Successful resuscitation of amniotic fluid embolism applying a new classification and management strategy
© The Author(s) 2015
Received: 11 May 2015
Accepted: 22 June 2015
Published: 27 August 2015
Amniotic fluid embolism (AFE) is a rare but life-threatening maternal emergency caused by the entry of amniotic fluid contents into the maternal circulation. The clinical manifestations of AFE are heterogeneous, leading to misdiagnosis or treatment delay. Kanayama and colleagues distinguished the cardiopulmonary collapse type (or classic type) from the disseminated intravascular coagulation (DIC) type of AFE on the basis of the presence of uterine atony and DIC in the latter prior to cardiopulmonary failure. We report a case of DIC-type AFE successfully treated by blood volume replacement and coagulation therapy. The patient was scheduled for elective cesarean delivery because of a previous cesarean section and moyamoya disease. Delivery was uneventful, but massive vaginal bleeding without clotting and ensuing hypovolemic shock occurred 4 h later. She was transferred to the operating room for emergency laparotomy, but sustained a cardiac arrest. The patient was successfully resuscitated and a hysterectomy performed. During surgery, the patient received fresh frozen plasma, platelets, fibrinogen, and antithrombin concentrate. In cardiopulmonary collapse type AFE, cardiopulmonary resuscitation without delay is important. In the present case of DIC-type AFE, however, early supplementation of clotting factors and platelets was critical for patient survival.
KeywordsAmniotic fluid embolism Disseminated intravascular coagulation (DIC) Uterine atony Cesarean delivery
Amniotic fluid embolism (AFE), a severe maternal reaction to amniotic fluid contents entering the circulation, occurs in only 2–8 of every 100,000 deliveries [1, 2]. However, AFE has a high mortality of 21.6 % in the United States and 24.3 % in Japan [3, 4]. The risk factors associated with AFE include advanced maternal age, placental abnormalities, operative deliveries, eclampsia, polyhydramnios, cervical lacerations, and uterine rupture . The three classic AFE symptoms are acute hypoxia, severe hypotension or cardiac arrest, and coagulopathy, which generally occur suddenly during labor (or pregnancy termination) or shortly after delivery . However, AFE has a wide spectrum of manifestations, and patients do not always follow the classic clinical course. On the basis of this clinical heterogeneity, it was recently suggested that AFE may involve disseminated intravascular coagulation (DIC), uterine atony, and (or) cardiopulmonary collapse . We present a case of AFE with cardiac arrest arising from DIC following elective cesarean delivery.
A 38-year-old woman (67.3 kg, 160 cm tall, and G3 P2) with moyamoya disease was scheduled for a repeat cesarean delivery. She gave us her history of frequent transient ischemic attacks during hyperventilation associated with moyamoya disease; therefore, a cesarean delivery under general anesthesia was planned to avoid ischemic attack during labor. She was not taking any herbal preparations or anticoagulants. Laboratory findings on admission were as follows: normal electrocardiogram and chest X-ray, hemoglobin 10.7 g/dL, platelet count 32.2 × 104/μL, fibrin degradation product (FDP) 6 μg/mL, D-dimer 2.2 μg/mL, fibrinogen 431 mg/dL, no urinary glucose or protein. At 38 weeks and 1 day of gestation, cesarean delivery was performed under general anesthesia without complications. The patient’s trachea was extubated and returned to the obstetrics ward.
Computed tomography after surgery revealed pulmonary embolism (PE) but no cerebral hemorrhage. Heparin therapy was initiated to maintain activated partial thromboplastin time (APTT) within the therapeutic target range of 50–70 s. Results of intraoperative maternal serum analysis were as follows: zinc coproporphyrin-1 (Zn-CP1) of 4 pmol/mL (normal, <1.6 pmol/mL), sialyl-Tn antigen (STN) 20.0 IU/mL (normal, <46 IU/mL), compliment factor 3 (C3) 58 mg/dL (normal, 80–140 mg/dL), C4 9 mg/dL (normal, 11–34 mg/dL), and interleukin-8 (IL-8) 405 pg/mL (normal, <20 pg/mL). Increased Zn-CP1 and IL-8 with decreased C3 and C4 strongly suggested AFE .
Seven days after the surgery, the patient’s trachea was extubated and discharged from the ICU. Anticoagulant therapy was switched from heparin infusion to warfarin. Eighteen days after surgery, she was discharged from the hospital.
