Spoken words are processed during dexmedetomidine-induced unresponsiveness.

BACKGROUND: Studying the effects of anaesthetic drugs on the processing of semantic stimuli could yield insights into how brain functions change in the transition from wakefulness to unresponsiveness. Here, we explored the N400 event-related potential during dexmedetomidine- and propofol-induced unresponsiveness. METHODS: Forty-seven healthy subjects were randomised to receive either dexmedetomidine (n=23) or propofol (n=24) in this open-label parallel-group study. Loss of responsiveness was achieved by stepwise increments of pseudo-steady-state plasma concentrations, and presumed loss of consciousness was induced using 1.5 times the concentration required for loss of responsiveness. Pre-recorded spoken sentences ending either with an expected (congruous) or an unexpected (incongruous) word were presented during unresponsiveness. The resulting electroencephalogram data were analysed for the presence of the N400 component, and for the N400 effect defined as the difference between the N400 components elicited by congruous and incongruous stimuli, in the time window 300-600 ms post-stimulus. Recognition of the presented stimuli was tested after recovery of responsiveness. RESULTS: The N400 effect was not observed during dexmedetomidine- or propofol-induced unresponsiveness. The N400 component, however, persisted during dexmedetomidine administration. The N400 component elicited by congruous stimuli during unresponsiveness in the dexmedetomidine group resembled the large component evoked by incongruous stimuli at the awake baseline. After recovery, no recognition of the stimuli heard during unresponsiveness occurred. CONCLUSIONS: Dexmedetomidine and propofol disrupt the discrimination of congruous and incongruous spoken sentences, and recognition memory at loss of responsiveness. However, the processing of words is partially preserved during dexmedetomidine-induced unresponsiveness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study.

INTRODUCTION: The highly selective α2-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMRglu) with three commonly used anaesthetic drugs at equi-sedative doses. METHODS: One hundred and sixty healthy male subjects were randomised to EC50 for verbal command of dexmedetomidine (1.5 ng ml-1; n=40), propofol (1.7 µg ml-1; n=40), sevoflurane (0.9% end-tidal; n=40) or S-ketamine (0.75 µg ml-1; n=20) or placebo (n=20). Anaesthetics were administered using target-controlled infusion or vapouriser with end-tidal monitoring. 18F-labelled fluorodeoxyglucose was administered 20 min after commencement of anaesthetic administration, and high-resolution positron emission tomography with arterial blood activity samples was used to quantify absolute CMRglu for whole brain and 15 brain regions. RESULTS: At the time of [F18]fluorodeoxyglucose injection, 55% of dexmedetomidine, 45% of propofol, 85% of sevoflurane, 45% of S-ketamine, and 0% of placebo subjects were unresponsive. Whole brain CMRglu was 63%, 71%, 71%, and 96% of placebo in the dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively (P<0.001 between the groups). The lowest CMRglu was observed in nearly all brain regions with dexmedetomidine (P<0.05 compared with all other groups). With S-ketamine, CMRglu did not differ from placebo. CONCLUSIONS: At equi-sedative doses in humans, potency in reducing CMRglu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia. CLINICAL TRIAL REGISTRATION: NCT02624401.

White matter damage of the brain is associated with poor outcome in vascular surgery patients with claudication: a pilot study.

