63 Other Embolic Syndromes
Air Embolism
Air embolism, the entry of gas into the vasculature, is a largely iatrogenic clinical entity that can result in serious morbidity and even mortality (Table 63-1).1 This is one of the most serious problems in diving medicine.2 The medical use of a variety of gases has created numerous types of gas embolisms, including carbon dioxide, nitrous oxide, and nitrogen emboli. There are two broad categories of gas embolism, venous and arterial, depending on the mechanism of gas entry and where the emboli ultimately lodge.
TABLE 63-1 Medical Specialties with Documented Cases of Gas Embolism
| Specialty | Mechanism of Gas Embolism |
|---|---|
| All medical specialties | Inadvertent entry of air through peripheral intravenous circuits |
| All surgical specialties | Intraoperative use of hydrogen peroxide, generating arterial and venous oxygen emboli |
| Anesthesiology | Entry of air through disconnected intravascular catheters, inadvertent infusion of air through intravascular catheters |
| Cardiac surgery | Entry of air into extracorporeal bypass pump circuit, incomplete removal of air from the heart after cardioplegic arrest, carbon dioxide–assisted harvesting of peripheral veins |
| Cardiology | Entry of air through intravascular catheters during angiographic studies and procedures |
| Critical care/pulmonology | Entry of air through disconnected intravascular catheters, pulmonary barotrauma, rupture of intraaortic balloon pumps, entry of air in extracorporeal membrane oxygenator (ECMO) circuit |
| Diving medicine and hyperbaric medicine | Pulmonary barotrauma, paradoxical embolism after decompression injury, entry of gas through disconnected intravascular catheters |
| Endoscopic/laparoscopic surgery | Entry of gas into veins or arteries during insufflation of body cavities |
| Gastroenterology | Entry of gas into veins during upper and lower endoscopies and endoscopic retrograde pancreatography (ERCP) |
| Neonatology/pediatrics | Pulmonary barotrauma in treatment of infants with premature lungs |
| Nephrology | Inadvertent entry of air through hemodialysis catheters and circuits on hemodialysis machine |
| Neurosurgery | Entry of air through incised veins and calvarial bone, especially during sitting craniotomies |
| Obstetrics/gynecology | Cesarean sections, gas insufflation into veins during endoscopic surgery, intravaginal/intrauterine gas insufflation during pregnancy |
| Otolaryngology | Laser (Nd:YAG) surgery on the larynx and trachea/bronchi |
| Orthopedics | Gas insufflation into veins during arthroscopy, total hip arthroplasty, prone spine surgery |
| Radiology | Injected air/gas as contrast agent, inadvertent injection of air during angiographic studies |
| Thoracic surgery | Entry of air into pulmonary vasculature during lung biopsies and video-assisted thoracoscopy (VATS), chest trauma (penetrating and blunt), lung transplants |
| Urology | Transurethral prostatectomy (TURP), radical prostatectomy |
| Vascular surgery | Entry of air during carotid endarterectomies |
Venous Gas Embolism
A venous gas embolism occurs as a result of the entry of gas into the systemic venous system.3 The gas is then transported to the lungs via the pulmonary arteries, causing interference in gas exchange, arrhythmias, pulmonary hypertension, right ventricular strain, and cardiac failure. Predispositions that allow entry of gas into the venous system include incision of noncollapsed veins and the presence of subatmospheric pressure in these vessels. These conditions occur when the surgical field is above the level of the heart (for instance, during neurosurgical operations performed in the sitting position).4 Other potential pathways include entry of air into central venous and hemodialysis catheters1 and entry of air into the veins of the myometrium in the peripartum period.1,5
Pathophysiology
The most common scenario for venous gas embolism is insidious, where there is continuous entry of small gas bubbles into the venous system. With rapid entry or larger volumes of gas, increasing strain on the right ventricle follows because of the migration of the emboli to the pulmonary circulation. Pulmonary arterial pressure increases, while increased resistance to right ventricle outflow causes diminished pulmonary venous return. This is reflected in decreased left ventricular preload, resulting in diminished cardiac output and, ultimately, systemic cardiovascular collapse.6 Quite often, tachyarrhythmias develop, but bradycardias are possible as well. When large quantities of gas/air (over 50 mL) are injected abruptly, acute cor pulmonale and/or asystole can occur.3 These alterations of lung vessel resistance and ventilation/perfusion mismatch in the lung cause intrapulmonary right-to-left shunt with increased alveolar dead space, leading to arterial hypoxia and hypercapnia.
