Determination of functional residual capacity by oxygen washin-washout: a validation study.

OBJECTIVE: To validate a new system for functional residual capacity (FRC) measurements using oxygen washin/washout in spontaneously breathing humans. The system (LUFU, Drägerwerk AG, Lübeck, Germany) consists of an unmodified EVITA 4 ventilator, a side-stream paramagnetic oxygen sensor and a dedicated software. DESIGN: Laboratory study and measurements in spontaneously breathing volunteers. SETTING: Pulmonary function laboratory of a university hospital. PARTICIPANTS: 20 healthy and 15 lung diseased volunteers. INTERVENTIONS: FRC was measured by LUFU (LUFU-FRC) and by helium dilution (He-FRC); intra-thoracic gas volume (ITGV) was determined by body plethysmography. Each measurement cycle consisted of four independent LUFU-FRC determinations (step change of FiO(2) from 0.21 to 0.5 and back and from 0.21 to 1.0 and back), two helium-dilution runs and two body box measurements. Repeatability and agreement between methods were determined by comparing different measurements of one technique and by comparing different techniques among each other. MEASUREMENTS AND RESULTS: Repeatability of LUFU-FRC was estimated by comparing washin to washout and the different FiO(2)steps. The difference of the means was 3.7% at the most. Agreement between methods resulted in the following differences (mean+/-standard deviation of differences) for healthy and lung-diseased volunteers, respectively: LUFU-FRC vs. He-FRC -0.40+/-0.50 L (0.02+/-0.95 L), LUFU-FRC vs. ITGV -0.43+/-0.54 L (-0.18+/-0.61 L) and He-FRC vs. ITGV -0.03+/-0.43 L (-0.20+/-0.98 L). CONCLUSIONS: LUFU is a non-invasive method for the determination of FRC that requires only minor additional equipment and no modification to the ventilator. It can be used in difficult conditions such as breathing patterns with variations from breath to breath. The results of this study show that LUFU is sufficiently reliable and repeatable to warrant its clinical application.

Enhanced central organ oxygenation after application of bovine cell-free hemoglobin HBOC-201.

PURPOSE: While the effects of dilutional anemia or isovolemic hemodilution (IHD) on the oxygen extraction and tissue oxygenation in peripheral organs after application of hemoglobin-based oxygen carriers like HBOC-201 have been studied intensively, little is known about tissue oxygenation properties of hemoglobin solutions in central organs like the liver. METHODS: Twelve Foxhounds were anesthetized and then randomized to either a control group without hemodilution (Group 1) or underwent first step isovolemic hemodilution (pulmonary artery occlusion pressure constant) with Ringer's solution (Group 2) to a hematocrit of 25% with second step infusion of HBOC-201 until a hemoglobin concentration of +0.6 g.dL(-1) was reached. Tissue oxygen tensions (tpO2) were measured in the gastrocnemius muscle using a polarographic needle probe, and in the liver using a flexible polarographic electrode. RESULTS: While arterial oxygen content and oxygen delivery decreased with hemodilution in Group 2, global liver and muscle oxygen extraction ratio increased after hemodilution and additional application of HBOC-201. Hemodilution and application of HBOC-201 provided augmentation of the mean liver tpO2 (baseline: 48 +/- 9, 20 min: 53 +/- 10, 60 min: 67 +/- 11*, 100 min: 68 +/- 7*; *P < 0.05 vs baseline and Group 1), while oxygen tensions in Group 1 remained unchanged. Oxygen tension in the skeletal muscle increased after hemodilution and additionally after application of HBOC-201 in comparison to baseline and to the control group (P < 0.05). CONCLUSION: In the present animal model, IHD with Ringer's solution and additional application of HBOC-201 increased oxygen extraction and tpO(2) in the liver and skeletal muscle, in parallel and in comparison with baseline values and a control group.

Suctioning through a double-lumen endotracheal tube helps to prevent alveolar collapse and to preserve ventilation.

