Critical Care in

Obstetrics:

An Innovative and Integrated Model for

Learning the Essentials

Amniotic Fluid Embolism

Gary A. Dildy, M.D. Professor

Vice Chairman of Quality & Patient Safety

Program Director, MFM Fellowship

Department of Obstetrics & Gynecology

Chief Quality Officer

Obstetrics & Gynecology

Baylor College of Medicine

Texas Children’s Hospital

I have no conflicts of interest to disclose

Disclosure

History

Incidence & Outcomes

Pathophysiology & Etiology

Diagnosis

Evaluation & Treatment

Summary

Evidence

Outline

Recognize typical clinical presentation

Develop a differential diagnosis

Know the range of reported incidences

Understand the morbidity and mortality

Learn how to initiate supportive

management

Learning Objectives

History

Historical References

JAMA 1941; 117: 1245-1254 & 1341-1345.

Brazil-Med 1926; 40 (11): 301–303.

Historical References

Literature Review

PubMed.gov accessed 29 November 2013

“preeclampsia” n = 29,248

http://www.spacetelescope.org/images/opo9607a/ http://www.oxforddictionaries.com/

A Nebulous Syndrome

Nebulous

adjective

in the form of a cloud or

haze; hazy

unclear, vague, or ill-

defined

Classic triad:

Hypoxia

Hypotension or hemodynamic collapse

Coagulopathy

Remains poorly understood: unpredictable, rare, acute, and lacks a gold standard diagnosis

There probably are formes frustes of AFE

“Let us be careful not to make it a waste basket for all cases of unexplained death in labor…”

Eastman, 1948

Key Points

Incidence &

Outcomes

1/8,000 to 1/80,000 deliveries

Maternal mortality up to 86%

A leading cause of U.S. maternal

mortality

11-14% of all maternal deaths

Most common cause of peripartum

death

Key Points

Incidence (per 100,000 maternities)

Australia, Canada, the Netherlands, UK & USA

Retrospective discharge database 5.5-6.1

~ 1:17,000

Validated case identification 1.9-2.5

~ 1:45,000

Incidence

Knight et al. Amniotic fluid embolism incidence, risk factors and outcomes: a review

and recommendations. BMC Pregnancy Childbirth 2012; Feb 10;12:7

If the difference between the above 2 rates is due solely to false

positives in the former, the incidence of AFE is overestimated by

62% in retrospective discharge database studies. (GAD)

Global Statistics

Country Time period Publication Contribution to

maternal

mortality (%)

Sweden 1951-1980 Hogberg, 1985 1-17

Japan 1964-1980 Shinagawa, 1983 5

USA 1979-1986 Atrash, 1990 8

Australia 1984-1993 Burrows, 1995 10

Singapore 1990-1999 Lau, 2002 31

UK 1994-1996 Dept Health, 1998 13

Poland 1991-2000 Troxzynski, 2003 22

USA 2000-2006 Clark, 2008 14

CAUSE OF DEATH Number % Complications of Preeclampsia 15 16

Amniotic fluid embolism 13 14

Obstetric hemorrhage 11 12

Cardiac disease 10 11

Pulmonary Thromboembolism 9 9

Non-obstetric infection 7 7

Obstetric infection 7 7

Accident/suicide 6 6

Medication error or Reaction 5 5

Ectopic pregnancy 1 1

Other 11 12

TOTAL 95 100

HCA, 2000-2006

Clark SL, Belfort MA, Dildy GA, Herbst MA, Meyers JA, Hankins GD. Maternal death in the 21st century: causes,

prevention, and relationship to cesarean delivery. Am J Obstet Gynecol 2008; 199(1):36.e1-5

Outcomes

0%

20%

40%

60%

80%

100%

Clark 1995 Tuffnell 2005

Maternal Outcome

0%

20%

40%

60%

80%

100%

Clark 1995 Tuffnell 2005

Fetal Outcome

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.

Tuffnell DJ. United kingdom amniotic fluid embolism register. BJOG 2005;112:1625-9.

