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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 21
| Issue : 2 | Page : 147-152 |
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A comparative study on the effects of intrathecal chloroprocaine alone and with fentanyl or clonidine for infraumbilical surgeries
Arvind Khare, Kavita Jain, Mukut Kanwar, Beena Thada, Veena Mathur, Maina Singh
Department of Anaesthesiology, JLN Medical College, Ajmer, Rajasthan, India
| Date of Submission | 18-Mar-2020 |
| Date of Decision | 26-May-2020 |
| Date of Acceptance | 26-Jun-2020 |
| Date of Web Publication | 19-Sep-2020 |
Correspondence Address:
Dr. Beena Thada
Iw/3/7 Behind Isolation Ward, JLN Hospital Campus, Ajmer - 305 001, Rajasthan
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/TheIAForum.TheIAForum_25_20
Background and Aims: Antioxidant- and preservative-free form of 2-chloroprocaine (1%) has been re-emerged as a short-acting local anesthetic for use in spinal anesthesia. This study aimed to compare the effects of intrathecal 2-chloroprocaine (1%) alone or with fentanyl or clonidine used as an adjuvant for infraumbilical surgeries.
Materials and Methods: Ninety patients of either sex aged between 18 and 60 years with American Society of Anesthesiologists Grade I or II scheduled for infraumbilical surgeries were randomly allocated into three groups (n = 30). Group C received intrathecal 1% 2-chloroprocaine 5 ml (50 mg) + 0.5 ml normal saline, Group CF received intrathecal 1% 2-chloroprocaine 5 ml (50 mg) + 0.5 ml fentanyl (25 μg), and Group CC received intrathecal 1% 2-chloroprocaine 5 ml (50 mg) + 0.5 ml clonidine (15 μg) diluted in normal saline. The onset and duration of sensory and motor blocks, time for demand of rescue analgesia, hemodynamics, and side effects were observed.
Results: The onset of sensory and motor blocks was significantly earlier, and the duration of sensory and blocks and time to demand of rescue analgesia were significantly prolonged in both Group CF and Group CC as compared to Group C. Among Groups CF and CC, the duration of sensory and blocks and time to demand of rescue analgesia were significantly prolonged in Group CC.
Conclusion: Intrathecal clonidine (15 μg) proved to be a better alternative to fentanyl (25 μg) used as an adjuvant to 1% 2-chloroprocaine for infraumbilical surgeries.
Keywords: 2-chloroprocaine, clonidine, fentanyl, motor block, sensory block, spinal anesthesia
How to cite this article:
Khare A, Jain K, Kanwar M, Thada B, Mathur V, Singh M. A comparative study on the effects of intrathecal chloroprocaine alone and with fentanyl or clonidine for infraumbilical surgeries. Indian Anaesth Forum 2020;21:147-52 |
How to cite this URL:
Khare A, Jain K, Kanwar M, Thada B, Mathur V, Singh M. A comparative study on the effects of intrathecal chloroprocaine alone and with fentanyl or clonidine for infraumbilical surgeries. Indian Anaesth Forum [serial online] 2020 [cited 2023 Jun 7];21:147-52. Available from: http://www.theiaforum.org/text.asp?2020/21/2/147/295381 |
| Introduction | |  |
Spinal anesthesia is a reliable and safe technique for infraumbilical surgeries.[1] Antioxidant- and preservative-free form of 1% 2-chloroprocaine is once again available for use in subarachnoid block[2] due to its rapid onset and short duration of action, a predictable block height, and time to complete regression. Hence, in this study, we have used intrathecal chloroprocaine 1% for infraumbilical surgeries. It is a local anesthetic with short duration of analgesia, so we tried to overcome this limitation by addition of intrathecal fentanyl or clonidine as an adjuvant to it.
Intrathecal fentanyl is adjuvant of choice among all opioids with local anesthetics as it improves the quality of sensory block and duration of analgesia without significantly prolonging motor recovery.[3],[4] However, pruritus, nausea, vomiting, and respiratory depression are other common side effects for which search for nonopioid adjuvant goes on.[5]
Intrathecal clonidine is an alternative to neuraxial opioid with local anesthetics for control of pain, and it prolongs both sensory and motor blockades and it has proven to be a potent analgesic and free of the opioid-related side effects.[5],[6]
Although literature is there with other local anesthetics such as bupivacaine or ropivacaine,[7],[8],[9] none of the studies have compared intrathecal fentanyl or intrathecal clonidine as an adjuvant to intrathecal 1% 2-chloroprocaine. Hence, based on the above hypothesis, this prospective randomized double-blind study was aimed to compare the effect of intrathecal 1% 2-chloroprocaine 50 mg alone and with fentanyl l 25 μg or clonidine 15 μg used as an adjuvant for infraumbilical surgeries for the duration of sensory block as the primary objective. The secondary objectives were onset of sensory block, onset and duration of motor block, hemodynamic effects (heart rate [HR] and blood pressure [BP]), postoperative return of voiding function, and adverse effects, if any.