Diagnosis
The so-called mill-wheel cardiac murmur, a continuous churning murmur, is relatively typical of venous gas embolism and can be auscultated by a precordial or esophageal stethoscope. A capnometric decrease of end-tidal carbon dioxide suggests ventilation/perfusion mismatching resulting from obstruction of the pulmonary arteries.7 Precordial Doppler ultrasonography is a sensitive and practical monitor to detect intracardiac air,1,8 but an even more sensitive and specific monitor in procedures with a high risk for gas embolism is transesophageal echocardiography (TEE). TEE is the current gold standard for detecting intracardiac gas; however, this technique requires significant training in application and interpretation to be effective.1,9
Treatment
When a diagnosis of venous gas embolism is considered (Table 63-2), further entry of gas into the venous circulation must be avoided. Catecholamine therapy and cardiopulmonary resuscitation should be initiated for cardiovascular collapse. Adequate oxygenation is often only possible with a significant increase in the oxygen concentration of the inspired gas (i.e., 100% oxygen); 100% oxygen also reduces the size of the gas embolism by increasing the gradient for nitrogen egress from the bubble.10 Rapid-volume resuscitation is recommended to elevate venous pressure, thus decreasing the continued entry of gas into the venous circulation. Some authors recommend attempting to evacuate air from the right ventricle by a central venous catheter (multi-orifice catheters may be more effective than a single lumen) or a pulmonary arterial catheter.11 A left-lateral decubitus position had been recommended in the past but has largely been abandoned because recent hemodynamic studies showed no benefit. Hyperbaric oxygen therapy is not a first-line treatment but may be a useful adjunct in severe cases and should certainly be considered if there are neurologic findings. If central nervous system symptoms are present, a paradoxical embolism should be presumed.
| Venous Gas Embolism | Arterial Gas Embolism | |
|---|---|---|
| Prevent further gas entry | Increase venous pressure (e.g., Valsalva, IV fluids) Identify and disable entryway for gas |
Identify and disable the entryway for gas |
| Definitive therapy | Supportive | Hyperbaric oxygen therapy as soon as the patient is stable for transfer to a hyperbaric oxygen facility |
| Supportive therapy | Oxygen, intravascular volume expansion, catecholamines | Oxygen, intravascular volume expansion, catecholamines |
| Positioning | Supine | Supine |
| Evacuation of embolized gas | Aspiration of multilumen central venous catheter; patient in left lateral decubitus position | Hyperbaric oxygen |
| Adjunctive therapy | Hyperbaric oxygen | Lidocaine, antiepileptics |
Paradoxical Embolism
A paradoxical embolism arises when air/gas entrained in the venous circulation enters the systemic arterial circulation, causing symptoms of end-artery obstruction. There are a number of mechanisms by which this can occur, such as the passage of gas across a patent foramen ovale to the systemic circulation. A patent foramen ovale is detectable in about 30% of the population and makes right-to-left shunting of gas bubbles possible.12 Elevated pulmonary arterial pressure due to a venous gas embolism may be reflected in elevated right atrial pressures predisposing to bubble transport across a patent foramen ovale. In addition, the decrease in left atrial pressure caused by mechanical ventilation and use of positive end-expiratory pressure may create a pressure gradient across the patent foramen ovale favoring passage of gas into the systemic circulation.1
Venous gas may enter the arterial circulation by overwhelming the filtering capacity of the lungs that normally prevents arterial gas emboli. Clinical cases are documented in which a fatal cerebral arterial gas embolism developed as the result of a large venous gas embolism, but no intracardiac defects or shunt mechanisms could be demonstrated.13 The filtration threshold of the pulmonary circulation for gas emboli can be affected by various anesthetic agents. In particular, in experimental studies, volatile anesthetics have been shown to reduce the threshold for spillover of venous bubbles into systemic arteries.14
Arterial Gas Embolism
Arterial gas embolism occurs though the entry of gas into the pulmonary veins or directly into the arteries of the systemic circulation. Mechanisms include overexpansion of the lung through decompression barotrauma in diving, pulmonary barotrauma from positive-pressure ventilation in critical care patients, and paradoxical embolism. Additionally, cardiac surgical procedures with extracorporeal bypass are a potential mechanism for these events.1 The entry of even small amounts of gas into the arterial system leads to a flow of gas bubbles into functional end arteries and occlusion of these vessels. Although possible in all arteries, the embolic obstruction of the coronary arteries or the nutritive arteries of the brain, termed cerebral arterial gas embolism, is especially critical and can be fatal owing to the vulnerability of these organs to short periods of hypoxia.
