High-dose Narcotic Anesthesia Research Articles

A comparison of sympathetic adrenal nerve responses to intravenous high-dose morphine and fentanyl administration in rats

We compared the effects of intravenous morphine (5 mg·kg(-1)) and fentanyl, (50μg·kg(-1)) on systolic blood pressure (SBP), heart rate (HR), and efferent sympathetic adrenal nerve action potentials (SANA) in rats. We also determined the extent of the reflex responses of these parameters of 9% carbon dioxide (CO2) challenge during the above narcotic anesthesia. In the morphine group, SBP was elevated and the elevated levels were maintained, while changes in SBP in the fentanyl group were not significant. In the morphine group, SANA showed initial stimulation and subsequent depression, while in the fentanyl group, SANA showed sustained depression. CO2 challenge induced only very small changes in SBP and HR, suggesting that during high-dose narcotic anesthesia the hypercapnic stimulus may not be reflected in circulatory parameters. In both groups, hypercapnia increased SANA to 30% of the baseline values from the pre-challenge level. However, these values were only 91% and 56% of the baseline value in the morphine and the fentanyl, groups, respectively.

Timing of Tracheal Extubation in Adult Cardiac Surgery Patients

In this article, we examine 14 studies conducted from 1974 to 1994 on "early" endotracheal extubation (0 to 12 hours postoperatively) in adult cardiac surgery patients. Aspects reviewed include: criteria for patient selection; criteria for extubation; analyses of feasibility and safety; effects of anesthetic technique; and patient morbidity. Advantages and disadvantages of early or "fast-track" extubation are discussed as are directions for future research. Selection criteria varied among studies; patients were most commonly excluded because of severe, preexisting pulmonary disease or ventricular dysfunction. Based on the studies examined, however, at least 70% to 80% of adult patients would meet selection criteria. Three universal criteria were applied in all studies: (1) patient is awake and responsive; (2) adequate gas exchange while breathing spontaneously; and (3) cardiovascular stability. To facilitate early extubation in appropriately selected patients, the choice of anesthetic technique and postoperative sedation technique appears to be important. Anesthetic techniques based on inhalational anesthetic agents, supplemented by moderate doses of narcotics, are more appropriate than high-dose narcotic anesthesia for early extubation protocols. Postoperative sedation with propofol, which has a rapid offset of action, may be particularly advantageous. Every published investigation has concluded that early extubation is safe, feasible, and desirable. Morbidity and mortality have not been shown to be affected by early extubation. Anesthetic technique and the patient's medical condition are the two major factors to consider in accomplishing early extubation.

Propofol and Fentanyl Anaesthesia for Patients with Low Cardiac Output State Undergoing Cardiac Surgery

Comment: After the original description of narcotic anesthesia for cardiac surgical patients by Lo-wenstein, narcotic anesthesia, often in the form of very high doses of narcotics with oxygen and muscle relaxant, has become a mainstay in clinical cardiac anesthesia. However, as the advantages of shorter durations of mechanical ventilation in the postoperative period become increasingly well recognized and established, it is appropriate for our cardiac anesthesiologists to reexamine this as the primary anesthetic technique for cardiac surgical patients. Indeed, many, if not most, cardiac anesthetics can be very safely and effectively conducted with a variety of anesthetic agents and adjuvants, many of which can actually allow return of the patient's normal respiratory function within minutes to hours after the surgical procedure. Given this, it is difficult to rationalize continued reliance on “monotherapy” in the form of high-dose narcotic anesthesia in today's world of increasing focus on costs associated with hospitalization and surgery, e.g., length of stay in the intensive care unit.

Plasma adenosine changes during cardiac surgery

Changes in plasma adenosine and inosine were measured during high-dose narcotic anesthesia and surgery for coronary artery bypass grafting (CABG), and mitral or aortic valve replacement (V). Arterial and mixed venous blood samples were obtained for measurement of adenosine and inosine at eight sampling intervals ranging from preanesthesia induction to discontinuation of cardiopulmonary bypass (CPB). Arterial but not mixed venous adenosine was markedly elevated in blood samples 10 minutes after intubation, but the fourfold elevation was significant only in the CABG patient group. Mixed venous inosine and adenosine were most consistently elevated in post-CPB samples. In a separate study of arterial adenosine changes during induction, a uniform drug administration protocol was used, and again adenosine was significantly increased immediately after intubation. It is possible that adenosine and perhaps inosine may contribute to cardiovascular responses following induction intubation and also after discontinuing CPB.