| Materials and Methods | | |
This prospective randomized double-blind study was approved by the local ethical committee of our institution, and written and informed consent of patients was taken. This study was registered at the Clinical Trials Registry-India (CTRI/2019/02/024049) and conducted between August 2018 and August 2019. A total of 90 patients of either sex, age between 18 and 60 years, belonging to American Society of Anesthesiologists (ASA) physical status I and II, scheduled for infraumbilical surgeries of short duration (<60 min) were included in this study. Any patient with known allergy to study drugs, all well-known contraindications to spinal anesthesia, patients with any deformity, and patients having cardiovascular, renal, and neurologic diseases were excluded.
The study population was randomly divided into three groups by a computer-generated table of random numbers (n = 30) in each group. 2-chloroprocaine group (Group C) received intrathecal administration of 1% 2-chloroprocaine 5 ml (50 mg) + 0.5 ml normal saline, 2-chloroprocaine + fentanyl group (Group CF) received intrathecal administration of 1% 2-chloroprocaine 5 ml (50 mg) + 0.5 ml injection fentanyl (25 μg), and 2-chloroprocaine + clonidine group (Group CC) received intrathecal administration of 1% 2-chloroprocaine 5 ml (50 mg) + 0.5 ml injection clonidine (15 μg) diluted in normal saline. To ensure double blinding, the study drug was prepared by an anesthesiologist and given by another anesthesiologist who were not involved in the study. All patients were kept nil by mouth for a minimum period of 6 h before the surgical procedure. After arrival of the patient in the operation theater, an intravenous cannula 20G was inserted and crystalloid infusion was started. All routine monitors such as electrocardiography, noninvasive BP, and pulse oximetry were connected, and baseline hemodynamic parameters were recorded. Injection midazolam 0.01 mg/kg intravenous was given to relieve anxiety as premedication. Under all aseptic precautions, spinal anesthesia was performed in a patient with sitting position at L3–L4 subarachnoid space using a 25G spinal needle. After clear and free cerebrospinal fluid flow achieved, patients received either 5 ml (50 mg) of 1% 2-chloroprocaine alone or along with adjuvant fentanyl (25 μg) or clonidine (15 μg) according to their group allocated. After the completion of spinal injection, the patients were immediately placed supine. The independent blinded observer evaluated the sensory and motor blocks every 2 min (min) for 10 min, then every 5 min for 20 min and then every 10 min for the next 30 min, and finally, every 15 min until the sensory block had regressed to the S2 dermatome. During surgery, the patient's HR, BP, and pulse oximetry were recorded at 1, 3, 5, 10, 15, 30, and 60 min and every 15 min. After achieving T10 level of sensory block, surgery was started.
Sensory block was assessed in dermatomal areas of T6 to S1 and S2 with a blunt 23G hypodermic needle using the following scaling system – 0 = normal sensation, 1 = loss of prick sensation (analgesia), and 2 = loss of touch sensation (anesthesia). The onset of sensory block was the time from intrathecal injection to the time taken to achieve T10 dermatome level. The duration of sensory block (was the time taken to regress sensory block up to S1 dermatome in the heel) was also noted. Motor block was assessed using the Modified Bromage Scale:[10] 1 – complete block (unable to move feet or knee), 2 – almost complete block (able to move feet only), 3 – partial block (just able to move knees), 4 – detectable weakness of hip flexion while supine (full flexion of knees), 5 – no detectable weakness of hip flexion while supine, and 6 – able to perform partial knee bend. The onset and duration of motor block were noted.
The Visual Analog Scale (VAS)[11] for pain assessment was recorded before the start of the procedure and postoperatively until the patient demanded rescue analgesia. Time to demand of rescue analgesia was defined as the time from intrathecal injection to the time when VAS score was recorded >3 (rescue analgesia). Time to return of voiding function postoperatively was assessed postoperatively by asking whether the patient was able to void or not. Side effects such as bradycardia (HR < 50 beats/min), hypotension (decrease in systolic BP > 30% from the baseline), nausea, vomiting, and pruritus were observed.
