KlinPadiatr/0748/7.1.2015/MPS
Original Article
The Cause of Acute Respiratory Failure Predicts the Outcome of Noninvasive Ventilation in Immunocompromised Children Die Ursache des Akuten Atemversagens sagt den Outcome von Nichtinvasiver Beatmung bei Kindern mit Immunsuppression vorher Authors
H. Fuchs1, J. Schoss2, M. R. Mendler2, W. Lindner2, R. Hopfner2, A. Schulz3, M. Hoenig3, D. Steinbach3, K.-M. Debatin3, H. D. Hummler2, M. Schmid2
Affiliations
1
Key words ▶ acute respiratory distress ● syndrome ▶ noninvasive ventilation ● ▶ non-invasive ventilation ● ▶ immunosuppression ● ▶ stem cell transplantation ● ▶ cancer ●
Abstract
Zusammenfassung
Background: Noninvasive ventilation (NIV) may be superior to conventional therapy in immunocompromised children with respiratory failure. Methods: Mortality, success rate, prognostic factors and side effects of NIV for acute respiratory failure (ARF) were investigated retrospectively in 41 in children with primary immunodeficiency, after stem cell transplantation or chemotherapy for oncologic disease. Results: In 11/41 (27 %) children invasive ventilation was avoided and patients were discharged from ICU. In children with NIV failure ICU-mortality was 19/30 (63 %). 8/11 (72 %) children with NIV success had recurrence of ARF after 27 days. Only 4/11 (36 %) children with first episode NIV success and 8/30 (27 %) with NIV failure survived to hospital discharge. Lower FiO2, SpO2/FiO2 and blood culture positive bacterial sepsis were predictive for NIV success, while fungal sepsis or culture negative ARF were predictive for NIV failure. We observed catecholamine treatment in 14/41 (34 %), pneumothorax in 2/41 (5 %), mediastinal emphysema in 3/41 (7 %), a life threatening nasopharyngeal hemorrhage and need for resuscitation during intubation in 5/41 (12 %) NIV-episodes. Conclusions: The prognosis of ARF in immunocompromised children remains guarded independent of initial success or failure of NIV due to a high rate of recurrent ARF. Reversible causes like bacterial sepsis had a higher NIV response rate. Relevant side effects of NIV were observed.
Hintergrund: Nichtinvasive Beatmung könnte gegenüber konventioneller Therapie eine Vorteil bei der Behandlung des Atemversagens bei immunsupprimierten Kindern haben. Methoden: Mortalität, Erfolgsrate, prognostische Faktoren und Nebenwirkungen von nichtinvasiver Beatmung (NIV) beim akuten Atemversagen (ARF) wurden retrospektiv in einer Kohorte von 41 Kindern mit primärem Immundefekt, nach onkologischer Therapie oder nach Stamm zelltransplantation untersucht. Ergebnisse: Bei 11/41 (27 %) konnte die Intubation vermieden werden und die Kinder wurden von der Intensivstation entlassen. Die Intensivmortalität der Kinder mit NIV-Versagen betrug 19/30 (63 %). 8/11 (72 %) Kinder mit NIV-Erfolg wurden nach im Median 27 Tagen mit erneutem Atemversagen auf die Intensivstation wiederaufgenommen und benötigten erneut NIV. Nur 4/11 (36 %) Kinder mit NIV-Erfolg in der ersten Episode und 8/30 (27 %) Kinder mit NIV-Versagen überlebten bis zur Krankenhausentlassung. Niedrigerer FiO2, SpO2/FiO2 und blutkulturpositive bakterielle Sepsis waren mit NIV-Erfolg, während Pilzinfektionen oder kultur-negatives Atemversagen mit NIV-Versagen assoziiert waren. Als Nebenwirkungen wurden Katecholaminbedarf in 14/41 (34 %), Pneumothorax in 2/41 (5 %), Mediastinalemphysem in 3/41 (7 %), und Notwendigkeit zur Reanimation im Rahmen der Intubation bei 5/41 (12 %) der NIV-Episoden beobachtet. Schlussfolgerung: Die Prognose des ARF bei immunsupprimierten Kindern ist eingeschränkt, unabhängig vom initialen Erfolg oder Versagen der NIV aufgrund der hohen Rate an Rezidiven des Atemversagens. Behandelbare Ursachen des Atemversagens wie bakterielle Sepsis hatten eine höhere Rate an NIV-Erfolg. Relevante Nebenwirkungen der NIV müssen beachtet werden.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1395692 Published online: 2015 Klin Padiatr © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Hans Fuchs, MD Neonatology and Pediatric Critical Care Center for Pediatrics Mathildenstrasse 1 79104 Freiburg Tel.: + 49/761/27045 190 Fax: + 49/761/270 43990 [email protected]
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▼
Fuchs H et al. The Cause of Acute … Klin Padiatr
