ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Pharmacologic management of pain during labor and delivery

Pharmacologic management of pain during labor and delivery
Literature review current through: Jan 2024.
This topic last updated: Sep 30, 2022.

INTRODUCTION — Multiple pharmacologic and non-pharmacologic options are available to help women manage pain during labor. This topic will discuss labor pain pathways, the consequences of labor pain, and options for pharmacologic management. Nonpharmacologic management of labor pain is discussed separately. (See "Nonpharmacologic approaches to management of labor pain".)

Neuraxial labor analgesia (eg, spinal, epidural, and combined spinal-epidural), which is a subset of pharmacologic management of labor pain, is discussed in detail separately. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)".)

MATERNAL PERCEPTION OF LABOR PAIN — The way pain is experienced is a reflection of the individual’s emotional, motivational, cognitive, social, and cultural circumstances [1]. Many women, especially nulliparas, rate the pain of labor as very severe or intolerable [2,3]. The pain of labor and delivery varies among women, and each of a woman’s labors may be quite different. As an example, an abnormal fetal presentation (eg, occiput posterior) is associated with more severe pain and may be present in one pregnancy, but not the next.

The American College of Obstetricians and Gynecologists (ACOG) notes that there is no other circumstance in which it is considered acceptable for an individual to experience severe pain, amenable to safe pain relief, while under a physician’s care [4]. ACOG supports the concept that maternal request alone is a sufficient medical indication for labor analgesia, and recognizes that the use of neuraxial labor analgesia does not cause an increase in the incidence of cesarean delivery.

Although lower levels of labor pain have been correlated with higher levels of childbirth satisfaction, higher levels of labor pain do not preclude an overall satisfying experience. When interviewed after delivery, mothers tend to downplay the intensity of their labor pain [5] and it is not the most important factor influencing satisfaction with the childbirth experience [6]. However, a sense of personal control over decision-making processes in labor has consistently been shown to correlate with overall maternal satisfaction with childbirth [7,8]. A study of 100 women undergoing vaginal delivery reported that satisfaction with pain relief was associated with feelings of being in control and having input in the decision-making process [8].

These findings suggest that women should be involved in the decision-making process regarding all aspects of childbirth, including pain relief. This can be accomplished by educating women about pain relief techniques during pregnancy, prior to the onset of labor, so that they can carefully consider their options before labor commences, as the pain and stress of labor may preclude detailed discussion of risks and benefits.  

PAIN PATHWAYS — Pain originates from different sites as the process of labor and delivery progresses.

First stage of labor — Pain during the first stage of labor is visceral or cramping. It originates in the uterus and cervix, and is produced by distention of uterine and cervical mechanoreceptors and by ischemia of uterine and cervical tissues. The pain signal enters the spinal cord after traversing the T10, T11, T12, and L1 white rami communicantes. In addition to the uterus, labor pain can be referred to the abdominal wall, lumbosacral region, iliac crests, gluteal areas, and thighs [9].

Transition (7 to 10 cm cervical dilation) refers to the shift from the late first stage to the second stage of labor. Transition is associated with greater nociceptive input as the parturient begins to experience somatic pain from vaginal distention.

Second stage of labor — Pain in the second stage of labor is reported as being more severe than first stage pain [9]. Second stage pain includes a combination of visceral pain from uterine contractions and cervical stretching, and somatic pain from distention of vaginal and perineal tissues. The somatic pain signal is transmitted to the spinal cord via the pudendal nerve (S2, S3, and S4). During the second stage of labor, the parturient also experiences rectal pressure and an urge to “bear down” and expel the fetus as the presenting part descends into the pelvic outlet.

ADVERSE CONSEQUENCES OF LABOR PAIN — The pain of labor produces physiologic changes, and may be associated with potential emotional distress and suffering, (table 1) [9]. Pain causes a neuroendocrine stress response, with effects on multiple maternal and fetal organ systems [9]. The cardiopulmonary physiologic responses to pain are usually well tolerated by healthy parturients with normal pregnancies, but may be of more concern in parturients with cardiopulmonary disease or preeclampsia and at risk fetuses. Most of these effects can be reduced or eliminated with effective pain relief. (See "Anesthesia for labor and delivery in high-risk heart disease: General considerations" and "Anesthesia for the patient with preeclampsia", section on 'Labor analgesia'.)

Hyperventilation — Intermittent hyperventilation consistently accompanies labor pain. The resultant hypocarbia can inhibit ventilatory drive and, in the absence of supplemental oxygen, can cause maternal and fetal hypoxemia [10,11]. Respiratory alkalosis shifts the oxyhemoglobin curve to the left, increasing the affinity of oxygen for maternal hemoglobin, thereby decreasing off-loading of oxygen across the placenta to the fetus. Severe maternal alkalosis can cause utero-placental vasoconstriction, resulting in decreased fetal blood flow and oxygen delivery [12]. Epidural analgesia reverses the adverse ventilatory effects of pain [13] and results in an increase in oxygen tension in both mother and fetus [14,15].

Neurohumoral effects — Neurohumoral responses to stress and pain may adversely affect placental perfusion and fetal oxygenation, and may be reversed by analgesia. Elevated plasma catecholamines increase maternal peripheral vascular resistance and decrease uteroplacental perfusion. Studies in pregnant sheep have found that pain increased circulating catecholamines and significantly decreased blood flow to the uterus [16]. In pregnant primates, stress and pain were shown to lower fetal oxygenation, cause fetal acidosis, and slow fetal heart rate [17,18]. Removal of the stressful stimulus or sedation with pentobarbital or nitrous oxide reversed these changes.

In a study of 103 nulliparous women with uncomplicated singleton pregnancy at term, stress hormone levels after delivery were lower in patients who underwent elective cesarean delivery with epidural anesthesia than in patients who had vaginal deliveries without analgesia, vaginal delivery with epidural analgesia, and patients who had instrumented deliveries with or without epidural analgesia [18]. The clinical significance of these results in the fetus is unclear.

Small human studies have reported that epidural and intrathecal fentanyl analgesia reduce concentrations of circulating maternal epinephrine, probably by reducing maternal pain and anxiety [19-21]. (See "Anesthesia for labor and delivery in high-risk heart disease: General considerations" and "Anesthesia for the patient with preeclampsia", section on 'Advantages of neuraxial labor analgesia'.)

Psychological effects — In addition to untoward physiological effects, unrelieved pain may also contribute to the development of postpartum psychological trauma.