Statistical analysis
Based on a previous study by Casati et al.,[12] the sample size was calculated to be 30 patients (n = 30) using Power and Sample Size Calculator (PS version 3.0.0.34) with power of 80% and 95% confidence level with α error of 0.05% test. Statistical analysis was carried out using SPSS software version 16.0 (SPSS Inc., Chicago, IL, USA). All the numerical data were expressed as mean ± standard deviation, whereas the categorical data were expressed as numbers or frequency (%). Standard qualitative and quantitative tests were used to compare the data (e.g., paired and unpaired Student's t-test and Chi-square test). Data were considered statistically significant, with P < 0.05.
| Results | | |
One hundred and twenty patients were assessed for eligibility, of which 30 patients were excluded since they did not fulfill the study criteria and the rest 90 patients were included in the study [Figure 1]. All groups were comparable in terms of demographic profile, duration, and type of surgery in all three groups, i.e., Group C, Group CF, and Group CC [Table 1]. The onset of sensory block was significantly earlier in both Group CF and Group CC as compared to Group C (P = 0.04). The mean time for two-segment regression and duration of sensory block were significantly prolonged in both Group CF and Group CC as compared to Group C (P = 0.001) [Table 2]. The onset of motor block was significantly earlier in both Group CF and Group CC as compared to Group C (P = 0.001). The duration of motor block, time for demand of rescue analgesia, and time to return of voiding functions were significantly prolonged in both Group CF and Group CC as compared to Group A (P = 0.001) [Table 3]. | Table 3: Motor blockade characteristics, time for demand of rescue analgesia, and time to return of voiding functions (mean±standard deviation)
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There was no significant difference in hemodynamic parameters such as mean HR [Figure 2] and mean BP [Figure 3] at different time intervals. Hypotension was more in Group C than Group CF, and CC, bradycardia, and pruritus were more in Group CF than Groups C and CC, but they were nonsignificant. Postdural puncture headache and transient neurological symptoms were not observed in any patients [Table 4].
| Discussion | | |
Majority of infraumbilical surgeries are done under spinal anesthesia using local anesthetic such as bupivacaine and ropivacaine with or without addition of adjuvant, and recently, 2-chloroprocaine 1% is also being used. Amino-ester local anesthetic 2-chloroprocaine has an early onset and short duration of action. Several case reports of neurological toxicity were noted in 1980 due to inadvertent intrathecal 2-chloroprocaine injections intended for epidural delivery[13],[14] which was attributed to its preservative sodium bisulfite.[15],[16] Antioxidant- and preservative-free form of 1% 2-chloroprocaine is once again available for use in subarachnoid block[2] as 10 mg/ml solution nowadays.
The aim of this study was to compare the effects of intrathecal 1% 2-chloroprocaine 5 ml (50 mg) alone and with fentanyl (25 μg) or clonidine (15 μg) used as an adjuvant for infraumbilical surgeries done under spinal anesthesia. The duration of sensory block was the primary objective of our study.
In our study, we found that the mean time of the onset of sensory block was 2.59 ± 0.90 min in Group C, 2.38 ± 0.70 min in Group CF, and 2.06 ± 0.47 min in Group CC, with P < 0.04, which was statistically significant. Thus, we observed that the onset of sensory block was significantly earlier in both Group CF and Group CC as compared to Group C. Among Groups CF and CC, there was no statistically significant difference in the onset of sensory block as their mean difference is 0.32, with P = 0.24. This parameter was explained by Casati et al.[12] study in which they evaluated the dose–response relationship of 2-chloroprocaine (doses 30 mg, 40 mg, and 50 mg). Onset time was similar in the three groups. In our study, the dose of 2-chloroprocaine was the same in all three groups, so the difference in the onset of sensory block was attributed by addition of fentanyl[3] or clonidine[5] with 2-chloroprocaine.
Vath and Kopacz[3] and Davis and Kopacz[5] found that the mean time for two-segment regression was shorter in the 2-chloroprocaine group than the fentanyl and clonidine groups, respectively, whereas Bajwa et al.[7] found that it was shorter in Group BF (132 ± 14.56 min.) than in Groups BC (136.56 ± 12.67 min), P = 0.35, which was not significantly similar to our study where it was 50.93 ± 10.14 min in Group C, 61.76 ± 8.79 min in Group CF, and 62.17 ± 7.04 min in Group CC, with P = 0.001, which was statistically significant. Thus, we observed that it was significantly prolonged in both Group CF and Group CC as compared to Group C. Among Groups CF and CC, it was more prolonged in Group CC but not statistically significant as their mean difference is − 0.405, with P = 1.0.
