Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

My name is Rahul Damania, a current 3rd-year pediatric critical care fellow and we are coming to you from Children’s Healthcare of Atlanta Emory University School of Medicine

Today’s episode is dedicated to the transition between NICU & PICU. We will focus on the ventilation of the ex-premature infant who graduated from NICU care and transitioned to the PICU.

I will turn it over to Rahul to start with our patient case.

  • Case: A 4-month-old ex-27 week baby boy is transferred to our PICU after an echo at an outside hospital showed elevated pulmonary pressures. The infant was born via a stat C-section due to maternal complications during pregnancy. His birth weight was 560 g. The patient was intubated shortly after delivery and had a protracted course in the NICU which included a sepsis rule out, increased ventilator settings, and a few weeks on inhaled nitric oxide (iNO).
  1. The intubation course was complicated pulmonary hemorrhage on day 1 after intubation. After such an extensive NICU course, thankfully, the infant survived & was sent home on 1/2 LPM NC, diuretics, albuterol, inhaled corticosteroids, Synthroid, multivitamin with iron as well as Vitamin D. The patient was able to tolerate breast milk via NG tube and had a home apnea monitor with pulse oximetry.
  • After about a week’s stay at home, the mother noted that the patient’s SPO2 was in the low 80s. The mother took the patient to the local hospital, where the patient was started on HFNC which improved his saturations. An echo done at the OSH showed elevated RV pressures (higher than the prior echo). The patient was subsequently transferred to our hospital for further management. At our hospital, the patient presented hypoxemic, tachycardic, and tachypneic. On physical exam: Baby appeared well developed, had a systolic murmur heard throughout the precordium, and there was increased WOB with significant intercostal retraction. There was no hepatosplenomegaly.
  • Due to worsening respiratory distress, and increasing FIO2 requirement despite maximum RAM cannula, the patient was intubated and placed on conventional MV. A blood gas prior to intubation revealed a pH of 7.1/PCO2 of 100. An arterial line and a central venous line were also placed for better access and monitoring. Initial vent settings post intubation PRVC ventilation: TV 32cc, (25/10), 0.7 time, rate 0 (patient sedated/paralyzed).

To summarize, What are some of the features in H&P that are concerning for you in this case:

  • Ex-27 week prematurity with a birth weight of 560 gms
  • Prolonged MV in the NICU
  • Home O2 requirement
  • Abnormal echo showing high pulmonary pressures
  • hypercarbia despite the use of RAM cannula

As mentioned, our patient was intubated, can you tell us pertinent diagnostics which were obtained?

  • CXR revealed: Hazy airspace opacification in the right upper lung concerning developing pneumonia. Streaky airspace opacity in the left lung base medially may represent atelectasis.

I do want to highlight that the intubation of an ex-premie especially with elevated RV pressures is a high-risk scenario, it is best managed by a provider with experience, in a very controlled setting with optimal team dynamics. Adequate preparation to optimize the patient prior to the intubation as well as the knowledge to manage the post intubation cardiopulmonary interactions are essential. I would highly advise you to re-visit our previous podcast on intubation of the high-risk PICU patient by Dr. Heather Viamonte. Like many Peds ICU conditions, the management of the EX-NICU graduate in the PICU is a multidisciplinary team sport.

Our patient likely has the diagnosis of Bronchopulmonary Dysplasia or BPD, Pradip, can you comment on the evolving definition of this diagnosis?

  • Let me first define BPD — Clinically, BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age. The literature stratifies the difference between old vs. new BPD definitions. In the old BPD, seen before the 1980s and in usually more mature infants – the pathogenesis is related to damage caused to the lungs from mechanical ventilation and/or oxygen resulting in inflammation/fibrosis. It can occur in premature as well as term infants. We see less of the old BPD due to the use of surfactant and HFOV use. In old BPD, we have e/o hyperinflation and diffuse parenchymal infiltrate -lung histology dilated distal airspace, fibrosis throughout the interstitium, and significant pulmonary arterial fibroproliferative disease

What about the new BPD?

New BPD: Refers to abnormal or arrest in lung development (fewer and larger alveoli) and decreased microvascular development in extremely low birth weight infants. In new BPD, we see more evidence of dilated distal lung, less evidence of fibrosis, more typically have an arrest of distal lung development, and still have vascular beds are abnormal. The key here is impaired lung surface area, decreased alveoli, and decreased vascular growth.

It is important to note that In severely affected infants, fibrosis, bronchial smooth muscle hypertrophy, and interstitial edema (“old” BPD) may be superimposed on the characteristic reduced numbers of alveoli and capillaries

Let’s transition and speak about the pathogenesis of BPD, Rahul, what are the key risk factors?

