Washington University Record, March 20, 2008

https://digitalcommons.wustl.edu/record/2136/thumbnail.jp

Tehohoitopotilaiden neuromonitorointi

In critical illness the risk of neurological insults is high, whether because of the illness itself, or as a treatment complication. As a result, the length of hospital stay and the risk of both further morbidity and mortality are all roughly doubled. One of the major challenges is the inability to monitor a sedated, mechanically ventilated patient’s neurological symptoms during intensive care treatment, due to a lack of reliable methods. The aims of this thesis research were to identify and test potential non-invasive methods, which would be predictive of neurological outcome, showing potential as neuromonitoring methods of critical care patients unable to self-report. As a guiding theme, all tested methods could be applied to actual critical care with relative ease. Patients were included from two groups with a notably high incidence of neurological complications, namely acute liver failure patients with hepatic encephalopathy (I), and aortic surgery patients operated during hypothermic circulatory arrest (II). The first group included 20 patients, and the latter 30 patients. Late mortality and quality of life was assessed for the aortic surgery patients (III), and the postoperative development of certain blood biomarkers (IV). The tested non-invasive neuromonitoring methods included electroencephalogram (EEG) variables from frontal or fronto-temporal abbreviated monitoring, frontal near-infrared spectroscopy, transcranial Doppler ultrasound measurements of the intracranial blood flow, and finally biomarkers. The last included established biomarkers with an association with neurological complications, namely neuron-specific enolase, and protein S100β, and several interesting biomarkers normally associated with tumours and pancreatitis. Of the tested methods, the frontal EEG variables showed greatest promise, but the addition of the temporal channels did not increase sensitivity. Spectral EEG variables were predictive of the stage of hepatic encephalopathy (I), while a novel EEG variable called wavelet subband entropy was predictive of neurological outcome (I). The hemispheric asymmetry of frontal EEG was reasonably predictive of neurological outcome after aortic surgery (II). None of the other tested methods were predictive of outcome (I, II, IV), except protein S100β, which was significantly higher in the poor outcome group 48 to 72 hours after hypothermic circulatory arrest (II). The quality of life of aortic surgery patients was good after 5 to 8 years, and comparable with the general population of chronically ill patients (III). The aim of this explorative research was to identify and test non-invasive neuromonitoring methods, suitable for use in critical care. Based on the results, frontal EEG variables are promising and predict the grade of hepatic encephalopathy and neurological outcome. The other tested methods were not predictive of neurological outcome. The long-term quality of life of aortic surgery patients is very good, despite the high risk for neurological complications.Kriittisissä sairauksissa neurologisen komplikaation riski on suuri, sekä itse kriittisen sairauden että varsinaisen hoidon seurauksena. Haittatapahtuman johdosta sairaalahoidon kesto sekä sairastuvuuden ja kuolleisuuden riskit kaksinkertaistuvat. Yksi suurimmista haasteista on luotettavien menetelmien puute, joilla voitaisiin arvioida mekaanisen hengitystuen varassa olevan ja rauhoittavia lääkkeitä saavan potilaan neurologisia oireita tehohoidon aikana. Tämän väitöskirjatyön tarkoituksena oli tunnistaa ja testata lupaavia ei-kajoavia menetelmiä, jotka ennustaisivat neurologista lopputulosta, ja jotka soveltuisivat kriittisesti sairaan tehohoitopotilaan neuromonitorointiin. Kantavana teemana kaikki testatut menetelmät voitaisiin soveltaa kliiniseen työhön suhteellisen helposti. Potilaita kerättiin kahteen ryhmään, joissa neurologisten komplikaatioiden esiintyvyys on huomattavan suuri. Ensimmäinen ryhmä käsitti akuuttia maksan vajaatoimintaa ja hepaattista enkefalopatiaa sairastavat potilaat (I), toinen hypotermisen verenkierron pysäytyksen aikana rinta-aortan leikkauksen läpikäyvät potilaat (II). Ensimmäiseen ryhmään kuului 20 potilasta, jälkimmäiseen 30 potilasta. Aorttaleikatuilta potilailta arvioitiin myös elämänlaatua sekä myöhäiskuolleisuutta (III), lisäksi tiettyjen biomerkkiaineiden aorttaleikkauksen jälkeistä kehitystä ja soveltuvuutta neuromonitorointiin arvioitiin yhdessä osatyössä (IV). Tutkimuksessa arvioituihin ei-kajoaviin neuromonitorointimenetelmiin lukeutuivat otsa- ja ohimolohkon elektroenkefalografia (EEG), lähi-infrapunaspektroskopia, transkraniaalinen Doppler-ultraäänimittaus sekä verestä mitattavat biomerkkiaineet. Biomerkkiaineet kattoivat sekä vakiintuneita aivovauriota heijastavia merkkiaineita (hermostoperäinen enolaasi, proteiini S100β) että useita mielenkiintoisia merkkiaineita, jotka liittyvät kasvaintauteihin ja haimatulehdukseen. Testatuista menetelmistä otsalohkon EEG muuttujat olivat lupaavia, mutta ohimolohkon EEG lisääminen ei parantanut menetelmien herkkyyttä. EEG spektrimuuttujat ennustivat hepaattisen enkefalopatian astetta (I) luotettavasti, kun taas kokeellinen EEG-muuttuja (aalloke-alitaajuuden entropia) ennusti luotettavasti neurologista lopputulosta akuutin maksan vajaatoimintaa sairastavilla potilailla (I). Otsalohkon aivopuoliskojen EEG-rekisteröinnin hetkellinen epäsymmetria ennusti kohtalaisella tarkkuudella neurologisten päätetapahtumien esiintymisen aorttaleikatuilla potilailla (II). Muut testatut menetelmät eivät ennustaneet neurologista lopputulemaa (I, II, IV), paitsi proteiini S100β, joka oli merkittävästi korkeampi 48–72 tuntia leikkauksen jälkeen niillä potilailla, joiden neurologinen toipuminen oli huono (IV). Aorttaleikattujen potilaiden elämänlaatu oli hyvä 5–8 vuotta leikkauksen jälkeen ja verrattavissa kroonisesti sairaan väestön elämänlaatuun (III). Tämän kartoittavan tutkimuksen tarkoituksena oli tunnistaa ja testata ei-kajoavia neuromonitorointimenetelmiä, jotka soveltuvat tehohoitoon. Tulosten perusteella otsalohkon EEG-muuttujat ennustavat hepaattisen enkefalopatian astetta sekä potilaan neurologista toipumista. Muut testatut menetelmät eivät ennustaneet neurologista toipumista luotettavasti. Aorttaleikattujen potilaiden pitkäaikainen (5–8 vuoden) terveyteen liittyvä elämänlaatu on erittäin hyvä, vaikka leikkaukseen liittyy korkea aivovaurion riski

