A Review of the Impact of Obstetric Anesthesia on Maternal and Neonatal Outcomes

Grace Lim, M.D., M.S.; Francesca L. Facco, M.D., M.S.; Naveen Nathan, M.D.; Jonathan H. Waters, M.D.; Cynthia A. Wong, M.D.; Holger K. Eltzschig, M.D., Ph.D.


Anesthesiology. 2018;129(1):192-215. 

In This Article

Anesthesia for Cesarean Delivery

Advances in Spinal Anesthesia for Cesarean Delivery

Single-shot spinal anesthesia is the most common technique for cesarean delivery due to its simplicity, quality of sensory blockade, and reliability. In contrast to epidural anesthesia, the total local anesthetic dose is lower; there is no risk for local anesthetic systemic toxicity and there is minimal fetal drug transfer.[12,112] The effective dose for hyperbaric bupivacaine in 95% of patients (ED95) is 13 mg when administered with intrathecal fentanyl and morphine. Higher doses (e.g., 15 mg) are associated with longer duration, but also with higher sensory blockade to cervical dermatomes, and a higher incidence and degree of hypotension.[113]

Adding a lipid-soluble opioid (e.g., fentanyl, sufentanil) to local anesthesia enhances intraoperative anesthesia by reducing the total dose of local anesthetic, reducing hypotension, nausea, and vomiting.[114] This enhanced anesthesia is associated with less stimulation upon surgical traction of the viscera, contributing to a lower rate of nausea, vomiting, and intraoperative supplemental analgesia compared to omission of intrathecal fentanyl or sufentanil.[114] Adding morphine (a water-soluble opioid) confers postoperative analgesia of up to 36 h.[115] Epinephrine (0.1 to 0.2 mg) is often added in clinical practice, producing a 15% increase in block duration and improving the quality of intraoperative analgesia, while increasing block recovery time.[116] Clonidine improves intraoperative analgesia and reduces shivering and hyperalgesia, but is associated with hypotension and sedation; its use in this setting is off-label.[117]

Conversion of Epidural Analgesia to Surgical Anesthesia

Epidural analgesia is converted to surgical anesthesia by administering high-concentration local anesthetic. Fifteen to 20 ml lidocaine, 2% with epinephrine 1:200,000 is commonly used. The addition of 8.4% sodium bicarbonate (1 ml for every 10 ml local anesthetic solution) alkalinizes the local anesthetic solution, which hastens onset of action. Fifteen to 20 ml 2-chloroprocaine, 3% may be used for urgent deliveries because of its shorter latency. Successful conversion to epidural anesthesia is critical to avoid general anesthesia; emergency general anesthesia is linked to poor outcomes (postoperative pain and sedation, intraoperative awareness, postpartum hemorrhage, and morbidity and mortality from aspiration or failed tracheal intubation). The ability to successfully convert epidural analgesia to anesthesia for intrapartum cesarean delivery has been proposed as a quality metric; in the United Kingdom, the National Institute for Health and Care Excellence guidelines state that general anesthesia should be used in less than 1% of all elective cesarean deliveries and less than 5% of emergency cesarean deliveries.[118]

Several risk factors for failed conversion include delivery urgency, supplemental analgesia during labor, initiation by epidural rather than combined spinal-epidural technique, and anesthesia by generalist compared with obstetric anesthesiologists.[11,12] In one study, generalist anesthesiologists had significantly increased risk for failed conversion of epidural analgesia to anesthesia for cesarean delivery (odds ratio 4.6, 95% CI 1.8 to 11.5).[11] Reasons for increased successful conversion by obstetric anesthesiologists may include increased likelihood to manipulate the catheter, active management of breakthrough labor pain, assessment of catheter functionality and analgesic quality throughout labor, integration of information on labor and maternal-fetal status into analgesia management, and enhanced team communication to anticipate intrapartum cesarean delivery.[11]

Intraoperative Hypotension: The Ideal Vasopressor for Cesarean Delivery

Hypotension after spinal anesthesia is caused by a decrease in systemic vascular resistance; cardiac output increases.[119] The ideal vasopressor to maintain uterine perfusion has been an area of intense research for several decades. Uteroplacental blood flow lacks autoregulation, making it directly dependent on uterine perfusion pressure and inversely proportional to uterine vascular resistance. Pure α1-adrenergic receptor agonists (phenylephrine) were expected to reduce uterine blood flow and induce fetal acidosis, and ephedrine was found to be superior to α1-agonists in fetal animal studies. The first human trials comparing phenylephrine and ephedrine were conducted in the late twentieth century. Neonatal outcomes (umbilical artery pH, base excess) were better in groups randomized to phenylephrine.[120–122] No study found neonatal depression despite very large maternal doses of phenylephrine (in one study the 75th percentile dose was 2,130 μg).[120–123] Consistently, the incidence of nausea and vomiting is lower with phenylephrine infusion. While maternal bradycardia occurred with phenylephrine, patients were asymptomatic and no adverse events were noted.