  • The important concept here is to understand the maternal fetal interface that can lead to premature birth. Determinants of disease include-Prenatal factors such as chorio-amniotic, fetal infection, IUGR, preeclampsia, maternal smoking/drug use with interplay from epigenetic/genetic factors, hyperoxia, inflammation, infection, ventilator induced lung injury can cause disruption of growth factor signaling pathways leading to changes in vascular growth, alveolar growth, and lung function.
  • There is a 43% incidence (unchanged in the last 50 years) of BPD born < 29 weeks of age. The earlier one is born, the more severe is the BPD. At autopsy, one can see Regions of Hyperinflation, areas of atelectatic/edema and have pseudo-fissures between them, and dilated distal airways with little septae (”alveolar simplification).

Pradip, as it seems the histological architecture of the lung is altered, can you comment on the persistent respiratory disease seen in BPD?

Patients with BPD can have persistent respiratory disease, which can be seen as prolonged respiratory support/NICU hospitalization, chronic respiratory distress, recurrent exacerbations, re-hospitalizations, exercise intolerance, wheezing, and increased susceptibility to chronic lung disease in adulthood. These patients may require long-term ventilatory support via an ETT or tracheostomy.

To highlight epidemiology, did you know that 58% of preterm infants are readmitted to the hospital within the first year of life. 20% of these were admitted to the PICU and 12% ended up on MV.

Pradip, we mentioned the use of mechanical ventilation in BPD. Let’s pivot today’s episode and focus on management, understanding how to invasively ventilate a patient with BPD. How can we use our understanding of ARDS (say in an adolescent) to understand the ventilation strategies in BPD?

If we look at the lungs of a teenager with ARDS and hypoxemia, we may see diffuse parenchymal infiltrates. In these patients, the CT is will show a heterogeneous disease. There is a portion of the lung which may be susceptible to atelectasis, gravity dependent, and is edematous. It is this baby lung that we want to ventilate and recruit without overstretching. It’s balance. This is why we use the ARDSnet protocol which involves low tidal volumes, typically 6-8 mL/kg. We use prone positioning and increased PEEP to help recruit the lungs.

Great, let’s contrast this with BPD, what are the radiographic and physiologic considerations in our patient who is now intubated in the PICU?

In BPD, the CT may show hyperinflation, diffuse infiltrates, peri-bronchial lesions, ground glass lesions, cystic lesions, etc. This is a stark contrast with ARDS. They can have large central airway diseases like tracheobronchomalacia, or subglottic or bronchial stenosis, and even granulomas. Patients with severe BPD can have small airway structural remodeling such as mucus gland hyperplasia and clinically we will see more secretions that are not cleared well due to ciliary dysfunction. These airways have an epithelial injury, edema, smooth muscle proliferation, broncho-constriction, and hyper-reactivity. The patients with BPD also have decreased alveolarization, decreased vascular growth (i.e. fewer vessels), abnormal vascular remodeling, tone, and reactivity as well as impaired lymphatic function. As these infants age, they can have sleep-disordered breathing, diaphragm dysfunction, and chest-wall instability. In summary, BPD affects not only the lung parenchyma, but the whole respiratory unit — pulmonary vessels, lymphatics, chest wall, and diaphragm!

Yes, it seems the take home is that the patient with severe BPD who is intubated in the PICU has vastly different physiologic and radiographic lesions compared to the run-of-the-mill teenager with acute ARDS. Hence a different ventilation and oxygenation strategy is required for the intubated BPD patient in the PICU. BPD subtypes include those with parenchymal lung disease, those with vascular disease (pulmonary arterial hypertension-evaluated at least initially with an echo), and those with airways disease (tracheo-bronchomalacia-evaluated by bronchoscopy). Additionally, a single patient may have more than one BPD subtype for example 28% can have all the above 3 subtypes. (Wu K et al. AJRCC Med 2020).

Before we dive deep into management how do you evaluate the underlying lung disease in patients with severe BPD?

We typically get CXR, blood gas, +/-Chest CT scan (may not require acutely), target SPO2 and PCO2, evaluate for chronic aspiration (ph probe, barium swallow, swallow study, etc.), sleep study, flexible bronchoscopy to evaluate structural airway disease as well as EKG, echocardiography, cardiac catheterization, etc may be required.

In terms of labs, lactates, BNP, and NT-pro BNP may be required on a case-by-case basis. Additionally, an Interstitial lung disease panel may also be required on a case-by-case basis. The management of the patient with severe BPD in the PICU is really a team sport, which involves the intensivist, the cardiologist, the pulmonologist, gastroenterologists, and support staff such as the speech therapist and the rehabilitation team. It also involves open discussions with family as these patients are hospitalized long term not infrequently. Family conferences at periodic intervals in collaboration with social workers can help optimize decision making, set goals of care, and allow for facilitation amongst teams.

