Comparison of Chloroprocaine Versus Lidocaine With Epinephrine, Sodium Bicarbonate, and Fentanyl for Epidural Extension Anesthesia in Elective Cesarean Delivery: A Randomized, Triple-blind, Noninferiority Study : Obstetric Anesthesia Digest

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Comparison of Chloroprocaine Versus Lidocaine With Epinephrine, Sodium Bicarbonate, and Fentanyl for Epidural Extension Anesthesia in Elective Cesarean Delivery: A Randomized, Triple-blind, Noninferiority Study

Sharawi, N.; Bansal, P.; Williams, M.; Spender, H.; Mhyre, J.

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doi: 10.1097/01.aoa.0000853444.72326.9d
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Abstract

Neuraxial analgesia is utilized in over 70% of labors in the United States. The authors of this study report a general consensus among their local and nonlocal peers that 3% chloroprocaine or CP, a local anesthetic with a quick preparation time, and 2% lidocaine, epinephrine, bicarbonate, and fentanyl, or LEBF, which needs additional preparation time, have similar onset times when used to convert epidural pain relief to epidural anesthesia for cesarean delivery (CD). To their knowledge, no study has confirmed this assumption. This study analyzes the onset times of CP and LEBF.

Willing participants who were above the age of 17, English speakers, and within physical boundaries were randomly assigned to receive either 20 mL of 3% CP and 4 mL of 0.9% sodium chloride or 20 mL of 2% lidocaine mixed with 0.15 mL of 0.1% epinephrine, 2 mL of 8.4% sodium bicarbonate, and 2 mL (100 μg) fentanyl (LEBF). The authors aimed to design a clinical model to study the local anesthetic speed of onset. Patients were administered a combined spinal-epidural with a 400 mL IV co-load of lactated Ringer’s solution, utilizing 150 ug of preservative-free morphine diluted into 1 mL of normal saline as the intrathecal dose. This was followed by an epidural administration 3 mL of 1.5% lidocaine epidural test dose, then a dose of 0.0625% bupivacaine with 2 µg/mL fentanyl to all patients 1 hour before CD. The anesthesiologist administered 500 mL of intravenous lactated Ringer’s solution to all patients while the investigator prepared the study drugs. An independent researcher numbered sealed and opaque envelopes only opened by an investigator directly before entry to the operating room; patients, surgeons, anesthesiologists, nurses, and data collectors were blinded to the contents of the envelope. Initially, 3 mL of either CP or LEBF were administered, followed by the remaining solution after 3 minutes over a 2-minute timeframe. Modified Bromage score and the Hollmén grading system assessed patient’s pain levels, and additional 5 mL of either CP or LEBF were administered if necessary. Postoperative medication involved oxytocin infusion, oral acetaminophen, and ibuprofen.

Collected measurements include the onset time to surgical anesthesia defined by sensory modality of touch and T7 dermatomal levels, intraoperative analgesia supplementation rate defined by additional medications to reduce significant pain or discomfort during CD, and the overall experience and satisfaction of both the mother and baby. Onset time to surgical anesthesia was measured by and analyzed through 2 sample t test, Kaplan-Meier survival analysis, a 90% confidence interval (CI) around group means, and an intention-to-treat analysis. Other data were analyzed through Wilcoxon rank-sum tests, Pearson χ2 tests, and Fisher exact tests. Seventy mothers were initially recruited for the study based on noninferiority 90% power calculations and withdrawal anticipation.

Overall, the mean onset time difference between CP and LEBF patients was 97 seconds with 90% CI of −10.6 to 204. The 204 upper limit was higher than the CI mean upper difference margin (max=3 min), resulting in insufficient evidence to conclude noninferiority between CP and LEBF for surgical anesthesia onset time. However, the study states CP administration in a CD emergency can still be useful. Mean onset time before bilateral sensory block at the T7 dermatome level produced similar results between the 2 groups. The CP group experienced 49 minute epidural infusion on average while the LEBF group experienced 48 minute epidural infusion on average. Out of 70 women recruited for the study, 33 CP patients and 34 LEBF patients completed all inclusion requirements. In all, 21% and 12% of patients required intraoperative supplementation due to pain during surgery for the CP and LEBF group respectively. Sensory block levels, duration of surgery, anesthesia induction to surgery time difference, cumulative dose of vasopressors, side effects patient satisfaction, oxycodone consumption, and neonatal outcomes were not impacted by the different local anesthesia solutions. In conclusion, more study is required to determine noninferiority between the 2 local anesthetics.