Outcomes- Maternal Mortality

Pathophysiology

& Etiology

Proposed Pathophysiology

Clark SL, Hankins GD, Dudley DA, Dildy GA, Porter TF. Amniotic fluid embolism: analysis of the national

registry. Am J Obstet Gynecol 1995;172(4 Pt 1):1158-67; discussion 1167-9

Anaphylaxis

(IgE)

Sepsis

(Endotoxin)

Amniotic Fluid

Embolism (various fetal elements)

Endogenous Mediator Release

Clinical Manifestations

Phase I

Vasoactive

substance(s)

Pulmonary vasospasm

Profound hypoxia

Pulmonary injury

Myocardial injury

Resolved in 15-30 min

Phase II

Left heart failure

Pulmonary edema/

ARDS

Coagulopathy

Proposed Pathophysiology

Clark et al. Hemodynamic alterations associated with amniotic fluid embolism: a reappraisal.

Am J Obstet Gynecol 1985;151:617-21.3

Hemodynamics

Clark et al. Hemodynamic alterations associated with amniotic fluid embolism: a reappraisal.

Am J Obstet Gynecol 1985;151:617-21.3

Hemodynamics

Nonpregnant (n = 10)

Nl 3rd Tri (n = 10)

AFE (n = 15)

MPAP 12 2 13 2 26 16

PCWP 6 2 8 2 19 9

PVR 119 47 78 22 176 72

LVSWI 41 8 48 6 26 19

Clark et al. Am J Obstet Gynecol 1988;158:1124-6.

Clark et al. Am J Obstet Gynecol 1989;161:1439-42.

Clark et al. Personal communication, unpublished data.

Animal studies- Inconsistent results

In vitro studies amniotic fluid:

Shortens whole blood clotting time

Has thromboplastin-like effect

Induces platelet aggregation & release of platelet

factor III

Activates complement cascade

Contains a direct factor X activating factor

Human studies

AFE coagulopathy probably similar to that in

severe placental abruption

Pathophysiology: Coagulopathy

2 cases of maternal death attributed to AFE

Supra-lethal levels maternal plasma TNF-α

(> 0.1 ng/mL) at admission

29 yo G3P1 at 41+ weeks 1 ng/mL

30 yo G3P2 at 28+ weeks 10 ng/mL

Etiology: Infection?

Romero et al. Am J Reprod Immunol 2010; 64: 113-125

Etiology: Oxytocics?

Clark et al. Am J Obstet Gynecol 1995; 172: 1158-69

As illustrated in this case, uterine hypertonicity

followed the initial signs and symptoms of AFE.

Kramer et al. Lancet 2006

Canada 1991-2002

Association: yes

Abenhaim et al. Am J Obstet Gynecol 2008

USA 1999-2003

Association: no

Knight et al. Obstet Gynecol 2010

UK 2005-2009

Association: yes

Etiology: Induction of Labor?

Prepidil Package Insert (02/09)

“The Clinician should be alert that the intracervical placement

of dinoprostone gel may result in inadvertent disruption and

subsequent embolization of antigenic tissue causing in rare

circumstances the development of Anaphylactoid

Syndrome of Pregnancy (Amniotic Fluid Embolism).”

Cervidil Package Insert (04/10)

“The Clinician should be alert that use of dinoprostone may

result in inadvertent disruption and subsequent embolization

of antigenic tissue causing in rare circumstances the

development of Anaphylactoid Syndrome of Pregnancy

(Amniotic Fluid Embolism).”

PGE, AFE & the FDA

Diagnosis

AFE Registry Entry Criteria

Acute hypotension or cardiac arrest

Acute hypoxia

Coagulopathy

Onset during labor, delivery, or 30 minutes

postpartum

Absence of any other explanation

Occurrence within 5 years of registry opening

Diagnostic Criteria

Clark et al. Am J Obstet Gynecol 1995; 172: 1158-69

Acute myocardial infarction

Anaphylactic shock

Anesthetic accident

Aspiration pneumonia

Placental abruption

Pulmonary thromboembolism

Septic shock

Differential Diagnosis

Histologic Findings of AFE

Diagnostic Criteria

Tuffnell D, Knight M, Plaat F. Amniotic fluid embolism - an update. Anaesthesia 2011;66(1):3-6

