Determination of the ED95 of intrathecal hyperbaric prilocaine with sufentanil for scheduled cesarean delivery: A dose-finding study based on the continual reassessment method

Abstract

Background – Scheduled cesarean section is routinely performed under spinal anesthesia using hyperbaric bupivacaine. The current study was undertaken to determine the clinically relevant 95% effective dose of intrathecal 2% hyperbaric prilocaine co-administered with sufentanil for scheduled cesarean section, using continual reassessment method.Methods – We conducted a dose-response, prospective, double-blinded study to determine the ED95 values of intrathecal hyperbaric prilocaine used with 2,5 mcg of sufentanil and 100 mcg of morphine for cesarean delivery. Each parturient enrolled in the study received an intrathecal dose of hyperbaric prilocaine determined by the CRM and the success or failure of the block was assessed as being the primary endpoint.Results – The doses given for each cohort varied from 35 to 50 mg of HP, according to the CRM, with a final ED95 lying between 45 and 50 mg of Prilocaine after completion of the 10 cohorts. Few side effects were reported and patients were globally satisfied.Conclusions – The ED95 of intrathecal hyperbaric prilocaine with sufentanil 2.5 μg and morphine 100 μg for elective cesarean delivery was found to be between 45 and 50 mg. It may be an interesting alternative to other long-lasting local anesthetics in this context.Trial registration – The study was registered on January 30, 2017 – retrospectively registered – and results posted at the public database clinicaltrials.gov (NCT03036384 – https://clinicaltrials.gov/ct2/show/NCT03036384).

Comparison of equipotent doses of intrathecal hyperbaric prilocaine 2% and hyperbaric bupivacaine 0.5% for elective caesarean section

“…The ED 95 of hyperbaric prilocaine was recently determined by our team to be 50 mg while combined with the same opioids. 19 With respect to motor block regression, the present findings corroborate recent studies, which established the intermediate-action profile of hyperbaric prilocaine. 14,17 Importantly, 2% hyperbaric prilocaine 50 mg allowed complete recovery from motor block 1 h earlier than bupivacaine, thus validating our superiority hypothesis for the primary outcome.…”

“…6,7,35 Our results highlight the better haemodynamic profile for prilocaine during C-section, confirming our previous ED 95 study findings. 19 This benefit was not observed by Chapron et al 30 who reported an 80% incidence of hypotension, similar for the two drugs, but this can reasonably be explained by the higher doses, which they used. 30 We did not observe a difference in vasopressor use, probably as we immediately treated nausea or dizziness, commonly considered as prodromes of hypotension, even before obtaining the blood pressure measurement.…”

“…Intending to ensure correct comparability, we used equipotent doses for bupivacaine and prilocaine, based on previous dose-finding studies for C-section. 19,[25][26][27] Regarding hyperbaric bupivacaine, depending on the assessment techniques and the associated opioid, the ED 95 has been estimated between 8.8 mg 27 and 11 mg. 25 For the purpose of the study, we chose a dose of 10 mg together with sufentanil 2.5 mg and morphine 100 mg, as adopted in our daily clinical practice. The ED 95 of hyperbaric prilocaine was recently determined by our team to be 50 mg while combined with the same opioids.…”

“…Although promptly attained T4 sensory block, a prerequisite for scheduled C-section, 20 is well established for bupivacaine, 28,31 it has not been reported after 50 mg of hyperbaric prilocaine until very recently in an obstetric population. 19,30 It could be argued that such thoracic local anaesthetic spread may be related to the physiology of the obstetric population. 28 The addition of sufentanil may have contributed to the enhanced anaesthetic quality of prilocaine as it is well acknowledged that opioids potentiate the effect of intrathecal local anaesthetics.…”

“…Considering that correct comparability of local anaesthetics in particular indications should be performed using equipotent doses, 18 we first recently determined the 95% effective dose (ED 95 ) of prilocaine combined with opioids to ensure adequate surgical anaesthesia. 19 The present study tested the hypothesis that hyperbaric prilocaine is superior to hyperbaric bupivacaine in offering earlier regression of motor block and recovery when comparing equipotent doses. We also assessed the effectiveness and characteristics of sensory block, and differences on maternal haemodynamics and side effects in both mother and newborn.…”