OBJECTIVE: Endotracheal suctioning can cause alveolar collapse and impede ventilation. One reason is the gas flow through a single-lumen endotracheal tube (ETT) provoking a gradient between airway opening and tracheal (P(tr)) pressures. Separately extending the patient tubing limbs of a suitable ventilator into the trachea via a double-lumen ETT should maintain P(tr). Can this technique reduce the side effects? DESIGN AND SETTING: Bench and animal studies in a university hospital laboratory. INTERVENTIONS: A lung model was ventilated via single and double-lumen ETTs. Closed-system suctioning was applied with catheters introduced into the single-lumen ETT or the expiratory lumen of the double-lumen ETT via swivel adapter. Seven anesthetized pigs (lungs lavaged) underwent three runs of ventilation and suctioning through (a, b) an 8.0-mm ID single-lumen ETT, (c) a double-lumen ETT (41Ch outer diameter, OD). In (a) the single-lumen ETT was disconnected for suctioning, in (b) and (c) ventilator mode was set to continuous positive airway pressure mode, and the ETTs remained connected. MEASUREMENTS AND RESULTS: Bench: Suction through single-lumen ETTs impaired ventilation and led to strongly negative P(tr) (common: -10 to -20 mbar); the double-lumen ETT technique maintained ventilation and pressures. ANIMALS: Lung gas content (computed tomography, n=4) and arterial oxygen partial pressure, initially 1462+/-65 ml/532+/-76 mmHg, were significantly reduced by suctioning through single-lumen ETT: to 302+/-79 ml/62+/-6 mmHg with disconnection and to 851+/-211 ml/158+/-107 mmHg with closed suction. With double-lumen ETT they remained at 1377+/-95 ml/521+/-56 mmHg. CONCLUSIONS: The double-lumen ETT technique minimizes side effects of suctioning by maintaining P(tr).

Ryanodine contracture threshold times for diagnosis of malignant hyperthermia susceptibility: an experimental approach from a single laboratory.

STUDY OBJECTIVES: To define threshold times for ryanodine contracture testing (RCT) using skeletal muscle specimens from malignant hyperthermia-susceptible (MHS) and control individuals. DESIGN: Prospective study. SETTING: Malignant hyperthermia (MH) laboratory at a university hospital. PATIENTS: 8 patients with previous fulminant MH and 53 control patients undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility. INTERVENTIONS: Biopsies of the quadriceps femoris muscle were performed with a 3-in-1 nerve block, with spinal anesthesia, or with trigger-free general anesthesia. MEASUREMENTS AND MAIN RESULTS: Patients were classified as MHS, MH normal (MHN), or MH equivocal (MHE) by the IVCT according to the protocol of the European MH Group (EMHG). Ryanodine 1 microM was added as a bolus to the organ bath to extra vital muscle specimens. Contracture levels were defined as: 1 = start of contracture (OT; min); 2 = time (min) to reach a contracture of 2 mN, and 3 = time (min) to reach a contracture of 10 mN. The effects of ryanodine on contracture responses were measured. Ryanodine induced contractures in all specimens. MHS specimens reached all defined contracture levels significantly sooner than did the controls. Ryanodine contracture test enables a clear discrimination of MHS specimens from controls at contracture levels of OT and 2 mN, whereas at 10 mN a small overlap was observed. CONCLUSIONS: Using this test, which is an experimental approach from a single laboratory, an assignment to MHS or MHN is possible. To define contracture levels for RCT more precisely and to agree on commonly used thresholds, multicenter studies with larger numbers of patients are required.

Histomorphologic examination of skeletal muscle preparations does not differentiate between malignant hyperthermia-susceptible and -normal patients.