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Schlüsselwörter ▶ akutes Atemversagen ● ▶ nichtinvasive Beatmung ● ▶ nicht-invasive Beatmung ● ▶ Immunsuppression ● ▶ Stammzelltransplantation ● ▶ Krebserkrankung ●
Department of Neonatology and Pediatric Critical Care, Center for Pediatrics, Freiburg, Germany Division of Neonatology and Pediatric Critical Care, University Medical Center Ulm, Germany 3 Department of Oncology and Stem Cell Transplantation, University Medical Center Ulm, Germany 2
Introduction
▼
Noninvasive ventilation (NIV) is considered as first line respiratory support for acute respiratory failure (ARF) in adult immunocompromised patients [5, 25]. Antonelli et al. randomized 40 patients with hypoxemic ARF after solid organ transplantation to NIV or standard therapy [2] and observed a decrease in mortality, a lower rate of intubation and a shorter Intensive Care Unit (ICU) stay amongst survivors. Similar findings were reported by Hilbert et al. in their randomized trial including 52 immunocompromised adult patients with ARF and pulmonary infiltrates: The use of NIV decreased intubation rate and mortality compared to standard therapy [12]. Several observational studies support these benefits [11, 18]. However, some more recent observational studies challenged the protective effect of NIV in this population [7, 30]. Depuy et al. retrospectively analysed 137 hematological patients with ARF. In multivariate regression analysis not the type of initial respiratory support but illness severity and organ failure were associated with mortality in his cohort [7]. Therefore, selection of patients as well as timing of the beginning of respiratory support [26] might be crucial factors for a successful noninvasive ventilatory approach. Several studies identified predictors of NIV success and failure in order to help choosing the appropriate patients [1, 3, 8, 11, 16, 17]. Limited data are available on the use of NIV in immunocompromised children. Feasibility of NIV for acute respiratory distress syndrome (ARDS) at young age in immunocompromised patients was demonstrated in observational studies [18, 21, 24]. Good tolerance of NIV and lack of major complications were reported. Recently, Piastra et al. identified the number of failing organs as strongest predictor of NIV failure in a cohort of immunocompromised children [21]. Because of these encouraging findings, we used NIV to treat respiratory failure in immunocompromised infants and children since 1999. The current retrospective analysis was performed to analyse outcome, prognostic factors for successful NIV and side effects in our cohort of immunocompromised pediatric patients treated with NIV.
Patients and methods
▼
This retrospective cohort study was approved by the ethics committee of the University of Ulm, Germany (No. 145/09). Immunocompromised patients treated with NIV for ARF at the level 3 pediatric intensive care unit of the Department for Pediatrics and Adolescent Medicine, xxx University between 1999 and 2007 were included. Immunosuppression was defined as primary immunodeficiency, ongoing chemotherapy for malignancy or ongoing treatment with allogenic SCT. Patients were excluded if NIV was used for less than 30 min as an intended bridge to immediate intubation. Medical records of included patients were reviewed. Only the first episode of NIV was analysed if repeated NIV treatment was necessary during the hospital course. Our hospital policy suggests NIV as first line support for ARF in immunocompromised patients on the ICU to avoid intubation and mechanical ventilation. In general NIV was delivered by full face masks. In young infants a nasopharyngeal tube (Vygon,ID 3.0–4.5 mm, Ecouen, France) or nasal prongs (Dräger, Lübeck, Germany) were used as interface, if no sufficient face mask fitting was possible. Ventilation was delivered using the Bipap Vision (Phillips Respironics, HamFuchs H et al. The Cause of Acute … Klin Padiatr
