EFFECT OF EPIDURAL DEXMEDETOMIDINE AND FENTANYL  INFUSION FOR POSTOPERATIVE ANALGESIA IN PATIENTS UNDERGOING UPPER ABDOMINAL SURGERIES: A RANDOMISED DOUBLE BLIND STUDY

INTRODUCTION

Wound complications are important causes of early and late postoperative morbidity and pain related concerns. Surgical wounds in normal, healthy individuals heal through an orderly sequence of physiologic events that includes inflammation, epithelialization, fibroplasia, and maturation. However, in this entire procedure pain also plays the crucial role. Mechanical failure or failure of wound healing at the surgical site can lead to disruption of the closure leading to seroma, hematoma, wound dehiscence, or hernia and again here pain is the important factor pointing out the abnormal physiology. ^[1]

Hence, the effective relief of pain is of the utmost importance to anyone treating patients undergoing surgery. Pain relief has significant physiological benefits; hence, monitoring of pain relief is increasingly becoming an important postoperative quality measure. The goal for postoperative pain management is to reduce or eliminate pain and discomfort with a minimum of side effects. Various agents (opioid vs. nonopioid), routes (oral, intravenous, neuraxial, regional) and modes (patient controlled vs. “as needed”) for the treatment of postoperative pain exist. Although traditionally the mainstay of postoperative analgesia is opioid based, increasingly more evidence exists to support a multimodal approach with the intent to reduce opioid side effects (such as nausea and ileus) and improve pain scores. Enhanced recovery protocols to reduce length of stay in colorectal surgery are becoming more prevalent and include multimodal opioid sparing regimens as a critical component. Familiarity with the efficacy of available agents and routes of administration is important to tailor the postoperative regimen to the needs of the individual patient. ^[2]

But use of opioids may have various undesirable effects like post-operative nausea and vomiting.

In a study conducted by Zeng et al.,^[3] comparing epidural dexmedetomidine infusion and fentanyl infusion after colonic resection surgery observed that epidural morphine group has higher incidence of nausea, vomiting and pruritus in comparison to epidural dexmedetomidine infusion in postoperative period with comparable pain scores nut with early recovery of gastrointestinal motility in dexmedetomidine group after colonic resection.

Zeng X et al., (2017)^[3]; Hetta DF et al., (2018)^[4]; Yousef AA et al., (2015)^[5]; Hetta DF et al., (2017)^[6]; Kiran S et al. (2018)^[7] found that epidural dexmedetomidine decrease postoperative VAS score and reduce requirement of rescue analagesia.

Hetta DF et al.,^[4] compared bupivacaine with bupivacaine + dexmedetomidine in epidural infusion in major abdominal cancer surgery and observed that dexmedetomidine added to bupivacaine significantly reduced morphine consumption, delayed time to first analgesic supplementation, and decreased pain intensity during the first 48 hours postoperatively without harmful derangement on hemodynamics.

So in this study we will compare the  effectiveness of  dexmedetomidine and fentanyl infusion for postoperative analgesia in patients undergoing upper abdominal surgeries.

AIMS AND OBJECTIVES

AIM

§  To compare the effectiveness of epidural dexmedetomidine and fentanyl infusion  postoperatively in patients undergoing upper abdominal surgeries 

OBJECTIVES

Primary Objective:  

§  To compare the postoperative pain using VAS score during rest and movement at different time postoperatively   

Secondary Objective:  

§  To assess rescue analgesia, sedation score, intraoperative and postoperative hemodynamics, bowel recovery time, nausea and vomiting.

METHODOLOGY

§  Study Settings: The study will be conducted in the operation theatre and post-operative care units of different departments of the University under the guidance of Department of Anesthesiology, King George’s Medical University, Lucknow.

§  Study design: Randomised double blinded comparative study.

§  Study duration:  1 Year

§  Sample size: 68

Sample size Calculation:

The sample size formulae used are as follows: (Bernard, 5th edition)^[8]

n=

n=  Sample size

σ = Standard Deviation

∆ = Difference of means

κ= Ratio

Z_1-α/2= Two sided Z value

Z_1-β= Power

•      Ethical approval: It will be taken from the Institutional Ethics Committee of the University.

Inclusion Criteria:

§  Patient of either gender of age between 18-65 years undergoing major upper abdominal cancer surgery and classified as American Society of Anesthesiologists (ASA) physical status class I–III.

Exclusion criteria:

§  Age less than 18 year or more than 65 year.

§  Patients with treatment of α-adrenergic antagonists.

§  History of arrhythmias, contraindications to placement of an epidural catheter (eg, coagulopathy, local infection, and vertebral anomalies), patients known to be allergic to bupivacaine, dexmedetomidine, or morphine, and patients treated with regular chronic pain medications.