Pathophysiology
Entry of gas into the aorta causes distribution of gas bubbles into nearly all organs. Small emboli in the vessels of the skeletal muscles or viscera are well tolerated, although organ dysfunction such as rhabdomyolysis and/or renal insufficiency may occur.15 Embolization to the cerebral or coronary circulation may result in severe morbidity or death. Embolization into the coronary arteries can induce electrocardiographic changes typical of ischemia and infarction, with arrhythmias, myocardial depression, cardiac failure, and cardiac arrest. Circulatory responses may also be seen with embolization to the cerebral vessels.16 Cerebral arterial gas embolization typically involves migration of gas to small arteries of the brain. The emboli generate pathology by two broad mechanisms: reduced perfusion distal to the obstruction and an inflammatory response to the bubble.1
Diagnosis
Differentiating a cerebral arterial gas embolism from cerebral infarct or intracerebral hemorrhage can sometimes be made using computed tomography (CT). However, pathologic changes are sometimes very subtle and not well visualized on CT, and the diagnosis of cerebral arterial gas embolism must be entertained early. Magnetic resonance imaging (MRI) can sometimes show local increase of water density concentrated in the injured tissue. But this method is not completely reliable and may fail when only mild symptoms are present. Another nonspecific finding is hemoconcentration with increased hematocrit, possibly the consequence of extravascular shift of fluid into the injured tissues.17
Treatment
Protection and maintenance of vital functions is the primary goal. For somnolent or comatose patients, endotracheal intubation should be performed to maintain adequate oxygenation and ventilation. Additionally, oxygen should be administered in as high a concentration as possible, ideally 100%.1,18 This is important not only to treat hypoxia and hypoxemia but also to create a steeper diffusion gradient favoring egress of gas from the bubble. Current therapeutic recommendations include maintenance of a flat supine position for these patients, because neither a head-down nor an elevated head position provides any cardiovascular benefit and may aggravate the cerebral insult.
Definitive treatment of arterial gas embolism is with hyperbaric oxygen therapy (HBOT),19,20 with best results reported when HBOT is initiated as early as possible. HBOT involves placing the patient in an environment pressurized above sea level pressure while breathing 100% oxygen. This therapy causes a mechanical diminution of the gas bubble by both raising the ambient pressure and creating systemic hyperoxia. Hyperoxia produces a diffusion gradient for oxygen into the gas bubble, as well as for egress of nitrogen (or other gas) from the bubble. Hyperoxia also enables significantly larger quantities of oxygen to be dissolved in the plasma and increases the diffusion distance of oxygen in tissues. Improved oxygen-carrying capacity and delivery are important to offsetting the embolic insult to the microvasculature.
Hyperbaric oxygen has other postulated benefits after arterial air embolism. These include anti-edema effects and reducing blood vessel permeability while supporting the integrity of the blood-brain barrier.21 In addition, there are experimental studies indicating that hyperbaric oxygen diminishes the adherent properties of leukocytes to the damaged endothelium.22
Further Therapeutic Measures
As a consequence of a gas embolism, hemoconcentration may occur, resulting in increased blood viscosity and further impairing the already compromised microcirculation. One important maneuver to optimize the microcirculation is therefore to achieve euvolemia. In animal studies, moderate hemodilution to a hematocrit of 30% leads to a reduction of the neurologic damage.23 It is therefore acceptable to decrease the hematocrit within certain limits. Placement of a central venous catheter is strongly recommended to properly assess central venous pressure (CVP). CVP should be kept around 12 mm Hg. As a further monitor of normovolemia, urine output should be maintained and monitored by Foley catheter.
Anticoagulants may be useful in the treatment of arterial gas embolism, although no randomized studies in humans have been published. In an animal model of cerebral arterial gas embolism, the clinical course was less severe if the animals had been pretreated with heparin24; however, increased hemorrhage in infarcted areas of the spine and the brain may preclude the use of heparin. Low-dose or low-molecular-weight heparin may be given to patients when clinically indicated.
The use of corticosteroids has been controversial for arterial gas embolism. Because corticosteroids appear to be without benefit in cytotoxic edema and potentially may aggravate neuronal ischemic injury, they are not indicated in arterial gas embolism.25 Although still experimental and an off-label use, there are suggestions that lidocaine may be beneficial.26,27 In animals receiving prophylactic doses of lidocaine, the depressant effects of gas embolism on somatosensory evoked potentials and elevations in intracranial pressure could both be attenuated. In a clinical trial, cerebral protection during cardiac operations was demonstrated.27 Therefore, a strong argument can be made for the administration of lidocaine in therapeutic concentrations after severe arterial gas embolism.
Fat Embolism Syndrome
Fat embolism syndrome (FES) is a clinical entity first described over 150 years ago by Bergmann.28 It is very important to differentiate FES, a complex with potentially catastrophic cardiopulmonary and cerebral dysfunction, from fat embolization, a far more common and often subclinical entity.29
FES is most frequently seen after lower extremity and pelvic trauma, intramedullary nailing of long-bone fractures, hip arthroplasty, and knee arthroplasty.30 However, FES has also been described in association with a diverse group of other medical conditions, including sickle cell disease, acute pancreatitis, and diabetes mellitus, and with liposuction procedures, burns, decompression sickness, and total parenteral nutrition infusion.31–33 In a retrospective review of patients with fractures of the long bones from trauma, the incidence of FES was 0.9%.34
Intramedullary orthopedic surgery is the most common iatrogenic cause of FES. In hip and knee arthroplasties, manipulation of the femoral components can generate intramedullary pressures exceeding 800 mm Hg. Cementing the prosthesis can raise the intramedullary pressure even further.35 However, one study suggested there is no additional risk of FES associated with cementing the prosthesis.36
The diagnosis of FES remains one of exclusion. A number of authors have suggested clinical criteria for diagnosing FES; most notable are Gurd,37 Schonfeld,38 and Lindeque.39 All include acute respiratory collapse as a major criterion. Schonfeld and Gurd both highlight the presence of petechiae in their criteria for FES. Petechiae, as mentioned earlier, are not a consistent sign of FES and present relatively late in the process. Laboratory tests that may help in making the diagnosis of FES include arterial blood gases (hypoxia), electrocardiogram (right-sided heart strain), chest radiograph (diffuse bilateral infiltrates and opacities), MRI (for signs of cerebral FES), and CT.40 Bronchoalveolar lavage (BAL) may help confirm the diagnosis by demonstrating fat droplets in alveolar macrophages, although the sensitivity and specificity of this test are unclear.41,42 Intraoperative transesophageal echocardiography (TEE) will demonstrate multiple echogenicities in the right heart chambers in the presence of fat embolization. It may also show paradoxical echogenic particles in the left heart chambers, should a patent foramen ovale or other means for right-to-left intracardiac shunting be present.43 A pulmonary arterial catheter may show elevations in right-sided heart pressures.44
Treatment of FES remains supportive; no specific drug regimens are recommended. Therapy should include maintaining an adequate cardiac preload and cardiac output with the use of inotropic agents if necessary. Some authors have suggested that volume expansion with albumin may be beneficial owing to albumin binding oleic acid, thereby decreasing its “edemogenic potential.”45 The severe hypoxemia associated with FES must be aggressively treated, usually with 100% oxygen via an endotracheal tube. Even with ideal pulmonary care, lung function may further deteriorate, with a clinical picture resembling acute respiratory distress syndrome. Prophylactic corticosteroid therapy may minimize the incidence of FES,46 though this remains controversial. Other therapeutic regimens used after the development of FES, including heparinization, dextran, and parenteral ethanol, cannot be recommended.
