Category : Original Articles

ORIGINAL ARTICLE – Midazolam as an adjuvant in supraclavicular brachial plexus block

Safiya I Shaikh, MD*, Veena K. MD, DA**

*Professor & HoD, **Registrar

Department of Anaesthesiology, KIMS Hubli.

Correspondence: Prof. Safiya I Shaikh, MD, Head, Department of Anaesthesiology,   KIMS Hubli (India); Phone:9448861706; e-mail: ssafiya11@yahoo.com

ABSTRACT

Background & Aims: Brachial plexus block is a useful alternative to general anaesthesia. Postoperative analgesia is an added advantage. Midazolam, a water soluble benzodiazepine has been used by various routes to prolong analgesia. The present study was undertaken to assess the analgesic efficacy of midazolam with bupivacaine in brachial plexus block.

Methods: A prospective, randomized, double blind study was done at Karnataka Institute of Medical Sciences (KIMS), Hubli (India), from 01 March 2008 to 01 March 2009, on 50 adult patients of ASA 1 and 2, aged between 18-65 years and scheduled for various upper limb surgeries. Patients were divided into two groups of 25 each. Group B received 30ml of inj. bupivacaine 0.5% +2ml normal saline and group BM received 30ml of inj. bupivacaine 0.5% + inj. midazolam (preservative free) 0.05mg/kg. Patients were observed for sedation, respiratory depression, pulse rate, SBP, DBP, duration of motor block, duration of pain relief and occurrence of any complications.

Results: Post operative analgesia was significantly longer (805.04175.75 min) in group BM, as compared to group B (502.2452.68 min) with p value <0.001. Pain score was significantly low in group BM (mean 1.6), compared to group B (mean 4.92) at 12 hours postoperatively. Onset of sensory block was 8.363.58 min and 8.52 4.18 min in group B and group BM respectively with p value >0.05. Hence there was no statistically significant difference. Onset of motor block in group B was 9.965.69 min and in group BM 7.92 5.68 min. and p value was >0.05 min.  Hence there was not statistically significant difference Mild respiratory depression and sedation occurred intraoperatively in group BM which required no active intervention.

Conclusion: Addition of midazolam 50mcg/kg to 30ml of bupivacaine 0.5% for supraclavicular brachial plexus block prolonged sensory blockade and post-operative analgesia without increasing the risk of adverse effects.

Key words: Bupivacaine; Midazolam; Supraclavicular brachial plexus block; Postoperative analgesia.

Citation: Shaikh SI, Veena K.  Midazolam as an adjuvant in supraclavicular brachial plexus block. Anaesth Pain & Intensive Care 2012;16(1):7-11.

INTRODUCTION

Brachial plexus block is a useful alternative to general anesthesia for upper limb surgeries providing complete muscle relaxation, stable intraoperative hemodynamics and smooth transition to postoperative pain relief1. Hence the need of the hour today for postoperative analgesia is the one which requires minimum technical intervention and expertise, gives good quality of analgesia, requires easily available drugs and equipments, cost effective, and has least side effects thereby has good patient and surgeon acceptance.

Midazolam a water soluble,  short acting benzodiazepine , produces analgesia by acting on gamma –amino butyric acid receptors (GABA). Extrasynaptic receptors for GABA  are present  on myelinated  axons of peripheral nerves. Midazolam used with local anesthetics (LA) through various routes in many studies has been shown to prolong post-operative analgesia. An earlier study was done by Koj Jarbo et al1. With this in mind, we conducted a study to evaluate the effects of adding midazolam to bupivacaine in brachial plexus block.

