Learning Objectives: After participating in this continuing professional development activity, the provider should be better able to:

1. Explain the neurophysiology and maternal/fetal effects of labor pain.

2. Describe assessment of the parturient for labor analgesia.

Labor pain is an intense, unpleasant experience with significant physiologic consequences on the mother and the fetus. Delivery was called poena magna by the Romans, which means "great pain" or "great punishment."1 Labor pain is subjective, with great interpersonal variability. It may also vary from pregnancy to pregnancy. Understanding the neurophysiology of labor pain and the maternal and fetal effects of pain is essential for all practitioners involved in the care of laboring patients. A thorough and focused assessment of the laboring patient before selecting and administering analgesic modality is essential to maximize efficacy and maternal satisfaction, without sacrificing maternal and fetal safety. In this article, we review the neurophysiology of labor pain, maternal and fetal effects of pain, and assessment of the parturient for labor analgesia.

Neurophysiology of Pain

Pain is defined as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.2 When stimulated by noxious stimuli, peripheral nociceptors transmit signals to the dorsal root ganglia of the spinal cord through lightly myelinated A[delta] or unmyelinated C fibers. From the dorsal root ganglia, the nerves follow the spinothalamic tract to the somatosensory cortex, where the perception of location, intensity, and duration of pain occurs.1

Labor pain can vary considerably in intensity among individuals. Nulliparous women tend to perceive labor pain as more severe compared with multiparous women, but this difference is very slight. This may be related to each woman's perception of pain experienced before labor. The emotional component of pain is dependent upon the individual and the situation.1 Neurophysiology of labor pain is summarized in Table 1.

Table 1. Neurophysiology of Labor Pain

Pain during the first stage of labor is attributable to multiple factors. It is mostly caused by stimulation of mechanical receptors in the uterus and cervix, which respond to stretch from uterine contractions. Pain is also caused by activation of chemoreceptors in the uterus that are stimulated by the release of neurotransmitters in response to uterine contractions. Afferent nerves transmit signals from the cervix and lower uterine segments. There is some evidence that uterine body afferents are denervated during pregnancy.1 Pain during the first stage of labor is mostly visceral pain. Uterine and cervical pain is transmitted via afferent nerves in the inferior hypogastric, middle hypogastric, aortic, and superior pelvic plexuses. They ultimately synapse in the dorsal horn of the spinal cord via the T10, T11, T12, and L1 nerve roots. Unmyelinated C fibers transmit painful stimuli via lower thoracic and lumbar sympathetic chains to posterior nerve roots of T10-L1.3 Early in labor, mostly T11 and T12 are affected. As labor progresses, T10 and L1 become more involved. Pain in the first stage of labor can be alleviated by blockade of spinal nerve roots (neuraxial blocks) or plexuses, or paracervical blockade.

The second stage of labor involves a more somatic component because of stretch in the vagina, pressure on the perineum, traction on uterine ligaments and pelvic organs, and distension of pelvic floor muscles. This stimulates the pudendal nerves, genital branch of the genitofemoral nerve, ilioinguinal nerve, and lateral femoral cutaneous nerve. Painful stimuli travel from the pelvic region to the dorsal horn cells and via the spinothalamic tract to the brain.3 Pressure at the lumbosacral plexus can cause neuropathic-like symptoms. During the second stage of labor, blockade of the pudendal nerves (S2-S4) and the nerve roots L1-L3 (which supply the other nerves involved in the second stage) can provide analgesia.4 However, because of the pressure of the presenting part on the cervix and lower uterus in addition to the perineum, blockade of T10-S4 during the second stage of labor is optimal for adequate analgesia.5

