Matthias Reyle-Hahn

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 &mgr;g) 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.

Xenon anaesthesia may preserve cardiovascular function in patients with heart failure

Background:  The hypothesis that xenon anaesthesia provided haemodynamic stability was tested in patients with heart failure in a prospective, randomized, single‐blind design.

Xenon does not impair the responsiveness of cardiac muscle bundles to positive inotropic and chronotropic stimulation.

Background Most volatile anesthetics exhibit a direct myocardial depressant effect. This side effect often limits their applicability in patients with impaired cardiac function. Xenon is a new gaseous anesthetic that did not show any adverse cardiovascular effects in clinical and experimental studies. The authors tested the hypothesis that xenon does not affect myocardial contractility or the positive inotropic effect of isoproterenol, calcium, and increase in pacing rate in isolated guinea pig ventricular muscle bundles. Methods Thin ventricular muscle bundles from guinea pig hearts with a mean diameter of 0.4–0.45 mm were prepared under stereomicroscopic control. Force of contraction and contraction times were studied in muscles superfused with medium equilibrated with either 65% xenon and 35% oxygen (xenon group), 1.2% isoflurane in oxygen (isoflurane group), or 65% nitrogen and 35% oxygen (control group). In addition, the positive inotropic effects of calcium, isoproterenol (10−10 − 3 × 10−8 m) and increasing frequency (0.5–2 Hz) were studied during xenon and isoflurane exposure. Results In contrast to isoflurane, xenon did not alter myocardial force of contraction or contraction times. The positive inotropic effect of isoproterenol, calcium, and increasing pacing frequencies did not differ between the muscles exposed to xenon and the control group. Isoflurane elicited the expected negative inotropic effect (30% reduction of force of contraction) but did not impair the response to inotropic stimuli. Conclusions Xenon does not alter myocardial contractility and the response to inotropic stimuli such as calcium, isoproterenol, or increase in pacing frequency in isolated guinea pig ventricular muscle bundles.

The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in Beagle dogs

The noble gas xenon seems to have minimal cardiovascular side-effects and so may be an ideal anaesthetic agent when investigating cardiovascular physiology. In comparison with standard modern anaesthetics, we investigated the haemodynamic and hormonal effects of xenon in Beagle dogs. After a 30 min baseline period, anaesthesia was induced with propofol and maintained with either (1) 1.2% isoflurane/70% nitrous oxide (N2O), (2) 0.8% isoflurane/0.5 µg/kg/min remifentanil or (3) 63% xenon/0.5 µg/kg/min remifentanil (n = 6 per group). Haemodynamics were recorded and blood samples taken before and 60 min after induction. Mean arterial blood pressure (MAP) was higher in conscious dogs than during isoflurane/N2O (86 ± 2 vs. 65 ± 2 mmHg, mean ± SEM) and isoflurane/remifentanil anaesthesia (95 ± 2 vs. 67 ± 3 mmHg), whereas MAP did not decrease significantly in response to xenon/remifentanil anaesthesia (96 ± 4 vs. 85 ± 6 mmHg). Bradycardia was present during isoflurane/remifentanil (54 ± 2/min) and xenon/remifentanil (40 ± 3/min), but not during isoflurane/N2O anaesthesia (98 ± 3/min, P < 0.05). Xenon/remifentanil anaesthesia induced the highest reduction in cardiac output (CO) (–61%), and the highest increase in systemic vascular resistance (+120%) among all treatment groups (P < 0.05). A simultaneous increase in endogenous adrenaline and noradrenaline concentrations could only be observed in the xenon/remifentanil group, whereas angiotensin II and vasopressin concentrations increased in all groups. In conclusion, xenon/remifentanil anaesthesia maintains MAP but reduces heart rate and CO and is associated with a considerable stimulation of vasopressor hormones in Beagle dogs. Therefore, xenon/remifentanil exerts a new quality of adverse haemodynamic effects different from volatile anaesthetics and may not perform better during studies of cardiovascular physiology.

Effect of PEEP and inhaled nitric oxide on pulmonary gas exchange during gaseous and partial liquid ventilation with small volumes of perfluorocarbon

Background: Partial liquid ventilation, positive end‐expiratory pressure (PEEP) and inhaled nitric oxide (NO) can improve ventilation/perfusion mismatch in acute lung injury (ALI). The aim of the present study was to compare gas exchange and hemodynamics in experimental ALI during gaseous and partial liquid ventilation at two different levels of PEEP, with and without the inhalation of nitric oxide.

