Out-of-hospital cardiac arrests in nursing homes and primary care facilities in Pirkanmaa, Finland.

BACKGROUND: Dispatching Emergency Medical Services to treat patients with deteriorating health in nursing homes and primary care facilities is common in Finland. We examined the cardiac arrest patients to describe this phenomenon. We had a special interest in patients for whom cardiopulmonary resuscitation was considered futile. METHODS: We conducted an observational study between 1 June 2013 and 31 May 2014 in the Pirkanmaa area. We included cases in which Emergency Medical Services participated in the treatment of cardiac arrest patients in nursing homes and primary care facilities. RESULTS: Emergency Medical Services attended to a total of 355 cardiac arrest patients, and 65 patients (18%) met the inclusion criteria. The included patients were generally older than 65 years, but otherwise heterogeneous. Nineteen patients (29%) had a valid do-not-attempt-resuscitation order, but paramedics were not informed about it in 10 (53%) of those cases. Eight (12%) of the 65 patients survived to hospital admission and 3 (5%) survived to hospital discharge with a neurologically favourable outcome. Two patients were alive 90 days after the cardiac arrest; both were younger than 70 years of age and had ventricular fibrillation as primary rhythm. There were no survivors in nursing homes. CONCLUSIONS: The do-not-attempt-resuscitation orders were often unavailable during a cardiopulmonary resuscitation attempt. Although resuscitation attempts were futile for patients in nursing homes, some patients in primary care facilities demonstrated a favourable outcome after cardiac arrest. Emergency Medical Services seem to be able to recognise potential survivors and focus resources on their treatment.

Assessment of futility in out-of-hospital cardiac arrest.

BACKGROUND: Our aim was to evaluate the impact of futile resuscitation attempts to the outcome calculations of attempted resuscitation in out-of-hospital cardiac arrest (OHCA). Defined as partial resuscitations, we focused on a subgroup of patients in whom cardiopulmonary resuscitation (CPR) was initiated, but further efforts were soon abandoned due to evidence of futility. METHODS: We conducted this study using the Utstein template during a 12-month study period. We compared the event characteristics between full and partial resuscitation attempts and determined the incidence, survival and neurological outcome. RESULTS: Emergency Medical Services (EMS) attended a total of 314 OHCA cases. In 34 cases, resuscitation was not attempted due to futility. Seventy-four cases were partial resuscitation attempts where resuscitation was soon discontinued due to dismal prognostic factors. Partial attempts were associated with an unwitnessed OHCA, prolonged downtime, end-stage malignant disease, multiple trauma, asystole or pulseless electrical activity as the initial rhythm, and a first responding unit being the first unit on the scene (P < 0.05, respectively). The calculation of survival to hospital discharge rate was 14% and increased 5% when partial resuscitation attempts were excluded from the analysis. Seventy-four percentage had a Cerebral Performance Category 1-2 at hospital discharge. Shockable initial rhythm, public location and bystander CPR had a positive impact on survival. CONCLUSIONS: Resuscitative efforts were considered futile in 11% of cases and resuscitation was discontinued due to evidence of futility in additional 24% cases based on additional information. Terminating resuscitation should be identified as a separate subgroup of OHCA cases to better reflect the outcome.

Thermal suit in preventing unintentional intraoperative hypothermia during general anaesthesia: a randomized controlled trial.

BACKGROUND: Unintentional perioperative hypothermia causes serious adverse effects to surgical patients. Thermal suit (T-Balance® ) is an option for passive warming perioperatively. We hypothesized that the thermal suit will not maintain normothermia more efficiently than conventional cotton clothes when also other preventive procedures against unintentional hypothermia are used. METHODS: One hundred patients were recruited to this prospective, randomized trial. They were allocated to the Thermal Suit group or a Control group wearing conventional hospital cotton clothes. All patients received our institution's standard treatment against unintentional hypothermia including a warming mattress, a forced-air upper body warming blanket and a warming device for intravenous fluids. Eardrum temperature was measured pre-operatively. In the operating room and post-anaesthesia care unit temperatures were measured from four locations: oesophagus, left axilla, dorsal surface of the left middle finger and dorsum of the left foot. The primary outcome measure was temperature change during robotic-assisted laparoscopic radical prostatectomy. RESULTS: The temperatures of 96 patients were analysed. There was no difference in mean core temperatures, axillary temperatures or skin temperatures on the finger between the groups. Only foot dorsum temperatures were significantly lower in the Thermal Suit group. Intraoperative temperature changes were similar in both groups. In the post-anaesthesia care unit temperature changes were minimal and they did not differ between the groups. CONCLUSION: Provided that standard preventive procedures in maintaining normothermia are effective the thermal suit does not provide any additional benefit over conventional cotton clothes during robotic-assisted laparoscopic radical prostatectomy.

