|Year : 2017 | Volume
| Issue : 1 | Page : 33-36
Effect of clonidine as an adjuvant for wound infiltration following caesarean section
MS Nataraj, Sathisha, RM Mohan Kumar
Department of Anaesthesiology, Employees' State Insurance Medical College, Bengaluru, Karnataka, India
|Date of Web Publication||1-Jun-2017|
M S Nataraj
Department of Anaesthesiology, Employees' State Insurance Medical College, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Context: Local anesthetics provide simple and safe means of postoperative analgesia when used for local infiltration. Role of clonidine as an adjuvant is being increasingly explored because of its peripheral action. Aims: To investigate the analgesic effect of clonidine when added to bupivacaine for wound infiltration following cesarean section. Settings and Design: A prospective, randomized double-blind study was conducted after Institutional Ethical committee approval. Materials and Methods: Sixty American Society of Anesthesiologists (ASA) physical status I or II parturients scheduled for elective cesarean delivery through pfennensteil incision were included after consent. Patients were randomly allocated to two groups; Group B (control group) received 30 ml of 0.25% bupivacaine for wound infiltration and Group C received 3 μg/kg clonidine mixed with 0.25% bupivacaine. Time to first request of analgesia, total tramadol consumption, visual analog scale (VAS) pain scores, sedation, any complications were recorded at 6th hourly interval till 24 hours. Statistical analysis used: Data and perioperative details are summarized as mean ± SD. Statistical analysis for significance was done using two sample unpaired t-test. Results: Demographic and surgical parameters were comparable. Time for first request of analgesia was prolonged in group C (254 ± 26 min vs group B 149 ± 12 min;P < 0.0001), total tramadol consumption was significantly less (P < 0.001), and pain scores were lower (P < 0.001) in clonidine group up to 12 h. Conclusions: Addition of 3 μg/kg of clonidine to 0.25% bupivacaine 30 ml for wound infiltration after cesarean section prolongs the duration of analgesia, reduces opioid consumption, and produces mild sedation without complications.
Keywords: Cesarean section, clonidine, wound infiltration
|How to cite this article:|
Nataraj M S, Sathisha, Mohan Kumar R M. Effect of clonidine as an adjuvant for wound infiltration following caesarean section. J Obstet Anaesth Crit Care 2017;7:33-6
|How to cite this URL:|
Nataraj M S, Sathisha, Mohan Kumar R M. Effect of clonidine as an adjuvant for wound infiltration following caesarean section. J Obstet Anaesth Crit Care [serial online] 2017 [cited 2020 Dec 3];7:33-6. Available from: https://www.joacc.com/text.asp?2017/7/1/33/207389
| Introduction|| |
Acute postoperative pain after caesarean section may delay the institution of breast feeding, patient recovery, and discharge from hospital. Local infiltration analgesia is an analgesic technique that has gained popularity since it was brought to attention by Kerr and Kohan in 2008. A multimodal approach using a combination of local anesthetic and opioid or nonopioid such as clonidine improves the quality of postoperative analgesia and minimizes adverse effects.
Clonidine, an alpha-2 adrenergic receptor agonist has potent analgesic properties. Addition of clonidine to local anesthetic increases the duration of anesthesia in intrathecal, epidural, and peripheral nerve blockade. Peripheral analgesic action of clonidine has been proposed after topical application and after intra-articular administration. Use of clonidine with local anesthetic for skin infiltration have shown conflicting results., This study was conducted to evaluate the effect of addition of clonidine to bupivacaine for wound infiltration following cesarean section.
| Patients and Methods|| |
The study was conducted between January 2014 and December 2016 after obtaining Institutional ethical committee approval. It was a randomized double-blind study. Sixty American Society of Anesthesiologists (ASA) physical status I or II parturients scheduled for elective lower segment caesarean delivery through Pfannensteil incision under spinal anesthesia were selected for the study. Exclusion criteria included body mass index >35 kg/m 2, major systemic disease, chronic pain disorders, patients receiving adrenoreceptor agonists or antagonists, and allergies to any medication included in the study protocol. All patients underwent preoperative assessment on the day prior to the surgery, and written informed consent was obtained for participation in the study. They received premedication with oral ranitidine 150 mg and metoclopramide 10 mg in the night and morning of the surgery. Patients were randomly allocated to two groups using a computer generated table of random numbers. Group B (control group) patients received 30 ml of 0.25% bupivacaine plain for wound infiltration at the end of the surgery. Group C patients received wound infiltration with 3 μg/kg clonidine mixed with 0.25% bupivacaine at the end of surgery. The person who prepared the study drug did not participate further in the study.