Die Entwöhnung von der Beatmung

Die maschinelle Beatmung gehort heute zu den intensivmedizinischen Routinemasnahmen bei der Behandlung der respiratorischen Insuffizienz. In den letzten Jahren konnte allerdings in einer Vielzahl von Untersuchungen gezeigt werden, das die Beatmungstherapie mit nennenswerten Risiken und unerwunschten Nebenwirkungen behaftet ist. Der wesentliche Faktor hierfur ist die Umkehrung der intrathorakalen Druckverhaltnisse wahrend der Beatmung mit positivem Druck mit den hieraus resultierenden negativen Ruckwirkungen auf das kardio-zirkulatorische System und die Organperfusion sowie der Gefahr, die Lunge mit hohen Drucken oder Volumina im Sinne eines Barotrauma oder Volutrauma zu schadigen. Zusatzlich konnte mehrfach gezeigt werden, das die Dauer der Intubation und Beatmung einen wesentlichen Risikofaktor fur die Entwicklung einer nosokomialen Pneumonie darstellt. Ruiz-Santana und Mitarbeiter [1] berichteten uber eine Zunahme der Pneumonierate von 8,5% in den ersten drei Tagen nach Intubation bis auf 45,6% nach dem vierzehnten Tag. Diese Befunde haben zu dem Grundsatz gefuhrt, die Dauer der maschinellen Beatmung zu verkurzen und somit den Patienten so schnell wie moglich zu extubieren.

Xenon/remifentanil anesthesia protects against adverse effects of losartan on hemodynamic challenges induced by anesthesia and acute blood loss.

The authors aimed to test the hypothesis that xenon anesthesia limits adverse hypotensive effects of losartan during acute hemorrhage. In six conscious unsedated Beagle dogs, the systemic and pulmonary circulation were monitored invasively, and two subsequent 60-min hypotensive challenges were performed by (a) induction (propofol) and maintenance of anesthesia with isoflurane/remifentanil or xenon/remifentanil and by (b) subsequent hemorrhage (20 mL kg−1 within 5 min) from a central vein. The same amount of blood was retransfused 1 h after hemorrhage. Experiments were performed with or without acute angiotensin II receptor subtype 1 blockade by i.v. losartan (100 &mgr;g·kg−1·min−1) starting 45 min before induction of anesthesia. Four experiments were performed in each individual dog. Xenon/remifentanil anesthesia provided higher baseline mean arterial blood pressure (85 ± 6 mmHg) than isoflurane/remifentanil anesthesia (67 ± 3 mmHg). In losartan-treated animals, isoflurane/remifentanil caused significant hypotension (42 ± 4 mmHg for isoflurane/remifentanil vs. 71 ± 6 mmHg for xenon/remifentanil). Independent of losartan, hemorrhage did not induce any further reduction of mean arterial blood pressure or cardiac output in either group. Spontaneous hemodynamic recovery was observed in all groups before retransfusion was started. Losartan did not alter the adrenaline, noradrenaline, and vasopressin response to acute hemorrhage. Losartan potentiates hypotension induced by isoflurane/remifentanil anesthesia but does not affect the hemodynamic stability during xenon/remifentanil anesthesia. Losartan does not deteriorate the hemodynamic adaptation to hemorrhage of 20 mL kg−1 during xenon/remifentanil and isoflurane/remifentanil anesthesia. Therefore, xenon/remifentanil anesthesia protects against circulatory side effects of losartan pretreatment and thus may afford safer therapeutic use of losartan during acute hemorrhage.ABBREVIATIONS-AT1 receptor-angiotensin II receptor subtype 1; CO-cardiac output; CVP-central venous pressure; HR-heart rate; I/R-isoflurane/remifentanil; MAP-mean arterial blood pressure; MPAP-mean pulmonary artery pressure; SVR-systemic vascular resistance; PCWP-pulmonary capillary wedge pressure; PVR-pulmonary vascular resistance; X/R-xenon/remifentanil