METHODOLOGY

After approval by the hospital ethical committee, a prospective, double blind, randomized study was carried out in KIMS (Karnataka Institute of Medical Sciences) Hubli (India),  from 01 March 2008 to 01 March 2009. Fifty adult patients of either sex,  aged 18-60 years, ASA physical status 1 and 2 and  scheduled for various upper limb surgeries were recruited for the study. We checked praevious year( i.e year 2007) hospital statistics. Considering 95% confidence interval and 9% allowable error and prevalence of 13% , worked out sample size was 54, hence we decided for a sample size to be 50. Patients having known allergy to test drugs, ASA grade 3 and 4 patients, patients on drugs that might have modified the pain perception, patients who refused to be enrolled in the study, patients with a history of substance abuse, coagulopathies, contralateral phrenic nerve or recurrent laryngeal nerve palsy, contralateral  pneumothorax or infection at the site of injection were excluded from the study

All enrolled patients were assessed by preanaesthetic examination. Informed consent was taken. Patients were premedicated with tab. diazepam 5mg orally 1 hour before surgery. Emergency drugs and equipments including facilities for GA were kept ready. Brachial plexus block was performed by supraclavicular approach. Double blind randomization was done. The trial was so planned that neither the doctors  (investigator) nor the participants (patients) were aware of the group allocation and drug received. The study drugs were prepared by an anesthesiologist not involved in performing the block, patient care or in data collection.

Patient was made to lay supine with head turned to opposite side with ipsilateral arm adducted. After aseptic preparation, midpoint of clavicle and interscalene groove was identified. At a point 1-1.5 cm posterior to midpoint of the clavicle, skin wheal was raised with local aneasthetic. A 22 gauge 4 cm short beveled needle was passed through the same point in a caudad, slightly medial and posterior direction until paresthesia was elicited. After negative aspiration for blood study medication was inj.ected.

Patients in group B received inj. bupivacaine 0.5% 30 ml + NS 2ml, patients in group BM received inj. bupivacaine 0.5% 30ml + inj. midazolam (preservative free) 0.05mg/kg. Heart rate, blood pressure and respiratory rate were recorded pre operatively, intra op every 10min upto the end of surgery and post operatively at 2h, 6h, 12h and 24 hrs. Onset of sensory block- time elapsed between injection of drug and complete loss of cold perception was tested by spirit soaked cotton on skin dermatomes C4-T2. Onset of motor block- time elapsed between injection of drug to complete motor block was tested by adduction of shoulder and flexion of forearm and hand against gravity. Sedation was assessed using sedation score described by Culebras et al2.( Awake and alert -1, Sedated and responding to verbal command-2, Sedated responding to mild stimulus-3, Sedated & responding to moderate to severe physical stimulus-4, Not arousable-5). Duration of sensory block – time elapsed between injection of drugs to appearance of pain requiring rescue analgesia. Duration of motor block- time elapsed between injection of drug to complete return of motor power. Pain was assessed by an anaesthesiologist performing the block, who was unaware of the study medications injected. Pain was assessed by numerical rating pain scale where zero represents no pain and 10 means worst possible pain. Duration of pain relief was taken from time of onset of sensory block to time of administration of rescue analgesic. Rescue analgesic was administered when pain score was 4 and above. Inj. diclofenac 75 mg IM was the rescue analgesic. At the end of 24 hours, anaesthesiologist who loaded the drugs revealed the contents of study medications and hence the group to which patient belonged could be notified.

Interval data are expressed as mean and standard deviation. Student’s ‘t’ test was used to compare the two groups. Chi square test was used for analysis of nonparametric data. A p value of < 0.05 was considered statistically significant.

RESULTS

Mean age was 34.40 yrs with a range of 18-60 years. Mean weight of group B and group BM patients was 58.4±6.07 and 59.3±6.79 kg respectively and was comparable between two groups. Duration of surgery was 65.6±16.84 min and 67±14.43 min in group B and group BM respectively and was comparable between two groups.

