Johanna Wennervirta

Hypothermia-treated cardiac arrest patients with good neurological outcome differ early in quantitative variables of EEG suppression and epileptiform activity.

Objective:To evaluate electroencephalogram-derived quantitative variables after out-of-hospital cardiac arrest. Design:Prospective study. Setting:University hospital intensive care unit. Patients:Thirty comatose adult patients resuscitated from a witnessed out-of-hospital ventricular fibrillation cardiac arrest and treated with induced hypothermia (33°C) for 24 hrs. Interventions:None. Measurements and Main Results:Electroencephalography was registered from the arrival at the intensive care unit until the patient was extubated or transferred to the ward, or 5 days had elapsed from cardiac arrest. Burst-suppression ratio, response entropy, state entropy, and wavelet subband entropy were derived. Serum neuron-specific enolase and protein 100B were measured. The Pulsatility Index of Transcranial Doppler Ultrasonography was used to estimate cerebral blood flow velocity. The Glasgow-Pittsburgh Cerebral Performance Categories was used to assess the neurologic outcome during 6 mos after cardiac arrest. Twenty patients had Cerebral Performance Categories of 1 to 2, one patient had a Cerebral Performance Categories of 3, and nine patients had died (Cerebral Performance Categories of 5). Burst-suppression ratio, response entropy, and state entropy already differed between good (Cerebral Performance Categories 1–2) and poor (Cerebral Performance Categories 3–5) outcome groups (p = .011, p = .011, p = .008) during the first 24 hrs after cardiac arrest. Wavelet subband entropy was higher in the good outcome group between 24 and 48 hrs after cardiac arrest (p = .050). All patients with status epilepticus died, and their wavelet subband entropy values were lower (p = .022). Protein 100B was lower in the good outcome group on arrival at ICU (p = .010). After hypothermia treatment, neuron-specific enolase and protein 100B values were lower (p = .002 for both) in the good outcome group. The Pulsatility Index was also lower in the good outcome group (p = .004). Conclusions:Quantitative electroencephalographic variables may be used to differentiate patients with good neurologic outcomes from those with poor outcomes after out-of-hospital cardiac arrest. The predictive values need to be determined in a larger, separate group of patients.

Surgical stress index as a measure of nociception/antinociception balance during general anesthesia

Background: No validated monitoring method is available for evaluating the nociception/antinociception balance. We assessed the surgical stress index (SSI), computed from finger photoplethysmographic waveform amplitudes and pulse‐to‐pulse intervals, in patients undergoing shoulder surgery under general anesthesia (GA) and interscalene plexus block and in patients with GA only.

Awareness and Recall in Outpatient Anesthesia

We studied the incidence of awareness and explicit recall during general anesthesia in outpatients versus inpatients undergoing surgery. During a 14.5-mo period, we structurally interviewed 1500 outpatients and 2343 inpatients. Among outpatients, there were five cases of awareness and recall (one with clear intraoperative recollections and four with doubtful intraoperative recollections). Of the inpatients, six reported awareness and recall (three with clear and three with doubtful intraoperative recollections). The incidence of clear intraoperative recollections was 0.07% in outpatients and 0.13% in inpatients. The difference in the incidence was not significant. Among outpatients, those with awareness and recall were given smaller doses of sevoflurane than those without awareness and recall (P < 0.05). In conclusion, awareness and recall are rare complications of general anesthesia, and outpatients are not at increased risk for this event compared with inpatients undergoing general anesthesia.

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00879892.

Regular tramadol use does not affect the propofol dose requirement for induction of anaesthesia.

Background and objectives: An increased risk of awareness during general anaesthesia in patients receiving tramadol has been reported. We studied whether tramadol affects the amount of propofol required for induction of anaesthesia. Methods: In this prospective controlled study, we evaluated 46 patients, half of whom used tramadol regularly. Entropy indices, state entropy and response entropy, were used to assess the level of hypnosis. Patients were anaesthetized with a propofol infusion (1 mg kg−1 min−1) until they first became unconscious, and further until they developed a burst suppression pattern in the electroencephalogram. The doses of propofol needed to reach these end‐points were recorded. Results: The amount (median, (range)) of propofol required for loss of consciousness was 2.0 (1.0‐5.5) mg kg−1 and 2.4 (0.9‐8.3) mg kg−1 (P = 0.95) in the tramadol users and controls, respectively. The amount of propofol required for burst suppression was 5.8 (3.9‐12.7) mg kg−1 and 6.4 (2.9‐15.1) mg kg−1 (P = 0.89) in the tramadol users and controls. There was no difference between the groups in state entropy and response entropy during different stages of induction of anaesthesia. Conclusions: Tramadol did not affect the dose of propofol required to achieve loss of consciousness or burst suppression pattern in electroencephalogram during induction of general anaesthesia. However, there was a ninefold inter‐individual variation in propofol dose requirement for loss of consciousness and a fivefold variation for reaching burst suppression. Due to extensive inter‐individual variability, monitoring the level of hypnosis during general anaesthesia using propofol may enhance the correct dosage.

Frontal electroencephalogram variables are associated with the outcome and stage of hepatic encephalopathy in acute liver failure

Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (PK) of 50% spectral edge frequency = 0.23, standard error (SE) = 0.03; PK of delta power = 0.76, SE = 0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (PK = 0.88, SE = 0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval = 0.1‐9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes. Liver Transpl 20:1256–1265, 2014.