Surgical pleth index in children younger than 24 months of age: a randomized double-blinded trial.

BACKGROUND: The surgical pleth index (SPI) is a measurement of intraoperative nociception. Evidence of its usability in children is limited. Given that the autonomic nervous system is still developing during the first years of life, the performance of the SPI on small children cannot be concluded from studies carried out in older age groups. METHODS: Thirty children aged <2 yr, planned for elective open inguinal hernia repair or open correction of undescended testicle, were recruited. The children were randomized into two groups; the saline group received ultrasound-guided saline injection in the ilioinguinal and iliohypogastric nerve region before surgery and ropivacaine after surgery, whereas the block group received the injections in the opposite order. The SPI was recorded blinded and was analysed at the time points of intubation, incision, and when signs of inadequate anti-nociception were observed. RESULTS: There was a significant increase in the SPI after intubation (P=0.019) and after incision in the saline group (P=0.048), but not at the time of surgical incision in the block group (P=0.177). An increase in the SPI was also seen at times of clinically apparent inadequate anti-nociception (P=0.008). The between-patient variability of the SPI was large. CONCLUSIONS: The SPI is reactive in small children after intubation and after surgical stimuli, but the reactivity of the SPI is rather small, and there is marked inter-individual variability in reactions. The reactivity is blunted by the use of ilioinguinal and iliohypogastric nerve block. CLINICAL TRIAL REGISTRATION: NCT02045810.

Comparison of Bispectral Index and Entropy values with electroencephalogram during surgical anaesthesia with sevoflurane.

BACKGROUND: Concomitantly recorded Bispectral Index® (BIS) and Entropy™ values sometimes show discordant trends during general anaesthesia. Previously, no attempt had been made to discover which EEG characteristics cause discrepancies between BIS and Entropy. We compared BIS and Entropy values, and analysed the changes in the raw EEG signal during surgical anaesthesia with sevoflurane. METHODS: In this prospective, open-label study, 65 patients receiving general anaesthesia with sevoflurane were enrolled. BIS, Entropy and multichannel digital EEG were recorded. Concurrent BIS and State Entropy (SE) values were selected. Whenever BIS and SE values showed ≥10-unit disagreement for ≥60 s, the raw EEG signal was analysed both in time and frequency domain. RESULTS: A ≥10-unit disagreement ≥60 s was detected 428 times in 51 patients. These 428 episodes accounted for 5158 (11%) out of 45 918 analysed index pairs. During EEG burst suppression, SE was higher than BIS in 35 out of 49 episodes. During delta-theta dominance, BIS was higher than SE in 141 out of 157 episodes. During alpha or beta activity, SE was higher than BIS in all 49 episodes. During electrocautery, both BIS and SE changed, sometimes in the opposite direction, but returned to baseline values after electrocautery. Electromyography caused index disagreement four times (BIS > SE). CONCLUSIONS: Certain specific EEG patterns, and artifacts, are associated with discrepancies between BIS and SE. Time and frequency domain analyses of the original EEG improve the interpretation of studies involving BIS, Entropy and other EEG-based indices. CLINICAL TRIAL REGISTRATIONCLINICALTRIALSGOVIDENTIFIER: NCT01077674.

Using a simplified pre-hospital 'MET' score to predict in-hospital care and outcomes.

