Fat embolism syndrome (FES) is a life-threatening condition in which multiorgan dysfunction manifests 48–72 hours after long bone or pelvis fractures. Right ventricular (RV) failure, especially in the setting of pulmonary hypertension, is a frequent feature of FES. We report our experience treating 2 young, previously healthy trauma patients who developed severe hypoxemia in the setting of FES. Neither patient had evidence of RV dysfunction on echocardiogram. The patients were treated with inhaled nitric oxide (NO), and their oxygenation significantly improved over the subsequent few days. Neither patient developed any cardiovascular compromise. Patients with FES that have severe hypoxemia and evidence of adult respiratory distress syndrome (ARDS) are likely at risk for developing RV failure. We recommend that these patients with FES and severe refractory hypoxemia should be treated with inhaled NO therapy prior to the onset of RV dysfunction.
Fat embolism syndrome (FES) is an acute, life-threatening condition characterized by a constellation of symptoms including petechial rash, neurologic dysfunction, thrombocytopenia and anemia, and pulmonary changes [
Patients with FES can rapidly deteriorate within a few hours after the onset of symptoms. Patients may develop acute pulmonary hypertension and subsequent acute right heart failure, cardiovascular collapse, or even death [
Here, we describe therapeutic management of refractory hypoxemia due to FES after trauma.
A 20-year-old previously healthy man was admitted to our general intensive care unit (ICU) with multiple traumatic injuries after a motor vehicle collision. On admission day, physical examination revealed a right open femur fracture and multiple facial bone fractures (zygoma, maxilla, and nasal bones). The patient was awake and oriented and hemodynamically stable and was oxygenating well on 5 L/min nasal cannula. The patient was transported to the operating room, where he underwent an external fixation of the right femur.
After the procedure, the patient was transported back to the ICU, intubated, and sedated. The following day, he subsequently became severely hypoxic (PO2/FiO2 ratio decreasing from 173 to 109, Figure
Two days after admission to the ICU, the patient remained intubated and was ventilated by pressure control mechanical ventilation mode (PC-CMV). The patient was hypoxic (O2 sat <90%) despite sedation with an infusion of fentanyl and midazolam and the following ventilator parameter settings: peak inspiratory pressure (PIP) of 40 cm H2O, FiO2 of 1.0, PO2/FiO2 ratios of 100–110, positive end-expiratory pressure (PEEP) of 12 cm H2O, respiratory rate (RR) of 16 breaths/min, I : E ratio of 1 : 1, and tidal volume (TV) of 6 mL/kg (weight of 90 kg). Inhaled NO therapy was immediately initiated to prevent further cardiovascular deterioration and worsening hypoxemia. The inhaled NO was started at a dose of 20 ppm and titrated up to 46 ppm to maintain O2 sat >90% on FiO2 of 0.6. The NO therapy was continued for 4 days with a remarkable improvement in arterial blood oxygenation (PO2/FiO2 ratio >200) with the following ventilator parameter settings: PIP of 29 cm H2O, FiO2 of 0.5, and PEEP of 8 cm H2O. Inhaled NO was gradually weaned down and discontinued after two days.
Over the following two weeks since admission to the ICU, the patient’s clinical condition improved (Figure
Changes in PO2/FiO2 ratio during the first patient’s ICU stay. Inhaled NO therapy was initiated on the second day of the patient’s hospitalization (represented by the first black arrow) due to severe unresponsive persistent hypoxemia (PO2/FiO2-110). By the fourth day after hospitalization, the PaO2/FiO2 ratio was improving and inhaled NO therapy was discontinued (represented by the second black arrow).
A 21-year-old previously healthy man was admitted to our hospital with an actively bleeding shrapnel wound of the lower extremities, right open femur fracture, and closed left tibia and fibula fractures. After an emergent external fixation of the right femur, primary damage control, and fluid resuscitation, the patient was transported to our ICU intubated.
Two days after ICU admission, the patient developed severe hypoxemia (FiO2/PO2 ratio 123, FiO2 0.7), thrombocytopenia (platelets 50,000
The patient remained intubated and sedated with an infusion of fentanyl and midazolam and was ventilated by PC-CMV with the following ventilator parameter settings: PIP of 42 cm H2O, FiO2 of 1.0, PEEP of 15 cm H2O, I : E ratio of 2 : 1, TV of 6 mL/kg (weight of 80 kg), and RR of 18 breaths/min. The patient developed persistent hypoxemia (O2 sat <90%), PO2/FiO2 ratio = 120 despite a FiO2 of 1.0, and inhaled NO therapy was immediately initiated. Inhaled NO was started at a dose of 20 ppm and titrated to 28–30 ppm to maintain O2 sat >90% on FiO2 of 0.6. Over the subsequent 72 hours, the patient’s oxygenation and respiratory functions remarkably improved (PO2/FiO2 ratio of 232, Figure
Over the next few weeks, the patient had a complete resolution of his hematologic abnormalities, and he was extubated. On discharge, the patient was following commands and opened his eyes spontaneously, but he had residual speech deficits (GCS of 11).
Changes in PO2/FiO2 ratio during the second patient’s ICU stay. Inhaled NO therapy was initiated on the third day of the patient’s hospitalization (represented by the first black arrow) due to severe unresponsive persistent hypoxemia (PO2/FiO2-120). By the sixth day after hospitalization, the PaO2/FiO2 ratio was improving and inhaled NO therapy was discontinued (represented by the second black arrow).
Acute FES was first described in 1862 by Zenker and systematically defined in 1974 by Guard and Wilson [
The risk factors for developing fatal RV dysfunction are poorly understood. Severe adult respiratory distress syndrome (ARDS) or mechanical obstruction to pulmonary artery flow by massive fat embolism (FES) may induce significant pulmonary hypertension and subsequent RV failure [
In both of our cases, FES was diagnosed after a traumatic injury and subsequent early external fixation of a femur fracture. The patients developed ARDS with severe hypoxemia, bilateral diffuse pulmonary infiltrates on CXR, and preserved RV and LV functions. Due to the patients’ life-threatening and refractory hypoxia, our primary therapeutic plan was initially aimed at managing the severe respiratory compromise. We suspected that, even in the presence of normal RV function on echocardiogram 72 hours after ICU admission, our patients were likely at risk for developing sudden RV failure due to persistent hypoxemia. In these patients, inhaled NO was used as a rescue therapy in the setting of severe pulmonary compromise and the suspected high risk of developing cardiovascular dysfunction.
Inhaled NO, a potent endogenous vasodilator, has resulted in clinical improvement of oxygenation in severe refractory hypoxemia in patients with ARDS [
In contrast to prior reports, in which NO therapy was initiated after the presence of RV failure, we initiated therapy before the onset of significant cardiovascular compromise. Our patients were likely at high risk for RV dysfunction due to acute ARDS and severe hypoxemia. After initiation of inhaled NO, neither patient developed cardiovascular dysfunction, and the patients’ respiratory condition greatly improved. Furthermore, quicker respiratory improvement due to inhaled NO therapy allowed rapid neurological recovery, which were confirmed by brain MRI scans in both patients.
NO is a safe therapy with a low risk of adverse side effects, including methemoglobinemia and withdrawal symptoms after discontinuation. We recommend that, in patients with FES and severe refractory hypoxemia, inhaled NO therapy could be safely used. Future studies should aim to identify the treatment and preventive effects of inhaled NO therapy in patients with FES who developed pulmonary hypertension and right heart failure.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Evgeni Brotfain and Leonid Koyfman contributed equally to the paper.