A study of Postoperative pain relief in caesarean section with intrathecal Midazolam. (A study of 50 cases).
Dr Komal S Shah
Assistant Professor Anaesthesia
Govt. Medical College
Background: Intrathecal Midazolam is a safe and effective anesthetic drug which can be used in the anaesthetic management for post operative pain relief in Caesarean section.
Aims: To assess the efficacy of Midazolam as an intrathecal anaesthetic drug and observe the onset and duration of sensory and motor blockade, the effect of Intrathecal Midazolam on cardiovascular and respiratory system and post operative pain relief after intrathecal Midazolam and the incidence of complications and side effect of intrathecal administered Midazolam.
Setting and Design: Anaesthetic from Department of Anesthesia and Surgeons and Orthopedic surgeons of Government Medical College Bhavnagar. Gujarat. India.
Material and methods: The 50 patients scheduled to undergo caesarean section delivery at Sir T Hospital, Bhavnagar were studied for postoperative analgesia provided by means of intrathecal Midazolam under spinal anaesthesia and belonged to ASA grade I and II. They were further divided in Group L patients receiving intrathecal Inj Lignocaine 5%heavy 1.2 ml + Inj Normal Saline 0.4ml with adrenaline rinsed syringe and Group LM patients receiving intrathecal Inj Lignocaine 5%heavy 1.2 ml + Inj Midazolam 0.4ml(2mg) preservative free with adrenaline rinsed syringe.
Result: 50 cases were been equally distributed in group L and LM each. The mean onset of sensory blockade was 133.75 ± 14.68 sec and in group LM was 155 ± 17.35 sec (p value <0.001). The VAS pain score was lower in the LM group compared to L group. The postoperative pain relief was significant in the LM group p <0.001.
Conclusion: Thus we conclude that intrathecal Midazolam causes rapid onset of sensory blockade and it significantly prolongs duration of sensory blockade. Addition of preservative free Midazolam provided an enhanced and increased duration of effective sensory analgesia without delaying recovery to ambulation and without any side effect and calm mental state thus promoting early mother-baby bonding and added advantage of low cost.
Keywords: Intrathecal Midazolam, caesarean section, postoperative pain relief.
Obstetric anaesthesia is a demanding but gratifying sub-specialty of anaesthesiology. Although most of the parturients are young and healthy, they nonetheless represent a high risk group of patients because pregnancy produces profound physiological changes that alter the usual responses of anaesthesia. Moreover anaesthesia care of pregnant patient is unique as two patients are cared for simultaneously.
Spinal anaesthesia is used extensively for caesarean section because it has distinct advantage over general anaesthesia. An awake mother at the birth of her child establishes early maternal and infant bonding and successful breast feeding.
It becomes a challenge after caesarean section delivery to provide postoperative pain relief without much sedation, respiratory depression or problems like nausea and vomiting so that early baby acceptance and care by mother is promoted.
Postoperative pain elicits a number of responses from the human body the most important of which are pain and metabolic stress response. It is associated with increased circulating catecholamine which results in tachycardia, hypertension and increased cardiac work leading to increased myocardial oxygen consumption. Severe pain causes restrictive lung defect and depressed diaphragmatic activity leading to hypoxia, hypercapnia, retention of secretions and atelectasis. The autonomic reflex response to pain results in gastro intestinal hypo motility leading to nausea, vomiting and ileus. Persistent pain is the most frequent cause of disability and it constitutes a major health and economic problem.
Provision of good pain relief leads to reduction in complication and morbidity and results in patient’s satisfaction which is an important component of good quality of care. Anaesthesiologist has got involved in providing postoperative pain relief because of their knowledge of pain physiology, pharmacology of anaesthetic and analgesic drugs. Despite ability to provide effective and safe analgesia, more widespread application of spinal and epidural opiates had been limited by side effect. Midazolam is potent short acting, water soluble non opiates benzodiazepine17, which has been used for potentiating the analgesic effect of local anesthetic induced Neuro axial blockade. Spinal analgesic effect of Midazolam is medicated by benzodiazepine- GABA receptor complex within the spinal cord . GABA receptors are abundant in dorsal root nerve cells and maximum concentration found in lamina-II of dorsal horn ganglia. Intrathecal Midazolam also has antinociceptive effect medicated via spinal $ opiate receptors 23. The use of Midazolam as postoperative analgesic by intrathecal route was first studied by Valentine J.M., Lyon G., Bellamy MC in human being in 1996 .
