The Effect of Intravenous Dexamethasone on Intraoperative and Early Postoperative Pain in Lumbar Spine Surgery: A Randomized Double-Blind Placebo-Controlled Study

Abstract

Background:

The surgical procedures of spine are generally associated with intense pain in the postoperative period. Opioids are commonly used for perioperative analgesia but are associated with many side effects. Co-analgesic drugs are used to decrease these side effects. One such supplemental drug is dexamethasone. Its strong anti-inflammatory effect contributes to perioperative analgesia.

Aim:

This study was done to evaluate the effect of intravenous (i.v.) dexamethasone on intraoperative and early postoperative pain in lumbar spine surgery.

Settings and Design:

This was a hospital-based randomized, double-blind, placebo-controlled study, done between June 2016 and December 2016 after permission of institutional ethical committee.

Materials and Methods:

This Study was conducted on 60 patients undergoing lumbar spine surgery, and randomization was done in two groups. Group A (study) received dexamethasone 2 ml (8 mg) i.v. and Group B (control) received 2 ml normal saline. Anesthesia technique and rescue analgesia regimen were standardized. Intraoperative pain was assessed by hemodynamic variability and postoperative pain by verbal rating score. All the quantitative data were analyzed using Student's t-test and all the qualitative data using Chi-square test.

Results:

Heart rate in the control group was significantly higher than the study group during intraoperative period. Mean pain scores in the early postoperative period were significantly higher in control group than the study group (P < 0.001). Mean time of first rescue analgesic in the postoperative period was 149.17 min and 34.33 min in the study group and control group, respectively (P < 0.001).

Conclusion:

Hence, we conclude that administration of 8 mg of preoperative i.v dexamethasone was effective in reducing intraoperative and early postoperative pain in the lumbar spine surgery.

INTRODUCTION

The surgical procedures of the spine are generally associated with intense pain in the postoperative period. Adequate analgesia in the postoperative period is the key for improved outcome in terms of comfortable stay in hospital, early ambulation, and early discharge and for preventing the development of chronic pain. Multiple groups of analgesics are available for postoperative analgesia with their inherent advantages and disadvantages which restrict their universal applicability.[1] Therefore, multimodal analgesia has been suggested to mitigate pain and reduce side effects.

Glucocorticoids by their strong anti-inflammatory effect have shown to reduce pain in the postoperative period. Dexamethasone is a powerful anti-inflammatory drug with long half-life and may be useful in lowering postoperative pain when used as a part of multimodal analgesia.[2] Previous studies have investigated the potential analgesic effect of single perioperative intravenous (i.v.) dose of dexamethasone in many surgeries. Waldron et al. performed a systemic review to evaluate impact of a single i.v. dose of dexamethasone on postoperative pain and adverse events with this treatment. A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits. Doses of dexamethasone ranged from 1.25 to 20 mg, with 8 mg being the most commonly used dose.[3] We hypothesized that the simple and inexpensive use of preoperative dexamethasone at low dose would be effective in reducing pain after lumbar spine surgery. With this background, we planned to evaluate the effect of single i.v. dose of dexamethasone on intraoperative and early postoperative (6 h) pain in patients undergoing lumbar spine surgery.