§  Non willing patents.

STUDY PROTOCOL

Ethical clearance and Informed consent will be taken.

The study will be done at King George’s Medical University, Lucknow.

The randomization of patients will be achieved by a statistician through a computer-generated list of random numbers and sealed envelopes. Patients will be allocated to two groups as follows:

After intravenous infusion of 1 L of normal saline, the patients will be placed in the sitting position. Under a strict aseptic precaution, thoracic spines from seven to ten will be identified (the inferior angle of the scapula is corresponding to the seventh thoracic vertebra). The preferred insertion site will be T8–T9 as per standard protocol. All patients will receive general anesthesia as per standard protocol. Observer and patients will be blind of study drug.

Epidural drug dose:  6ml bolus followed by initiation @ 6ml/hr for first 24 hrs.

Rescue Analgesia: Inj PCM 1gm IV will be given if VAS > 3 at any time during the study period.

Monitoring:

Intraoperative and Postoperative haemodynamic.

Postoperative VAS score (static and dynamic).

Sedation Score.

Bowel recovery time.

Requirment of rescue analgesia.

Side effect: Nausea, Vomiting, Hypotension, Bradycardia.

Statistical Analysis: Data will be entered in Microsoft Excel and analyzed using statistical software SPSS version 15 (Chicago, IL, USA).  Statistical analysis will be performed using SPSS software (SPSS Inc., Chicago, IL, USA) for Windows program (15.0 version). The continuous variables will be evaluated by mean (standard deviation) or range value when required. The dichotomous variables will be presented in number/frequency and will be analyzed using Chi-square or Fisher Extract test. For comparison of the means between the two groups, analysis by Student t-test, Mann-Whitney U test, and Spearman correlation with 95% confidence interval will be used. A p-value of < 0.05 or 0.001 will be regarded as significant.

FLOWCHART OF METHODOLOGY

REVIEW OF LITERATURE

Zeng et al., 2017^[3] in a study aimed to assess the systemic and analgesic effects of epidural dexmedetomidine in thoracic epidural anaesthesia (TEA) combined with total intravenous anaesthesia during thoracic surgery. Seventy-one patients undergoing open thoracotomy were included in this study and randomly divided into three groups: Control group (Group C): patients received TEA with levobupivacaine alone and were intravenously infused with saline; Epidural group (Group E): patients received TEA with levobupivacaine and dexmedetomidine, and were intravenously infused with saline; Intravenous group (group V): patients received TEA with levobupivacaine alone and were intravenously infused with dexmedetomidine. The doses of propofol used in the induction and maintenance of general anaesthesia, cardiovascular response, dose and first time of postoperative analgesia and verbal rating scale were recorded. The induction and maintenance were significantly lower in the Groups E and V. Verbal rating scale and postoperative analgesic requirements were significantly lower in Group E than in Groups C and V. Patients in Group C had more severe cardiovascular responses, as compared with Groups E and V. Epidural administration of dexmedetomidine reduced the induction and maintenance of propofol, and inhibited the cardiovascular response after intubation and extubation. Moreover, epidural dexmedetomidine provided better analgesia after open thoracotomy.

Diab Fuad Hetta et al, 2018 ^[4] were scheduled for major upper abdominal cancer surgery were allocated to groups and the cumulative morphine consumption, the time to first analgesic request, and the VAS pain score were evaluated. After the complete study they observed that the results were astonishing as the cumulative morphine consumption was significantly reduced in group bupivacaine + dexmedetomidine compared with group bupivacaine: mean ± SD of 10.40±5.16 mg vs 23.23±8.37 mg with an estimated difference (95% CI) of –12.83 (−16.43, –9.24), (P<0.001). The time to the first analgesic demand was significantly delayed in group bupivacaine + dexmedetomidine compared with group bupivacaine: median (IQR) of 6 (1.75, 8.25) h vs 1 (0, 4) h, (P<0.001). The mean collapsed over time of overall VAS pain scores at rest and movement was significantly reduced in group bupivacaine + dexmedetomidine compared with group bupivacaine : mean ± SE of 1.6±0.08 vs 2.38±0.08 with an estimated difference (95% CI) of −0.8 (−1, –0.86), (P<0.001), and mean ± SE of 2.17±0.07 vs 3.25±0.07 with an estimated difference (95% CI) of −1.1 (−1.27, – 0.89), (P<0.001), respectively. Hence, they stated that the epidural infusion of dexmedetomidine added to bupivacaine for patients undergoing major abdominal cancer surgery significantly reduced morphine consumption, delayed time to first analgesic supplementation, and decreased pain intensity during the first 48 hours postoperatively without harmful derangement on hemodynamics.

