Pediatric Acute Respiratory Distress Syndrome in ... - IngentaConnect

2 downloads 0 Views 428KB Size Report
vided calfactant free of charge for a study of acute lung injury in pediatric hematopoietic stem cell transplant patients). Dr. Cheifetz received funding from Philips ...
Pediatric Acute Respiratory Distress Syndrome in Pediatric Allogeneic Hematopoietic Stem Cell Transplants: A Multicenter Study* Courtney M. Rowan, MD1; Lincoln S. Smith, MD2; Ashley Loomis, MD3; Jennifer McArthur, DO4; Shira J. Gertz, MD5; Julie C. Fitzgerald, MD, PhD6; Mara E. Nitu, MD1; Elizabeth A. S. Moser, MS7; Deyin D. Hsing, MD8; Christine N. Duncan, MD9; Kris M. Mahadeo, MD, MPH10; Jerelyn Moffet, NP11; Mark W. Hall, MD12; Emily L. Pinos, CRNP, MSN13; Robert F. Tamburro, MD13; Ira M. Cheifetz, MD14; on behalf of the Investigators of the Pediatric Acute Lung Injury and Sepsis Network *See also p. 379. 1 Division of Critical Care, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis IN. 2 Division of Pediatric Critical Care Medicine, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA. 3 Division of Critical Care, Department of Pediatrics, Masonic Children’s Hospital, University of Minnesota, Minneapolis, MN. 4 Division of Critical Care, Department of Pediatrics, St. Jude’s Children’s Research Hospital, Memphis, TN. 5 Division of Critical Care, Department of Pediatrics, Joseph M Sanzari Children’s Hospital at Hackensack University Medical Center, Bergen County, NJ. 6 Division of Critical Care, Department of Anesthesia, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 7 Department of Biostatistics, Indiana University, Indianapolis IN. 8 Division of Critical Care, Department of Pediatrics, Weil Cornell Medical College, New York Presbyterian Hospital, New York City, NY. 9 Division of Oncology, Department of Pediatrics, Dana-Farber Cancer Institute Harvard University, Boston, MA. 10 Division of Oncology, Department of Pediatrics, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY. 11 Division of Blood and Marrow Transplant, Department of Pediatrics, Duke Children’s Hospital, Duke University, Durham, NC. 12 Division of Critical Care, Department of Pediatrics, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH. 13 Division of Critical Care, Department of Pediatrics, Penn State Hershey Children’s Hospital, Pennsylvania State University College of Medicine, Hershey, PA. 14 Division of Critical Care, Department of Pediatrics, Duke Children’s Hospital, Duke University, Durham, NC. This study was performed at the following institutions: Riley Hospital for Children at Indiana University School of Medicine; Joseph M Sanzari Children’s Hospital at Hackensack University Medical Center; Medical College of Wisconsin, Children’s Hospital of Wisconsin; Children’s Hospital of Philadelphia University of Pennsylvania Perelman School of Medicine; University of Minnesota, Masonic Children’s Hospital; Weil Cornell Medical College, New York Presbyterian Hospital; Dana-Farber Cancer Institute; Children’s Hospital of Los Angeles; University of Washington and Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000001061

Seattle Children’s Hospital; Duke Children’s Hospital; Nationwide Children’s Hospital; Penn State Children’s Hospital. Ms. Moser’s institution received funding from which a percentage of Her salary is supported by the section of pediatric critical care at Riley Hospital for her role as a biostatistician. Dr. Tamburro received funding from Springer Publishing. His institution received support from ONY, LLC (provided calfactant free of charge for a study of acute lung injury in pediatric hematopoietic stem cell transplant patients). Dr. Cheifetz received funding from Philips (medical advisor) and Ikaria (medical advisor). His institution received funding from Hill-Rom (research grant). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: [email protected]