BACKGROUND: Medical emergency team (MET) activation criteria serve as a predictor of serious adverse events on hospital wards and in the emergency department (ED). We aimed to determine whether in-hospital MET activation criteria would be useful in identifying patients at risk in pre-hospital care. METHODS: The data were collected retrospectively from 610 adult patients treated by physician-staffed helicopter emergency medical services. Pre-hospital vital signs were compared with MET activation criteria and scored accordingly to receive a simplified pre-hospital 'MET' score. The primary outcome measure was hospital mortality. The secondary outcome measures were admission to intensive care unit and the length of ED stay, intensive care unit (ICU) stay and hospital stay. The simplified pre-hospital 'MET' score was also compared with Emergency Severity Index (ESI) used as a triage tool in ED. RESULTS: Higher simplified pre-hospital 'MET' scores were associated with hospital mortality (P<0.001), the need for ICU treatment (P<0.001) and a more urgent ESI class in the ED (P<0.001). Higher simplified pre-hospital 'MET' scores were associated with shorter stay in the ED (P<0.001), longer stay in the ICU (P<0.001) and longer hospital stay (P<0.001). A simplified pre-hospital 'MET' score was an independent predictor for hospital mortality (odds ratio 2.42, confidence interval 1.84 3.18, P<0.001), regardless of age or patient's previous overall physical health classified by American Society of Anesthesiologists physical status classification system. CONCLUSION: A simplified pre-hospital 'MET' score is a predictor for patient outcome and could serve as a risk assessment tool for the health care provider on-scene.

One-year outcome after prehospital intubation.

BACKGROUND: The aim of physician staffed emergency medical services (EMS) is to supplement other EMS units in the care of prehospital patients. The need for advanced airway management in critical prehospital patients can be considered as one indicator of the severity of the patient's condition. Our primary aim was to study the long-term outcome of critically ill patients (excluding cardiac arrest) who were intubated by EMS physicians in the prehospital setting. METHODS: Data of 845 patients, whose airways were secured by the EMS physicians during a 5-year (2007-2011) period, were retrospectively evaluated. After exclusions, the outcome of 483 patients (8.9% of all patients treated by EMS) was studied. Evaluation was based on hospital patient records 1 year after the incident. For assessment of neurological outcome, a modified Glasgow Outcome Score (GOS) was used. Time and cause of death were recorded. RESULTS: 55.3% of the study patients had a good neurological recovery (GOS 4-5) with independent life 1 year after the event. The overall 1-year mortality (GOS 1) was 35.0%. Poor neurological outcome (GOS 2-3) was found in 9.7% of the patients. Patients with intoxication or convulsions survived best, while those with suspected intracranial pathology had the worst prognosis. Of all survivors, 85% recovered well. CONCLUSION: The majority of the study patients had a favourable neurological recovery with independent life at 1 year after the incident. More than 80% of all deaths occurred within 30 days of the incident.

The effects of propofol vs. sevoflurane on post-operative pain and need of opioid.

BACKGROUND: Post-operative pain continues to be a major problem. Some previous studies have suggested that patients anaesthetised with propofol have less pain after surgery than those anesthetised with volatiles. However, the results of previous studies are conflicting. We designed a large-scale trial to study, whether propofol or sevoflurane is more analgesic than the other. We measured opioid consumption in the acute post-operative phase after laparoscopic hysterectomy. METHODS: In a randomised, prospective single-blind trial, we evaluated the consumption of oxycodone and pain intensity in 148 women for 20 h after laparoscopic hysterectomy under propofol or sevoflurane anaesthesia. The primary endpoint was the cumulative amount of oxycodone consumed. Secondary endpoints were pain scores [numeric rating scale (NRS)] at rest and with coughing, severity of nausea and state of sedation. RESULTS: The consumption of oxycodone and the NRS pain scores did not differ between the groups. The oxycodone consumed during first 20 h after surgery was 42.5 (95% confidence interval 38.3-46.6) mg and 42.8 (37.3-48.4) mg in propofol- and sevoflurane-anaesthetised patients, respectively (P = 0.919). NRS scores for nausea were higher in the patients receiving sevoflurane during the first 60 min in the post-anaesthesia care unit, leading to higher consumption of rescue antiemetics. Sedation scores differed in favour of sevoflurane only at 4 h time point after anaesthesia. Patient characteristics did not differ. CONCLUSIONS: In this study, comparing sevoflurane with propofol for maintenance of general anaesthesia, the choice of anaesthetic had no effect on the requirement of oxycodone or intensity of pain after surgery.

Can electromyographic arousal be detected visually on the Datex-Ohmeda S/5™ anesthesia monitor?