Evaluation &

Treatment

Initial Evaluation

CBC & platelet

count

Fibrinogen and FSP

PT, PTT, and INR

Blood type & cross

Arterial blood gas

Serum electrolytes

Cardiac enzymes

Chest X-ray

12-lead EKG

Echocardiogram

Initial treatment is supportive

CPR, high FiO2

Treat left ventricular failure

Volume expansion, inotropes

Fetal management

Cardiac arrest: perimortem C/S

ABC’s + D

Hemodynamically unstable: individualize

Treatment

0%

20%

40%

60%

80%

100%

< 5

5 to 15

16 to 25

26 to 35

36 to 54

Neonatal Survival

0%

20%

40%

60%

80%

100%

0 to 5

6 to 10

11 to 15

16 to 20

21+

Katz VJ et al. Obstet Gynecol 1986; 68: 571-6

Clark SL et al. Am J Obstet Gynecol 1995; 172: 1158-69

Arrest-to-Delivery Interval

Intact vs. Impaired

Cardiopulmonary

bypass

Hemofiltration

Recombinant Factor VIIa

Nitric oxide

High-dose

corticosteroids

Treatment: case reports

Eason MP. The death of Mrs. Smith. Acad Med 2005;80(9):865.

Daniels K, Parness AJ. Development and use of mechanical devices for

simulation of seizure and hemorrhage in obstetrical team training. Simul

Healthc 2008;3(1):42-6.

Fransen et al. Effect of obstetric team training on team performance and

medical technical skills: a randomised controlled trial. BJOG

2012;119(11):1387-93.

Bolden et al. Making the case for obstetric "response teams" and simulation in

labor and delivery: management of catastrophic amniotic fluid embolism

during labor. J Clin Anesth 2012;24(6):517-8.

Simulation & Team Training

1992 Clark AJOG 0/2

1995 Burrows ANZJOG 0/1

1998 Duffy AIC 0/2

1998 Collier AIC 0/1

2000 Stiller JRM 0/1

2005 Demianczuk JOGC 0/1

2006 Abecassis IJOA 0/1

Recurrence Risk

Maximum Risk with 95% CL: “Rule of 3” (3/n)*100 = 33%

Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting

zero numerators. JAMA 1983;249(13):1743-5

The Future

Objective - To develop a UK-wide Obstetric

Surveillance System to describe the

epidemiology of a variety of uncommon

disorders of pregnancy.

Mission - to improve the care given to women,

their babies and their families, by advancing

knowledge and contributing to the evidence

base about serious, rare disorders in

pregnancy including near-miss events, through

international co-operation and collaborative

working.

Mission - AFE Foundation exists to spur clinical

research, raise awareness, provide clinical

and patient based information and offer

supportive services to those affected by or

interested in Amniotic Fluid Embolism http://www.afesupport.org

http://www.npeu.ox.ac.uk/inoss

https://www.npeu.ox.adc.uk/ukoss

AFE Foundation & BCM partnered to create a new

registry

The AFE Registry opened 2 August 2013

Cases are collected and abstracted

Cases are categorized (Classic v Atypical v Unlikely AFE)

Future Plans

AFE families Bio-Bank (store serum/plasma and DNA)

Network for collection of specimens from acute AFE cases

AFE Registry at BCM

Summary

Thought to follow maternal exposure to fetal antigens

Pathophysiology similar to anaphylaxis & septic shock

Treatment is generally supportive

Maternal-fetal morbidity & mortality frequent

OB teams should be prepared for acute emergencies

Team training & simulation training may be helpful

Better predictive and diagnostic tests are needed

Current efforts are being invested in improved diagnostic tests and treatment

Summary

All recommendations GRADE 1C

Evidence

All recommendations are GRADE 1C

(strong recommendation, low-quality evidence).

Thank You for Your Attention!

Planning Committee

Mike Foley, Director Shad Deering, co-Director

Helen Feltovich, co-Director Bill Goodnight, co-Director

Loralei Thornburg, Content co-Chair Deirdre Lyell, Content co-Chair

Suneet Chauhan, Testing Chair Mary d’Alton

Daniel O’Keeffe Andrew Satin

Barbara Shaw