Objective: Immunodeficiency is both a preexisting condition and a risk factor for mortality in pediatric acute respiratory distress syndrome. We describe a series of pediatric allogeneic hematopoietic stem cell transplant patients with pediatric acute respiratory distress syndrome based on the recent Pediatric Acute Lung Injury Consensus Conference guidelines with the objective to better define survival of this population. Design: Secondary analysis of a retrospective database. Setting: Twelve U.S. pediatric centers. Patients: Pediatric allogeneic hematopoietic stem cell transplant recipients requiring mechanical ventilation. Interventions: None. Measurements and Main Results: During the first week of mechanical ventilation, patients were categorized as: no pediatric acute respiratory distress syndrome or mild, moderate, or severe pediatric acute respiratory distress syndrome based on oxygenation index or oxygen saturation index. Univariable logistic regression evaluated the association between pediatric acute respiratory distress syndrome and PICU mortality. A total of 91.5% of the 211 patients met criteria for pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference definition: 61.1% were severe, 27.5% moderate, and 11.4% mild. Overall survival was 39.3%. Survival decreased with worsening pediatric acute respiratory distress syndrome: no pediatric acute respira-

304 www.pccmjournal.org April 2017 • Volume 18 • Number 4 Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited

Feature Articles tory distress syndrome 66.7%, mild 63.6%, odds ratio = 1.1 (95% CI, 0.3–4.2; p = 0.84), moderate 52.8%, odds ratio = 1.8 (95% CI, 0.6–5.5; p = 0.31), and severe 24.6%, odds ratio = 6.1 (95% CI, 2.1–17.8; p < 0.001). Nonsurvivors were more likely to have multiple consecutive days at moderate and severe pediatric acute respiratory distress syndrome (p < 0.001). Moderate and severe patients had longer PICU length of stay (p = 0.01) and longer mechanical ventilation course (p = 0.02) when compared with those with mild or no pediatric acute respiratory distress syndrome. Nonsurvivors had a higher median maximum oxygenation index than survivors at 28.6 (interquartile range, 15.5–49.9) versus 15.0 (interquartile range, 8.4–29.6) (p < 0.0001). Conclusion: In this multicenter cohort, the majority of pediatric allogeneic hematopoietic stem cell transplant patients with respiratory failure met oxygenation criteria for pediatric acute respiratory distress syndrome based on the Pediatric Acute Lung Injury Consensus Conference definition within the first week of invasive mechanical ventilation. Length of invasive mechanical ventilation, length of PICU stay, and mortality increased as the severity of pediatric acute respiratory distress syndrome worsened. (Pediatr Crit Care Med 2017; 18:304–309) Key Words: acute respiratory distress syndrome; critical care; hematopoietic stem cell transplantation; mortality; respiratory insufficiency

A

cute respiratory distress syndrome (ARDS) was defined in 1994 by the American European Consensus Conference as a “syndrome of inflammation and increased permeability that is associated with a constellation of clinical, radiologic, and physiologic abnormalities that cannot be explained by, but may coexist with, left atrial or pulmonary capillary hypertension” (1). However, specific pediatric considerations were lacking from this definition. The subsequently published Berlin criteria also lacked pediatric consideration (2). The Pediatric Acute Lung Injury Consensus Conference (PALICC) recently published guidelines to better define pediatric ARDS (PARDS) (3). Stratification of PARDS into mild, moderate, and severe risk groups is based on oxygenation index (OI) or oxygen saturation index (OSI), when OI is not available. Diffuse lung injury can be a major complication of pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients, occurring in 25–55% of HSCT recipients (4–9). The majority (73–88%) of HSCT admissions to PICUs are secondary to pulmonary complications (10–13). These studies report general pulmonary complications, not specifically PARDS. However, it is likely that this patient population is at higher risk of developing PARDS than the general pediatric population. Previously reported incidences for PARDS in general pediatric patients range between 2.0 and 12.8 per 100,000 person-years (14–18). Many studies demonstrate immunodeficiency to be both a preexisting condition and a risk factor for mortality in ARDS (15, 18–28). The original published study from this dataset described a high mortality rate of approximately 60% for HSCT patients requiring mechanical ventilation with a median length of ventilation of 10 Pediatric Critical Care Medicine