Aims of Study:
To observe the effect of intrathecal Midazolam on onset and duration of sensory and motor block, effect on cardiovascular and respiratory system, study of postoperative pain relief after intrathecal Midazolam. To compare the APGAR score of baby between two groups. To study the incidence of complications and side effects of intrathecal administered Midazolam.
Materials and Method
In a prospective randomized comparative clinical study, 50 patients scheduled to undergo caesarean section delivery at Sir T Hospital, Bhavnagar were studied for postoperative analgesia provided by means of intrathecal Midazolam under spinal anaesthesia. The patients belonged to ASA grade I or II.
All patients were subjected to thorough pre-anaesthetic assessment in detail through history taking and physical examination and relevant investigation. Informed consent was been taken as per the norms.
Patients were then randomly allocated into two groups L and LM of 25 each.
Group L Inj lignocaine 5% heavy 1.2ml+ Inj Normal saline 0.4ml with adrenaline rinsed syringe intrathecal.
Group LM Inj lignocaine 5% heavy 1.2ml+ Inj Midazolam 0.4ml (2mg) preservative free with adrenaline rinsed syringe intrathecal.
Premedication: all patients were premedicated 1/2hr before subarachnoid block with Inj ranitidine 1mg/Kg + Inj Ondansetron 0.1mg/kg – intravenously.
Anaesthetic technique: All patients were shifted in Operation theatre in lateral position. After placement of noninvasive monitors, IV access was established and patients were preloaded by compound ringer lactate solution 10-15 ml/kg body weight. Under due aseptic and antiseptic precautions and with patient in left lateral position sub- arachnoid puncture was performed at L 3-4 interspace with 23-26 G spinal needle using midline approach. The drug was installed as per the group L and LM.
Immediately after subarachnoid injection patient were placed in the supine position with a wedge placed under right hip. All patients received supplementation O2 (3lit/min) by O2 mask till the delivery of baby. Pulse rate, blood pressure and respiratory rate were recorded immediately after intrathecal injection.
The segmental sensory level of anaesthesia was assessed by the patient’s response to pinprick and motor block was assessed by using modified Bromage scale.
APGAR Score of the baby were recorded at 1st and 5th min after delivery. APGAR score helps in easy assessment and quick decision for resuscitation of the needy neonates.
After completion of surgery all patients were shifted to the recovery room and were monitored for the vitals signs, SpO2, level of sedation, duration of motor blockade, duration of sensory blockade and total duration of analgesia was studied at a regular interval up to 24 hours. Each patient was carefully questioned about pain relief in form of complete analgesia and it was assessed by the Visual Analogue scale (VAS) from 0 to 10, with 0 being no pain and 10- worst possible pain.
Any patient demanding supplementary analgesia or having a pain score of more than five on the VAS was given additional analgesia in the form of Inj Diclofenac sodium 75mg IM/IV.
Data were analyzed by using un-paired “t” test and p value <0.05 was considered statically significant.
Observation and Results
All patients were observed up to 24 hours post operatively and the following results were recorded in both the groups L and LM respectively.
The distribution of patient with respect to age was comparable in both the groups i.e. p value >0.05. Mean age in group L was 24 ± 3.93 year and group LM was 24.08 ± 3.23 year.
The distribution of patient with respect to weight and height was comparable in both the groups. The mean duration of surgical procedure was 60.20 ± 10.75 min and 60.80 ± 12.04min in group L and LM resp., which was comparable in both group with p value >0.05.
The mean onset of sensory blockade in group L was 133.75 ± 14.68 sec and in group LM was 115.21 ± 17.35 sec which was statistically significant in favour of Midazolam group ( p value <0.001). Mean onset of motor blockade in group L and group LM is statically comparable with p value >0.05.
Intraoperavite in pulse rate there was statically difference observed at 1 hr and 1.30 hr in group L patients than the group LM ( p<0.001). Intraoperavite blood pressure at 1.30 hr post intrathecal injection, rise in systolic blood pressure in group L was stastically significantly as compared to group LM (p<0.05). There was no statistically significant difference observed in percent saturation of haemoglobin between two groups.
