Published: 2016-12-27

Observation on analgesic efficacy and adverse effects of intrathecal administration of bupivacaine versus bupivacaine-midazolam combination in lower limb surgeries in a tertiary care hospital

Md. Mohsin, Rekha Kumari


Background: Postoperative pain relief can improve functionality, reduce physiological and emotional morbidity and improve quality of life. Neuraxial blocks not only reduce the incidence of venous thrombosis, pulmonary embolism, cardiac complications, bleeding transfusion requirements and respiratory depressions but also provide effective postoperative analgesia. One of the methods of providing postoperative is to prolong the duration of intrathecally administered bupivacaine by using additives such as opioids such as midazolam, clonidine and ketamine. Intrathecal administration of midazolam induces antinociceptive effects in humans. The present study was undertaken to evaluate the additive analgesic effects of intrathecal midazolam in combination with bupivacaine in lower limb surgeries in a tertiary care hospital and to compare the results with the use of bupivacaine alone. The aim of this study was to observe and compare the quality of spinal anaesthesia and occurrence of side effects in thirty cases administered with bupivacaine and thirty cases administered with bupivacaine-midazolam combination.

Methods: Sixty cases admitted for lower limb surgery were divided into equal groups I and II. Cases in group I received intrathecal bupivacaine while those in group II received intrathecal combination of bupivacaine and midazolam. Data regarding quality of anesthesia and side effects were recorded and compared.

Results: There was a significantly higher duration of a pain-free period in cases administered with intrathecal combination of bupivacaine and midazolam.

Conclusions: Addition of preservative free midazolam to 0.5% hyperbaric bupivacaine for subarachnoid block prolongs the duration of effective analgesia as compared to bupivacaine alone. The utilization of intrathecal midazolam also decreases the incidence of postoperative nausea-vomiting.



Anaesthesia, Bupivacaine, Combination, Intrathecal, Midazolam

Full Text:



Walser A. Quinazolines and benzodiazepines. Synthesis and reactions of imidazole. J Org Chem. 1978;43(5):936-44.

Reves JG. Midazolam: Pharmacology and uses. Anaesthesiology. 1985;62(3):310-324.

Greenblatt DJ. Drug therapy: Current status of benzodiazepines. The New Eng J Med. 1983;309(6):354-8.

Arendt RM. In vitro correlates of benzodiazepines serebrospinal fluid uptake. J Pharm Exp Ther. 1983;227(1):98-106.

Mendelson WB. Neuropharmacology of sleep induction by benzodiazepines. Crit Rev Neurobiol. 1992; 6(4):221-32.

Strange PG. Dopamine receptor reaction at the biochemical level. Trends in Pharm Sc. 1991;12(2):48-9.

Rudolph U. A new benzodiazepine pharmacology. J Pharm & Exp Ther. 2002;300(1):2-8.

Goodchild CS. Antinciception by intrathecal midazolam. The Br J Anaesth. 1996;77(6):758-63.

Dahl JB. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing spinal anaesthesia. Anaesthesiology. 1999;91(6):1919-27.

Niv D. Depression of nociceptive of sympathetic reflexes by intrathecal midazolam. The Br J Anaes. 1983;55(6):541-7.

Faull RLM. Benzodiazepine receptors in the human spinal cord. Neuroscience. 1986;17(3):791-802.

Muller H. Spasticity treatments with spinal morphine or midazolam. Anaesthetist. 1986;35(5):306-16.

Noble J. The effects of intrathecal midazolam on sympathetic nervous system reflexes in man. The Br J of Clin Pharm. 1987;23(3):279-85.

Serrao JM. Naloxone anatagonizes the spinal analgesic effects of midazolam. The Br J Anaesth. 1989;62(2):233-4.

Walvogel HJ. GABA and benzodiazepine receptors in the human spinal cord. Neuroscience. 1990; 39(2):361-85.