days (29). Additionally, this study showed that, even at the beginning of mechanical ventilation, both survivors and nonsurvivors had elevated peak inspiratory pressures as well as a median starting OI of almost 12 in both groups. The recent definition of PARDS was derived and validated from retrospective data from a general population of children with severe acute hypoxemic respiratory failure. Therefore, we sought to further investigate whether the new PARDS severity criteria discriminate mortality in this unique, critically ill population. The objective of this study is to use the PALICC definition of PARDS to describe a population of pediatric HSCT recipients requiring invasive mechanical ventilation (IMV) with a focus on the stratification of severity and associated mortality of PARDS using a multicenter retrospective database. We hypothesize that this population has a higher prevalence of PARDS, higher percentage of patients with increased severity, and higher associated mortality than the general PICU population.

MATERIALS AND METHODS Twelve centers contributed data to a retrospective, multicenter database of allogeneic HSCT recipients admitted to the PICU posttransplant with the diagnosis of acute respiratory failure. This is a secondary analysis of a retrospective cohort study. Institutional Review Board approval was obtained at each center prior to study participation. Each institution contributed up to 25 of their most recent consecutive stem cell transplant recipients requiring mechanical ventilation. The range of patients contributed by center was 6–25 patients with a median contribution of 18.5 patients per center. Inclusion criteria were HSCT performed for all indications (malignant and nonmalignant), age 1 month to 21 years, and the need for IMV. Patients intubated for reasons other than critical illness (i.e., procedure) and autologous transplants were excluded. Due to advances in hematopoietic cell transplantation, patients who received transplantation prior to January 1, 2009 were excluded. The first week of IMV was examined. Data abstracted included age, sex, diagnosis leading to transplant, source of transplant, length of PICU stay, length of IMV, survival to PICU discharge, and use of high frequency oscillatory ventilation (HFOV), renal replacement therapy, and extracorporeal membrane oxygenation (ECMO). Ventilator settings, oxygen saturation from pulse oximeter (Spo2), and arterial blood gas data (when available) were documented every 6 hours for the first 5 days of IMV and then daily for the remaining days of ventilation. These data were used to calculate the OI and OSI using the following equations: OI = (Fio2 × mean airway pressure × 100)/Pao2 and OSI = (Fio2 × mean airway pressure × 100)/Spo2. The OSI was calculated only when the Spo2 less than 97% (30). The first week of mechanical ventilation was investigated, and patients were categorized into the following groups: no PARDS, mild PARDS, moderate PARDS, or severe PARDS, based on the worst OI data during the first week of mechanical ventilation, or OSI when OI was not available. Descriptive statistics using medians and interquartile ranges (IQRs) were calculated for www.pccmjournal.org

305

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited

Rowan et al

continuous variables. The groups were compared using the Kruskal-Wallis test. Categorical variables were displayed as frequencies and percentages and were compared using chi-square or Fisher exact test where appropriate. Odds ratio (OR) with 95% CIs for mortality was calculated for each group of PARDS, and compared with patients without PARDS. A p value of less than 0.05 was considered statistically significant. Statistical Package of the Social Science (SPSS) Statistical software for Windows, version 20.0 (SPSS, Chicago, IL) and Microsoft Office Excel (Microsoft, Redmond, WA) were used for all analyses.

RESULTS The original database held 222 patients. Eleven were excluded due to lack of OI or OSI data. A total of 211 patients were included in the analysis. The vast majority, 91.5% (n = 193),

met OI or OSI criteria for the diagnosis of PARDS. Of those who met diagnostic criteria for PARDS, 61.1% (n = 118) were severe, 27.5% (n = 53) moderate, and 11.4% (n = 22) mild. Demographics for the entire cohort categorized by PARDS group are described in Table 1. Patients with severe PARDS were slightly older than those with mild to moderate PARDS but similar in age to those with no PARDS. Being transplanted for an oncologic diagnosis versus a nonmalignant reason was not associated with development or severity of PARDS (p = 0.45). However, the percentage of patients with acute myeloid leukemia increased with the severity of PARDS. The PICU survival rate for the entire cohort was 39.3%. The survival rate did not change over time with 41% survival in the first half and 38% survival in the second half of the study period (p = 0.5). Survival decreased with worsening severity of

