Editorial commentary on: Using dexamethasone as an adjuvant to levobupivacaine in epidural anesthesia to change the pain intensity and duration in painless labor.

Severe excruciating pain being the essential hallmark of labor, many methods have been tried to mitigate this pain while facilitating a safe delivery of the neonate. Cesarean section comes with its own benefits but also with its own costs, which are well known. Neuraxial analgesia is established for a number of decades now as the gold standard for conducting “painless labor,” predominantly by epidural route or by combined spinal–epidural analgesia. Local anesthetic agents such as bupivacaine and more recently ropivacaine and levobupivacaine, with relatively better safety profiles, are routinely used for producing such analgesia in consenting parturients without contraindications.[1]

However, this is not in itself the end of the road because of the constant endeavor to further enhance the quality and quantity of pain relief, while not compromising the safety of both the mother and the fetus. Herein, lies the rationale for trials of several “adjuvant” drugs alongside the local anesthetic agent. The word “adjuvant” was initially used in the context of cancer treatment, as an additional agent or therapy that could improve the body's response to the primary cancer treatment modality, for example, adjuvant radiotherapy added to the primary chemotherapy to enhance the chances of survival. However, the meaning and application of the word adjuvant has now extended to any additional drug, agent, or therapy used in conjunction with the primary drug, agent, or therapy to enhance the effectiveness of the treatment.

In the context of labor analgesia, several such adjuvants have been studied in the past, most notably opioids such as fentanyl, which is now used commonly along with local anesthetics in many centers. However, one has to be careful because of potentially debilitating adverse effects of strong opioids on the mother and fetus. Other adjuvants include clonidine, neostigmine, epinephrine, and magnesium sulfate. However, other than fentanyl, none of the adjuvants studied has passed the test of time and acceptability, hence the search continues.[23]

In this issue of the Journal, a randomized double-blind controlled trial from a teaching hospital in Cairo, Egypt, looks at the analgesic efficacy and short-term safety of adjuvant epidural fixed-dose (8 mg) dexamethasone in addition to 0.125% levobupivacaine in laboring parturients. The primary outcome was duration of analgesia, calculated as the time of onset of pain relief (visual analog scale pain score <4 on a 0–10 scale) to the time to the first top-up dose on patient request. The secondary outcome was the total dose of levobupivacaine needed through the labor till delivery, at which point the study was terminated. Apgar score in 1 and 5 min, umbilical vein blood–gas analysis, and maternal satisfaction on a 4-point scale were also noted. The dexamethasone group had a significantly longer duration of analgesia and significantly lower consumption of local anesthetic. There were no statistical differences between the two groups regarding hemodynamics, pain score, neonatal outcome, and complications. However, only three complications – nausea, vomiting, and shivering – were noted. Data on maternal satisfaction were not presented, stating that in both groups “maternal satisfaction was achieved in all patients.” Duration of labor was not noted, though one of the stated hypotheses of the study was “it (adjuvant epidural dexamethasone) will neither increase the time to delivery nor the fetal outcome.” More importantly, the dose of levobupivacaine needed to be duration adjusted; prolonged labor in one group would have biased the consumption of the drug to a higher side.

The exact mechanism of epidurally administered dexamethasone is not known, but is important to ponder so as to adjust the timing and dosing of the drug. Steroids ultimately exert their action by influencing gene transcription. The steroid receptor complex enters the cell nucleus and binds to the chromosomes, affecting the genetic machinery.[4] This should require some time for their actions to be manifested. Other speculations regarding their mechanism of action include a direct action on the nociceptive C-fibers by blocking their ectopic discharge or an anti-prostaglandin mechanism of anti-inflammatory action.[56] This may be studied in the future by altering the route, mode, timing of administration, and dose of dexamethasone. Long-term safety observations, especially on the neonates, are also needed, beyond the 5-min Apgar scores.

There is a reasonable scientific evidence database now to suggest that dexamethasone, administered intravenously or in nerve blocks, prolongs the duration of analgesia and improves postoperative or postblock pain control.[7] Evidence of its efficacy through the epidural route is less robust but available.[8] Studies have been lacking so far to apply this knowledge in the context of labor analgesia. This study adds some welcome fuel to the newly ignited fire, and more evidence is urgently required now to bolster the evidence base in this important area. Such evidence must come from different countries with different regulations on drug usage and with variations in study designs so that the confidence in this finding may be buttressed (or weakened!), and hopefully that can throw some light on the possible mechanism of action as well.