High-dose Opioid Anesthesia Research Articles

Fentanyl - Based Cardiac Anesthesia Provides Higher Recovery Compared with Morphine in Elective CABG Surgery Patients

Background : High-dose opioid anesthesia during cardiac surgery has been the mainstay of cardiacanesthesia for decades due to its ability to preserve hemodynamic stability and attenuate hormonal andmetabolic response to surgical stress. The hypothesis of this study is that the use of fentanyl as part of abalanced anesthetic would lead to improved patient health status and recovery during the first 3 daysafter cardiac surgery with CPB compared with morphine. Quality of recovery was assessed using theQoR-40 questionnaire administered preoperatively and daily on postoperative days 1–3. Hemodynamicvariables, duration of tracheal intubation, organ morbidities, intensive care unit (ICU) and hospitallength of stay were evaluated. Methods: This comparative randomized double blind study was conducted in the department ofcardiothoracic vascular anaesthesia and critical care of Apollo Hospitals,Dhaka on 100 patientsundergoing elective CABG. Study period was (January-July), 2019. The study was approved by theinstitutional review board, and informed consent was obtained from all subjects. One hundred patientspresenting for elective CABG surgery, between the ages of 18 and 79, were enrolled in the study. Exclusioncriteria included (1) concurrent valvular surgery or the presence of valvular disease, (2) reoperativeprocedures, (3) unstable angina or elevated cardiac enzymes within 48 hours of surgery, (4) morphine orfentanyl allergy, (5) the need for an intra-aortic balloon pump or inotropic agents preoperatively, (6)psychiatric or central nervous system disturbances precluding completion of the QoR-40. Results: Compared with patients given morphine, those receiving fentanyl had higher global QoR-40scores on postoperative days 1 (174.8 vs 162.5, P 0.001), 2 (175 vs 166.1, P 0.001), and 3 (178.1 vs 167.3,P 0.001). Differences between the groups were observed in the QoR-40 dimensions of emotional state,physical comfort, and pain . Postoperative visual analog scale pain scores, use of pain medication in theICU and surgical ward, and postoperative febrile reactions were reduced significantly in the fentanylgroup . No differences between the groups were noted in duration of tracheal intubation,ICU and hospitallength of stay, or postoperativecomplications. Conclusion: Continuous intravenous infusions of fentanyl have been used to provide intraoperativeanalgesia also give good-to-excellent postoperative analgesia furthermore early extubation and the qualityof postoperative recovery in cardiac surgical patients can be enhanced when fentanyl is used as part of abalanced anesthetic. JBSA 2020; 33(1): 28-35

Does high-dose opioid anesthesia exacerbate ischemic spinal cord injury in rabbits?

Intrathecal morphine given during a post-ischemic period has been reported to have the potential to exacerbate ischemic spinal cord injury. However, it remains unknown whether synthetic opioids administered systemically exacerbate ischemic injury. We sought to compare the damage of the spinal cord after transient spinal cord ischemia in rabbits anesthetized with three different regimens; isoflurane, fentanyl with isoflurane, and remifentanil with isoflurane. We assigned rabbits to three groups (n = 9 in each); an isoflurane group (isoflurane 1 minimum alveolar concentration [MAC]), a fentanyl group (isoflurane 0.5 MAC + 100 microg x kg(-1) i.v. fentanyl given over 30 min before aortic occlusion), and a remifentanil group (isoflurane 0.5 MAC + 1 microg x kg(-1) x min(-1) i.v. remifentanil started 30 min before aortic occlusion and maintained until 1 h after reperfusion). Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Hindlimb motor function (score range: 4, normal to 0, paraplegia) was assessed daily for 7 days, and then the number of normal neurons in the anterior spinal cord was counted. Severe motor dysfunction (score < or = 1) was observed in seven, four, and five animals in the isoflurane, fentanyl, and remifentanil groups, respectively. There were no significant intergroup differences in neurological scores. There were no differences in the numbers of normal neurons among the three groups (22 +/- 22, 42 +/- 30, 33 +/- 28, respectively). Our results suggest that neither i.v. fentanyl nor i.v. remifentanil added to 0.5 MAC isoflurane exacerbated ischemic spinal cord injury in rabbits when compared to 1 MAC isoflurane.