Table 1. Demographics Displayed by Pediatric Acute Respiratory Distress Syndrome Category

Demographic Variable

Entire Cohort (n = 211)

Survivors

83 (39.3)

Age

8.7 (2.1–15.9) 10.5 (1.8–16.2)

Male gender

125 (59.2)

No PARDS (n = 18)

12 (66.7) 12 (66.7)

Mild PARDS (n = 22)

Moderate PARDS (n = 53)

Severe PARDS (n = 118)

14 (63.6)

28 (52.8)

29 (24.6)

7.0 (3.7–17.1)

7.3 (1.9–15.6)

12 (54.5)

36 (67.9)

10.0 (2.7–15.9) 61 (51.7)

Transplant diagnosis 52 (24.6)

5 (27.8)

5 (22.7)

12 (22.6)

30 (25.4)

  Acute myeloid leukemia

42 (19.9)

1 (5.6)

2 (9.1)

8 (15.1)

31 (26.3)

 Hemophagocytic lymphohistiocytosis

17 (8.1)

3 (16.7)

2 (9.1)

5 (9.4)

7 (5.9)

 Immunodeficiency

22 (10.4)

2 (11.1)

2 (9.1)

9 (17.0)

9 (7.6)

  Bone marrow failure

21 (10.0)

2 (11.1)

3 (13.6)

5 (9.4)

11 (9.3)

  Myeloproliferative syndrome

4 (1.9)

2 (11.1)

0 (0.0)

0 (0.0)

2 (1.7)

 Lymphomas

8 (3.8)

1 (5.6)

3 (13.6)

2 (3.8)

2 (1.7)

  Metabolic disorders

17 (8.1)

0 (0.0)

0 (0.0)

4 (7.5)

13 (11.0)

 Hemoglobinopathies

10 (4.7)

2 (11.1)

2 (9.1)

2 (3.8)

4 (3.4)

8 (3.8)

0 (0.0)

1 (4.5)

3 (5.7)

4 (3.4)

10 (4.7)

0 (0.0)

2 (9.1)

3 (5.7)

5 (4.2)

 Other

< 0.001 0.04 0.20 0.04

  Acute lymphoblastic leukemia

  Myelodysplastic syndrome

p

Source of transplant

0.30

  Bone marrow

97 (46.0)

8 (44.4)

14 (63.6)

24 (45.3)

51 (43.2)

  Cord blood

82 (38.9)

5 (27.8)

6 (27.3)

19 (35.8)

52 (44.1)

  Peripheral blood

32 (15.2)

5 (27.8)

2 (9.1)

10 (18.9)

15 (12.7)

Related donor

46 (21.8)

5 (27.8)

7 (31.8)

12 (22.6)

22 (18.6)

0.09

Respiratory infection

77 (36.5)

4 (22.2)

5 (22.7)

19 (35.8)

49 (41.5)

0.20

High frequency oscillatory ventilation

82 (38.9)

0 (0.0)

1 (4.5)

9 (17.0)

72 (61.0)

< 0.001

PARDS = pediatric acute respiratory distress syndrome. Values displayed are frequencies with percentages in parenthesis or as medians with interquartile ranges. Categorical variables compared using chi-square or extended Fisher exact test where appropriate.

306

www.pccmjournal.org

April 2017 • Volume 18 • Number 4

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited

Feature Articles

Table 2. Morbidity and Motality Displayed by Pediatric Acute Respiratory Distress Syndrome Category

PARDS Total % Category Patients Survival (n)

Length of IMV

Ventilator-Free Days

High Frequency Oscillatory Ventila- Renal ReVasotion Within First placement active Week IMV, % Therapy, % Agents, %

Length of PICU Stay

No PARDS

18

66.7 (12)

4 (3.0–9.8)

19.5 (0–24.0)

11 (4.0–34.5)

0

22.2

33.3

Mild PARDS

22

63.7 (14)

5 (3.0–10.8)

20.5 (0–24.0)

10 (4.3–15.8)

0

27.3

40.9

Moderate PARDS

53

52.8 (28)

