Kapil Rastogi1, Alok Kumar Bharti2, Yashpal Singh3, Pushkar Ranjan4
Kapil Rastogi [kapil.gsvm@gmail.com]
Alok Kumar Bharti [alok.bharti48@gmail.com]
Yashpal Singh [dryashacin1999@rediffmail.com]
Pushkar Ranjan [pushkarranjanbhu@gmail.com]
1-Assistant Professor, Dept. of Anesthesiology, Integral Institute of Medical Science and Research, Lucknow, UP, India.
2-Assistant Professor, Dept. of Anesthesiology and Critical Care, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar-800013, India.
3-Associate Professor, Dept of Anesthesiology, AIIMS. Gorakhpur, UP, India.
4-Professor, Dept, of Anesthesiology, IMS, BHU, Varanasi.
Correspondence: Dr Alok Kumar Bharti;
E-mail: alok.bharti48@gmail.com; Mobile: +91 9307645596
Abstract
Background: Intrathecal Bupivacaine is most commonly used local anesthetic for lower segment cesarean section (LSCS) but there is constant endeavour for search of a local anesthetic (LA) which has improved safety profile for mother as well as foetus. So far many adjuvants like fentanyl, morphine or tramadol etc. has been used with intrathecal LA to prolong intraoperative anesthesia and postoperative analgesia. The available literature lacks information on use of dexmedetomidine as adjuvants with isobaric levobupivacaine. So we plan study to compare dexmedetomidine and fentanyl added to 0.5% isobaric intrathecal levobupivacaine in spinal anesthesia for LSCS.
Methodology: After Institutional ethical committee approval and informed written consent, patient were divided into three equal groups: Group L; to receive 2.5 ml of 0.5% of isobaric levobupivacaine intrathecally; Group LD to receive 2.5 ml of 0.5% of isobaric levobupivacaine and 5 µg dexmedetomidine intrathecally and Group LF to receive 2.5 ml of 0.5% of isobaric levobupivacaine and 25 µg fentanyl intrathecally. Primary outcome was measured as duration of sensory and motor blockade from the time of intrathecal administered of drugs. Statistical analysis was performed by using chi-square test or Fischer's exact test and One-way ANOVA or Kruskal Wallis test as applicable. A p value of < 0.05 was considered as statistically significant.
Results: Duration of sensory and motor blockade was significantly prolonged (p < 0.001) in Group LD as compared to Group LF or L. Onset of sensory and motor blockade was earlier in Group LF as compared to Group LD and L (p < 0.001). Time to first rescue analgesia was prolonged in Group LD than Group LF and L (p < 0.001).
Conclusion: Intrathecal dexmedetomidine produce prolonged blockade as well as postoperative analgesia thanl fentanyl when used as adjuvants to 0.5% isobaric levobupivacaine in elective cesarean section.
Key words: Cesarean section, Dexmedetomidine, Fentanyl, Intrathecal Analgesia; levobupivacaine; Spinal Anesthesia
Citation: Rastogi K, BhartiAK, Singh Y, Ranjan P. Comparison of dexmedetomidine and fentanyl as adjuvants to intrathecal levobupivacaine in lower segment cesarean section: A prospective, randomized double blind study. Anaesth. pain intensive care 2020;24(3):383-388.
Introduction
Subarachnoid block is the most widely used regional anesthetic procedure for lower abdominal and lower limb surgery including lower segment cesarean section (LSCS).1 It provide rapid onset, consistent sensory and motor blockade with adequate muscle relaxation and for all types of surgery below the level of umbilicus.
Regional anesthesia is safer than general anesthesia and having advantage of the parturient being awake during the birth process.2 Intrathecal local anesthetics (LA) alone are not enough for effective postoperative analgesia and higher dose of LA are also associated with hemodynamic instability, which can lead to unfavourable maternal and foetal outcome. So far many adjuncts have been used to augment the analgesia produced by intrathecal LA and to reduce their adverse effects.3 The very latest addition to LA used for labour analgesia is levobupivacaine, which is the left-turning molecule of bupivacaine.4 Levobupivacaine seems identical to bupivacaine in potency and shows longer duration of action on neural tissue. Because bupivacaine is a racemic mixture of both the left- and right-turning molecules, it has been recently referred to as racemic bupivacaine to further distinguish it from levobupivacaine.4 Isobaric levobupivacaine has less cardiotoxicity propensity and less chance of cephalic spread, favour particularly in LSCS.
