Each year, one individual is honored by the Society for Obstetric Anesthesia and Perinatology (SOAP) to review publications from the preceding calendar year related to maternal-fetal medicine, and of interest to anesthesiologists who provide peripartum anesthesia care. The most significant manuscripts are summarized during the Gerard W. Ostheimer lecture given at the SOAP annual meeting. The themes presented in this manuscript include maternal mortality, postpartum hemorrhage (PPH), venous thromboembolism (VTE), spinal-induced hypotension, postpartum care including opioid use, postcesarean analgesia, and postpartum depression (PPD). Priority was given to original articles published in high impact journals that present novel findings, impact clinical practice, represent technical advances, or test an interesting hypothesis. The syllabus summarizing 152 selected articles from 2018 that accompanied the lecture is submitted as Supplemental Digital Content, Document, https://links.lww.com/AA/D31.
The maternal mortality rate in the United States is currently higher than other developed nations, possibly in part due to better case ascertainment.1 On December 21, 2018, President Trump signed the Preventing Maternal Deaths Act of 2018 to provide federal funding to states to identify and review maternal deaths, enabling recommendations for improved care.
According to the 2018 report of the Maternal Mortality Review Committees (MMRCs),2 30 US states and some cities have MMRCs. Nine states (Colorado, Delaware, Georgia, Hawaii, Illinois, North Carolina, Ohio, South Carolina, and Utah) published their review of 680 maternal deaths.2 More than two-thirds were considered preventable deaths, including common causes such as hemorrhage and cardiovascular disease. While 38% of deaths occurred during pregnancy, predominantly due to hemorrhage and cardiovascular disease, 45% occurred postpartum up to 42 days, mainly due to infection, and 17% were late deaths (42–365 days after pregnancy), chiefly due to cardiomyopathy. The report highlights the importance of surveillance for late deaths that would otherwise be missed if the World Health Organization (WHO) surveillance period of only up to 42 days was used.
The State of Illinois published a report of 93 deaths occurring within 1 year of pregnancy. Thirty-seven were pregnancy related, 28 were pregnancy associated (unrelated to violent causes), and 28 were pregnancy associated (related to homicide, suicide, or drug overdoses).3 Advanced maternal age, higher body mass index (BMI), high school education only, and Medicaid insurance were associated with higher likelihood of maternal death. In contrast to the available US data, in Illinois, the pregnancy-related maternal mortality ratio is 7 times higher for African American women than Caucasian women. These racial disparities are discussed in a bundle released by the Council on Patient Safety, containing action-based solutions to address disparities.4 Case vignettes highlight significant care disparities and make for a chilling read.3 The California Pregnancy-Associated Mortality Review (2002–2007) included >1000 maternal deaths occurring during pregnancy and up to 1 year postpartum.5 After MMRC review, many deaths that were recorded on the death certificates as due to preeclampsia were found to be due to other causes. Although most women who died were considered “not low risk,” meaning they had some comorbidities, MMRC considered that 41% of the deaths were potentially preventable. Examples of potentially preventable deaths included untreated hypertension, delayed recognition of PPH, and deficient VTE prophylaxis. Clinical warning signs were ignored or recognized late, and institutions were unprepared for obstetric emergencies. In California, investments in maternal public health care and toolkits6 have led to a decline in maternal death rates since 2008 to 7.3 per 100,000 live births, compared with 22.0 per 100,000 live births in the United States as a whole.5 Both the California Maternal Quality Care Collaborative (CMQCC)6 and National Council on Patient Safety have safety bundles available for implementation at the hospital level.7
The UK confidential enquires for the period from 2014 to 2016 reported 259 maternal deaths among 2,301,628 maternities; the mortality ratio was 9.8 per 100,000 maternities (95% confidence interval [CI], 8.5–11.1) during pregnancy and up to 42 days postpartum.8 Cardiac disease remained the most frequent cause of death (2.4 deaths per 100,000 maternities, 95% CI, 1.8–3.1), followed by VTE (1.3 per 100,000 maternities, 95% CI, 1.0–2.0), which was the most frequent direct cause of death. Suicide was the third most frequent direct cause of maternal death up to 42 days postpartum (0.7 per 100,000 maternities, 95% CI, 0.4–1.1), and the leading direct cause when including late maternal deaths up to 1 year postpartum (2.8 deaths per 100,000 maternities, 95% CI, 2.2–3.5). Despite free universal health care in the United Kingdom, ethnic disparities were highlighted, with a maternal death rate of 8 per 100,000 maternities for Caucasians; 15 per 100,000 for Asians; and 40 per 100,000 for black women.
