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  IN THIS Article
 ::  Abstract
 ::  Subjects and Met...
 ::  Results
 ::  Discussion
 ::  Acknowledgements
 ::  References

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Year : 2003  |  Volume : 49  |  Issue : 3  |  Page : 211-213

Effect of Epidural Morphine on Minimum Alveolar Concentration of Isoflurane in Humans

Departments of Anaesthesiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029

Correspondence Address:
A-1/250 Safdarjang Enclave, New Delhi - 110 029
[email protected]

  ::  Abstract

BACKGROUND AND AIMS: The anaesthetic potency of volatile anaesthetic agents is measured by the minimum alveolar concentration (MAC) required to suppress response in 50% of subjects. We studied the effect of epidural morphine on MAC of isoflurane in humans. SETTINGS AND DESIGN: A prospective single-blind study designed to study the effect of epidural morphine on MAC of isoflurane. SUBJECTS AND METHODS: Forty-eight patients were randomly divided into two groups – Group I patients received 3 mg morphine in 10 ml saline, and Group II patients received 10 ml saline epidurally. Anaesthesia was induced with isoflurane in oxygen and nitrous oxide. Later nitrous oxide was discontinued and MAC of isoflurane determined using modified Dixon’s method of sequential sampling. RESULTS: Epidural morphine resulted in a significant reduction in MAC of isoflurane, 0.98 vs. 1.14 in control group (p<0.05). CONCLUSIONS: Epidural administration of 3 mg morphine in 10 ml saline decreased the MAC of isoflurane.

How to cite this article:
Kashyap L, Pawar D K, Kaul H L, Mohan V K, Dwivedi S N. Effect of Epidural Morphine on Minimum Alveolar Concentration of Isoflurane in Humans . J Postgrad Med 2003;49:211-3

How to cite this URL:
Kashyap L, Pawar D K, Kaul H L, Mohan V K, Dwivedi S N. Effect of Epidural Morphine on Minimum Alveolar Concentration of Isoflurane in Humans . J Postgrad Med [serial online] 2003 [cited 2023 Sep 30];49:211-3. Available from:

The minimum alveolar concentration (MAC) of volatile anaesthetics is reduced by opiates as shown in animal and human studies.[1],[2],[3],[4] One study showed that the intrathecal administration of morphine reduced the MAC of halothane[5] in humans. On the other hand, Licina and colleagues found that intrathecal morphine did not reduce MAC of halothane in humans.[6] Epidural morphine has been effective in reducing the MAC of halothane by 28% in humans.[7] However, the effect of epidural morphine on MAC of isoflurane in humans has not been studied. Epidural morphine is widely used for intraoperative and postoperative analgesia since it provides a stable intraoperative course and excellent postoperative analgesia. The present study was designed to evaluate the effect of epidural administration of morphine on MAC of isoflurane in humans.