The efffects of global northermic hyperfusion on the processed electroencephalogram in patients

This study examined the effects of global normothermic hypoperfusion on the compressed spectral array (CSA) processed electroencephalogram (EEG) during high-dose narcotic anesthesia. Fifteen patients undergoing cardiac electrophysiologic surgery were studied. The patients were anesthetized with a standard high-dose narcotic technique and then connected to a Nicolet Pathfinder I CSA EEG analysis system using seven subdermal electrodes in a modified International 10–20 configuration. There were 167 intervals of profound hypotension ranging from 8 to 96 seconds. During these periods the cerebral perfusion pressure was almost zero. Despite 38 intervals up to 32 seconds long, 6 of the 15 patients had no EEG changes. Overall, there were 36 (21.6%) ischemic EEG recordings. None of the patients developed neurological complications. The incidence of EEG changes was much lower than expected from other studies. Either the processed EEG was inherently insensitive, the high-dose narcotic masked the processed previously unknown protective effect.

A randomized double-blind comparison of fentanyl- and sufentanil-oxygen anesthesia for abdominal aortic surgery

Twenty-four patients undergoing abdominal aortic surgery for aneurysm or occlusive vascular disease entered a randomized, double-blind protocol comparing high-dose narcotic anesthesia with fentanyl (125 μg/kg) or sufentanil (25 μg/kg). All patients received perioperative β-adrenergic blockade therapy. Hemodynamic and electrocardiographic (leads 11 and V 5) responses to induction, intubation, skin incision, aortic cross-clamping, and declamping were studied. Sufentanil produced a transient decrease in mean arterial pressure and a significant reduction of systemic vascular resistance during induction. However, no significant hemodynamic differences were observed between the two groups during intubation, or at any other time during surgery. To maintain mean arterial pressure within 20% of the awake control value, the fentanyl group required an average infusion of 1.0 ± 1.1 μg/kg/min of nitroglycerin compared with 1.7 ± 2.8 μg/kg/min for the sufentanil group. Low-dose isoflurane was required in 30% of patients in the fentanyl group, compared with 41 % of the sufentanil group, for control of blood pressure. The multiple-bolus technique of narcotic administration resulted in a wide but parallel range of plasma concentrations from induction to the end of surgery with both narcotics. Mean plasma fentanyl concentrations varied between 7.2 ± 1.4 ng/mL and 26.5 ± 7.9 ng/mL, and mean sufentanil plasma concentrations varied between 1.0 ± 0.1 ng/mL and 10.6 ± 7.2 ng/mL throughout surgery. Within this range of narcotic serum levels, the authors were unable to identify a specific threshold level for either narcotic above which hemodynamic responses were consistently attenuated. A low incidence (4.5%) of intraoperative myocardial ischemia was observed. It is concluded that sufentanil and fentanyl are not different at blunting hemodynamic responses during aortic surgery. When supplemented by low doses of nitroglycerin and isoflurane, both narcotics provide anesthesia characterized by good hemodynamic control and a low incidence of myocardial ischemia.

Suppression of natural killer cell activity by high-dose narcotic anesthesia in rats

Suppression of natural killer (NK) cell activity in the postoperative period has been reported in several clinical studies. Endogenous opioids and cerebral injection of morphine have been shown to suppress NK cell activity. Since high-dose opiates are commonly used in anesthetic practice, we sought to determine the effects of three narcotic agents on NK cell activity. Male rats were injected subcutaneously with morphine (30 mg/kg), fentanyl (0.3 mg/kg), or sufentanil (0.06 mg/kg). Three, 12, or 24 h later the cytotoxic activity of splenic NK cells was measured in a 4-h chromium-51 release assay using radiolabeled target cells. All three drugs significantly suppressed NK cytotoxicity at 3 h after administration; this effect was blocked by an opiate antagonist, naltrexone. Fentanyl and sufentanil also caused a significant suppression 12 h after drug administration. By 24 h NK activity of all groups returned to normal values. Interferon is known to augment NK cell activity. Therefore, in another experiment rats were given an interferon inducer, polyinosinic:polycytidylic acid (poly I:C), to determine if it would alter the effects of these narcotics on splenic NK activity. Poly I:C treatment increased NK cytotoxicity to above baseline; fentanyl in these animals reduced NK activity and brought it back to control levels. These findings suggest that clinically used high-dose narcotic anesthesia can suppress NK cytotoxic activity and that pretreatment with interferon can attenuate this suppression.

