A comparison of efficacy of parenteral and perineural dexmedetomidine with 0.25% ropivacaine for post-thyroidectomy analgesia using bilateral superficial cervical plexus block

Abstract

Background and Aims:

Opioids are conventionally used for post-thyroidectomy pain, regional anesthesia is becoming popular due to its feasibility and efficacy in minimizing use of opioids and hence its side effects. This study compared analgesic efficacy of bilateral superficial cervical plexus block (BSCPB) using perineural and parenteral dexmedetomidine with 0.25% ropivacaine in thyroidectomy patients.

Material and Methods:

In this double-blind study, 60 American Society of Anesthesiologists (ASA) physical status I and II thyroidectomy patients, aged 18–65 years were randomized into two groups. Group A (n = 30) received BSCPB with 0.25% ropivacaine, 10 mL on each side with dexmedetomidine 0.5 μg/kg IV infusion. Group B (n = 30) received 0.25% ropivacaine plus dexmedetomidine 0.5 μg/kg, ten mL on each side. Duration of analgesia by measuring pain visual analog scores (VAS), total dose of analgesic requirement, Haemodynamics parameters and adverse events were recorded for 24 h. Categorical variables were analyzed using Chi-square test and continuous variables were computed as mean with standard deviation and analyzed using independent sample t-test. Mann-Whitney U test was used for analysis of ordinal variables.

Results:

Time to rescue analgesia was longer in Group B (18.6 ± 3.27 h) as compared to Group A (10.2 ± 2.11 h) (P < 0.001). Total analgesic dose required was also found to be lesser in Group B (50.83 ± 20.37 mg) as compared to Group A (73.33 ± 18.27 mg) (P < 0.001). No significant hemodynamic changes or side effects were observed in both groups; (P > 0.05).

Conclusion:

Perineural dexmedetomidine with ropivacaine in BSCPB significantly prolonged the duration of analgesia with reduced rescue analgesic requirement.

Introduction

Thyroidectomy causes mild to moderate incisional pain, combined with pain in the neck region due to orotracheal intubation and hyperextension during surgery.^[1] During the first 24 h after surgery, most patients require opioid or non-opioid analgesics.

The Superficial Cervical Plexus Block (SCPB) is a practical regional anesthetic technique that imparts appropriate analgesia in various head and neck surgeries. It’s easy to learn, master and accounts for only trivial complications which are avoidable with appropriate asepsis and following the correct procedural steps. Unilateral or bilateral superficial CPB can be used for dispensing analgesia for surgeries such as thyroidectomy, minimally invasive parathyroidectomy, tympanomastoid surgery along with CEA, tracheostomy, etc.^[2]

Superficial cervical plexus block administered bilaterally has a two-pronged advantage. It potentially reduces the amount of inhaled anesthetics intra-operatively,^[3] in turn, maintaining the hemodynamic parameters as well as minimizing analgesic requirements post-operatively without the conceivable major complications.^[1,4,5]

Dexmedetomidine, S-enantiomer of medetomidine is a newer highly selective α2-agonist, which has wide applications as a premedication, as an adjuvant to general anesthesia and as a neuraxial adjuvant as it provides stable hemodynamic conditions, good quality of intraoperative and prolonged postoperative analgesia with minimal side effects.^[6] There is a paucity of studies using dexmedetomidine in combination with ropivacaine and whether its efficacy is better using perineural or parenteral use.

This study was undertaken with the aim to investigate the efficacy of post-thyroidectomy analgesia of bilateral superficial cervical plexus block (BSCPB) using 0.25% ropivacaine with parenteral or perineural dexmedetomidine by measuring postoperative pain visual analog scores (VAS) and 24-hr postoperative analgesic requirement. The primary outcome measure of our study was duration of postoperative analgesia, whereas secondary outcome measures were number of doses of rescue analgesic requirement in 24 h, incidence of postoperative nausea and vomiting (PONV), intraoperative hemodynamic changes and postoperative side effects if any.

