pulmonary vascular disease || embolism of fat, air, or amniotic fluid

Fat Embolism

Symptoms consistent with fat embolism weredescribed as early as 1861 by F.A. Zenker in a rail-road worker who suffered a thoracolumbar crushinjury. However, the fat embolism syndrome wasnot defined until it was described by Von Bergmanin 1873 in a patient with a femoral fracture. Thediagnosis was confirmed by postmortem examina-tion. Although the disease has been recognized forover a century, it still remains a significant diag-nostic challenge for physicians.

The term “fat embolism” refers to globules offree fat within the vasculature (FIGURE 20-1). Thedisease typically occurs following long bone frac-ture or orthopedic surgery. However, it has alsobeen described as a complication of liposuction,pancreatitis, and osteomyelitis.1-3 Findings of dysp-nea and hypoxemia vary from mild to extremelysevere, and fat globules in the pulmonary circula-tion can pass into the systemic circulation toembolize to the brain and skin. The classic onset offat embolism syndrome consists of an asympto-matic interval followed by pulmonary, neurologic,and dermatologic manifestations.

Epidemiology

Fat embolism occurs in nearly all patients withbone fractures and during many orthopedic pro-cedures.4,5 However, most patients with fatemboli are asymptomatic, and less than 20 per-cent develop overt fat embolism syndrome.5 Thetrue incidence of fat embolism syndromeremains unknown, because many mild cases gounrecognized.

Fat embolism syndrome is most likely to occurafter severe trauma. Multiple skeletal fracturesincrease the risk of fat embolism syndrome,because a larger amount of fat is released into themarrow vessels.5 In individuals with significanttrauma, the incidence of fat embolism syndrome isestimated at 20 percent when multiple fractures arepresent, and 0.5 to 20 percent with a single frac-ture.5,6 Fat embolism syndrome is more likely tooccur after closed, rather than open, fractures andin patients with fractures involving the middle andproximal parts of the femoral shaft. However, fatembolism syndrome can occur following minorinjury, particularly in patients with underlying pul-monary vascular disease.

In addition to trauma, fat embolism can occur fol-lowing liposuction or in patients with pancreatitis,fatty liver, or osteomyelitis.1-3 Furthermore, fatemboli may be a cause of acute chest syndromeassociated with sickle cell disease7 (see Chapter 12).

Clinical Picture and Diagnosis

The classic triad of fat embolism syndrome consistsof hypoxemia, neurologic abnormalities, and apetechial rash. The syndrome typically follows abiphasic course. Most patients are asymptomaticfor 12 to 24 hours following embolization, and insome cases symptoms can be delayed as long as 3days.8 The clinical picture may be subclinical, mild,or fulminant.

Pulmonary manifestations, including dyspnea,tachypnea, and hypoxemia, occur in 90 percentof patients with fat embolism and are often theearliest findings. Arterial hypoxemia in thesepatients has been attributed to ventilation-perfusionmismatch and intrapulmonary shunting. Cough,

305

C h a p t e r

Embolism of Fat, Air, or Amniotic Fluid

Alix Ashare, MD,

James Carroll, MD

20

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306 PULMONARY VASCULAR DISEASE

hemoptysis, and pleuritic chest pain may developbut are less common. On physical examination,inspiratory crackles are a common finding. A pleu-ral rub occasionally can be heard. Approximately50 percent of patients with fat embolism secondary toa long bone fracture develop acute respiratory dis-tress syndrome (ARDS) and require mechanicalventilation.9

Neurologic symptoms develop in up to 85 per-cent of patients with pulmonary manifestations.6

Symptoms typically occur after the onset of respira-tory symptoms. Patients usually become confused,followed by an altered level of consciousness.Seizures and focal neurologic deficits have also beendescribed. In most cases, the neurologic findings arereversible and resolve in tandem with the respira-tory manifestations.

Skin involvement is also frequent, occurring in20 to 50 percent of patients with pulmonary mani-festations.6 Skin disease typically appears as apetechial rash. It is often a late and transient findingand occurs 2 to 3 days after embolization. Thepetechiae result from the occlusion of skin capillar-ies by fat globules, resulting in the extravasation oferythrocytes. Petechiae are most prominent alongthe axillary folds, conjunctiva, and retina.

