COMPARISON of ROPIVACAINE and LIDOCAINE SENSORY and MOTOR BLOCK and POST OPERATIVE ANALGESIC REQUIREMENT in INTRA- VENOUS REGIONAL ANESTHESIA Salah M

Home , Ropivacaine

AAMJ, Vol. 10, N. 2, April, 2012, Supple ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ COMPARISON OF ROPIVACAINE AND LIDOCAINE SENSORY AND MOTOR BLOCK AND POST OPERATIVE ANALGESIC REQUIREMENT IN INTRA- VENOUS REGIONAL ANESTHESIA Salah M. kamal Department of Anesthesia and Intensive care, Faculty of Medicine, (boys) Al Azhar University, Cairo, Egypt. ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ ABSTRACT Objectives:This study was conducted to compare the analgesic and motor block efficacy and the post operative analgesic requirement of ropivacaine with that of Lidocaine in intravenous regional anesthesia. Methodology: Sixty patients of ASA physical status I and II, aged 20-50 years undergoing ambulatory surgery in the forearm and hand were randomly allocated into two equal groups 30 patients each. Patients in each group received either 30 ml of 1% lidocaine or 30 ml of 0.2% ropivacaine. The onset, duration and recovery times of sensory and motor block, time to the request for first analgesic requirement, incidence of rescue medication and total analgesic consumption in first 24 hours were recorded. Results: The result obtained revealed that, the recovery time of sensory block was significantly prolonged in ropivacaine group than in lidocaine group, but the onset of sensory block was delayed in ropivacaine group as compared to patients in lidocaine group. No significant difference between the groups as regard the motor block onset, but the motor recovery time was significantly prolonged in ropivacaine group compared to lidocaine group. Time to the request for first analgesic was significantly more prolonged and the incidence of rescue medication and total analgesic consumption was significantly lower in patients receiving ropivacaine than in those receiving lidocaine. Conclusion: It was found that ropivacaine is a good

399

Salah M. kamal ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ alternative to Lidocaine for intravenous regional anesthesia and provides a more prolonged post-tourniquet release pain relief as compared to Lidocaine. Key words: Ropivacaine; Intravenous regional anesthesia; sensory; motor; Lidocaine; INTRODUCTION Intravenous regional anesthesia (IVRA) was first described by August Bier in 1908, who discovered a very effective method for complete anesthesia and motor paralysis of the hand and forearm and called it “Direct Vein Anesthesia” 1. He used procaine, the first safe injectable local anesthetic that had been synthesized in 1904. However, the technique did not become popular until it was reintroduced by Holms in1963 using lidocaine as an anesthetic agent. IVRA is suitable for operations of the distal extremities, in situations where it is safe and easy to apply an occlusive tourniquet. It is mainly used for surgical procedures of the upper extremity, but it can also be used for procedures involving the lower extremity 1. IVRA is defined as a technique of producing surgical anesthesia by intravenous injection of local anesthetic into a limb whose circulation has been interrupted by a tourniquet. In addition, it is a simple, safe (2), reliable (3), and an effective technique that can easy be controlled by anesthesiologist. This technique has some disadvantages as, local anesthetic (LA) toxicity, slow onset, poor muscle relaxation, tourniquet pain which is dull aching sensation arising from the tourniquet site due to ischemia of muscles and nerves. This pain limits this technique to surgeries lasting for less than 90 min.4, 5 . In addition, it provides only minimal postoperative pain relief after tourniquet release6. IVRA is often a safer option than general anesthesia; particularly if the patient is elderly, or has cardiovascular, respiratory or any other medical disorders.7 In fact it is ideal anesthetic technique for short surgical procedures involving distal extremities on day care basis.8

400

AAMJ, Vol. 10, N. 2, April, 2012, Supple ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ The ideal drug for IVRA should have rapid onset of action, reduced dose of local anesthetic, prolonged analgesia after removal of tourniquet and wide safety margin. So, the lidocaine is the most widely used local anesthetic for IVRA. However, ropivacaine is a newly amide local anesthetic that is structurally related to bupivacaine with duration of anesthesia almost as long as that of bupivacaine, however, with less central nervus system (CNS) and cardiovascular system (CVS) toxicity because it is pure S- enuntiomer.9 Bupivacaine has been used for intravenous regional anesthesia and provides sustained analgesia after tourniquet release. However, reports of seizures and cardiac arrest after intravascular absorption have resulted in eventual discontinuation of bupivacaine for IVRA.10-11 The clinical use of ropivacaine is well established in epidural anesthesia and peripheral nerve blocks. Therefore, the use of a local anesthetic that would provide longer lasting post tourniquet release analgesia and with least incidence of toxic effects prompted the effort to study the effectiveness of ropivacaine in intravenous regional anesthesia.