Material and Methods

A prospective, randomized double blind study was undertaken after obtaining due approval from the Institutional Ethical Committee, J.L.N. Medical College, Ajmer, Rajasthan, IRB approval number: 979/ Acad-III/ MCA/2019 (Date: 15.05.19). CTRI registration number for this trial is CTRI/2020/02/023300. Practices followed were in accordance with the standard ethical protocols of the responsible committee. All adult patients who underwent thyroid surgery from February to November 2020, were included in this study. Patients with ASA physical status III or above, retrosternal goiter, age >65 years, thyroid malignancy requiring neck dissections or with a known history of sensitivity or contraindications to the drugs used were excluded.

A total of 30 ASA I and ASA II euthyroid patients were assigned randomly to either Group A or Group B using computer-generated table of random numbers. Group A received parenteral dexmedetomidine 0.5 μg/kg as IV infusion over ten minutes and BSCPB with 0.25% ropivacaine (10 mL on each side), whereas patients in Group B received BSCPB with 0.25% ropivacaine (19 mL) and 0.5 μg/kg dexmedetomidine made up to 1 mL (total volume, 20 mL; 10 mL on each side) [Flow Chart 1].

Flow chart 1.

Consort flow diagram

Thorough preoperative evaluation along with written and informed consent was taken from all patients before the start of the procedure. Patients were kept nil per oral for 6 h before surgery. On arrival of the patient in the operation theatre all standard ASA monitors including pulse oximetry, electrocardiography and non-invasive blood pressure were connected along with a neuromuscular monitor (Drager, Infinity Trident NMT Smart Pod). Baseline heart rate (HR), blood pressure (NIBP), oxygen saturation (SpO₂) and electrocardiogram were recorded. An intravenous cannula of 18 or 20 G was secured.

Twenty minutes prior to induction, Group A received an intravenous (IV) infusion of dexmedetomidine 0.5 μg/kg and Group B received normal saline as placebo over 15-20 minutes. Pre- anesthetic medications included injections midazolam 0.02 mg/kg, fentanyl 2 μg/kg and 1% xylocard 1 mL intravenously (IV) were administered along with preoxygenation for five minutes with 100% oxygen.

Induction of general anesthesia was achieved with 2 mg/kg propofol IV followed by vecuronium 0.1 mg/kg IV. After successful induction, tracheal intubation was performed with an appropriately sized endotracheal tube. Anesthesia was maintained with sevoflurane, a mixture of O2:N2O in the ratio 50:50 and intermittent bolus dose of vecuronium at a dose of 0.01 mg/kg IV. Vitals were monitored throughout the intraoperative period.

After confirmation of endotracheal tube placement, patient’s head was placed facing away from the side to be blocked. With the anesthesiologist standing at the head end of the patient, the site where bilateral superficial cervical plexus block (BSCPB) is to be performed, was painted with 5% Povidone – Iodine followed by spirit and draped. A 24-gauge, one-and-a-half inch short bevel needle was inserted into the mid-portion of the posterior border of the sternocleidomastoid muscle, at the midpoint of the line joining the mastoid process and C-6 transverse process. Five mL of anesthetic drug was injected subcutaneously, horizontally and the other five mL injected cephalad toward the tragus of ipsilateral ear and caudad toward the sternal notch in a “fan” fashion.

The same technique was used to perform the block on the contralateral side and the time was noted. Group A (n = 30) received BSCPB with 0.25% ropivacaine, 10 mL on each side. [Ropivacaine 0.5%, 10 mL (50 mg) + 0.9% normal saline, 10 mL (total volume 20 mL) and an IV infusion of dexmedetomidine 0.5 mcg/kg. On the other hand, Group B (n = 30) received 0.25% ropivacaine plus dexmedetomidine 0.5 μg/kg, 10 mL on each side. Ropivacaine 0.5%, 9.5 mL (45 mg) + 0.9% normal saline 9.5 mL + 0.5 μg/kg dexmedetomidine made up to 1 mL (total volume 20 mL) and an infusion of normal saline as placebo. For example: If a patient weighs 60 kg, then 1 mL of dexmedetomidine (100 mcg) was diluted to 3 mL, and 1 mL (33 μg) was given in the infusion (Group A) or the drug syringe (Group B). Drugs were filled and injected by a different anesthesiologist to reduce subjective and objective bias. This is to emphasize that this is a double blind study.

