Review of the ATHOS 3 trial

Written by: Saabir Kaskar, MD (NUEM ‘23) Edited by: Amanda Randolph, MD (NUEM ‘20)
Expert Commentary by: Matt McCauley, MD (NUEM’ 21)

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Review of the ATHOS 3 Trial: Angiotensin II for the Treatment of Vasodilatory Shock

Angiotensin, first isolated in the late 1930s, in recent years has become the new innovative vasopressor used in intensive care units, a change driven largely by the results of the ATHOS-3 trial. The ATHOS-3 trial in 2017 explored the efficacy of angiotensin II as a vasopressor for severe vasodilatory shock.  Severe shock is defined as persistent hypotension requiring vasopressors to maintain a mean arterial pressure of 65mmHg and serum lactate <2 despite adequate volume resuscitation.  Two classes of vasopressors have been used in the past for hypotension. They are catecholamines and vasopressin-like peptides. The human body, however, employs a third class which is angiotensin.  Angiotensin II is an octapeptide hormone and a potent vasopressor that is an integral component of the renin-angiotensin-aldosterone system. It works by activating the ANGII type 1 receptor which subsequently activates a G coupled protein pathway and phospholipase C, thereby inducing vasoconstriction. 

The ATHOS-3 trial compared the efficacy and safety of angiotensin II versus placebo in catecholamine-resistant hypotension, which is defined as an inadequate response to standard doses of vasopressors. The study was designed as a phase III multicenter randomized placebo control trial taking place across 75 intensive care units in the United States from 2015 to 2017. The three main inclusion criteria were catecholamine-resistant hypotension (defined as >0.2ug/kg/min of norepinephrine or equivalent for 6-48 hours to maintain a MAP 55-70 mmHg), adequate volume resuscitation (25mL/kg of crystalloid), and features of vasodilatory shock (mixed venous O2 >70% and CVP >8mmHg or cardiac index >2.3 L/min/m2).

Patients in vasodilatory shock that met the criteria of catecholamine-resistant hypotension were randomized to treatment with angiotensin II or placebo. Angiotensin II was initiated at an infusion rate of 20ng/kg/min and adjusted during the first three hours to increase MAP to at least 75mmHg. The primary outcome of the study was the response in MAP three hours after the start of angiotensin II infusion. A response was deemed as a MAP increase of 10mmHg from baseline or a MAP over 75mmHg without an increase in baseline vasopressor infusions. During the first three hours, the angiotensin II group had a significantly greater increase in MAP than placebo (12.5mmHg vs 2.9 mmHg). Angiotensin II also allowed for rapid increases in MAP which permitted decreases in doses of baseline catecholamine vasopressor. Additionally, improvement in the cardiovascular SOFA score was significantly greater in the angiotensin II group than in the placebo group. However, the overall SOFA score did not differ between groups. Rates of adverse events such as tachyarrhythmias, distal ischemia, ventricular tachycardia, and atrial fibrillation were similar in the angiotensin II and placebo groups. Overall serious adverse events that included infectious, cardiac, respiratory, gastrointestinal, or neurologic events were reported in 60.7% of patients who received angiotensin II and 67.1% of patients who received placebo. 

The strengths and limitations of the ATHOS 3 trial are critical to how its author’s conclusions should be interpreted. The strengths of the study include that it was a randomized double-blind control trial examining a new class of vasopressor for refractory vasodilatory shock. Refractory shock is a common condition with high mortality, and so the investigation of an additional treatment modality can be of great clinical impact. However, one limitation of the study was that it was underpowered to demonstrate a mortality difference. It showed improvement in blood pressure which is a clinically important parameter but not a patient-oriented outcome. Interestingly, when vasopressin was studied in 2008, it similarly did not show a mortality benefit when added to norepinephrine infusion in septic shock2. It did, however, show a decrease in norepinephrine dosing which parallels the findings of the ATHOS 3 trial.

