British Journal of Anaesthesia 1991; 67: 269-276
COMPARISON OF SUFENTANIL-NITROUS OXIDE ANAESTHESIA WITH FENTANYL-NITROUS OXIDE ANAESTHESIA IN GERIATRIC PATIENTS UNDERGOING MAJOR ABDOMINAL SURGERYf
Anaesthesia in geriatric patients requires minimal depression of cardiac and circulatory functions, as cardiovascular reserve is diminished in old age We have measured haemodynamic changes and [1]. Often, a balanced technique using fentanyl is plasma concentrations of catecholamines during used in these patients, as fentanyl has a rapid sufentanil-nitrous oxide and fentanyl-nitrous onset of action [2], good cardiovascular stability oxide anaesthesia in a controlled, randomized, [2-4] and does not release histamine [5]. However, double-blind study of 20 geriatric patients (age fentanyl-nitrous oxide-neuromuscular blocker 65-86 yr) undergoing major abdominal surgery. anaesthesia may not block sympathoadrenal reFentanyl 7 /ig kg'1 followed by infusion of 3 fig sponses to surgical stimulation and may result in kg'1 h~' was compared with sufentanil 1 fxg kg'1 prolonged respiratory depression during the postfollowed by 0.4 ng kg~1 h~1. The opioid was operative period. supplemented with 60-67% nitrous oxide in Anaesthesia with sufentanil (the 5-10 times oxygen. Haemodynamic changes, plasma conmore potent N-4-thienyl derivative of fentanyl) centrations of catecholamines (by high pressure has been reported to produce better suppression liquid chromatography) and opioids (by radioof stress responses than fentanyl [6-9], and greater immunoassay), and myocardial lactate extraction postoperative analgesia with less respiratory dewere measured in the awake state, and at defined pression [10]; in other studies no difference was times during anaesthesia and surgery. Haemonoted [3, 11-15]. However, most of the previous dynamic state was stable during induction and studies have been performed in patients undertrachea/ intubation in both groups, while during going coronary artery bypass grafting using high stressful operative periods there were increases doses of the opioid. in mean arterial pressure (17% in the fentanyl This study was designed to compare the effects group; 11% in the sufentanil group), heart rate of the two opioids in geriatric patients using (fentanyl 20%, sufentanil 14%) and plasma concentrations of catecholamines (adrenaline: standard doses. SUMMARY
fentanyl 316%, sufentanil 86%; noradrenaline: fentanyl 78%, sufentanil 186%) in both groups. Sufentanil was similar to fentanyl in attenuating the haemodynamic and hormonal responses to surgical stimulation. In two patients in the fentanyl group and three in the sufentanil group, myocardial lactate production was observed temporarily, indicating myocardial ischaemia caused by surgical stress. KEY WORDS Anaesthesia: geriatric. Analgesics: fentanyl, sufentanil. Surgery: haemodynamic responses, hormonal responses.
DANIELA KlETZMANN, M.D.; REINHARD LARSEN*, M.D.; JORG RATHGEBER, M.D.; M. BOLTE, M.D.; D. KETTLER, M.D. ; De-
partment of Anacsthesiology, University of Gottingen, Robert-Koch-Strafle 40, D-3400 Gottingen, Germany. Accepted for Publication: February 18, 1991. 'Present address: Department of Anaesthesiology, University of Homburg, Oscar-Orth-StraBe, D-6650 Homburg/ Saar, Germany. tResults presented in pan at the 11th Annual Meeting of the European Academy of Anaesthesiologists, Bonn, August 31, 1989.