Amniotic Fluid Embolism
Amniotic fluid embolism was first described by Meyer47 in 1926 and involves the introduction of amniotic fluid into the maternal circulation. In 1941, it was further characterized by two pathologists, Steiner and Lushbaugh, who reported the histologic findings in 42 women who died during the third trimester of pregnancy.48 Nine of the women were found to have squamous cells and eosinophilic material possibly of fetal origin in their lungs. The pathologists suggested that this was a syndrome associated with tumultuous labor in multiparous older women. This description became the basis for the “classic” amniotic fluid embolism (AFE).
Estimates for the incidence of amniotic fluid embolism vary from 1 in 8000 to 1 in 80,000 pregnancies. It is currently the most common cause of peripartum deaths.49 Clark and colleagues, reviewing the national registry of AFE, suggested the descriptive terminology “syndrome of acute peripartum cardiovascular collapse and coagulopathy” to describe AFE. They determined, in contrast to previously accepted notions, that no demographic variables, including maternal age, parity, race, or route of delivery of the infant, predicted elevated risk of AFE.49 Fetal elements were present in the pulmonary vasculature of 73% of the patients with AFE. Interestingly, the syndrome was not associated more frequently with vasopressin-induced labor, nor was cesarean section an apparent risk factor. The authors did note a strong temporal association to placement of intrauterine monitoring devices or artificial rupture of membranes and presentation of AFE symptoms. A significant association was made between AFE and male sex of the fetus.
Amniotic fluid embolism may present initially as seizures or seizure-like states or with cardiopulmonary symptoms including acute dyspnea, hypotension, pulmonary edema, or cardiac arrest.50 Cardiac events are relatively evenly distributed between pulseless electrical activity, severe bradycardias, ventricular tachycardias, and asystole.
Patients with AFE who survive the initial insult usually proceed to a consumption coagulopathy. This is associated with fibrinogen depletion, increased fibrin split products, elevation of prothrombin and activated partial thromboplastin times, as well as decreased platelet levels.51
Unlike other embolic diseases discussed in this chapter, exposure to fetal products usually does not generate the AFE syndrome. In fact, it has been demonstrated that amniotic fluid infusion into the maternal circulation is generally innocuous.52 This is fortunate because the outcome, over 50 years since the syndrome was described, remains dismal. Fewer than 15% of women who are stricken with AFE survive neurologically intact.53
Clark and colleagues49 have suggested that AFE may share similar mechanisms to septic shock and other anaphylactoid responses. The premise is that fetal components in the amniotic fluid initiate a complex inflammatory cascade with resultant cardiopulmonary collapse. The coagulopathy may be due to the activation of clotting cascades by amniotic fluid containing platelet factor III, factor X-like properties, as well as functionally active tissue factor.53,54 Tissue factor when combined with maternal factor VII will activate the extrinsic coagulation pathway.53
The diagnosis of AFE is primarily one of exclusion. It should be entertained in any pregnant woman who experiences acute cardiovascular collapse or coagulopathy. It has been described in women undergoing first-trimester therapeutic abortions as well as during the peripartum period. There is no definitive diagnostic test for AFE. Demonstrating fetal matter in the pulmonary vasculature on autopsy supports the diagnosis but is nonspecific.55 Aspirating from a wedged pulmonary artery catheter or sampling mixed venous blood for fetal elements may also help support the diagnosis,56 although in one study only 50% of patients being resuscitated for presumed AFE had fetal elements aspirated by a wedged pulmonary artery catheter.
