Extracorporeal Therapies for Amniotic Fluid Embolism.

BACKGROUND: Amniotic fluid embolism (AFE) is a catastrophic disease with significant mortality. Because the cardiopulmonary dysfunction associated with AFE is self-limited, the disease could be well suited to the use of extracorporeal therapies. CASE: A woman progressed into cardiac arrest immediately after an elective cesarean delivery. Owing to severe hypoxemia and hypotension, AFE was suspected and peripheral venoarterial extracorporeal membrane oxygenation was quickly initiated. Subsequent evolution was complicated by intrabdominal bleeding, which required massive transfusion and multiple surgeries. The patient recovered well, with a healthy newborn. We have identified 19 similar cases in the literature and present their outcomes as a series. CONCLUSION: Extracorporeal therapies can support severely ill women affected by AFE and could be considered even in the presence of disseminated intravascular coagulation and bleeding.

Amniotic fluid embolism: despite progress, challenges remain.

PURPOSE OF REVIEW: This article reviews the incidence, pathophysiology, risk factors, diagnosis, and management of amniotic fluid embolism (AFE). RECENT FINDINGS: AFE is a leading cause of maternal morbidity and mortality despite an incidence of approximately 7 to 8 per 100,000 births. Recent reevaluation of AFE suggests that the presence of fetal tissue in maternal circulation alone is not sufficient to cause the clinical syndrome, but rather an individual's response to this fetal tissue. The 'anaphylactoid reaction' associated with AFE shares many clinical and metabolic aspects of septic shock. Acute dyspnea followed by cardiovascular collapse, coagulopathy, and neurological symptoms, such as coma and seizures may all be associated with the clinical AFE syndrome. Specific biochemical markers have been described, but are of limited clinical value because of the rapid progression of the disease process. Treatment is based on an interdisciplinary approach that consists of a combination of prompt, aggressive hemodynamic resuscitation, provision of end-organ support, correction of hemostatic disorders, and delivery. SUMMARY: Although AFE cannot be prevented, early diagnosis and intervention may lead to better outcomes for both the mother and the fetus. Clinical suspicion, traditional laboratory data, or intravascular cellular debris (demonstrated only in 50% of patients) are insufficient to make a definitive diagnosis of AFE. An evolving array of novel biomarkers may help differentiate AFE from other conditions, but none of them currently provide sufficient 'early warning' ability to make real-time impact on diagnosis and/or treatment of AFE.

Amniotic components in the uterine vasculature and their role in amniotic fluid embolism.

AIM: To evaluate whether the presence of amniotic components in the maternal uterine vasculature could be a specific pathological indicator for amniotic fluid embolism (AFE). METHODS: Medical records of patients treated between January 2006 and March 2013 were retrospectively examined to identify patients who underwent post-partum hysterectomy or autopsy due to maternal death. Three subjects with AFE with disseminated intravascular coagulation (DIC)-type post-partum hemorrhage (PPH), and 13 non-AFE subjects were included in analysis. Histochemical staining using hematoxylin-eosin (HE) and alcian blue, and immunohistochemical staining for sialyl-Tn were conducted to detect amniotic components in the maternal uterine vasculature. RESULTS: Alcian blue was positive for amniotic components in the uterine vasculature of all subjects with AFE and of several subjects without AFE. Similarly, HE and sialyl-Tn were negative in some AFE subjects and positive in some non-AFE subjects. CONCLUSIONS: The presence of maternal intravascular fetal material is not a specific indicator for AFE with DIC-type PPH. Therefore, the presence of fetal components in the uterine vasculature is unlikely to be a definitive indicator for AFE.

Amniotic fluid embolism induces uterine anaphylaxis and atony following cervical laceration.

Amniotic fluid embolism (AFE) is a rare, high-risk obstetric complication primarily found in the lungs and potentially related to anaphylaxis. Tryptase release from the mast cell reflects anaphylaxis. Case report and findings: A female, aged over 40 years, presented with uterine atony and lethal hemorrhage after induced vaginal labor. Cervical laceration was accompanied by severe hemorrhage. Stromal edema and myometrial swelling were consistent with uterine atony. Alcian blue staining and zinc coproporphyrin immunostaining disclosed AFE, which was more prominent in the uterus than in the lungs. Tryptase immunostaining was diffuse and prominent around the activated mast cells (halos) in the uterus, including the cervix. Similar distribution of findings on the AFE markers, tryptase halos, complement receptor C5aR, and atony in the uterus suggested the causality of AFE to anaphylaxis, complement activation and atony. It is probable that disseminated intravascular coagulation (DIC), induced by AFE, uterine atony and cervical laceration, caused the lethal hemorrhage. It is likely that AFE, in association with cervical laceration, induces uterine anaphylaxis, complement activation, atony, DIC and lethal hemorrhage.