An additional point of contention with the ATHOS 3 trial is that the manuscript does not report an increase in thrombotic risk. It has been shown that angiotensin II increases thrombin formation and impairs thrombolysis3. The FDA even reports angiotensin II has a risk for thrombosis as there was a higher incidence (13% vs 5%) of arterial and venous thrombotic events in the angiotensin II vs placebo group in the ATHOS 3 trial itself. For this reason, the FDA recommends concurrent VTE prophylaxis with the use of angiotensin II. Further data regarding the thrombotic risk of angiotensin II would be helpful to determine which patient populations the vasopressor should be avoided in. 

Overall, the author’s conclusion in the ATHOS 3 trial is that angiotensin II increased blood pressure in patients with a vasodilatory shock that did not respond to high doses of conventional vasopressors. It has been shown to raise mean arterial pressure over 75 mm Hg or by an increase of 10 mm Hg within three hours. The ATHOS 3 trial, however, did not demonstrate a mortality benefit when using angiotensin II. Further studies are needed to elucidate whether Angiotensin II truly improves patient outcomes in vasodilatory shock. 

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Expert Commentary

Thank you for this great summary of the ATHOS 3 trial. While this trial paved the way for the clinical use of angiotensin II as a vasopressor, you’ve raised some salient points as to why we should approach this emerging intervention with skepticism. The biggest shortcoming in my mind is the primary outcome of the study; it’s not particularly impressive that a vasopressor resulted in higher blood pressures compared to a placebo. Mortality benefit is an extremely elusive goal in critical care research1 but that doesn’t discount the fact that ATHOS 3 wasn’t designed to demonstrate an improvement in any patient-oriented outcome. ICU length of stay, hospital length of stay, ventilator-dependent days, or rate of renal replacement therapy: these are all things that matter to our patients and to our health systems and they are more fruitful targets when we investigate interventions. 

There’s been some study of angiotensin II in the years since it has landed in our hospital formularies and there has not been robust data supporting its use. Some of the most recent data come from a multi-center retrospective study that includes patients from Northwestern. This review of 270 patients receiving angiotensin II demonstrated that 67% of patients were able to maintain a MAP of 65 with stable or reduced vasopressor doses. Univariate analysis showed that these patients that responded did have a statistically significant mortality benefit over the patients deemed nonresponders (41% vs 25%)2. If we are going to find a benefit of this drug, further study predicting which patients will be responders is necessary but this study did note that patients already receiving vasopressin and those with lower lactates (6.5 vs 9.5) were more likely to respond. Outside of septic shock, there is interest in the use of angiotensin II in refractory vasoplegia associated with post-cardiac surgery3 and anti-hypertensive overdose4. These are, of course, only hypothesis-generating. 

But what does that mean to us clinically in the ED and ICU? This data shows us that angiotensin II can make the blood pressure better but I would never let it distract you from the things we know matter in sepsis resuscitation. Source control timely antibiotics, rational fluid resuscitation, and ruling out other causes of vasopressor refractory shock to include anaphylaxis, hemorrhage, adrenal insufficiency, LVOT obstruction, and any other cause of cardiogenic shock need to be ruled out and addressed. In my personal practice, I make sure to optimize these and start vasopressin shortly after the initiation of norepinephrine. In a patient already on vaso that has stopped responding to escalating doses of norepinephrine, I reach for my ultrasound probe and reassure myself that there isn’t significant sepsis-related myocardial dysfunction because those patients may benefit from a trial of an inotrope like epinephrine. In those with a good cardiac squeeze, I think it’s appropriate to discuss with your intensivist and clinical pharmacist the utility of adding angiotensin II as part of a kitchen-sink approach. Until we have more data about the benefits of this extremely expensive intervention, I wouldn’t lose sleep if you’re unable to secure it for your patient.

