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Einfluss des EEG-Monitorings auf das Dosierverhalten bei intravenöser Anästhesie – Eine multizentrische Analyse
Abstract
Einleitung: Es sollte geprüft werden, ob das EEG-Monitoring das Dosierverhalten bei Propofolnarkosen beeinflusst, unter besonderer Berücksichtigung von Alter, Geschlecht, Propofol-Applikationsform und Opioidauswahl.
Methodik: In 32 Zentren erhielten 3 542 Patienten Narkosen entweder als total-intravenöse Anästhesie (TIVA) oder target-controlled infusion (TCI). Die Steuerung erfolgte bei 472 Anästhesien nach klinischen Kriterien mit verblindet registriertem EEG, bei 3 070 Anästhesien mithilfe des EEG. Als EEG-Monitor wurde der Narcotrend® verwendet, der eine Einteilung des Narkose-EEG von Stadium A (wach) bis F (sehr tiefe Hypnose) vornimmt.
Ergebnisse: Ohne EEG-Monitoring lagen 5,9% der Narkosen im sehr flachen B/C-Bereich (erhöhtes Awareness-Risiko), 18,7% dagegen im Burst-Suppression-Bereich (individuelle Überdosierung der Allgemeinanästhesie, Stadium F). 67,2% hatten mit D/E ein dem Tiefschlaf entsprechendes Stadium. Durch das EEG-Monitoring änderte sich in den Zentren die Propofoldosierung um −28,4% bis +86,2%. Bei EEG-gesteuerten Narkosen erhielten Frauen im Mittel mehr Propofol als Männer und hatten kürzere Aufwachzeiten. Zudem nahmen die Propofoldosierungen mit zunehmendem Alter stärker ab als ohne EEG, wobei sich die Dosierungen von Frauen und Männern mit steigendem Lebensalter anglichen. Das kurzwirksame Opioid Remifentanil führte im Vergleich zu Fentanyl zu einer signifikanten Reduzierung von Propofolbedarf und Aufwachzeit. Das EEG-Monitoring bewirkte bei der TCI eine deutliche Abnahme des Propofolverbrauchs.
Diskussion: Nach klinischen Kriterien geführte Narkosen waren in erheblicher Zahl zu flach oder zu tief. Das EEG-Monitoring führte zu wesentlichen Änderungen im Dosierverhalten der Zentren.
Schlussfolgerung: Mithilfe des EEG-Monitorings lässt sich der individuelle Propofolbedarf in Abhängigkeit von Geschlecht, Alter und der Opioidauswahl ermitteln.
In this chapter, two kinds of cerebral monitoring are presented: electroencephalography (EEG) monitoring and intracranial pressure (ICP) monitoring. EEG monitoring is used in the operating room to assess the depth of hypnosis during anesthesia and to detect effects of hypoxia and of induced hypothermia. In intensive care unit patients, EEG monitoring can be used for the control of sedation, for therapy control, e.g. in status epilepticus, for the assessment of the patient’s current clinical status and trends thereof, and as an exploratory diagnostic tool with respect to epileptiform activity and focal brain disorders. Hypnotic drug effects are accompanied in a dose related manner by a slowing of the EEG. These EEG changes can be classified automatically. Especially through the automatic interpretation, EEG monitoring can be carried out as a routine method for patient monitoring with little effort. The aim of detecting and treating elevated ICP is to avoid secondary damage to the brain. The most common indication for ICP monitoring is trauma to the head. Methods for ICP measurement with higher invasiveness include intraventricular, intraparenchymal, or subdural catheter localisations. A less invasive method is epidural cerebral pressure measurement.
Die Registrierung der Hirnströme (Elektroenzephalogramm, EEG) eignet sich zur Patientenüberwachung im Operationssaal und auf
der Intensivstation (Freye u. Levy 2005).
It has repeatedly been shown that female patients wake up faster from propofol anaesthesia than male patients. The reason for this is not clear. It is possible that female patients have a more rapid decline in plasma propofol concentration after termination of an infusion, or there could be gender differences in the sensitivity to propofol, making women wake up at higher concentrations. We tested the hypothesis that women wake up faster because of a more rapid decline in plasma propofol.
Sixty adult patients (30 female and 30 male; ASA I or II) undergoing lower limb surgery under regional anaesthesia, were enrolled in an open study. Propofol was given as the only hypnotic drug, administered by the plasma target control system (TCI) Diprifusor, titrated to bispectral index (BIS) values of 40-60. Blood samples for propofol measurements were taken just before the propofol infusion was stopped and when the patients woke up.
The female patients woke up faster than the male patients (5.6 vs 8.2 min, P=0.003). The plasma propofol concentration declined more rapidly in the women (P=0.02). An additional significant finding was that the TCI algorithm had a better fit for the women than for the men, with a median prediction error (MDPE) of 2% in the female patients compared with 40% in the male patients (P<0.001). At emergence the men had a significantly higher measured propofol concentration than the women (P=0.05).
The female patients had a more rapid decline in plasma propofol at the end of infusion. Gender differences in pharmacokinetics could explain the faster emergence for female patients after propofol anaesthesia, and gender differences in propofol sensitivity may also be present.
