Pulmonary embolism in a newborn Daniela Dinu 1, Martha Douglas-Escobar 1, Henri Justino 2 Sections of Neonatology 1 and Cardiology 2, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital Houston, TX
Background Pulmonary embolism Rare and often overlooked condition in children. 0.86 / 10000 pediatric hospital admissions are complicated by pulmonary embolism with a high mortality (30%). True incidence in newborns is unknown, and likely underestimated because: symptoms are subtle or masked by a primary respiratory disorder there is a low index of suspicion Even with increasing awareness pulmonary embolism remains a diagnostic challenge due to: non-specific symptoms wide range of risk factors lack of an algorithm to rule out or confirm it limitations resulting from the fact that most data about diagnostic methods were evaluated based on adults
Case presentation – History 1 month old boy presented to the ED with a history of vomiting and diarrhea for 3 days. 10 days prior to this admission, the infant: had similar complaints was admitted to another hospital for 3 days was discharged with presumptive diagnosis of rotavirus gastroenteritis Birth history: full term baby, born via spontaneous vaginal delivery, no perinatal complications. Clinical course – Emergency Department severely dehydrated, capillary refill 4 sec, unobtainable BP received 3 boluses of normal saline (60 ml/kg) underwent a full sepsis work-up and was started on IV antibiotics CXR unremarkable initial blood gas showed severe metabolic acidosis 6.9/26/35/6/-24 lactate = 1.7, ammonia = 58, glucose = 165
Clinical course – NICU admission After initial resuscitation in the emergency room: vital signs were stable (T = 97.9, HR = 145, RR = 42, BP = 90/60, O 2 Sat = 97% on room air) continued on IV fluids and antibiotics received bicarbonate bolus for metabolic acidosis repeat blood gas after volume resuscitation showed unchanged metabolic acidosis: 6.94/31/24/7/-25 platelet count on admission: 289000 6 hours after NICU admission he suddenly decompensated: O 2 saturations 40-50% despite 100 FiO 2 very poor perfusion agonal breathing Emergently intubated, first ABG post-intubation: pH < 6.8, bicarbonate and base excess not calculated (too low). After stabilization PICC line placed for vascular access.
Clinical course – day 1 Metabolic acidosis persisted despite multiple bicarbonate boluses (pH: < 6.8 – 7.14, BE: -25 – -7). Developed lactic acidosis, genetic consult was done, but a metabolic disease seemed unlikely; plasma aminoacids and urine organic acids were sent. Echocardiogram showed: significant elevated RV pressures (leftward bowing of the ventricular septum and right to left shunting through PFO) depressed RV systolic function concern for “moderate hypoplasia of the proximal right pulmonary artery” and “significant distal hypoplasia of the right pulmonary artery”. iNO was started to control the pulmonary hypertension. He developed hypotension and dopamine was started. Started developing thrombocytopenia (platelet count = 79000 – 94000).
Clinical course – day 2 Remained on mechanical ventilation. Metabolic acidosis was better controlled on bicarbonate drip (bicarbonate range: 21 – 29, base excess range: -9 – -2). Continued to have hypotension on pressor support (dopamine) and Milrinone was added for inotropic support. Developed multiorgan failure with: oliguric renal failure (creatinine = 1.4) increased liver enzymes (ALT = 1316, AST = 6575, albumin < 1.5) coagulopathy (PT/PTT/INR = 31.8/44.9/2.9) Thrombocytopenia persisted (platelet count = 62000 – 72000).
Clinical course – day 3 Repeated echocardiogram (due to lack of response to iNO) showed: large echogenic mass in the right pulmonary artery, nearly occluding the lumen moderately depressed RV systolic function abnormal spectral Doppler in the proximal left pulmonary artery with continuous diastolic flow and low systolic peak velocity Platelets = 53000, PT/PTT/INR = 19.8/32.6/1.6, fibrinogen = 95, D-Dimer > 20, protein C = 19, protein S = 22, AT III = 40. Due to significant degree of renal impairment (creatinine clearance = 13), a CT with contrast was contraindicated, therefore he underwent cardiac catheterization.
