Department of Anesthesiology, Dicle University, Diyarbakir, Turkey Korespondenca/ Correspondence: dr. Feyzi CeLik DicLe University Medical School, Department of Anesthesiology and Reanimation Diyarbakir, Turkey TeL: +090 412 2248001 Fax: +090 412 2488523 Email: drfeyziceLik@ gmaiL.com Ključne besede: operacija koLka, Levobupivakain, bupivakain, spinaLna anestezija Key words: hip surgery, Levobupivacaine, bupivacaine, spinaL anesthesia Citirajte kot/Cite as: Zdrav Vestn 2013; 82: page 732-8 Prispelo: 19. juL. 2012, Sprejeto: 9. juL. 2013 Comparison of the effectiveness of intrathecal bupivacaine and levobupivacaine in hip surgery Primerjava učinkovitosti intratekalne aplikacije bupivakaina in levobupivakaina pri operacijah kolka Feyzi Celik, Haktan Karaman, Adnan Tufek, Gonul Olmez Kavak, Zeynep Baysal Yildirim, Orhan Tokgoz, Abdulmenap Guzel Abstract Purpose: We aimed to compare the anesthetic and hemodynamic effects of intrathecally administered levobupivacaine and bupivacaine in combination with fentanyl in hip surgery. Subjects and methods: Sixty patients categorized as class 1 or 2 according to the American Society of Anesthesiologists (ASA) Physical Status classification, aged between 18 and 65 years and scheduled for hip surgery were randomly assigned to two groups. Patients in Group I received spinal anesthesia with 0.5 % bupivacaine 12.5 mg + fentanyl 10 pg (total 2.6 ml), and patients in Group II received 0.5 % levobupivacaine 12.5 mg + fentanyl 10 pg (total 2.6 ml) intrathecally. The level of sensory block and motor block was evaluated, and hemodynamic data were recorded. Results: The onset of sensory block and the time to two-segment regression were similar between the two groups. In the levobupivacaine group, the time to motor block onset was longer and the motor block regression time was shorter than that of bupivacaine group. The groups were similar with respect to hemodynamic data. Conclusion: We consider that levobupivacaine may be a good alternative to bupivacaine, particularly in surgical procedures where less motor block development is desired. Introduction Stereoisomers of local anesthetic drugs used in regional anesthesia procedures have been developed to avoid toxicity and negative effects on hemodynamic parameters.1 Levobupivacaine - the S(-)-enantiomer of bupivacaine - is a local anesthetic with low- Izvleček Namen: Naš namen je bil primerjati anestezijske in hemodinamične učinke intratekalne aplikacije levobupivakaina in bupivakaina v kombinaciji s fentanilom pri operacijah kolka. Preiskovanci in metode: Šestdeset bolnikov, razvrščenih glede na fizično stanje po klasifikaciji Ameriškega združenja anestezologov (ASA) v razred 1 ali 2, starih med 18 in 65 let, pri katerih je bila načrtovana operacija kolka, je bilo randomi-ziranih v dve skupini. Bolniki v 1. skupini so prejeli spinalno anestezijo z 12,5 mg 0,5 % bupivakaina + 10 pg fentanila (skupaj 2,6 ml), bolniki v 2. skupini pa 12,5 mg 0,5 % levobupivakaina + 10 pg fentanila (skupaj 2,6 ml), intratekalno. Ocenjevali smo senzorično in motorično blokado in beležili hemodinamične podatke. Rezultati: Nastop senzoričnega bloka in čas do dvosegmentne regresije sta bila pri obeh skupinah podobna. V skupini z levobupivakainom je bil čas do nastopa motorične blokade daljši, re-gresija motoričnega bloka pa krajša kot pri skupini z bupivakainom. Hemodinamični podatki so bili pri obeh skupinah podobni. Zaključek: Menimo, da je lahko levobupivaka-in dobra alternativa bupivakainu, posebej še pri kirurških posegih, kjer želimo doseči manj motorične blokade. er plasma clearance and a shorter elimination half-life. Although bupivacaine is a frequently used and highly safe local anesthetic used in regional anesthesia procedures, its erroneous intravenous injection may result in fatal cardiotoxicity.2'3 In many studies of levobupivacaine and bupivacaine, levobupivacaine has been suggested to display less cardiovascular and central nervous system adverse effects compared to bupivacaine, although the onset and duration of their effects are identical; thus levobupivacaine has been suggested to be a new alternative for patients with cardiovascular pathologies.4 Levobupivacaine has been used in epidural and peripheral nerve blocks, and information on its intrathecal use is limited.5 We aimed to compare the effects of intra-thecally administered levobupivacaine and bupivacaine in combination with fentanyl on the hemodynamic parameters, sensory and motor block times and systemic and neurological side effects in adult patients undergoing hip surgery. Subjects and methods A total of 60 ASA I-II patients aged