The diagnosis of fat embolism syndrome usu-ally is made on the basis of clinical characteristics:respiratory and neurologic symptoms followinglong bone fracture are suggestive of fat embolism.The petechial rash is considered pathognomonic,but it occurs in less than 50 percent of cases. Gurdand Wilson10 established a set of diagnostic crite-ria for fat embolism syndrome, but these criteriahave not been well validated and rarely are usedclinically.11

The chest radiograph usually is not helpful inestablishing the diagnosis. A minority of patients’radiographs demonstrate patchy airspace disease,but most have normal chest radiograph findings.Ventilation-perfusion scans may show subseg-mental perfusion defects with normal ventilation.High-resolution computed tomography (CT) of thechest may show ground glass infiltrates,12 but thisis not a specific finding.

No laboratory test is specific for the diagnosis offat embolism syndrome. Thrombocytopenia andanemia are common findings, and disseminatedintravascular coagulation (DIC) and hemolyticanemia may occur. Hypocalcemia can developbecause of the affinity of calcium ions for free fattyacids. Lipiduria occurs commonly. Circulating fatlevels have not been found to correlate with thepresence or severity of fat embolism syndrome.

Several studies have suggested that recovery offat globules from wedged pulmonary artery catheteror bronchoalveolar lavage specimens may assist inestablishing the diagnosis. However, fat globulesare present in the blood in patients with long bonefractures independent of whether the fat embolismsyndrome develops.9 Similarly, lipid-laden macro-phages in bronchoalveolar lavage fluid can befound in a variety of conditions, and the sensitivityand specificity of their presence for the diagnosis offat embolism syndrome is not known.13-15

In summary, the diagnosis of fat embolism syn-drome is based upon pulmonary, neurologic, anddermatologic manifestations in the appropriateclinical setting. Physicians should have a highindex of suspicion in any patient who developsdyspnea or hypoxia after experiencing trauma orundergoing orthopedic surgery.

Figure 20-1. High-power photomicrographs reveal numerous fat emboli within pulmonary capillaries. The patient wasan unrestrained driver in a high speed motor vehicle accident and suffered multiple fractures. (Sudan IIIstain.) (Courtesy of Dr. Giuseppe G. Pietra.) (See Color Plate 11).

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307CHAPTER 20 EMBOLISM OF FAT, AIR, OR AMNIOTIC FLUID

Pathophysiology

Marrow contents commonly enter the circulation fol-lowing a fracture or when the medullary cavity isreamed during placement of an internal fixationdevice. Both of these cause increased pressure withinthe medullary cavity, thereby permitting entry ofmarrow fat into torn vessels. However, the mecha-nism by which fat in the blood produces the severeclinical manifestations of the syndrome is not entirelyclear.5 Two main hypotheses have been advanced:

1. The “mechanical” theory suggests that fat fromtraumatized marrow is forced into torn venouschannels that remain open because they areattached to the surrounding bone. The increasedintramedullary pressure pushes the marrow intothe sinusoid. From there, fat travels to the pul-monary circulation and mechanically occludesthe pulmonary capillaries. Evidence supportingthe mechanical theory includes visualization ofmarrow fat in the femoral vein within seconds ofintramedullary manipulation.5 In addition, trans-esophageal echocardiograms performed duringorthopedic procedures have demonstrated thatechogenic material passes through the heart atthe time a guide wire is inserted into the bonemarrow canal for intramedullary nailing.16 Themain criticism of this theory is that the eventsrelated to mechanical obstruction appear to occurat the time of injury, while the symptoms of fatembolism syndrome are delayed 12-24 hours.

2. The “toxic mediator” theory hypothesizes thatfat embolism syndrome occurs as a result ofhydrolysis of fat to more toxic free fatty acidsand other species. Circulating free fatty acids aredirectly toxic to pneumocytes and capillaryendothelium in the lung.17 In animal models,free fatty acids have been associated with ARDS.This theory is supported by the delayed appear-ance of rash, neurologic dysfunction, and pro-gressive respiratory failure.