Advanced Signal Processing and Control in Anaesthesia

This thesis comprises three major stages: classification of depth of anaesthesia (DOA); modelling a typical patient’s behaviour during a surgical procedure; and control of DOAwith simultaneous administration of propofol and remifentanil. Clinical data gathered in theoperating theatre was used in this project. Multiresolution wavelet analysis was used to extract meaningful features from the auditory evoked potentials (AEP). These features were classified into different DOA levels using a fuzzy relational classifier (FRC). The FRC uses fuzzy clustering and fuzzy relational composition. The FRC had a good performance and was able to distinguish between the DOA levels. A hybrid patient model was developed for the induction and maintenance phase of anaesthesia. An adaptive network-based fuzzy inference system was used to adapt Takagi-Sugeno-Kang (TSK) fuzzy models relating systolic arterial pressure (SAP), heart rate (HR), and the wavelet extracted AEP features with the effect concentrations of propofol and remifentanil. The effect of surgical stimuli on SAP and HR, and the analgesic properties of remifentanil were described by Mamdani fuzzy models, constructed with anaesthetist cooperation. The model proved to be adequate, reflecting the effect of drugs and surgical stimuli. A multivariable fuzzy controller was developed for the simultaneous administration of propofol and remifentanil. The controller is based on linguistic rules that interact with three decision tables, one of which represents a fuzzy PI controller. The infusion rates of the two drugs are determined according to the DOA level and surgical stimulus. Remifentanil is titrated according to the required analgesia level and its synergistic interaction with propofol. The controller was able to adequately achieve and maintain the target DOA level, under different conditions. Overall, it was possible to model the interaction between propofol and remifentanil, and to successfully use this model to develop a closed-loop system in anaesthesia

