Evaluation of Addition of Sodium Bicarbonate to Dexamethasone and Ropivacaine in Supraclavicular Brachial Plexus Block for Upper Limb Orthopedic Procedures.

BACKGROUND: Peripheral nerve blocks have taken over as the principle technique for upper limb surgeries. A number of adjuvants have been tried individually, but very few studies have investigated the cumulative effect of two or more adjuvants given together along with local anesthetic. AIM: This study aimed to evaluate the effect of addition of sodium bicarbonate to dexamethasone and ropivacaine in supraclavicular brachial plexus block. SETTINGS AND
DESIGN: This was a prospective, randomized, double-blind study that comprised 90 American Society of Anaesthesiologist (ASA) 1 and 2 patients posted upper limb orthopedic procedures.
MATERIALS AND METHODS: Ninety ASA 1 and 2 patients were selected and divided into three groups of 30 each: Group R received 30 mL of 0.75% ropivacaine plus 4 mL normal saline; Group RD 30 mL of 0.75% ropivacaine, 2 mL normal saline and 2 mL of dexamethasone were given; Group RB 30 mL of 0.75% ropivacaine plus 2 mL of dexamethasone and 2 mL of sodium bicarbonate. Onset and duration of sensory and motor block and postoperative pain scores were studied in each group. STATISTICAL ANALYSIS: Student's independent t-test was employed for comparing the continuous variables and Chi-square test for the categorical variables. Kruskal-Wallis test was used for postoperative pain score data.
RESULTS: Addition of sodium bicarbonate to dexamethasone and ropivacaine quickens onset and prolongs duration of sensory and motor block.
CONCLUSION: Sodium bicarbonate produces a synergistic and potentiating effect with dexamethasone as adjuvant in supraclavicular brachial plexus block. Copyright:

INTRODUCTION

The quest for searching newer and safer anesthetic agents has always been one of the primary needs in anesthesiology practice. At one point of time, general anesthesia was one of the most common methods employed to provide anesthesia for upper limb surgeries. With the introduction of newer and safer local anesthetics with better advantages, regional anesthesia has taken over as the principle technique for upper limb surgeries. Peripheral nerve blocks provide longer and localized pain relief and also avoid the side effects of systemic medications.

Brachial plexus block is a versatile and reliable regional anesthetic technique with multiple applications. The advantages are effective analgesia with good motor blockade, awake patient, extended postoperative analgesia, early ambulation, early resumption of oral feeding, and more cardiovascular and respiratory stability.

A variety of local anesthetics have been used for nerve blocks. Bupivacaine is the most commonly used local anesthetic with lower incidence of postoperative complications. Apart from bupivacaine, ropivacaine and lignocaine have also been put into clinical practice. The major limiting factors with the use of local anaesthetics are their short duration of action and delayed onset. To overcome these shortcomings, adjuvants such as opioids, magnesium, ketamine, and clonidine have been tried.

Opioids have the disadvantage of causing respiratory depression, nausea, pruritus, and urinary retention. Ketamine may cause hallucinations, hypersalivation, and associated laryngospasm. Clonidine and dexmedetomidine cause adverse effects such as sedation, bradycardia, and hypotension.[1] The adverse effects of neuraxial use of magnesium sulfate are identified as bradycardia, hypotension, headache, disorientation, and periumbilical burning pain.[2]

Dexamethasone is a corticosteroid with analgesic, anti-inflammatory, and anti-emetic properties. It has found common use in the prophylaxis and treatment of postoperative nausea and vomiting and reducing postextubation airway edema.

Sodium bicarbonate is an alkali that causes alkalinisation of local anesthetics. Alkalinization allows the pH of injected solution to quickly approach normal tissue pH, which in turn liberates the free base and causes ion trapping. This increases the proportion of drug available to cross the lipid membrane of nerve cells. Thus, theoretically, addition of sodium bicarbonate should lead to more rapid drug diffusion and a quicker onset of nerve block.

While workers such as Kumar et al.[3] and Biradar et al.[4] studied the addition of dexamethasone to ropivacaine and lignocaine, respectively. Contreras-Domínguez et al.[5] and Devaram et al.[6] evaluated the addition of sodium bicarbonate to mepivacaine and lignocaine, respectively. Hence, both dexamethasone and sodium bicarbonate have been studied individually as adjuvants in peripheral nerve blocks with favorable results. We decided to investigate the net result when both these adjuvants are used together.