In the operating room, all parturients were monitored by noninvasive blood pressure, electrocardiogram, and pulse oximetry. 18 G intravenous (IV) access was secured and Ringer's lactate preload of 10 ml/kg body weight was given. Spinal anesthesia was performed in left lateral position at L2-L3 or L3-L4 interspace with 0.5% hyperbaric bupivacaine 2 ml. The parturients were placed in a supine position with a wedge under right buttock for left uterine displacement and supplemental oxygen was delivered through a facemask at 5 L/min. Surgery was allowed to proceed after T4 to T6 sensory blockade to pinprick sensation had been established. Intravenous crystalloids and ephedrine were administered as needed to treat hypotension. All patients received intravenous infusion of oxytocin 10 intrauterine after delivery. Intravenous metoclopramide 10 mg was administered intraoperatively for nausea or vomiting. At the beginning of wound closure 30 ml of the study drug was infiltrated into skin and subcutaneous planes. Postoperative analgesia was provided with diclofenac suppository 100 mg 12th hourly and intravenous paracetamol 1 g 8th hourly. Additional doses of 50 mg intravenous tramadol was given on demand for breakthrough pain.
Postoperatively, patients were evaluated for pain, sedation and any complications like bradycardia for the first 24 hours by an investigator blinded to the group assignment. Pain levels at rest and on coughing were quantified on a 10 cm visual analog scale (VAS) pain score with 0 representing no pain and 10 representing the worst imaginable pain. Sedation level was evaluated on a 4 point scale (1 = fully awake; 2 = somnolent but responds to verbal command; 3 = somnolent but responds to tactile stimuli; and 4 = somnolent but responds to painful stimuli).
Time to first request of analgesia after surgery, total tramadol consumption in 24 h, and VAS pain scores at rest and on coughing were recorded at 6th hourly interval till 24 hours.
Demographic data and perioperative details are summarized as mean ± SD. Statistical analysis for significance was done using two sample unpaired t-test. Pain scores were analysed using Mann–Whitney Rank Sum test. P < 0.05 was considered as significant and P < 0.005 was considered as highly significant. Chi square test and Fischer exact test were applied as applicable.
| Results|| |
The demographic characteristics like age, height, and weight were comparable between the groups and statistically not significant (P > 0.05) [Table 1].
Spinal block characteristics showed no difference in terms of duration for two segment regression (P = 0.228) and complete regression of the block (P = 0.742) between the two groups.
There was a significant increase in the duration of analgesia in the clonidine group (group C) compared to the control group. The analgesic duration in group C lasted for 254.00 ± 26.87 min compared to 149.67 ± 12.02 min in the control group, which is statistically very significant (P < 0.001).
The total tramadol consumption in the first 24 h in group C is (73.33 ± 31.99) mg compared to (203.33 ± 35.187) mg in the control group, which is highly significant (P < 0.001).
The sedation score at 1 hour after surgery in clonidine group was two (P = 0.03) compared to one in control group. There was no incidence postoperative nausea or vomiting in both the groups [Table 2].
| Discussion|| |
Local anesthetic infiltration into surgical wounds is a relatively low risk and cost effective method to provide postoperative analgesia following gynecological and general surgeries. By adding various adjuvants such as epinephrine, opioids, clonidine, and the duration of analgesia can be prolonged.
Clonidine, an alpha-2 adrenergic agonist, was initially used for its antihypertensive properties. The large expression of alpha-2 receptors in the central nervous system, i.e., loecus coeruleus and dorsal horn of the spinal cord, has eventually focused the interest of that drug on centrally mediated sedation and analgesia. Specific peripheral effects of clonidine appear less obvious because alpha-2 adrenoreceptors are not present on the axon of the normal peripheral nerve. In one study, clonidine without LA given through an interscalene catheter provided better analgesia compared with the systemic administration of the same dose. Similarly, in healthy volunteers, sensory, and motor block were significantly prolonged when clonidine alone was administered into the axillary plexus sheath. Data from clinical and experimental trials testing the effect of peripheral clonidine alone have remained inconclusive.
Clonidine increases the risk of bradycardia, arterial hypotension, and sedation, and it is most likely the result of systemic reabsorption. For rational decision-making it is important to know how often these adverse effects happen, whether they depend on the dose of clonidine, and whether they are clinically relevant. These typical, clonidine-related, adverse effects may be considered as minor harm. However, they all have the potential to interfere with early mobilization. Clonidine in a dose of more than 300 μg is associated more frequently with these adverse effects. In our study, we used a dose of 150 μg which is considered safe.
The possible effect of clonidine in extending duration of peripheral nerve blocks is attributed to the enhancing effect on bupivacaine induced inhibition of C-fiber action potential, release of encephalin-like substances which produce a peripheral analgesic effect. Clonidine also inhibits the release of norepinephrine from prejunctional alpha 2-adrenoreceptors in the periphery.
In our study, we observed patients who received 3 μg/kg clonidine as an adjuvant with 0.25% bupivacaine for wound infiltration following caesarean section showed a significant prolongation of analgesia (P < 0.001) and decrease in total tramadol consumption over 24 h (P < 0.001) and an acceptable level of postoperative sedation without any adverse effects.
