Acta Anaesthesiol &and 1990: 34: 253-256
Comparison of the effects of fentanyl on respiratory mechanics under propofol or thiopental anaesthesia I. CIGARINI, F. BONNET, A. M. LORINO, A. HARFand J. M. DESMONTS Departments of Anesthesiology and Physiology and INSERM U 29, Hopital Henri Mondor, Creteil and Department of Anesthesiology Hopital Bichat, Pans, France
Twenty patients were randomly anaesthetized with either thiopental 5 mg/kg followed by a 15 mg/kg/h continuous infusion, or propofol 2.5 mg/kg followed by a 9 mg/kg/h continuous infusion, paralysed with vecuronium 0.1 mg/kg, intubated and ventilated with nitrous oxide 50% in oxygen. Fifteen minutes after induction, fentanyl 5 pg/kg was injected. Inspiratory tracheal pressure (PT), gas flow (V) and volume (V) were continuously measured while the lungs were inflated with a constant inspiratory flow ventilator. Respiratory compliance (Crs) and resistance (Rrs) were calculated from the regression of P T on V. I n both groups Crs decreased following anaesthesia. Fentanyl injection elicited an increase in Rrs (from 1.04 k 0.70 to 1.63 t 0.92 kPa . I - ' . s) and a further decrease in Crs (from 0.55 0.30 to 0.42 f 0.10 1. kPa-') in the thiopental group but not in the propofol group (Rrs: 1.26 f 0.69 to 1.08 f 0.44 kPa . 1 - . s, Crs: 0.49 2 0.1 1 to 0.48k0.13 1 'kPa-'). These results suggest that the dose of propofol administered in this study may prevent fentanyl-induced bronchoconstriction.
'
Received 25 M q , accepted f o r publication 15 October 1989
Key words: Anesthetic agents: propofol; bronchomotor tone; compliance
Many anaesthetic agents can modify bronchomotor tone either by their own action or by interference with other stimuli (1). Most of them increase bronchomotor tone but only a few have overt bronchodilating properties (2, 3). Anaesthetic induction is a period especially at risk for bronchoconstriction because many different stimuli are simultaneously applied on airways. Anaesthetic induction often needs to be rapid, well controlled and managed. Propofol, (2-6 disopropylphenol), is a convenient, short-acting intravenous sedative hypnotic agent (4). Recently available in a new formulation as an aqueous emulsion, it does not provoke histamine release which was a possible side effect in the previous formulation including cremophor E. L. as a solvent (5, 6). We were therefore interested to evaluate the effect on respiratory mechanics of this new hypnotic agent, versus thiopental as a reference agent. PATIENTS AND METHODS Patients and anaesthetic procedures Twenty A.S.A. 1-11 patients were included in the study after obtaining approval from our local ethical committee and informed consent from the patients. Patients were excluded from the protocol if they had any history of asthma or allergy or if they were being treated with betaadrenergic blocking agents. All the patients were premedi-
-
resistance; respiratory mechanics.
cated orally with flunitrazepam 1 mg. Patients were allocated randomly to two groups according to the anaesthetic procedure. In the first group ( n = lo), induction of anaesthesia was performed with thiopental 5 mg/kg. Tracheal intubation was facilitated by vecuronium 0.1 mg/kg. A 15 mg/kg/h continuous infusion of thiopental followed anaesthetic induction. I n the second group (n = lo), patients received propofo12.5 mg/kg and vecuronium 0.1 mg/kg for induction and orotracheal intubation followed by a 9 mg/kg/h continuous infusion of propofol. In both groups controlled ventilation was maintained with a CPU I ventilator (Ohmeda) delivering nitrous oxide 50% in oxygen ( 7 ) . Ventilatory parameters were set as follows: tidal volume ( V T ) = 8 ml/kg, I / E = 1/2, respiratory rate= 12/min. Additional doses of 0.05 mg/kg vecuronium were administered if necessary during the study to block any response to the twitch stimulation. Fifteen minutes after induction of anesthesia, 5 pg/kg fentanyl were injected i.v. Surgery began 20 min after fentanyl injection. Measurements of respiratory mechanics Tracheal pressure (PT) was measured with a differential pressure with transducer (Validyne M P 45 5 kPa), and inspiratory flow a Fleisch no. 2 pneumotachograph connected to a Validyne differential pressure transducer ( M P 45 f 0.2 kPa). Pressure and flow signals were low-pass filtered, and sampled at 16 Hz for 20 s by an analogdigital converter; the sampled data were fed into a n Apple I1 microcomputer (Apple Computer Inc, Cupertino, California, USA). Online integration of yielded the instantaneous inspiratory volume, (8). Respiratory compliance (Crs) and resistance (Rrs) measurement was based on the general equation of motion of the respiratory system (including the endotracheal tube) under mechanical ventilation:
(v)