In our study, we aimed at studying the effect of addition of sodium bicarbonate to dexamethasone and ropivacaine in supraclavicular brachial plexus block.

MATERIALS AND METHODS

After obtaining approval of Institutional Ethical Committee (L no 28/2019-2020) and informed written consent from all patients, this study was conducted in the department of anesthesia between June 2019 and October 2020. This was a prospective, randomized, double-blind study.

Ninety American Society of Anesthesiologist (ASA) physical status Class I and II patients aged 18–60 years of either sex, who were scheduled for upper limb orthopedic surgeries, were selected for the purpose of this study.

The inclusion criteria were:

Written informed consent from the patient

ASA physical status Class I and II

Patients aged 18–60 years of either sex

Patients scheduled for elective upper limb orthopedic surgeries.

The exclusion criteria were as follows:

Patient refusal

Patients with any neurological or bleeding disorder

Allergy to local anesthetic drug

Infection at puncture site

Body mass index (BMI) >35 kg.m−2.

Using GPOWER software version 3.0.10 (Heinrich Heine University Dusseldorf, Germany), it was estimated that the least number of patients required in each group with effect size of 0.25, 80% power, and 5% significance level is 30. Since we had to compare three groups in our study, we included 90 patients in our study.

The patients were randomly allocated into three study groups:

Group R: Patients received 30 mL of 0.75% ropivacaine + 4 mL normal saline

Group D: Patients received 30 mL of 0.75% ropivacaine + 2 ml (8 mg) dexamethasone + 2 mL normal saline

Group DB: Patients received 30 mL of 0.75% ropivacaine + 2 mL (8 mg) dexamethasone + 2 mL (2 meq) of 8.4% (1 meql− 1) sodium bicarbonate.

Randomization was achieved by pulling out opaque envelops from a partially sealed box. Blinding was done by the preparation of medication according to the assigned group by one anesthesiologist while performance of the block and administration of the drug was done by another anesthesiologist who was unaware of the group allocation. Data collection was done by the second anesthesiologist.

All the study participants underwent a preanesthetic visit during which their basic demographic characteristics (age, sex, and BMI) were noted and they were explained about the Visual Analog Scale (VAS) in detail. The patients were kept fasting 8 h before surgery and given tablet alprazolam 0.25 mg night before surgery.

On the morning of surgery, an 18G cannula was secured, and patients were premedicated with injection pantoprazole 40 mg intravenous (i.v). Upon being shifted to operation theater, all routine monitoring, namely heart rate (HR), noninvasive blood pressure, pulse oxymetry (SpO2), and electrocardiogram were started.

The patients were kept in the supine position without a pillow, arm adducted by the side with head turned slightly to the opposite side. The supraclavicular area was aseptically prepared and draped. The anesthesiologist stood at the side of the patient to be blocked, facing the head of the patient. The blocks were administered by an experienced anesthesiologist using an Inmed nerve stimulator and 22G 5 cm insulated needle for identifying the plexus location.

The subclavian artery was palpated in the supraclavicular fossa approximately 1 cm above the midclavicular point. A wheal was raised at this point with 2 mL of 2% lignocaine. The 22G insulated needle was introduced just lateral to subclavian artery pulsation and directed caudal, downward, and medially toward the first rib. The stimulating current was initially set at 1 mA until distal motor response was observed. The position of the needle was said to be satisfactory when current equal to or <0.5 mA elicited a motor response. Here anesthetic solution was injected slowly in small increments of 3 mL, after negative aspiration for blood before administering each small bolus of anesthetic drug.

The following parameters were noted:

Time of onset of sensory block was recorded by pinprick using a blunt 25G hypodermic needle in dermatomes C4-T2 every 1 min till the blockade occurs. The onset of sensory block was taken as the time of injection of drug to time of loss of pain on pinprick. The sensory block was assessed and scored as follows:

0-No pain

1-Mild grimace

2-Moderate pain withdrawal

3-Severe pain.

Time of onset of motor block was taken as the time from drug injection to complete loss of motor power

The time to demand of rescue analgesia was noted

Duration of sensory block was taken as the time from the time of onset of sensory block to recurrence of pain to needle prick. This was recorded after the completion of surgery every hour for the first 3 h and then every 2 hourly till the return of pin prick

Duration of analgesia was taken from the onset of complete sensory block to the demand of first rescue analgesic

VAS scoring was done at the end of surgery and then every hour for the first 3 h and then every two hourly till the demand of rescue analgesia

Duration of motor block was taken as time from onset of complete motor block to the return of full motor power. This was assessed postoperatively every hour for 3 h and then every 2 hourly till the patient was able to move his fingers or raise his hand

The HR, systolic and diastolic blood pressure, mean arterial pressure, and arterial saturation (SpO2) were recorded every 5 min intraoperatively for the first 15 min, thereafter every 15 min until the end of surgery.