BACKGROUND: It has been suggested that malignant hyperthermia (MH) can be diagnosed by specific myopathologic alterations. The purpose of this study was to investigate whether there are characteristic myopathologic changes in skeletal muscles of MH-susceptible (MHS) compared with MH-normal (MHN) patients. METHODS: Four hundred forty patients with clinical suspicion of MH were classified as MHN, MH equivocal (MHE), or MHS by the in vitro contracture test with halothane and caffeine. In addition, a small muscle sample excised from each patient was analyzed by histologic, histochemical, immunohistochemical, and computer-aided morphometric methods. RESULTS: MHN was diagnosed in 243 patients, MHE was diagnosed in 65, and MHS was diagnosed in 132. No myopathologic abnormalities were found in 53.5% of the MHN, 53.9% of the MHE, and 56.1% of the MHS patients. Thirty-five percent of all patients showed one, 9.8% showed two, and only 0.9% showed three different pathologic findings within skeletal muscle preparations. The frequency of pathologic findings did not differ between the MHN and the MHS patients; only fiber type I predominance was observed more often in MHN. MHE patients could not be assigned to a diagnostic group by detection of myopathologic alterations. In six clinically unaffected patients, a former unrecognized myopathy, such as central core disease, was diagnosed. This disease is characterized by a specific alteration (cores). CONCLUSIONS: Histologic differences between MHS and MHN statuses could not be demonstrated in this study. Histopathologic examinations can neither improve the diagnosis of MH nor contribute to a better definition of the MH status. However, histopathologic examinations might be useful to detect formerly unrecognized specific myopathies.

Comparative evaluation of Narcotrend, Bispectral Index, and classical electroencephalographic variables during induction, maintenance, and emergence of a propofol/remifentanil anesthesia.

UNLABELLED: In the present study, we sought to compare the abilities of Narcotrend (NT) with the Bispectral Index (BIS) electroencephalographic system to monitor depth of consciousness immediately before induction of anesthesia until extubation during a standardized anesthetic. We investigated 26 patients undergoing laminectomy. Investigated states of anesthesia were: awake, loss of response, loss of eyelash reflex, steady-state anesthesia, first reaction, and extubation during emergence. NT, BIS, spectral edge frequency, median frequency, relative power in delta, theta, alpha, beta, and hemodynamics were recorded simultaneously. The ability of all variables to distinguish between awake versus loss of response, awake versus loss of eyelash reflex, awake versus steady-state anesthesia, steady-state anesthesia versus first reaction and extubation were analyzed with the prediction probability. Effects of remifentanil during propofol infusion were investigated with Friedman's and post hoc with Wilcoxon's test. Only NT and BIS were able to distinguish all investigated states accurately with a prediction probability >0.95. After start of remifentanil infusion, only hemodynamics changed statistically significantly (P < 0.05). NT and BIS are more reliable indicators for the assessment of anesthetic states than classical electroencephalographic variables and hemodynamics, whereas the analgesic potency of depth of anesthesia could not be detected by NT and BIS. IMPLICATIONS: The modern electroencephalographic monitoring systems Narcotrend and Bispectral Index are more reliable indicators for the assessment of anesthetic states than classical electroencephalographic and hemodynamic variables to predict anesthetic conditions from before induction of anesthesia until extubation during a standardized anesthetic regime with propofol and remifentanil. The analgesic potency of depth of anesthesia could not be detected by Narcotrend and Bispectral Index.

Ventilation performance of a mixed group of operators using a new rescue breathing device-the glossopalatinal tube.