14 (5.0–21.0)

0 (0–17.0)

19 (13.0–46.0)

3.4

36.5

50.9

Severe PARDS

118

24.6 (29)

5 (6.0–26.0)

0 (0–0)

19 (10.0–33.8)

55.9

41.0

74.6

< 0.001

0.01

p

< 0.0001

0.01

< 0.0001

0.33

0.0001

IMV = invasive mechanical ventilation, PARDS = pediatric acute respiratory distress syndrome. Numbers displayed are medians with interquartile ranges represented in parenthesis or as percentages. p value obtained with Kruskal-Wallis test or with chisquare/Fisher exact test where appropriate.

PARDS (p < 0.001) (Table 2). Using intubated HSCT patients without PARDS as the reference population, there was no difference in the OR of mortality between HSCT patients with no PARDS versus mild PARDS (mild OR = 1.1 [95% CI, 0.3– 4.2; p = 0.84] and no PARDS vs moderate OR = 1.8 [95% CI, 6–5.5; p = 0.31]) PARDS group. The severe PARDS group had a significantly higher risk of mortality with an OR of 6.1 (95% CI, 2.1–17.8; p < 0.001). The nonsurvivors were more likely to have multiple, consecutive days at moderate and severe PARDS (p < 0.001). The majority, 70.5% (n = 136), met PARDS criteria by day 1 of mechanical ventilation, and 89.1% (n = 172) Table 3.

met criteria by day 3. The median day for initial occurrence and worst PARDS was 1 for both survivors and nonsurvivors. However, a larger portion of nonsurvivors continued to have worsening PARDS after the initial diagnosis (Table 3). The patients with moderate or severe PARDS received longer and more intense critical care interventions. The moderate and severe PARDS patients had a longer PICU length of stay (p = 0.01) and a longer course of mechanical ventilation (p = 0.01) (Table 2). Additionally, those with moderate and severe PARDS had significantly fewer ventilator-free days at 28 days (p < 0.0001) (Table 2). There was an increased use of HFOV and vasoactive agents with

Comparison of Survivors to Nonsurvivors

PARDS Variable

p

Survivors (n = 83) Nonsurvivors (n = 128)

PARDS category  None

12 (14.5)

6 (4.7)

< 0.001

 Mild

14 (16.9)

8 (6.3)

 Moderate

28 (33.7)

25 (19.5)

 Severe

29 (34.9)

89 (69.5)

  Oxygenation index

57 (80.3)

109 (89.3)

  Oxygen saturation index

14 (19.7)

13 (10.7)

Consecutive days at highest PARDS category

1.0 (1.0–3.0)

2.0 (1.0–4.0)

< 0.01

Total days at highest PARDS category

1.5 (1.0–3.3)

2.0 (1.0–4.0)

0.01

Total days at moderate to severe PARDS

1.5 (1.0–5.0)

4.0 (1.0–7.0)

< 0.001

Day of IMV at first occurrence of any PARDS category

1.0 (1.0–1.0)

1.0 (1.0–1.0)

0.63

Day of IMV at first occurrence of worst PARDS category

1.0 (1.0–1.0)

1.0 (1.0–2.0)

0.21

PARDS category diagnosed by

Patients with worsening PARDS category after initial diagnosis of PARDS, %

12.7

0.08

29.5

0.008

IMV = invasive mechanical ventilation, PARDS = pediatric acute respiratory distress syndrome. Values displayed are frequencies with percentages or medians with interquartile range. All results presented in table are from the first week of invasive mechanical ventilation.

Pediatric Critical Care Medicine

www.pccmjournal.org

307

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited

Rowan et al

worsening severity of PARDS; however, the use of renal replacement therapy was similar among PARDS groups (Table 2). HFOV was used in 68 patients with moderate or severe PARDS during the first week of mechanical ventilation. This group of the patients had a very high mortality rate of 70.6%. Three patients, all with severe PARDS, were placed on ECMO with 100% mortality. During the first 7 days of ventilation, 174 patients had data to calculate an OI. The median OI during this time was 24.1 (IQR, 12.4–42.9). When examining the maximum OI during this period, there was a significant difference between survivors and nonsurvivors (15.0 [IQR, 8.4–29.6] vs 28.6 [IQR, 15.5–49.9]; p < 0.0001, respectively). Survivors were also more likely to transition to a less severe category of PARDS at 48 hours after diagnosis of PARDS (64.0% vs 47.8%; p = 0.045).