An excellent review summarized the role and care opportunities for the obstetric anesthesiologist in crises situations including airway management, vascular access, blood product administration, and transthoracic echocardiography.9
Amniotic Fluid Embolism
The Society for Maternal-Fetal Medicine (SMFM) proposed diagnostic criteria in 2016, to be used in research when reporting amniotic fluid embolism (AFE).10 All 4 criteria are required if the diagnosis of AFE is to be assigned for research purposes: cardiorespiratory arrest or severe comprise; documented disseminated intravascular coagulation (DIC) detected before significant hemorrhage; clinical onset within 30 minutes of placental delivery; and no fever. The SMFM document discusses detailed pathological findings such as fetal debris in the maternal circulation that are nonspecific to AFE. A French review11 investigated 36 potential AFE cases according to whether the 4 SMFM diagnostic research criteria were present.10 These maternal deaths, comprising 1:10 maternal deaths in France (0.95 of 100,000 live births), revealed that only 1 of 3 women assigned a diagnosis of AFE exhibited all 4 SMFM criteria. Although documented DIC was absent for 14 women, 10 had clinical coagulopathy. One woman had an autopsy consistent with AFE, and her cardiac arrest occurred 4 days postpartum. Collapse was the first sign of AFE in 50% of cases and occurred in all but 1 case. Importantly, although not an SMFM diagnostic research criteria to diagnose AFE, premonitory signs (neurological signs, fainting, and sense of doom) occurred in 3 quarters of the women. This study confirmed that AFE remains a clinical diagnosis and that although SMFM criteria may be used for research purposes, actual AFE cases may be missed using these criteria alone. Documented coagulopathy is required to confirm AFE; however, in severe cases, the patient may not survive the cardiovascular insult until coagulopathy is apparent. The criteria to diagnose AFE differ between countries, for example, according to criteria in the United Kingdom and Australia, AFE can be diagnosed through fetal squames in the lungs, and in Japan, AFE can be a diagnosis of exclusion.10 Because variants of AFE exist, treatment should not be withheld if a patient is missing a required element of the definition.
Cardiac Arrest in Pregnancy
An audit of a nonmandatory US reporting system identified 462 maternal cardiac arrests among all in-hospital cardiac arrests (2006–2016).12 No predisposing conditions existed for 32%, whereas 36% had respiratory insufficiency, 33% had hypotension/hypoperfusion, 13% diabetes mellitus, 9% renal insufficiency, 8% an acute central nervous system nonstroke event, and 7% had cardiac disease. Most arrests, 94%, were witnessed; and 31% occurred in the labor and delivery unit. Given the high proportion of witnessed arrests, a surprise finding was that the first identified rhythm was pulseless electrical activity in 51% of cases, and ventricular fibrillation in only 7%. Return of spontaneous circulation occurred in 74%, but only 41% survived to hospital discharge. Management of maternal cardiac arrest requires modifications in pregnant women, including relief of aortocaval compression by manual uterine displacement and delivery. Perimortem cesarean delivery to evacuate the uterus should be considered if return of spontaneous circulation has not occurred at 4 minutes after onset of cardiac arrest (witnessed) or the start of resuscitative efforts (unwitnessed), for improved maternal survival after 20 weeks’ gestation.13,14
The most frequent cause of maternal mortality worldwide is PPH.15 PPH definitions, associated vital signs, and treatment paradigms,15–17 vary between major international organizations including the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians & Gynaecologists (RCOG), the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the Society of Obstetricians and Gynecologists of Canada, and the French College of Gynaecologists and Obstetricians.16
Prophylactic Strategies for PPH After Vaginal Delivery
Three large randomized-controlled trials (RCTs) investigated prophylactic strategies to reduce PPH after vaginal delivery.18–20 Two compared uterotonics,18,19 and the other compared tranexamic acid (TXA) versus placebo in addition to routine uterotonics.20 The first study was a multinational noninferiority RCT,18 comparing intramuscular (IM) administration of either oxytocin 10 units (n = 14,768) or heat-stable carbetocin 100 µg (n = 14,771). Heat-stable carbetocin does not require cold storage and although not currently included in WHO PPH prevention guidelines, it may confer advantages where refrigeration is unavailable. This noninferiority trial tested whether the new treatment (heat-stable carbetocin) is not less effective than currently used IM oxytocin.