INTRODUCTION: We studied how effectively a mixed group of helpers could ventilate a manikin with a new rescue breathing device after a short period of instruction. The device consists of a mouthcap, a "glossopalatinal tube" (GPT) reaching between tongue and palate and a connector for a bag, ventilator or the rescuers mouth. Rather than reaching behind the tongue like an oropharyngeal airway (OP), it is able to scoop the tongue off the posterior pharyngeal wall when tilted by the rescuer. It was compared with a conventional face mask with an OP. METHODS: The study made use of an anaesthesia simulator (MedSim Ltd., Israel) and a manikin. 46 subjects with different professional backgrounds (anaesthesia nurses, medical students, emergency medical technicians (EMTs), physicians training for anaesthesiology) underwent a standard introduction to the GPT and OP (lecture with demonstration on an intubation trainer, illustrated brochure). They ventilated the manikin for 5 min each using the bag plus GPT and the OP plus face mask, respectively, in random order after the simulator had been made apnoeic and the simulated arterial oxygen saturation (S(aO(2))) had dropped to 80%. The actions and the results (tidal volumes (V(t)), S(aO(2))) were recorded on video. The subjects graded difficulty of operation and fatigue on a visual analogue scale (VAS). RESULTS AND CONCLUSIONS: Mean V(t) with the OP plus mask amounted to 463 (230-688 ml), with GPT to 426 (243-610 ml) (median [10-90% percentiles]) (P=0.047). No differences were observed with respect to the time a S(aO(2))> or =90% was maintained (OP plus mask: 255 (139-266 s), GPT: 255 (90-269 s)) or the grades for fatigue (OP plus mask: 58% of VAS, GPT: 48% of VAS, median) and difficulty (OP plus mask: 16% of VAS, GPT: 21% of VAS). Performance and grades were scattered over a wide range. Success with the two devices was correlated, but the subjects judgement tended to diverge. The GPT is an easy to learn alternative to conventional devices and might be helpful in clinical emergencies, including situations of unexpectedly difficult ventilation.

Upper airway patency during ventilation with a new airway device-the glossopalatinal tube.

INTRODUCTION: We studied a new rescue breathing device consisting of a mouthcap and a "glossopalatinal" tube reaching between tongue and palate (the "GPT"), with a connector for a bag, ventilator or rescuers mouth. By tilting the connector in a cranial direction, the tongue can be "scooped" out of the hypopharynx. The study was to test the efficacy and the ease of application of the GPT in anaesthetised patients. It was compared with a conventional face mask with and without an oropharyngeal (OP) airway. METHODS: 19 patients (ethics committee approval, informed consent) anaesthetised for elective surgery were ventilated using an anaesthesia circuit and Ventilog (Draeger) through the GPT and via a face mask (Laerdal) with and without an OP tube. Flow and pressures at the airway opening, in the hypopharynx and the trachea were measured, and the resistance was derived. In addition, the relations of the devices to the anatomical structures were visualised by fibrescope, and ease of operation and fit on the face were scored. RESULTS AND CONCLUSIONS: Inspiratory resistance with the GPT and mask did not differ (1.31+/-0.96 vs. 1.38+/-0.66 kPa s/l at 1 l/s, mean+/-standard deviation (S.D.); reduction of resistance by "scooping" the tongue through angulation of the GPT (to 0.64+/-0.32; P<0.05 vs. GPT without angulation) was equivalent to that by an OP tube used with the mask (to 0.68+/-0.26; P<0.05 vs. mask solo). Pharyngoscopy showed that the effectiveness of the GPT depended on the individual anatomy. The angulating motion caused some fatigue. The GPT is an alternative to established breathing adjuncts; despite not protruding into the pharynx it can enhance airway patency like an OP.

Narcotrend and Bispectral Index monitor are superior to classic electroencephalographic parameters for the assessment of anesthetic states during propofol-remifentanil anesthesia.

BACKGROUND: A new electroencephalogram monitor, the Narcotrend, was developed to measure anesthetic depth. The authors compared the Narcotrend, the Bispectral Index, and classic electroencephalographic and hemodynamic parameters during anesthesia with propofol and remifentanil. METHODS: The authors investigated 25 patients undergoing laminectomy at different anesthetic states: awake, steady state anesthesia, first reaction during emergence, and extubation. Narcotrend value; BIS; relative power (percent) in delta, theta, alpha, and beta; median frequency; spectral edge frequency; and hemodynamic parameters were recorded simultaneously. The ability of the classic and processed electroencephalographic and hemodynamic parameters to predict the clinically relevant anesthetic states of awake, steady state anesthesia, first reaction, and extubation was tested using prediction probability. RESULTS: Only the Narcotrend was able to differentiate between awake versus steady state anesthesia and steady state anesthesia versus first reaction/extubation with a prediction probability value of more than 0.90. CONCLUSIONS: Modern electroencephalographic parameters, especially Narcotrend, are more reliable indicators for the clinical assessment of anesthetic states than classic parameters.

Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy").

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") can mediate acute toxic effects such as muscle rigidity, metabolic acidosis, and hyperthermia. Because of close clinical similarities, an association between MDMA intoxication and malignant hyperthermia (MH) was suggested. The aim of this study was to investigate whether MDMA is a trigger of MH in susceptible swine. METHODS: MH-nontriggering general anesthesia was performed in six MH-susceptible (MHS) and six MH-normal swine. The animals were exposed to MDMA in cumulative doses of 0.5, 1, 2, 4, 8, and 12 mg/kg. The clinical occurrence of MH was defined by achievement of two of three conditions: central venous Pco2 >/=75 mmHg, central venous pH /= 2.0 degrees C. Once MH occurred, a standardized therapy with dantrolene, sodium bicarbonate, and hyperventilation with 100% oxygen was initialized. RESULTS: Administration of 8 mg/kg MDMA triggered MH in all MHS swine. The MH-normal swine also developed clinical signs of hypermetabolism, but even after administration of 12 mg/kg MDMA, changes were moderate compared with the MHS swine. Dantrolene therapy of MDMA-induced MH crisis in the MHS swine partially counteracted the clinical signs of MH immediately. CONCLUSIONS: MDMA induces MH in genetically susceptible swine in relevant doses. Therefore, MHS patients should avoid use of MDMA or related drugs. Patients with a personal or family history of MDMA-induced hyperthermia should be tested for a diagnosis of MH susceptibility. Dantrolene is effective in therapy of MDMA-induced porcine MH.

ARX-derived auditory evoked potential index and bispectral index during the induction of anesthesia with propofol and remifentanil.

UNLABELLED: A new commercial auditory evoked potential (AEP) monitor (A-line AEP monitor) was developed to calculate an index (ARX AEP index; AAI) by automatically using the amplitudes and latencies of the AEP. We investigated 30 patients before spine surgery. AAI; bispectral index (BIS); relative (%) delta, theta, alpha, and beta; spectral edge frequency; median frequency; mean arterial blood pressure; heart rate; and oxygen saturation were obtained simultaneously during stepwise (1.0 micro g/mL) induction of target-controlled propofol concentration until 5.0 micro g/mL, followed by an infusion of 0.3 micro g. kg(-1). min(-1) of remifentanil. Every minute, the patients were asked to squeeze the observer's hand. Prediction probability (Pk), receiver operating characteristic, and logistic regression were used to calculate the probability to predict the conditions AWAKE, UNCONSCIOUSNESS (first loss of hand squeeze), and steady-state ANESTHESIA (5.0 micro g/mL of propofol and 0.3 micro g. kg(-1). min(-1) of remifentanil). Although a statistically significant difference among the conditions was observed for AAI, BIS, mean arterial blood pressure, median frequency, and %alpha, only AAI and BIS were able to distinguish UNCONSCIOUSNESS versus AWAKE and ANESTHESIA versus AWAKE with better than Pk = 0.90. The modern electroencephalographic variables AAI and BIS were superior to the classic electroencephalographic and hemodynamic variables to distinguish the observed anesthetic conditions. IMPLICATIONS: The modern electroencephalographic ARX-derived auditory evoked potential index and the bispectral index were superior to the classic electroencephalographic and hemodynamic variables for predicting anesthetic conditions. Variables derived from the auditory evoked potential did not provide an advantage over variables derived from spontaneous electroencephalogram.

In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine.

BACKGROUND: In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated. METHODS: Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C. RESULTS: Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure. CONCLUSIONS: The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.