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
D. KIETZMANN, R. LARSEN, J. RATHGEBER, M. BOLTE AND D. KETTLER
BRITISH JOURNAL OF ANAESTHESIA
270 PATIENTS AND METHODS
TABLE I. Patient characteristics and duration of anaesthesia
Sex (M/F) Age (yr) Mean Range Weight (kg) Mean Range Hypertension Angina Coronary heart disease Myocardial infarction > 6 months earlier Diabetes mellitus Chronic obstructive lung disease Duration of operation (h) Mean (SD) Range Upper abdominal surgery Lower abdominal surgery Blood loss (ml) Mean (SD)
Sufentanil group (n = 10)
Fentanyl group (n = 10)
8/2
5/5
75 67-81
75 65-86
74 50-84 5 3 5
69 60-86 5 3 4
3 2
1 1
2
1
3.3 (2.3) 1.0-6.5 6 4
2.8 (1.3) 1.7-6.0 4 6
830 (620)
880 (570)
Monitors and measurements
A three-lead electrocardiograph (Hellige) and a Lifescan brain activity monitor (Braun) were attached in the induction room, and the following catheters were inserted percutaneously under local anaesthesia: a Goodale-Lubin catheter (7French gauge, USCI) into the coronary sinus via the right internal jugular vein for blood sampling; a flow-directed pulmonary artery catheter (Vygon quadruple thermodilution Thermocath) via the left internal jugular vein for measurement of pulmonary artery pressure, pulmonary capillary wedge pressure, right atrial pressure and cardiac output (the position of the catheters was confirmed by fiuoroscopy); a 20-gauge indwelling cannula into the non-dominant radial artery for continuous monitoring of arterial pressure and blood sampling; and two 14-gauge indwelling cannulae into peripheral veins for administration of drugs and fluids. The processed EEG and its median frequency were displayed continuously on the Lifescan monitor. The ECG, systemic arterial, pulmonary arterial and central venous pressures were displayed continuously on the patient monitor and recorded simultaneously on a 10-channel chart recorder (Hellige). Cardiac output was measured by the thermodilution technique using 10 ml of saline solution at 0 °C (cardiac output computer, Fisher BN 7206); the mean of three consecutive values was taken. Measurements of cardiac output and wedge pressure were performed at the end of expiration. After each measurement of cardiovascular variables, blood samples were obtained simultaneously from the coronary sinus and the radial artery and analysed for Po s , Pcot, pH, base excess and standard bicarbonate (IL 282, Instrumentation Laboratories), electrolyte concentrations by flame photometry (IL 543, Instrum. Lab.), and lactate (standard test combination, Boehringer). Arterial samples were obtained for measurement of plasma concentrations of catecholamines (by high pressure liquid chromatography with fluorescence detection [16]) and fentanyl or sufentanil (by radioimmunoassay, Janssen). Procedure
Baseline measurements were made after 30 min of rest; after preoxygenation, pancuronium 1 mg was given i.v. as a bolus dose for precurarization. In the fentanyl group, anaesthesia was induced
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
Patients After approval by the Gottingen University Human Subjects Review Committee and written informed consent, we studied 20 ASA II or III patients (aged at least 65 yr) undergoing major abdominal surgery in a controlled, randomized, double-blind study. Surgery comprised: gastrectomy, partial pancreatectomy, partial resection of intestine or exploratory laparotomy (inoperable cases). The types of operation and blood loss were similar in both groups (table I). Patients with coronary heart disease were included in the study; those with angina at rest, heart failure, valvular heart disease or arrythmias were excluded. There were no significant differences between groups in age, body weight or pre-existing disease states (table I). The patients were allocated to one of the two groups at random, but there was by chance a different sex ratio between the groups. All patients were premedicated with lormetazepam 2 mg by mouth the night before the operation and also 1 h before arrival in the anaesthetic room. All patients received 750-1000 ml of a balanced electrolyte solution during insertion of catheters and the resting period.