After surgery was completed and signs of recovery from neuromuscular blockade were noted, residual paralysis was reversed with injection neostigmine and injection glycopyrrolate. Once the patient was fully awake and TOF ratio of one was achieved, endotracheal tube cuff was deflated and the patient was extubated. The patient was then shifted to PACU when they were hemodynamically stable and responsive. Non-invasive blood pressure, heart rate, SpO2 and VAS were noted once immediately after shifting to PACU, then at 30, 60 and 90 mins and subsequently every 2 h postoperatively till 24 h.

Post-operatively duration of analgesia (time from the end of the surgery to the first analgesic request) was assessed using the Visual Analog Score. Rescue analgesic, tablet, if patient was allowed oral intake; or injection diclofenac was administered if patient reported a VAS ≥4. Total analgesic dose consumed in milligrams, incidence of postoperative nausea and vomiting (PONV) or other side effects and hemodynamic parameters were recorded for 24 h post-operatively. Ondansetron (0.15 mg/kg) was given to manage PONV. Hypotension was defined as more than 20% fall in mean arterial pressure (MAP) and it was managed either with the administration of colloid. Bradycardia was defined as heart rate below 50 beats/min and was managed with inj. atropine 0.6 mg IV stat.

Statistical analysis

Based on a study by Andrieu G et al.^[4] and to show a power of 0.9 and type-1 error of 0.05, allowing a 10% dropout rate. Categorical/Nominal variables were expressed as number or percentage; analyzed using Chi-square test and continuous variables were computed as mean with standard deviation and analyzed using independent sample t-test for comparison between the two groups. Mann–Whitney U test was used for analysis of ordinal variables like VAS score. Level of significance was set at P ≤ 0.05. All statistical analyses were done using Epi Info version 7.2.1.0 for Windows.

Results

The demographic profiles and peri-induction data were comparable between two groups with a P value > 0.05 [Table 1]. Female predominance was noted among patients as thyroid disease is more prevalent in them, but there was no statistical difference between two groups.

Table 1.

Demographic profile and duration of surgery in two groups

Parameters	Group A (n=30)	Group B (n=30)	P
Age (years)	41.4±13.3	40.0±12.2	0.889 (NS)
Gender (M/F)¶	2/28	2/28	1.00 (NS)
Weight (kg)	54.4±8.60	58.20±11.9	0.162 (NS)
ASA (I/II)¶	27/3	24/6	0.472 (NS)
Duration of surgery (min)	95.3±34.9	95.2±30.1	0.994 (NS)
Duration of anesthesia (min)	107.4±36.5	109±29.1	0.852 (NS)
Types of surgery (Subtotal thyroidectomy/Completion thyroidectomy/total thyroidectomy/Right hemithyroidectomy/left hemithyroidectomy)	1/1/3/14/11	1/1/3/17/8	0.998 (NS)

*Group A - Ropivacaine and Parenteral dexmedetomidine; Group B - Ropivacaine and Perineural dexmedetomidine. ^†S - Significant, NS - Non-significant, ^§Values are expressed as Mean±SD or number. ^¶F-Female; M - Male; ASA - American Society of Anesthesiologists

There was a statistically significant difference in regards to mean duration of analgesia between the two groups. In Group B, it was found to be (1116.5 ± 196.2) minutes which was significantly prolonged than that in Group A (614.4 ± 126.6 min) (P < 0.001). The total dose of rescue analgesic required in 24 h were lesser in group B (50.83 ± 20.37 mg) in comparison to group A (73.33 ± 18.27 mg), which was statistically highly significant. (P < 0.001) [Table 2 and Figure 1] (unpaired Student’s t test).

