Comparison between Dexmedetomidine and Clonidine as an Adjuvant to Ropivacaine in Ultrasound-Guided Adductor Canal Block for Postoperative Analgesia in Total Knee Replacement: A Randomized Controlled Trial.

Background: Total knee replacement (TKR) surgeries are associated with significant postoperative pain. Ultrasound-guided adductor canal block is associated with better pain scores. The addition of Clonidine and Dexmedetomidine as additives to local anesthetics was the recent focus of interest. However, there are minimal studies comparing the duration of analgesia as additives to Ropivacaine in ultrasound-guided adductor canal block for TKRs. Materials and
Methods: Prospective, randomized, double-blind design was followed. One hundred and two American Society of Anesthesiologists I to III patients undergoing unilateral TKR surgeries were included in the study and randomized into two groups. Group C received Clonidine 150 mcg and Group D received Dexmedetomidine 100 mcg as an add on to 30 mL of 0.2% ropivacaine for adductor canal block. Postoperatively, duration of analgesia, sedation score, rescue analgesic requirement, hemodynamics, and any other adverse effects were monitored.
Results: The total duration of analgesia in Group D (16.01 h [standard deviation [S. D]-0.5]) was significantly higher as compared to Group C (13.02 h [S. D-0.5]) (P < 0.0001). The numerical rating score (NRS) was significantly lower in Group D compared to Group C (P < 0.05) at multiple postoperative timelines. Group D (2.25(S. D-0.44)) had better sedation scores as compared to Group C (2 [S. D-0]) (P = 0.001).
Conclusion: Dexmedetomidine has longer duration, lower pain, and better sedation scores as compared to clonidine in adductor canal blocks for postoperative pain relief in TKR surgeries. Copyright:

INTRODUCTION

Total knee replacement (TKR) surgeries can be performed under satisfactory anesthetic conditions using general, regional, and peripheral nerve block anesthesia. However, postoperative pain and anesthetic side effects remain a problem. Adductor canal block involves the unilateral administration of local anesthetics to the nerves without intervening the central nervous system.[1] The adductor canal block, being segmental in nature, can be expected to produce some advantages regarding hemodynamic stability and may be an alternative to other postoperative analgesia techniques.[2] This procedure allows avoiding the use of polypharmacy and can be used as an alternative method in patients with unstable cardiovascular systems. Wang et al. observed that adductor canal block has minimal effect on quadriceps muscle as compared to femoral nerve block.[3] Forouzan et al. highlighted that ultrasound-guided adductor canal block is associated with better pain scores.[4] Clonidine and Dexmedetomidine as additives to local anesthetics were the recent focus of interest.[567] However, there are minimal studies comparing the effect of additives to ropivacaine in prolonging the duration of postoperative analgesia in adductor canal block for TKR surgeries.

Objectives

The primary objective is to compare the duration of analgesia of Clonidine and Dexmedetomidine as an adjuvant to 0.2% Ropivacaine in the adductor canal block for postoperative pain relief in TKR surgeries. The secondary objective is to compare the hemodynamic parameters, sedation scores, and adverse effects between the groups.

MATERIALS AND METHODS

A double-blind, randomized prospective clinical study was planned among 102 American Society of Anesthesiologists (ASA) physical status classes I to III patients undergoing unilateral TKR surgeries. Patients with known allergy to local anesthetics, peripheral neuropathy, coagulopathy, infection at the site of block, and severe uncontrolled medical or psychiatric comorbidities were excluded from the study.

The study was approved by the Institutional Ethics Committee and registered with Clinical Trials Registry of India (CTRI number: CTRI/2021/09/036159).

