Adding Clonidine to Lidocaine for Intravenous Regional Anesthesia Prevents Tourniquet Pain : Anesthesia & Analgesia

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Regional Anesthesia and Pain Management

Adding Clonidine to Lidocaine for Intravenous Regional Anesthesia Prevents Tourniquet Pain

Gentili, Marc MD; Bernard, Jean-Marc MD, PhD; Bonnet, Francis MD

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Anesthesia & Analgesia 88(6):p 1327-1330, June 1999. | DOI: 10.1213/00000539-199906000-00024
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Tourniquet pain often complicates the use of the pneumatic tourniquet during surgical procedures performed under IV regional anesthesia.Clonidine-containing local anesthetic solutions have better analgesic properties than plain solutions when used for spinal, epidural, or peripheral blocks. We tested the hypothesis that the addition of clonidine may improve the quality of IV regional anesthesia, especially tourniquet tolerance. Forty patients were allocated randomly in a double-blinded, randomized study to receive 40 mL of 0.5% lidocaine and either 1 mL of isotonic saline or clonidine (150 [micro sign]g). A double-cuffed tourniquet was kept inflated until patients complained of pain, leading to release of the distal cuff. Pain at the tourniquet site, at the surgical site, and in the distal part of the arm was rated on a visual analog scale (VAS) and a verbal rating scale (VRS) every 15 min during tourniquet placement and every 15 min for 1 h after tourniquet deflation. Motor blockade, sedation, arterial pressure, and heart rate were also recorded. VAS and VRS scores were significantly lower in the clonidine group 30 and 45 min after tourniquet inflation. The tolerance for the distal tourniquet was also significantly longer in the clonidine group (median [range]: 22 [10-40] vs 10 [5-20] min; P < 0.05); motor blockade was comparable between the two groups. Pain was not different in the two groups after tourniquet release. The clonidine group experienced a higher degree of sedation. We conclude that clonidine improves tourniquet tolerance when added to a local anesthetic solution. Implications: A 150-[micro sign]g dose of clonidine added to lidocaine improved tourniquet tolerance during IV regional anesthesia.

(Anesth Analg 1999;88:1327-30)

Tourniquet pain is a common problem complicating the use of a pneumatic tourniquet during surgical procedures involving the upper or lower limb [1,2]. Tourniquet pain is described as a dull and aching pain sensation that increases in severity with duration of the tourniquet inflation despite otherwise adequate regional anesthesia [2,3]. After tourniquet deflation, a different pain sensation is reported associated with reperfusion of the limb. This sensation is often reported as an intense tingling. Although tourniquet pain is poorly understood, it is thought to be related to impulse propagation via small, unmyelinated nerve fibers. To improve the quality of IV regional anesthesia (IVRA) block, the addition of various opioids to local anesthetics has been investigated with controversial results. A recent meta-analysis concluded that opioids lack a significant effect in this setting [4].

Clonidine induces analgesia mainly through stimulation of alpha2-adrenergic receptors in the dorsal horn of the spinal cord. It also depresses nerve fiber action potentials, especially in small, unmyelinated C fibers [5,6]. Clonidine has been used as an adjunct to local anesthetics to strengthen sensory block and to prolong its duration. We therefore conducted a prospective study to examine the effect of clonidine combined with lidocaine for IVRA on the quality of regional block.


Forty ASA physical status I patients scheduled for surgery of the hand or the forearm (i.e., carpal tunnel release and tendon release or transfer) were included in this double-blinded study after informed consent and ethical committee approval. They were randomly allocated to two groups to receive 0.5% plain lidocaine or clonidine-containing lidocaine solution. Patients previously treated with opioids, clonidine and related compounds, guanethidine, beta-blockers, and calcium channel blockers were excluded from the study, as were those patients suffering from peripheral or central neurological disease or cardiac conduction block. After application of routine monitors, a double tourniquet was positioned on the upper operative arm. The upper limb was elevated and wrapped with an Esmarch bandage for exsanguination. A proximal and a distal tourniquet were both inflated to 250 mm Hg. IVRA was performed with 40 mL of lidocaine 0.5% and either 1 mL of isotonic saline or clonidine (150 [micro sign]g). Anesthetic solutions were administered by an anesthetist blinded as to whether they contained clonidine. Pain was assessed at the site of tourniquet placement, at the operative site, and in the upper limb using a visual analog scale (VAS) graded from 0 to 100 and a verbal rating scale (VRS) graded as 0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain, 4 = excruciating pain. Pain rating was performed every 15 min during the hour after tourniquet placement and every 15 min during the hour after tourniquet release. When patients complained of pain at the tourniquet site, the proximal tourniquet was deflated. The distal tourniquet was eventually released if the previous maneuver did not achieve pain relief. The duration of tourniquet tolerance was the time elapsed between tourniquet placement and proximal tourniquet release. When patients complained of pain postoperatively, they received 2 g of paracetamol orally and were subsequently treated on demand with the same drug. The duration of analgesia was the time elapsed between tourniquet release and the first oral intake of paracetamol.