COMMENT

Neuraxial analgesia and anesthesia are the best friends of a woman in labor and for those scheduled to undergo a CD. Anesthesiologists try to provide optimal pain relief to the parturient, without exposing the pregnant patient to toxic reactions or interfering with the progress of delivery. This requires a balancing act of ingenuity and flexibility knowing which technique and medication formula would best suit the parturient in this specific situation and at the same time protecting mother and fetus from any harm, taking into account the specific situation of the labor suite and operating room area.

The authors (Sharawi et al.) should be congratulated on the great lengths they have gone to, in creating their clinical model of a labor epidural that requires topping-up for CD. An ideal mixture for epidural top-up is simple to prepare, has a rapid onset and provides effective anesthesia during the surgery. Depending on the clinical context, recommended times of decision-to-delivery should be <30 minutes (category 1 CD) and up to 75 minutes (category 2 CD).2 Two regimens are used in the author’s institution, that is, 3% CP or a mixture of 2% LEBF. This study probed to find an answer to “Is CP a noninferior formula to LEBF in terms of onset time to surgical anesthesia, when used to convert epidural analgesia to epidural anesthesia for cesarean delivery?” Both anesthesia solutions provided rapid onset epidural extension anesthesia for CD. However, noninferiority of CP to LEBF was not demonstrated by the authors, with the upper limit of the 95% CI being above the noninferiority margin of 3 minutes.

It is common practice to top-up an existing labor epidural, if a CD is needed in a parturient. The exact manner in which a top-up is performed will be influenced by many considerations and only some of those are within the control of the anesthesiologist. Institutional differences will determine the proximity of the birth suite to the operating rooms and the time-pressure to achieve surgical anesthesia will vary between individual cases and obstetricians. More so than ever, supply-chain restrictions may reduce the range of medications available to the anesthesiologist. Importantly, anesthesiologists must be aware of the potential for drug preparation or drug administration errors—wrong drug and/or wrong route errors—and how urgency may increase the potential for such errors. Numerous aspects need to be considered: (a) logistics; (b) technical; and (c) choice of medication. What is the local situation? What is the exact request of the obstetrician? Is the labor suite equipped with an operating room for CD or do we need to transfer the pregnant woman to a different level in the hospital? Where are the top-ups given (labor suite or in the operating room)? What exactly is administered regarding epidural anesthesia solution? What is the best local anesthetic solution for the given situation? Can we top-up as soon as practically and safely possible? Do we need to use a test dose or not? Do we use incremental bolus doses? How are we monitoring the patient? How much time are we given by the obstetrician (decision-to-delivery interval)? Do we use top-ups or do we need to use a different technique (repeat epidural; combined-spinal epidural), especially if the labor epidural was not producing a satisfactory outcome regarding pain relief? What happens is the epidural catheter is dislocated? When are we satisfied with the level and intensity of the block? When do we allow the obstetrician to start the CD? Do we have extra drug preparation time, as this may offset some of the time saved and there is always that potential risk of error and safety implications when mixing medications under the stress of an emergency situation?

Successful conversion of a labor epidural into an effective epidural for CD is a useful measure of quality of obstetric patient care. However, there is not one recipe to cover all problems, as anesthesiologists are confronted with unique situations in a large range of patients, obstetricians and hospitals in different situations, all with their specific particularities. This requires an experienced obstetric anesthesiologist to guarantee an optimal approach. Early inspection, testing and recognition of a poorly functioning epidural catheter is essential. Meticulous management of the epidural top-up is required, which only can be achieved after gaining adequate experience. The anesthesiologist needs to be familiar with the choice of the local anesthetic solution, the available preparations, and the use of correct doses. One needs to know how to best manage an epidural if there are missed sensory segments, unilateral blockade, or if there is an insufficient cephalad dermatomal sensory level to touch.

A safe approach is to use incremental doses to top-up an epidural, whereby each dose is a test dose. This protects the patients from harm due to accidental local anesthetic toxicity or a high block. Each top-up needs to be evaluated for bilateral and progressively cephalad blockade over a time interval, suitable to the urgency of the CD. Importantly, clinicians must accept that there is a failure rate for epidural top-up and inadequate intra-operative neuraxial block must be managed in a patient-focused manner. This individualized anesthesia management is the key to optimizing maternal and fetal outcomes.

Comment by Professor André Van Zundert & Associate Professor Victoria Eley

Keywords:

Regional Anesthesia for Cesarean Section; Pharmacology

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