Noninferiority margins were defined for 2 primary outcomes. The first primary outcome was the rate of PPH ≥500 mL measured using a collecting drape, and/or the administration of additional uterotonic agent; the noninferiority margin was defined as a relative risk (RR) of 1.16. The rate of PPH/additional uterotonic agent was 14.5% for heat-stable carbetocin versus 14.4% with oxytocin, RR 1.01 (95% CI, 0.95–1.06), P = .81. Because the upper limit of the 95% CI (1.06) was less than the noninferiority margin (1.16), the trial confirmed that IM heat-stable carbetocin is noninferior to IM oxytocin. The second primary outcome, estimated blood loss (EBL) ≥1000 mL, had frequencies of 1.51% for heat-stable carbetocin versus 1.45% for oxytocin, RR 1.04 (95% CI, 0.87–1.25), P = .03. For this outcome, the observed upper limit of the 95% CI of 1.25 exceeded the noninferiority margin of 1.23, thus, the trial had insufficient statistical power to support a claim of noninferiority.
The sponsoring drug company committed to providing heat-stable carbetocin at a reasonable cost in low-income countries pending study findings. One major study limitation was that the advantages of heat-stable carbetocin were not investigated in this study as both drugs were cooled as part of the study protocol, to maintain blinding. Carbetocin is not available in the United States; the drug manufacturer has not yet submitted an application to the US Food and Drug Administration.
Intravenous (IV) oxytocin is recommended by the WHO for PPH prophylaxis after vaginal delivery, yet IM administration is recommended by RCOG.19 In a single-center RCT,19 10 units oxytocin were administered immediately after vaginal delivery either IV slowly (n = 517) over 1 minute or IM (n = 518). The primary outcome, PPH ≥500 mL measured using a collecting bag, was 18.8% for IV oxytocin versus 23.2% for IM oxytocin, adjusted odds ratio (aOR) 0.75 (95% CI, 0.55–1.03), P = .07. Secondary outcomes were significant: severe PPH (≥1000 mL) 4.6% vs 8.1%, aOR 0.54 (95% CI, 0.32–0.91), P = .02; and blood transfusion 1.5% vs 4.4%, aOR 0.31 (95% CI, 0.13–0.7), P = .005 for IV and IM oxytocin, respectively. The authors concluded that IV was superior to IM oxytocin to prevent severe PPH; number needed to treat was 29 (95% CI, 16–201). The incidence of side effects, including hypotension and tachycardia, was not increased for IV versus IM administration. Administration of oxytocin 10 units IV as a bolus, even slowly over 1 minute, may cause demand myocardial ischemia and/or cardiovascular collapse, particularly in hemodynamically unstable women, thus smaller IV bolus doses or IV infusions are recommended.
TXA administered in addition to uterotonic agents is recommended to treat PPH.21 However, its prophylactic effect to prevent PPH after vaginal delivery is unknown. In a French multicenter RCT,20 women received IV TXA 1G (n = 1461) versus placebo (n = 1473), 2 minutes after term vaginal delivery, in addition to routine uterotonic agents. The primary outcome, PPH ≥500 mL measured using a collecting bag, occurred in 8.1% after TXA and 9.8% after placebo, RR 0.83 (95% CI, 0.68–1.01), P = .07. Secondary outcomes included clinical assessment of PPH (whether the provider considered that significant PPH had occurred): 7.8% after TXA versus 10.4% after placebo, unadjusted RR 0.74 (95% CI, 0.61–0.91), P = .0004 and additional uterotonic agent administration: 7.2% after TXA versus 9.7% after placebo, unadjusted RR 0.75 (95% CI, 0.61–0.92), P = .006. Other secondary outcomes, including total EBL and emergency postpartum interventions, were not different between the groups. This study included all women after vaginal delivery, not just those at high-risk for PPH, and further trials are required for the high-risk population.