Absolutely, it is a team sport!

Now Pradip, you mentioned the radiographic and lab evaluation of these patients who have chronic lung disease. As we think about continuous monitoring in the PICU, do you have some management pearls?

It is important to prevent hyperoxia by targeting an SPO2 of 92-94%. We also should avoid accepting an SPO2 of 90% as that can cause pulmonary hyper-vascular reactivity and these children can have marked vasospasm. We allow for permissive hypercapnia but avoid marked spikes or swings in PCO2 as long as pH is buffered. If PCO2 is chronically elevated its effect on PHTN is unclear. Elevated PCO2 may be a biomarker for severe parenchymal lung disease.

Rahul, we mentioned in the pathogenesis the abnormal vascular development in the pulmonary circuit, can you comment on the cardiopulmonary interactions seen in a patient with BPD?

In patients with severe BPD, we have High pulmonary artery pressures due to lung disease. Remember these children will have hyperinflation in some areas, atelectasis, and fluctuations in O2 and CO2. This can create chronic heart disease as well. Particularly RV dysfunction. Patients downstream can have issues with LV contractility as we have at times an exaggerated systolic interdependence which can affect LV contractility. The LV diastolic dysfunction may be due to persistent pulmonary edema. As these children are premature, it is also important to assess for abnormalities in cardiac development. These children will frequently have shunts. ASD, VSD, PDAs for example. The L to R shunting may create over-circulation, and in times of crises, these shunts may reverse leading to hypoxemia. Fortunately, when children have these shunts, they serve as “pop-offs” during times of increased pulmonary pressure. As we mentioned cath as one of our diagnostics it is important to assess for pulmonary vein stenosis as this fixed anatomic defect can further contribute to high pulmonary artery pressures.

In a summary, remember that the RV is relatively afterload sensitive and the LV is more sensitive to changes in preload!

As we set titrate the ventilator in our patient with BPD, Pradip, what strategies are you going to use for effective oxygenation and ventilation?

The biggest point before we go into the specific ventilator strategies is the heterogeneity of lung disease. This is not a two-compartment model as seen in ARDS. There is marked variability of regional time constants, and as mentioned, airway secretions, and pulmonary hypertension in many cases. Some areas of the lung may have normal compliance and resistance, whereas others may have poor compliance and high resistance. In this heterogeneous disease, there are also significant areas of high compliance and low resistance. So if we ventilate these patients with BPD with low tidal volumes, rapid rates, and low iTimes (similar to ARDS), we run the risk of having worse distribution of gas, increased dead space ventilation, hypercarbia, the need for higher FiO2 and radiographically progressive atelectasis.

As such, it is important for users to manage the patient with severe, chronic BPD with high TV. This allows for more gas to fill the lungs. Couple this high tidal volume, usually 8-10 mL/kg with higher iTimes and low rates to decrease the risk of atelectasis.

Ok, to summarize here, BPD patients, in general, have higher iTimes, higher tidal volumes, and low rates. This is to especially account for the areas of the lungs with higher time constants.

Rahul, real quick what is the definition of a time constant?

  • The time constant is the time required for inflation of alveoli up to 63% of the final volume, or deflation by 63%. It is the product of resistance and compliance. For a normal set of lungs as a whole, the normal time constant is 0.1-0.2 seconds. In BPD, these children have varied, heterogenous time constants.

Rahul what about PEEP use in the intubated BPD patient?

  • These patients in general require higher PEEP. It opens the airways and along with larger lung volumes has a tethering effect. This stretching effect with high peep may favor airflow and improves gas exchange. Like you frequently preach on rounds Pradip, PEEP is your friend! High PEEP with high rates can lead to air trapping and dynamic hyperinflation, so continue to reassess your patient, serial gas, x-rays, and ventilator scalars to determine the optimal rate to set on the ventilator in addition to the PEEP.

Let’s take a holistic picture now, Pradip, beyond the ventilator, what do we have to consider?

  • Don’t rush towards extubation, but work to reduce distress, retractions, and “dyspnea”; at times growth with optimal nutrition is very beneficial. We need to optimize therapies such as OT and PT. but also consider the desaturations/increased PVR which may ensue during this hands-on care. We should focus on weaning sedation and NMB as tolerated.
  • These children are in the PICU at times for long periods, so optimize day night cycles, sleep hygiene, lab schedules, and most importantly bonding with family & caregivers. Don’t forget to catch up on immunizations and ROP care. Remember Rahul, we are pediatricians first!!

I love these points, it is really a team effort. As we conclude this episode, in your opinion what does successful care of the BPD patient in the PICU look like?

