European Journal of Cardiovascular Medicine

IVRA is almost 100 years old, yet the technique remains a useful tool in modern anaesthesia¹. IVRA is safe, technically simple, and cost effective compared to general anaesthesia² with success rates of 94 to 98% for upper and lower limb surgeries. ³ It also provides bloodless field during surgery. Its limitations are systemic toxicity, tourniquet pain and inability to provide postoperative analgesia. To overcome these  disadvantages many modalities have been tried with varying degrees of efficacy  like alteration in percentage of local anaesthetics, ⁴different local anaesthetics were tried like Ropivacaine⁵ in low doses, modification of technique⁶ and  addition of many adjuvants⁷ like opioids, sodium bicarbonate, Acetyl NSAID’S,  Muscle relaxants, Ketorolac, ⁸ Ketamine⁹, Clonidine¹⁰ and Dexmedetomidine. ¹¹ A study was conducted to assess the effect of 0.5% lignocaine injected at start of  IVRA and compare it with 0.5% lignocaine injected at start of IVRA followed by  administration of clonidine (150µg) 10 min before closure of wound with respect to quality and duration of post operative analgesia, tourniquet pain,  need for analgesic supplements, post-operative sedation and adverse effects if any.

Institutional ethical committee approval was taken for this prospective , randomised, double blind study. Written informed consent was obtained from the patients. Patients aged between 15-55 years undergoing upper limb surgery were included. Patients with contraindications to tourniquet application like sickle cell anemia, cellulitis,  sepsis were excluded.  Patients were kept nil per mouth as per standard guidelines. In the operating room,  patients were monitored for mean arterial blood pressure(MAP), oxygen saturation (Spo₂)  and heart rate (HR). Two 20 G cannulae were placed: one was in a vein on the dorsum of the  operative hand and the other in the opposite hand for crystalloid infusion. Inj fentanyl 50 µg IV was given. The operative arm was elevated for 2 min and was then exsanguinated with an  Esmarch bandage¹². A pneumatic double tourniquet was then placed around the upper arm,  and the proximal cuff was inflated to 150 mm Hg above the systolic blood pressure of the  patient. Circulatory isolation of the arm was verified by inspection , absence of a radial pulse,  and a loss of the pulse oximetry tracing in the ipsilateral index finger.

In GROUP I,0.5% lignocaine 40ml was administered at the start of IVRA and 15ml  normal saline 10min before expected end of procedure on the same side as IVRA.  In GROUP II,0.5% lignocaine 40ml was administered at the start of IVRA and 150  µg of clonidine made up to 15ml with normal saline 10min before expected end of  procedure.  IVRA solutions were injected over 90 sec.  After complete sensory and motor blocks were achieved, the distal tourniquet was  inflated to 250 mm Hg and the proximal tourniquet was released. Heart rate, blood pressure and oxygen saturation (SPO₂) are monitored using  ECG,NIBP and pulse oximeter.  Sensory block was evaluated with pinprick testing every 30 s until the start of surgery  with a 22 –gauge needle in the median, ulnar, and radial nerve –innervated areas of  the hand and forearm.¹³ Motor function was assessed by asking the subjects to flex and extend their wrist  and fingers; complete motor block was determined to be when no voluntary  movement was possible.¹³

Sensory block onset time was noted as the time elapsed from injection of study drug  to sensory block achieved in all innervated areas,and motor block onset time was the  time elapsed from injection of study drug to complete motor block.¹³ Pain at the surgical site and due to tourniquet was assessed with visual analog  scale¹³(VAS) (0=No pain and 10=worst pain imaginable).  If the patient reported VAS >4, 1µg/kg of fentanyl was given intraoperatively.During  surgery, 6mg IV Mephentermine was given for hypotension (systolic arterial blood  pressure <90mmhg).0.6mg IV atropine was given for bradycardia (HR<50/Min),and  4 mg IV Ondansetron for nausea and vomiting. Oxygen was administered with a face  mask in case SpO₂ was lower than 91%.  The tourniquet was not deflated before 30 min. At the end of surgery, the tourniquet  deflation was performed by cyclic deflation technique.¹³  Sensory recovery time was noted (time elapsed after tourniquet deflation up to  recovery of pain in all innervated areas determined by pinprick test, performed every  30s). motor block recovery time was noted(the time elapsed after tourniquet deflation  up to movement of fingers).¹³

Patients were assessed for 8 hrs after tourniquet was deflated for MAP, HR, SpO₂,  VAS at 1,3,5,10,15,30,60minutes,2,4,6&8hrs. Patients were  questioned for pain and if VAS was >4, 50mg of IV Tramadol was administered.