Table 2.

Comparison of duration of analgesia and rescue analgesic requirement in two groups

Parameters	Group A (n=30)	Group B (n=30)	P
Duration of analgesia (min)	614.4 ± 126.6	1116.5 ± 196.2	<0.001 (S)¶
Total Amount of rescue analgesic in 1st 24 h	73.33±18.27	50.83±20.37	<0.001(S)¶

*Group A - Ropivacaine and Parenteral dexmedetomidine; Group B - Ropivacaine and Perineural dexmedetomidine. ^§Values are expressed as Mean±SD. ^†S - Significant, NS - Non-significant. ^¶Unpaired Student’s t test used for statistical analysis

Figure 1.

Comparison of mean duration of analgesia (h) among study groups

Patients in Group B also recorded significantly lower VAS scores (P < 0.005) in the postoperative period for first 24 h. No patient had pain scores ≥4 till first 6 h in both groups. It is revealed that mean VAS score at 16, 18, 20 and 22 h postoperatively were statistically significantly lower (P < 0.01) in group B as compared to group A. The difference in mean VAS score was comparable for the remaining duration of post-operative monitoring (P > 0.05) [Figure 2].

Figure 2.

Comparison of postoperative VAS score among study groups

The hemodynamic parameters were stable throughout and comparable in both the groups (P > 0.05) [Figure 3]. The incidence of postoperative nausea & vomiting was substantially lower and comparable (26.7% vs 36.6%) in both the groups over first 24 h [Figure 4]. Hypotension was observed in Group A intraoperatively although it was not seen postoperatively [Figure 4 and Table 3]. There were no incidences of bradycardia, respiratory depression, hematoma in any group.

Figure 3.

Comparison of intraoperative hemodynamics (SBP, DBP and MAP) in two groups *Group A- Ropivacaine and Parenteral dexmedetomidine; Group B- Ropivacaine and Perineural dexmedetomidine **SBP-Systolic Blood Pressure; DBP- Diastolic Blood Pressure; MAP-Mean Arterial Pressure

Figure 4.

Frequency of adverse event among study groups * Group A- Ropivacaine and Parenteral dexmedetomidine; Group B- Ropivacaine and Perineural dexmedetomidine § Values are expressed as Mean ± SD † S- Significant, NS- Non-significant ¶ Unpaired student t-test used for statistical analysis

Table 3.

Frequency of adverse event among study groups

Adverse events	Group A		Group B		P
	n	%	n	%
Hypotension	19	63.3	7	23.3	0.004 (S)
Nausea	5	16.7	7	23.3	0.748
Vomiting	3	10	4	13.3	1.000

Discussion

Modern anesthetic practices and management aim to dramatically revolutionize the mitigation of postoperative pain by pre-emptively engaging the anti-nociceptive mechanisms,^[7] providing adequate sedation and analgesia, thereby decreasing morbidity, hospital stay and complications in the postoperative period.

We observed that superficial cervical plexus block performed bilaterally in patients undergoing thyroidectomy results in prolonged duration of analgesia in the postoperative period. We also reported reduced requirement of non-opioid analgesics, diminished incidence of PONV, better hemodynamic stability without any undue sedation or respiratory depression.

Ropivacaine is a newer and longer acting amide with a safer cardiac profile.^[8] Due to its unique pharmacologic properties (less lipophilic than bupivacaine and stereoselective, so higher threshold for cardiotoxicity and CNS toxicity) and fewer side effects, it is being preferred by anesthesiologists for peripheral nerve blocks worldwide. Dexmedetomidine, an alpha 2 adrenergic receptor agonist has been safely used intravenously in the dose of 1 µg/kg (loading) followed by 0.2-0.7 µg/kg/hr (maintenance) as well as perineurally in the dose of 1 µg/kg. The most frequently reported side effects are hypotension, hypertension, bradycardia, dry mouth, nausea, arrhythmias, respiratory depression among others.^[9] Dexmedetomidine has been used safely as an adjuvant to bupivacaine^[10] and levobupivacaine^[11] without any neurological side effects.^[10,11] There is a paucity of studies using dexmedetomidine in combination with ropivacaine in BSCPB.