References

1. Chawla LS et al. Intravenous Angiotensin II for the Treatment of High-Output Shock (ATHOS Trial): A Pilot Study. Crit Care 2014; 18(5): 534. PMID: 25286986

2. Russell JA et al. Vasopressin Versus Norepinephrine Infusion in Patients with Septic Shock. NEJM 2008; 358(9): 877 – 87. PMID: 18305265

3. Celi A et al. Angiotensin II, Tissue Factor and the Thrombotic Paradox of Hypertension. Expert Review of Cardiovascular Therapy 2010; 8(12): 1723-9 PMID: 21108554

4. Santacruz CA, Pereira AJ, Celis E, Vincent JL. Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review. Crit Care Med. 2019;47(12):1680-1691. doi:10.1097/CCM.0000000000004000

5. Wieruszewski PM, Wittwer ED, Kashani KB, et al. Angiotensin II Infusion for Shock: A Multicenter Study of Postmarketing Use. Chest. 2021;159(2):596-605. doi:10.1016/j.chest.2020.08.2074

6. Papazisi O, Palmen M, Danser AHJ. The Use of Angiotensin II for the Treatment of Post-cardiopulmonary Bypass Vasoplegia. Cardiovasc Drugs Ther. Published online October 21, 2020. doi:10.1007/s10557-020-07098-3

7. Carpenter JE, Murray BP, Saghafi R, et al. Successful Treatment of Antihypertensive Overdose Using Intravenous Angiotensin II. J Emerg Med. 2019;57(3):339-344. doi:10.1016/j.jemermed.2019.05.027

Matt McCauley, MD

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Kaskar, S. Randolph, A. (2022, Feb 14). Review of ATHOS 3 trial. [NUEM Blog. Expert Commentary by McCauley, M]. Retrieved from http://www.nuemblog.com/blog/review-athos3-trial.

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Peripheral Vasopressors: Do I need that central line?

Written by: Saabir Kaskar, MD (NUEM ‘23) Edited by: Abiye Ibiebele, MD (NUEM ‘21) Expert Commentary by: Marc Sala, MD

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Vasopressors have been used to treat shock since the early 1900s and continue to remain a mainstay of management of distributive shock. Traditionally, these medicines have been delivered through central venous catheters primarily due to the perceived risks of peripheral infusion, which include potential extravasation of vasoactive medicines and subsequent tissue necrosis. However, central venous catheter insertion is accompanied by its own risks such as pneumothorax, infection and carotid artery insertion and dilation. There is also a risk to delaying vasopressor initiation in hypotensive patients which is why vasopressors are often now started peripherally until central access can be attained.

Peripheral administration of vasopressors has classically been reserved for less potent vasoconstrictors such as phenylephrine and vasopressin. Fear of extravasation and tissue injury often is a cause for concern prior to starting norepinephrine, epinephrine or dopamine peripherally. The perceived harm from administrating these medicines peripherally largely stems from case reports over the past 60 years. However, what does the latest evidence tell us? Is this fear warranted or is it just a myth? Can we send our patients in shock up to the ICUs without central access?

One prospective observational study conducted at Long Island Jewish Medical Center evaluated the safety of vasoactive medication administered through peripheral IV sites. [1] The study monitored the use of vasopressors (norepinephrine, dopamine, and phenylephrine) in an intensive care unit with a total of 734 patients observed. The study incorporated an interdisciplinary protocol between pharmacy, nursing, physicians for administering vasoactive medicines through a peripheral IV. The protocol required that nursing staff examine the PIV access site every two hours, IV size be either 18 or 20 gauge, and utilize upper extremity vein sites with over 4mm vein diameter visualized via ultrasound. During the time of the study, 783 out of 953 patients received vasopressors for 49 +/- 22 hours through peripheral IV. While anatomic position of access site was not formally recorded, most IVs were placed in the upper arm basilic or cephalic vein. Peripheral vasopressors were only allowed to run for 72 hours before running centrally. Of the 783 patients, infiltration of the PIV occurred in 19 (2%) patients. All 19 had prompt local injection of phentolamine and application of nitroglycerin paste at the site of extravasation. No tissue injury was noted at the site of extravasation in any of the 19 cases.

This study shows that administration of vasopressors peripherally is feasible with a low risk if proper precautions are taken. The risk of extravasation and tissue necrosis is still present especially in ED’s and ICUs where such rigorous protocols are not in effect. However, this study demonstrates that vasopressor use may not be an automatic indication for central venous catheter insertion.