Steiner and Lushbaugh (1941) first reported the cases of eight women who died unexpectedly from “obstetric shock” associated with fetal material in pulmonary vessels . They concluded that pulmonary embolism from particulate matter in amniotic fluid was the most likely cause of death. Since then, many investigators have tried to clarify the pathophysiology of AFE, but the etiology remains controversial. Recent studies suggest that, in addition to mechanical obstruction of pulmonary vessels, AFE can also result from a systemic inflammatory response syndrome (SIRS), manifesting as anaphylaxis or septic shock . Thus, Clark suggests the term “anaphylactoid syndrome of pregnancy” to better describe the pathophysiology of AFE .
New classification of amniotic fluid embolism
Time from symptom onset to cardiac arrest
Cardiopulmonary collapse type (Classic type)
• Sudden dyspnea
Very short (0–60 min in typical cases)
• Amniotic components in pulmonary vessels
Cardiopulmonary resuscitation including inotropes
• Severe hypotension (including cardiac arrest)
• Massive bleeding without clotting
• Amniotic components in uterus and/or uterine vessels
Volume resuscitation including supplement of platelets and clotting factors
• Uterine atony
• Thrombus in uterine vessels
• Intestinal edema in uterus
To manage hemorrhage during surgery, transfusion of PRBCs is recommended to maintain oxygen transport at first, and coagulation tests and platelet count should be obtained before administering FFP and platelets . However, many AFE patients require immediate FFP and platelet transfusion as well as packed red cells due to the consumption of coagulation factors at the early stage of AFE. The blood transfusion strategy for AFE patients is thus similar to the massive transfusion protocol for trauma patients, in which disruption of hemostasis occurs because of dilution coagulopathy, inflammatory mediator activation, hyperfibriolysis, thrombocytopenia, and metabolic abnormalities . In our case, we recognized that vaginal bleeding without clotting was an early sign of DIC-type AFE and promptly initiated transfusion of PRBCs and FFP (1:1), platelets, fibrinogen, and antithrombin concentrate.
The diagnosis of AFE is based primarily on clinical observation. In the past, the detection of fetal squamous cells in the maternal pulmonary circulation was considered a definitive diagnostic finding of AFE. However, a recent study detected fetal squamous cells in only 50 % AFE patients during the aspiration of pulmonary artery blood , whereas another report found that the presence of squamous cells in the maternal circulation was not always associated with AFE . Although there is no gold standard diagnostic marker for AFE, we believe that changes in a number of serum factors are strongly indicative of AFE, including Zn-CP1, STN, C3, C4, and IL-8. Meconium is rich in Zn-CP1 , and STN is a sugar chain of the mucin-type glycoprotein that recognizes mucin in the meconium/amniotic fluid . We thus propose that STN and Zn-CP1 in the maternal circulation are suggestive of AFE . Benson et al. reported that C3 and C4 levels in AFE patients were significantly lower than normal , suggesting that complement activation has an important role in the pathophysiology of AFE. Amniotic fluid components can also activate immune cells associated with allergic reactions, which produce large amounts of bradykinin and inflammatory cytokines such as IL-8 . Recently, C1 estarase inhibitor activity (C1INH) was suggested as a prognostic marker of AFE . In addition to serum factors, histological observation revealed edematous changes exist in the uterine smooth muscle and amniotic fluid components and fetal epithelial cells in the uterine vessels in this patient are suggestive of DIC-type AFE .
In this particular case patient, the reasons for cardiac arrest are unclear. The possibilities include superimposed cardiopulmonary type AFE and pulmonary thromboembolism. Although the patient showed no symptoms of deep vein thrombosis (DVT) before cesarean delivery, preoperative D-dimer levels were elevated; hence, DVT is possible. Interestingly, both serum FDP and D-dimer decreased promptly after administration of fibrinogen and antithrombin concentrate. The onset of cardiac arrest was more than 4 h after delivery, not sudden, and initial symptoms was massive bleeding without clotting, we considered cardiac arrest was due to hypovolemic shock. We cannot entirely exclude the classic type of AFE as the causation of cardiac arrest, although initial manifestation, change of serum factors, and histological observations in uterus are suggestive of DIC-type AFE. Appropriate treatment for DIC at the right time might lead to her recovery from DIC.
