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Dexamethasone with bupivacaine increases duration of analgesia in ultrasound-guided interscalene brachial plexus blockade

Vieira, Peter A; Pulai, Istvan; Tsao, George C; Manikantan, Poornachandran; Keller, Brunella; Connelly, Neil Roy

European Journal of Anaesthesiology: March 2010 - Volume 27 - Issue 3 - p 285–288
doi: 10.1097/EJA.0b013e3283350c38
Regional Anaesthesia
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Background and objective Dexamethasone has been shown to prolong the duration of postoperative analgesia when given as an adjunct for peripheral nerve blocks. However, it has not been evaluated when given in conjunction with bupivacaine and clonidine to provide blockade of the brachial plexus at the interscalene level. The purpose of this investigation was to determine whether the addition of dexamethasone to interscalene brachial plexus block would prolong the duration of sensory analgesia in a group of patients undergoing outpatient shoulder arthroscopy.

Methods This prospective, randomized, double-blind investigation was performed on 88 individuals undergoing shoulder arthroscopy. Patients received interscalene brachial plexus block using 20 ml of bupivacaine 5 mg ml−1 with 1: 200 000 epinephrine and clonidine 75 μg. Patients were randomly assigned to receive either dexamethasone 8 mg or 0.9% NaCl as an adjuvant to the mixture. After discharge, patients recorded pain scores and analgesic consumption in a diary and estimated the time at which they perceived that the sensory block from the interscalene brachial plexus block resolved. This was based on pain, recovery of sensation and strength in the arm. Variables measured included demographics, timed pain intensity measurements, postoperative analgesic consumption, duration of analgesia and patient satisfaction.

Results Dexamethasone prolonged median sensory (1457 vs. 833 min, P < 0.0001) and motor (1374 vs. 827 min, P < 0.0001) blockade compared with the control. At 24 h, the dexamethasone group had lower median verbal analogue scale scores compared with control (3.0 vs. 6.0). At 48 h, the two groups had similar median pain scores (4.0 vs. 5.0, dexamethasone vs. control, respectively). The opioid requirement in oxycodone equivalency was lower in the dexamethasone group than in the control group for the first 24 h, and similar thereafter. Median patient satisfaction scores were not significantly different between the two groups at 48 h (9.5 vs. 8.0, dexamethasone vs. control, respectively).

Conclusion The addition of dexamethasone to a bupivacaine–epinephrine–clonidine interscalene block prolongs sensory block and reduces opioid use.

From the Department of Anesthesiology, Baystate Medical Center (GCT, PAV, IP, PM, NRC) and Department of Nursing, Baystate Medical Center (BK), Springfield, Massachusetts, USA

Received 7 June, 2009

Revised 2 November, 2009

Accepted 5 November, 2009

Correspondence to Neil Roy Connelly, MD, Department of Anesthesiology, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199, USA Tel: +1 413 794 3520; fax: +1 413 794 5349; e-mail: neil.roy.connelly@bhs.org

Accepted for presentation at the Annual meeting of the American Society of Anesthesiologists, 17–21 October 2009, New Orleans, Louisiana.

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Introduction

Regional anaesthesia has gained much popularity in outpatient orthopaedic surgery. Increasing duration of local anaesthetic action is desired for prolongation of postoperative patient comfort, as well as decreasing perioperative opioid consumption and subsequent side effects. A number of adjuvant medications have been used in an attempt to prolong regional blockade. Vasoconstrictors, such as epinephrine, classically have been used to decrease systemic absorption of local anaesthetics by vasoconstricting blood vessels, usually resulting in prolonged analgesia. Epinephrine not only acts as a vasoconstrictor but may also produce analgesia through an α2 adrenergic mechanism.1 Epinephrine may facilitate the uptake of the local anaesthetic into nerves. The addition of epinephrine prolongs duration of subcutaneous infiltration of local anaesthesia.2

Clonidine has mixed α1 and α2 agonist effects at both presynaptic and postsynaptic receptors as well as effects on a number of other specific receptors. Its mechanism of action and effects are complex.3 However, when added to intermediate-acting local anaesthetics, clonidine appears to prolong duration of anaesthesia and postoperative analgesia4–6 by a local effect.

The reports of the addition of corticosteroids as an adjuvant to local anaesthetic for peripheral nerve blocks are very limited, and the mechanism of action is not clearly understood. Dexamethasone microspheres have been found to prolong duration of bupivacaine intercostal nerve blocks in animals7,8 and humans.9,10 Dexamethasone has also been found to prolong the duration of lidocaine axillary blocks11 and intravenous regional anaesthesia (IVRA).12

There are no studies assessing the analgesic effects and duration of analgesia of dexamethasone when used as an adjunct to a combination of both local anaesthetics and clonidine. The purpose of this study was to evaluate whether dexamethasone administered in addition to both bupivacaine and clonidine, given via an interscalene block for patients undergoing ambulatory shoulder surgery, would prolong sensory analgesia.