Table I Changes in Visual Analogue Score.0.16 ± 0.37
|Time||Group L Mean +/- SD||Group LM Mean +/- SD||P Value||Inference|
|45 min||0.16+/- 0,47||0 +/- 0||>0.05||NS|
|1hr||1.16 +/- 1.55||0 +/- 0||<0.05||S|
|1.30 hr||2.76 +/- 2.05||0 +/- 0||<0.001||S|
|Post op||0.48 ± 0.77||0 ± 0||<0.05||S|
|2 hr||1.88 ± 2 0||44 ± 1.04||<0.001||S|
|2.30hr||0.84 ± 1.57||1.16 ± 1.90||>0.05||NS|
|3 hr||0.36 ± 0.7||1 ± 1.5||>0.05||NS|
|3.30hr||0.04 ± 0.2||0.56 ± 1||>0.05||NS|
|4 hr||0.28 ± 0.46||0.2 ± 0.4||>0.05||NS|
|5 hrs||0.08 ± 0.27||0.76 ± 1.9||>0.05||NS|
|6 hrs||0.16 ± 0.62||0.12 ± 0.6||>0.05||NS|
|8hr||0.32+_0.63||0 ± 0||>0.05||NS|
|10 hr||1.08 ± 1.32||0 ± 0||>0.05||NS|
|12 hr||0.56 ± 0.96||>0.05||NS|
|16 hr||0.4 ± 1.04||0.16 +/-0.37||>0.05||NS|
|20 hrs||0.4 ± 0.65||0.24 ± 0.44||>0.05||NS|
|24 hr||0.28 ± 0.61||0.12 ± 0.33||>0.05||NS|
VAS pain score was lower in group LM at 1.30 hr, 2 hr, 2.30 hrs as compared to group L.
Table II Duration of sensory blockade.
No of patients
No of patients.
|Mean ± SD||103.2 ± 12.49||118.8 ± 18.83|
P Value <0.05 #
The duration of sensory blockade in the group LM was stastically significant compared to group L. the duration of motor blockade was not significant in both the groups with p value >0.05.
Table III Requirement of rescue anaesthesia.
|Time after IT injection||GROUP L||GROUP LM|
|NO of patient||%||No of patient||%|
In group L 80 % of the patient require rescue analgesics by 2 hrs while in group LM only 8% required rescue analgesic. By 2.30 hrs all the patients in group L had received rescue analgesic whereas in group LM 24% had received rescue analgesic. In all the patient group L , mean duration of pain free period was 95.8 ± 24.90 min and in group LM it was 207.2 ± 68.85 min, the difference is statistically highly significant (p<0.001) in favour of Midazolam group. The APGAR score of baby at 1st min and at 5th min in both groups was comparable.
Summary and Conclusion
In present study 25 patients were studied for effect of intrathecal Midazolam and Lignocaine in study group compared to 25 in control group who received intrathecal Lignocaine alone and the following conclusion is drawn after comparing both studies.
• Addition of preservative free Midazolam intrathecally provided enhanced and increased duration of effective sensory analgesia without delaying recovery.
• No cardio respiratory depression was found while using Midazolam intrathecally.
• Post operative analgesia is superior and of improved quality with addition of Midazolam along with hyperbaric Lignocaine for spinal anaesthesia for caesarean section delivery.
• No depressant effect on the neonate was seen with intrathecal Midazolam.
• Less nausea mad vomiting and clam mental state were added advantages with use of intrathecal Midazolam, thus promoting baby acceptance and care by mother at the earliest opportunity.
Intrathecal Midazolam provides an excellent and prolonged analgesia, without any side effects like nausea, vomiting or any neurological sequel with clam mental state and added advantage with low cost.
1. Adrent RM, Greenblatt DJ,DEjong RH, et al : In vitro correlates of benzodiazepine CSF uptake, paharmacodynamic action and peripheral distribution. J. Pharma. Exp. Ther: 1983, 227: 98-108.
2. Anjana Sen, A Rudra, S Sarkar et al: Intrathecal Midazolam for post operative pain relief in caesarean section delivery. JIMA: 2001; 99(12): 683-686.
3. Allohon H, Gismar Ziegler, Ulrich Klotz: Midazolam for maintancence of anaesthesia. British Jr. Anaesth: 1986; 58: 1109-1115.
4. Bahar M. Cohen ML, Grinsphon Y, Chanimov M: Spinal anaesthesia with Midazolam in the rat. Canadian Journal Anaesthesia: 1994; 44: 208-215.