MATERIALS AND METHODS

This hospital-based, prospective, randomized, double-blind, placebo-controlled study was conducted with due permission from the institutional ethics committee and research review board and with written informed consent. The sample size was calculated to be 25 subjects in each of the two group at α (alpha) error 0.05 and power 80% assuming detectable difference in the mean pain score to be 1.7 and standard deviation (SD) 2.1 as per the reference article.[4] Hence, for the study purpose, 30 subjects in each of the two groups of American Society of Anesthesiologists (ASA) Class I and II patients between the ages of 18 and 70 years undergoing lumbar spine surgery under general anesthesia were recruited. The exclusion criteria were history of taking steroids, anticipated difficult intubation, deaf and dumb patient, and duration of surgery >3 h. Group A received dexamethasone (8 mg) 2 mL i.v. and Group B received 2 mL normal saline i.v. The randomization was done by a computer-generated random number table, and the random numbers were kept in sequentially numbered opaque envelopes. Envelope was opened and the patient was allocated to one of the two groups (according to the random number table) before shifting inside the operation room. Anesthesiologist assessing the analgesic effect and patients were blinded to the allocated group. Each patient had a preanesthetic checkup. All patients were explained about the anesthetic technique and verbal rating scale (VRS) for pain, in which 0 means no pain and 10 means worst imaginable pain.[5] Each patient was kept overnight fasting. On arrival in the operation theater, standard monitoring devices including electrocardiogram, noninvasive blood pressure (BP), and pulse oximetry were attached. Baseline parameters (heart rate [HR], systolic BP [SBP], diastolic BP [DBP], and mean arterial pressure [MAP]) were also recorded. Two i.v lines were secured and Ringer lactate drip was started. The study drug was prepared in identical syringes of 2 mL for each group.

Randomized group allocation and study drug preparation in identical syringes were done by the person not involved in the study. Each patient was premedicated with glycopyrrolate 0.2 mg i.v. + midazolam 1 mg i.v. + fentanyl 1.5 mg/kg i.v. The study drug was administered according to group allocation. Any complaint of perineal pruritus was recorded. The patient was preoxygenated for 5 min before starting induction. Anesthesia was induced with propofol 2 mg/kg i.v. in both groups. Rocuronium 0.6 mg/kg i.v. was administered to facilitate endotracheal intubation. Intubation was done with cuffed endotracheal tube of appropriate size after direct laryngoscopy. Anesthesia was maintained with 50% N₂O in oxygen and 1–2.5% sevoflurane. Ventilation was volume controlled, tidal volume was kept between 8 and 10 ml/kg, and respiratory rate was set to achieve normocapnia (EtCO₂ 30–40 mmHg). Intraoperative monitoring included electrocardiography, noninvasive BP, pulse oximetry, and capnography. If hemodynamic variables (HR, BP) escalated above 20% of baseline value, bolus dose of fentanyl 30 μg i.v. was given. HR, SBP, DBP, and MAP were recorded at regular interval. Number of the patients who required additional dose of fentanyl was recorded. Reversal was done with neostigmine 2.5 mg i.v. + glycopyrrolate 0.5 mg i.v. only after onset of spontaneous respiration.

Extubation was done when fully satisfied with patient recovery according to the standard criteria.

Pain assessment was done by VRS score, in which 0 means no pain and 10 means worst imaginable pain.[5] VRS was taken 5 min after extubation (0 h). Then, the patient was shifted to recovery room. VRS reading was taken at 30 min, 1 h, 2 h, and 6 h postoperatively. Rescue analgesia with diclofenac sodium 75 mg i.m. was given if patient had VRS score of three or above. Time of first rescue analgesic in the postoperative period was noted.

Blood sugar was checked at 6 h and 24 h postoperatively for hyperglycemia.

Each patient was followed up for 7 days postoperatively for wound healing. If healing did not occur within 7 days, it was labeled as delayed wound healing.

Statistical analysis

All the data were entered into a Microsoft Excel Spread Sheet and were analyzed statistically using Primer software and XLstat (Addinsoft 40, rue Damrémont 75018 Paris, France). All the quantitative data were summarized in the form of mean ± SD. The difference between mean values of both groups was analyzed using Student's t-test. All the qualitative data (sex and ASA class) were summarized in the form of number and percentage. The differences between proportions were analyzed using Chi-square test. The levels of significance and α error were kept 95% and 5%, respectively, for all statistical analysis. P < 0.05 was considered significant and P > 0.05 as nonsignificant.

RESULTS

There were no dropouts, and all patients completed the study. The two groups were comparable for demographic data and baseline variables [Table 1]. No statistical difference was observed between ASA status and baseline hemodynamic variables. Average duration of surgery was also not significantly different between the two groups.

