Year : 2011 | Volume
| Issue : 4 | Page : 382-386
Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in orthopedic surgery
Nadia Bani-hashem1, Bahman Hassan-nasab1, Ebrahim Alijan Pour1, Parviz Amri Maleh1, Aliakbar Nabavi2, Ali Jabbari3
1 Department of Anesthesiology, Babol University of Medical Sciences, Babol, Iran
2 Department of Anesthesiology, Tehran, Iran
3 Babol University of Medical Sciences and Researcher of Deputy of Treatment, Golestan University of Medical Sciences, Golestan, Iran
Anesthesiology Department, Flat 2, Rohani Hospital, Ganj, Afroz Blv, Daneshgah Sq, Babol city, Mazandaran Province
|Date of Web Publication||8-Nov-2011|
Objectives: Spinal anesthesia has the advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anesthetic. Intrathecal local anesthetics have limited duration. Different additives have been used to prolong spinal anesthesia. The effect of corticosteroids in prolonging the analgesic effects of local anesthetics in peripheral nerves is well documented. The purpose of this investigation was to determine whether the addition of dexamethasone to intrathecal bupivacaine would prolong the duration of sensory analgesia or not. Methods: We conducted a randomized, prospective, double-blind, case-control, clinical trial. A total of 50 patients were scheduled for orthopedic surgery under spinal anesthesia. The patients were randomly allocated to receive 15 mg hyperbaric bupivacaine 0.5% with 2 cc normal saline (control group) or 15 mg hyperbaric bupivacaine 0.5% plus 8 mg dexamethasone (case group) intrathecally. The patients were evaluated for quality, quantity, and duration of block; blood pressure, heart rate, nausea, and vomiting or other complications. Results: There were no signification differences in demographic data, sensory level, and onset time of the sensory block between two groups. Sensory block duration in the case group was 119±10.69 minutes and in the control group was 89.44±8.37 minutes which was significantly higher in the case group (P<0.001). The duration of analgesia was 401.92±72.44 minutes in the case group; whereas it was 202±43.67 minutes in the control group (P<0.001). The frequency of complications was not different between two groups. Conclusion: This study has shown that the addition of intrathecal dexamethasone to bupivacaine significantly improved the duration of sensory block in spinal anesthesia without any changes in onset time and complications.
Keywords: Bupivacaine, dexamethasone, intrathecal, sensory block, spinal anesthesia
|How to cite this article:|
Bani-hashem N, Hassan-nasab B, Pour EA, Maleh PA, Nabavi A, Jabbari A. Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in orthopedic surgery. Saudi J Anaesth 2011;5:382-6
|How to cite this URL:|
Bani-hashem N, Hassan-nasab B, Pour EA, Maleh PA, Nabavi A, Jabbari A. Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in orthopedic surgery. Saudi J Anaesth [serial online] 2011 [cited 2014 Nov 25];5:382-6. Available from: http://www.saudija.org/text.asp?2011/5/4/382/87267
| Introduction|| |
Spinal anesthesia is the most consistent block for lower abdomen and orthopedic surgery. Spinal anesthesia avoids the risks of general anesthesia such as aspiration of gastric contents and difficulty with airway management.  Bupivacaine is appropriate for procedures lasting up to 90-120 minutes. ,, Therefore, various additives such as epinephrine, phenylephrine, clonidine, opioids, etc. were added to local anesthetics. ,,, The additions of epinephrine to local anesthesia cause tachycardia, pallor, and hypertension, which can be risky in patients with cardiovascular disease.  Intrathecal opioid administration has central and respiratory depression effects. Recently, some studies reported the effects of corticosteroids in quality and quantity of the sensory block in the peripheral nerves. ,,
Dexamethasone relieves pain by reducing inflammation and blocking transmission of nociceptive C-fibers and by suppressing ectopic neural discharge.  It has been shown that the duration of postoperative analgesia was prolonged when dexamethasone is given as an adjunct for peripheral nerve blocks. , Although dexamethasone has been used intrathecally for many years, it has not been evaluated when it was given in conjunction with bupivacaine intrathecally. The purpose of this investigation was to evaluate the effect of conjugation of dexamethasone with bupivacaine on the duration and onset time of spinal anesthesia.
| Methods|| |
Fifty patients with class American Society of Anesthesiologist (ASA) I-II, between 18 and 55 years old, scheduled for orthopedic surgery under spinal anesthesia, were included in this prospective, randomized, double-blind clinical trial. The orthopedic procedures were on lower limbs with surgery duration around 30-70 minutes. After ethic committee approval, written informed consent was obtained from each patient preoperatively.