Patient-controlled epidural analgesia reduces analgesic requirements compared to continuous epidural infusion after major abdominal surgery.

PURPOSE: To compare the quality of pain relief and incidence of side effects between 24-hr postoperative continuous epidural infusion (CEI) and subsequent patient-controlled epidural analgesia (PCEA) with different analgesics after major abdominal surgery. METHODS: Twenty-eight women undergoing extended gynecological tumour surgery received postoperative CEI with 0.15 mL x kg(-1) x hr(-1) 0.2% ropivacaine (R: n = 14) or 0.125% bupivacaine plus 0.5 micro g x mL(-1) sufentanil (BS: n = 14) during 24 postoperative hours. Twenty-four hours later, postoperative pain management was switched to PCEA without background infusion and 5 mL single bolus application of R or BS every 20 min at most. Visual analogue scales (VAS; 1-100 mm) were assessed by patients at rest and on coughing after 24 hr of CEI and PCEA. Side effects, doses of local anesthetics and opioids were recorded and plasma concentrations of total and unbound ropivacaine and bupivacaine were measured. RESULTS: Patients required lower doses of each respective analgesic medication with PCEA (R: 108 +/- 30 mL; BS: 110 +/- 28 mL) than with CEI (R: 234 +/- 40; BS: 260 +/- 45; P < 0.01). Ropivacaine plasma concentrations were lower 24 hr after PCEA when compared with CEI (P < 0.01). No patient after PCEA but two after CEI (n = 4; NS) presented motor block. PCEA with R provided better postoperative pain relief than CEI (37 +/- 32 vs 59+/-27, P < 0.05). No difference in parenteral opioid rescue medication between CEI and PCEA was seen. CONCLUSION: PCEA in comparison to preceding CEI provides equivalent analgesia with lower local anesthetic doses and plasma levels, and without motor blocking side effects, irrespective of the applied drug regimen.

Somatosensory evoked potentials as predictor of systemic inflammatory response syndrome in pigs?

OBJECTIVE: Sepsis or systemic inflammatory response syndrome (SIRS) is often associated with encephalopathy (70%), which has been described as an early symptom resulting in several diseases. The present study investigated somatosensory evoked potentials (SEP) as an indicator or even a predictor of cerebral dysfunction evaluated in an experimental model of SIRS in pigs. METHODS: Eight Göttinger minipigs were included in the study. SIRS was mediated by induction of pancreatitis due to injection (ductus pancreaticus) of 500 mg/kg sodium taurocholate and 2.5 IU/kg enterokinase. Monitored parameters were: arterial blood-central venous-pulmonary arterial pressure, and cardiac output, systemic vascular resistance, and body temperature. SEP were recorded from centroparietal vs. frontal areas after electrical stimulation of the right forepaw. RESULTS: At least 33% loss of vascular resistance from baseline (SIRS criteria) occurred in all animals within 4-18 h. Baseline recordings in all anesthetized animals indicated primary cortical responses to electrical stimuli identified by peak latencies between 15-20 ms (SEP(P15-20)). Attenuations in the amplitudes with significant median decreases of 46% were observed at least 4 h before the defined hemodynamic SIRS criteria. CONCLUSIONS: The present data show a trend for the attenuation in SEP amplitudes as an indicator of systemic inflammatory response. SEP monitoring may be a sensitive marker of developing early changes in cerebral function due to SIRS-related encephalopathy.

Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis.

