Effect of dexamethasone on analgesic efficacy of transverse abdominis plane block in laparoscopic gynecological procedures: A prospective randomized clinical study.

BACKGROUND AND AIMS: Dexamethasone has been increasingly used as an adjuvant to local anesthetics in peripheral nerve blocks with various studies showing an opioid sparing the effect of intravenous (IV) dexamethasone as well in a multimodal analgesia technique. It is not clear whether this effect of dexamethasone is because of its peripheral action or because of its systemic absorption. In our study, we compared the effectiveness of dexamethasone on duration of analgesia when used as an adjuvant with local anesthetic in transverse abdominis plane block (TAP) versus when given systemically by IV route along with block only, in patients undergoing laparoscopic gynecological procedures under general anesthesia (GA).
MATERIAL AND METHODS: This is a prospective, randomized, parallel treatment, double-blinded study. The primary outcome of our study was the time to administration of first rescue analgesia. Forty patients were randomly assigned to perineural (PN) and IV Group using a computer-generated random numbers table and allocated using sealed opaque envelopes technique. After induction of GA, PN group received ultrasound guided TAP block with 15 ml of 0.25% levobupivacaine plus 4 mg (1 ml) dexamethasone on each side. Patients in IV group received TAP block on both sides with 15 ml of 0.25% levobupivacaine and 8 mg IV dexamethasone.
RESULTS: Time to request for first rescue analgesia was 6.63 ± 1.5 h in PN group and 5.04 ± 1.7 h in IV group. Pain scores were comparable in both the groups.
CONCLUSION: Dexamethasone administered in either of the routes has comparative effect on quality of analgesia of TAP block with 0.25% levobupivacaine.

Introduction

Although laparoscopic surgery is a minimally invasive procedure, acute surgical pain is common especially in the first postoperative day.[1] Postoperative pain following laparoscopic surgeries is of multifocal origin, with both parietal and visceral components, however, several studies have proven the opioid sparing effect with transverse abdominis plane (TAP) block in laparoscopic surgeries.[2]

Dexamethasone has shown to prolong the analgesia time when used as an adjuvant to local anesthetics (LA) in peripheral nerve blocks.[34] A number of studies have also shown an opioid sparing effect of steroids, when used intravenously perioperatively.[5] Hence, it is not known whether the effect of perineural (PN) administered dexamethasone is because of its peripheral action or because of its systemic absorption. We hypothesized that analgesic efficacy of intravenous (IV) dexamethasone would be equivalent to its PN administration, when added as an adjuvant with TAP block given to treat pain after laparoscopic gynecological procedures in a multimodal analgesic technique. The primary outcome of our study was the time to request of first rescue analgesic. Secondary outcome measures were the total amount of rescue analgesic required in 1st 24 h postoperatively, the pain scores assessed by visual analogue score (VAS), incidence of nausea, and vomiting.

Material and Methods

This prospective, randomized, parallel treatment, double-blinded study was carried out at a tertiary care teaching hospital between 1st July 2014 and 30th June 2015. It was conducted after approval by the hospital ethical committee (NK/1607/MD/10089-90) and patient's written informed consent. Women with infertility of American society of anesthesiologists (ASA) physical status 1 or 2 undergoing laparoscopic gynecological procedures under general anesthesia (GA) were included in the study. Those with local infection at the site of injection, morbid obesity (body mass index >35 kg/m2), allergy to LA, patient refusal, severe respiratory or cardiac disorders, pre-existing neurological deficits, liver or renal insufficiency, pre-existing diabetics, patient on steroid treatment for any reason, perioperative use of steroids were excluded from the study.

Laparoscopic gynecological procedures were done on outpatient basis. Patients were educated about reporting of pain on the 11-point VAS, where 0 = no pain and 10 = worst imaginable pain in the pre-anesthesia check-up clinics. All the patients were kept fasting overnight (8 h for solids and 2 h for clear liquids). Forty patients were randomly assigned to one of either 2 groups (Group PN and Group IV) using a computer-generated random numbers table. The group allocation was concealed using sealed opaque envelopes technique. The patient, anesthesiologist performing the blocks, intraoperative anesthesiologists, surgeons, nurses, and data collecting person were blinded to the group allocation.

