Effect of Two drugs infusion for postoperative analgesia in patients undergoing upper abdominal surgeries

Not yet recruiting

• Conditions: Other specified diseases of the digestive system,

• Registration Number: CTRI/2022/07/043764
• Lead Sponsor: Department of Anaesthesiology

Brief Summary

**EFFECTOF EPIDURAL DEXMEDETOMIDINE AND FENTANYL INFUSION FOR POSTOPERATIVE ANALGESIA IN PATIENTS UNDERGOING UPPERABDOMINAL SURGERIES: A RANDOMISED DOUBLE BLIND STUDY**

**INTRODUCTION**

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

Hence, the effective relief of pain is of the utmostimportance to anyone treating patients undergoing surgery. Pain relief hassignificant physiological benefits; hence, monitoring of pain relief isincreasingly becoming an important postoperative quality measure. The goal forpostoperative pain management is to reduce or eliminate pain and discomfortwith a minimum of side effects. Various agents (opioid vs. nonopioid), routes(oral, intravenous, neuraxial, regional) and modes (patient controlled vs. “asneededâ€) for the treatment of postoperative pain exist. Although traditionallythe mainstay of postoperative analgesia is opioid based, increasingly moreevidence exists to support a multimodal approach with the intent to reduceopioid side effects (such as nausea and ileus) and improve pain scores.Enhanced recovery protocols to reduce length of stay in colorectal surgery arebecoming more prevalent and include multimodal opioid sparing regimens as acritical component. Familiarity with the efficacy of available agents androutes of administration is important to tailor the postoperative regimen tothe needs of the individual patient. [2]

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

In astudy conducted by Zeng et al.,[3] comparing epiduraldexmedetomidine infusion and fentanyl infusion after colonic resection surgeryobserved that epidural morphine group has higher incidence of nausea, vomitingand pruritus in comparison to epidural dexmedetomidine infusion inpostoperative period with comparable pain scores nut with early recovery ofgastrointestinal motility in dexmedetomidine group after colonic resection.

Zeng Xet al., (2017)[3]; Hetta DF et al., (2018)[4]; Yousef AAet al., (2015)[5]; Hetta DF et al., (2017)[6]; Kiran S etal. (2018)[7] found that epidural dexmedetomidine decreasepostoperative VAS score and reduce requirement of rescue analagesia.

HettaDF et al.,[4] compared bupivacaine with bupivacaine + dexmedetomidinein epidural infusion in major abdominal cancer surgery and observed thatdexmedetomidine added to bupivacaine significantly reduced morphineconsumption, delayed time to first analgesic supplementation, and decreasedpain intensity during the first 48 hours postoperatively without harmfulderangement on hemodynamics.

So inthis study we will compare the effectiveness of  dexmedetomidineand fentanyl infusion for postoperative analgesia in patients undergoing upperabdominal surgeries.

**AIMS AND OBJECTIVES**

**AIM**

§  Tocompare the effectiveness of epidural dexmedetomidine and fentanylinfusion  postoperatively in patientsundergoing upper abdominal surgeries

**OBJECTIVES**

**PrimaryObjective:**

§  Tocompare the postoperative pain using VAS score during rest and movement atdifferent time postoperatively

**SecondaryObjective:**

§  Toassess rescue analgesia, sedation score, intraoperative and postoperativehemodynamics, bowel recovery time, nausea and vomiting.

 **METHODOLOGY**

§  **StudySettings:** The study will be conducted in theoperation theatre and post-operative care units of different departments of theUniversity under the guidance of Department of Anesthesiology, King George’s MedicalUniversity, Lucknow.

 Â§  **Studydesign:** Randomised double blinded comparativestudy.

 Â§  **Studyduration:** 1 Year

 Â§  **Samplesize**: 68

**Samplesize Calculation:**

  **The sample sizeformulae used are as follows: (Bernard, 5th edition)[8]**

| |

| --- |

|

n=

 n=  Sample size

σ = Standard Deviation

∆ = Difference of means

κ= Ratio

Z1-α/2= Twosided Z value

Z1-β= Power

    

| | | | | | |

| --- | --- | --- | --- | --- | --- |

|**Confidence Interval (2-sided)**

**95%**

|**Power**

90%

|

|**VAS at Rest at 48hrs min (****Hetta et al., 2018)[4]**

**Dexmedetomidine Group**

**Control Group**

**Difference\***

|Mean

0.77

1.3

-0.53

|Standard deviation

0.57

0.75

|Variance

0.324

0.562

|

---

|**Total sample size**

**68**

|

---

  â€¢      **Ethicalapproval**: It will be taken from theInstitutional Ethics Committee of the University.

                                                                          **Inclusion Criteria:**

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

 **Exclusion criteria:**

§  Ageless than 18 year or more than 65 year.

§  Patientswith treatment of α-adrenergic antagonists.

§  Historyof arrhythmias, contraindications to placement of an epidural catheter (eg,coagulopathy, local infection, and vertebral anomalies), patients known to beallergic to bupivacaine, dexmedetomidine, or morphine, and patients treatedwith regular chronic pain medications.

