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Query: UMLS:C0278134 (anesthesia)
 110,339 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review illustrates current approaches to the study of the disposition in man of the strong analagesics morphine and methadone and the narcotic antagonist naloxone. Morphine administered orally is rapidly absorbed but equally rapidly metabolised to morphine glucuronide. This contributes to the diminished oral efficacy of morphine. Following intramuscular administration morphine is very rapidly absorbed. After intravenous injection, the serum levels of morphine during the first 10 minutes are higher and more variable in older patients. The half-life of morphine between 20 minutes and 6 hours is 2 to 3 hours and this value does not appear to be influenced by the age of the patient. Similar half-lives for morphine have been reported to normal volunteers and in anaethetised patients who received morphine. Thus, surgical anaesthesia may not markedly influence morphine half-life and disposition. Based on urinary excretion data in man, accelerated morphine metabolism and excretion do not contribute to morphine tolerance. Methadone is now widely used in the treatment of narcotic abuse. The half-life of methadone averages 25 hours. The prolonged retention of methadone in the plasma may be related to its extensive binding to plasma proteins. With chronic dosing, studies in both animals and man indicate an increase in the metabolism of methadone. Unlike morphine, the urinary excretion of methadone increases with acidification of the urine. Women may metabolise methadone to a greater extent than do men. With the exception of pupillary effects, the plasma levels of methadone correlate poorly with its pharmacological activity. There is a marked variation in methadone plasma levels between patients and within the same patient. Naloxone rapidly disappears from the serum in man and the initial distribution phase has a half-life of 4 minutes. The half-life of naloxone in serum following distribution is 64 minutes. Based on animal studies, the rapid onset of the narcotic antagonist action of naloxone can be related to its rapid entry into the brain, whereas its potency stems in part from its high lipid solubility which allows a high brain concentration to be achieved. The short duration of action of naloxone may result from its rapid egress from the brain.
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PMID:The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. 1 57

In anaesthesiology of today, due to the increased use of strong analgetics, it is necessary to have an effective antagonist for mini- mizing the danger of respiratory depression in postoperative period. Naloxone, ( Narcan , R-Endo Laboratories Inc., Subsidiary of E. J. du Pont de Nemours and Co., (Inc.), USA), a new narcotic antagonist was investigated in this study. It has been applied to 58 patients in cases of respiratory depression at the end of anaesthesia in which fentanyl was given, (these cases constituted 14% of all anaesthesias). Fentanyl was given intravenously in fractional doses, (fig 1), during NLA, and other general anaesthesias, for operation and diagnostic examination ( exeption of cardiosurgery), in children and adolescents from two month-to nineteen years of age, (tab. 1.). Naloxone was given intravenously, in fractional doses from 1 microgram to 5 micrograms/kg body weight. As a criterium of an antidepressive effect of Naloxone--in addition to clinical evaluation, blood gases analyses and continuous capnographic recording has been accepted. In all 58 cases diminition of respiratory depression was observed 2-3 min. after injected each dose of Naloxone. Respiratory rate increased from 15 to 22/min. concentration of CO2 in expired gases decreased from 5-6% to 4,5%, (fig. 2 and 3), and regain of consciousness, and return of intensive reaction to endotracheal tube stimulation was observed. Naloxone produced neither changes in the cardiovascular system, nor side effects. Based on these results Naloxone has been suggested as an effective narcotic antagonist. It increase of the possibility of applying strong analgetics in children--allowing to keep a steady level of anaesthesia with easy elimination respiratory depression in the desired period of time.
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PMID:[Naloxone as a drug for improving anesthesia results in children]. 26 40

To determine whether naloxone when perfused through the cerebroventricular system would modify the circulatory and hypnotic effects of halothane, the authors studied its effect in six trained dogs. Naloxone, 20 microgram/ml, was perfused through the fourth cerebral ventricle in three and through the third cerebral and lateral ventricles in three other dogs when awake and during halothane anesthesia (0.75--0.82 vol per cent in oxygen). Blood pressure, heart rate, and circulatory responses to bilateral occlusion of the carotid arteries were measured. The state of consciousness was evaluated by the animals behavior and the EEG. Arterial hypotension, bradycardia, depressed baroreceptor responses, and EEG synchronization associated with halothane anesthesia were reversed when naloxone was perfused through the fourth ventricle. To maintain comparable depths of anesthesia the halothane concentration had to be doubled during naloxone perfusion. No change in the circulatory or hypnotic effects of halothane occurred when the third ventricle was perfused with naloxone. It is concluded that opiate receptors in structures bordering the fourth cerebral ventricle may be important modulators of inhalational anesthesia.
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PMID:Perfusion of naloxone through the fourth cerebral ventricle reverses the circulatory and hypnotic effects of halothane in dogs. 45 93