Treatment of AFE is largely supportive. Initial cardiopulmonary resuscitation should be performed, with left lateral displacement to maintain uterine perfusion and venous return. Management should be directed toward maintaining oxygenation, usually with 100% oxygen through an endotracheal tube. Additional cardiovascular support should be initiated rapidly with volume and pressors if necessary. If the fetus has not yet been delivered, this should be accomplished by emergent cesarean section.57 An arterial line and pulmonary catheter may help guide therapy.55 Epinephrine may be a first-line agent of choice, as it is in other anaphylactoid reactions. Corticosteroids may be helpful, but therapeutic heparinization to minimize consumption coagulopathy remains controversial.55
It is vital to aggressively follow the coagulation profile and treat the disseminated intravascular coagulation (DIC) that frequently ensues once the initial cardiovascular collapse has been managed. The mortality from DIC may be as great as 75% in spite of optimal therapy.53 Treatment is usually with blood components, including red blood cells followed by platelets, fresh frozen plasma, and cryoprecipitate.58 Use of recombinant factor VIIa59 and aprotinin60 have been reported in the literature, but studies are lacking. Recently, aprotinin has been withdrawn from the market based on increased adverse events compared to other antifibrinolytics.
Key Points
Conde-Agudelo A, Romero R. Amniotic fluid embolism: an evidence-based review. Am J Obstet Gynecol. 2009;201(5):445.e1-445.e13.
Georgopoulos D, Bouros D. Fat embolism syndrome: clinical examination is still the preferable diagnostic method (editorial). Chest. 2003;123(4):982-983.
Kim YH, Oh SW, Kim JS. Prevalence of fat embolism following bilateral simultaneous and unilateral total hip arthroplasty performed with or without cement. J Bone Joint Surg Am. 2002;84-A(8):1372-1379.
Muth CM, Shank ES. Gas embolism. N Engl J Med. 2000;342(7):476-482.
1 Muth CM, Shank ES. Gas embolism. N Engl J Med. 2000;342(7):476-482.
2 Melamed Y, Shupak A, Bitterman H. Medical problems associated with underwater diving. N Engl J Med. 1992;326:30-34.
3 Palmon SC, Moore LE, Lundberg J, Toung T. Venous air embolism: A review. J Clin Anesth. 1997;9:251-257.
4 Porter JM, Pidgeon C, Cunningham AJ. The sitting position in neurosurgery: A critical appraisal. Br J Anaesth. 1999;82:117-128.
5 Weissman A, Kol S, Peretz BA. Gas embolism in obstetrics and gynecology: A review. J Reprod Med. 1996;41:103-111.
6 Durant TM, Long J, Oppenheimer MJ. Pulmonary (venous) air embolism. Am Heart J. 1947;33:269-281.
7 Shapiro HM, Drummond JC. Neurosurgical anesthesia and intracranial hypertension. In: Miller RD, editor. Anesthesia. 3rd ed. New York: Churchill Livingstone; 1990:1746-1747.
8 Gildenberg PL, O’Brien RP, Britt WJ, Frost EA. The efficacy of Doppler monitoring for the detection of venous air embolism. J Neurosurg. 1981;54:75-78.
9 Mammoto T, Hayashi Y, Ohnishi Y, Kuro M. Incidence of venous and paradoxical air embolism in neurosurgical patients in the sitting position: Detection by transesophageal echocardiography. Acta Anaesth Scand. 1998;42:643-647.
10 Van Liew HD, Conkin J, Burkard ME. The oxygen window and decompression bubbles: Estimates and significance. Aviat Space Environ Med. 1993;64:859-865.
11 De Angelis, J. A simple and rapid method for evacuation of embolized air. Anesthesiology. 1975;43:110-111.
12 Gronert GA, Messick JM, Cucchiara RF, Michenfelder JD. Paradoxical air embolism from a patent foramen ovale. Anesthesiology. 1979;50:548-549.
13 Tommasino C, Rizzardi D, Beretta L, et al. Cerebral ischemia after venous air embolism in the absence of intracardial defects. J Neurosurg Anesthesiol. 1996;8:30-34.