BACKGROUND: Electroencephalogram (EEG)-based depth of anaesthesia monitoring is susceptible to contaminating electromyographic (EMG) activity. Many authorities have suggested that anaesthesiologists using these monitors should interpret the raw EEG waveform seen on the anaesthesia monitor. METHODS: In 34 patients anaesthetized with propofol using two doses of rocuronium (0.6 and 1.2 mg/kg), we studied whether the EMG arousal can be detected visually on the anaesthesia monitor. The Bispectral Index (BIS) and Entropy biosignals on the monitor were recorded with a video camera, and the one-channel EEG recorded by the Entropy strip was collected on a laptop computer. The recordings and the one-channel EEG were analyzed offline by two experts (anaesthesiologist and neurophysiologist), both with a long experience on anaesthesia-related EEG. RESULTS: EMG arousal existed in 14/34 and 13/33 patients in the BIS and Entropy biosignals, respectively. The anaesthesiologist detected EMG on the monitor in 7/14 patients with BIS (sensitivity 50%) and in 4/13 patients with Entropy (31%). The clinical neurophysiologist detected EMG in 6/14 (43%) patients with BIS and in 5/13 (38%) with Entropy. The specificity of the EMG analyses was 55 and 65% with BIS, and 85 and 90% with Entropy. EMG arousal was detected in BIS biosignal in 10/17 and 4/17 patients with 0.6 and 1.2 mg/kg doses of rocuronium (P = 0.04). CONCLUSIONS: In contrast to many EEG phenomena, EMG activity cannot be accurately detected visually from the raw EEG on the anaesthesia monitor. Further development in the quality of the anaesthesia monitors is warranted.

Elevated BIS and Entropy values after sugammadex or neostigmine: an electroencephalographic or electromyographic phenomenon?

BACKGROUND: Sugammadex is designed to antagonize neuromuscular blockade (NMB) induced by rocuronium or vecuronium. In clinical practice, we have noticed a rise in the numerical values of bispectral index (BIS) and Entropy, two electroencephalogram (EEG) - based depth of anesthesia monitors, during the reversal of the NMB with sugammadex. The aim of this prospective, randomized, double-blind study was to test this impression and to compare the effects of sugammadex and neostigmine on the BIS and Entropy values during the reversal of the NMB. METHODS: Thirty patients undergoing gynecological operations were studied. Patients were anesthetized with target-controlled infusions of propofol and remifentanil, and rocuronium was used to induce NMB. After operation, during light propofol-remifentanil anesthesia, NMB was antagonized with sugammadex or neostigmine. During the following 5 min, the numerical values of BIS, BIS electromyographic (BIS EMG) and Entropy were recorded on a laptop computer, as well as the biosignal recorded by the Entropy strip. The Entropy biosignal was studied off-line both in time and frequency domain to see if NMB reversal causes changes in EEG. RESULTS: In some patients, administration of sugammadex or neostigmine caused a significant rise in the numerical values of BIS, BIS EMG and Entropy. This phenomenon was most likely caused by increased electromyographic (EMG) activity. The administration of sugammadex or neostigmine appeared to have only minimal effect on EEG. CONCLUSION: The EMG contamination of EEG causes BIS and Entropy values to rise during reversal of rocuronium-induced NMB in light propofol-remifentanil anesthesia.

Explaining Entropy responses after a noxious stimulus, with or without neuromuscular blocking agents, by means of the raw electroencephalographic and electromyographic characteristics.

BACKGROUND: Entropy™, an anaesthetic EEG monitoring method, yields two parameters: State Entropy (SE) and Response Entropy (RE). SE reflects the hypnotic level of the patient. RE covers also the EMG-dominant part of the frequency spectrum, reflecting the upper facial EMG response to noxious stimulation. We studied the EEG, EMG, and Entropy values before and after skin incision, and the effect of rocuronium on Entropy and EMG at skin incision during sevoflurane-nitrous oxide (N2O) anaesthesia. METHODS: Thirty-eight patients were anaesthetized with sevoflurane-N2O or sevoflurane-N2O-rocuronium. The biosignal was stored and analysed off-line to detect EEG patterns, EMG, and artifacts. The signal, its power spectrum, SE, RE, and RE-SE values were analysed before and after skin incision. The EEG arousal was classified as ß (increase in over 8 Hz activity and decrease in under 4 Hz activity with a typical ß pattern) or δ (increase in under 4 Hz activity with the characteristic rhythmic δ pattern and a decrease in over 8 Hz activity). RESULTS: The EEG arousal appeared in 17 of 19 and 15 of 19 patients (NS), and the EMG arousal in 0 of 19 and 13 of 19 patients (P<0.01) with and without rocuronium, respectively. Both ß (n=30) and EMG arousals increased SE and RE. The δ arousal (n=2) decreased both SE and RE. A significant increase in RE-SE values was only seen in patients without rocuronium. CONCLUSIONS: During sevoflurane-N2O anaesthesia, both EEG and EMG arousals were seen. ß and δ arousals had opposite effects on the Entropy values. The EMG arousal was abolished by rocuronium at the train of four level 0/4.

