High-dose Fentanyl Anesthesia Research Articles

Naloxone reversal of opioid anesthesia revisited: clinical evaluation and plasma concentration analysis of continuous naloxone infusion after anesthesia with high-dose fentanyl.

In spite of several advantages, the need for postoperative ventilatory support limits the use of high-dose opioid anesthesia. We prospectively evaluated the effectiveness of naloxone infusion for the reversal of high-dose fentanyl anesthesia. Anesthesia was maintained with fentanyl in patients undergoing major abdominal surgery. After anesthesia, the trachea was extubated when intravenous naloxone, which was titrated in separate 50- micro g doses, established an acceptable level of consciousness and arterial blood gas (ABG) status under spontaneous respiration; this was followed by continuous infusion started at the rate of the sum of the bolus doses per hour. The naloxone infusion was terminated based on evaluation of the level of consciousness, ABG, and acute abstinence symptoms. Postoperative pain was evaluated using self-reported four-step categorical terms (none, mild, moderate, and severe). Plasma concentrations of fentanyl and naloxone were analyzed in 12 patients, using high-performance liquid chromatography. Fifty-seven out of 59 eligible patients were successfully extubated at 34 +/- 14 min after termination of fentanyl (total dose, 127 +/- 64 micro g.kg(-1); mean +/- SD) with naloxone (total bolus, 3.4 +/- 2.6 micro g.kg(-1)). All these patients recovered fully without ventilatory support under the naloxone infusion, which was terminated at 11 +/- 7 h. The reduction of the naloxone infusion rate effectively relieved the increased pain, and no supplemental analgesic was used in any patients during the naloxone infusion. Pharmacokinetic analysis did not indicate any correlations between plasma fentanyl and naloxone concentrations. The results suggest that naloxone infusion with individual dose titration facilitates the use of high-dose opioid anesthesia, maintaining the advantager of this anesthesia.

Effect of epidural analgesia and high-dose fentanyl anaesthesia on hormonal and haemodynamic response to abdominal surgery

Effect of epidural analgesia and high-dose fentanyl anaesthesia on hormonal and haemodynamic response to abdominal surgery

Early aggressive nutrition in the neonate.

1. Patti J. Thureen, MD* 1. 2. *Associate Professor, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO. After completing this article, readers should be able to: 1. Describe the possible long-term effects of suboptimal nutrition in preterm infants and critically ill term neonates. 2. Explain why the current standard for postnatal nutrition in preterm infants may not be adequate for postnatal growth. 3. List the the lower limit at which to start intravenous protein delivery in very low-birthweight infants. 4. Characterize the commonly used definition for minimal enteral nutrition. 5. List the advantages of minimal enteral nutrition compared with exclusive total parenteral nutrition for the neonate. Nutritional practices vary dramatically among neonatal intensive care units (NICUs) in the United States. In many institutions, nutrition is introduced only gradually over the first weeks of life because of concerns of nutrient intolerance by the very preterm or ill infant who is fed intravenously and the risk of necrotizing enterocolitis (NEC) in preterm infants who are fed enterally. Often this period of nutritional deficiency is accepted as inevitable in this population. However, such a strategy of cautious nutrition might lead to a period of early malnutrition from which the neonate has a prolonged recovery and may have long-term adverse consequences. In many neonates this period of early nutritional deprivation need not be inescapable. Many neonatologists will consider the early feeding strategies for the NICU population suggested in this article to be somewhat aggressive. The premise for these recommendations for extremely low-birthweight (ELBW) infants is that avoiding early malnutrition has both short- and long-term benefits for the neonate. This strategy involves initiating total parenteral nutrition (TPN) in the first hours after birth and administering it in conjunction with initially small, and then advancing, enteral feedings beginning on the first or second day of life. Use of TPN is a means to achieve rapid, maximal nutrition, and early enteral feedings are designed to prime the gut and …

Endogenous morphine levels increase following cardiac surgery as part of the antiinflammatory response?

