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Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total i.v. anaesthesia in the pig.
British Journal of Anaesthesia 1997; 78: 326–327
Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total i.v. anaesthesia in the pig
T. MARX, G. FROEBA, D. WAGNER, S. BAEDER, A. GOERTZ AND M. GEORGIEFF
Summary In order to investigate haemodynamic response and catecholamine release during anaesthesia with xenon, we conducted a study on 28 pigs which were allocated randomly to one of four groups: total i.v. anaesthesia with pentobarbitone and buprenorphine, and xenon anaesthesia with inspiratory concentrations of 30%, 50% or 70%, respectively, supplemented with pentobarbitone. Haemodynamic variables were measured using arterial and Swan Ganz catheters. Depth of anaesthesia was monitored using spectral edge frequency analysis. Plasma concentrations of dopamine, noradrenaline and adrenaline were measured by high pressure liquid chromatography. All haemodynamic variables and plasma concentrations of dopamine and noradrenaline remained within normal limits. Adrenaline concentrations were reduced significantly in all groups. Xenon anaesthesia was associated with a high degree of cardiovascular stability. Significant reduction in adrenaline concentrations at inspiratory xenon concentrations of 30% and 50% can be explained by analgesic effects of xenon below its MAC value. (Br. J. Anaesth. 1997; 78: 326–327) Key words Anaesthetics volatile, xenon. Sympathetic nervous system, catecholamines. Cardiovascular system, effects. Pig.
To investigate dose-dependent influences of xenon anaesthesia on haemodynamic variables and catecholamine release, we studied different concentrations of xenon in an animal experiment. In a study performed with 70% xenon supplemented by fentanyl, heart beat frequencies (HBF), arterial pressure and plasma catecholamine concentrations were measured, and the data compared with values obtained during nitrous oxide anaesthesia. Increases in noradrenaline concentrations, decreases in plasma adrenaline concentrations and a tendency for the HBF to decrease were seen. The cumulative dose of fentanyl was reduced by 80% in the xenon group.1 2 Cardiac contractility, monitored by transoesophageal echocardiography, was not influenced by xenon anaesthesia.3
Methods and results We studied 28 pigs, aged 12–16 weeks, weighing
34.5–42.9 kg which were allocated randomly to one of four groups: group 1, total i.v. anaesthesia; group 2, anaesthesia with inspiratory xenon concentrations of 30%; group 3, 50% xenon; group 4, 70% xenon. Anaesthesia was induced with a bolus dose of pentobarbitone 8 mg kg91 and buprenorphine 0.01 mg kg91 i.v. Neuromuscular block was produced with a single dose of alcuronium 0.25 mg kg91. Anaesthesia was maintained with a constant infusion of pentobarbitone 0.2 mg kg91 min91. The rate of infusion was adjusted to the level of anaesthesia. Depth of anaesthesia was assessed using a spectral edge frequency SEF95 monitor. Intermittent positive pressure ventilation was carried out using a partial rebreathing system and ventilation volume was adjusted to achieve normocapnia. Inspiratory and expiratory xenon concentrations were measured by mass spectrometry. A Swan-Ganz catheter was placed via the right internal jugular vein and a cannula was inserted into the right femoral artery. After these procedures the animals were left unstimulated for 60 min. The femoral artery was then dissected by open surgery under anaesthesia according to the randomization. At the request of the Animal Care Commission, animals in the TIVA group received an additional analgesic dose of buprenorphine 0.01 mg kg91 before skin incision. In the xenon groups, no additional analgesia was given. Serum concentrations of adrenaline, noradrenaline and dopamine were measured using high pressure liquid chromatography (HPLC) (table 1). The detection limit of each catecholamine was 2 pg ml91; accuracy was 3.9% for noradrenaline, 5.2% for adrenaline and 5.0% for dopamine.
Comment We observed a significant reduction in plasma adrenaline concentrations during xenon anaesthesia, not only at inspiratory concentrations of approximately 1 MAC, but even at subanaesthetic concentrations of 30% and 50%. Because all animals in the xenon groups received significantly less pentobarbitone than THOMAS MARX, MD, GEBHARD FROEBA MD, DORIS WAGNER, STEFAN BAEDER, BS, AXEL GOERTZ, MD, MICHAEL GEORGIEFF, MD, University of Ulm, Universitaetsklinik fuer Anaesthesiologie, Postfach 3880, 89070 Ulm, Germany. Accepted for publication: October 30, 1996.
