Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 7  |  Issue : 3  |  Page : 417-422

Comparison of a single injection of morphine versus ketamine or neostigmine into the epidural space on postoperative analgesia and hormonal stress response after spinal anesthesia


Department of Anesthesia and Intensive Care Medicine, Ain Shams University, Cairo, Egypt

Date of Submission24-May-2014
Date of Acceptance12-Jun-2014
Date of Web Publication27-Aug-2014

Correspondence Address:
Ahmed M El-Sayed
Department of Anesthesia and Intensive Care Medicine, Ain Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.139584

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  Abstract 

Background
In patients undergoing lower extremity orthopedic procedures who receive spinal anesthesia, an epidural injection of morphine, ketamine, or neostigmine has an effect on postoperative analgesia duration and hormonal stress response.
Patients and methods
We carried out a prospective, randomized study comparing the effects of addition of 0.6 mg morphine versus 50 mg ketamine versus 60 μg neostigmine into the epidural space in patients who received spinal anesthesia in terms of postoperative analgesia duration and hormonal stress response.
Results
There was marked prolongation in the postoperative analgesia (428 ± 257) and attenuation of the hormonal stress response in the morphine group compared with the other groups. Also, neostigmine led to prolongation of postoperative analgesia and attenuation of stress response but less than morphine (363 ± 119).
Conclusion
The preemptive morphine injection into the epidural space could attenuate hormonal stress response and led to prolongation in the postoperative analgesia period.

Keywords: epidural morphine, hormonal stress response, postoperative analgesia, spinal anesthesia


How to cite this article:
El-Kady GA, El-Shafaey MA, El-Sayed AM. Comparison of a single injection of morphine versus ketamine or neostigmine into the epidural space on postoperative analgesia and hormonal stress response after spinal anesthesia. Ain-Shams J Anaesthesiol 2014;7:417-22

How to cite this URL:
El-Kady GA, El-Shafaey MA, El-Sayed AM. Comparison of a single injection of morphine versus ketamine or neostigmine into the epidural space on postoperative analgesia and hormonal stress response after spinal anesthesia. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 Jun 24];7:417-22. Available from: http://www.asja.eg.net/text.asp?2014/7/3/417/139584


  Introduction Top


Surgical trauma elicits a metabolic response by activation of the sympathetic and somatic nervous system and through local trauma. The neuroendocrine stress response begins during surgery, with elevated stress hormones maintained for postoperative days. Clinical consequences of the 'stress response' include hypertension, tachycardia, arrhythmias, possibly myocardial ischemia, protein catabolism, immune system suppression, and impaired renal excretory function [1].

The use of perioperative epidural anesthesia and analgesia can attenuate the pathophysiologic response to surgery and may be associated with a reduction in mortality and morbidity when compared with analgesia with systemic (opioid) agents [2].

A single injection of a hydrophilic opioid such as morphine typically provides 12-18 h of analgesia and would be useful for postoperative analgesia in surgical inpatients with appropriate monitoring of side effects [3].

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  Patients and methods Top


Patients were enrolled from the Ain Shams University Hospitals between February 2011 and April 2013. The study was approved by the Ain Shams University research ethics committee. The study was carried out on 80 patients who underwent lower orthopedic procedures after obtaining an informed written consent from every patient.

Inclusion criteria: patients with ASA physical status I, between 20 and 65 years of age, of both sexes were included. Patients younger than 20 years of age and older than 65 years of age, ASA physical status more than I, those with coagulopathy or local infection, hypersensitivity to any of the drugs used, those refusing to participate, and pregnant and lactating women were excluded.

Study design

The study was carried out on 80 patients in whom combined lumbar spinal/epidural anesthesia was planned. The epidural test drug was diluted in normal saline to a final volume of 10 ml. After injecting the epidural test drug, spinal anesthesia was induced using a 25- or 27-G intrathecal needle into the interspace below the epidural level, and 15 mg of hyperbaric bupivacaine (3 ml) was injected.