METHODOLOGY This study was conducted in Al-Husain hospital, Faculty of medicine, Al Azhar University, Cairo, Egypt, from January 2010 to April 2012. After institutional ethical committee approval and written informed consent, a total number of 60 patients ASA physical status I and II, aged 20 to 50 years undergoing ambulatory surgery in forearm and hand were recruited in the study. The patients were randomly divided into two groups. As this study was not blinded and the group size was specific, randomization was done on the basis of allocating alternate patient to either of the groups. Lidocaine Group (Group L): Patients in this group received 30 ml of lidocaine 1% (2mg/kg) this group consisted of 30 patients.

401

Salah M. kamal ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ Ropivacaine Group (Group R): Patients in this group received 30 ml of ropivacaine 0.2% (2mg/kg). This group also consisted of 30 patients. All the patients were clinically evaluated and investigated before undergoing surgery as per the protocol. Exclusion criteria conclude patients with Raynaud’s disease, sickle cell disease, myasthenia gravis, uncompensated cardiac disease, diabetes mellitus, liver and renal insufficiency and those with history of allergic reaction to lidocaine or ropivacaine. The tourniquet was checked for any leaks. All the drugs and equipment needed for resuscitation were kept available before start of anesthesia. On admission to the operating room, non-invasive blood pressure, electrocardiogram and peripheral oxygen saturation monitoring was started. Intravenous access using 20G cannula was established in the non surgical arm and an intravenous infusion of crystalloid was started. The operative arm was cannulated by a 22 G cannula in the dorsum of the hand then elevated for 5 minutes, and using an Esmarch bandage, the venous blood of the arm was emptied. Then, a double-pneumatic tourniquet was applied. The proximal tourniquet was inflated to a pressure of 100 mmHg higher than systolic blood pressure. Isolation of the arm was confirmed by inspection, lack of radial pulse, and failure of pulse oximetry tracing of the ipsilateral index finger. After inflation of the proximal pneumatic tourniquet and release of the Esmarch bandage, patients in group L (n= 30) received 1% lidocaine 2 mg/kg for IVRA, patients in group R (n = 30) received 0.2% ropivacaine 2 mg/kg and in all groups normal saline was added to make up a total volume of 30 mL. The prepared solutions were administered over 60 second by an anesthesiologist who was blinded to the drug being administered. After anesthesia was achieved, the distal tourniquet was inflated to 100 mmHg higher than systolic pressure, and the proximal tourniquet was deflated. Time at

402

AAMJ, Vol. 10, N. 2, April, 2012, Supple ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ inflation of tourniquet and drug administration was noted. The distal tourniquet was not deflated before 30 min and was not inflated for more than 90 min. Tourniquet deflation was carried out by cyclic deflation at 10 second intervals. Sensory block was assessed by pinprick test using 22G gauge short- beveled needle every 30s after injection of drug to note the time of onset, and after tourniquet deflation to note the time of return of sensations. The patient’s response was evaluated in the dermatomal sensory distribution of the ulnar, median, and radial nerves. Sensory block onset time was the time from injection of the study drug until sensory block in all dermatomes. Duration of sensory block was taken as the time interval from cessation of pinprick sensation in all dermatomes until the return of pinprick sensation. Motor block was assessed by testing hand grip strength and muscle power. Individual muscle groups were tested as follows: thumb opposition (median nerve), little finger flexion and finger abduction-adduction (ulnar nerve), wrist extension (radial nerve), and elbow flexion (musculocutaneous nerve), every minute after administration of drug to note the time of onset, and after deflation of tourniquet to assess the time of return of motor functions. Complete motor block was recorded when no voluntary movement was possible. Motor block onset time was the time from injection of drug until complete motor block was achieved. Duration of motor block was the time interval from cessation of finger and wrist movements until return of these movements. Recovery time of sensory block is the time from tourniquet deflation to the return of pain in all dermatomes and it was determined by pinprick test. However, the recovery time of motor block is the time from tourniquet deflation to the return of fingers movement.

403

Salah M. kamal ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ Pain was assessed for postoperative pain up to 24 hours using the visual analogue scale (VAS) where a score of zero was given for no pain and 10 for worst pain imaginable. Patients were advised to receive 50 mg of nonsteroidal anti-inflammatory drug (diclofenac sodium) intramuscular (IM) at VAS of more than 3 as rescue medication. Time to the request for first analgesic after tourniquet deflation and total analgesic consumption in 24 hours was noted in all patients.

Statistical Analysis:

Statistical presentation and analysis of the present study was conducted, using the mean, standard Deviation, student t-test and chi-square by SPSS V10.

Mean =  x n

Where  = sum & n = number of observations.

Standard Deviation [SD] :

 x - x 2 SD  n 1

Student t-test [Unpaired]:

X - X t  1 2 SE1 2  SE2 2

Where:

X1 = Mean of the first group .

X 2 = Mean of the second group .

SE1 = Standard error of the first group.

SE2 = Standard error of the second group.

404

Chi-square

The hypothesis that the row and column variables are independent, without indicating strength or direction of the relationship. Pearson chi-square and likelihood-ratio chi-square. Fisher's exact test and Yates' corrected chi-square are computed for 2x2 tables. P value <0.05 was considered statistically significant

RESULTS Demographic data of the groups were statistically comparable for age, weight, height, and sex ratio with no significant difference between the two groups. [Table 1]. Table 1. Demographic data, patient characteristics, and types of surgeries Ropivacaine 0.2% P value Lidocaine 1% (n = 30) (n = 30) Age (yrs) 41.4 ±17.1 41.9 ± 14.1 0.902 0.751 Gender (F/M) (n) 12/8 10/10

Weight (kg) 64.55 ± 13.3 67.7 ±13.18 0.360 Height (cm) 157.3 ± 6.41 158.4 ± 6.59 0.514 Type of surgery tenolysis 7 6 0.984

carpal tunnel release 6 7 0.754

ganglionectomy 7 7 1.000

Surgical times 0.362 28.1± 2.8 27.4 ± 3.1 (min) Data are means ± SD.

405

Salah M. kamal ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ There was no significant difference as regard the onset of anesthesia between the groups after injection of the studied drugs it was 7.1±3.3 min and 6.2± 2.8 min in ropivacaine and lidocaine group respectively, However the recovery of sensory block was significantly prolonged in ropivacaine group compared to lidocaine group it was (12.5 ± 4.6 min) and at (10.3 ± 1.4 min) respectively. [Table 2] Fig 1. Table 2. Interval between local anesthetic injection and surgical incision, onset of sensory block, sensory recovery time and total tourniquet times.

Ropivacaine 0.2% Lidocaine 1%

(n = 30) (n = 30) P value

Interval between local anesthetic injection and 0.076 surgical incision (min) 13.1±2.4 12.2 ±1.3

0.259 Sensory block onset (min) 7.1 ± 3.3 6.2 ± 2.8 Sensory recovery time 12.5 ± 4.6 10.3 ± 1.4 <0.05* (min)

Total tourniquet times 0.269 45.8 ± 5.2 47.2 ± 4.5 (min)

Ropivacaine 0.2% 18 Lidocaine 1% 16 14 12 10 8 6 4 2 0 Sensory block onset (min) Sensory recovery time (min)

Fig 1. Sensory block onset and recovery time

406

AAMJ, Vol. 10, N. 2, April, 2012, Supple ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ There was no significant difference between the groups as regard motor block onset time it was started after (9.8 ± 1.3) min. and (10.2 ± 1.5) min. in lidocaine and ropivacaine group respectively. However there was statistical significant difference between the groups as regard the motor block recovery time it was (7.1 ± 1.5min) and (9.0 ± 1.6 min) in lidocaine and ropivacaine group respectively. [Table 3], Fig 2. Table 3. motor block onset and recovery time Ropivacaine 0.2% Lidocaine 1% P value (n = 30) (n = 30) Motor block 10.2 ± 1.5 9.8 ± 1.3 0.274 onset time (min) Motor block recovery time 9.0 ± 1.6 7.1 ± 1.5 <0.001* (min)

14 Ropivacaine 0.2% Lidocaine 1% 12

2 0 FigMotor 2. block motor onset block time (min) onset and recoveryMotor blocktime. recovery time (min) The time to the request for first analgesic was also significantly prolonged in ropivacaine group as compared to lidocaine group. None of the patients from either group required rescue analgesic intraoperatively. The total number of patients requiring analgesics was significantly less in ropivacaine group, 53 %( 16) compared to lidocaine group (80%) 24 patients

407

Salah M. kamal ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ requiring an analgesic dose of nonsteroidal anti inflammatory over 24 hour. [Table 4]. Table 4: Showing number of patients requiring analgesic Total no of Group n (%) P value patients ropivacaine 16(53%) 30 <0.05* lidocaine 24(80%) 30 Total analgesic consumption (diclofenac sodium 50mg) in 24 hours, in ropivacaine group was 800 mg and 1200 mg in lidocaine group.