  ::   Subjects and Methods

The study was randomised, parallel group, assessor blind and initiated after approval of the institutional board and written, informed consent from participating subjects. Forty-eight patients of physical ASA status I and II who underwent upper abdominal surgery were prospectively studied. Patients with a history of daily intake of opioids and those suffering from major systemic illness were excluded from the study. These patients were randomly divided into two groups of 24 patients each - Group I and II. Patients in Group I received 3 mg morphine in 10 ml saline through an epidural catheter and patients in Group II received 10 ml saline only. The anaesthesiologist was blinded to the group to which the patient belonged.
An epidural catheter was inserted in L 2-3 or L3-4 after infiltration of 2 ml of 1% lignocaine with the patient in the lateral position. Monitoring included pulse, electrocardiogram, non-invasive blood pressure, oxygen saturation, and temperature by Datex Cardiocap II monitor. End-tidal carbon dioxide, isoflurane concentration and MAC were measured by Datex Capnomac monitor. Neuromuscular blockade monitoring was done by myotest using train of monitoring. Anaesthesia was induced with isoflurane in oxygen and nitrous oxide. Two patients in Group I and one patient in Group II had to be given injectable thiopentone 50 -100 mg along with isoflurane during induction. The trachea was intubated after administration of suxamethonium 1.5 mg/kg and spraying vocal cords with 2% lignocaine. Subsequently, nitrous oxide was discontinued and oxygen flow was set at 4 L/min. Now the anaesthesia was maintained with oxygen and isoflurane. The isoflurane concentration was adjusted to maintain a pre-selected end-tidal concentration for 15 minutes before incision in an attempt to reach equilibrium between alveolar gas (end-tidal), arterial blood and brain. Ventilation was controlled to maintain an end-tidal concentration of 30-35 mm Hg. Gas samples were obtained from a catheter located at the proximal end of the endotracheal tube and MAC was analysed at each tidal concentration by an infrared multigas monitor (Capnomac Datex). The MAC was determined as in previous studies.[7],[8]
MAC for humans is defined as the alveolar anaesthetic concentration at which 50% of patients moved in response to a surgical incision.[8] End-tidal concentration of isoflurane was adjusted to obtain a preselected MAC on Capnomac monitor. Dixon's “up-down method” was used for the sequential sampling of quantal response data. In this technique, the result of each trial determines the concentration sample on subsequent trial. If a patient at a preselected MAC of isoflurane moved at skin incision, the next patient in the same treatment group was tested at 0.1% higher MAC of isoflurane. The testing of MAC was started at 1.1 MAC of isoflurane in patients of both the groups. MAC was later decreased or increased by 0.1%. At each MAC setting, 6 patients were tested in each group. MAC was calculated by Dixon's “up- down” method.[9],[10] A neutral observer, blinded to the nature of the drug administered epidurally determined the presence or absence of gross purposeful movement. A positive response was considered to be “gross purposeful muscular movement” usually of the head or extremities.[9] The anaesthesia management subsequent to the skin incision was left to the anaesthesiologist taking care of the patient. The placement of the epidural catheter was verified by administering 10 ml of 2% lignocaine with adrenaline.
MAC of isoflurane for each group was calculated by a modification of Dixon's method for sequential sampling of quantal response data.[9],[10] The age, weight, preoperative haemoglobin, injection to incision time, temperature at incision, pre-incision heart rate and pre-incision systolic blood pressure were analysed by SPSS version 9 using Mann-Whitney U Wilcoxon test and a p<0.05 was considered significant. The comparison of MAC between the groups was carried out using unpaired 't' test.

  ::   Results  Top

The two groups were comparable with respect to age, weight, sex, pre-incision temperature, heart rate and systolic blood pressure (P < 0.05, [Table - 1]). There was no significant difference in the time for epidural administration of morphine or saline to skin incision (Group I- 63.79+17.09 min vs. Group II- 57.04+18.18 min). Mean (SEM) calculated MAC of isoflurane in patients who received 3 mg of epidural morphine was 0.98(0.05) while the MAC of isoflurane in patients who received saline was 1.14 (0.01) (p<0.05) [Figure - 1]. The MAC of isoflurane was significantly decreased in Group I than in Group II. The heart rate immediately before incision was 61+12 beats/min in Group I and 68+7 beats/min in Group II. The pre-incision systolic blood pressure was 95.36+5.8 mm Hg in Group I and 94.32+16.44 mm Hg in Group II.
The recovery of all patients was uneventful. One patient had pruritus during the postoperative period, which was treated with an anti-histaminic and calamine lotion locally. No patient had respiratory depression postoperatively. Urinary retention, a common problem following epidural morphine, could not be evaluated as most patients were catheterised.

  ::   Discussion  Top

MAC has gained wide acceptance and has become the primary index of anaesthetic potency. MAC applies equally to all inhaled anaesthetics. It is easily reproducible in the laboratory making it attractive to those involved in research. MAC of inhalational agents is not affected by the duration of anaesthesia, sex and type of stimulation provided a supramaximal stimulus is applied. It is decreased by advanced age, hypoxia, anaemia and hypothermia. MAC is also decreased by narcotics, ketamine, sedatives, tranquillisers and anti-hypertensive agents like clonidine and methyldopa.
MAC of volatile anaesthetic agents is reduced by up to 60% by opioids given as pre-medication or as an intravenous administration prior to the induction of anaesthesia. The maximum reduction in MAC is produced by morphine, pethidine, fentanyl, alfentanyl and sufentanyl.[8] The reduction in MAC by systemic narcotics is well proven but there are only a few studies about the effect of intrathecal or epidural narcotics on the MAC of inhalational agents.[5],[6],[7],[11]
Opiates injected intrathecally or epidurally produce profound and prolonged analgesia. These opiates act on the opiate receptors located in the brain and the spinal cord with the highest concentrations in the periaqueductal grey matter and substantia gelatinosa respectively.[13] The effect of intrathecal and epidural morphine on MAC of halothane has been studied in animals and humans.[5],[6],[7],[11] Licina et al attributed the reduction in the MAC in an earlier study to dextrose diluting the local sodium concentration in the subarachnoid space.[6] Epidural morphine in the dose of 0.1mg/kg produces a significant reduction (p<0.001) in the MAC of halothane in dogs.[11] The effect of epidural morphine on the MAC of halothane in humans has been studied by Schwieger and colleagues.[7] They found that epidural morphine in a dose of 4 mg in 10 ml saline given 98 + 33 minutes before surgical incision reduced the MAC of halothane by 28% (0.57 vs. 0.78, p<0.05).
Isoflurane is currently the most used volatile anaesthetic agent because of its safety profile. Isoflurane is a volatile methyl ethyl ether, synthesized by Terrel and colleagues in 1965 and introduced into clinical practice in 1981. Isoflurane is an inhalational anaesthetic agent of intermediate potency. The MAC of isoflurane varies with age being 1.15 in the 30-55 years age group.[12] The MAC of isoflurane does not appear to be significantly affected by gender, although pregnancy may reduce MAC by 40%.[13] In this study, the distribution of males and females is similar in both the groups, therefore sex distribution is unlikely to affect MAC. MAC of isoflurane was 1.14 in the control group. There was a reduction in the MAC to 0.98 in patients receiving epidural morphine. This reduction may be due to the use of epidural morphine. We thus conclude that epidural administration of 3 mg morphine in 10 ml saline decreased the minimum alveolar concentration (MAC) of isoflurane in humans.

