Wolfram Wilhelm

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®, or solely by clinical parameters. Anesthesia was induced with 0.4 &mgr;g · kg−1 · min−1 remifentanil and a propofol target-controlled infusion at 3.5 &mgr;g/ml. After intubation, remifentanil was reduced to 0.2 &mgr;g · kg−1 · min−1, whereas the propofol infusion was adjusted according to clinical parameters or to the following target values: during maintenance to D0 (Narcotrend) or 50 (BIS®); 15 min before the end of surgery to C1 (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 · kg−1 · h−1vs. Narcotrend, 4.5 ± 1.1 mg · kg−1 · h−1 or BIS®, 4.8 ± 1.0 mg · kg−1 · 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.

Spectral entropy and bispectral index as measures of the electroencephalographic effects of sevoflurane.

Background:Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8–32 Hz and a response entropy (RE) computed over the frequency range of 0.8–47 Hz. The authors investigated the dose–response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS). Methods:Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability. Results:State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 ± 0.09 and 0.86 ± 0.10 for SE and RE, respectively) than for BIS (0.85 ± 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 ± 0.05 and 0.82 ± 0.06 for SE and RE, respectively, and 0.80 ± 0.06 for BIS. Conclusion:State entropy and RE seem to be useful electroencephalographic measures of sevoflurane drug effect.

The efficacy of the non-opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy.

In this prospective, double-blind, randomized, placebo-controlled study we compared the efficacy of three IV non-opioid analgesics for postoperative pain relief after lumbar microdiscectomy. Eighty healthy patients were randomly divided into 4 treatment groups (n = 20 each) to receive either parecoxib 40 mg, paracetamol 1 g, metamizol 1 g, or placebo IV 45 min before the end of surgery. In the postanesthesia care unit (PACU) patients were treated using patient-controlled analgesia (PCA) with piritramide. In the metamizol group the pain score at arrival in the PACU was significantly lower compared with the paracetamol, parecoxib, and placebo groups. In addition, in the metamizol group significantly fewer patients required additional PCA compared with the other groups studied. However, in those patients who required additional pain therapy in the four treatment groups, there was no significant difference in time to first request for piritramide and cumulative consumption of piritramide as assessed by the PCA data in the PACU. The incidence of adverse side effects was infrequent in all groups. These results suggest that in patients undergoing lumbar microdiscectomy, metamizol is superior to parecoxib, paracetamol, and placebo for immediate postoperative pain relief with minimal side effects.

A risk adapted approach reduces the overall institutional incidence of postoperative nausea and vomiting

PurposeRoutine prophylactic antiemetic treatment of surgical patients appears justified only in case of an increased risk of postoperative nausea and vomiting (PONV.). The objective of this investigation was to assess the feasibility and efficacy of a dichotomized risk score adapted management of PONV. based on ondansetron prophylaxis and treatment with respect to the overall institutional rate of PONV.MethodsAfter estimating the individual PONV. risk by a simplified score, 162 adult patients scheduled for elective surgery received either 4 mg ondansetron intravenously (two to four risk factors = high-risk) or no prophylaxis (zero to one risk factor = low-risk). For antiemetic treatment ondansetron was given intravenously and orally. Incidence of PONV. was recorded during the first 24 hr after recovery.ResultsData from 159 subjects were analyzed with 44 patients classified as low-risk and 115 patients classified as high-risk. Nine low-risk and 58 high-risk patients experienced PONV. The expected institutional PONV. incidence of 47% was reduced to 36%. Treatment with ondansetron was necessary in seven low-risk and 37 high-risk patients with a complete response rate of 71% (lowrisk) and 43% (high-risk).ConclusionProviding antiemetic prophylaxis with ondansetron to high-risk patients strictly based on a simplified risk score can reduce the overall institutional rate of PONV. However, classifying patients into two groups while using ondansetron as the single antiemetic in the high-risk group appears to be of limited efficacy as the incidence of PONV in high-risk patients is still double that of low-risk patients.RésuméObjectifLe traitement antiémétique préventif courant des opérés semble justifié seulement en cas de risque accru de nausées et de vomissements postopératoires (NVPO). Nous voulions évaiuer la faisabilité et l’efficacité d’un traitement, adapté aux scores de risque dichotomique de NVPO, fondé sur une action préventive et thérapeutique avec l’ondansétron en regard du taux global de NVPO à l’hôpital.MéthodeAprès avoir estimé le potentiel individuel de NVPO par un score simplifié, 162 adultes devant subir une intervention chirurgicale réglée ont reçu soit 4 mg d’ondansétron par voie intraveineuse (de deux à quatre facteurs de risque = haut risque) ou aucune prophylaxie (zéro ou un facteur de risque = faible risque). Comme antiémétique, l’ondansétron a été administré par voie intraveineuse et orale. L’incidence des NVPO a été notée pendant les 24 premières heures après la récupération.RésultatsLes données de 159 sujets ont été analysées dont celles de 44 patients à faible risque et 115 à haut risque. Neuf patients à faible risque et 58 à haut risque ont eu des NVPO. L’incidence attendue de NVPO de 47 % a été réduite à 36 %. Le traitement avec l’ondansétron a été nécessaire chez sept patients à faible risque et 37 à haut risque pour un taux de réponse complet de 71 % (faible risque) et 43 % (haut risque).ConclusionL’administration préventive d’antiémétique avec ondansétron aux patients à haut risque, fondée strictement sur un score de risque simplifié, peut réduire le taux global de NVPO à l’hôpital. Mais la répartition des patients en deux groupes et l’utilisation d’ondansétron antiémétique chez les patients à haut risque seulement nous semble d’efficacité limitée, étant donné que l’incidence de NVPO chez ces patients demeure deux fois plus élevée que chez les patients à faible risque.

