Venous thromboembolism (VTE) is a leading cause of maternal mortality and severe morbidity, and its incidence increased >70% between 1998 and 2009.1 Unfortunately, preventing maternal VTE presents a challenge because most of the evidence that guides decision-making is based on observational studies, expert opinion, or data extrapolated from nonpregnant patients.2 There exists a need for well-designed, large randomized control trials to determine optimal prophylaxis strategies. Nevertheless, population-level evidence does support the use of universal mechanical VTE thromboprophylaxis for patients undergoing cesarean delivery and targeted pharmacologic prophylaxis for women with additional risk factors. For example, widespread thromboprophylaxis in the United Kingdom was effective in decreasing its maternal deaths,3 suggesting that implementing thromboprophylaxis protocols can reduce maternal mortality.
In response to these findings, several organizations have published recommendations regarding thromboprophylaxis including the National Partnership for Maternal Safety (NPMS). NPMS publishes bundles, a set of evidence-based practices that improve outcomes, on a variety of pertinent topics including obstetric hemorrhage and severe hypertension in pregnancy with plans for many more. In 2016, NPMS published the VTE bundle4 in 4 high-impact journals (anesthesia-, obstetrics-, midwifery-, and nursing-related) simultaneously. The bundle recommends early ambulation, pneumatic compression devices, and risk stratification regarding pharmacological thromboprophylaxis. Consequently, the proportion of parturients receiving anticoagulation therapy surrounding delivery will likely increase, complicating the safe administration of neuraxial anesthesia. Therefore, the Society for Obstetric Anesthesia and Perinatology (SOAP) has published a consensus statement in this month’s Anesthesia & Analgesia exploring such concerns.5
This response by SOAP is of the utmost importance. To date, no other American recommendations clearly discuss the risks and benefits of proceeding with neuraxial anesthesia specifically in obstetric patients receiving thromboprophylactic therapy. Working since May of 2015, the writing group meticulously worked to bridge disparate and frequently conflicting recommendations from The American Society for Regional Anesthesia (ASRA)6 with those of the NPMS,4 the American College of Obstetrics and Gynecology, and the American College of Chest Physicians.
To date, the ASRA practice guidelines have served as the authoritative document to guide safe neuraxial blockade for all patients receiving anticoagulant therapy. The recommendations have been applied in pregnancy despite the fact that ASRA acknowledges that the evidence is too limited to make any recommendations in this setting: “Unfortunately, there is a paucity of data regarding…pregnancy.”6 Also, the ASRA document conflicts with the NPMS guidelines by stating “in most women, the benefits of thromboprophylaxis do not outweigh the maternal and fetal risks,”6 whereas the NPMS publication clearly recommends it for many pregnant women.4 The contradictions lead individual clinicians to disparate conclusions, and leave obstetricians and patients frustrated and in distress when anesthesiologists covering labor and delivery units change clinical plans and decline to perform expected neuraxial block procedures.
It seems evident that extrapolating data from nonpregnant women is fraught with potential for error. The parturient’s normal physiology is altered, rendering her hypercoagulable. The hypercoagulability of pregnancy may make neuraxial procedures safer in parturients than nonpregnant patients. Spinal epidural hematoma leading to permanent neurologic dysfunction is the most feared catastrophic complication from placing a neuraxial block. Fortunately, it is quite rare among parturients, estimated to occur at a rate of 1:250,000 in the obstetric population7 as compared to the much higher rate of 1:3600 identified in elderly women undergoing total knee replacements.8 To more clearly define the risk of neuraxial blockade in the presence of pharmacologic VTE prophylaxis, the authors of the SOAP Consensus Statement completed a systematic review of clinical trials, observational studies, case series, case reports, and the American Society of Anesthesiology Closed Claims Database; their extensive search failed to identity even 1 report of a spinal epidural hematoma in a parturient receiving thromboprophylaxis with unfractionated heparin or low-molecular-weight heparin.9
Pharmacokinetics are also affected. Increased renal blood flow and renal function accelerate clearance of anticoagulants. Consequently, a pregnant woman may have a smaller change in her activated partial thromboplastic time as compared to a nonpregnant woman receiving the same dose of unfractionated heparin.10 Additionally, the low-molecular-weight heparin, enoxaparin, causes a lower peak anti-Xa activity in pregnant patients than nonpregnant patients.11 Accelerated clearance in the second half of pregnancy has led some obstetricians to use twice-daily (as opposed to once-daily) enoxaparin dosing for the purpose of thromboprophylaxis, further confusing management decisions for safe neuraxial blockade.
