Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

Welcome to our episode of a three-year-old girl presenting with a cough and difficulty breathing

Here's the case presented by Rahul:

A previously healthy 3-year-old girl presented to the OSH for difficulty breathing. She had a two-day h/o of cough (worse at night) and congestion but no fever. She has no h/o of emesis, h/o recent travel, or exposure to some/toxins. Initially, she received steroids, albuterol, and O2 but due to continued worsening of breathing and hypoxia-She was transferred to our PICU for initiation of High Flow Nasal Cannula. She has no allergies and her immunizations are up to date. There is a strong family history of asthma and atopic dermatitis. The mother also noted that the patient has h/o of coughing episodes while playing outside with her siblings.

Initial Vitals: Temp 37.9, HR 100, BP 97/73, respiratory rate 49, SPO2 98% on 15LPM HFNC at 60% FIO2 , weight 17.5kg

On PE: The child is awake, playful. she is tachycardic with no murmur. She has subcostal, intercostal, supra-sternal retractions. There is bilateral symmetric chest expansion. The air entry is decreased with diffuse (B) wheeze. There is atopic dermatitis in the flexor areas of the elbows/knees. The rest of the physical examination was normal. No hepatosplenomegaly.

Viral panel: positive for HMP, SARS COV-2 negative

CXR: Atelectasis superimposed upon viral pneumonitis versus multifocal bronchopneumonia. No evidence of parapneumonic effusion or air leak.

CBC and BMP are normal.

To summarize key elements from this case, this 3-year-old girl has:

• Cough and congestion
• Increased WOB and difficulty breathing
• Hypoxia
• No fever or rash
• No recent ingestions or exposure to tobacco smoke
• All of which brings up a concern for a lower airway obstructive process most likely acute asthma

Let's transition into some history and physical exam components of this case?

Rahul, what are key history features in this child who presents with increased work of breathing?

• Cough and congestion
• Difficulty breathing
• No h/o suggestive of atopic dermatitis
• Increased WOB: retractions (subcostal, intercostal, suprasternal). Important to note there is no nasal flaring, head bobbing or grunting.
• Decreased AE
• Diffuse (B) wheezing. No subcutaneous emphysema on palpation of the chest or cervical region.
• Hypoxia needing oxygen
• Atopic dermatitis
• No crackles
• No hepatomegaly
• No altered mental status

Not all respiratory distress arises within the respiratory tract. Important physical examination to note in any infant or toddler with increased work of breathing is to palpate for hepatomegaly as well as carefully listen for bilateral inspiratory crackles. The presence of hepatomegaly or (B) crackles should raise concern for myocarditis or congestive heart failure. In Newborns with respiratory distress-always make a habit to feel femoral pulses. Acidosis, intracranial hemorrhage, foreign body, panic attacks can also present as respiratory distress.

To continue with our case, Pradip, the patient’s labs/diagnostic were consistent with:

• CBC, BMP were normal
• Respiratory viral panel positive for HMP virus, Negative for SARS-COV-2
• Chest radiograph: Atelectasis superimposed upon viral pneumonitis versus multifocal bronchopneumonia

OK, to summarize, we have: A 3-year-old with acute respiratory distress, wheezing, hypoxia after 2 days h/o of cough/congestion.

Rahul, let's start with a short multiple-choice question:

A 15-year-old teenager with know h/o asthma presents to the ED in severe respiratory distress, increased work of breathing, hypoxia, and diffuse wheezing. Of the following the presentation that would most likely require intubation in this teenager include-

• A) Inability to talk in complete sentences
• B) A blood gas that shows hypocapnia and mild respiratory alkalosis
• C) Presence of pulsus paradoxus
• D) Deteriorating mental status

Rahul, this is an excellent question. The correct answer here is D-Deteriorating mental status. While choice A-inability to talk in complete sentences as well as Choice C-presence of pulsus paradoxus in a patient with asthma correlate with severity of acute asthma, those choices are not indications for intubation. In early asthma -in a patient who is tachypneic and breathing hard the blood gas should have hypocapnia and a mild respiratory alkalosis. I would be more worried about a normal gas or a rising PCO2 in a patient with status asthmaticus.

So just for our listeners, indications for intubation and mechanical ventilation in a child with asthma should be based on clinical judgment and include: cardiac and respiratory arrest; severe hypoxia as well as rapid deterioration in the child’s mental status. Progressive exhaustion despite maximal therapy constitutes a relative indication for intubation on a case-by-case basis. The traditional rule that respiratory acidosis dictates intubation has become outdated.

