|Year : 2015 | Volume
| Issue : 2 | Page : 178-184
Comparison of levobupivacaine and levobupivacaine with fentanyl in infraumbilical surgeries under spinal anaesthesia
Joginder Pal Attri, Gagandeep Kaur, Sarabjit Kaur, Ravneet Kaur, Brij Mohan, Kamaljyoti Kashyap
Department of Anaesthesia, Government Medical College, Amritsar, Punjab, India
|Date of Web Publication||6-May-2015|
Joginder Pal Attri
Department of Anaesthesia, Government Medical College, Amritsar - 143 001, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Intrathecal opioids added to low dose local anesthetics in spinal anaesthesia intensifies sensory block without affecting sympathetic blockade. Aim was to evaluate the safety and efficacy of intrathecal levobupivacaine plain versus levobupivacaine plus fentanyl in infraumbilical surgeries.
Materials and Methods: In a prospective randomized double blind study, 100 patients of American Society of Anesthesiologists grades I and II of either sex, 20-65 years of age were included after approval from the Ethics Committee. Informed consent was taken and patients were randomly divided into two groups of 50 each, to receive either 2 ml of 0.5% isobaric levobupivacaine (group L) or 2 ml of 0.5% isobaric levobupivacaine + 25 μg fentanyl (group LF) intrathecally. Patients were monitored for sensory and motor block characteristics, postoperative analgesia, haemodynamics and side effects and complications for 24 h.
Results: Onset of sensory block and time to maximum sensory block was rapid in group LF (4.8 ± 1.50 and 8.46 ± 1.87 min) as compared to group L (7.6 ± 1.46 and 15.80 ± 2.43 min) (P < 0.000). Maximum sensory block was T6 in group LF and T8 in group L. Maximum Bromage score was 2 in both groups but was achieved earlier in group LF (P < 0.000). Duration of sensory and motor block was significantly prolonged in group LF (270.98 ± 28.60 and 188.52 ± 9.81 min) as compared to group L (197.58 ± 11.20 and 152.76 ± 9.79 min). Total duration of analgesia was also prolonged in group LF (265.16 ± 26.18 min) as compared to group L (168.16 ± 11.08 min). Patients remained haemodynamically stable and side effects and complications were comparable in both groups. Data was analyzed using "Chi-square test" and "unpaired t-test."
Conclusion: Addition of fentanyl to levobupivacaine leads to early onset and prolonged duration of sensory and motor block as well as postoperative analgesia with stable haemodynamics and minimal side effects.
Keywords: Fentanyl, infraumbilical surgeries, levobupivacaine, local anaesthetics, spinal anaesthesia
|How to cite this article:|
Attri JP, Kaur G, Kaur S, Kaur R, Mohan B, Kashyap K. Comparison of levobupivacaine and levobupivacaine with fentanyl in infraumbilical surgeries under spinal anaesthesia. Anesth Essays Res 2015;9:178-84
|How to cite this URL:|
Attri JP, Kaur G, Kaur S, Kaur R, Mohan B, Kashyap K. Comparison of levobupivacaine and levobupivacaine with fentanyl in infraumbilical surgeries under spinal anaesthesia. Anesth Essays Res [serial online] 2015 [cited 2021 Apr 23];9:178-84. Available from: https://www.aeronline.org/text.asp?2015/9/2/178/152148
| Introduction|| |
Spinal anaesthesia is the most commonly used technique for infraumbilical surgeries because of its unmatchable reliability, cost effectiveness, effective analgesia, muscle relaxation and prolonged postoperative analgesia.  Recent advances in anesthesia has allowed more surgeries to be performed on day case basis.  The properties of an anaesthetic agent used for day case surgeries in spinal anaesthesia should have decreased incidence of anaesthesia related complications, should provide adequate postoperative analgesia and allow early patient discharge.  Levobupivacaine, a pure S(−) enantiomer of bupivacaine is a long acting amide local anesthetic which produces differential neuraxial block, that is, early onset and prolonged duration of sensory block with shorter duration of motor block and lower cardiac toxicity.  Levobupivacaine has been widely used in ambulatory surgeries after the development of low dose spinal anaesthesia technique. , To improve the block characteristics of intrathecally administered low dose local anaesthetics, addition of adjuvant is must. Intrathecal opioids enhance sensory block without prolonging motor and sympathetic block. , Among them, Fentanyl has rapid onset of action, binds strongly to plasma proteins and potentiates the afferent sensory blockade thus facilitates reduction in the dose of local anesthetics. , Literature is available where spinal block characteristics of plain levobupivacaine were compared with fentanyl as an adjuvant to decreased doses of levobupivacaine given intrathecally. ,,, The aim of the present study was to evaluate the safety and efficacy of equal doses of levobupivacaine plain (10 mg) and levobupivacaine (10 mg) plus fentanyl 25 μg, with respect to onset and duration of sensory and motor block, postoperative analgesia, hemodynamic parameters and side effects and complications in spinal anesthesia.