Commonly used analgesic modalities include systemic agents, inhaled agents, and regional blocks. Intravenously administered agents such as opioids may reduce the intensity of labor pain. However, IV opioids usually do not provide complete relief of labor pain. Dose-dependent adverse effects of IV opioids include sedation, nausea, vomiting, maternal and neonatal respiratory depression, and delayed gastricemptying. Regional anesthesia, when properly conducted, provides relatively superior analgesia with fewer systemic effects to the mother and the fetus. Regional anesthesia blocks the afferent conduction of the painful stimulus before entering the nociceptive pathways in the central nervous system. Thus, it effectively blunts the hemodynamic response to pain, leading to a reduction in maternal catecholamine levels and improvement of uteroplacental perfusion.6

Maternal and Fetal Effects of Pain

Pain leads to the release of plasma catecholamines, such as epinephrine, which can increase systemic vascular resistance (SVR). This can lead to a decrease in uteroplacental perfusion. Temporary hyperventilation associated with the pain of uterine contractions can lead to increased oxygen consumption, alkalosis, left displacement of maternal oxygen-hemoglobin dissociation curve, and transient hypoxemia, which can affect both the mother and the fetus. Parturients are at increased risk of pulmonary aspiration because of mechanical effects of the gravid uterus on the stomach and gastroesophageal junction in addition to the effect of progesterone on the lower esophageal sphincter. The anxiety caused by the pain of labor can increase the secretion of gastrin and decrease gastrointestinal motility. This may further increase the risk of pulmonary aspiration in parturients. Maternal and fetal effects of labor pain are summarized in Table 2. Effectively managing labor pain can minimize the impact of these adverse effects on maternal and fetal well-being.

Table 2. Maternal and Fetal Effects of Pain

Labor pain can affect the labor and delivery process through variable mechanisms. Neurotransmitters are released by the sympathetic nervous system in response to the pain of labor. These include epinephrine, which causes tocolysis because of the activation of [beta]₂ receptors in the uterus. Labor pain leads to an increase in the release of oxytocin. Labor pain does not have a direct effect on the fetus because there is no direct neural pathway from the mother to the fetus. However, its effects on maternal physiology can have consequences on the fetus. Labor pain can lead to a reduction in uteroplacental perfusion, which is caused by oxytocin-mediated increase in uterine contractions, epinephrine-mediated uterine artery vasoconstriction, and alkalosis and hypoxemia from hyperventilation. Oxytocin-mediated increase in uterine contractions is reduced by epinephrine's tocolytic effect.1

Postdelivery pain is common and usually is acute, but it can convert to chronic pain. The more severe the acute pain associated with labor, the more likely the patient is to develop chronic pain. Chronic pain can be defined as pain that continues beyond the normal course of the acute disease process after the usual healing time has elapsed. Pain after delivery can be caused by multiple factors. Acute pain is due to tissue damage. Inflammatory pain usually occurs secondary to direct tissue trauma, causing release of inflammatory mediators. This causes local sensitization and continued pain after tissue damage has healed. Complex mechanisms cause both a loss of sensation and hypersensitivity in the affected area.5

Factors associated with an increase in the incidence of postdelivery pain include older age, heavier weight, and pain earlier in pregnancy. Previous chronic pain is not a risk factor for new persistent postpartum pain. Chronic pain is caused by tissue injury, distortion of pelvic anatomy, adhesions to bladder, round ligaments, and other surrounding structures, or myofascial pain at the incision site.

Rates of chronic pain after vaginal delivery (4%) and cesarean delivery (6%) are relatively similar, based on multiple small studies.5 A large, multicenter trial by Eisenach and colleagues7 analyzed incidence of development of chronic pain 8 weeks after vaginal or cesarean delivery. The incidence of postpartum pain was 10.9% and 9.8% at 36 hours and at 8 weeks, respectively. There was no significant difference in the incidence of chronic pain at 8 weeks on the basis of mode of delivery. However, the more severe the pain at 36 hours after delivery, the higher the incidence of chronic pain at 8 weeks postpartum. This suggests that careful management of acute labor pain may decrease the incidence of chronic pain postpartum.