The administration of parenteral or perineural dexmedetomidine with ropivacaine in BSCPB lengthened duration of postoperative analgesia as substantiated by our study. Analgesia was assessed using VAS score and whenever the VAS ≥4, time was noted and inj. diclofenac sodium 75 mg IM or tablet diclofenac 50 mg orally after 6 h was given as rescue analgesia. The mean duration of analgesia in group B (1116.5 ± 196.2 min) as compared to group A (614.4 ± 126.6 mins) was significantly (P < 0.0001) prolonged.

This result was further supported by similar results of previous studies done by Andrieu et al. and Santosh et al. Andrieu et al.^[4] documented lesser median pain scores and decreased intraoperative and postoperative analgesic requirements with the addition of clonidine (another α₂-agonist) to ropivacaine. Santosh et al.^[5] reported significantly prolonged duration of analgesia with perineural 0.5 μg/kg dexmedetomidine with ropivacaine (1696.2 ± 100.2 min) as compared to only ropivacaine (967.8 ± 81.6 min). This difference can be attributed to the fact that they used ropivacaine in the concentration 0.5% where we used 0.25% with the same dose of dexmedetomidine. The addition of dexmedetomidine prolonged the duration of analgesia by nearly 75% in this study.^[5]

An animal study conducted by Ishii et al.^[12] studied action of parenteral dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord and found that the analgesic effect of the α₂-agonists is mediated through stimulation of the α_2C and α_2A receptor in the dorsal horn, thus directly suppressing pain transmission by reducing the release of pro-nociceptive transmitters like substance-P and glutamate, and hyperpolarization of interneurons.

Brummett et al.^[13] described the analgesia prolongation by perineural dexmedetomidine attributing it to the blocking of the hyperpolarization-activated cation current. Dexmedetomidine reduces the peak amplitude of compound action potential’s reversibility in a concentration-dependent manner, thereby prolonging the duration of blockade.^[14] It also reduces local inflammation and prolongs the duration of nerve block through vasoconstriction (mediated by its α₂-agonist action) by maintaining the local concentration of the local anesthetic and inhibiting the nociceptive impulse transmission along myelinated C fibers.^[15]

BSCPB has been recognized to be instrumental in lengthening the time to first analgesic request as depicted by similar experiments. Shih et al.^[1] compared the time to first analgesic request in BSCPB using bupivacaine and levobupivacaine with control and found it to be 360.8 mins and 410.1 mins respectively compared to control which showed duration of analgesia of 82.1 mins (P < 0.001). Kannan et al.^[3] used 0.25% bupivacaine in BSCPB and found prolonged duration of analgesia at 361.6 mins compared to 151.0 min with control.

The mean total analgesic dose of analgesic, tablet or injection diclofenac given in first 24 h in Group A (73.33 ± 18.27 mg) was more than Group B (50.83 ± 20.37 mg), P < 0.001. This is also reflected in other studies namely Karthikeyan et al.,^[16], Kale et al.,^[17] Cai et al.,^[18] & Goulart et al.^[19]

The VAS scores were statistically significantly different at 10–12 h and at 16–22 h in the postoperative period and were significantly lower in Group B as compared to Group A (P < 0.05), post-operatively, up to first request for rescue analgesic; this finding correlated with the duration of analgesia. Reduction in postoperative VAS scores was documented by other studies especially in the first 24 h.^[1,5,16]

Patients having retrosternal extension, large thyroid swelling and obese patients having difficult airway are already at risk of airway compromise in which narcotics are relatively contraindicated. The use of pre-incision BSCPB prevents central sensitization and results in diminished perioperative dose of analgesics.^[7] It was also reported that non-opioid analgesics provided satisfactory analgesia in the postoperative period with BSCPB. Moreover, the declining trend in the use of opioids prevents the incidence of nausea and vomiting, thus improving patient’s condition in the immediate post-operative period.