It is likely that both mechanisms contribute to fatembolism syndrome. The initial mild respiratorysymptoms may be caused by mechanical obstructionby multiple fat globules that are too large to traversethe pulmonary capillaries. Because fat globules aredeformable, they may not occlude the vasculaturecompletely and, therefore, the obstruction may beincomplete. The later onset of neurologic, dermato-logic, and severe respiratory symptoms may be aresult of hydrolysis of fat to free fatty acids. Thesefree fatty acids can then migrate to other organs viathe systemic circulation.

Management and Prevention

Management of fat embolism syndrome is usuallysupportive, including maintenance of intravascu-lar volume and mechanical ventilation as required.Mortality is estimated to be 15 percent or less withmeticulous supportive care.5

The risk for developing fat embolism syndromeis thought to be reduced by early immobilizationand operative correction of long bone fractures.18,19

Limiting elevation of intraosseous pressure duringorthopedic surgery via a number of techniquesmay reduce the release of intramedullary fatinto the circulation and decrease the risk of fatembolism syndrome.20 Glucocorticoids have beeneffective in preventing fat embolism syndrome inseveral trials,21,22 but their routine prophylactic useremains controversial due to the risk of steroid-related complications. There is no evidence thatglucocorticoids are beneficial in managing estab-lished fat embolism syndrome.

Air Embolism

Gas embolism occurs as a result of entrainment ofgas, typically air, into the vasculature. The firstclinical report of air embolism dates from 1821 andresulted in death.23 Most cases are related to med-ical procedures or rapid ascent during underwaterdiving.

Air embolism can be divided further intovenous air embolism and arterial air embolism.The two are distinguished both by the mechanismof air entry into the vasculature and the vascularsite where the emboli lodge. This chapter will focuson venous air embolism because of its greater rele-vance to the pulmonary circulation.

Epidemiology

The most common risk factor for air entry into thevenous circulation is a procedure involving the inci-sion or puncture of large, non-collapsed veins whenthe pressure within those veins is subatmospheric.24

Many surgical procedures have been implicated,including neurosurgical, gynecologic, and ortho-pedic interventions. Neurosurgical procedures per-formed in the sitting position have the greatestincidence of venous air embolism, estimated as highas 80 percent for posterior fossa surgery in this ori-entation.25 Venous air embolism also may occur dur-ing neurosurgical procedures in the lateral, supine,

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or prone positions. Similarly, air may enter the veinsof the myometrium during delivery, and one studyreported the incidence of venous air embolism inwomen undergoing cesarean section to be 40 per-cent.26 During hip replacement surgery, the incidenceof venous air embolism is as high as 30 percent.27

Venous air embolism can occur during place-ment, maintenance, or removal of a central venouscatheter.28 A spontaneously breathing patientgenerates negative intrathoracic pressure duringinspiration, and pressure within the central veinsmay be subatmospheric, particularly if the veinsare above the heart and the patient is hypovolemic.In such a situation, significant quantities of air canrapidly enter the venous circulation.

Although gas embolism usually is caused byentrainment of air, other gases also can gain accessto the venous circulation. During laparoscopic pro-cedures, insufflation of carbon dioxide maintainsintraabdominal pressure greater than venous pres-sure. If there is venous injury during the pro-cedure, carbon dioxide can gain entry into thevenous circulation.27 The precise incidence of thiscomplication is unknown.

During diving, air embolism can result from dis-tention and rupture of the alveoli by expandinggases during ascent. An individual who has airflowobstruction and cannot exhale fully on ascent has anincreased likelihood of barotrauma on ascent, whichcan result in an arterial or venous air embolism.29

Pulmonary air embolism can also be a manifestationof decompression sickness, resulting from the for-mation of nitrogen bubbles following rapid ascentfrom a dive. This form of decompression sickness iscommonly referred to as “the chokes.”

Clinical Manifestations and Diagnosis

Clinical manifestations of air embolism are non-specific. In a conscious patient, air embolism isaccompanied by symptoms of dyspnea and chestpain. Signs of mild air embolism include tachypneaand diaphoresis. A more severe air embolism cancause hypotension, cardiac arrest, or electrocardio-graphic changes such as tachyarrhythmias, atri-oventricular block, or right ventricular strain.27

On physical examination, a “mill wheel” or “millpond” murmur may be auscultated. This is asplashing sound caused by air in the cardiac cham-bers and is typically a late sign.24 These findings ina patient at risk should prompt the physician toconsider air embolism. Because definitive diag-nostic measures require time, management shouldbegin as soon as air embolism is suspected.

