“Pain is replicated as a sense of human nervousness towards hazard to their physical or existential unit”.
Pain relief in the surgical field and postoperative period is the eventual apprehension for the patient and anesthetist. Postoperative pain is acute in character which gets elicited due to an inflammatory reaction associated with surgical trauma, thereby activating an afferent dorsal horn neuron an essential component of pain reception pathway.[2,3]
Accurate knowledge on pain physiology helped in the arrival of an idea of preemptive analgesia, which works by minimizing the durability and magnitude of pain, by demolishing the origin of central sensitization due to surgical stimulus with the medication given before the stimulus. Gabapentinoids acts via the coupling of alpha two and delta subunit present in the calcium channel. Which constrain the discharge of excitatory neurotransmitters thereby modulating neuronal impulses involved in pain transmission.[5,6]
Various prior reviews depicted that gabapentin and pregabalin ominously condense the postoperative rescue analgesic necessity and upsurge the time for postoperative analgesia.[7,8,9,10] Thus, this study was conducted to appraise the supremacy among the drugs for postoperative analgesia.
The Primary objective of our study was to compare the intensity of postoperative pain among 3 groups by numeric pain intensity scale (NPIS) for 24 h. The Secondary objective was to compare parameters like the time interval between the subarachnoid block and first rescue analgesic, Total dosage of rescue analgesics given in first 24 h, Sedation score of the drug and Presence of any adverse effects among the groups.
Materials and Methods
This was a prospective double-blinded randomized control trail conducted over a time scale of 2 years, after obtaining approval from the Institutional Ethical Committee (IEC No: 2019/435, dated-January 25, 2019). The trial was registered in the Clinical Trial Registry–India, before starting enrollment of five patients (CTRI/2019/03/018053).
Seventy-two patients of both the sexes between 18 and 60 years of age with body mass index (BMI) of 18–25 years belonging to physical status of the American society of Anesthesiologist (ASA) Class I and II posted for lower abdominal surgeries under subarachnoid block were included in the study. Patients with ASA III and above, Pregnancy, lactating mothers, systemic diseases, known psychiatric disorder, all neuropathies, drug allergies and who were already on tablet pregabalin and tablet gabapentin were excluded from the study. Participants were informed about the study in detail in their own language and valid consent was obtained. All enrolled patients were randomly allocated into either of three groups by computer-generated list of random numbers. Each group consisted of 24 patients each.
- Group 1: Received oral tablet pregabalin 150 mg
- Group 2: Received oral tablet gabapentin 600 mg
- Group 3: Received oral placebo drug (tablet B-complex).
All patients were kept nil per oral for 8 h before surgery. Patients of each group received single dose of their respective drug 2 h before subarachnoid block with sips of water. No other premedication was given to patients to avoid the influence of other medications on the study drugs. The interpretation of NPIS was enlightened prior the procedure to the patients taken up for the study to assess the pain experienced by them in postoperative period. The first mark “0” means “no pain,” mark “5” means “moderate pain,” and mark “10” means “severe pain” Patients were shifted to operating room, and vitals such as heart rate (HR), blood pressure, oxygen saturation, and respiratory rate were monitored and IV line was secured. Patients received subarachnoid block of 3.5 ml of 0.5% heavy bupivacaine in L3-4 intervertebral space under strict aseptic conditions with 25-gauge quincke's spinal needle. No other medications, analgesics, and sedatives were given during procedure. Duration of surgery was also noted. In cases of failed spinal, inadequate level of block, prolonged surgery patient was converted to general anesthesia and was considered as dropouts from the study. The patient pulse rate, blood pressure, oxygen saturation and electrocardiogram was monitored with planet 60/star 60 mointer, SANKRAY Technologies Pvt, Ltd, India. Any reduction of 20% of mean arterial pressure from the baseline was promptly treated with IV fluids. If not effective, injection ephedrine 6 mg was given in incremental dosages, and HR <50 was treated with 0.6 mg injection atropine.