Long-term psychosocial outcomes after intraoperative awareness with recall.

BACKGROUND:Posttraumatic stress disorder, a common psychiatric disorder in the general population, may follow a traumatic experience of awareness with recall during general anesthesia. METHODS:We conducted a matched cohort design with 9 subjects after intraoperative awareness with recall during general anesthesia. A psychiatric diagnostic interview and questionnaire were performed on 9 matched controls and 9 subjects, a median of 17.2 years from their documented awareness episode. The subjects and the matched controls completed a battery of questionnaires related to psychosocial well-being, after which they participated in a diagnostic Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders. RESULTS:Patients with awareness did not seem to differ from their matched controls in subsequent psychosocial outcome, psychiatric morbidity, or quality of life. CONCLUSIONS:We found no indication that intraoperative awareness with recall had any deleterious long-term effects on patients’ psychosocial outcome.

Prediction of poor outcome using detector of epileptiform EEG in ICU patients resuscitated after cardiac arrest

Assessing the brain status of patients admitted to intensive care unit (ICU) after out-of-hospital cardiac arrest is challenging. We had earlier found wavelet subband entropy (WSE) to be a useful tool for quantifying the epileptiform content of EEG during anesthesia. In this paper, WSE was applied for EEG of ICU patients to study its prognostic value. During their stay in ICU, EEG was recorded from 20 patients resuscitated after out-of-hospital cardiac arrest. For the analysis, the patients were divided into subgroups of poor outcome (persistent vegetative state, N=4) and good outcome (regain of consciousness, N=16). WSE for each 5-sec segment of EEG was calculated and also the average of WSE for each hour. Also, similar results were calculated for EEG powers in the bands 16-32 Hz and 1-60 Hz to be used as references. The statistical analysis was made by comparing the medians of the distributions of average WSE of each hour between poor and good outcome groups. The median of WSE of poor outcome group was significantly lower than that of good outcome group. The reference indicators did not show significant differences between the groups. The results suggest that WSE can be a valuable prognostic indicator for detecting the patients with poor outcome.

The performance of Bispectral Index in children during equi-MAC halothane vs. sevoflurane anaesthesia

Background and objective: The reliability of the Bispectral Index for evaluating and monitoring the depth of general anaesthesia in children is not as great as for that in adults. Therefore we analysed Bispectral Index performance in children by comparing changes in Bispectral Index values during a standardized and equipotent anaesthetic regimen using either halothane or sevoflurane for the induction and maintenance of general anaesthesia. Special interest was focussed on excitation during induction, and whether it was associated with simultaneous changes in Bispectral Index scores. Methods: Twenty children (3‐15 yr, ASA I‐II) scheduled for general surgery were randomly allocated to either halothane (10 patients) or sevoflurane group (10 patients). Anaesthesia was induced by 3% halothane or 7% sevoflurane, either agent administered with 50% N2O in oxygen for 5 min, the period from the beginning of induction until intubation. Thereafter, anaesthesia was maintained by the respective volatile agent at 1 MAC (minimum alveolar concentration; in addition to 70% N2O in oxygen) and supplemented with remifentanil infusion adjusted to maintain the heart rate and mean arterial pressure to within 20% of the baseline values. Excitation at induction was defined as involuntary muscular movements. Results: Sevoflurane induction produced a more rapid depression in Bispectral Index than halothane, the mean difference being greatest (47 Bispectral Index score) at 105 s. Excitation occurred in three patients during sevoflurane induction, which coincided with increases in Bispectral Index values in two of the three patients. During the maintenance phase at 1 MAC, the Bispectral Index (mean ± SD) was 57±7 for halothane and 47±9 for sevoflurane (P < 0.05). The remifentanil doses did not differ between both groups. Conclusion: In children, halothane anaesthesia was associated with higher Bispectral Index values than sevoflurane when administered at 1 MAC. Large individual variation in Bispectral Index occurred within both groups. Due to these limitations, one should be cautious when interpreting paediatric Bispectral Index data.

Long-Term Survival and Quality of Life After Hypothermic Circulatory Arrest in Aortic Surgery:

Background and Aims: Hypothermic circulatory arrest carries a high risk of mortality and neurological complications. An important part of assessing surgical treatment is the evaluation of long-term survival and postoperative health-related quality of life. Material and Methods: In this prospective study, 30 patients undergoing hypothermic circulatory arrest during surgery of the thoracic aorta, and 31 comparison patients undergoing elective coronary artery surgery without hypothermic circulatory arrest were evaluated for long-term survival and health-related quality of life, using the RAND 36-Item Health Survey questionnaire. The results were compared to national age- and sex-matched reference populations of the chronically ill and healthy adults. Results: After 4.6–8.0 years, available study (88%) and comparison (59%) patients were interviewed. The life expectancy was similar with 4- and 8-year survival of 90%, and 87% for the study group, and 94%, and 94% for the comparison group, respectively (log rank test, p = 0.62). The RAND-36 scores for study and comparison groups were congruent in all dimensions, describing physical, mental, and social domains. The study patients’ health-related quality of life results were similar to the national reference population with chronic illnesses. Conclusion: After hypothermic circulatory arrest, patients undergoing surgery of the thoracic aorta achieve a similar long-term life expectancy and health-related quality of life as do patients undergoing coronary surgery without hypothermic circulatory arrest, and a health-related quality of life similar to the national reference population with chronic illnesses. These results justify operative treatment in this high-risk patient population.