|Ahead of print publication
Comparative study of two different doses of dexmedetomidine as an adjuvant to bupivacaine in the peripheral nerve block
Arijit Ray1, Sachin Narayan Kulkarni1, Kaminder Bir Kaur2, Debashish Paul2, Shalendra Singh2, Shazia Khan3
1 Department of Anaesthesiology and Critical Care, INHS Asvini, Mumbai, Maharashtra, India
2 Department of Anaesthesiology and Critical Care, Armed Forces Medical College, Pune, Maharashtra, India
3 Department of Anaesthesiology, Army Hospital (Research and Referral), New Delhi, India
|Date of Submission||13-Feb-2020|
|Date of Decision||06-Mar-2020|
|Date of Acceptance||07-Jun-2020|
|Date of Web Publication||30-Sep-2020|
Department of Anaesthesiology and Critical Care, Armed Forces Medical College, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: The duration of analgesia in the brachial plexus block (BPB) with local anesthetics (LAs) only is not sufficient to avoid the requirement of analgesia for breakthrough pain. Dexmedetomidine (DEX) is an upcoming adjuvant with long-acting LA to reduce the requirement of analgesics in the postoperative period. However, there is no documented consensus about the dose of DEX in this regard. Aim: We compared two doses of DEX with LA in the BPB to find out the effectiveness of analgesia and other effects. Materials and Methods: All patients were separated into two groups, namely Group A (0.5 μg/kg DEX added to 20 mL of 0.25% bupivacaine) and Group B (1.0 μg/kg DEX added to 20 mL of 0.25% bupivacaine). Thirty patients in each group were analyzed. The sample size was estimated with a type I error of 0.05 and a power of the study as 80%. Statistical analysis was performed using SPSS (version 13.0) software. Rescue analgesia was decided as injection morphine (0.05–0.15 mg/kg) intramuscularly as indicated. Results: The mean time of onset of sensory analgesia (18.04 ± 3.195 vs. 12.20 ± 1.848 min) and motor blockade (23.7 ± 2.8 vs. 17.3 ± 1.7 min) were comparable (P < 0.05); however, the duration for the motor (668.0 ± 22.7 vs. 702.0 ± 111.6 min) and sensory blockade (734.8 ± 47.9 vs. 755.6 ± 126.8 min) and time to first demand of analgesics were insignificant. Conclusion: A dose of 1.0 μg/kg DEX has no added benefit when compared with a lower dose of 0.5 μg/kg DEX as an adjuvant to LA.
Keywords: Adjuvant, analgesia, bupivacaine, dexmedetomidine, nerve block
|How to cite this URL:|
Ray A, Kulkarni SN, Kaur KB, Paul D, Singh S, Khan S. Comparative study of two different doses of dexmedetomidine as an adjuvant to bupivacaine in the peripheral nerve block. J Mar Med Soc [Epub ahead of print] [cited 2020 Dec 4]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=296797
| Introduction|| |
The supraclavicular approach of the brachial plexus block (BPB) is the most common and the most effective block for all segments of the upper limb. Regional blocks, namely BPB, negate the unwanted effects of general anesthesia and provide excellent analgesia during the postoperative period, hence doing away with the use of opioid analgesics and their ill effects such as nausea, vomiting, pruritus, and respiratory depression.,,
Regional blocks with long-acting local anesthetics (LAs) are helpful to achieve surgical anesthesia and improved and longer duration of postoperative analgesia. The idea behind using an adjuvant with LA is to reduce the requirement of analgesics in the postsurgical period. A drug-like opioid for perioperative pain can present with ill effects, such as respiratory complications, nausea, and vomiting, and with longer duration of hospital stay. In practice, single-shot administration of the drug is better accepted than a continuous catheter placement technique, which has possible higher infection rates and needs more postoperative care.