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Patients and methods

This was a prospective, randomized, double-blinded study conducted after Institutional Review Board approval was obtained. Written informed consent was obtained from 120 American Society of Anesthesiologists (ASA) physical status I, II or III patients more than 18 years of age who were scheduled for an outpatient shoulder arthroscopy. Patients with a contraindication to bupivacaine, epinephrine, clonidine or dexamethasone were excluded. Pregnancy tests were performed on the day of surgery for all women of childbearing potential. Pregnant patients were excluded from this study. Eighty-eight patients completed the study.

Prior to initiation of this study, a power analysis was performed. The power of the study was set at 90%, with an α of 0.05. On the basis of our unpublished institutional results, the baseline duration of interscalene blocks was 18 ± 8.5 h. We were interested in an analgesic difference of 6 h. This yielded a required sample size of 88 patients.

Following arrival in the preoperative nerve block room, patients were monitored with oxygen saturation, ECG and noninvasive blood pressure (BP). Interscalene block was performed with the patients in the supine position. The brachial plexus, at the level of the trunks, was identified between the anterior and middle scalene muscles with ultrasound (GE LOGIQ e system, Piscataway, New Jersey, USA). The skin injection site was prepared with an antiseptic solution, and then subcutaneously infiltrated with 1 ml of 2% lidocaine. A 5.08 cm, 22-G regional block needle was visualized using an in-plane technique while simultaneously visualizing the brachial plexus with ultrasound. Patients received a total injection volume of 20 ml with frequent aspirates during the injection.

Patients were allocated into two groups in a controlled, randomized, double-blind design using a computer-generated randomization list to receive either one of the two solutions:

  1. bupivacaine 5 mg ml−1 with epinephrine 5 μg ml−1, clonidine 75 μg and 2 ml preservative free 0.9% NaCl (control group) and
  2. bupivacaine 5 mg ml−1 with epinephrine 5 μg ml−1, clonidine 75 μg and dexamethasone 8 mg (dexamethasone group).

All local anaesthetic solutions and adjuvant medications were prepared by an anaesthesiologist not involved in the performance of brachial plexus block or data collection.

In the operating room, standard monitoring was applied (pulse oximetry, ECG and noninvasive BP monitoring) and the patients received a general anaesthetic induction by propofol, and maintenance with sevoflurane, desflurane or propofol, with nitrous oxide. Patients did not receive any preoperative or intraoperative opioids. Intubation was facilitated with rocuronium. At the conclusion of the procedure, the neuromuscular block was antagonized with neostigmine and glycopyrrolate.

Postoperative pain was measured by verbal analogue scores (VAS) (with 0 representing ‘no pain’ and 10 representing ‘worst imaginable pain’). Pain scores were obtained on arrival in the postanaesthesia care unit (PACU), 1 and 2 h postoperatively, at the time of PACU discharge and at 24 and 48 h postoperatively. If the patient had a pain score of more than 3 during the postoperative admission, the interscalene block was repeated, and the patient was not included in the data analysis. The amount of postoperative analgesics required by the patients was recorded. Pain and number of oral analgesics were evaluated by telephone survey at 24 and 48 postoperative hours.

At the time of discharge, patients were given a diary in order to accurately record pain scores and opioid analgesic consumption (hydrocodone, oxycodone and hydromorphone) and to accurately determine the time at which they perceived that the sensory and motor block resolved (based on an increase in pain, sensation and strength in the arm). Patient satisfaction with pain management was determined on PACU discharge and at 48 h postoperatively on a numerical satisfaction score (with 0 representing ‘completely unsatisfied’ and 10 representing ‘completely satisfied’).

Patients were instructed to take an oral analgesic if their pain score was greater than 3. Consumption of postoperative opioid medication was adjusted to an equipotent amount of oxycodone (hydrocodone 1 mg = oxycodone 0.66 mg; hydromorphone 1 mg = oxycodone 2.66 mg).

Nonparametric testing (Mann–Whitney U test) was utilized to evaluate the pain scores, opioid consumption and sensory and motor duration. Demographic (height, weight, block time and procedure time) data were analysed using Student's t-test. A chi-squared test was used to analyse sex and the satisfaction scores. Nonparametric data are presented as the median with the interquartile range (IQR), that is, 25th–75th percentile. Statistical significance was determined at the P value of less than 0.05 level.

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Results

One hundred and twenty patients enrolled in the study to obtain 88 patients who had reliable data. Of the 32 patients (n = 17 in the control group and n = 15 in dexamethasone group) who were dropped, 19 patients had protocol failure (patients inadvertently received prophylactic oxycontin), four patients required a repeat interscalene block in the PACU (three in control and one in dexamethasone), one patient's surgery was cancelled after shoulder manipulation by the surgeon, two patients told us that they would not take opioids postoperatively irrespective of their pain and six patients were unable to provide accurate information at the time of their telephone survey.

