Modern labor epidural analgesia: implications for labor outcomes and maternal-fetal health.

Epidural analgesia is an important means of pain control during labor throughout the world. Over its historic development, it has been implicated in several undesirable outcomes, including prolongation of labor and increased need for operative delivery. These effects have emerged in some retrospective and observational studies, but such methods of investigation are highly prone to bias and are particularly ill-suited for the study of labor analgesia. In high-quality studies, including Cochrane reviews and meta-analyses, epidural analgesia has been suggested to extend the first stage of labor by 30 minutes and the second stage by 15 minutes, when compared with alternative forms of analgesia. Although this may be a reproducible effect, it may be argued that it is clinically negligible. With respect to mode of delivery, similar high-quality studies have consistently shown no increased risk of cesarean delivery associated with epidural analgesia. Some forms of epidural analgesia were associated with higher risk of assisted vaginal delivery, but the use of newer modalities has been shown to abolish this effect. Specific advancements have centered on reducing total anesthetic consumption, given that local anesthetic-induced motor block is theorized to interfere with maternal expulsive efforts in the second stage of labor. These measures include the use of low-concentration local anesthetic solutions equivalent to ≤0.1% bupivacaine, shown in meta-analyses to lead to no higher risk of assisted vaginal delivery relative to nonepidural analgesia. Additional advancements in the maintenance of analgesia include programmed intermittent epidural bolus and patient-controlled epidural analgesia, the combination of which has been shown to reduce the risk of assisted vaginal delivery, also likely mediated by reduction in local anesthetic dose. These techniques have gained popularity in the past two decades, such that studies published since 2005 show no higher risk of assisted vaginal delivery with epidural than with opioid analgesia (as reported in a Cochrane review). Labor epidural analgesia has implications for maternal and fetal health perinatally. It is known to result in transient maternal hypotension (particularly with initiation), which may progress to the level of necessitating fluid or vasopressor therapy. This is not clearly associated with any adverse outcomes. There is also a consistently higher incidence of fever in parturients receiving neuraxial anesthesia, likely of noninfectious origin, which has similarly not been associated with adverse neonatal outcomes. Finally, neonates of parturients who receive epidural analgesia have been shown to have no worse Apgar scores and more favorable acid-base status than their counterparts. These observations should serve to reassure providers that modern labor analgesia, as currently understood, is not consistently associated with any significant adverse outcomes for the parturient or fetus. In this review, we describe variations of modern labor epidural analgesia, conduct an in-depth review of current literature on its use, and explore the most up-to-date evidence on its implications for the progression and outcomes of labor, including the pertinent maternal and fetal side effects.

Neuraxial labor analgesia: Maintenance techniques.

Since the advent of neuraxial analgesia for labor, approaches to maintaining intrapartum pain relief have seen significant advancement. Through pharmacologic innovations and improved drug delivery mechanisms, current neuraxial labor analgesia maintenance techniques have been shaped by efforts to maximize patient comfort during the birthing process, while minimizing undesirable side effects and promoting the unimpeded progress of labor. To these ends, a modern anesthesiologist may avail themselves of several techniques, including programmed intermittent epidural bolus (PIEB), patient controlled epidural analgesia (PCEA) and dilute concentration local anesthetic + opioid epidural solutions. We explore the historical development and the evidential underpinnings of these techniques, in addition to several contemporary neuraxial labor analgesia practices. We also summarize current understanding of the effects these interventions have on maternal/fetal health and the labor course, as well as several important aspects of analgesic safety and monitoring.

A survey of labour epidural practices at obstetric anesthesia fellowship programs in the United States.