Ephedrine is associated with fetal acidosis due to placental transfer and direct fetal metabolism activation, but not from uterine blood flow perturbation.[124] Experts conclude the efficacy and safety of phenylephrine make it superior for systemic vascular resistance restoration after spinal anesthesia.[125,126] Prophylactic phenylephrine infusions (vs. intermittent boluses) are effective in preventing hypotension and require fewer anesthesia provider interventions.[127] The current evidence supports prophylactic phenylephrine, titrated to maintain blood pressure near baseline (the usual dose range is 25 to 100 μg/min).[125–128]

Notably, most research comparing vasopressor therapy for cesarean delivery has been in healthy women undergoing elective cesarean delivery. Investigations for neonatal outcomes in maternal-fetal dyads with compromised placental function (e.g., preeclampsia) have been lacking. In 2017, a randomized double-blind trial compared phenylephrine and ephedrine infusion strategies in women with preeclampsia presenting for cesarean delivery under spinal anesthesia.[129] There were no differences in umbilical arterial pH between groups. Similarly, among women with preeclampsia with severe features who also had nonreassuring fetal status, a bolus dose of phenylephrine to treat spinal anesthesia-induced hypotension did not result in better fetal acid-base status compared with ephedrine.[130] It appears that for preeclamptic patients undergoing cesarean delivery, fetal outcomes are not influenced by choice of phenylephrine or ephedrine for prevention or treatment of spinal-anesthesia induced hypotension.

Several investigators suggest norepinephrine has characteristics of the "ideal" vasopressor to prevent and treat hypotension, but current evidence is limited.[128] In one trial, patients receiving norepinephrine had higher heart rate and cardiac output compared with phenylephrine.[131] The incidence of nausea and vomiting did not differ. Norepinephrine use was associated with lower umbilical artery and vein plasma catecholamine concentration and higher umbilical venous pH and oxygen content, potentially indicating higher uteroplacental oxygen delivery; the absolute differences were small (oxygen content phenylephrine, 11.8 ml/dl; oxygen content norepinephrine, 12.7 ml/dl; P = 0.047).[131] In a study on postspinal anesthesia hypotension in cesarean delivery, norepinephrine 8 μg was equivalent to phenylephrine 100 μg for the treatment of the first episode of hypotension.[132] Considering the existence of a highly effective standard (phenylephrine infusion), additional accumulation of evidence is necessary before norepinephrine becomes a new standard.[128]

Supplemental Oxygen

While supplemental oxygen is often routinely applied during cesarean delivery, evidence supporting improvement in maternal and neonatal outcomes is lacking, and some suggest it may cause harm by promoting free-radical generation and lipid peroxidation.[133,134] A trial of 80% versus 30% oxygen during cesarean delivery did not prevent wound infections or endometritis.[135] A meta-analysis of 11 trials of supplemental oxygen found no benefit for maternal desaturation and neonatal Apgar scores.[136] No convincing evidence of harm was identified, although higher maternal and neonatal markers of free-radicals were measured when supplemental oxygen was administered; the clinical significance of these findings is not clear. Data are lacking on the benefits or harms of supplemental oxygen in women with comorbid conditions (e.g., preeclampsia, obesity, labor with nonreassuring fetal heart rate tracing) or in intrauterine resuscitation. Theoretically, these neonates may be at increased risk of harm with hyperoxia because of greater lipid peroxidation from ischemia-reperfusion injury. The available evidence suggests that routine supplemental oxygen for scheduled, healthy cesarean deliveries with neuraxial anesthesia is not beneficial,[136] and its elimination may improve patient comfort.

Postcesarean Delivery Pain and Analgesia

Pain after cesarean delivery is heterogeneous in expression and intensity. The ability to predict the severity and chronicity of postcesarean delivery pain has the potential to personalize anesthetic care by identifying the patients at highest risk for severe pain and debilitation. Recent work has focused on psychometric and psychophysical profiling. Expected postoperative pain, baseline anxiety, and baseline fear of pain are independent predictors for increased postoperative opioid use, accounting for 40% of variance in postoperative pain and opioid used.[137] Pan et al. validated a three-item questionnaire predicting pain after cesarean delivery;[138] a follow-up study applied the questionnaire to a tailored analgesia regimen targeted at women at high risk for severe postcesarean delivery pain.[139] This type of work is key to advancing individualized pain management strategies in obstetrics.

Multimodal analgesia is the gold standard for postcesarean delivery analgesia.[140] A common strategy uses neuraxial morphine, scheduled nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen, and limits systemic opioids to the treatment of breakthrough pain. Neuraxial morphine is the most effective component of postcesarean delivery analgesia.[141,142] It is easy to administer, inexpensive, and provides superior and prolonged analgesia for both static and dynamic pain.[142] Its dynamic pain advantage is important for functional mobility in this population. Neuraxial morphine-related side effects include pruritus, nausea, urinary retention, and respiratory depression, although the risk for the latter is significantly lower when morphine is administered neuraxially than systemically.[143,144] Side effects are dose-dependent; high-dose intrathecal morphine (more than 100 μg) has longer-lasting analgesia (4.5 h) compared with low-dose morphine (50 to 100 μg), but is associated with a higher rate of pruritus and vomiting.[145] Pain scores and supplemental systemic morphine consumption do not differ between the high- and low-doses.

NSAIDs such as ketorolac, diclofenac, and ibuprofen are essential components of multimodal postcesarean delivery analgesia. Their use spares opioids by up to 50%, translating to a 30% reduction of opioid-related side effects such as vomiting and sedation.[146] The package insert for ketorolac states that practitioners should "exercise caution when ketorolac is administered to a nursing woman."[147] The excretion of ketorolac in breast milk is minimal and the American Academy of Pediatrics lists ketorolac as, "usually compatible with breastfeeding."[147,148] Given the safety profile of ketorolac is unlikely to be different from ibuprofen, an NSAID widely used in the postpartum period, we routinely use ketorolac in our practice if contraindications are not present. Contraindications to NSAIDs include renal disease (e.g., renal dysfunction in preeclampsia) and a history of Roux-en-Y gastric bypass surgery.

The use of acetaminophen also exhibits opioid-sparing effects by up to 20% and has an additive effect when administered concomitantly with NSAIDs.[149] Scheduling NSAIDs and acetaminophen after cesarean delivery confers greater reductions in supplemental opioid use compared to pro re nata administration.[150]

Peripheral Nerve Blocks for Postcesarean Delivery Analgesia

When other postcesarean delivery pain management modalities are compared to neuraxial morphine, neuraxial morphine consistently performs best for analgesic quality (Figure 4). Nevertheless, alternative modes of postcesarean delivery analgesia have been proposed. Peripheral nerve blocks for Pfannenstiel and low-transverse incisional pain have been examined, including transversus abdominis plane, quadratus lumborum, and ilioinguinal-iliohypogastric blocks, and continuous wound infiltration. Transversus abdominis plane block is not superior to intrathecal morphine for postcesarean delivery analgesia. In a comparison of intrathecal morphine combined with ropivacaine transversus abdominis plane block to intrathecal morphine combined with a sham block, there were no differences in pain with movement at 24 h, and no differences in supplemental opioid dose.[151] Two meta-analyses concluded that transversus abdominis plane block is not superior to intrathecal morphine, but transversus abdominis plane block may be useful when neuraxial morphine is not part of the pain management strategy (e.g., cesarean delivery with general anesthesia, contraindications to neuraxial morphine).[152,153] The likely explanation for these findings is that transversus abdominis plane block is useful for treating incisional pain, but not visceral pain. A transversus abdominis plane block may be helpful for "rescue" analgesia for breakthrough pain after neuraxial morphine.[154] Transversus abdominis plane block may be associated with subclinical signs of local anesthetic systemic toxicity, therefore, patients must be monitored closely after transversus abdominis plane block.[155] Considering the evidence, the addition of transversus abdominis plane block to the gold standard (multimodal analgesia) is not routinely necessary for effective postcesarean delivery analgesia.

Figure 4.

Postcesarean delivery pain management options and anatomical locations of peripheral nerve blocks. PCEA = patient-controlled epidural analgesia.

A quadratus lumborum block may have advantages over the transversus abdominis plane block because of its more superficial location (easier ultrasound visualization, theoretically improved safety). It involves deposition of local anesthetic into the fascial plane located between the quadratus lumborum and erector spinae muscles; this space is continuous with the paravertebral space, thus enhancing medication spread to the include the sympathetic chain. In two randomized trials, quadratus lumborum block combined with spinal anesthesia was found to be superior to spinal anesthesia alone, and to transversus abdominis plane block with spinal anesthesia.[156,157] A major limitation of these trials was the absence of comparison to intrathecal morphine (spinal anesthesia regimens did not have intrathecal morphine), therefore, no conclusions currently can be made about the superiority of the block to current standard of care.

Local anesthetic wound infiltration may be beneficial if cesarean delivery is performed under general anesthesia, but not under spinal anesthesia.[158] Continuous wound infiltration improves pain on movement and reduces opioid use, but high infusion rates required to achieve this benefit lead to wound leakage, and low patient and practitioner acceptability.[158] Risk for surgical site infection is not increased, but these studies have not been powered for this outcome.[159] Continuous wound infusion is less effective than parenteral morphine and NSAIDs.[158] Most trials have not included neuraxial morphine comparisons, so no definitive comments can be made about superiority to neuraxial morphine. Similar to other nerve blocks, trials comparing ilioinguinal-iliohypogastric blocks to intrathecal morphine have not shown a benefit, but these blocks may have a role in rescue analgesia.[160–163] Overall, while multimodal analgesia with neuraxial morphine, NSAIDs, and acetaminophen is the gold standard for postcesarean delivery pain, supplemental analgesia using transversus abdominis plane, quadratus lumborum, ilioinguinal-iliohypogastric blocks, or wound infiltration may be useful in cases of breakthrough pain, or when the gold standard multimodal analgesia cannot be delivered (e.g., cesarean delivery under general anesthesia, contraindications to NSAID administration).