Motor blockade was assessed on a 3-point scale (0 = normal finger motility, 1 = decrease motility, 2 = complete motor blockade). At the end of the procedure, surgeons were asked to qualify the operative conditions as 0 = perfect, 1 = acceptable, 2 = difficult. Heart rate and SaO2 were monitored continuously, and arterial pressure was measured every 5 min. These variables and sedation score (0 = fully awake, 1 = drowsy, 2 = asleep but responsive to command, 3 = asleep but responsive to a glabellar tap) were recorded every 15 min. Hypotension (systolic arterial pressure <75 mm Hg) was treated with IV ephedrine (3- to 9-mg bolus), bradycardia (heart rate <45 bpm) was treated with IV atropine 0.5 mg, and SaO2 <91% was treated with O2 supplementation via a face mask.

We used an unpaired Student's t-test to compare patient demographics and a Mann-Whitney U-test to compare the durations of tourniquet tolerance and tourniquet placement. Categorical data (e.g., VRS, sedation scores, motor blockade) were compared using a contingency table. A two-way analysis of variance and a modified t-test were used for hemodynamics comparison, and a Kruskall-Wallis analysis and a Friedman test were used to compare VAS scores. P < 0.05 was considered significant.


Patient demographics were comparable between the two groups: age 41 +/- 18 vs 51 +/- 18 yr; height 157 +/- 31 vs 166 +/- 9 cm; weight 72 +/- 27 vs 68 +/- 9 kg in the lidocaine plain solution and clonidine-containing solution groups, respectively. The distal tourniquet tolerance was better in the group receiving the clonidine-containing lidocaine solution compared with the group receiving the lidocaine plain solution (median [range]: 22 [10-50] vs 10 [5-20] min; P < 0.05). The duration of the proximal tourniquet placement was 60 [47-60] and 55 [35-60] min (P < 0.05) in the clonidine and control groups, respectively. The duration of postoperative analgesia (delay before the first paracetamol request) was not statistically different between the two groups (control group 6 +/- 2 min, clonidine group 12 +/- 12 min) and the difference in the total dose of paracetamol was not significant (2.7 +/- 1.1 vs 2.1 +/- 0.6 g in the control and clonidine groups, respectively; P = 0.059). VAS and VRS scores for tourniquet pain and pain in the extremity were lower in the clonidine group (Table 1, Figure 1 and Figure 2), whereas no differences were noted in pain at the surgical site. Postoperatively, there were no differences in VAS and VRS scores (Table 1).

Table 1:
Pain Scores
Figure 1:
Changes in visual analog scale scores in the two groups of patients during tourniquet placement and after tourniquet release. Values are represented as box plots (25th-75th percentile). Bars = medians and the 10th and 90th percentiles, [white circle] = extreme values. *Significant difference between the two groups.
Figure 2:
Changes in verbal rating scale scores in the two groups of patients during tourniquet placement and after tourniquet release. Values are represented as box plots (25th-75th percentile). Bars = medians and the 10th and 90th percentiles, [white circle] = extreme values. *Significant difference between the two groups.

Motor blockade was comparable in the two groups (Table 2). Postoperative sedation scores were higher in the clonidine group (Table 2). Heart rate and arterial pressure did not change during the study, and no difference was documented between the two groups, except 60 min after tourniquet deflation for diastolic arterial pressure (lower in the clonidine group).

Table 2:
Sedation (0-4) and Motor Blockade (0-3) Scores


Our study shows that adding clonidine to lidocaine improves IVRA. Tourniquet pain was dramatically reduced by the clonidine-containing lidocaine solution.

Intrathecal clonidine combined with local anesthetic and oral clonidine combined with spinal anesthesia have been shown to decrease the incidence of tourniquet pain in the lower limb [7,8]. In these circumstances, the clonidine effect could be related to a depression of the activity of wide dynamic range neurons of the dorsal horn of the spinal cord evoked by nociceptive stimulation [9]. Clonidine has also been reported to depress nerve action potentials, especially in C fibers, by a mechanism independent of the stimulation of alpha2-adrenergic receptors [5,6]. This mechanism accounts for strengthening of the local anesthetic block achieved by perineural administration of the drug and could be implicated in the effect seen in our study. Finally, alpha2-adrenergic receptors located at nerve endings may play a role in the analgesic effect of the drug by preventing norepinephrine release [10]. One could argue that a third group of patients receiving subcutaneous or IV clonidine might have helped to differentiate between a local and systemic effect of the drug. However, it is unlikely that improvement in the local anesthetic block induced by clonidine could be related to a mechanism other than the local effect of the drug because the tourniquet placement prevents whole body distribution of clonidine through the bloodstream.