In summary, these 3 RCTs18–20 randomized more than 30,000 women after vaginal delivery; there was no significant benefit using 1 specific prophylactic uterotonic, or using TXA versus placebo, to reduce the risk of PPH ≥500 mL. Rates of PPH were higher than reported in population studies.22,23 This can be attributed to the use of a precise collection system in each of the studies, confirming that clinical estimation of EBL is imprecise, and that visual estimation delays diagnosis of PPH.15
Blood Lactate and PPH
Blood lactate rises in the presence of tissue hypoxia, as a by-product of anaerobic metabolism, and has been used to guide transfusion in trauma patients, as lactate is a marker of compromised tissue perfusion.24 To investigate the utility of lactate levels in PPH, a single-center retrospective analysis identified 302 women with PPH and a blood lactate measurement.25 The primary outcome of massive blood transfusion (dichotomous outcome) was defined as >10 units of packed red blood cells within 24 hours of PPH, and occurred in 101 (33%) women. The initial median lactate value was 2.2 mM (interquartile range [IQR], 1.7–3.3) in the nonmassive transfusion group versus 4.5 mM (IQR, 2.9–6.4) in the massive transfusion group, P < .001. Two variables were associated with massive blood transfusion requirement: blood lactate, odds ratio (OR) 1.56 (95% CI, 1.31–1.87) and shock index, OR 10.25 (95% CI, 3.69–28.45). The shock index, defined as heart rate (HR) divided by systolic blood pressure (SBP), should be further investigated for management of obstetric hemorrhage.26
PPH Population Studies
Maternal characteristics such as race and BMI are risk factors for PPH. Prepregnancy BMI was investigated in a California population database of more than 2 million women.27 The overall rate of PPH was 2.8%. Maternal obesity appeared to have only a modest effect on hemorrhage risk. Compared to women with normal weight, the aOR for hemorrhage in overweight women was 1.06 (99% CI, 1.04–1.08) and for class I obesity (BMI between 30 and 34.9 kg/m2) was 1.08 (99% CI, 1.05–1.11). After vaginal delivery, obese women had increased odds of hemorrhage up to 19%, whereas in cesarean deliveries, obesity was associated with a 14% decreased odds of hemorrhage.
A national population database of women with PPH was investigated for the association between severe maternal morbidity and race.23 The primary outcome was the presence of any of one of the 21 US Centers for Disease Control and Prevention (CDC) diagnoses of severe maternal morbidity (including shock, stroke, and heart failure).28 The PPH rate was 3.2% among more than 11 million deliveries. Non-Hispanic African American women were at highest risk for severe maternal morbidity including transfusion: RR 1.28 (95% CI, 1.25–1.31); adjusted risk ratio (aRR) 1.24 (95% CI, 1.22–1.27).
Pulmonary Embolus Is a Clinical Diagnosis
One case vignette in the State of Illinois MMR3 presented Jasmine, a young African American woman with antenatal clinical presentation consistent with deep vein thrombosis (DVT). Her symptoms were wrongly ascribed on multiple occasions and Jasmine died of a pulmonary embolism (PE) 18 days postpartum. This case illustrates the importance of clinical suspicion to enable a diagnosis of PE. Historically, validated models for diagnosing PE have excluded pregnant women; specific and sensitive tests to confirm PE in pregnancy are lacking.
