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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 2  |  Issue : 3  |  Page : 73-78

Evaluation of the efficacy of dexmedetomidine infusion on the quality of balanced anesthesia and postmastectomy pain


Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission21-Jul-2015
Date of Acceptance19-Aug-2015
Date of Web Publication30-Dec-2015

Correspondence Address:
Ashraf E Alzeftawy
MD, Anesthesia and Surgical Intensive Care Department, Faculty of Medicine, Tanta University, 31120 Tanta
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2356-9115.172793

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  Abstract 

Background
The authors studied the effect of intraoperative infusion of dexmedetomidine on the quality of anesthesia, anesthetic requirements in patients undergoing radical mastectomy, and its effect on acute and chronic postmastectomy pain.
Patients and methods
A total of 76 female patients undergoing radical mastectomy were randomly classified into two groups: group I received intraoperative dexmedetomidine infusion and group II, the control group, received an infusion of normal saline. Heart rate, mean arterial blood pressure, end tidal isoflurane concentration, amount of fentanyl and muscle relaxant increments, recovery characteristics, quality of postoperative analgesia for 3 days, and incidence of side effects were recorded. Incidence of chronic pain was reported after 6 months.
Results
There was a significant decrease in mean arterial blood pressure and heart rate in group I from 1 min after skin incision and onwards. Extubation time and response to verbal command were significantly shorter in the dexmedetomidine group than in the control group (P = 0.003 and P < 0.0001, respectively), and end tidal concentration of isoflurane was significantly lower in group I (P < 0.0001). There was a significant decrease in fentanyl requirement in the operating room in group I (P < 0.0001). Time to first analgesia was significantly longer in group I (P < 0.0001). There was a significant decrease in postoperative analgesic requirement and a better quality of analgesia in the dexmedetomidine group (P < 0.0001). Pain scores at 6 months were comparable in both groups.
Conclusion
This study showed that the use of intravenous dexmedetomidine had a sparing effect on anesthetic and analgesic requirements with hemodynamic stability effect and no protective effect from the development of chronic pain.

Keywords: Acute, balanced anesthesia, chronic, dexmedetomidine, postmastectomy pain


How to cite this article:
Alzeftawy AE, Elsheikh NA. Evaluation of the efficacy of dexmedetomidine infusion on the quality of balanced anesthesia and postmastectomy pain. Res Opin Anesth Intensive Care 2015;2:73-8

How to cite this URL:
Alzeftawy AE, Elsheikh NA. Evaluation of the efficacy of dexmedetomidine infusion on the quality of balanced anesthesia and postmastectomy pain. Res Opin Anesth Intensive Care [serial online] 2015 [cited 2017 Aug 18];2:73-8. Available from: http://www.roaic.eg.net/text.asp?2015/2/3/73/172793


  Introduction Top


Dexmedetomidine, a selective α-2 adrenoceptor agonist, has analgesic, sedative, and anxiolytic properties. Various studies have investigated its role in the perioperative period as regards its sedative and analgesic-sparing effect [1],[2].

Modified radical mastectomy with axillary node dissection is currently the commonly used surgical procedure for the management of breast cancer. Severity of postoperative pain may influence the development of chronic postmastectomy pain, which is commonly reported [3]. Pre-emptive analgesia has been shown to be efficacious in reducing postoperative pain [4], and may be effective in reducing the incidence of chronic neuropathic pain [5].

However, the effect of dexmedetomidine on chronic pain has not been one of the main endpoints of any trial on dexmedetomidine. Thus, one of the purposes of this study was to assess whether the analgesic-sparing effect of perioperatively administered dexmedetomidine has any impact on the occurrence of chronic pain in cases undergoing modified radical mastectomy for breast cancer.

In this randomized double-blind trial, the authors studied the effect of intraoperative use of dexmedetomidine on the quality of anesthesia with respect to maintenance, recovery, its ability to reduce isoflurane, narcotic, and muscle relaxant requirements in patients undergoing radical mastectomy surgery, and its effect on acute postoperative pain and incidence of postmastectomy chronic pain.


  Patients and methods Top


After approval of our institutional ethical committee, written informed consent was obtained from the patients. This study was performed on 76 female patients of ASA physical status I and II undergoing radical mastectomy for breast cancer with axillary lymph node involvement.

Patients with hypertension on β-blockers, heart block, renal disease, hepatic disease, and morbid obesity were excluded from the study.

Upon arrival to the operating room, the baseline monitoring including ECG, mean arterial blood pressure (MABP), and pulse oximetry were started. One intravenous cannula was inserted for fluid and drug administration and another cannula for the study drug administration was inserted in the arm opposite to the side of the operation.