Remifentanil or sufentanil for coronary surgery

High-dose opioid anaesthesia contributes to decreasing metabolic and hormonal stress responses in patients undergoing cardiac surgery. However, the increase in context-sensitive half-life of opioids given as a high-dose regimen can affect postoperative respiratory recovery. In contrast, remifentanil can be given in high doses without prolonging context-sensitive half-life due to its rapid metabolism. Therefore, we performed a prospective, randomized trial to compare anaesthesia consisting of propofol/remifentanil or propofol/sufentanil with regard to postoperative respiratory function and outcome. Patients undergoing coronary artery bypass grafting were randomized to a propofol/remifentanil (0.5-1.0 microg kg(-1) min(-1)) or propofol/sufentanil (30-40 ng kg(-1) min(-1)) based anaesthetic. Carbon dioxide response, forced expiratory volume in one second, vital capacity, and functional residual capacity were measured 1 day prior to the operation, 1 h before extubation, 1, 24 and 72 h after extubation. In addition, the incidence of atelectasis, pulmonary infiltrates, intensive care unit and postoperative length of stay were compared. Patients and physicians were blinded to the treatment group. Twenty-five patients in each treatment group completed the study. There was no difference between patients of the treatment groups regarding demographics, risk- or pain scores. In all patients, carbon dioxide response, forced expiratory volume in one second, vital capacity and functional residual capacity were decreased postoperatively compared to baseline. Patients randomized to remifentanil had less depression of carbon dioxide response, less atelectasis and shorter postoperative length of stay (12 d vs. 10 d) than after sufentanil (P < 0.05). Intraoperative use of high-dose remifentanil for coronary artery bypass grafting may be associated with improved recovery of pulmonary function and shorter postoperative hospital length of stay than sufentanil.

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 high dose remifentanil or sufentanil on postoperative pulmonary function in patients undergoing coronary surgery

Intraoperative use of high dose opioid anesthesia is common practice for hemodynamic control in patients undergoing coronary artery bypass grafting (CABG). It is unclear whether postoperative pulmonary function is affected by this practice. Remifentanil is an ultra-short acting μ-agonistic opioid [1]. We hypothesized that remifentanil is associated with improved pulmonary function, compared with longer acting opioids. Therefore, we performed a controlled randomized trial to evaluate pulmonary function in patients undergoing CABG with high dose remifentanil versus sufentanil.

Total Intravenous Anesthesia with Propofol and Remifentanil for Short Painful Procedures: Does High-Dose Opioid Anesthesia Increase Speed of Recovery?

Total Intravenous Anesthesia with Propofol and Remifentanil for Short Painful Procedures: Does High-Dose Opioid Anesthesia Increase Speed of Recovery?

Morbidity outcome in patients with hypertrophic obstructive cardiomyopathy undergoing cardiac septal myectomy: Early-extubation anesthesia versus high-dose opioid anesthesia technique