v
v
254
I. CIGARINI E T AL.
v
PT=v/Crs+(Rrs+Rt) v + K t IvI, where Rt and Kt are the Rohrer’s constants characterizing the non-linear flow resistance of the endotracheal tube. For each size of endotracheal tube, Rt and Kt were previously determined in the course of constant flow experiments conducted on an isolated tube with a 50% mixture of nitrous oxide in oxygen (9). Each tube was submitted to different constant flow rates (100 to 1000 ml/s), and the Rohrer’s constants were assessed from experimental pressure-flow (P-v) data, by linear regression analysis of P/v on Respiratory compliance and resistance were measured using the constant inspiratory flow method proposed by Rossi et al. (9). Respiratory compliance was calculated as the inverse of the slope of the regression of PT on over the 40-90y0 range of the inspiratory time of each cycle, where inspiratory flow was constant and pressure was a linear function of time. Rrs was taken as the ratio of the regression line intercept on the pressure axis to the constant flow, corrected for the non-linear resistance of the endotracheal tube calculated for the corresponding constant flow. The mechanical parameters were continuously monitored. Data were validated only when the correlation coefficient of the linear regression of PT on 0 was higher than 0.98.
v.
v
Plan of investigation After orotracheal intubation, a 15-min period was planned before fentanyl injection in order to obtain a respiratory mechanical steady state. Since fentanyl has been demonstrated to increase bronchomotor tone (10, I l ) , and therefore airway resistance, the administration of fentanyl was considered as a bronchoconstrictive challenge. The mean values of the mechanical parameters were obtained over the following time intervals: TO corresponded to the 3 min immediately following orotracheal intubation, TI corresponded to the last 3 min preceding fentanyl injection, and T2, T3, T4, T5 and T6 respectively to the 5 consecutive 2-min intervals following fentanyl injection. Thus, the changes in respiratory mechanics were continuously monitored over a 10-min period after fentanyl injection. Blood samples were collected at TO, TI, T2, T6 and stored at 4°C for subsequent measurements of plasma concentrations of propofol by high pressure liquid chromatography (12). Comparison of data was performed between TO and T1 and between TI and T 2 - 3 4 5 in each group and between the two groups at each time interval. Statistical analysis was performed using a one-way analysis of variance and a Student’s paired t-test. P < 0.05 was considered significant.
