High-dose Fentanyl Anesthesia Research Articles

Effects of High-Dose Fentanyl Anaesthesia on the Established Metabolic and Endocrine Response to Surgery

Effects of High-Dose Fentanyl Anaesthesia on the Established Metabolic and Endocrine Response to Surgery

Nalbuphine Antagonism of Ventilatory Depression Following High-dose Fentanyl Anesthesia

Nalbuphine Antagonism of Ventilatory Depression Following High-dose Fentanyl Anesthesia

Midazolam as adjunct to high-dose fentanyl anaesthesia for coronary artery bypass grafting operation.

The usefulness of midazolam as an adjunct during high-dose fentanyl anaesthesia was studied by following the changes in the haemodynamics and total body oxygenation after an intravenous injection of 0.075 mg/kg and 0.15 mg/kg of midazolam during the induction of fentanyl (75 micrograms/kg)-oxygen anaesthesia for a coronary artery bypass operation. These responses were then compared to the changes seen in patients receiving the same fentanyl anaesthesia without the midazolam. A rapid decline after the midazolam injection was seen in the mean systemic arterial pressure (24-32%--the lowest individual value was 45 mmHg (6.0 kPa)) and in the systolic and diastolic pulmonary arterial pressures (29-33% and 30-31%) in 1-3 min. As measured 10 min after the midazolam injection, a decrease from the baseline was seen in the stroke index (25-30%), in the left ventricular stroke work index (46-42%) and in the right ventricular stroke work index (48-61%). These haemodynamic variables remained on a lower level throughout the study period (40 min) in the midazolam patients as compared to the controls. The tissue oxygenation seemed to be sufficient in all groups during the study period. An intravenous injection of a relatively low dose of midazolam during the induction of high-dose fentanyl anaesthesia seems to be followed by rapidly increased venous pooling and a moderately to severely decreased systemic arterial pressure. Based on the results of this study, midazolam cannot be recommended as an adjunct during high-dose fentanyl anaesthesia.

Metoprolol Medication and Coronary Artery Bypass Grafting Operation

Twenty patients undergoing a coronary artery bypass grafting operation with high-dose fentanyl anaesthesia, all on long-term metoprolol medication, were randomly divided into a metoprolol group (last metoprolol dose given 1.5 h before the anaesthesia) and a control group (last metoprolol dose 12 h before the anaesthesia). Haemodynamics were measured and the ECG was recorded serially in order to compare the responses to the anaesthesia induction and skin incision in these two groups and to evaluate possible harmful effects of the maintained metoprolol medication. The ECG showed ischaemic signs in five control group patients during the anaesthesia induction; these patients also had a relatively high rate-pressure product. No metoprolol group patient developed ECG changes indicative of ischaemia at this stage, despite a low plasma metoprolol concentration in two patients. Surgical stimulation caused no signs of myocardial ischaemia in either group. There were no inter-group differences in the haemodynamics or oxygen transportation. No harmful effects of the maintained metoprolol on the post-bypass cardiac performance nor on the occurrence of rhythm or conduction disturbances could be seen, although a high plasma metoprolol concentration was maintained in several metoprolol group patients over the bypass time. It is concluded that continuation of long-term metoprolol medication up to 1.5 h before high-dose fentanyl anaesthesia for coronary artery bypass grafting has no harmful effects on the haemodynamics during the operation or the restoration of the cardiac function after the cardiopulmonary bypass, but it evidently does help to maintain the myocardial oxygen supply/demand balance during the anaesthesia induction.

Effects of High-Dose Fentanyl Anaesthesia on the Established Metabolic and Endocrine Response to Surgery

The effect of the administration of fentanyl 50 micrograms/kg body weight on the established metabolic response to pelvic surgery was investigated. In comparison with a control group of patients in whom anaesthesia was supplemented with halothane, fentanyl was associated with a significant decrease in only blood lactate concentrations and heart rate. There were no significant differences in blood glucose, plasma non-esterified fatty acids, and plasma cortisol values between the two anaesthetic techniques. It is concluded that the administration of high-dose fentanyl has little effect on the established metabolic response to surgery, compared with the marked changes observed when the same dose is given before the onset of surgical stimulation.

Myocardial metabolism and haemodynamic responses during high-dose fentanyl anaesthesia for coronary patients.