D-dimer is not currently recommended to diagnose PE in this population due to unreliability. A prospective multicenter European study recruited pregnant women (n = 395) with acute onset or worsening shortness of breath or chest pain of unknown cause, for suspected PE.29 The revised Geneva score,30 unvalidated in pregnancy, was used to determine pretest probability of PE: low/intermediate (0–10 points) or high (≥11 points). Women with negative D-dimer (<500 µg/L) and low/intermediate pretest probability were defined as negative for PE, excluded from further testing, and did not receive anticoagulant therapy. Women with high pretest probability or positive D-dimer, ≥500 µg/L, underwent sequential tests beginning with bilateral compression leg ultrasound. If negative, a computerized tomography pulmonary angiogram (CTPA) was performed, and if inconclusive, a lung ventilation/perfusion (V/Q) scan was performed. All women were followed up for 3 months; the primary outcome, the rate of VTE diagnosed among women with low pretest probability, was 0.0% (95% CI, 0.0–1.0). Overall, 93% had PE excluded and 7% had a diagnosis of PE. Future research should evaluate standardized combinations of clinical patterns with sequential tests to reliably exclude or diagnose PE in pregnant women.31
Neuraxial Block and Recommendations for Pregnant Women Receiving Thromboprophylaxis
Low molecular weight heparin for VTE prophylaxis is increasingly used for pregnant women.32 The 2018 SOAP Consensus statement33 emphasized the low risk of spinal epidural hematoma in pregnant women, 200,000–1:250,000, and highlighted the importance of early assessment to enable timely decisions regarding neuraxial block for labor and delivery for women receiving VTE prophylaxis. The statement endorsed clinicians making balanced decisions weighing up the risk of spinal epidural hematoma versus risks of general anesthesia.
MANAGEMENT OF SPINAL-INDUCED HYPOTENSION
An international consensus statement on the management of spinal-induced hypotension during cesarean delivery was published in Anaesthesia in 2018.34 Key recommendations of the consensus statement included using phenylephrine rather than ephedrine, administered as prophylaxis rather than therapeutic bolus; with colloid preload or crystalloid coload and performing left uterine displacement. The aim is maintenance of SBP ≥90% following accurate prespinal anesthesia blood pressure (BP) assessment and avoidance of SBP <80% of the baseline measurement.34 In an editorial accompanying this consensus statement, Campbell and Stocks35 stated: “If we were to choose one thing in our obstetric anesthetic careers which has revolutionized our practice, it would be the introduction of phenylephrine infusions to prevent hypotension during cesarean delivery under spinal anesthesia.” Aggressive BP control improves maternal comfort during the procedure.
Vasopressors for Women With Preeclampsia
Among healthy women, maternal hemodynamic parameters are improved when phenylephrine is used to manage spinal hypotension35; however, the benefits among preeclamptics were not known. Most studies considered a neonatal outcome when investigating spinal-induced hypotension. Dyer et al36 performed an RCT to investigate maternal hemodynamic parameters using phenylephrine versus ephedrine to treat spinal hypotension in 42 women with severe preeclampsia undergoing cesarean delivery between 28- and 34-weeks’ gestational age. Participants were assessed using noninvasive cardiac output (CO) monitoring to measure changes in cardiac parameters in response to spinal anesthesia. Increases of CO and HR were noted for all women; yet despite a 300 mL colloid preload, 20 of 42 experienced hypotension (mean arterial pressure [MAP] ≤80% or <110 mm Hg). These 20 women were randomized to receive phenylephrine (n = 10) versus ephedrine (n = 10) bolus, and the mean % change in cardiac index was assessed. Phenylephrine more effectively reversed maternal hemodynamics back toward the baseline values measured before induction of spinal anesthesia, reducing the cardiac index by 12.0% (standard deviation [SD] 7.4%), versus an added 2.6% (SD 6.0%) increase for ephedrine.
Typically, preeclamptics experience less hypotension than healthy women during initiation of spinal anesthesia. Two RCTs investigated the optimal vasopressor, phenylephrine versus ephedrine, to manage hypotension in preeclamptics. First, Dyer et al37 studied preeclamptics with severe features undergoing urgent cesarean delivery for fetal distress. Among the 129 recruited women, 47% had hypotension (drop in MAP ≥20% or <100 mm Hg) after spinal anesthesia despite a small fluid bolus. These women were randomized to receive treatment boluses of either 50–100 µg of phenylephrine (n = 31) or 7.5–15 mg of ephedrine (n = 29).37 There was a nonsignificant difference for the primary outcome: mean (SD) umbilical artery (UA) base excess, −4.9 (3.7) mmol/L for phenylephrine versus −6.0 (4.6) mmol/L with ephedrine; mean difference (MD) 1.16 (95% CI, 1.00–3.32). Thus, neonatal acid-base status was similar whether phenylephrine or ephedrine was used to treat spinal hypotension among preeclamptics undergoing cesarean delivery for fetal compromise. The authors also discussed the particulars of obtaining informed consent in this emergency situation.