Neuraxial anesthetic procedures may also provide more benefits to the obstetric patient than the nonpregnant surgical patient. Neuraxial labor analgesia remains the most efficacious treatment available to treat severe labor pain.12 Neonates born to mothers with epidurals do not require active resuscitation as often as neonates born to mothers receiving systemic opioids.12 Women with comorbidities who are at high risk for an urgent cesarean delivery (eg, preeclampsia, obesity) or women with risk factors for difficult airway management (eg, preeclampsia, obesity) may benefit from an in situ epidural catheter to avoid a general anesthetic and its associated complications including aspiration, failure to oxygenate, hypertensive crisis, or stroke. Airway management disasters persist as a leading cause of anesthesia-related maternal mortality,3,13 despite advances in airway management leading to improved outcomes over the past 4 decades.14 Outcomes after general anesthesia for cesarean delivery remain persistently worse than those after regional techniques.15
The SOAP Consensus Statement brings together multiple lines of evidence to outline a sequence of strategies that clinicians may use to navigate tradeoffs among the risk of VTE, the effects of pharmacologic anticoagulation, complications of general anesthesia, and the remote risk of epidural hematoma. The statement focuses on decision-making strategies, rather than prescriptive recommendations, for 2 reasons. First, clinical management is frequently complex in this population, given competing risks and evolving delivery management plans. Second, complete consensus proved elusive, despite months of negotiation and evidence review. For example, an early electronic version of the fourth ASRA Guideline recommends waiting 4–6 hours in women receiving unfractionated heparin 5000 units subcutaneously daily before proceeding with neuraxial anesthesia. The SOAP statement, however, states that clinicians can proceed with neuraxial anesthesia without delay if the surgical case is urgent and the risks of potential general anesthesia are perceived to be high. Given that millions of women have received uncomplicated neuraxial blockade without regard to the timing of low-dose unfractionated heparin, some experts on the taskforce felt that the recommendations should be to proceed without delay even in elective cases, due to the lack of evidence of the need to delay. This truth in transparency within the document allows clinicians room to make their own risk and benefit judgments. Certainly, this is an area in which patient engagement and shared decision-making will help to ensure an optimal tradeoff between these competing remote but catastrophic risks.
Skeptics may criticize the VTE bundle or this consensus statement on safe neuraxial blockade because strong evidence to make class IA recommendations does not exist. However, given the limitations of conducting randomized controlled trials that would be adequately powered to study these rare events, it is difficult to make class IA recommendations. Furthermore, despite this limitation, the incorporation of past bundles into everyday practice has yielded benefits in improving outcomes.3 This improvement can be at least partially attributed to increasing awareness and communication, and emphasizing a multidisciplinary approach to preventing and treating these events.
The SOAP Consensus Statement on VTE does an excellent job highlighting the importance of multidisciplinary care. Everyone on the team including patients, obstetricians, midwives, anesthesia providers, and nurses needs to know when the last dose of an anticoagulant has been administered to a pregnant patient and which patients may not be candidates for neuraxial anesthesia. The best manner in which this information is delivered (eg, via electronic medical record or via direct communication or both) will vary in different practice settings. Antepartum patients require a new level of attention from anesthesiologists, given the recommendation for routine anticoagulation in this population, and the speed with which the clinical goals may change from expected management to impending delivery.