Anaesthesia with different concentrations of xenon
327
Table 1 Haemodynamic variables (cardiac index, mean arterial pressure, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR)), plasma catecholamine concentrations and dose of additional i.v. pentobarbitone (median (25th–75th percentiles). *P:0.05 compared with control Group
Cardiac index (litre min91 m2) Mean arterial pressure (mm Hg) Mean pulmonary pressure (mm Hg) SVR (dyn s cm95) PVR (dyn s cm95) Adrenaline (pg ml91) Dopamine (pg ml91) Noradrenaline (pg ml91) Infusion rate of pentobarbitone (mg kg91 min91)
Control
TIVA
Xenon 30%
Xenon 50%
Xenon 70%
4.90 (4.51–5.60) 105.0 (96.0–110.0) 19.0 (15.75–21.25) 1366.5 (1175.0–1560.0) 188.0 (159.0–224.5) 84.0 (40.8–223.0) 73.5 (49.5–126.0) 48.0 (31.0–76.0) 0.470 (0.38–0.48)
4.92 (4.23–5.31) 96.0 (87.0–103.0) 17.0 (15.0–19.0) 1419.0 (1175.75–1561.25) 186.0 (154.75–220.0) 15.0* (15.0–46.8) 130.5 (86.5–177.0) 40.0 (30.8–71.3) 0.234* (0.22–0.24)
4.79 (4.41–5.0) 104.0 (97.0–109.0) 20.0 (18.0–21.0) 1463.0 (1273.25–1517.0) 176.0 (161.25–189.0) 39.0* (15.5–53.0) 85.0 (53.0–131.0) 52.5 (36.5–66.0) 0.12* (0.11–0.17)
4.31 (4.05–4.65) 109.50 (107.0–115.0) 20.50 (18.0–22.0) 1486.5 (1327.0–1653.0) 210.0 (179.25–243.0) 17.0* (15.0–32.5) 63.5 (47.5–110.5) 30.0* (21.0–47.0) 0.092* (0.07–0.10)
4.46 (4.29–4.83) 110.0 (98.0–114.0) 21.0 (19.0–22.0) 1475.0 (1423.25–1790.75) 220.5 (208.0–238.0) 15.0* (15.0–48.0) 77.0 (45.5–112.5) 42.5 (29.0–62.0) 0.093* (0.06–0.12)
those in the TIVA group, although no additional buprenorphine was given, the decrease in adrenaline concentrations in the xenon groups may have been produced by the analgesic effects of xenon, even in concentrations below its MAC value.4 All haemodynamic variables were not influenced by xenon anaesthesia and remained at normal values for conscious pigs and during anaesthesia. Because infusion rates of pentobarbitone of up to 0.6 mg kg91 min91 are known not to influence mean arterial pressure and cardiac output,5 the influence of additional pentobarbitone infusion on haemodynamic values may be regarded as unimportant in our study. Therefore, we found that xenon was an inhalation anaesthetic with little influence on the cardiovascular system. This may represent an important difference to other inhalation anaesthetics.6
Acknowledgement The study was supported by the Deutsche Bundesstiftung Umwelt (German Federal Foundation for Environmental Protection), Osnabrueck, Germany
References 1. Boomsma F, Rupreht J, Man in T’Veld AJ, De Jong FH, Dzoljic M, Lachmann B. Haemodynamic and neurohumeral effects of xenon anaesthesia. Anaesthesia 1990; 45: 273–278. 2. Lachmann B, Armbruster S, Schairer W, Landstra M, Trowburst A, van Daal GJ, Kusuma A, Erdmann W. Safety and efficacy of xenon in routine use as an inhalational agent. Lancet 1990; 335: 1413–1415. 3. Luttropp HH, Romner B, Perhag L, Eskilsson J, Frederiksen S, Werner O. Left ventricular performance and cerebral haemodynamics during xenon anaesthesia. Anaesthesia 1993; 48: 1045–1049. 4. Yagi M, Mahimo T, Kawaguchi T, Yoshiva T. Analgesic and hypnotic effects of subanaesthetic concentrations of xenon in human volunteers; comparison with nitrous oxide. British Journal of Anaesthesia 1995; 74: 670–673. 5. Todd MM, Drummond JC. Hemodynamic effects of high dose pentobarbital: studies in elective neurosurgical patients. Neurosurgery 1987; 20: 559–563. 6. Pagel PS, Kampine JP, Schmeling WT, Warltier DC. Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane and enflurane in the chronically instrumented dog. Anesthesiology 1991; 74: 539–551.
Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total i.v. anaesthesia in the pig
T. MARX, G. FROEBA, D. WAGNER, S. BAEDER, A. GOERTZ AND M. GEORGIEFF
Summary In order to investigate haemodynamic response and catecholamine release during anaesthesia with xenon, we conducted a study on 28 pigs which were allocated randomly to one of four groups: total i.v. anaesthesia with pentobarbitone and buprenorphine, and xenon anaesthesia with inspiratory concentrations of 30%, 50% or 70%, respectively, supplemented with pentobarbitone. Haemodynamic variables were measured using arterial and Swan Ganz catheters. Depth of anaesthesia was monitored using spectral edge frequency analysis. Plasma concentrations of dopamine, noradrenaline and adrenaline were measured by high pressure liquid chromatography. All haemodynamic variables and plasma concentrations of dopamine and noradrenaline remained within normal limits. Adrenaline concentrations were reduced significantly in all groups. Xenon anaesthesia was associated with a high degree of cardiovascular stability. Significant reduction in adrenaline concentrations at inspiratory xenon concentrations of 30% and 50% can be explained by analgesic effects of xenon below its MAC value. (Br. J. Anaesth. 1997; 78: 326–327) Key words Anaesthetics volatile, xenon. Sympathetic nervous system, catecholamines. Cardiovascular system, effects. Pig.
To investigate dose-dependent influences of xenon anaesthesia on haemodynamic variables and catecholamine release, we studied different concentrations of xenon in an animal experiment. In a study performed with 70% xenon supplemented by fentanyl, heart beat frequencies (HBF), arterial pressure and plasma catecholamine concentrations were measured, and the data compared with values obtained during nitrous oxide anaesthesia. Increases in noradrenaline concentrations, decreases in plasma adrenaline concentrations and a tendency for the HBF to decrease were seen. The cumulative dose of fentanyl was reduced by 80% in the xenon group.1 2 Cardiac contractility, monitored by transoesophageal echocardiography, was not influenced by xenon anaesthesia.3
Methods and results We studied 28 pigs, aged 12–16 weeks, weighing
34.5–42.9 kg which were allocated randomly to one of four groups: group 1, total i.v. anaesthesia; group 2, anaesthesia with inspiratory xenon concentrations of 30%; group 3, 50% xenon; group 4, 70% xenon. Anaesthesia was induced with a bolus dose of pentobarbitone 8 mg kg91 and buprenorphine 0.01 mg kg91 i.v. Neuromuscular block was produced with a single dose of alcuronium 0.25 mg kg91. Anaesthesia was maintained with a constant infusion of pentobarbitone 0.2 mg kg91 min91. The rate of infusion was adjusted to the level of anaesthesia. Depth of anaesthesia was assessed using a spectral edge frequency SEF95 monitor. Intermittent positive pressure ventilation was carried out using a partial rebreathing system and ventilation volume was adjusted to achieve normocapnia. Inspiratory and expiratory xenon concentrations were measured by mass spectrometry. A Swan-Ganz catheter was placed via the right internal jugular vein and a cannula was inserted into the right femoral artery. After these procedures the animals were left unstimulated for 60 min. The femoral artery was then dissected by open surgery under anaesthesia according to the randomization. At the request of the Animal Care Commission, animals in the TIVA group received an additional analgesic dose of buprenorphine 0.01 mg kg91 before skin incision. In the xenon groups, no additional analgesia was given. Serum concentrations of adrenaline, noradrenaline and dopamine were measured using high pressure liquid chromatography (HPLC) (table 1). The detection limit of each catecholamine was 2 pg ml91; accuracy was 3.9% for noradrenaline, 5.2% for adrenaline and 5.0% for dopamine.
Comment We observed a significant reduction in plasma adrenaline concentrations during xenon anaesthesia, not only at inspiratory concentrations of approximately 1 MAC, but even at subanaesthetic concentrations of 30% and 50%. Because all animals in the xenon groups received significantly less pentobarbitone than THOMAS MARX, MD, GEBHARD FROEBA MD, DORIS WAGNER, STEFAN BAEDER, BS, AXEL GOERTZ, MD, MICHAEL GEORGIEFF, MD, University of Ulm, Universitaetsklinik fuer Anaesthesiologie, Postfach 3880, 89070 Ulm, Germany. Accepted for publication: October 30, 1996.