It has been well documented that the combination of fentanyl and LA administered intrathecally has synergistic analgesic effects.anes5] Fentanyl is a lipophilic μ-receptor agonist opioid. Intrathecally, fentanyl exerts its effect by combining with opioid receptors in the dorsal horn of spinal cord and may have a supra spinal spread and action. Dexmedetomidine is a highly selective α2–adrenoreceptor agonist recently used as adjuvant with intrathecal LA and found to be prolong the duration of sensory and motor blockade as well as provides hemodynamic stability during intraoperative period.6-10 It also produces dose-dependent sedation, anxiolysis and analgesia (involving spinal and supraspinal sites) without respiratory depression.
Review of literature on use of dexmedetomidine as adjuvants with 0.5% isobaric intrathecal levobupivacaine in LSCS is scarce. So we plan this study to compare dexmedetomidine with fentanyl as an adjuvant to intrathecal isobaric 0.5% ropivacaine.
Material and methods
After Institutional ethical committee approval and informed written consent, 60 female patients were enrolled in this prospective randomized double blinded controlled study. Inclusion criteria includes full term pregnant patient of American Society of Anesthesiology (ASA) grade 1 and 2, between age group of 20-40 years, scheduled for elective LSCS. Exclusion criteria includes patient refusal, having allergy to studied drugs, any contraindication to spinal anesthesia, pregnancy with associated medical problems like eclampsia, pre-eclampsia, diabetes etc.
All patients were randomly assigned into three equal groups (n = 20) to receive spinal anesthesia: Group L to receive 2.5 ml of 0.5% of isobaric levobupivacaine; Group LD to receive 2.5 ml of 0.5% of isobaric levobupivacaine plus 5 µg dexmedetomidine and Group LF to receive 2.5 ml of 0.5% of isobaric levobupivacaine plus 25 µg fentanyl .intrathecally. Each group will receive total volume of 3.0 ml. Randomization was performed my anesthesiologist involved in drug preparations. Other investigator involved in the procedure and monitoring was unaware of group allocation. Patients were also blinded to drug regimen given in spinal anesthesia.
On arrival to operating room, standard monitor were placed and baseline parameters recorded. Peripheral 18G intravenous (IV) catheter was established and all patients preloaded with lactated ringer solution 10 ml/kg. Before spinal anesthesia patients were explained about the procedure and methodology of monitoring methods. In the left lateral decubitus position under standard aseptic precautions, using a midline approach lumbar puncture was performed at L3-L4 or L4-L5 intervertebral space by 25G Quincke spinal needle (BD, Gurgaon, Haryana, India). Having confirmed the free flow of cerebrospinal fluid through the spinal needle, the studied drug solution was injected intrathecally over a period of 10–15second and patients were turned to the supine position with wedge on right side.
Primary outcome included the comparison of the block characteristics and duration of postoperative analgesia. Secondary outcome was to compare the hemodynamic parameters, time to first rescue analgesia and adverse effects of dexmedetomidine or fentanyl given intrathecally with isobaric 0.5% levobupivacaine.
The level of sensory bock assessed bilaterally in mid clavicular line, by loss of pinprick sensation to 23 gauge hypodermic needle and dermatomes levels were tested every 2 min until the highest level had stabilized by consecutive tests. The highest dermatome level of sensory blockade, the time to reach this level from the time of injection, time to S1 level sensory regression was recorded. The motor dermatome level was assessed using Modified Bromage scale. The time to reach Bromage scale 3 before surgery and Bromage 0 in post anesthesia care unit (PACU) was recorded. On achieving T-6 sensory blockade level and Bromage scale 3 surgery was allowed. Sedation was assessed by a modified Ramsay sedation scale. Pain was assessed using VAS (0 to 10) scale at time of incision and at completion of surgery. After surgery patient was shifted to post anesthesia care unit (PACU) and observed for hemodynamic parameters, duration of sensory block, duration of motor block, degree of postoperative analgesia and need of rescue analgesic. Hypotension, defined as a decrease of systolic blood pressure by more than 30% from baseline or a fall below 90 mmHg, was treated with incremental IV doses of ephedrine 5 mg and IV fluid as required. Bradycardia, defined as heart rate < 50 bpm, was treated with IV atropine 0.3-0.6 mg. The incidence of adverse effects, such as nausea, vomiting, shivering, pruritus, respiratory depression, sedation, and hypotension was recorded.