Although prophylactic vasopressor infusions are recommended to avoid spinal-induced hypotension, anesthesiologists may be reluctant to use them in preeclamptics. Higgins et al38 randomized preeclamptics (with or without severe features) undergoing cesarean delivery to receive a prophylactic infusion of 100 µg/mL of phenylephrine (n = 54) vs 8 mg/mL of ephedrine (n = 54) (relative potency 80:1). The protocol stipulated initiation of the prophylactic infusion only if SBP was <160 mm Hg, initiated at a rate of 1 mL/min for 2 minutes immediately after spinal anesthesia injection, and adjusted thereafter according to SBP, with a goal of maintaining SBP ≥80% baseline, but <160 mm Hg.38 There was no difference in the primary outcome, UA pH phenylephrine:ephedrine ratio, 1.002 (95% CI, 0.997–1.007). In contrast to healthy women, in mothers with preeclampsia, phenylephrine prophylaxis did not confer advantages for neonatal acid-base status compared to ephedrine.
Intraoperative Nausea and Vomiting
Although intraoperative nausea and vomiting (IONV) are common after spinal anesthesia, it is rarely considered as the primary study outcome. A multicenter RCT compared 100 µg of therapeutic phenylephrine bolus (n = 79) vs 100 µg/mL of prophylactic infusion (n = 81) at an initial rate of 30 mL/h in obese women (>35 kg/m2).39 Significantly fewer women receiving infusions (46%) had IONV versus women receiving boluses (75%), RR 0.61 (95% CI, 0.47–0.08), P < .001. As expected, hypotension occurred less frequently in the infusion group. Specifically there was less predelivery hypotension 22 (27%) vs 59 (75%), RR 0.36 (95% CI, 0.25–0.53), P < .001; and postdelivery hypotension 6 (7%) for infusions versus 34 (43%) for boluses, RR 0.17 (0.08–0.39), P < .0001. The rate of spinal-induced hypotension was unexpectedly higher than in a previous study performed by the same authors in nonobese women.40 The authors speculated that the sympathectomy may have been more extensive in this obese study cohort.
Norepinephrine Prophylactic Infusions
Although the consensus statement34 suggested using prophylactic phenylephrine infusions, and did not recommend norepinephrine infusions based on current evidence, the purported advantage of norepinephrine is fewer episodes of maternal bradycardia. A single-center RCT,41 randomized healthy women undergoing elective cesarean delivery between 2014 and 2016 to receive either prophylactic norepinephrine 5 µg/mL infusion, started at 30 mL/h (n = 43), vs 5 µg/mL bolus of 1 mL therapeutic norepinephrine (n = 37) according to a BP rescue protocol. The primary outcome, incidence of BP <80% baseline, occurred in 17% receiving prophylaxis and 66% receiving therapeutic norepinephrine, P < .001. Prophylactic norepinephrine infusion was associated with less hypotension than treatment. An accompanying editorial discussed the advantage of norepinephrine due to reduced incidence of bradycardia while acknowledging the reticence currently to use norepinephrine in routine clinical practice.42
POSTPARTUM PAIN AND ANALGESIA
The Fourth Trimester
The postpartum “fourth trimester” was the focus of several ACOG statements and bulletins in 2018.43–45 Postpartum complications are discussed, including bowel and bladder incontinence, along with educational tools and strategies, such as an ACOG Postpartum ToolKit.46 A New England Journal of Medicine editorial discussed the importance of care recommendations in the United States, where maternity leave is relatively short, and social inequalities frequently impact optimum postpartum care.47
Postpartum Opioid Use
Wide variations in pain intensity and experience are recognized after both vaginal and cesarean delivery. Multimodal analgesia is recommended by ACOG, and opioids should be reserved for severe pain.43 CDC reported that across the United States, rates of opioid use disorder more than quadrupled among delivery hospitalizations; Vermont, West Virginia, New Mexico, and Maine have seen the greatest rise from 1994 to 2014.48
Women rarely need opioid analgesia after vaginal delivery. In this single-center, case-control study of in-hospital postpartum prescriptions for opioid-naive women after vaginal delivery (n = 9038),49 a specific order was required to administer opioids after vaginal delivery. Overall, 20% of women with normal noncomplicated vaginal delivery received an opioid postpartum. Nonsteroidal anti-inflammatory drugs (NSAIDs) were prescribed for 97% of women, acetaminophen for 26%, and opioids for 25%. Factors associated with opioid use included high BMI and delivery complications (such as perineal tear or PPH). Higher number of acetaminophen (aOR, 0.81 [95% CI, 0.77–0.85]) and NSAIDs (aOR, 0.92 [95% CI, 0.87–0.96]) doses and more senior practitioner prescribing (OR, 0.46 [95% CI, 0.29–0.73]) were associated with lower likelihood of in-hospital opioid prescription after vaginal delivery.