DISCUSSION This large, 12-center study is the first to describe PARDS in mechanically ventilated HSCT patients. Using the criteria recommended by PALICC, we describe short-term outcomes (mortality, length of PICU stay, and length of mechanical ventilation) of PARDS in a high-risk population. Mortality in the pediatric HSCT recipient with respiratory failure remains high and seems to be associated with severity of PARDS. This article is a descriptive study and can serve as a first step toward optimization of care. The existing datasets used to derive and validate the PALICC definition of PARDS suggest that the mortality of mild, moderate, and severe PARDS are 12%, 22%, and 29%, respectively. This study suggests that moderate and severe PARDS criteria (47.2% and 75.4% vs 33.3%) discriminate mortality in the HSCT population, but the mild PARDS criteria does not (36.3% vs 33%). However, these data also suggest that 81% of mechanically ventilated HSCT patients have moderate or severe PARDS. The diagnosis of PARDS is quite common in the intubated pediatric HSCT patient with over 91% of our cohort identified within the first week of IMV. Although our study was not designed to specifically measure prevalence, this occurrence of PARDS in the mechanically ventilated pediatric HSCT patient seems vastly higher than what is reported among the general PICU population requiring IMV. For example, in a large, single center, retrospective review of 1,833 mechanically ventilated children, only 7% (129/1,833 patients) met criteria for ARDS based on the Berlin criteria (31). Two thirds of these ARDS patients survived. Similarly, a large pediatric cross-sectional study found that 20.2% of mechanically ventilated children were diagnosed with acute lung injury or ARDS using the American European consensus criteria (27). In contrast, the vast majority of the HSCT cohort described in this report not only has PARDS but also a high proportion (> 60%) met criteria for severe PARDS. The studies used by the PALICC group to validate the OI cutoff for the severe category of PARDS described a prevalence of 16.4–55% in different pediatric cohorts suffering from PARDS (15–17, 32, 33). This difference is not surprising given that immunodeficiency is an established risk factor for poor oxygenation and the development of ARDS (15, 18, 27, 308

www.pccmjournal.org

34). These children clearly have a higher acuity of lung disease, supported by the diagnosis and categorization of PARDS. It is well documented that children who have undergone HSCT and subsequently require mechanical ventilation continue to have an unacceptable mortality rate (10–13, 29). Their immunodeficiency, disrupted inflammatory response, risk of other organ injury, complications from HSCT, and overall state of health likely place these patients at higher risk for critical illness. With specific regard to PARDS, this cohort also has higher mortality than reported in the literature in a similar time frame. The studies published after 2009 in the United States, most comparable to our cohort, report overall mortality of 11.3–50% with PARDS (18, 35–37). Even considering the set of validation studies used for PALICC, the overall mortality for those with severe PARDS was 29.3% (38). In fact, the mortality was consistently higher for the HSCT patients in each of the PARDS categories when compared with the validation set, thereby reiterating the severity of not only lung disease, but perhaps, overall illness as well in this unique patient population. It is also interesting that those with mild PARDS faired similarly to those with no PARDS in terms of mortality, length of mechanical ventilation, length of PICU stay, and ventilatorfree days. The reason for this is unclear. Perhaps, these children have disease processes more closely linked to those with no PARDS. Further investigation into the PICU course and cause of mortality for those who died would be needed to help elucidate this reason. Additionally, these categorizations were based on new guidelines that have not been prospectively tested. Our analysis is limited by all the weaknesses inherent with a retrospective study design. For example, the retrospective data collection limited the availability and consistency of the arterial blood gas data needed to calculate the OI. OSI was collected when arterial blood gas data were not available. However, this too was limited by the number of time points when the oxygen saturation values were greater than 97%. Clearly, a prospective trial would appear indicated to confirm these findings. Additionally, it would have been beneficial to incorporate fluid overload data into this analysis to determine its effect on the development and severity of PARDS. This would be an important variable to include in future study designs.