Preoperatively, patients were counselled and familiarized with the use of Numerical Rating Score (NRS) pain score for the assessment of postoperative pain. After obtaining written informed consent, patients were randomly divided into two groups, Group C (Clonidine) and Group D (Dexmedetomidine) using the sealed envelope technique. A sealed envelope was randomly selected and opened by an assistant, with instructions to draw up the relevant drug. The syringe was labeled with the patient's name and handed to the investigator who performed the block. An independent observer (anesthetist posted on duty, not included in the study) then observed pain scores, sedation scores and any adverse events till 24 h. Blinding was opened at the end of the study. On arrival to the operating room, baseline parameters were recorded for all patients, wide bore intravenous (i.v.) cannula secured and intravenous fluids started. All patients were given subarachnoid block under strict aseptic precautions as the standard anesthetic technique. Postsurgery with patient in Frog leg position, under strict aseptic precautions, high-frequency (10–5MHz) linear transducer probe was placed centrally at the mid-thigh level to identify the femur. The probe was then slid medially to identify the femoral artery which lies in the adductor canal. Using a 20 G locoplex needle, in an in-plane approach, the needle was advanced from lateral to medial side to lie just lateral or superficial to femoral artery beneath the sartorius muscle in the adductor canal, which is where the saphenous nerve may be visible. After negative aspiration for blood, a test dose of local anesthetic was injected to observe spread around the nerve. If no nerve was visible, then study drug was injected around the femoral artery. After ensuring the correct spread, the remaining drug solution with specific adjuvant was injected. Group C received 30 mL of Ropivacaine 0.2% with Clonidine 150 mcg and Group D received 30 mL of Ropivacaine 0.2% with Dexmedetomidine 100 mcg. Pain score was assessed every 2 h till 24 h by NRS with 0 being no pain and 10 being worst imaginable pain. Rescue analgesia (Injection Paracetamol 1 g [i.v.]) was given when NRS >5. Sedation scores were assessed using Modified Ramsay sedation score. Hemodynamic parameters and adverse effects (nausea, vomiting, bradycardia, and hypotension) were observed after shifting to the postoperative unit 2nd hourly for 24 h. The data were collected using a patient information sheet developed for the study and entered in Excel sheets. The data were analyzed using the SPSS statistics for Windows, version 16.0 (SPSS Inc., Chicago, Ill, USA) Student t-test was used to test the significant differences between the two groups with 95% confidence interval.

RESULTS

The total number of patients included for the study was 102, and there were no dropouts from the study. The age, gender, and ASA distribution across the groups were not significantly different [Table 1]. The Consolidated Standards of Reporting Trials diagram is represented in Figure 1.

Table 1

Distribution of age, gender, and American Society of Anesthesiologists grading between the groups

	Group D	Group C	P (χ2)
Mean age (years)±SD	63.7±9.6	62.9±7.6	0.6
Gender
Male	28	24	0.4 (0.62)
Female	23	27
ASA grading
I	23	27	0.7 (0.66)
II	24	21
III	4	3

SD: Standard deviation, ASA: American Society of Anesthesiologist

Figure 1

Consolidated standard of reporting trials flow chart representing enrollment, allocation and analysis of the participants

The duration of analgesia (in hours) was significantly higher in Dexmedetomidine group (16.01 ± 0.5) as compared to Clonidine group (13.02 ± 0.5) (P < 0.0001). The mean NRS scores were lower in Group D as compared to Group C at 8, 10, 12, 14, 16, and 24 h (P < 0.05). Sedation scores were better in Group D compared to Group C till 4 h with maximum sedation at 2nd h. The comparison between the groups on different variables was represented in Table 2. The total amount of the rescue analgesia is the number of doses of (i.v.) paracetamol 1 g required to control the pain.

Table 2

Comparison of outcomes between the Group D (Dexmedetomidine) and Group C (Clonidine)

Variables	Group D	Group C	P
Duration of analgesia (h)	16.01±0.545	13.021±0.543	<0.0001
Total amount of rescue analgesia required (g)	1.117±0.325	1.921±0.716	<0.0001
Modified Ramsay sedation score (h)
2	2.7±0.4	2.1±0.3	0.0001
4	1.8±0.4	1±0	0.0001
6	1±0	1±0	-
NRS for pain (h)
2	0	0	-
4	0	0	-
6	0	0.4509±0.50	-
8	0.529±0.50	0.901±0.30	<0.0001
10	1.137±0.490	2.274±0.568	<0.0001
12	2.470±0.504	4.235±0.619	<0.0001
14	2.607±0.493	3.960±0.196	<0.0001
16	4.039±0.564	3.784±0.415	0.012
18	3.666±0.476	3.647±0.482	0.834
20	3.568±0.500	3.607±0.493	0.68
22	3.450±0.50	3.568±0.5	0.618
24	3.647±0.48	3.764±0.42	0.186

Ramsay sedation score for the assessment of level of sedation. NRS: Numeric Rating Scale

Two out of 51 patients in the Dexmedetomidine group experienced bradycardia (treated with injection glycopyrrolate 0.2 mg [i.v.] bolus) and no other adverse effects observed in either group during the study. There were no significant differences in mean arterial pressure scores between the groups at various time points, as illustrated in Table 3.

Table 3

Comparison of mean arterial pressures between Group D (Dexmedetomidine) and Group C (Clonidine)

MAP (h)	Group D	Group C	P
0	93.88±7.37	95.62±7.56	0.24
2	85.29±7.53	86.74±7.65	0.34
4	83±7.73	84.31±7.43	0.38
6	81.90±7.36	82.35±7.14	0.75
8	78.17±8.38	79.21±8.58	0.54
10	77.80±8.59	78.74±8.43	0.58
12	77.31±8.65	78.31±9.03	0.57
14	76.60±8.21	77.66±8.63	0.53
16	77.39±8.40	78.43±8.70	0.54

MAP: Mean arterial pressures

DISCUSSION

In this randomized double-blind control study, we found that Dexmedetomidine is better than Clonidine as an additive to Ropivacaine for postoperative pain relief in TKR. Dexmedetomidine had a longer duration of analgesia, better sedation score, and lower pain scores than clonidine.