Table 1: Demographic data of the patients

Parameter Group B Group BM P value
Mean age (years) 32.52±12.69 33.28±10.91 >0.05
Mean weight (kgs) 58.4±6.07 59.3±6.79 >0.05
Male:Female

P value <0.05- Statistically  significant

P value <0.001- Statistically  highly significant

Figure I: Weight distribution of the patients



Table 2: Comparison of main outcomes in two groups

Outcome Group B Group BM P value
Mean duration of surgery (min) 65.6±16.84 67±14.43 >0.05
Mean onset of sensory block (min) 8.36±3.58 8.52±4.18 >0.05
Mean onset of motor block (min) 9.96±5.69 7.92±5.68 >0.05
Mean duration of motor block (min) 450.48±57.95 608.96±157.75 <0.001
Duration of pain relief (min) 502.24±52.68 805.04±175.75 <0.001
Sedation score One Three >0.05
Numerical  rating pain scale score 

at 12 hours

4.36 1.44 <0.001

P value <0.05- Statistically  significant

P value <0.001- Statistically  highly significant

The mean onset of sensory block in two groups was equivalent with statistically no significant difference (p>0.05) ( 8.36±3.58 min vs. 8.52±4.18 min). The mean onset of motor block was faster in group BM (7.92±5.68 min) as compared to group B (7.96±5.69 min) but it was not statistically significant (p>0.05). Mean duration of motor block in group BM patients was significantly longer (608.96±157.75 min) compared to patients in group B (450.48±57.95 min).

There was a statistically significant decrease in the respiratory rate from base line in group BM from 10min to 30min after injection (P<0.001). During remaining time respiration remained normal between two groups and was comparable.

Table 3 :  Respiratory rate (per min)

Time (min) Group B 

Mean ±SD

Group BM` 

Mean ±SD

‘t’ value ‘p’ value
Baseline 14.8 ± 1.5 14.6 ±0.92 0.57 >0.05
5 14.8 ±1.5 14.6 ±1.22 0.51 >0.05
10 10.8 ±1.47 13.2 ±1.0 4.57 <0.001
20 15.1 ±1.83 12.4 ±0.76 6.75 <0.001
30 14.8 ±1.41 13.0 ±1.02 5.14 <0.001
60 14.0 ±2.2 14.0 ±0 0 >0.05
120 13.9 ±1.42 14.0 ±1.32 0.263 >0.05
360 13.9 ±1.44 14.1 ±0.40 0.66 >0.05
720 13.9 ±1.42 14.1 ±0.40 0.66 >0.05
1440 14.8 ±1.49 13.1 ±0.40 0.33 >0.05

Patients in group BM had significantly high sedation score (2.2± 0.5) than patients in group B.

Figure II: Comparison of sedation score

Duration of pain relief in group BM was significantly longer than in group B (805.04±175.75min vs. 502.24±52.68min). Time to analgesia was more in group BM than in group B. In  Immediate post operative period and at two hours the pain score was zero in both groups and was comparable. Patients in group  BM had significantly less pain scores at 6hr, 12hr and 24hrs compared to patients in group B.

Table 4: Numerical Rating Pain Scale Scores

Time Group B Group BM p value
6hr 4.12 0.24 <0.001
12hr 4.36 1.44
24hr 2.84 1.56

 

DISCUSSION

Pain is an inevitable consequence of surgery. Opioids and nonsteroidal anti inflammatory drugs (NSAIDs) singly or in combination provide good analgesia but cause various side effects. Most surgeries on forearm and hand are intermediate and minor surgeries and have relatively short duration of severe postoperative pain.2 Supraclavicular approach is attractive due to its effectiveness, cost, performance, margin of safety.3 It is carried out at the level of nerve trunks where it is more compact, resulting in homogeneous spread of anaesthetic throughout the plexus with a fast onset and complete block.4 Of various local anaesthetics used for brachial plexus block bupivacaine5 is a reliable, versatile, long acting local anaesthetic, when used in correct dosage for caudal, spinal, epidural and peripheral nerve blocks. Various adjuncts like midazolam,1 tramadol,6,7 clonidine,8 buprenorphine9, morphine10, pethidine11, fentanyl, sufentanyl have been shown to prolong post operative analgesia. Addition of hyaluronidase12has produced significant decrease in duration of anaesthesia. Midazolam, a water soluble, short acting benzodiazepine, produces analgesia by acting on gamma amino butyric acid (GABA) receptors.13 Extrasynaptic receptors for GABA are present on myelinated axons of peripheral nerves.14,15 Midazolam used with local anaesthetic in intrathecal16, caudal17 and epidural18routes in various studies has shown to prolong post operative analgesia.