The patients were monitored for bradycardia, hypotension, convulsions, drowsiness, or any other complications for 24 h postoperatively. Patients who did not develop complete sensory and motor block even after 30 min of block administration were excluded from the study and given general anesthesia.

The primary outcome of our study was the duration of analgesia. Whereas onset of sensory and motor block, duration of sensory and motor block, VAS scoring, and any untoward side effects such as convulsions and neurological complications were the secondary outcomes of this study.

Statistical analysis

The recorded data were compiled and entered in a spreadsheet (Micro Excel) and then exported to the data editor of SPSS version 20.0 (SPAA Inc., Chicago, Illinois, USA). Continuous variables (age, BMI, duration of sensory and motor block, and analgesia) were expressed as mean ± standard deviation and categorical variables (gender and ASA) were summarized as frequencies and percentages. Student's independent t-test was employed for comparing the continuous variables. The Chi-square test was applied for comparing the categorical variables. Kruskal–Wallis test was used for postoperative pain score as data were expressed as median and range. P < 0.05 was considered statistically significant. All P values were two tailed.

RESULTS

A total 90 patients who were scheduled for elective upper limb orthopedic surgeries were included in this study. Patients in all the groups were comparable with respect to all demographic characteristics: age, sex, weight, and ASA physical status class [Table 1].

Table 1

Comparison of baseline demographic variables between group ropivacaine, group ropivacaine + dexamethasone and ropivacaine + dexamethasone + sodium bicarbonate (n=30)

	Group R	Group D	Group DB	P
Age	46.70±6.87	45.20±6.07	47.50±7.20	0.706
Weight	67.80±7.80	66.81±7.68	67.60±6.85	0.562
Sex (female/male)	16/14	14/16	17/13	0.465
ASA status, n (%)
ASA 1	17 (56)	16 (53.3)	18 (60)	0.321
ASA II	13 (43)	14 (46.6)	12 (40)

The data are expressed as mean±SD and analyzed using unpaired t-test or as n (%) and analyzed using Chi square test. ASA: American Society of Anaesthesiologist, Group R: Ropivacaine, Group D: Ropivacaine + dexamethasone, Group DB: Ropivacaine + dexamethasone + sodium bicarbonate, SD: Standard deviation

Out of all 90 patients, 2 (2.2%) had nerve sparing and thus received general anesthesia. These patients were excluded from the study.

The onset of sensory block was fastest in Group DB (dexamethasone plus bicarbonate) 3.43 ± 0.85 min, followed by Group D (dexamethasone + ropivacaine) – 5.68 ± 0.68 min and longest in Group R (ropivacaine alone) – 10.63 ± 0.79 min [Table 2].

Table 2

Comparison of onset and duration of sensory and motor block and duration of analgesia between group ropivacaine, group ropivacaine + dexamethasone and ropivacaine + dexamethasone + sodium bicarbonate

	Group R	Group D	Group DB	P
Onset of sensory block (min)	10.63±0.79	5.68±0.68	3.43±0.85	<0.001*
Onset of motor block (min)	14.56±0.82	6.67±0.38	4.68±0.52	<0.001*
Duration of sensory block (min)	280±25.40	605±86.40	1175±106.7	<0.001*
Duration of motor block (min)	250±32.60	520±56.50	920±88.68	<0.001*
Duration of analgesia (min)	320±22.40	685±62.30	1285±102.70	<0.001*

*Statistically significant. The data are expressed as mean±SD and analyzed using unpaired t-test. Group R: Ropivacaine, Group D: Ropivacaine + dexamethasone, Group DB: Ropivacaine + dexamethasone + sodium bicarbonate, SD: Standard deviation

The duration of sensory block was the longest with Group DB (dexamethasone + bicarbonate) – 1175 ± 106.7 min; followed by Group D (dexamethasone + ropivacaine) 605 ± 86.40 min and shortest in Group R (ropivacaine alone) 280 ± 25.40 min. Similarly, the duration of analgesia in Group DB and Group D was significantly longer than in group R-320 ± 22.40 min; also Group DB provided significantly longer analgesia 1285 ± 102.70 min than Group D 685 ± 62.30 min [Table 2].

