Amniotic fluid embolism rescued by venoarterial extracorporeal membrane oxygenation

To our knowledge, this is the largest and most detailed follow-up study of catastrophic AFE patients requiring ECMO. AFE is a rare ECMO indication but is associated with a 70% survival rate at hospital discharge despite an extreme pre-ECMO severity. In this rare per-delivery complication, our results support the use of VA-ECMO despite intense DIC and active bleeding. Besides, physicians should be aware that these patients would need massive blood product transfusion during the first ECMO days. However, long-term HRQL was lower than age-matched controls and still profoundly impaired in the role-physical, bodily pain, and general health components when compared to other survivors rescued by ECMO.

The diagnosis of AFE is challenging as there are widely varying criteria for the diagnosis of AFE [5], most of AFE definitions are nonspecific, biological markers may not be specific to AFE [18], and exhaustive searches for alternative diagnoses are not uniformly done in a context of critically ill patients. For these reasons, we decided to restrict our inclusion criteria to the most recent definition proposed by Clark et al. [5]. These uniform diagnostic criteria help to prevent the inclusion of patients with alternative diagnoses such as hypovolemic shock secondary to postpartum hemorrhage, anesthetic accident, pulmonary thromboembolism, septic, and anaphylactic shock. For instance, we excluded 3 patients for whom AFE diagnosis was retained in the medical record without strictly fulfilling all of our AFE criteria. Two of them did not have DIC and one had fever, which could have been compatible with anaphylactic shock and septic shock, respectively. Several studies suggest a role for IGFBP-1 in the development of multiple organ dysfunction [19]. As detection of squamous cells into the maternal circulation or in the lungs requires procedural skill and may not be specific to AFE [20, 21], a high concentration of serum IGFBP-1 levels has been proposed for the diagnosis of AFE [18]. However, serum markers could be sometimes difficult to interpret since massive transfusion often occurred, distorting maternal serum dosages. Because of the lack of a systematic measure of IGFBP-1 and inconsistent quantitative measurement in all pregnant women on ECMO during the study period, this biomarker was not retained as an inclusion criterion.

Extracorporeal life support has been successfully used in pregnant and postpartum patients for a variety of indications [22]. Despite an extreme severity at the time of ECMO initiation, the 70% survival rate observed in this series is similar to the case-fatality reported in other case series (11–43%) with patients with lower severity [1, 18]. By aggressively treating bleeding events and judiciously managing systemic anticoagulation, ECMO appears adequate to rescue very severe AFE. Indeed, AFE is a self-resolving disease affecting the pulmonary and cardiovascular systems with most death and complications occurring during the first 24 h [1]. Our results reinforce that high bleeding risk should not be seen as an absolute contraindication to use ECMO [23]. However, ECMO management should be wisely adapted to these complex situations with DIC, thrombocytopenia, and frequent ongoing bleeding. An anticoagulation-free ECMO strategy, which combines no heparin bolus at cannulation and no anticoagulation as long as there are bleeding and/or DIC appears mandatory. This strategy on VA-ECMO is feasible and has been reported with other ECMO indications such as trauma [24] or refractory pulmonary embolism despite thrombolysis [25]. As reported in our results, massive transfusion of fresh frozen plasma, platelets, red blood cell packs, and fibrinogen, as well as arterial embolization or surgical hemostasis is frequently needed before or during cardiopulmonary support by VA-ECMO.

The favorable survival of these very severe patients should not overshadow that the long-term HRQL was still impaired compared with that of sex-and age-matched controls, especially concerning SF-36 general health, vitality, role-physical and social functioning, while mental health and role-emotional were considered satisfactory. Although differences in case mixes make comparisons between series difficult we observed that our patient’s SF-36 scores were worse than those reported by ARDS or septic shock survivors rescued by VV or VA-ECMO, respectively [12, 13]. Muscle weakness, chronic fatigue, and pain still significantly impact work or daily activities after a median of 44 months after ICU discharge. Previous studies also highlighted that women who give birth with severe obstetrical adverse events are at higher risk of long-term physical and mental health sequels compared to uncomplicated obstetrical populations [26]. In our population, only 60% of these young women returned to their previous work. These results highlight the urgent need for studies focusing on the establishment of customized, patient-centered, rehabilitation programs that could help improve long-term postpartum health-related quality of life [27‐29].

We are aware that our study has limitations. First, AFE is a relatively rare disease that has limited our sample size. Second, our patients were treated in high-volume, experienced ECMO centers. Because better post-ECMO outcomes have been reported in such centers [30], caution is required when extrapolating these results to less-experienced ECMO centers. Third, the sole strict clinical-biological definition of AFE may have led to underreporting some cases. Therefore, we cannot rule out that more AFE cases could have been included with other AFE definitions or based on serum biomarkers. Lastly, the self-assessed, persistently impaired physical health and vitality might not be specific to ECMO itself but may represent sequelae of any severe disease requiring high doses of vasopressors, transfusion, and prolonged ICU stays as well as psychological and somatic sequelae after a highly complicated delivery.

In conclusion, the survival of ECMO-rescued pregnant women with catastrophic AFE in our experienced centers was 70%. Ongoing bleeding, need for massive transfusion and DIC should not refrain physicians to early contact a Mobile Circulatory Assistance Units to prompty initiate VA-ECMO in these severely ill patients with cardiopulmonary dysfunction and high bleeding risk. However, general health, vitality, and role-physical impairment reported after long-term follow-up emphasizes the importance to integrate these young patients into customized, patient-centered, rehabilitation programs after ICU discharge.