COMPARISON OF SUFENTANIL AND FENTANYL IN GERIATRIC PATIENTS
271
1
Data analysis
Cardiac index was calculated by dividing cardiac output by the body surface area. The myocardial lactate extraction was calculated by dividing the arterial-coronary sinus blood lactate concentration difference by the arterial lactate concentration and multiplying by 100. All data are given as mean (SD). The MannWhitney U test was used to compare data of all patients between groups. The Wilcoxon test was used for statistical analysis of the data within each group at different times of measurement. P < 0.05 was taken as significant. RESULTS
Both groups were similar in age, body weight and number of patients with hypertension or coronary heart disease (table I). No patient suffered from angina during the preoperative period or the period of observation. Arterial pressure was increased in three patients in the fentanyl and two in the sufentanil group on arrival in the anaesthetic room and remained increased even after a resting period of 30 min. These patients were known to be hypertensive. Baseline cardiac index was increased in 50% of the patients (fig. 1). This is not surprising, as the normal value for cardiac index of approximately 3.0 litre min"1 m"2 may increase by nearly 50% with anxiety [17]. (Nearly all patients were undergoing surgery for malignancy.) One patient in the fentanyl group and three in the sufentanil group developed chest wall rigidity after administration of the opioid. There were no significant differences between the groups during the study. Haemodynamic variables remained stable with both drugs after induction, tracheal intubation and the beginning of the operation (figs 1-3; table II). Severe surgical stimulation (measurement VI) resulted in increases in arterial pressure (mean values for fentanyl and sufentanil, respectively, 17% and 11 %) (fig. 2), heart rate (fentanyl 20 %, sufentanil 14%) (fig. 3), and plasma concentrations of adrenaline (fentanyl 316%, sufentanil 86%) (table III, fig. 4) and noradrenaline (fentanyl 78%, sufentanil 186%) (fig. 5), compared with baseline values. In two patients in each group, additional boluses of the opioid failed to attenuate these reactions and halothane or nitroglycerin was given to these patients for approximately 32 min (mean) after measurement VI.
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
with fentanyl 7 ug kg" followed by a continuous infusion of 3 ug kg"1 h"1 for maintenance. In the sufentanil group, patients received 1 ug kg"1 as a bolus and 0.4 ug kg"1 h"1 for maintenance. As the anaesthetic potency of sufentanil was considered to be approximately 7 times that of fentanyl, this dose regimen was assumed to be equipotent [11]. The drugs were diluted such that the volumes administered were equal in both groups, and the syringes were labelled as "opioid" to preserve the double-blind nature of the study. After injection of the opioid, assisted ventilation via a face mask was used to maintain P a ^ , at 5.0-5.3 kPa as confirmed by arterial blood-gas analyses and continuous measurement of the end-expiratory carbon dioxide concentration (Multicap monitor, Datex). Five minutes after injection of the opioid and after completion of the second measurements, etomidate 0.2 mg kg"1 and suxamethonium 1 mg kg"1 were given in both groups. The trachea was intubated and anaesthesia was maintained with 60-67 % of nitrous oxide in oxygen to the end of operation and with the opioid infusion to approximately 30 min before the end of operation. The infusion rate was increased and additional boluses of fentanyl 0.15 mg or sufentanil 21 ug were administered when signs of insufficient depth of anaesthesia developed—notably: increase in systolic arterial pressure by more than 15%; tachycardia if not caused by deficiency of volume or blood loss; tears; sweating; movement; increase in EEG median frequency up to the individual baseline value. All patients were given pancuronium. This anaesthetic technique resulted in an average consumption of fentanyl 390 ug h"1 or sufentanil 59 ug h"1 during a mean time of anaesthesia of 3.9 (SD 1.3) h (fentanyl) or 4.3 (2.1) h (sufentanil). Measurements were performed at the following times: I = baseline values in the awake patients after insertion of the catheters and a resting period of 30 min; II = 5 min after injection of the opioid bolus; 111=2 min after tracheal intubation; IV = 5 min before the beginning of surgery; V = 2 min after skin incision; VI = 2 min after opening of the peritoneum; VII = 2 min after the end of the operation (defined as the end of the skin suture) and termination of the administration of nitrous oxide.
