Biomedical subjects

Reinhard Larsen

Publications and source records attributed to Reinhard Larsen.

9 recordsLinked to original sources

PubMed2007

Interleukin-1beta and tetradecanoylphorbol acetate-induced biosynthesis of tumor necrosis factor alpha in human hepatoma cells involves the transcription factors ATF2 and c-Jun and stress-activated protein kinases.

The proinflammatory cytokine tumor necrosis factor (TNF) alpha is mainly produced in cells from the monocyte/macrophage lineage. TNFalpha is also a key signaling molecule in the liver functioning as an important physiological and pathogenic mediator. In hepatocytes or human hepatoma cells TNFalpha is expressed at extremely low levels but TNFalpha biosynthesis can be induced by interleukin (IL)-1beta or 12-O-tetradecanoylphorbol-13-acetate (TPA). Here, we show that IL-1beta and TPA stimulated TNFalpha gene transcription in hepatoma cells mediated by a composite TPA-responsive element/cAMP response element. Both IL-1beta and TPA triggered phosphorylation and activation of the basic region leucine zipper transcription factors c-Jun and ATF2 and expression of dominant-negative mutants of c-Jun and ATF2-reduced TNFalpha promoter activity and secretion of TNFalpha. Expression of the nuclear dual-specific MAP kinase phosphatase-1 (MKP-1) blocked TNFalpha promoter activity and TNFalpha secretion following IL-1beta or TPA stimulation, indicating that MKP-1 functions as a nuclear shut-of-device of IL-1beta and TPA-induced TNFalpha expression.

Activating Transcription Factor 2↗

PubMed2006

Does the timing of tracheal intubation based on neuromuscular monitoring decrease laryngeal injury? A randomized, prospective, controlled trial.

Vocal cord injuries (VCI) and postoperative hoarseness (PH) are common complications after general anesthesia. Poor muscle relaxation at the moment of tracheal intubation may result in VCI. There is a large interindividual variation in neuromuscular depression after administration of neuromuscular blocking drugs. Therefore, the optimal individual timing of tracheal intubation based on neuromuscular monitoring (monitoring) may decrease VCI. In this prospective trial, 60 patients were randomized into 2 groups: Monitoring group: tracheal intubation at maximum block based on monitoring after atracurium 0.5 mg/kg and 2-min group: tracheal intubation 2 min after injection of atracurium 0.5 mg/kg. Intubating conditions were evaluated with the Copenhagen score. VCI were examined by stroboscopy before and 24 and 72 h after surgery. PH was assessed at 24, 48, and 72 h after surgery by a standardized interview. Excellent intubating conditions were significantly increased in the monitoring group compared with the 2-min group: 8 versus 2 patients, respectively (P = 0.036). The incidence of PH between the study groups was comparable: 7 (monitoring) versus 8 patients (2-min) (P = 0.860). Similar findings were observed for VCI: 9 versus 5 patients; respectively (P = 0.268); type of VCI: thickening of the vocal cords: 8 (monitoring) versus 5 (2-min) patients (P = 0.423), hematomas: 2 patients in each group (not significant). The present study demonstrated that neuromuscular monitoring improved endotracheal intubating conditions. However, tracheal intubation at maximum intensity of neuromuscular block was not associated with a decrease in vocal cord injuries.

Adult↗

PubMed2006

A-line, bispectral index, and estimated effect-site concentrations: a prediction of clinical end-points of anesthesia.

Autoregressive modeling with exogenous input of middle-latency auditory evoked potentials (A-Line AEP index, AAI) has been developed for monitoring depth of anesthesia. We investigated the prediction of recovery and dose-response relationship of desflurane and AAI or bispectral index (BIS) values. Twenty adult men scheduled for radical prostatectomy were recruited. To minimize opioid effects, analgesia was provided by a concurrent epidural in addition to the general anesthetic. Electrodes for AAI and BIS monitoring and a headphone for auditory stimuli were applied. Propofol and remifentanil were used for anesthetic induction. Maintenance of anesthesia was with desflurane only. For comparison to AAI and BIS monitor parameters, pharmacokinetic models for desflurane and propofol distribution and effect-site concentrations were used to predict clinical end-points (Prediction probability P(K)). Patients opened their eyes at an AAI value of 47 +/- 20 and a BIS value of 77 +/- 14 (mean +/- sd), and the prediction probability for eye opening was P(K) = 0.81 for AAI, P(K) = 0.89 for BIS, and P(K) = 0.91 for desflurane effect-site concentration. The opening of eyes was best predicted by the calculated desflurane effect-site concentration. The relationship between predicted desflurane effect-site concentration versus AAI and BIS was calculated by nonlinear regression analysis (r = 0.75 for AAI and r = 0.80 for BIS). The correlation between BIS and clinical end-points of anesthesia or the desflurane effect-compartment concentration is better than for the AAI.