Objective: Anesthetic management of patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing septal myectomy is challenging. The morbidity outcome of early-extubation anesthesia (EEA), or fast tracking, versus high-dose opioid (HDO) anesthesia was studied. Design: Retrospective study. Setting: University teaching hospital. Participants: One hundred seventy-five cardiac septal myectomy patients (EEA, n = 53; HDO, n = 122). Interventions: EEA technique consisted of low-dose fentanyl, 10 to 15 μg/kg; propofol infusion; midazolam; and inhalation agent. HDO technique consisted of fentanyl, 50 to 100 μg/kg, and benzodiazepines, with or without an inhalation agent. Demographic data, preoperative symptoms, and data on anesthesia management and postoperative complications were recorded. Measurements and Main Results: There were no differences between the groups (EEA v HDO, respectively) regarding age, sex, preoperative symptoms (dyspnea, 89% v 79%; palpitations, 28% v 26%; angina, 47% v 61%; syncope, 47% v 41%), redo surgery, or combined surgery. Mean ± standard deviation time to tracheal extubation was 7.2 ± 5.3 hours in EEA versus 19.4 ± 10.5 hours in HDO patients ( p < 0.0001). Intensive care unit (ICU) stay was significantly shorter in EEA versus HDO patients (2.2 v 3.0 days; p < 0.005), with the trend toward earlier hospital discharge (9.7 v 11.3 days; p = 0.09). There was a high requirement for temporary pacing in both groups immediately postoperatively (EEA, 60% v HDO, 48%; p > 0.08). Permanent pacemaker insertion postoperatively was required in 7 of 53 patients (13%) in the EEA group and 11 of 122 patients (9%) in the HDO group ( p > 0.25). Atrial arrhythmias occurred postoperatively in 25% of EEA patients versus 34% of HDO patients ( p > 0.08). Conclusion: EEA facilitates earlier tracheal extubation by 12 hours in patients with HOCM undergoing septal myectomy, significantly shortening ICU stay by 1 day without increasing perioperative cardiac morbidity or mortality.

Is there a role for highdose opioid anaesthesia in the 1990’s?

Is there a role for highdose opioid anaesthesia in the 1990’s?

Propofol-fentanyl versus isoflurane-fentanyl anesthesia for coronary artery bypass grafting: Effect on myocardial contractility and peripheral hemodynamics

To avoid intraoperative awareness and postoperative respiratory depression from high-dose opioid anesthesia, propofol (P), or isoflurane (I) has been combined with moderatedose opioid with varying results. However, the effects of both P and I on myocardial contractility and left ventricular afterload have not been completely quantified. The end-systolic pressure-diameter relationship (ESPDR) of the left ventricle (LV) is a reliable method to quantitatively assess LV contractility because it is relatively independent of changes in preload and incorporates afterload changes. The purpose of this study was to quantify the cardiodynamic effects of propofol-fentanyl (PF) anesthesia in comparison with isoflurane-fentanyl (IF) anesthesia in patients undergoing coronary artery bypass grafting (CABG). Thirty patients with normal or moderately impaired LV function (ejection fraction ≥40% with LV end-diastolic pressure ≤18 mmHg, no preoperative akinesia or dyskinesia) undergoing elective CABG were studied. After premedication with flunitrazepam, 2 mg orally, all patients were induced with thiopental, 1 mg/kg, fentanyl, 20 μg/kg, and vecuronium, 0.1 mg/kg, and were ventilated with oxygen/air (F 1O 2 0.6). Anesthesia was maintained throughout the procedure with a zero-order intravenous (IV) continuous infusion of P, 3 mg/kg/h (PF group), or with isoflurane inhalation of 0.6% (IF group), supplemented by intermittent boluses (5 μg/kg) of fentanyl (up to a total maintenance dose of 30 μg/kg). After intubation, a cross-section of the LV was visualized by two-dimensional transesophageal echocardiography and an m-mode echocardiogram was obtained at the maximum anterior-posterior diameter. The radial artery pressure tracing and the ECG were simultaneously recorded with the M mode. Slope of ESPDR (Ees) and fractional shortening (FS) were measured before (T 0) and during P or I administration (T 1). A contemporary full hemodynamic profile using a pulmonary artery catheter was obtained at T 0 and T 1. Statistical significance was tested with a t test for paired data. No patient experienced awareness of any intraoperative events. There were no significant differences between T 0 and T 1 hemodynamic parameters in both PF and IF groups. No significant decrease of myocardial contractility, measured by Ees (15.3% with P vs. 11.1% with I), was seen at T 1, together with unchanged filling pressures (CVP and PCWP). Coronary perfusion pressure (CPP), as a myocardial perfusion index, was unmodified after both anesthetic drugs. In conclusion, low doses of P or I combined with moderate doses of fentanyl (up to 50 μg/kg) give adequate levels of anesthesia and good hemodynamic stability. Slightly depressed contractility together with an unchanged CPP suggest a good myocardial oxygen balance (MDO 2/MVO 2) for both techniques.

