Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 10  |  Issue : 1  |  Page : 15-19

Postoperative analgesic effect of dexmedetomidine in patients undergoing cardiac surgery


1 Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Cardiothoracic Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Web Publication3-Aug-2018

Correspondence Address:
Assem A Moharram
Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, 11828
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.238449

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  Abstract 


Aim Open heart surgeries are painful procedures that require a large dose of analgesics. The aim of this study was to investigate the effect of postoperative dexmedetomidine (DEX) on the analgesic requirements in postcardiac surgery patients.
Settings and design This prospective, randomized, double-blind study was conducted on 60 patients scheduled for elective coronary artery bypass graft surgery at the Cardiothoracic Surgery Unit, Ain Shams University Hospital.
Patients and methods this study, group D (n=30) received DEX diluted to 4 μg/ml and infused at a rate of 0.1–0.2 μg/kg/h, whereas group C (n=30) received an equal volume of saline at an infusion rate of 0.1–0.2 μg/kg/h immediately from the end of surgery and postoperatively in the ICU thereafter. Postoperative analgesia was assessed using the Numeric Pain Intensity Scale, and sedation was assessed using the Modified Ramsay Score at T1, T2, T3, T4, T5, and T6 for the first 24 h, as well as postoperative rescue morphine analgesic requirements.
Statistical analysis Analysis of data was performed using the Student t-test for independent samples for parametric data and using the χ2-tests for categorical data.
Results There was a significant decrease in the pain scores in group D compared with group C (P<0.001). Morphine rescue analgesia was needed in 10% of patients in group D and in 95% of patients in group C, with a significant reduction in time to extubation and ICU length of stay in group D. The incidence of postoperative nausea and vomiting was lower in group D compared with group C but did not reach statistical significance.
Conclusion Adding DEX after coronary artery bypass graft decreased both postoperative analgesic requirement and pain score without hemodynamic effects.

Keywords: coronary artery bypass graft, dexmedetomidine, pain score, postoperative analgesia


How to cite this article:
Moharram AA, El Midany AA. Postoperative analgesic effect of dexmedetomidine in patients undergoing cardiac surgery. Ain-Shams J Anaesthesiol 2017;10:15-9

How to cite this URL:
Moharram AA, El Midany AA. Postoperative analgesic effect of dexmedetomidine in patients undergoing cardiac surgery. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2018 Nov 20];10:15-9. Available from: http://www.asja.eg.net/text.asp?2017/10/1/15/238449




  Introduction Top


Open heart surgery including sternotomy is a painful procedure that requires large doses of analgesics that can delay fast-track recovery [1]. Opioids are known to have a dose-dependent analgesic effect associated with side effects such as drowsiness, nausea, vomiting, depressed gastrointestinal motility, respiratory depression, and hemodynamic effects, especially with larger doses [2]. Nonopioid analgesics are used as opioid adjuncts to decrease opioid consumption, but their efficacy may be limited with potentially serious adverse effects such as increased bleeding and renal failure [3].

Dexmedetomidine (DEX) is a highly selective α2-receptor agonist that provides better sedation, analgesia, and anxiolytic effect compared with clonidine. This property is considered unique among sedatives used for intensive care patients [4],[5]. DEX decreased both postoperative sedative and analgesic requirements after noncardiac surgery, with minimal hemodynamic and respiratory effect [6]. In addition, patients treated with DEX experienced sedation, lower incidence of delirium, easier extubation, and a lower incidence of mortality [7].

The aim of this randomized, prospective, double-blind study was to investigate the effect of postoperative DEX on the analgesic requirement in postcardiac surgery patients.