In a study conducted by Raghuwanshi et al., clonidine was used in a dose of 30 μg for wound infiltration following tympanoplasty along with 12 ml of 2% lignocaine. They observed decrease in pain scores in the first hour following infiltration. The total analgesic requirement over 24 h did not show significant difference. This is in contrast to our study where there was significant decrease in the total dose of tramadol consumption over 24 h and also a significant increase in the duration of analgesia for more than 4 h. The dose of clonidine used in our study was 150 μg, which was more compared to 30 μg in their study. We chose 3 μg/kg of clonidine for wound infiltration similar to the one used by Elliot  in their study on addition of clonidine for wound infiltration following hernia repair. They did not observe any change in analgesic duration or the requirement of analgesics. In fact there was a higher incidence of adverse effects in clonidine group such as bradycardia requiring treatment. This is in contract to our study where no the patients in clonidine group had any adverse events.
Clonidine when used in a dose of 1 μg/kg with 1% ropivacaine for peritonsillar fossa infiltration by Gionnoni et al. was shown to prolong the duration of analgesia without any adverse effects (P < 0.05). This finding is similar to our study suggesting a peripheral action of clonidine. Bharti et al. used clonidine in a dose of 3 μg/kg intravenous or for wound infiltration following open cholecystectomy under general anesthesia for postoperative pain relief. They observed that clonidine when used both as intravenous route or following wound infiltration provided effective postoperative analgesia. The incidence of adverse effects was less with wound infiltration. This supports our finding of peripheral analgesic action of clonidine without adverse effects.
Selvaraj studied the effect of clonidine for postoperative analgesia when used as an adjuvant for local anesthesia in wound infiltration. One hundred patients scheduled for abdominal hysterectomy were randomized to receive either clonidine 3 μg/kg with bupivacaine 0.25% 45 ml or bupivacaine alone. Patients in the clonidine group had better pain score, longer duration of analgesia, and required less of rescue analgesia.
| Conclusion|| |
To conclude, addition of 3 μg/kg of clonidine to 0.25% bupivacaine 30 ml for wound infiltration after cesarean section under spinal anesthesia prolongs the duration of analgesia, reduces opioid consumption and produces mild sedation without complications.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Kehlat H, Dahl JB. Anaesthesia and challenges in postoperative recovery. Lancet 2003;362:1921-8.
White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg 2005;101:S5-22.
Peden CJ. Prys-Roberts C. The alpha-2 adrenoceptor agonists and anaesthesia. In: Prys-Roberts C, Brown BR Jr, editors. International Practice of Anaesthesia. Oxford: Butterworth Heinemann; 1996. pp. 1-14.
Eisenach JC, De Kock M, Klimscha W. α2-Adrenergic agonists for regional anesthesia; a clinical review of clonidine (1984-1995). Anesthesiology 1996;85:655-74.
Gentili M, Juhel A, Bonnet F. Peripheral analgesic effect of intra-articular clonidine. Pain 1996;64:593-6.
Elliot S, Eckersall S, Fligelstone L, Jothilingam S. Does the addition of clonidine affect duration of analgesia of bupivacaine wound infiltration in inguinal hernia surgery? Br J Anaesth 1997;79:446-9.
Giannoni C, White S, Enneking KF, Morey T. Ropivacaine with or without clonidine improves paediatric tonsillectomy pain. Arch Otolaryngol Head Neck Surg 2001;127:1265-70.
Waite A, Gilliver SC, Masterson GR, Hardman MJ, Ashcroft GS. Clinically relevant doses of lidocaine and bupivacaine do not impair cutaneous wound healing in mice. Br J Anaesth 2010;104:768-73.
Ozyilmaz K, Ayoglu H, Okyay RD, Yurtlu S, Koksal B, Hanci V, et al
. Postoperative analgesic effects of wound infiltration with tramadol and levobupivacaine in lumbar disk surgeries. J Neurosurg Anesthesiol 2012;24:331-5.
Eisenach JC, De Kock M, Klimscha W. Alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology 1996;85:655-74.
Iskandar H, Benard A, Ruel-Raymond J, Cochard G, Manaud B. The analgesic effect of interscalene block using clonidine as an analgesic for shoulder arthroscopy. Anesth Analg 2003;96:260-2.
Hutschala D, Mascher H, Schmetterer L, Klimscha W, Fleck T, Eichler HG, et al
. Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism in healthy volunteers. Eur J Anaesthesiol 2004;21:198-204.
Bernard JM, Macaire P. Dose range effects of clonidine added to lidocaine for brachial plexus block. Anesthesiology 1997;87:277-84.
Raghuwanshi SK, Chakravarty N, Asati DP, Bankwar V. Use of clonidine as an adjuvant to infiltration anaesthesia in tympanoplasty: A randomized double blind study. Ind J Otolaryngol Head Neck Surg 2014;66:57-62.
Bharti N, Dontukurthy S, Bala I, Singh G. Postoperative analgesic effect of intravenous clonidine compared with clonidine administration in wound infiltration for open choleystectomy. Br J Anaesth 2013. doi: 10.1093/bja/aet130.
Selvaraj V. Evaluation of clonidine as an adjuvant to bupivacaine in wound infiltration for providing postoperative analgesia after abdominal hysterectomy. Anesth Essays Res 2016;10:408-13.
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[Table 1], [Table 2]