Low-middle income countries, specifically India is witnessing a significant increase in number of TKR surgeries in the last decade.[8] TKR is associated with significant postsurgery pain. Prolonged pain is associated with significant morbidity and poor patient outcomes.[9] Therefore, adequate management of pain is important and regional anesthesia offers effective solutions. A recent systematic review by Zhao et al. reported that the adductor canal blocks and femoral blocks are two commonly used procedures for postoperative pain relief in TKR surgeries. However, the pain control and ambulatory ability is similar between the procedures.[1011] Adductor canal block is relatively new, attractive alternative procedure and is associated with minimal effect on quadriceps strength and faster recovery.[3121314] In our study, all the patients had good postoperative pain control.

Alpha-2 (α2) adrenergic receptor agonists have been the recent focus of interest for their sedative, analgesic, perioperative sympatholytic, and cardiovascular stabilizing effects with reduced anesthetic requirements. The effect of clonidine in the peripheral nerve block may be explained by four mechanisms including centrally mediated analgesia, α2b receptor-mediated vasoconstriction, attenuation of the inflammatory response, and direct action on the nerve.[5] Dexmedetomidine is a potent α2 adrenoceptor agonist which is approximately eight times more selective toward the α2 adrenoceptor than clonidine. Dexmedetomidine has also been reported to enhance sensory and motor blockade along with increasing the duration of analgesia.[6] The anesthetic requirements get reduced to a large extent by the usage of α2 agonists, because of their analgesic properties and augmentation of the local anesthetic effect. They cause hyperpolarization of the nerve tissue by altering the trans-membrane potential and ion conductance and also cause sedation by inhibiting the release of nor-epinephrine at locus coeruleus in the brain stem. Sedation gives an extraadvantage for regional anesthesia, as it reduces the stress associated with surgery, but associated bradycardia and hypotension need to be monitored. Hence, in this study, we wanted to compare two alpha 2 receptor agonists, i.e., Dexmedetomidine and Clonidine as an adjuvant to ropivacaine in ultrasound-guided adductor canal block for postoperative analgesia in TKR surgeries.

Kataria et al. have observed by adding Dexmedetomidine 100 mcg has prolonged the duration of sensory and motor block and postoperative analgesia than Clonidine 150 mcg to Levobupivacaine in supraclavicular brachial plexus block.[7] Pöpping et al. in his meta-analysis on clonidine as an adjuvant in peripheral nerve blocks has observed that 150 mcg is the most commonly used dosage and has found to increase the duration of analgesia significantly.[5] Helal et al. in their study observed by adding 100 mcg Dexmedetomidine to 0.5% bupivacaine for ultrasound-guided combined femoral and sciatic block for below knee surgery prolonged duration of analgesia.[15] Based on the above studies, we also used 100 mcg of Dexmedetomidine and 150 mcg of Clonidine to Ropivacaine in adductor canal block.

Our findings highlight dexmedetomidine provides longer duration of analgesia and lower pain scores. In addition, the requirement of rescue analgesia required is lesser and better sedation scores with Dexmedetomidine. These findings are comparable to the previous studies, which found Dexmedetomidine superior to Clonidine as an adjuvant to Bupivacaine/Ropivacaine for epidural anesthesia in lower limb orthopedic surgeries.[16171819] While most studies used epidural technique for postoperative analgesia, our study findings are more important as we highlight the efficacy of adductor canal block among patients. In addition, study by Chaudhary et al., comparing Dexmedetomidine with Clonidine in femoral nerve blocks underscored the advantages of Dexmedetomidine.[20]

Only two patients in the Dexmedetomidine had transient bradycardia. Otherwise, both the groups had similar hemodynamic stability without significant adverse effects. Similar results were observed in the previous studies by Arunkumar et al. and Sarma et al.[2122]

The strengths of the study include strict randomization and blinding protocols followed during the study procedure. As our center is a specialized tertiary care orthopedic institute, we were able to achieve adequate sample size to meet the 80% power of the study. Finally, the structured assessment used during the study increases the internal validity of the study findings.

CONCLUSION

Dexmedetomidine has longer duration, lower pain, and better sedation scores compared to Clonidine in adductor canal blocks for postoperative pain relief in TKR surgeries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.