  ::   Acknowledgements Top

This study was funded by a grant from the All India Institute of Medical Sciences, New Delhi, India.

  ::   References Top

1.Murphy MR, Hug CC Jr. The enflurane sparing effect of morphine, butorphanol and nalbuphine. Anesthesiology 1982;57:489-92.   Back to cited text no. 1  [PUBMED]  
2.Saidman LJ, Eger EI II. Effect of nitrous oxide and of narcotic premedication on the alveolar concentration of halothane required for anesthesia. Anesthesiology 1964;25:302-6.   Back to cited text no. 2    
3.Schwieger IM, Szlam F, Hug CC Jr. Absence of agonistic or antagonistic effect of flumezanil (RO-15-1788) in dogs anesthetized with enflurane, isoflurane or fentanyl- enflurane. Anesthesiology 1989;70:477-80.   Back to cited text no. 3  [PUBMED]  
4.Hoffman JC, DiFazio CA. The anesthesia sparing effect of pentazocine, meperidine and morphine. Arch Int Pharmacoodyn Ther 1970;186:261-8.   Back to cited text no. 4  [PUBMED]  
5.Drasner K, Bernards CM, Ozanne GM. Intrathecal morphine reduces the minimum alveolar concentration of halothane in humans. Anesthesiology 1988;69:310-2.   Back to cited text no. 5  [PUBMED]  
6.Licina MG, Schubert A, Tobin JE, Nicodemus HF, Spitzer L. Intrathecal morphine does not reduce minimum alveolar concentration of halothane in humans: results of a double study. Anesthesiology 1991;74:660-3.  Back to cited text no. 6  [PUBMED]  
7.Schwieger IM, Klopfenstein CE, Forster A. Epidural morphine reduces halothane MAC in humans. Can J Anesth 1992;39:911-4.   Back to cited text no. 7  [PUBMED]  
8.Eger EI II, Saidman LJ, Brandstater B. Minimum alveolar concentration: a standard of anesthetic potency. Anesthesiology 1965;26:  Back to cited text no. 8    
9.756-63.  Back to cited text no. 9    
10.Dixon DJ, Massey FJ Jr. Sensitivity Experiments. In: Dixon DJ, Massey FJ Jr, editors. Introduction to Statistical Analysis. New York: McGraw- Hill; 1957. pp. 318-27.   Back to cited text no. 10    
11.Dixon WJ. Quantal-response variable experimentation: The Up-and-Down method. In: McArthur JW, Colton T, editors Statistics in Endocrinology. Cambridge: MIT Press; 1970. pp. 251-67.  Back to cited text no. 11    
12.Valverde A, Dyson DH, McDonell WN. Epidural morphine reduces halothane MAC in the dog. Can J Anaesth 1989;36:629-32.   Back to cited text no. 12  [PUBMED]  
13.Stevens WC, Dolan WM, Gibbons RT, White A, Eger EI, Miller RD, et al. Minimum alveolar concentrations (MAC) of isoflurane with and without nitrous oxide in patients of various ages. Anesthesiology 1975;42:197-200.  Back to cited text no. 13    
14.Palahnuik RJ, Shnider SM, Eger EI II. Pregnancy decreases the requirement for inhaled anesthetic agents. Anesthesiology 1974;41:82-3.  Back to cited text no. 14    

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