Fentanyl (mean dose 109 micrograms X kg-1) and oxygen were given to ten patients having coronary vein grafts. Serial studies were done before, during and after operation, of central and mean arterial pressures (MAP), cardiac index (CI) and coronary sinus flow (CBF) by thermodilution, myocardial oxygen consumption (MVO2) and lactate extraction (MLE). On induction CI and stroke work index decreased, but heart rate and MAP were unchanged as systemic resistance increased. Mean MAP and heart rate remained at the awake levels. Mean CBF remained unchanged along with stable MAP and coronary resistance. Oxygen content of CS blood increased on induction and remained elevated until the incision; it was above the awake level early postoperatively. MVO2 was low normal when the patients were awake and remained so. Normal MLE continued with a few exceptions. High-dose fentanyl did not uniformly abolish autonomic reflexes. Heavy premedication, complete beta adrenergic blockade and a high initial doses of fentanyl plus its continued infusion, aided in retaining a hypodynamic circulation and myocardial oxygenation.

Cardiovascular Effects of Pancuronium and Vecuronium During High-Dose Fentanyl Anesthesia

To define the role of muscle relaxants in hemodynamic responses to high-dose (75 micrograms/kg) fentanyl anesthesia, we compared the circulatory effects of pancuronium (Pc) with those of vecuronium (Vc) in patients about to undergo coronary artery bypass surgery. The first measurements were made while the patients were awake. Thereafter the patients were anesthetized with fentanyl, intubated under succinylcholine relaxation and mechanically ventilated with a mixture of oxygen in air (FIO2 0.50). Ten minutes after completion of the fentanyl injection, the second set of measurements was made. Immediately thereafter, 0.1 mg/kg of either Pc (n = 10) or Vc (n = 10) was given, and no relaxant was administered to 10 control patients. Heart rate (HR) and cardiac index (CI), which had decreased significantly after fentanyl induction, decreased further after Vc, the latter decreases being significantly greater than the decreases in HR and CI observed in control patients. After Pc, HR and CI increased to control awake levels; rate-pressure product also increased and stroke index decreased. Five of ten patients receiving Vc had a HR below 45 beats/min; HRs this low were not seen in patients given Pc. Neither Pc nor Vc affected systemic vascular resistance, but filling pressures of the heart decreased abruptly after both relaxants. We conclude that if maintenance of preanesthetic hemodynamic status is the objective of anesthetic management of patients having coronary artery bypass surgery, Pc helps to achieve this objective during high-dose fentanyl anesthesia. On the other hand, many patients with limited coronary vascular reserve may well benefit from the negative chronotropic effect of Vc.

Lorazepam and high-dose fentanyl anaesthesia: effects on haemodynamics and oxygen transportation in patients undergoing coronary revascularization.

The effects of intravenous lorazepam (0.05 mg/kg) on haemodynamics and oxygen transportation were studied in a group of 11 patients undergoing a coronary artery bypass grafting operation with high-dose fentanyl anaesthesia and compared to the changes in another group of 11 patients receiving the same anaesthesia, but saline instead of lorazepam. The measurements were made under stable haemodynamic conditions before the injection of lorazepam or saline, and repeated 5, 20 and 40 min after the injection. Lorazepam caused a slight decrease in the systemic and pulmonary arterial pressures and in the left ventricular stroke work index, as compared to the control group. The ECG or the rate-pressure product did not show changes indicative of myocardial oxygen supply/demand imbalance in either group. There was a similar decrease in the systemic oxygen transportation and an increase in the arterio-venous oxygen content difference in both groups, but the unchanged systemic oxygen consumption and arterial lactate level suggest a well-maintained tissue oxygenation. It is concluded that intravenous lorazepam does not cause important haemodynamic untoward effects as an adjunct to high-dose fentanyl anaesthesia in patients undergoing coronary artery bypass grafting.

The effect of population habits on side effects and narcotic requirements during high-dose fentanyl anaesthesia.

We measured and compared the anaesthetic requirements, incidences of chest wall rigidity and intraoperative hypertension, and time for recovery from anaesthesia after high dose fentanyl-oxygen anaesthesia in patients with and without histories of smoking, alcoholic intake and caffeine consumption who were undergoing coronary artery bypass grafting operations. Patients without a history of smoking and alcohol or caffeine intake required less fentanyl for induction and maintenance of anaesthesia and experienced less chest wall rigidity and hypertension than similar patients who had been chronically exposed to and/or consumed these agents. Pretreatment with more pancuronium (1.5 vs 1.0 mg/70 kg) prior to anaesthetic induction and increased fentanyl (3 X vs 1 X the "sleep" dose) administered after anaesthetic induction but before incision reduced the incidences of chest wall rigidity and intraoperative hypertension in patients with positive histories of exposure to the agents to values similar to patients without histories of exposure. Our findings suggest that population habits may affect the incidence of undesirable side effects during high dose fentanyl anaesthesia but that modifications in anaesthetic technique can minimize or eliminate these problems.

