|Year : 2013 | Volume
| Issue : 1 | Page : 27-31
Bupivacaine sparing effect of intrathecal midazolam in sub-arachnoid block for cesarean section
Manoj K Sanwal, Neha Baduni, Aruna Jain
Department of Anesthesiology and Intensive Care, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India
|Date of Web Publication||1-Jul-2013|
Gh12/183, Paschim, Vihar, New Delhi - 110 087
Source of Support: None, Conflict of Interest: None
Background: Hypotension during subarachnoid block for caesarean section (CS) is the most common and potentially dangerous complication. Bupivacaine has been implicated for this effect in a dose dependent manner. Hypotension can be prevented by using lower doses of bupivacaine with intrathecal midazolam as an adjuvant drug, though the optimum dose-ratio of bupivacaine with midazolam remains unaddressed.
Materials and Methods: A prospective, randomized, double-blind study was conducted enrolling 120 consecutive ASA grade I obstetric patients undergoing elective CS in a tertiary care hospital. A baseline supine position noninvasive blood pressure (BP) was recorded. All patients were preloaded with 500 ml of lactated Ringers' solution. Varying doses of 0.5% hyperbaric bupivacaine were used (7.5mg in group II, 6mg in group III and 5mg in group IV), in combination with 2mg midazolam in each group. Appropriately matched controls were given 11mg bupivacaine alone (Group I). Intra-operatively, BP was measured at every 2 minutes till 30 minutes and every 10 minutes thereafter. Hypotensive episodes [Systolic BP (SBP) < 100 mmHg] were recorded in each group. Quality of surgical anesthesia was graded as "excellent", "good" and "poor" as per the validated scoring system. The outcomes in different groups were compared by one-way ANOVA . intra group comparisons were done with t test
Results: All the four groups had 30 patients each. The incidence of hypotension was significantly lower in the groups using low-dose bupivacaine and midazolam, with a lesser fall in SBP than group I. Onset of sensory and motor blocks, and quality of surgical anesthesia were unaffected in group II while significant deterioration was noticed in groups III and IV.
Conclusion: We found that 7.5 mg bupivacaine with 2 mg midazolam is the optimum dose ratio combination to be used in subarachnoid block for caesarean section.
Keywords: Cesarean section, intrathecal, midazolam, sub-arachnoid block
|How to cite this article:|
Sanwal MK, Baduni N, Jain A. Bupivacaine sparing effect of intrathecal midazolam in sub-arachnoid block for cesarean section. J Obstet Anaesth Crit Care 2013;3:27-31
|How to cite this URL:|
Sanwal MK, Baduni N, Jain A. Bupivacaine sparing effect of intrathecal midazolam in sub-arachnoid block for cesarean section. J Obstet Anaesth Crit Care [serial online] 2013 [cited 2018 Mar 17];3:27-31. Available from: http://www.joacc.com/text.asp?2013/3/1/27/114288
| Introduction|| |
Hypotension is the most common and potentially dangerous side effect of sub-arachnoid block (SAB), especially in pregnant patients. Intrathecal adjuvants such as opioids, ketamine, clonidine, and neostigmine, not only provide faster onset time and prolonged analgesia, but also reduce the risk of local anesthetic toxicity, significant hypotension, and profound motor blockade. However, their use is limited because of side effects such as urinary retention, nausea, vomiting, pruritis, and respiratory depression. In the quest for a newer, safer local anesthetic additive, researchers have found that benzodiazepines lead to segmental block of nociception without any adverse effect on the cardiovascular and respiratory systems. We conducted this study to investigate the feasibility of decreasing the dose of bupivacaine for sub-arachnoid block, thus decreasing the incidence of hypotension, by addition of preservative free midazolam in sub-arachnoid block for cesarean section.
