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ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 3  |  Page : 577-581

Effects of regional analgesia versus intravenous morphine on electroencephalographic waves in response to noxious stimuli during general anesthesia


Department of Anesthesiology and Intensive Care, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt

Date of Submission05-Jan-2014
Date of Acceptance10-Mar-2014
Date of Web Publication26-Nov-2014

Correspondence Address:
Mohammed M Abdalla
9 Anwar Alsadat St, Albatanoon, Shebin Elkom, Menoufiya
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.145517

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  Abstract 

Objectives
We used the unprocessed electroencephalographic (EEG) analysis during general anesthesia (GA) to assess the effects of regional analgesia versus morphine (intravenously) on EEG waves in response to noxious stimuli (endotracheal intubation and skin incision).
Background
Noxious stimuli during GA cause EEG changes that represent the cerebral processing of noxious stimuli. Interpreting these changes could maintain balance between too much and too little anesthetics or using specific techniques (e.g. regional analgesia).
Materials and methods
Sixty consenting ASA I or II adult patients undergoing lower abdominal surgery were randomly assigned into two groups: the epidural group received 15 ml bupivacaine 0.25% epidurally to attain sensory analgesia up to T6 followed by induction of GA and the morphine group received intravenous morphine (0.1 mg/kg), 5 min before induction of GA. Arterial blood pressure, heart rate, respiratory rate, arterial O 2 saturation, and end-tidal CO 2 were monitored. EEG recordings were analyzed for the 10 Hz score, high-frequency variability index (HFVI), and delta power at different time points (1 min before and after the noxious stimuli).
Results
Within the same group, comparing the prenoxious with postnoxious stimuli, EEG changes showed highly significant statistical difference in both groups (e.g. in the epidural group, 10 Hz score changed by intubation from 0.27 ± 0.04 to 0.21 ± 0.03 and by incision from 0.31 ± 0.04 to 0.28 ± 0.03) - that is, marked decrease in its value. Comparing EEG parameters between both groups was insignificant. Comparing the preintubation and postintubation difference between both groups showed significant statistical difference regarding 10 Hz score (epidural = 0.06 ± 0.02 > morphine = 0.05 ± 0.01) and no significance regarding HFVI and delta power. Comparing the preincision and postincision difference between both groups showed significant statistical difference regarding 10 Hz score (epidural = 0.03 ± 0.01 < morphine = 0.05 ± 0.01) and HFVI (epidural = 0.80 ± 0.16 < morphine = 1.0 ± 0.17) and high significance regarding delta power (epidural = 15.0 ± 2.77 < morphine = 25.0 ± 6.64).
Conclusion
Using unprocessed EEG for monitoring the intraoperative adequacy of analgesia showed less response to noxious stimuli with epidural analgesia than systemic opioids as reflected by less EEG changes in the epidural group.

Keywords: anesthesia, electroencephalography, noxious stimuli, regional analgesia


How to cite this article:
Afifi MH, Rady AA, Koptan HM, Alahmar A, Abdalla MM. Effects of regional analgesia versus intravenous morphine on electroencephalographic waves in response to noxious stimuli during general anesthesia. Menoufia Med J 2014;27:577-81

How to cite this URL:
Afifi MH, Rady AA, Koptan HM, Alahmar A, Abdalla MM. Effects of regional analgesia versus intravenous morphine on electroencephalographic waves in response to noxious stimuli during general anesthesia. Menoufia Med J [serial online] 2014 [cited 2020 Feb 24];27:577-81. Available from: http://www.mmj.eg.net/text.asp?2014/27/3/577/145517


  Introduction Top


Detection and assessment of nociception represent one of the present challenges in anesthetic practice. The most reliable sign, somatic movement, is abolished by neuromuscular block. Other clinical signs of nociception during general anesthesia (GA), such as hemodynamic or autonomic reactions, are nonspecific, often occurring late, and are difficult to interpret. Noxious stimuli cause changes in the electroencephalogram (EEG). The typical EEG response to noxious stimuli is desynchronizations - a shift toward high-frequency, low-amplitude activity. This change in activity is thought to represent the cerebral processing of noxious stimuli, which would be associated with pain in conscious individuals. Less commonly, synchronization is reported - a shift in the EEG toward high-amplitude, low-frequency activity [1] .

Natural sleep spindle frequency tends to be higher (~14 Hz) than the distorted 'sleep spindle-like' waveforms generated during anesthesia (~10 Hz). During anesthesia, episodic 10 Hz activity and episodes of burst suppression or near-burst suppression occur commonly. Both these patterns are very likely to be due to anesthetic drug effects on ion channels, similar to sleep spindles and the 'up-down' oscillations seen during some phases of natural sleep [2] .

