Nonthrombotic embolism

The blockage of blood vessels by fat, air, or amniotic fluid is an uncommon but potentially life-threatening event. Fat emboli mostly originate from the bone marrow in patients with long bone fractures. Air can enter the circulatory system as a result of invasive procedures (e.g., vascular surgery or catheterization, neurological surgery), trauma, or rapid ascent when diving (decompression illness), while amniotic fluid emboli typically occur during labor. The emboli usually lodge within the pulmonary arteries and cause right ventricular outflow obstruction and circulatory collapse. General clinical features of nonthrombotic embolisms include acute onset of hypoxia, hypotension, and neurological symptoms (e.g., altered mental status, seizures). Characteristic clinical findings include a nondependent petechial rash on the upper body in fat embolism, the mill wheel sign in venous air embolism, signs of stroke in arterial air embolism, and disseminated intravascular coagulation in amniotic fluid embolism. Nonthrombotic embolisms are primarily a clinical diagnosis, but results of arterial blood gas analysis, ECG, and chest imaging (e.g., chest x-ray, CT) can support the diagnosis and rule out alternative causes. Management is mainly supportive and includes oxygenation, mechanical ventilation, and, if necessary, administration of vasopressors. Nonthrombotic embolisms have a high mortality rate.

For thromboembolic diseases, see “Pulmonary embolism,” “Thromboembolic stroke,” “Acute mesenteric artery embolism,” “Acute limb ischemia,” and “Retinal vessel occlusion.”

See also “Septic emboli.”

Both arterial air embolism and venous air embolism can be caused by laparoscopic surgery, cardiac and vascular surgery, endoscopic procedures, ECMO, and diving-related injuries.

Fat embolism, air embolism, and AFE are all clinical diagnoses.

Definition ^[1]

A potentially life-threatening condition caused by the entry of fat cells, usually from bone marrow, into the circulatory system

Etiology ^[1]

• Traumatic (95% of cases)
  • Most commonly long bone fractures (e.g., femoral fracture)
  • Orthopedic surgeries
  • Bone marrow transplant
• Nontraumatic
  • Sickle cell crisis
  • Others: pancreatitis, osteomyelitis, parenteral lipid infusion

Early operative fixation is recommended in patients with long bone fractures to reduce the risk of fat embolism syndrome. ^[10]

Pathophysiology

• Traumatic fat embolism: fat cells from bone marrow enter systemic circulation and occlude the pulmonary arterioles → right heart failure and pulmonary edema
• Nontraumatic fat embolism: ↑ cytokine levels (e.g., CRP, TNF) → agglutination of chylomicrons in the circulation → fat emboli formation
• Lipases metabolize the lodged fat cells (in pulmonary arterioles) → release of free fatty acids → pulmonary arteriolar endothelial injury → acute lung injury/respiratory distress
• Dermatologic and neurological manifestations (see “Clinical features”): The exact mechanism is unknown but may be due to paradoxical embolisms or biochemical factors (e.g., systemic cytokine release). ^[11]
• Distention of thrombi-occluded capillaries → ↑ intracapillary pressure → extravasation of RBCs into the skin → petechial rash

Clinical features ^[1][2][3]

Symptoms develop within 12–72 hours of the inciting event.

• Classic triad: Components typically develop sequentially.
  • Respiratory distress (in up to 95% of patients)
    • Tachypnea, dyspnea
    • Hypoxemia, cyanosis
    • Diffuse crackles
  • Neurological symptoms (in up to 80% of patients)
    • Altered mental status (e.g., confusion, lethargy or restlessness, coma)
    • Seizures
    • Focal neurological deficits
  • Petechial rash (in up to 50% of patients) ^[2][3]
    • Appears 3–5 days after the onset of respiratory distress
    • Mainly seen on the axillae, chest wall, head, neck, conjunctiva, and/or buccal mucosa.
• Other features: fever, retinopathy, cor pulmonale

Fulminant fat embolism syndrome can manifest with ARDS, shock, signs of acute heart failure, and/or DIC. ^[1]

Diagnosis ^[1][2][3]

Fat embolism is a clinical diagnosis; rule out other life-threatening causes of dyspnea and critical causes of altered mental status.

Diagnostic criteria

Gurd's criteria and Schonfeld's criteria are commonly used, however, neither has been prospectively validated.

Gurd's criteria

1 major plus 4 minor criteria are required for the diagnosis. ^[12]

• Major criteria
  • Petechial rash
  • Respiratory insufficiency
  • Neurological symptoms (see “Clinical features”)
• Minor criteria
  • Fever
  • Tachycardia
  • Acute anemia
  • Acute thrombocytopenia
  • Increased ESR
  • Renal abnormalities (e.g. anuria, oliguria, lipiduria)
  • Retinal changes (petechiae or fat)
  • Fat globules in sputum

Schonfeld's criteria

Laboratory studies ^[2][3]

• CBC: anemia, thrombocytopenia
• ESR: increased
• Blood, urine, and/or sputum microscopy: Fat droplets may be seen but are not specific for fat embolism syndrome.