Rahul, can you comment on the commonly used Clinical Respiratory Score (CRS) ?

The Clinical Respiratory Score (CRS) is a tool that was developed based on the National Asthma Education Program’s guidelines for the diagnosis and management of asthma. The CRS contains six equally weighted variables. It uses both objective and subjective criteria when evaluating a child with asthma to calculate a score. A CRS assessment requires a member of the care team to calculate a respiratory rate and record the room air oxygen saturation using a pulse oximeter. Auscultation of the lung fields, assessing the use of accessory muscles, mental status, and the child’s color also contribute to the CRS. Respiratory rate scores are differentiated by normal values for age. Each of the 6 categories are then categorized as mild (score = 0), moderate (score = 1), or severe distress (score = 2), and the total score is calculated from 0 to 12. The CRS is a reliable asthma severity scoring tool for pediatric patients presenting with an acute asthma exacerbation when utilized across care team members. (McLaughlin P. et al Journal of Asthma 2021).

Rahul also what are risk factors for severe acute asthma?

In a review by Werner H (Chest 2001; 119:1913-1929), risk factors for acute severe asthma were classified as medical factors include: Previous attack with severe, unexpected, rapid deterioration, respiratory failure, seizure or LOC, attacks precipitated by food.

Psychosocial factors: denial or failure to perceive the severity of illness associated depression or psychiatric disorders, non-compliance, dysfunctional family unit, inner-city residents

Ethnic factors: Nonwhite children.

A study by Grunwell et al (PCCM 2018) reports risk factors for PICU admission, with or without intubation. These include hospitalization in past 12months, a h/o pneumonia, chronic asthma severity on high dose ICS, a father with asthma, living in a region with a high burden of poverty, and being of black race.

In a more recent study, Grunwell J. et al ( J Allergy Clin Immunol Pract. 2021) reported on school Age children at risk for asthma exacerbation. The authors identified Four latent classes with differing demographic features, sensitization and Type-2 inflammatory markers, prior exacerbation severity and healthcare utilization, and lung function. They found that children with exacerbation-prone asthma were present in each latent class, but were most strongly represented in the latent classes with multiple sensitization and airflow limitation.

Rahul, can you explain the pathophysiology of acute asthma in terms of lung mechanics/gas exchange and cardiopulmonary interactions.

Acute asthma there is (1) Inflammation is triggered by a respiratory virus, cigarette smoke, air pollution, allergens, etc. IL-4, IL-5, IL-8, IL-13 primarily mediate inflammation, amplified by increased production of IgE by B cells. There is bronchospasm due to airway hyper-responsiveness, (3) Hyper-secretion of mucous plugging the airways (worsened by dehydration due to increased insensible

Airway obstruction leads to hyperinflation with resultant dead space ventilation. In fact, hyperinflation results in the conversion of lung segments from West zone 3 and two to West zone 1, thus increasing the V/Q mismatch. The Increase in respiratory rates in response to impaired ventilation results in dynamic hyperinflation and air trapping due to prolonged expiratory times.

Hyperinflation leads to the flattened diaphragm, which becomes inefficient for optimal respiratory function. Diaphragmatic fatigue is further exacerbated by acidosis, hypoxia, and dehydration.

VQ mismatching: Mucus plugging results in VQ mismatching due to atelectasis and intrapulmonary shunting

PVR is elevated due to increased lung volumes worsened by acidosis and hypoxia, adding to the VQ mismatch by decreasing blood flow(Q). The use of albuterol can further worsen VQ mismatch

In spontaneously breathing children with acute severe asthma, the pleural pressures can be as negative as -35cm H2O. The negative pleural pressure increases the (L) ventricular afterload, which favors the trans-capillary filtration of edema fluid into the airspaces resulting in a high risk for the development of pulmonary edema. Due to hypoxic pulmonary vasoconstriction, acidosis, and increased lung volume, the RV afterload is also increased.

Pulsus paradoxus is not specific for acute asthma. It can also be seen in cardiac tamponade, pulmonary embolus, and tension PTC. Fall in arterial systolic blood pressure with inspiration of > 10mm Hg (normal <10 mmHg). Hyperinflation leads to the expansion of vascular beds. During inspiration, the increased RV preload leads to the septum bowing into the LV thus decreasing LV preload and exacerbating the normal physiologic drop in BP with inspiration. LV preload may be further compromised by increased pulmonary vascular bed compliance and increased (L) ventricular afterload.

As you think about our case, what would be your differential in a patient with respiratory distress and/or wheezing?