between 18 and 65 years were included in the study after approval had been obtained from the ethics committee of the Research Hospital, Dicle University, and written informed consents from the patients were obtained. Patients who had cardiovascular diseases, neuromuscular or neuropsychiatric diseases and peripheral neuropathy, alcohol and/or drug addiction, a history of operations on the lumbar spine, contraindications for regional anesthesia, and a history of allergy to local anesthetics, who were shorter than 155 cm or taller than 190 cm, and had a body Table 1: Demographic data and duration of surgery. mass index > 30, were excluded from the study. At the preoperative visit, all patients were informed about the anesthesia method and the verbal rating scale (VRS) that would be used for postoperative pain assessment. All patients underwent standard monitoring using electrocardiography, pulse-oximetry and non-invasive blood pressure measurements. All patients were administered 0.05 mg/kg midazolam intravenously to the dorsum of the hand through a 20-gauge needle. Next, 5 ml/kg hydroxy-acetyl starch and 5 ml/kg 0.9 % NaCl were administered within approximately 30 min. An infusion of 5 ml/kg/hour 0.9 % NaCl was administered during the operation. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and heart rates (HRs) of the patients were recorded. Spinal anesthesia was performed in the sitting position in all patients. The puncture site was disinfected using 10 % povidone-iodine (IsoSol®), and the L3-4 lumbar space was accessed through a 26-gauge spinal needle following local anesthesia. After free cerebrospinal fluid flow had been observed, Group I patients received 0.5 % bupivacaine 12.5 mg + fentanyl 10 ^g (total 2.6 ml) and Group II patients received 0.5 % levobupiva-caine 12.5 mg + fentanyl 10 ^g (total 2.6 ml) intrathecally. Patients were laid in the supine position and SAP, DAP, MAP, HR and SpO2 values were recorded at 2, 5, and 10 min, and at every 5 min thereafter. The level of sensory block was assessed using the pin-prick Group I (n = 30) Group II (n = 30) p Age (year) 58 ± 13.8 56 ± 15.3 0.58 Height (cm) 167 ± 7.5 165 ± 8.0 0.32 Weight (kg) 71 ± 12.3 76 ± 11.9 0.19 MaLe/FemaLe 20/10 17/13 0.42 ASA I/II/III 10/18 /2 13/15/2 0.30 Duration of surgery (min) 59 ± 10 61 ± 10 0.06 Values are given as mean ± standart deviation. ASA, American Society of Anesthesiologists test, and surgery was initiated when the level of sensory block reached T6. Patients were administered 3 L/min oxygen via a facial mask during the operation. A more than 20 % reduction in basal SAP was accepted as hypotension, and 5-10 mg of ephedrine were applied if hypotension developed. An HR of less than 50 beats per min was accepted as bradycardia, and 0.5 mg of Atropine IV was administered if bradycardia developed. The degree of motor block was assessed using a four-point modified Bromage scale by asking the patient to flex the hip, knee, and ankle joints (0: full flexion of the knees and feet; 1: just able to flex knees, full flexion of feet; 2: unable to flex knees, flexion of feet; 3: unable to move legs or feet, full motor block) after the patient was placed into the supine position at 5, 10, and 15 min after spinal anesthesia. The sensory block level was measured using pin-prick testing and was recorded. Time to two-segment regression of the sensory block and side effects, such as hypotension, bradycardia, nausea and vomiting, were recorded. Postoperative pain was assessed using the VRS (0: no pain, 1: mild pain, 2: moderate pain, 3: severe pain, 4: intolerable pain). Patients were observed for ~i h in the post-anesthesia care unit after the end of the operation, and motor and sensory block regression times, hemodynamic parameters, Table 2: Data of groups related to spinal anesthesia and time to first postoperative analgesic requirement were recorded. All intraoperative and postoperative assessments were evaluated by an unbiased observer who was blinded to the study groups. Analysis Statistical analyses were performed using the SPSS 15.0 for Windows software package (SPSS Inc., Chicago, IL, USA). The mean and standard deviation were calculated for descriptive statistics of constant variables. Compatibility of groups to a normal distribution was determined using the Kol-mogorov-Smirnov test. Student's f-test was used for comparison of the mean values between two groups. Yates correction and chi-squared test were used for analysis of cross-tabs. A p value less than 0.05 was deemed to indicate statistical significance. Results Demographic data and operative times were similar between the two groups (Table 1). No statistically significant difference was found between the groups in terms of time to the start of the operation, sensory block elevation time to T10, time to two-segment regression of the sensory block (T10-T12), intraoperatively used fluids, amount of ephedrine used, and time to first postoperative analgesic requirement (Table 2). No Group I (n = 30) Group II (n = 30) P Time up to T10 level of sensorial block. 