| Materials and methods|| |
In a prospective randomized double blind study, 100 patients of American Society of Anesthesiologists grades I and II of either sex, in the age group of 20-65 years scheduled for elective infraumbilical surgeries under spinal anesthesia were included after approval from the Institutional Ethics Committee. Patients with unwillingness for the procedure, coagulation or neurological disorders, septicemia, deformity or previous surgery of spine, morbid obesity, pregnancy and allergy to the study drug were excluded from the study. Informed written consent was taken from all the patients and were randomly divided into two groups of 50 each using a computer generated table of random numbers.
Group L (n = 50) received 2 ml of 0.5% isobaric levobupivacaine (10 mg) plus 0.5 ml normal saline and group LF (n = 50) received 2 ml of 0.5% isobaric levobupivacaine (10 mg) plus 0.5 ml fentanyl (25 μg) intrathecally. Total volume of the drug was kept constant as 2.5 ml in both groups to avoid bias during drug administration.
A day before surgery detailed preanaesthetic check-up was done. General physical examination along with proper systemic examination, assessment of airway and local examination of lumbar spine was done. Relevant investigations were reviewed. Visual analogue scale (VAS) was explained to the patients to determine the level of analgesia in the postoperative period. It was carried out with a 0-10 cm line. The first end mark "0" means "no pain" and the end marked "10" means "severe pain." Patients were asked to restrict solids and fluids by mouth at least 6 h before surgery.
On the day of surgery, patients were shifted to operation theatre after giving injection glycopyrrolate 0.2 mg intramuscularly 45 min before surgery. Multipara monitor was attached and baseline respiratory rate, heart rate (HR), noninvasive systolic and diastolic blood pressure (SBP and DBP), peripheral oxygen saturation and electrocardiography (ECG) were recorded and continuous monitoring was started. Intravenous (IV) line was secured with 18 gauge intracath and injection midazolam 0.04 mg/kg body weight was given IV. Patients were preloaded with 10 ml/kg body weight of Ringer lactate solution over 15-20 min. Under all aseptic precautions, spinal anaesthesia was given in L3 and L4 space with 25 gauge or 26 gauge Quincke spinal needle via midline approach in lateral decubitus position. On free flow of cerebrospinal fluid, study drug was injected intrathecally. In group L, 2 ml of 0.5% isobaric levobupivacaine plus 0.5 ml of normal saline and in group LF 2 ml of 0.5% isobaric levobupivacaine plus 0.5 ml fentanyl (25 μg) was given. Study drug was prepared in similar syringes keeping the drug volume constant by an anesthesiologist, who then handed over the syringe to another anaesthesiologist who performed the spinal block and also monitored all the patient variables. Patients were immediately turned to supine position and oxygen was started at the rate of 6 L/min. Continuous monitoring of respiratory rate, HR, noninvasive SBP and DBP, SpO 2 and ECG was done at 0 min, 3 min and 5 min, then at an interval of every 5 min up to 30 min and then every 15 min till the end of surgery. Bradycardia (defined as HR <60 bpm) was treated with injection atropine sulphate 0.6 mg IV. Hypotension (defined as fall in SBP >20% from baseline) was treated with additional Ringer's lactate solution and injection ephedrine 5 mg IV titrated according to blood pressure.
Sensory block was assessed by loss of sensation to pin prick in the midline every 2 min for first 10 min and then at an interval of 5 min till no change in level occurred. Onset of sensory block (when patient does not feel pin prick at T10 level), highest level of sensory block achieved, time to maximum sensory block, regression of sensory block to T10 and total duration of sensory block (regression to S1 dermatome) was noted.