The patients were classified randomly into two equal groups. Group I, the dexmedetomidine group, and group II, the placebo group.

This was a prospective, randomized study. Sealed envelope method was used to allocate participants to the respective groups. The randomization was performed with a computer-generated system. This was a double-blind design in which the patients, anesthesiologist, and postoperative assessors were blinded to the management protocol. An independent chief nurse, who did not participate in the clinical trial, read the number contained in the envelope and assigned patients to the respective groups.

For induction of anesthesia, preoxygenation through a face mask with 100% oxygen for 3 min, followed by intravenous administration of midazolam 1-2 mg and fentanyl 1 μg/kg, was carried out. Propofol (10 mg/ml) was then given at a dose of 2 mg/kg slowly until loss of eyelash reflex. Cisatracurium was given at a dose of 0.1-0.2 mg/kg. Patients were assisted manually with a face mask with 100% O 2 and 2% isoflurane. Endotracheal intubation was performed using an appropriate size cuffed endotracheal tube after full muscle relaxation detected by loss of train of four (TOF) responses was obtained. Patients were then ventilated mechanically using the volume-controlled mode with a tidal volume of 6 ml/kg, respiratory rate (RR) of 12, and I : E ratio of 1 : 2. Anesthesia was then maintained with isoflurane with 50% O 2 air mixture, increments of fentanyl 0.5 μg/kg, and increments of cisatracurium 0.03 mg/kg for muscle relaxation.

Study protocol

In group I, dexmedetomidine infusion was started with a loading dose of 1 μg/kg in 20 ml normal saline for 10 min before skin incision and then continued as an infusion of 0.2 μg/kg/h until the end of surgical procedure.

In group II, similar volumes and infusion rates of normal saline were administered.

In both groups, end tidal isoflurane concentration was manipulated to maintain adequate depth of anesthesia guided by the bispectral index (BIS) of 40-60. Fluid transfusion at a rate of 2 ml/kg/h Ringer solution was maintained and blood loss was replaced with either Ringer's solution at a ratio 3 : 1 or colloids at a ratio of 1 : 1.

Intraoperative monitoring included ECG, noninvasive blood pressure, pulse oximetry, capnography, end tidal isoflurane concentration, TOF ratio, and the BIS.

At the end of the surgery (closure of skin incision), anesthesia was discontinued and infusions stopped. Reversal of muscle relaxants was performed using 0.04-0.08 mg/kg of neostigmine with atropine (0.02 mg/kg) 1-2 mg after regain of spontaneous respiration. Suctioning and endotracheal extubation were performed after achieving a TOF ratio of 0.9. The patients were then administered a face mask and transferred to the postanesthesia care unit for further monitoring and assessment until they were ready to be transferred to the ward.

Postoperatively, the patients were given analgesia based on visual analogue scale (VAS) assessment in the form a titrated dose of morphine (2 mg bolus at 5-min intervals) until the VAS was 3 or less, and then 20-50 μg/kg of morphine was given intravenously as necessary to relieve pain, if the patient had developed VAS greater than 3 for the first 72 h after surgery. Moreover, the patient received diclofenac sodium 75 mg intramuscularly once daily as a fixed analgesic regimen.

The following parameters were recorded and analyzed

Hemodyamics, including MABP and heart rate (HR), were assessed at the following times: T0 = preinduction, T1 = postintubation, T2 = 1 min after skin incision, T3 = 10 min intraoperatively, T4 = 25 min intraoperatively, T5 = 40 min intraoperatively, T6 = 60 min intraoperatively, T7 = 75 min intraoperatively, T8 = 90 min intraoperatively, T9 = 105 min intraoperatively, T10 = 120 min intraoperatively, T11 = 135 min intraoperatively, T12 = immediate postoperatively, and T13 = 15 min postoperatively.

End tidal isoflurane concentration to maintain a BIS of 40-60, amount of fentanyl increments and amount of muscle relaxant were recorded.

Recovery characteristics as regards time of extubation and time to response to verbal command were also recorded.

Postoperative measurements included time to first analgesia and VAS [6].

