The Role of Isofloring in the Treatment of Asthma

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, which is Part 2 of our acute severe asthma management. Today we discuss invasive mechanical ventilation of the acute asthmatic.

A patient with a history of asthma presents to the PICU with decreased air entry. Somnolence. Hypercarbia and drooling. The patient is hypoxemic and has see-saw breathing.

Rahul: Let’s dive right into this. What are the indications for intubating a child with acute severe asthma?

Absolute indications include:

• Altered mental status which may be preceded by obtundation, agitation
• Cardiac and respiratory arrest

Relative indications decided on a case by case basis:

Progressive exhaustion-despite, despite maximal therapy. Profound hypoxemia refractory to supplemental oxygen administration, and respiratory failure.

The decision to intubate should not be solely determined based on blood gas results.

Pradip, can you shed light on how we prepare for the intubation of the patient with acute severe asthma?

Rahul, first and foremost- we take the intubation of an asthmatic very seriously. In fact we try the whole “kitchen sink” to avoid intubation. But there will be times when we have to intubate especially for the indications you mentioned above.

The intubation will worsen the patient’s bronchospasm, put the patient at risk for barotrauma as well as cardiovascular collapse.

Preparation is the key- A team huddle and mapping prior to proceeding to intubate is the key. Every person in the room should have clear roles and responsibilities. Scenarios of what to do if “X” happens should be clearly laid out to the team by the team leader (preferably the attending or a senior fellow). The senior-most experienced person should manage the airway. At least two dedicated RTs to provide bag-mask ventilation as well as manage the ventilator are required. Nursing roles to push meds, chart the vitals and other activities as well a role for the resource nurses to help in case of cardiac arrest should be clearly laid out. Additionally, facilities that have access to isoflurane should have that ready to go. We typically give a heads up to our ECMO team to be on stand-by.

Prior to Intubation: Have central access or multiple large-bore PIVs if possible. Keep crystalloids boluses ready for hypotension. We also have peri-arrest epinephrine as well as an epinephrine infusion ready for any hypotension, bradycardia, or cardiac arrest. For intubation, we typically use Ketamine, fentanyl, and rocuronium (some centers may use succinylcholine). We use cuffed endotracheal tube. We don't bag-mask at fast rates but rather wait for a full expiration prior to the next breath being delivered. These patients require slow respiratory rates with very prolonged expiratory times to allow for adequate gas exchange and lung volumes. A helpful technique is to use a stethoscope to auscultate at the lower neck for the disappearance of expiratory wheezes prior to starting the next inspiration. We sometimes place a nasogastric tube to prevent gastric distension.

If there is hypoxemia, hypotension, not improving with fluids, ventilator manipulation, - A consideration for tension pneumothorax should be given especially if there is asymmetric chest rise. Bedside POCUS can be used to make a diagnosis.

Intubation of an asthmatic is a high-risk procedure and requires a team approach, proactiveness, and anticipation. Intubation should be approached cautiously in patients with severe acute asthma exacerbations because manipulation of the airway can cause laryngospasm and worsening bronchoconstriction.

Rahul, what are some of the principles we should all follow prior to initiation of mechanical ventilation in an asthmatic after intubation?

It is important to note that most complications of intubating an asthmatic happen in the immediate post-intubation period. Hypoxemia, hypotension, tension PTX/air leaks as well as cardiac arrest can happen immediately upon initiation of positive pressure ventilation. An important cause of hypotension is hyperinflation and decreased venous return. So slowing down manual bag-mask ventilation of even disconnecting the bag and allowing for a brief period of apnea while applying manual pressure to the rib cage may help decrease hyperinflation. Hypotension should respond to fluid boluses and decrease manual bagging.