Women who experience unrelieved pain during childbirth may be more likely to develop postpartum depression [22,23]. In a study of 1288 women following vaginal or cesarean delivery, the severity of acute postpartum pain, rather than the mode of delivery, correlated with the incidence of postpartum depression [24]. However, some studies have not found neuraxial analgesia to be protective against developing postpartum depression [25],.One study identified an increased risk of postpartum depression in women who had planned to avoid but then received epidural labor analgesia [26]. These disparate findings may be explained by many confounding variables and methodological challenges inherent to such studies [27]. (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Risk factors'.)

The reported prevalence of posttraumatic stress disorder (PTSD) after childbirth varies depending on the definition used. Its occurrence has profound effects on the mother and baby [28,29]. The etiology of PTSD is complex and multifactorial. Although unrelieved pain during childbirth has been associated PTSD [30], most studies have not identified pain per se as an independent variable. (See "Overview of the postpartum period: Disorders and complications", section on 'Mental health issues'.)

PLAN FOR LABOR ANALGESIA — For most healthy patients, the selected method for pain relief during labor is simply a matter of patient choice. Some women prefer to avoid pharmacologic pain management completely. Others decide to wait to see how well they tolerate labor and ask for systemic analgesics or neuraxial analgesia as needed. Still other patients want complete pain relief as soon as possible during labor; for these patients neuraxial analgesia is usually the best choice.

Neuraxial analgesia provides more consistently effective labor analgesia than other options. Neuraxial analgesia with low concentration local anesthetic does not increase the risk of cesarean delivery or instrumental delivery, but is associated with possible side effects and complications, which are discussed in detail separately. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics".)

Systemic analgesics may be associated with sedation and respiratory depression, and are transferred across the placenta to the fetus. (See 'Systemic analgesics' below.) However, systemic analgesics or nerve blocks may be beneficial for patients who prefer less invasive analgesic techniques (compared with neuraxial analgesia), or in whom neuraxial techniques are not reasonable options due to coagulopathy or anatomic abnormalities (eg, spinal deformity or hardware).

Neuraxial analgesia may be medically indicated for patients with anticipated difficulty with intubation, a history of malignant hyperthermia or some cardiovascular and respiratory disorders, and for prevention of autonomic hyperreflexia in women with a high spinal cord lesion [31]. Neuraxial anesthesia is also preferred for women with preeclampsia [31]. These issues are discussed separately. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)", section on 'Preparation for surgical anesthesia' and "Anesthesia for labor and delivery in high-risk heart disease: General considerations" and "Anesthesia for adults with chronic spinal cord injury", section on 'Analgesia for labor and delivery' and "Anesthesia for the patient with preeclampsia", section on 'Labor analgesia'.)

Management of labor pain may be challenging in patients who are opioid tolerant or take methadone or buprenorphine for management of opioid use disorder, and is discussed separately. (See "Opioid use disorder: Overview of treatment during pregnancy", section on 'Analgesia and anesthesia'.)

Efficacy of systemic analgesia is discussed below.

PHARMACOLOGIC OPTIONS FOR LABOR ANALGESIA — Pharmacologic approaches to manage childbirth pain can be broadly classified as either systemic or locoregional. Systemic administration includes parenteral and inhalation routes. Locoregional analgesic techniques consist of neuraxial techniques (ie, epidural, spinal, combined spinal-epidural, or dural puncture epidural [32]) and pudendal and paracervical nerve blocks . We suggest the use of neuraxial analgesia for parturients who desire pharmacologic management of labor pain, because of optimal analgesia and minimal side effects for the parturient and fetus.

PATIENTS WITH CONFIRMED OR SUSPECTED COVID-19 — Understanding of coronavirus disease 2019 (COVID-19) is evolving. UpToDate has added information on many aspects of COVID-19, including infection control, airway and other aspects of anesthetic management, intensive care, and obstetric issues. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)", section on 'Patients with COVID-19' and "COVID-19: Overview of pregnancy issues".)  

A primary concern when caring for patients with COVID-19 is avoidance of aerosolization of airway secretions, which is likely to occur during endotracheal intubation for general anesthesia. COVID-19 is not a contraindication to neuraxial anesthesia. Early epidural analgesia may reduce the need for general anesthesia and airway management, should emergency cesarean delivery become necessary.

The Society for Obstetric Anesthesia and Perinatology and Society for Maternal Fetal Medicine have created COVID-19 guidance that includes recommendations for appropriate personal protective equipment for health care workers caring for laboring patients. For patients with confirmed or suspected COVID-19, health care workers should use contact and droplet precautions (ie, gown, gloves, surgical mask, face shield or goggles). During the patient’s second stage of labor and during episodes of deep respiratory efforts, health care workers should also use airborne precautions (ie, N95 mask or powered air purifying respirator [PAPR], where available), in addition to contact and droplet precautions.

Important considerations for obstetric anesthesia and for obstetric care in patients with known or suspected COVID-19 are discussed separately. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)", section on 'Patients with COVID-19' and "COVID-19: Intrapartum and postpartum issues", section on 'Approach to infection control'.)

REGIONAL ANALGESIA TECHNIQUES

Neuraxial analgesia — Neuraxial techniques provide unparalleled pain relief for labor and delivery when actively managed by a provider and replaced when malfunctioning [33]. The use of neuraxial labor analgesia varies by country. In a 2016 obstetric anesthesia workforce survey in the United States, spinal, epidural, or combined spinal-epidural was used for more than 70 percent of women who gave birth [34]. In contrast, according to the National Health Service Maternity Statistics for 2017 to 2018, approximately 40 percent of parturients in the United Kingdom had neuraxial labor analgesia [35].

The risks and benefits of initiation of neuraxial blockade in laboring women must be considered on a case-by-case basis. Although there are few contraindications to neuraxial labor analgesia, in certain settings such as coagulopathy, increased intracranial pressure, or skin infection of the lower back, the advantages of neuraxial analgesia must be weighed against its risks. These issues are discussed separately. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Spinal epidural hematoma' and "Obstetric and nonobstetric anesthesia for patients with neurologic disorders", section on 'Neuraxial anesthesia for patients with brain tumors' and "Serious neurologic complications of neuraxial anesthesia procedures in obstetric patients", section on 'Risk factors for spinal epidural abscess'.)

Neuraxial analgesia for labor, delivery, and instrumental delivery is discussed in depth separately. (See "Neuraxial analgesia for labor and delivery (including instrumental delivery)".)

Pudendal nerve block — Bilateral pudendal nerve blocks are useful for alleviating pain arising from vaginal and perineal distention during the second stage of labor [33]. They may be used as a supplement for epidural analgesia if the sacral nerves are not sufficiently anesthetized. Pudendal nerve blocks may also be performed to provide analgesia for low forceps delivery, but they are inadequate for mid-forceps delivery (rarely performed). (See "Pudendal and paracervical block" and "Assisted (operative) vaginal birth", section on 'Forceps'.)

Paracervical block — Paracervical block is no longer used for labor analgesia in the United States, in part because of a high incidence of fetal bradycardia. Paracervical block for labor analgesia is discussed separately. (See "Pudendal and paracervical block", section on 'Active phase of labor'.)

SYSTEMIC ANALGESICS — The most commonly used systemic labor analgesics are opioids and mixed opioid agonists-antagonists. Inhaled nitrous oxide may be an option as well. A list of systemic analgesics used in labor and delivery is provided in the table (table 2). The most commonly used medications are discussed here.

Opioid analgesia — Patients desiring pain relief during labor are likely to be offered opioids when neuraxial analgesia is not an option. Opioids have the advantages of ease of administration, wide availability, lower cost, and are less invasive than neuraxial techniques, though substantial relief of labor pain is generally not achieved. In one study of women who received meperidine or morphine for labor analgesia, the opioid resulted in somnolence with little change in pain scores [36]. Opioids cross the placenta, which may be manifested in utero by decreased fetal heart rate variability and in the neonate by respiratory depression and neurobehavioral changes [37,38].

A 2018 systematic review found that parenteral opioids (intramuscular [IM] or intravenous [IV], including patient controlled analgesia) during labor provided some pain relief and moderate satisfaction with analgesia, although up to two-thirds of women who received opioids reported moderate or severe pain and/or poor or moderate pain relief one or two hours after administration [39]. Opioids were associated with maternal nausea, vomiting, and drowsiness. The review did not identify the ideal parenteral opioid for pain relief during labor and delivery, and the overall quality of the data was low to very low.

Opioid administration should be considered carefully close to delivery, since it is preferable to avoid sedation while the parturient is pushing, and fetal effects may be prolonged if opioids are administered near delivery [4].

Patient controlled analgesia (PCA) — Use of a PCA pump allows the patient to self-administer a programmed dose of IV medication with lockout intervals between doses. This method of opioid administration is the most effective option for the parturient in whom neuraxial analgesia is contraindicated, not desired, or not available [40-42]. PCA provides rapid onset of analgesia, better control of pain relative to side effects than intermittent parenteral opioid injection, and a sense of control for the patient [43]. Shorter-acting opioids (eg, fentanyl or remifentanil) are preferred in the labor setting to allow rapid changes in plasma levels to match the changing clinical need.

Remifentanil PCA — The author uses remifentanil PCA as the option for patients who require systemic opioid labor analgesia, as it has rapid onset, ultrashort duration, and is metabolized rapidly [44]. Remifentanil PCA is less effective than neuraxial analgesia, but more effective than long-acting opioid analgesia or nitrous oxide [43,45,46]. However, remifentanil is a potent respiratory depressant; oxygenation and respiratory rate should be continuously monitored when remifentanil PCA is used [47-49], and one to one nursing care is indicated.

Remifentanil is metabolized by nonspecific plasma and tissue esterases, so although it rapidly crosses the placenta, it is metabolized rapidly in the fetus [50]. Onset occurs in 30 to 60 seconds, with peak effect at 2.5 minutes [51]. A dose initiated at the beginning of one contraction likely exerts its analgesic effect during the subsequent contraction, but parturients effectively learn when to self-administer a dose [52]. Published regimens for remifentanil PCA include bolus doses of 10 to 50 mcg, lockout times of one to five minutes, and no background infusion [52,53]. No loading dose is necessary for remifentanil PCA for labor analgesia. The PCA protocol used by the European RemiPCA SAFE Network hospitals includes bolus doses of 10 to 30 mcg IV remifentanil, a lockout interval of two minutes, and no background infusion [54]. A lockout interval of at least three minutes will prevent administration of additional doses before peak analgesic effects and maximal side effects have occurred [55]. A practical issue with using remifentanil PCA is that the desired lockout interval may be shorter than is permitted by some PCA pumps.

Risk of respiratory depression – Multiple studies have reported respiratory depression in parturients who received remifentanil PCA, and there are at least four case reports of maternal respiratory or cardiac arrest during remifentanil PCA [55-57]. Examples of studies of remifentanil PCA labor analgesia include the following:

In a trial comparing remifentanil PCA (20 to 60 mcg demand dose, lockout interval one to two minutes) with epidural analgesia for labor, 9 out of 19 of the patients using remifentanil had episodes of apnea during the first two hours of PCA use [41].

In another trial, approximately 1400 patients were randomly assigned to receive remifentanil PCA (30 mcg on request with three minute lockout interval) or epidural analgesia on request [42]. For those who received analgesia, overall satisfaction with pain relief was significantly higher for epidural analgesia, and oxygen saturation was significantly lower (SpO2 <92 percent) in patients who used remifentanil [42].

In the RESPITE trial, 400 patients were randomly assigned to receive remifentanil PCA (40 mcg bolus, two minute lockout interval) or meperidine (100 mg intramuscular, up to every four hours) for labor analgesia [49]. Supplemental oxygen was required to treat low SpO2 in 41 percent of patients who received remifentanil, compared with 1 percent of patients who received meperidine. Patients who received remifentanil were significantly less likely to progress to epidural analgesia, and less likely to require instrumental delivery. There were no differences in neonatal outcome.

In response to the introduction of remifentanil for labor analgesia, the RemiPCA SAFE Network of hospitals and registry was created in 2009 in Switzerland and Germany [54]. Participating hospitals followed a multidisciplinary protocol for remifentanil administration, which was modified over time as relevant literature was published. An audit of outcomes for 5740 cases reported to the network between 2010 and 2015 found that maternal hypoxia (SpO2 <94 percent) occurred in 25 percent of patients. Neonatal resuscitation thought to be related to remifentanil was required in 0.3 percent, and supplemental oxygen was required in 5 percent of neonates. Based on their data, recommendations for practice include no background infusion, no other concomitant analgesic use (including nitrous oxide), maximum bolus dose of 30 mcg, lockout interval of two minutes, constant one-on-one nursing care, continuous SpO2 monitoring, and no supplemental O2 unless SpO2 saturation <94 percent.

We begin our remifentanil PCA with a demand bolus dose of 20 mcg and increase or decrease for pain or somnolence, respectively. At the author’s institution, patients who receive remifentanil PCA are monitored with continuous pulse oximetry and one-on-one nursing to monitor respiratory status. We avoid prophylactic administration of supplemental oxygen as it may mask diagnosis of inadequate ventilation in patients monitored with pulse oximetry alone. In one study including parturients receiving IV PCA remifentanil, end-tidal CO2 monitoring detected most episodes of apnea, while pulse oximetry missed most episodes of apnea [56]. Supplemental oxygen should be administered and the bolus demand of remifentanil should be decreased if the parturient becomes drowsy between contractions, if the arterial oxygen saturation (SaO2) falls below 94 percent, or if the respiratory rate falls below 10 per minute in a sedated parturient.

Fentanyl PCA — Fentanyl PCA is an alternative to remifentanil; it provides effective pain relief and low risk of side effects, although data are limited to a few small studies. Fentanyl has rapid onset, relatively short duration of action (though longer than remifentanil), and lacks active metabolites. Typical regimens for fentanyl PCA include a 50 to 100 mcg initial loading dose, demand doses of 10 to 25 mcg, and lockout intervals of 5 to 10 minutes, without a background infusion [58-60]. The author initiates fentanyl PCA with a demand dose of 20 mcg, a lockout interval of 5 minutes, and no background infusion. If necessary, we increase the demand dose in 10 mcg increments to optimize pain control. Small studies have found fentanyl PCA to provide either more effective analgesia or fewer side effects than PCA morphine, meperidine, or alfentanil [61-63].

We monitor patients who receive fentanyl PCA as we would for patients who receive bolus dose systemic opioids; labor nurses monitor the level of sedations and respiratory status.

There is insufficient evidence to compare efficacy and side-effects of fentanyl PCA to remifentanil PCA.

Intermittent bolus opioid — Systemic opioids used to manage labor pain have traditionally been administered by the subcutaneous, IM, or IV routes. This method of administration continues to be offered in many locations where more effective neuraxial analgesia or PCA opioids are not available due to lack of skilled personnel, equipment, or cost considerations. The subcutaneous and IM routes are relatively safe and simple to use, but involve painful injections, delay in onset, and variable absorption leading to unpredictable plasma levels. IV injection has a faster onset with less variability of peak concentrations, and thus the ability to titrate doses to effect.

Choice of opioid — For patients in whom neuraxial analgesia and PCA are not options, we prefer to use IV doses of mixed agonist-antagonists (eg, nalbuphine 2.5 to 10 mg IV) every 2 to 4 hours, depending on the level of analgesia and maternal sedation [4]. There is a dose ceiling effect with regard to respiratory depression in contrast to longer-acting opioids such as morphine [64]. Similar to other opioids, nalbuphine is associated with opioid side effects in the mother and fetus; maternal dysphoria may be particularly disconcerting.

Fentanyl has been used to provide labor pain relief, but due to its short duration of action it is more suited for IV PCA administration. (See 'Patient controlled analgesia (PCA)' above.)  

Morphine may be used to provide labor analgesia; however, lack of efficacy at nonsedating doses and maternal and neonatal side effects have resulted in decreased usage in many labor units where superior means of analgesia, such as regional techniques, are available [36,65].

Meperidine is commonly administered for labor analgesia in the United Kingdom [39], while it has fallen out of favor in the United States. We avoid meperidine because of potential side effects in both the parturient and the neonate, although it is the most commonly prescribed opioid for labor pain relief worldwide [66]. Neonatal effects are primarily related to accumulation of the very long acting metabolite, normeperidine. Classic teaching is that meperidine should be administered within one hour or more than four hours before delivery as meperidine reaches a maximal concentration in the fetus from two to three hours after maternal dosing. However, normeperidine may affect neonatal behavior and hinder breastfeeding regardless of the timing of maternal administration [67-69]. In addition, unlike meperidine, normeperidine is not reversed by naloxone. Potential side effects (eg, serotonergic crisis, seizures, and normeperidine neurotoxicity) and multiple drug interactions (eg, monoamine oxidase inhibitors [MAOIs]) are additional reasons to avoid meperidine. Evidence increasingly suggests that other opioids may provide superior analgesia, compared with meperidine [70].

Acetaminophen and nonsteroidal anti-inflammatory drugs — The literature regarding the efficacy of nonopioid analgesics (ie, acetaminophen and nonsteroidal anti-inflammatory drugs [NSAIDs]) is limited. NSAIDs are avoided during labor because of their potential for precipitating premature closure of the ductus arteriosus [71]. We do not offer acetaminophen for labor analgesia because of its limited efficacy.

Several small studies have reported that intravenous acetaminophen provides modest reduction in visual analogue scale (VAS) pain scores, compared with placebo [72,73].

Studies comparing acetaminophen with opioids for labor analgesia have shown mixed results. In one small study, 40 laboring women were randomly assigned to receive acetaminophen or morphine during the first stage of labor. There were no differences in VAS scores or side effects between the groups, but 50 percent of the patients who received acetaminophen required rescue analgesia within 120 minutes of initial drug administration [74], compared with 18 percent of those who received morphine. In contrast, studies that compared acetaminophen with tramadol [75] and pethidine (meperidine) [76] have reported comparable reduction in VAS scores for one to two hours, with fewer maternal side effects in those who received acetaminophen.

Sedatives and analgesic adjuncts — Various agents have been used to minimize opioid side effects or provide sedation, relief from anxiety, or analgesia during labor. Nonopioid agents (eg, promethazine, a phenothiazine, or hydroxyzine, an antihistamine) are often administered in combination with an opioid to potentiate analgesia and decrease nausea and nausea and vomiting [33]. They are less effective used alone than opioids, although they appear to provide some relief [77].

Scopolamine is a muscarinic anticholinergic drug that induces a dissociative state. Scopolamine was used in combination with an opioid for “twilight sleep,” a technique popularized at the beginning of the 20th century, but it causes delirium and extreme agitation, sedation, and amnesia, and is rarely used for labor analgesia today.

Ketamine is a phencyclidine derivative that produces a dissociative state and analgesia. It is a potent amnestic, and has a rapid onset of action (less than one minute after intravenous administration). Ketamine tends to preserve airway reflexes, but also increases airway secretions, which may lead to laryngospasm. Its propensity to produce psychotomimetic effects may be prevented with coadministration of benzodiazepines. Ketamine will induce general anesthesia at doses of 1 mg/kg IV, but lower doses (0.1 to 0.2 mg/kg IV titrated to effect) may be used to provide analgesia for vaginal delivery or minor operative procedures, such as manual uterine exploration.

Benzodiazepines (eg, midazolam and diazepam) are anxiolytics that may be used for sedation during vaginal delivery. Midazolam is preferred because it is nonirritating to veins, and has a short duration of action. Similar to ketamine, benzodiazepines at high doses are potent amnestics that may impair the mother’s memory of the birth if administered during labor. Relatively low doses should not produce amnesia. As an example, in a study of patients undergoing planned cesarean delivery, a combination of 0.02 mg x kg–1 midazolam and 1 mcg/kg fentanyl IV prior to administration of spinal anesthesia did not affect maternal recall of the birth [78]. In addition, airway reflexes are obtunded, which is a risk factor for aspiration, especially since parturients in labor typically have increased gastric contents and delayed gastric emptying.

Nitrous oxide — Nitrous oxide inhalation analgesia (usually a blend of 50 percent nitrous oxide and 50 percent oxygen gas) for labor pain has been used for decades in Great Britain, Scandinavia, Australia, New Zealand, Canada, and other countries, but less commonly in the United States [79-81]. A number of institutions in the United States have made nitrous oxide available for labor analgesia, partly due to approval of new nitrous oxide administration systems for delivery room use by the US Food and Drug Administration (FDA) [82].

Nitrous oxide administration technique The parturient self-administers the anesthetic gas, as needed, using a hand-held face mask over her nose and mouth or a mouthpiece. A demand valve on the portable gas tank opens with inhalation and closes with exhalation. Correctly timing each inhalation is important because analgesia takes up to 50 seconds to take effect [83]. Thus, peak analgesia will occur out of phase with uterine contractions if the gas is administered with onset of contractions, which usually peak 30 seconds after they begin and last one minute.

Due to the time lag for nitrous oxide to take effect, inhalation should begin approximately 30 seconds before the contraction is expected to begin and should cease as the contraction begins to recede. This makes use of nitrous oxide particularly challenging during the second stage, as the parturient needs to be alert to push during the contraction.

Safety of nitrous oxide The safety of this technique for the parturient depends on the fact that she will be unable to hold the mask if she becomes too drowsy, and thus will cease to inhale the anesthetic. Because nitrous oxide is eliminated quickly via the lungs, it does not accumulate in the mother or fetus/neonate or cause newborn depression [80,84]. Nitrous oxide does not affect uterine contractile activity.

The effects of exposure of the neonatal brain to low levels of nitrous oxide, and the effects of low dose environmental exposure of hospital personnel, are not known. (See "Neurotoxic effects of anesthetics on the developing brain".)

A blender device with a gas scavenging system is essential during nitrous oxide administration and is required by the FDA. The scavenging should reduce the exposure of labor room staff to nitrous oxide. However, the venting of the gas from the hospital into the atmosphere causes environmental pollution.

Side effects of nitrous oxide include nausea in 5 to 40 percent of women and vomiting in up to 15 percent [81]. Pulse oximetry should be used to monitor all parturients who receive nitrous oxide. It should not be used in women with oxygen saturation <95 percent or in patients with respiratory compromise, and should be used with caution in combination with opioids because of the added risk of respiratory depression.

The American Society of Anesthesiologists (ASA) Committee on Obstetrical Anesthesia recommends that health care facilities have written protocols for use of nitrous oxide and that nursing and obstetric providers be educated on its safe use, with periodic assessment of competence [85]. Use of inhaled nitrous oxide for labor analgesia should conform to sedation policies established by the institution’s Department of Anesthesiology.

Efficacy of nitrous oxide for labor analgesia The analgesic efficacy of nitrous oxide for labor is unclear. Systematic reviews have found that it relieves labor pain to a significant degree in most patients, but does not provide complete analgesia for many [84,86-88], and some women do not respond at all. Few fair or good quality studies are available and they do not provide clear, quantitative, objective evidence of its analgesic efficacy for the relief of labor pain. Nevertheless, for women who choose to avoid or delay neuraxial analgesia, for those who have contraindications, or for those who do not have access to neuraxial analgesia, nitrous oxide may provide an alternative means for some pain relief. An impact study of nitrous oxide found that the rate of neuraxial analgesia utilization was not affected by the introduction of nitrous oxide at a busy United States academic medical center [89].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Labor" and "Society guideline links: COVID-19 – Index of guideline topics" and "Society guideline links: Obstetric anesthesia".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topic (see "Patient education: Labor and childbirth (The Basics)" and "Patient education: Managing pain during labor and childbirth (The Basics)")

PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Managing pain during labor and delivery".)

SUMMARY AND RECOMMENDATIONS

Antenatal patient education – Patients should be provided with information about pain relief options prior to the onset of labor, so they can make informed decisions about the choices for labor analgesia. (See 'Introduction' above.)

Characteristics of labor pain – The first stage of labor causes visceral pain, arising from distention and ischemia of uterine and cervical tissues. Somatic pain occurs in addition to visceral pain during the second stage of labor, as the vagina, perineum, pelvic floor, and ligaments are stretched. (See 'Pain pathways' above.)

Labor pain produces physiologic effects, including hyperventilation and increased catecholamine levels. Such effects are usually well tolerated by healthy parturients with normal pregnancies, but may be problematic for parturients with medical comorbidities (eg, some cardiac lesions, preeclampsia). Labor pain can also cause psychological effects (eg, postpartum depression and posttraumatic stress disorder). (See 'Adverse consequences of labor pain' above.)

Neuraxial analgesia – Neuraxial analgesic techniques (ie, epidural, spinal, and combined spinal-epidural) are the most effective means of relieving the pain of labor and delivery. We suggest the use of neuraxial analgesia to manage the pain of labor and delivery for parturients who desire pharmacologic analgesia, in the absence of a contraindication (Grade 2C). (See 'Neuraxial analgesia' above.)