Motor block was assessed by using the modified Bromage scale,  every 2 min up to 20 min and then at an interval of 10 min till the completion of surgery. Modified Bromage scale was taken as: 0 - No paralysis: Able to flex hips/knees/ankles, 1 - able to move knees, unable to raise extended legs, 2 - able to flex ankles, unable to flex knees, 3 - unable to move any part of limb - complete block. Maximum motor block achieved, time to maximum motor block and total duration of motor block (motor recovery to Bromage  was noted. All parameters were noted by taking the time of giving the study drug intrathecally as time 0. Surgery was allowed to start when sensory block to T10 dermatome was achieved. During intraoperative period, if any patient felt pain then injection ketamine was given IV as supplementary analgesia. It was repeated twice and if adequate analgesia was not achieved then patients were given general anaesthesia and were excluded from the study. The quality of surgical analgesia was assessed and graded as: Excellent - No supplementary drugs required, good - Analgesic required, fair - More than one analgesic required, poor - General anesthesia required.
In the postoperative period, patients were monitored for haemodynamic parameters and postoperative using VAS score, every 15 min for 120 min, then half hourly for 180 min, hourly for 12 h and thereafter every 3 hourly till 24 h of surgery in both groups. Rescue analgesia in the form of injection diclofenac 75 mg or if needed injection tramadol hydrochloride intramuscularly was given when VAS >3 in both groups. Time at which patient demanded first dose of rescue analgesia was taken as total duration of analgesia. Number of doses of rescue analgesia required in the postoperative period was also noted. Patients were monitored for any side effects or complications like hypotension, bradycardia, nausea, vomiting, sedation, urinary retention, pruritis, headache, backache and neurological changes for 24 h.
At the end of the study, patient satisfaction score was generated by general questioning of the patients regarding their experience of anesthesia during intra- and post-operative period. It was analyzed as: 5 - Very satisfied, 4 - satisfied, 3 - neutral, 2 - dissatisfied, 1 - very dissatisfied.
Power analysis was done. Effective size/power of the study was determined by taking in to account the mean onset of sensory block, mean duration of sensory block and total duration of analgesia. The power was well above 90% by taking α error 0.05. The data from the present study was systematically collected, compiled and statistically analyzed using software IBM SPSS 17.0 (IBM Chicago SPSS Inc) to draw relevant conclusions. Data was expressed as mean and standard deviation, number and percentages. The patient characteristics (nonparametric data) was analysed using the "Chi-square tests" and the inter group comparison of the parametric data was done using the "unpaired t-test." The P value was finally determined to evaluate the level of significance. P < 0.05 was considered as significant at 5% significance level; P < 0.01 was considered significant at 1% significance level and P < 0.001 was considered highly significant.
| Results|| |
In the present study, both groups were comparable with respect to demographic characteristics, baseline haemodynamic parameters and duration of surgery as shown in [Table 1]. Surgical procedures performed on patients in both groups were comparable. Most commonly performed surgery was inguinal hernia repair [Table 2]. After administering the study drug intrathecally, the mean time taken for onset of sensory block to T10 dermatome and the time to maximum sensory block in group L was more as compared to group LF and the difference was highly significant (P = 0.000). However the median maximum sensory level reached in group L was T8 dermatome and in group LF was T6 dermatome. Median maximum motor block achieved in both the groups was Bromage 2. But the mean time taken for achieving Bromage 2 motor block was more in group L as compared to group LF and the difference was highly significant (P = 0.000). Regression of sensory block to T10 dermatome was significantly prolonged in group LF (106.62 ± 6.17 min) when compared to group L (95.58 ± 5.32 min) (P = 0.000). The total duration of sensory block (regression of sensory block to S1 dermatome) and total duration of motor block was also significantly prolonged in group LF as compared to group L (P = 0.000). Motor and sensory block parameters are shown in [Table 3].
|Table 3: Sensory and motor block characteristics in group L and group LF|
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Visual analog scale score was used to monitor the patients for postoperative pain. VAS was 0 at 90 min of the study period then it started increasing in both the groups. VAS was on higher side in group L as compared to group LF till 180 min. (P = 0.000) and patients demanded first dose of rescue analgesia at 180 min. After this interval, VAS was on significantly higher side in group LF (P = 0.000) and patient demanded first dose of rescue analgesia at 5 th h of the study period as shown in [Figure 1]. Hence duration of analgesia was significantly prolonged in group LF (265.16 ± 26.18 min) as compared to group L (168.16 ± 11.08 min), (P = 0.000). The total number of doses of rescue analgesia required in 24 h was also significantly less in group LF as compared to group L (P = 0.000) [Table 3]. Quality of surgical analgesia was excellent in both groups as none of the patient required supplementary analgesia intraoperatively.