Aged↗

PubMed2005

Acute pancreatitis induced by short-term propofol administration.

The incidence of a drug-induced pancreatitis is rare and so far more than 85 different drugs have been reported to have induced pancreatitis. Some case reports consider a relationship between propofol and acute pancreatitis. However, in these cases a number of different drugs were coadministered, thus preventing a clear causal link being established. We report a case of a drug-induced acute pancreatitis that was most likely triggered by a single dosage of propofol. It occurred in a young girl who underwent elective magnetic resonance imaging. She developed pancreatitis within hours after exposure to propofol. Other possible triggers, e.g. gallstones or infection were ruled out. Physicians should consider pancreatitis as a potentially life-threatening adverse event associated with propofol sedation, which is nowadays extensively used.

Acute Disease↗

PubMed2005

Narcotrend or bispectral index monitoring during desflurane-remifentanil anesthesia: a comparison with a standard practice protocol.

UNLABELLED: Bispectral Index (BIS) (Aspect Medical Systems, Newton, MA) and Narcotrend (MonitorTechnik, Bad Bramstedt, Germany) are monitoring devices that were, as others, designed to assess the depth of anesthesia. Meanwhile, a number of studies indicate that with total IV anesthesia, BIS and Narcotrend have comparable effects on drug consumption and recovery times whereas comparative clinical data for volatile anesthetics are still missing. Therefore, we designed the present prospective, randomized, and double-blinded study to compare the effects of BIS and Narcotrend monitoring during desflurane-remifentanil anesthesia and versus a standard anesthetic practice protocol. One-hundred-twenty adult patients scheduled for minor orthopedic surgery were randomized to receive a desflurane-remifentanil anesthetic controlled either by Narcotrend or by BIS or solely by clinical variables. Anesthesia was induced with 0.4 microg x kg(-1) x min(-1) remifentanil and 2 mg/kg propofol. After tracheal intubation, remifentanil was infused at a constant rate of 0.2 microg x kg(-1) x min(-1) whereas desflurane in 1.5 L/min O(2)/air was adjusted according to clinical variables or the following target values: during maintenance of anesthesia to a value of "D(0)" (Narcotrend) or "50" (BIS), 15 min before the end of surgery to "C(1)" (Narcotrend) or "60" (BIS), whereas in the standard protocol group, desflurane was controlled according to clinical variables, e.g., heart rate, arterial blood pressure, movements. Recovery times and desflurane consumption were recorded by a blinded investigator. The desflurane vaporizer was weighed before and after anesthesia and consumption per minute was calculated. Data are mean +/- sd. The groups were comparable for demographic data, duration of anesthesia, and mean remifentanil dosages. Compared with standard practice, patients with Narcotrend or BIS monitoring needed significantly less desflurane (standard practice 443 +/- 71 mg/min, Narcotrend 374 +/- 124 mg/min, BIS monitoring 416 +/- 99 mg/min desflurane [both P < 0.05]). However, recovery times were not significantly different between the groups, e.g., opening of eyes 4.7 +/- 2.2 versus 3.7 +/- 2.0 versus 4.2 +/- 2.1 min. During desflurane-remifentanil anesthesia, Narcotrend and BIS monitoring seem to be equally effective compared with standard anesthetic practice: BIS and Narcotrend allow for a small reduction of desflurane consumption whereas recovery times are only slightly reduced. IMPLICATIONS: Monitoring the electroencephalogram with Narcotrend or Bispectral Index during desflurane-remifentanil anesthesia only slightly reduces recovery times when compared with a standard practice protocol.