Patients with history of long-term steroid therapy, allergy to the drugs, uncontrolled hypertension, neurologic or psychological disorders, spinal column surgery, low back pain, alcohol abuse, opium addict or using any drug that modifies pain perception were excluded from the study.
Patients were randomly allocated into two groups, intrathecal bupivacaine- dexamethasone as the case group and intrathecal bupivacaine- normal saline as the control group.
After IV line preparation, a 5 cc/kg lactated ringers solution was infused to all patients. Patients received no premedication, and upon arrival of patients into the operating room, ECG, peripheral oxygen saturation (SPO 2 ), and noninvasive arterial blood pressure (NIBP) were monitored and recorded at 5-minute intervals until the end of surgery and vital signs were recorded every 15 minutes in the Post Anesthesia Care Unit (PACU).
Spinal anesthesia was performed in the sitting position at L 4 -L 5 level through a midline approach using a 25-gauge Quincke spinal needle. Patients of the control group received 15 mg (3 ml) of 0.5% hyperbaric bupivacaine diluted in preservative free normal saline (2 ml) and patients of the case group received 15 mg (3 ml) of 0.5% hyperbaric bupivacaine and 8 mg preservative free dexamethasone with the Dexadic brand name (2 ml), overall 5 ml volume intrathecally. To facilitate the double-blinding method, the medication was prepared and injected by an anesthesiologist who was not involved in the study. After performance of the spinal anesthesia patients were kept in supine position and oxygen 3-5 L min -1 was given through a face mask. The sensory block level was assessed by a pin prick test by a short bevel needle along the mid-axillary line bilaterally. The sensory block level was controlled every 30 seconds for 20 minutes; then it was evaluated every 5 minutes until a 4 sensory level regression from highest level or to the end of the surgery. Onset time was defined from the time of injection of drugs into the intrathecal space to the peak of sensory and motor block (highest dermatome level) and the duration of sensory block was defined from peak of sensory block up to 4 sensory level regressions or when the patients feel pain in the field of surgery.
Hypotension, a 30% decrease in systolic blood pressure from base line or systolic blood pressure <100 mm Hg and bradycardia, HR<50 beats/min was treated by IV ephedrine 5-10 mg plus crystalloid fluids; and IV atropine 0.5 mg respectively. Nausea and vomiting were also evaluated and were treated with 0.15 mg /kg IV metoclopramide.
After 4 dermatome block regression, pain assessment intraoperatively or in PACU was done using the visual analogue pain scale (VAS) between 0-10 (0 = no pain, 10 = the most severe pain) every 1 hour. If the postoperative VAS was higher than 6, it was treated by morphine 2 mg IV. Patients were observed at the time of discharge from hospital and 1 month later and asked about any neurologic deficit.
The demographic data of patients were studied for each of the two groups. Continues covariates such as age, weight, height, and BMI were compared using the analysis of variance T-test. Onset time, sensory block duration, and duration of analgesia were analyzed by a T-test as appropriate, with the P value reported at the 95% confidence interval. For categorical covariates (sex, nausea/vomiting, hypotension, bradycardia, use of ephedrine, the use of atropine), the comparison was studied using a chi-squared test or Fisher's exact test. Sensory level compared by Mann-Whitney test. The significance level was defined as a P value less than 0.05. To calculate the sample size, a power analysis of α=0.05 and β=0.80 showed that 25 patients per study group were needed to detect the difference between two groups.
| Results|| |
All patients (n=50) completed the study; there was no statistical difference in patients' demographics [Table 1]. The onset time of sensory block was 11.2±2.0 minutes for the case group and 10.9±1.8 minutes for the control Group (P=0.57). The maximum sensory level was between T 4 and T 10 in both groups and there was no significant difference (P=0.76) [Figure 1].
|Figure 1: Sensory block level in the bupivacaine-dexamethasone versus bupivacaine-normal saline group|
Click here to view
The duration of the sensory block was 119.1±10.6 minutes in the case group and 89.4±8.3 minutes in the control group with a P value less than 0.001; also pain-free period in the case group was more than that in the control group(P<0.001). Receiving time to VAS >6 and the first analgesic dose prescription in the case group was significantly longer than that in the control group (P<0.001) [Table 2]. Hypotension was mild to moderate in both groups and was not different; except one patient in the control group who had a mean arterial pressure less than 60 mmHg and required 20 mg IV ephedrine to restore his blood pressure [Table 3].
|Table 2: Comparison of onset time, duration of sensory block and pain free period between two groups|
Click here to view
|Table 3: Incidence of adverse events between two groups during the study period|
Click here to view
Two patients in the case group and three patients in the control group complained of postdural puncture headache which was treated by hydration and simple analgesia. Other complications such as bradycardia, nausea, and vomiting were not different between the two groups [Table 3] and no neurologic deficit was observed in any patients.
| Discussion|| |
Present results in this study showed that the supplementation of spinal bupivacaine with 8 mg dexamethasone significantly prolonged sensory block and postoperative analgesia compared with intrathecal bupivacaine, without any effects on the onset time of sensory block in orthopedic surgery.