Our estimated sample size was based on to study efficacy in term of degree of sensory and motor blockade among the group. For sample size calculation, we defined a relevant clinical difference of 20% in degree of blockade among the three groups. Thus sample size of 15 per group with effect size of 20 provided 90% power for detecting significant differences at any point of time between three groups at alpha level of 0.05. 60 patients were randomly allocated into one of the three groups using sealed envelope based on computer generated random number.
Statistical analysis
Statistical analysis was done with the statistical package for the social science system version SPSS 17.0. Continuous variables are presented as mean ± SD, and categorical variables are presented as absolute numbers and percentage. The comparison of normally distributed continuous variables between the groups was performed using One-Way ANOVA or Kruskal Wallis test. Nominal categorical data between the groups were compared using Chi-square test or Fischer’s exact test. P value of < 0.05 was considered as statistically significant.
Results
Out of 65 patients, 60 completed study successfully (Figure 1). The study groups were comparable in terms of demographic profile and baseline parameters (Table 1). Time required to achieve highest level of sensory block was least in Group LF (3.35 ± 0.36), maximum in Group L (5.56 ± 0.91) and highly significant between three groups (p < 0.001) (Table 2). Average time required to achieve Bromage scale 3 varied similarly, least in Group LF (2.94 ± 0.30) and statistically highly significant between three groups (p < 0.001) (Table 2). The time required for sensory regression to S1 level (duration of sensory block) was maximum in group LD (316.10 ± 24.34) and highly significant between three groups (p < 001) (Table 2). The time required to reach Bromage scale 0 (duration of motor block) was highest in Group LD followed by LF and L (265.05 ± 12.68 vs. 203.25 ± 23.80 vs. 176.00 ± 18.61) and statistically significant between three groups (p < 0.001) (Table 2). Time required for first analgesic requirement (duration of analgesia) was highly significant difference between groups (p < 0.001), highest in Group LD (275.75 ± 20.21) and lowest in Group L (199.00 ± 18.68) (Table 2). There were no statistically significant differences in hemodynamic parameters and associated adverse events between three groups (Table 3).
Discussion
There was continuous effort to find out local anesthetic, having less chance of cardiotoxicity and less cephalic spread. Levo-bupivacaine is a long acting amide LA and S-enantiomer of bupivacaine, having less chance of cardiotoxicity and less cephalic spread. So we conducted this trial to study the comparative efficacy of Levobupivacaine with adjuvant dexmedetomidine or fentanyl intrathecally for LSCS.
In this present study, mean duration of sensory (time to regression to S1 dermatome) and motor blockade (time to regression to Bromage scale 0) was found to be prolonged for Group LD than Group LF or L. This explains that intrathecal dexmedetomidine prolongs the duration of local anesthetic more in comparison to fentanyl. This study is supported by Gupta et al. they studied the analgesic effects of dexmedetomidine (5 µg) or fentanyl (25 µg) given intrathecally with hyperbaric 0.5% bupivacaine (12.5 mg). They concluded that intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability, and reduced demand for rescue analgesics in 24 h as compared to fentanyl.11 Our study is further strengthened by Ramadan et al. they evaluated the effects of adding dexmedetomidine (5 µg) versus fentanyl (25 µg) to intrathecal bupivacaine ( 10 mg) on spinal block characteristics and neonatal outcome in uncomplicated cesarean delivery and concluded the dexmedetomidine group had significant longer sensory and motor block times than fentanyl group or control group. No adverse effects on mothers or babies were noticed among three groups.12
Table 1: Comparison of demographic data and baseline parameters between the groups. (n = 20)
Data presented as mean ± SD. *Group L versus Group LD, **Group L versus Group LF, # Group LD versus Group LF. P < 0.05 considered as significant. SD = Standard Deviation, BMI = Body Mass Index, HR = Heart Rate, MAP = Mean Arterial Pressure. Pearson's chi-square test and ANOVA test was used for analysis as required.
