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.

Disclosures

Anesthesiology. 2018;129(1):192-215. 

In This Article

Anesthesiology Contributions to Maternal Safety

Mortality Due to Anesthesia

Anesthesia-related maternal mortality has decreased significantly over the last half-century. Maternal mortality ratios due to anesthesia in the United States are currently estimated at 1.0 per million live births—a 59% reduction from the period of 1979 to 1990.[5] Morbidity and mortality associated with modern-day anesthesia care are often associated with complications of neuraxial anesthesia (e.g., high or total spinal anesthesia after failed epidural anesthesia and unrecognized spinal catheters).[5,102,185] Importantly, anesthesiologists continue to play a key role in the prevention of non–anesthesia-related direct and indirect maternal deaths, such as those caused by hemorrhage, hemodynamic instability, critical illness, and sepsis.[5,102]

Postpartum Hemorrhage and Patient Blood Management

Postpartum hemorrhage is a leading cause of maternal morbidity, cardiac arrest, and mortality worldwide. It accounts for approximately 12.5% of pregnancy-related deaths (1.8 deaths per 100,000 live births) in the United States.[186] Most cases of hemorrhage-related maternal mortality are preventable.[186] Protocolized approaches to postpartum hemorrhage have been developed, which have been shown to result in improved outcomes in many settings.[187] The National Partnership for Maternal Safety is a multidisciplinary work group including anesthesiologists, maternal-fetal medicine specialists, obstetricians, nurses, and nurse-midwives. The group has provided a consensus bundle on best practices for obstetric hemorrhage.[188] Despite the evidence showing improvement in outcomes, there appears to be limited adoption of these protocols; in 2014, only 67% of academic obstetric anesthesia units in the United States reported the use of a postpartum hemorrhage protocol, with greater use in hospitals with delivery volumes more than 3,000 per year.[189] Additional work to identify barriers to protocol adoption in low-volume centers will shed light on implementation strategies.

Maternal hematologic physiology differs from the nonpregnant state; severe obstetric hemorrhage is more likely to be associated with early hypofibrinogenemia.[190,191] In the setting of postpartum hemorrhage, early assessment of fibrinogen levels should be undertaken; levels less than 200 mg/dl should prompt aggressive monitoring and treatment. The American Society of Anesthesiologists guidelines specify that fibrinogen levels should be treated early in obstetric hemorrhage.[192] Over-transfusion and under-resuscitation both carry risks. Efforts aimed at avoiding over-transfusion are likely in the best interest of the parturient as restrictive transfusion strategies are linked to lower risks for infections, cardiac events, and death.[193,194] However, this goal must be balanced with risk of under-resuscitation, because maternal death from hemorrhage is often attributable to delayed recognition and under-resuscitation.[102]

Professional society guidelines for obstetric blood management differ from each other and from nonobstetric guidelines.[191] The American College of Obstetricians and Gynecologists specifically recommends cell salvage for women with rare antibodies and if banked blood is not available, and for women who refuse allogeneic transfusion.[195] Cell salvage may also limit allogeneic blood consumption and be cost-saving.[196,197] Point-of-care testing has gained attention for its potential use in postpartum hemorrhage due to rapid results and detection of hyperfibrinolysis. Viscoelastic tests (thromboelastography) may be useful in assessing clot strength and thrombin generation.[198] However, in major obstetric hemorrhage, laboratory testing performed better at detecting large aberrations in coagulation values, which correlated better with estimated blood loss, than thromboelastography.[199] Point-of-care testing to guide component transfusion in obstetric hemorrhage may mitigate allogeneic transfusion, but whether laboratory-guided transfusion improves maternal outcomes has not been well studied.

The administration of antifibrinolytic agents (tranexamic acid) in obstetric hemorrhage has received recent attention. Its prophylactic use in planned cesarean deliveries leads to clinically insignificant bleeding differences.[200] Thromboembolic complication data in this population have been lacking. In 2017, results were published from the World Maternal Antifibrinolytic Trial, which compared tranexamic acid versus placebo in 20,060 women with a clinical diagnosis of postpartum hemorrhage;[201] 198 hospitals in 21 countries were included, primarily low-resource settings with high rates of maternal hemorrhage deaths. Women randomly received tranexamic acid 1 g or placebo. Death due to hemorrhage was significantly reduced in women who received tranexamic acid (1.5% vs. 1.9%; risk ratio, 0.81; 95% CI, 0.65 to 1.00; P = 0.045). The need for laparotomy to control bleeding was reduced (risk ratio 0.64; 95% CI, 0.49 to 0.85; P = 0.002). Importantly, maternal death was reduced by 31% if tranexamic acid was given within 3 h of birth. Tranexamic acid was beneficial regardless of cause of hemorrhage (e.g., trauma, atony). The risk of hysterectomy and thromboembolic events were not different. The authors concluded that tranexamic acid should be given as soon as possible in postpartum hemorrhage regardless of cause, or after any bleeding associated with hemodynamic instability. This conclusion is consistent with our own clinical practice. Tranexamic acid is likely safe in obstetrics; whether the benefit of preventing death due to bleeding can be extrapolated to well-resourced countries is unknown.