Systemic opioids (table 2)

General considerations – Systemic opioids can provide some pain relief, with moderate maternal satisfaction. Opioids are widely available and less invasive than neuraxial analgesia, and may be beneficial for patients in whom neuraxial techniques are contraindicated or unavailable. Opioids can cause nausea, vomiting, drowsiness, and respiratory depression. They cross the placenta and can cause decreased fetal heart rate variability and neonatal respiratory depression. Opioid administration should be considered carefully near the time of delivery, as it is preferable to have the parturient unsedated during pushing, and fetal effects may be prolonged if opioids are administered near delivery. (See 'Opioid analgesia' above.)

IV bolus versus patient controlled analgesia (PCA) – Opioids may be administered by intermittent parenteral bolus doses or by IV PCA. PCA provides rapid onset of analgesia, better pain control, and a greater sense of control for the patient, compared with bolus administration. (See 'Intermittent bolus opioid' above and 'Patient controlled analgesia (PCA)' above.)

Opioids for PCA – Short-acting opioids are usually used for PCA for labor analgesia.

Remifentanil PCA is the option we prefer for opioid analgesia. Remifentanil is an ultrashort-acting opioid, used for labor with demand doses of 15 to 50 mcg, and lockout intervals of one to five minutes. No loading dose is necessary for remifentanil PCA. There is a relatively high incidence of respiratory depression with remifentanil PCA. (See 'Remifentanil PCA' above.)

Fentanyl PCA for labor is an alternative to remifentanil PCA, and is used with a loading dose of 50 to 100 mcg IV, demand dose of 10 to 25 mcg, and lockout of 5 to 10 minutes. (See 'Fentanyl PCA' above.)

Opioids for intermittent bolus – For patients in whom neuraxial analgesia and PCA are not options, we prefer to administer mixed agonist-antagonist opioids (eg, nalbuphine 2.5 to 10 mg IV every two to four hours depending on analgesia and maternal sedation), because they cause less maternal respiratory depression than long-acting opioids such as morphine. (See 'Intermittent bolus opioid' above.)

Nitrous oxide – The efficacy of labor pain relief with nitrous oxide is variable; nitrous oxide provides less effective pain relief than neuraxial analgesia. The most common side effects are nausea and vomiting, and patients who use nitrous oxide must be monitored for respiratory depression, especially when it is administered in combination with opioids. The effects of nitrous oxide on the fetal brain, as it is used for labor analgesia, are unknown. (See 'Nitrous oxide' above.)