Table 2: Comparativef block characteristics and time to 1st analgesic requirements (n = 20)
Data presented as mean ± SD. *Group L versus Group LD, **Group L versus Group LF, # Group LD versus Group LF. P < 0.05 considered as significant. SD = Standard Deviation. ANOVA test was used for comparison between three groups.
Table 3: Comparative frequency of side effects between three groups. (n = 20)
Data presented as mean ± SD or number or percentage. *Group L versus Group LD, **Group L versus Group LF, # Group LD versus Group LF. P < 0.05 considered as significant. SD = Standard Deviation.
How dexmedetomidine prolongs the sensory and motor blockade is not known exactly. Best possible mechanism may be the, analgesia produced by α2 agonists occurs as a result of decreased release of C-fiber transmitters and hyperpolarization of postsynaptic dorsal horn neurons. It has been postulated that binding of α2 agonist agents to the dorsal horn motor neurons results in the prolongation of motor blockade of LA.13,14 They also exhibit anesthetic-sparing and hemodynamic- stabilizing effects.anes15,16
Mean time of sensory and motor blockade was significantly lower in Group LF than Group LD or Group L. Contrary to our finding, other studies report that time of onset of sensory and motor blockade was earlier in dexmedetomidine group than fentanyl group.17,18 The differences in sensory and motor onset time could be due to use of isobaric levobupivacaine (0.5%), volume of used diluent, rapidity of intrathecal injection and more lipophilic nature of fentanyl.
In our study, the time to first analgesic requirement was significantly prolonged in Group LD than Group LF or L. This is supported by study done by Rahimzadeh et al. they studied the comparative addition of dexmedetomidine (5 µg) and fentanyl (25 µg) to intrathecal 2.5 ml bupivacaine 0.5% in orthopedic procedure in lower limbs and concluded that first rescue analgesic request was prolonged in dexmedetomidine group than fentanyl group.19
The sedation scores of patients in Group LD were significantly better than in Group L and Group LF. This clearly shows that intrathecal dexmedetomidine provides better sedation to patients than intrathecal fentanyl, which can be very useful in patients undergoing cesarean section. In all three groups, the newborns had no signs of fetal distress, evidenced by Apgar score more than 7 at 1 min which infers the advantageous use of dexmedetomidine over other adjuvants and similar results were supported by other study.20-21 The incidence of side effects like nausea and vomiting, hypotension, bradycardia, respiratory depression, shivering and pruritus were not significantly different among the groups.
Limitations
As the present study contributes to the existing knowledge on α2 agonists, certain limitations must be taken into consideration. All the patients included in the study were ASA physical status I and II; as such caution must be exerted while generalizing the results to ASA physical status III and IV patients. It was conducted on patients scheduled for LSCS and it is possible that the level of surgery might alter the perception of post-operative pain. Therefore further future clinical studies are needed to determine the equivalent doses of dexmedetomidine and fentanyl for different types of neuraxial blockade. We did not compared 24 hour analgesic requirements between groups.
Conclusion
We conclude that 5μg dexmedetomidine seems to be the most attractive alternative to 25μg fentanyl as an adjuvant to intrathecal levobupivacaine in cesarean section. It provides good quality of intraoperative and postoperative analgesia, sedation, hemodynamic stability, minimal side effects, and no change in Apgar scoring.
Conflict of Interest: None
Financial Support: Nil
Authors’ contribution
KR: Content of work, Data collection
AKB: Concept, manuscript writing, editing
YS: Data analysis and interpretation
PR: Study design
References
Kapil Rastogi [kapil.gsvm@gmail.com]
Alok Kumar Bharti [alok.bharti48@gmail.com]
Yashpal Singh [dryashacin1999@rediffmail.com]
Pushkar Ranjan [pushkarranjanbhu@gmail.com]
1-Assistant Professor, Dept. of Anesthesiology, Integral Institute of Medical Science and Research, Lucknow, UP, India.
2-Assistant Professor, Dept. of Anesthesiology and Critical Care, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar-800013, India.
3-Associate Professor, Dept of Anesthesiology, AIIMS. Gorakhpur, UP, India.
4-Professor, Dept, of Anesthesiology, IMS, BHU, Varanasi.