A more recent systematic review of peripheral vasopressor safety was recently published in Emergency Medicine Australia. [2] The review incorporated seven observational studies, roughly 1300 patients, that reported the incidence of adverse events for the continuous infusion of peripheral vasopressors including the above study.  The major finding was that extravasation events were uncommon (3.4%) and that no significant tissue necrosis or distal ischemia was reported. However, the data analyzed in this review comes from studies with mixed methodology quality and with limited duration of infusion. Five of the seven studies had peripheral vasopressor administration for less than 24 hours.

At its current state, the quality of data reviewing the safety profile of peripheral vasopressors is not universally high. However, the observational data we do have reports low incidence of complications which should be reassuring for clinicians especially when starting these medicines for short periods of time and as a bridge to possible central infusion. Early peripheral infusion should be given more consideration as delaying vasopressor administration has been shown to increase mortality in septic shock. [3] While further research is certainly needed in this field, the current state of data should at least quell some concerns of the perceived risks of peripheral vasopressor administration.

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Expert Commentary

Dr. Kaskar does a great job summarizing several of the major studies that can inform how we approach the infusion of peripheral vasoactive drugs in lieu of a central catheter. I can only assume we could agree one area of common ground, which is that if central access is in place, this should be used for the vasoactive infusion, given that the occurrence of tissue complications, while probably rare, can be limb-threatening.  An additional prospective study I would mention is by Medlej et al [1] where the authors prospectively studied ED patients managed for a variety of shock states with peripherally administered vasoactive agents and found that 3/55 (5.45% of total, and 6% of those receiving norepinephrine) had extravasation.  None had serious complications, but notably among the three events, all three used 20G IVs and two occurred using hand veins. This relatively small and heterogeneous study would indicate that extravasation is uncommon and when it occurs, is not particularly morbid, even with norepinephrine. 

Finally, another recent study notable for its cohort took place in the operating room context. Here, medical records of over 14,000 patients who received peripheral norepinephrine to manage hypotension associated with general anesthesia in two European academic centers were studied retrospectively for complications. Only five patients (0.035%) had extravasation, wherein the median infusion duration was 20 minutes, and none of whom had a significant complication from the extravasation. They calculated an estimated a risk of 1-8 events per 10,000 patients. 

What do all of these studies have in common that I think belies the true incidence of complications associated with peripheral vasoactive drugs? Vigilance. While it’s true that peripheral norepinephrine infusion may not result in serious tissue necrosis when given in the context of a formal clinical study (especially one that takes place in an operating room with continuous monitoring by anesthesia!), what about when the infusion goes unnoticed during a night shift with a high patient to nurse ratio?  In this case, I would argue that the closer to a “real-world experience” we can get with these studies, the better. 

I would also mention that a mentor of mine once theorized the “sunset” of crash central lines as the use of intraosseous catheters became more common in adults in the past decade.  While intraosseous catheters are not without their own complications, it is worth mentioning their role in this conversation as we move forward in thinking about how to transition patients safely from the ED to ICU with several different options for vascular access in lieu of a controlled, sterile central line placement. 

References:

1. Medlej et al. Complications From Administration of Vasopressors Through Peripheral Venous Catheters: An Observational Study.  The Journal of Emergency Medicine 2017; 54(1): 47-53.

2. Pancaro et al. Risk of Major Complications After Perioperative Norepinephrine Infusion Through Peripheral Intravenous Lines in a Multicenter Study. Anesthesia and Analgesia 2019; Published ahead of print.

Marc Sala, MD

Assistant Professor of Medicine

Pulmonary and Critical Care

Northwestern University Feinberg School of Medicine

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Kaskar, S. Ibiebele, A. (2020, Oct 12). Peripheral Vasopressors: Do I need that central line? [NUEM Blog. Expert Commentary by Sala, M]. Retrieved from http://www.nuemblog.com/blog/abdominal-imaging.