To prevent arousal, the noxious stimulus needs to be inhibited to reach cortical structures. This is either achieved by the action of opioids on opiate receptors within the spinal cord or by the blockade of peripheral nerves by local anesthetics. Both mechanisms attenuate (opioids) or abolish (local anesthetics) the nociceptive input to ascending spinothalamic pathways [3] .

The aim of the study was to compare EEG changes in anesthetized patients with regional analgesia with those with intravenous morphine analgesia and to detect to which extent nerve block could abolish noxious stimuli as reflected on the EEG changes.


  Materials and methods Top


This study was carried out in Menoufiya University Hospitals from March 2010 to April 2013, after obtaining ethics committee approval and informed written consent. Sixty ASA physical status I or II patients aged 18-50 years of both sex, who were scheduled for elective lower abdominal surgery, were included in the study. Exclusion criteria included pre-existing hypertension, neurological disease, severe reflux esophagitis, drug abuse, chronic analgesic or hypnotic use, BMI greater than 30, coagulopathy, and ischemic heart disease.

Electroencephalography

While the patient was lying supine on the operating room table, the nurse applied the 22 EEG surface electrodes on the head using a specific paste for this; the electrodes were connected to the EEG box, which was connected through USB cable to the computer where the EEG program is present, and then turned on to show EEG patterns.

Anesthesia

The routine monitoring included ECG, SPO 2 , and noninvasive blood pressure. All patients received intravenous premedication with 0.03 mg/kg of midazolam followed by a 7 ml/kg infusion of lactated Ringer's solution. Patients were randomly assigned into two groups (n = 30 each). In the epidural group, an epidural catheter was inserted at the level of L3-L4 or L4-L5 lumbar interspaces, and 15 ml of plain bupivacaine (0.25%) was injected into the epidural space aiming at attaining sensory block to pinprick up to the level of T6. In the morphine group, intravenous morphine (0.1 mg/kg) was administered, 5 min before induction of GA. A standardized anesthetic technique was applied to both groups. On induction of anesthesia, fentanyl (1.5 μg/kg) intravenous was injected followed by intravenous propofol (2.5 mg/kg). Neuromuscular blockade was established with intravenous atracurium (0.5 mg/kg). After clinical confirmation of adequate muscle relaxation, laryngoscopy and tracheal intubation were achieved (any displaced electrode after laryngoscopy caused by head and neck manipulations was replaced again correctly to avoid false EEG traces) followed by maintenance with isoflurane (1 MAC) on controlled ventilation. End-tidal CO 2 (EtCO 2 ) monitoring was then applied.

Electroencephalographic monitoring (for the period of study)

The EEG recordings initiated just before induction of GA and continued for 2 min after the surgical incision at which point the study ceased and the operation and anesthesia continued as per clinical routine. We defined two different events of noxious stimulation: (a) laryngoscopy/intubation (ETT) and (b) surgical incision (incision). We selected two segments of the EEG, before and after the stimulus, for analysis. The prenoxious stimulus period consisted of the 1-min EEG segment 70-10 s before initial laryngoscopy or before incision. The postnoxious stimulus period was the 1-min segment beginning 40 s after successful intubation or after incision. The analysis was performed using unprocessed EEG (Model: JE-921A; Nihon Kohden). We quantified the pattern of EEG in 5 s segments, using three parameters, namely:

  1. 10 Hz score: The amount of each EEG segment in which 'spindle-like' patterns were detected. We examined 'spindle-like' activity at a frequency of 10 Hz.
  2. High-frequency variability index (HFVI): Alterations between hyperpolarized (so-called 'down') states and high firing (up) states and the upper and lower envelopes were measured. Our index of the 'amplitude' of the 'up-down' states was calculated each 5 s and defined by the equation: HFVI = (upper envelope-lower envelope)/lower envelope.
  3. Delta: The absolute amount of delta power.


Data were collected, tabulated, and statistically analyzed by IBM personal computer and statistical package SPSS version 16 using Student's t-test, the χ2 -test, paired t-test, Pearson's correlation analysis (r), and P-value (significant: P < 0.05, insignificant: P > 0.05, highly significant: P < 0.01).


  Results Top


Patients in both groups were matched for age, weight, and sex with no statistically significant difference (P > 0.05) ([Table 1]).
Table 1: Patients' characteristics


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There were no statistically significant differences between the two groups regarding the hemodynamic changes (heart rate, blood pressure, SaO 2 , and EtCO 2 ), the baseline values, and the values measured 1 min before and after intubation or incision (P > 0.05).

