Pediatric Neurogenic Pulmonary Edema After Brain Tumor Removal Complicated with Severe Myocardial Injury: A Case Report

Introduction

Neurogenic pulmonary edema (NPE) is a rare complication associated with neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. In the previous case reports of pediatric NPE associated with febrile seizure, 2 children in 3 reported cases required mechanical ventilation for life-threatening respiratory distress. However, mechanical ventilation in both children was discontinued within 10 or 18 h after the onset of NPE, and they had no neurological deficiency [1,2]. In addition, NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation caused by neurological insults [2–4]. Here, we present a pediatric case of NPE after removal of a brain tumor complicated with severe myocardial injury diagnosed by abnormally elevated levels of cardiac troponin. In this case, although the LV contraction was globally reduced at the emergence of NPE, it was simultaneously improved with the termination of 4-day mechanical ventilation for NPE. However, the overloading stress to the LV wall was sustained, which was suggested by the long-term preservation of the elevated serum brain natriuretic peptide (BNP) level. We are unaware of the serial measurement of cardiac biomarkers in previous reports for an extended period exceeding the acute phase of NPE. Therefore, we have also described the serial variations in cardiac troponin and BNP levels following the development of NPE in our pediatric patient.

Case Report

A 6-year-old boy (height, 111 cm; body weight, 19.4 kg) had a headache and subsequently experienced disorientation. He had no remarkable medical history. Brain computed tomography (CT) showed a brain tumor in the cerebellar vermis complicated by hydrocephalus (Figure 1). He successfully underwent tumor removal surgery under general anesthesia, which lasted 10 h 12 min. The total fluid infusion volume was 1102 mL, and the blood loss volume was approximately 225 mL throughout the surgery. He was transferred while unconscious to the intensive care unit (ICU) and received mechanical ventilation. His hematocrit was 29.8% at that time, and his serum creatine level was 0.65 mg/dl. Thereafter, a combined solution of 10% glycerin, 5% fructose 50 ml, and dexamethasone 0.83 mg was intravenously administered for the prevention of cerebral edema. Twelve hours later, a postoperative brain CT showed improvement of hydrocephalus, and both the intraventricular drainage tube and subcutaneous tube were withdrawn. After confirming that he had almost alert consciousness with comfortable respiration, he was weaned from mechanical ventilation. He was discharged from the ICU to the pediatric unit because he experienced intense anxiety without his mother’s care.

At midnight on the same discharge day, he experienced a convulsion, which was managed with intravenous administration of midazolam 2 mg, and his upper airway was patent after resolution of the convulsion. Four hours later, his respiratory condition worsened with desaturation of less than 90% SpO2 under an oxygen face mask, and massive cerebrospinal fluid leakage from the wound was observed, which suggested a transiently increased intracranial pressure. Emergency chest and brain CT revealed wide-spread consolidation in the bilateral lung fields, indicating severe pulmonary edema (Figure 2) and slight worsening of hydrocephalus. Because his desatu-ration was not improved, we tried to support his respiration with a high-flow nasal cannula. However, approximately 9 h after the onset of his dyspnea, he was intubated after read-mission to the ICU, and massive serous secretions were aspirated from the tracheal tube. We did not observe any gastric content-like fluids in the aspirated secretions. Mechanical ventilation with a positive end-expiratory pressure of 8 cm H2O for treating NPE was immediately started. The PaO2/FiO2 (P/F) ratio at the inspired oxygen fraction 1.0 was 124. Simultaneously, transthoracic echocardiography (TTE) showed impaired global LV contraction, with an ejection fraction (EF) of 48.2% and dilated left ventricular and atrial cavities. He received inotropic support with dobutamine of 2 µg/kg/min and milrinone of 0.22 µg/kg/min, and intermittent administration of furosemide, of which the total dose per day was 15–20 mg. His daily urine volume was 709–2136 ml, and on the third day in the ICU, the daily difference between infused fluid volume and urine volume reached 608 ml/day. On the fourth day of ICU stay, his pulmonary congestion showed improvement on chest radiography, and the P/F ratio was 465. Mechanical ventilation was then discontinued, and his spontaneous breathing was stable. The next day, after confirming the improved contraction of LV by TTE, he was discharged to the pediatric unit. Histologically, the brain tumor was diagnosed as medulloblastoma, and he received chemotherapy combined with radiation therapy, without adverse events. Approximately 6 months later, he was discharged from our hospital.