Dynamic Hyperinflation: Severe airflow obstruction results in incomplete exhalation resulting in dynamic hyperinflation (DHI). Progressive DHI leads to an end-expiratory lung volume reaching a new equilibrium that exceeds the functional residual capacity. In the early stages of asthma, the increased lung volume increases pulmonary elastic recoil pressure thus increasing pulmonary expiratory flow and expanding small airways thus decreasing expiratory resistance. Thus lung volume will reach a point where the entire tidal volume can be expired during the available exhalation time. However, this process becomes maladaptive in severe asthmatic such that hyperinflation required to maintain normocapnia cannot be maintained as it would expand total lung capacity

Positive pressure ventilation worsens DHI especially if ventilator settings are aimed at normocapnia. This will also increase the risk of hypotension and pneumothorax. The initial rule of thumb would be to use low Tidal volumes and low respiratory rates to allow for controlled hypoventilation and permissive hypercapnia.

Pradip, with the above is mind what are your initial ventilator settings?

We typically use pressure regulated volume control (PRVC) to set a TV of 8-12m//kg (reduce to generate a plateau pressure of ~30 cm H2O), respiratory rate of 6-10/minute time of 1-1.5 seconds, which allows for an expiratory time of 4-9seconds. in the patient with NMB, we set PEEP initially at zero. Peak pressures in the 50s are expected initially due to airflow obstruction but plateau pressures of 30 or below should be reassuring.

An inspiratory hold will determine the plateau pressure whereas an expiratory hold will give us information about the auto-PEEP. The applied PEEP should be set below the auto peep in a spontaneously breathing patient in order to decrease the trigger work.

Another ventilation strategy, which is comfortable for the patient is the use of pressure support ventilation with PEEP. PEEP narrows the gap between proximal and distal airway pressures during the hyperinflated obstructed state. Pressure support facilitates inspiration while decreasing the work of breathing. The patient determines the time, respiratory rate, and depth. of each breath.

In summary: RR 10-12/min; Tidal volume: 6 to 8 mL/kg; set the sensitivity for triggering a ventilator-assisted breath at -2. Allow increased expiratory time by decreasing the I:E ratio (1:3 or 1:4 up to 1:5).

Rahul, What are the variables you closely monitor during the ventilation of a child with acute severe asthma?

Frequent auscultation of the patients’s chest at the bedside, observing vital signs including hemodynamics is helpful. Watching flow volume, PV loops gives useful information about patient’s condition. Monitoring peak-to-plateau pressure differences tell us about improvement in airway resistance. in response to therapy.

Following the capnography waveform can give us information about lung emptying.

Rahul, what are the sedation-analgesia-neuromuscular blockade therapies used in the child intubated for Near-fatal asthma.

We prefer to use ketamine with low-dose benzodiazepines such as midazolam. We initially chemically paralyze the patient using rocuronium to abolish spontaneous respirations which can add to the DHI and hypercapnia. If we use isoflurane gas we D/C all other sedatives a, analgesics and NMBs. The use of steroids along with NMB can add to the neuromuscular weakness in such critically ill patients. Consideration for early stooping of NMB should be given.

Pradip, can you talk about the use of isoflurane in a child with NEAR fatal asthma?

Inhalational anesthetics such as isoflurane can be delivered by means of an anesthesia machine that feeds into the low-pressure gas port of a conventional mechanical ventilator or via a dedicated anesthesia ventilator with its own vaporizer. Isoflurane is preferred over others has it has no negative inotropic effects although it can cause hypotension due to peripheral vasodilatation. Typical concentration used is 0.5-2%. Appropriate scavenging of the waste gas is important so as to not expose the staff. The exact mechanism of action remains unclear. although studies indicate that inhaled anesthetics reduce vagal tone and reflexes as well as alter circulating catecholamines and ß receptor sensitivity. Inhaled anesthetics may also have a direct relaxation effect on the airway smooth muscle. Potential neurotoxicity especially in the very young is a concern and withdrawal with prolonged use has been seen. Improvement is seen as early as within 30 minutes of initiation of isoflurane and typically by 12 hours. Some refractory cases may need isoflurane for 2-3 days. Inhaled anesthetics should not be used in patients at risk for malignant hyperthermia.

To summarize, isoflurane is an inhaled anesthetic that can be employed in near-fatal asthma by creating smooth muscle relaxation in the respiratory tree. As isoflurane is a potent anesthetic that has a smooth muscle relaxation effect, we must be mindful of the 

Rahul, what is the role of ECMO in NEAR Fatal asthma?