| Materials and Methods|| |
After gaining approval from the institutional ethical committee and written, informed consent from the patients, 120 healthy parturients of American Society of Anesthesiologists (ASA) grade I, undergoing elective cesarean sections were selected for this double blind, prospective, randomized case control study in a tertiary care hospital. Patients with any contraindication to regional anesthesia, chronically on benzodiazepines, with history of drug or alcohol abuse, with pre-eclampsia, weighing >90 Kg, less than 150 cm or more than 165 cm in height, with any incidence of fetal compromise, or any other major systemic illness were excluded from this study. They were kept fasting overnight and given tablet rantidine 150 mg and metoclopromide 10 mg night before surgery and injection ranitidine 50 mg and metoclopramide 10 mg intravenously 45 minutes prior to surgery. In the operating room, standard monitors (electrocardiogram, non invasive blood pressure, and pulse oximeter) were attached to the patients, and baseline readings were recorded. The patients were randomly allocated into four groups of 30 each, in a double blind manner using sealed envelopes. An observer, not involved with the study, prepared the drugs. Group I (control group) received 2.2 ml of 0.5% bupivacaine (hyperbaric). Group II, III, and IV received 1.5 ml, 1.2 ml, and 1.0 ml of bupivacaine (heavy), respectively, along with 2 mg of preservative free midazolam. They were co-loaded with 15 ml/kg of lactated Ringer's solution over 20 minutes. A sub-arachnoid block was instituted in the left lateral position in L3-L4 interspace using 25 G spinal needle under full aseptic precautions. After obtaining free flow of cerebrospinal fluid, the study drug was injected slowly and the patient was turned supine. The time of onset of sensory blockade (time taken for complete loss of pin prick sensation at T6 level), duration of sensory block (time taken for sensory block to regress below T12), motor blockade (time taken to achieve Bromage motor score = 3, [Table 1]), duration of motor blockade (Bromage motor score = 0), quality of surgical anesthesia (excellent, good, and poor), newborn Apgar Scores, any side effects (nausea, vomiting, urinary retention, sedation, and pruritis), sedation score using Ramsay sedation score [Table 2], duration of effective analgesia (the time for rescue analgesia-intraoperatively-intravenous fentanyl 1.5 μg/kg and postoperatively-intramuscular diclofenac 1.5 mg/kg) were noted. Pain was assessed using Visual Analog Scale (0-no pain, 10-maximum pain). In case of inadequate effect of SAB intraoperatively, general anesthesia was administered to the patient. Pulse rate (PR), blood pressure (BP), and respiratory rate (RR) were monitored every 3 minutes intraoperatively and every 10 minutes postoperatively along with a continuous monitoring of the electrocardiograph and pulse oximetry. Hypotension was defined as a fall in systolic BP by more than 25% from the baseline and was managed with intravenous crystalloids and incremental doses of ephedrine. Respiratory depression was defined as a respiratory rate <10 breaths/minute.
The statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software version 12.0 for windows. The sample size was determined using Altmann's normograph with power of 80% and deducing a standardized difference as the ratio between smallest clinically worthwhile difference and standard deviation. Intergroup comparisons were done using analysis of variance (ANOVA) test and intra group comparisons with Students' t-test. A p-value of <0.05 was considered statistically significant.
| Results|| |
The four groups were comparable with respect to age, weight, height, length of spine and the duration of surgery [Table 3].
Two patients in group III and six in group IV had no/inadequate motor and/or sensory blockade and had to be given general anesthesia. The time of onset of sensory block was quickest in group I (1.86 ± 0.41 min.) and slowest in group IV. It was statistically significant between groups I and III, and I and IV. The onset of motor blockade was significantly increased in groups III and IV when compared to control group. Duration of sensory blockade was significantly less in all three test groups. Duration of motor blockade was significantly shorter in groups III and IV. Duration of effective analgesia was significantly prolonged in group II when compared to group I, whereas, it was significantly shortened in groups III and IV. Sedation scores were comparable in all the groups [Table 4].
All babies approached an Apgar score of 9 at five minutes. All patients had a fall in systolic BP after the institution of SAB [Figure 1], maximum in group I where 8 patients (26.67%) had hypotension which was treated with intravenous fluids or ephedrine. Two patients in group II, one in group III and none in group IV had statistically significant fall in blood pressure [Table 4]. The dose of ephedrine required was also higher in control group.
