|Year : 2019 | Volume
| Issue : 2 | Page : 81-85
Comparison between epidural ropivacaine and ropivacaine–clonidine combination for infraumbilical surgeries: A randomized clinical study
Neeraj Kumar1, Omprakash Sanjeev2, Abhyuday Kumar3, Sashi Kant4, Vinod Kumar Verma4, Ajit Kumar Gupta4
1 Department of Trauma and Emergency (Anaesthesiology), All India Institute of Medical Sciences, Patna, Bihar, India
2 Department of Emergency Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Department of Anaesthesiology, All India Institute of Medical Sciences, Patna, Bihar, India
4 Department of Anaesthesiology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
|Date of Submission||29-Mar-2019|
|Date of Decision||18-May-2019|
|Date of Acceptance||08-Jul-2019|
|Date of Web Publication||7-Aug-2019|
Dr. Neeraj Kumar
Department of Trauma and Emergency (Anaesthesiology), All India Institute of Medical Sciences, Patna, Biha
Source of Support: None, Conflict of Interest: None
Introduction: Lower abdominal and lower limb surgeries may be performed under local, regional (spinal or epidural) or general anaesthesia, but neuraxial blockade is preferred mode of anaesthesia. Major advantage of epidural anaesthesia over spinal anaesthesia is the ability to titrate the extent and duration of anaesthesia. Aims and Objective: The primary outcome of the study was to measure the duration of sensory analgesia. The secondary outcomes were onset of sensory block, onset of motor block, highest level of sensory block, degree of motor block, duration of motor block, and quality of sensory blockage as measured by visual analog scale. Material and Methods: After getting institutional ethical clearance from our institute and proper written consent from each patient a total of 80 patients who underwent infraumbilical surgeries. A total of 80 patients who underwent infraumbilical surgeries were included randomly into two clinical study groups comprising 40 patients in each study group. Epidural anaesthesia was administered with 20ml of Ropivacaine 0.75% (GROUP-R) and 20 ml of epidural Ropivacaine 0.75% and Clonidine 75mcg combination (GROUP-RC). Statistical Analysis: Statistical comparison was made by comparison between groups by applying chi-square test to a contingency table for categorical data and two sample t–test and independent t-test for numerical data. Result: A total of 102 patients were assessed for eligibility, of which 16 patients did not meet the inclusion criteria and 6 patients were excluded during the study period. The groups was comparable with regard to demographic data and incidences of side effects except for the higher incidence of dry mouth in patients of RC group. Onset of analgesia was much shorter in RC group with prolonged duration of analgesia. The incidence of bradycardia and hypotension was more in RC group as compared to R group which was statistically significant. Conclusion: The addition of 75mcg clonidine to isobaric epidural ropivacaine results in longer, complete and effective analgesia with similar block properties and helped to reduce the effective dose of ropivacaine when compared with plain ropivacaine for infraumbilical surgery
Keywords: Clonidine, epidural anesthesia, ropivacaine
|How to cite this article:|
Kumar N, Sanjeev O, Kumar A, Kant S, Verma VK, Gupta AK. Comparison between epidural ropivacaine and ropivacaine–clonidine combination for infraumbilical surgeries: A randomized clinical study. Indian J Pain 2019;33:81-5
|How to cite this URL:|
Kumar N, Sanjeev O, Kumar A, Kant S, Verma VK, Gupta AK. Comparison between epidural ropivacaine and ropivacaine–clonidine combination for infraumbilical surgeries: A randomized clinical study. Indian J Pain [serial online] 2019 [cited 2019 Nov 16];33:81-5. Available from: http://www.indianjpain.org/text.asp?2019/33/2/81/264075
| Introduction|| |
Neuraxial blockade is a preferred mode of anesthesia for lower abdominal and lower limb surgeries though it can be done under local, regional, or general anesthesia. Spinal anesthesia provides rapid onset of block but has some disadvantages such as hemodynamic instability, unpredictable level of block height and limited duration of action. Epidural anesthesia has advantage of ability to titrate the duration and extent of anesthesia over spinal anesthesia. Epidural analgesia provides better postoperative analgesia than parenteral opioids.
Ropivacaine (1-propyl-2',6'-pipecoloxylidide hydrochloride monohydrate) is a new, long-acting local anesthetic, structurally very similar to other pipecoloxylidide derivatives, first synthesized by Ekenstam et al. It is the first pure S-enantiomer and in comparison to bupivacaine has similar analgesic properties, lesser motor blockade, and decreased propensity of cardiotoxicity., Clonidine is an alpha-2 adrenoreceptor and imidazoline receptor agonist which has analgesic, sedative property without significant respiratory depression and minimum alveolar concentration-sparing effect. After its administration into the subarachnoid or epidural space, clonidine provides a substantial antinociceptive effect by acting on alpha-2 receptors in the dorsal horn of spinal cord and brain stem nuclei implicated in pain., Clonidine administered as an adjuvant with local anesthetic ropivacaine prolongs the duration of analgesia. A combination of epidural clonidine with bupivacaine as well as epidural ropivacaine with various adjuvants has been extensively studied for labor analgesia. We hypothesized that admixture of clonidine to epidural ropivacaine will provide optimal block characteristics for infraumbilical surgeries. Hence, this study was designed to evaluate the combination of clonidine with epidural ropivacaine in comparison to ropivacaine alone for block characteristics, hemodynamics, and any adverse events.