Maternal death following cardiopulmonary collapse after delivery: amniotic fluid embolism or septic shock due to intrauterine infection?

PROBLEM: The amniotic fluid embolism (AFE) syndrome is a catastrophic complication of pregnancy frequently associated with maternal death. The causes and mechanisms of disease responsible for this syndrome remain elusive. METHOD OF STUDY: We report two cases of maternal deaths attributed to AFE: (1) one woman presented with spontaneous labor at term, developed intrapartum fever, and after delivery had sudden cardiovascular collapse and disseminated intravascular coagulation (DIC), leading to death; (2) another woman presented with preterm labor and foul-smelling amniotic fluid, underwent a Cesarean section for fetal distress, and also had postpartum cardiovascular collapse and DIC, leading to death. RESULTS: Of major importance is that in both cases, the maternal plasma concentration of tumor necrosis factor-alpha at the time of admission to the hospital and when patients had no clinical evidence of infection was in the lethal range (a lethal range is considered to be above 0.1 ng/mL). CONCLUSION: We propose that subclinical intraamniotic infection may be a cause of postpartum cardiovascular collapse and DIC and resemble AFE. Thus, some patients with the clinical diagnosis of AFE may have infection/systemic inflammation as a mechanism of disease. These observations have implications for the understanding of the mechanisms of disease of patients who develop cardiovascular collapse and DIC, frequently attributed to AFE. It may be possible to identify a subset of patients who have biochemical and immunological evidence of systemic inflammation at the time of admission, and before a catastrophic event occurs.

Embolia de líquido amniótico: Criterio diagnóstico en dos casos fatales / Amniotic fluid embolism: Diagnostic criteria in two fatal cases

La embolia de líquido amniótico continúa siendo una causa importante de mortalidad materna. Presentamos la información obtenida por medio de la cateterización cardíaca derecha y la ecocardiografía, en dos pacientes que desarrollaron embolia de líquido amniótico y fallecieron por shock y coagulación intravascular diseminada a pesar del tratamiento intensivo. Aunque la fisiopatología continúa siendo discutida, la embolia por líquido amniótico se puede diagnosticar y manejar a partir de los valores hemodinámicos y el ecocardiograma.

Amniotic fluid embolism still remains an important cause of maternal mortality. We present information obtained by echocardiography and right cardiac catheterization of two patients who developed amniotic fluid embolism and died from shock and disseminated intravascular coagulation despite intensive medical treatment. Although the pathophysiology remains controversial, amniotic fluid embolism can be presumptively diagnosed and managed with hemodynamic values and echocardiography.

Unusual pulmonary embolism: septic pulmonary embolism and amniotic fluid embolism.

BACKGROUND: Septic and amniotic fluid emboli are rare sources of pulmonary embolism (PE), so the present study sought to elucidate the background of these cases. METHODS AND RESULTS: A total of 11,367 PE cases were identified from 396,982 postmortem examinations. The incidence of septic PE was 247 (2.2%) of the total. The origin of infection was found in 85.6% of the cases. Fungal embolus was detected more often than bacterial embolus. The most frequently detected fungus was aspergillus (20.8%). The primary disease associated with fungal embolus was leukemia (43.2%). The incidence of PE cases associated with pregnancy and/or delivery was 89 (0.8%) of the total PE cases. Among them, amniotic fluid embolism was found in 33 (73.3%) of 45 PE cases with vaginal delivery, and in 7 (21.2%) of 33 PE cases with cesarean delivery (p<0.0001). CONCLUSION: Fungal embolus was more frequent than bacterial embolus, and leukemia was most frequent as the primary disease in cases of fungal embolus. The main cause of PE in cesarean section cases was thrombotic embolism, and the main cause in vaginal delivery cases was amniotic fluid embolism.

Perioperative vasovagal syncope with focus on obstetric anesthesia.