The psychological effects of labor pain should not be undermined. These effects vary significantly among women. Women who perceive severe labor pain may have resultant depression and anxiety about future pregnancies. Postpartum depression may have severe consequences for both the mother and the infant. The psychological consequences of continued postpartum pain include interference with ability to care for the infant, possible prolonged hospitalization, and difficulty with performance of activities of daily living. The multicenter trial by Eisenach and colleagues7 also analyzed the incidence of depression at 8 weeks postpartum and demonstrated that the incidence was 11.2%. Postpartum depression at 8 weeks was meaningfully (but not significantly) associated with severity of postpartum pain. Mode of delivery did not significantly affect the incidence. Adequate pain management may also help reduce morbidity and mortality related to the depression.1

Assessment of the Parturient for Labor Analgesia

A focused clinical evaluation of the parturient for labor analgesia should be performed before the administration of labor analgesia. This includes chart review, history, and physical examination. In some cases subspecialty consults may be required before proceeding with the analgesic modality for labor. A thorough preoperative evaluation of the parturient is essential for choosing the most appropriate analgesic modality for labor pain. Although the evaluation is usually performed by the anesthesiologist, it is important that obstetricians are aware of the key aspects of the evaluation and major patient safety concerns as part of multidisciplinary care of the patient.

Neurologic Disease

Patients with preexisting neurologic disease can be challenging to manage when it comes to labor analgesia. It is important to note any neurologic condition a patient may have and what are the signs and symptoms the patient has. A risk/benefit assessment should be made for each patient and situation. Multiple sclerosis occurs more frequently in women than in men and usually is diagnosed in childbearing years (average age of onset is 32 years).8 The disease is characterized by exacerbations and remissions. Some triggers for exacerbation include surgery, infection, fever, trauma, and emotional stress. Perioperative causes of exacerbations are usually pain and stress. Disease relapse rates during pregnancy are 3 times higher than those in nonpregnant patients.

Epidural analgesia has been performed in laboring patients with multiple sclerosis without sequelae. Although previous literature demonstrated that spinal anesthesia can cause exacerbations of the disease, more recent studies have demonstrated that it does not increase the incidence. However, this information is based on several case reports and literature reviews; no formal large-scale studies have been performed. Hebl and colleagues9 conducted a retrospective review of patients with central nervous system disorders who received neuraxial anesthesia. Twenty-five percent of the 139 patients had multiple sclerosis and the mean age was 60 years. The study did not find any new or worsened symptoms related to the neurologic disorder after neuraxial anesthesia. However, this study had a minority of patients with multiple sclerosis and only 9 of the patients were laboring. Of those, 1 patient had a spinal block for cesarean delivery, and 8 had labor epidural blocks. Lu and colleagues8 investigated the use of epidural and spinal anesthesia for labor and cesarean delivery in parturients with multiple sclerosis. Although the study was not designed to look at outcomes, it did demonstrate that use of spinal for cesarean delivery in patients with multiple sclerosis was similar to the use of spinal in parturients without multiple sclerosis, suggesting that current practice is adapting to newer literature.

Patients with an intracranial mass or edema can develop increased intracranial pressure (ICP) with uterine contractions. These patients can benefit from epidural analgesia, which can attenuate the increase in ICP related to contractions. However, given the elevated ICP, accidental (or deliberate in the case of a spinal) dural puncture may increase the risk of cerebral herniation because of cerebrospinal fluid leak. A careful risk/benefit assessment and multidisciplinary management approach involving the neurologist or the neurosurgeon before labor analgesia is the safest approach in these patients.

Many laboring patients have a history of back surgery. Neuraxial analgesia may be challenging because of hardware in the spinal canal and scar tissue preventing proper placement of the catheter. It is recommended to go above or below the site of the surgery, although this may be difficult in patients with multilevel surgery (such as scoliosis repair). Indwelling epidural catheters can track infection to existing hardware. Thus, careful attention to antiseptic technique and maintenance of antiseptic conditions during the labor process is essential. Patients who have surgically untreated scoliosis can be very difficult to place neuraxial analgesia because of severe malrotation of the spinal canal.10 Several reports have demonstrated difficulty with epidural placement, higher incidence of failed or inadequate analgesia, and unintentional dural puncture in patients with scoliosis.