CONCLUSION In this multicenter cohort, the overwhelming majority (91.5%) of pediatric allogeneic HSCT patients who develop respiratory failure meet PARDS criteria within the first week of IMV. These data suggest that the prevalence of PARDS among mechanically ventilated HSCT patients is several-fold higher than that of the general PICU population of mechanically ventilated patients. The results of this study also suggest that of those with ARDS, HSCT patients are much more likely to have severe disease when compared with the general PICU population of ARDS patients. Both morbidity and mortality increased as the severity of PARDS worsened. HSCT patients in the severe PARDS category remained in the PICU longer, had longer courses of mechanical ventilation, were more likely to be placed on HFOV, and were April 2017 • Volume 18 • Number 4

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited

Feature Articles

more likely to die. This cohort adds to the existing evidence of the association between immunodeficiency and severity/mortality of ARDS, also highlighted by the higher distribution of severe PARDS. Additionally, our study offers evidence that stratification of PARDS severity based on PALICC recommendations identifies risk of mortality in the pediatric HSCT population.

REFERENCES

1. Bernard GR, Artigas A, Brigham KL, et al: Report of the AmericanEuropean consensus conference on ARDS: Definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee. Intensive Care Med 1994; 20:225–232 2. Force ADT, Ranieri VM, Rubenfeld GD, et al: Acute respiratory distress syndrome: The Berlin Definition. JAMA 2012; 307:2526–2533 3. 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; 16:428–439 4. Clark JG, Madtes DK, Martin TR, et al: Idiopathic pneumonia after bone marrow transplantation: Cytokine activation and lipopolysaccharide amplification in the bronchoalveolar compartment. Crit Care Med 1999; 27:1800–1806 5. Crawford SW, Clark JG: Bronchiolitis associated with bone marrow transplantation. Clin Chest Med 1993; 14:741–749 6. Weiner RS, Bortin MM, Gale RP, et al: Interstitial pneumonitis after bone marrow transplantation. Assessment of risk factors. Ann Intern Med 1986; 104:168–175 7. Quabeck K: The lung as a critical organ in marrow transplantation. Bone Marrow Transplant 1994; 14(Suppl 4):S19–S28 8. Crawford SW, Hackman RC: Clinical course of idiopathic pneumonia after bone marrow transplantation. Am Rev Respir Dis 1993; 147:1393–1400 9. Kantrow SP, Hackman RC, Boeckh M, et al: Idiopathic pneumonia syndrome: Changing spectrum of lung injury after marrow transplantation. Transplantation 1997; 63:1079–1086 10. Chima RS, Daniels RC, Kim MO, et al: Improved outcomes for stem cell transplant recipients requiring pediatric intensive care. Pediatr Crit Care Med 2012; 13:e336–e342 11. Diaz MA, Vicent MG, Prudencio M, et al: Predicting factors for admission to an intensive care unit and clinical outcome in pediatric patients receiving hematopoietic stem cell transplantation. Haematologica 2002; 87:292–298 12. Duncan CN, Lehmann LE, Cheifetz IM, et al; Pediatric Acute Lung Injury and Sepsis (PALISI) Network: Clinical outcomes of children receiving intensive cardiopulmonary support during hematopoietic stem cell transplant. Pediatr Crit Care Med 2013; 14:261–267 13. Lamas A, Otheo E, Ros P, et al: Prognosis of child recipients of hematopoietic stem cell transplantation requiring intensive care. Intensive Care Med 2003; 29:91–96 14. Bindl L, Dresbach K, Lentze MJ: Incidence of acute respiratory distress syndrome in German children and adolescents: A populationbased study. Crit Care Med 2005; 33:209–312 15. Erickson S, Schibler A, Numa A, et al; Paediatric Study Group; Australian and New Zealand Intensive Care Society: Acute lung injury in pediatric intensive care in Australia and New Zealand: A prospective, multicenter, observational study. Pediatr Crit Care Med 2007; 8:317–323 16. Kneyber MC, Brouwers AG, Caris JA, et al: Acute respiratory distress syndrome: Is it underrecognized in the pediatric intensive care unit? Intensive Care Med 2008; 34:751–754 17. López-Fernández Y, Azagra AM, de la Oliva P, et al; Pediatric Acute Lung Injury Epidemiology and Natural History (PED-ALIEN) Network: Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children. Crit Care Med 2012; 40:3238–3245 18. Zimmerman JJ, Akhtar SR, Caldwell E, et al: Incidence and outcomes of pediatric acute lung injury. Pediatrics 2009; 124:87–95 19. Bersten AD, Edibam C, Hunt T, et al; Australian and New Zealand Intensive Care Society Clinical Trials Group: Incidence and mortality of