Imaging

• CXR: bilateral diffuse or patchy infiltrates ^[2][3]
• High-resolution CT chest ^[2][3]
  • Patchy ground glass opacities and consolidations
  • Interlobular septal thickening with a crazy-paving pattern
• Neuroimaging: Consider for patients with neurological symptoms. ^[2][3]
  • CT head: typically normal
  • MRI brain: often shows a starfield pattern with multiple punctate lesions

Management ^[1][2][3]

Management is primarily supportive, as there are no specific treatments for fat embolism syndrome.

• Acute stabilization
  • ABCDE assessment
  • Initiate management of respiratory failure (e.g., management of ARDS).
  • Provide immediate hemodynamic support.
  • Begin initial management of altered mental status and treatment of acute seizures.
• Supportive care and disposition
  • Admit to the ICU for monitoring and continued management.
  • Perform frequent neurological examination and consider invasive ICP monitoring.
  • Provide supportive care for the critically ill patient.

Prognosis ^[1][3]

Fat embolism syndrome is usually self-limited.

• Mortality rates are < 10% with appropriate ICU management.
• Respiratory, neurological, and dermatologic manifestations are usually fully reversible.

Definition ^[4][5]

A rare and potentially life-threatening condition caused by the entry of gas into the systemic venous circulation

Etiology ^[4][5]

• Iatrogenic
  • Surgery
    • Neurosurgical procedures (highest risk)
    • Cardiac or vascular surgery
    • Laparoscopic surgery
  • Endoscopic procedures
  • Vascular catheterization procedures
    • Central venous catheter insertion and removal
    • Hemodialysis line placement
    • Extracorporeal membrane oxygenation
  • Infusion-related errors: accidental injection of air
• Trauma: Penetrating trauma that lacerates a vein can allow air to enter from the external environment.
• Diving: rapid ascent, leading to decompression sickness
• Intentional injection of air (suicidal or homicidal intent)

Pathophysiology ^[4][6]

• Air enters the venous system → travels to right ventricle → right ventricular outflow obstruction → circulatory collapse
• Acute cor pulmonale and circulatory collapse typically only occur with large volume embolisms.
• Small volume emboli may be asymptomatic or cause transient or minimal symptoms.

Clinical features ^[4][6]

• Signs of acute right ventricular outflow tract obstruction
  • Sudden hypotension
  • Jugular venous distention
  • Cardiac arrhythmia or arrest
• Clinical features of pulmonary embolism, including:
  • Signs of respiratory distress
  • Signs of intraoperative PE
• Mill wheel sign
• Patients with paradoxical embolism: clinical features of arterial air embolism are also present

Diagnostic studies ^[4][6]

Venous air embolism is a clinical diagnosis. Exclude other immediately life-threatening causes of dyspnea or shock.

• Chest imaging: evidence of air (hyperlucencies) in the right cardiac chambers and pulmonary arteries
  • Chest x-ray: low sensitivity; most appear normal
  • Chest CT: higher sensitivity; however, findings may not be clinically significant ^[4][6]
• Echocardiography: evidence of air in the right cardiac chambers
• ECG: may show high-risk ECG signs of PE
• ABG analysis: hypoxemia and hypercarbia

Management ^[4][5][6]

For patients with evidence of arterial ischemia (suggesting paradoxical embolism) also see “Management” in “Arterial air embolism.”

• Initial stabilization
  • ABCDE approach: CPR; , mechanical ventilation, and immediate hemodynamic support as needed
  • Administer 100% oxygen therapy. ^[4][6]
  • Place the patient in the left lateral decubitus position and Trendelenburg position. ^[4]
  • Prevent further entry of air into the circulation.
    • If a recently removed catheter is suspected as the source, apply an impermeable dressing to the site and hold pressure to prevent further bubble entry.
    • Drop any suspected IV infusion source to below heart level.
  • Provide rapid volume expansion with IV fluid resuscitation. ^[5]
  • Consider air aspiration through a central venous catheter; to evacuate air from the right heart
• Definitive care and disposition: Specialist consultation (e.g., anesthesiology, critical care) typically required
  • Severe cases: Transfer for hyperbaric oxygen therapy. ^[4][5]
  • All other patients: Admit to the ICU for monitoring and continued treatment.