BRITISH JOURNAL OF ANAESTHESIA
272
8-
Sufentanil
Fentanyl
'c 6 E CD
x
4
CD
c
IV V VI VII VI VII I I Measurement time FIG. 1. Cardiac index. I = Awake; II =• 5 min after induction; III = 2 min after intubation; IV = 5 min before skin incision; V =• 2 min after incision; VI = 2 min after opening of the peritoneum and insertion of hooks; VII = 2 min after the end of the operation. No significant difference between groups. III
IV
V
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
O
TABLE II. Haemodynamic variables (mean (5D)) after sufentanil (S) (n = 10) or fentanyl (F) (n = 10). I = Awake; 11=5 nan after injection of opioid; III = 2 min after intubation; IV = 5 min before the operation; V = 2 min after skin incision; VI = 2 min after opening of the peritoneum and insertion of hooks; VII = end of operation. P < 0.05: *compared with I Group Heart rate 1 (beat min" ) Systolic arterial pressure (mm Hg) Diastolic arterial pressure (mm Hg) Mean arterial pressure (mm Hg) Mean pulmonary arterial pressure (mm Hg) Mean pulmonary capillary wedge pressure (mm Hg) Central venous pressure (mm Hg) Cardiac index (litre min"1 m"1)
S F S F S F S F S F S F S F S F
I 77 74 168 165 79 73 109 109 21 21 12 11 5.6 5.9 5.0 4.7
II
(12) (10) (19) (30) (6)
(12) (11) (18) (5) (3) (4) (3)
(2.8) (3.2) (1.2) (1.3)
79 73 156 159 71 72 104 108 24 24 13 14 7.8 9.1 5.0 4.5
(13) (12) (35) (33) (8)
(12) (17) (17) (9) (6) (6) (3)
(3.6) (3.9)* (1.1) (1.0)
There was no correlation between arterial pressure, heart rate, catecholamine concentrations and E E C Patients with known hypertension had greater mean baseline values of arterial pressure (fentanyl 117 mmHg; sufentanil 116 mm Hg) than the other patients (102 mm Hg and 101 mm Hg, respectively). At measurement IV, when the relative depth of anaesthesia was maximum, mean arterial pressure was not significantly different for hypertensive patients (fentanyl 98 mm Hg, sufentanil 93 mm Hg) compared with normotensive subjects (fentanyl 90 and sufentanil 95 mm Hg).
III 74 69 158 167 68 76 97 105 24 25 12 12 6.6 9.2 4.6 3.9
(12) (16) (34) (45) (8)
(18) (12) (26) (6) (7) (6) (3)
(2.4) (3.5)* (1.3) (1.0)
IV 68 60 132 138 66 71 94 94 23 19 12 12 8.0 8.6 3.7 3.0
(12)* (8)* (40)* (27)* (15) (12) (19)* (13)* (10) (3) (3) (2)
(1.9)* (2.0)* (1.2)* (0.7)*
VI 68 69 146 152 76 77 99 107 25 22 14 16
(13)* (13) (30) (29) (16) (16) (17) (16) (9) (3) (4) (2)
10.9 (3.4)* 10.6 (2.3)* 3.7 (1.1)* 3.6 (1.2)*
88 89 176 179 82 87 121 127 30 28 17 20
11.0 13.6 5.2 4.4
(19) (15) (48) (46) (24) (25) (28) (20)* (13)* (5)* (6)* (4)* (2.9)* (3.4)* (1.6) (1.3)
VII 93 89 164 173 84 81 111 119 24 20 12 12 8.8 8.6 4.1 4.5
(23) (20) (37) (27) (14) (20) (18) (20) (8) (4) (4) (5)
(3.7)* (2.9) (1.4) (1.4)
Surgical stimulation (measurement VI), however, caused greater increases in mean arterial pressure in hypertensive patients (fentanyl 139 mm Hg, sufentanil 133 mmHg) than in other patients (fentanyl 116 and sufentanil 108 mm Hg). Sufentanil was not superior to fentanyl in preventing increases in arterial pressure. At the end of the operation (measurement VII), heart rates and plasma concentrations of catecholamines were maximum. Nearly all patients (eight receiving fentanyl, seven receiving sufentanil) were awake, most of these breathing spontaneously (six re-
273
COMPARISON OF SUFENTANIL AND FENTANYL IN GERIATRIC PATIENTS Fentanyl
Sufentanil
150-
100-
e
50Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
a c to
a)
I
II
III I V
V
VI VII I II Measurement time
IV
V
VI VII
FIG. 2. Mean arterial pressure. (For explanation of measurement times, see legend to figure 1.) No significant difference between groups.