Characterisation of awakening from anaesthesia in infants

There is uncertainty about the doses of anaesthetic drugs required for unconsciousness in infants. It is important to both avoid inadequate doses leading to intraoperative awareness and also excess doses that may harm the developing brain. Depth of anaesthesia monitoring has been developed in adults based upon electroencephalography (EEG). The EEG of infants is different and few data are available. Heart rate variability (HRV) using the ECG is another non-invasive tool that could be used in infants. The hypothesis of this thesis is that EEG and HRV could help predict or warn of awakening after anaesthesia. Awakening was defined by a panel of experts as at least 2 of crying, coughing, vigorous limb movements, eyes open or looking around. A suitable clinical model of awakening from anaesthesia was determined in a series of pilot studies. Intubated infants anaesthetised with sevoflurane were studied after surgery. Tickling the foot proved a reliable stimulus to cause awakening. EEG and HRV were monitored at the end of surgery during emergence. Events and behaviour were videoed and characteristics of EEG and HRV were identified. After awakening began EMG and other interference made signals difficult to interpret. In all infants there was negligible EEG power in frequencies higher than 20Hz and most power was in frequencies less than 5Hz. Infants older than 52 weeks post menstrual age (PMA) had an oscillatory characteristic within the 5 to 20 Hz range during anaesthesia that reduced in power appreciably as sevoflurane levels decreased; power in 5-20 Hz reduced to less than 100 μV2 before awakening began which may provide a potential warning of awakening. Infants less than 52 weeks PMA had low EEG power in 5-20 Hz throughout. EEG power in this frequency band during anaesthesia increases with age. HRV was low during anaesthesia but increased before awakening began. HRV low frequency power increased in bursts as anaesthesia levels decreased. A case report demonstrated the potential value of P5-20Hz and LF HRV band power in the development of intraoperative depth of anaesthesia monitoring in infants older than 52 weeks PMA

Acute lung injury in paediatric intensive care: course and outcome

Introduction: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) carry a high morbidity and mortality (10-90%). ALI is characterised by non-cardiogenic pulmonary oedema and refractory hypoxaemia of multifactorial aetiology [1]. There is limited data about outcome particularly in children. Methods This retrospective cohort study of 85 randomly selected patients with respiratory failure recruited from a prospectively collected database represents 7.1% of 1187 admissions. They include those treated with High Frequency Oscillation Ventilation (HFOV). The patients were admitted between 1 November 1998 and 31 October 2000. Results: Of the 85, 49 developed acute lung injury and 47 had ARDS. There were 26 males and 23 females with a median age and weight of 7.7 months (range 1 day-12.8 years) and 8 kg (range 0.8-40 kg). There were 7 deaths giving a crude mortality of 14.3%, all of which fulfilled the Consensus I [1] criteria for ARDS. Pulmonary occlusion pressures were not routinely measured. The A-a gradient and PaO2/FiO2 ratio (median + [95% CI]) were 37.46 [31.82-43.1] kPa and 19.12 [15.26-22.98] kPa respectively. The non-survivors had a significantly lower PaO2/FiO2 ratio (13 [6.07-19.93] kPa) compared to survivors (23.85 [19.57-28.13] kPa) (P = 0.03) and had a higher A-a gradient (51.05 [35.68-66.42] kPa) compared to survivors (36.07 [30.2-41.94]) kPa though not significant (P = 0.06). Twenty-nine patients (59.2%) were oscillated (Sensormedics 3100A) including all 7 non-survivors. There was no difference in ventilation requirements for CMV prior to oscillation. Seventeen of the 49 (34.7%) were treated with Nitric Oxide including 5 out of 7 non-survivors (71.4%). The median (95% CI) number of failed organs was 3 (1.96-4.04) for non-survivors compared to 1 (0.62-1.62) for survivors (P = 0.03). There were 27 patients with isolated respiratory failure all of whom survived. Six (85.7%) of the non-survivors also required cardiovascular support.Conclusion: A crude mortality of 14.3% compares favourably to published data. The A-a gradient and PaO2/FiO2 ratio may be of help in morbidity scoring in paediatric ARDS. Use of Nitric Oxide and HFOV is associated with increased mortality, which probably relates to the severity of disease. Multiple organ failure particularly respiratory and cardiac disease is associated with increased mortality. ARDS with isolated respiratory failure carries a good prognosis in children