The place for short-acting opioids: special emphasis on remifentanil.

Pain is among the worst possible experiences for the critically ill. Therefore, nearly all intensive care patients receive some kind of pain relief, and opioids are most frequently administered. Morphine has a number of important adverse effects, including histamine release, pruritus, constipation, and, in particular, accumulation of morphine-6-glucuronide in patients with renal impairment. Hence, it is not an ideal analgesic for use in critically ill patients. Although the synthetic opioids fentanyl, alfentanil, and sufentanil have better profiles, they undergo hepatic metabolism and their continuous infusion also leads to accumulation and prolonged drug effects. Various attempts have been made to limit these adverse effects, including daily interruption of infusion of sedatives and analgesics, intermittent bolus injections rather than continuous infusions, and selection of a ventilatory support pattern that allows more spontaneous ventilation. However, these techniques at best only limit the effects of drug accumulation, but they do not solve the problem. Another type of approach is to use remifentanil in critically ill patients. Remifentanil is metabolized by unspecific blood and tissue esterases and undergoes rapid metabolism, independent of the duration of infusion or any organ insufficiency. There are data indicating that remifentanil can be used for analgesia and sedation in all kinds of adult intensive care unit patients, and that its use will result in rapid and predictable offset of effect. This may permit both a significant reduction in weaning and extubation times, and clear differentiation between over-sedation and brain dysfunction. This article provides an overview of the use of short-acting opioids in the intensive care unit, with special emphasis on remifentanil. It summarizes the currently available study data regarding remifentanil and provides recommendations for clinical use of this agent.

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

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 &mgr;g/mL (smallest) to 6.3 ± 1.3 &mgr;g/mL (largest) during these subsequent increases and decreases of propofol. In terms of prediction probability (PK) the performance of the Narcotrend index (PK = 0.88 ± 0.03) to predict propofol effect site concentrations was comparable to the BIS (PK = 0.85 ± 0.04). Using the respective EEG index as a measure of drug effect the mean ke0 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.

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 &mgr;g · kg−1 · min−1) 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 &mgr;g/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.

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

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 &mgr;g · kg−1 · min−1 remifentanil and 2 mg/kg propofol. After tracheal intubation, remifentanil was infused at a constant rate of 0.2 &mgr;g · kg−1 · min−1 whereas desflurane in 1.5 L/min O2/air was adjusted according to clinical variables or the following target values: during maintenance of anesthesia to a value of “D0” (Narcotrend) or “50” (BIS), 15 min before the end of surgery to “C1” (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.

Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass.

We investigated the specificity for gram-negative stimuli as well as the contribution of signal transduction pathways for leukocyte hyporesponsiveness in sepsis or following cardiopulmonary bypass (CPB). Whole blood of nine patients undergoing CPB and 25 patients with severe sepsis was stimulated ex vivo with LPS (E. coli O111:B4) or with Staphylococcus aureus Cowan strain I (SAC-I) lysate in the absence or presence of inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), or protein-tyrosine phosphatase (PTP). Both toxins stimulated a TNF-&agr; response through PTK signaling. Although suppression of the cytokine response was similar for LPS and SAC-I after CPB, it was significantly more pronounced for SAC-I in sepsis. Inhibition of PTP failed to increase TNF-&agr; upon LPS, whereas a moderate increase was observed with SAC-I. Impaired TNF-&agr; responses occur in sepsis and after CPB. Although this has primarily been reported for gram-negative stimuli, our data suggest that this is even more pronounced for gram-positive stimuli in severe sepsis. Although PTK was the predominant signaling pathway, inhibition of PTP only partially restored the TNF-&agr; response to SAC-I. Our results suggest that cellular mechanisms underlying monocyte deactivation are different in sepsis or following CPB and are discriminate for gram-positive and gram-negative toxins.

General anesthesia versus monitored anesthesia care with remifentanil for assisted reproductive technologies: effect on pregnancy rate

STUDY OBJECTIVES To compare the outcome of assisted reproductive technology procedures in women who undergo monitored anesthesia care (MAC) with remifentanil versus general anesthesia. DESIGN Retrospective data analysis. SETTING University hospital. PATIENTS 251 ASA physical status I and II women participating in an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) program. INTERVENTIONS During the first phase of the study, all patients underwent general anesthesia induction with alfentanil, propofol, and nitrous oxide, which was maintained with isoflurane or propofol infusion. In the second phase of the study, all patients received a standardized MAC technique with a remifentanil infusion; local anesthetics were not used. MEASUREMENTS The primary endpoint was pregnancy rate per transfer. The number of oocytes collected, fertilized, and cleaved was recorded, as was the number of oocytes transferred. MAIN RESULTS Patients who underwent MAC had a greater pregnancy rate with IVF (28.2 vs. 16.3%), with ICSI (32.2% vs. 18.8%), and overall (30.6% vs. 17.9%). CONCLUSIONS Pregnancy rates in women undergoing transvaginal oocyte retrieval for assisted reproductive technologies were significantly higher with a remifentanil-based MAC technique than with a general anesthetic technique.