Facial muscle activity, Response Entropy, and State Entropy indices during noxious stimuli in propofol-nitrous oxide or propofol-nitrous oxide-remifentanil anaesthesia without neuromuscular block.

BACKGROUND: Entropy is an anaesthetic EEG monitoring method, calculating two numerical parameters: State Entropy (SE, range 0-91) and Response Entropy (RE, range 0-100). Low Entropy numbers indicate unconsciousness. SE uses the frequency range 0.8-32 Hz, representing predominantly the EEG activity. RE is calculated at 0.8-47 Hz, consisting of both EEG and facial EMG. RE-SE difference (RE-SE) can indicate EMG, reflecting nociception. We studied RE-SE and EMG in patients anaesthetized without neuromuscular blockers. METHODS: Thirty-one women were studied in propofol-nitrous oxide (P) or propofol-nitrous oxide-remifentanil (PR) anaesthesia. Target SE value was 40-60. RE-SE was measured before and after endotracheal intubation, and before and after the commencement of surgery. The spectral content of the signal was analysed off-line. Appearance of EMG on EEG was verified visually. RESULTS: RE, SE, and RE-SE increased during intubation in both groups. Elevated RE was followed by increased SE values in most cases. In these patients, spectral analysis of the signal revealed increased activity starting from low (<20 Hz) frequency area up to the highest measured frequencies. This was associated with appearance of EMG in raw signal. No spectral alterations or EMG were seen in patients with stable Entropy values. CONCLUSIONS: Increased RE is followed by increased SE at nociceptive stimuli in patients not receiving neuromuscular blockers. Owing to their overlapping power spectra, the contribution of EMG and EEG cannot be accurately separated with frequency analysis in the range of 10-40 Hz.

Photoplethysmography and nociception.

Photoplethysmography (PPG), i.e. pulse oximetric wave, is a non-invasive technique that is used in anaesthesia monitoring primarily to monitor blood oxygenation. The PPG waveform resembles that of the arterial blood pressure but instead of pressure it is related to the volume changes in the measurement site and hence contains information related to the peripheral blood circulation, including skin vasomotion, which is controlled by the sympathetic nervous system. Because of this link, skin vasomotor response and PPG amplitude response have been associated with nociception under general anaesthesia. Recently, there has been interest in monitoring nociception during general anaesthesia. In many of the published studies, PPG waveform information has been included. The focus of this topical review is to provide an overview on the information embedded in the PPG waveform especially in the context of the autonomic nervous system and analgesia monitoring.

Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial.

BACKGROUND: Intravenous infusion of ice-cold fluid is considered a feasible method to induce mild therapeutic hypothermia in cardiac arrest survivors. However, only one randomized controlled trial evaluating this treatment exists. Furthermore, the implementation rate of prehospital cooling is low. The aim of this study was to evaluate the efficacy and safety of this method in comparison with conventional therapy with spontaneous cooling often observed in prehospital patients. METHODS: A randomized controlled trial was conducted in a physician-staffed helicopter emergency medical service. After successful initial resuscitation, patients were randomized to receive either +4 degrees C Ringer's solution with a target temperature of 33 degrees C or conventional fluid therapy. As an endpoint, nasopharyngeal temperature was recorded at the time of hospital admission. RESULTS: Out of 44 screened patients, 19 were analysed in the treatment group and 18 in the control group. The two groups were comparable in terms of baseline characteristics. The core temperature was markedly lower in the hypothermia group at the time of hospital admission (34.1+/-0.9 degrees C vs. 35.2+/-0.8 degrees C, P<0.001) after a comparable duration of transportation. Otherwise, there were no significant differences between the groups regarding safety or secondary outcome measures such as neurological outcome and mortality. CONCLUSION: Spontaneous cooling alone is insufficient to induce therapeutic hypothermia before hospital admission. Infusion of ice-cold fluid after return of spontaneous circulation was found to be well tolerated and effective. This method of cooling should be considered as an important first link in the 'cold chain' of prehospital comatose cardiac arrest survivors.

Increase in high frequency EEG activity explains the poor performance of EEG spectral entropy monitor during S-ketamine anesthesia.