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References

1. Cardenas-Garcia J, Schaub KF, Belchikov YG, Narasimhan M, Koenig SJ, Mayo PH. Safety of peripheral intravenous administration of vasoactive medication. Journal of hospital medicine. 2015; 10(9):581-5

2. Tian DH, Smyth C, Keijzers G, et al. Safety of peripheral administration of vasopressor medications: A systematic review. Emergency medicine Australasia. 2019

3. Beck V, Chateau D, Bryson GL et al. Timing of vasopressor initiation and mortality in septic shock: a cohort study. Crit. Care 2014; 18: R97.

Little Lungs, Little Differences: Initiating Emergency Department Mechanical Ventilation in the Pediatric Patient

Written by: Matt McCauley MD (PGY-3) Edited by: Jacob Stelter, MD (NUEM ‘19) Expert commentary by: Katie Wolfe, MD

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Airway management of pediatric patients is a reasonable source of anxiety for the emergency physician. Children are intubated three to six times less often than adult emergency department patients [1]. Hence, it stands to reason that EP experience with mechanically ventilated children can be scarce [2] . Additionally, evidence driven practice in pediatric mechanical ventilation is limited and practice patterns vary between institutions and providers. These unknowns can make the prospect of managing these patients even more intimidating [3].  However, pediatric ventilator management is largely driven by data extrapolated from adults, which should come as a relief to the EP [4]. By keeping in mind small differences in pediatric physiology and keeping the consulting intensivist (and Broselow Tape) close at hand, an EP can effectively initiate mechanical ventilation in the smallest and most anxiety-provoking patients. 

Getting Help

Like the Fat Man said in House of God: “[Disposition] comes first.” The intubated child is bound for a pediatric ICU and hopefully the accepting pediatric intensivist is already aware of any intubated patient and can be a great deal of help and support as you work together to make your patient safe for transfer upstairs or across town. Although the use of a Broselow tape and other height based methods of estimating body weight for drug dosing is fraught with error 5, the Broselow’s color coding allows for quick estimation of ideal body weight (IBW) that is required to calculate ideal tidal volumes.

Choosing a Mode  

As mentioned, practice patterns related to pediatric ventilator management vary greatly [3]. The most commonly used modes for emergency pediatric ventilation include pressure assist control ventilation (PCV), volume control ventilation (VCV), and pressure regulated volume control ventilation (PRVC) [2]. PCV is typically favored in neonates and infants while volume modes are preferred in larger children [2]. When utilizing PCV, the provider sets the, inspiratory rate, inspiratory time, and inspiratory pressure meaning that the delivered tidal volume is dependent on the lung compliance of the patient [6]. This means that worsening compliance results in low tidal volumes. (Table 1) 

Vt = Compliance x Delta Pressure

In contrast, VCV ventilation requires that the physician set the  inspiratory rate, inspiratory flow rate, tidal volume, and PEEP. The ventilator delivers a fixed flow of air until the desired tidal volume is reached. This means that worsening compliance results in higher airway pressures (Table 1) [1]. The final commonly used mode for ventilating pediatric lungs is PRVC which, rather than requiring a set inspiratory flow rate like most volume controlled modes, utilizes a set inspiratory time, a targeted tidal volume, and a range of allowed pressures. With each breath the ventilator delivers a decelerating breath over the set time at an inspiratory pressure within the allowed range. If the resulting tidal volume is too high, the next breath is delivered with less pressure, if the volume falls short of the targeted tidal volume, the next breath is delivered with more pressure (Table 1) [6].

Finally, synchronized intermittent mandatory ventilation (SIMV) is often added to the above modes in pediatric ventilation. In SIMV, any time the patient initiates breaths within the set  respiratory rate, a pressure supported breath (usually at 5-10 mmHg) is given rather than the full volume or pressure controlled breath. Pediatric patients are more likely than their adult counterparts to over-breathe the set respiratory rate, putting them at risk of breath stacking from large volume breaths. SIMV can help to mitigate this risk [2]. Despite all this complexity, there is a paucity of good evidence for or against any particular mode for ventilation the critically ill child [4]. This should reassure the EP to choose their most familiar ventilator mode in conjunction with their intensivist. 