5. Batra YK, Jain K, Chari P, Dhillon MS: addition of Midazolam to Bupivacaine produces better post operative analgesia with prolonging recovery. Int J. of Clin. Pharmacol. Ther: 1999: 37(10): 519-523.
6. Bharti N, Madam R, Mohanty PR, and Kaul HL: Intrathecal Midazolam added to Bupivacaine improves the duration and quality of spinal anaesthesia. Acta Anaesthisiol. Scand : 2003: Oct. 47(9) : 1101-5.
7. Benjamin Blackman MD., John E., Mahaffey MD., J David Baker III MD: Clinical comparison of Midazolam hydrochloride and Midazolam male ate for anaesthesia induction: Acta Anaesth. Scand: 1984; 22: 52-53.
8. Boralessa H, Senior DF, Whitwam JG: Cardiovascular response to intubation. Anaesthesia: 1938; 38: 626-627.
9. CS Goodchild, Nobel J: Effect of intrathecal Midazolam on sympathetic nervous system in man. British J. of Clinical Pharmac: 1987; 23(3): 279-85.
10. D Bhattacharya, B. Biswas, A Banerjee: Intrathecal Midazolam with Bupivacaine increases the analgesic effect of spinal blockade after major gynaecological surgery. J. Anaesthesia Cli. Pharmacol: 2002; 18(2): 183-186.
11. Dundee JW and Wilson DB: Amnesic action of Midazolam. British Jr Anaesthesia: 1983; 35: 459-461.
12. JW Villiger: Benzodiazepine receptor in human spinal cord. Neuroscience: 1986; 17: 791-802.
13. Gelman S, Reeve JG, Harris D: Circulatory response to Midazolam anaesthesia: Emphasis on canine splanchnic circulation. Anaesth. Analg: 1983; 62: 135-139.
14. Greenblatt DJ, Abernethy DR, Hurmatz JS: Effect of age, gender and obesity on Midazolam Kinetics. Anaesthesiology: 1984; 61: 27-35.
15. Goodchild CS, Guo Z, Musgreave A, Gent JP. Antinociception by intrathecal Midazolam involves endogenous neurotransmitters acting at spinal cord delta opoid receptors. Br Jr Anaesth.: 1996; 77: 758-63.
16. Haghighi M, Mohammadzadeh A, Naderi B et al: Effect of intrathecal Midazolam on caesarean pain control. Medical faculty Journal of Guilan University of Medical Science. Vol 11. No. 44.
17. Hoffman WE, Aibercht RE et al: The effect of Midazolam on cerebral blood flow and oxygen consumption and its interaction with nitrous oxide. Anaesthesia and Analgeia: 1986; 65: 729-733.
18. Serro JM, Mckenzie JM, Gent JP, and Goodchild CS: Intrathecal Midazolam in rat: An investigation of possible neurotoxic effect. Eur J. Anaesth: 1990; 7: 115-22.
19. Serro JM, Marks RL, Goodchild CS: Intrathecal Midazolam for treatment of chronic mechanical low back pain. Pain: 1992; 48: 5-12.
20. Karovits J, Scott H, Minor sequelae of central neural block. In: Adams AP, Coshman JN editors; Recent advances in Anaesthesia and Analgesia 21: 2000; 197.
21. Ligouri GA, Zayas VM, Chisholm MF. Transient neurologic symptoms after spinal anaesthesia with mepivacaine and Lignocaine. Anaesthesiology 1998; 88: 619-623.
22. Mary JJ, William C, Satterfield, Walter B B et al: Toxicity and efficacy of intrathecal Midazolam. Pain Med: 2004; 3(2).
23. Mc Donald SB, Neal JM: Spinal anaesthesia in ambulatory setting. Current Anaesthesiology reports 2001; 1: 33-37.
24. Pert CB, Synder SH: Opiate receptor demonstrated in nervous tissue. Science: 1973; 179:1011.
25. Pollock JE, Transient Neurological symptoms. Etiology, risk factors and management. Reg Anaesth Pain Med 2002; 27: 568-575.
26. Valentine JM, Lyons G, Bellamy MC: Effect of intrathecal Midazolam o postoperative pain. Eur Jr. Anaesthesiology: 1981; 55: a262.
First Published October 2009
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