Prognosis

Air embolism has a high mortality rate (∼ 20%). ^[13]

Definition ^[4][5]

A rare and potentially life-threatening condition caused by the entry of gas into the pulmonary veins or directly into the systemic arterial circulation

Etiology ^[4][5]

• Iatrogenic
  • Surgery
    • Cardiac or vascular surgery
    • Laparoscopic surgery
  • Endoscopic procedures
  • Arterial catheterization procedures
    • Arterial angiography
    • Extracorporeal membrane oxygenation
  • Ventilator-induced lung injury (barotrauma)
• Paradoxical embolism: in patients with venous air embolism ^[4][6]
• Trauma: Blunt or penetrating trauma leading to arterial laceration or torn lung parenchyma.
• Diving: rapid ascent, leading to decompression illness
• Intentional injection of air (suicidal or homicidal intent)

Pathophysiology ^[4]

• Air enters the arterial system → obstruction of end-organ arterioles or capillaries → ischemic damage
• Ischemia and infarction may occur even with small-volume embolisms.

Clinical features ^[4]

• Most common: focal neurological deficits, altered mental status, seizures, coma
  • Symptoms can vary depending on the amount of air involved
  • For examples of focal neurological deficit patterns, see “Clinical features of stroke by affected vessel” and “Lacunar syndromes.”
• Clinical features of the following:
  • Acute heart failure, myocardial infarction, arrhythmias
  • Acute kidney failure
  • Retinal infarction

Diagnostic studies ^[4]

Arterial air embolism is a clinical diagnosis. Exclude other critical causes of altered mental status.

• CT brain, abdomen, or pelvis: may show ischemic changes in the affected organs
• ECG: may show ischemic ECG changes
• Echocardiography: may show evidence of air in the left cardiac chambers
• Fundoscopic examination: : may show air bubbles within retinal vessels ^[14]

Management ^[4][5][6]

See also “Diving-related injuries.”

• Initial stabilization
  • ABCDE approach: CPR; , mechanical ventilation, and immediate hemodynamic support as needed
  • Administer 100% oxygen therapy. ^[4][6]
  • Place the patient in the supine position. ^[5][6]
  • Prevent further air entry into the circulation.
    • If a recently removed catheter is suspected as the source, apply an impermeable dressing to the site and hold pressure to prevent further bubble entry.
    • For air entering through an arterial catheter: Stop flush and open the rotating hemostatic valve. ^[4]
  • Provide IV fluid therapy with colloid solution as needed to maintain normovolemia. ^[5][6]
  • Maintain cerebral perfusion with permissive hypertension or vasopressors as needed. ^[6]
• Definitive care and disposition: Transfer for hyperbaric oxygen therapy (treatment of choice) as soon as clinically stable. ^[5][6]

Hyperbaric oxygen therapy is the treatment of choice for all patients with symptomatic arterial air embolism. ^[5][6]

Prognosis

Air embolism has a high mortality rate (∼ 20%). ^[13]

Definition ^[7][8]

A rare life-threatening condition caused by the entry of fetal cells and debris (from amniotic fluid) into maternal circulation ^[8]

Pathophysiology

• Desquamated fetal cells or lanugo from amniotic fluid enter maternal circulation and embolize to the pulmonary arterioles → increased pulmonary arterial pressure, right heart failure, and pulmonary edema
• Entry of procoagulants (thromboplastin) from amniotic fluid into maternal circulation → diffuse intravascular coagulation
• Entry of leukotrienes from amniotic fluid into maternal circulation → triggering of an immune response → pulmonary vasospasm, alveolar capillary damage (pulmonary edema), and hypotension

Risk factors ^[7][8][9]

• Maternal age > 30 years
• Multiparity
• Complicated labor (e.g., placenta previa/abruption, forceps delivery, cesarean delivery, eclampsia)
• Invasive procedures (e.g., amniocentesis, abortion)
• Blunt abdominal trauma

Clinical features ^[7][8]

AFE typically manifests during labor or immediately after delivery but can occur up to 48 hours postpartum.

• Acute respiratory distress syndrome
  • Dyspnea, tachypnea, cough
  • Hypoxia, cyanosis
  • Basal crepitations
• Cardiovascular collapse: hypotension; , arrhythmias, cardiac arrest
• Neurological symptoms: altered mental status, seizures
• Clinical features of disseminated intravascular coagulation (DIC)
• Multiorgan dysfunction
• Nonspecific symptoms (e.g., anxiety, a sense of impending doom)
• Fetal distress: decelerations on cardiotocography

AFE typically manifests with a classic triad of sudden hypoxia and hypotension followed by coagulopathy. ^[7][8]

Diagnosis ^[7][8][9]

General principles

• AFE is a clinical diagnosis based on the sudden onset of typical peripartum clinical features. ^[7][9]
• Supportive studies are used to help guide management and rule out complications.
• Exclude other immediately life-threatening causes of dyspnea, etiologies of shock, and critical causes of altered mental status.