Vasovagal syncope refers to a reflex cardiovascular depression that gives rise to loss of consciousness with bradycardia and profound vasodilatation. This response commonly occurs during regional anesthesia, hemorrhage or supine inferior vena cava compression in pregnancy. The changes in circulatory response from the normal maintenance of arterial pressure to parasympathetic activation and sympathetic inhibition may cause severe hypotension. This change is triggered by reduced cardiac venous return as well as episodes of emotional stress, excitement or pain. Occasionally, these vasovagal responses may be unpredictable and may dramatically proceed to asystole with circulatory collapse, and may even result in death. In these circumstances, hypotension may be more severe than that caused by bradycardia alone, because of unappreciated vasodilatation. Regional anesthesia, decreased venous return, hemorrhage and abnormal fetal presentation cumulatively increase the risk of vasovagal syncope in cesarean section patients. When a vasovagal response occurs, ephedrine is the drug of first choice because of its combined action on the heart and peripheral blood vessels. Epinephrine must be used early in established cardiac arrest, especially after high regional anesthesia.

Disseminated intravascular coagulation: a review of etiology, pathophysiology, diagnosis, and management: guidelines for care.

The pathophysiologic mechanisms, clinical, and laboratory manifestations of DIC are complex in part due to interrelationships within the hemostasis system. Only by clearly understanding these extraordinarily complex pathophysiologic interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Many therapeutic decisions to be made are controversial and lack validation. Nevertheless, newer antithrombotic agents, and agents that can block, blunt, or modify cytokine activity and the activity of vasoactive substances appear to be of value. The complexity and variable degree of clinical expression suggests that therapy should be individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis and hemodynamics and other appropriate clinical parameters. At present, treatment of the triggering event, low-dose heparin or antithrombin concentrate and wise choice of components when indicated appear to be the most effective modes of therapy.

Immunologic studies in presumed amniotic fluid embolism.

OBJECTIVE: To evaluate the potential role of immunologic mechanisms that involve mast cell degranulation (anaphylaxis) or complement activation in the mechanism of amniotic fluid embolism. METHODS: This study was a case series of nine women with presumed amniotic fluid embolism and a control group of 22 women who had normal labor. Women were from community and tertiary referral hospitals in Japan and the United States. Main outcome measures were maternal peripartum complement levels (C3 and C4), serum levels of tryptase, urinary histamine concentrations, and serum levels of a fetal antigen (sialyl Tn). RESULTS: Serum tryptase and urinary histamine measurements were negative in women with amniotic fluid embolism; seven of nine had elevated levels of fetal antigen. All eight who had serum available for testing had abnormally low levels of complement. Mean C3 level of 44.0 mg/dL and C4 level of 10.7 mg/dL were significantly lower than corresponding postpartum control values of 117.3 mg/dL and 29.4 mg/dL (P =.018 for C3, P =.012 for C4). Postpartum C3 and C4 levels decreased by 8% and 5%, respectively, compared with intrapartum values (P =.003 for C3, P =.021 for C4) but were still within normal range. CONCLUSION: Serologic findings suggest a role for complement activation in the mechanism of amniotic fluid embolism. Laboratory data from this series did not implicate mast cell degranulation (anaphylaxis) in the pathophysiology of the disease.

Monitoring for suspected pulmonary embolism.

It is fortunate that serious embolic phenomena are uncommon because, with the exception of neurosurgery in the sitting position and cardiac surgery, thoracic echocardiography and the precordial Doppler device, the most sensitive indicators of embolism, are seldom used. Vigilance is required of the anesthesiologist to recognize the rapid fall in end-tidal PCO2, the usual first indicator of a clinically significant PE. Any sudden deterioration in the patient's vital signs should include embolism in the differential diagnosis, particularly during procedures that carry a high risk of the complication.

Syndromes of disseminated intravascular coagulation in obstetrics, pregnancy, and gynecology. Objective criteria for diagnosis and management.

This article presents current understanding of the causes, pathophysiology, clinical, and laboratory diagnosis, and management of fulminant and low-grade DIC, as they apply to obstetric, pregnant, and gynecologic patients. General medical complications leading to DIC, which may often be seen in these patients, are also discussed. Considerable attention has been given to interrelationships within the hemostasis system. Only by clearly understanding these pathophysiologic interrelationships can the obstetrician/gynecologist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Objective clinical and laboratory criteria for diagnosis of DIC have been outlined to eliminate unnecessary confusion and the need to make empiric decisions regarding the diagnosis. Particularly in the obstetric patient, if a condition is observed that is associated with DIC, or if any suspicion of DIC arises from either clinical or laboratory findings, it is imperative to monitor the patient carefully with clinical and laboratory tools to assess any progression to a catastrophic event. In most instances of DIC in obstetric patients, the disease can be ameliorated easily at early stages. Many therapeutic decisions are straightforward, particularly in obstetric and gynecologic patients. For more serious and complicated cases of DIC in these patients, however, efficacy and choices of therapy will remain unclear until more information is published regarding response rates and survival patterns. Also, therapy must be highly individualized according to the nature of DIC, patient's age, origin of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Finally, many syndromes that are often categorized as organ-specific disorders and are sometimes identified as independent disease entities, such as AFE syndrome, HELLP syndrome, adult shock lung syndrome, eclampsia, and many others, either share common pathophysiology with DIC or are simply a form of DIC. These entities represent the varied modes of clinical expression of DIC and illustrate the diverse clinical and anatomic manifestations of this syndrome.