Several experiments demonstrated analgesic effects of steroids in neuroaxial and peripheral block. ,,, Movafegh et al. reported that the addition of dexamethasone (8 mg) to lidocaine for spinal anesthesia provided significant prolongation of sensory and motor block in comparison with plain lidocaine and there is no difference between dexamethasone-lidocaine 5% and epinephrine (0.2 mg) - lidocaine 5% in sensory and motor block duration. Consequently, the onset time of sensory and motor blockade were similar among these three groups. 
Corticosteroids cause skin vasoconstriction on topical application. The vasoconstriction effects of topical steroids are mediated by occupancy of classical glucocorticoid receptors. , In our study, dexamethasone produced a significant prolonged sensory block which can be explained by vasoconstriction mechanism, in contrast with traditional theory of steroid action; steroids bind to intracellular receptors and modulate nuclear transcription. 
Mirzaie et al. reported that corticosteroids and bupivacaine can diminish the incidence of back pain after laminectomy in the immediately postoperative period.  Kotani et al. administered methylprednisolone with bupivacaine intrathecally in patients with postherpetic neuralgia. They concluded that this combination induced excellent and long-lasting analgesia. 
Taguchi et al. reported that intrathecal injection of betamethasone successfully decreased the pain score in three patients with intractable cancer pain  Another study reported that epidural dexamethasone (5 mg) reduces postoperative pain score and morphine consumption following laparoscopic cholecystectomy with no apparent side effects  Atsuhrio reported that intrathecal or epidural methylprednisolone decreased continuous pain and allodynia in patients with postherpetic neuralgia. The analgesia was much greater in the intrathecal group compared to the epidural group. Interleukin 8 in the CSF decreased significantly in the intrathecal group as compared to the epidural group. 
Steroids have a powerful anti inflammatory as well as analgesic property but the mechanism of the analgesia induced by corticosteroid is not fully understood. , Epidural steroids were used for back pain treatment. Intrathecal dexamethasone may influence intraspinal prostaglandin production. Acute noxious stimulation of peripheral tissues leads to sensitization of dorsal horn neurons of the spinal cord by the release of substances such as glutamate and aspartate. These amino acids activate N-methyl-D-Aspartate receptors resulting in calcium ion influx which leads to activation of phospholipase A2, which converts membrane phospholipase to arachidonic acid. Corticosteroids are capable of reducing prostaglandin synthesis by inhibition of phospholipase A2 through the production of calcium-dependent phospholipid binding proteins called annexins and by the inhibition of cyclooxygenases during inflammation. 
Some authors also believe that analgesic properties of corticosteroids are the results of their systemic effects.  The block prolonging effect may be due to its local action on nerve fibers.  Previous works demonstrated that addition of dexamethasone to local anesthetics prolonged duration of blockade of peripheral nerves. A study in supra-clavicular block suggests that the addition of dexamethasone to bupivacaine significantly prolonged duration of analgesia.  Another study in axillary block reported that dexamethasone when added to lidocaine significantly prolongs duration of analgesia without any change in onset. 
In animal experiments, triamcinolone  did not induce spinal neurotoxicity, whereas repeated high-dose intrathecal injections of betamethasone  caused histopathological changes of the spinal cord. Intrathecal injection of steroids was frequently used for the treatment of mumps meningitis, chronic lymphocytic leukemia and central nervous involvement in lupus erythematosus.  Like our finding, some of the studies did not reported any considerable complication for intrathecal dexamethasone. Kotani et al. found no complication in patients who received intrathecal methyl prednisolone.  Also Sugita did not find complication after intrathecal injections of 8 mg dexamethasone in patients with posttraumatic visual disturbance. 
| Conclusion|| |
In our investigation, we utilized the combination of bupivacaine and 8 mg dexamethasone intrathecally. We found that the addition of dexamethasone significantly prolongs the duration of sensory block and decreases opioid requirements in postoperative management. Further studies are needed to evaluate the optimal dose of dexamethasone to be used in spinal anesthesia.