Exogenous morphine downregulates the activity of immunocompetent cells such as lymphocytes, granulocytes and macrophages. Furthermore, morphine increases the secretion of CRH, ACTH and glucocorticoids, i.e. substances with inhibitory effects on the immune system. In the present study we tested the hypothesis that endogenous morphine production is increased as part of the antiinflammatory response to cardiac surgery. Sixteen patients submitted to elective coronary artery bypass grafting (CABG) surgery were randomized to either thoracic epidural analgesia combined with general anaesthesia (group I) or high-dose fentanyl anaesthesia (group II). Patients in group I did not receive morphine while patients in group II received systemic morphine for postoperative pain relief. From each patient 18 blood samples were taken perioperatively and tested for morphine. Furthermore, monocyte function with respect to motility and shape was determined by computer-assisted image analysis. A steep increase in plasma morphine concentrations was demonstrated on the first postoperative day in patients in group I (not given morphine). Plasma morphine levels remained significantly elevated during the following five postoperative days. Patients in group II given morphine as pain treatment showed a larger and earlier morphine peak related to the morphine administration. Computer-assisted image analysis of leukocyte behaviour revealed a biphasic increase in cell motility. In conclusion, we demonstrate for the first time that endogenous morphine levels increase after the trauma of surgery. We surmise that morphine is part of the antiinflammatory response to cardiac surgery.

Cardiovascular Effects of Pancuronium, Vecuronium and Pipecuronium during High-Dose Fentanyl Anesthesia in Neonates, Infants and Children

Cardiovascular Effects of Pancuronium, Vecuronium and Pipecuronium during High-Dose Fentanyl Anesthesia in Neonates, Infants and Children

High-dose fentanyl does not suppress interleukin-1 beta-induced increases in plasma ACTH and corticosterone in rats.

High-dose fentanyl anesthesia is reported to attenuate the metabolic and endocrinal responses to surgery. Interleukin-1 (IL-1) is one of the key mediators in the immunoneuroendocrine system, and may be involved in the stress responses to surgery. We studied whether high-dose fentanyl may influence the IL-1 beta-induced alterations in plasma ACTH and corticosterone in rats. Plasma ACTH, corticosterone, blood pressure, heart rate and acid-base status were determined in either awake or fentanyl-anesthetized animals immediately before and after either phosphate buffered saline or IL-1 beta administration. Fentanyl anesthesia was induced by bolus intravenous injections of fentanyl at 50 micrograms/kg and pancuronium bromide at 0.2 mg/kg, and maintained by continuous administrations of fentanyl at 100 or 200 micrograms.kg-1.h-1 and pancuronium bromide at 0.4 microgram.kg-1.h-1. In awake rats, IL-1 beta at incremental doses of 0.25, 0.5 and 1 microgram/kg increased plasma ACTH in a dose-dependent manner, but heat-inactivated IL-1 beta at 4 micrograms/kg did not influence plasma ACTH. A noxious stimulus with tail clamping for 30 min did not significantly alter plasma ACTH in fentanyl-anesthetized rats. Fentanyl reduced the basal plasma corticosterone, but it did not modulate the increases in plasma ACTH and corticosterone after the administration of IL-1 beta at 1 microgram/kg. Fentanyl moderately increased the basal blood pressure and heart rate, but it moderately attenuated the IL-1 beta-induced elevations of blood pressure and heart rate. IL-1 beta moderately decreased PCO2 in awake animals. Fentanyl anesthesia, which is able to suppress the endocrine responses to noxious stimuli, does not attenuate the IL-1 beta-mediated activation of the pituitary-adrenal axis in rats.

Effects of thoracic epidural analgesia on coronary hemodynamics and myocardial metabolism in coronary artery bypass surgery

A possible influence of thoracic epidural analgesia on coronary hemodynamics and myocardial metabolism in coronary artery bypass grafting was investigated. The study was prospective and randomized. The study was performed in a university hospital. Thirty male patients less than 65 years of age and with ejection fraction greater than 0.5 participated. They were randomized into 3 groups: the high fentanyl (HF) group receiving high-dose fentanyl (55 micrograms/kg) anesthesia, the HF + thoracic epidural analgesia (TEA) group receiving the same general anesthesia plus thoracic epidural analgesia, and the low-fentanyl (LF) + TEA group receiving low-dose fentanyl (15 micrograms/kg) anesthesia plus thoracic epidural analgesia. A thoracic epidural catheter, a peripheral and central venous catheter, a radial artery catheter, a thermodilution pulmonary artery catheter, and a coronary sinus reverse thermodilution catheter were inserted. Coronary circulatory parameters, myocardial oxygenation, and myocardial substrate utilization were investigated before bypass and for 9 hours after bypass. Before bypass, the most striking finding was a reduction in myocardial lactate extraction in all groups, but also coronary flow and myocardial oxygen consumption decreased compared with baseline. After bypass, the only significant finding was a lower coronary vascular resistance early postoperatively in the epidural groups, but coronary blood flow was adequate in all groups. Myocardial metabolism was essentially unchanged both with and without epidural analgesia after bypass. With regard to the coronary circulation and myocardial metabolism, no hard data supporting the use of thoracic epidural analgesia in coronary artery bypass grafting were found.