Various adjuvants have been studied for prolonging the effect of regional blocks.,, Alpha (α) 2-adrenoceptor agonists such as clonidine and dexmedetomidine (DEX) are the two most popular drugs. They have shown sedation, analgesia, sympatholysis, cardiac stabilization, and anesthetic-sparing properties. Out of these, DEX, an imidazole compound, is more selective (eight times more selective than clonidine). DEX causes analgesia by its action at supraspinal (locus ceruleus) or at the spinal level or even at the peripheral α2 receptors by the reduction of transmission of nociceptive stimuli.
However, in the literature, there has been no concurrence revealed about the optimum dose of DEX as an adjuvant to LA in the BPB.
This prospective, double-blinded study was carried out to compare the two different doses of DEX added to 20 mL of 0.25% bupivacaine − 0.5 and 1.0 μg/kg, with regard to duration and onset of sensory and motor blockade, hemodynamic changes, quality of analgesia, and the requirement of rescue analgesia and adverse effects.
In this study, the primary objective was to compare the characteristics of sensory and motor blockade in both groups. Secondary objectives included (1) the comparison of the total doses of rescue analgesia in the first 24 h, (2) the assessment of side effects such as sedation, bradycardia, and hypotension, and (3) the comparison of visual analog scale (VAS) scores between the groups.
| Materials and Methods|| |
This prospective study was carried out in a tertiary care hospital, after taking approval from the institutional ethical committee and written informed consent from the patients. A total of 69 patients aged 18–64 years, undergoing surgeries for upper limbs, and in American Society of Anesthesiologist (ASA) Physical Status I and II, were enrolled in this study.
Patients with body mass index ≥30 kg/m2, with history of known allergy or hypersensitivity against amino-amide LA or DEX, on nonsteroidal anti-inflammatory drug (for the last 2 weeks), or with history of coagulopathy or clinically relevant electrocardiogram (ECG) abnormality were excluded from the study.
During the study period, patients fulfilling the study protocol were allocated into two groups using random sampling by drawing one out of the two labeled cards (A and B) from a sealed opaque envelope before the procedure.
The study drug DEX, mixed in 20 mL of 0.25% bupivacaine, was prepared by an anesthesiologist. Data were collected by an independent anesthesiologist who was blinded about the allocation of groups. The patients or the nursing staff in the postoperative care unit were also blinded about the same.
In the operation theater, the standard anesthetic technique was followed, and standard ASA monitors and baseline parameters such as ECG, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) were recorded. Five minutes before the procedure, injection midazolam 1 mg intravenous (IV) was administered to all the patients. The same parameters were recorded in the perioperative period.
Using peripheral nerve stimulator (Stimuplex DIG RC, B Braun Medical Inc., Malaysia) and under ultrasonography (USG) guidance (Fujifilm, Sonosite Turbo), BPB was carried out by supraclavicular approach. The pinprick test was used to assess the onset of sensory block, and the ability to flex the elbow and hand was used for rating of the motor blockade. The duration of the blockade was evaluated every hour until the recovery of the sensations.
The onset of sensory blockade was defined as the period from the end of blockade injection to an endorsement of sensory block by loss of awareness to pinprick response, and the onset of motor blockade was the time from the end of blockade injection to absolute motor paralysis of wrist and hand.
The duration of sensory blockade was taken from the time between the sensory blockade and the absolute return of the pinprick response. The duration of motor blockade was taken as time from maximum motor blockade to free movement of wrist and fingers. Duration of analgesia was taken as the interval from the commencement of the sensory blockade to the initial dose of rescue analgesia administered to the patient. To assess the sedation in patients, Ramsay sedation scale was used for a range of 1–6 as follows: 1 – Anxious, agitated or restless; 2 – Cooperative, oriented, and quiet; 3 – Responsive to commands only; 4 – Brisk response to a light glabellar tap or loud auditory stimulus; and 6 – No response to a light glabellar tap or loud auditory stimulus.