Postoperative pain at rest and movement was evaluated using a 10 cm unmarked line, in which 0 = no pain and 10 cm = worst pain imaginable, at 6 h interval on the first day postoperatively and then daily for 2 days. Movement consisted of abduction of the arm on the operated side by 90°. Patients were evaluated 6 months later for incidence of chronic postmastectomy pain using a short questionnaire [Table 1].
Table 1: Chronic pain questionnaire [7]

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Amount of morphine usage during the first 72 h postoperatively and incidence of sedation were recorded. Sedation scores were rated using the sedation scale [8]: awake and alert = 0; sleepy/responds = 1; asleep but easily roused = 2; and deep sleep = 3. Sedation was defined as a sedation score greater than 0 at any postoperative time point. Respiratory depression and postoperative nausea and vomiting (PONV) were recorded. Respiratory depression was defined as a respiratory rate less than 8 breaths/min and/or PaCO 2 greater than 45 mmHg. PONV was measured using a categorical scoring system [9]: none = 0; mild = 1; moderate = 2; and severe = 3. Detection of nausea occurred when nausea score was greater than 0 at any time point postoperatively.

The primary outcome measures included end tidal isoflurane concentration, intraoperative fentanyl and muscle relaxant consumption, VAS scores at rest and movement, and postoperative opioid consumption during the first 72 h. The secondary outcome measures included, extubation time, PONV, sedation, respiratory depression, and chronic postoperative pain at 6 months after surgery.

Statistical analysis

The sample size selected was calculated on the basis of the assumption that 34 patients per group were needed to have an 80% chance of detecting a 35% reduction in 24-h morphine consumption at a 5% significance level. To avoid bias resulted from patient drop out, 10% was added to the patient number and therefore 38 patients were enrolled in each group. Data were analyzed using SPSS 15.0 software (SPSS Inc., 233 South Wacker Drive, 11th Floor, Chicago, IL, USA), with Fisher's exact test, unpaired t-test, and Mann-Whitney test, as appropriate; a P value less than 0.05 was considered to be statistically significant.


  Results Top


This study was completed on 73 patients. Two patients in group I and one patient in group II declined to attend for chronic pain assessment. The characteristics of these patients are shown in [Table 2]. Statistical analysis revealed no significant differences between groups as regards demographic data, duration of the operative procedure, duration of anesthesia, and ASA status of the patients.
Table 2: Demographic data and duration of surgery and anesthesia

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Hemodynamic profile, including MABP and HR, in the two groups were comparable as regards the preoperative and postintubation assessment values. There was a significant decrease in MABP and HR in group I compared with group II from 1 min after skin incision assessment value onwards. None of the patients in group I developed either hypotension (more than 20% drop in MABP than preanesthetic values) or bradycardia below 50 beats/min [Table 3] and [Table 4].

As regards maintenance measurements, the end tidal concentration of isoflurane was significantly lower in group I to maintain a BIS of 40-50 compared with that in group II (P < 0.0001). There was a significant decrease in fentanyl requirement in the operating room in group I than in group II (117.5 ± 16.4 and 221 ± 23.6, respectively) (P < 0.0001) [Table 3]. However, muscle relaxant consumption was comparable in both groups (P = 0.36) [Table 5].
Table 3: Mean arterial blood pressure changes in both groups

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Table 4: Heart rate changes in both groups

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Table 5: Anesthetic data, time to first analgesic requirement, incidence of nausea and vomiting, and total morphine
consumption


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Times to endotracheal extubation and response to verbal command were significantly shorter in group I than in group II (P = 0.003 and P < 0.0001, respectively). Meanwhile, the time to first analgesia requirements was significantly longer in group I than in group II (P < 0.0001) [Table 5].

There was a significant decrease in analgesic requirement in the recovery room in the dexmedetomidine group; intravenous morphine requirement was 6.3 ± 1.6 and 10.4 ± 1.7 mg (mean ± SD) in group I and group II, respectively (P < 0.0001). The total morphine consumption in the ward during the first 72 h was significantly reduced in the dexmedetomidine group (mean ± SD) (20.5 ± 4.2 and 38 ± 5.4 mg in groups I and II, respectively) (P < 0.0001).

The data on postoperative pain at rest and movement are shown in scores at 6, 12, 18, 24, 48, and 72 h, and the scores were statistically significantly higher in the control group than in the dexmedetomidine group (P < 0.0001) [Figure 1] and [Figure 2].
Figure 1: The visual analogue scale (VAS) scores at rest in both groups at 6, 12, 18, and 24 h postoperatively, on the second and third postoperat ive days.

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Figure 2: The visual analogue scale (VAS) scores at movement in both groups at 6, 12, 18, and 24 h postoperatively, on the second and third postoperat ive days.

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Nausea and vomiting was comparable. However, the incidence of sedation (sedation score>0) was noted to be higher in the control group (38%) in comparison with the other group (12%) on the first postoperative day (P < 0.0001) as correlated to decrease in opioid consumption. However, on the second and third days postoperatively, all patients in the two groups had score 0 (awake and alert). No reported incidence of respiratory depression was detected in both groups.