14 Katz J, Leiman BC, Butler BD. Effects of inhalation anesthetics on filtration of venous gas emboli by the pulmonary vasculature. Br J Anaesth. 1988;61:200-205.
15 Shank ES, Muth CM. Case report on a diver with decompression injury, elevation of serum transaminases, and rhabdomyolysis. Ann Emerg Med. 2001;37:533-536.
16 Evans DE, Kobrine A, Weathersby PK, Bradley ME. Cardiovascular effects of cerebral air embolism. Stroke. 1981;122:338-344.
17 Smith RM, Van Hoesen KB, Neuman TS. Arterial gas embolism and hemoconcentration. J Emerg Med. 1994;12:147-153.
18 Annane D, Trouché G, Delisle F, et al. Effects of mechanical ventilation with normobaric oxygen therapy on the rate of air removal from cerebral arteries. Crit Care Med. 1994;22:851-857.
19 Shank ES, Muth CM. Decompression illness, iatrogenic gas embolism, and carbon monoxide poisoning: The role of hyperbaric oxygen therapy. Int Anesth Clin. 2000;38:111-138.
20 Tetzlaff K, Shank ES, Muth CM. Evaluation and management of decompression illness–an intensivist’s perspective. Intensive Care Med. 2003;29(12):2128-2136.
21 Mink RB, Dutka AJ. Hyperbaric oxygen after global cerebral ischemia in rabbits reduces brain vascular permeability and blood flow. Stroke. 1995;26:2307-2312.
22 Thom SR, Mendiguren I, Hardy K. Inhibition of human neutrophil beta2-integrin-dependent adherence by hyperbaric O2. Am J Physiol. 1997;273:C770-C777.
23 Reasoner DK, Ryu KH, Hindman BJ, et al. Marked hemodilution increases neurologic injury after focal cerebral ischemia in rabbits. Anesth Analg. 1996;82:61-67.
24 Ryu KH, Hindman BJ, Reasoner DK, Dexter F. Heparin reduces neurological impairment after cerebral arterial embolism in the rabbit. Stroke. 1996;27:303-330.
25 Sapolsky RM, Pulsinelly WA. Glucocorticoids potentiate ischemic injury to neurons: Therapeutic implications. Science. 1985;229:1397-1400.
26 McDermott JJ, Dutka AJ, Evans DE, Flynn ET. Treatment of cerebral air embolism with lidocaine and hyperbaric oxygen. Undersea Biomed Res. 1990;17:525-534.
27 Mitchell SJ, Pellett O, Gorman DF. Cerebral protection by lidocaine during cardiac operations. Ann Thorac Surg. 1999;67:1117-1124.
28 Bergmann E. Ein Fall todtlicher Fettembolie. Berl Med Wochenschr. 1873;10:385-387.
29 Federico A. Fat embolism versus fat embolization following total hip arthroplasty (letter). J Bone Joint Surg Am. 2003;85:569.
30 Johnson MJ, Lucas GL. Fat embolism syndrome. Orthopedics. 1996;19:41-50.
31 Levy DL. The fat embolism syndrome: A review. Clin Orthop. 1990;261:281-286.
32 Jenkins K, Chung F, Wennberg R, et al. Fat embolism syndrome and elective knee arthroplasty. Can J Anesth. 2002;49:19-24.
33 Platt MS, Kohler LJ, Ruiz R, et al. Deaths associated with liposuction: Case reports and review of the literature. J Forensic Sci. 2002;47:205-207.
34 Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome: A 10-year review. Arch Surg. 1997;132:435-439.
35 Koessler MJ, Pitto RP. Fat and bone marrow embolism in total hip arthroplasty. Acta Orthop Belg. 2001;67:97-109.
36 Kim YH, Oh SW, Kim JS. Prevalence of fat embolism following bilateral simultaneous and unilateral total hip arthroplasty performed with or without cement. J Bone Joint Surg Am. 2002;8:1372-1379.
37 Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br. 1974;56:408-416.