Ten-centimeter VAS (0 – no pain to 10 – worst imaginable pain) was used to assess the postoperative pain where mild pain was considered when VAS score was in the range 1–3; moderate pain when VAS score was in the range of 4–6; and severe pain was recorded when VAS score is >7. VAS scores were recorded at 2, 4, 6, 8, 10, and 12 h postoperatively. The first dose of postoperative rescue analgesia was given based on the VAS score ≥4 or on-demand made by the patient (whichever was earlier) and repeated if required.
Morphine with a dose of 0.1 mg/kg intramuscularly was given as rescue analgesia, whenever essential. Postoperative parameters were noted every hour for the first 6 h and thereafter every 2 hourly till the patient's need for rescue analgesia. The occurrence of side effects (bradycardia, hypotension, and sedation) was recorded. A drop in HR by 20% of the baseline HR value or an absolute decrease of HR <50 beats per min was labeled as bradycardia, which was managed by injection atropine 0.6 mg (IV bolus). A decrease in MAP by 20% from the baseline value or an absolute drop in MAP <60 mmHg was defined as hypotension, which was addressed by a bolus of IV crystalloids or increment doses of injection mephentermine 3 mg IV.
The sample size was determined based on a pilot study of 10 patients (5 in each group). The duration of analgesia in a pilot study in two groups was 710.9 ± 158.2 and 750.2 ± 141.4 min, respectively. To detect an observed difference of 20% in the length of postoperative analgesia between the groups, with a power of study 80% and a type I error of 0.05, the sample size required was minimum 30 patients in each group. Statistical analysis was performed using SPSS (version 13.0) software (IBM, USA), and graphs were produced using Microsoft Excel for MAC 2011 (version 14.1.2, Microsoft Corporation, USA). Parametric data were recorded as arithmetic mean ± standard deviation (SD) and were analyzed by Chi-square test. Demographic data such as age, height, and weight were recorded using mean and SD and were compared using a t-test. Data such as VAS score, nausea, vomiting, and sedation were analyzed using the Mann–Whitney test. A P < 0.05 in the study was considered as statistically significant.
| Results|| |
The block was performed in 69 patients, of which five patients were excluded as surgical anesthesia was inadequate and the technique was changed to general anesthesia. Four patients were excluded from the study due to error in gathering data [Figure 1]. Thirty patients in each group were included in the study. In between the two groups, there was no statistically significant variation in demographics (age, sex, weight, duration of surgery, and ASA grade) and baseline vital signs (SBP, DBP, MAP, HR, and SpO2) [Table 1] and [Table 2].
|Table 1: Distribution of subjects according to demographic profile and surgical data|
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The study showed that DEX as an adjuvant in doses of 0.5 mcg/kg body weight (Group A) lags behind 1.0 mcg/kg of DEX (Group B) when the initial block characteristics were compared. There was a statistically significant variation in the meantime of onset of sensory analgesia and meantime for motor blockade, with P < 0.05; however, the duration of analgesia for both sensory and motor blockade was comparable between the groups [Table 3].
The two groups were comparable for the first dose of analgesic and the total requirement of rescue analgesia in 24 h (statistically nonsignificant P value). This suggests that 1.0 mcg dose of DEX as an adjuvant has no added advantage over 0.5 mcg dose in the postoperative period. While analyzing mean Ramsay sedation score in the two groups, it was found that the number of patients with significant sedation score was higher in Group B [Table 4].
The quality of block for the observed period, i.e., initial 12 h, was comparable between the groups, though the VAS score was always lesser in Group B using a higher dose of DEX [Figure 2] and [Table 5].
|Figure 2: Comparison of Post operative VAS Score between two groups at 2,4,6,8,10 and at 12hrs|
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|Table 5: Visual analog scale score in both the groups at 2, 4, 6, 8, 10, and 12 h|
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| Discussion|| |
Various doses of DEX have been studied ranging from 0.5 to 2.0 μg/kg. Minimal side effects have been noted with a dose of 150 μg. Yet, some studies have brought out that even a dose of 30 μg can have side effects and hence a hindrance toward its use in daycare surgeries.