| Materials and Methods|| |
After getting Institutional Ethical Approval (letter no. IGIMS/IEC/21/2012) and Clinical Trial Registry India (CTRI/2013/12/004219). We enrolled 102 healthy patients aged between 18 and 60 years, of either sex, of American Society of Anesthesiologists (ASA) Grade I or II scheduled for infraumbilical surgeries. This double-blind randomized controlled clinical trial was conducted during year 2012-2014. A written informed consent of the patient and their relatives was also taken. Patients with a history of end-organ dysfunction, morbid obesity, pregnancy, hypersensitivity to study drugs, and general contraindication to epidural anesthesia were excluded. After enrollment in the study, patients were explained about procedure and postoperative pain assessment on 10 points of which 0 indicates “no pain” and 10 represented “maximum unbearable pain.”
All patients were randomly (computer-generated randomization and concealment via sealed opaque envelope technique) assigned to two equal groups to receive epidural anesthesia: Group R to receive 20 ml of 0.75% ropivacaine and Group RC to receive 20 ml of 0.75% ropivacaine plus clonidine 75 μg through epidural catheter to epidural space. Randomization was performed by an anesthesiologist not involved in studied drug preparation. Further procedure and monitoring were performed by another investigator unaware of group allocation; patients were also blinded to the drug regimen utilized for epidural anesthesia.
Premedications included tablet alprazolam (0.25 mg) and tablet ranitidine (150 mg) administered orally with a sip of water on the evening before surgery. Intravenous access was secured using 18G cannula in a nondominant hand and the patient was preloaded with 10 ml/kg lactated Ringer's solution. Patients were placed in the lateral decubitus position, and an 18G Tuohy needle (Epican Tuohy Needle® 18G; Braun, Melsungen, Germany) was introduced at the L3–L4 or L4–L5 interspace in the midline under all aseptic and antiseptic precautions. Epidural catheter was placed after locating the epidural space with the loss of resistance technique (using a syringe containing air). After ensuring no cerebrospinal fluid or blood backflow from the epidural catheter, a test dose of 3 ml lignocaine containing epinephrine (1:200,000) was administered through epidural catheter. The electrocardiogram (ECG) was observed for 2–3 min for tachycardia or any T-wave change. In the absence of significant ECG change, patients were turned in the supine position, and allocated drug was administered over 3 min. Intraoperative fluid was given according to Holliday-Segar formula. General anesthesia was planned in case of failed or inadequate block and the patient was excluded from the study. The time of epidural injection of the study drug was noted as “zero time.”
The onset of sensory block was tested using pinprick method with a 27G hypodermic needle. The time of onset was taken from zero time to loss of bilateral pinprick sensation. The time interval from zero time to the patient's inability to lift the straight extended leg (modified Bromage scale 1) was recorded as onset time for motor block. The highest level of sensory blockade was noted and recorded after the onset of motor block. Degree of motor block was assessed by the modified Bromage scale: 0 – able to raise leg straight, full flexion of knees and feet (full movement); 1 – inability to raise leg, just able to flex knees, full flexion of feet; 2 – unable to flex knees, but some flexion of feet possible; and 3 – unable to move legs or feet (no movement). The duration of motor block was taken from zero time to complete regression of motor block (ability to lift the extended leg, i.e., modi fied Bromage scale 0). The duration of sensory analgesia was noted and recorded from the time when epidural drug was given to postoperative follow-up till the patient complained of pain. Heart rate, blood pressure, and respiratory rate were monitored at 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, and 180 min after administration of epidural block.
The primary outcome of the study was to measure the duration of sensory analgesia. The secondary outcomes were onset of sensory block, onset of motor block, highest level of sensory block, degree of motor block, duration of motor block, and quality of sensory blockage as measured by visual analog scale. Hemodynamic parameters (heart rate and blood pressure) and adverse effects such as respiratory depression, nausea, vomiting, sedation, retention of urine, hypotension, and bradycardia were observed for, recorded, and treated accordingly.
The sample size was calculated to be 26 in each group considering a projected difference of 15% between the two groups for the duration of analgesia to be significant at 95% confidence limits, a Type 1 error of 0.05, and a power of 90%. To avoid sampling error, this value was multiplied by 1.5, and 40 patients were included in each study group. Re-randomization was done for the patients who were excluded from the study.