Oxygen consumption following pediatric cardiac surgery

Metabolic responses during recovery from cardiac operations for various congenital heart defects were studied in 30 mechanically ventilated pediatric patients in two groups: infants 1 year or less (group I) and children more than 1 year old (group II). Oxygen consumption (VO 2) and carbon dioxide production (VCO 2) were measured using a pediatric metabolic monitor intermittently after induction of anesthesia, after skin closure, 2 to 4 hours postoperatively, and on the first postoperative morning in the pediatric intensive care unit. Energy expenditure and respiratory quotient were determined from respiratory gas measurements. Rectal and skin temperatures and hemodynamic variables were recorded at the same time. VO 2 increased during rewarming 2 to 4 hours after the operation by 12 ± 15% in group I and by 24 ± 19% in group II, while rectal temperature increased by 2.0 ± 1.2°C and 1.8 ± 1.4°C, respectively. No further increase in VO 2 occurred until the first postoperative morning. A hypermetabolic response was not seen in all cases despite marked thermal changes. High-dose fentanyl anesthesia partly explains the low responses. On the other hand, low cardiac output may also compromise oxygen supply. Sixty-three percent of infants were treated for cardiac failure before surgery and 75% needed inotropic support immediately after the operation. Low central venous oxyhemoglobin saturation values (S CVO 2 < 60%) were observed during rewarming, indicating an increase in oxygen extraction secondary to an increased oxygen demand in the brain during recovery from anesthesia, and a low cardiac output or delayed restoration of cerebral blood flow after CPB and deep hypothermia.

Thoracic epidural analgesia in aortocoronary bypass surgery II: effects on the endocrine metabolic response

Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may-in part-be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS). Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 micrograms.kg-1) anaesthesia, the HF+TEA group with the same fentanyl dose+TEA with 10 ml bupivacain 5 mg.ml-1, followed by 4 ml every hour, and the LF+TEA group receiving fentanyl 15 micrograms.kg-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively. A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and cortisol was noticed in all groups, but the increase was delayed in the epidural groups. Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone.

Thoracic epidural analgesia in aortocoronary bypass surgery I: haemodynamic effects

Tachycardia and hypertension may cause myocardial ischaemia in patients with coronary heart disease going through major surgery. Thoracic epidural analgesia (TEA) has been reported to be beneficial in this situation. The haemodynamic effects of TEA in aortocoronary bypass surgery were investigated in 30 male patients < 65 years old and with ejection fraction > 0.5. They were randomized into 3 groups: the high dose fentanyl (HF) group receiving high-dose fentanyl (55 micrograms.kg-1) anaesthesia, the HF+TEA group receiving the same fentanyl dose+TEA with 10 ml bupivacaine 5 mg.ml-1 followed by 4 ml every hour, and the low dose fentanyl (LF) + TEA group receiving low-dose fentanyl (15 micrograms.kg-1) anaesthesia+TEA. Haemodynamic parameters, the use of vasoactive and inotropic drugs and fluid balance were followed during the operation and for 20 h postoperatively. Before bypass the only significant difference between groups was a higher mean pulmonary arterial pressure in the HF+TEA group and a lower systemic vascular resistance (SVR) in the LF+TEA group, both compared to the HF group. 89% of epidural group patients needed small doses of ephedrine whereas more HF group patients were given nitroglycerine. During bypass SVR and mean arterial pressure (MAP) were significantly higher and pump flow lower in the HF group compared to the LF+TEA group. More ketanserin to HF group patients and methoxamine to epidural group patients were given. After bypass heart rate increased in all groups. Lower MAP 0.5 h after bypass and higher filling pressures in the early post bypass period in the epidural groups, most pronounced in the HF+TEA group, were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Propofol and fentanyl anaesthesia for patients with low cardiac output state undergoing cardiac surgery: comparison with high-dose fentanyl anaesthesia

We have compared the haemodynamic effects of an infusion of propofol 8 mg kg-1 h-1 followed by 4 mg kg-1 h-1 and fentanyl 15 micrograms kg-1 (group 1) with midazolam 3-6 mg and fentanyl 60 micrograms kg-1 (group 2) in patients with a low cardiac output state undergoing cardiac surgery. Heart rate was lower in group 1 throughout the period before cardiopulmonary bypass. There were no significant differences between the groups in other measured variables. Arterial pressure decreased in both groups after induction, by 21% in group 1 and 18% in group 2. Thermodilution assessment of right ventricular ejection fraction was unchanged. Myocardial contractility was not affected adversely. Patients in group 1 who received an infusion of propofol and a smaller dose of fentanyl awakened sooner and the trachea was extubated earlier.