IMPAIRED B LYMPHOCYTE FUNCTION DURING OPEN-HEART SURGERY: Effects of Anaesthesia and Surgery

B lymphocyte function in vitro was measured in patients undergoing open-heart surgery. Conventional balanced anaesthesia, or high-dose fentanyl anaesthesia was used. Pokeweed mitogen (PWM) induced lymphocyte transformation was depressed at the end of the operation, but the response to formalinized Staphylococcus aureus Cowan I (StaCw) was not. The numbers of immunoglobulin producing and secreting cells measured by an indirect protein A plaque-forming cell assay decreased after PWM-stimulation, but remained unchanged after StaCw stimulation at the end of the operation. IgG, IgM and IgA secretion by PWM- and StaCw-stimulated lymphocytes, into the culture medium, was depressed in the period after operation. Depressed immune functions occurred after open-heart surgery, but not in association with anaesthesia alone before surgery. The decreases were not mediated by hydrocortisone-sensitive suppressor cells. Minor differences between the two anaesthetic techniques were found in lymphocyte proliferative responses.

Effects of high-dose fentanyl anaesthesia on the established metabolic and endocrine response to surgery.

The effect of the administration of fentanyl 50 micrograms/kg body weight on the established metabolic response to pelvic surgery was investigated. In comparison with a control group of patients in whom anaesthesia was supplemented with halothane, fentanyl was associated with a significant decrease in only blood lactate concentrations and heart rate. There were no significant differences in blood glucose, plasma non-esterified fatty acids, and plasma cortisol values between the two anaesthetic techniques. It is concluded that the administration of high-dose fentanyl has little effect on the established metabolic response to surgery, compared with the marked changes observed when the same dose is given before the onset of surgical stimulation.

Cardiovascular Effects of Pancuronium and Vecuronium during High-Dose Fentanyl Anesthesia

To define the role of muscle relaxants in hemodynamic responses to high-dose (75 μg/kg) fentanyl anesthesia, we compared the circulatory effects of pancuronium (Pc) with those of vecuronium (Vc) in patients about to undergo coronary artery bypass surgery. The first measurements were made while the patients were awake. Thereafter the patients were anesthetized with fentanyl, intubated under succinylcholine relaxation and mechanically ventilated with a mixture of oxygen in air (Flo2 0.50). Ten minutes after completion of the fentanyl injection, the second set of measurements was made. Immediately thereafter, 0.1 mg/kg of either Pc (n = 10) or Vc (n = 10) was given, and no relaxant was administered to 10 control patients. Heart rate (HR) and cardiac index (CI), which had decreased significantly after fentanyl induction, decreased further after Vc, the latter decreases being significantly greater than the decreases in HR and CI observed in control patients. After Pc, HR and CI increased to control a wake levels; rate-pressure product also increased and stroke index decreased. Five of ten patients receiving Vc had a HR below 45 beats/min; HRs this low were not seen in patients given Pc. Neither Pc nor Vc affected systemic vascular resistance, but filling pressures of the heart decreased abruptly after both relax-ants. We conclude that if maintenance of preanesthetic hemodynamic status is the objective of anesthetic management of patients having coronary artery bypass surgery, Pc helps to achieve this objective during high-dose fentanyl anesthesia. On the other hand, many patients with limited coronary vascular reserve may well benefit from the negative chronotropic effect of Vc.