burg, Germany), Servo I (Maquet, Rastatt, Germany) or Evita 4 (Dräger, Lübeck, Germany). The preferred mode was pressure support ventilation. Expiratory and inspiratory pressures were set at a level achieving sufficient arterial saturation and ventilation and are given below. Inhaled oxygen/air was humidified. Standard monitoring during NIV included SpO2, heart rate, respiratory rate, ECG, noninvasive blood pressure, transcutaneous PCO2 and repeated chest x-rays and blood gases. If hypotension occurred requiring treatment with catecholamines, continuous invasive blood pressure monitoring was started. A nasogastric tube was inserted in cases of recurrent vomiting. Sedative drugs (benzodiazepines, opioids, barbiturates, ketamine, neuroleptics) were given when required. Failure of NIV was defined as need for endotracheal intubation followed by mechanical ventilation. The threshold for intubation was decided by the attending physician, but by unit policy frequently was not undertaken until there was inability to achieve a SpO2 > 85 % despite fraction of inspired oxygen (FiO2) > 0.8–1.0 or if the PCO2 was > 80 mm Hg. All patients received standard routine care for ARDS and their underlying condition according to local hospital guidelines. This included a low tidal volume strategy, high frequency oscillation ventilation in selected patients, permission of hypercapnia, frequent prone position. In general a diagnostic workup was performed including repeated bronchioalveolar lavage and/or lung biopsies in selected patients. Most patients received broad spectrum antibacterial therapy, antifugal therapy and antiviral therapies. Immunosuppression including steroids or other immunosuppressants were given if indicated. PRISM III 24 score and PELOD were calculated [15, 22] and the number of failing organs were determined [10]. Blood cultures positive up to 7 days prior to ARF were considered to be related to this episode of ARF. Suspected sepsis was defined as high fever and chills in the neutropenic patient with clinical response to antibiotics but failure to draw cultures prior to start of anti biotics. The diagnosis of viral pneumonia was based on detection of viral antigens, PCR or positive viral cultures in tracheal secretions or bronchoalveolar lavage. The diagnosis of fungal infection was based on the detection of Candia species in the blood culture, of Pneumocystis jirovecii in the bronchoalveolar lavage. Systemic aspergillosis was either diagnosed post mortem by histology or the diagnosis was based on very typical radiological findings. Prior invasive mechanical ventilation was defined as extubation from mechanical ventilation up to 48 h before beginning of NIV that was instituted for recurrence of respiratory failure. Cardiopulmonary resuscitation at intubation included treatment with high dose epinephrine and/or chest compressions related to the intubation procedure. Statistics: Data were processed in Excel (Microsoft, Redmond, WA). Mean and interquartile ranges are given. Statistical analysis was performed using the t-test, u-test, Χ2-test or fishers exact test as appropriate. A 2-way repeated measures ANOVA (TukeyTest for subsequent multiple comparison procedure) was used to analyze repeated measurements. Data were analyzed using SigmaStat V2.03 (Systat Software, San Jose, California).
Results
▼
During the study period a total of 123 immunocompromised pediatric patients were admitted to the pediatric ICU during 168 episodes. Respiratory support was necessary in 84 children
Downloaded by: Universite Laval. Copyrighted material.
KlinPadiatr/0748/7.1.2015/MPS
Original Article
KlinPadiatr/0748/7.1.2015/MPS
Table 1 Patient data. patients (n) age (years) weight (kg) male/female (n) allogenic stem cell transplantation (n) primary immunodeficiency (n) SCID (T-neg, B-pos; common γ-chain, unkown defect) SCID (T-neg, B-neg; RAG1-deficiency) MHCII-deficiency Hyper IgM-syndrome CID (B-neg) Wiscott-Aldrich-Syndrome immunodeficieny with severe autoimmunity chronic granulomatous disease acute leukemia (n) ALL-high risk (n) ALL-relapse (n) AML-relapse (n) other (n) SAA (n) Fanconi anemia (n) congenital haemolytic anemia (n) sideroblastic anemia (n) thalassemia (n) osteopetrosis (n) non-stem cell transplantation (n) primary immunodeficiency (n) SCID (T-neg, B-pos; Il-7-receptor deficiency) (n) SCID (T-neg, B-neg; unknown defect) (n) CID (bicytopenia) (n) acute leukemia (n) ALL (n) AML (n) other (n) Langerhans cell histiocytosis (n) Hodgkin disease (n) osteopetrosis (n) prior mechanical ventilation (n)
41 8.7 (1.1;11.9) 24.4 (7.4;38.8) 26/15 29 12 5 1 1 1 1 1 1 1 10 2 6 2 7 1 1 1 1 1 2 12 3 1 1 1 6 3 3 3 1 1 1 7
