European Journal of Cardiovascular Medicine

Preeclampsia, which affects 5% to 7% of pregnancies, is a significant cause of maternal and neonatal morbidity and mortality.^[1] Characterized by hypertension and proteinuria after 20 weeks’ gestation, the pathophysiologic basis of preeclampsia is deranged angiogenesis with incomplete trophoblastic invasion leading to small, constricted myometrial spiral arteries with exaggerated vasomotor responsiveness, superficial placentation, and placental hypoperfusion. Symptomatic pre-eclampsia reflects widespread endothelial dysfunction, in which placenta-derived mediators cause multisystem organ dysfunction.^[2] In severe instances, pre-eclampsia can precipitate complications such as hemolysis (red blood cell breakdown), thrombocytopenia (low blood platelet count), hepatic impairment, renal dysfunction, edema, pulmonary edema leading to respiratory distress, or visual disturbances. The correct management of delivery and choosing the appropriate anesthetic method to achieve analgesia and maintain the health of the mother and fetus during caesarean section are of great importance. For caesarean section patients, spinal anesthesia is a reliable and safer procedure than general anesthesia.^[3,4]

Ropivacaine is a relatively newer long-acting amide local anesthetic, which has a wide margin of safety. It is a long-acting amide local anesthetic being alike to bupivacaine in structural and pharmacodynamics. Levobupivacaine is newer LA that had been approved for intrathecal administration in recent years. Levobupivacaine is pure S (-) enantiomer of bupivacaine.^[5] The levobupivacaine is a high potency, long-acting LA. In this study, our primary focus is on assessing hemodynamic stability during Lower Segment Caesarean Section (LSCS). Through exploring the hemodynamic effects of these alternative drugs compared to traditional bupivacaine, we seek to enhance our understanding of their efficacy and safety profiles in the context of spinal anesthesia for LSCS in preeclamptic patients.

After approval from Institutional Ethical Committee, 80 parturients were included in the prospective, randomized, double-blinded study from June 2023 to December 2023 in the Maternal and Child Health wing of Sir Sunder Lal Hospital. The parturients were randomly divided by computer-generated random number technique into two groups, each of which contained 40 parturients by using sequentially numbered envelopes.

Group L received levobupivacaine 0.5% (hyperbaric) 1.4 ml with fentanyl 0.4 ml (50 mcg/ml) as additive intrathecally

Group R received ropivacaine 0.75% (hyperbaric) 1.4 ml with fentanyl 0.4 ml (50 mcg/ml) as additive intrathecally

Parturients and observers were blinded to the experimental medication. Drugs were prepared by an anesthesiologist who is not involved in the study, the syringes containing the drugs were having similar appearance and equal volumes.

Parturients of ASA grade 2 and 3, aged 25-40 years and those who gave written informed consent were included in the study. Parturients with multifetal pregnancy, HELLP syndrome, hepatic or renal involvement, pulmonary edema and cyanosis, contraindication for neuraxial block and eclampsia were excluded from the study.^[6-9]

After receiving the parturients into the operation theatre, intravenous access was done and infusion of crystalloids was started. ASA standards monitors were attached including electrocardiogram, non-invasive blood pressure, pulse oximetry and baseline vitals were recorded. All the parturients were premedicated with ranitidine 50 mg and metoclopramide 10 mg slow infusion intravenously as per hospital protocol.

Group L received subarachnoid block under all aseptic precautions by midline approach in the sitting position at level L2-L3. Quincke spinal needle 27 G was used for administering subarachnoid block. Injection levobupivacaine 0.5% (hyperbaric) 1.4 ml along with injection fentanyl 0.4 ml (50 mcg/ml) as additive was administered intrathecally after adequate clear CSF flow was established. Group R received subarachnoid block under all aseptic precautions by midline approach in the sitting position at level L2-L3. Quincke spinal needle 27 G was used for administering subarachnoid block. Injection ropivacaine 0.75% (hyperbaric) 1.4 ml along with injection fentanyl 0.4 ml (50 mcg/ml) as additive was administered intrathecally after adequate clear CSF flow was established. Parturients received oxygen with help of oxygen mask till the delivery of neonate. After giving spinal anaesthesia vital parameters were noted every 5 minutes till 360 minutes. Injection ondansetron 4 mg was slowly administered intravenously to all parturients. Sensory block was assessed with help of blunt needle every 1 min till T6 level was achieved and time was noted as onset time for sensory block. Motor block was assessed according to modified Bromage scale (0-able to lift extended leg, 1-just able to flex knee, 2-no knee movement and some movement at ankle, 3-complete lower limb paralysis) and surgery was started once Bromage scale 2 was established. Adverse events such as hypotension, bradycardia, chest discomfort, nausea, vomiting etc were recorded and managed. Hypotension was managed with Phenylephrine 25 mcg bolus when blood pressure falls 20% below the baseline value. Maintenance and replacement fluid was administered as per requirement of individual parturients.

Post-operatively all parturients were monitored in PACU for 6 hours as per hospital protocol and then shifted to ward when they meet the discharge criteria of transfer from PACU. Combination of Paracetamol 1000mg and tramadol 50 mg was given intravenously as rescue analgesic once they complain of mild but tolerable pain (VAS 3).