  1. Lowe NK. The nature of labor pain. Am J Obstet Gynecol 2002; 186:S16.
  2. Ranta P, Spalding M, Kangas-Saarela T, et al. Maternal expectations and experiences of labour pain--options of 1091 Finnish parturients. Acta Anaesthesiol Scand 1995; 39:60.
  3. Melzack R, Taenzer P, Feldman P, Kinch RA. Labour is still painful after prepared childbirth training. Can Med Assoc J 1981; 125:357.
  4. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 209: Obstetric Analgesia and Anesthesia. Obstet Gynecol 2019; 133:e208.
  5. Waldenström U. Women's memory of childbirth at two months and one year after the birth. Birth 2003; 30:248.
  6. Hodnett ED. Pain and women's satisfaction with the experience of childbirth: a systematic review. Am J Obstet Gynecol 2002; 186:S160.
  7. Goodman P, Mackey MC, Tavakoli AS. Factors related to childbirth satisfaction. J Adv Nurs 2004; 46:212.
  8. McCrea BH, Wright ME. Satisfaction in childbirth and perceptions of personal control in pain relief during labour. J Adv Nurs 1999; 29:877.
  9. Brownridge P. The nature and consequences of childbirth pain. Eur J Obstet Gynecol Reprod Biol 1995; 59 Suppl:S9.
  10. Rooth G. Maternal hypoxaemia during labor. Padiatr Padol 1982; 17:231.
  11. Minnich ME, Brown M, Clark RB, et al. Oxygen desaturation in women in labor. J Reprod Med 1990; 35:693.
  12. Tomimatsu T, Kakigano A, Mimura K, et al. Maternal carbon dioxide level during labor and its possible effect on fetal cerebral oxygenation: mini review. J Obstet Gynaecol Res 2013; 39:1.
  13. Hägerdal M, Morgan CW, Sumner AE, Gutsche BB. Minute ventilation and oxygen consumption during labor with epidural analgesia. Anesthesiology 1983; 59:425.
  14. Reynolds F, Sharma SK, Seed PT. Analgesia in labour and fetal acid-base balance: a meta-analysis comparing epidural with systemic opioid analgesia. BJOG 2002; 109:1344.
  15. Bergmans MG, van Geijn HP, Hasaart TH, et al. Fetal and maternal transcutaneous PCO2 levels during labour and the influence of epidural analgesia. Eur J Obstet Gynecol Reprod Biol 1996; 67:127.
  16. Shnider SM, Wright RG, Levinson G, et al. Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe. Anesthesiology 1979; 50:524.
  17. Morishima HO, Yeh MN, James LS. Reduced uterine blood flow and fetal hypoxemia with acute maternal stress: experimental observation in the pregnant baboon. Am J Obstet Gynecol 1979; 134:270.
  18. Vogl SE, Worda C, Egarter C, et al. Mode of delivery is associated with maternal and fetal endocrine stress response. BJOG 2006; 113:441.
  19. Shnider SM, Abboud TK, Artal R, et al. Maternal catecholamines decrease during labor after lumbar epidural anesthesia. Am J Obstet Gynecol 1983; 147:13.
  20. Jouppila R, Puolakka J, Kauppila A, Vuori J. Maternal and umbilical cord plasma noradrenaline concentrations during labour with and without segmental extradural analgesia, and during caesarean section. Br J Anaesth 1984; 56:251.
  21. Cascio M, Pygon B, Bernett C, Ramanathan S. Labour analgesia with intrathecal fentanyl decreases maternal stress. Can J Anaesth 1997; 44:605.
  22. Hiltunen P, Raudaskoski T, Ebeling H, Moilanen I. Does pain relief during delivery decrease the risk of postnatal depression? Acta Obstet Gynecol Scand 2004; 83:257.
  23. Suhitharan T, Pham TP, Chen H, et al. Investigating analgesic and psychological factors associated with risk of postpartum depression development: a case-control study. Neuropsychiatr Dis Treat 2016; 12:1333.
  24. Eisenach JC, Pan PH, Smiley R, et al. Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain 2008; 140:87.
  25. Nahirney M, Metcalfe A, Chaput KH. Administration of epidural labor analgesia is not associated with a decreased risk of postpartum depression in an urban Canadian population of mothers: a secondary analysis of prospective cohort data. Local Reg Anesth 2017; 10:99.
  26. Orbach-Zinger S, Landau R, Harousch AB, et al. The Relationship Between Women's Intention to Request a Labor Epidural Analgesia, Actually Delivering With Labor Epidural Analgesia, and Postpartum Depression at 6 Weeks: A Prospective Observational Study. Anesth Analg 2018; 126:1590.
  27. Lim G, Levine MD, Mascha EJ, Wasan AD. Labor Pain, Analgesia, and Postpartum Depression: Are We Asking the Right Questions? Anesth Analg 2020; 130:610.
  28. Yildiz PD, Ayers S, Phillips L. The prevalence of posttraumatic stress disorder in pregnancy and after birth: A systematic review and meta-analysis. J Affect Disord 2017; 208:634.
  29. Cook N, Ayers S, Horsch A. Maternal posttraumatic stress disorder during the perinatal period and child outcomes: A systematic review. J Affect Disord 2018; 225:18.
  30. Soet JE, Brack GA, DiIorio C. Prevalence and predictors of women's experience of psychological trauma during childbirth. Birth 2003; 30:36.
  31. Goetzl LM, ACOG Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists Number 36, July 2002. Obstetric analgesia and anesthesia. Obstet Gynecol 2002; 100:177.
  32. Chau A, Bibbo C, Huang CC, et al. Dural Puncture Epidural Technique Improves Labor Analgesia Quality With Fewer Side Effects Compared With Epidural and Combined Spinal Epidural Techniques: A Randomized Clinical Trial. Anesth Analg 2017; 124:560.
  33. Jones L, Othman M, Dowswell T, et al. Pain management for women in labour: an overview of systematic reviews. Cochrane Database Syst Rev 2012; :CD009234.
  34. Traynor AJ, Aragon M, Ghosh D, et al. Obstetric Anesthesia Workforce Survey: A 30-Year Update. Anesth Analg 2016; 122:1939.
  35. NHS Maternity Statistics, England - 2020-21. https://digital.nhs.uk/data-and-information/publications/statistical/nhs-maternity-statistics/2020-21#resources (Accessed on September 26, 2022).
  36. Olofsson C, Ekblom A, Ekman-Ordeberg G, et al. Lack of analgesic effect of systemically administered morphine or pethidine on labour pain. Br J Obstet Gynaecol 1996; 103:968.
  37. Petrie RH, Yeh SY, Murata Y, et al. The effect of drugs on fetal heart rate variability. Am J Obstet Gynecol 1978; 130:294.
  38. Mattingly JE, D'Alessio J, Ramanathan J. Effects of obstetric analgesics and anesthetics on the neonate : a review. Paediatr Drugs 2003; 5:615.
  39. Smith LA, Burns E, Cuthbert A. Parenteral opioids for maternal pain management in labour. Cochrane Database Syst Rev 2018; 6:CD007396.
  40. Liu ZQ, Chen XB, Li HB, et al. A comparison of remifentanil parturient-controlled intravenous analgesia with epidural analgesia: a meta-analysis of randomized controlled trials. Anesth Analg 2014; 118:598.
  41. Stocki D, Matot I, Einav S, et al. A randomized controlled trial of the efficacy and respiratory effects of patient-controlled intravenous remifentanil analgesia and patient-controlled epidural analgesia in laboring women. Anesth Analg 2014; 118:589.
  42. Freeman LM, Bloemenkamp KW, Franssen MT, et al. Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial. BMJ 2015; 350:h846.
  43. Schnabel A, Hahn N, Broscheit J, et al. Remifentanil for labour analgesia: a meta-analysis of randomised controlled trials. Eur J Anaesthesiol 2012; 29:177.
  44. Volikas I, Butwick A, Wilkinson C, et al. Maternal and neonatal side-effects of remifentanil patient-controlled analgesia in labour. Br J Anaesth 2005; 95:504.
  45. Weibel S, Jelting Y, Afshari A, et al. Patient-controlled analgesia with remifentanil versus alternative parenteral methods for pain management in labour. Cochrane Database Syst Rev 2017; 4:CD011989.