There were no differences in demographics, duration of surgery, block time or procedure time (Table 1). The sensory block was longer in the dexamethasone group than in the control group (1457 min, IQR 1324–1910 min vs. 833 min, IQR 726–1086 min, P < 0.0001, Figs 1 and 2). The motor block also lasted longer in the dexamethasone group, although not to the same extent (1374 min, IQR 1155–1559 min vs. 827 min, IQR 727–1049 min, P < 0.0001).

Table 1

Table 1

Fig. 1

Fig. 1

Fig. 2

Fig. 2

There were 39 patients who underwent rotator cuff repair surgery (19 in control vs. 20 in dexamethasone) and 49 patients who underwent arthroscopy and subacromial decompression (25 in control vs. 24 in dexamethasone).

There was no difference between the groups in preoperative pain or pain at any time in the PACU. Postoperative pain scores at 24 h after surgery did differ by group: the dexamethasone group had a VAS score of 3.0 (IQR 0.3–5.0), whereas the control group's pain score was 6.0 (IQR 4.0–7.4, P < 0.0001). There was no difference in pain at 48 h following surgery: 4.0 with IQR 2.0–6.0, and 5.0 with IQR 3.0–7.0 in the dexamethasone and control groups, respectively.

The 24 h opioid requirement in oxycodone equivalency was lower in the dexamethasone group (0 mg, IQR 0–10 mg vs. 30 mg, IQR 13–50 mg, P < 0.0001). The opioid requirement between 24 and 48 h was similar (25 mg, IQR 0–35 mg vs. 25 mg, IQR 5–40 mg, dexamethasone vs. control, respectively). Total opioid requirement was less in the dexamethasone group (25 mg, IQR 5–50 mg vs. 53 mg, IQR 30–84 mg). There were three patients in the control group and 26 patients in the dexamethasone group who did not take any opioids during the first 24 postoperative hours (P < 0.0001). There were three patients in the control group and 12 patients in the dexamethasone group who did not take any opioids between 24 and 48 postoperative hours (P < 0.01). Patient satisfaction was not significantly different at 48 h (9.5, IQR 8–10 vs. 8.0, IQR 8–10, dexamethasone vs. control, respectively).

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Discussion

In the current study, we investigated whether the duration of analgesia could be extended by adding 8 mg of dexamethasone to 5 mg ml−1 of bupivacaine (with 1: 200 000 epinephrine) with 75 μg clonidine to provide for an ultrasound-guided interscalene brachial plexus block. The dexamethasone group had an approximately 12 h longer sensory duration and needed less postoperative opioids.

The mechanism of analgesia produced by corticosteroids is not fully understood. The prolonged axillary bupivacaine analgesia is suspected to be mediated by the inhibition of synthesis and/or release of various inflammatory mediators; this effect has been proposed to last up to 48 h.13 In our study, however, we did not expect such significant prolongation, given the dexamethasone we were using is water-soluble, unlike the microsphere emulsions used in other studies.7–10 Interestingly, the blockade-prolonging effects of glucocorticoids have been reported to be related to the rank-ordering of their anti-inflammatory effects and are completely reversed by administration of a specific antagonist.14

When dexamethasone was added to lidocaine IVRA, it prolonged motor and sensory blockade and resulted in significantly less mean postoperative analgesic requirements.12 Dexamethasone with lidocaine in an axillary brachial plexus block prolongs both the sensory and motor block duration.11 When added to a supraclavicular bupivacaine with epinephrine brachial plexus block, dexamethasone significantly prolonged the duration of analgesia.15 None of these studies, including the current one, can rule out a systemic effect for the improved analgesia found from peripherally administered steroids. Corticosteroids cause some vasoconstriction, probably mediated by occupancy of classical glucocorticoid receptors rather than by nonspecific pharmacological mechanisms.16,17 We doubt that, in the current study, dexamethasone-induced vasoconstriction is solely responsible for block prolongation, as we also used the vasoconstrictors epinephrine and clonidine.

The safety of dexamethasone use in a nerve sheath may raise some concerns. In animal experiments, triamcinolone18 did not induce spinal neurotoxicity, whereas repeated high-dose intrathecal injections of betamethasone19 caused histopathological changes of the spinal cord. However, no neurological disorders were found following multiple intrathecal injections of dexamethasone (8 mg) for treatment of posttraumatic visual disturbance.20 Further studies are necessary to fully address these concerns. Dexamethasone rarely causes nerve injury, and, when it does, it usually occurs in the context of needle trauma.21,22 However, in our study, the occurrence of needle trauma is unlikely, as we utilized direct ultrasound visualization during performance of the block.

In our study, we utilized the combination of bupivacaine, epinephrine, clonidine and dexamethasone. We found that the addition of dexamethasone significantly prolongs the duration of sensory block and decreases opioid requirements.

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Acknowledgements

This study was supported by departmental funding. No commercial or noncommercial funding was received in support of this study.

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References

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Keywords:

ambulatory; anaesthesia; analgesia; brachial plexus; clonidine; orthopaedic; regional

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