OBJECTIVE: To evaluate the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on immunoparalysis as defined by a sustained decrease of HLA-DR expression on monocytes in patients with severe sepsis. DESIGN: Prospective, non-randomised observational study. SETTING: Two anaesthesiological intensive care units of a university hospital. INTERVENTION: Administration of a daily dose of 5 micro g/kg rhGM-CSF over a period of 3 days. PATIENTS: Nine consecutive patients with severe sepsis and a documented HLA-DR expression on peripheral monocytes of less than 150 mean fluorescence intensity (MFI) over a period of at least 48 h prior to intervention. MEASUREMENTS AND RESULTS: Mean MFI was 69.4+/-13.2 24 h before and 56.7+/-8.2 on the day of the administration of 5 micro g/kg rhGM-CSF. Within 24 h a significant increase of HLA-DR expression to a mean of 327.7+/-78.8 MFI was observed in all patients. This increase was maintained on days 2-10. It was accompanied by a significant rise in white blood count. The ex vivo TNF-alpha production in whole blood after lipopolysaccharide (LPS)-stimulation increased significantly from a mean of 82+/-29.2 pg/ml to 793+/-546.8 pg/ml. Apart from febrile reactions in two patients, no side effects were recorded. No increases of pro-inflammatory markers (IL-6, C-reactive protein, LPS-binding protein, procalcitonin) were observed. SOFA values before and after rhGM-CSF did not differ significantly. The mortality rate was 33%. CONCLUSION: This preliminary study demonstrates that rhGM-CSF upregulates HLA-DR expression on monocytes in septic patients with multi-organ dysfunction. Moreover, with the concomitant increase of the ex vivo whole blood TNF-alpha response, this upregulation of a monocytic activation marker is paralleled by a functional recovery.

Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery.

BACKGROUND: All general anesthetics used are known to have a negative inotropic side effect. Since xenon does not have a negative inotropic effect, it could be an interesting future general anesthetic. The aim of this clinical multicenter trial was to test the hypothesis of whether recovery after xenon anesthesia is faster compared with an accepted, standardized anesthetic regimen and that it is as effective and safe. METHOD: A total of 224 patients in six centers were included in the protocol. They were randomly assigned to receive either xenon (60 +/- 5%) in oxygen or isoflurane (end-tidal concentration, 0.5%) combined with nitrous oxide (60 +/- 5%). Sufentanil (10 mcirog) was intravenously injected if indicated by defined criteria. Hemodynamic, respiratory, and recovery parameters, the amount of sufentanil, and side effects were assessed. RESULTS: The recovery parameters demonstrated a statistically significant faster recovery from xenon anesthesia when compared with isoflurane-nitrous oxide. The additional amount of sufentanil did not differ between both anesthesia regimens. Hemodynamics and respiratory parameters remained stable throughout administration of both anesthesia regimens, with advantages for the xenon group. Side effects occurred to the same extent with xenon in oxygen and isoflurane-nitrous oxide. CONCLUSION: This first randomized controlled multicenter trial on the use of xenon as an inhalational anesthetic confirms, in a large group of patients, that xenon in oxygen provides effective and safe anesthesia, with the advantage of a more rapid recovery when compared with anesthesia using isoflurane-nitrous oxide.

Narcotrend, bispectral index, and classical electroencephalogram variables during emergence from propofol/remifentanil anesthesia.

UNLABELLED: The aim of this study was to investigate modern and classical electroencephalographic (EEG) variables in response to remifentanil and propofol infusions. We hypothesized that modern EEG variables may indicate the effects of propofol but not of remifentanil. Twenty-five patients were included in the study after the end of elective spine surgery without any surgical stimulation. Baseline values were defined with remifentanil 0.3 microg. kg(-1). min(-1) and target-controlled infusion of propofol 3.0 microg/mL. EEG changes were evaluated 1, 3, 5, 7, and 9 min after the stop of remifentanil infusion, followed by a step-by-step reduction (0.2 microg/mL) every 3 min of target-controlled infusion propofol. Narcotrend (NT; classifying EEG stages from awake to deep anesthesia), bispectral index (BIS), EEG spectral frequency bands (%), 50% (Median) and 95% percentiles (spectral edge frequency), mean arterial blood pressure, heart rate, and oxygen saturation were detected at every time point. The end of remifentanil application resulted in significant increases in %alpha, spectral edge frequency, mean arterial blood pressure, and %theta and decreases in %delta (P < 0.05). NT, BIS, Median, heart rate, and oxygen saturation were unchanged. Decreases in propofol concentration were associated with statistically significant increases in NT and BIS (P < 0.05). Thus, the sedative-hypnotic component of propofol could be estimated by modern EEG variables (NT and BIS), whereas the analgesic component provided by remifentanil was not indicated. However, during conditions without surgical stimulation, neither NT nor BIS provided an adequate assessment of the depth of anesthesia when a remifentanil infusion was used. IMPLICATIONS: We investigated modern and classical electroencephalographic (EEG) variables during emergence from propofol/remifentanil anesthesia. Modern EEG variables indicate changes of infusion in propofol, but not in remifentanil. Thus, modern EEG variables did not provide an adequate assessment of depth of anesthesia when remifentanil was used.