Correspondence: Dr Alok Kumar Bharti;
E-mail: alok.bharti48@gmail.com; Mobile: +91 9307645596
Abstract
Background: Intrathecal Bupivacaine is most commonly used local anesthetic for lower segment cesarean section (LSCS) but there is constant endeavour for search of a local anesthetic (LA) which has improved safety profile for mother as well as foetus. So far many adjuvants like fentanyl, morphine or tramadol etc. has been used with intrathecal LA to prolong intraoperative anesthesia and postoperative analgesia. The available literature lacks information on use of dexmedetomidine as adjuvants with isobaric levobupivacaine. So we plan study to compare dexmedetomidine and fentanyl added to 0.5% isobaric intrathecal levobupivacaine in spinal anesthesia for LSCS.
Methodology: After Institutional ethical committee approval and informed written consent, patient were divided into three equal groups: Group L; to receive 2.5 ml of 0.5% of isobaric levobupivacaine intrathecally; Group LD to receive 2.5 ml of 0.5% of isobaric levobupivacaine and 5 µg dexmedetomidine intrathecally and Group LF to receive 2.5 ml of 0.5% of isobaric levobupivacaine and 25 µg fentanyl intrathecally. Primary outcome was measured as duration of sensory and motor blockade from the time of intrathecal administered of drugs. Statistical analysis was performed by using chi-square test or Fischer's exact test and One-way ANOVA or Kruskal Wallis test as applicable. A p value of < 0.05 was considered as statistically significant.
Results: Duration of sensory and motor blockade was significantly prolonged (p < 0.001) in Group LD as compared to Group LF or L. Onset of sensory and motor blockade was earlier in Group LF as compared to Group LD and L (p < 0.001). Time to first rescue analgesia was prolonged in Group LD than Group LF and L (p < 0.001).
Conclusion: Intrathecal dexmedetomidine produce prolonged blockade as well as postoperative analgesia thanl fentanyl when used as adjuvants to 0.5% isobaric levobupivacaine in elective cesarean section.
Key words: Cesarean section, Dexmedetomidine, Fentanyl, Intrathecal Analgesia; levobupivacaine; Spinal Anesthesia
Citation: Rastogi K, BhartiAK, Singh Y, Ranjan P. Comparison of dexmedetomidine and fentanyl as adjuvants to intrathecal levobupivacaine in lower segment cesarean section: A prospective, randomized double blind study. Anaesth. pain intensive care 2020;24(3):383-388.
Introduction
Subarachnoid block is the most widely used regional anesthetic procedure for lower abdominal and lower limb surgery including lower segment cesarean section (LSCS).1 It provide rapid onset, consistent sensory and motor blockade with adequate muscle relaxation and for all types of surgery below the level of umbilicus.
Regional anesthesia is safer than general anesthesia and having advantage of the parturient being awake during the birth process.2 Intrathecal local anesthetics (LA) alone are not enough for effective postoperative analgesia and higher dose of LA are also associated with hemodynamic instability, which can lead to unfavourable maternal and foetal outcome. So far many adjuncts have been used to augment the analgesia produced by intrathecal LA and to reduce their adverse effects.3 The very latest addition to LA used for labour analgesia is levobupivacaine, which is the left-turning molecule of bupivacaine.4 Levobupivacaine seems identical to bupivacaine in potency and shows longer duration of action on neural tissue. Because bupivacaine is a racemic mixture of both the left- and right-turning molecules, it has been recently referred to as racemic bupivacaine to further distinguish it from levobupivacaine.4 Isobaric levobupivacaine has less cardiotoxicity propensity and less chance of cephalic spread, favour particularly in LSCS.
It has been well documented that the combination of fentanyl and LA administered intrathecally has synergistic analgesic effects.anes5] Fentanyl is a lipophilic μ-receptor agonist opioid. Intrathecally, fentanyl exerts its effect by combining with opioid receptors in the dorsal horn of spinal cord and may have a supra spinal spread and action. Dexmedetomidine is a highly selective α2–adrenoreceptor agonist recently used as adjuvant with intrathecal LA and found to be prolong the duration of sensory and motor blockade as well as provides hemodynamic stability during intraoperative period.6-10 It also produces dose-dependent sedation, anxiolysis and analgesia (involving spinal and supraspinal sites) without respiratory depression.
Review of literature on use of dexmedetomidine as adjuvants with 0.5% isobaric intrathecal levobupivacaine in LSCS is scarce. So we plan this study to compare dexmedetomidine with fentanyl as an adjuvant to intrathecal isobaric 0.5% ropivacaine.
Material and methods
After Institutional ethical committee approval and informed written consent, 60 female patients were enrolled in this prospective randomized double blinded controlled study. Inclusion criteria includes full term pregnant patient of American Society of Anesthesiology (ASA) grade 1 and 2, between age group of 20-40 years, scheduled for elective LSCS. Exclusion criteria includes patient refusal, having allergy to studied drugs, any contraindication to spinal anesthesia, pregnancy with associated medical problems like eclampsia, pre-eclampsia, diabetes etc.
All patients were randomly assigned into three equal groups (n = 20) to receive spinal anesthesia: Group L to receive 2.5 ml of 0.5% of isobaric levobupivacaine; Group LD to receive 2.5 ml of 0.5% of isobaric levobupivacaine plus 5 µg dexmedetomidine and Group LF to receive 2.5 ml of 0.5% of isobaric levobupivacaine plus 25 µg fentanyl .intrathecally. Each group will receive total volume of 3.0 ml. Randomization was performed my anesthesiologist involved in drug preparations. Other investigator involved in the procedure and monitoring was unaware of group allocation. Patients were also blinded to drug regimen given in spinal anesthesia.
On arrival to operating room, standard monitor were placed and baseline parameters recorded. Peripheral 18G intravenous (IV) catheter was established and all patients preloaded with lactated ringer solution 10 ml/kg. Before spinal anesthesia patients were explained about the procedure and methodology of monitoring methods. In the left lateral decubitus position under standard aseptic precautions, using a midline approach lumbar puncture was performed at L3-L4 or L4-L5 intervertebral space by 25G Quincke spinal needle (BD, Gurgaon, Haryana, India). Having confirmed the free flow of cerebrospinal fluid through the spinal needle, the studied drug solution was injected intrathecally over a period of 10–15second and patients were turned to the supine position with wedge on right side.
Primary outcome included the comparison of the block characteristics and duration of postoperative analgesia. Secondary outcome was to compare the hemodynamic parameters, time to first rescue analgesia and adverse effects of dexmedetomidine or fentanyl given intrathecally with isobaric 0.5% levobupivacaine.
The level of sensory bock assessed bilaterally in mid clavicular line, by loss of pinprick sensation to 23 gauge hypodermic needle and dermatomes levels were tested every 2 min until the highest level had stabilized by consecutive tests. The highest dermatome level of sensory blockade, the time to reach this level from the time of injection, time to S1 level sensory regression was recorded. The motor dermatome level was assessed using Modified Bromage scale. The time to reach Bromage scale 3 before surgery and Bromage 0 in post anesthesia care unit (PACU) was recorded. On achieving T-6 sensory blockade level and Bromage scale 3 surgery was allowed. Sedation was assessed by a modified Ramsay sedation scale. Pain was assessed using VAS (0 to 10) scale at time of incision and at completion of surgery. After surgery patient was shifted to post anesthesia care unit (PACU) and observed for hemodynamic parameters, duration of sensory block, duration of motor block, degree of postoperative analgesia and need of rescue analgesic. Hypotension, defined as a decrease of systolic blood pressure by more than 30% from baseline or a fall below 90 mmHg, was treated with incremental IV doses of ephedrine 5 mg and IV fluid as required. Bradycardia, defined as heart rate < 50 bpm, was treated with IV atropine 0.3-0.6 mg. The incidence of adverse effects, such as nausea, vomiting, shivering, pruritus, respiratory depression, sedation, and hypotension was recorded.
Our estimated sample size was based on to study efficacy in term of degree of sensory and motor blockade among the group. For sample size calculation, we defined a relevant clinical difference of 20% in degree of blockade among the three groups. Thus sample size of 15 per group with effect size of 20 provided 90% power for detecting significant differences at any point of time between three groups at alpha level of 0.05. 60 patients were randomly allocated into one of the three groups using sealed envelope based on computer generated random number.