Choosing Age-Appropriate settings

Since pediatric respiratory rates vary wildly from adults, one should take the patient’s age into account when initiating mechanical ventilation (table 2) . With the exception of children with obstructive pathophysiology, the physician should attempt to match the patient’s pre-intubation minute ventilation [2]. Tidal volume goals for pediatric patients do not vary much from adults with most data being extrapolated from adult studies [4] and large trials have been unable to establish as safe threshold for tidal volume [8].  The  Pediatric Acute Lung Injury Consensus Conference (PALICC) recommends targeting 5-8cc/kg of ideal body weight (IBW) for most children either by setting a tidal volume in VCV or altering driving pressures for pressure controlled modes to target tidal volumes in this range for most patients [9]. Just as in adult patients, the intubating physician can set initial FiO2 at 100% to overcome hypoxia caused by peri-intubation apnea and then quickly down titrate targeting a SpO2 of 92-97% [9] .

If ventilating pediatric patients with pressure controlled ventilation, initially inspiratory times can be found on the Broselow or in a PALS manual 10 (table 3). If a volume controlled mode of ventilation is desired, inspiratory flow can be titrated to achieve a inspiratory to expiratory time ratio of 1:2 [2].  After initial setup, arterial blood gas analysis, continuous end-tidal CO2 measurement, and a chest X ray to evaluate tube positioning are just as critical here as they are in the adult patient. 

Ventilating the Child with Refractory Hypoxemia 

While most pediatric patients will be relatively straightforward to ventilate, the patient intubated for infectious pathologies like pneumonia or bronchiolitis is at risk for ARDS and should be approached with lung-protective ventilation strategies in mind.  Victims of drowning are similarly at risk and fall under the category of patients requiring lung-protective settings [11]. There is no pediatric equivalent for the ARDSnet trial [12] so adult data has been extrapolated to be applied to pediatric patients [3] making this familiar territory for the adult emergency physician. 

While most children will tolerate levels of PEEP between 3-5cmH204, PALICC recommends that children at risk of ARDS receive moderately elevated levels of PEEP  between 10-15cmH2O with an SPO2 goal between 88-92% for kids requiring PEEP more than 10mmH2O [9]. In order to assess the extent of lung injury, an inspiratory hold maneuver can be used to determine lung compliance which is typically 1.5-3.0/cmH2O/kg for an infant [2]. If the EP notes decreased compliance, tidal volumes closer to 3-6cc/kg should be targeted [9]. If these measures fail to improve oxygenation, inspiratory time can be increased in order to target an inspiratory to expiratory ratio closer to 1:2. With the exception of children with elevated intracranial pressure (ICP), congenital heart disease, or  pulmonary hypertension, permissive hypercapnea is acceptable as long as the pH remains > 7.2 [4].  

Ventilating the Child with Obstructive Physiology 

Endotracheal intubation of the asthmatic child is thankfully a rare event but one that portends to a high mortality [13]. At baseline, children exhibit higher airway resistance than their adult counterparts [2] and the even higher airway resistance in asthmatic patients creates high levels of intrinsic PEEP while increases the risk of breath stacking and pneumothorax [14]. If the patient’s respiratory rate is too high, lungs will remain progressively inflated at end expiration. This increases intra-thoracic pressure thereby decreasing preload and precipitating cardiovascular collapse. The level of this intrinsic PEEP can be assessed with an expiratory hold maneuver (Figure 1). To do this, the ventilator occludes the expiratory port at the end of exhalation allowing the alveolar and airway pressures to equilibrate. The total pressure at this moment minus the set PEEP on the ventilator represents the intrinsic PEEP [7].  More simply, a flow/time curve that fails to return to baseline prior to the onset of inspiration may signal to the EP that there may be high levels of intrinsic PEEP 2. (Figure 2) 

To counteract this, asthmatics and other patients with obstructive physiology will need respiratory rates far below median age values. In one series of asthmatic children aged as young as nine months, rates as low as 8-12 breaths per minute were used [15]. In order to further facilitate full expiration, the I:E ratio should be increased to target values as low as 1:4-5 [15]. High levels of PEEP are typically not required in these patients and use of low to zero PEEP has been documented [14]. Hypercapnea should be expected and is allowable in these patients [14]. 

