Background: Bupivacaine is the most popular local anaesthetic agent in subarachnoid block in obstetrics patient undergoing elective LSCS. There is constant search for newer anaesthetic agent providing effective intraoperative block, postoperative analgesia & minimal side effects. Effective postoperative analgesia facilitates early mobilization of the mother, prevents postoperative morbidity, increases patient satisfaction, and decreases the duration of hospital stay. In some studies, levobupivacaine is found to have prolonged postoperative analgesia & lesser CVS & CNS toxicity, but there is very limited study for its use in post caesarean delivery. So, we    designed a prospective, randomized, double blind study to evaluate the effect of intrathecal heavy levobupivacaine vs intrathecal heavy bupivacaine for postoperative analgesia in LSCS. Following approval by the Institutional Ethics Committee, study would be completed in the period of 18 months. After taking written and informed consent from the patient, this study will be conducted in pregnant females who undergo elective caesarean delivery. Assessment of pain will be done by a 10- point numerical rating scale (NRS); 0= no pain, 10 = worst imaginable pain and consumption of rescue analgesic. Motor block will be assessed by Bromage score. Postoperative complication like PONV, sedation will be compared in both the groups.

Introduction

Spinal anaesthesia / Subarachnoid block (SAB) for caesarean section is the preferred technique for majority of anaesthesiologist primarily due to decreased maternal morbidity compared to general anaesthesia. The goal of spinal anaesthesia for caesarean section is the provision of effective surgical anaesthesia & postoperative analgesia with minimal maternal & fetal side effects Bupivacaine is an amide local anaesthetic. It is presented as racemic mixture composed of 50% of the S isomer & 50% of the R isomer. Clinical studies demonstrate that large proportion of bupivacaine toxicity is due to its dextrorotatory isomer R (+). So had more toxicity if accidental intravascular injection occurs. Levobupivacaine (S -) has more specific effect on sensory rather than motor nerve fibre due to its faster protein binding rate , so have longer postoperative analgesic effect & lesser toxicity. Maternal pain is the most common reason for patient’s dissatisfaction. Adequate post-operative analgesia in the obstetric patients is crucial as they have different surgical recovery needs which include breastfeeding and new-born care.  opioid related side effects such as nausea, vomiting, sedation, pruritus, urinary retention and respiratory depression is troublesome for patient. Lower segment caesarean section is the common surgical procedure for delivery of baby. Literature suggests that up to 80% patients experience significant pain (VAS score >5) after LSCS. So to compare the postoperative analgesia of intrathecal levobupivacaine with morphine vs bupivacaine with morphine, we designed a randomized prospective double blind study in parturient posted for elective LSCS. We hypothesize that heavy levobupivacaine with morphine is better than heavy bupivacaine with morphine for providing postoperative analgesia following LSCS and plan to conduct this double blind randomised controlled study.

 Aims and Objectives:

Primary objective:

§  To study the analgesics efficacy intrathecal heavy levobupivacaine with morphine Vs. heavy bupivacaine with morphine after caesarean section in term of time for first rescue analgesic demand

Secondary objectives:

§   Onset and total duration of motor and sensory block in both groups.

§  SAB related immediate hypotension (% drop in mean BP every 5 min,  over 20 mins after SAB & cumulative vasopressor use (phenylephrine) and its effect on fetal PH.

§  Pain assessment by NRS in both groups.

§  On demand analgesic (aqueous inj diclofenac 75 mg in 50 ml NS slow IV over 15 mins), total analgesic consumption, in terms of no of doses given in both groups over 24 hrs will be compared.

§  Satisfaction score of patients in both the groups at 24 hrs

§   Analgesic related side effects:  Incidence of PONV, level of sedation, respiratory depression, itching etc

Place of Study: MRH OT and PMSSY ICU of SGPGIMS, LUCKNOW

Duration of study: One year

Study design: Prospective Randomized controlled double-blind study

Materials and Methods

After approval from the ethical committee of SGPGIMS, and written informed consent, 80 term Pregnant females aged 18-40 yrs, primigravida with singleton pregnancy undergoing elective LSCS surgeries will be enrolled and will be divided equally by using computer generated randomization in two groups as follows:

Group B (N=40): will be given Spinal anaesthesia: 1.5 ml heavy bupivacaine (0.5%) with 100 mcg morphine, before surgery with 27 pencil tip spinal needle at L1-L2 level.

Group L (N=40): will be given Spinal anaesthesia: 1.5ml heavy Levobupivacaine (0.5%) with morphine 100 mcg, before surgery with 27 pencil tip spinal needle at L1-L2 level.