Electroencephalographic parameters

Within the same group, comparing the prenoxious with postnoxious stimuli (intubation and incision), EEG parameters (10 Hz score, HFVI, and delta power) showed highly significant statistical difference in both groups (P < 0.001). There was a marked decrease in their values from preintubation to postintubation or incision ([Table 2]).
Table 2: Electroencephalographic parameters


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Comparing EEG parameters between both groups showed no significant statistical difference (P > 0.05).

Comparing the preintubation and postintubation difference in 10 Hz score between both groups showed significant statistical difference (P < 0.005). Its value in the epidural group was more than that in the morphine group - that is, lesser changes occurred in the morphine group from preintubation to postintubation. There was no significance in the preintubation and postintubation difference regarding HFVI and delta power between both groups (P > 0.05).

Comparing the preincision and postincision difference between both groups showed significant statistical difference regarding 10 Hz score and HFVI (P < 0.05). Their values in the epidural group were lower than that in the morphine group - that is, lesser changes occurred in the epidural group from preincision to postincision. There was high significance in the preincision and postincision difference regarding the delta power between both groups (P < 0.001). Its values in the epidural group were markedly lower than that in the morphine group - that is, markedly lesser changes occurred in the epidural group from preincision to postincision.


  Discussion Top


In the present study, within each group, the changes from prenoxious to postnoxious 10 Hz score, HFVI, and delta power values were of high significance - that is, there was a marked decrease in these values from the prenoxious to postnoxious period (intubation and incision). Regarding the preintubation and postintubation difference, the change in the 10 Hz score value from the preintubation to postintubation period was less in the morphine group than in the epidural group - that is, the decrease in the sleep spindle was less in the morphine group, which means less response to intubation. The preintubation and postintubation difference regarding HFVI and delta power values showed no significant difference between the epidural and morphine groups. The preincision and postincision differences regarding the 10 Hz score, HFVI, and delta power were lower in the epidural than in the morphine group. This indicates that little change occurred in the epidural group (i.e. the decrease in the sleep spindle, burst-suppression-like fluctuations, and delta power were less in the epidural group, which means less response to incision). The EEG patterns regarding the three measured parameters, 10 Hz score, HFVI, and delta power, showed no significant difference between the epidural and nonepidural groups during the period of prenoxious and postnoxious stimuli (intubation and incision). We used the timing of noxious stimuli as the intubation timing and the skin incision timing because those are the most stressing events. In addition, many artifacts during the surgery would affect EEG waves badly.

Suraphong and Yodying [4] made a study to provide basic information about bilateral frontal cerebral electrical activity after induction, before and after skin incision, and at a steady state during sevoflurane anesthesia at the EtCO 2 concentration 1, 1.2, 1.4, and 1.6 MAC and showed a consistency in decreasing frequencies and increasing amplitudes of both hemispheres of the groups with higher MAC values. The noxious stimuli, during GA, are either due to endotracheal intubation or surgical incision. Surgical stimulation during standardized isoflurane-nitrous oxide anesthesia increased delta and decreased alpha activities with lower EEG frequencies, whereas delta activity was lost with higher EEG frequencies in the frontotemporal brain regions during intubation under anesthesia with thiopental/nitrous oxide. During induction of anesthesia with thiopental/fentanyl, alpha activity was most reduced in the temporal and occipital regions. The most prominent EEG changes after intubation were an increase in alpha and a decrease in delta power. The largest changes were in the frontal and temporal leads for alpha and in the frontal and central leads for delta [5] . In our study, a standardized anesthetic technique was used in both groups.

A study was conducted on 30 patients (comparing low-dose and high-dose fentanyl) by Sleigh and his colleagues who found that both ETT and incision resulted in a significant decrease in 10 Hz score, whereas incision, but not intubation, resulted in a significant decrease in HFVI and no statistically significant change in delta for either incision or intubation. This differed from our study that showed highly significant changes between prenoxious and postnoxious stimuli regarding all EEG parameters used. This might be due to the small sample of this study. They also found that the nociception-induced reduction in spindles was lesser in the high-dose fentanyl group. This was in agreement with our study as the morphine group showed less nociception-induced reduction in spindles after intubation due to the added analgesic effect of morphine to that of fentanyl of induction (morphine effect). Morphine was given 5 min before induction to guarantee the peak effect of morphine at time of incision (peak effect after 20 min). Because morphine has a rapid onset of action (2-3 min), it added an analgesic effect to that of fentanyl of induction and diminished the response to intubation with less change in the sleep spindle of the EEG. This added an advantage to the morphine group and explained the significant difference between both groups [6] .

Our study was in agreement with a study conducted by Sarιn-Koivuniemi et al. [7] who combined ECG, photoplethysmography, and EEG aiming at evaluating response index of nociception during GA, comparing preindex and postindex values of certain noxious stimuli with the average index values, finding that the postevent values of the index for intubation and skin incision were higher than its intrasurgery baseline, whereas pre-event values remained unchanged.

There was better analgesic effect due to epidural analgesia on the skin incision than the systemic opioid effect of the morphine group - that is, the epidural analgesia offered a great benefit in decreasing arousal response. This was in agreement with a study conducted by Maiko et al. [8] who found a statistically significant decrease in bispectral index (BIS) and suppression of adrenosympathetic activity during upper abdominal surgery after epidural injection of lidocaine, which suggests that the epidural administration of lidocaine would contribute to the disappearance of the arousal response - that is, BIS might be affected by the epidural analgesia.

We compared the peri-incision changes of our study with those of another study conducted on 116 adult patients having GA maintained with either desflurane or propofol, and the EEG was quantified using seven estimated parameters: slope and intercept of the underlying nonoscillatory power spectrum, amplitude, and frequency of the episodic frontal alpha oscillation, peak power in the delta waveband, HFVI, and BIS. It showed that incision was associated with decreased episodic frontal alpha activity and high-frequency variability. The effects of the incision were independent of the type of drug used for maintenance of anesthesia and on the preincision BIS. This effect is not strongly modified by the depth of anesthesia, as estimated by the BIS [9] . In this study, significant changes occurred in EEG due to incision, despite the administered anesthetic drugs and the good depth of anesthesia detected by BIS, the thing that necessitates the use of other drugs or maneuvers as analgesics to make a little change between the preincision and postincision periods. This was performed and confirmed in our study using the epidural analgesia.

We concluded that epidural analgesia has led to less response to noxious stimuli than systemic opioids as reflected by less EEG changes in the epidural group.

In our study, we supposed a target and tried to achieve a goal; epidural analgesia is better than systemic opioids in achieving good analgesia, confirmed not by clinical assessments or pain scores, but by inspecting the center and the processor of all sensations, the brain, through its mirror, the EEG. However, a hidden goal could be that this study might be a nucleus for further studies to achieve perfection by giving the analgesics with the adequate dosing, timing, and method confirming adequate analgesia to make GA resembling natural sleep.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.Bischoff P, Kochs E, Droese D, Meyer-Moldenhauer W, Schulte EJ. Topographica-quantitative EEG-Analyse der paradoxen Arousal reaktion. Der Anesthetist 1993; 42 :142-148.  Back to cited text no. 1
    
2.Hayashi K, Sawa T, Matsuura M. Anesthesia depth-dependent features of electroencephalographic bicoherence spectrum during sevoflurane anesthesia. Anesthesiology 2008; 108 :841-850.  Back to cited text no. 2
    
3.Ghoneim MM. Awareness during anesthesia. Anesthesiology 2000; 92 :597-602.  Back to cited text no. 3
    
4.Suraphong L, Yodying P. Cerebral electrical activity as a tool in evaluating anesthetic effect during balanced anesthesia with sevoflurane. J Med Assoc Thai 2005; 88 :1574-1581.  Back to cited text no. 4
    
5.Wilder-Smith OH, Hagon O, Tassonyi E. EEG arousal during laryngoscopy and intubation: comparison of thiopentone or propofol supplemented with nitrous oxide. Br J Anaesth 1995; 75 :441-446.  Back to cited text no. 5
    
6.MacKay EC, Sleigh JW, Voss LJ, Barnard JP. Episodic waveforms in the electroencephalogram during general anesthesia: a study of patterns of response to noxious stimuli. Anaesth Intensive Care 2010; 38 :102-112.  Back to cited text no. 6
    
7.Sarén-Koivuniemi TJ, Yli-Hankala AM, Van Gils MJ. Increased variation of the response index of nociception during noxious stimulation in patients during general anesthesia. Comput Methods Programs Biomed 2011; 104 :154-160.  Back to cited text no. 7
    
8.Maiko S, Toshiya K Yoshio T. Epidural analgesia-EEG bispectral response during surgery under sevoflurane anesthesia. Anesthesiology 2002; 96 :A551.  Back to cited text no. 8
    
9.Sleigh JW, Leslie K, Voss L. The effect of skin incision on the electroencephalogram during general anesthesia maintained with propofol or desflurane. J Clin Monit Comput 2010; 24 :307-318.  Back to cited text no. 9
    



 
 
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