PURPOSE: Labour epidural analgesia (LEA) is an evolving field. Various neuraxial techniques and dosing regimens are available to the modern obstetric anesthesia provider, allowing for significant practice variability. To begin a search for consensus on optimal care, we sought to query fellowship training practices for LEA. METHODS: We conducted an electronic survey of institutions with American Council for Graduate Medical Education-accredited obstetric anesthesiology fellowship programs. We studied the frequency of epidural initiation techniques, including combined spinal epidural (CSE), dural puncture epidural, and epidural bolus. For maintenance techniques, we appraised the use of continuous epidural infusion, programmed intermittent bolus (PIEB), and patient-controlled epidural analgesia (PCEA). RESULTS: Of 40 institutions surveyed, we received 32 responses (80% response rate). Twenty-eight of 40 (70%) were included in the analysis. A plurality of institutions (12/28; 43%) preferred CSE, and among those who used CSE, 23/27 (85%) included intrathecal opioids. A majority of institutions used protocols with PIEB (55%), while almost all (92%) used PCEA. Most participants (88%) reported using dilute concentration maintenance infusions of 0.1% bupivacaine/ropivacaine or less. CONCLUSION: Despite significant variability in LEA practice, some clear patterns emerged in our survey, including preference for opioid-containing CSE and maintenance with PIEB, PCEA, and dilute epidural solutions.

RéSUMé: OBJECTIF: L'analgésie péridurale obstétricale (APO) est un domaine en évolution. Diverses techniques neuraxiales et posologies sont disponibles pour le praticien en anesthésie obstétricale moderne, ce qui permet une variabilité significative de la pratique. Pour démarrer une recherche de consensus sur les soins optimaux, nous avons cherché à déterminer les pratiques d'APO dans le cadre de formation des fellows. MéTHODE: Nous avons réalisé une enquête électronique auprès d'établissements possédant des programmes de fellowship en anesthésiologie obstétricale accrédités par l'American Council for Graduate Medical Education. Nous avons étudié la fréquence des techniques de péridurale, notamment de rachi-péridurale combinée (RPC), de péridurale avec ponction durale et de bolus péridural. Pour les techniques de maintien, nous avons évalué l'utilisation de l'analgésie péridurale par perfusion continue, l'administration programmée de bolus périduraux (PIEB; programmed intermittent epidural bolus) et l'analgésie péridurale contrôlée par la patiente (APCP). RéSULTATS: Sur les 40 établissements sondés, nous avons reçu 32 réponses (taux de réponse de 80 %). Vingt-huit des 40 (70 %) établissements ont été inclus dans l'analyse. Plusieurs institutions (12/28; 43 %) ont répondu qu'elles préféraient la RPC, et parmi celles qui utilisaient la RPC, 23/27 (85 %) incluaient des opioïdes intrathécaux. La majorité des établissements utilisaient des protocoles avec le PIEB (55 %), tandis que presque tous (92 %) utilisaient l'APCP. La plupart des établissements participants (88 %) ont rapporté utiliser des perfusions de maintien à des concentrations diluées de bupivacaïne/ropivacaïne de 0,1 % ou moins. CONCLUSION: Malgré une variabilité significative dans la pratique de l'APO, certaines tendances claires ont émergé dans notre sondage, notamment une préférence pour les RPC contenant des opioïdes et le maintien avec un PIEB, une APCP et des solutions péridurales diluées.

The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases.

Increased airway smooth muscle (ASM) contractility and the development of airway hyperresponsiveness (AHR) are cardinal features of asthma, but the signaling pathways that promote these changes are poorly understood. Tyrosine phosphorylation is tightly regulated by the opposing actions of protein tyrosine kinases and phosphatases, but little is known about whether tyrosine phosphatases influence AHR. Here, we demonstrate that genetic inactivation of receptor-like protein tyrosine phosphatase J (Ptprj), which encodes CD148, protected mice from the development of increased AHR in two different asthma models. Surprisingly, CD148 deficiency minimally affected the inflammatory response to allergen, but significantly altered baseline pulmonary resistance. Mice specifically lacking CD148 in smooth muscle had decreased AHR, and the frequency of calcium oscillations in CD148-deficient ASM was substantially attenuated, suggesting that signaling pathway alterations may underlie ASM contractility. Biochemical analysis of CD148-deficient ASM revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SRC family kinases (SFKs), implicating CD148 as a critical positive regulator of SFK signaling in ASM. The effect of CD148 deficiency on ASM contractility could be mimicked by treatment of both mouse trachea and human bronchi with specific SFK inhibitors. Our studies identify CD148 and the SFKs it regulates in ASM as potential targets for the treatment of AHR.