Renal and amniotic fluid responses to umbilicoplacental embolization for 20 days in fetal sheep.

We determined the effects of placental insufficiency induced by umbilicoplacental embolization on fetal renal function and amniotic fluid volume and composition. Pregnant ewes underwent surgery at 115 +/- 2 days after mating (term approximately 147 days) for implantation of fetal vascular, bladder, and amniotic sac catheters. We studied five fetuses from 120 to 140 days during umbilicoplacental embolization and six control fetuses. Umbilicoplacental embolization reduced fetal arterial partial pressure of oxygen from 24.1 +/- 0.5 mmHg (pretreatment) to 14.6 +/- 0.2 mmHg. Fetal body weights were reduced to 80% of control values. Urine production and glomerular filtration rate in treated fetuses were significantly lower than in controls at 135 days of gestation. Amniotic fluid volume was not different between embolized and control animals. Fetal urine production in treated fetuses, when adjusted for body weight, was not different from that in control fetuses. We conclude that, in fetal growth restriction, reduced kidney weight, rather than hypoxemia per se is responsible for reduced urine production, which, if severe and prolonged, may contribute to oligohydramnios.

[Effects of amniotic fluid embolism-like plasma on isolated perfused rabbit lungs].

OBJECTIVE: In order to investigate whether amniotic fluid could induce the release of mediators from blood cells which would damage the lungs, an isolated perfused rabbit lung (IPRL) was exposed to amniotic fluid embolism-like plasma (AFEP) and the injury of AFEP to lungs and the protective effects of ibuprofen were studied. METHODS: 10 ml human amniotic fluid and 50 ml heparized rabbit blood were incubated together with or without ibuprofen (600 micrograms) at 37 degrees C for 30 min and centrifuged. Supernatants were taken and were referred to as AFEP or ibuprofen AFEP. IPRL was perfused with AFEP, ibuprofen AFEP, simple amniotic fluid (SAF), supernatant of amniotic fluid (SnAF), rabbit plasma (RP) and control NS. The changes of pulmonary artery pressure (PAP), respiratory pressure (RP) and lung weight were recorded by computer and compared with control NS group. RESULTS: In groups of SAF, SnAF and RP PAPs were slightly elevated (0.13-0.6 kPa, P > 0.05), and lung weights were not changed. AFEP induced the increase of PAP (3.52 +/- 0.64 kPa, P < 0.05) and lung weight (4.0 +/- 1.0 g, P < 0.01) with the development of lung edema. Administration of ibuprofen prevented partially the APEP-induced increase of PAP (1.87 +/- 0.43 kPa, P < 0.05) and lung weight (0.4 +/- 0.3 g, P < 0.01). CONCLUSION: Amniotic fluid may induce the release of mediators from blood cells, and the latter is the important cause resulting in the pathological changes of lungs in amniotic fluid embolism. Ibuprofen may reduce partially the APEP-induced lung injury.

Unusual forms of pulmonary embolism.

The first word of the title, unusual, captures the theme of this article. The entities discussed here: fat embolism, tumor embolism, venous air embolism, and amniotic fluid embolism, as well as other unusual embolic events are uncommon disorders that occur in specific circumscribed clinical settings. We have attempted to provide a cognitive jolt to remind the reader to consider these unusual events in appropriate differential diagnoses. No laboratory test, physical finding, or patient complaint will yield a timely diagnosis. Yet, these entities can be acutely life threatening; swift recognition is imperative. Timely and effective therapy rests on the clinical certainty that a test is not likely to establish. It is, perhaps, the greatest demand placed upon the agile clinical mind--to think of it!

Amniotic fluid embolism associated with castor oil ingestion.

We report a case of an amniotic fluid embolism (AFE) causing a cardiorespiratory arrest associated temporally with ingestion of castor oil in a full-term normal pregnancy. Risk factors usually associated with AFE were not found in this patient.