38 Schonfeld SA, Ploysongsang Y, DiLisio R, et al. Fat embolism prophylaxis with corticosteroids: A prospective study in high risk patients. Ann Intern Med. 1983;99:438-443.
39 Lindeque BGP, Schoeman HS, Dommisse GF, et al. Fat embolism and the fat embolism syndrome: A double blind therapeutic study. J Bone Joint Surg Br. 1987;69:128-131.
40 Malagari K, Economopoulos N, Stoupis C, et al. High resolution CT findings in mild pulmonary fat embolism. Chest. 2003;123:1196-1201.
41 Mimoz O, Edouard A, Beydon L. Contribution of bronchoalveolar lavage to the diagnosis of posttraumatic pulmonary fat embolism. Intensive Care Med. 1995;21:973-980.
42 Georgopoulos D, Bouros D. Fat embolism syndrome: Clinical examination is still the preferable diagnostic method (editorial). Chest. 2003;123:982-983.
43 Pell A, Hughes D, Keating J, et al. Fulminating fat embolism syndrome caused by paradoxical embolism through a patent foramen ovale. N Engl J Med. 1993;329:926-929.
44 Ereth MH, Weber JG, Abel MD, et al. Cemented versus non-cemented total hip arthroplasty—embolism, hemodynamics, and intrapulmonary shunting. Mayo Clin Proc. 1992;67:1066-1074.
45 Habashi NM, Andrews PL, Scalea TM. Therapeutic aspects of fat embolism syndrome. Injury. 2006 Oct;37(Suppl 4)):S68-S73.
46 Bederman SS, McKee MD, Schemitsch EH, Bhandari M. Do corticosteroids reduce the risk of fat embolism syndrome in poly-trauma patients? A meta-analysis. J Bone Joint Surg Br. 2009;91-B:254-a.
47 Meyer JR. Embolis pulmonary—casepsa. Brazil Med. 1926;2:301-303.
48 Steiner PE, Lushbaugh CC. Maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics. JAMA. 1941;117:1245-1254. 1341-1345
49 Clark SL, Hankins GD, Dudley DA, et al. Amniotic fluid embolism: Analysis of the national registry. Am J Obstet Gynecol. 1995;172:1158-1169.
50 Conde-Agudelo A, Romero R. Amniotic fluid embolism: an evidence-based review. Am J Obstet Gynecol. 2009;201:445.e1-445.e13.
51 Annecke T, Geisenberger T, Kurzl R, Penning R, Heindl B. Algorithm-based coagulation management of catastrophic amniotic fluid embolism. Blood Coagul Fibrinolysis. 2010;21:95-100.
52 Clark SL. New concept of amniotic fluid embolism: A review. Obstet Gynecol Surv. 1990;45:360-368.
53 Gist RS, Stafford IP, Leibowitz AB, Bellin Y. Amniotic fluid embolism. Anesth Analg. 2009 May;108(5):1599-1602.
54 Green BT, Umana E. Amniotic fluid embolism. South Med J. 2000;93:721-723.
55 Gei AF, Vadhera RB, Hankins GD. Embolism during pregnancy: Thrombus, air, and amniotic fluid. Anesth Clin North Am. 2003;21:165-182.
56 Fletcher SJ, Parr MJ. Amniotic fluid embolism: A case report and review. Resuscitation. 2000;43:141-146.
57 Davies MG, Harrison JC. Amniotic fluid embolism: Maternal mortality revisited. Br J Hosp Med. 1992;47:775-776.
58 Rodgers GP, Heymach GJIII. Cryoprecipitate therapy in amniotic fluid embolization. Am J Med. 1984;76:916-920.
59 Prosper SC, Goudge CS, Lupo VR. Recombinant factor VIIa to successfully manage disseminated intravascular coagulation from amniotic fluid embolism. Obstet Gynecol. 2007 Feb;109(2 Pt2):524-525.
60 Stroup J, Haraway D, Beal JM. Aprotinin in the management of coagulopathy associated with amniotic fluid embolism. Pharmacotherapy. 2006;26:689-693.