  Patients and methods Top


The protocol was approved by our Institutional Review Board and written informed consent was obtained from patients. Sixty patients scheduled for elective coronary artery bypass graft (CABG) surgery at the Cardiothoracic Surgery Unit, Ain Shams University Hospital, from December 2010 to March 2012, were included in the study. Patients between 50 and 75 years of age of both sex who manifested good left ventricular function with an ejection fraction greater than 35% were included in this double-blinded prospective study. Patients receiving corticosteroids, those having severe asthma, diabetes, or obstructive pulmonary disease, patients undergoing emergency cardiac surgery, patients who underwent angiography within 24 h before the study, and patients with impaired renal function (creatinine >2.0 mg/dl) or impaired liver function (serum transaminase >50 U/l) were excluded from the study. Patients in the study groups were instructed on the use of Numeric Pain Intensity Scale (NPIS), which ranged from no pain (0) to severe pain (10), and Modified Ramsay Score (MRS) used to assess sedation, which ranged from 1 to 6: 1, anxious/agitated; 2, cooperative oriented; 3, responds to commands only; 4, asleep with brisk response to light glabellar tap (LGT); 5, sluggish response to LGT; and 6, asleep, no response to LGT.

Before induction of anesthesia, all patients in the study group were routinely monitored using ECG, pulse-oximetry, and continuous invasive blood pressure using an intra-arterial catheter connected to strain gauge pressure transducers. Muscle relaxation was monitored with a nerve stimulator (Fisher Paykel model NS242, Auckland, New Zealand +64 95 74 01 00). Anesthetic technique was standardized for all patients using intravenous fentanyl (5–10 μg/kg), sodium thiopental (1–2 mg/kg), and vecuronium (0.1 mg/kg) as a muscle relaxant, and additional doses were given using the train-of-four monitoring with a nerve stimulator. Patients were ventilated with oxygen/air (inspired oxygen fraction 0.5%), tidal volume 5–7.5 ml/kg at normocapnia using controlled ventilation, and capnography and serial arterial blood gas were performed to adjust mechanical ventilation and electrolyte balance. Anesthesia was maintained with inhaled sevoflurane 1–2%. Fentanyl (2 μg/kg) was administered before sternotomy. Midazolam 0.05 mg/kg was administered before sternotomy, 2 mg during rewarming, and 2 mg during sternal closure.

All CABG procedures were performed through median sternotomy. Cardiopulmonary bypass (CPB) with nonpulsatile perfusion flow (2.2−2.4 l/min/m2) was conducted using membrane oxygenators with arterial line filtration, and mean arterial pressure (MAP) was kept between 50 and 70 mmHg. Mild systemic hypothermia (32−35°C) was used during CPB. Cardiac arrest was achieved by delivering a high-potassium-containing cold blood cardioplegic solution antegrade into the aortic root.

Surgical techniques were the same in all cases and conducted by the same group of surgeons who were blinded to the study medication. All distal anastomoses were completed before the aortic cross-clamp was removed, whereas proximal anastomoses were performed on partial clamp. At the end of the procedure, heparin was neutralized using protamine until activated clotting time was less than 180 s, and patients were then randomized by opening sequentially numbered opaque envelopes into the two parallel groups. Group D received DEX diluted to a concentration of 4 μg/ml and infused at a rate of 0.1–0.2 μg/kg/h, whereas group C received an equal volume of saline at an infusion rate of 0.1–0.2 μg/kg/h as a placebo immediately from the end of surgery and postoperatively in the ICU thereafter. At the end of surgery, patients in both groups received morphine bolus dose of 20 μg/kg, followed by morphine infusion (prepared as10 μg/kg/ml) at a rate 20 μg/kg/h. Patients were transferred to the ICU on mechanical ventilation. In the ICU, all patients were monitored with MAP and the heart rate (HR) hourly over 24 h and weaned when they were fully awake, hemodynamically stable with full recovery of muscular forces, and met the weaning and extubation criteria according to the protocols of the ICU. Morphine infusion was stopped in both groups 4 h before transfer to ward.

Pain assessment was carried out using the NPIS, whereas MRS was used for sedation that was measured on 1st (T1), 3rd (T2), 6th (T3), 12th (T4), 18th (T5), and 24th (T6) hour. Patients received morphine sulfate (20 μg/kg) rescue analgesia if the NPIS was greater than 4, whereas MRS was maintained at 3 before extubation and 2 after extubation using rescue midazolam of 1 mg. Duration of surgery, duration of anesthesia, CPB time, time to first analgesic requirement, frequency and dosage of sedatives and analgesics given, time to extubation, ICU length of stay, episodes of bradycardia (defined as a decrease in the HR <20% from the baseline), episodes of hypotension (defined as a decrease in the systolic blood pressure <20% from the baseline), and postoperative nausea or vomiting were recorded by the ICU team blinded to study medication.