Early Warning Systems

The Modified Early Obstetric Warning System was first described and recommended by the United Kingdom's Confidential Enquiries into Maternal and Child Health, a national program that investigated all maternal deaths and other adverse outcomes.[102] The group recognized that late recognition of maternal morbidity was contributing to poor outcomes and recommended a warning/screening system that included vital signs parameters (e.g., temperature, blood pressure, respirations, neurologic response, and urine output). A study published in 2011 validated these parameters and established threshold for elevated morbidity.[202] The parameters performed well as a screening tool, with a sensitivity of 89%, specificity of 79%, and negative predictive value of 98%. In the United States, modifications were proposed by the National Partnership for Maternal Safety, based on expert consensus from a multidisciplinary group of obstetricians, nurses, midwives, and anesthesiologists.[203,204] The group recommend immediate action if any of the maternal early warning criteria in figure 5 were met. Anesthesia providers are instrumental to early hemorrhage recognition, treatment, and implementation of Maternal Early Warning Systems and should actively participate in establishing these systems.

Figure 5.

Maternal Early Warning Criteria. The presence of any of these abnormal "triggers" should activate an immediate bedside evaluation by a physician or qualified clinician who can accelerate care toward prompt diagnosis and treatment of the underlying condition. Considerations for potential differential diagnoses are noted. Any nurse or clinician who is concerned about maternal status should feel empowered to raise concerns up the chain of command to achieve an appropriate response. Mechanisms for escalating notifications should be established. The triggers listed are not comprehensive for all possible obstetrical scenarios and are not intended to replace clinical judgement. Adapted with permission from Mhyre JM, D'Oria R, Hameed AB, Lappen JR, Holley SL, Hunter SK, Jones RL, King JC, D'Alton ME: The maternal early warning criteria: a proposal from the national partnership for maternal safety. Obstet Gynecol 2014; 124:782–6.204

Oxytocin Protocols

Active management of the third stage of labor reduces postpartum hemorrhage risk. Prophylactic uterotonic agents (oxytocin) are given and controlled umbilical cord traction for placenta delivery is performed. Studies published in the past decade, primarily by anesthesiologists, have identified safe methods for oxytocin administration for active management of the third stage of labor. The motivation to provide safe oxytocin doses stems from the uncommon but severe side effects associated with oxytocin, including dose-dependent cardiac conduction abnormalities, coronary vasospasm, and severe acute hyponatremia leading to seizures (oxytocin bears structural similarity to vasopressin).[205] Furthermore, high doses of oxytocin are not necessary to achieve clinical gains for active management of the third stage of labor. A randomized trial compared oxytocin administration using a "rule-of-threes" algorithm to "wide open" infusion of oxytocin (30 units in 500 ml normal saline). In the "rule-of-threes" group, a 3-unit/3 ml oxytocin bolus was administered immediately after cesarean delivery, with optional repeat boluses of 3-unit/3 ml oxytocin at 3 min and at 6 min after delivery. This approach resulted in uterine tone at 3, 6, 9, and 12 min after delivery that was no less adequate than standard treatment. The control group received significantly more oxytocin, while there were no differences in blood loss or need for additional uterotonic agents.[206]

Oxytocin is often given as an infusion due to its short half-life of 1 to 5 min, thus a low-dose infusion protocol has been studied. George et al. estimated that the oxytocin infusion ED90 for satisfactory uterine tone in women undergoing elective cesarean delivery is 0.3 units/min (18 units/h).[207] Pre–post studies following the institutional introduction of low-dose oxytocin infusion protocols have found reduced total dose of oxytocin with no impact on rates of postpartum hemorrhage, volume of estimated blood loss, or secondary uterotonic administration.[208,209]

Oxytocin receptor desensitization may explain the risk for postpartum hemorrhage from refractory atony in intrapartum cesarean delivery following oxytocin exposure during labor.[210,211] In vitro tests involving human myometrial strips exposed to 2 h of oxytocin pretreatment versus control demonstrated that the motility index (frequency × amplitude) of strips not exposed to oxytocin were significantly greater than those pretreated with oxytocin.[212,213] In vitro testing has not identified whether "resting periods" are effective in resensitizing myometrium. Therefore, giving more oxytocin in the setting of desensitization may not achieve the desired effect of increased uterine tone; in these cases, a different uterotonic agent that works by a different mechanism is indicated. In another study, the ED90 of oxytocin infusion for women with prior labor exposure to oxytocin was 44 units/h, much higher than the ED90 for women without prior exposure to oxytocin.[214] However, this higher dose is associated with more side effects, including nausea, vomiting, and ST segment depression. Further in vivo and in vitro investigations may elucidate the clinical significance of oxytocin desensitization, and may inform oxytocin protocols for women exposed to oxytocin during labor.

Safety Bundles

The National Partnership for Maternal Safety's goal is to reduce maternal morbidity and mortality in the United States. The United States is the only country in the developed world that has had increasing rates of maternal mortality since 1990. The maternal mortality ratio in the United States was 12.4 per 100,000 live births (95% CI, 11.1 to 13.9) in 1990; by 2013, it increased to 18.5 (95% CI, 14.8 to 22.9).[215] Maternal morbidity and mortality are frequently preventable, and guidance on best practices is instrumental in preventing maternal deaths.[187] The National Partnership for Maternal Safety has developed safety "bundles" for maternal care in the areas of obstetric hemorrhage, hypertension in pregnancy, perinatal depression and anxiety, reduction of primary cesarean birth, support after a severe maternal event, and venous thromboembolism.[216–218] Bundles are based on the best available evidence and are endorsed by multiple professional groups including the American College of Obstetricians and Gynecologists, the American Society of Anesthesiologists, the American College of Nurse-Midwives, and the Association of Women's Health, Obstetric, and Neonatal Nurses, among others. Each bundle is organized into five major areas: readiness, recognition, response, reporting, and systems learning. The resources are free and openly available to the public at www.safehealthcareforeverywoman.org (accessed March 9, 2018). Given the anesthesia provider's expertise in resuscitation and systems-based response, we are ideal participants in multidisciplinary shared leadership strategies to implement these bundles.

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