After induction of GA, patients in Group PN received ultrasound guided TAP block with 15 ml of 0.25% levobupivacaine (Levo Anawin, Neon Laboratories Limited, India) plus 4 mg (1 ml) PN dexamethasone (preservative methyl and phenyl paraben, decoin, Biocare, India) on either side and 2 ml of normal saline IV. Patients in Group IV received TAP block with 15 ml of 0.25% levobupivacaine plus 1 ml of normal saline on each side and 8 mg (2 ml) dexamethasone IV.

Study drugs were prepared by an independent anesthesiologist who was not involved in administrating the drug and in the postoperative follow-up of the patients. A second anesthesiologist blinded to the study drug preparation, administered the drug, and followed the patients postoperatively.

Standardized balanced anesthesia technique with muscle relaxation and endotracheal intubation was used in both the groups. GA was maintained with isoflurane and nitrous oxide in O2 with target Minimum alveolar concentration (MAC) of 1–1.3. Heart rate (HR) and non-invasive blood pressure were maintained within 20% of the baseline. Surgical procedure was done in 30 to 45 degree trendelenburg position. Carboperitonium was achieved, and intra-abdominal pressure was maintained between 10 to 12 mmHg. In addition, 20 min before the completion of the surgery IV ondansetron 0.1 mg/kg and IV diclofenac 75 mg were given. At the end of the surgery, residual neuromuscular blockade was reversed with IV neostigmine 50 mic/kg and IV glycopyrolate 10 mic/kg, and patients were extubated after return of spontaneous respiration and consciousness.

TAP block was performed with linear probe (7–12 Hz) with Sonosite Turbo (Washington, USA) ultrasound machine. Ultrasonographic probe was applied transversely at the midpoint between the costal margin and the iliac crest on the mid-axillary line. Using an in plane technique and after identification of the plane between the internal oblique and transverse abdominis muscle block was performed with a 23G spinal needle (Quincke, USA).

In the post-anesthesia care unit (PACU), patients were monitored for BP, HR, and VAS score for pain during rest and cough, severity of nausea and vomiting [Annexure 1] every 15 min for 1 h and at 2 h, 4 h, and 6 h. Rescue analgesic IV tramadol 2 mg/kg was administered when VAS was >3 for initial 6 post-operative hours.[6] Patients were discharged from the PACU after 6 h, with advice to take oral paracetamol 500 mg as and when VAS >3 was observed by the patient. They were contacted over phone at 24 h to enquire about pain scores and paracetamol consumption. Time to first rescue analgesia and the 24 h analgesic consumption were recorded. Any incidence of nausea, vomiting, and complications associated with the procedure such as LA toxicity, hyperglycemias, and infection were recorded.

0	No nausea or vomiting
1	Nausea present no vomiting
2	Vomiting with or without nausea
(Self-made)

Statistical analysis

The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 20.0 for Windows).

The addition of dexamethasone irrespective of route of administration causes prolongation of duration of analgesia of TAP block. If there is truly no difference between the PN and IV dexamethasone treatment, then 36 patients are required to be 90% sure that the limits of a two-sided 90% confidence interval will exclude a difference in means of more than 100 min in the treatment parallel design study (assuming the SD of 90 min). (https://www.sealedenvelope.com/power/continuous-equivalence/) Keeping in view the loss to follow-up of cases, 40 patients were enrolled in the study, and 20 patients were recruited in each group.

The variables were checked for normality with Kolmogorov-Smirnov test. Parametric data including age, weight, duration of surgery, intraoperative fentanyl, intraoperative propofol, time to first rescue analgesia (h), total number of times analgesic administered (Paracetamol(PCM) + Tramadol), total number of times (PCM) administered, and PCM consumption (g) were depicted as mean and standard deviation and compared using independent student's t test. Non-parametric data including the VAS scores were depicted as median and range and were compared using Mann-Whitney U test. The Chi-square test was used to compare the incidence of complications between the two groups. The value P < 0.05 was taken as statistically significant.