Placement of epidural needle

In the sitting position, L2-L3 was identified. Skin was sterilized with betadine and then local infiltration using 3 ml of lidocaine 2% was performed. Identification of epidural space was performed using an 18-G Tuoghy needle inserted into the midline using the loss of resistance technique. The needle with the stylet in place was passed through the skin, subcutaneous tissue, supraspinous ligament, and interspinous ligament noted by an increase in tissue resistance; then, the stylet was removed, and a syringe filled with ˜2 ml of air was attached to the hub of the needle and slowly advanced 1 mm at a time with repeated attempts at injection met with resistance. When the needle penetrated the ligamentum flavum and entered the epidural space, there was sudden loss of resistance to pressure on the plunger of the needle.

Using a computer-generated list, the patients were assigned randomly and evenly to four groups: A, B, C, and D according to the test drug injected epidurally as follows:

Group A (control group): included 20 patients who received 10 ml of normal saline epidurally.

Group B (morphine group): included 20 patients who received 0.6 mg morphine epidurally.

Group C (ketamine group): included 20 patients who received 50 mg ketamine epidurally.

Group D (neostigmine group): included 20 patients who received 60 μg neostigmine epidurally.

Anesthesia was induced by administering spinal anesthesia in all patients in the interspace below. After identification of the subarachnoid space by free flow of cerebrospinal fluid, 3 ml of hyperbaric bupivacaine 0.5% was injected slowly.

All healthcare personnel providing direct patient care and the patients were blinded to the epidural medications administered. All medications were prepared by pharmacy staff not participating in the study, except for preparation of the drugs. They received and kept the computer-generated table of random numbers, according to which random group assignment was performed.

Using a computer-generated list, the patients were assigned randomly and evenly to four groups: A, B, C, and D.

Monitoring and data collection

Intraoperatively, noninvasive blood pressure monitoring was performed every 5 min, with continuous monitoring of heart rate, oxygen saturation, and 5-lead ECG, respiratory rate, and assessment of sensory level by pin prick at 5 and 10 min after the subarachnoid injection. For the first 24 h postoperatively, the following were monitored: noninvasive blood pressure, heart rate, respiratory rate every 15 min during the first hour and then hourly, nausea, vomiting, pruritus, hypotension, visual analog scale (VAS) score for pain every 30 min in the first hour, then hourly, and time from intrathecal injection till the need for first rescue analgesic.

Laboratory measurements

Serum cortisol level was measured preoperatively, 30 min after skin incision, 6 h postoperatively, and at 12 h postoperatively. Serum glucose level was measured preoperatively, 30 min after skin incision, 6 h postoperatively, and at 12 h postoperatively.

Statistical analysis

Sample size

Epicalc 2000 Software was used with the following inputs: type I error (α) of 5% with a confidence level of 95%. The power of the study was 90% (power of test), with a type II error (β) of 10%. The minimal sample size was 80.

All data were collected and analyzed using SPSS (version 13.0; SPSS Inc., Chicago, Illinois, USA) for Windows. Numerical variables were presented as mean and SD. Analysis of variance was used to make comparisons between groups for numerical variables. Analysis of categorical data was carried out using the Tukey test.


  Results Top


For demographic data, age, weight, and sex showed no statistically significant differences between the four groups [Table 1].
Table 1 Comparison between the four groups in demographic data

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For sensory level at 5 and 10 min after the subarachinoid injection, there was no significant difference among the four groups at 5 and 10 min after the subarachinoid injection.