The quality of surgical anesthesia was excellent in all patients of groups I and II and more than 70% in group III [Figure 2]. One patient in group II had shivering [Table 5], whereas, in group I, four patients had nausea/vomiting and one had shivering.
| Discussion|| |
Regional anesthesia is highly popular for cesarean deliveries because of the high morbidity and mortality associated with general anesthesia. However, the main drawback of spinal anesthesia, particularly in parturients, is hypotension caused by blockade of sympathetic output. Decreasing the dose of local anesthetic decreases the magnitude of hypotension but compromises upon the quality of anesthesia. Recently, intrathecal midazolam has been shown to potentiate the effect of local anesthetics in SAB by acting through BZD-GABA receptor complex at spinal cord level leading to segmental analgesia, without any neurotoxic effects. ,
Many studies have concluded that the addition of 1 or 2 mg of intrathecal midazolam significantly prolongs the duration of analgesia, be it abdominal or orthopedic surgeries, or chronic pain. ,, The earliest study using midazolam as spinal additive in obstetric patients was conducted by Valentine et al., in 52 patients undergoing elective cesarean sections. They found a significant decrease in postoperative pain and analgesic requirement with midazolam.  Prakash et al., conducted a prospective, randomized controlled trial in 60 patients undergoing elective cesarean section and observed a significant difference in the duration of analgesia (6.1 ± 1.0 hours) when 2.0 mg of midazolam to SAB as compared to bupivacaine alone (3.8 ± 0.5 hours). 
Tucker et al., also concluded that the addition of intrathecal midazolam increased the potency and duration of analgesia of intrathecal fentanyl for labor analgesia without any maternal or fetal adverse events. 
We also found a significant increase in the duration of analgesia with 2 mg of midazolam. However, reduction in the dose of bupivacaine beyond 7.5 mg (1.5 ml) led to a reduction in the duration of effective analgesia. More so, on decreasing the dose of bupivacaine, there was a proportional decrease in the incidence of hypotension. Group II provided the adequate balance of effective analgesia and hypotension.
The onset of sensory block was comparable with 2 mg midazolam (1.96 ± 0.31 min) as compared to control group (1.86 ± 0.41 min), similar to the findings of Bharti et al.,  and contrary to Vaswani et al., who reported a faster onset of sensory block with midazolam (2.26 ± 0.19 min vs 3.41 ± 0.41 min in control group). 
The addition of intrathecal midazolam also decreased the incidence of side effects such as nausea and vomiting, similar to the findings of Prakash et al., and Bharti et al., and unlike Yun et al., and Shadangi et al., who did not find any significant difference in the incidence of side effects. ,,, No difference in sedation levels was found in the four groups, similar to Prakash et al., and Shadangi et al. ,
To conclude, with intrathecal midazolam 2 mg, it is possible to reduce the dose of bupivacaine from 2.2 mg to 1.5 mg to provide the same surgical anesthesia but with fewer incidence of hypotension and other side effects.
| References|| |
|1.||Johansen MJ, Gradert TL, Satterfield WC. Safety and efficacy of continuous intrathecal midazolam infusion in the sheep model. Anesth Analg 2004;98:1528-35. |
|2.||Tucker AP, Lai C, Nadeson R, Goodchild CS. Intrathecal midazolam I: A cohort study investigating safety. Anesth Analg 2004;98:1512-20. |
|3.||Yun MJ, Kim YJ, Kim JH, Kim KO, Oh AY, Park HP. Intrathecal midazolam added to bupivacaine prolongs the duration of spinal blockade to T10 dermatome in orthopedic patients. Korean J Anesthesiol 2007;53:S22-8. |
|4.||Shadangi BK, Garg R, Pandey R, Das T. Effects of intrathecal midazolam in spinal anesthesia: A prospective randomized case control study. Singapore Med J 2011;52:432-5. |
|5.||Dureja GP, Usmani H, Khan M, Tahseen M, Jamal A. Efficacy of intrathecal midazolam with or without epidural methylprednisolone for management of post-herpetic neuralgia involving lumbosacral dermatomes. Pain Physician 2010;13:213-21. |
|6.||Valentine JM, Lyons G, Bellamy NC. The effect of intrathecal pain on postoperative pain. Eur J Anaesthesiol 1996;13:589-93. |
|7.||Prakash H, Joshi N, Gogia AR, Singh R. Analgesic efficacy of two doses of intrathecal midazolam with bupivacaine in patients undergoing cesarean delivery. Reg Anesth Pain Med 2006;31:221-6. |
|8.||Bharti N, Madan R, Mohanty PR, Kaul HL. Intrathecal midazolam added to bupivacaine improves duration and quality of spinal anaesthesia. Acta Anaesthesiol Scand 2003;47:1101-5. |
|9.||Vaswani RK, Raiger LK, Bajaj P. The effect of intrathecal midazolam on postoperative pain relief in orthopedic surgery. Hosp Today 2002;4:217-20. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]