OBJECTIVE: Peripheral arterial disease (PAD) is a systemic atherosclerotic syndrome with high post-operative morbidity and mortality. Fractional anisotropy (FA), an index measured by magnetic resonance diffusion tensor imaging (DTI), has been shown to be exceedingly sensitive to microstructural damage in brain white matter tracts. It is hypothesized that pre-operative white matter damage is more extensive in PAD patients scheduled for vascular surgery who experience an adverse long-term outcome. METHODS: Preoperative FA values were obtained in 24 consecutive PAD patients (age >40 years) scheduled for elective infrainguinal revascularization surgery and in 15 healthy age matched participants. All patients had their clinical history taken and underwent physical examination and laboratory tests. After surgery, patients were followed for a median of 52 months (range 40-63) and major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. RESULTS: There were no statistically significant differences in baseline demographic or clinical variables between the MACCE group and the non-MACCE group. During follow up, eight PAD patients suffered a MACCE and they had lower FA values than patients without MACCE or healthy controls (mean ± SD 0.370 ± 0.017 vs. 0.392 ± 0.023 vs. 0.412 ± 0.018, p = .036 and p = .00007, respectively). Voxelwise analysis of the FA data revealed diffuse spatial distribution of white matter damage in PAD patients. There was no statistically significant association between the FA values and other clinical variables. CONCLUSION: Microstructural white matter damage was associated with poor outcome in PAD patients with claudication requiring surgical revascularization, and its extent may have clinical value in risk stratification.

Cardiomyocyte apoptosis after cardioplegic ischemia: comparison to unprotected regional ischemia-reperfusion.

BACKGROUND: Cardiomyocyte apoptosis might contribute to left ventricular (LV) dysfunction following cardiac surgery. Magnetic resonance imaging is considered the most accurate method of determining LV function. We compared apoptosis (by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, TUNEL, staining and detection of caspase 3 activation) and LV function after regional ischemia-reperfusion (I-R) and global cardioplegic ischemia. METHODS: Pigs were randomized to undergo regional myocardial I-R for 20 + 20 min, global myocardial ischemia with cardiopulmonary bypass (CPB) for 40 min or CPB without ischemia (control), followed by 274 min of reperfusion. RESULTS: Compared with the control group, the number of TUNEL-positive cardiomyocytes was higher in the global ischemia group with CPB (0.024 ± 0.014%; p = 0.02) and further increased in areas of unprotected regional I-R (0.444 ± 0.562%; p = 0.003, vs. control). Myocytes with active caspase 3 were detected after global and regional ischemia. The global ejection fraction did not differ between CPB and regional I-R groups. CONCLUSIONS: The use of cardioplegia and CPB efficiently protects the heart from global I-R-induced cardiomyocyte apoptosis during open heart surgery.

Analysis of heart rate variability dynamics during propofol and dexmedetomidine anesthesia.

It has been observed that heart rate variability (HRV) diminishes during anesthesia, but the exact mechanisms causing it are not completely understood. The aim of this paper was to study the dynamics of HRV during low dose propofol (N=9) and dexmedetomidine (N=8) anesthesia by using state-of-the-art time-varying methods, and thereby ultimately try to improve the safety of anesthesia. The time-varying spectrum is estimated by using a Kalman smoother approach. The results show that there is an overall increase in HRV and decrease in heart rate prior to loss of consciousness. For dexmedetomidine these changes are more considerable than for propofol. For dexmedetomidine the variability also seems to start decreasing right after loss of consciousness, whereas for propofol HRV continues increasing.

The effects of surgical levels of sevoflurane and propofol anaesthesia on heart rate variability.

BACKGROUND AND OBJECTIVE: We compared heart rate dynamics during surgical levels of propofol and sevoflurane anaesthesia in a highly standardized setting. METHODS: We recorded electrocardiography from 24 anaesthetized healthy male subjects. In the first parallel part of the study, the subjects were anaesthetized either with sevoflurane (n = 8) or propofol (n = 8) targeted to match 1.0, 1.5 and 2.0 minimal alveolar concentration/effective concentration 50. In the second part, a separate group (n = 8) underwent four different anaesthetic regimens targeted to bispectral index 40: sevoflurane alone, sevoflurane + 70% nitrous oxide, propofol alone and propofol + 70% nitrous oxide. The electrocardiography data were analysed using conventional time and frequency domain methods, and the approximate entropy method, which estimates the complexity of the data. RESULTS: The induction of anaesthesia was followed by an overall reduction of heart rate variability, evident in all frequency bands in the spectral analysis, and also in the time domain measures. Approximate entropy decreased at 1 effective concentration 50 with propofol and at 2 minimal alveolar concentration with sevoflurane. In the second part of the study, the time domain variables and high-frequency spectral power were all similarly reduced by sevoflurane and propofol anaesthesia, with and without nitrous oxide. Approximate entropy tended to decrease during propofol anaesthesia. CONCLUSIONS: Hypnotic levels of sevoflurane and propofol anaesthesia suppressed the heart rate variability measured using conventional analysis methods. Deeper surgical levels of anaesthesia also reduce the complexity of heart rate variability.