  • Successful treatment with BPD is synonymous with good supportive care — we want to do no harm. In this setting, we want ”minimal impact respiratory support”. Prevention of harm, prevention of infection, prevention of right heart failure, excellent nutrition for growth and repair as well as developmental assistance. You will frequently be coordinating care with your NICU or PICU dietitians.
  • Having a primary intensivist as a caregiver and a familiar team to quarterback multi-specialty care should be a feasible goal. An optimal team has PICU, pulmonary, cardiology, GI/nutrition, surgery, respiratory, nursing, neonatology, and even palliative care. These subspecialties are so helpful along with developmentalists, pharmacists, case managers, social workers, PT, OT, and speech. As families may be in the hospital for a while, I have had great success not only to be team-based but to be transparent — these families especially should be the center of family-centered rounds. Have a roadmap from PICU admission to home and follow-up. What are the goals these children need to accomplish?

Yes, in our PICU we have frequently seen a sticker chart. A posted sign which can orient all team members to daily or weekly goals.

Yes, Rahul, I want to emphasize weekly meetings with care teams where we can discuss the pros and cons of different approaches. Collaboration with neonatology colleagues is invaluable. Some institutions are developing BPD or chronic lung units within their PICU.

As mentioned, stability in ventilated BPD patients includes tolerance of therapies, care and handling with minimal desaturations/cyanosis or distress. Over time, there may be less reliance on blood gas. We want to trend growth parameters such as weight and length. These children may be on diuretics IV or enterally and thus, we want to hit a sweet spot for fluid balance. Minimize FiO2 and at times we can allow permissive increases in peak pressures. Remember these children have regional over-distension and phasic stretch which may combat increased peak pressures. This is in contrast to ARDS.

Rahul, I feel like this can be an episode on its own, however, do you mind commenting on the use of tracheostomy?

Absolutely. I first off want to highlight that this management decision requires transparency and a team-based approach which includes the identification of family/caregivers. A patient requiring prolonged invasive or non-invasive ventilation, frequent bursts of steroids to prevent reintubation, pulmonary hypertension requiring medications, along with other patient-specific factors may need tracheostomy after a few months of life. One large study (Donda K. et al. Peds Pulmonology 2021) reported that 1.4% of patients with BPD had a tracheostomy (87/68K patients studied). It seems that the BPD population necessitating trach, however, is growing.

Rahul, let’s bring it home, what a great episode. Do you mind summarizing our management take-aways? In patients with severe late established BPD due to regional heterogeneity: we should ventilate with higher tidal volumes (10-12ml/kg), lower rates (favors better emptying), longer inspiratory times (> 0.6secs), and increased PEEP. When a patient with severe BPD is ventilated with these settings it can help improve the FRC thus improving RV performance also. Goals for gas exchange include SPO@ 92-95%, allowing for reasonable hypercapnia. After the patient is stabilized long-term focus is less on the acute improvement of blood gases but more on tolerance of ventilation.

This concludes our episode today on ventilation of the Ex-premie in the PICU. We hope you found value in this short podcast. We welcome you to share your feedback & place a review on our podcast at our website www.picudoconcall.org. PICU Doc on Call is co-hosted by Dr. Pradip Kamat, and my co-host Dr. Rahul Damania. Stay tuned for our next episode! Thank you

Reference Articles 

Thébaud B, Goss KN, Laughon M, Whitsett JA, Abman SH, Steinhorn RH, Aschner JL, Davis PG, McGrath-Morrow SA, Soll RF, Jobe AH. Bronchopulmonary dysplasia. Nat Rev Dis Primers. 2019 Nov 14;5(1):78. doi: 10.1038/s41572-019-0127-7. PMID: 31727986; PMCID: PMC6986462.

Sindelar R, Shepherd EG, Ågren J, Panitch HB, Abman SH, Nelin LD; Bronchopulmonary Dysplasia Collaborative. Established severe BPD: is there a way out? Change of ventilatory paradigms. Pediatr Res. 2021 Dec;90(6):1139-1146. doi: 10.1038/s41390-021-01558-8. Epub 2021 May 19. PMID: 34012026.

Baker CD, Abman SH. Impaired pulmonary vascular development in bronchopulmonary dysplasia. Neonatology. 2015;107(4):344-51. doi: 10.1159/000381129. Epub 2015 Jun 5. PMID: 26044102; PMCID: PMC4469359.

Donda K, Agyemang CO, Adjetey NA, Agyekum A, Princewill N, Ayensu M, Bray L, Yagnik PJ, Bhatt P, Dapaah-Siakwan F. Tracheostomy trends in preterm infants with bronchopulmonary dysplasia in the United States: 2008-2017. Pediatr Pulmonol. 2021 May;56(5):1008-1017. doi: 10.1002/ppul.25273. Epub 2021 Feb 1. PMID: 33524218.