Statistical analysis
Statistical analysis was done with the statistical package for the social science system version SPSS 17.0. Continuous variables are presented as mean ± SD, and categorical variables are presented as absolute numbers and percentage. The comparison of normally distributed continuous variables between the groups was performed using One-Way ANOVA or Kruskal Wallis test. Nominal categorical data between the groups were compared using Chi-square test or Fischer’s exact test. P value of < 0.05 was considered as statistically significant.
Results
Out of 65 patients, 60 completed study successfully (Figure 1). The study groups were comparable in terms of demographic profile and baseline parameters (Table 1). Time required to achieve highest level of sensory block was least in Group LF (3.35 ± 0.36), maximum in Group L (5.56 ± 0.91) and highly significant between three groups (p < 0.001) (Table 2). Average time required to achieve Bromage scale 3 varied similarly, least in Group LF (2.94 ± 0.30) and statistically highly significant between three groups (p < 0.001) (Table 2). The time required for sensory regression to S1 level (duration of sensory block) was maximum in group LD (316.10 ± 24.34) and highly significant between three groups (p < 001) (Table 2). The time required to reach Bromage scale 0 (duration of motor block) was highest in Group LD followed by LF and L (265.05 ± 12.68 vs. 203.25 ± 23.80 vs. 176.00 ± 18.61) and statistically significant between three groups (p < 0.001) (Table 2). Time required for first analgesic requirement (duration of analgesia) was highly significant difference between groups (p < 0.001), highest in Group LD (275.75 ± 20.21) and lowest in Group L (199.00 ± 18.68) (Table 2). There were no statistically significant differences in hemodynamic parameters and associated adverse events between three groups (Table 3).
Discussion
There was continuous effort to find out local anesthetic, having less chance of cardiotoxicity and less cephalic spread. Levo-bupivacaine is a long acting amide LA and S-enantiomer of bupivacaine, having less chance of cardiotoxicity and less cephalic spread. So we conducted this trial to study the comparative efficacy of Levobupivacaine with adjuvant dexmedetomidine or fentanyl intrathecally for LSCS.
In this present study, mean duration of sensory (time to regression to S1 dermatome) and motor blockade (time to regression to Bromage scale 0) was found to be prolonged for Group LD than Group LF or L. This explains that intrathecal dexmedetomidine prolongs the duration of local anesthetic more in comparison to fentanyl. This study is supported by Gupta et al. they studied the analgesic effects of dexmedetomidine (5 µg) or fentanyl (25 µg) given intrathecally with hyperbaric 0.5% bupivacaine (12.5 mg). They concluded that intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability, and reduced demand for rescue analgesics in 24 h as compared to fentanyl.11 Our study is further strengthened by Ramadan et al. they evaluated the effects of adding dexmedetomidine (5 µg) versus fentanyl (25 µg) to intrathecal bupivacaine ( 10 mg) on spinal block characteristics and neonatal outcome in uncomplicated cesarean delivery and concluded the dexmedetomidine group had significant longer sensory and motor block times than fentanyl group or control group. No adverse effects on mothers or babies were noticed among three groups.12
Table 1: Comparison of demographic data and baseline parameters between the groups. (n = 20)
| Parameter | Group L | Group LD | Group LF | P value |
| Age (Year) | 27.10 ± 4.15 | 27.10 ± 3.85 | 27.75 ± 3.98 | 1.00*,**,# |
| Weight (Kg) | 57.00 ± 5.75 | 54.20 ± 4.50 | 55.55 ± 5.25 | 0.28*, 1.00**. # |
| Height (Cm) | 154.10 ± 3.50 | 155.90 ± 5.79 | 155.25 ± 4.26 | 0.67*, 1.00**, # |
| BMI | 23.92 ± 2.18 | 22.33 ± 1.70 | 22.89 ± 1.82 | 0.03*, 1.00**, 0.28# |
| Baseline HR (beats/min) | 85.55 ± 6.12 | 85.45 ± 7.84 | 82.85 ± 7.05 | 0.96*, 0.20**, 0.28# |
| Baseline MAP (mmHg) | 95.90 ± 2.19 | 94.95 ± 6.37 | 94.90 ± 5.04 | 0.53*, 0.42**, 0.98# |
Table 2: Comparativef block characteristics and time to 1st analgesic requirements (n = 20)
| Parameter | Group L | Group LD | Group LF | P value |