The definitive diagnosis of air embolism can bemade by echocardiography, and intraoperativetransthoracic echocardiography should be con-sidered during high-risk surgeries, such as seatedneurosurgical procedures. A properly positionedprecordial Doppler ultrasound device can detectas little as 0.25 mL of air injected into the venouscirculation.30 Transesophageal echocardiographyis a more sensitive technique, although it is amore invasive procedure and its intraoperativeutility is limited by its expense. Although radio-graphs may be normal in patients with airembolism, CT may show small amounts of air in thein the pulmonary arteries or right side of the heart.31

Chest radiographs are relatively insensitive.

Pathophysiology

Factors that determine the severity of illness follow-ing venous air embolism include the volume of airentrained, the rate of air entrainment, the position ofthe patient at the time, and the patient’s underlyingcardiopulmonary reserve. The lethal volume of airin animals depends on the rate of injection. Wheninjected rapidly, injection of 7.5 mL/kg of air intodogs has been uniformly fatal.27 However, dogs areable to tolerate 1,400 mL of air injected over a periodof hours. The absolute volume of air tolerated inhumans is not known; however, there have beencase reports demonstrating that accidental injectionof 300 mL of air can be fatal.

The most common cause of death from massiveair embolism is circulatory collapse due to rightventricular outflow obstruction. The rate of entrain-ment appears to be critical in this process. Rapidentrainment of air into the venous circulationcauses an acute rise in pulmonary artery pressureswithin 60 seconds.27 In addition, the large volumeof air trapped in the pulmonary vasculature mayobstruct the right ventricular outflow tract. Both theincreased pulmonary artery pressures and the rightventricular outflow obstruction put increased strainon the right ventricle and decrease pulmonaryvenous return. This results in decreased left ventric-ular preload and decreased cardiac output. Theoccluded pulmonary vasculature can cause ventila-tion-perfusion mismatch, resulting in hypoxemia.When air is entrained more slowly, the pulmonaryartery pressures increase less rapidly. Typically, pul-monary artery pressures peak after 10 minutes andthen slowly decline. Tachyarrhythmias occur com-monly, and their severity is related to the volume ofair entrained. Bradycardia can occur and is consid-ered an ominous sign.


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The position of the patient is an important factorin air entrainment. Procedures performed with thepatient in the seated position are associated withthe highest risk for air embolism. A greater pressuregradient between the procedural site and the rightatrial pressure is associated with a greater potentialfor entrainment of air. Hypovolemia will exacerbatethis by further reducing the right atrial pressure.

Another related factor is whether the patient isbreathing spontaneously. A spontaneously breath-ing person generates negative intrathoracic pres-sure during inspiration that can draw air into thevessel if a catheter or other route of air entry isopen. In addition, air entrainment may cause chestpain and dyspnea and lead the patient to gasp,resulting in even greater negative intrathoracicpressure and further air entrainment.

Air embolism can cause ARDS. Entrapment ofair bubbles in the pulmonary circulation may leadto release of vasoactive mediators, increasingalveolar capillary permeability and resulting inpulmonary edema. Furthermore, these mediatorsmay recruit activated neutrophils to the pulmonaryvasculature, resulting in inflammation and furtherlung damage.23

In diving, the mechanism is slightly different. Indeep water divers breathe compressed air atgreater-than-ambient pressure, and excess air dis-solves in blood and tissue. If the diver ascends toorapidly, gas emerges from solution and forms smallbubbles. Nitrogen bubbles are the slowest to becleared and can cause air embolism in the mannerdiscussed above.

Every venous air embolism has the potential todevelop into an arterial air embolism. If the fil-tering capacity of the pulmonary capillary bed isoverwhelmed, air bubbles can pass to the arterialcirculation. This can also occur due to the presenceof a right-to-left shunt, including a patent foramenovale. When air bubbles enter the systemic cir-culation, they distribute to nearly all organs.Embolization to the cerebral or coronary circula-tion may result in focal ischemia with significantmorbidity and mortality.