Results

Out of 40 enrolled patients who underwent laparoscopic gynecological procedures under GA, 36 patients were analyzed. The demographic characteristics and intraoperative data were comparable in both groups. The patients in both the groups had similar requirement of fentanyl [Table 1]. A statistically significant (P < 0.05) difference was observed in the time to request for first rescue analgesic, with the time being 6.632 ± 1.5 h in PN Group and 5.04 ± 1.7 h in IV Group. Paracetamol consumption in the first 24 h postoperative hours was less in PN Group as compared to IV Group (0.736 ± 0.25 vs. 0.964 ± 0.133), with the difference being statistically significant, P < 0.05 [Table 2].

Table 1

Patient demographics and intraoperative data

Variables	PN Group (n=19)	IV Group (n=17)
Age (Years)	28.63±3.18	27.71±3.74
Weight (Kg)	52.89±3.14	56.24±5.96
ASA status (I/II)	20/0	16/1
Diagnosis infertility (Primary:Secondary)	16:3	11:6
Duration of surgery (min)	79.21±15.02	90.59±27.49
Intraoperative fentanyl (µg)	102±6	110±10
Intraoperative propofol (mg)	92±16	91±11

Values are expressed as mean±SD, ratio, and absolute numbers. ASA=American society of anaesthesiologists, PN=Perineural, IV=Intravenous

Table 2

Postoperative analgesic consumption

Rescue analgesic requirement	PN Group (n=19)	IV Group (n=17)	P
Time to first rescue analgesia (h)	6.63±1.75	5.05±1.07	0.006
Total number of times analgesic administered (PCM + Tramadol)	1.63±0.49	1.94±0.24	0.026
Total number of times (PCM) administered	1.47±0.512	1.92±0.26	0.03
Number of patients requiring tramadol	0/19	3/17	0.00
PCM consumption (g)	0.736±0.25	0.964±0.133	0.03

PCM=paracetamol, PN=Perineural, IV=Intravenous. Values are expressed as mean±SD, ratio, and analyzed using independent t-test

There was no statistically significant difference in VAS score at rest among the two groups at all the points except at 12 h (P < 0.05), where the mean VAS score of PN Group was lesser than IV Group [Table 3]. There was no statistically significant difference in VAS score with cough among the two groups at all the points of time except at 4 and 12 h (P < 0.05), where the mean VAS score of PN Group was lesser than IV Group [Table 4]. At most of the time points in 24 h postoperatively, the median VAS score was <3 on rest and cough. None of the patients in either of the groups had nausea or vomiting.

Table 3

VAS score at rest

Time	PN Group (n=19)	IV Group (n=17)	P
0 min	0,0-0	0,0-0	-
15 min	0,0-0	0,0-1	0.505
30 min	0,0-1	1,0-2	0.129
45 min	0,1-1	1,0-2	0.08
60 min	0,0-2	1,0-2	0.09
120 min	1, 0-2	2,1-3	0.08
240 min	1,1-2	2,2-5	0.02
360 min	2,1-3	2,1-3	0.235
480 min	2,1-3	2,1-3	0.316
720 min	2,1-3	2,2-3	0.047
1440 min	3,1-4	2,1-3	0.264

Values are expressed as median and range and analyzed using Mann-Whitney U test, statistically significant P<0.05, VAS=Visual analogue scale, PN=Perineural, IV=Intravenous

Table 4

VAS score on coughing

Time	PN Group (n=19)	IV Group (n=17)	P
0 min	0,0	0,0-1	-
15 min	0,0-1	0,0-2	0.505
30 min	0,0-1	1,0-3	0.129
45 min	1,0-3	2,0-3	0.08
60 min	2,1-3	2,1-3	0.09
120 min	2,2-3	3,2-3	0.08
240 min	3,2-4	3,3-6	0.02
360 min	3,2-4	2,1-4	0.235
480 min	3,2-4	3,2-4	0.316
720 min	3,2-5	3,1-4	0.047
1440 min	4,1-5	3,2-4	0.264

Values are expressed as median and range and analyzed using Mann-Whitney U test, statistically significant P<0.05. VAS=Visual analogue scale, PN=Perineural, IV=Intravenous

