Fluid Overload and Respiratory Morbidity vs Mortality in PICU
This is the largest retrospective study to date investigating fluid overload and outcome in a cohort of undifferentiated critically ill children. Our study demonstrated that although degree of fluid overload at 48 hours is associated with both OI at 48 hours and length of ventilation in survivors, there was no association with mortality. Despite weak R values, the association between fluid overload and OI and length of invasive ventilation was significant and confirmed in the regression models.
Our study is consistent with Arikan et al's smaller retrospective study of fluid overload in 80 general PICU patients. The patients included in the study by Arikan et al and our study were both representative of admissions to a general PICU, with a similar spread of diagnoses. Our cohort was younger, had a lower OI, and was ventilated for a shorter period of time. Primary respiratory pathology was the most common diagnosis in both studies, and in both, there was a significant association between fluid overload and pulmonary dysfunction. The study by Arikan et al investigated fluid overload up to 14 days from admission.
We chose to focus on early fluid overload as most critically ill children in the United Kingdom spend less than 7 days in PICU. Also, accurate measurement of fluid balance is an ongoing nursing challenge, particularly as insensible losses cannot be measured and as long-stay patients in particular often do not have urinary catheters. It is possible that in some other studies of fluid overload in ventilated children, in which many patients reached their "peak fluid overload" after day 5 of admission, this is due to inaccurate measurement. For example, in the PALISI study, children were found to be a mean of 136 mL/kg positive at the time of extubation, with a range of –358 to +2,228 mL/kg. Such a wide range casts doubt on the validity of the overall findings. Our own data demonstrated that fluid overload progressively increased over admission in long-stay patients (data not shown). We suspect that this is due to inaccurate charting of fluid balance once patients no longer have a urinary catheter and stools become solid, rather than ongoing excess fluid administration beyond the first 48 hours. It is for this reason that we decided to focus our study on mechanically ventilated patients in the first 48 hours of admission and in patients with an arterial catheter in situ—in our unit, such patients always have a urinary catheter in situ and fluid balance calculation is therefore at its most reliable.
The %FO at 48 hours in our study is similar to that found in other studies which have also chosen to focus on early rather than late fluid overload; for example, the 75% quartile of fluid overload was 11% on day 2 in the study by Arikan et al and the mean cumulative fluid overload at day 3 in the study by Valentine et al was 8.5% ± 10.5%.
The observation that %FO is associated with vasoactive drug use is interesting, and the significance is not clear. There are a two possible explanations—first, that fluid bolus therapy is being given at the point the Starling curve is flat, or in other words, a failure to respond to fluids alerts the clinician that vasoactive drugs are required; or second, that patients on vasoactive drugs are more unwell with more capillary leak and simply require increased fluids. Without data on timing of fluid versus vasoactive drug therapy, it is not possible to comment further. Future prospective studies with improved hemodynamic monitoring may help to dissect this association.
A strength of this study is its relevance and general applicability to critically ill children. Our large cohort included patients with a broad range of diagnoses, other than postoperative cardiac patients, as our unit does not have a cardiac surgical or extracorporeal membrane oxygenation program. The study also demonstrates proof of concept for utilization of a PICU clinical information system for retrospective studies of this nature.
Discussion
This is the largest retrospective study to date investigating fluid overload and outcome in a cohort of undifferentiated critically ill children. Our study demonstrated that although degree of fluid overload at 48 hours is associated with both OI at 48 hours and length of ventilation in survivors, there was no association with mortality. Despite weak R values, the association between fluid overload and OI and length of invasive ventilation was significant and confirmed in the regression models.
Our study is consistent with Arikan et al's smaller retrospective study of fluid overload in 80 general PICU patients. The patients included in the study by Arikan et al and our study were both representative of admissions to a general PICU, with a similar spread of diagnoses. Our cohort was younger, had a lower OI, and was ventilated for a shorter period of time. Primary respiratory pathology was the most common diagnosis in both studies, and in both, there was a significant association between fluid overload and pulmonary dysfunction. The study by Arikan et al investigated fluid overload up to 14 days from admission.
We chose to focus on early fluid overload as most critically ill children in the United Kingdom spend less than 7 days in PICU. Also, accurate measurement of fluid balance is an ongoing nursing challenge, particularly as insensible losses cannot be measured and as long-stay patients in particular often do not have urinary catheters. It is possible that in some other studies of fluid overload in ventilated children, in which many patients reached their "peak fluid overload" after day 5 of admission, this is due to inaccurate measurement. For example, in the PALISI study, children were found to be a mean of 136 mL/kg positive at the time of extubation, with a range of –358 to +2,228 mL/kg. Such a wide range casts doubt on the validity of the overall findings. Our own data demonstrated that fluid overload progressively increased over admission in long-stay patients (data not shown). We suspect that this is due to inaccurate charting of fluid balance once patients no longer have a urinary catheter and stools become solid, rather than ongoing excess fluid administration beyond the first 48 hours. It is for this reason that we decided to focus our study on mechanically ventilated patients in the first 48 hours of admission and in patients with an arterial catheter in situ—in our unit, such patients always have a urinary catheter in situ and fluid balance calculation is therefore at its most reliable.
The %FO at 48 hours in our study is similar to that found in other studies which have also chosen to focus on early rather than late fluid overload; for example, the 75% quartile of fluid overload was 11% on day 2 in the study by Arikan et al and the mean cumulative fluid overload at day 3 in the study by Valentine et al was 8.5% ± 10.5%.
The observation that %FO is associated with vasoactive drug use is interesting, and the significance is not clear. There are a two possible explanations—first, that fluid bolus therapy is being given at the point the Starling curve is flat, or in other words, a failure to respond to fluids alerts the clinician that vasoactive drugs are required; or second, that patients on vasoactive drugs are more unwell with more capillary leak and simply require increased fluids. Without data on timing of fluid versus vasoactive drug therapy, it is not possible to comment further. Future prospective studies with improved hemodynamic monitoring may help to dissect this association.
A strength of this study is its relevance and general applicability to critically ill children. Our large cohort included patients with a broad range of diagnoses, other than postoperative cardiac patients, as our unit does not have a cardiac surgical or extracorporeal membrane oxygenation program. The study also demonstrates proof of concept for utilization of a PICU clinical information system for retrospective studies of this nature.
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