Postpartum opioids are not limited to in-hospital prescribing. Using an insurance claims database across the United States and Puerto Rico,50 all women with vaginal delivery (n = 1345,244) were identified between 2003 and 2015. Within 1 week of discharge, 28.5% (95% CI, 28.4–28.6) filled an opioid prescription; geographic location accounted for the strongest risk difference (RD). Women on benzodiazepines or antidepressants were more likely to fill opioid prescriptions, as were women who had a tubal ligation before discharge for the delivery hospitalization, operative vaginal delivery, and with perineal tears. However, less than 20% who filled opioid prescriptions had tubal ligations, perineal tears, or operative vaginal delivery. Codeine was the prescribed opioid in 15% of cases. Codeine is no longer recommended for breastfeeding mothers due to potential for neonatal respiratory depression; a recent US Food and Drug Administration warning was issued to this effect.51 The reasons for opioid prescriptions were not reported.
Neuraxial Opioids for Postpartum Analgesia After Cesarean Delivery
The most efficacious post cesarean delivery analgesia regime is an intrathecal hydrophilic opioid with either morphine or diamorphine.52,53 However, risks of respiratory depression may dissuade anesthesiologists from its use.53 A systematic review of clinically significant respiratory depression (CSRD)54 following neuraxial opioid administration (epidural or intrathecal) identified 75 studies reporting administration of neuraxial morphine or diamorphine for postpartum cesarean analgesia. Sixteen cases of CSRD were identified, a rate of 8.67 per 10,000 cases (95% CI, 4.20–15.16). The doses of opioids varied, and among the 16 cases, 14 received high doses and only 2 received low dose, ≤150 µg intrathecal morphine. There were no cases of CSRD with neuraxial diamorphine, possibly due to an advantageous safety profile or fewer reports. SOAP recently published a consensus statement discussing respiratory monitoring for women who received neuraxial opioids after cesarean delivery. These are more lenient than the American Society of Anesthesiologists (ASA) recommendations for healthy women.52,53
Truncal Blocks for Postpartum Analgesia After Cesarean Delivery
Women unable to receive intrathecal morphine should receive an alternative efficacious analgesic. Quadratus lumborum block (QLB) for postcesarean delivery analgesia was investigated in a single-center RCT.55 All women undergoing cesarean delivery received intrathecal plain 10 mg of bupivacaine without neuraxial morphine, followed by either bilateral QLB with ropivacaine or bilateral placebo saline injection. The primary outcome, cumulative opioid consumption, was significantly reduced after QLB, ratio of means 0.60 (95% CI, 0.3–0.97), P = .04, when administered as part of a multimodal analgesic strategy. The transabdominus plane (TAP) block for post cesarean delivery analgesia was investigated in a meta-analysis of 14 studies,56 using high or low dose local analgesia TAP block (n = 389) versus controls without TAP block (n = 381). High-dose TAP block was >50 mg of bupivacaine equivalents per block side, and low dose was ≤50 mg of bupivacaine equivalents per block side. The primary outcome, 24-hour postcesarean delivery morphine equivalent consumption, was significantly lower in both the low-dose and high-dose TAP block groups versus control; high-dose MD −22.41 (95% CI, 38.56−6.26), P = .007, I2 = 93%, and low-dose MD −16.29 (95% CI, 29.74 to −2.84), P = .02, I2= 98%. There was no difference for the effect sizes for the 2 groups, I2 = 0, P = .57. Thus, benefit of high-dose compared to low-dose TAP block was not demonstrated. High-dose TAP block has been associated with clinically toxic levels of local anesthetics agents,57 thus, in the absence of analgesic benefit, high-dose TAP block should be avoided. A Practice Advisory from the American Society of Regional Anesthesia & Pain Medicine (ASRA) reported that local anesthetic systemic toxicity (LAST) may be less frequent than previously reported.58 One-third of patients present with central nervous and cardiovascular system symptoms; although presentation may be atypical and delayed up to an hour. If in doubt of the diagnosis, lipid emulsion should be administered.