Discussion

A number of previous studies have shown that single bolus injection of LA in TAP block can provide pain relief for about 3–4 h irrespective of the LA used.[789] In comparison to these studies, our study shows that the addition of dexamethasone in any form, IV or PN, causes prolongation of duration of analgesia. In another study by Kawahara et al., the authors studied the analgesic efficacy of ultrasound-guided TAP block after gynecologic laparoscopic surgery and found a significant reduction of tramadol consumption in the 0–6 h postoperative time period, specifying that the TAP block was possibly most effective for early postoperative pain.[10] In our study, we found that there was a statistically significant prolongation in the time to first request for rescue analgesic in PN Group (6.632 ± 1.5 h) as compared to the IV Group (5.04 ± 1.7 h) with the total rescue analgesic consumption also being less in the PN Group. Postoperative VAS pain scores at rest and on cough were <3 in both the groups most of the times in the first 24 h. Although mean difference in time to first rescue analgesic and paracetamol consumption looks clinically insignificant, low VAS scores seem to have clinical significance in a day care patient population who become home ready within 6 h.

Dexamethasone, a commonly used adjuvant, is known to extend the analgesia time when added to LA for different blocks. In a meta-analysis of randomized controlled trials on effects of combination of dexamethasone with local anesthetic solution for peripheral nerve (brachial plexus) blocks showed that it prolongs the block duration.[11] Parrington et al. observed that the addition of dexamethasone to 30 ml of 1.5% mepivacaine in a supraclavicular brachial plexus block prolonged the duration of analgesia [104 min (1.6 h)].[3] Cummings and colleagues observed a 1.9-fold and 1.5-fold increase in the duration of analgesia in interscalene block when dexamethasone (8 mg) was added to ropivacaine (30 ml, 0.5%) and bupivacaine (30 ml, 0.5%).[12] Akkaya et al. studied the effect of addition of dexamethasone (16 mg) to levo-bupivacaine (30 ml 0.25%) and compared it to control of TAP block with LA alone in patients undergoing lower segment caesarean section. The time before the administration of the first additional analgesic dose was prolonged, and pain scores and total consumption of tramadol were significantly lower in the dexamethasone group (13 h) compared to the levobupivacaine group (6).[13] Compared to our study, duration of analgesia was prolonged in this study in both PN and control group. This could be because Akkaya et al. administered TAP block at the end of surgery, whereas we had given the block after induction of GA. Further, as compared to our study, Akkaya et al. used higher volume of LA (30 ml vs. 60 ml) and higher dose of dexamethasone (8 mg vs. 16 mg). To the best of knowledge of authors, this is the first study comparing the additive effect of dexamethasone administration by various routes along with TAP block. In our study, dexamethasone did not seem to significantly prolong the analgesia time, independent of mode of administration, but it improved the quality of analgesia as depicted by the VAS in the first 24 h which is <3.

It is well-known that IV dexamethasone in an intermediate dose of 0.1–0.21 mg/kg has an opioid sparing effect when added to a multimodal regimen.[5141516] Similarly, we also used an intermediate dose of dexamethasone (8 mg) in our study.

In a single-injection peripheral nerve block (interscalene, supraclavicular, and ankle) with long-acting LA, the effectiveness of IV dexamethasone in prolonging the duration of analgesia is similar to PN dexamethasone.[171819]

The precise mechanism of action of dexamethasone added to LA is unknown. Some studies have described a direct effect of glucocorticoids on nerve conduction, whereas others have reported that dexamethasone leads to PN vasoconstriction with concomitant slower absorption of the administered LA.

In our study, we administered dexamethasone (8 mg) in either route after induction of GA. The nausea and vomiting were nil in both the groups. This could be because of less opioid consumption as well as because of the well-known antiemetic effect of dexamethasone.[2021]

Limitations

We did not have a control group of TAP block with levobupivacaine alone. All our participants being outpatients were discharged from hospital after 6 h of surgery as per our hospital protocol. The patients were contacted telephonically to know about pain scores and analgesic consumption. Thus, another limitation of our study could be recall bias with regard to VAS score and analgesic consumption. Our study was limited to first 24 h postoperatively; hence, we could not observe their prolonged effect as suggested by other studies.[12]

Conclusion

The administration of dexamethasone in either route PN or IV in patients receiving bilateral TAP block with levobupivacaine improves the quality of analgesia in patients undergoing laparoscopic gynecological surgeries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical committee approval

Chairperson Name: Dr. NanditaKakkar

Institute: Postgraduate Institute of Medical Education and Research, Chandigarh.

Ethical approval number: (NK/1607/MD/10089-90).