Prevention is critical during procedures that placepatients at high risk for air embolism. There are twokey ways to prevent venous embolism. First, it isimportant to take measures to decrease the pressuregradient between the procedural site and the rightatrium. Maintaining adequate intravascular volumeby intravenous hydration will help prevent further

decline in right atrial pressure. Using the Trendelen-burg position for central line insertion and otherprocedures also can help prevent air entrainment.

Second, minimizing the amount of time thatthe vessel is open to atmospheric pressure willdecrease the opportunity for entrainment of air.During central line insertion, the needle andcatheter should be occluded at all times. Duringremoval of a central line, the patient should exhaleto prevent air entry on inspiration.

Once air embolism has occurred, the primarymanagement is prevention of further air entrain-ment. A secondary goal is to decrease the volumeof air within the body. If the air embolism occursintraoperatively, the surgeon should flood theoperative field with saline to help prevent furtherair entry. Volume expansion is recommended toincrease right atrial pressure. If possible, thepatient should be positioned with the operative sitebelow the level of the heart. It may be helpful toplace the patient in the left lateral decubitus posi-tion to prevent obstruction of the right ventricularoutflow tract. Aspiration of 50 percent of the airentrained from an appropriately placed right atrialcatheter has been described,27 but achieving theseresults in an emergency situation is challenging.

Supportive therapy for cardiovascular compro-mise, dysrhythmias, and respiratory failure should beinitiated. Many patients require mechanical ventila-tion. Catecholamines may be required to maintainblood pressure. Supplemental oxygen should begiven to produce adequate oxygenation. In the caseof decompression sickness, supplemental oxygenmay reduce the severity of the air embolism by allow-ing more rapid nitrogen egress from bubbles.24

Hyperbaric oxygen therapy may be employedas adjunctive therapy in severe cases of venous airembolism to help decrease the size of air bubbles inthe bloodstream. However, its use usually isreserved for patients with arterial air embolismwho have neurologic or cardiac findings.

Amniotic Fluid Embolism

Amniotic fluid embolism is a rare clinical entity, withdevastating consequences at a time of anticipatedjoy. Timely diagnosis can be challenging and requiresa high index of suspicion. The syndrome was firstdescribed in 1926, when Meyer reported fetal cellulardebris within the maternal circulation in a patientwho experienced peripartum dyspnea and hypo-tension.32 Steiner and Lushbaugh published alandmark autopsy case series in 1941. They found


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squamous cells, mucin, and amorphous debriswithin the pulmonary vasculature and concludedthat maternal death resulted from the systemicembolization of fetal products and amniotic fluid.33

More recent work has called to question the mech-anism underlying the severe hypotension character-istic of this syndrome. The term “anaphylactoidsyndrome of pregnancy” has been suggested toemphasize the cytokine-mediated mechanisms forsystemic hypotension and coagulopathy.34

Epidemiology

Amniotic fluid embolism has a reported incidencebetween 1 in 8,000 to 1 in 10,000 pregnancies.Mortality from amniotic fluid embolism in symp-tomatic women has been estimated as high as80 percent. The syndrome may be responsible for15 percent of maternal deaths.35 The incidence ofsubclinical amniotic fluid embolism is unknown.

Because the syndrome is so rare, no single insti-tution (let alone practitioner) has had sufficientexperience to define the risk factors or the preciseclinical course of amniotic fluid embolism. Reviewof a national registry of amniotic fluid embolismcases failed to disclose predisposing factors,34

although earlier reports had suggested advancingmaternal age, multiparity, large fetal size, vigorouslabor, the use of oxytocic drugs, and secondtrimester dilation and curettage procedures aspotential associations. Seventy percent of cases ofamniotic fluid embolism occur during labor, with11 percent following vaginal delivery and 19 per-cent following cesarean section.34

Clinical Picture and Diagnosis

Patients with amniotic fluid embolism classicallyhave a sudden onset of progressive dyspnea,hypoxia, and cyanosis, and a cough progressivelyproductive of frothy sputum. Oxygen saturationmonitoring and arterial blood gas analysis de-monstrate hypoxemia. Mental status changes mayoccur, with up to 20 percent of patients developingseizures. This is followed rapidly by progressivehypotension (out of proportion to blood loss) lead-ing to cardiopulmonary arrest.34,36 Radiographicfindings are nonspecific and can span the spectrumfrom clear lung fields to diffuse abnormalities con-sistent with ARDS.