150 -i
Fentanyl
Sufentanil
c E 100
COMPARISON OF SUFENTANIL-NITROUS OXIDE ANAESTHESIA WITH FENTANYL-NITROUS OXIDE ANAESTHESIA IN GERIATRIC PATIENTS UNDERGOING MAJOR ABDOMINAL SURGERYf
Anaesthesia in geriatric patients requires minimal depression of cardiac and circulatory functions, as cardiovascular reserve is diminished in old age We have measured haemodynamic changes and [1]. Often, a balanced technique using fentanyl is plasma concentrations of catecholamines during used in these patients, as fentanyl has a rapid sufentanil-nitrous oxide and fentanyl-nitrous onset of action [2], good cardiovascular stability oxide anaesthesia in a controlled, randomized, [2-4] and does not release histamine [5]. However, double-blind study of 20 geriatric patients (age fentanyl-nitrous oxide-neuromuscular blocker 65-86 yr) undergoing major abdominal surgery. anaesthesia may not block sympathoadrenal reFentanyl 7 /ig kg'1 followed by infusion of 3 fig sponses to surgical stimulation and may result in kg'1 h~' was compared with sufentanil 1 fxg kg'1 prolonged respiratory depression during the postfollowed by 0.4 ng kg~1 h~1. The opioid was operative period. supplemented with 60-67% nitrous oxide in Anaesthesia with sufentanil (the 5-10 times oxygen. Haemodynamic changes, plasma conmore potent N-4-thienyl derivative of fentanyl) centrations of catecholamines (by high pressure has been reported to produce better suppression liquid chromatography) and opioids (by radioof stress responses than fentanyl [6-9], and greater immunoassay), and myocardial lactate extraction postoperative analgesia with less respiratory dewere measured in the awake state, and at defined pression [10]; in other studies no difference was times during anaesthesia and surgery. Haemonoted [3, 11-15]. However, most of the previous dynamic state was stable during induction and studies have been performed in patients undertrachea/ intubation in both groups, while during going coronary artery bypass grafting using high stressful operative periods there were increases doses of the opioid. in mean arterial pressure (17% in the fentanyl This study was designed to compare the effects group; 11% in the sufentanil group), heart rate of the two opioids in geriatric patients using (fentanyl 20%, sufentanil 14%) and plasma concentrations of catecholamines (adrenaline: standard doses. SUMMARY
fentanyl 316%, sufentanil 86%; noradrenaline: fentanyl 78%, sufentanil 186%) in both groups. Sufentanil was similar to fentanyl in attenuating the haemodynamic and hormonal responses to surgical stimulation. In two patients in the fentanyl group and three in the sufentanil group, myocardial lactate production was observed temporarily, indicating myocardial ischaemia caused by surgical stress. KEY WORDS Anaesthesia: geriatric. Analgesics: fentanyl, sufentanil. Surgery: haemodynamic responses, hormonal responses.
DANIELA KlETZMANN, M.D.; REINHARD LARSEN*, M.D.; JORG RATHGEBER, M.D.; M. BOLTE, M.D.; D. KETTLER, M.D. ; De-
partment of Anacsthesiology, University of Gottingen, Robert-Koch-Strafle 40, D-3400 Gottingen, Germany. Accepted for Publication: February 18, 1991. 'Present address: Department of Anaesthesiology, University of Homburg, Oscar-Orth-StraBe, D-6650 Homburg/ Saar, Germany. tResults presented in pan at the 11th Annual Meeting of the European Academy of Anaesthesiologists, Bonn, August 31, 1989.