§  Nonwilling patents.

  **STUDYPROTOCOL**

Ethical clearance andInformed consent will be taken.

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

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

 

| | |

| --- | --- |

|**Group-F**

**bupivacaine +  fentanyl**

(n=34)

Patients will received perioperative epidural analgesia with bupivacaine (0.1%) **+** fentanyl 2μg/ml for 24 hrs @6ml/hr

|**Group-D**

**bupivacaine + dexmedetomidine**

(n=34)

Patients will received perioperative epidural analgesia with bupivacaine (0.1%) and + dexmedetomidine 0.5 μg/ml @ 6ml/hr

 After intravenous infusion of 1 L of normalsaline, the patients will be placed in the sitting position. Under a strictaseptic precaution, thoracic spines from seven to ten will be identified (theinferior angle of the scapula is corresponding to the seventh thoracicvertebra). The preferred insertion site will be T8–T9 as per standard protocol.All patients will receive general anesthesia as per standard protocol. Observerand patients will be blind of study drug.

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

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

**Monitoring:**

Intraoperative andPostoperative haemodynamic.

Postoperative VAS score(static and dynamic).

Sedation Score.

Bowel recovery time.

Requirment of rescueanalgesia.

Side effect: Nausea,Vomiting, Hypotension, Bradycardia.

**Statistical Analysis**:Data will be entered in Microsoft Excel and analyzed using statistical softwareSPSS 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 variableswill be evaluated by mean (standard deviation) or range value when required.The dichotomous variables will be presented in number/frequency and will beanalyzed using Chi-square or Fisher Extract test. For comparison of the meansbetween the two groups, analysis by Student t-test, Mann-Whitney U test, andSpearman 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**

**Zenget al., 2017[3]** in a study aimedto assess the systemic and analgesiceffects of epidural dexmedetomidine in thoracic epidural anaesthesia (TEA)combined with total intravenous anaesthesia during thoracic surgery. Seventy-onepatients undergoing open thoracotomy were included in this study and randomlydivided into three groups: Control group (Group C): patients received TEA withlevobupivacaine alone and were intravenously infused with saline; Epiduralgroup (Group E): patients received TEA with levobupivacaine anddexmedetomidine, and were intravenously infused with saline; Intravenous group(group V): patients received TEA with levobupivacaine alone and wereintravenously infused with dexmedetomidine. The doses of propofol used in theinduction and maintenance of general anaesthesia, cardiovascular response, doseand first time of postoperative analgesia and verbal rating scale wererecorded. The induction and maintenance were significantly lower in the GroupsE and V. Verbal rating scale and postoperative analgesic requirements weresignificantly lower in Group E than in Groups C and V. Patients in Group C hadmore severe cardiovascular responses, as compared with Groups E and V. Epiduraladministration of dexmedetomidine reduced the induction and maintenance ofpropofol, and inhibited the cardiovascular response after intubation andextubation. Moreover, epidural dexmedetomidine provided better analgesia afteropen thoracotomy.

**Diab Fuad Hetta et al, 2018 [4]**were scheduled for major upper abdominal cancer surgery were allocated togroups and the cumulative morphine consumption, the time to first analgesicrequest, and the VAS pain score were evaluated. After the complete study theyobserved that the results were astonishing as the cumulative morphineconsumption was significantly reduced in group bupivacaine + dexmedetomidinecompared with group bupivacaine: mean ± SD of 10.40±5.16 mg vs 23.23±8.37 mgwith 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 groupbupivacaine + dexmedetomidine compared with group bupivacaine: median (IQR) of6 (1.75, 8.25) h vs 1 (0, 4) h, (P<0.001). The mean collapsed over time ofoverall VAS pain scores at rest and movement was significantly reduced in groupbupivacaine + dexmedetomidine compared with group bupivacaine : mean ± SE of1.6±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 estimateddifference (95% CI) of −1.1 (−1.27, – 0.89), (P<0.001), respectively. Hence,they stated that the epidural infusion of dexmedetomidine added to bupivacainefor patients undergoing major abdominal cancer surgery significantly reducedmorphine consumption, delayed time to first analgesic supplementation, anddecreased pain intensity during the first 48 hours postoperatively withoutharmful derangement on hemodynamics.

 **Ayman Abdelmaksoud Yousef et al, 2015 [5]**performed a study with 80 healthy women at term that were randomly assignedinto two groups: a control group (n = 40; “Bup/Fen groupâ€) received combinedspinal–epidural anesthesia with intrathecal hyperbaric bupivacaine 5 mg and anepidural mixture of 10 mL plain bupivacaine 0.25 % and fentanyl 50 μg, whereasthe study group (n = 40; “Dex/Bup/Fen groupâ€) received 1 mL epiduraldexmedetomidine 0.5 μg/ kg in addition. And observed that there was nostatistically significant difference between the groups regarding blockcharacteristics. Significantly less intraoperative and postoperative fentanylwere required by the Dex/Bup/Fen group (P = 0.015 and P = 0.0011,respectively). There was no statistically significant difference between thegroups regarding sedation score or the incidences of hypotension, nausea andvomiting, dizziness, and pruritus. Hence, they concluded that, addition ofmini-dose epidural dexmedetomidine 0.5 μg/kg as a single injection tobupivacaine fentanyl in women undergoing elective cesarean section withcombined spinal–epidural anesthesia improved intraoperative conditions and thequality of postoperative analgesia.