PONV was assessed using a four-point scale previously used by Shih et al.^[1] and Goulart et al.^[19] The scores was graded as: 1 for no nausea, 2 for mild nausea, 3 for severe nausea and 4 for retching and/or vomiting. Severe PONV was defined as grades 3 and 4; and rescue antiemetic Inj. Ondansetron 8 mg IV was administered. Other complications like pain during swallowing were reported in few patients in the first 24 h which subsided with use of lozenges.

We observed incidence of nausea to be 16.67% in Group A compared to 23.33% in Group B (P > 0.05). The incidence of vomiting was found to be 10% in Group A, whereas in Group B, it was 13.3% (P > 0.05).

Previous studies have shown that the frequency of occurrence of PONV in thyroid surgeries as high as 75%.^[17] This may be attributed to inadequate or unsatisfactory postoperative analgesia and subsequent opioid supplementation & use of nitrous oxide and volatile anesthetics.^[18] The incidence of PONV was significantly reduced in both the groups. Also, the incidence appeared to be lesser in Group A where inj dexmedetomidine 0.5 μg/kg was administered parenterally.

The antiemetic action of dexmedetomidine may be ascribed to the modulation of neurotransmitters. Postsynaptic α_2A-receptors on 5-HT cell elements, functioning as heteroreceptors, directly mediate the dexmedetomidine-induced reduction of 5-HT release in the dorsal and median raphe nucleus.^[20] In addition, dexmedetomidine modulates dopamine release by dose-dependently decreasing extracellular dopamine levels in the nucleus accumbens and suppresses the histamine-induced expression of the pro-inflammatory cytokine interleukin-6.^[21] Besides this, clinical studies support an opioid- and anesthetic-saving effect as the underlying mechanism of the antiemetic effect of dexmedetomidine.^[20]

Intraoperatively the mean SBP and DBP were significantly (P < 0.001) decreased in group A after the synergistic effect of injection dexmedetomidine, injection propofol, and vecuronium when compared to group B from 5 to 90 mins. Also, the mean MAP was also significantly (P < 0.05) decreased by dexmedetomidine infusion given preoperatively in group A when compared to group B from 5 to 45 min. Despite lower SBP and DBP in group A, none of the patients had hypotension. Postoperatively there was no significant difference (P > 0.05) in the mean SBP and DBP of both the groups at all times.

A statistically significant difference was observed in mean arterial pressures between the two groups postoperatively at all time intervals (P < 0.05), indicating the effect of IV dexmedetomidine causing persistent hypotension when used as an anesthetic adjuvant in small doses. Dexmedetomidine infusions result in reversible sedation, mild analgesia, and memory impairment without cardiorespiratory compromise. It also has minimum alveolar anesthetic concentration (MAC)-sparing properties.^[22]

Approximately 63.3% of the patients experienced hypotension in Group A, whereas only 23.3% experienced hypotension in Group B (P < 0.05) indicating the pronounced effect of IV dexmedetomidine.

It was discerned that dexmedetomidine given perineurally attributed to enhanced postoperative analgesia when compared with parenteral route.

Limitations of our study included excluding patients above the age of 65 years and patients belonging to ASA physical status III and above, as the findings of our study cannot be extrapolated to patients with co-morbidities. The absence of a control group may have affected the results. Moreover, ultrasound guidance would have been useful for better quality of block, because of its ease of visualization of anatomical structures as well as the spread of the local anesthetic. Few experiments have been conducted to describe the difference in mechanism of action of parenteral and perineural dexmedetomidine especially associated with cervical plexus blocks.

Conclusions

Dexmedetomidine as an adjuvant in superficial cervical plexus block administered bilaterally imparted superior analgesia and decreased opioid usage without potential side effects or complications and may be used as a pre-emptive analgesic technique in thyroid surgeries. The effect was more pronounced when dexmedetomidine was given perineurally than parenterally.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.