Adolescent↗

PubMed2004

Application of Bispectral Index and Narcotrend index to the measurement of the electroencephalographic effects of isoflurane with and without burst suppression.

BACKGROUND: The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) has recently been introduced as an intraoperative monitor of anesthetic state, based on a classification scheme originally developed for visual assessment of the electroencephalogram. The authors compared the performance of the Narcotrend index (software version 4.0) to the Bispectral Index (BIS, version XP; Aspect Medical Systems, Natick, MA) as electroencephalographic measures of isoflurane drug effect during general anesthesia. METHODS: The authors observed 15 adult patients scheduled to undergo radical prostatectomy with a combined epidural-isoflurane general anesthesia technique. At least 45 min after induction of general anesthesia, during a phase of constant surgical stimulation, end-tidal isoflurane concentrations were varied between 0.5 and 2.0 multiples of minimum alveolar concentration, and the BIS and the Narcotrend index were recorded. The prediction probability (PK) was calculated for the BIS and the Narcotrend index to predict isoflurane effect compartment concentration for each measure. The correlation analysis of the BIS and the Narcotrend index with the isoflurane effect compartment concentration was obtained by pharmacodynamic modeling based on two sigmoidal curves to account for the discontinuity in both indices with the onset of burst suppression. RESULTS: The prediction probabilities were indistinguishable (BIS PK = 0.72 +/- 0.07 (mean +/- SD); range, 0.61-0.84; Narcotrend index PK = 0.72 +/- 0.10; range, 0.51-0.87), as were the correlations between the electroencephalographic measures and isoflurane effect compartment concentrations (BIS R = 0.82 +/- 0.12; Narcotrend index R = 0.85 +/- 0.09). The pharmacodynamic models for the BIS and the Narcotrend index yielded nearly identical results. CONCLUSIONS: The BIS and the Narcotrend index detected the electroencephalographic effects of isoflurane equally. Combining two fractional sigmoid Emax models adequately described the data before and after the onset of burst suppression.

Aged↗

PubMed2004

Impact of bispectral index monitoring on stress response and propofol consumption in patients undergoing coronary artery bypass surgery.

BACKGROUND: Bispectral Index (BIS)-titrated administration allows a reduction of propofol infusion rates in patients undergoing surgery. Resulting differences in anesthetic depth might affect the stress response to surgery involving neural circuitry not reflected in the electroencephalogram. METHODS: Forty patients scheduled to undergo elective coronary artery bypass grafting receiving a background infusion of remifentanil (0.3 microg . kg . min) were anesthetized with intravenous propofol delivered by target-controlled infusion according to the Marsh pharmacokinetic model under BIS monitoring. In a randomized, prospective design, 20 patients received propofol at a target concentration of 3 microg/ml, whereas in 20 patients propofol was titrated to maintain a BIS value of 40-50. Plasma concentrations of propofol (by means of gas chromatography-mass spectrometry), epinephrine, norepinephrine (by means of high-pressure liquid chromatography), cortisol (by means of radioimmunoassay), and interleukins 6 and 10 (by means of enzyme-linked immunosorbent assay) were measured repeatedly throughout surgery. RESULTS: BIS monitoring allowed a 30% reduction of propofol infusion rates and a similar decrease in plasma propofol concentrations in the BIS group without affecting the stress response to surgery for the group mean. None of the patients reported awareness during a standardized interview. Interestingly, propofol-remifentanil anesthesia blunted the release of epinephrine and cortisol to bypass surgery completely even when the propofol infusion rate was reduced according to BIS values. CONCLUSIONS: Total intravenous anesthesia using propofol-remifentanil effectively attenuates the neurohumoral stress response to coronary bypass surgery involving cardiopulmonary bypass. Titration of propofol using BIS allows for significant reduction of propofol consumption, with only minor effects on stress response under these conditions.

Aged↗

PubMed2004

Narcotrend index versus bispectral index as electroencephalogram measures of anesthetic drug effect during propofol anesthesia.