DISCUSSION All Regional anesthesia is based on the concept that pain is carried by the nerve fibers which are amenable to be interrupted anywhere along their pathway. Local anesthetics such as lidocaine and prilocaine are commonly administered for IVRA. However, lidocaine, the most often used local anesthetic for IVRA has a relatively short duration of action which may affect the duration of intraoperative and post tourniquet release analgesia and tourniquet tolerance.9 Theoretically it would be beneficial to use long acting drugs such as bupivacaine, but it is considered too risky for IVRA because it binds to sodium channels of the myocardium and may lead to irreversible cardiac arrest if the bupivacaine escapes into the systemic circulation11. Ropivacaine has a similar duration of action as that of bupivacaine, but with less depression of cardiac conduction presumably because it is a pure S-enantiomer.9 Data from this study show that ropivacaine 0.2% produce anesthesia of similar quality to that achieved with a conventional dose of lidocaine during IVRA but with more long-lasting residual analgesia. In current study the two groups did not differ with respect to age, gender, duration of surgery and the average period of tourniquet inflation.

408

AAMJ, Vol. 10, N. 2, April, 2012, Supple ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ There was no significant difference in onset of motor block between the two groups, this result correlate with those of Ibrahim Asik et al12 and Peter AG et al13 who also found no significant difference in onset of motor block between the two groups and they found no significant difference in the duration of motor block. However this result contradict with the result in this study where it was found that, the duration of motor block was significantly prolonged in ropivacaine group than in lidocaine group, and this result correlate with those of MacMillan et al14 who found that, motor block was prolonged with ropivacaine. The onset of sensory block was delayed (7.1± 3.3 min) in ropivacaine group as compared to Lidocaine group where it was quicker (6.2± 2.8 min) on the average. The rapid onset of sensory block with lidocaine may be attributed to its pKa value (7.86)15 which is close to physiological pH. Due to this property, the ionized fraction of Lidocaine increases, leading to a quicker penetration into nerves and rapid onset as compared to ropivacaine. The recovery time of sensory block in ropivacaine group was significantly prolonged as compared to Lidocaine group, the longer duration of residual analgesia after tourniquet release with ropivacaine may be attributed to more complete and persistent binding and slower release into systemic circulation.16 The potency of ropivacaine is 3 times that of lidocaine.16 and the concentration used was 0.2% solution as it closely achieves equipotency with the typically used concentration of lidocaine for IVRA. The terminal half life of ropivacaine after IV administration is longer (108 min) 17 as compared to lidocaine, which also leads to its prolonged action. The results obtained in this study correlate with those of Ibrahim Asik et al12 and Peter AG et al13 who found that recovery time of sensory block was significantly prolonged in ropivacaine group.

409

Salah M. kamal ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ In current study, it was found that, time to the request for first analgesic was also prolonged in ropivacaine group and the incidence of rescue analgesic and total analgesic consumption were significantly lower in patients who received ropivacaine. It correlates with the result found by Peter AG13 and Ibrahim Asik12 in their studies. In the present study no seizures or cardiotoxic effects were observed in any group with the doses used and this correlates with the results obtained by Peter G et al18 in their study upon central nervous system side effects and the result of Atanassoff et al19 who reported a lower incidence of CNS side effects in volunteers who received IVRA with 40 mL. of ropivacaine 0.2% versus lidocaine. This may be attributed to the less lipid solubility of ropivacaine, where it was intermediate between that of lidocaine and bupivacaine and about one half to one third that of bupivacaine.20 the low lipid solubility of ropivacaine explains its higher threshold for CNS. Ropivacaine is extensively (94%) bound to plasma proteins and as the systemic toxicity is related to unbound drug concentration, the clinical safety profile of ropivacaine may be more favorable21.

CONCLUSION In conclusion, Ropivacaine is a long-acting local anesthetic with a marked differential blockade between sensory and motor fibers, and it provide prolonged recovery time of sensory block and a lesser need for rescue analgesics make ropivacaine an effective alternative to lidocaine in IVRA.