Instantaneous beat-to-beat variability reflects vagal tone during hyperbaric hyperoxia.

Hyperbaric hyperoxia affects heart rate variability (HRV) by increasing parasympathetic activity. The purpose of this study was to evaluate the applicability of instantaneous beat-to-beat variability (SD1 of Poincaré plot analysis) in detecting changes in vagal tone and to evaluate possible changes in the fractality of heart rate dynamics (alpha1 of detrended fluctuation analysis) during hyperbaric hyperoxia. Continuous three-lead ECG recordings were taken in ten divers who were treated at 2.5 ATA with air (PO2 47 kPa) and oxygen (PO2 235 kPa) for 60 min. Power spectral analysis, Poincaré plot analysis and alpha1 were analyzed before compression, after 30 min and after 55 min at 2.5 ATA. Correlations between the variables were calculated after 55 min exposure. SD1 and high frequency (HF) power increased significantly but alpha1 decreased during hyperbaric hyperoxia (PO2 235 kPa). HF power and SD1 also correlated significantly. However, HF power and SD1 correlated inversely with alpha1. During hyperbaric hyperoxia, SD1 reflects vagal activity and can be used instead of HF power, if stationary conditions cannot be achieved. The decreasing alpha1 indicates more random heart rate dynamics during hyperbaric hyperoxia.

Epidural infusion of bupivacaine and fentanyl reduces perioperative myocardial ischaemia in elderly patients with hip fracture--a randomized controlled trial.

BACKGROUND: Perioperative myocardial ischaemia is an important risk factor for cardiac morbidity and mortality after noncardiac surgery. The impact of analgesic management on the incidence and severity of cardiac ischemia was studied in 77 elderly patients undergoing surgical treatment of traumatic hip fracture. METHODS: After hospital admission and written consent, patients were randomised to conventional analgesic regimen (intramuscular oxycodone, OPI group) or continuous epidural infusion of bupivacaine/fentanyl (EPI group). The analgesic regimens were started preoperatively. Patients were operated under spinal anaesthesia and the treatments were continued three days postoperatively. ECG was continuously recorded. ST segment depression of > or = 0.1 mV or elevation of > or = 0.2 mV lasting > or = 1 min were considered as ischaemic episodes. Nocturnal arterial oxygen saturation (SaO2) was recorded perioperatively, and subjective pain was assessed every morning using a visual analogue scale (VAS). RESULTS: Fifty-nine (OPI 30, EPI 29) patients were evaluable for efficacy. Thirteen patients (43%) in the OPI and 12 patients (41%) in the EPI group had ischaemic episodes (NS). However, significantly more patients in the OPI group had ischaemic episodes during the surgery (8 vs. 0 in the EPI group, P=0.005). The median (quartal deviation) total ischaemic burden (i.e. integral of ST-change vs. time) in patients with ischaemic episodes was ten times larger in the OPI group (340 [342] mm x min) compared with the EPI group (30 [36] mm x min) (P=0.002). There were no significant differences between the groups in average heart rates or in heart rates at the start of ischaemic episodes or in maximal heart rates during the attacks. Average nocturnal SaO2 was similar in the two groups and there were no differences in the number of hypoxaemic (SaO2<90%) episodes. Preoperatively there were no differences in subjective pain, but postoperative and average perioperative VAS scores for pain were almost 40% lower in the EPI group (P=0.006). Perioperative myocardial infarctions were not detected. CONCLUSIONS: Continuous epidural bupivacaine/fentanyl analgesic regimen, started preoperatively, reduces the amount of myocardial ischaemia in elderly patients with hip fracture.