Anaesthesia with different concentrations of xenon
327
Table 1 Haemodynamic variables (cardiac index, mean arterial pressure, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR)), plasma catecholamine concentrations and dose of additional i.v. pentobarbitone (median (25th–75th percentiles). *P:0.05 compared with control Group
Cardiac index (litre min91 m2) Mean arterial pressure (mm Hg) Mean pulmonary pressure (mm Hg) SVR (dyn s cm95) PVR (dyn s cm95) Adrenaline (pg ml91) Dopamine (pg ml91) Noradrenaline (pg ml91) Infusion rate of pentobarbitone (mg kg91 min91)
Control
TIVA
Xenon 30%
Xenon 50%
Xenon 70%
4.90 (4.51–5.60) 105.0 (96.0–110.0) 19.0 (15.75–21.25) 1366.5 (1175.0–1560.0) 188.0 (159.0–224.5) 84.0 (40.8–223.0) 73.5 (49.5–126.0) 48.0 (31.0–76.0) 0.470 (0.38–0.48)
4.92 (4.23–5.31) 96.0 (87.0–103.0) 17.0 (15.0–19.0) 1419.0 (1175.75–1561.25) 186.0 (154.75–220.0) 15.0* (15.0–46.8) 130.5 (86.5–177.0) 40.0 (30.8–71.3) 0.234* (0.22–0.24)
4.79 (4.41–5.0) 104.0 (97.0–109.0) 20.0 (18.0–21.0) 1463.0 (1273.25–1517.0) 176.0 (161.25–189.0) 39.0* (15.5–53.0) 85.0 (53.0–131.0) 52.5 (36.5–66.0) 0.12* (0.11–0.17)
4.31 (4.05–4.65) 109.50 (107.0–115.0) 20.50 (18.0–22.0) 1486.5 (1327.0–1653.0) 210.0 (179.25–243.0) 17.0* (15.0–32.5) 63.5 (47.5–110.5) 30.0* (21.0–47.0) 0.092* (0.07–0.10)
4.46 (4.29–4.83) 110.0 (98.0–114.0) 21.0 (19.0–22.0) 1475.0 (1423.25–1790.75) 220.5 (208.0–238.0) 15.0* (15.0–48.0) 77.0 (45.5–112.5) 42.5 (29.0–62.0) 0.093* (0.06–0.12)
those in the TIVA group, although no additional buprenorphine was given, the decrease in adrenaline concentrations in the xenon groups may have been produced by the analgesic effects of xenon, even in concentrations below its MAC value.4 All haemodynamic variables were not influenced by xenon anaesthesia and remained at normal values for conscious pigs and during anaesthesia. Because infusion rates of pentobarbitone of up to 0.6 mg kg91 min91 are known not to influence mean arterial pressure and cardiac output,5 the influence of additional pentobarbitone infusion on haemodynamic values may be regarded as unimportant in our study. Therefore, we found that xenon was an inhalation anaesthetic with little influence on the cardiovascular system. This may represent an important difference to other inhalation anaesthetics.6
Acknowledgement The study was supported by the Deutsche Bundesstiftung Umwelt (German Federal Foundation for Environmental Protection), Osnabrueck, Germany
References 1. Boomsma F, Rupreht J, Man in T’Veld AJ, De Jong FH, Dzoljic M, Lachmann B. Haemodynamic and neurohumeral effects of xenon anaesthesia. Anaesthesia 1990; 45: 273–278. 2. Lachmann B, Armbruster S, Schairer W, Landstra M, Trowburst A, van Daal GJ, Kusuma A, Erdmann W. Safety and efficacy of xenon in routine use as an inhalational agent. Lancet 1990; 335: 1413–1415. 3. Luttropp HH, Romner B, Perhag L, Eskilsson J, Frederiksen S, Werner O. Left ventricular performance and cerebral haemodynamics during xenon anaesthesia. Anaesthesia 1993; 48: 1045–1049. 4. Yagi M, Mahimo T, Kawaguchi T, Yoshiva T. Analgesic and hypnotic effects of subanaesthetic concentrations of xenon in human volunteers; comparison with nitrous oxide. British Journal of Anaesthesia 1995; 74: 670–673. 5. Todd MM, Drummond JC. Hemodynamic effects of high dose pentobarbital: studies in elective neurosurgical patients. Neurosurgery 1987; 20: 559–563. 6. Pagel PS, Kampine JP, Schmeling WT, Warltier DC. Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane and enflurane in the chronically instrumented dog. Anesthesiology 1991; 74: 539–551.