Table 1: Demography of the patients

The demographic data of the patients were comparable between the two groups.

Table 2: Time for First Analgesic administration After Tourniquet  Release. 

Almost all the patients in the Group I required analgesic within 15 minutes, as  compared to Group II where < 50% of patients needed analgesia (Fisher Exact Test  –p value 0.00001). Duration of analgesia extended upto a further 5 min period in  Group II. There was a small difference in VAS scores  at 11-15 min and 16-20 min among the groups.

Table 3 : Tourniquet Pain (VAS), in Intra operative and Postoperative  periods.

None of the patients in both groups complained of significant tourniquet pain intraoperatively but all of them (37 each) expressed feeling of discomfort at  tourniquet site both intraoperatively and after torniquet release. The VAS scores for  tourniquet pain were significantly less in Group II compared to Group I in the  postoperative period and was statistically significant.

Table 4 : Characteristics of Sensory and Motor blockade. 

The recovery of both sensory (15.63±1.63 min) and motor block(11.45±1.54 min)  was delayed in Group II compared to recovery of sensory (13.53±1.96 min) and  motor (9.35±1.59 min) block of Group I respectively and this difference was found  to be statistically significant.

Table 5 : Intraoperative HR Changes(Beats/min). 

There was no difference with respect to heartrate in intraoperative period. However,during the time interval of 75-90 min, the heart rate was less in Group II compared to  Group I.

Table 6 : Intra-operative changes in Systolic and Diastolic Blood Pressure (mm of Hg).

Table 7 : Intraoperative MAP Changes (mm of Hg). 

There was no significant difference with respect to systolic blood pressure in intra operative period at different time intervals. However during the time interval of 75-90  min the systolic BP was less in Group II compared to Group I.There was no  significant difference with respect to Diastolic BP in intra operative period at  different time Intervals, however during the time interval of 15-60 min the diastolic  blood pressure was less in Group II compared to Group I. There was no  difference with respect to MAP in intraoperative period at different time intervals, however during the time interval of 10-60 min the MAP was less in Group II  compared to Group I.

Table 8 : Post operative changes in Heart rate (Beats/min). 

There was increase in HR during the 10-30 min time interval in postoperative  period in both the groups.

Table 9: Post operative Systolic and Diastolic Blood Pressure changes (mm of Hg) . 

Table 10 : Post operative Mean arterial pressure changes(mm of Hg) . 

There was no difference with respect to Systolic BP in Postoperative period.  However during the time interval of 6-8 hr, the SBP was less in Group II compared  to Group I. It was high in both groups during the time interval of10-30 min. There was  no difference with respect to Diastolic BP in Post operative period. However during  the time interval of 4-8hr, the DBP was less in Group II compared to Group I. It was  high in both groups during the time interval of10-30 min.

There was no difference with respect to in MAP in Postoperative period. However  during the time interval of 6-8hr ,the MAP was less in Group II compared to Group I.  It was high in both groups during the time interval of 10-30 min.

We did not observe any significant difference between the two groups with respect to SpO2 both intraoperatively and postoperatively.

Disadvantages with IVRA were LA toxicity, tourniquet pain and lack of postoperative analgesia. Various modalities were tried to overcome these disadvantages, like change of local anaesthetic, modification of technique, addition of adjuvants and priming technique. 

Lignocaine is considered one of the least toxic LA agents. Dosage of 1-2 mg/kg is  used  for  treating  ventricular  arrhythmias  or  attenuating  the cardiovascular response to endotracheal intubation. In IVRA with conventionally placed tourniquet over the upper arm a relatively large dose of 3 mg/kg is required to ensure adequate analgesia.³ 0.5% lignocaine 40 ml was used in the present study based on effective results in previous studies ^(3,10,14,). The present investigation was aimed to study the effect of delayed administration of clonidine(150µg) to IVRA 10 minutes before closure of the wound after the initial administration of lignocaine. Clonidine has been reported to depress nerve action potentials, especially in C fibres, by a mechanism independent of α₂ adrenergic receptors^15,16. This mechanism accounts for strengthening of the local anesthetic block achieved by perineural administration of the drugs. α₂ adrenergic receptors located at the nerve endings may play a role in analgesic effect of the drugs by preventing norepinephrine release¹⁷. Clonidine enhances peripheral nerve block of local anesthetics by selectively blocking conduction of Aδ and C fibres¹⁵. Clonidine also causes vasoconstriction thereby reducing the vascular uptake of local anaesthetics¹⁸. Because clonidine inhibits the release of norepinephrine from prejuntional α2 adrenoceptors in the periphery¹⁹, it may potentially inhibit neural activity in nociceptive pathway. 