Effect of Epidural Analgesia on Postoperative Insulin Resistance as Evaluated by Insulin Clamp Technique

Comment It is known that epidural anesthesia and postoperative analgesia can suppress the endocrine responses to surgical stimulation. High-dose narcotic anesthesia can do this also. This report confirms these effects with epidural anesthetics and narcotics and helps delineate the mechanism for postoperative insulin resistance. The insulin clamp technique is an interesting way of looking at this. It remains to be seen, however, whether reduction of this “stress response” in the perioperative period will actually result in less patient morbidity. Mark A. Rockoff, M.D.

Effects of isoflurane and halothane on coronary vascular resistance and collateral myocardial blood flow: their capacity to induce coronary steal.

Some coronary vasodilators, paradoxically, may endanger patients with coronary artery disease by causing "coronary steal." To determine the capacity of isoflurane and halothane to cause coronary steal, the authors studied their effects on coronary vascular resistance (CVR), diastolic coronary artery pressure, and collateral myocardial blood flow. Using ameroid constrictors, chronic occlusions of the left anterior descending (LAD) coronary artery were created in ten dogs. Six to eight weeks after implantation, the dogs were anesthetized with fentanyl and pentobarbital, and a stenosis was created on the circumflex (Cx) coronary artery. Isoflurane and halothane were each administered in doses of 0.5 and 1.5 MAC. Diastolic aortic pressure was held constant. Using small catheters in the circumflex and LAD coronary arteries, the authors measured diastolic coronary artery pressures. Collateral myocardial blood flow was measured by the microsphere method. In this model, halothane and isoflurane minimally affect CVR. The maximum change in CVR, which was found during 1.5 MAC isoflurane, was -8% (not significant). Diastolic coronary pressures distal to the Cx stenosis (54.5 +/- 11.5 mmHg) and distal to the LAD occlusion (44.5 +/- 5.2 mmHg) did not change significantly with either isoflurane or halothane. Transmural collateral blood flow distal to the LAD occlusion (0.51 +/- 0.11 cc.g-1.min-1) was unaltered by either drug. There was no evidence of coronary steal. Epicardial ECG S-T segments showed no evidence of ischemia. The finding of minimal direct effects of halothane and isoflurane on CVR, diastolic coronary pressure, and collateral myocardial blood flow suggest that, under the conditions of this study, neither agent, when used as an adjuvant to high-dose narcotic anesthesia, is likely to cause myocardial ischemia by a coronary "steal" mechanism.

The role of the nucleus raphe pontis and the caudate nucleus in alfentanil rigidity in the rat

Attempts to eliminate or reduce the rigidity with high-dose narcotic anesthesia in the operating room have been only partially successful. Previous investigations of opioid receptor sites mediating this rigidity have implicated two central regions: the nucleus raphe pontis (NRP) within the reticular formation and the caudate nucleus (CN) within the basal ganglia. The present study used systematically administered alfentanil (ALF), a potent, short-acting fentanyl analog, and intracerebrally infused methylnaloxonium (MN), a quaternary derivative of naloxone, to elucidate further the functional role of the NRP and CN in rigidity. ALF (0.5 mg/kg s.c.) produced a reliable model of rigidity, as documented by gastrocnemius electromyography. The onset of this rigidity was within 60 s of ALF administration, with a total duration of approximately 40–50 min. Intracerebroventricular (i.c.v.) injections of 2.0 or 4.0 μg of MN 15 min prior to ALF treatment prevented rigidity, while 0.125 or 0.5 μg had no significant effect on rigidity. MN injected directly into the NRP at doses as low as 0.125 μg significantly antagonized ALF-induced rigidity, while injections of MN into the caudate nucleus at doses as high as 4.0 μg failed to antagonize ALF-induced rigidity. These observations demonstrate that injection of MN into the NRP is at least 16-fold more effective in blocking ALF-induced rigidity than MN injected into the ventricle and, more importantly, at least 32-fold more effective than MN injected into the CN. The results suggest that the NRP may be an important site for the neural control of muscular rigidity associated with high-dose narcotic administration.