Intraoperative and Postoperative Effects of Vancomycin Administration in Cardiac Surgery Patients

ROMANELLI, V. A.; HOWIE, M. B.; MYEROWITZ, P. D.; ZVARA, D. A.; REZAEI, A.; JACKMAN, D. L.; SINCLAIR, D. S.; MCSWEENEY, T. D. Author Information

The effects of low-dose midazolam for induction of high-dose fentanyl anesthesia for coronary artery bypass graft.

A small dose of midazolam 0.06 mg/kg or diazepam 0.15 mg/kg was used for induction of high-dose fentanyl (50 μg/kg) anesthesia in patients undergoing coronary artery bypass grafting operation. Hemodynamic variables were measured 5 min after the injection of midazolam or diazepam, after the end of the fentanyl infusion, and following endotracheal intubation. Midazolam and diazepam caused a slight but significant decrease in mean arterial pressure (-9.8%) and -11.8%), respectively) and a further significant depression was observed in the diazepam group but not in the midazolam group after fentanyl. Although the cardiac index was maintained in patients who received madazolam, a significant decrease was observed in the diazepam group (-28.5%) after administration of fentanyl. Heart rate was decreased in the diazepam group but not in the midazolam group. Therefore, a small dose of midazolam may be a suitable induction agent for high-dose fentanyl anesthesia in patients with coronary artery disease.

Binding of Fentanyl and Pethidine to Muscarinic Receptors in Rat Brain

Symptoms similar to the central anticholinergic syndrome are often seen after high dose fentanyl anesthesia. Therefore, the binding of fentanyl, alfentanil, pethidine and morphine to opioid and muscarinic receptors was investigated in rat brain homogenate with [3H]naloxone and [3H]QNB as the radioligands, respectively. Both pethidine and fentanyl inhibited [3H]QNB binding with Ki values in the micromolar range. Alfentanil and morphine had no affinity for muscarinic receptors. The ratio of the Ki values for muscarinic receptors versus opioid receptors was 2.5 for pethidine and 88 for fentanyl. It is concluded that binding of fentanyl to muscarinic receptors is likely to occur during high-dose fentanyl anesthesia.

The effects of low-dose midazolam for induction of high-dose fentanyl anesthesia for coronary artery bypass graft

The effects of low-dose midazolam for induction of high-dose fentanyl anesthesia for coronary artery bypass graft

Fentanyl and pethidine are antagonists on muscarinic receptors in guinea-pig ileum.

In order to evaluate the anticholinergic effect of fentanyl and pethidine, the influence of these drugs on the cumulative dose-response curves of carbacholine on the guinea-pig ileum has been investigated. Fentanyl and pethidine displaced the dose-response curve for carbacholine to the right in a parallel fashion, indicating competitive antagonism. Dissociation constants determined by an agonist EC versus antagonist plot were 0.22 mumol/l for fentanyl and 1.4 mumol/l for pethidine. It is concluded that during high-dose fentanyl anaesthesia, fentanyl may bind to muscarinic receptors and thereby produce a central anticholinergic syndrome. An additional finding was that the maximal response to carbacholine increased significantly when combined with pethidine.

The effects of propofol compared to high-dose fentanyl anesthesia on rheologic parameters in coronary artery surgery