We studied two doses of DEX (0.5 and 1.0 μg/kg), as an adjuvant with LA in the BPB. Our study shows that the lesser dose, viz., 0.5 μg/kg dose, of DEX offers comparable perioperative sensory and motor blockade assessment with postoperative analgesia when compared to the higher dose, viz., 1.0 μg/kg of DEX. Keplinger etal. revealed the dose dependency of DEX when administered as an adjuvant to ropivacaine for ulnar nerve block. In their study, all volunteers received a block with 22.5 mg ropivacaine alone (R) or mixed with 50/100/150 μg of DEX. There was a dose-dependent significant increase in the mean duration (SD) of analgesia with DEX: 8.7 h, 16.4 h (50 μg), 20.4 h (100 μg), and 21.2 h (150 μg). Brummett et al. have demonstrated a dose-dependent increase in the analgesic effects of perineural DEX (0.5, 2, 6, and 20 μg/kg) for sciatic nerve blocks on rats.
In our study, we found that the effectiveness of the perioperative analgesia and duration for motor and sensory blockade in both study groups were very well comparable [Table 3].
Nallam et al., in their study, have compared two doses of DEX (1 vs. 2 μg/kg) as an adjuvant to 0.5% levobupivacaine in peripheral nerve stimulator-guided supraclavicular brachial plexus block (SBPB). They concluded that larger dose augmented analgesic duration, but the incidence of complication such as bradycardia and hypotension also increased.
Kaur et al. studied the effects of 1 μg/kg DEX added to 0.25% levobupivacaine in BPB, shortening the onset of the motor and sensory blockade and enhancing the duration of sensory, motor block, and analgesia. They hypothesized that DEX may help reduce the total concentration of levobupivacaine from 0.5% to 0.25%. Kathuria et al. found that the addition of DEX (50 μg) to 30 mL ropivacaine 0.5% in USG-guided supraclavicular BPB resulted in a quick onset and prolonged duration of blockade and analgesia. Unlike our study, all of these studies were done using a single dose of DEX and did not attempt to compare different doses.
Similarly, Sinha et al. compared two doses of DEX (1.0 vs. 2.0 μg/kg) as an adjuvant to levobupivacaine in the BPB and they concluded that increased dose of DEX does not prolong the duration of analgesia, but incidences of hypotension and bradycardia are more. Hence, a lower dose of 1 μg/kg DEX added to 0.5% levobupivacaine was opined as a good balance between safety and efficacy.
In our study, most of the cases required the first dose of analgesics after 12 h (post-BPB), and both the groups were found comparable for the total requirement of rescue analgesia in 24 h which may be due to the precise deposition of the drug-using ultrasound, irrespective of the dosage used. USG-guided peripheral nerve block is now considered the gold standard of regional anesthesia.
In our study, while analyzing Ramsay sedation score in between the groups, Group B sedation score was found significantly on the higher side (P = 0.047). Further, the incidence of hypotension and bradycardia was more in Group B, although not statistically significant. Sinha et al. observed the same findings in their study. We believe that undesirable effects here are mainly due to the lipophilic nature of DEX and the larger available amount of drug for absorption due to the precise deposition of drugs. Due to central-stimulating action on α2 inhibitory neurons, there is a reduction in sympathetic outflow, leading to these undesirable effects. Plasma levels of the drug after the block were not assessed in our study; hence, we cannot comment if the effect was due to perineural action or systemic absorption. A small sample size and not analyzing the implications of the hazardous effect of DEX are the limitations of our study.
| Conclusion|| |
DEX, when added to LA at a dose of 0.5 μg/kg in the BPB, is found to be a safer dose than 1 μg/kg with fewer side effects, and both doses are comparable for perioperative analgesia. Both doses reduce the requirement of rescue analgesia in the postoperative period. However, DEX at a dose of 1 mcg/kg has more sedative potential, the benefit of which is yet to be determined.
We would like to acknowledge the support and guidance of Surg Cmde (Dr) Rahul Ray, Commanding Officer, INHS Kalyani.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]