•      Each group will receive 24 hrs post operatively: IV PCM 1 gm/ 6hrly and on demand analgesic: inj Diclofenac 75 mg iv diluted in 50 ml NS over 15 mins  with lockout  interval of 8 hrs

Methodology in details: All patients will undergo routine pre-anesthetic check-up and preoperative workup, standard for elective LSCS. Patients will receive oral ranitidine 150 mg and Tab Metoclopramide 10 mg on the evening before and again on the morning of surgery. On arrival in the operating room, physiological monitoring (pulse oximetry, continuous ECG and non-invasive blood pressure measurement) will be started.  Spinal anaesthesia will be given in the left lateral position, the midline, at level of L1-L2 intervertebral spaces with 27 G pencil tip needle, in heavy bupivacaine group ( group B) 1.5ml heavy bupivacaine (0.5%) with 100 mcg morphine will be given. In levobupivacaine group (group L ) levo-bupivacaine 1.5 ml with 100 mcg morphine will be given. Patients will be immediately placed in supine position and spinal anaesthesia will be considered successful when a bilateral sensory block to T6 asses by loss of cold [by sprit swab] and touch (blunt pain) discrimination will be established motor block upto T10 level measured by Bromage score and vitals will be monitored.  After surgery is conducted in both the groups data will be collected as working Proforma below and will be given PCM 1 gm/ 6hrly & on demand analgesic: inj diclofenac 75 mg diluted in 50 ml NS over 15 mins

Inclusion criteria

•      Term pregnant female                              

•      Primary gravida 

•      Singleton pregnancy

•      Pfannenstiel incision

•      ASA physical status I or II

Exclusion criteria:

•      Patient refusal to participate

•      ASA grade 3 or 4

•      Patient with coagulopathy, anatomical spine abnormalities, local infection in spine , pt who used anticoagulants or were unable to comprehend or use the verbal rating pain scoring system

•      Patients with ASA III and IV

Sample size:  A study conducted by Duggal R, et al. (2015); showed that postoperative duration of sensory block (first analgesic requirement) was reported to be 80.03±8.12 minutes and 103.47±10.18 minutes respectively (Cohen d effect size of the mean difference = 2.54). In the present study, assuming effect size of 0.80 (lower effect size increase the required sample size), at minimum two side 95% confidence interval, and 90% power of the study, estimated sample size for each group to be 34 [Total 68]. Finally, 80 patients to be randomized in the study with 40 patients in group1 and 40 patients in group2. Sample size was estimated using software “Power analysis and sample size, version-16 (PASS-16)”.

Statistical analysis: Mean and standard deviation (SD) or median (interquartile range) will be used for continuous variables depend on normality status. Categorical variables will be presented in number (%). Chi square test / Fisher exact test will be used to compare the proportions between the groups. Independent samples t test or its non-parametric tests to be used to compare the means or medians between the study groups. Two-way repeated measures ANOVA / Linear mixed model to be used to test the association between study groups and change in the measurements over the time points. All statistical analyses will be performed using SPSS software for windows version 23.0 (SPSS, Chicago, IL), with a significance level at two sided of 0.05.

Aassessment after the block

ü  Motor block (Bromage score) &sensory block onset & duration     

ü  Hemodynamic variables (intraoperative) :  % MBP  drop 5,10,15,20 mins & fetal PH , cumulative vasopressor use (phenylephrine).  HR, RR, SPO2%  & non-invasive BP (SBP,DBP,MBP)

ü  Pain assessment by NRS score upto 24 hrs

ü  Patient satisfaction score at 24 hr

ü  Time for first analgesic demand, total analgesic comsumption in terms of no of doses (inj aqueous diclofenac 75 mg diluted in 50 ml NS slow IV over 15 mins)

ü  PONV score

ü  Ramsay sedation score

ü  Respiratory depression

ü  Any other side effects : urinary retention & pruritis

                                                           WORKING PROFORMA

Patient Data:

Name:______________________      Age/ Sex:__________Weight:____Kg        Height(cm) :               BMI :

Date:  _____________CR No: ______________________

ASA grading: ______, Investigations: Platelet, INR, Hb

Obstetrics details:

Surgery: __________________

Duration of surgery:

Any other information

Data will be collected:

References;

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2.      Frawley G, Smith KR, Ingelmo P. Relative potencies of bupivacaine, levobupivacaine, and ropivacaine for neonatal spinal anaesthesia. Br J Anaesth. 2009;103(5):731-8.

3.      Alley EA, Kopacz DJ, McDonald SB, Liu SS. Hyperbaric spinal levobupivacaine: a comparison to racemic bupivacaine in volunteers. Anesth Analg. 2002 ;94(1):188-93/

4.      Vanna O, Chumsang L, Thongmee S. Levobupivacaine and bupivacaine in spinal anesthesia for transurethral endoscopic surgery. J Med Assoc Thai. 2006 ;89(8):1133-9.

5.      Ture P, Ramaswamy AH, Shaikh SI, Alur JB, Ture AV. Comparative evaluation of anaesthetic efficacy and haemodynamic effects of a combination of isobaric bupivacaine with buprenorphine vs. isobaric levobupivacaine with buprenorphine for spinal anaesthesia - A double blinded randomised clinical trial. Indian J Anaesth. 2019 ;63(1):49-54.

6.      del-Rio-Vellosillo M, Garcia-Medina JJ, Pinazo-Duran MD, Abengochea-Cotaina A. Doses and effects of levobupivacaine and bupivacaine for spinal anaesthesia. Br J Anaesth. 2014 ;113(3):521-2.