Non-invasive and Invasive Ventilation in the Pediatric BMT Population

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat.And my name is Rahul Damania, we come to you from Children's Healthcare of Atlanta/Emory University School of Medicine. Today's episode is dedicated to Noninvasive and Invasive ventilation in children post-hematopoietic cell transplantation.We are delighted to be joined by Dr. Courtney Rowan, MD, MSCR, Associate Professor of Pediatrics, and the Director of the Pediatric Critical care Fellowship at Indiana University School of Medicine/Riley Children’s Health.Dr. Rowan's research interest is in improving the outcomes of immunocompromised children with respiratory failure. She is active in this field of research and has led and participated in multi-centered studies. She is the co-chair of the committee of the hematopoietic cell transplantation subgroup of the Pediatric acute lung injury and sepsis investigators network. In our podcast today we will be asking Dr. Rowan about the findings of her recent study published in the journal-Frontiers in Oncology reporting on the risk factors for noninvasive ventilation failure in children post hematopoietic cell transplant.She is on twitter @CmRowan.Patient CaseI will turn it over to Rahul to start with our patient case...A 15-year-old female with a history of AML s/p Allogeneic hematopoietic stem cell transplantation T+15 days presents with tachypnea and a new O2 requirement. She has been on the BMT floor for 48 hrs after being admitted for respiratory distress and fevers. Her blood cultures are negative but she is febrile intermittently. Her CXR shows nonspecific haziness, no focal opacity, and underinflation. Her weight is up 2KG in the last 48 hours. She is found to have increased work of breathing and mild desaturations to 88%. She is placed on HFNC and continued on broad-spectrum antibiotics. A respiratory viral panel and Sars-CoV-2 PCR is sent. Transfer to the Pediatric ICU is initiated.Episode DialogueDr. Rowan, welcome to our PICU Doc on-call podcast.Dr. Rowan: Thanks Rahul & Pradip for having me. I am delighted to be here to discuss one of my favorite topics. I have no conflicts of interest but I have funding from the NHLBI.Today we will be discussing the up-to-date evidence for NIV (HFNC and NIPPV) use in children who have had BMT. Additionally, we will also be discussing the use of invasive MV strategies including HFOV in the pediatric BMT population. To start us off, Dr. Rowan, why is the BMT cohort different from other patients admitted to the PICU?There is an increase in the # of patients undergoing BMT as indications for BMT are being expanded to different disease processes. The Etiologies for lung disease in BMT patients can be infectious (common organisms as well as opportunistic organisms). They can have lung disease from non-infectious causes and even fluid overload from renal dysfunction/medications given and there is a constant threat of alloreactivity which can manifest as GVHD or engraftment syndrome. 75% of PICU admits of immunocompromised children come from the heme-onc inpatient services. BMT patients have a higher risk to progress to ARDS. Recent reports show the incidence of ARDS in the intubated BMT population reaching upwards of 92%. These patients are also at high risk for MODS and can have a mortality rate close to 60%.💡 To summarize, the BMT population is a unique ever-growing population that represents a relatively large cohort of immunocompromised children in the PICU with a risk of high mortality. As we have set this basis, we will be focusing the rest of our episode on the need for early recognition and intervention in this special population.Dr. Rowan: A common conundrum faced by the PICU team given limited resources and bed availability is when to transfer a patient with BMT to the PICU especially when they start requiring respiratory support on the floor. Are there any risk factors we as PICU physicians need to know which can help us transfer a child from the BMT floor to the PICU in a time-appropriate manner?Dr. Rowan: This is a great question. We have had a few studies examining this very question. In a paper we published in Pediatr Blood Cancer in 2017, we evaluated 87 allogeneic HCT recipients to investigate the association of clinical risk factors with the development of respiratory failure.Of the 87 allogeneic HCT recipients, 22 (25%) developed respiratory failure. The group with respiratory failure had a significantly higher percent weight gain increase at multiple time points.The odds ratio, (OR) for respiratory, failure increased with increasing percentage peak weight gain. We also found that the OR for respiratory failure in patients requiring more than 1 liter supplemental O2 is 25.3 (6.5, 98.7).We concluded that the percent weight gain and need for supplemental oxygen is highly associated with the development of respiratory failure in pediatric HCT recipients. Additionally, Dr. Algunik et al, have reported (PCCM 2016) that Pediatric Early Warning Score is highly correlated with the need for unplanned PICU transfer in hospitalized oncology and hematopoietic stem cell transplant patients. Additionally, the authors also reported an association between higher scores and PICU mortality. In another study, Dr. Algunik et al (Cancer 2017)reported that PEWS accurately predicted the need for unplanned PICU transfer in pediatric oncology patients in this resource-limited setting, with abnormal results beginning 24 hours before PICU admission and higher scores predicting the severity of illness at the time of PICU admission, need for PICU interventions, and mortality.Cater et al (PCCM 2018) showed that adding weight gain to PEWs (cutoff of 8) score can increase specificity as well as the AUC to predict children with BMT at risk for clinical deterioration.💡 Key points from these studies which we can clinically apply — trending of weights and attention to respiratory support and PEWS. Contingency planning and prompt recognition of when to initiate a transfer from floor to PICU is essential in intervening early.Dr. Rowan: What are the advantages of early transfer of BMT patients to the PICU?A controlled transfer with the pediatric patient not in extremis allows for opportunities and time for in-depth multidisciplinary discussion.This also allocates time for goals of care discussions.We need to balance this with bed availability, familial stress of transitioning their stay from the floor to the PICU and introduction of a new care team being us in the PICU.Dr. Rowan: In the case above, our patient was started on non-invasive PPV and antibiotics prior to transfer to the PICU. Could you comment on the ideal interface to provide respiratory support in our patient in this case?Little data for BMT pediatric patients for NIV compared to adults. Adult studies show that there is no difference between HFNC and standard O2 (Lemiale CCM 2017) in terms of intubation rate /mortality. Similarly, a large RCT in 776 immunocompromised adults which compared HFNC to standard O2 therapy showed no difference to 28-day mortality, LOS (ICU) stay, patient comfort or dyspnea scores (Azoulay E JAMA 2018).As mentioned there is Limited Pediatric data on HFNC use in BMT patients however we can extrapolate that the pediatric BMT population are not merely "tiny adults" and have different respiratory mechanics as well as a physiologic reserve.Multiple RCT of NIV vs supplemental O2 (374 organ transplant patients) (Antonelli JAMA 2015) showed no difference in intubation rates or mortality. Frat (Lancet 2016): Compared Adults on HFNC to NIV via supplemental O2 in 82 immunocompromised adults. They concluded that those on supplemental O2 had the highest risk for intubation and worst survival. A study by Squadrone V., et al in Intensive Care Med, published in 2010 Compared early 40 adults with BMT who were placed on CPAP were less likely to go to ICU, less likely to be intubated, and had better survival.Pediatric data on NIV is limited however a study by Pancera and colleagues published in 2008 in the journal of Pediatric Heme Onc concluded that the use of BIPAP in the pediatric oncology...