Einleitung: Es sollte geklärt werden, inwieweit eine Dosierung des Hypnotikums Propofol entsprechend dem Alter und dem Allgemeinzustand der Patienten mithilfe einer EEG-gestützten Narkoseüberwachung individuell vorgenommen werden kann. Methodik: Während Narkosen mit dem Opioid Remifentanil und dem Hypnotikum Propofol wurde das EEG bei 92 Patienten im Alter von 16 - 84 Jahren (ASA I - IV, 39 m., 53 w.) kontinuierlich mit dem EEG-Monitor Narcotrend® registriert. Die Propofolzufuhr erfolgte mittels einer TCI-Pumpe Diprifusor® und richtete sich nach dem EEG. Angestrebt waren EEG-Stadien im Bereich D2/E0, welche der tiefen Narkose zugeordnet werden. Untersucht wurden Propofoldosierungen und Aufwachzeiten in Abhängigkeit vom Alter und der ASA-Gruppe. Ergebnisse: Der Propofolbedarf nahm pro Lebensdekade um 4,1 % ab (20-Jährige: 3,13 µg/ml, 80-Jährige: 2,45 µg/ml). Die Zeiten vom Ende der Propofolzufuhr bis zum Öffnen der Augen und bis zur Extubation unterschieden sich weder in den ASA-Gruppen I, II und III/IV noch in den Altersgruppen ≤ 50, 51 - 70 und > 70 Jahre signifikant. Bei einer mittleren Remifentanildosierung von 0,22 ± 0,07 µg/kg KG/min betrug der mittlere TCI-Propofolblutspiegel 2,74 ± 0,51 µg/ml. Diskussion: Mithilfe des EEG-Monitorings lässt sich bei der Propofol/Remifentanil-Anästhesie eine altersgerechte und dem Allgemeinzustand angepasste Propofoldosierung ermitteln. Schlussfolgerung: Die routinemäßige Anwendung der EEG-gestützten Narkoseüberwachung kann hinsichtlich einer Optimierung perioperativer Abläufe, sowohl bei Eingriffen mit geplantem postoperativen stationären Aufenthalt als auch bei ambulanten Anästhesien, einen wesentlichen Beitrag leisten.
Impacts of hypnotic drugs on brain function are reflected in the EEG. The EEG monitor Narcotrend performs an automatic classification of the EEG using a scale which was proposed by Kugler for visual evaluation of the EEG. In this article the results of a validation study of the automatic classification algorithms implemented in the EEG monitor Narcotrend are presented. Visual and automatic classification of EEG data recorded in routine clinical practice were compared. The correlation between visual and automatic assessment was high (Spearman rank correlation r = 0.90, prediction probability Pk = 0.90) and a sufficient agreement between visual and automatic assessment was achieved for 92% of the analysed EEG epochs. The results of the study suggest that the automatic classification algorithms implemented in the EEG monitor Narcotrend yield a reliable assessment of the depth of hypnosis.
The Narcotrend is a new EEG monitor designed to measure the hypnotic component of anaesthesia; however, a major clinical evaluation is still missing. This prospective multicentre study was designed to investigate the feasibility of Narcotrend monitoring in a large number of patients under different clinical conditions and to define its impact on recovery times after propofol-based total intravenous anaesthesia.
After legal authority approval and patients'informed consent had been obtained, total intravenous anaesthesia was induced and maintained with propofol and an opioid analgesic at the discretion of the attending anaesthesiologist. In the first 10-15 patients of each centre the anaesthesiologist was blinded to the Narcotrend recordings and propofol was dosed according to clinical needs. In the following patients propofol was infused at a rate sufficient to achieve a target Narcotrend stage of D or E. With termination of propofol infusion,recovery times were recorded and analysed for the patients with or without Narcotrend monitoring; in addition, recovery times were analysed depending on the Narcotrend stage at the moment of termination of propofol infusion.
In total, 4,630 adult patients were studied at 46 institutions, 521 without and 4,109 with Narcotrend monitoring. Demographic data and duration of anaesthesia were comparable. Emergence from anaesthesia was significantly shorter in Narcotrend monitored patients, e.g.opening eyes after 9.8+/-5.9 (mean+/-SD) vs.11.8+/-7.1 min. In addition,awakening was significantly more rapid when the propofol infusion was stopped at a lower level of hypnosis as indicated by Narcotrend monitoring, e.g.opening eyes after 7.1+/-4.5 min with stage C instead of 17.0+/-7.4 min with stage F.
The EEG monitor Narcotrend can be used for adult patients of different ages and during various surgical procedures.Narcotrend monitoring facilitates a reduction of recovery times after propofol-based total intravenous anaesthesia,presumably by allowing for an individual titration of the propofol dosage. Moreover, it appears that the profile of recovery can be optimised when at the end of surgery,the propofol infusion is controlled to Narcotrend stage C instead of D, E, or F.
The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need for research.
Basis for this paper was obtained by Medline searches using the key words 'human' and 'gender' or 'sex,' combined with individual drug names. The reference lists of these papers were further checked for other relevant studies.
Females have 20-30% greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuronium. When rapid onset of or short duration of action is very important, gender-modified dosing may be considered. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30-40% in males compared with females in order to achieve similar recovery times. Females are more sensitive than males to opioid receptor agonists, as shown for morphine as well as for a number of kappa (OP2) receptor agonists. On this basis, males will be expected to require 30-40% higher doses of opioid analgesics than females to achieve similar pain relief. On the other hand, females may experience respiratory depression and other adverse effects more easily if they are given the same doses as males.
These examples illustrate that gender should be taken into account as a factor that may be predictive for the dosage of several anesthetic drugs. Moreover, there is an obvious need for more research in this area in order to further optimize drug treatment in anesthesia.