After surgery, the patient was shifted to the postoperative ward. Pain assessment was done on the basis of NPIS score 2nd and every 4th h postoperatively. Analgesics were given on demand as and when the patient complained of pain with injection tramadol 2 mg/kg IM. If the patient complained of pain within 6 h of rescue analgesic, it was managed by injection paracetamol 1 g infusion. The time interval between subarachnoid block to 1st rescue analgesics was noted and the sum of all doses of analgesics used was also noted in each group. Assessment of sedation score was done at 1, 2, 4, 8, 12, 16, and 24 h using sedation scores: 0 = alert, conversant, 1 = awake but drowsy, 2 = asleep but arousable, and 3 = asleep and not arousable. Side effects and complications like diplopia, nausea, vomiting, diarrhea, Confusion and respiratory depression (defined as Ventilatory frequency <8 bpm and oxygen saturation <90% without oxygen supplementation) were noted. The severity of postoperative nausea and vomiting was graded on a 4-point ordinal scale; [0 = no nausea/vomiting; 1 = mild nausea; 2 = moderate nausea; 3 = severe nausea with vomiting] treated with injection metoclopramide 10 mg. Monitoring of vitals was done for 24 h postoperatively. One anesthesiologist decided and gave oral premedication and another anesthesiologist recorded and evaluated the data, which was done to blind the group allocation.
Statistical analysis was done using software SPSS version 16 using Chi-square test/Fisher's exact test or one-way analysis of variance test/Kruskal–Wallis test. The sample size was calculated on the basis of a previous study, in which the mean and standard deviation of time taken for first rescue analgesics was 8.98 ± 5.38 in the gabapentin group and 14.17 ± 6.67 in the pregabalin group, respectively, with power of 80%, significance of 5%, and confidence interval (CI) of 95%. Twenty-four patients were to be included in each group considering the possible dropouts (10%). Hence, the total sample size was 72 patients. A statistically significant difference was considered when P < 0.05.
Among the 85 patients who were screened for eligibility, 72 patients were enrolled into three groups, 24 patients in each group after excluding possible dropouts [Figure 1]. The groups were comparable with respect to demographic characteristics such as age, height, weight, BMI, gender, and duration of surgery [Table 1]. No significant differences were found between three groups in terms of HR, systolic and diastolic blood pressure (SBP and DBP), mean arterial blood pressure (MABP), and SpO2 during intraoperative period.
Sedation score was only more on of pregabalin and gabapentin groups in contrast to placebo group at 15 (P < 0.01) (CI: 0.64–0.87), 30 (P < 0.001) (CI: 1.74–2.03), and 60 (P < 0.046) (CI: 1.99–2.30) minutes with clinical significance [Table 2]. The type of surgery conducted in three groups was also similar [Figure 2]. Postoperatively, no significant differences were found between three groups in terms of HR, MABP, and SpO2. Clinically significant reduction in SBP and DBP was seen in pregabalin and gabapentin groups in all time trends expect 24th hour in SBP which was normal.
Sedation score was lesser in pregabalin and gabapentin groups at 2 h (P < 0.02) (CI: 0.87–1.16) and 24th (P < 0.02) (CI: 1.05–1.35) hour than the placebo group due to the increased use of rescue analgesics by the placebo group postoperatively with a statistically significant difference [Table 3].
The intensity of pain perceived by patients in terms of NPIS score showed both pregabalin and gabapentin groups had lesser NPIS score compared to the placebo group at 4th h (P = −0.01) (CI: 1.92–192.61), 8th h (P = −0.02) (CI: 3.56–4.69), 16th h (P = −0.03) (CI: 1.88–2.84), and 20th h (P = −0.013) (CI: 2.7–83.89). At the 2nd h (P = −0.04) (CI: 2.38–3.40), the placebo group showed lesser NPIS score compared to the other groups with the use of rescue analgesics. The difference was statistically significant (P < 0.05). Among the both groups, the pregabalin group showed a reduced pain score [Table 4].
There was a significant difference in duration of analgesia in regards to time for first rescue analgesia in the placebo group were maximum among 11 subjects (45.8%) was at 3 h while, in gabapentin group 11 (45.8%) was from 3 h 30 min to 4 h and in pregabalin group 10 (41.7%) was around 4 h 30 min and P < 0.001 (CI: 3.56–3.91) which was highly significant [Figure 3].
The total doses of rescue analgesia were significantly lesser in pregabalin and gabapentin groups compared to placebo group with clinical significance (P < 0.001) (CI: 2.53–2.86). Among 24 subjects in each group, maximum 17 (70.8%) of them in Pregabalin group received 2 doses, while in Gabapentin group 11 (45.8%) of them received 2 doses and 14 (58.3%)subjects in placebo group received 3 doses of rescue analgesics respectively [Figure 4].
No side effects of nausea/vomiting, diplopia, confusion, or respiratory depression were noted in any of the subjects in the study population.
In this study, we compared the efficacy of postoperative analgesiaamong the groups and infer that pregabalin was superior in all facets significantly.
In 24 h NPIS scores were significantly lesser in Pregabalin than other groups except at 2nd h where palcebo group had lesser NIPS score than other groups due to early requirement of rescue analgesia.
The outcome also abetted that Pregabalin delays the inception of rescue analgesics greater (4 h 30 min) than other two groups (P < 0.001) along with minimal necessity for rescue doses (2 doses) (P < 0.001).
The sedative score was also more in the Pregabalin group at 15, 30 and 60 min intra-operatively and 2nd and 24th hour postoperatively (P < 0.05) along with nil toxic effects in any groups.
These outcomes were analogous to studies of Saraswat and Arora, which inferred that Pregabalin (300 mg) is highly proficient in minimizing the pain, analgesic requisites and time of analgesia than gabapentin (1200 mg).
Dauri et al. study inferred the superiority of gaba-pentanoids in minimizing pain post-surgical phase with least opioid requisite. Pregabalin 2 capsules 150 mg was equally effectual in minimizing post-surgical pain than 2\ capsules of gabapentin 300mg. The necessity for additional pain relief was also minimal than gabapentin as per Routray et al. study. Between them, pregabalin was extra efficient as identical in our study. Similarly, on reviewing, the Ozgencil et al.'s study also showed pregabalin 300 mg had higher pain, chills, and stress-relieving property along with minimizing opioid requisite and maximal patient fulfillment than gabapentin 1200 mg.
Chizh etal.'s study also inferred that pregabalin plus parecoxib resulted in decreased sensitivity to pain. While Jokela et al.'s study review also favored our study results as perioperative usage of Pregabalin 600 mg produced desired analgesia along with some side effects like dizziness, blurred vision and headache. While our study had no adverse reactions. In our study, Pregabalin group had more sedation score at 15, 30 and 60 min intra-operatively and 2nd and 24th h postoperatively (P < 0.05). While this was diverse from above cited articles[18,19,20,21] with better sedation. There were some limitations in our study.
Failed to do assessment of stress levels with the help of presence of catecholamine's which would have made our result clearer. Follow-up period should have detected in the pregabalin group in comparison withe been included to see the analgesic effect. The use of single dose of pregabalin and gabapentin made it difficult to draw a conclusion about the long-term effects and optimal dose. There were some limitations of the study, considering a larger sample would have identified the possibility of adverse reactions and optimal dose.
The follow-up for the long-term complications and any use in chronic pain would have added more value to the result. Further research with other subsequent pain scales would have validated the result.
We conclude that dose-response relationship the gabapentin group, with other pain parameters it reveals that the single dose of Pregabalin was successful in postoperative analgesia, without any adverse effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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