Sample size calculation was conducted based on the results of a study done by Gautier P and De Cock M^[10] who conducted study on 90 parturients with 30 parturients in each group. The sample size was chosen so as to maintain the overall alpha error <0.05 and power (1−beta) >0.9 and to provide useful additional safety and tolerability data. We enrolled 45 parturients in each group to compensate for parturients if any excluded during the study. Data are presented as median (range), mean (SD), or frequencies as appropriate. Binomial data were compared using χ2 or Fisher's test. Block characteristics were compared using the Kruskal–Wallis one-way analysis. In the event of a significant difference, post hoc comparisons were performed using the two-tailed Mann–Whitney U-test with a Bonferroni correction for multiple two-way testing. A P-value of <0.05 was considered statistically significant. Data were analyzed using a standard computer-based statistics package (Stats Direct statistical software version 2.5.5)

Eighty parturients enrolled in the study were allocated randomly into group L and group R of 40 each (Figure 1).

The baseline demographic parameters in both groups were comparable (Table 1).

No significant differences were observed between group L and group R in terms of age, gender, height, weight, ASA physical status and comorbidity.

Primary Objectives

The primary objective was to compare the hemodynamic effects (effect on heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure) of levobupivacaine and ropivacaine when administered intrathecally in parturients with pre-eclampsia undergoing LSCS. The data revealed that (Table 2) heart rate and systolic blood pressure changes were statistically significant during the intraoperative period between the two groups but no parturients developed significant drop-in heart rate and systolic blood pressure that required intervention. Intraoperative heart rate was insignificantly different between both groups till 10 minutes after drug administration while from 15 minutes till 6 hours postoperatively there was significant difference in heart rate (p < 0.05). The decrease in heart rate and systolic blood pressure was more in Group R from baseline value. The systolic blood pressure was significantly different at 5 and 10 minutes and again from 25 minutes till 240 minutes (p < 0.05). The data analyzed for diastolic blood pressure (Table 4) which revealed statistically significant difference at 5 and 10 minutes (p < 0.05) otherwise it was insignificantly different at other time intervals (p > 0.05). The mean blood pressure (Table5) was not statistically significant during the entire intraoperative and postoperative period (p > 0.05).

Secondary Objectives

The secondary outcomes was to compare the effects of levobupivacaine and ropivacaine on onset time to sensory block, onset time for motor block, duration of anaesthesia and duration of analgesia between the two groups. The mean time for the onset of sensory blockade until reaching T6 was recorded for both Group L and Group R was 3.07 ± 0.9 and 4.4 ± 0.4 minutes respectively (p < 0.05). Group L had a mean onset time of motor blockade at 3.8 ± 0.7 minutes, whereas Group R showed a slightly delayed onset with a mean of 5.1 ± 0.7 minutes (p < 0.05). Group L and Group R had a mean duration of anesthesia of 45.1 ± 4.5 and 49.7 ± 8.2 minutes (p < 0.05), respectively. The duration of effective analgesia was assessed in both Group L and Group R. Group L exhibited a mean duration of 4.4 ± 0.6 hours, whereas Group R had a slightly shorter mean duration of 3.5 ± 0.6 hours (p < 0.05) (Table 6).

Spinal anesthesia is most commonly used technique in parturients undergoing caesarean section due to its efficacy in providing surgical anesthesia and postoperative pain relief while minimizing adverse effects on mothers and neonates, as compared to general anesthesia.

The variation in systolic blood pressure values from baseline was significantly less in levobupivacaine group compared to ropivacaine. Although the fall in diastolic blood pressure from baseline was significant during the intraoperative period (particularly at 5 and 10 min) between the levobupivacaine and ropivacaine group, the changes in mean arterial pressure were not significant during the entire intraoperative period. Levobupivacaine provided better hemodynamic stability as compared to ropivacaine in parturients with preeclampsia undergoing caesarean surgeries.

In 2023, Jaafarpour M et al^[11] conducted a study to determine the comparative effect of intrathecal hyperbaric bupivacaine versus hyperbaric ropivacaine on maternal and neonatal outcomes after caesarean section. They concluded that ropivacaine and bupivacaine are effective in caesarean section, ropivacaine is more favorable because of less hemodynamic changes, less duration of sensory and motor block, and fewer side effects, which are effective in parturients recovery. In 2023, Dikkala D B et al^[7] compared the efficacy of 0.5% levobupivacaine and 0.75% ropivacaine after intrathecal administration in elective lower limb surgeries. They concluded that levobupivacaine is more cardiostable with stable hemodynamic profile compared to ropivacaine. In 2020, Karthik T et al^[12-13] conducted a study to compare 0.5% hyperbaric Bupivacaine and 0.5% isobaric Levobupivacaine for elective caesarean sections under spinal anaesthesia. They concluded that isobaric levobupivacaine is a better alternative for caesarean section.

LIMITATIONS

Parturients with pre-eclampsia do have underlying hepatic impairment and renal dysfunction which might have altered effects on pharmacokinetics and pharmacodynamics of the drugs used in the study which was not considered in this study. This study included a small sample size. More RCTs with large sample size are needed to substantiate our study.

Ropivacaine and levobupivacaine are the newest drugs utilized for neuraxial blockade, and they have demonstrated a superior pharmacological safety profile. Levobupivacaine emerges as the more favorable option when considering cardiostability and hemodynamic stability. This indicates a lower risk of adverse cardiovascular events, making it a safer choice for patients with underlying cardiac concerns. Additionally, levobupivacaine exhibits a more rapid onset of sensory blockade and motor blockade, which can be beneficial in clinical settings requiring prompt anesthetic action. Furthermore, levobupivacaine offers a prolonged duration of analgesia compared to ropivacaine. This extended analgesic effect can improve patient comfort and reduce the need for additional doses or supplementary analgesics, thereby enhancing overall patient management and satisfaction.

Source of Funding

None.

Conflict of Interest:

None.

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