Fluid Overload in Pediatric Acute Respiratory Distress Syndrome after Allogeneic Hematopoietic Cell Transplantation

Abstract

The aim of the study is to examine the relationship between fluid overload (FO) and severity of respiratory dysfunction in children posthematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS). This investigation was a secondary analysis of a multicenter retrospective cohort of children (1month to 21 years) postallogeneic HCT with PARDS receiving invasive mechanical ventilation (IMV) from 2009 to 2014. Daily FO % (FO%) and daily oxygenation index (OI) were calculated for each patient up to the first week of IMV (day 0 = intubation). Linear mixed-effect regression was employed to examine whether FO% and OI were associated on any day during the study period. In total, 158 patients were included. Severe PARDS represented 63% of the cohort and had higher mortality (78 vs. 42%, p <0.001), fewer ventilator free days at 28 (0 [IQR: 0–0] vs. 14 [IQR: 0–23], p <0.001), and 60 days (0 [IQR: 0–27] v. 45 [IQR: 0–55], p <0.001) relative to nonsevere PARDS. Increasing FO% was strongly associated with higher OI (p <0.001). For children with 10% FO, OI was higher by nearly 5 points (adjusted β, 4.6, 95% CI: [2.9, 6.3]). In subgroup analyses, the association between FO% and OI was strongest among severe PARDS (p <0.001) and during the first 3 days elapsed from intubation (p <0.001). FO% was associated with lower PaO₂/FiO₂ (adjusted β, −1.92, 95% CI: [−3.11, −0.73], p = 0.002), but not mean airway pressure (p = 0.746). In a multicenter cohort of children post-HCT with PARDS, FO was independently associated with oxygenation impairment. The associations were strongest among children with severe PARDS and early in the course of IMV.

Keywords

pediatric acute respiratory distress syndrome - fluid overload - hematopoietic cell transplantation - mechanical ventilation