RESULTS The two groups were comparable for demographic data. The first group (thiopental) included nine women and one man with a mean age of 44 f 7 years, a mean weight of 65 f 10 kg and a mean height of 170 f 8 cm. The second group (propofol) included nine women and one man with a mean age of 40 f 8 years, a mean weight of 66 f 12 kg and a mean height of 165 f 5 cm. Over the period preceding fentanyl injection (TOT l ) , maximal tracheal pressure (PT max), Rrs and Crs were not significantly different in both groups of patients (Table 1). Over this period (TO-Tl), in both groups, Crs decreased while no significant change was observed in PTmax and Rrs values (Table 1). I n the thiopental group, fentanyl injection elicited marked
Fig. 1. Change over time of inspiratory respiratory resistance (mean i s.e.mean) during thiopental and propofol anaesthesia. TI: before fentanyl administration. T2-T6: after fentanyl administration. Each point represents a 2-min period average. *P
Comparison of the effects of fentanyl on respiratory mechanics under propofol or thiopental anaesthesia I. CIGARINI, F. BONNET, A. M. LORINO, A. HARFand J. M. DESMONTS Departments of Anesthesiology and Physiology and INSERM U 29, Hopital Henri Mondor, Creteil and Department of Anesthesiology Hopital Bichat, Pans, France
Twenty patients were randomly anaesthetized with either thiopental 5 mg/kg followed by a 15 mg/kg/h continuous infusion, or propofol 2.5 mg/kg followed by a 9 mg/kg/h continuous infusion, paralysed with vecuronium 0.1 mg/kg, intubated and ventilated with nitrous oxide 50% in oxygen. Fifteen minutes after induction, fentanyl 5 pg/kg was injected. Inspiratory tracheal pressure (PT), gas flow (V) and volume (V) were continuously measured while the lungs were inflated with a constant inspiratory flow ventilator. Respiratory compliance (Crs) and resistance (Rrs) were calculated from the regression of P T on V. I n both groups Crs decreased following anaesthesia. Fentanyl injection elicited an increase in Rrs (from 1.04 k 0.70 to 1.63 t 0.92 kPa . I - ' . s) and a further decrease in Crs (from 0.55 0.30 to 0.42 f 0.10 1. kPa-') in the thiopental group but not in the propofol group (Rrs: 1.26 f 0.69 to 1.08 f 0.44 kPa . 1 - . s, Crs: 0.49 2 0.1 1 to 0.48k0.13 1 'kPa-'). These results suggest that the dose of propofol administered in this study may prevent fentanyl-induced bronchoconstriction.
'
Received 25 M q , accepted f o r publication 15 October 1989
Key words: Anesthetic agents: propofol; bronchomotor tone; compliance
Many anaesthetic agents can modify bronchomotor tone either by their own action or by interference with other stimuli (1). Most of them increase bronchomotor tone but only a few have overt bronchodilating properties (2, 3). Anaesthetic induction is a period especially at risk for bronchoconstriction because many different stimuli are simultaneously applied on airways. Anaesthetic induction often needs to be rapid, well controlled and managed. Propofol, (2-6 disopropylphenol), is a convenient, short-acting intravenous sedative hypnotic agent (4). Recently available in a new formulation as an aqueous emulsion, it does not provoke histamine release which was a possible side effect in the previous formulation including cremophor E. L. as a solvent (5, 6). We were therefore interested to evaluate the effect on respiratory mechanics of this new hypnotic agent, versus thiopental as a reference agent. PATIENTS AND METHODS Patients and anaesthetic procedures Twenty A.S.A. 1-11 patients were included in the study after obtaining approval from our local ethical committee and informed consent from the patients. Patients were excluded from the protocol if they had any history of asthma or allergy or if they were being treated with betaadrenergic blocking agents. All the patients were premedi-
-
resistance; respiratory mechanics.
cated orally with flunitrazepam 1 mg. Patients were allocated randomly to two groups according to the anaesthetic procedure. In the first group ( n = lo), induction of anaesthesia was performed with thiopental 5 mg/kg. Tracheal intubation was facilitated by vecuronium 0.1 mg/kg. A 15 mg/kg/h continuous infusion of thiopental followed anaesthetic induction. I n the second group (n = lo), patients received propofo12.5 mg/kg and vecuronium 0.1 mg/kg for induction and orotracheal intubation followed by a 9 mg/kg/h continuous infusion of propofol. In both groups controlled ventilation was maintained with a CPU I ventilator (Ohmeda) delivering nitrous oxide 50% in oxygen ( 7 ) . Ventilatory parameters were set as follows: tidal volume ( V T ) = 8 ml/kg, I / E = 1/2, respiratory rate= 12/min. Additional doses of 0.05 mg/kg vecuronium were administered if necessary during the study to block any response to the twitch stimulation. Fifteen minutes after induction of anesthesia, 5 pg/kg fentanyl were injected i.v. Surgery began 20 min after fentanyl injection. Measurements of respiratory mechanics Tracheal pressure (PT) was measured with a differential pressure with transducer (Validyne M P 45 5 kPa), and inspiratory flow a Fleisch no. 2 pneumotachograph connected to a Validyne differential pressure transducer ( M P 45 f 0.2 kPa). Pressure and flow signals were low-pass filtered, and sampled at 16 Hz for 20 s by an analogdigital converter; the sampled data were fed into a n Apple I1 microcomputer (Apple Computer Inc, Cupertino, California, USA). Online integration of yielded the instantaneous inspiratory volume, (8). Respiratory compliance (Crs) and resistance (Rrs) measurement was based on the general equation of motion of the respiratory system (including the endotracheal tube) under mechanical ventilation:
(v)