     **Hetta et al., 2017[6] in** a randomized, double-blind study aimed to evaluate the effect ofadding dexmedetomidine (DEX) to bupivacaine on the quality of spermatic cordblock anesthesia and postoperative analgesia. Patients were divided into twogroups: group B received 10 mL of bupivacaine 0.25% for spermatic cord blockand 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) forspermatic cord block, and for masking purposes, the patients received isotonicsaline intravenously. They observed that time to first rescue analgesic wassignificantly 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 24hours was significantly lower in group BD compared with group B, 8.13±4.45versus 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 incomparison with group B at all measured time points, VAS 2 hours (1.28±0.9 vs1.92±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 DEXto bupivacaine 0.25% in spermatic cord block for intrascrotal surgeriesresulted in delay of first analgesic supplementation, reduction ofpostoperative analgesic consumption as well as improvement of the success rateof the block.

 **Kiranet al., 2018,[7]** in a study divided thepatients undergoing infraumbilical surgeries into three groups ‑ Group R (n =25): received 18 ml of 0.5% ropivacaine for epidural anesthesia and 10 ml of0.1% ropivacaine boluses for postoperative analgesia; Group RF (n = 25):received 18 ml of 0.5% ropivacaine with 20 μg fentanyl for epidural anesthesiaand 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 μgdexmedetomidine for epidural anesthesia and 10 ml of 0.1% ropivacaine with 5 μgdexmedetomidine 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 todegree 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 minwas 4% and 48% in RF and RD Groups, respectively (P < 0.001). They concludedthat Epidural anesthesia achieved with 10 μg dexmedetomidine as an additive to0.5% ropivacaine is more effective with respect to duration and intensity ofanalgesia when compared to 0.5% ropivacaine alone or addition of 20 μg fentanylto 0.5% ropivacaine

             REFERENCES

 1.      VelnarT, Bailey T, Smrkolj V. The wound healing process: an overview of the cellularand molecular mechanisms. Journal of International Medical Research. 2009Oct;37(5):1528-42.

2.     Garimella V, Cellini C. Postoperative pain control.Clinics in colon and rectal surgery. 2013 Sep;26(3):191.

3.     Zeng X, Jiang J, Yang L,Ding W. Epidural dexmedetomidine reduces the requirement of propofol duringtotal intravenous anaesthesia and improves analgesia after surgery in patientsundergoing open thoracic surgery. Scientific reports. 2017 Jun 21;7(1):1-9.

4.     Hetta DF, Fares KM,Abedalmohsen AM, Abdel-Wahab AH, Elfadl GM, Ali WN. Epidural dexmedetomidineinfusion for perioperative analgesia in patients undergoing abdominal cancersurgery: randomized trial. Journal of pain research. 2018;11:2675.

5.     Yousef AA, Salem HA, Moustafa MZ. Effect of mini-dose epiduraldexmedetomidine in elective cesarean section using combined spinal–epiduralanesthesia: a randomized double-blinded controlled study. Journal ofanesthesia. 2015 Oct 1;29(5):708-14.

6.      Hetta DF, Kamal EE, Mahran AM, Ahmed DG,Elawamy A, Abdelraouf AM. Efficacy of local dexmedetomidine add-on forspermatic cord block anesthesia in patients undergoing intrascrotal surgeries:randomized controlled multicenter clinical trial. J Pain Res. 2017 Nov8;10:2621-2628. doi: 10.2147/JPR.S145305. PMID: 29184438; PMCID: PMC5687449.

7.      KiranS, Jinjil K, Tandon U, Kar S. Evaluation of dexmedetomidine and fentanyl asadditives to ropivacaine for epidural anesthesia and postoperative analgesia. JAnaesthesiol Clin Pharmacol 2018;34:41-5

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9.      SekharDP, Kumar L, Kesavan R, Purushottaman S, Mohammed ZU, Rajan S. Comparison ofthe analgesic efficacy of a single dose of epidural dexmedetomidine versusfentanyl as an adjuvant to bupivacaine in abdominal surgery. Anesth Essays Res2019;13:465-70.

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2022-05-07
• Study Start: 2022-07-15

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 68

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 & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
different time postoperatively	4 weeks
To compare the postoperative pain using VAS score during rest and movement at	4 weeks

Secondary Outcome Measures

Name	Time	Method
To assess rescue analgesia, sedation score, intraoperative and postoperative	hemodynamics, bowel recovery time, nausea and vomiting

Trial Locations

Locations (1)

Department of Anaesthesiology; 🇮🇳 Lucknow, UTTAR PRADESH, India

Department of Anaesthesiology

🇮🇳Lucknow, UTTAR PRADESH, India

Dr Reetu Verma

Principal investigator

9473641975

reetuverma1998@gmail.com