  46. Volmanen P, Akural E, Raudaskoski T, et al. Comparison of remifentanil and nitrous oxide in labour analgesia. Acta Anaesthesiol Scand 2005; 49:453.
  47. Birnbach DJ, Ranasinghe JS. Is remifentanil a safe and effective alternative to neuraxial labor analgesia? It all depends. Anesth Analg 2014; 118:491.
  48. Van de Velde M, Carvalho B. Remifentanil for labor analgesia: an evidence-based narrative review. Int J Obstet Anesth 2016; 25:66.
  49. Wilson MJA, MacArthur C, Hewitt CA, et al. Intravenous remifentanil patient-controlled analgesia versus intramuscular pethidine for pain relief in labour (RESPITE): an open-label, multicentre, randomised controlled trial. Lancet 2018; 392:662.
  50. Kan RE, Hughes SC, Rosen MA, et al. Intravenous remifentanil: placental transfer, maternal and neonatal effects. Anesthesiology 1998; 88:1467.
  51. Babenco HD, Conard PF, Gross JB. The pharmacodynamic effect of a remifentanil bolus on ventilatory control. Anesthesiology 2000; 92:393.
  52. Hill D. The use of remifentanil in obstetrics. Anesthesiol Clin 2008; 26:169.
  53. Hinova A, Fernando R. Systemic remifentanil for labor analgesia. Anesth Analg 2009; 109:1925.
  54. Melber AA, Jelting Y, Huber M, et al. Remifentanil patient-controlled analgesia in labour: six-year audit of outcome data of the RemiPCA SAFE Network (2010-2015). Int J Obstet Anesth 2019; 39:12.
  55. Muchatuta NA, Kinsella SM. Remifentanil for labour analgesia: time to draw breath? Anaesthesia 2013; 68:231.
  56. Weiniger CF, Carvalho B, Stocki D, Einav S. Analysis of Physiological Respiratory Variable Alarm Alerts Among Laboring Women Receiving Remifentanil. Anesth Analg 2017; 124:1211.
  57. Logtenberg SLM, Vink ML, Godfried MB, et al. Serious adverse events attributed to remifentanil patient-controlled analgesia during labour in The Netherlands. Int J Obstet Anesth 2019; 39:22.
  58. Miyakoshi K, Tanaka M, Morisaki H, et al. Perinatal outcomes: intravenous patient-controlled fentanyl versus no analgesia in labor. J Obstet Gynaecol Res 2013; 39:783.
  59. Nikkola EM, Ekblad UU, Kero PO, et al. Intravenous fentanyl PCA during labour. Can J Anaesth 1997; 44:1248.
  60. Rayburn WF, Smith CV, Leuschen MP, et al. Comparison of patient-controlled and nurse-administered analgesia using intravenous fentanyl during labor. Anesthesiol Rev 1991; 18:31.
  61. Castro C, Tharmaratnam U, Brockhurst N, et al. Patient-controlled analgesia with fentanyl provides effective analgesia for second trimester labour: a randomized controlled study. Can J Anaesth 2003; 50:1039.
  62. Douma MR, Verwey RA, Kam-Endtz CE, et al. Obstetric analgesia: a comparison of patient-controlled meperidine, remifentanil, and fentanyl in labour. Br J Anaesth 2010; 104:209.
  63. Morley-Forster PK, Reid DW, Vandeberghe H. A comparison of patient-controlled analgesia fentanyl and alfentanil for labour analgesia. Can J Anaesth 2000; 47:113.
  64. Davis MP, Fernandez C, Regel S, McPherson ML. Does nalbuphine have a niche in managing pain? J Opioid Manag 2018; 14:143.
  65. Ullman R, Smith LA, Burns E, et al. Parenteral opioids for maternal pain relief in labour. Cochrane Database Syst Rev 2010; :CD007396.
  66. Bricker L, Lavender T. Parenteral opioids for labor pain relief: a systematic review. Am J Obstet Gynecol 2002; 186:S94.
  67. Caldwell J, Wakile LA, Notarianni LJ, et al. Maternal and neonatal disposition of pethidine in childbirth--a study using quantitative gas chromatography-mass spectrometry. Life Sci 1978; 22:589.
  68. Kuhnert BR, Linn PL, Kennard MJ, Kuhnert PM. Effects of low doses of meperidine on neonatal behavior. Anesth Analg 1985; 64:335.
  69. Nissen E, Widström AM, Lilja G, et al. Effects of routinely given pethidine during labour on infants' developing breastfeeding behaviour. Effects of dose-delivery time interval and various concentrations of pethidine/norpethidine in cord plasma. Acta Paediatr 1997; 86:201.
  70. Fleet J, Belan I, Jones MJ, et al. A comparison of fentanyl with pethidine for pain relief during childbirth: a randomised controlled trial. BJOG 2015; 122:983.
  71. Koren G, Florescu A, Costei AM, et al. Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother 2006; 40:824.
  72. Zutshi V, Rani KU, Marwah S, Patel M. Efficacy of Intravenous Infusion of Acetaminophen for Intrapartum Analgesia. J Clin Diagn Res 2016; 10:QC18.
  73. Abd-El-Maeboud KH, Elbohoty AE, Mohammed WE, et al. Intravenous infusion of paracetamol for intrapartum analgesia. J Obstet Gynaecol Res 2014; 40:2152.
  74. Ankumah NE, Tsao M, Hutchinson M, et al. Intravenous Acetaminophen versus Morphine for Analgesia in Labor: A Randomized Trial. Am J Perinatol 2017; 34:38.
  75. Kaur Makkar J, Jain K, Bhatia N, et al. Comparison of analgesic efficacy of paracetamol and tramadol for pain relief in active labor. J Clin Anesth 2015; 27:159.
  76. Elbohoty AE, Abd-Elrazek H, Abd-El-Gawad M, et al. Intravenous infusion of paracetamol versus intravenous pethidine as an intrapartum analgesic in the first stage of labor. Int J Gynaecol Obstet 2012; 118:7.
  77. Othman M, Jones L, Neilson JP. Non-opioid drugs for pain management in labour. Cochrane Database Syst Rev 2012; :CD009223.
  78. Frölich MA, Burchfield DJ, Euliano TY, Caton D. A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neonatal effects. Can J Anaesth 2006; 53:79.
  79. Rooks JP. Nitrous oxide for pain in labor--why not in the United States? Birth 2007; 34:3.
  80. Rooks JP. Safety and risks of nitrous oxide labor analgesia: a review. J Midwifery Womens Health 2011; 56:557.
  81. Likis FE, Andrews JC, Collins MR, et al. Nitrous oxide for the management of labor pain: a systematic review. Anesth Analg 2014; 118:153.
  82. Collins MR, Starr SA, Bishop JT, Baysinger CL. Nitrous oxide for labor analgesia: expanding analgesic options for women in the United States. Rev Obstet Gynecol 2012; 5:e126.
  83. Waud BE, Waud DR. Calculated kinetics of distribution of nitrous oxide and methoxyflurane during intermittent administration in obstetrics. Anesthesiology 1970; 32:306.
  84. Rosen MA. Nitrous oxide for relief of labor pain: a systematic review. Am J Obstet Gynecol 2002; 186:S110.
  85. American Society of Anesthesiologists (ASA) Committee on Obstetrical Anesthesia www.asahq.org/For-Members/Clinical-Information/Nitrous-Oxide.aspx) (Accessed on April 03, 2012).
  86. Kronberg JE, Thompson DEA. Is nitrous oxide an effective analgesic for labor? A qualitative systematic review. In: Evidence-based obstetric anesthesia, 2nd ed, Halpern SH, Douglas MJ (Eds), Blackwell, Massachusetts 2006. p.38.
  87. Likis FE, Andrews JA, Collins MR, Lewis, RM, Seroogy JJ, Starr SA, Walden RR, McPheeters ML. Nitrous Oxide for the Management of Labor Pain. Comparative Effectiveness Review No. 67. (Prepared by the Vanderbilt Evidence-based Practice Center under Contract No. 290-2007-10065-I.) AHRQ Publication No. 12-EHC071-EF. Rockville, MD: Agency for Healthcare Research and Quality; August 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm.
  88. Klomp T, van Poppel M, Jones L, et al. Inhaled analgesia for pain management in labour. Cochrane Database Syst Rev 2012; :CD009351.
  89. Bobb LE, Farber MK, McGovern C, Camann W. Does nitrous oxide labor analgesia influence the pattern of neuraxial analgesia usage? An impact study at an academic medical center. J Clin Anesth 2016; 35:54.
Topic 4468 Version 66.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