Descriptive statistics such as mean, median, and range were calculated for the study outcomes. Statistical comparison was made by comparison between the groups by applying Chi-square test to a contingency table for categorical data and two-sample t-test and independent t-test for numerical data.
| Results|| |
A total of 102 patients were assessed for eligibility, of which 16 patients did not meet the inclusion criteria and 6 patients were excluded during the study period, as shown in consort diagram [Figure 1]. The study groups were comparable in terms of demographic profile, baseline hemodynamic variables, ASA status, and type of surgical procedure [Table 1].
The onset of sensory block was shorter in Group RC as compared to Group R. The mean time for onset of sensory block was 12.90 ± 1.39 in Group R and 8.05 ± 1.45 min in Group RC, and the difference between the two groups was very highly significant (P < 0.0001) [Table 2]. However, once sensory level was established at T6–T7 level, there was no noticeable difference in sensory anesthesia in either of the group throughout the surgical procedure [Table 3]. The onset of motor block was shorter in Group RC as compared to Group R. The mean time for onset of motor block was 30.25 ± 2.35 min in Group R and 28.23 ± 2.91 min in Group RC, and the difference between the two groups was highly significant (P < 0.001) [Table 4]. The duration of motor block was 281.25 ± 25.58 min in Group R and 244.88 ± 6.51 min in Group RC, and it was statistically very highly significant between the two groups (P < 0.0001) [Table 4]. The mean duration of sensory analgesia was 362.60 ± 5.96 min in Group R and 451.10 ± 13.79 min in Group RC and statistically very highly significant between the two groups (P < 0.0001) [Table 2]. Baseline hemodynamics was comparable between the two groups. Five minutes after epidural drug administration we observed fall in systolic blood pressure in both groups but more pronounced in Group RC which remains significant till 30 min after drug administration. After that, systolic blood pressure was comparable between the two groups [Table 5].
|Table 5: Comparison of systolic blood pressure between the groups at different time intervals|
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| Discussion|| |
Epidural analgesia with local anesthetics has the advantages of optimal perioperative conditions with better postoperative outcome with fewer occurrences of complications. Addition of adjuvant to local anesthetic epidurals increases the duration of analgesia and intensity of the block with minimal stress response, thereby resulting in early ambulation and less postoperative morbidity. Although intrathecal clonidine as an adjuvant to ropivacaine has been studied extensively, there is a paucity of literature on the epidural use of ropivacaine and clonidine for infraumbilical surgeries.
There are numerous studies on the use of epidural ropivacaine for inducing painless labor and deliveries, but literature available for infraumbilical surgeries are not much. Although ropivacaine is slightly less potent as compared to bupivacaine, its pharmacological profile is almost comparable to the latter. Various studies and literary evidence have concluded that cardiotoxicity of ropivacaine is far less than that of bupivacaine., The dose of ropivacaine is much higher as compared to bupivacaine when used epidurally.
Clonidine is an alpha-2 adrenoceptor agonist, which was widely used as an antihypertensive and also being used as an adjunct to local anesthetics in neuraxial block. A study by Brichant et al. concluded that 75 μg of clonidine is the optimal epidural dose when added to bupivacaine for analgesia, as smaller doses were not serving the purpose of adequate analgesia while larger doses were associated with bradycardia, hypotension, sedation, and other side effects. Hence, we administered a single dose of 75 μg for operative purpose while top-up doses of 50 μg clonidine were administered with 0. 2% ropivacaine for the postoperative pain relief.
In our study, the mean time for onset of sensory and motor block in Group RC is significantly earlier than Group R which explains that clonidine intensifies the block characteristics. Our result of the study was similar to the result studied by Bajwa et al.
The mean duration of motor (281.25 ± 25.0 vs. 244.88 ± 6.51 min) and sensory block (451.10 ± 13.79 vs. 362.60 ± 5.96 min) was significantly prolonged in Group RC than Group R. The result of our study was similar to other study authored by Bajwa et al. and Ogun et al.
In our study, the incidence of slight tachycardia was comparable in both the groups up to 20 min, which can be explained on the basis of sympathetic block in the lower extremities and decreased venous return. There were no episodes of bradycardia in either group. A study by Sia concluded that clonidine does not produce an additional hypotensive effect when combined with local anesthetics, and there is a potential for exacerbating hemodynamic depression from the combination of intrathecal clonidine with opioids. None of our patients experienced respiratory depression, and the mean RR between both the groups was statistically not significant and was similar to studies conducted by Katz et al., Brockway et al., and by Finucane et al.
Our study has two main limitations. First, patient and surgeon satisfaction was not checked. Second, the sample size was very small and these results may vary from investigations performed on other ethnic groups due to variations in pain or drug sensitivity.
| Conclusion|| |
Thus, we conclude that clonidine augments the efficacy of epidural ropivacaine that leads to better response in term of block onset, duration, and other block characteristics without any undesirable side effect in Group RC.
We would like to express special thanks to all consultants of the anesthesia department for helping and guiding us to write this manuscript. We would also like to thank all technical staff, without whom the study could not have been completed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]