Cardiac catheterization: absent flow to the right lung and left lower lobe
Clinical course In the cardiac catheterization lab he underwent attempted thrombectomy, but not much clot was retrieved, and he became unstable with catheters placed into the pulmonary arteries; angiography showed he had significant proximal and distal clot burden in the RPA, and LLPA. TPA was started: initially infused at 0.1 mg/kg/h IV for 12 hours via PICC line TPA then infused at 0.05 mg/kg/h IV via a 3 Fr catheter placed in MPA for 24 hours returned to catheterization laboratory twice during TPA infusion for repeat angiography and clot maceration by balloon angioplasty He was started on heparin drip which was continued for 20 days CT angiogram showed partial resolution of the clot switched to Lovenox SQ.
Summary of hospital course Respiratory Required mechanical ventilation for 14 days. Developed bilateral pleural effusions that required drainage, complicated by bilateral pneumopericardium and pneumothorax. Post-extubation received supplemental oxygen via nasal cannula for another 8 days, then weaned to room air. Cardiovascular From day 1 of admission required vasopressor support (dopamine, epinephrine), gradually weaned after thrombectomy. Required inotropic support with Milrinone for 14 days. Pulmonary hypertension gradually improved after thrombolysis.
Summary of hospital course Infectious disease Blood, urine, stool, CSF, viral cultures, and HSV PCR were negative. Received 72h of Vancomycin and 10 days of Cefotaxime IV. Hematological The etiology of the hypercoagulability remained unknown, initially thought to be infectious, and possibly due to dehydration. Protein C and S, lipoprotein A, homocysteine, anticardiolipin panel were normal. Prothrombin mutation and Factor V Leiden mutation analyses negative. Received TPA IV and through catheter, then heparin IV followed by SQ Lovenox. Discharged home on Lovenox, will have repeat testing for protein C and S at 3 months of age.
Summary of hospital course Genetics Plasma amino acids and urine organic acids were sent initially due to severe metabolic acidosis unresponsive to bicarbonate infusion and lactic acidosis (lactate level = 7). Although initial testing was abnormal, repeat testing showed normal results, and newborn screening was normal. Renal Had oliguric renal failure shortly after hospital admission (peak creatinine = 1.9), which improved. Required Lasix and peritoneal dialysis for a brief period for volume overload. Developed hypertension treated with Captopril, which was continued on discharge. Renal sonogram and Doppler were unremarkable.
Conclusions The diagnosis of pulmonary embolism was not considered initially, in a newborn with: severe dehydration (risk factor for thrombosis) and shock suspicious echocardiogram (pulmonary hypertension and right ventricular enlargement) evidence of ventilation/perfusion mismatch lack of response of pulmonary hypertension to iNO evidence of consumption coagulopathy age group that placed him at higher risk Timely diagnosis and intervention (thrombolytic and/or anticoagulant therapy, or catheter-based or surgical intervention) could change the outcome in a potentially lethal condition.
Conclusions To our knowledge this is the first case of pulmonary embolism in a newborn with no genetic predisposing factors for thrombosis, no proven infectious cause and no cardiac defect, managed successfully via catheter thrombolysis. Pulmonary embolism should be considered in the differential diagnosis in newborns that present with shock, severe metabolic acidosis with evidence of ventilation/perfusion mismatch, and pulmonary hypertension unresponsive to conventional therapy. remains one of the most commonly missed diagnosis with the highest rate of discrepancy between the clinical and post-mortem diagnosis. additional diagnostic testing should be performed if there is clinical suspicion of pulmonary embolism. CT angiogram is gold standard, with high sensitivity and specificity, but carries a high radiation dose in a group particularly susceptible to radiation. Catheterization also carries radiation risk, but allows for possible thrombectomy or thrombus maceration to assist with thrombolysis.
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