Figure 3 shows the time course of serum levels of high-sensitivity cardiac troponin I (hs-cTn I) and BNP, which are cardiac biomarkers associated with myocardial injury, probably induced by the neurological insult following the brain tumor removal. Both hs-cTn I and BNP levels showed peak values on the first day of ICU stay and then gradually decreased. Although the LV contraction improved with an EF of 58%, and dobutamine infusion was terminated on the fifth day of ICU stay, the BNP level remained at around 500 pg/mL from the third day to the fifth day of ICU stay. However, the BNP level gradually decreased, and the milrinone infusion was discontinued on the fifth day after ICU discharge. On the same day, TTE showed an EF of 60%, with a respiratory variation of the diameter of the inferior vena cava. The administration of intravenous furosemide of a total daily dose of 24 mg continued until the eleventh day after ICU discharge, and daily urine volume was maintained at over 700 ml/day. Consequently, it took 16 days from the emergence of NPE to return to an approximate standard range (36.9 pg/mL).

Discussion

Neurological insults, such as traumatic brain injury and subarachnoid hemorrhage (SAH), cause central sympathetic over-activity, dramatically increasing pulmonary vascular pressure and accelerating fluid leakage in the alveolar capillaries, and this is considered the primary pathologic mechanism for NPE. The main cerebral regions contributing to these alternations are the hypothalamus and medulla oblongata, which are related to sympathetic activation [3].

In our patient, we believe that the prior convulsion at midnight on the same discharge day increased the intraventricular pressure, as evidenced by the finding of concurrent cerebrospinal fluid leakage, and probably altered the regulation of sympathetic activity in the hypothalamus or medulla oblongata. Consequently, the transient convulsion triggered the development of NPE in this case. In several previous pediatric cases [1,2,5], prolonged convulsions were reported to have induced NPE. However, the convulsion in our patient was quickly resolved with the intravenous administration of midazolam. As our patient had a brain tumor in the cerebellar vermis complicated by hydrocephalus close to the medulla oblongata, he might have been made vulnerable to NPE even by minor derangement such as a transient convulsion.

NPE frequently accompanies LV dysfunction, which a globally reduced EF denotes. During emerging NPE, our patient experienced an acute myocardial injury diagnosed by highly elevated hs-cTn I levels, which may also be induced by an over-sympathetic response to the myocardium derived from NPE pathology. We believe that an ischemic coronary event did not cause the myocardial injury in our patient because he was a previously healthy child and had no symptoms of coronary disease after the recovery of NPE. In adult patients with intracranial hemorrhage and SAH, the incidence of abnormal elevation of the cTn level has been reported to range from 20% to 40% [4,7–9]. A significantly increased hs-cTn level has been shown to positively affect cardiopulmonary complications and poor outcomes [7–9]. Stroke-induced heart injury is associated with systemic and local mechanisms in the myocardium, including inflammation and abnormal autonomic function [9].

They may not wholly differ between adults and children, and there may be several similar processes of inducing myocardial injury, even in children with neurological insults.

In our patient, the peak hs-cTn I level (1611.6 pg/mL) after the emergence of NPE indicated the severity of the myocardial injury, and it was approximately 42 times higher than the standard upper limit. As the myocardium was extremely injured, the BNP level greatly increased (2106 pg/mL) due to secretion from impaired myocardial cells under LV wall stress, representing the severity of LV dysfunction [10]. However, it took 16 days for the serum BNP level to decrease to under 50 pg/ml. Such a sustained high serum BNP level indicates the prolonged overloading stress to the LV wall, and he might have been at risk of heart failure. Therefore, we should carefully monitor serial changes in cardiac biomarkers when managing a pediatric patient with NPE complicated with severe myocardial injury.

Conclusions

We managed a pediatric case of NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. The NPE might have been triggered by the short period of convulsion followed by the increased intracranial pressure. The patient required mechanical ventilation for 4 days. Simultaneously, the patient had a severe myocardial injury diagnosed by highly elevated hs-cTn I combined with a high serum BNP level. Despite the improvement of respiratory insufficiency and LV contraction, the abnormally increased BNP level remained for approximately 2 weeks. Therefore, we recommend serial measurement of both hs-cTn and BNP, even in a pediatric patient with NPE, because of the possible prolonged overloading stress to the LV wall exceeding the acute phase of NPE.