In conclusion, we describe a case of DIC-type AFE. Unlike cardiopulmonary type AFE, uterine atony and DIC were the initial symptoms. Early diagnosis and prompt administration of blood products, including clotting factors and platelets, are essential for patient recovery.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-chief of this journal.
amniotic fluid embolism
activated partial thromboplastin time
C1 estarase inhibitor activity
compliment factor 3
compliment factor 4
diastolic blood pressure
disseminated intravascular coagulation
deep vein thrombosis
fibrin degradation products
fresh frozen plasma
intensive care unit
packed red blood cells
systolic blood pressure
systemic inflammatory response syndrome
- SpO2 :
peripheral cappilary oxygen saturation
We thank Hideyuki Shimazaki, MD, PhD (Associate professor of Laboratory Medicine, National Defense Medical College Hospital, Saitama, Japan) and Kuniaki Nakanishi, MD, PhD (Professor of Laboratory Medicine, National Defense Medical College Hospital, Saitama, Japan) for their excellent technical help with this case report. This work is attributed to and supported by the Department of Anesthesiology, National Defense Medical College. This case report has not been published elsewhere.
- Rath WH, Hoferr S, Sinicina I. Amniotic fluid embolism: an interdisciplinary challenge: epidemiology, diagnosis and treatment. Dtsch Arztebl Int. 2014;111:126–32.PubMed CentralPubMedGoogle Scholar
- Clark SL. Amniotic fluid embolism. Obstet Gynecol. 2014;123:337–48.View ArticlePubMedGoogle Scholar
- Abenhaim HA, Azoulay L, Kramer MS, Leduc L. Incidence and risk factors of amniotic fluid embolisms: a population-based study on 3 million births in the United States. Am J Obstet Gynecol. 2008;199:49. e41–48.PubMedGoogle Scholar
- Kanayama N, Inori J, Ishibashi-Ueda H, Takeuchi M, Nakayama M, Kimura S, et al. Maternal death analysis from the Japanese autopsy registry for recent 16 years: significance of amniotic fluid embolism. J Obstet Gynaecol Res. 2011;37:58–63.View ArticlePubMedGoogle Scholar
- Conde-Agudelo A, Romero R. Amniotic fluid embolism: an evidence-based review. Am J Obstet Gynecol. 2009;201:445. e441-413.PubMed CentralPubMedGoogle Scholar
- Clark SL, Hankins GD, Dudley DA, Dildy GA, Porter TF. Amniotic fluid embolism: analysis of the national registry. Am J Obstet Gynecol. 1995;172:1158–67. discussion 1167-1159.View ArticlePubMedGoogle Scholar
- Kanayama N, Tamura N. Amniotic fluid embolism: pathophysiology and new strategies for management. J Obstet Gynaecol Res. 2014;40:1507–17.View ArticlePubMedGoogle Scholar
- Steiner PE, Lushbaugh CC. Landmark article, Oct. 1941: maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics. By Paul E. Steiner and C. C. Lushbaugh. JAMA. 1986;255:2187–203.View ArticlePubMedGoogle Scholar
- American Society of Anesthesiologists Task Force on Perioperative Blood T, Adjuvant T. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006;105:198–208.View ArticleGoogle Scholar
- Pham HP, Shaz BH. Update on massive transfusion. Br J Anaesth. 2013;111 Suppl 1:i71–82.View ArticlePubMedGoogle Scholar
- Lee W, Ginsburg KA, Cotton DB, Kaufman RH. Squamous and trophoblastic cells in the maternal pulmonary circulation identified by invasive hemodynamic monitoring during the peripartum period. Am J Obstet Gynecol. 1986;155:999–1001.View ArticlePubMedGoogle Scholar
- Kanayama N, Yamazaki T, Naruse H, Sumimoto K, Horiuchi K, Terao T. Determining zinc coproporphyrin in maternal plasma--a new method for diagnosing amniotic fluid embolism. Clin Chem. 1992;38:526–9.PubMedGoogle Scholar
- Kobayashi H, Ohi H, Terao T. A simple, noninvasive, sensitive method for diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc alpha 2-6GalNAc. Am J Obstet Gynecol. 1993;168:848–53.View ArticlePubMedGoogle Scholar
- Benson MD, Kobayashi H, Silver RK, Oi H, Greenberger PA, Terao T. Immunologic studies in presumed amniotic fluid embolism. Obstet Gynecol. 2001;97:510–4.View ArticlePubMedGoogle Scholar
- Tamura N, Kimura S, Farhana M, Uchida T, Suzuki K, Sugihara K, et al. C1 esterase inhibitor activity in amniotic fluid embolism*. Crit Care Med. 2014;42:1392–6.View ArticlePubMedGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.