Some refractory cases of NFA that do not respond to isoflurane or have severe air leaks, cardiac arrest may be candidates for ECMO. Mechanical ventilation of patients with NFA is challenging, and high ventilator settings may cause lung injury and hemodynamic instability secondary to barotrauma and dynamic hyperinflation.

A more recent ELSO registry query (Crit Care. 2017;21(1):297.) for ECMO support for adults with asthma found successful decannulation in 86.7% and survival to discharge of 83.5%, with nonsurvivors being older in age, with lower pH and higher PEEP, higher post-ECMO oxygen requirement, and post ECMO driving pressures significantly associated with in-hospital mortality. The use of full-flow VV ECMO for refractory asthma in children is not uncommon and has been described previously as case reports and small studies. An ELSO registry report (published in CCM 2009) on ECMO use in children with SA reported a median time of ECMO support of 94 hours and was associated with 94% survival. Nine percent of the children placed on ECMO had a cardiorespiratory arrest before ECMO initiation. The presence of cardiorespiratory arrest or neurological injury was not associated with higher mortality.

A more recent study of children with rhinovirus (Pediatric pulmonology 2020) reported a survival rate of 100%.

Pradip, as these patients have hypoventilation due to obstruction, what are some of the cutting-edge therapies recently highlighted in the literature?

ECCO2R (or AVCCO2R-requires double lumen cannula) is a more recent strategy and is designed to remove CO2, but, unlike ECMO, does not provide significant oxygenation. Essentially, ECCO2R consists of a drainage cannula placed in a large central vein, a pump, a membrane lung, and a return cannula, or a double lumen VV cannula. Blood is pumped through the membrane and CO2 is removed by diffusion. In contrast to ECMO, where the need for oxygenation requires high blood flow rates, ECCO2R allows much lower blood flow rates. ECCO2R does not provide for oxygenation which ultimately most NFA patients require due to viral or bacterial infection, as well as doesn't provide hemodynamic support as ECMO would. There are no randomized controlled trials or large studies to compare the outcomes of ECMO versus ECCO2R in children with asthma to assess the superiority or benefit of one over the other.

In Chapter 50 in Furhman, Zimmerman’s textbook of Pediatric Critical Care, Dr. Steve Shein, and colleagues highlight that the use of extracorporeal life support (ECLS) has been reported in the management of the very few patients with near-fatal asthma who continue to exhibit a profound degree of clinical instability despite maximal therapy. Moreover, only 4% of patients in the Extracorporeal Life Support Organization registry have had runs for near-fatal Asthma. The survival rate for persons with near-fatal asthma necessitating ECLS is approximately 81%, which is remarkable considering that the vast majority of these patients were extraordinarily sick and had failed to respond to very aggressive treatment.

To Summarize:

1. Intubation of an asthmatic is a high-risk procedure and requires a team approach, proactiveness, and anticipation.
2. Ventilator strategies include allowing time for expiration by modulating the I:E ratio and decreasing the RR and TV.
3. Isoflurane & ECMO are last-ditch efforts in near-fatal asthma and should be performed in quaternary care facilities.

• References:
• Medar SS, Peek GJ, Rastogi D. Extracorporeal and advanced therapies for progressive refractory near-fatal acute severe asthma in children. Pediatr Pulmonol. 2020 Jun;55(6):1311-1319. doi: 10.1002/ppul.24751. Epub 2020 Mar 30. PMID: 32227683.
• Werner HA. Status asthmaticus in children: a review. Chest. 2001 Jun;119(6):1913-29. doi: 10.1378/chest.119.6.1913. PMID: 11399724.
• Demoule A, Brochard L, Dres M, Heunks L, Jubran A, Laghi F, Mekontso-Dessap A, Nava S, Ouanes-Besbes L, Peñuelas O, Piquilloud L, Vassilakopoulos T, Mancebo J. How to ventilate obstructive and asthmatic patients. Intensive Care Med. 2020 Dec;46(12):2436-2449. doi: 10.1007/s00134-020-06291-0. Epub 2020 Nov 9. PMID: 33169215; PMCID: PMC7652057.

More information can be found

• Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 50 entitled Asthma

This concludes our episode on Near-Fatal Asthma. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!