|Figure 1: Line diagram showing mean visual analog scale (VAS) scores in group L and group LF. Mean VAS score at various time intervals. VAS was 0 and comparable for 90 and 105 min in both groups. VAS started increasing in group L and was >3 at 180 min and patient demanded first dose of rescue analgesia. In group LF, VAS was >3 at 5th h and first dose of rescue analgesia was given. Group LF required less number of doses of rescue analgesia as compared to group L. P =0.001. Group L: Levobupivacaine, Group LF: Levobupivacaine + fentanyl|
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Patients were monitored for hemodynamic parameters at various time intervals starting from baseline till 24 h. There was no significant change in HR from baseline in both the groups throughout the study period. Five patients (10%) in group LF and two patients (4%) in group L (P = 0.24) developed bradycardia during initial 10-15 min interval intraoperatively for which injection atropine sulphate was given. Mean doses of atropine given in group LF was 1.7 mg and in group L was 1 mg. SBP and DBP also remained stable and comparable throughout the study as shown in [Figure 2]. In group L, 4 (8%) patients and in group LF, 6 (12%) patients (P = 0.50) had fall in SBP during 10-15 min interval intraoperativety and the percentage fall in SBP and DBP at 10 and 15 min was also comparable in both groups. Oxygen, addition IV fluids and injection ephedrine was given for treating hypotension. Total dose of ephedrine given in two groups was comparable, in group L was 15 mg and in group LF was 20 mg. Respiratory rate and SpO 2 was monitored and remained stable and comparable and none of the patient developed respiratory depression in both groups.
|Figure 2: Mean heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in group L and group LF intraoperatively. Mean HR, SBP and DBP at various time intervals. Vitals remained stable and comparable at all intervals. Five patients (10%) in Group LF and two patients (4%) in Group L developed bradycardia, (P = 0.24). Four (8%) patients in Group L and 6 (12%) patients in Group LF (P = 0.50) had fall in SBP. Group L: Levobupivacaine, Group LF: Levobupivacaine + fentanyl|
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Patients were monitored for side effect and complications for 24 h. None of the patient had nausea and vomiting, headache or backache in the postoperative period. Four (8%) patients in group LF had pruritis in the postoperative period whereas none of the patient in group L had pruritis. (P = 0.04). Incidence of urinary retention in group LF was 6% (3 patients) and in group L, urinary retention was not reported in any patient (P = 0.07). At the end of the study, patient satisfaction score was comparable (in group L: 4.63 ± 0.67 and in group LF: 4.67 ± 0.66; P = 0.847) in both the groups as patients were satisfied with anaesthesia and analgesia in both groups.
| Discussion|| |
Spinal anaesthesia is a commonly used technique for infraumbilical surgeries, as it provides faster and effective onset of sensory and motor block and prolonged postoperative analgesia.  Levobupivacaine is a preferred local anaesthetic due to its longer sensory block, lower cardiac and central nervous system toxicity and shorter motor block. It produces localized anesthesia by blocking the transmission of action potential in sensory, motor and sympathetic nerve fibers, by inhibiting the passage of sodium through voltage sensitive ion channels in the neuronal membrane.  The duration of action of levobupivacaine is dose dependent and it was found that 10 mg is the minimum dose for effective sensory and motor block in spinal anesthesia.  Intrathecal opioids as an adjuvant to low dose local anesthetics, produces a synergistic effect by acting directly on the opioid receptors in the spinal cord.  Fentanyl, stimulates both μ1 and μ2 receptors and potentiates the afferent sensory blockade.  Studies reported that addition of 25 μg fentanyl to LA improves anesthesia quality and prolongs postoperative analgesia without prolonging the time to void.  Inspired by the above findings, we selected 10 mg dose of levobupivacaine and compared it with 10 mg levobupivacaine plus 25 μg fentanyl given intrathecally for spinal block characteristics.
The results of the present study demonstrated that addition of fentanyl to levobupivacaine improves the sensory and motor block characteristics, prolongs postoperative analgesia with decreased requirement of rescue analgesics in the postoperative period, without increasing the incidence of side effect and complications.
In the present study, time to onset of sensory block and the time to achieve maximum sensory and motor block was more rapid, the duration of sensory and motor block and postoperative analgesia was more prolonged in levobupivacaine and fentanyl group as compared to plain levobupivacaine group. Maximum sensory level in group L was T8 and in group LF was T6 dermatome but the maximum motor block was Bromage 2 in both groups. Requirement of postoperative rescue analgesics was also less in group LF.
