HFMD is characterized by fever and rashes of hands, feet, mouth and buttocks, a condition that is highly infectious and predominant in preschool kids. With timely diagnosis and treatment, the patients can fully recover[14]. However, a few patients can have central nervous system dysfunction[15] and acute pulmonary edema, which are the main causes of death[16, 17]. According to the HFMD guideline, severe cases at stages 3 and 4 should be admitted to ICU promptly. EV71 is one of the main viruses that cause HFMD, ranking first in its etiology, and is easily worsened by encephalitis. When the brain stem is involved, HFMD is likely to give rise to neurogenic pulmonary edema[18-21]. Some of the stage 3 and 4 HFMD patients needed vasoactive agents to sustain a normal blood pressure and were considered hemodynamically unstable, so PiCCO technique which was designed for hemodynamic monitoring was considered. The purpose of PiCCO monitoring was to investigate whether it can help better fluid management and facilitate quicker relief of the disease. Detecting the risk factors of acute pulmonary edema, in young children with HFMD as early as possible, and administering effective intervention and timely treatment have an important role in reducing mortality. To our knowledge, this is the first report of PiCCO hemodynamic monitoring in preschool children.
The patients included in our study were divided into a PiCCO group and a control group, to assess the value of applying PiCCO. Though PiCCO did not shorten the length of ICU stay, reduce the cases of mechanical ventilation or the cases of vasoactive drugs usage, some interesting results were still obtained. 1) PiCCO monitoring reduced the cases of patients with fluid overload, which is probably due to the real-time monitoring of EVLWI, GEDVI, CVP and other volume related indicators. 2) PiCCO monitoring helped reduce the duration of mechanical ventilation, which may be due to the fact that PiCCO enabled the optimization of fluid management and the rapid relief of pulmonary edema. Dynamic monitoring suggested that EVLWI decreased gradually over time, which confirmed the reduction of pulmonary edema. 3) Through linear regression analysis, it was found that with the gradual recovery of CI, VLWI gradually decreased, which may indicate that viral myocarditis cannot be excluded in severe HFMD, and there is the possibility that cardiogenic pulmonary edema existed in the course of the disease.
PiCCO was a routine invasive technique in the critical care field, but it was seldom applied in general wards. So PiCCO catheter was usually inserted to patients after they were transferred to ICU. However, we agree that if PiCCO could be implanted earlier, the fluid management could be done better, and this may be beneficial to stage 3 and 4 severe HFMD patients. In our department, 4 ℃ saline was injected every 6 hours to measure hemodynamic parameters of PiCCO. It’s a habitual routine, which was not mandatory. However, as PiCCO was only applied to potential circulation unstable patients, when the medical resource was sufficient, longer interval was not considered unless the condition of the patients had been improved significantly.
In 2001, Wu et.al reported that in the 5 children with EV71-caused HFMD, Swan Ganz catheter monitoring and magnetic resonance showed that severe HFMD was complicated with brainstem encephalitis and acute pulmonary edema[22]. The results showed that tachycardia and low SI were the two most common clinical manifestations. However, due to the normal pulmonary artery wedge pressure (PAWP) and CI, there was no significant increase in vessel resistance. Therefore, they concluded that the cause of acute pulmonary edema was not cardiogenic. PiCCO hemodynamics monitoring has been widely used in clinical settings, especially in ICU[23, 24]. Assessment of extravascular lung water (EVLW) by pulmonary thermal-dilution technology [25] has been confirmed by many basic experiments. Its application makes bedside EVLW evaluation a routine requirement in critical care medicine[24, 26].
In addition to treatment such as dehydration, anti-viral and anti-bacterial infections, and mechanical ventilation, some patients were also administered with immunoglobulin, and/or methylprednisolone in this study. With reference to PiCCO monitoring, the children also received cardiotonic, and/or diuretics therapy. Fluid management by PiCCO succeeded as patients’ pulse slowed, CI and SI increased, and EVLWI, GEDVI and SVRI decreased. In this study, the corresponding decrease of lung fluid may be interpreted as the recovery of heart function. The decline of GEDVI after treatment may suggest that when the patients reached stages 3 or 4 diagnosis, the volume of the left ventricle became enlarged[27]. Hence, based on the findings of this study, it is possible to speculate that the cause of pulmonary edema in children with severe HFMD is not only neurogenic but also cardiogenic. The presence of pulmonary edema may be easily confirmed by a combination of high EVLWI and a chest x-ray.
Similar to the study of Wu et.al[22], the 8 patients showed tachycardia and low cardiac output on admission, and CI was slightly lower than the normal range. The results of PiCCO showed that CI decreased, while GEDVI increased, which was consistent with the results of some studies—indicating that the left ventricle enlarged and its systolic function was impaired in children with severe HFMD. At present, HFMD is still common in southern China[28, 29],and severe HFMD is still the main cause of death in children. Clinically, the condition of severe HFMD patients with acute pulmonary edema are more severe, as the central nervous system damage and left ventricular systolic dysfunction are more common in these patients[30]. This study confirmed the feasibility of PiCCO hemodynamic monitoring in young children. Although there is no known reference interval of parameters of PiCCO for young children, the trend of PiCCO parameters still can provide markers for guiding fluid management. Volume management, under the guidance of PiCCO, may reduce the fluid overload in children with severe HFMD, relieve pulmonary edema more swiftly, and lower the duration of mechanical ventilation.
Finally, the limitations of this study are as follows: 1) This was a retrospective study, with a small number of cases included, thus the conclusions need to be verified by larger studies. 2) Only successfully treated cases were included, hence the impact of PiCCO on mortality has not been evaluated. 3) PiCCO catheter implant is an invasive procedure; with the rise of non-invasive hemodynamic monitoring techniques, especially in children, its prospects are not so optimistic. 4) Due to limited medical resources, synchronous re-examination of cardiac ultrasound was not accomplished for both groups; therefore, some parameters of PICCO and ultrasound results may be quite different. 5) With the popularity of vaccines and hygiene improvement, the incidence of HFMD is decreasing in Guangdong, and follow-up studies may be difficult to carry out.