9 ± 2 10 ± 3 0.54 Surgery onset time (min) 10 ± 1.8 9.83 ± 1.7 0.36 Time up to 2 segment regression (min) 63 ± 7 62 ± 8 0.56 Crystalloid (ml) 706 ± 218 700 ± 218 0.90 Colloid (ml) 133 ± 224 100±203 0.54 Ephedrine (mg) 1.8 ± 3.8 1 ± 2.4 0.31 First postoperative analgesic time (min) 233 ± 23 242 ± 16 0.10 Time up to motor block regression (min) 182.06 ± 14,12 132.26 ± 9.78 0.001 Values are given as mean ± standart deviation. Table 3: Bromage ScaLe of Both Groups (0-3 Score) Bromage scale G I (n = 30) G II (n = 30) G I (n = 30) G II (n = 30) ASA 30.min 0 score 25 30 0 score 0 0 1 score 5 0 X2 = 3.49 1 score 0 0 X2= 0.218 2 score 0 0 P = 0.06 2 score 3 2 P = 0.640 3 score 0 0 3 score 27 28 5 min 40 min 0 score 1 11 0 score 0 0 1 score 24 19 X2 = 13.91 1 score 0 0 X2 = 0.315 2 score 5 0 P = 0.001* 2 score 2 1 P = 0.554 3 score 0 0 3 score 28 29 8 min 50 min 0 score 0 2 0 score 0 0 1 score 8 20 X2 = 13.67 1 score 0 0 X2 = 0.315 2score 22 8 P = 0.001* 2score 1 1 P = 0.554 3 score 0 0 3 score 28 29 10 min 60 min 0 score 0 0 0 score 0 0 1 score 1 6 X2 = 4.87 1 score 0 0 X2 = 0.315 2 score 28 24 P = 0.087 2 score 1 1 P = 0.554 3 score 1 0 3 score 28 29 15 min PO 5 min 0 score 0 0 0 score 0 0 1 score 0 4 X2 = 9.40 1 score 0 0 X2 = 0.000 2 score 17 22 P = 0.009* 2 score 2 2 P = 1.000 3 score 13 4 3 score 28 28 20 min PO 15 min 0 score 0 0 0 score 0 0 1 score 0 0 X2 = 9.40 1 score 0 0 X2 = 2.308 2 score 9 9 P = 0.611 2 score 2 6 P = 0.128 3 score 21 21 3 score 28 24 25 min PO 30 min 0 score 0 0 0 score 0 0 1 score 0 0 X2 = 1.176 1 score 0 0 X2 = 10.817 2 score 3 6 P = 0.278 2 score 9 26 P=0.000 3 score 27 24 3 score 21 4 ASA: After Spinal Anesthesia;X2: chi-squared test Figure 1: Mean arterial pressure values of groups. PO: post-operative period. significant difference was found between the groups in terms of the mean arterial pressure and heart rate values measured at all times (Figures 1 and 2). The times to motor block development at 5, 10, and 15 min following spinal anesthesia were significantly shorter in Group I. (p values at 5, 10, and 15 min were 0.001, 0.007, and 0.009, respectively). Motor block was observed in 29 patients in the bupivacaine group and 19 patients in the bupivacaine group at 5 min following spinal anesthesia (Bromage 1-2) (p < 0.01). Motor block developed in all patients in the bupivacaine group and 28 patients in the levobupivacaine group at 8 min following spinal anesthesia (Bromage 1-2) (p = 0.42). At 15 min following spinal anesthesia, full motor block developed in all patients of the bupivacaine group but in only four patients of the levobupivacaine group (Bromage 3) (p < 0.001) (Table 3). The motor block regression time was 182.06 ± 14.12 in the bupivacaine group and 132.26 ± 9.78 min in the levobupivacaine group (p = 0.001) (Table 2). The groups were similar in terms of postoperative pain levels (p > 0.05). Discussion In many studies of levobupivacaine and bupivacaine, levobupivacaine has been suggested to result in fewer cardiovascular and central nervous system adverse effects than bupivacaine, although the onset and duration of the effects are identical, and so levobupivacaine has been suggested to be a new alternative for patients with cardiovascular pathologies.4 However, studies regarding these adverse effects are ongoing, and few have evaluated levobupivacaine in patients with cardiovascular pathologies. Clinical studies using levobupivacaine and bupivacaine demonstrated similar effects when the drugs were used at a 0.5 % concentration/'5 In our study, we used these drugs at the same volume and concentration by adding 10 |g of fentanyl to both local anesthetic agents. In our study, the local anesthetic and hemodynamic effects of intrathecally administered fentanyl with levobupivacaine or bupi-vacaine were found to be similar. This result is consistent with previous reports/-6 In spinal anesthesia, use of lipophilic opioids in combination with local anesthetics improves the quality of local anesthesia without prolonging the duration of motor block. The recovery time of motor block also improves.3 Opioid addition in spinal anesthesia has been shown to improve blood pressure stability and the