Median (interquartile range); SCID = severe combined immunodeficiency; CID = combined immunodeficiency; ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia
uring 119 admissions. 56 of these patients died (66 %). In 41 d children during 60 admissions NIV was part of the respiratory management. Patient data of the 41 patients treated with NIV are given in ▶ Table 1. During their first episode of pediatric ICU admission ● endotracheal intubation and mechanical ventilation could be avoided in 11/41 (27 %) children. These 11 children were discharged alive from the ICU. 30/41 (73 %) failed NIV and required invasive ventilation. NIV failure occurred after 31 (11;79) h. The latest failure was due to deteriorating respiratory function in a patient with interstitial pneumonia after 18 days of NIV. The ICUmortality of children with NIV failure was 19/30 (63 %; ● ▶ Fig. 1). However, 8/11 (72 %) of the patients with initial NIV success had recurrence of ARF after 27 (7;304) days requiring noninvasive or subsequent invasive ventilation again. Finally, 4/11 (36 %) children with initial NIV success and 8/30 (27 %) children with initial ▶ Fig. 1). Therefore, NIV failure survived to hospital discharge ( ● the hospital survival rate of this cohort of immunocompromised children with first episode ICU admission for ARF and treated with NIV was 12/41 (29 %). ▶ Table 2 shows characteristics of patients with NIV success or ● failure. Lower FiO2 and higher SpO2/FiO2 at presentation predicted first episode NIV success, while acidosis or level of PCO2 did not. Changes in SpO2/FiO2, pH, PCO2, respiratory rate, systolic blood pressure after 2–4 h were not different between groups. However, the heart rate decreased more in patients with NIV ▶ Table 2, ● ▶ Fig. 2). success ( ● Patients with subsequent NIV success had lower PRISM III 24h scores at admission and lower maximum PELOD scores throughout the hospital course. The number of failing organs at admission was not statistically different. Leukopenia or thrombocytopenia was not associated with NIV response, nor was mechanical ventilation up to 48 h prior to NIV. Blood culture positive sepsis (Staphylococcus epidermidis, n = 2; Streptococcus viridans, n = 1; Streptococcus oralis n = 1) and highly suspected bacterial sepsis (n = 2) was associated with NIV success. Viral pneumonia was not associated with NIV response. Fungal infection and ARF ▶ Table 2). without infection were associated with NIV failure ( ● We observed hypotension with need for catecholamine treatment in 14/41 (34 %), pneumothorax in 2/41 (5 %), mediastinal
Children after chemotherapy for mailgnancy or SCT with ARF treated with NIV (n =41) NIV-Success n= 11/41 (27 %) Survival n=11/11 (100 %) Discharged from PICU n = 11/11 (100 %)
NIV-Failure n =30/41 (73%) Survival n= 11/30 (37%) Discharged from PICU n= 11/30 (37%)
Mortality
Fig. 1 Survival rates. Patient survival is given for patients with NIV success and NIV failure. Mean (Min; Max) are given * . SCT = stem cell transplantation; ARF = acute respiratory failure; d = days.
19/41 (46%)
27 (7;304) d* Relapse-ARF n= 8/11 (72 %) Survival n= 3/8 (54 %) Discharged from PICU n = 3/8 (54 %)
Death from reasons other than ARF n=2/11 (18 %) Discharged from hospital n=4/11 (36 %)
n= 24/41 (59%)
Death from reasons other than ARF n = 3/30 (10%) Discharged from hospital n = 8/30 (27%)
n= 29/41 (71%)
Fuchs H et al. The Cause of Acute … Klin Padiatr
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Original Article
KlinPadiatr/0748/7.1.2015/MPS
age weight male PRISM III 24 Score PELOD Score number of failing organs ≥ 2 allogenic SCT primary immunodeficiency leukemia prior invasive mechanical ventilation leukopenia ( 2 BC positive sepsis/ fever in aplasia fungal infection/ culture negative viral pneumonia SCT leukemia immunodeficiency air leak during NIV resuscitation at intubation
6 month mortality
0.0 2.29
– (0.58;9.02)
0.6 2.12
(0.14;2.45) (0.47;9.5)
6.56 1.36
(1.61;26.71) (0.39;4.7)
2.4 1.56
(0.65;8.81) (0.43;5.6)
0.0
–
0.52
(0.09;3.0)
1.71
(0.49;6.0)
1.56
(0.43;5.6)
1.45 1.87 0.41 0.77 2.1 2.1
(0.4;5.33) (0.46;7.6) (0.11;0.57) (0.21;2.82) (0.31;14.2) (0.31;14.2)
1.06 3.68 1.0 0.93 0.85 2.54
(0.28;4.06) (0.9;15.01) (0.27;3.69) (0.26;3.44) (0.12;5.75) (0.25;25.17)
Odds ratio (95 %, confidence interval); BK = blood culture; SCT = stem cell transplantation; NIV = noninvasive ventilation
(11;72) h; P
Original Article
The Cause of Acute Respiratory Failure Predicts the Outcome of Noninvasive Ventilation in Immunocompromised Children Die Ursache des Akuten Atemversagens sagt den Outcome von Nichtinvasiver Beatmung bei Kindern mit Immunsuppression vorher Authors
H. Fuchs1, J. Schoss2, M. R. Mendler2, W. Lindner2, R. Hopfner2, A. Schulz3, M. Hoenig3, D. Steinbach3, K.-M. Debatin3, H. D. Hummler2, M. Schmid2
Affiliations
1
Key words ▶ acute respiratory distress ● syndrome ▶ noninvasive ventilation ● ▶ non-invasive ventilation ● ▶ immunosuppression ● ▶ stem cell transplantation ● ▶ cancer ●
Abstract
Zusammenfassung
Background: Noninvasive ventilation (NIV) may be superior to conventional therapy in immunocompromised children with respiratory failure. Methods: Mortality, success rate, prognostic factors and side effects of NIV for acute respiratory failure (ARF) were investigated retrospectively in 41 in children with primary immunodeficiency, after stem cell transplantation or chemotherapy for oncologic disease. Results: In 11/41 (27 %) children invasive ventilation was avoided and patients were discharged from ICU. In children with NIV failure ICU-mortality was 19/30 (63 %). 8/11 (72 %) children with NIV success had recurrence of ARF after 27 days. Only 4/11 (36 %) children with first episode NIV success and 8/30 (27 %) with NIV failure survived to hospital discharge. Lower FiO2, SpO2/FiO2 and blood culture positive bacterial sepsis were predictive for NIV success, while fungal sepsis or culture negative ARF were predictive for NIV failure. We observed catecholamine treatment in 14/41 (34 %), pneumothorax in 2/41 (5 %), mediastinal emphysema in 3/41 (7 %), a life threatening nasopharyngeal hemorrhage and need for resuscitation during intubation in 5/41 (12 %) NIV-episodes. Conclusions: The prognosis of ARF in immunocompromised children remains guarded independent of initial success or failure of NIV due to a high rate of recurrent ARF. Reversible causes like bacterial sepsis had a higher NIV response rate. Relevant side effects of NIV were observed.
Hintergrund: Nichtinvasive Beatmung könnte gegenüber konventioneller Therapie eine Vorteil bei der Behandlung des Atemversagens bei immunsupprimierten Kindern haben. Methoden: Mortalität, Erfolgsrate, prognostische Faktoren und Nebenwirkungen von nichtinvasiver Beatmung (NIV) beim akuten Atemversagen (ARF) wurden retrospektiv in einer Kohorte von 41 Kindern mit primärem Immundefekt, nach onkologischer Therapie oder nach Stamm zelltransplantation untersucht. Ergebnisse: Bei 11/41 (27 %) konnte die Intubation vermieden werden und die Kinder wurden von der Intensivstation entlassen. Die Intensivmortalität der Kinder mit NIV-Versagen betrug 19/30 (63 %). 8/11 (72 %) Kinder mit NIV-Erfolg wurden nach im Median 27 Tagen mit erneutem Atemversagen auf die Intensivstation wiederaufgenommen und benötigten erneut NIV. Nur 4/11 (36 %) Kinder mit NIV-Erfolg in der ersten Episode und 8/30 (27 %) Kinder mit NIV-Versagen überlebten bis zur Krankenhausentlassung. Niedrigerer FiO2, SpO2/FiO2 und blutkulturpositive bakterielle Sepsis waren mit NIV-Erfolg, während Pilzinfektionen oder kultur-negatives Atemversagen mit NIV-Versagen assoziiert waren. Als Nebenwirkungen wurden Katecholaminbedarf in 14/41 (34 %), Pneumothorax in 2/41 (5 %), Mediastinalemphysem in 3/41 (7 %), und Notwendigkeit zur Reanimation im Rahmen der Intubation bei 5/41 (12 %) der NIV-Episoden beobachtet. Schlussfolgerung: Die Prognose des ARF bei immunsupprimierten Kindern ist eingeschränkt, unabhängig vom initialen Erfolg oder Versagen der NIV aufgrund der hohen Rate an Rezidiven des Atemversagens. Behandelbare Ursachen des Atemversagens wie bakterielle Sepsis hatten eine höhere Rate an NIV-Erfolg. Relevante Nebenwirkungen der NIV müssen beachtet werden.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1395692 Published online: 2015 Klin Padiatr © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Hans Fuchs, MD Neonatology and Pediatric Critical Care Center for Pediatrics Mathildenstrasse 1 79104 Freiburg Tel.: + 49/761/27045 190 Fax: + 49/761/270 43990 [email protected]
▼
▼
Fuchs H et al. The Cause of Acute … Klin Padiatr
Downloaded by: Universite Laval. Copyrighted material.