Table 1.

Demographic data and other baseline variables

Intraoperative pain was assessed on the basis of hemodynamic parameters. HR in the control group was significantly higher than study group during intraoperative period [Figure 1]. SBP, DBP, and mean arterial BP were comparable in two groups with statistically insignificant difference.

Figure 1.

Graph showing the trend of heart rate at different time intervals

Ten patients (33.33%) in Group A and 25 patients (83.33%) in Group B required rescue analgesic during intraoperative period. The difference was statistically significant (P < 0.001). VRS score for pain during postoperative first 2 h were significantly higher in the Group B than Group A, and the difference in mean VRS score was statistically significant (P < 0.001) up to 2 h. At 6 h, the difference between the two groups was statistically insignificant [Figure 2 and Table 2]. The mean time to first rescue analgesic in minutes and SD in Group A was 149.17 ± 113.09 and in Group B was 34 ± 33.08. The statistical analysis revealed significant difference between two groups (P < 0.001) [Figure 3, Table 3].

Figure 2.

Graph showing verbal rating scale score for pain in the postoperative period

Table 2.

Verbal rating scale score for pain in postoperative period

Figure 3.

Graph showing time of first rescue analgesic in postoperative period

Table 3.

Time of first rescue analgesic in postoperative period

Five patients in Group A and none of patients in Group B complained of perineal pruritus just after administration of the study drug. Blood sugar level was higher in Group A than Group B at 6h and 24 h, but difference was not statistically significant (P = 0.202 and P = 0.465). None of the patients had delayed wound healing in both the groups.

DISCUSSION

This study demonstrates that preoperative i.v administration of 8 mg dexamethasone significantly reduced intraoperative and postoperative pain and delayed the time to first analgesic dose in the postoperative period. A number of recent studies have investigated the potential analgesic benefit of a single perioperative dose of dexamethasone on postoperative pain and some of them have inconclusive findings.[6,7,8,9,10,11]

Steroid therapy has been postulated to reduce inflammation and scar tissue formation that contributes to postoperative pain.[1] The analgesic effects of glucocorticoids are mainly provided through the peripheral inhibition of phospholipase enzyme, thereby decreasing the products of the cyclooxygenase and lipoxygenase pathways in inflammatory response. Apart from anti-inflammatory effects, steroids supposedly decrease the release of substance P at dorsal root ganglion which may further contribute to its analgesic effect.[12]

Steroids along with local anesthetics have been applied by many neurosurgeons to decrease postoperative pain following lumbar discectomy to reduce traumatic nerve root inflammation.[2] Watters et al.[13] used oral and i.v. dexamethasone and suggested that it is safe and effective adjunct in the postoperative management of primary lumbar disc surgery. In our study, we used single dose of i.v. dexamethasone preoperatively. Aminmansour et al.[14] had revealed that intraoperative administration of very high dose of (40 mg) dexamethasone reduced radicular pain and opioid requirement following surgery for herniated disc. Karst et al.[15] found that patients who had been treated with dexamethasone (20–80 mg) intraoperatively required less postoperative patient-controlled analgesia (PCA) and had lower pain scores than a group without such treatment. Our results coincide with their results though we used lower dose of dexamethasone (8 mg). Tolver et al.[16] failed to show any clinical effect of dexamethasone on early postoperative pain following laparoscopic repair of inguinal hernia. The authors attributed this effect to suboptimal dosage (8 mg) and timing (median times 37 min before skin incision) of administration of dexamethasone. On the contrary, same 8 mg of dexamethasone has been found to be sufficient to reduce postoperative pain and opioid consumption after laparoscopic cholecystectomy,[6,17,18] laparoscopic hysterectomy,[7] molar tooth extraction,[19] and mastectomy.[20] Dexamethasone modulates the inflammatory stress response by inhibitory pro-inflammatory mediators such as interleukins, C-reactive protein, tumor necrosis factor α, and leukocyte receptors, but laparoscopic inguinal hernia repair as a minimally invasive procedure may not induce a high inflammatory stress response, resulting in the effects of dexamethasone being clinically insignificant.

