour and control patients. METHODS: We enrolled 20 patients with a frontal brain tumour and 20 control patients. Bilateral BIS measurements were done during induction of propofol anaesthesia, during recovery of consciousness, and during a second induction of anaesthesia. The isolated-forearm test was used to determine the moments of LOC1, ROC, and LOC2. Arterial blood samples were obtained every 4 min for determination of measured propofol concentrations. RESULTS: The median BIS values recorded at LOC1, ROC, and LOC2 did not differ between the groups. There were no significant inter-hemispheric differences in BIS in tumour and control patients. The median [inter-quartile range (IQR)] total propofol doses at LOC1 were 82 (75-92) and 78 (68-91) mg in tumour and control patients, respectively. The median (IQR) measured plasma propofol concentrations at LOC1 were 12 (9-14) and 13 (11-15) µg ml(-1) in the tumour and control groups, respectively. CONCLUSIONS: The presence of a frontal brain tumour did not affect ipsilateral BIS values, and so need not influence the placement of unilateral BIS electrodes if BIS monitoring is used to titrate propofol anaesthesia.