Edwards M. Mechanism by which midazolam causes spinally mediated anaesthesia. Anaesthesiology. 1990;73(2):273-7.

Malinovsky JM. Ketamine and midazolam neurotoxicity in the rabbit. Anaesthesiology. 1991;75(1):91-7.

Erdine S. Neurotoxicity of midazolam in the rabbi. Pain, 1999; 80(1):91-97.

Schoeffler S. Subarachnoid midazolam: Histologic study in rats. Regional Anaes. 1991;16(6):329-32.

Aguilar JL. Difficult management of pain following sacrococcygeal chordoma. Pain. 1994;59(2):317-20

Svensson BA. Chronic subarachnoid midazolam in the rat. Regional Anaes. 1995;20(5):426-34.

Valentine JM. The effect of intrathecal midazolam on postoperative pain. Eur J Anaesth. 1996;13(6):589-93.

Borg PAJ. Long term intrathecal administration of midazolam and clonidine. Clin J Pain. 1996;12(1):63-8.

Tunali Y. Histological changes following epidural injection of midazolam in the neonatal rabbit. Paed Anaes. 1997;7(5):385-9.

Bahar M. Spinal anaesthesia with midazolam in the rat. Canadian J Anaes. 1997;44(2):208-15.

Hanoaka K. Continuous administration of bupivacaine and midazolam for postoperative analgesia. Acta Anaes Sc. 1999; 43(5):568-72.

Hanoaka K. In vitro changes in the transparency and pH of cerebrospinal fluid caused by adding midazolam. Eur J Anaes. 1998;15(1):27-31.

Oral N. Comparison of caudal bupivacaine, bupivacaine-midazolam and bupivacaine-morphine mixtures for postoperative analgesia in children. Eur J Anaes. 1998;15(1):161-5.

Batra YK. Addition of intrathecal midazolam to bupivacaine produces better postoperative analgesia without prolonging recovery. Int J Clin Pharm & Ther. 1999;37(10):519-23.

Kim MH. Intrathecal midazolam increases the analgesic effect of spinal blockade with bupivacaine in patients undergoing haemorrhoidectomy. The Br J Anaes. 2001;86(1):77-9.

Sen A. Intrathecal midazolam for postoperative pain relief in caesarean section delivery. J Ind Med Asso. 2001;99(12):683-6.

Batra YK. A comparative study of caudal bupivacaine and midazolam-bupivacaine mixture for post operative analgesia in children undergoing genitourinary surgery. Int J Clin Pharm & Ther. 2001;39(3):116-20.

Shah FR. Improvement in postoperative pain relief by addition of midazolam to and intrathecal administration of buprenorphine and bupivacaine. Eur J Anaes. 2003;20(11):904-10.

Bharti N. Intrathecal midazolam added to bupivacaine improves duration and quality of spinal anaesthesia. Acta Anaes Sc. 2003; 47(9):1101-5.

Tucker AP. Intrathecal midazolam: A cohort study investigation safety. Anaes & Analgesia. 2004;98(6):1512-20.

Tucker AP. Intrathecal midazolam: Combination with intrathecal fentanyl for labor pain. Anaes & Analgesia. 2004;98(6):1521-7.

Sanli I. The analgesic and sedative effects of intrathecal midazolam in perianal surgery. Eur J Anaes. 2004;21(8):658-62.

Agrawal N. Effect of intrathecal midazolam-bupivacaine on postoperative analgesia. Ind J Anaesth. 2005;49(1):37-9.

Prakash S. Analgesic efficacy of two doses of intrathecal midazolam with bupivacaine in patients undergoing caesarean delivery. Regional Anaes & Pain Med. 2006;31(3):221-6.

Prakash S. The effect of intrathecal midazolam 2.5 mg with hyperbaric bupivacaine on postoperative pain relief in patients undergoing orthopaedic surgery. The Internet J of Anaes. 2007;14(2):1-5.