Jokela et al.[21] performed a dose-ranging study in women undergoing laparoscopic hysterectomy and demonstrated that high dose of dexamethasone (15 mg) had an apparent opioid-sparing effect but no effect on VAS scores of pain and time to first rescue analgesic. This could possibly be due to the use of PCA for postoperative pain management, which allowed the patients to dose the opioid to the level of pain relief they desired. Another possible reason for the lack of effect of dexamethasone on pain score in their study can be low degree of invasiveness and weak inflammatory response of laparoscopic procedure as compared to open surgery.

The onset of action of dexamethasone is thought to be 1–2 h allowing time to diffuse across the cell membrane and alter gene transcription. Waldron et al.[3] suggested that administration of steroid 60 min before surgical trauma may be important in minimizing pain and inflammation. The timing of administration varies in different studies from 2 h before induction[17] to immediately before induction.[4,22,23] Some authors have given it postoperatively.[24]

The optimal analgesic dose of dexamethasone has not been determined yet. Many randomized trials and meta-analyses have recommended 8 mg of dexamethasone (i.v.) for postoperative analgesia.[3] Jokela et al.[21] studied three different doses to identify the effective analgesic dose of dexamethasone after laparoscopic hysterectomy. Asad and Khan[4] suggested that different surgeries may require different doses depending upon the tissue trauma so that the dose that is adequate for one procedure may not be enough for another. In our study, 8 mg dexamethasone was sufficient to reduce intraoperative and early postoperative pain.

Time of first rescue analgesic requirement in the postoperative period was significantly higher in Dexamethasone group than control group. Mean HR and MAP were also significantly higher in control group during postoperative period. Waldron et al.[3] performed a systemic review and meta-analysis and found that patients treated with dexamethasone had a significantly longer time to first dose of analgesic.[7,21,25,26,27,28,29] However, Jokela et al.[21] found that time to the first rescue analgesic dose was equal in all the four study groups.

It was observed that the mean HR and requirement of rescue analgesic during intraoperative period were significantly more in the control group. Thus, the trend of hemodynamic variables during intraoperative and postoperative period also supported the analgesic effect of dexamethasone. Our results are comparable to AsadandKhan.[4]

Five patients in the study group complained of perineal pruritus just after injection of dexamethasone. Perineal pruritus is an unusual reaction which may occur immediately after bolus injection of dexamethasone sodium phosphate. Perron et al.[30] also observed similar finding in their study. The pharmacological phenomenon could be related to the phosphate ester of the corticosteroid since perineal irritation has been described with hydrocortisone-21-phosphate sodium and prednisolone phosphate.[31] Fortunately, this adverse effect can be diminished or even abolished by giving dexamethasone diluted in 50 mL of fluid over 5–10 min.[31,32,33] None of the patients had any adverse effects related to rise in blood sugar or infectious complications. Glucocorticoids can give a marked but transient elevation in blood glucose.[34] However, in our study, administration of dexamethasone was not associated with a significant rise in blood sugar. None of the patients had delayed wound healing in both the groups. Waldron et al.[3] also reported the same. Most evidence in the literature also indicates that single doses of corticosteroids are unlikely to impair wound healing in man.[35]

Limitations of the study were that patient satisfaction and dynamic pain were not observed. We used a simple method of assessment for administrating the additional intraoperative analgesia. The management of postoperative pain in the developing countriesbecome difficult due to erratic availability of potent narcotic analgesic drugs and their derivatives. Dexamethasone is easily available, which when used as a co-analgesic reduces the narcotic dose requirement.

CONCLUSION

We conclude that preoperative i.v. dexamethasone (single dose) is effective in reducing intraoperative pain and maintaining good analgesia in early postoperative period after lumbar spine surgery without apparent side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.