Pain remains undertreated in developing countries.19 Acute pain of surgery if poorly managed leads to various hemodynamic respiratory and autonomic changes that disturb the physiological homeostasis of various organ systems.20 Development of chronic pain and psychological trauma are the long term squeals of acute post-op pain. Since long, physicians have tried to alleviate pain in patients by various drugs and techniques, each having its own advantages and disadvantages.

Brachial plexus block provides intense analgesia, motor blockade without significant hemodynamic changes, airway manipulation and polypharmacy. Bupivacaine is the most commonly used long acting LA that is safe, effective and versatile if used in proper doses.5 Midazolam is a water soluble, short acting BZD that has a PH dependent ring opening phenomenon. The ring remains open at pH < 4 making it highly water soluble approximately 5 mg/ml,21 the ring closes at pH >4 making it more lipid soluble at physiological pH.

In a study by Koj Jorbo et al1 midazolam added to bupivacaine in supraclavicular brachial plexus block has enhanced the onset of sensory block and motor block which was  statistically significant (p<0.05). In the present study, there was no statistically significant difference in onset of sensory block between the two groups. The onset of motor block was earlier in Group BM but it was not statistically significant (p>0.05). This could be due to location of motor fibers in the mantle layer and sensory fibers in the core.4

There were no statistically significant hemodynamic changes in both groups. This is in correlation with a study by Koj Jarbo et al1. In another study by Batra et al16 when midazolam was added to intrathecal bupivacaine, there were no statistically significant difference in hemodynamic or respiratory parameters between two groups.

The mean respiratory rate decreased in group BM from baseline between 10-30 min. This did not require any ventilatory assistance except for face mask oxygenation for that period. Maximum sedation seen was 3 (three), most of other patients were asleep and responding to verbal commands. All patients in group B were awake with sedation score of 1(one). There was no sedation in both groups in the postoperative period. This correlates with the study by Koj Jarbo et al1. Adding midazolam increased not only analgesia but also provided sedation which was an added advantage. This effect was also observed in a study by Nishiyama.T et al18.

Sedation and respiratory depression in group BM could be due to systemic absorption and depression of respiratory center. Transient effect may be due to rapid, high rate of clearance of midazolam (6-11 ml/kg/min).15

There was statistically significant prolongation of motor block in group BM than in group B. This observation is in contrast to observation by Koj Jabo et al1 in which duration of motor block was similar in both groups.

Group BM had prolonged analgesia which was statistically significant (P<0.001), this also correlates well with vatious studies.1,16,18 Patients in group BM had significantly less pain scores than patients in group B. Only one patient required rescue analgesia in group BM. Time to administration of rescue analgesia was delayed in group BM than in group B as also observed in a study by M Naguib et al17. This observation also correlates with a study by koj Jarbo et al1. Midazolam may produce antinociception by acting on GABA receptors located on peripheral nerves.14,15

In the present study there was no adverse effects, either due to drugs or the technique, except for mild respiratory depression, which was treatable with oxygen supplement via face mask and few incidences of vascular tap while performing brachial plexus block for which a transient topical pressure was applied. This can be minimized by the use of a nerve stimulator or ultrasound guided technique.

CONCLUSION

In conclusion, addition of midazolam to bupivacaine 0.5% for supraclavicular brachial plexus block prolongs sensory blockade and post-operative analgesia without increasing the risk of adverse effects.