LABOR ANALGESIA AND PPD
ACOG recommends that all women be screened carefully for PPD using a validated tool at least once during the postpartum period, and pregnant women who underwent screening before delivery require reassessment after delivery for PPD.45 Ten percent of postpartum women meet criteria for major depressive disorders.45 Two studies investigated the relationship between labor analgesia and PPD using the Edinburgh postpartum depression score (EPDS) 6 weeks postpartum.59,60 In a single-center prospective longitudinal study,59 1326 postpartum women were asked which labor analgesia, if any, they had intended to use. Most women (1058) had received epidural analgesia, but 439 had not, including 328 women who had wanted/did not receive epidural analgesia. The rate of positive EPDS screen ≥10 at 6 weeks in the study cohort was 87 of 1326 (6.6%). This rate was similar among women whose antepartum expectations were met versus women with unmet antepartum expectations, relative RD 1.8% (95% CI, 3–7). However, unmet expectations with labor analgesia provision was a risk factor positive EPDS screen. Women who wanted/did not receive epidural analgesia had a higher rate of elevated EPDS at 6 weeks when compared with those women who had not wanted/did not receive epidural analgesia, with an RD of 5.4% (95% CI, 1.1–9.8), P = .014.
The second study examined women who received epidural analgesia, n = 201, and had pain scores assessed before and after epidural analgesia placement.60 The percent change in pain (PIP) was calculated (difference between baseline and subsequent pain scores over time); a positive score reflected good analgesia and a negative score the opposite. There was a positive relationship between PIP and positive EPDS score at 6 weeks postpartum in simple linear regression, r = 0.025, P = .002. This observational study suggested that good labor analgesia was associated with reduced frequency of positive EPDS score at 6 weeks postpartum.
CONCLUSIONS AND RECOMMENDATIONS
Recommendations and Suggested Areas for Future Research
|Clinical or Research Focus
||Anesthesiologists should use prophylactic phenylephrine infusions during elective cesarean delivery.
||Ensure appropriate equipment in resuscitation carts to enable perimortem cesarean delivery.
||Pulmonary embolism is a clinical diagnosis: use a structured algorithm to diagnose pulmonary embolism, including D-dimer measurements.
||Women receiving thromboprophylaxis should have antenatal assessment to facilitate timely anesthesia strategies.
||Focus and target postpartum opioid prescribing.
||Use multimodal postcesarean delivery analgesia, preferably with neuraxial hydrophilic opioids (morphine or diamorphine).
||Measure blood lactate in postpartum hemorrhage and consider using shock index to recognize women with obstetric hemorrhage.
||Study the impact of labor analgesia on postpartum depression.
||Identify and evaluate evidence-based strategies to reduce racial and ethnic disparities in severe maternal morbidity and mortality.
In conclusion, review of the articles published in 2018 suggests that anesthesiologists have many opportunities to impact maternal care and outcomes, as highlighted in this review. The Table summarizes several evidence-based clinical practice recommendations and research focus areas from the 2018 obstetric anesthesia literature.
I acknowledge the SOAP board of directors for the honor and the opportunity to review the 2018 literature and to present the What’s New in Obstetric Anesthesia Gerard W. Ostheimer lecture in 2019. I acknowledge my husband, Dr Paul Spencer, and our lively, lovely children: your support and understanding are boundless and gratefully received.
Name: Carolyn F. Weiniger, MB ChB.
Contribution: This author drafted, wrote, and approved the manuscript.
This manuscript was handled by: Jill M. Mhyre, MD.
1. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006-2010. Obstet Gynecol. 2015;125:5–12.
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