Propofol has previously been found to decrease hematocrit values. Because hematocrit is an important determinant of blood viscosity, lower hematocrits may cause a decrease in blood viscosity, improving blood flow and oxygen delivery. This phenomenon may be beneficial in certain intraoperative situations. To study the influence of two anesthetic techniques on a variety of rheologic parameters, 32 patients scheduled for coronary artery bypass grafting (CABG) were divided into two groups. Group I (n = 18) was induced with high-dose fentanyl anesthesia (100 μg/kg), and group II (n = 16) with a combination of propofol and fentanyl anesthesia (1 to 1.5 mg/kg and 35 to 50 μg/kg, respectively). Maintenance anesthesia continued with infusions of the same drugs. Blood and plasma viscosity, hematocrit, erythrocyte aggregation factor, and erythrocyte deformability were measured preoperatively, intraoperatively, and up to 48 hours postoperatively. Whole blood viscosity was corrected to a standard hematocrit of 0.45. The two groups were comparable with respect to age, bypass duration, blood loss, urine output, transfusions, and fluid management. Erythrocyte deformability did not decrease during or after cardiopulmonary bypass (CPB). In both groups, hematocrit and blood and plasma viscosity were decreased significantly during and after CPB ( P < 0.01) and returned to baseline levels 48 hours after surgery. After induction and before CPB, blood viscosity was only decreased in group 11. However, the corrected blood viscosity was significantly elevated at all shear rates in group II compared to group I at 24 and 48 hours postoperatively ( P < 0.01). In group II at these sampling times, this parameter was also significantly elevated compared to preoperative values. The results show that in group II the postanesthetic, preoperative decrease in hematocrit was accompanied by the expected decrease in whole blood viscosity. On the other hand, the late postoperative viscosity was shown to be too high for the accompanying hematocrit. This could compromise oxygen delivery to the myocardial muscle. Thus, propofol, with its known negative circulatory effects, may not be the drug of choice for CABG.

Changes in free and total catecholamine concentrations in plasma in patients undergoing coronary artery bypass grafting under high-dose fentanyl anesthesia.

We measured free and total catecholamine in ten patients undergoing coronary artery-bypass grafting under high-dose fentanyl (93.9 +/- 2.2 microg.kg(-1), mean +/- SE) anesthesia. Arterial blood samples were obtained: 1) before induction of anesthesia (control), 2) 1 min after intubation, 3) 1 min after skin incision, 4) 1 min after median sternotomy and, 5) just before termination of cardiopulmonary bypass (CPB). The concentrations of free and total catecholamine were measured by HPLC using fully automated analyzer, 8030-TOHSO. Free and total catecholamine concentrations did not change significantly before CPB. At the termination of CPB, however, the levels in free dopamine, norepinephrine and epinephrine all increased several fold as compared with control. Similarly, total norepinephrine and epinephrine also increased at the end of PCB, while total dopamine did not change. Present results indicated that 1) the measurement of free CAs is more significant than the measurement of total CAs for the assessment of sympathoadrenal responses to surgical stimuli, and that 2) high-doses of fentanyl produce hemodynamic stability by suppressing sympathoadrenal responses elicited by the usual surgical procedures. However, stress triggered by CPB could not be suppressed totally by fentanyl even with high dose.

Regional EEG Response to the Induction of High-Dose Fentanyl Anesthesia Evaluated by a New Brain Function Monitoring System

Regional EEG Response to the Induction of High-Dose Fentanyl Anesthesia Evaluated by a New Brain Function Monitoring System

Hemodynamic responses to pancuronium and vecuronium during high-dose fentanyl anesthesia for coronary artery bypass grafting

The hemodynamic and electrocardiographic (ECG) effects of pancuronium and vecuronium were compared during high-dose fentanyl anesthesia for coronary artery bypass grafting (CABG) surgery. Forty-eight morphine-scopolamine premedicated patients scheduled for elective CABG were anesthetized with fentanyl (100 μ/kg) in divided doses, and either of two muscle relaxants, pancuronium (n = 26; 0.10 mg/kg) or vecuronium (n = 22; 0.09 mg/kg). Hemodynamic data, blood gas samples, and ECG tracings were obtained at the following intervals: (1) control; (2) prior to intubation; (3) 1 minute after intubation; (4) prior to sternotomy; and (5) 1 minute after sternotomy. In the pancuronium group, heart rate (HR), cardiac index (CI), and rate-pressure product (RPP) were increased after induction of anesthesia and following intubation. Eleven patients (42.3%) displayed ischemic ST segment changes. Four patients in this group developed tachycardia and hypertension to an extent requiring pharmacological intervention. Vecuronium-treated patients displayed no increases in HR, MAP, and RPP, and a decrease in CI. Only one patient (5.6%) developed evidence of ischemic ECG changes. Four patients in the vecuronium group, all receiving preoperative β-blocker therapy, became hypotensive and bradycardic after the induction of anesthesia. The present investigation confirms the increased incidence of myocardial ischemia during high-dose fentanyl-pancuronium anesthesia. Although vecuronium was associated with fewer myocardial ischemic changes, the occurrence of bradycardia and hypotension in some patients receiving preoperative β-adrenergic blocking drugs remains a concern.