Cardiovascular Disease

Patients with cardiac disease should be evaluated by a cardiologist before delivery and should be monitored closely during the peripartum period. Patients with aortic stenosis have a fixed cardiac output state and are dependent on the SVR to maintain perfusion of the vital organs. Regional anesthesia can lead to reduction in the SVR and hypotension. Patients with mild and moderate aortic stenosis can receive epidural analgesia, but must be monitored closely. Epidurals are relatively contraindicated in patients with critical aortic stenosis (valve area <0.7 cm², or transvalvular gradient >40 mm Hg), secondary pulmonary hypertension, and Eisenmenger syndrome.

Epidural analgesia is acceptable for most other cardiac conditions. Patients with aortic and mitral regurgitation benefit from reduction in SVR associated with labor epidural analgesia, as it reduces the volume of regurgitant blood across the incompetent valve. Particular attention to volume status is required in these patients to maintain optimal cardiac preload while avoiding fluid overload. Invasive hemodynamic monitoring may be required in certain cardiac conditions.11

Hepatic Disease

Patients with hepatic disease should be monitored closely during pregnancy and labor. Advanced cirrhosis may lead to coagulopathy and esophageal varices. Coagulation factors and platelet count should be checked when the patient with advanced hepatic disease is admitted for delivery.12

Obesity

Obese parturients are at increased risk of a multitude of complications, including macrosomia, shoulder dystocia, prolonged labor, and a higher cesarean delivery rate. Obese patients tend to be difficult to intubate in emergent situations such as high/total spinal or emergency cesarean delivery. Placing neuraxial labor analgesia or anesthesia for cesarean delivery may be difficult in obese patients.13 Because of the aforementioned reasons, obese patients with a difficult airway should be identified and considered for epidural analgesia early in labor.

Sepsis

Maternal sepsis can increase vascular permeability leading to noncardiogenic pulmonary edema and respiratory distress. These patients may need to be intubated if respiratory failure ensues. Sepsis often causes a decrease in SVR. This may be severely potentiated by neuraxial analgesia, which can further decrease SVR.14 Conditions that preclude neuraxial regional anesthesia in a septic patient include hemodynamic instability, lack of patient cooperation, coagulopathy, respiratory failure, and systemic bacteremia.

Hematologic Disease

Coagulopathies can significantly complicate pain management during labor. Patients with bleeding disorders such as von Willebrand disease, thrombocytopenia, immune thrombocytopenic purpura, and hemophilia are at increased risk of spinal hematomas secondary to neuraxial analgesia. Spinal hematoma can cause significant, permanent neurologic damage. Patients with coagulopathies should be evaluated by a hematologist before presentation for delivery. Although preexisting coagulopathy is not a contraindication to neuraxial analgesia, careful evaluation by the anesthesiologist along with a review of the hematologist's recommendations should occur.15 According to the consensus statement released by the Australian Haemophilia Center Directors' Organization, coagulation factors should be in the normal range during the period the epidural catheter is in the patient and for 12 hours after (if mild bleeding disorder) or 24 hours after (if moderate to severe bleeding disorder) epidural catheter removal.16

Patients with hypercoagulable states such as protein C and S deficiency, factor V Leiden deficiency, and antiphospholipid antibody syndrome are often placed on anticoagulants during pregnancy. These patients are at increased risk of thrombotic events because of the hypercoagulable state associated with pregnancy. Anticoagulants can increase the risk for spinal hematomas. The American Society of Regional Anesthesia and Pain Medicine (ASRA) published guidelines for neuraxial analgesia and anticoagulation. ASRA recommendations are summarized in Table 3.