Propofol versus midazolam for intensive care unit sedation after coronary artery bypass grafting

To compare the safety and effectiveness of propofol (2,6-diisopropylphenol) to midazolam for sedation of mechanically ventilated patients after coronary artery bypass grafting. Open, randomized, prospective trial. Cardiothoracic intensive care unit (ICU), Cleveland Clinic Foundation. Eighty-four patients with normal or moderately impaired left ventricular function who underwent elective coronary artery bypass graft surgery under high-dose opioid anesthesia. Patients were randomly selected to receive either propofol (mean loading dose 0.24 mg/kg; mean maintenance dose 0.76 mg/kg/hr) or midazolam (mean loading dose 0.012 mg/kg; mean maintenance dose 0.018 mg/kg/hr). Infusion rates were titrated to keep patients comfortable, drowsy, and responsive to verbal stimulation. Study duration, 8 to 12 hrs; infusions were started in the ICU when patients were awake and hemodynamically stable. During therapy, both groups had lower mean arterial pressures and heart rates compared with baseline measurements; however, the propofol group had significantly lower heart rates than the midazolam group during the first 2 hrs of infusion. The propofol group also had significantly lower blood pressure measurements 5 and 10 mins after the initial dose, although there was no difference during infusion. Baseline cardiac output was measured before starting the infusion, and measurements were repeated during continuous infusion at 4, 8, and 12 hrs. Cardiac output values were similar. Propofol maintenance infusions ranged from 3 to 30 micrograms/kg/min and midazolam infusions ranged from 0.1 to 0.7 micrograms/kg/min. At these infusion rates. both groups had adequate sedation, based on nurse and patient evaluations; however, the propofol group used significantly lower total doses of sodium nitroprusside and supplemental opioids. Both propofol and midazolam provided safe and effective sedation of coronary artery bypass graft patients recovering from high-dose opioid anesthesia. The reduced need for both antihypertensive medication and opioids seen in the propofol group may be advantageous. However, the hypotension seen after the initial bolus dose of propofol may be a concern. No difference between the two drugs could be demonstrated in time to extubation or ICU discharge, although it is probable that time to extubation was governed more by residual operative opioids than the study agents.

Anaesthesia for coronary artery surgery--a plea for a goal-directed approach.

The purpose of the current literature review was to examine whether changes in current anaesthetic techniques are warranted for patients undergoing coronary artery surgery in light of recent information presented in the literature. The objectives of a cardiac anaesthetic technique are to maintain haemodynamic stability and myocardial oxygen balance, minimize the incidence and severity of ischaemic episodes, be aware of cardiopulmonary bypass-induced pharmacokinetic changes, and facilitate early tracheal extubation if appropriate. Many techniques have been utilized. Provided attention is paid to the details of managing myocardial oxygen supply and demand, none has emerged as superior in preventing intraoperative myocardial ischaemia. Silent myocardial ischaemia (i.e., ischaemia occurring in the absence of haemodynamic aberrations) is common throughout the perioperative period and may occur even in the presence of an appropriately used anaesthetic technique. The incidence and severity appear to be greatest in the postoperative period when the effects of anaesthesia are dissipating. The use of high-dose opioid anaesthesia may no longer be the most appropriate technique to facilitate the anaesthetic objectives. The role of pain management in altering the incidence of ischaemia requires further study. Increased waiting lists for cardiac surgery and ever-diminishing resources should prompt a re-evaluation of early extubation (i.e., within eight hours) as a method of improving utilization of scarce ICU resources. It is suggested that this should be possible with currently available agents to achieve the anaesthetic objectives. Future suggestions for research in this area are made.