| References|| |
|1.||Brown D.L. Spinal, Epidural and caudal anesthesia. In: Miller RD, (editor). Miller's Anesthesia 7 th ed, Philadelphia: Churchill living stone; 2010. p. 1611-38. |
|2.||Murali KT, Panda NB, Batra YK, Rajeev S. Combination of low doses of intrathecal Ketamine and midazolam with bupivacaine improves postoperative analgesia in orthopedic surgery. Eur J Anesthesiol 2008;25:299-306. |
|3.||Chakraborty S, Chakrabarti J, Bhattacharya D. Intrathecal tramadol added to bupivacaine as spinal anesthetic increases analgesic effect of the spinal blockade after major gynecological surgeries. Indian J pharmacol 2008;40:180-2. |
|4.||Yu SC, Ngan Kee WD, Kwan AS. Addition of meperidine to bupivacaine for spinal anesthesia for cesarean section. Br j Anesth 2002;88:379-83. |
|5.||Alhashemi JA, Kaki AM. Effect of intrathecal tramadol administration post operative pain after transurethral resection of prostate. Br J Anesth 2003;91:536-40. |
|6.||Golwala MP, Swadia VN, Aditi A, Dhimar, Sridbar NV. Pain relief by dexamethasone as an adjuvant to local anesthetics in supraclavicular brachial plexus block. J Anesth Clin Pharmacol 2009;25:285-8. |
|7.||Vieira PA, Pulai I, Tsao GC, Manikantan P, Keller B, Connelly NR. Dexamethasone with bupivacaine increases duration of analgesia in ultrasound-guided interscalene brachial plexus blockade. Eur J Anaesthesiol 2010;27:285-8. |
|8.||Bromage PR. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia. Acta Anesthesiol Scand Suppl 1965;16:55-69. |
|9.||Glasser RS, Knego RS, Delashaw JB, Fessler RG. The perioperative use of corticosteroids and bupivacaine in the management of lumbar disc disease. J Neurosurg 1993;78:383-7. |
|10.||Castillo J, Curley J, Hotz J, Uezono M, Tigner J, Chasin M, et al. Glucocorticoids prolong rat sciatic nerve blockade in vivo from bupivacaine microspheres. Anesthesiology 1996;85:1157-66. |
|11.||Droger C, Benziger D, Gao F, Berde CB. Prolonged intercostals nerve blockade in sheep using controlled-release of bupivacaine and dexamethasone from polymer microspheres. Anesthesiology1998;89:969-74. |
|12.||Kopacz DJ, Lacouture PG, Wu D, Nandy P, Swanton R, Landau C. The dose response and effects of dexamethasone on bupivacaine microcapsules for intercostals blockade (T 9 to T 11 ) in healthy volunteers. Anesth Analg 2003;96:576-82. |
|13.||Movafegh A, Ghafari MH. A comparison of the sensory and motor blockade duration of intrathecal lidocaine 5% plus epinephrine and lidocaine 5% plus dexamethasone. Int J pharmacol 2005;1:346-9. |
|14.||Marks R, Barlow JW, Funder JW. Steroid-induced vasoconstriction: Glucocorticoid antagonist studies. J Clin Endocrinol Metab 1982;54:1075-7. |
|15.||Seidenari S, Di Nardo A, Mantovani L, Giannetti A. Parallel intraindividual evaluation of the vasoconstrictory action and the anti-allergic activity of topical corticosteroids. Exp Dermatol 1997;6:75-80. |
|16.||Taguchi H, Shingu K, Okuda H, Matsumoto H. Analgesia for pelvic and perineal cancer pain by intrathecal steroid injection. Acta Anaesthesiol Scand 2002;46:190-3. |
|17.||Mirzai H, Tekin I, Alincak H. Perioperative use of corticosteroid and bupivacaine combination in lumbar disc surgery. Spine 2002;27:343-6. |
|18.||Kotani N, Kushikata T, Hashimoto H, Kimura F, Muraoka M, Yodono M, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000;343:1514-9. |
|19.||Taguchi H, Shingu K, Okuda H, Matsumoto H. Analgesia for pelvic and perineal cancer pain by intrathecal steroid injection. Acta Anaesthesiol Scand 2002;46:190-3. |
|20.||Thomas S, Beevi S. Epidural dexamethasone reduces postoperative pain and analgesic requirements. Can J Anaesth 2006;53:899-905. |