410

AAMJ, Vol. 10, N. 2, April, 2012, Supple ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ REFERENCES 1. Brown BL, and Fink BR. The history of neural blockade and pain management. In: Cousins MJ, Bridenbaugh PO, editors. Neural blockade in Clinical Anesthesia and Management of Pain. 3rd ed.Philadelphia: Lippincott-Raven; 1998. p. 3-34. 2. Catteral WA, and Mackie K. Local Anesthetics: in: Hardman JG, Limbird LE, Gilman AF, eds.; the pharmacological basis of therapeutics, 10th edition. New York, NY: McGraw-Hill; 2001:370 - 87. 3. Chan VWS, Weisbrod MJ, Kaszas Z, and Dragomir C. Comparison of ropivacaine and Lidocaine for Intravenous Regional Anesthesia in volunteers. A Preliminary Study on Anesthetic Efficacy and Blood Level. Anesthesiology 1999;90: 160. 4. Heath ML : Deaths after intravenous regional anesthesia. BMJ 1982;285:913-4. 5. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51: 285-7. 6. Henderson AM. Adverse reaction to bupivacaine: Complication of intravenous regional analgesia. BMJ 1980; 281:1043-44 7. Ware RJ. Intravenous regional analgesia using bupivacaine. A double blind comparison with lignocaine. Anesthesia 1979; 34:231-5. 8. Evans CJ,Dewar JA,Boys RN, and Scot DB: Residual nerve block following intravenous regional anesthesia : Br. J Anaesth 1974;46:668- 70. 9. Reiz S, Haggmark S, Johansson G, and Nath S. Cardiotoxicity of ropivacaine: a new amide local anesthetic agent. Acta Anaesthesiology Scand 1989;33:93-8 10 .Arlander E, Ekström G, Alm C, Carrillo JA, Bielenstein M, Böttiger Y, et al. Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a

411

Salah M. kamal ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ minor extent by CYP3A4:An interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther 1998;64:484-91. 11. Knudsen K, Beckman Suurkula M, Blomberg S, Sjovall J, and Edvardsson N. Central nervous and cardiovascular effects of IV infusions of ropivacaine, bupivacaine and placebo in volunteers . Br J Anaesth 1997;78:507-14. 12. Asik I, Kocum AI, Goktug A, Turhan KS, and Alkis N. Comparison of ropivacaine 0.2% and 0.25% with lidocaine 0.5% for intravenous regional anesthesia. Journal of Clinical Anesthesia 2009;21:401-7. 13. Peter AG, Carlos O, Bande MC, Hartmannsgruber MW, and Halaszynski MT. Ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in outpatient surgery. Anesthesiology 2001; 95(3):627- 631. 14. MacMillan LB, Kitto KF, The effect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25% bupivacaine on sensory and motor block in volunteer: a double blind study.regional anesthesia 2010,21:14-26 15. Clark N. Intravenous regional anesthesia – Bier’s block. Update in Anesthesia 2002; 15: 28-29. 16. Simpson D, Curran MP, Oldfield V, and Keating GM. Ropivacaine : A review of its use in regional anesthesia and acute pain management. Drugs 2005; 65:2675-717 17. Hartmanns gruber MW, Silverman DG, Halaszynski TM, Bobart V, Brull SJ, Wilkerson C, et al. Comparison of ropivacaine 0.2% and Lidocaine 0.5% for intravenous regional anesthesia in volunteers. Anesthesia Analg.1999; 89:727-31. 18. Peter G Atanassoff PG, and Maximilian WB Hartmannsgruber. Central nervous system side effects are less important after iv regional

412

AAMJ, Vol. 10, N. 2, April, 2012, Supple ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ anesthesia with ropivacaine 0.2% compared to lidocaine 0.5% in volunteers. Can J Anesth 2002; 49:169-72. 19. Atanassoff PG, Ocampo CA, Bande MC, Hartmannsgruber MW, and Halaszynski TM. Ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in outpatient surgery. Anesthesiology 2001; 95:627-31. 20. Agasti TK. Local anesthetic agents: Text book of Anesthesia for postgraduates by TK Agasti 1st edition, Jaypee brothers med publisher, New Delhi-India- 2011, chapter 13:p. 318. 21. Greengrass R, Steele S, Moretti G, Grant S, Klein S, and Nielsen K. Peripheral nerve blocks. Textbook of Regional Anesthesia and acute pain management, McGraw Hill Professional, 2009:p.354-356.

413