Schlüsselwörter ▶ akutes Atemversagen ● ▶ nichtinvasive Beatmung ● ▶ nicht-invasive Beatmung ● ▶ Immunsuppression ● ▶ Stammzelltransplantation ● ▶ Krebserkrankung ●
Department of Neonatology and Pediatric Critical Care, Center for Pediatrics, Freiburg, Germany Division of Neonatology and Pediatric Critical Care, University Medical Center Ulm, Germany 3 Department of Oncology and Stem Cell Transplantation, University Medical Center Ulm, Germany 2
Introduction
▼
Noninvasive ventilation (NIV) is considered as first line respiratory support for acute respiratory failure (ARF) in adult immunocompromised patients [5, 25]. Antonelli et al. randomized 40 patients with hypoxemic ARF after solid organ transplantation to NIV or standard therapy [2] and observed a decrease in mortality, a lower rate of intubation and a shorter Intensive Care Unit (ICU) stay amongst survivors. Similar findings were reported by Hilbert et al. in their randomized trial including 52 immunocompromised adult patients with ARF and pulmonary infiltrates: The use of NIV decreased intubation rate and mortality compared to standard therapy [12]. Several observational studies support these benefits [11, 18]. However, some more recent observational studies challenged the protective effect of NIV in this population [7, 30]. Depuy et al. retrospectively analysed 137 hematological patients with ARF. In multivariate regression analysis not the type of initial respiratory support but illness severity and organ failure were associated with mortality in his cohort [7]. Therefore, selection of patients as well as timing of the beginning of respiratory support [26] might be crucial factors for a successful noninvasive ventilatory approach. Several studies identified predictors of NIV success and failure in order to help choosing the appropriate patients [1, 3, 8, 11, 16, 17]. Limited data are available on the use of NIV in immunocompromised children. Feasibility of NIV for acute respiratory distress syndrome (ARDS) at young age in immunocompromised patients was demonstrated in observational studies [18, 21, 24]. Good tolerance of NIV and lack of major complications were reported. Recently, Piastra et al. identified the number of failing organs as strongest predictor of NIV failure in a cohort of immunocompromised children [21]. Because of these encouraging findings, we used NIV to treat respiratory failure in immunocompromised infants and children since 1999. The current retrospective analysis was performed to analyse outcome, prognostic factors for successful NIV and side effects in our cohort of immunocompromised pediatric patients treated with NIV.
Patients and methods
▼
This retrospective cohort study was approved by the ethics committee of the University of Ulm, Germany (No. 145/09). Immunocompromised patients treated with NIV for ARF at the level 3 pediatric intensive care unit of the Department for Pediatrics and Adolescent Medicine, xxx University between 1999 and 2007 were included. Immunosuppression was defined as primary immunodeficiency, ongoing chemotherapy for malignancy or ongoing treatment with allogenic SCT. Patients were excluded if NIV was used for less than 30 min as an intended bridge to immediate intubation. Medical records of included patients were reviewed. Only the first episode of NIV was analysed if repeated NIV treatment was necessary during the hospital course. Our hospital policy suggests NIV as first line support for ARF in immunocompromised patients on the ICU to avoid intubation and mechanical ventilation. In general NIV was delivered by full face masks. In young infants a nasopharyngeal tube (Vygon,ID 3.0–4.5 mm, Ecouen, France) or nasal prongs (Dräger, Lübeck, Germany) were used as interface, if no sufficient face mask fitting was possible. Ventilation was delivered using the Bipap Vision (Phillips Respironics, HamFuchs H et al. The Cause of Acute … Klin Padiatr
