Comparison of two concentrations of isobaric intrathecal levobupivacaine for vaginal hysterectomy :Suman Chattopadhyay, Bibhas Halder, Gobindo Chandra Saha, Sukla Karmakar, Subrata Pahari, Indian Journal of Pain

ORIGINAL ARTICLE
Year : 2013 | Volume : 27 | Issue : 3 | Page : 154--158

Comparison of two concentrations of isobaric intrathecal levobupivacaine for vaginal hysterectomy

Suman Chattopadhyay¹, Bibhas Halder², Gobindo Chandra Saha³, Sukla Karmakar³, Subrata Pahari⁴,
¹ Associate Professor of Anaesthesiology, Medical College, Kolkata, West Bengal, India
² Postgraduate Trainee in Anaesthesiology, Medical College, Kolkata, West Bengal, India
³ Department of Anaesthesiology, Medical College, Kolkata, West Bengal, India
⁴ Professor and Head of Anaesthesiology, Medical College, Kolkata, West Bengal, India

Correspondence Address:
Suman Chattopadhyay
BC 103, Salt Lake, Kolkata - 700 064, West Bengal
India

Abstract

This study was performed to compare the anesthetic efficacy and safety of two concentrations of local anesthetic agent levobupivacaine in patients undergoing vaginal hysterectomy. Forty-four patients of ASA I and II, were randomized to receive an intrathecal injection of one of two local anesthetic solutions. Each patient in Group A (n = 22) received 2 ml of isobaric levobupivacaine 5 mg/ml (10 mg) with 25 μg of fentanyl, while each patient in Group B (n = 22) received 4 ml of isobaric levobupivacaune 2.5 mg/ml (10 mg) with 25 μg of fentanyl. The onset and duration of sensory block at dermatome level T10, maximum upper spread of sensory block, time for two segment regression of sensory block as well as the onset, intensity and duration of motor block were recorded, as were any adverse effects, such as bradycardia, hypotension, nausea, and/or vomiting, etc. The onset of sensory block was similar in both the groups. The onset of motor block was significantly faster in group A compared with that in group B. The duration of sensory and motor blockade was of shorter duration in group B (P < 0.05). However, patients in group A required more use of a vasoactive drug (phenylephrine) compared with group B.

How to cite this article:
Chattopadhyay S, Halder B, Saha GC, Karmakar S, Pahari S. Comparison of two concentrations of isobaric intrathecal levobupivacaine for vaginal hysterectomy.Indian J Pain 2013;27:154-158

How to cite this URL:
Chattopadhyay S, Halder B, Saha GC, Karmakar S, Pahari S. Comparison of two concentrations of isobaric intrathecal levobupivacaine for vaginal hysterectomy. Indian J Pain [serial online] 2013 [cited 2023 Mar 23 ];27:154-158
Available from: https://www.indianjpain.org/text.asp?2013/27/3/154/124600

Full Text

Introduction

Spinal anesthesia is widely used for lower abdominal and lower limb surgery providing a fast onset and effective sensory and motor blockade. Bupivacaine is available as a racemic mixture of its enantiomers, dextrobupivacaine, and levobupivacaine. In the past few years, its pure S-enantiomers ropivacaine and levobupivacaine have been introduced into clinical practice, [1],[2],[3],[4] because of their lower toxic effects for cardiovascular and central nervous system. The clinical profile of spinal bupivacaine and levobupivacaine has been evaluated in volunteers and clinical studies and found to be effective in patients undergoing lower abdomen surgery, day care gynecology procedures, inguinal hernia repair, and lower limb procedures. [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16]

In our country, levobupivacaine is available in preservative-free isobaric form (Levo-Anawin TM ) in two concentrations (5 mg/ml = 0.5% and 2.5 mg/ml = 0.25%) packaged in 10 ml ampoules. The idea of this study developed when accidentally drug from the 2.5 mg/ml ampoule was administered intrathecally instead of the planned 5 mg/ml dosage and surprisingly found to be effective.

Previous studies have found low dose bupivacaine to be effective in lower abdominal surgery including vaginal hysterectomy. A low dosage of 10 mg bupivacaine has been used in multiple studies. [17],[18] We presumed that levobupicaine being an equipotent isomer of bupivacine [8] would also be effective in a similar dosage, although there is a definite dearth of literature in this regard. However, a few studies suggest that low dose levobupivacaine (4 mg and onwards) is clinically effective. [6],[9],[10],[11],[12],[13],[14]

The aim of the present study was to compare the safety and efficacy of two concentrations of levobupivacaine (0.5% and 0.25%) with a similar low dose of 10 mg in patients undergoing vaginal hysterectomy under spinal anesthesia.

Material and Methods

With the approval of the Institutional Ethical Committee and written informed consent of the patient, 46 ASA physical status I-II patients, scheduled for elective vaginal hysterectomy under spinal anesthesia, were prospectively enrolled. Patients who had contraindications to spinal anesthesia, allergy to amide local anesthetics, having poor exercise tolerance, and a significant history of drug abuse were excluded. Exclusion criteria also included obesity (body mass index (BMI) > 30 kg/m 2 ), as well as diabetic, neurological, and other conditions known to be associated with either absolute or relative contraindication of spinal anesthesia.