Pediatric Critical Care Medicine

acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med 2002; 165:443–448 20. Bindl L, Buderus S, Dahlem P, et al; ESPNIC ARDS Database Group: Gender-based differences in children with sepsis and ARDS: The ESPNIC ARDS Database Group. Intensive Care Med 2003; 29:1770–1773 21. Brun-Buisson C, Minelli C, Bertolini G, et al; ALIVE Study Group: Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med 2004; 30:51–61 22. DeBruin W, Notterman DA, Magid M, et al: Acute hypoxemic respiratory failure in infants and children: Clinical and pathologic characteristics. Crit Care Med 1992; 20:1223–1234 23. Flori H, Dahmer MK, Sapru A, et al: Comorbidities and assessment of severity of pediatric acute respiratory distress syndrome: Proceedings from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 2015; 16(5 Suppl 1):S41–S50 24. Keenan SP: Noninvasive positive pressure ventilation in acute respiratory failure. JAMA 2000; 284:2376–2378 25. Luhr OR, Antonsen K, Karlsson M, et al: Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group. Am J Respir Crit Care Med 1999; 159:1849–1861 26. Nichols DG, Walker LK, Wingard JR, et al: Predictors of acute respiratory failure after bone marrow transplantation in children. Crit Care Med 1994; 22:1485–1491 27. Santschi M, Jouvet P, Leclerc F, et al; PALIVE Investigators; Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI); European Society of Pediatric and Neonatal Intensive Care (ESPNIC): Acute lung injury in children: Therapeutic practice and feasibility of international clinical trials. Pediatr Crit Care Med 2010; 11:681–689 28. Timmons OD, Havens PL, Fackler JC: Predicting death in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group. Extracorporeal Life Support Organization. Chest 1995; 108:789–797 29. 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; 17:294–302 30. Thomas NJ, Shaffer ML, Willson DF, et al: Defining acute lung disease in children with the oxygenation saturation index. Pediatr Crit Care Med 2010; 11:12–17 31. Khemani RG, Rubin S, Belani S, et al: Pulse oximetry vs. PaO2 metrics in mechanically ventilated children: Berlin definition of ARDS and mortality risk. Intensive Care Med 2015; 41:94–102 32. Curley MA, Hibberd PL, Fineman LD, et al: Effect of prone positioning on clinical outcomes in children with acute lung injury: A randomized controlled trial. JAMA 2005; 294:229–237 33. Flori HR, Glidden DV, Rutherford GW, et al: Pediatric acute lung injury: Prospective evaluation of risk factors associated with mortality. Am J Respir Crit Care Med 2005; 171:995–1001 34. Trachsel D, McCrindle BW, Nakagawa S, et al: Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2005; 172:206–211 35. Hall MW, Geyer SM, Guo CY, et al; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network PICFlu Study Investigators: Innate immune function and mortality in critically ill children with influenza: A multicenter study. Crit Care Med 2013; 41:224–236 36. Khemani RG, Conti D, Alonzo TA, et al: Effect of tidal volume in children with acute hypoxemic respiratory failure. Intensive Care Med 2009; 35:1428–1437 37. 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; 40:2883–2889 38. Khemani RG, Smith LS, Zimmerman JJ, et al: 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 www.pccmjournal.org

309

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited