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Year : 2022  |  Volume : 13  |  Issue : 1  |  Page : 1-7

A comparative evaluation of oral clonidine and oral gabapentin as a premedication on postoperative analgesia duration in patients undergoing spinal anesthesia

1 Department of Anesthesiology and Critical Care, ESIC Medical College and Hospital, Kolkata, West Bengal, India
2 Department of Pediatric Medicine, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal, India
3 Department of Pediatric Surgery, R G Kar Medical College, Kolkata, West Bengal, India
4 Department of Anesthesiology, R G Kar Medical College, Kolkata, West Bengal, India
5 Department of Pediatric Medicine, R G Kar Medical College, Kolkata, West Bengal, India

Date of Submission04-Mar-2022
Date of Acceptance28-Jun-2022
Date of Web Publication02-Sep-2022

Correspondence Address:
Dr. Pankaj Kumar Halder
Saroda Pally, Baruipur, Kolkata - 700 144, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjmsr.mjmsr_15_22

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Background and Objectives: Premedication with oral clonidine or gabapentin reduces the perioperative pain and decreases the requirement of analgesics. Our study aims at comparing the efficacy of oral clonidine and oral gabapentin for postoperative analgesia duration in surgeries done under spinal anesthesia. Materials and Methods: A prospective, double-blinded study was conducted in randomly selected 100 patients undergoing spinal anesthesia for any surgery (excluding cesarean section). Group C received 100 μg oral clonidine and Group G received 600 mg oral gabapentin, 1 h before spinal anesthesia. Blood pressure, heart rate, and Spo2 were recorded at 0, 15, 30, and 60 min interval. Visual analog scale (VAS) was documented for pain assessment at 2, 4, 6, 8, and 24 h from the time of onset of spinal anesthesia. The number of rescue analgesic doses required in 24 h postoperatively was noted. The data regarding the patient's demography, changes in the hemodynamics, VAS score, and requirement of rescue analgesia were analyzed. Results: There was no statistically significant difference in the hemodynamic changes with either group. The mean VAS score in the first postoperative hour was significantly higher for Group C than Group G (P < 0.0001). The mean requirement of rescue analgesic doses per patient was 3.00 ± 0.35 and 1.84 ± 0.58 in Groups C and G, respectively (P < 0.0001). Conclusions: Oral gabapentin is more effective than oral clonidine as a premedication in patients undergoing spinal anesthesia belonging to American Society of Anesthesiologists I and II.

Keywords: Anesthesia, clonidine, duration, gabapentin, premedication, requirement, spinal

How to cite this article:
Das R, Paul K, Halder PK, Choudhury A, Roy S, Debbarma A. A comparative evaluation of oral clonidine and oral gabapentin as a premedication on postoperative analgesia duration in patients undergoing spinal anesthesia. Muller J Med Sci Res 2022;13:1-7

How to cite this URL:
Das R, Paul K, Halder PK, Choudhury A, Roy S, Debbarma A. A comparative evaluation of oral clonidine and oral gabapentin as a premedication on postoperative analgesia duration in patients undergoing spinal anesthesia. Muller J Med Sci Res [serial online] 2022 [cited 2022 Dec 5];13:1-7. Available from: https://www.mjmsr.net/text.asp?2022/13/1/1/355291

  Introduction Top

Pain is an unpleasant feeling for patients undergoing any surgical procedure. Poorly managed pain can have a negative impact on physical and psychological consequences for the patients. The management of pain is a major challenge to an anesthesiologist because of insufficient knowledge of evaluation and nursing by the nurses and health-care providers during the immediate postoperative period.[1] Adequate analgesia and pain management have significant physiological benefits for the patients (promote the healing process, early mobilization, and smooth recovery). The intention for postoperative pain management is to reduce or abolish pain and discomfort with various drugs like opioid/nonopioid (oral/intravenous) and methods, e.g., neuraxial block/peripheral nerve block.[2] Regional anesthesia (e.g., epidural anesthesia and spinal anesthesia) is now preferred over general anesthesia for lower limb or lower abdominal surgeries. Multimodal approaches have been developed with the intent to reduce the side effects of opioids in the postoperative period. A premedication with gabapentin/clonidine before regional anesthesia to lower the visual analog scale (VAS) score and less opioid consumption is described by Mishra et al. in 2016.[3] Gabapentin blocks the tonic phase of nociception exerting an inhibitory effect in neuropathic pain models of mechanical hyperalgesia and mechanical allodynia. It reduces the analgesic requirement postoperatively and delays the onset of pain. On the other hand, clonidine causes prolonged analgesia and decreased analgesic consumption due to increasing presynaptic α2 receptor activation and downregulating neurotransmitter release.[4] Blaudszun et al. described that systemic dexmedetomidine (alpha 2 agonists) can decrease postoperative opioid consumption, pain intensity, and nausea.[5] This study explores the comparative result of premedication of oral gabapentin and oral clonidine in patients of American Society of Anesthesiologists (ASA) I and II undergoing spinal anesthesia.

  Materials and Methods Top

This prospective, double-blinded study was conducted from January 2019 to December 2021, and approval from institutional ethics committee was taken beforehand (approval no.-KPCMCH/IEC/451). The sample size was calculated with the help of a website, and 100 patients of ASA physical status I and II were randomly allocated into two groups. Group C patients received tablet clonidine (100 μgm) and Group G patients received tablet gabapentin (600 mg) one hour before the spinal anesthesia as a premedication. The data capture sheet contained information on patients' age, sex, changes in heart rate (HR), blood pressure (BP), arterial oxygen saturation (SpO2), VAS (1–10), number of rescue analgesia in the first 24 h, and any adverse reaction.

Study population

This study included patients of either sex, aged between 18 and 65 years, and undergoing any surgery (except cesarean section) that can be done under spinal anesthesia. Inclusion criteria were patients belonging to ASA I and II, undergoing elective surgical procedures, orthopedic procedures, and gynecological procedures under spinal anesthesia. We excluded patients who were having (i) any contraindications for spinal anesthesia, (ii) allergic to clonidine, gabapentin, and analgesics used, (iii) patients undergoing emergency surgical procedures, (iv) patients having initial HR <50 beats/min and BP <100/60 mmHg, and (v) and patients not giving consent for this study.

Study technique

A preanesthetic evaluation was done and written informed consent was taken from all patients who fulfilled the inclusion criteria. They were enrolled and randomized using computer-generated charts with an allocation ratio of 1:1 into either of the two groups. Group C (n = 50) received tablet clonidine (100 μg) orally 1 h before administration of spinal anesthesia with sips of water and Group G (n = 50) received tablet gabapentin (600 mg) orally 1 h before administration of spinal anesthesia with sips of water. All patients were given aspiration prophylaxis before the procedure with tablet ranitidine (150 mg) and tablet metoclopramide (10 mg), which have no drug interaction with clonidine or gabapentin. The anesthesiologist conducting the case as well as recording the data was unaware of the study drug being administered for premedication.

VAS was explained to the patients during preoperative visit and also in the preparation room. In the operation room, an intravenous line with an 18G cannula was secured, and standard monitoring was done using five-lead electrocardiogram, pulse, oxygen saturation, and noninvasive blood pressure monitoring. Baseline values were recorded. Coloading was done with Ringer's lactate solution 10 ml/kg before the spinal anesthesia. Spinal needle of 25G (Quincke or Whitacre) was inserted in L3-L4 or L4-L5 intervertebral space (prior skin infiltration with 2% lignocaine), and 3 ml of 0.5% bupivacaine heavy (15 mg) was injected. Maintenance fluid was administered with Ringer's lactate solution at the rate of 6 ml/kg/h. Hypotension (if any) was managed with an injection of mephentermine 3 mg in an aliquot. Perioperative monitoring of pulse, BP, and SpO2 was done at every 3-min intervals. The parameters were recorded at 15 min, 30 min, and 1-h interval after administration of spinal anesthesia. The pain was assessed by VAS in the immediate postoperative period and at 2, 4, 6, 8, and 24 h thereafter. Any patient with VAS scores of more than three was administered injection diclofenac 1 mg/kg intramuscularly as a rescue analgesic. The time for the first dose of rescue analgesia was noted by the attending nurse.

Study variables

Background variables of each patient including age, gender, type of surgery, and type of oral premedication were recorded. Other variables such as pain score (VAS), number of rescue analgesic doses required within the first 24 h of surgery, hypotensive episode (decrease in the mean arterial pressure [MAP] of more than 20% drop from preanesthetic value), bradycardia (HR <50 beats/min), and hypoxemia (decrease in SpO2 below 90% at room air) were taken into consideration for statistical analysis.

Statistical analysis

For statistical analysis, the data were entered into a Microsoft Excel (2019 MSO Version 2201 Build 16.0.14827.20198 64-bit, Microsoft Corporation, Redmond, WA, USA) and then analyzed by SPSS (version 27.0; SPSS Inc., Chicago, IL, USA). GraphPad Prism (version 5, GraphPad Software, Inc., CA, USA) was used for the 2D graphing. Numerical data were presented as mean ± SD and categorical variables were expressed as frequencies and percentages. Parametric data were analyzed using an independent Student's t-test. Nonparametric/unpaired proportions data were compared by the Chi-square test. P ≤ 0.05 was considered statistically significant.

  Results Top

One hundred patients were taken into the study cohort dividing them equally in Group C and G. The male-female ratio in Group C and Group G was 19 (38%):22 (44%) and 31 (62%):28 (56%) [Table 1], respectively. The mean age of Group C and Group G was 48.70 ± 11.40 and 47.26 ± 12.73, respectively. There was no significant difference between Group C and G with respect to age (P = 0.5527) or sex distribution (P = 0.5418).
Table 1: Association of gender in Group C and Group G (n=100)

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The changes in MAP, HR, and SpO2 at different time intervals (0, 15, 30, and 60 min) are elaborated in [Figure 1],[Figure 2],[Figure 3] as well as in [Table 2],[Table 3],[Table 4], respectively. Group G had a lower MAP at 60 min than Group C. The mean HR at 60 min was high in Group C than Group G. Although the Group G had a higher mean SpO2 at 15 min, their mean SpO2 fell behind the mean SpO2 of the Group C at 30 min. However, neither of these results were statistically significant across the groups. The mean VAS score for Group C was steadily higher than the Group G in the first 24 h except for a relative reversal of peak at 6 h [Figure 4]. The difference in VAS score between the groups was significant at every point except at the second postoperative hour [Table 5]. 90% of the Group G patients needed two or fewer rescue analgesic doses. Whereas, three or more rescue analgesic doses were needed in 94% of patients in Group C. There was a significant association between the choice of premedication and the number of rescue analgesic doses (Pearson X2 (3) = 71.07, P < 0.001) as illustrated in [Table 6].
Figure 1: Variation of mean arterial pressure at different time interval for Group C and G (n = 100)

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Figure 2: Variation of mean heart rate at different time intervals in Group C and G (n = 100)

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Figure 3: Variation of mean saturation at different time interval for Group C and G (n = 100)

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Figure 4: Variation in mean VAS at different time intervals for Group C and G (n = 100). VAS: Visual analog scale

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Table 2: Distribution of mean arterial pressure at 0, 15, 30, and 60 min in Group C and G (n=100)

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Table 3: Distribution of mean heart rate at 0, 15, 30, and 60 min in Group C and G (n=100)

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Table 4: Distribution of mean arterial oxygen saturation at 0, 15, 30, and 60 min in Group C and G (n=100)

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Table 5: Distribution of mean visual analog scale at 2, 4, 6, 8, and 24 h in Group C and G (n=100)

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Table 6: Association between rescue analgesics in Group C and G (n=100)

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  Discussion Top

Pain is an unpleasant sensory and emotional experience of the patients due to actual or potential tissue damage. Any tissue injury stimulates peripheral and central pain pathways due to feelings of fear, anxiety, and frustration and that activates the responses in the pain matrix. Poorly controlled postoperative pain evokes a neuroendocrine response and leads to delayed wound healing, increased incidence of deep vein thrombosis, vascular graft failure, depression of the immune system, and other systemic effects.[6] Thus, pain management is a pivotal integrant of postoperative care. The main objective of the anesthesiologist is to minimize pain and enhance the patient's overall sense of well-being. It has been proclaimed that perioperative pain management should be “procedure-specific,” which means that a specific procedure should be redesigned for a particular surgery as a specific analgesic (opioids and nonsteroidal anti-inflammatory drugs) has distinct effects depending on the nature of the surgery. Opioids are being used for a long time which has several side effects such as sedation, respiratory depression, pruritus, and constipation. Various techniques are also adopted now (systemic opioid, nonsteroidal anti-inflammatory drugs, regional analgesia, and multimodal analgesia) to standardize the anesthesia.[7]

Multimodal analgesia is gaining popularity, having maximum benefit, and becoming mainspring for the postoperative pain management. Clonidine and gabapentin have recently become a part of a multimodal analgesic regimen as preemptive analgesics.[8],[9] In the preemptive analgesia technique, additional use of an analgesic protects against the effect of subsequent unpleasant stimuli on the nociceptive system that could amplify pain.[10] Several studies have shown that gabapentin is useful as an analgesic for diabetic neuropathy, neuropathic pain, neuralgia, and reflex sympathetic dystrophy. It is used for relieving postoperative hyperalgesia and allodynia since 2002.[11] It impedes central neuronal sensitization and hyperalgesia by acting on voltage-dependent calcium channels at postsynaptic and presynaptic junctions and decreases the excitatory (glutamate, substance P, and calcitonin gene-related peptide-mediated) transmission in the spinal cord.[12] Oral gabapentin can have a dose-dependent effect on nucleus tractus solitarii and other autonomic functions in the central nervous system that can lower the BP.[13] Turan et al. found that patients receiving preemptive oral gabapentin have lower VAS scores and require less rescue analgesic (Tramadol) than that of the placebo-controlled group.[14] In 2008, Mohammadi and Seyedi proved that administration of oral gabapentin decreases postoperative pain, analgesic requirement, and antiemetic medication in the postoperative period.[15]

On the other hand, clonidine inhibits neurotransmission in both A-delta and C fibers and surges the inhibitory effect of local anesthetic on C-fiber.[16] The peak plasma concentration of clonidine is achieved within 1–3 h of oral administration with 100% bioavailability. It blocks the release of norepinephrine from the nerve terminals leading to hypotension and bradycardia.[17] We observed a few variations in hemodynamics (HR, MAP, and SPO2) in both groups C and G, but that was not statistically significant (P > 0.05). Both clonidine and gabapentin can maintain perioperative hemodynamic stability. Clonidine, by virtue of its ability to decrease sympathetic outflow, maintains stable hemodynamics in the perioperative period.[18] However, Dobrydnjov et al. observed pronounced hypotension after oral administration of clonidine.[19] In 2011, Gupta et al. showed that premedication with clonidine is useful in maintaining the hemodynamic response during laryngoscopy and laparoscopy.[20]

The HR and BP can be affected by the age and gender of a study population. The female population has a lower BP compared to men in their twenties. Females are protected from major cardiovascular diseases until after menopause.[21] Similarly, the older-age group often has a high BP due to structural changes in the arteries, especially with large artery stiffness.[22] In our study, the basic demographic profile (age and gender) was comparable in two groups. The difference of mean age in Group C and Group G was not statistically significant (P = 0.7908). Similarly, the association of gender between the two groups was not statistically significant (P = 0.5418).

For perioperative pain management, several pain scoring systems are available. Among them, VAS scoring is the most reliable and easy to implement. The VAS is a subjective measure for acute as well as chronic pain. It is assessed by a mark on a 10-cm line that represents a continuum between “no pain” and “worst pain.”[23] We used VAS scoring for the quantitative assessment of postoperative pain in addition to the assessment of clinically important physiological variables. In our study, the differences in VAS scores among the two groups were not significant at 2 h. However, Group G had a lower VAS score value than that of Group C after 4, 6, 8, and 24 h of spinal anesthesia.

In 2008, Mohammadi and Seyedi showed that patients receiving oral gabapentin felt less postoperative pain and required less morphine consumption in comparison to patients receiving oral clonidine.[24] In 2019, Bala et al. concluded that a single dose of pregabalin or clonidine as a preemptive analgesic is an effective, reasonable, and safe strategy for reducing postoperative pain and analgesic consumption in patients undergoing spinal instrumentation. They also concluded that pregabalin is superior to clonidine in terms of postoperative pain reduction evaluated by VAS score.[25]

Our results also showed that the requirement of a number of rescue analgesic doses in Group G was less (mean, 1.84) than that of Group C (mean, 3) within the first 24 h of spinal anesthesia. Analysis of the distribution of requirement of rescue analgesic among the two groups was statistically significant (P < 0.0001). Similar to our study, Singh et al. conducted a randomized double-blinded study in patients of ASA I and II, aged 20–58 years, undergoing knee arthroscopic repair under epidural anesthesia. They found less time lapse for the onset of complete sensory block and complete motor block in patients with oral gabapentin (300 mg) than oral clonidine (100 μg). They concluded that oral gabapentin is better than oral clonidine as a preemptive adjuvant for providing postoperative analgesia and sedation.[26] In our study, we observed a lower VAS score and less requirement of rescue analgesic in patients receiving gabapentin than clonidine. Furthermore, there is no postoperative nausea and vomiting in both the groups in our study. In 2015, another study was conducted by Gosai et al. with patients of ASA I and II, comparing the efficacy of oral clonidine (200 μg) and gabapentin (600 mg) with a control (placebo) group. They observed that oral gabapentin significantly decreased postoperative pain (VAS) and diclofenac consumption (rescue analgesic) in comparison to oral clonidine and placebo.[27]

  Conclusions Top

Both the drugs of our study are effective in providing postoperative analgesia. Oral gabapentin is more effective than oral clonidine as a premedication for providing postoperative analgesia in patients belonging to the age group of 18–65 years, ASA I and II, undergoing spinal anesthesia for surgery. The rescue analgesic requirement is also less in patients receiving gabapentin than clonidine. There is no postoperative nausea and vomiting observed in both the groups. However, a larger study population with a randomized control group could capitulate a stronger advisory result.


This was a single-centered study. There was no control group in our study, which could have a better impact on the result and analysis. This study had a small sample size (n = 100), which was probably ineffectual to draw a tangible verdict.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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