burg, Germany), Servo I (Maquet, Rastatt, Germany) or Evita 4 (Dräger, Lübeck, Germany). The preferred mode was pressure support ventilation. Expiratory and inspiratory pressures were set at a level achieving sufficient arterial saturation and ventilation and are given below. Inhaled oxygen/air was humidified. Standard monitoring during NIV included SpO2, heart rate, respiratory rate, ECG, noninvasive blood pressure, transcutaneous PCO2 and repeated chest x-rays and blood gases. If hypotension occurred requiring treatment with catecholamines, continuous invasive blood pressure monitoring was started. A nasogastric tube was inserted in cases of recurrent vomiting. Sedative drugs (benzodiazepines, opioids, barbiturates, ketamine, neuroleptics) were given when required. Failure of NIV was defined as need for endotracheal intubation followed by mechanical ventilation. The threshold for intubation was decided by the attending physician, but by unit policy frequently was not undertaken until there was inability to achieve a SpO2 > 85 % despite fraction of inspired oxygen (FiO2) > 0.8–1.0 or if the PCO2 was > 80 mm Hg. All patients received standard routine care for ARDS and their underlying condition according to local hospital guidelines. This included a low tidal volume strategy, high frequency oscillation ventilation in selected patients, permission of hypercapnia, frequent prone position. In general a diagnostic workup was performed including repeated bronchioalveolar lavage and/or lung biopsies in selected patients. Most patients received broad spectrum antibacterial therapy, antifugal therapy and antiviral therapies. Immunosuppression including steroids or other immunosuppressants were given if indicated. PRISM III 24 score and PELOD were calculated [15, 22] and the number of failing organs were determined [10]. Blood cultures positive up to 7 days prior to ARF were considered to be related to this episode of ARF. Suspected sepsis was defined as high fever and chills in the neutropenic patient with clinical response to antibiotics but failure to draw cultures prior to start of anti biotics. The diagnosis of viral pneumonia was based on detection of viral antigens, PCR or positive viral cultures in tracheal secretions or bronchoalveolar lavage. The diagnosis of fungal infection was based on the detection of Candia species in the blood culture, of Pneumocystis jirovecii in the bronchoalveolar lavage. Systemic aspergillosis was either diagnosed post mortem by histology or the diagnosis was based on very typical radiological findings. Prior invasive mechanical ventilation was defined as extubation from mechanical ventilation up to 48 h before beginning of NIV that was instituted for recurrence of respiratory failure. Cardiopulmonary resuscitation at intubation included treatment with high dose epinephrine and/or chest compressions related to the intubation procedure. Statistics: Data were processed in Excel (Microsoft, Redmond, WA). Mean and interquartile ranges are given. Statistical analysis was performed using the t-test, u-test, Χ2-test or fishers exact test as appropriate. A 2-way repeated measures ANOVA (TukeyTest for subsequent multiple comparison procedure) was used to analyze repeated measurements. Data were analyzed using SigmaStat V2.03 (Systat Software, San Jose, California).
Results
▼
During the study period a total of 123 immunocompromised pediatric patients were admitted to the pediatric ICU during 168 episodes. Respiratory support was necessary in 84 children
Downloaded by: Universite Laval. Copyrighted material.
KlinPadiatr/0748/7.1.2015/MPS
Original Article
KlinPadiatr/0748/7.1.2015/MPS
Table 1 Patient data. patients (n) age (years) weight (kg) male/female (n) allogenic stem cell transplantation (n) primary immunodeficiency (n) SCID (T-neg, B-pos; common γ-chain, unkown defect) SCID (T-neg, B-neg; RAG1-deficiency) MHCII-deficiency Hyper IgM-syndrome CID (B-neg) Wiscott-Aldrich-Syndrome immunodeficieny with severe autoimmunity chronic granulomatous disease acute leukemia (n) ALL-high risk (n) ALL-relapse (n) AML-relapse (n) other (n) SAA (n) Fanconi anemia (n) congenital haemolytic anemia (n) sideroblastic anemia (n) thalassemia (n) osteopetrosis (n) non-stem cell transplantation (n) primary immunodeficiency (n) SCID (T-neg, B-pos; Il-7-receptor deficiency) (n) SCID (T-neg, B-neg; unknown defect) (n) CID (bicytopenia) (n) acute leukemia (n) ALL (n) AML (n) other (n) Langerhans cell histiocytosis (n) Hodgkin disease (n) osteopetrosis (n) prior mechanical ventilation (n)
41 8.7 (1.1;11.9) 24.4 (7.4;38.8) 26/15 29 12 5 1 1 1 1 1 1 1 10 2 6 2 7 1 1 1 1 1 2 12 3 1 1 1 6 3 3 3 1 1 1 7