Statistical analysis

Data were analyzed using computer statistical software system statistical packages for the social sciences (SPSS, version 16; SPSS Inc., Chicago, Illinois, USA). The sample size was calculated with a group sample sizes of 25 and 3, to achieve a 92% power to detect a difference of −360.0 between the null hypothesis that both group means are 120.0, and the alternative hypothesis that the mean of group C is 480.0, with an estimated group SDs of 60.0 and 100.0 and with a significance level (α) of 0.05 using a two-sided two-sample t-test. Five percent was added to the sample to cover for possible dropouts. Data were presented as mean±SD, median, numbers, and percentage. Analysis of data between the groups was performed using the Student t-test for independent samples for parametric data (age, weight, height, duration of anesthesia, duration of surgery, CPB time, MAP, HR, duration of intubation, ICU stay, and the dose of morphine sulfate rescue analgesia), and the χ2-tests for categorical data (sex, hypotension, bradycardia, postoperative nausea, and vomiting). A P-value less than 0.05 was considered statistically significant.


  Results Top


There were no significant differences between the two groups with respect to their age, sex, weight, height, left ventricular ejection fraction, duration of anesthesia, duration of surgery, and CPB time ([Table 1]).
Table 1 Patient characteristics

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Postoperatively, there was no significant difference between the two groups with respect to MAP, episodes of bradycardia or hypotension as well as the percentage of patients requiring glyceryl nitrate, sodium nitroprusside, dopamine, noradrenaline, adrenaline, and esmolol. However, there was a significant decrease in the HR, median MRS, NPIS, time to extubation, and ICU length of stay in group D compared with group C ([Table 2]).
Table 2 Postoperative data

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Patients in group C and group D experienced a period of analgesia during the first 3 h after surgery as assessed using the NPIS at T1 and T2, and then the NPIS severity increased gradually until the 6th hour (T3). Subsequently, pain severity decreased until it disappeared at the 18th hour (T5) postoperatively. Group D experienced a significantly (P<0.001) reduced pain compared with group C at any of the given time intervals. NPIS was significantly reduced in group D compared with group C at T1, T2, T3, and T4 postoperatively ([Table 3]). Time to first morphine rescue analgesia was not significantly different (P=0.1) between the two groups [210 (45) min in group D compared with 196 (53) min in group C).
Table 3 The numeric Pain Intensity Scale measured during 24 h in the intensive care unit after cardiac surgery

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There was a significant reduction in postoperative analgesic requirements in group D compared with group C (P=0.04), as only 10% of the patients in group D needed rescue morphine for analgesia, whereas 95% of the patients in group C required rescue morphine for analgesia. Moreover, there was a decrease in the need for midazolam rescue sedation in group D (14%) compared with group C (48%); however this did not reach statistical significance (P=0.06) ([Figure 1]). There was a significant reduction in MRS in group D compared with group C on T1, T2, T3, and T4 postoperatively ([Table 4]).
Figure 1 Incidence of need to rescue analgesia and sedation in both groups.

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Table 4 The Modified Ramsay Sedation Scale measured during 24 h in the intensive care unit after cardiac surgery

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Among the patients who needed the analgesics, there was a significant reduction in morphine sulfate dose in group D (5.9±1.2 mg) compared with 11.8±3 mg in group C (P<0.001), with a reduction in postoperative nausea and vomiting in group D (2; 7%) compared with group C (4; 13%); however, it did not reach statistical significance (P=0.08).


  Discussion Top


This study shows that the addition of DEX infusion following CABG operation was associated with a reduction in morphine consumption and pain severity as assessed with pain scores, with a significant reduction in the time to extubation and the length of ICU stay. The number of patients suffering from postoperative nausea and vomiting was also less in group D compared with group C, but did not reach statistical significance.