Hemodynamic responses to reversal of phenoperidine-nitrous oxide anesthesia were studied in 14 adult patients before and after naloxone administration (1.5 +/- 0.25 microgram/kg), and, at comparable intervals, in 11 control patients who were permitted to resume respiration spontaneously. Naloxone reversal resulted in significant increases in heart rate (31%), cardiac index (50%), left ventricular stroke work index (53%), and systemic blood pressure (21%), compared with initial values. The heart rate-systolic arterial pressure product, an indirect index of myocardial oxygen consumption, increased significantly (77%). However, changes of similar magnitude occurred after spontaneous recovery in control patients, in whom the only significant treatment-related difference was a longer recovery time. Whether naloxone is used or not, the observed hemodynamic changes may be harmful to patients who have diminished cardiac reserve.
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PMID:Hemodynamic responses to low doses of naloxone after narcotic-nitrous oxide anesthesia. 66 33

It has been reported that naloxone antagonizes general anesthesia in rats when the tail clamp is used as a painful stimulus to assess anesthesia. The authors' hypothesis is that this antagonism is to the analgesic component of anesthesia only, and that anesthesia assessed by a non-painful stimulus would not be antagonized by naloxone. Therefore, the anesthetic potency of nitrous oxide in mice was measured using loss of the righting reflex as a non-painful stimulus. Naloxone, 2 and 16 mg/kg, intraperitoneally, failed to antagonize nitrous oxide anesthesia measured 14--39 min after injection. Thus, 19 min after injection of naloxone, 2 mg/kg, the nitrous oxide ED50 was 1.25 +/- 0.0600 atm (n = 35), compared with 1.19 +/- 0.059 atm (n = 35) after injection of saline solution (control). Following naloxone, 16 mg/kg, the nitrous oxide ED50 was 1.18 +/- 0.059 atm (n =35), compared with 1.22 +/- 0.059 atm (n = 35) for saline solution. At neither dose of naloxone was the ED50 different from the control ED50, a finding that supports the author's hypothesis.
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PMID:Naloxone has no effect on nitrous oxide anesthesia. 66 51

The postoperative respiratory depressant effect of fentanyl in combination with flunitrazepam (Rohypnol) was assessed in awake and in unconscious patients. In awake patients respiratory function was measured with blood-gas analyses. For measurements in unconscious patients the administration of nitrous oxide/oxygen was continued postoperatively and the respiratory depression was judged from the increase in respiratory minute volume after the i.v. administration of 0.05 mg naloxone (Narcan). In the group of awake patients blood-gasvalues were within the normal range after anaesthesia with flunitrazepam (1 mg) and fentanyl (0.80 mcg/kg body weight/10 min anaesthesia; last fentanyl given 40 min before the end of the operation), and the administration of naloxone was without any effect. If, however, naloxone was given while the patients were kept under light nitrous oxide/oxygen anaesthesia, the effect was different. The respiratory minute volume was considerably less than its predicted value in all groups of patients having received fentanyl, and naloxone caused a marked increase in respiratory minute volume and in respiratory rate. In a group of patients which have received no opiate but enflurane, naloxone showed no effect. After premedication with pethidine as compared with flunitrazepam the effect of naloxone on ventilation was more pronounced. This marked difference in the postoperative effect of fentanyl on ventilation depending on the state of consciousness has to be attributed to an interaction between a residual respiratory depressant effect of fentanyl and the effect of unconsciousness. Since after the combined use of flunitrazepam and fentanyl deep postoperative sleep occurs quite frequent, a residual effect of fentanyl should always be antagonized with naloxone to protect the patients from a possible hazardous effect of this interaction.
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PMID:[Respiratory depression after fentanyl and antagonism by naloxone (author's transl)]. 67 31

A consecutive series of 273 anaesthetics is presented. All patients were given moderate doses of droperidol and fentanyl intravenously to supplement nitrous oxide and oxygen anaesthesia. 28.6% of the patients needed reversal of the analgesic respiratory depressant effect at the end of anaesthesia to establish stable spontaneous respiration. The opiate antagonist, naloxone hydrochloride (Narcan), was found to give rapid and reliable reversal of the respiratory depression. A mean dose of 2 mug/kg body weight of naloxone was found adequate in that no patient required further doses in the post-operative period in order to maintain adequate ventilation. Neither does the dose seem to have been too large. Patients in the naloxone group had no need for additional analgesics during the first 5 3/4 hours postoperatively, as compared to the painfree interval of 3 1/4 hours in the control group.
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PMID:Postanaesthetic use of naloxone hydrochloride after moderate doses of fentanyl. 96 33