Median (interquartile range); SCID = severe combined immunodeficiency; CID = combined immunodeficiency; ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia
uring 119 admissions. 56 of these patients died (66 %). In 41 d children during 60 admissions NIV was part of the respiratory management. Patient data of the 41 patients treated with NIV are given in ▶ Table 1. During their first episode of pediatric ICU admission ● endotracheal intubation and mechanical ventilation could be avoided in 11/41 (27 %) children. These 11 children were discharged alive from the ICU. 30/41 (73 %) failed NIV and required invasive ventilation. NIV failure occurred after 31 (11;79) h. The latest failure was due to deteriorating respiratory function in a patient with interstitial pneumonia after 18 days of NIV. The ICUmortality of children with NIV failure was 19/30 (63 %; ● ▶ Fig. 1). However, 8/11 (72 %) of the patients with initial NIV success had recurrence of ARF after 27 (7;304) days requiring noninvasive or subsequent invasive ventilation again. Finally, 4/11 (36 %) children with initial NIV success and 8/30 (27 %) children with initial ▶ Fig. 1). Therefore, NIV failure survived to hospital discharge ( ● the hospital survival rate of this cohort of immunocompromised children with first episode ICU admission for ARF and treated with NIV was 12/41 (29 %). ▶ Table 2 shows characteristics of patients with NIV success or ● failure. Lower FiO2 and higher SpO2/FiO2 at presentation predicted first episode NIV success, while acidosis or level of PCO2 did not. Changes in SpO2/FiO2, pH, PCO2, respiratory rate, systolic blood pressure after 2–4 h were not different between groups. However, the heart rate decreased more in patients with NIV ▶ Table 2, ● ▶ Fig. 2). success ( ● Patients with subsequent NIV success had lower PRISM III 24h scores at admission and lower maximum PELOD scores throughout the hospital course. The number of failing organs at admission was not statistically different. Leukopenia or thrombocytopenia was not associated with NIV response, nor was mechanical ventilation up to 48 h prior to NIV. Blood culture positive sepsis (Staphylococcus epidermidis, n = 2; Streptococcus viridans, n = 1; Streptococcus oralis n = 1) and highly suspected bacterial sepsis (n = 2) was associated with NIV success. Viral pneumonia was not associated with NIV response. Fungal infection and ARF ▶ Table 2). without infection were associated with NIV failure ( ● We observed hypotension with need for catecholamine treatment in 14/41 (34 %), pneumothorax in 2/41 (5 %), mediastinal
Children after chemotherapy for mailgnancy or SCT with ARF treated with NIV (n =41) NIV-Success n= 11/41 (27 %) Survival n=11/11 (100 %) Discharged from PICU n = 11/11 (100 %)
NIV-Failure n =30/41 (73%) Survival n= 11/30 (37%) Discharged from PICU n= 11/30 (37%)
Mortality
Fig. 1 Survival rates. Patient survival is given for patients with NIV success and NIV failure. Mean (Min; Max) are given * . SCT = stem cell transplantation; ARF = acute respiratory failure; d = days.
19/41 (46%)
27 (7;304) d* Relapse-ARF n= 8/11 (72 %) Survival n= 3/8 (54 %) Discharged from PICU n = 3/8 (54 %)
Death from reasons other than ARF n=2/11 (18 %) Discharged from hospital n=4/11 (36 %)
n= 24/41 (59%)
Death from reasons other than ARF n = 3/30 (10%) Discharged from hospital n = 8/30 (27%)
n= 29/41 (71%)
Fuchs H et al. The Cause of Acute … Klin Padiatr
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Original Article
KlinPadiatr/0748/7.1.2015/MPS
age weight male PRISM III 24 Score PELOD Score number of failing organs ≥ 2 allogenic SCT primary immunodeficiency leukemia prior invasive mechanical ventilation leukopenia ( 2 BC positive sepsis/ fever in aplasia fungal infection/ culture negative viral pneumonia SCT leukemia immunodeficiency air leak during NIV resuscitation at intubation
6 month mortality
0.0 2.29
– (0.58;9.02)
0.6 2.12
(0.14;2.45) (0.47;9.5)
6.56 1.36
(1.61;26.71) (0.39;4.7)
2.4 1.56
(0.65;8.81) (0.43;5.6)
0.0
–
0.52
(0.09;3.0)
1.71
(0.49;6.0)
1.56
(0.43;5.6)
1.45 1.87 0.41 0.77 2.1 2.1
(0.4;5.33) (0.46;7.6) (0.11;0.57) (0.21;2.82) (0.31;14.2) (0.31;14.2)
1.06 3.68 1.0 0.93 0.85 2.54
(0.28;4.06) (0.9;15.01) (0.27;3.69) (0.26;3.44) (0.12;5.75) (0.25;25.17)
Odds ratio (95 %, confidence interval); BK = blood culture; SCT = stem cell transplantation; NIV = noninvasive ventilation
(11;72) h; P