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
D. KIETZMANN, R. LARSEN, J. RATHGEBER, M. BOLTE AND D. KETTLER
BRITISH JOURNAL OF ANAESTHESIA
270 PATIENTS AND METHODS
TABLE I. Patient characteristics and duration of anaesthesia
Sex (M/F) Age (yr) Mean Range Weight (kg) Mean Range Hypertension Angina Coronary heart disease Myocardial infarction > 6 months earlier Diabetes mellitus Chronic obstructive lung disease Duration of operation (h) Mean (SD) Range Upper abdominal surgery Lower abdominal surgery Blood loss (ml) Mean (SD)
Sufentanil group (n = 10)
Fentanyl group (n = 10)
8/2
5/5
75 67-81
75 65-86
74 50-84 5 3 5
69 60-86 5 3 4
3 2
1 1
2
1
3.3 (2.3) 1.0-6.5 6 4
2.8 (1.3) 1.7-6.0 4 6
830 (620)
880 (570)
Monitors and measurements
A three-lead electrocardiograph (Hellige) and a Lifescan brain activity monitor (Braun) were attached in the induction room, and the following catheters were inserted percutaneously under local anaesthesia: a Goodale-Lubin catheter (7French gauge, USCI) into the coronary sinus via the right internal jugular vein for blood sampling; a flow-directed pulmonary artery catheter (Vygon quadruple thermodilution Thermocath) via the left internal jugular vein for measurement of pulmonary artery pressure, pulmonary capillary wedge pressure, right atrial pressure and cardiac output (the position of the catheters was confirmed by fiuoroscopy); a 20-gauge indwelling cannula into the non-dominant radial artery for continuous monitoring of arterial pressure and blood sampling; and two 14-gauge indwelling cannulae into peripheral veins for administration of drugs and fluids. The processed EEG and its median frequency were displayed continuously on the Lifescan monitor. The ECG, systemic arterial, pulmonary arterial and central venous pressures were displayed continuously on the patient monitor and recorded simultaneously on a 10-channel chart recorder (Hellige). Cardiac output was measured by the thermodilution technique using 10 ml of saline solution at 0 °C (cardiac output computer, Fisher BN 7206); the mean of three consecutive values was taken. Measurements of cardiac output and wedge pressure were performed at the end of expiration. After each measurement of cardiovascular variables, blood samples were obtained simultaneously from the coronary sinus and the radial artery and analysed for Po s , Pcot, pH, base excess and standard bicarbonate (IL 282, Instrumentation Laboratories), electrolyte concentrations by flame photometry (IL 543, Instrum. Lab.), and lactate (standard test combination, Boehringer). Arterial samples were obtained for measurement of plasma concentrations of catecholamines (by high pressure liquid chromatography with fluorescence detection [16]) and fentanyl or sufentanil (by radioimmunoassay, Janssen). Procedure
Baseline measurements were made after 30 min of rest; after preoxygenation, pancuronium 1 mg was given i.v. as a bolus dose for precurarization. In the fentanyl group, anaesthesia was induced
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
Patients After approval by the Gottingen University Human Subjects Review Committee and written informed consent, we studied 20 ASA II or III patients (aged at least 65 yr) undergoing major abdominal surgery in a controlled, randomized, double-blind study. Surgery comprised: gastrectomy, partial pancreatectomy, partial resection of intestine or exploratory laparotomy (inoperable cases). The types of operation and blood loss were similar in both groups (table I). Patients with coronary heart disease were included in the study; those with angina at rest, heart failure, valvular heart disease or arrythmias were excluded. There were no significant differences between groups in age, body weight or pre-existing disease states (table I). The patients were allocated to one of the two groups at random, but there was by chance a different sex ratio between the groups. All patients were premedicated with lormetazepam 2 mg by mouth the night before the operation and also 1 h before arrival in the anaesthetic room. All patients received 750-1000 ml of a balanced electrolyte solution during insertion of catheters and the resting period.