This consensus statement not only highlights the importance of thromboprophylaxis and timing of neuraxial blockade but also emphasizes a larger culture shift within the United States toward increased focus on maternal safety. With maternal mortality in this country on the rise as opposed to declining like it is in most other developed nations across this world, it is imperative that all clinicians work as part of a team to optimize maternal safety. More than ever, anesthesiologists must function as peripartum physicians in all aspects of care.
Name: Jennifer M. Banayan, MD.
Contribution: This author helped conceptualize the editorial.
Name: Barbara M. Scavone, MD.
Contribution: This author edited, contributed to, and approved the final manuscript.
Name: Jill M. Mhyre, MD.
Contribution: This author edited, contributed to, and approved the final manuscript.
This manuscript was handled by: Jean-Francois Pittet, MD.
1. Callaghan WM, Creanga AA, Kuklina EV. Severe maternal morbidity among delivery and postpartum hospitalizations in the United States. Obstet Gynecol. 2012;120:1029–1036.
2. Bates SM, Middeldorp S, Rodger M, James AH, Greer I. Guidance for the treatment and prevention of obstetric-associated venous thromboembolism. J Thromb Thrombolysis. 2016;41:92–128.
3. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom. BJOG. 2011;118suppl 11–203.
4. D’Alton ME, Friedman AM, Smiley RM, et al. National partnership for maternal safety: consensus bundle on venous thromboembolism. Anesth Analg. 2016;123:942–949.
5. Leffert L, Butwick A, Carvalho B, et al. The Society for Obstetric Anesthesia and Perinatology consensus statement on the anesthetic management of pregnant and postpartum women receiving thromboprophylaxis or higher dose anticoagulants. Anesth Analg. 2018;126:928–944.
6. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35:64–101.
7. D’Angelo R, Smiley RM, Riley ET, Segal S. Serious complications related to obstetric anesthesia: the serious complication repository project of the Society for Obstetric Anesthesia and Perinatology. Anesthesiology. 2014;120:1505–1512.
8. Moen V, Dahlgren N, Irestedt L. Severe neurological complications after central neuraxial blockades in Sweden 1990-1999. Anesthesiology. 2004;101:950–959.
9. Leffert LR, Dubois HM, Butwick AJ, Carvalho B, Houle TT, Landau R. Neuraxial anesthesia in obstetric patients receiving thromboprophylaxis with unfractionated or low-molecular-weight heparin: a systematic review of spinal epidural hematoma. Anesth Analg. 2017;125:223–231.
10. Brancazio LR, Roperti KA, Stierer R, Laifer SA. Pharmacokinetics and pharmacodynamics of subcutaneous heparin during the early third trimester of pregnancy. Am J Obstet Gynecol. 1995;173:1240–1245.
11. Lebaudy C, Hulot JS, Amoura Z, et al. Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy. Clin Pharmacol Ther. 2008;84:370–377.
12. Halpern SH, Muir H, Breen TW, et al. A multicenter randomized controlled trial comparing patient-controlled epidural with intravenous analgesia for pain relief in labor. Anesth Analg. 2004;99:1532–1538.
13. Hawkins JL, Chang J, Palmer SK, Gibbs CP, Callaghan WM. Anesthesia-related maternal mortality in the United States: 1979-2002. Obstet Gynecol. 2011;117:69–74.
14. Mushambi MC, Kinsella SM, Popat M, et al; Obstetric Anaesthetists’ Association; Difficult Airway Society. Obstetric Anaesthetists’ Association and Difficult Airway Society guidelines for the management of difficult and failed tracheal intubation in obstetrics. Anaesthesia. 2015;70:1286–1306.
15. Guglielminotti J, Wong CA, Landau R, Li G. Temporal trends in anesthesia-related adverse events in cesarean deliveries, New York State, 2003-2012. Anesthesiology. 2015;123:1013–1023.