Publication History

Received: 13 March 2022

Accepted: 23 August 2022

Article published online:
11 October 2022

• References

• 1 Khandelwal P, Millard HR, Thiel E. et al. Hematopoietic stem cell transplantation activity in pediatric cancer between 2008 and 2014 in the United States: a center for international blood and marrow transplant research report. Biol Blood Marrow Transplant 2017; 23 (08) 1342-1349
• 2 Zinter MS, Dvorak CC, Spicer A, Cowan MJ, Sapru A. New insights into multicenter PICU mortality among pediatric hematopoietic stem cell transplant patients. Crit Care Med 2015; 43 (09) 1986-1994
• 3 Zinter MS, Logan BR, Fretham C. et al. Comprehensive prognostication in critically ill pediatric hematopoietic cell transplant patients: results from merging the center for international blood and marrow transplant research (CIBMTR) and virtual pediatric systems (VPS) registries. Biol Blood Marrow Transplant 2020; 26 (02) 333-342
• 4 Rowan CM, Gertz SJ, McArthur J. et al; Investigators of the Pediatric Acute Lung Injury and Sepsis Network. Invasive mechanical ventilation and mortality in pediatric hematopoietic stem cell transplantation: a multicenter study. Pediatr Crit Care Med 2016; 17 (04) 294-302
• 5 Fitch T, Myers KC, Dewan M, Towe C, Dandoy C. Pulmonary complications after pediatric stem cell transplant. Front Oncol 2021; 11: 755878
• 6 Rowan CM, Smith LS, Loomis A. et al; Investigators of the Pediatric Acute Lung Injury and Sepsis Network. Pediatric acute respiratory distress syndrome in pediatric allogeneic hematopoietic stem cell transplants: a multicenter study. Pediatr Crit Care Med 2017; 18 (04) 304-309
• 7 Khemani RG, Smith L, López-Fernández YM. et al; Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology (PARDIE) Investigators, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. Lancet Respir Med 2019; 7 (02) 115-128
• 8 Alobaidi R, Morgan C, Basu RK. et al. Association between fluid balance and outcomes in critically ill children: a systematic review and meta-analysis. JAMA Pediatr 2018; 172 (03) 257-268
• 9 Michael M, Kuehnle I, Goldstein SL. Fluid overload and acute renal failure in pediatric stem cell transplant patients. Pediatr Nephrol 2004; 19 (01) 91-95
• 10 Nürnberger W, Willers R, Burdach S, Göbel U. Risk factors for capillary leakage syndrome after bone marrow transplantation. Ann Hematol 1997; 74 (05) 221-224
• 11 Schots R, Kaufman L, Van Riet I. et al. Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation. Leukemia 2003; 17 (06) 1150-1156
• 12 Luft T, Dreger P, Radujkovic A. Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation. Bone Marrow Transplant 2021; 56 (10) 2326-2335
• 13 Valentine SL, Sapru A, Higgerson RA. et al; Pediatric Acute Lung Injury and Sepsis Investigator's (PALISI) Network, Acute Respiratory Distress Syndrome Clinical Research Network (ARDSNet). Fluid balance in critically ill children with acute lung injury. Crit Care Med 2012; 40 (10) 2883-2889
• 14 Seitz KP, Caldwell ES, Hough CL. Fluid management in ARDS: an evaluation of current practice and the association between early diuretic use and hospital mortality. J Intensive Care 2020; 8: 78
• 15 Sallee CJ, Smith LS, Rowan CM. et al. Early cumulative fluid balance and outcomes in pediatric allogeneic hematopoietic cell transplant recipients with acute respiratory failure: a multicenter study. Front Oncol 2021; 11: 705602
• 16 Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342 (18) 1334-1349
• 17 Jozwiak M, Silva S, Persichini R. et al. Extravascular lung water is an independent prognostic factor in patients with acute respiratory distress syndrome. Crit Care Med 2013; 41 (02) 472-480
• 18 Jozwiak M, Teboul JL, Monnet X. Extravascular lung water in critical care: recent advances and clinical applications. Ann Intensive Care 2015; 5 (01) 38
• 19 Wiedemann HP, Wheeler AP, Bernard GR. et al; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354 (24) 2564-2575
• 20 Khemani RG, Smith LS, Zimmerman JJ, Erickson S, Group PALICC. Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 2015; 16 (5, suppl 1): S23-S40
• 21 Goldstein SL, Currier H, Graf Cd, Cosio CC, Brewer ED, Sachdeva R. Outcome in children receiving continuous venovenous hemofiltration. Pediatrics 2001; 107 (06) 1309-1312
• 22 Group PALICC. Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 2015; 16 (05) 428-439
• 23 Rowan CM, McArthur J, Hsing DD. et al; Investigators of the Pediatric Acute Lung Injury and Sepsis Network. Acute respiratory failure in pediatric hematopoietic cell transplantation: a multicenter study. Crit Care Med 2018; 46 (10) e967-e974
• 24 Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, Jefferson LS, Loftis LL. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 2012; 13 (03) 253-258
• 25 Malbrain MLNG, Van Regenmortel N, Saugel B. et al. Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy. Ann Intensive Care 2018; 8 (01) 66
• 26 Bagshaw SM, Brophy PD, Cruz D, Ronco C. Fluid balance as a biomarker: impact of fluid overload on outcome in critically ill patients with acute kidney injury. Crit Care 2008; 12 (04) 169
• 27 Sutherland SM, Zappitelli M, Alexander SR. et al. Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 2010; 55 (02) 316-325
• 28 Bagshaw SM, Wald R, Adhikari NKJ. et al; STARRT-AKI Investigators, Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group, United Kingdom Critical Care Research Group, Canadian Nephrology Trials Network, Irish Critical Care Trials Group. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med 2020; 383 (03) 240-251
• 29 Aspesberro F, Guthrie KA, Woolfrey AE, Brogan TV, Roberts JS. Outcome of pediatric hematopoietic stem cell transplant recipients requiring mechanical ventilation. J Intensive Care Med 2014; 29 (01) 31-37
• 30 Elbahlawan L, West NK, Avent Y. et al. Impact of continuous renal replacement therapy on oxygenation in children with acute lung injury after allogeneic hematopoietic stem cell transplantation. Pediatr Blood Cancer 2010; 55 (03) 540-545
• 31 Black CG, Thomas NJ, Yehya N. Timing and clinical significance of fluid overload in pediatric acute respiratory distress syndrome. Pediatr Crit Care Med 2021; 22 (09) 795-805
• 32 Zinter MS, Spicer A, Orwoll BO. et al. Plasma angiopoietin-2 outperforms other markers of endothelial injury in prognosticating pediatric ARDS mortality. Am J Physiol Lung Cell Mol Physiol 2016; 310 (03) L224-L231
• 33 Calfee CS, Gallagher D, Abbott J, Thompson BT, Matthay MA, Network NA. NHLBI ARDS Network. Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance. Crit Care Med 2012; 40 (06) 1731-1737
• 34 Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 163 (06) 1376-1383
• 35 Prewitt RM, McCarthy J, Wood LD. Treatment of acute low pressure pulmonary edema in dogs: relative effects of hydrostatic and oncotic pressure, nitroprusside, and positive end-expiratory pressure. J Clin Invest 1981; 67 (02) 409-418
• 36 Kuebler WM, Ying X, Singh B, Issekutz AC, Bhattacharya J. Pressure is proinflammatory in lung venular capillaries. J Clin Invest 1999; 104 (04) 495-502
• 37 Yehya N, Harhay MO, Klein MJ. et al; Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology (PARDIE) V1 Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Predicting mortality in children with pediatric acute respiratory distress syndrome: a pediatric acute respiratory distress syndrome incidence and epidemiology study. Crit Care Med 2020; 48 (06) e514-e522
• 38 Spicer AC, Calfee CS, Zinter MS. et al. A simple and robust bedside model for mortality risk in pediatric patients with acute respiratory distress syndrome. Pediatr Crit Care Med 2016; 17 (10) 907-916