Correlation properties and complexity of perioperative RR-interval dynamics in coronary artery bypass surgery patients.

BACKGROUND: Dynamic measures of heart rate variability (HRV) may uncover abnormalities that are not easily detectable with traditional time and frequency domain measures. The purpose of this study was to characterize changes in RR-interval dynamics in the immediate postoperative phase of coronary artery bypass graft (CABG) surgery using traditional and selected newer dynamic measures of HRV. METHODS: Continuous 24-h electrocardiograph recordings were performed in 40 elective CABG surgery patients up to 72 h postoperatively. In one half of the patients, Holter recordings were initiated 12-40 h before the surgery. Time and frequency domain measures of HRV were assessed. The dynamic measures included a quantitative and visual analysis of Poincaré plots, measurement of short- and intermediate-term fractal-like scaling exponents (alpha1 and alpha2), the slope (beta) of the power-law regression line of RR-interval dynamics, and approximate entropy. RESULTS: The SD of RR intervals (P < 0.001) and the ultra-low-, very-low-, low-, and high-frequency power (P < 0.01, P < 0.001, P < 0.001, P < 0.01, respectively) measures in the first postoperative 24 h decreased from the preoperative values. Analysis of Poincaré plots revealed increased randomness in beat-to-beat heart rate behavior demonstrated by an increase in the ratio between short-term and long-term HRV (P < 0.001) after CABG. Average scaling exponent alpha1 of the 3 postoperative days decreased significantly after CABG (from 1.22 +/- 0.15 to 0.85 +/- 0.20, P < 0.001), indicating increased randomness of short-term heart rate dynamics (i.e., loss of fractal-like heart rate dynamics). Reduced scaling exponent alpha1 of the first postoperative 24 h was the best HRV measure in differentiating between the patients that had normal ( 48 h, n = 7) intensive care unit stay (0.85 +/- 0.17 vs. 0.68 +/- 0.18; P < 0.05). In stepwise multivariate logistic regression analysis including typical clinical predictors, alpha1 was the most significant independent predictor (P < 0.05) of long intensive care unit stay. None of the preoperative HRV measures were able to predict prolonged intensive care unit stays. CONCLUSIONS: In the selected group of patients studied, a decrease in overall HRV was associated with altered nonlinear heart rate dynamics after CABG surgery. Current results suggest that a more random short-term heart rate behavior may be associated with a complicated clinical course. Analysis of fractal-like dynamics of heart rate may provide new perspectives in detecting abnormal cardiovascular function after CABG.

Difficult airway in a patient with Marshall-Smith syndrome.

Marshall-Smith syndrome is a rare clinical disorder characterized by accelerated bone maturation, dysmorphic facial features, airway abnormalities and death in early infancy because of respiratory complications. Although patients with Marshall-Smith syndrome have several features with potential anaesthetic problems, previous reports about anaesthetic management of these patients do not exist. We present a case, in which severe hypoxia developed rapidly after routine anaesthesia induction in an eight-month-old male infant with this syndrome. After several unsuccessful attempts the airway was finally secured by blind oral intubation. After 2 weeks, laryngeal anatomy was examined with fibreoptic laryngoscopy which revealed significant laryngomalacia. Laryngoscopy was performed without problems with ketamine anaesthesia and spontaneous breathing. The possibility of a compromised airway should always be borne in mind when anaesthetizing patients with Marshall-Smith syndrome. Anaesthesia maintaining spontaneous breathing is safest for children with this syndrome. If tracheal intubation or muscle relaxation is required, precautions are needed to maintain a patent airway. Muscle relaxants should possibly be avoided before intubation.