v
v
254
I. CIGARINI E T AL.
v
PT=v/Crs+(Rrs+Rt) v + K t IvI, where Rt and Kt are the Rohrer’s constants characterizing the non-linear flow resistance of the endotracheal tube. For each size of endotracheal tube, Rt and Kt were previously determined in the course of constant flow experiments conducted on an isolated tube with a 50% mixture of nitrous oxide in oxygen (9). Each tube was submitted to different constant flow rates (100 to 1000 ml/s), and the Rohrer’s constants were assessed from experimental pressure-flow (P-v) data, by linear regression analysis of P/v on Respiratory compliance and resistance were measured using the constant inspiratory flow method proposed by Rossi et al. (9). Respiratory compliance was calculated as the inverse of the slope of the regression of PT on over the 40-90y0 range of the inspiratory time of each cycle, where inspiratory flow was constant and pressure was a linear function of time. Rrs was taken as the ratio of the regression line intercept on the pressure axis to the constant flow, corrected for the non-linear resistance of the endotracheal tube calculated for the corresponding constant flow. The mechanical parameters were continuously monitored. Data were validated only when the correlation coefficient of the linear regression of PT on 0 was higher than 0.98.
v.
v
Plan of investigation After orotracheal intubation, a 15-min period was planned before fentanyl injection in order to obtain a respiratory mechanical steady state. Since fentanyl has been demonstrated to increase bronchomotor tone (10, I l ) , and therefore airway resistance, the administration of fentanyl was considered as a bronchoconstrictive challenge. The mean values of the mechanical parameters were obtained over the following time intervals: TO corresponded to the 3 min immediately following orotracheal intubation, TI corresponded to the last 3 min preceding fentanyl injection, and T2, T3, T4, T5 and T6 respectively to the 5 consecutive 2-min intervals following fentanyl injection. Thus, the changes in respiratory mechanics were continuously monitored over a 10-min period after fentanyl injection. Blood samples were collected at TO, TI, T2, T6 and stored at 4°C for subsequent measurements of plasma concentrations of propofol by high pressure liquid chromatography (12). Comparison of data was performed between TO and T1 and between TI and T 2 - 3 4 5 in each group and between the two groups at each time interval. Statistical analysis was performed using a one-way analysis of variance and a Student’s paired t-test. P < 0.05 was considered significant.
RESULTS The two groups were comparable for demographic data. The first group (thiopental) included nine women and one man with a mean age of 44 f 7 years, a mean weight of 65 f 10 kg and a mean height of 170 f 8 cm. The second group (propofol) included nine women and one man with a mean age of 40 f 8 years, a mean weight of 66 f 12 kg and a mean height of 165 f 5 cm. Over the period preceding fentanyl injection (TOT l ) , maximal tracheal pressure (PT max), Rrs and Crs were not significantly different in both groups of patients (Table 1). Over this period (TO-Tl), in both groups, Crs decreased while no significant change was observed in PTmax and Rrs values (Table 1). I n the thiopental group, fentanyl injection elicited marked
Fig. 1. Change over time of inspiratory respiratory resistance (mean i s.e.mean) during thiopental and propofol anaesthesia. TI: before fentanyl administration. T2-T6: after fentanyl administration. Each point represents a 2-min period average. *P