Con: Midazolam is not the sedative of choice to supplement narcotic anesthesia

T HE DOSE-RESPONSE curve for narcotic or opioid anesthesia is not linear but reaches a plateau beyond a certain plasma concentration.‘J In patients undergoing cardiac surgery, increasing the plasma concentration of fentanyl above 20 ng/mL had little effect on the incidence of hypertension following sternotomy or aortic dissection.2,3 Similarly, high-dose opioid anesthesia using sufentanil or alfentanil has not suppressed breakthrough hypertension.4v5 Episodes of patient awareness are associated with this anesthetic technique,6 and also time to extubation is prolonged. If increasing the dose of opioid does not produce better suppression of hemodynamic responses to noxious stimuli, it seems more appropriate that a smaller dose of opioid is used to provide analgesia and another agent to provide anesthesia. Providing unconsciousness and amnesia is essential during highly stressful cardiac surgery, and, because opioids, by the nature of their action, are not expected to produce these effects,’ the addition of a hypnotic drug to a moderate or balanced dose of opioid would seem to be a logical approach to anesthetizing patients. The application of balanced total intravenous anesthesia in the context of cardiac surgery has in the past been limited by the availability of agents that are pharmacokinetically suited to continuous infusion. The advent of new short-acting drugs means that the component of hypnosis, analgesia and reflex suppression can now be provided by infusions that are independently titrated. Analgesia is provided by either a continuous infusion or by intermittent injection of one of the opioids, but using much lower total doses. The adjuvants frequently used are midazolams or propofol.’ Although midazolam is a good sedative and provides amnesia, it does have hemodynamic side effects that may not be beneficial during anesthesia for cardiac surgery. Midazolam exerts its major hemodynamic effects at the peripheral level with a small decrease in systemic vascular resistance but marked venodilatation.8J0 By decreasing the venous return, preload is reduced, which may contribute to a fall in cardiac output and blood pressure. Maintenance of the cardiac output greatly depends on compensatory mechanisms such as increased baroreceptor activity, blood mobilization from the splanchnic area and increased sympathetic tone. In patients with hypovolemia, hypertension and P-adrenergic blockade, impairment of these compensatory mechanisms has been reported to induce serious hypotensive episodes.” These have been described in patients with severe noncardiac systemic illness, in whom midazolam

Stress responses to surgery lowered by high dose opioid anaesthesia

Stress responses to surgery lowered by high dose opioid anaesthesia

THE AUDITORY STEADY STATE RESPONSE DURING SUFENTANIL ANAESTHESIA

The auditory steady state response (ASSR) is a sinusoidal evoked potential elicited by rapidly repeated auditory stimuli. The ASSR was recorded in eight patients during high-dose sufentanil anaesthesia for cardiac surgery in order to assess its usefulness as a measure of the level of consciousness. The electroencephalogram (EEG) was recorded for comparison. The ASSR was present before induction in all patients. It was attenuated severely or possibly abolished with loss of consciousness, and reappeared at low amplitude 5-10 min later and remained attenuated until the end of surgery. The amplitude increased with early signs of awakening in the Intensive Care Unit. With few exceptions, changes in the simultaneously recorded EEG were similar to those of the ASSR. The ASSR deserves further evaluation as a tool for monitoring level of consciousness during high-dose opioid anaesthesia.

Alfentanil for Cesarean Section Complicated by Severe Aortic Stenosis

Anesthesia for cesarean section in patients with severe aortic stenosis may be hazardous as a result of hypotension associated with conduction anesthesia or hypertension and tachycardia associated with endotracheal intubation in general anesthesia. The current report deals with the use of high-dose opioid anesthesia to produce maternal hemodynamic stability.

ELECTROENCEPHALOGRAPHIC EFFECTS OF SUFENTANIL ANAESTHESIA IN MAN

The effects of anaesthesia with sufentanil 15 micrograms kg-1, air and oxygen on the electroencephalograph were studied in 12 patients before and after cardiopulmonary bypass. The e.e.g. responses were characterized by high voltage, slow delta waves. Although the mean power in the delta band declined with time, the contribution of delta power to total power in the frequency range 0.5-40 Hz remained constant until the onset of cardiopulmonary bypass. Sharp waves of uncertain neurophysiological significance were seen. They were not associated with clinical signs of epileptic activity. The use of the e.e.g. response as a monitor of "depth of anaesthesia" during high-dose opioid anaesthesia may become possible.