Table 3. Effects of Maternal Medication on Neuraxial Analgesic Techniques*

Preeclampsia

One of the hallmarks of preeclampsia is decreased uteroplacental blood flow, which can compromise the fetus during labor. A benefit of epidural analgesia is reduction in uteroplacental vascular resistance. There has been some controversy whether epidural analgesia is beneficial or detrimental in patients with preeclampsia. Because labor epidural analgesia causes sympathetic blockade of the thoracic sympathetic chain, it frequently leads to relative hypotension due to a decrease in SVR. Hypotension in a patient with intravascular volume contraction from preeclampsia can further reduce uteroplacental perfusion. Severe preeclampsia is associated with increased frequency and severity of hypotension and fetal heart rate abnormalities after epidural placement.17 However, because of the pain relief provided by epidural analgesia, maternal catecholamines are decreased, potentially improving uteroplacental perfusion.18

When evaluating patients with preeclampsia for neuraxial analgesia, it is important to assess the severity of the disease and evaluate the patient for hematologic abnormalities. Platelet count, coagulation profile, and fibrinogen levels should be assessed, especially in patients with severe preeclampsia.

Uterine Rupture

Uterine rupture can lead to significant maternal morbidity and neonatal mortality. Risk factors for uterine rupture include previous cesarean delivery, malpresentation, and second-stage dystocia.19 Signs and symptoms of uterine rupture usually include nonreassuring fetal heart rate tracing, maternal hemodynamic instability, and disproportionate abdominal pain. Patients who have labor analgesia in the form of epidural typically experience a severely reduced sensation of contraction-related pain. However, several case reports of patients with effective labor epidural analgesia experiencing uterine rupture demonstrate that patients can feel the pain (often referred to the shoulder via the phrenic nerve) of a uterine rupture. JS Crawford introduced the term "epidural sieve" in 1976 to describe the blockade of physiologic pain from epidural blockade but the ability to sensate pathologic pain.19 Uterine rupture should be considered in the differential diagnosis in high-risk patients who report abdominal or referred shoulder pain with functioning epidural analgesia.20

Maternal Drug Abuse

Parturients with previous or current history of drug abuse develop tolerance to the effect of IV agents especially opioids. Unless contraindicated, regional anesthesia is the analgesic modality of choice in this population because it relies primarily on local anesthetics.

Maternal Medications

Systemic medications administered to the mother may have substantial effects on the mother and the fetus. Systemic analgesics with sedative effects may interfere with the ability of the mother to provide informed consent for regional anesthesia. Sedatives may cause neonatal respiratory depression.

Most notably, anticoagulation therapy may have the greatest impact on the choice and timing of neuraxial analgesia for labor. Anesthesiologists and obstetricians should be well acquainted with guidelines for management of anticoagulation therapy with regional anesthesia. ASRA guidelines pertinent to labor analgesia are summarized in Table 3. Communication among various specialists managing the laboring patient is the key to effective and safe labor analgesia. If the informed consent for neuraxial labor analgesia has not been obtained, it is prudent that the obstetric service informs the anesthesiology service before administering systemic analgesics. This will provide the means to explain the procedure to the patient, answer all questions, and properly obtain informed consent.

Obtaining Informed Consent for Neuraxial Labor Analgesia

It is essential that a laboring patient clearly understands the benefits and risks of labor pain management options. A thorough discussion of the potential complications should also occur. There has been controversy whether a patient can consent when under the psychological influence of labor pain. Studies have demonstrated that the pain of labor does not affect the ability of the laboring patient to understand the process. Ideally, the patient should receive written information about the risks and benefits of labor analgesia during a prenatal appointment to allow adequate time for questions and review of all options before making an informed decision.21 Informed consent for epidural analgesia should include benefits to the patient, benefits to the fetus and labor process, risks and adverse effects of epidural, information pertinent to the specific medical condition of the patient, and alternatives to epidural analgesia and other information requested by the patient.22

Conclusion

Labor pain is a complex and intense, unpleasant experience that should be well understood by all providers caring for the laboring patient. Alleviating the pain to minimize maternal and fetal stresses is an important goal and should be an integral aspect of labor management. A thorough and focused evaluation of the parturient for labor and analgesia is critical to achieving this goal safely.

References