If AFE is suspected clinically, do not delay treatment to obtain diagnostic studies. ^[7][9]

Laboratory studies

• Arterial blood gas analysis: hypoxemia, acid-base disorders
• CBC: anemia, thrombocytopenia
• Coagulation studies: ↑ aPTT, ↑ PT, ↓ fibrinogen (see also “Diagnostics in DIC”)
• Type and screen including pretransfusion crossmatch
• Cardiac enzymes: may be elevated
• Pulmonary artery blood sample: presence of squamous cells, hair, or other fetal debris in maternal blood ^[7][8]

Imaging

• CXR: typically shows bilateral opacities similar to pulmonary edema from other causes ^[9]
• Bedside echocardiography: brief phase of right ventricular dysfunction often followed by severe left ventricular dysfunction ^[7][9]
• CTA chest: to rule out thrombotic pulmonary embolism
• ECG: to assess for arrhythmias and/or myocardial infarction

Differential diagnosis ^[7][9]

• Placental abruption or uterine rupture
• Postpartum hemorrhage or peripartum hemorrhage
• Air embolism or pulmonary embolism
• Septic shock or anaphylaxis
• Transfusion reaction
• Peripartum cardiomyopathy or myocardial infarction
• Anesthetic complications (e.g., total spinal anesthesia)
• Eclampsia

Management ^[7]

AFE is a life-threatening condition and must be treated as an emergency.

• ABCDE survey
  • Respiratory support and immediate hemodynamic support as needed.
  • Obtain immediate obstetrics, critical care, and anesthesia consults.
  • Prepare for emergency delivery.
• Management of cardiac arrest in pregnancy
  • Initiate CPR.
  • Perform left uterine displacement.
  • Consider perimortem cesarean delivery if indicated. ^[7]
• Management of cardiogenic shock ^[7]
  • Initial phase (RV dysfunction predominates): Consider inodilators to reduce pulmonary vascular resistance.
  • Later phase (LV dysfunction predominates): Consider inoconstrictors to treat hypotension and maintain coronary perfusion.
• Treatment of DIC
  • Manage refractory uterine bleeding in close cooperation with obstetrics. ^[7]
  • See also “Postpartum hemorrhage” and “Management of antepartum hemorrhage.”
• Disposition
  • Undelivered patients: urgent transfer to the operating room for cesarean delivery or assisted vaginal delivery ^[7]
  • Postpartum patients: Transfer to the ICU for postresuscitation care.

Prognosis

• High maternal mortality rate
• Neurological deficits in surviving infants

• Definition: respiratory insufficiency because of embolization of bone cement material or indirect systemic effects after bone cement implantation
• Occurrence: after orthopedic procedures using bone cement material
• Pathophysiology: direct mechanical embolization and thermal effects or an immunological-mediated release of vasoactive substances; often associated with fat embolism
• Clinical features
  • Symptoms of a pulmonary embolism
  • Acute respiratory distress syndrome
• Diagnostics: CT pulmonary angiogram for the detection of mechanical embolization
• Treatment
  • Supportive (intensive care) measures, including mechanical ventilation and catecholamine therapy
  • If necessary, interventional or surgical removal of the embolic cement material

• Follow ABCDE approach.
• Start ACLS for cardiac arrest (including steps for cardiac arrest in pregnancy).
• Provide respiratory support.
  • 100% oxygen for all patients
  • Intubation and mechanical ventilation for respiratory failure
  • Management of ARDS as needed
• Provide immediate hemodynamic support with IV fluids and pressors as needed.
• Begin neuroprotective measures as needed, e.g., maintain cerebral perfusion pressure, invasive ICP monitoring.
• Determine the underlying cause through clinical evaluation and bedside diagnostic studies, e.g., portable CXR, POCUS, ABG, ECG.
• Consider other supportive diagnostic studies once stabilized, e.g., neuroimaging, CTA chest.
• If air embolism is suspected, begin temporizing measures.
  • Patient positioning: supine position for arterial air embolism, left lateral decubitus position and Trendelenburg position for venous air embolism
  • Apply an occlusive dressing to open wounds or catheter sites.
  • PIV infusions: Drop infusion source below heart level.
  • Arterial lines: Stop flush and open the rotating hemostatic valve.
  • Consider right heart air aspiration through CVC for venous air embolism.
• Manage complications.
  • Fat embolism: Treat acute seizures.
  • AFE: Treat DIC and manage cardiogenic shock.
• Arrange for definitive treatment and disposition, e.g.:
  • Fat embolism: ICU admission
  • Air embolism: HBOT (at a capable facility)
  • AFE: emergency delivery by OB/GYN, treatment of uterine bleeding
  • Cement embolism: removal by surgery or interventional radiology