|21.||Kikuchi A, Kotani N, Sato T, Takamura K, Sakai I, Matsuki A. Comparative therapeutic evaluation intrathecal versus epidural methylprednisolone for long Term analgesia in patients with intractable post herpetic neuralgia. Reg Anesth Pain Med 1999;24:287-93. |
|22.||McCormack K. The spinal actions of nonsteroidal anti-inflammatory drugs and the dissociation between their anti-inflammatory and analgesic effects. Drugs 1994;47:28-45. |
|23.||Ahlgren SC, Wang JF, Levine JD. C-fiber mechanical stimulusresponse functions are different in inflammatory versus neuropathic hyperalgesia in the rat. Neuroscience 1997;76:285-90. |
|24.||Yao XL, Cowan MJ, Glawin MT, Lawrence MM, Angus CW, Shelhamer JH. Dexamethasone alters arachidonate release from human epithelial cells by induction of P11 protein synthesis and inhibition of phospholipas A 2 activity. J Biol Chem1999;274:17202-8. |
|25.||Baxendale BR, Vater M, Lavery KM. Dexamethasone reduces pain and swelling following extraction of third molar teeth. Anesthesia 1993;48:961-4. |
|26.||Kopacz DJ, Lacouture PG, WU D, Nandy P, Swanton R. The dose response and effects of dexamethasone on bupivacaine microcapsules for intercostals blockade in healthy volunteers. Anesth Analg 2003;96:576-82. |
|27.||Movafegh A, Razazian M, Hajimaohamadi F, Mysamie A. Dexamethasone added to lidocaine prolongs axillary bracial plexus blockage. Anesth Analg 2006;102:263-7. |
|28.||Abram SE, Marsala M, Yaksh TL. Analgesic and neurotoxic effects of intrathecal corticosteroids in rats. Anesthesiology 1994;81:1198-205. |
|29.||Latham JM, Fraser RD, Moore RJ, Blumbergs PC, Bogduk N. The pathologic effects of intrathecal betamethasone. Spine (Phila Pa 1976) 1997;22:1558-62. |
|30.||Dong Y, Zhang X, Tang F, Tian X, Zhao Y, Zhang F. Intrathecal injection with methotrexate plus dexamethasone in the treatment of central nervous system involvement in systemic lupus erythematosus . Chin Med J 2001;114:764-6. |
|31.||Sugita K, Kobayashi S, Yokoko A, Inoue T. Intrathecal steroid therapy for post traumatic visual disturbance. Neuronchirurgia (Stuttg) 1983;26:112-7. |
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
| ||Christopher D. Noss,Lindsay D. MacKenzie,Mark A. Kostash |
| ||Regional Anesthesia and Pain Medicine. 2014; 39(6): 540 |
||The Effects of Glucocorticoids on Neuropathic Pain
| ||Mienke Rijsdijk,Albert J. M. van Wijck,Cornelis J. Kalkman,Tony L. Yaksh |
| ||Anesthesia & Analgesia. 2014; 118(5): 1097 |
||Comparison of Postoperative Analgesic Effect of Dexamethasone and Fentanyl Added to Lidocaine through Axillary Block in Forearm Fracture
| ||Siamak Yaghoobi,Mahyar Seddighi,Zohreh Yazdi,Razieh Ghafouri,Marzieh Beigom Khezri |
| ||Pain Research and Treatment. 2013; 2013: 1 |
||Comparison between intrathecal and intravenous betamethasone for post-operative pain following cesarean section: A randomized clinical trial
| ||Naghibi, T. and Dobakhti, F. and Mazloomzadeh, S. and Dabiri, A. and Molai, B. |
| ||Pakistan Journal of Medical Sciences. 2013; 29(2): 514-518 |
||Intrathecal magnetic drug targeting using gold-coated magnetite nanoparticles in a human spine model
| ||Eric Lueshen,Indu Venugopal,Joseph Kanikunnel,Tejen Soni,Ali Alaraj,Andreas Linninger |
| ||Nanomedicine. 2013; : 1 |
||Spinal Cannabinoid Receptor Type 2 Agonist Reduces Mechanical Allodynia and Induces Mitogen-Activated Protein Kinase Phosphatases in a Rat Model of Neuropathic Pain
| ||Russell P. Landry,Elena Martinez,Joyce A. DeLeo,E. Alfonso Romero-Sandoval |
| ||The Journal of Pain. 2012; 13(9): 836 |
||Spinal cannabinoid receptor type 2 agonist reduces mechanical allodynia and induces mitogen-activated protein kinase phosphatases in a rat model of neuropathic pain
| ||Landry, R.P. and Martinez, E. and Deleo, J.A. and Romero-Sandoval, E.A. |
| ||Journal of Pain. 2012; 13(9): 836-848 |