Development of a highly sensitive gas chromatography-mass spectrometry method preceded by solid-phase microextraction for the analysis of propofol in low-volume cerebral microdialysate samples.

To date, the commonly used intravenous anesthetic propofol has been widely studied, and fundamental pharmacodynamic and pharmacokinetic characteristics of the drug are known. However, propofol has not yet been quantified in vivo in the target organ, the human brain. Here, cerebral microdialysis offers the unique opportunity to sample propofol in the living human organism. Therefore, a highly sensitive analytical method for propofol quantitation in small sample volumes of 30 µL, based on direct immersion solid-phase microextraction was developed. Preconcentration was followed by gas chromatographic separation and mass spectrometric detection of the compound. This optimized method provided a linear range between the lower limit of detection (50 ng/L) and 200 µg/L. Matrix-matched calibration was used to compensate recovery issues. A precision of 2.7% relative standard deviation between five consecutive measurements and an interday precision of 6.4% relative standard deviation could be achieved. Furthermore, the permeability of propofol through a cerebral microdialysate system was tested. In summary, the developed method to analyze cerebral microdialysate samples, allows the in vivo quantitation of propofol in the living human brain. Additionally the calculation of extracellular fluid levels is enabled since the recovery of the cerebral microdialysis regarding propofol was determined.

Analgosedation of adult patients with elevated intracranial pressure : Survey of current clinical practice in Austria.

BACKGROUND: Analgesia and sedation are key items in intensive care. Recently published S3 guidelines specifically address treatment of patients with elevated intracranial pressure. METHODS: The Austrian Society of Anesthesiology, Resuscitation and Intensive Care Medicine carried out an online survey of neurointensive care units in Austria in order to evaluate the current state of practice in the areas of analgosedation and delirium management in this high-risk patient group. RESULTS: The response rate was 88%. Induction of anesthesia in patients with elevated intracranial pressure is carried out with propofol/fentanyl/rocuronium in >80% of the intensive care units (ICU), 60% use midazolam, 33.3% use esketamine, 13.3% use barbiturates and 6.7% use etomidate. For maintenance of analgosedation up to 72 h, propofol is used by 80% of the ICUs, followed by remifentanil (46.7%), sufentanil (40%) and fentanyl (6.7%). For long-term sedation, 86.7% of ICUs use midazolam, 73.3% sufentanil and 73.3% esketamine. For sedation periods longer than 7 days, 21.4% of ICUs use propofol. Reasons for discontinuing propofol are signs of rhabdomyolysis (92.9%), green urine, elevated liver enzymes (71.4% each) and elevated triglycerides (57.1%). Muscle relaxants are only used during invasive procedures. Inducing a barbiturate coma is rated as a last resort by 53.3% of respondents. The monitoring methods used are bispectral index (BIS™, 61.5% of ICUs), somatosensory-evoked potentials (SSEP, 53.8%), processed electroencephalography (EEG, 38.5%), intraparenchymal partial pressure of oxygen (pO2, 38.5%) and microdialysis (23.1%). Sedation and analgesia are scored using the Richmond agitation and sedation score (RASS, 86.7%), sedation agitation scale (SAS, 6.7%) or numeric rating scale (NRS, 50%) and behavioral pain scale (BPS, 42.9%), visual analogue scale (VAS), critical care pain observation tool (CCPOT, each 14.3%) and verbal rating scale (VRS, 7.1%). Delirium monitoring is done using the confusion assessment method for intensive care units (CAM-ICU, 46.2%) and intensive care delirium screening checklist (ICDSC, 7.7%). Of the ICUs 46.2% do not carry out delirium monitoring. CONCLUSION: We found good general compliance with the recommendations of the current S3 guidelines. Room for improvement exists in monitoring and the use of scores to detect delirium.

Current practice in neurocritical care of patients with subarachnoid haemorrhage and severe traumatic brain injury : Results of the Austrian Neurosurvey Study.

OBJECTIVES: The task force Neuroanaesthesia of the Austrian Society of Anaesthesiology, Resuscitation and Intensive Care Medicine (ÖGARI) is aiming to develop and provide recommendations in order to improve neurocritical care in Austria. Thus, a survey on neurocritical care concepts in Austria regarding intensive care of subarachnoid haemorrhage (SAH) and severe traumatic brain injury (TBI) was performed to assess the current status. METHODS: An online internet questionnaire comprising 59 items on current concepts of SAH and TBI critical care was sent to 117 anaesthesiology departments. RESULTS: The survey was answered by 30 (25.6 %) of the hospitals, 24 (80 %) of them treating patients with SAH and/or TBI. Data from ten SAH centres reveal that definitive care was achieved within 24 h in all hospitals; a case load >50 per year is noted in 70 % of intensive care units (ICU). In all, 50 % of departments employ written protocols for treatment. Regarding the treatment of TBI patients, 14 answers were received, indicating that 42.9 % of departments provide care for >50 patients per year. Time between arrival and CT scan is <30 min in all hospitals, and 28.6 % of departments rely on written protocols. Only 14.3 % of hospitals report about routine morbidity and mortality rounds. While the neurologic status is assessed at discharge from the ICU, there is no evaluation of 1­year outcome. CONCLUSIONS: Definitive care of SAH and TBI patients is achieved timely in Austria. When compared with SAH, more hospitals with lower case loads take care of TBI patients. Written guidelines and protocols at institutional level are often missing. Since routine morbidity and mortality conferences are sparse, and long-term outcome is not assessed, there is room for improvement.

Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury.

Concentration-time profiles of unbound doripenem were determined by microdialysis in the cerebral interstitium of five patients with acute brain injury. The ratio of the area under the concentration-time curve in brain to that in plasma (AUC(brain)/AUC(plasma)) was 0.17 in one patient and 0.01 in the remaining four patients. Based on the percentage of the dosing interval during which the doripenem concentration exceeded a certain minimum inhibitory concentration (T>MIC), a value of ≥35% of the dosing interval was reached for pathogens with MICs up to 0.05 mg/L. The present data indicate that breakpoints based on concentrations of doripenem in plasma may overestimate antimicrobial activity in brain parenchyma.

Comparison of the EasyTube and endotracheal tube during general anesthesia in fasted adult patients.

STUDY OBJECTIVE: To evaluate the effectiveness, safety, ease of placement, and ventilatory parameters of a new alternate airway device, the EasyTube (EzT; Teleflex Ruesch, Research Triangle Park, NC), in comparison to the endotracheal tube (ETT). DESIGN: Prospective, randomized controlled trial. SETTING: University Hospital. SUBJECTS: 200 adult ASA physical status I and II patients scheduled for surgery. INTERVENTIONS: Patients were randomized to two groups, one to receive ventilation via the EzT (n = 100) or the ETT (n = 100). After preoxygenation and induction with fentanyl and propofol, patients received muscle relaxation. The respective airway device was then inserted and mechanical ventilation was instituted. MEASUREMENTS: Ease of insertion, number of insertion maneuvers, time until airtight seal of the airway was achieved, duration of surgery, leak pressure as well as arterial oxygen saturation (SpO(2)), and end-tidal carbon dioxide (ETCO(2)) data, were recorded. MAIN RESULTS: Mallampati airway class was higher in the EzT group (P < 0.029), while thyromental distance showed no difference between the two groups. Ease of insertion was noted in the EzT group (P < 0.043). Number of insertions was equal in both groups; insertion time was shorter with the EzT (15.5 +/- 3.6 sec vs. 19.3 +/- 4.6 sec; P < 0.0001). Leak pressure and SpO(2) were not significantly different, while ETCO(2) was lower with the ETT (P < 0.024). Adjustments had to be made for two EzT group patients. No difference in frequency of laryngo-pharyngeal discomfort was observed in either group. CONCLUSION: Insertion of an EzT appears to reduce time and facilitate placement of an airway device when compared with direct laryngoscopy and tracheal intubation.

Temporal artery versus bladder thermometry during perioperative and intensive care unit monitoring.

BACKGROUND: Core temperature measurements are an important component of perioperative patient monitoring. It is fairly easy to obtain core temperature measurements invasively in anesthetized patients. However, such measurements are more difficult to obtain noninvasively in awake patients. Recently, a new version of a temporal artery thermometer for noninvasive core temperature measurements (TemporalScanner TAT-5000) was introduced with accuracy and precision advertised as being comparable to invasive core temperature measurements. In this study, we sought to determine if this new thermometer is an acceptable substitute for invasive bladder temperature measurement. METHODS: In 35 patients undergoing neurosurgical interventions and 35 patients in the neurosurgical intensive care unit, measurements from the temporal artery thermometer were compared with those from a bladder thermometer. Four measurements were obtained from each patient. RESULTS: Overall 280 measurement pairs were obtained. The mean bias between the methods was 0.07 degrees C +/- 0.79 degrees C; the limits of agreement were approximately 3 times greater than the a priori defined limit of +/-0.5 degrees C (-1.48 to 1.62). The sensitivity for detecting fever (core temperature >37.8 degrees C) using the temporal artery thermometer was 0.72, and the specificity was 0.97. The positive predictive value for fever was 0.89; the negative predictive value was 0.94. The sensitivity for detecting hypothermia (core temperature <35.5 degrees C) was 0.29, and the specificity was 0.95. The positive predictive value for hypothermia was 0.31, and the negative predictive value was 0.95. CONCLUSIONS: The results of this study do not support the use of temporal artery thermometry for perioperative core temperature monitoring; the temporal artery thermometer does not provide information that is an adequate substitute for core temperature measurement by a bladder thermometer.

High-dose remifentanil does not impair cerebrovascular carbon dioxide reactivity in healthy male volunteers.

