Milrinone Therapy for Enterovirus 71-Induced Pulmonary Edema and/or Neurogenic Shock in Children

Yu, Chia-Yi; Khanh, Truong Huu; Thoa, Le Phan Kim; Tseng, Fan-Chen; Wang, Shih Min; Thinh, Le Quoc; Lin, Chung-Cherng; Wu, Han Chieh; Wang, Jen Ren; Hưng, Nguyễn Thành; Thuong, Tang Chi; Chang, Chung Ming; Su, Ih Jen; Liu, Ching Chuan

doi:10.1097/ccm.0b013e31828a2a85

Cited by 33 publications

(22 citation statements)

References 35 publications

(35 reference statements)

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“…The effectiveness and efficacy of milrinone treatment in patients with EV71-related PE has been proven in historically controlled [5] and randomized controlled studies [35]. The influence of selective PDE4 inhibitors and nonselective PDE inhibitors on the activity of immune cells, including lymphocytes, has been studied extensively [36], [37].…”

Section: Discussionmentioning

confidence: 99%

The Clinical Correlation of Regulatory T Cells and Cyclic Adenosine Monophosphate in Enterovirus 71 Infection

et al. 2014

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BackgroundBrainstem encephalitis (BE) and pulmonary edema (PE) are notable complications of enterovirus 71 (EV71) infection.ObjectiveThis study investigated the immunoregulatory characterizations of EV71 neurological complications by disease severity and milrinone treatment.Study DesignPatients <18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the hand, foot, and mouth disease (HFMD) or BE group, and the autonomic nervous system (ANS) dysregulation or PE group. Cytokine and cyclic adenosine monophosphate (cAMP) levels, and the regulatory T cell (Tregs) profiles of the patients were determined.ResultsPatients with ANS dysregulation or PE exhibited significantly low frequency of CD4+CD25+Foxp3+ and CD4+Foxp3+ T cells compared with patients with HFMD or BE. The expression frequency of CD4−CD8− was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+Foxp3+ increased markedly after milrinone treatment, and was associated with reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE; however, cAMP levels increased after milrinone treatment.ConclusionsThese findings suggested decreased different regulatory T populations and cAMP expression correlate with increased EV71 disease severity. Improved outcome after milrinone treatment may associate with increased regulatory T populations, cAMP expression and modulation of cytokines levels.

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Section: Discussionmentioning

confidence: 99%

The Clinical Correlation of Regulatory T Cells and Cyclic Adenosine Monophosphate in Enterovirus 71 Infection

et al. 2014

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“…These include enterovirus (EV)-71-induced brainstem encephalitis [20], subarachnoid bleeding (SAB) [21], intracerebral bleeding (ICB) [22], traumatic brain injury (TBI) [23], ischemic stroke [24], epilepsy [25], subdural hematoma [26], epidural hematoma [27], cerebral or spinal surgery [28], ce- rebral mass lesion [29], or other rarer causes (Table 1). According to a study of 36 patients with SAB-triggered NPE, predictors for the occurrence of NPE in patients with SAB were World Federation of Neurological Surgeons class, total power, and normalized low-frequency component [30].…”

Section: Types Of Triggers Of Npementioning

confidence: 99%

“…Since steroids may be beneficial for certain neurological conditions, such as multiple sclerosis or mass lesions with concomitant edema, and harmful in other conditions, such as TBI, application of steroids in NPE patients must be individualized [2]. In a recent study of 22 children with EV-71-induced brainstem encephalitis and NPE, the administration of milrinone resulted in a significantly better outcome with lower 1-week mortality than in controls receiving conventional treatment [20].…”

Section: Conventional Strategiesmentioning

confidence: 99%

Neurological Perspectives of Neurogenic Pulmonary Edema

Finsterer¹

2019

Eur Neurol

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Background: Neurogenic pulmonary edema (NPE) is characterized by acute respiratory distress triggered by acute, severe compromise of the central nervous system (CNS). This review aims at summarizing and discussing recent and previous findings about the type and frequency of CNS triggers of NPE, pathogenesis, diagnosis, treatment, and outcome of patients experiencing NPE. Key Messages: NPE is diagnosed in the presence of pink, frothy sputum, pulmonary edema, bilateral opacities on X-ray, PaO2:PiO2 <200 mm Hg, acute CNS compromise with increased intra-cranial pressure, rapid resolution within 48–72 h, and the absence of alternative causes of respiratory distress. The most common cerebral triggers of NPE include enterovirus-71-associated brainstem encephalitis, subarachnoid bleeding, intracerebral bleeding, traumatic brain injury, epilepsy, ischemic stroke, intracranial/spinal surgery, multiple sclerosis, electroconvulsive therapy, subdural/epidural hematoma, intoxication, hypoxia, and hydrocephalus. Simultaneous treatment of CNS and pulmonary compromise is required. Cerebral treatment involves infectiologists, neurologists, and neurosurgeons. Pulmonary treatment is mainly supportive, but if ineffective, extracorporeal membrane oxygenation or thermodilution are alternative options. Applying intensive care measures, the outcome of NPE has improved. Summary: CNS-disease triggering NPE is more variegated than anticipated. Delineation of NPE from other pulmonary or cardiac conditions mimicking NPE is crucial to take appropriate measures and improve the outcome of these patients.

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“…There is no specific antiviral treatment available till now. The remaining small proportion of children with HFMD progressing to potentially fatal cardiopulmonary failure requires intensive care including ventilation and newer therapy including milrinone [21]. The early onset of myoclonic jerk (during sleep in early stage and later also in awake state), truncal ataxia and wandering eyes (rotatory eye movement without fixation) are the early manifestation of fatal disease course [22].…”

Section: Managementmentioning

confidence: 99%

Hand, Foot and Mouth Disease: A case report

Sah¹

2017

Janaki Med. Coll. J. Med. Sci.

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Hand, foot & mouth disease (HFMD) is a common emerging infectious disease caused by intestinal viruses of the picornaviridae family. A strain of Coxsackie virus (A16, A5, A6) is chiefly instrumental for producing this condition however more severe form is caused by Enterovirus-71. Though HFMD is a mild disease and can often be effectively and competently managed in an outpatient setting, recent outbreaks in the western pacific region with fatal form of disease have attracted the concern about the clinical assessment and appropriate management of HFMD. Early detection and good clinical judgments not only can prevent the fatal progression but also can reduce overall morbidity and mortality regarding HFMD. I am presenting a case report of the afore mentioned disease and the subsequent early clinical manifestation of the fatal form of HFMD to enlighten on the nature of the disease so that early diagnosis and management of the condition can be carried out to halt the disease progression and prevention for the betterment of children especially under five years.

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Milrinone Therapy for Enterovirus 71-Induced Pulmonary Edema and/or Neurogenic Shock in Children

Abstract: Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.

Cited by 33 publications

References 35 publications

The Clinical Correlation of Regulatory T Cells and Cyclic Adenosine Monophosphate in Enterovirus 71 Infection

The Clinical Correlation of Regulatory T Cells and Cyclic Adenosine Monophosphate in Enterovirus 71 Infection

Neurological Perspectives of Neurogenic Pulmonary Edema

Hand, Foot and Mouth Disease: A case report

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