The onset of motor block was shortest in Group DB – 4.68 ± 0.52 min followed by Group D – 6.67 ± 0.38 min, whereas it was 14.56 ± 0.82 min in Group R [Table 2].

The duration of motor block was significantly longer in Group DB (920 ± 88.68 min) and Group D (520 ± 56.50 min) than in Group R (250 ± 32.60 min). Furthermore, Group DB showed longer duration of motor block than Group D.

VAS score comparison shows the scores to be comparable in all three groups up to 4 h. Beyond that, the scores were significantly lower in Group DB and Group D than in Group R. Group DB had significantly low scores up to 20 h, whereas Group D showed low scores up to 10 h [Table 3].

Table 3

Comparison of visual analogue scale between group ropivacaine, group ropivacaine + dexamethasone and ropivacaine + dexamethasone + sodium bicarbonate

VAS score	Group R	Group D	Group DB	P
Immediate postoperative	0 (0-0)	0 (0-0)	0 (0-0)	0.768
2 h	0 (0-0)	0 (0-0)	0 (0-0)	0.768
4 h	0 (0-0)	0 (0-0)	0 (0-0)	0.768
8 h	5 (4-5)	0 (0-0)	0 (0-0)	<0.001*
10 h	7 (7-7)	4 (3-4)	0 (0-0)	<0.001*
14 h	8 (8-8)	5 (4-5)	0 (0-0)	<0.001*
18 h	10 (10-10)	6 (6-6)	3 (2-3)	<0.001*
20 h	10 (10-10)	7 (7-7)	5 (5-5)	<0.001*

*Statistically significant. Data expressed as median and IQR. Analyzed by kruskal wallis test. VAS: Visual Analogue Scale, Group R: Ropivacaine, Group D: Ropivacaine + dexamethasone, Group DB: Ropivacaine + dexamethasone + sodium bicarbonate, IQR: Interquartile range

There was no incidence of convulsions, drowsiness, or any other postoperative complications in any patient.

DISCUSSION

Supraclavicular blocks are performed at the level of brachial plexus trunks. As with other approaches, this technique has also seen modifications with respect to technique and use of drugs. Local anesthetics alone provide good operative conditions but have shorter duration of action as compared to when additives are used. In our study, we intended to study the effect of dexamethasone and sodium bicarbonate when given together in addition to ropivacaine in supraclavicular brachial plexus block.

Despite the advent of ultrasound, nerve stimulator technique remains popular and has been shown to have 98% success rate.[7] This corresponds with 2% failure rate seen in our study. Hence, we chose the nerve stimulator technique for the administration of supraclavicular blocks in this study.

The demographic data including age, weight, sex, and ASA grading were comparable in all three groups.

Dexamethasone is a glucocorticoid that possesses potent anti-inflammatory and immunosuppressive properties. However, it has also shown analgesic properties when given i.v. and in peripheral nerve blocks. We chose a dose of 8 mg of dexamethasone in our study because this dose has been found to be safe in adults. Studies have shown that adverse effects with a single dose of dexamethasone were rare, and short-term use (<24 h) of dexamethasone was not associated with adrenal suppression.[8]

In our study, addition of dexamethasone to ropivacaine (Group D) produced a faster onset and also prolonged the duration of block. Subsequently, VAS scores were significantly lower in Group D than plain ropivacaine group.

The prolongation of the effect of local anesthetic by the addition of dexamethasone, as seen in Group D in our study, has also been seen by multiple workers. Mathew et al.[9] compared intravenous dexamethasone and perineural dexamethasone in supraclavicular block and found that the perineural dexamethasone group had a faster onset of sensory and motor blocks. Pathak et al.[10] noticed significant prolongation of sensory and motor block when dexamethasone was added to a mixture of 1.5% adrenalized xylocaine and 0.5% bupivacaine. Kumar et al.[3] studied the addition of dexamethasone to ropivacaine, whereas Movafegh et al.[11] added dexamethasone to lidocaine. Both of them concluded that irrespective of the local anaesthetic used, dexamethasone not only quickened the onset of block but also increased its duration. Vieira et al.[12] observed that adding dexamethasone to a mixture of bupivacaine, clonidine, and epinephrine produced 1.7-fold prolongation in the interscalene block duration. However, their results should be interpreted in light of the alpha agonists added in the drug mixture.