Following arrival in the anesthetic room, I.V. access was established and an infusion of 500 ml Ringer's lactate (RL) commenced. Patients were premedicated with 2 mg of midazolam intravenously and placed in the sitting position. After skin infiltration with 2% plain lignocaine, a 20 G introducer needle was inserted at the L3/4 interspace in the midline through which a 25G Whitacre needle (BD TM ) was passed. Correct needle placement was identified by free flow of cerebrospinal fluid and 10 mg of the study drug with 25 μg of fentanyl was injected over 10 s.

Using a sealed envelope technique, patients were randomly allocated to two groups: 23 patients in group A received plain levobupivacaine 10 mg (2 ml isobaric 0.5%), while 23 patients in group B received plain levobupivacaine 10 mg (4 ml isobaric 0.25%). All solutions were prepared in a sterile manner in an adjacent room by an anesthesiologist not involved in the subsequent evaluation of the study-patient. A senior anesthesist not involved in the current study gave the spinal drugs from the covered and labeled syringes. After the injection of the drug, the spinal needle was removed and the patient was placed supine. One patient from each group was excluded from the study, due to insufficient height of the sensory block. All statistical analyses were therefore based on 22 patients in each group.

Standard monitoring was used throughout the operation. Electrocardiography (ECG) and pulse oximetry were monitored continuously while noninvasive blood pressure (NIBP) was measured at 5-min intervals. Heart rate and arterial pressure were recorded before intrathecal injection, 5 min after the intrathecal drug administration, and thereafter every 5 min till the end of the operation and 1 h after the end of the operation, at the ward. Any hypotension (mean arterial pressure 25% of baseline) or bradycardia (heart rate less than 50/min) were treated with phenylephrine 0.2 mg boluses or atropine 0.6 mg increments. A decrease in SpO 2 to < 94% was treated with supplemental oxygen via a poly mask.

The level of sensory block was evaluated by loss of pinprick sensation (20-gauge hypodermic needle). The test was performed every 2 min till loss of discrimination to pinprick and then every 15 min postoperatively until its full recovery. We checked bilaterally S1, L3, T12, T10, T8, T6 or higher (T4) dermatomes by needle protrusion. The time for two-segment regression from the highest sensory block achieved was also noted. Motor blockade was assessed using a modified Bromage scale (0 = no motor block, 1 = hip blocked, 2 = hip and knee blocked, 3 = hip, knee and ankle blocked). The maximum Bromage score reached and duration of the motor block (from spinal injection until Bromage 0 score) were registered every 5 min after drug's injection and every 15 min postoperatively until full recovery.

The onset time of sensory or motor blockade was defined as the interval between intrathecal administration and time to achieve T10 level block, or a Bromage score of 3, respectively. The duration of sensory blockade was defined as the interval from intrathecal administration to the point of complete resolution of the sensory block as manifested by requirement of supplementary 'rescue' analgesia. The duration of motor blockade was defined as the interval from intrathecal administration to the point of complete resolution of the motor block as manifested by return of the Bromage score back to zero. The maximum level of sensory block, the onset time, the duration of sensory and motor blockade, as well as the interval from intrathecal administration to the point of a two-segment regression of sensory blockade were noted. The occurrence of adverse events, including bradycardia, hypotension, decrease in oxygen saturation SpO 2 < 94%, tremor, and any other complication was also recorded.

Statistics

All statistical analyses were performed using the SPSS version 10.1.4 for windows (SPSS Inc., Chicago, Illinois®). Age, weight, height, and BMI as well as ASA physical status were analyzed using chi-square frequencies test. We analyzed systolic, diastolic, and mean arterial pressure, as well as heart rate and surgical time, using analysis of variance (ANOVA) repeated measures test with correction according to Bonferroni. Onset time, spread, and duration of either motor or sensory blocks as well as use of vasoconstrictive drugs or atropine were analyzed with chi-square or student's t-test. The minimum sample size of 21 was based on previous dose response studies [4],[14],[16] on levobupivacaine with α value set at 0.05, and 80% power to detect a 25% reduction in the incidence of complete motor block. Side effects' incidence was analyzed using Fischer's exact test. Significance was defined as P < 0.05.

Results

The demographic characteristics of the two groups were comparable in terms of age, height, weight, gender, BMI, and ASA physical status. Time of surgery was also comparable [Table 1].{Table 1}

The onset of sensory bock was similar in the two groups (6.9 ± 1.7 vs. 6.4 ± 1.5 min). The onset of motor block (time to achieve a Bromage score of 3) was significantly faster in group A: 8.9 ± 5 min compared with 12.8 ± 7 min in group B (P < 0.05). The mean time of onset to achieve a Bromage score of 1 or of 2 was 3.8 ± 1 min and 3.9 ± 1 min in group A, and 5.5 ± 1 min and 5.3 ± 2 min in group B, respectively. These differences were not significant.