In our study, almost all the patients in the Group I (34/37) required analgesics within 15 minutes as compared to Group II where less than 50% of patients needed analgesics. However, the duration of analgesia extended only upto a further 5 minutes period in group II.The VAS scores in Group II at 11-15 minutes time interval was 4.2±0.66 and at 16-20minutes time interval it was 4.4±0.65 and it was less compared to Group I where the VAS scores were 4.46±0.64 at 11-15 minutes time interval and 4.49±0.64 at 16-20 minutes time interval but it was statistically not significant, which is comparable with that of Marc Gentili et al¹⁰ where clonidine was administered with local anaesthetic at the beginning of IVRA reported a duration of post operative analgesia was not statistically significant between the two groups (for Lignocaine alone it was 6±2 min and for Lignocaine with clonidine it was 12±12 min).In another study by Samkaoui MA et al²⁰, where clonidine was administered with local anaesthetic at the beginning of IVRA, the time to first analgesic request after deflation of tourniquet was similar in two groups(for Lignocaine alone it was at 38±15 min and for Lignocaine with clonidine it was at 44±19 min) ,however their VAS scores were 5.2 in Lignocaine alone group and 6.8 , in Lignocaine with clonidine group at those time intervals which explains the delay in first analgesic request in their study .  

The lack of adequate duration of post operative analgesia when clonidine was administered with local anaesthetic at the beginning of IVRA is possibly because of the rapid washout of the local anaesthetic and clonidine once the tourniquet is released¹⁰ and possibly some mass of both the drugs attached to neural tissues in the IVRA extremity causing less mass to be available for systemic effects. Taking this factor into consideration, the administration of clonidine was delayed to till 10 minutes before closure of wound so that the drug is available for action within the IVRA extremity and then in the system in sufficient concentrations. This obviously did not occur in the present study as there was no associated significant prolongation of analgesia. The actual serum concentrations of the clonidine and local anaesthetic if assessed after tourniquet release would be helpful in confirming this hypothesis. 

The tourniquet pain in our patients in both the groups was insignificant, however the VAS scores for Group II (1.67±0.92) was less than Group I(1.88±0.61) which were comparable with previous studies by Gentili et al¹⁰ and Lurie et al²¹ who suggested that clonidine improved tourniquet pain tolerance. 

In Group I , in our study, the mean onset time for sensory block was 9.58±1.53 min and mean onset time for motor block was 14.65±1.79min.The sensory block recovery time was 13.53±1.96min and motor block recovery time was 9.35±1.59min.This was comparable with a study by Santosh MCB et al⁵³ in which he has administered 0.5% Lignocaine alone for IVRA, where mean onset time for sensory block was 7.12±0.75 min and mean onset time for motor block was 11.93±0.87min,the sensory block recovery time was 10.57±0.81 and motor block recovery time was 7.64±0.83min. 

However in a study by Huseyinsen et al¹³, with 0.5%Lignocaine alone for IVRA the onset time for sensory block was 7±3 min and onset time for motor block was 12±4 min¹³  which were comparable with our study, but the sensory block recovery time was faster( 5±3 min) and motor block recovery time was faster ( 6±2 min), compared to Group I in our study. In Group II, in our study ,the mean onset time for sensory block was 10.25±1.19 min and mean onset time for motor block was 15.03±1.31min.The sensory block recovery time was 15.63±1.63min and motor block recovery time was 11.45±1.54min.The sensory and motor blockade was delayed in Group II compared to Group I in our study. The onset times for sensory and motor blocks were not assessed in other similar studies. 

Post operative monitoring was continued for any adverse effects like bradycardia, hypotension, sedation and respiratory depression keeping in mind the risk of systemic effects of clonidine after the tourniquet deflation. There were no significant adverse effects in either groups both intraoperatively and postoperatively. Similarly there were no significant adverse effects in a study by Ivie CS et al .²² 

There was no significant difference with respect to Systolic, Diastolic Blood Pressure and Mean arterial pressure, Heart Rate and Arterial O₂ Saturation at different time intervals of the study period, except for increase in HR and Blood pressures during the time interval of 10-30 min postoperatively, this is because of pain at the surgical site after deflation of tourniquet. Similar observations were found with respect to Blood pressure, Heart rate and Arterial O₂ Saturation in studies by Marc Gentiliet al¹⁰ and Ivie CS et al .²² 

Addition of 150 µg of clonidine 10min before expected end of procedure with IVRA using 40 ml of 0.5% lignocaine did not significantly improve the duration, and quality of post-operative analgesia. Also, there was  no difference in tourniquet pain score at the end of surgery and in the immediate post operative period in both the groups. No significant changes in MAP, HR, and SpO₂ were observed. 

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