Evidence for a spontaneous C1840-T mutation in the RYR1 gene after DNA fingerprinting in a malignant hyperthermia susceptible family.

Malignant hyperthermia (MH) is a potentially lethal inherited pharmacogenetic syndrome due to a dysfunction of the intracellular calcium regulation of skeletal muscle following administration of volatile anaesthetics and depolarizing muscle relaxants. The ryanodine receptor of skeletal muscle (RYR1), which is an intracellular calcium release channel, has been proposed to be a candidate structure for the MH defect. In some families with a history of MH a C1840-T nucleotide exchange has been found in the RYR1 gene which cosegregates with the MH susceptible phenotype. Sixteen individuals (5 males and 11 females; age 8-68 years, 7 MH susceptible, 9 MH non-susceptible) of a family with a history of MH were screened for the C1840-T mutation in the RYR1 gene using standard methods. DNA fingerprinting was performed in order to verify the kinship. MH susceptibility was determined using the standard in vitro contracture test with halothane and caffeine. The present article describes a German MH pedigree carrying a spontaneous C1840-T mutation. The mutation was detected in one individual of the third generation. This person was classified as MH susceptible according to the in vitro contracture test protocol. None of the other family members (6 MH susceptible and 9 MH non-susceptible persons), including the parents of the child carrying the mutation, presented the C to T nucleotide exchange at position 1840.This novel observation clearly demonstrates that only the detection of the C1840-T mutation may lead to the diagnosis of MH susceptibility, but missing the mutation does not justify diagnosing a patient as non-susceptible within a single pedigree.

Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations.

BACKGROUND: More than 20 mutations in the gene encoding for the ryanodine receptor (RYR1), a Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, have been found to be associated with malignant hyperthermia (MH). This study was designed to investigate the effects of different mutations in the RYR1 gene on contracture development in in vitro contracture tests (IVCT) with halothane, caffeine, and ryanodine. METHODS: Ninety-three MH-susceptible (MHS) patients, diagnosed by the standard IVCT with halothane and caffeine, were included in this prospective study. Surplus muscle specimens were used for an IVCT with 1 microm ryanodine. The contracture course during the ryanodine IVCT was described by the attainment of different time points: onset time of contracture and times when contracture reached 2 mN or 10 mN. In addition, all patients were screened for mutations of the RYR1 gene. RESULTS: In 36 patients, four different mutations of the RYR1 gene (C487-T, G1021-A, C1840-T, G7300-A) were found. The IVCT threshold concentrations of halothane and caffeine were lower in patients with the C487-T mutation compared with patients without a detected mutation in the RYR1 gene. In the IVCT with ryanodine, contracture levels of 2 mN and 10 mN were reached earlier in muscle specimens from patients with C487-T, C1840-T, and G7300-A mutations compared with specimens from patients with the G1021-A mutation and patients without detected mutation in the RYR1 gene. CONCLUSIONS: The differences between the groups in the halothane and caffeine IVCT threshold concentrations and in the time course of contracture development in the ryanodine IVCT underline the hypothesis that certain mutations in the RYR1 gene could make the ryanodine receptor more sensitive to specific ligands. This may be an explanation for varying clinical symptoms of MH crisis in humans.