Impact of timing of multimodal analgesia in enhanced recovery after cesarean delivery protocols on postoperative opioids: A single center before-and-after study.

STUDY OBJECTIVE: Enhanced recovery after cesarean delivery (ERAC) programs aim to decrease maternal morbidity and aid in maternal recovery and return to baseline. Multimodal analgesia is an important element of ERAC protocols, but no consensus exists on the timing of medication administration. We compared maternal pain outcomes following scheduled cesarean delivery with modification of the timing of administration of multimodal analgesia with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. DESIGN: Before-and-after study. SETTING: Labor and delivery unit at a single academic institution. INTERVENTION: NSAIDs and acetaminophen were administered as a fixed-interval alternating regimen every 3 h for the initial ERAC group (ERAC 1) and fixed-interval combined regimen every 6 h for the modified ERAC group (ERAC 2). ERAC 1 and ERAC 2 groups were compared to historical controls (Pre-ERAC). PATIENTS: 520 women undergoing scheduled cesarean delivery (Pre-ERAC n = 179, ERAC 1 n = 179, and ERAC 2 n = 162). MEASUREMENTS: The primary outcomes were postoperative total and daily opioid utilization as measured in morphine milligram equivalents (MME). Secondary outcomes included postoperative length of stay, maximum pain scores, and racial disparities in care. MAIN RESULTS: The modified schedule of non-opioid analgesics involving combined administration (ERAC 2) versus alternating administration (ERAC 1) of multimodal analgesia resulted in decreased total postoperative opioid utilization (median = 26.3 vs 52.5 MME, Bonferroni corrected P = 0.002). Total postoperative opioid utilization among the ERAC 2 group was also significantly reduced compared to the Pre-ERAC group (median = 26.3 vs 105.0 MME, Bonferroni corrected P < 0.0001). CONCLUSIONS: Multidisciplinary teams developing or modifying ERAC protocols for scheduled cesarean delivery should consider a combined administration at fixed intervals of NSAIDs and acetaminophen throughout the hospital stay to optimize postoperative pain management.

Sulfasalazine blocks the development of tactile allodynia in diabetic rats.

OBJECTIVE: Diabetic neuropathy is manifested either by loss of nociception (painless syndrome) or by mechanical hyperalgesia and tactile allodynia (pain in response to nonpainful stimuli). While therapies with vasodilators or neurotrophins reverse some functional and metabolic abnormalities in diabetic nerves, they only partially ameliorate neuropathic pain. The reported link between nociception and targets of the anti-inflammatory drug sulfasalazine prompted us to investigate its effect on neuropathic pain in diabetes. RESEARCH DESIGN AND METHODS: We examined the effects of sulfasalazine, salicylates, and the poly(ADP-ribose) polymerase-1 inhibitor PJ34 on altered nociception in streptozotocin-induced diabetic rats. We also evaluated the levels of sulfasalazine targets in sciatic nerves and dorsal root ganglia (DRG) of treated animals. Finally, we analyzed the development of tactile allodynia in diabetic mice lacking expression of the sulfasalazine target nuclear factor-kappaB (NF-kappaB) p50. RESULTS: Sulfasalazine completely blocked the development of tactile allodynia in diabetic rats, whereas relatively minor effects were observed with other salicylates and PJ34. Along with the behavioral findings, sciatic nerves and DRG from sulfasalazine-treated diabetic rats displayed a decrease in NF-kappaB p50 expression compared with untreated diabetic animals. Importantly, the absence of tactile allodynia in diabetic NF-kappaB p50(-/-) mice supported a role for NF-kappaB in diabetic neuropathy. Sulfasalazine treatment also increased inosine levels in sciatic nerves of diabetic rats. CONCLUSIONS: The complete inhibition of tactile allodynia in experimental diabetes by sulfasalazine may stem from its ability to regulate both NF-kappaB and inosine. Sulfasalazine might be useful in the treatment of nociceptive alterations in diabetic patients.