Vath and Kopacz[3] and Davis and Kopacz[5] found that the duration of sensory block was shorter in the 2-chloroprocaine group than with the fentanyl and clonidine groups, respectively. In our study, it was 91.56 ± 16.87 min in Group C, 130.80 ± 23.49 min in Group CF, and 146.03 ± 22.46 min in Group CC, with P = 0.001, which was statistically significant. Thus, we observed that it was significantly prolonged in both Group CF and Group CC as compared to Group C. Among Groups CF and CC, it was more prolonged in Group CC as their mean difference is − 15.23, with P = 0.019, which was statistically significant, suggesting that intrathecal clonidine prolongs sensory block more than fentanyl. Our result also coincides with the results shown by other authors Bajwa et al.,[7] Routray et al.,[8] Bathari et al.,[9] and Kaushik[17] where they found that the duration of sensory block was more prolonged in the clonidine group as compared to the fentanyl group (P <0.05).
Routray et al.[8] and Bajwa et al.[7] found that the mean time of the onset of motor block was comparable in both Group C and Group F (P > 0.05) similar to our study where it was 3.07 ± 0.65 min in Group C, 2.45 ± 0.66 min in Group CF, and 2.34 ± 0.65 min in Group CC, with P = 0.001, which was statistically significant. Thus, we observed that it was significantly earlier in both Group CF and Group CC as compared to Group C. Among Groups CF and CC, there was no statistical significant difference in the onset of motor block as their mean difference is 0.11, with P = 1.0. This finding could be attributed to alpha-adrenergic action of clonidine.[18],[19]
Davis and Kopacz et al.[5] found that the duration of motor block was prolonged in group 2-chloroprocaine + clonidine as compared with group 2-chloroprocaine, with P = 0.0038. Routray et al.[8] found that it was prolonged in Group C as compared to Group F, which was statistically significant (P <0.001) similar to our study where it was 78.73 ± 19.36 min in Group C, 122.66 ± 13.91 min in Group CF, and 138.5 ± 15.4 min in Group CC, with P = 0.001, which was statistically significant. Thus, we observed that it was significantly prolonged in both Group CF and Group CC as compared to Group C. Among Groups CF and CC, it was more prolonged in Group CC as their mean difference is − 15.83, with P = 0.001, which was statistically significant due to alpha-adrenergic action of clonidine.[18],[19]
In our study, the mean time to demand of rescue analgesia was 90.48 ± 17.97 min in Group C, 128 ± 15.81 min in Group CF, and 140 ± 15.42 min in Group CC, with P = 0.001 (S). Thus, we observed that it was significantly prolonged in both Group CF and Group CC as compared to Group C. Among Groups CF and CC, it was more prolonged in Group CC as their mean difference is − 14.83, with P = 0.001 (S), which was statistically significant. Similar results were observed by other authors Bajwa et al.,[7] Routray et al.,[8] Bathari et al.,[9] and Kaushik[17] where they found that it was longer in the clonidine group as compared to the fentanyl group (P <0.05).
In our study, the time to return of voiding function was 212.9 ± 43.7 min in Group C, 267.3 ± 83.0 min in Group CF, and 268.8 ± 58.0 min in Group CC, with P = 0.001, which was statistically significant. Thus, we observed that it was significantly earlier in Group C due to rapid hydrolysis of 2-chloroprocaine hydrochloride by pseudocholinesterase in plasma[20] similar to Vath and Kopacz[3] and Davis and Kopacz[5] studies.
In our study, there was no significant difference in hemodynamic parameters (mean HR and mean BP) among the three groups at different time intervals similar to other studies.[3],[5],[8] None of the patients had residual neurological deficit, postdural puncture headache, or transient neurological symptom.
| Conclusion | | |
Intrathecal clonidine proved to be a better alternative when used as an adjuvant to 1% 2-chloroprocaine for infraumbilical surgeries done under spinal anesthesia as it was associated with similar onset but prolonged duration of sensory and motor block along with prolong duration of time to demand of rescue analgesia without increasing time to return of voiding function with stable hemodynamics and minimal adverse effects as compared to intrathecal fentanyl.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflict of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]
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