Patients in group B had a shorter duration of sensory as well as motor block than patients of group A (121.4 ± 10 vs. 150.6 ± 14 min and 108.8 ± 11 vs. 130.6 ± 12 min; P < 0.05). Time for two-segment regression of sensory blockade (from T8 to T10) was similar between the groups (64.1 ± 9 vs. 60.1 ± 10 min). These block characteristics are depicted in [Table 2].{Table 2}

[Table 3] denotes the hemodynamic characteristics of the two groups. The baseline hemodynamic parameters were similar in between the two groups. There was a slight reduction in mean arterial blood pressures after the spinal injection in all groups, though there were no significant intergroup differences in mean heart rates or mean arterial blood pressure values intraoperatively. Intraoperative hypotension requiring treatment with intravenous phenylephrine occurred more often in the group A levobupivacaine group (18.2% vs. 5.5% of patients, respectively; P = 0.02). Bradycardia was similar among the groups.

The most commonly reported adverse events were nausea, vomiting, tremor, and decrease in oxygen saturation SpO 2 <94%. These events were equally distributed between groups.{Table 3}

Discussion

There is no study till date on the efficacy of 0.25% levobupivacaine being given intrathecally. The present study is the first, to our knowledge, to compare the efficacy and safety of these two concentrations of glucose-free levobupivacaine (0.25% and 0.5%) in patients undergoing lower abdominal surgery under spinal anesthesia.

The most important determinant of both successful surgical anesthesia and time until recovery is the dose of local anesthetic drug. [19] Using an intrathecal opioid reduces the period of recumbency after spinal anesthesia, by allowing early ambulation, and results in decrease in the incidence of postdural puncture headache [20] and the duration of hospital stay.

We have chosen the dose of 25 μg of fentanyl as most studies have shown that this dose provides maximum duration of postoperative analgesia with minimal side effects like respiratory depression and pruritis. [21],[22] There was evidence of a dose response relationship in a study by Belzarena [23] where higher doses were associated with increased analgesia but with increased pruritis. In addition to minimal side effects, the ideal intrathecal opiate should have a rapid onset and a long duration of action, thus providing improved intra- and postoperative analgesia.

Sensory block in the present study was tested using loss of sensation to pin-prick as used by others. [16] The choice of this method, instead of others (such as loss of sensation to ice, pain perception, tetanic twitch, or chemical irritation with capsaicin) was based on the reliability and easy application of the pinprick method.

As a new drug, levobupivacaine is bound by the directive of the European Economic Community, which states that concentrations of hydrates and salts must be expressed in terms of milligrams of active moiety. Thus, an ampoule of 0.5% levobupivacaine contains 5 mg/ml of free base, whereas ampoules of the same concentration of both racemic bupivacaine and ropivacaine, because registration of these drugs predates the directive, contain 5 mg/ml of the hydrochloride salt. Thus an ampoule of levobupivacaine contains 11% more molecules of local anesthetic than an ampoule of racemic bupivacaine of apparently the same percentage concentration. [7]

This study shows that the intrathecal administration of either doses of 10 mg levobupivacaine [0.5% levobupivacaine 2 ml (group A) and 0.25% levobupivacaine 4 ml (group B)] was well tolerated and provided an adequate block for vaginal hysterectomy in all but one patient in each group. Intergroup differences were insignificant both with regard to the onset time of sensory blockade and grade 1 and grade 2 motor blockade. The cephalic spread of sensory block was similar in all groups.

The 10 mg (2 ml of levobupivacaine 0.5%) dose was similar to the study by Onur et al., [12] and the 11 mg (2.2 ml of levobupivacaine 0.5%) dose of the Cuvas et al., [5] study. The group A patients had similar onset times and duration of sensory and motor blockade, as well as two segment sensory regression as in the two studies. All these studies used fentanyl as an adjuvant with levobupivacaine.

However, the onset of complete (grade 3) motor block was significantly faster in group A compared with that in group B. The duration of sensory and motor blockade was of shorter duration in group B (P < 0.05). The incidence of hypotension was higher in group A with four patients (18.2%) requiring phenylephrine compared with 5.5% (one patient) in group B.

The shorter duration of sensory and motor blockade by 0.25% intrathecal bupivacaine may be explained by other studies on intrathecal bupivacaine dilution with saline by Ben-David et al. [19] Levobupivacaine, being similar to bupivacaine, [7],[8] is expected to have similar dose responses to dilution.

The most commonly reported adverse events, nausea, vomiting, tremor, and decrease in oxygen saturation SpO 2 <94% were equally distributed between the three groups. These results correlate well with those reported by other investigators. [5],[6],[7],[8],[9],[10],[11],[12],[13],[14]

In conclusion, intrathecal administration of either 2 ml of 0.5% levobupivacaine, or 4 ml of 0.25% levobupivacaine was well-tolerated and provided similar, effective anesthesia for vaginal hysterectomy. The lower concentration of levobupivacaine had a shorter duration of both sensory motor block, with a more stable hemodynamic profile making it an ideal intrathecal drug for day care surgery. However, further studies needs to substantiate this assumption.

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