COMPARISON OF SUFENTANIL AND FENTANYL IN GERIATRIC PATIENTS
271
1
Data analysis
Cardiac index was calculated by dividing cardiac output by the body surface area. The myocardial lactate extraction was calculated by dividing the arterial-coronary sinus blood lactate concentration difference by the arterial lactate concentration and multiplying by 100. All data are given as mean (SD). The MannWhitney U test was used to compare data of all patients between groups. The Wilcoxon test was used for statistical analysis of the data within each group at different times of measurement. P < 0.05 was taken as significant. RESULTS
Both groups were similar in age, body weight and number of patients with hypertension or coronary heart disease (table I). No patient suffered from angina during the preoperative period or the period of observation. Arterial pressure was increased in three patients in the fentanyl and two in the sufentanil group on arrival in the anaesthetic room and remained increased even after a resting period of 30 min. These patients were known to be hypertensive. Baseline cardiac index was increased in 50% of the patients (fig. 1). This is not surprising, as the normal value for cardiac index of approximately 3.0 litre min"1 m"2 may increase by nearly 50% with anxiety [17]. (Nearly all patients were undergoing surgery for malignancy.) One patient in the fentanyl group and three in the sufentanil group developed chest wall rigidity after administration of the opioid. There were no significant differences between the groups during the study. Haemodynamic variables remained stable with both drugs after induction, tracheal intubation and the beginning of the operation (figs 1-3; table II). Severe surgical stimulation (measurement VI) resulted in increases in arterial pressure (mean values for fentanyl and sufentanil, respectively, 17% and 11 %) (fig. 2), heart rate (fentanyl 20 %, sufentanil 14%) (fig. 3), and plasma concentrations of adrenaline (fentanyl 316%, sufentanil 86%) (table III, fig. 4) and noradrenaline (fentanyl 78%, sufentanil 186%) (fig. 5), compared with baseline values. In two patients in each group, additional boluses of the opioid failed to attenuate these reactions and halothane or nitroglycerin was given to these patients for approximately 32 min (mean) after measurement VI.
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
with fentanyl 7 ug kg" followed by a continuous infusion of 3 ug kg"1 h"1 for maintenance. In the sufentanil group, patients received 1 ug kg"1 as a bolus and 0.4 ug kg"1 h"1 for maintenance. As the anaesthetic potency of sufentanil was considered to be approximately 7 times that of fentanyl, this dose regimen was assumed to be equipotent [11]. The drugs were diluted such that the volumes administered were equal in both groups, and the syringes were labelled as "opioid" to preserve the double-blind nature of the study. After injection of the opioid, assisted ventilation via a face mask was used to maintain P a ^ , at 5.0-5.3 kPa as confirmed by arterial blood-gas analyses and continuous measurement of the end-expiratory carbon dioxide concentration (Multicap monitor, Datex). Five minutes after injection of the opioid and after completion of the second measurements, etomidate 0.2 mg kg"1 and suxamethonium 1 mg kg"1 were given in both groups. The trachea was intubated and anaesthesia was maintained with 60-67 % of nitrous oxide in oxygen to the end of operation and with the opioid infusion to approximately 30 min before the end of operation. The infusion rate was increased and additional boluses of fentanyl 0.15 mg or sufentanil 21 ug were administered when signs of insufficient depth of anaesthesia developed—notably: increase in systolic arterial pressure by more than 15%; tachycardia if not caused by deficiency of volume or blood loss; tears; sweating; movement; increase in EEG median frequency up to the individual baseline value. All patients were given pancuronium. This anaesthetic technique resulted in an average consumption of fentanyl 390 ug h"1 or sufentanil 59 ug h"1 during a mean time of anaesthesia of 3.9 (SD 1.3) h (fentanyl) or 4.3 (2.1) h (sufentanil). Measurements were performed at the following times: I = baseline values in the awake patients after insertion of the catheters and a resting period of 30 min; II = 5 min after injection of the opioid bolus; 111=2 min after tracheal intubation; IV = 5 min before the beginning of surgery; V = 2 min after skin incision; VI = 2 min after opening of the peritoneum; VII = 2 min after the end of the operation (defined as the end of the skin suture) and termination of the administration of nitrous oxide.