In terms of the heart rate and mean blood pressure ([Table 2] and [Table 3]), the difference was significant in values at 4, 6, 8, and 12 h after the end of surgery between group A and group B, at 4 and 6 h after the end of surgery between group A and group C, at 4, 6, and 8 h after the end of surgery between group A and group D, at 8 and 12 h after the end of surgery between group B and group C, at 12 h after the end of surgery between group B and group D, and at 8 h after the end of surgery between group C and group D.
Table 2 Comparison between all four groups in the mean heart rate at the same time intervals

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Table 3 Comparison between all four groups in the mean blood pressure at the same time intervals (preoperatively, 2, 4, 6, 8, and 12 h after the end of surgery)

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In terms of the VAS score for pain [Table 4], there was a significant difference in the VAS score values at 2, 4, 6, and 12 h after the end of surgery between group A and group B, at 2 and 4 h after the end of surgery between group A and group C, at 2, 4, and 6 h after the end of surgery between group A and group D, at 6 and 12 h after the end of surgery between group B and group C, at 12 h after the end of surgery between group B and group D, and at 6 h after the end of surgery between group C and group D.
Table 4 Comparison between all four groups in the visual analog scale score at the same time intervals (preoperatively, 2, 4, 6, 12, and 24 h after the end of surgery)

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In terms of time till first rescue analgesia, there was a significant difference between group A and B, a significant difference between group A and D, a significant difference between group B and C, and a significant difference between group C and D.

In terms of the time till first rescue analgesia [Table 5], there was a significant difference between group A and B, a significant difference between group A and D, a significant difference between group B and C, and a significant difference between group C and D.
Table 5 Difference between the groups in time till fi rst rescue analgesic

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In terms of cortisol levels, [Table 4] shows a significant difference in the values of serum cortisol level at 6 and 12 h after surgical stimulus between group A and group B, a nonsignificant difference in the values of serum cortisol between group A and group C, a significant difference in the values of serum cortisol level at 6 h after surgical stimulus between group A and group D, a significant difference at 6 and 12 h after surgical stimulus between group B and group C, a significant difference in values at 12 h after surgical stimulus between group B and group D, and a significant difference in values at 6 h after surgical stimulus between group C and group D [Table 6].
Table 6 Comparison between the cortisol level after surgical stimulus at the same time intervals (30 min, 6, and 12 h) in all four groups

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In terms of random blood sugar, there was a significant difference in random blood sugar values at 4, 6, and 12 h after the end of surgery between group A and group B, at 4 h after the end of surgery between group A and group C, at 4 and 6 h after the end of surgery between group A and group D, at 6 and 12 h after the end of surgery between group B and group C, at 12 h after the end of surgery between group B and group D, and at 6 h after the end of surgery between group C and group D [Table 7].
Table 7 Comparison between all four groups in random blood sugar at the same time intervals (preoperatively, 2, 4, 6, and 12 h after the end of surgery)

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  Discussion Top


Preemptive analgesia is suggested to attenuate peripheral and central sensitization to pain. The treatment should cover the entire duration of high-intensity noxious stimulation that can lead to establishment of centraland peripheral sensitization caused by incisional or inflammatory injuries during surgery and the initial postoperative period. Several reports have documented the positive effects of preemptive analgesia on postoperative immune function [4,5].

Hemodynamic variables are largely affected by the presence or absence of pain as well as increases in stress-related hormones.

There was a significant difference in VAS between the neostigmine group and the ketamine, group being higher in the ketamine group, which is in agreement with the study carried out by Kirdemir et al. [6] on 30 patients who were divided into three groups according to the epidural drug injected: ketamine, neostigmine, and control groups. The VAS score was significantly lower in the neostigmine group than in the ketamine group.

In this study, the duration of postoperative analgesia was defined as the mean time from intrathecal injection until the request of the first rescue analgesic. The first rescue analgesic was administered when the VAS score reached 3; 1 g of paracetamol was administered by the intravenous infusion route.

The highest duration was for the morphine group (432 ± 257) and the neostigmine group (358 ± 113), which were significant in comparison with the control and ketamine groups.

This is in agreement with the study carried out by Omais et al. [7] in which they compared morphine (428 ± 297) and neostigmine (363 ± 119) epidurally.