| Time to reach highest level of sensory block (minute) | 5.56 ± 0.91 | 4.49 ± 0.53 | 3.35 ± 0.36 | < 0.001*,**,# |
| Time to reach Bromage 3 before surgery (Minute) | 4.74 ± 0.87 | 3.90 ± 0.48 | 2.94 ± 0.30 | < 0.001*,**,# |
| Time to S1 level sensory regression (Minute) | 189.25 ± 22.20 | 316.10 ± 24.34 | 244.25 ± 25.09 | < 0.001*,**,# |
| Time to reach Bromage 0 after surgery (minute) | 176.00 ± 18.61 | 265.05 ± 12.68 | 203.25 ± 23.80 | < 0.001*,**,# |
| Time of first analgesic requirements (minutes) | 199.00 ± 18.68 | 275.75 ± 20.21 | 244.00 ± 16.67 | < 0.001*,**,# |
Table 3: Comparative frequency of side effects between three groups. (n = 20)
| Parameter | Group L | Group LD | Group LF | P value |
| Hypotension | 2 (10) | 3 (15) | 3 (15) | 0.86 |
| Nausea/Vomiting | 2 (10) | 1 (5) | 3 (15) | 0.57 |
| Shivering | 2 (10) | 0 (0) | 1 (5) | 0.35 |
| Reparatory depression | 0 (0) | 0 (0) | 2 (10) | 0.13 |
How dexmedetomidine prolongs the sensory and motor blockade is not known exactly. Best possible mechanism may be the, analgesia produced by α2 agonists occurs as a result of decreased release of C-fiber transmitters and hyperpolarization of postsynaptic dorsal horn neurons. It has been postulated that binding of α2 agonist agents to the dorsal horn motor neurons results in the prolongation of motor blockade of LA.13,14 They also exhibit anesthetic-sparing and hemodynamic- stabilizing effects.anes15,16
Mean time of sensory and motor blockade was significantly lower in Group LF than Group LD or Group L. Contrary to our finding, other studies report that time of onset of sensory and motor blockade was earlier in dexmedetomidine group than fentanyl group.17,18 The differences in sensory and motor onset time could be due to use of isobaric levobupivacaine (0.5%), volume of used diluent, rapidity of intrathecal injection and more lipophilic nature of fentanyl.
In our study, the time to first analgesic requirement was significantly prolonged in Group LD than Group LF or L. This is supported by study done by Rahimzadeh et al. they studied the comparative addition of dexmedetomidine (5 µg) and fentanyl (25 µg) to intrathecal 2.5 ml bupivacaine 0.5% in orthopedic procedure in lower limbs and concluded that first rescue analgesic request was prolonged in dexmedetomidine group than fentanyl group.19
The sedation scores of patients in Group LD were significantly better than in Group L and Group LF. This clearly shows that intrathecal dexmedetomidine provides better sedation to patients than intrathecal fentanyl, which can be very useful in patients undergoing cesarean section. In all three groups, the newborns had no signs of fetal distress, evidenced by Apgar score more than 7 at 1 min which infers the advantageous use of dexmedetomidine over other adjuvants and similar results were supported by other study.20-21 The incidence of side effects like nausea and vomiting, hypotension, bradycardia, respiratory depression, shivering and pruritus were not significantly different among the groups.
Limitations
As the present study contributes to the existing knowledge on α2 agonists, certain limitations must be taken into consideration. All the patients included in the study were ASA physical status I and II; as such caution must be exerted while generalizing the results to ASA physical status III and IV patients. It was conducted on patients scheduled for LSCS and it is possible that the level of surgery might alter the perception of post-operative pain. Therefore further future clinical studies are needed to determine the equivalent doses of dexmedetomidine and fentanyl for different types of neuraxial blockade. We did not compared 24 hour analgesic requirements between groups.
Conclusion
We conclude that 5μg dexmedetomidine seems to be the most attractive alternative to 25μg fentanyl as an adjuvant to intrathecal levobupivacaine in cesarean section. It provides good quality of intraoperative and postoperative analgesia, sedation, hemodynamic stability, minimal side effects, and no change in Apgar scoring.
Conflict of Interest: None
Financial Support: Nil
Authors’ contribution
KR: Content of work, Data collection
AKB: Concept, manuscript writing, editing
YS: Data analysis and interpretation
PR: Study design
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