BACKGROUND: Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv). METHODS: Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 microg x kg-1 x min-1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics. RESULTS: Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 microg x kg-1 x min-1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypocapnia to hypercapnia, indicating that cerebrovascular reactivity remained intact. The average slopes of rCBF reactivity were 0.56 +/- 0.27 and 0.49 +/- 0.28 ml. 100 g-1 x min-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.9 +/- 0.8 and 1.6 +/- 0.5, respectively). The average slopes for mean CBFv reactivity were 1.61 +/- 0.95 and 1.54 +/- 0.83 cm x s-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.86 +/- 0.59 and 1.79 +/- 0.59, respectively). Preanesthesia and postanesthesia values of rCBF and mean CBFv did not differ. CONCLUSION: High-dose remifentanil decreases rCBF and mean CBFv without impairing cerebrovascular carbon dioxide reactivity. This, together with its known short duration of action, makes remifentanil a useful agent in the intensive care unit when sedation that can be titrated rapidly is required.

Awake nasotracheal fiberoptic intubation: patient comfort, intubating conditions, and hemodynamic stability during conscious sedation with remifentanil.

Awake nasotracheal fiberoptic intubation requires an anesthetic management that provides sufficient patient comfort, adequate intubating conditions, and stable hemodynamics. Short-acting and easily titratable analgesics are excellent choices for this maneuver. In this study, our aim was to determine an appropriate dosage regimen of remifentanil for awake nasotracheal fiberoptic intubation. For that reason, we compared two different dosage regimens. Twenty-four patients were randomly assigned to receive remifentanil 0.75 micro g/kg in bolus, followed by a continuous infusion of 0.075 micro g x kg(-1) x min(-1) (Group L), or remifentanil 1.5 micro g/kg in bolus, followed by a continuous infusion of 0.15 micro g x kg(-1) x min(-1) (Group H). All patients were premedicated with midazolam 0.05 mg/kg IV and glycopyrrolate 0.2 mg IV. Both dosage regimens ensured patient comfort and sedation. Discomfort did not differ between groups. Patients in Group H were sedated more profoundly. Hemodynamic stability was maintained with both remifentanil doses. Intubating conditions were adequate in all patients and comparable between the groups. The large dosage regimen did not result in any additional benefit compared with the small dosage. For awake nasotracheal fiberoptic intubation, we therefore recommend remifentanil 0.75 micro g/kg in bolus followed by continuous infusion of 0.075 micro g x kg(-1) x min(-1), supplemented with midazolam 0.05 mg/kg.

Dielectric properties of porcine brain tissue in the transition from life to death at frequencies from 800 to 1900 MHz.

Ten experiments on pigs were performed to investigate possible postmortem changes of the dielectric properties of brain gray matter in the frequency range of 800-1900 MHz. After keeping the animals in stable anaesthesia for at least 45 min, they were euthanatised by an intravenous injection of hypertonic potassium chloride (KCl), causing cardiac arrest within 3 min. Measurements of the dielectric properties were performed repeatedly from at least 45 min prior to death to 18 h after euthanasia. The anaesthesia regimen was chosen to minimize influence on brain tissue characteristics such as brain water content, intracranial blood volume, and cerebral blood flow. The data showed a decline of mean gray matter equivalent conductivity of about 15% at 900 MHz and about 11% at 1800 MHz within the first hour after death. The decline in permittivity was less pronounced (about 3-4%) and almost frequency independent. The results indicate that in vitro measurements of dielectric properties of brain tissue underestimate equivalent conductivity as well as permittivity of living tissue. These changes may affect the generally accepted data of dielectric properties of brain tissue widely used in RF dosimetry.

Prone position in subarachnoid hemorrhage patients with acute respiratory distress syndrome: effects on cerebral tissue oxygenation and intracranial pressure.

OBJECTIVE: To analyze the effect of prone position on cerebral perfusion pressure and brain tissue oxygen partial pressure in subarachnoid hemorrhage patients with acute respiratory distress syndrome (ARDS). DESIGN: Clinical study with retrospective data analysis. SETTING: Neurosurgical intensive care unit of a primary level university hospital. PATIENTS: Sixteen patients treated for intracranial aneurysm rupture with initial Hunt and Hess grade III or worse who developed ARDS within 2 wks after the bleeding. INTERVENTIONS: Routine neurosurgical intensive care treatment for subarachnoid hemorrhage and posthemorrhagic vasospasm including cerebral monitoring with continuous intracranial pressure and brain tissue oxygen partial pressure recordings. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial oxygenation, ventilatory setting, intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen partial pressure in the supine as well as in the prone position were analyzed and compared. A significant increase in Pao(2) from 97.3 +/- 20.7 torr (mean +/- sd) in the supine position to 126.6 +/- 31.7 torr in the prone position was joined by a significant increase in brain tissue oxygen partial pressure from 26.8 +/- 10.9 torr to 31.6 +/- 12.2 torr (both p <.0001), whereas intracranial pressure increased from 9.3 +/- 5.2 mm Hg to 14.8 +/- 6.7 mm Hg and cerebral perfusion pressure decreased from 73.0 +/- 10.5 mm Hg to 67.7 +/- 10.7 mm Hg (both p <.0001). CONCLUSIONS: The beneficial effect of prone positioning on cerebral tissue oxygenation by increasing arterial oxygenation appears to outweigh the expected adverse effect of prone positioning on cerebral tissue oxygenation by decreasing cerebral perfusion pressure in ARDS patients.