We found that all the epidural drugs used led to prolongation in postoperative analgesia, being maximum in the morphine group and minimum in the ketamine group.

The cortisol level was expected to increase (as its secretion is increased from the adrenal gland) (normal 90-220 ng/ml). The insulin level was expected to decrease (as stress response leads to insulin resistance) (normal 9-12 μIU/ml)) and blood sugar was expected to increase (normal <200 mg/dl).

The blood samples for blood sugar were measured directly using a hemotest.

In terms of endocrinal stress response, the present study found a significant reduction in stress response assessed by serum cortisol and blood glucose levels among the patients.

Loick et al. [8] reported that high thoracic epidural anesthesia attenuates the perioperative stress response by sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting.

Poon et al. [9] reported that epidural or spinal anesthesia can markedly suppress the increase of many of the stress hormones; also studies carried out by Enquist et al. [10] showed the blocking effect of epidural analgesia on the adrenocortcial and hyperglycemic responses to surgery.

Effect of average 4 h that extends postoperatively by the addition of morphine 0.6 mg to reach average 7 h, and reaches average 5 h by the addition of neostigmine 60 μg.


  Conclusion Top


The current study suggests that spinal anesthesia with hyperbaric bupivacaine 0.5% concentration had a good, but limited analgesic effect of average 4 h extends postoperatively by the addition of morphine 0.6 mg to reach average 7 h and reaches average 5 h by the addition of neostigmine 60 μg.

There is definite attenuation of stress response by prolonged pain-free time periods, apparent from the lower values of stress hormones such as cortisol and random blood glucose in the group that received morphine as an additive, greater than the group that received ketamine or neostigmine, whereas morphine and neostigmine groups showed a marked difference compared with spinal anesthesia alone.


  Acknowledgements Top


 
  References Top

1.Grass JA. The role of epidural anesthesia and analgesia in postoperative outcome. Anesthesiol Clin North America 2000; 18:407-428.  Back to cited text no. 1
[PUBMED]    
2. Wu CL, Fleisher LA. Outcomes research in regional anesthesia and analgesia. Anesth Analg. 2000; 91:1232-1242.  Back to cited text no. 2
    
3. Bernards CM. Understanding the physiology and pharmacology of epidural and intrathecal opioids. Best Prac Res Clin Anaesthesiol 2002; 16:489-505.  Back to cited text no. 3
    
4. Beilin B, Bessler H, Mayburd E, et al. Effects of preemptive analgesia on pain and cytokine production in the postoperative period. Anesthesiology 2003; 98:151-155.  Back to cited text no. 4
    
5. Raja SN, Meyer RA, Campbell JN. Peripheral mechanisms of somatic pain. Anesthesiology 1988; 68: 571-590.  Back to cited text no. 5
    
6. Kirdemir P, Ozkocak I, Demir T, et al. Comparison of postoperative analgesic effect of preemptively used epidural ketamine and neostigmine. J Clin Anesth 2000; 12:543-548.  Back to cited text no. 6
    
7. Omais M, Lauretti G, Paccola C. Epidural morphine and neostigmine for postoperative analgesia after orthopedic surgery. Anesth Analg 2002; 95:1698-1701.  Back to cited text no. 7
    
8. Loick HM, Schmidt C, Van Aken H. High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting. Anesth Analg 1999; 88:701-709.  Back to cited text no. 8
    
9. Poon KS, Chang WK, Chen YC, et al. Evaluation of stress response to surgery under general anesthesia combined with spinal analgesia. Acta Anaesthesiol Sin 1995; 33:85-90.  Back to cited text no. 9
    
10.Enquist A, Brandt MR, Fernandes A. The blocking effect of epidural analgesia on the adrenocortcial and hyperglycaemic responses to surgery. Acta Anaesthesiol Scand 1987; 21:330-335.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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  In this article
   Abstract
  Introduction
  Patients and methods
  Results
  Discussion
  Conclusion
  Acknowledgements
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