Observations on the Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clinical Studies on Healthy Volunteers and Intensive Care Patients

Patients treated in intensive care units require sedation and analgesia. However, sedative drugs also have potential adverse effects, and there is no single ideal sedativeanalgesic drug for these patients. Dexmedetomidine is an apha2-adrenoceptor agonist licenced for sedation of intensive care patients and patients undergoing surgery and other invasive procedures. Several routes of parenteral administration (intravenous, intramuscular, subcutaneous and intranasal) have been utilized. In the present series of studies, the pharmacokinetics and pharmacodynamics of intranasally administered dexmedetomidine as well as the gastrointestinal effects of intravenous dexmedetomidine were determined in healthy volunteers. Pharmacokinetics of dexmedetomidine during long lasting, high-dose infusions were characterized in intensive care patients. The bioavailability of intranasal dexmedetomidine was relatively good (65%), but interindividual variation was large. Dexmedetomidine significantly inhibited gastric emptying and gastrointestinal transit. In intensive care patients, the elimination half-life of dexmedetomidine was somewhat longer than reported for infusions of shorter duration and in less ill patients or healthy volunteers. Dexmedetomidine appeared to have linear pharmacokinetics up to the studied dose rate of 2.5 μg/kg/h. Dexmedetomidine clearance was decreasing with age and its volume of distribution was increased in hypoalbuminaemic patients, resulting in a longer elimination half-life and context-sensitive half-time. Intranasally administered dexmedetomidine was efficacious and well tolerated, making it appropriate for clinical situations requiring light sedation. The clinical significance of the gastrointestinal inhibitory effects of dexmedetomidine should be further evaluated in intensive care patients. The possibility of potentially altered potency and effect duration should be taken into account when administering dexmedetomidine to elderly or hypoalbuminaemic patients.Siirretty Doriast

Brain–Computer Interface (BCI) Applications in Mapping of Epileptic Brain Networks Based on Intracranial-EEG: An Update

The main applications of the Brain–Computer Interface (BCI) have been in the domain of rehabilitation, control of prosthetics, and in neuro-feedback. Only a few clinical applications presently exist for the management of drug-resistant epilepsy. Epilepsy surgery can be a life-changing procedure in the subset of millions of patients who are medically intractable. Recording of seizures and localization of the Seizure Onset Zone (SOZ) in the subgroup of “surgical” patients, who require intracranial-EEG (icEEG) evaluations, remain to date the best available surrogate marker of the epileptogenic tissue. icEEG presents certain risks and challenges making it a frontier that will benefit from optimization. Despite the presentation of several novel biomarkers for the localization of epileptic brain regions (HFOs-spikes vs. Spikes for instance), integration of most in practices is not at the prime time as it requires a degree of knowledge about signal and computation. The clinical care remains inspired by the original practices of recording the seizures and expert visual analysis of rhythms at onset. It is becoming increasingly evident, however, that there is more to infer from the large amount of EEG data sampled at rates in the order of less than 1 ms and collected over several days of invasive EEG recordings than commonly done in practice. This opens the door for interesting areas at the intersection of neuroscience, computation, engineering and clinical care. Brain–Computer interface (BCI) has the potential of enabling the processing of a large amount of data in a short period of time and providing insights that are not possible otherwise by human expert readers. Our practices suggest that implementation of BCI and Real-Time processing of EEG data is possible and suitable for most standard clinical applications, in fact, often the performance is comparable to a highly qualified human readers with the advantage of producing the results in real-time reliably and tirelessly. This is of utmost importance in specific environments such as in the operating room (OR) among other applications. In this review, we will present the readers with potential targets for BCI in caring for patients with surgical epilepsy