Ayman Abdelmaksoud Yousef et al, 2015 ^[5] performed a study with 80 healthy women at term that were randomly assigned into two groups: a control group (n = 40; “Bup/Fen group”) received combined spinal–epidural anesthesia with intrathecal hyperbaric bupivacaine 5 mg and an epidural mixture of 10 mL plain bupivacaine 0.25 % and fentanyl 50 μg, whereas the study group (n = 40; “Dex/Bup/Fen group”) received 1 mL epidural dexmedetomidine 0.5 μg/ kg in addition. And observed that there was no statistically significant difference between the groups regarding block characteristics. Significantly less intraoperative and postoperative fentanyl were required by the Dex/Bup/Fen group (P = 0.015 and P = 0.0011, respectively). There was no statistically significant difference between the groups regarding sedation score or the incidences of hypotension, nausea and vomiting, dizziness, and pruritus. Hence, they concluded that, addition of mini-dose epidural dexmedetomidine 0.5 μg/kg as a single injection to bupivacaine fentanyl in women undergoing elective cesarean section with combined spinal–epidural anesthesia improved intraoperative conditions and the quality of postoperative analgesia.

Hetta et al., 2017^[6] in a randomized, double-blind study aimed to evaluate the effect of adding dexmedetomidine (DEX) to bupivacaine on the quality of spermatic cord block anesthesia and postoperative analgesia. Patients were divided into two groups: group B received 10 mL of bupivacaine 0.25% for spermatic cord block and intravenous 50 µg of DEX and group BD received 10 mL of bupivacaine 0.25% added to 50 µg of DEX (9.5 mL bupivacaine 0. 25% + 0.5 mL [50 µg] DEX) for spermatic cord block, and for masking purposes, the patients received isotonic saline intravenously. They observed that time to first rescue analgesic was significantly delayed in group BD in comparison with group B, median (interquartile) range, 7 (6-12) hours versus 6 (5-7) hours, (p=0.000), the mean cumulative morphine consumption (mg) in the first postoperative 24 hours was significantly lower in group BD compared with group B, 8.13±4.45 versus 12.7±3.79, with a mean difference (95% CI) of -4.57 (-6.06 to -3.07) (p=0.000); also, there was a significant reduction of VAS pain score in group BD in comparison with group B at all measured time points, VAS 2 hours (1.28±0.9 vs 1.92±0.8), VAS 6 hours (2.62±1.5 vs 3.93±1.2), VAS 12 hours (2.40±1.1 vs 3.57±0.65), VAS 24 hours (1.90±0.68 vs 2.53±0.62) (p=0.000).  they concluded that addition of 50 µg of DEX to bupivacaine 0.25% in spermatic cord block for intrascrotal surgeries resulted in delay of first analgesic supplementation, reduction of postoperative analgesic consumption as well as improvement of the success rate of the block.

Kiran et al., 2018,^[7] in a study divided the patients undergoing infraumbilical surgeries into three groups ‑ Group R (n = 25): received 18 ml of 0.5% ropivacaine for epidural anesthesia and 10 ml of 0.1% ropivacaine boluses for postoperative analgesia; Group RF (n = 25): received 18 ml of 0.5% ropivacaine with 20 μg fentanyl for epidural anesthesia and 10 ml of 0.1% ropivacaine with 10 μg fentanyl boluses for postoperative analgesia; and Group RD (n = 25): received 18 ml of 0.5% ropivacaine with 10 μg dexmedetomidine for epidural anesthesia and 10 ml of 0.1% ropivacaine with 5 μg dexmedetomidine boluses for postoperative analgesia. They observed the  mean  time  for  onset  of  sensory  block,  in  minutes,  was  18.6  ±  4.4  in  R  Group,  12.8  ±  1.8  in  RF  Group  and  10.8 ± 2.7 in RD Group (P < 0.001). There was a statistically significant difference with regard to degree of motor block, with RD Group faring better than RF Group and R Group. The mean time to rescue analgesia, in minutes, was 139.8 ± 21.4 in Group R, 243 ± 29.7 in Group RF, and 312.4 ± 30.2 in Group RD (P <   0.001). Incidence of hypotension at 10 min was 4% and 48% in RF and RD Groups, respectively (P < 0.001). They concluded that Epidural anesthesia achieved with 10 μg dexmedetomidine as an additive to 0.5% ropivacaine is more effective with respect to duration and intensity of analgesia when compared to 0.5% ropivacaine alone or addition of 20 μg fentanyl to 0.5% ropivacaine

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