Acute lung injury following the use of granulocyte-macrophage colony-stimulating factor
A 77-year-old Black female with a past medical history significant for hypertension, peripheral vascular disease, hypercholesterolemia, chronic obstructive pulmonary disease (COPD) without recent exacerbation and gastroesophageal reflux disease. Her history is negative for coronary disease, stroke or diabetes. She presented with an acute osteomyelitis of the left foot, which required debridement of the 2nd and 3rd metatarsal bones. The social history revealed a former smoker, with a 70-pack-year smoking history who quit 1 year ago and denied alcohol use. Her surgical history was significant for a left femoral-popliteal bypass followed by a transmetatarsal amputation for gangrenous toes.\nPre-operative evaluation showed a chest X-ray significant for cardiomegaly []. A transthoracic echocardiogram revealed an ejection fraction of 55%, with moderate concentric left ventricular hypertrophy, Grade I diastolic dysfunction, trace mitral regurgitation, trace tricuspid regurgitation and no evidence of aortic regurgitation. Laboratory data showed a white blood cell count of 12.1 × 103/μL and a normal albumin of 3.6 g/dL.\nShe underwent a 17 min operative procedure under local anesthesia with midazolam and ketamine for sedation. This consisted of a debridement of the osteomyelitis of the left foot at the previous amputation site without any blood loss. At the conclusion of the debridement, 500 μg recombinant GM-CSF (sargramostim [Leukine, Genzyme]), which was injected locally into the operative site to stimulate wound healing (off label use). Intraoperatively, the patient was hemodynamically stable without hypotension and received minimal intravenous fluid.\nAfter a brief period in the post-anesthesia care unit, where the patient was asymptomatic and hemodynamically stable with oxygen saturation of 95% by pulse oximetry via 3 L nasal cannula, patient was transferred to floor care. Twenty-two hours post-operatively, she developed acute onset of severe dyspnea with respiratory distress manifested by hypertension (blood pressure 180/95 mmHg), tachycardia (heart rate of 122), diaphoresis and tachypnea (respiratory rate of 26). Auscultation revealed diffuse rales without inspiratory or expiratory wheeze or stridor. Cardiovascular examination was negative for jugular venous distension and the absence of an S3 gallop. Oxygen saturation was 90% on a 50% FiO2 via an oxygen venturi mask and an arterial blood gas performed revealed a pH 7.35, PaO2 76 mmHg and PCO2 56 mmHg and the PaO2/FIO2 ratio was 152 with a calculated A-a gradient of 217.5 mmHg (expected 18.7 mmHg adjusted for age). Repeat laboratory studies showed a leukocytosis, with the white blood cell count of 23.6. A chest X-ray revealed an interval development of bilateral fluffy infiltrates consistent with acute pulmonary edema []. A 12 lead electrocardiogram showed no evidence of ischemia and serial cardiac biomarkers were negative. A repeat echo showed no changes from the prior study, with a preserved ejection fraction of 55%. Patient was placed on non-invasive ventilation (bilevel positive airway pressure [BIPAP] mode, inspiratory positive airway pressure = 12 cm H2O, expiratory positive airway pressure = 5 cm H2O, FiO2= 50%), given furosemide 40 mg intravenously and promptly transferred to the surgical intensive care unit.\nThe following day, despite negative fluid balance and BIPAP ventilation, the PaO2/FIO2 ratio remained low at 132, without any evidence of radiographic improvement. Given the absence of fluid overload, a lack of response to diuresis, no cardiogenic dysfunction and no apparent clinical exacerbation of COPD and given the temporal sequence of the event after the GM-CSF injection, a presumptive diagnosis of ALI was suspected and high dose methylprednisolone 500 mg once daily for 5 days was initiated. Over the next 5 days, the patient's symptoms improved and she was gradually weaned off BIPAP to nasal cannula, with daily chest X-rays confirming radiographic clearing of the ALI with resolution of the bilateral pulmonary infiltrates [].