Discussion
bradycardia, labor pain, pain, agitation, pruritus, schizophrenia, Hypotension, urinary retention
DISORDER, ADVERSE EFFECTS, RESPIRATORY DEPRESSION, COMPLICATIONS
Opioids and alpha 2 agonists as epidural adjuvants were found to produce potent analgesic effects. These adjuvants not only improve the onset and duration of the block, but also reduce the need for other enteral or parental analgesics and gain better patient satisfaction [The current study investigated the addition of either nalbuphine or DEX to epidural bupivacaine on the duration of postoperative analgesia in patients scheduled for lower limb orthopedic surgeries. Our results proved that the addition of both nalbuphine and DEX faster the onset and prolonged the duration of analgesia than bupivacaine alone. The time required for the onset of sensory block was (12.17 ± 1.27, 13.39 ± 1.27, and 17.83 ± 2.53 min. in DEX, nalbuphine, and control groups respectively) and the duration of epidural analgesia was 365.87 ± 18.01 min in DEX group versus 318 > 38 ± 22.54 min in nalbuphine group and 241.3 ± 14.24 min in control group. Therefore, the fastest onset and longest duration were obtained in the DEX group.Since, the discovery of opioid receptors in the brain and spinal cord, the postoperative analgesia field has changed with several opioids have been studied as adjuvants to local anesthetics in order to minimize side effects and prolong the duration of both intraoperative and postoperative analgesia. Nalbuphine is an opioid with agonistic action at kappa and antagonistic action at µ receptors that was found to provide adequate analgesia in visceral nociception and to improve postoperative analgesia [DEX could be an opioid-sparing epidural adjuvant that produces its analgesic effect by hyperpolarization of post-synaptic dorsal horn neurons and inhibiting the release of C fibers transmission [In the present study, the number of top-up doses and the VAS scores were also significantly lower in DEX group patients, and the persistence of pain after 3 top-up doses with the need for ketorolac was significantly different between the three groups where it was highly needed with larger doses in control group when compared to nalbuphine and DEX groups.However, in this study, the level of sedation was higher in DEX group, which could be attributed to the highly selective α-2 adrenergic agonist action with sedative, sympatholytic and analgesic effects, while nalbuphine is a µ receptor antagonist that has a ceiling effect on sedation where additional sedation does not increase with dose increasing [Regarding adverse effects, the incidence of bradycardia in our study was significantly common in DEX group patients which is explained by the DEX central action decreasing the sympathetic outflow and norepinephrine release, as found in several previous studies [Hypotension was observed more often in control group patients however it was not statistically significant between groups. This shows that the epidural administration of DEX and nalbuphine in their respective doses we opted to use in our study were safe in providing hemodynamically stable perioperative period. Additionally, the incidence of adverse effects and complications in our study were minimal and managed appropriately and because of fewer side-effects in DEX group, high degrees of satisfaction were obtained in this group.Therefore, our findings support that the addition of either nalbuphine or dexmedetomidine to epidural bupivacaine was effective for postoperative analgesia and the earlier onset as well as the longest analgesic duration with fewer side effects and higher patient satisfaction scores were observed in DEX group. This is in line with the results of Khobragade et al., who compared the addition of DEX and nalbuphine to bupivacaine in epidural anesthesia for infraumbilical and lower limb surgeries and found that the onset of sensory block was significantly earlier, and the analgesia duration was significantly prolonged in DEX group versus nalbuphine group (10.06 ± 4.42 versus 13.88 ± 7.83 min., and 353.86 ± 51.36 versus 295.28 ± 65.95 min for the onset and duration of analgesia respectively) with stable hemodynamics and fewer side effects in DEX patients concluding that DEX is a better adjuvant than nalbuphine for epidural anesthesia [DEX and nalbuphine were also investigated as epidural adjuvants to 0.25% bupivacaine for labor analgesia by El Fawal and his colleagues concluding that both provided satisfactory labor analgesia without severe side effects and that DEX has a faster onset than nalbuphine [Despite the aforementioned studies supporting the epidural use of either DEX or nalbuphine with no harm, up to the best of authors’ knowledge DEX and nalbuphine are currently not approved by FDA for epidural administration. Nalbuphine was approved by FDA for moderate to severe pain that requires an opioid agent when other alternative treatments have been inadequate in 1998 and DEX was initially approved in 1999 for short-term sedation (< 24 h) in ICUs and in 2022, FDA approved its sublingual formulation for acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. Although they are widely used in anesthesia as an adjuvant in neuraxial blocks as well as the outcome of most studies is encouraging, FDA did not approve their off-label use as an epidural adjuvant. Several nalbuphine non-FDA approved uses do exist, such as treatment of labor pain, opioid-induced respiratory depression, opioid-induced urinary retention, and pruritus linked to neuraxial opioid administration as well as it is increasingly used during neuraxial blocks due to its high safety. Also, epidural DEX was demonstrated in various studies to be well tolerated. Hence, FDA approval is required for the uncontroversial use of both DEX and nalbuphine in anesthesia practice.The limitations of our study are the relatively small sample size of patients who were included, the subjectivity of VAS for pain assessment with a variable level of understanding between patients, and there are no available comparisons of equipotent dosing of epidural nalbuphine versus dexmedetomidine.