BRITISH JOURNAL OF ANAESTHESIA
272
8-
Sufentanil
Fentanyl
'c 6 E CD
x
4
CD
c
IV V VI VII VI VII I I Measurement time FIG. 1. Cardiac index. I = Awake; II =• 5 min after induction; III = 2 min after intubation; IV = 5 min before skin incision; V =• 2 min after incision; VI = 2 min after opening of the peritoneum and insertion of hooks; VII = 2 min after the end of the operation. No significant difference between groups. III
IV
V
Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
O
TABLE II. Haemodynamic variables (mean (5D)) after sufentanil (S) (n = 10) or fentanyl (F) (n = 10). I = Awake; 11=5 nan after injection of opioid; III = 2 min after intubation; IV = 5 min before the operation; V = 2 min after skin incision; VI = 2 min after opening of the peritoneum and insertion of hooks; VII = end of operation. P < 0.05: *compared with I Group Heart rate 1 (beat min" ) Systolic arterial pressure (mm Hg) Diastolic arterial pressure (mm Hg) Mean arterial pressure (mm Hg) Mean pulmonary arterial pressure (mm Hg) Mean pulmonary capillary wedge pressure (mm Hg) Central venous pressure (mm Hg) Cardiac index (litre min"1 m"1)
S F S F S F S F S F S F S F S F
I 77 74 168 165 79 73 109 109 21 21 12 11 5.6 5.9 5.0 4.7
II
(12) (10) (19) (30) (6)
(12) (11) (18) (5) (3) (4) (3)
(2.8) (3.2) (1.2) (1.3)
79 73 156 159 71 72 104 108 24 24 13 14 7.8 9.1 5.0 4.5
(13) (12) (35) (33) (8)
(12) (17) (17) (9) (6) (6) (3)
(3.6) (3.9)* (1.1) (1.0)
There was no correlation between arterial pressure, heart rate, catecholamine concentrations and E E C Patients with known hypertension had greater mean baseline values of arterial pressure (fentanyl 117 mmHg; sufentanil 116 mm Hg) than the other patients (102 mm Hg and 101 mm Hg, respectively). At measurement IV, when the relative depth of anaesthesia was maximum, mean arterial pressure was not significantly different for hypertensive patients (fentanyl 98 mm Hg, sufentanil 93 mm Hg) compared with normotensive subjects (fentanyl 90 and sufentanil 95 mm Hg).
III 74 69 158 167 68 76 97 105 24 25 12 12 6.6 9.2 4.6 3.9
(12) (16) (34) (45) (8)
(18) (12) (26) (6) (7) (6) (3)
(2.4) (3.5)* (1.3) (1.0)
IV 68 60 132 138 66 71 94 94 23 19 12 12 8.0 8.6 3.7 3.0
(12)* (8)* (40)* (27)* (15) (12) (19)* (13)* (10) (3) (3) (2)
(1.9)* (2.0)* (1.2)* (0.7)*
VI 68 69 146 152 76 77 99 107 25 22 14 16
(13)* (13) (30) (29) (16) (16) (17) (16) (9) (3) (4) (2)
10.9 (3.4)* 10.6 (2.3)* 3.7 (1.1)* 3.6 (1.2)*
88 89 176 179 82 87 121 127 30 28 17 20
11.0 13.6 5.2 4.4
(19) (15) (48) (46) (24) (25) (28) (20)* (13)* (5)* (6)* (4)* (2.9)* (3.4)* (1.6) (1.3)
VII 93 89 164 173 84 81 111 119 24 20 12 12 8.8 8.6 4.1 4.5
(23) (20) (37) (27) (14) (20) (18) (20) (8) (4) (4) (5)
(3.7)* (2.9) (1.4) (1.4)
Surgical stimulation (measurement VI), however, caused greater increases in mean arterial pressure in hypertensive patients (fentanyl 139 mm Hg, sufentanil 133 mmHg) than in other patients (fentanyl 116 and sufentanil 108 mm Hg). Sufentanil was not superior to fentanyl in preventing increases in arterial pressure. At the end of the operation (measurement VII), heart rates and plasma concentrations of catecholamines were maximum. Nearly all patients (eight receiving fentanyl, seven receiving sufentanil) were awake, most of these breathing spontaneously (six re-
273
COMPARISON OF SUFENTANIL AND FENTANYL IN GERIATRIC PATIENTS Fentanyl
Sufentanil
150-
100-
e
50Downloaded from http://bja.oxfordjournals.org/ at Indiana University Library on July 14, 2015
a c to
a)
I
II
III I V
V
VI VII I II Measurement time
IV
V
VI VII
FIG. 2. Mean arterial pressure. (For explanation of measurement times, see legend to figure 1.) No significant difference between groups.
150 -i
Fentanyl
Sufentanil
c E 100