Ozyilkan et al.,  compared 2.2 ml of levobupivacaine plain with 10 μg fentanyl or 2.5 μg sufentanil as adjuvant in spinal anesthesia for caesarean section. Onset of sensory and motor block was achieved more rapidly in fentanyl and sufentanil group (P < 0.001). Duration of sensory and motor block and time for first analgesic requirement was longer in adjuvant groups as compared to plain group (P < 0.001). Akan et al.  while using 10 mg plain levobupivacaine and comparing it with 7.5 mg levobupivacaine plus 25 μg fentanyl and 7.5 mg levobupivacaine plus 2.5 μg sufentanil in patients undergoing transurethral resection of the prostate under spinal anaesthesia concluded that combining lower doses of levobupivacaine with fentanyl and sufentanil provides faster onset of sensory block, lower frequency and shorter duration of motor block and prolonged analgesia time. However in the present study, motor block duration was prolonged in group LF as compared to group L. This difference might be due to the use of equal doses of levobupivacaine in both groups. Cuvas et al.,  also added 15 μg fentanyl to lower dose of levobupivacaine 2.3 ml and compared it with 2.5 ml of plain levobupivacaine. The time to onset of sensory and motor block, regression of sensory block to S1 was similar in both groups. Duration of motor block was shorter in fentanyl group. Again the dose of levobupivacaine used was less in this group. Addition of fentanyl to levobupivacaine resulted in higher sensory level (T6) as compared to plain levobupivacaine (T9) which was almost similar to the findings of the present study (T6 in group LF and T8 in group L). The difference in the level of sensory block in both the groups can be explained by the difference in the baricity of the injected solutions. Opioids are hypobaric and when added to hypobaric LA will make the mixture more hypobaric thus altering the density of resulting solution which effects the direction and extent of spread in spinal block. Girgin et al.,  while using 5 mg levobupivacaine plus 25 μg fentanyl and 7.5 mg levobupivacaine plain demonstrated that maximum sensory level was T7 and T6 respectively; however the maximum motor block achieved was Bromage 2 in both groups. In this study maximum sensory level achieved was lower in combination group which might be due to the low dose of levobupivacaine used in this group.
Heart rate and blood pressure remained stable and comparable in both the groups intraoperatively as well as postoperatively. Bradycardia was observed in 5 (10%) patients in group LF and 2 (4%) patients in group L and hypotension was seen in 4 (8%) patients in group L and 6 (12%) patients in group LF. Similar findings were reported by a previous study, where incidence of bradycardia was 15% when 10 mg of levobupivacaine was given intrathecally.  Chattopadhyay et al.  concluded that addition of fentanyl to levobupivacaine does not increase the incidence of bradycardia. Akan et al.  also concluded that there was no significant difference in the mean heart and blood pressure in plain levobupivacaine group and levobupivacaine plus fentanyl group. Similar results were reported by Cuvas et al.  and Lee et al. 
The most common side effect observed with intrathecal fentanyl was pruritus which was observed in 4 (8%) patients in group LF and none in group L (P = 0.004). Pruritus as a side effect of intrathecal fentanyl was reported by previous studies also. ,, Second most commonly occurring side effect of spinal anaesthesia is delayed micturition. With addition of 25 μg fentanyl to 5 mg levobupivacaine, Girgin et al.  did not reported urinary retention in any patient. In the present study, only 3 (6%) patients in group LF and none of the patient in group L had delayed micturition but the difference was statistically nonsignificant. No other side effect and complications were observed in both the groups. Patients were satisfied with the surgical analgesia and postoperative analgesia in both the groups. Similar patient satisfaction scores were reported by Lee et al.  and Cuvas et al. 
Limitation of our study was that we did not compare the two groups for achieving home discharge criteria. Hence, we were not able to evaluate the effect of fentanyl added to levobupivacaine on the recovery profile of patients from spinal block.
| Conclusion|| |
Both regimes were effective in providing surgical anaesthesia and haemodynamic stability, but group LF offered an advantage of rapid onset of sensory and motor block and prolonged duration of sensory block and postoperative analgesia, thus decreasing the doses of rescue analgesia in the postoperative period. However, prolonged motor block was unwanted as it delays early ambulation.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]