• Foreign body (unilateral wheezing, h/o choking/coughing while eating or playing).
• Non-respiratory causes of respiratory distress include: CNS causes such as intracranial hemorrhage, airway obstruction, air leaks, acidosis, panic attacks, cardiac causes such as myocarditis, congestive heart failure. A detailed h/o and physical examination with pertinent imaging will help with the diagnosis in the above conditions.

Wheezing in asthmatics occurs due to turbulent airflow in the intrathoracic airways and bilateral. NOT all wheezing is Asthma! If wheezing is asymmetric caregivers should consider the diagnosis of a foreign body, PTX, mucous plugging, or atelectasis. The degree of wheezing correlates poorly with asthma severity. If there is no airflow, no wheezing will be heard and the patient may have a silent chest, which is an ominous sign. If a patient who previously had loud wheezing but has now worsening work of breathing, a reduction in wheezing may be a harbinger of respiratory failure.

• Pradip If you had to work up this patient with acute asthma what would be your diagnostic approach?
• Really don’t need a lot of investigations in the routine asthma admission to the PICU. Some may not even get a chest radiograph or a viral panel. CXR may be indicated if the clinical exam suggests an air leak (such as crepitus or asymmetry of chest rise).
• Frequent repeat assessments at the bedside after an intervention is the most important. Close observation of respiratory effort, pulse oximetry, and alertness serve as continuous clinical correlates of pulmonary gas exchange.
• Blood gas: Typically in early asthma we see hypocarbia with mild respiratory alkalosis. If the patient clinically worsens one may see initially a normal PCO2 followed by hypercarbia and hypoxemia. Routine blood gases are not indicated in acute severe asthma and one single abnormal blood gas should not be used as an indicator to decide the need for mechanical ventilation. As the patient worsens, one may see a mixed picture of respiratory acidosis with metabolic acidosis.
• Lactic acidosis: Serum lactates should not be routinely obtained in acute severe asthma as some degree of lactic acidosis is common in acute severe asthma due to the use of albuterol and adrenergic stimulation (Type B lactic acidosis(associated with adrenergic stimulation and occurring with normal oxygen delivery)) Meert K et al (PCCM 2012).
• Routine BMP/CBC is not required. Hypokalemia may be seen due to continuous albuterol use. If there is dehydration, BUN may be elevated. If a CBC is obtained- there may be leucocytosis from stress or use of steroids. rarely eosinophil count may be elevated in atopic patients.
• Rahul If our history, physical, and diagnostic investigation led us to acute severe asthma as our diagnosis what would be your general management of framework?
• Status asthmaticus is now replaced by the term acute severe asthma and is defined as an asthma attack unresponsive to repeated doses of beta-agonists and requiring hospital admission. Critical asthma is defined as acute severe asthma which requires intensive care admission. Near-Fatal asthma is defined as critical asthma that requires endotracheal tube intubation and mechanical ventilation. General principles of good PICU care should be followed. O2, albuterol, and steroids are the mainstays of therapy in acute severe asthma.
• O2 for hypoxia. Can be given with nebulizer treatments and continuously between the treatments.
• Fluids: Patients with acute severe asthma have dehydration (insensible losses or decreased PO intake). Fluids also help loosen the mucus in the airways.
• Corticosteroids: IV methylprednisolone 0.5-1mg/kg/dose Q6 followed by PO when the patient is able to take PO. Continue for 5-7days. It is not necessary to continue home ICS when the patient is acutely ill and on IV steroids in the PICU.
• Albuterol nebulizer therapy is used initially over 20minutes at 0.05-0.15mg/kg. less than 10% of the inhaled drug is deposited in the lungs. After initial series of 3 albuterol treatments, continuous albuterol nebulization is started at a dose range of 0.15-0.45mg/kg/hr (maximum of 20mg/hr). albuterol is a 50:50 mixture of R-albuterol and S-albuterol. The R-albuterol, also called levalbuterol, is the enantiomer that causes broncho-dilation, whereas the S-albuterol is the inert form and may contribute to adverse events. We do not recommend the use of Levalbuterol as there is no advantage of its use over albuterol. Levalbuterol doesn’t cause less tachycardia than racemic albuterol and continues to have a higher cost compared to R-albuterol. In patients who do not improve with albuterol or have poor air entry, to begin with, I start IV terbutaline. I give 5-10mcg/kg IV bolus followed by an infusion at 0.1-4mcg/kg/min. I do not use IV epinephrine due to its greater affinity for beta-1 compared to terbutaline.

So let's summarize A, B, C — in parallel, we optimize anti-inflammatory &...