Diazepam-Fentanyl Interaction-Hemodynamic and Hormonal Effects in Coronary Artery Surgery

Diazepam has been reported to produce hypotension when administered with anesthetic doses of fentanyl. Twenty patients undergoing coronary bypass surgery were randomly assigned to one of four treatment groups: group 1, no diazepam; groups 2, 3, and 4, 0.125, 0.25, and 0.5 mg X kg -1 of diazepam, respectively. All patients then received 50 micrograms X kg -1 fentanyl at 400 micrograms X min -1 and 0.4 mg X kg -1 metocurine at 2 mg X min -1. Hemodynamic parameters were recorded and blood was sampled for measurement of plasma catecholamine and histamine concentrations. Heart rate, cardiac index, stroke volume index, central venous pressure, pulmonary arterial and wedge pressures, and pulmonary vascular resistance did not change significantly in any group. Patients in groups 2-4 had significant decreases in mean arterial pressure and systemic vascular resistance during fentanyl infusion. These hemodynamic changes were accompanied by decreases in plasma epinephrine and norepinephrine levels. These hemodynamic and hormonal changes did not occur in patients given fentanyl only. Plasma histamine levels did not change significantly in any group. Caution should be used when diazepam in doses as small as 0.125 mg X kg -1 are combined with high-dose fentanyl anesthesia.

CHANGES IN CARDIAC OUTPUT AND SYSTEMIC ARTERIAL PRESSURE AFTER INSERTION OF ACRYLIC CEMENT DURING TRIMETAPHAN, SODIUM NITROPRUSSIDE AND GLYCEROL TRINITRATE-INDUCED HYPOTENSION: A comparison with changes during normotension

The effects of implantation of acrylic monomer on the cardiovascular response were studied in 37 patients undergoing hip arthroplasty and receiving high-dose fentanyl anaesthesia, under normotensive conditions or during hypotension induced by trimetaphan (TMP), sodium nitroprusside or nitroglycerine. Heart rate, mean arterial pressure (MAP), the ventricular stroke volume (SV) and the cardiac output (CO) were monitored before, and at 1, 2, 4, 6, and 8-min intervals after the insertion of the acrylic cement into the acetabulum or the neck of femur. There was a moderate decrease in MAP after insertion into the acetabulum under normotensive conditions and TMP-induced hypotension, while the reduction in pressure was significant after the cement's application in the femur. Heart rate did not change on insertion of the monomer in any of the patients. Moderate decreases in SV and CO were observed during normotension or TMP-induced hypotension. There were no significant changes in the cardiovascular haemodynamics on the insertion of the acrylic material under hypotension induced by nitroprusside or nitroglycerine.

Blood Pressure Response and Plasma Fentanyl Concentrations during High-and Very High-Dose Fentanyl Anesthesia for Coronary Artery Surgery

We examined whether different plasma fentanyl concentrations could maintain hemodynamic stability during coronary artery surgery. Two randomly selected groups of 10 patients were studied. Patients in group 1 received a single 75-micrograms/kg intravenous dose of fentanyl; patients in group 2 received the same dose but it was followed by an infusion of fentanyl at a rate of 0.75 micrograms/kg/min. The total dose of fentanyl in group 2 was 162 +/- 6.5 micrograms/kg (mean +/- SEM). At some point during surgery, all 10 patients in group 1 and 7 of 10 patients in group 2 had a hypertensive response. Plasma fentanyl concentrations in the two groups were not significantly different in the period 10-45 min after induction of anesthesia. At 60 min, corresponding to the time of aortic root dissection, mean plasma fentanyl concentration was statistically significantly lower in group 1 than in group 2 (13.5 +/- 1.4 ng/ml and 24 +/- 2.3 ng/ml, respectively, P less than 0.01). However, no significant difference was observed in the frequency of hypertensive response between the two groups in the period before cardiopulmonary bypass. During cardiopulmonary bypass, plasma fentanyl concentrations in group 1 were 2-3 times lower than those in group 2, and hypertension was observed in all 10 patients in group 1 but in only 2 patients in group 2 (P less than 0.05). Patients in group 1 were ventilated for 16.6 +/- 1.5 h, and those in group 2 for 19.1 +/- 1.8 h, postoperatively (P greater than 0.05). Six patients in group 1 required vasodilating drugs, whereas eight patients in group 2 required alpha-adrenergic agonists. Although the plasma fentanyl concentrations achieved were not successful in totally suppressing a hypertensive response, this study suggests that a plasma fentanyl concentration might be attainable to effect this.