Postcardiac surgery is a stressful condition that necessitates appropriate sedation and pain control to avoid increase in catecholamine release that might lead to an increase in the total peripheral vascular resistance, HR, and the risk for myocardial infarction and mortality [8]. In a study by Arain et al. [8], there was a transient increase in blood pressure in the DEX group that was related to the activation of α2 agonist on the smooth muscles of the vessels’ walls, which led to transient vasoconstriction and increased MAP [8].

In this study, no significant difference was found between the two groups with respect to MAP and HR, which could be explained by attributing the hemodynamic changes in MAP and HR to postsurgical stress, the surgical procedure itself, or pre-existing hypertension, as this occurred in both groups. Moreover, the decrease in MAP and HR was related to the more gradual central effect of DEX in group D, which was similar to the decrease in MAP in group C patients who were dependent on morphine as a main analgesic, with its direct vasodilating effect, considering that there was no significant difference in the number of patients receiving inotropes and vasodilators between the two groups [9].

The hemodynamic effects of DEX was investigated by Mukhtar et al. [10], who showed that intraoperative DEX infusion attenuated the hemodynamic and neuroendocrine response to surgical and CPB. Shehabi et al. [11] found that DEX reduced the duration but not the incidence of delirium after cardiac surgery, with effective analgesia sedation, less hypertension, less vasopressor requirement, and more bradycardia compared with morphine regimen. Barletta et al. [12] also showed that DEX decreased cardiac index and HR for patients undergoing prolonged procedures. Moreover, in a study by Maldonado et al. [13], DEX caused a higher rate of adverse hemodynamic events, which might be a concern in hemodynamically unstable patients.

In the present study, DEX decreased the postoperative analgesic requirements and only 10% of patients in group D required a postoperative rescue morphine sulfate analgesia, with a significant reduction in the dose of rescue morphine analgesic requirement in group D compared with group C, in which 95% of patients required postoperative rescue morphine sulfate analgesia. The pattern of pain in both groups was almost the same, which means that DEX did not alter the trend of the pain, but just decreased the intensity, and almost both groups needed to receive analgesics at same time intervals when NPIS was greater than 4, in agreement with a study by Abd Aziz et al. [9].

DEX was reported to decrease the length of ICU stay in comparison with the usage of other sedatives and analgesics such as midazolam and morphine [9], simulating the current study, in which patients in group D had shorter time to extubation and shorter ICU stay. Moreover, Lin et al. [14] showed that DEX administration had facilitated the weaning process from mechanical ventilator, and decreased the risk for delirium, ventricular tachycardia, and hyperglycemia following cardiac surgery [14].

The current study has potential limitations. Although a prospective placebo-controlled one, it lacked an active control as well as outcome measurement (morbidity or mortality and cost-effectiveness). Further studies are warranted using the active control of other postoperative analgesic regimens and to study cost-effectiveness.


  Conclusion Top


We concluded that adding DEX after CABG decreased both postoperative analgesic requirements and pain score without hemodynamic effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There was no conflicts of interest.



 
  References Top

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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. 8
    
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Abd Aziz N, Chue MC, Yong CY, Hassan Y, Awaisu A, Hassan J, Kamarulzaman MH. Efficacy and safety of dexmedetomidine versus morphine in post-operative cardiac surgery patients. Int J Clin Pharm 2011; 33:150–154.  Back to cited text no. 9
    
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Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M et al. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine compared morphine-DEXCOM study). Anesthesiology 2009; 111:1075–1084.  Back to cited text no. 11
    
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Barletta JF, Miedema SL, Wiseman D, Heiser JC, McAllen KJ. Impact of dexmedetomidine on analgesic requirements in patients after cardiac surgery in a fast-track recovery room setting. Pharmacotherapy 2009; 29:1427–1432.  Back to cited text no. 12
    
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Maldonado J, van der Starre PJ, Wysong A. Postoperative sedation and the incidence of ICU delirium in cardiac surgery patients. Anesthesiology 2003; 99:A465.  Back to cited text no. 13
    
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Lin YY, He B, Chen J, Wang ZN. Can dexmedetomidine be a safe and efficacious sedative agent in post-cardiac surgery patients? a meta-analysis Crit Care 2012; 16:R169.  Back to cited text no. 14
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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