Narcotic-supplemented balanced anesthesia is increasing in popularity; however, the narcotic must frequently be antagonized postoperatively. Authorities differ in their recommendations as to dose and as to mode and duration of administration of the narcotic antagonist. In the present study of 58 patients undergoing narcotic-supplemented anesthesia, 60 percent of 42 fentanyl patients and 81 percent of 16 morphine patients required postsurgical naloxone for respiratory inadequacy. Naloxone dosage was initially 1.5 mug/kg IV, with repeat IV doses of 1.5 mug/kg, when needed, at 3-minute intervals, until a regular respiratory rate greater than 15 breaths/min was attained. None of the fentanyl patients and only 25 percent (4/16) of the morphine patients required additional naloxone in the recovery room. For the latter, the dose of naloxone previously administered was given IM and proved satisfactory. Additional analgesia was needed by 12 percent (7/58) of the patients during the recovery room stay. Judicious naloxone titration permitted respiratory adequacy to coexist with analgesia after narcotic-supplemented anesthesia.
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PMID:Naloxone antagonism after narcotic-supplemented anesthesia. 103 95

We evaluated in human monocytes the effect of high doses of alfentanyl on the expression of vimentin filaments, the phagocytic activity and the membrane display of HLA-DR molecules in the subjects undergoing surgery. The study was performed on 30 patients, ASAI-II. The patients received 100 mcg/kg i.v. of Alfentanil and the maintenance of anaesthesia was made with Alfentanil (2-3 mcg/kg/min.). The patients were randomized in two groups. The patients were ventilated with N2O:O2 (1:1) (Group I) or air: O2 (1:1) (Group II). After surgery, all patients of the Group II received Naloxone (0.2-0.4 mg). Central venous blood samples were obtained before induction, one and two hours after induction of anaesthesia and at the end of surgery. Separation of monocytes was performed according to Boyum technique. CD35 and HLA-DR molecules and vimentin filaments were studied by indirect immunofluorescence method using monoclonal antibodies. Percentage of positive cells were read with a cytofluorometer. The phagocytic function of monocytes was determined by ingestion of latex particles. Cortisol and ACTH plasma levels were determined by RIA. High doses of Alfentanyl depress phagocytic function and membrane display of CD35 and HLA-DR molecules in monocyte and induce marked changes in the organization of vimentin filaments in these cells in patients undergoing surgery. This monocytic depression was more marked in the patients ventilated with N2O. In our results there was uninhibition of ACTH and cortisol plasma levels responses to surgical stress by Alfentanil administration. Since the effects of Alfentanil were reversed by Naloxone, an opioid receptor mechanism seems to mediate these events.
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PMID:[Depression of the mononuclear phagocyte system caused by high doses of narcotics]. 133 12

Acute hypertensive responses during nitrous oxide-opioid-relaxant anesthesia are a common clinical problem. In adult men undergoing radical prostatectomy procedures and anesthetized with a standardized technique, we evaluated the effectiveness of alfentanil, isoflurane, and trimethaphan in treating acute hemodynamic and stress hormone responses to surgical stimulation. Stress hormone concentrations were measured 1 min before skin incision, after the onset of an acute hypertensive response, and after returning the mean arterial pressure to within 10% of the preincision values with one of the three treatment modalities. Pretreatment plasma alfentanil concentrations (151 +/- 47 to 156 +/- 47 ng.ml-1) and end-tidal nitrous oxide concentrations (66 +/- 2 to 68 +/- 2%) were similar in all three groups. Acute hypertensive events were associated with significantly increased concentrations of catecholamines and vasopressin (antidiuretic hormone [ADH]). Whereas intravenous alfentanil returned all hormone concentrations to preincision values, norepinephrine and glucose concentrations were significantly increased after adjunctive isoflurane administration. Although trimethaphan decreased the norepinephrine concentration, the epinephrine, beta-endorphin, cortisol, ADH, and glucose concentrations were significantly increased compared to preincision values. However, the persistent elevation in the posttreatment ADH concentration in the trimethaphan group was the only significant difference between the three groups. Mean (+/- standard deviation) times to awakening (2.8 +/- 3.3 to 3.8 +/- 4.2 min), extubation (8.1 +/- 4.8 to 10.3 +/- 8.5 min), and orientation (19.6 +/- 20.4 to 24.6 +/- 19.1 min) were similar in all three groups. Naloxone was required more frequently in patients in the alfentanil (35%) and isoflurane (24%) groups than in the trimethaphan group (4%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of stress response during balanced anesthesia. Comparative effects of isoflurane, alfentanil, and trimethaphan. 134 82


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