REFERENCES

  1. Koj J, Yatindra KB, Nidhi BP. Brachial plexus block with midazolam and bupivacaine improves analgesia. Can J Anesth 2005;52:822-6.
  2. Brown DL, Bridenbaugh LD. The upper extremity: The somatic  block. In: Cousins MJ, Bridenbaugh LD, (ed). Neural blockad  in clinical anesthesia and management of pain. 3rd ed.Philadelphia: Lippincott-Raven Publishers; 1998; 345-71.
  3. Kothari D. Supraclavicular brachial  plexus blocka -a new approach.  Indian J. Anaesth. 2003;47(4):287-88.
  4. Radha S, Alon PW. Pharmacokinetics of LA during plexus blocks.  Anaesth Analg 1977;56:852-61.
  5. Moore DC, Bridenbaugh LD, Thompson GE, Balfour RI and  Horton WG. Bupivacaine: A Review of 11,080 Cases. Anesth Analg 1978;57:42-53.
  6. Suman C, Mitra LG, Biswas BN, Majumder P. Tramadol as an adjuvant for brachial plexus block. J.      Anaesth. Clin pharmacol 2007;23(2):187-89.
  7. Robaux S, Blunt C, Viel E, et al. Tramadol added to 1.5% mepivacaine for axillary brachial plexus block     improves post operative analgesia dose dependently.  Anaesth Analgesia 2004; 98(4):1172-7
  8. Hutschala DMascher HSchmetterer L, et al. Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism. Eur J Anaesthesiol. 2004;21(3):198-204.
  9. Candido KD, Franco CD, Khan MA, Winnie AP, Raja DS. Buprenorphine added to LA for brachial plexus block to provide post op analgesia in outpatients. Reg Anesth Pain Med. 2001;26(4):352-6.

10.  Bazin JEMassoni CBruelle PFenies VGroslier DSchoeffler P. The addition of opioids to LA in brachial plexus block the comparative study of effects of morphine, buprenorphine and sufentanyl. Anaesthesia 1997;52(9):858-62.

11.  Sadeghi SA, Soleimani AA and Soleimani M. Supplemental pethidine, fentanyl to LA in supraclavicular block. Acta Medica Iranica 2003;41(2);134-37.

12.  Keeler JFSimpson KHEllis FRKay SP. Effect of addition of hyaluronidase to bupivacaine during axillary brachial plexus block. Br J Anaesth. 1992;68(1):68-71.

13.  Edwards M, Serrao JM, Gent JP, Goodchild CS. On the mechanism by which midazolam causes spinally mediated analgesia. Anesthesiology 1990;73:273-7.

14.  Morris ME, Di Costanzo G A, Fox S, Werman R. Depolarising action of GABA on myelinated fibers   of peripheral nerves. Brain Res 1983; 278(1-2): 117-26.

15.  Liske S, Morris ME. Extra synaptic effects of GABA agonists on myelinated axons of peripheral nerves. Can J Physiol Pharmacol. 1994;72(4):368-74.

16.  Batra YK, Jain K, Chari P, Dhillon MS, Shaheen B, Reddy GM. Addition of intrathecal midazolam to bupivacaine produces better postoperative analgesia without prolonging recovery. Int J Clin Pharmacol Ther 1999;37:519-23.

17.  Naguib Mel Gammal MElhattab YSSeraj M. Midazolam for caudal analgesia in children: Comparison with caudal bupivacaine. Can J Anaesth. 1995;42(9):758-64.

18.  Nishiyama T, Matsukawa T, Hanoaka K. Effects of adding midazolam on postop analgesia with two different doses of bupivacaine. J Clin Anesth. 2002;14(2):92-7.

19.  Size MSoyannwo OAJustins DM. Pain management in developing countries. Anaesthesia. 2007;62 Suppl 1:38-43.

20.  Dejong RHWagman IH. Physiological mechanisms of peripheral nerve block by local anaesthetics.Anaesthesiology 1963;24:684-727

21.  Tucker AP, Mezzatesta J, Nadeson R, Goodchild CS. Intrathecal midazolam II: combination with intrathecal fentanyl for labor  pain. Anesth Analg 2004;98:1521-7.