In Vitro Model for Cardiac Function under Xenon Anesthesia

To the Editor:—In his editorial, Eisenach highlighted an interesting paradox; while attempting to produce profound analgesia with high doses of potent opioids, it is possible to produce a “preemptive hyperalgesic” effect. In the two human studies referenced, high doses of systemic remifentanil and fentanyl produced acute hyperalgesia. In a previous human study, we found evidence that intrathecal fentanyl administration can produce acute spinal hyperalgesia. Administration of 25 mg intrathecal fentanyl during Cesarean section increased postoperative intravenous morphine requirements by 63% between 6 and 23 h postdelivery. In his editorial, Bernards mentions his concern that “alfentanil and sufentanil (and to some extent fentanyl)” are used in the epidural space, “. . .despite mounting evidence that these opioids do not produce analgesia by a selective spinal mechanism.” However, there is evidence that epidural fentanyl, when it is administered in the minimal effective dose, has a selective spinal action. In humans, lumbar cerebrospinal fluid levels of fentanyl increase rapidly after epidural fentanyl administration, and Bernards and Sorkin have shown that, in pigs, “epidural fentanyl moves rapidly from the epidural space to the spinal cord.” Prolonged postoperative epidural fentanyl administration can produce plasma levels similar to those of systemic administration. However, spinal cord levels of fentanyl still would be expected to be higher after epidural than after systemic administration. It is therefore surprising that the analgesic effectiveness of epidural and systemic fentanyl often are reported to be comparable, even if plasma levels are similar. This is especially so if, as suggested by Bernards, there is synergy between spinal and supraspinal opioid analgesia in humans. It may be that, by producing relatively high spinal compared with systemic levels of fentanyl, epidural fentanyl administration can induce acute selective spinal hyperalgesia. The greater the magnitude of selective spinal hyperalgesia induced, the smaller the difference in analgesic effectiveness of epidural and systemic fentanyl would be. This could help to explain why several studies have not found a difference between epidural and systemic fentanyl analgesia. Administration of epidural fentanyl in the minimal effective dose may limit the development of spinal hyperalgesia, thereby facilitating selective spinal analgesia. David W. Cooper, M.B.B.S., F.R.C.A., Consultant Anaesthetist, Department of Anaesthesia, South Cleveland Hospital, Middlesbrough, Cleveland, United Kingdom dr_david_cooper@hotmail.com

Die Entwöhnung von der Beatmung Teil 1

Die maschinelle Beatmung gehört heute zu den intensivmedizinischen Routinemaßnahmen bei der Behandlung der respiratorischen Insuffizienz. In den letzten Jahren konnte allerdings in einer Vielzahl von Untersuchungen gezeigt werden, daß die Beatmungstherapie mit nennenswerten Risiken und unerwünschten Nebenwirkungen behaftet ist. Der wesentliche Faktor hierfür ist die Umkehrung der intrathorakalen Druckverhältnisse während der Beatmung mit positivem Druck mit den hieraus resultierenden negativen Rückwirkungen auf das kardio-zirkulatorische System und die Organperfusion sowie der Gefahr, die Lunge mit hohen Drücken oder Volumina im Sinne eines Barotrauma oder Volutrauma zu schädigen. Zusätzlich konnte mehrfach gezeigt werden, daß die Dauer der Intubation und Beatmung einen wesentlichen Risikofaktor für die Entwicklung einer nosokomialen Pneumonie darstellt. Ruiz-Santana und Mitarbeiter [1] berichteten über eine Zunahme der Pneumonierate von 8,5% in den ersten drei Tagen nach Intubation bis auf 45,6% nach dem vierzehnten Tag. Diese Befunde haben zu dem Grundsatz geführt, die Dauer der maschinellen Beatmung zu verkürzen und somit den Patienten so schnell wie möglich zu extubieren.

Xenon does not increase heart rate-corrected cardiac QT interval in volunteers and in patients free of cardiovascular disease.

Background:Impaired cardiac repolarization, indicated by prolonged QT interval, may cause critical ventricular arrhythmias. Many anesthetics increase the QT interval by blockade of rapidly acting potassium rectifier channels. Although xenon does not affect these channels in isolated cardiomyocytes, the authors hypothesized that xenon increases the QT interval by direct and/or indirect sympathomimetic effects. Thus, the authors tested the hypothesis that xenon alters the heart rate–corrected cardiac QT (QTc) interval in anesthetic concentrations. Methods:The effect of xenon on the QTc interval was evaluated in eight healthy volunteers and in 35 patients undergoing abdominal or trauma surgery. The QTc interval was recorded on subjects in awake state, after their denitrogenation, and during xenon monoanesthesia (FetXe > 0.65). In patients, the QTc interval was recorded while awake, after anesthesia induction with propofol and remifentanil, and during steady state of xenon/remifentanil anesthesia (FetXe > 0.65). The QTc interval was determined from three consecutive cardiac intervals on electrocardiogram printouts in a blinded manner and corrected with Bazett formula. Results:In healthy volunteers, xenon did not alter the QTc interval (mean difference: +0.11 ms [95% CI, −22.4 to 22.7]). In patients, after anesthesia induction with propofol/remifentanil, no alteration of QTc interval was noted. After propofol was replaced with xenon, the QTc interval remained unaffected (417 ± 32 ms vs. awake: 414 ± 25 ms) with a mean difference of 4.4 ms (95% CI, −4.6 to 13.5). Conclusion:Xenon monoanesthesia in healthy volunteers and xenon/remifentanil anesthesia in patients without clinically relevant cardiovascular disease do not increase QTc interval.