The mechanism of potentiation of sensory and motor block by dexamethasone is not clear. Steroid-induced vasoconstriction reducing the absorption of local anesthetic could be one of the contributing factors. Honorio[13] concluded that steroids produce analgesia by blocking transmission in nociceptive c-fibers. It was proposed that steroids do so by increasing the activity of inhibitory potassium channels on nociceptive C-fiber and inhibit synthesis and/or release of various inflammatory mediators.[14] This could be the reason for the prolongation of sensory block seen in Group D in our study.

Our study showed that addition of sodium bicarbonate to dexamethasone produces a synergistic effect. There was not only a faster onset of the block but also potentiation in the duration of analgesia. The prolonged duration of analgesia translated in the significantly low postoperative VAS scores in group DB.

Sodium bicarbonate works by alkalinisation of local anaesthetic. Alkalinization of local anesthetics raise the pH of the solution and has been shown to increase the speed of nerve blocks. The pH of the injected solution more quickly approaches that of the normal tissue pH. It liberates the free base and causes ion trapping. This changes the ratio of nonionized to ionized species in solution and increases the proportion of drug able to cross the lipid membrane of nerve cells. The faster formation of a mixture with charged and uncharged forms results in more rapid drug diffusion and a quicker onset of nerve blocking.

Devaram et al.[15] studied the effect of addition of sodium bicarbonate to lignocaine and found it to provide a quicker onset as well as prolong the duration of action of the local anaesthetic. Manjunath et al.[16] added sodium bicarbonate to a mixture of lignocaine and bupivacaine and observed results similar to Devaram et al. However, Ninan and Kurien[17] compared addition of sodium bicarbonate and potassium chloride to bupivacaine and concluded that addition of potassium chloride had significant clinical advantage over alkalinised bupivacaine. They further noted that alkalinized bupivacaine did not have any advantage over plain bupivacaine.

The mechanism of potentiation of the effect of dexamethasone by the addition of sodium bicarbonate is not clear and remains a matter of future research. However, one possible mechanism could be that the alkalinized local anesthetic rapidly reaches the nerve membrane in a greater concentration and thus inhibits pain transmission by inhibiting the sodium channels. This might be having a synergising effect with dexamethasone, whose proposed mechanism is also inhibition of nociceptive transmission by action on potassium channels. Whether this could be the only mechanism or there could be other interactions possibly between dexamethasone and sodium bicarbonate remains a subject of study and debate.

The results of VAS scores and demand of first rescue analgesic (duration of analgesia) also showed that addition of sodium bicarbonate to dexamethasone and ropivacaine mixture showed maximum duration of analgesia with significantly less postoperative VAS scores than dexamethasone group. Plain ropivacaine group had the shortest duration of analgesia.

Another important observation made during this study was that, irrespective of the group, the duration of sensory block was longer than the duration of motor block. This is because the minimal effective concentration of local anesthetics for motor fibers which are larger is greater than for the sensory fibers which are smaller. Hence, the motor function returns before sensory function.[18]

Despite the concerns regarding the off label use of perineural adjuvants, safety profile of dexamethasone has been promising. Most of the cases of corticosteroid mediated neurotoxicity have been attributed to the vehicle polyethylene glycol and preservative benzyl alcohol in the commercial steroid preparations and also to the particulate steroid matter in the precipitate;[1920] neither of which is present in the commercial formulation of dexamethasone we used. Furthermore, there have not been any verified reports about sodium bicarbonate induced nerve damage. Accordingly, none of the patients in our study showed any signs of neurotoxicity in the postoperative period.

Limitations

However, our study has a few limitations:

First, patients in our study were monitored for neurotoxicity for 24 h postoperatively. Despite the absence of any documented side effects with the off-label use of dexamethasone, postoperative monitoring period should be longer to rule out late onset neuropathic effects, if any.

Second, along with neurotoxic effects, patients should also have been monitored for other serious adverse effects associated with dexamethasone use such as adrenal suppression and hyperglycemia. Even though it has been reported that the incidence of these effects is negligible with the short-term use (<24 h) of single bolus dose, their possibility cannot be ruled out entirely.

Third, ultrasound guidance should have been used for the administration of block. This would not only reduce the volume of injectate but also would make block administration easy especially in obese patients where identification of landmarks becomes difficult

CONCLUSION

Addition of sodium bicarbonate to dexamethasone and ropivacaine not only quickens the onset but also prolongs the duration of sensory and motor block. It also leads to low postoperative VAS scores and hence has a significant analgesic sparing effect postoperatively.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.