Up to 40 percent of those who recover from hemo-dynamic collapse develop a coagulopathy, rangingfrom mild (subclinical laboratory abnormalities) to

clinically severe, with fulminant DIC developing in10 percent.37 Laboratory abnormalities are consistentwith DIC, including elevated fibrin degradationproduct levels, elevated D-dimer values, decreasedfibrinogen levels, thrombocytopenia, and prolongedprothrombin and activated partial thromboplastintimes. This coagulopathy, when superimposed uponongoing uterine blood loss, can be immediately lifethreatening.

Sufficient multiorgan hypoperfusion may occurduring amniotic fluid embolism to result in multi-organ system failure. Survivors of the syndromeoften face prolonged lung injury secondary toARDS. A high percentage of survivors face perma-nent neurologic damage.34

The diagnosis of amniotic fluid embolism is clini-cal, with a particularly high degree of suspicion attimes of greatest risk: during labor, within 30 min-utes of delivery, or during a second trimester dilationand curettage. Clues to the diagnosis include acutehypoxia, acute hypotension (out of proportion toblood loss), cardiopulmonary arrest, or worseningcoagulopathy. The differential diagnosis includeshemorrhagic shock, sepsis, placental abruption, pul-monary thromboembolism, aspiration of gastriccontents, eclampsia, and the syndrome of hemolysis,elevated liver enzymes, and thrombocytopenia(HELLP). Rarely, anaphylaxis, anesthetic drug effect,peripartum myocardial infarction, or a stroke mayoccur in a similar fashion.36

Laboratory testing is rarely helpful in diag-nosing amniotic fluid embolism. No abnormalitieson common laboratory tests are specific. A mono-clonal antibody, TKH-2, has been developedagainst amniotic fluid-derived mucin38 and can beapplied to blood from the maternal pulmonaryartery to help diagnose amniotic fluid embolism.However, its limited availability precludes theclinical utility of this test.35 Likewise, cytologicexamination from pulmonary arterial catheterwedge aspirate is unlikely to provide a timelydiagnosis, and amniotic debris can be found in theabsence of clinical manifestations of amniotic fluidembolism.

Pathophysiology

The pathophysiology of this syndrome remainspoorly understood. Initially, embolization of amni-otic fluid and fetal products to the pulmonary vas-culature with mechanical obstruction causing acutecor pulmonale and subsequent hemodynamic col-lapse was thought to be a sufficient explanation.Early autopsy studies revealed mucin, squamous


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cells, and cellular debris within the pulmonary vas-culature.33 Subsequent studies using a wedged pul-monary artery catheter isolated squamous cellsin pulmonary arterial blood aspirates.39 However,hemodynamic profiles in women suffering fromamniotic fluid embolism demonstrated reducedleft (rather than right) ventricular ejection fractionand elevated pulmonary capillary wedge pressure,inconsistent with pure mechanical obstruction ofthe pulmonary arteries and acute right-sided heartfailure.40

Fetal products within the pulmonary vascula-ture may not be enough to cause respiratory failureand hemodynamic collapse, because fetal productshave been identified within the pulmonary circula-tion of women who have died during labor of othermedical causes, without clinical evidence of amni-otic fluid embolism. Cytologic confirmation reliesupon the identification of fetal squamous cells, yetdistinguishing between maternal and fetal squa-mous cells can be difficult.41,42

Pathogenesis is believed related to the emboliza-tion of cytokines, which are present in amnioticfluid at higher concentration than in maternalblood. Two cytokines appear to be key in patho-genesis: endothelin-1 (a potent vasoconstrictor ofpulmonary and coronary arterial beds) and tissuefactor (an activator of the extrinsic coagulationpathway). Endothelin-1 is present in amniotic fluidat concentrations 10 to 100 times higher than insimultaneously measured maternal plasma levels,43

while tissue factor is present in amniotic fluid atconcentrations up to 45 times higher than in mater-nal blood plasma.44

The initiating step in amniotic fluid embolism isthought to be entry of amniotic fluid into maternalcirculation. Throughout gestation, the fetal mem-branes isolate amniotic fluid from the maternal cir-culation. At delivery, uterine vessels are exposed.Incomplete collapse of these vessels or tears in thelower uterine segment and endocervix provideportals for entry of amniotic fluid into maternalcirculation.45