OBJECTIVE: To study the effects of S-ketamine on the EEG and to investigate whether spectral entropy of the EEG can be used to assess the depth of hypnosis during S-ketamine anesthesia. METHODS: The effects of sub-anesthetic (159 (21); mean (SD) ng/ml) and anesthetic (1,959 (442) ng/ml) serum concentrations of S-ketamine on state entropy (SE), response entropy (RE) and classical EEG spectral power variables (recorded using the Entropy Module, GE Healthcare, Helsinki, Finland) were studied in 8 healthy males. These EEG data were compared with EEG recordings from 6 matching subjects anesthetized with propofol. RESULTS: The entropy values decreased from the baseline SE 85 (3) and RE 96 (3) to SE 55 (18) and RE 72 (17) during S-ketamine anesthesia but both inter- and intra-individual variation of entropy indices was wide and their specificity to indicate unconsciousness was poor. Propofol induced more pronounced increase in delta power (P<0.02) than S-ketamine, whereas anesthetic S-ketamine induced more high frequency EEG activity in the gamma band (P<0.001). Relative power of 20-70 Hz EEG activity was associated with high SE (P=0.02) and RE (P=0.03) values during S-ketamine anesthesia. CONCLUSIONS: These differences in low and high frequency EEG power bands probably explain why entropy monitor, while adequate for propofol, is not suitable for assessing the depth of S-ketamine anesthesia. SIGNIFICANCE: The entropy monitor is not adequate for monitoring S-ketamine-induced hypnosis.

Propofol anesthesia induces phase synchronization changes in EEG.

OBJECTIVE: Phase coupling between EEG channel pairs in various frequency bands was evaluated during propofol anesthetic induction and recovery periods. METHODS: Twenty-three patients participated in the study. Phase synchronization indices based on the Hilbert transform were investigated on frequency bands 0.05-1 Hz, 1-4 Hz, 4-8 Hz, 8-12 Hz and 12-16 Hz for all pairs of the 9 EEG channels covering midline and frontal areas. A straight line was used to approximate the index values as a function of time and the Sign Test statistics were applied to the slope parameters. RESULTS: Systematic phase synchronization changes were detected. Generally, phase synchronization in the sub-delta band decreased during the induction and increased during the recovery, while the directions were reversed in the alpha band. The changes were dependent on the channel pair. In the delta, theta and beta bands, the changes were aligned more irregularly than in the sub-delta or in the alpha bands. Highly asymmetric behavior between the induction and the recovery periods was also observed in these bands. CONCLUSIONS: Induction and recovery from propofol anesthesia changes the phase synchronization between the EEG channels. The passband and location-specific behavior of these changes reveals the effects of the anesthetic to the different neural mechanisms.

DC-level detection of burst-suppression EEG.

The EEG signal is usually recorded with low time constant analog prefilters to avoid low frequency artefacts. During this kind of recording the frequency components below the cutoff frequency of the analog prefilter (usually below about 1 to 3 Hz) are lost. By visual examination of some experimental recordings taken with a higher time constant, it was noticed that during burst-suppression EEG the DC-level of the signal rises sharply when the burst begins and falls when the burst ends. Thus, a burst actually consists of a mixed frequency discharge on a pulse-like DC-shift. We developed a filter algorithm to estimate the change in the DC-level during bursts as accurately as possible.

Nonlinear interpretation of respiratory sinus arrhythmia in anesthesia.

A non-parametric method is presented for modelling nonlinear dynamic mechanisms of respiratory sinus arrhythmia (RSA) in anesthesia caused by positive pressure ventilation. RR interval sequences are shown with Tsay's linearity test to contain both short-term and long-term nonlinear components, which cannot completely be modelled with optimal linear methods. The nonlinear approach is based on Wiener's theory for broad-band random input signal. The input-output model is formed for tracheal pressure and RR interval sequence. Second-order and third-order nonlinearities in RSA fluctuation are found and demonstrated.

Neurophysiology of anaesthesia.

Methods of clinical neurophysiology are important in studying basic problems of anaesthesia such as the problem of the depth of anaesthesia, Some of the problems of clinical neurophysiology in awake subjects, such as the generators of somatosensory evoked potentials or cognitive evoked potentials, may be resolved by recording during EEG suppression. Finally, the mechanisms by which some anaesthetics produce epileptic phenomena (others or even the same agents may suppress epileptic activity) can only be resolved by EEG and EP recordings in human subjects, and by simultaneous recordings of intracellular and extracellular potentials in animals.