Myocardial Blood Flow and Oxygen Consumption during High-Dose Fentanyl Anesthesia in Patients with Coronary Artery Disease

Myocardial Blood Flow and Oxygen Consumption during High-Dose Fentanyl Anesthesia in Patients with Coronary Artery Disease

Histamine Release During Morphine and Fentanyl Anesthesia

High doses of morphine produced peripheral vasodilation and frequently significant hypotension. These effects are thought to be due, in part, to the release of histamine. One putative advantage of high-dose fentanyl anesthesia is its relatively small effect on peripheral vascular resistance. In a randomized study, the authors examined the possibility that the hemodynamic differences between morphine and fentanyl might be attributable to histamine release. Fifteen patients were studied prior to coronary artery bypass surgery. Subjects received in infusion of morphine (1 mg . kg-1, iv at 100 micrograms . kg-1 . min-1 [n = 8]) or fentanyl (50 micrograms . kg-1 at 5 micrograms . kg-1 . min-1 [n = 7]). Patients in the morphine group had an average 750 per cent peak increase in plasma histamine accompanied by a significant decrease in mean arterial pressure (-27 mmHg- and systemic vascular resistance (-520 dyne . s . cm-5). The greatest decrease in systemic vascular resistance occurred in those patients with the highest levels of plasma histamine (r = -0.81). Patients in the fentanyl group had no change in plasma histamine and no decrease in arterial pressure or systemic vascular resistance. Cardiac output and heart rate were comparable between the two groups. Differences in the release of histamine account for most, if not all, of the different effects of morphine and fentanyl on the peripheral vasculature.

Haemodynamic and plasma vasopressin responses with high-dose fentanyl anaesthesia during aorto-coronary bypass operations.

Twelve male patients were given high dose fentanyl (75-100 microgram.kg-1) anaesthesia with oxygen during elective aorto-coronary bypass operations, and their haemodynamic and vasopressin responses were determined during induction, sternotomy, cardiopulmonary bypass, post-bypass and recovery periods. For comparison, a group of 12 male patients were anaesthetized with morphine, halothane 0.5 per cent, nitrous oxide and oxygen, and were similarly studied. Significant alterations in haemodynamics included increased mean arterial pressure after sternotomy in the fentanyl group, increased heart rate in both groups, increased systemic vascular resistance after sternotomy only in the halothane group, and decreased left ventricular stroke work index in both groups following induction, bypass, and during the recovery periods. Plasma vasopressin levels increased significantly in both groups during the bypass period, but returned to baseline levels following bypass. Serum sodium and osmolality did not change significantly, and urinary sodium and potassium excretion rose with the progress of the operation in both groups. A positive correlation was found between mean arterial pressure and vasopressin only in the halothane group. Systemic vascular resistance was correlated to vasopressin levels in both groups. Vasopressin response in both groups was similar, with significant but relatively low increases in levels during cardiopulmonary bypass. Fentanyl-oxygen anaesthesia did not provide haemodynamic stability in eight of 12 patients.

High Dose Fentanyl Anaesthesia with Oxygen for Aorto-Coronary Bypass Surgery

High Dose Fentanyl Anaesthesia with Oxygen for Aorto-Coronary Bypass Surgery

Myocardial blood flow and oxygen consumption during high-dose fentanyl anesthesia in patients with coronary artery disease.

The effects of high-dose fentanyl-oxygen anesthesia (100 micrograms/kg) on myocardial blood flow (argon washin), myocardial oxygen consumption, myocardial lactate balance, and cardiovascular dynamics were studied in nine patients undergoing three-vessel coronary artery bypass operations. All patients had been on maintenance doses of a beta-receptor blocker (pindolol). Except for pindolol all medication had been discontinued 48 hours prior to the study. Measurements were performed in the awake state, after 10 micrograms/kg fentanyl, after 100 micrograms/kg fentanyl, and during sternotomy. Moderate doses of fentanyl (10 micrograms/kg) produced minimal changes in myocardial blood flow, myocardial oxygen consumption, and cardiovascular dynamics; myocardial oxygen balance as well maintained. Large doses of fentanyl (100 micrograms/kg) produced a 16 per cent decrease in mean aortic pressure, cardiac index did not change significantly, while stroke volume index decreased by 23 per cent. Myocardial oxygen consumption decreased by 14 per cent and myocardial blood flow by 10 per cent. Myocardial lactate production was observed in five patients, indicating myocardial ischemia. During sternotomy arterial pressure and heart rate increased 8 per cent and 29 per cent, respectively, resulting in an increase in myocardial work, as reflected by a 38 per cent increase in myocardial oxygen consumption and by a 54 per cent increase in myocardial blood flow. Myocardial lactate production was observed in seven of nine patients. Our data demonstrate that in patients on maintenance doses of beta-receptor blockers, large doses of fentanyl as the sole "anesthetic" produce incomplete anesthesia and fail to protect the myocardium from ischemia due to noxious stimuli during coronary artery surgery.