Pain scores at movement were 2.6 ± 1.2 and 2.8 ± 1.6 (P = 0.5) in groups I and II, respectively, and pain scores at rest were 1.4 ± 0.9 and 1.3 ± 0.7 (P = 0.6) in groups I and II, respectively. At 6 months, pain scores were comparable in both groups. Incidence of different types of chronic pain was comparable in both groups (P > 0.05) [Table 6].
Table 6: Chronic pain characteristics in each group of patients 6 months postoperatively

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  Discussion Top


In the present study, dexmedetomidine reduced anesthetic requirements and shortened recovery time. The anesthetic-sparing effect of dexmedetomidine was documented in many previous studies: 25% reduction in maintenance concentrations of isoflurane [10], 35-50% reduction in isoflurane concentrations [11], and 17% reduction in sevoflurane requirements [12].

The use of intraoperative dexmedetomidine was associated with greater hemodynamic stability in the present study and this was attributed to the attenuation of the stress-induced sympathoadrenal responses to surgery and recovery [13], and this in accordance with the results of a previous study [14]. Hemodynamic stability may be also attributed to the timing of use of dexmedetomidine in the present study after induction and intubation and not before induction, which may lead to the incidence of hypotension. There was no reported difference between the two groups in muscle relaxant consumption in the present study as well as in previous study [15].

Incidence of nausea and vomiting was comparable in both groups. In contrast to our study, Massad et al. [16] evaluated the effect of adding dexmedetomidine to a balanced technique on postoperative nausea and vomiting after surgeries and revealed that the incidence of postoperative nausea and vomiting decreased significantly in the dexmedetomidine group. However, Keles et al. [17] denied any antiemetic role of dexmedetomidine. Such difference in the results might be partially attributed to the use of different anesthetic drugs.

The incidence of sedation was noted to be higher in the control group (38%) in comparison with the other group (12%) on the first postoperative day as seen in the decreased opioid consumption in group I, but it was comparable on the second and third postoperative days because of less clinical difference in opioid consumption in the two groups.

The results of this study indicated that dexmedetomidine decreased pain scores at movement and rest and morphine and analgesic consumption in the acute phase, but had no significant effect on the incidence of chronic pain. To our knowledge, this is the first study to evaluate the effect of dexmedetomidine on the incidence of chronic pain.

Other results in the literature support the results of the present study as regards reduction in postoperative analgesic consumption. It is emphasized that, when dexmedetomidine is used intraoperatively, the consumption of analgesics during the postoperative period is less [11],[18],[19],[20] and the time to first analgesic requirements was prolonged [21].

This study concluded that the use of intravenous dexmedetomidine had sparing effect on anesthetic and analgesic requirements with hemodynamic stability effect and no protective effect from development of chronic pain. Further trials on larger number of patients are warranted to elucidate the effect of dexmedetomidine in vulnerable group of patients susceptible to the development of chronic pain such as post-thoracotomy and postherniorraphy pain.


  Acknowledgements Top


Ashraf E. Alzeftawy: Conception, design; drafting of the article; revision of the article, literature search, analysis and interpretation of the data, manuscript editing.

Nabil A. Elsheikh: Literature search, analysis and interpretation of data.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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2.
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Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and perioperative fentanyl. Br J Anaesth 1992; 68:126-131.  Back to cited text no. 13
    
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Talke P, Chen R, Thomas B, et al. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000; 90:834-839.  Back to cited text no. 14
    
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17.
Keles GT , Ozer M, Dede G, Temiz C, Horasan GD, Civi M. Balanced anesthesia with dexmedetomidine added desflurane or sevoflurane in spinal surgery. J Anesth Clin Res 2012; 3:6.  Back to cited text no. 17
    
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Ozkose Z, Demir FS, Pampal K, Yardým S. Hemodynamic and anesthetic advantages of dexmedetomidine, an alpha 2-agonist, for surgery in prone position. Tohoku J Exp Med 2006; 210:153-160.  Back to cited text no. 18
    
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Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg 2004; 98:153-158.  Back to cited text no. 19
    
20.
Turgut N, Türkmen A, Gökkaya S, Altan A, Hatiboðlu MA. Dexmedetomidine-based versus fentanyl-based total intravenous anesthesia for lumbar laminectomy. Minerva Anestesiol 2008; 74:469-474.  Back to cited text no. 20
    
21.
Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999; 54:1136-1142.  Back to cited text no. 21
    


    Figures

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    Tables

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