In contrast to tourniquet tolerance, pain at the operative site was not different in the two groups of patients in this study. In fact, the low VAS pain scores in the two groups made it difficult to demonstrate a difference when adding an adjuvant to the local anesthetic solution.

After tourniquet release, pain developed rapidly in the two groups but did not achieve the values observed with maintenance of the inflated tourniquet. It is conceivable that a rapid washout of the anesthetic solution impaired the prolongation of the analgesic effect of clonidine. A weak advantage related to a trend toward lower requirements for rescue medication was nevertheless suggested in the clonidine group. In a study focusing on postoperative analgesia, Reuben et al. [11] documented lower pain scores and lower analgesic consumption in patients who received clonidine and lidocaine, which suggests a persisting effect of clonidine.

Two previous studies concerning the addition of clonidine to local anesthetic solution for IVRA failed to document any significant effect of the drug [12,13]. In the first, a dose of clonidine (2 [micro sign]g/kg) comparable to that used in the current study was administered to patients in combination with prilocaine 0.5% [13]. No significant differences between sensory and motor block or postoperative pain were documented. In the second study, clonidine 150 [micro sign]g used as an adjuvant to prilocaine 1% was compared with a plain solution of prilocaine and with three other additives: sufentanil, tenoxicam, and bupivacaine 0.25% [11]. Postoperative pain scores were marginally lower in the clonidine plus tenoxicam group. Neither study carefully examined tourniquet pain, which may explain their negative results. In addition, the tourniquet inflation time was shorter in these studies than in our study. Because the incidence and intensity of tourniquet pain increase with time, a longer duration of tourniquet inflation might have documented the analgesic effect of clonidine. In agreement with these two previous studies, we also documented that motor block was comparable in the two groups, as was postoperative pain.

Kleinschmidt et al. [13] also reported that tourniquet release was followed by moderate hypotension, which was not noticed in the current study. We postulate that, in our study, the duration of tourniquet inflation may have decreased the release of clonidine into the bloodstream. The occurrence of sedation after tourniquet release is nevertheless indicative of some systemic effect of clonidine that was not sufficient to produce significant analgesia.

We conclude that clonidine combined with a local anesthetic may prevent tourniquet pain in patients undergoing IVRA. This combination could be especially useful when tourniquet use is prolonged.


1. Hutchinson DT, McClinton MA. Upper extremity tourniquet tolerance. J Hand Surg Am 1993;18:206-10.
2. De Jong RH, Cullen SC. Theoretical aspects of bizarre pain phenomena during low spinal anesthesia. Anesthesiology 1963;24:628-35.
3. Crews JC, Hilgenhurst G, Leavitt B, et al. Tourniquet pain: the response to the maintenance of tourniquet inflation on the upper extremity in volunteers. Reg Anesth 1991;16:314-7.
4. Picard PR, Tramer MR, McQuay HJ, Moore RA. Analgesic efficacy of peripheral opioids (all except intra-articular): a quantitative systematic review of randomised controlled trials. Pain 1997;72:309-18.
5. Butterworth JF, Strichartz GR. The alpha2-adrenergic agonists clonidine and guanfacine produce tonic and phasic block of conduction in rat sciatic nerve fibers. Anesth Analg 1993;76:295-301.
6. Gaumann DE, Brunet P, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg 1992;74:719-25.
7. Bonnet F, Diallo A, Saada M, et al. Prevention of tourniquet pain by spinal isobaric bupivacaine with clonidine. Br J Anaesth 1989;63:93-6.
8. Liu S, Chiu AA, Neal JM, et al. Oral clonidine prolongs lidocaine spinal anesthesia in human volunteers. Anesthesiology 1995;82:1353-9.
9. Murata K, Nakagawa I, Kumeta Y, et al. Intrathecal clonidine suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats. Anesth Analg 1989;69:185-91.
10. Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science 1991;251:1608-10.
11. Reuben SS, Klatt ML, Klatt JL, et al. Intravenous regional anesthesia with lidocaine and clonidine [abstract]. Anesthesiology 1998;89:857.
12. Hoffmann V, Vercauteren M, Van Steenberge A, Adriansen H. Intravenous regional anaesthesia: evaluation of four different additives to prilocaine. Acta Anaesthesiol Belg 1997;48:71-6.
13. Kleinschmidt S, Stockl W, Wilhelm W, Larsen R. The addition of clonidine to prilocaine for regional anaesthesia. Eur J Anaesthesiol 1997;14:40-6.
© 1999 International Anesthesia Research Society