UNLABELLED: The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) performs an automatic analysis of the electroencephalogram (EEG) during anesthesia based on a visual assessment of the raw EEG. Its newest software version 4.0 includes a dimensionless index that, similar to the bispectral index (BIS), ranges from 100 (awake) to 0. We compared the performance of Narcotrend index and BIS as EEG measures of anesthetic drug effect during propofol anesthesia. Eighteen adult patients scheduled for radical prostatectomy were investigated. An epidural catheter was placed in the lumbar space and electrodes for BIS (version XP; Aspect Medical Systems, Natick, MA) and Narcotrend were positioned as recommended by the manufacturers. Narcotrend index, BIS values, and propofol plasma and effect site concentrations as parallelly simulated by Rugloop software (Department of Anesthesia, Ghent University, Belgium) were automatically recorded in intervals of 5 s. Induction of anesthesia consisted of a fentanyl bolus and a propofol infusion. After endotracheal intubation, patients received 15 mL bupivacaine 0.5% epidurally, and 45 min later propofol dosages were subsequently increased and decreased twice. Simulated propofol effect site concentrations ranged from 2.0 +/- 0.4 microg/mL (smallest) to 6.3 +/- 1.3 microg/mL (largest) during these subsequent increases and decreases of propofol. In terms of prediction probability (P(K)) the performance of the Narcotrend index (P(K) = 0.88 +/- 0.03) to predict propofol effect site concentrations was comparable to the BIS (P(K) = 0.85 +/- 0.04). Using the respective EEG index as a measure of drug effect the mean k(e0) was calculated as 0.20 +/- 0.05 min(-1) for Narcotrend index and 0.16 +/- 0.07 min(-1) for BIS. In the observed propofol concentration range Narcotrend index detected differences in EEG dynamics as well as BIS. IMPLICATIONS: This study in 18 adult patients undergoing radical prostatectomy describes the relationship between Narcotrend index and bispectral index versus predicted propofol effect compartment concentrations. In terms of prediction probability, the performance of the Narcotrend index and the bispectral index to predict propofol effect site concentrations was comparable.

Aged↗

PubMed2003

Narcotrend monitoring allows faster emergence and a reduction of drug consumption in propofol-remifentanil anesthesia.

BACKGROUND: The Narcotrend is a new electroencephalographic monitor designed to measure depth of anesthesia, based on a six-letter classification from A (awake) to F (increasing burst suppression) including 14 substages. This study was designed to investigate the impact of Narcotrend monitoring on recovery times and propofol consumption in comparison to Bispectral Index (BIS) monitoring or standard anesthetic practice. METHODS: With institutional review board approval and written informed consent, 120 adult patients scheduled to undergo minor orthopedic surgery were randomized to receive a propofol-remifentanil anesthetic controlled by Narcotrend, by BIS(R), or solely by clinical parameters. Anesthesia was induced with 0.4 micro x kg-1 x min-1 remifentanil and a propofol target-controlled infusion at 3.5 microg/ml. After intubation, remifentanil was reduced to 0.2 micro x kg-1 x min-1, whereas the propofol infusion was adjusted according to clinical parameters or to the following target values: during maintenance to D(0) (Narcotrend) or 50 (BIS); 15 min before the end of surgery to C(1) (Narcotrend) or 60 (BIS). Recovery times were recorded by a blinded investigator, and average normalized propofol consumption was calculated from induction and maintenance doses. RESULTS: The groups were comparable for demographic data, duration of anesthesia, and mean remifentanil dosages. Compared with standard practice, patients with Narcotrend or BIS monitoring needed significantly less propofol (standard practice, 6.8 +/- 1.2 mg x kg-1 x h-1 vs. Narcotrend, 4.5 +/- 1.1 mg x kg-1 x h-1 or BIS(R), 4.8 +/- 1.0 mg x kg-1 x h-1; P < 0.001), opened their eyes earlier (9.3 +/- 5.2 vs. 3.4 +/- 2.2 or 3.5 +/- 2.9 min), and were extubated sooner (9.7 +/- 5.3 vs. 3.7 +/- 2.2 or 4.1 +/- 2.9 min). CONCLUSIONS: The results indicate that Narcotrend and BIS monitoring are equally effective to facilitate a significant reduction of recovery times and propofol consumption when used for guidance of propofol titration during a propofol-remifentanil anesthetic.

Adult↗