Once in the maternal circulation, amniotic fluidand fetal products travel through the circulationto the pulmonary arteries. Acutely increasedendothelin-1 levels within the pulmonary vascula-ture may cause pulmonary artery vasoconstriction,resulting in acute pulmonary hypertension, severehypoxia, and right heart strain. A goat model ofamniotic fluid embolism supports this theory.46

Human data are not available, because of delays inpulmonary artery catheter placement during thistransient event.47 Alternatively, it has been sug-gested that hypoxia from amniotic fluid embolism

could, itself, serve as a stimulus for endogenousproduction of endothelin-1 by the pulmonaryvasculature.48

Hemodynamic collapse quickly follows. Thismay be due to coronary artery vasoconstrictionfrom elevated levels of circulating endothelin-1. Asa result of coronary artery vasoconstriction, leftventricular systolic function is impaired, resultingin decreased cardiac output and elevated left atrialand pulmonary capillary wedge pressures. Thesehemodynamic findings are reported in humansand animals.40

Survivors of acute hypoxia and hemodynamiccollapse face severe DIC, which occurs in up to 40percent of patients.34 Amniotic tissue factor entersthe systemic circulation through breaks in the fetal-maternal barrier. Once in the maternal circulation,the balance between tissue factor and tissue factorpathway inhibitor shifts to cause activation of theextrinsic coagulation pathway. Coagulopathy canrange from mild changes in laboratory tests tosevere DIC. Postpartum uterine atony may worsenblood loss.


No specific therapy has been proven beneficial inthe management or prevention of amniotic fluidembolism. The rapid progression from acutedyspnea to fatal hemodynamic collapse requiresprompt and vigorous resuscitation. Adequate sup-port is rarely available outside of an intensive careunit; transfer to an intensive care unit is warrantedas soon as the diagnosis is suspected. Resuscitationshould proceed with basic and advanced cardiaclife support algorithms, with an awareness thatthe patient is at risk for sudden hemodynamiccollapse.

The initial goal of therapy is to maintain oxy-genation and perfusion of vital organ systems. Anexperienced practitioner should rapidly initiateendotracheal intubation and mechanical ventila-tion if hypoxia persists despite high-concentrationoxygen supplementation or if the normal airwayprotective reflexes are impaired. Airway hyper-emia during pregnancy may complicate airwaymanagement, and the increased vascularity maypredispose to bleeding. Vocal cord and airwayedema also may hinder endotracheal tube inser-tion, and a smaller-than-usual endotracheal tubeshould be used for intubation.49

Because patients frequently have elements ofhypovolemia from blood loss, as well as bothcardiogenic and noncardiogenic pulmonary edema,


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pulmonary artery catheterization may be requiredto help guide resuscitative efforts. Hypovolemiashould be corrected with isotonic crystalloid fluidto maintain a mean arterial pressure adequate forvital organ perfusion. Vasopressor agents such asdobutamine, dopamine, or norepinephrine may berequired if hypotension does not resolve with crys-talloid fluid infusion. Initial goals of therapyshould be to maintain a mean arterial pressure of60 mmHg and urine output of 50 mL per hour.47 Thegravid uterus can impair venous return to the heartthrough compression of the inferior vena cava.50

In a patient with critical hypotension or hypoxia,emergent cesarean delivery should be considered.

Use of inhaled nitric oxide or other inhaledpulmonary vasodilators during the hypoxic phaseof amniotic fluid embolism has been proposed tomanage acute pulmonary hypertension and thusimprove gas exchange and cardiac function.However, experience in this population is limited,and no firm recommendations can be given in thisregard.51

Management of the DIC associated with amni-otic fluid embolism is supportive in nature.Frequent serial monitoring of blood counts andDIC parameters is appropriate, with use of bloodproducts when necessary. There are no data to sup-port the routine use of glucocorticoids, althoughthey may be considered if acute adrenal insuffi-ciency is suspected in the hypotensive patient withsevere coagulopathy.47,52 Uterine atony may con-tribute to ongoing hemorrhage, and oxytocin orsimilar agents may be useful in diminishing bloodloss.35

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pulmonary vascular disease || embolism of fat, air, or amniotic fluid

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