quality of anesthesia by reducing the required local anesthetic dose due to its synergistic effect with local Figure 2: Heart rate values of groups PO: post-operative period. anesthetics without causing sympathetic blockade.7'8'9 In our study, we considered that the stability of the hemodynamic parameters and the lack of difference observed between the two groups was likely due to adequate hydration prior to spinal anesthesia. In the study by Glaser et aZ.4, the anesthetic and hemodynamic efficacy of intra-thecally administered 0.5 % levobupiva-caine (3.5 ml) and 0.5 % bupivacaine (3.5 ml) were compared in 80 patients who underwent hip surgery; the onset and duration of sensory and motor blocks were similar in both groups. In the study of Lee et aZ.6, the anesthetic and hemodynamic efficacy of intrathecally administered 0.5 % levobu-pivacaine (2.6 ml) and 0.5 % bupivacaine (2.6 ml) were compared in 50 patients who underwent urological operations; the onset and duration of sensory and motor blocks were similar in both groups. In our study, no significant difference was found between the sensory block times of both local anesthetics; this result is consistent with previous reports.4-6 The drug doses used in the above trials are different from our study. Moreover, fentanil was not used. This could explain why these results were different from our study. Liao et aZ.10 found the onset of motor block to be longer, and the motor block regression time to be shorter, with levobupi- vacaine than with bupivacaine. Erbay et aZ1 used intrathecal bupivacaine and levobu-pivacaine in 50 patients who underwent transurethral surgery and found the motor block regression time to be shorter in the le-vobupivacaine group. Lee et aZ.6 did not find a difference between the onset and duration of motor block between bupivacaine and levobupivacaine. In our study, the motor block onset time was found to be longer, and the motor block regression time was found to be shorter in the levobupivacaine group (levobupivacaine: 132.26 ± 9.78 min; bupivacaine: 182.06 ± 14.12 min) (p = 0.001). Our study is similar to Liao and Erbay's study in term of the dose of drug and adjuvant agent used. This could explain why our results were similar to both the above mentioned studies. These studies of levobupivacaine reported different results with respect to motor block timing. More detailed studies of the factors underlying the differences in the results and choosing drugs according to the characteristics and duration of surgical intervention are therefore important." Recovery of motor block after spinal anesthesia is important for early mobilization. Thus, it may also be effective for reducing the postoperative complications (e.g., thrombo-embolic events and pulmonary complications) that can occur in the elderly. The incidence of adverse effects associated with the two local anesthetics, levobupi-vacaine and bupivacaine, has been reported to be similar.4-6'10'11 Our results are consistent with previous reports. The effects of drugs may vary among studies due to differences in patients' characteristics, patients' emotional status, position of the body, adjuvant drugs, local anesthetic baricity, the spinal level of intrathecal injection, surgical procedures, surgical stimulation, and tolerance of side effects."'^ Because of this, we believe that it is possible to References 1. Katzung BC, Masters SB, Trevor AJ. Basic and Clinical Pharmacolog: Drugs that act in the central nervus system. In: Drasner K, 12th eds. Local Anesthetics. USA: McGrow-Hill; 2010. p. 449. 2. Morrison SG, Dominguez JJ, Frascarolo P, Reiz S. A comparison of the electrocardiographic car-diotoxic effects of racemic bupivacaine, levobu-pivacaine and ropivacaine in anesthetized swine. Anesth Analg 2000; 90: 1308-14. 3. Swester S, Olin BR. Drug factors and comparison. 50th ed. Philadelphia: Medical Comp; 1996. p. 285 4. Glaser C, Marhofer P, Zimpfer G, Heinz MT, Sitzwohl C, Kapral S, et al. Levobupivicaine Versus Racemic Bupivicaine for Spinal Anesthesia. Ane-sth Analg 2002; 94: 194-8. 5. Fattorini F, Ricci Z, Rocco A, Romano R, Pascarel-la MA, Pinto G. Levobupivacaine versus racemic Bupivacaine forspinal anaesthesia in orthopaedic major surgery. Minerva Anestesiol 2006; 72: 637-44. 6. Lee YY, Muchhal K, Chan CK. Levobupivacaine versus racemic bupivacaine in spinal anaesthesia for urological surgery. Anaesth Intensive Care 2003; 31: 637-41. 7. Hamber EA, Viscomi CM. Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med 1999; 24: 255-63. 8. Ben-David B, Miller G, Gavriel R, Gurevitch A. 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