Prolonged mechanical ventilation of the pediatric patient exhibits far more complexities than this blog post covers and is beyond the scope of most emergency medicine practice. However, by relying on evidence driven practice for adult intubated patients with close guidance from a pediatric intensivist and pediatric resuscitation reference, the initial steps and safe monitoring of the intubated child are well within the abilities of the emergency physician. 

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Expert Commentary

Thank you for this concise summary of mechanical ventilation in children. As noted, while this is an infrequent occurrence, the initial management of a ventilated child is incredibly important. 

In choosing initial ventilator settings, the key is decision and reassessment. Most modes of ventilation will work in most children. However, careful attention to what support you’re providing your patient with and what the results of that support are, is vital. Personally, I like using PRVC mode because it adjusts support in children with changing lung compliance without a lot of manipulation required by the physician. But, in any mode of ventilation you can make adjustments as you note changes in compliance. In pressure mode, watch your tidal volumes and in volume control or PRVC, monitor your peak pressures (along with your saturations and end tidal) to see if you’re achieving your goals. Use of SIMV versus AC modes of ventilation are important in the weaning phase of ventilation but less important as you’re initiating mechanical ventilation as the patient is typically neuromuscularly blocked. I also want to emphasize the importance of weaning supplemental oxygen as soon as possible in order to understand the adequacy of your support from an oxygenation and ventilation standpoint. Hypoxemia is bad but so is hyperoxia and masking hypoventilation.

While the research in pediatric ARDS is not as robust as in adults, there is a growing body of literature describing epidemiology and current practice.[1] Current management strategies continue to be extrapolated from adult data- including lung protective strategies of permissive hypoxemia and hypercarbia (tidal volumes 3-6 cc/kg, saturations >92% in mild pARDS and >88% in severe pARDS, pH > 7.2 with exceptions for specific populations including those with pulmonary hypertension).[2] Restrictive fluid strategies (after initial resuscitation) and adequate sedation are recommended. There is ongoing research regarding the use of HFOV and prone positioning in pARDS but this is outside the scope of emergency department care.

The intubated asthmatic remains a source of anxiety among many pediatric intensivists. Key takeaways are low respiratory rate to allow for full exhalation and prevent air trapping and matching intrinsic PEEP. Permissive hypercapnia is appropriate in these patients and their CO2 should be measured by blood gas; recognizing that there is a significant amount of dead space and end tidal may be falsely reassuring/low. When intubating patient with obstructive physiology, it’s also important to ensure adequate preload and have a high suspicion for pneumothorax if they decompensate. Utilizing ketamine for sedation can be useful in these patients and has the advantages of bronchodilation and not significantly suppressing their respiratory drive, allowing them to participate in setting their inspiratory/expiratory times. 

Final thought: don’t hesitate to ask for help- from the pediatric intensivists in house or over the phone- we are happy to collaborate!

References:

1. Khemani RG, Smith L, Lopez-Fernandez YM, et al. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. Lancet Respir Med. 2019 Feb;7(2):115-128. doi: 10.1016/S2213-2600(18)30344-8. Epub 2018 Oct 22.

2. Orloff KE, Turner DA, Rehder KJ. The Current State of Pediatric Acute Respiratory Distress Syndrome. Pediatr Allergy Immunol Pulmonol. 2019 Jun 1; 32(2): 35–44. doi: 10.1089/ped.2019.0999. Epub 2019 Jun 17.

Dr. Katie Wolfe, MD

Attending Physician

Pediatric Critical Care

Ann & Robert H. Lurie Children's Hospital of Chicago

Instructor of Pediatrics (Critical Care)

Northwestern University Feinberg School of Medicine

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How To Cite This Post

[Peer-Reviewed, Web Publication] McCauley, M. Stelter, J. (2020, Feb 3). Initiating Emergency Department Mechanical Ventilation in the Pediatric Patient. [NUEM Blog. Expert Commentary by Wolfe, K]. Retrieved from http://www.nuemblog.com/blog/ped-mech-vent.

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References

1. Losek J.D., Olson L.R., Dobson J.V., et al: Tracheal intubation practice and maintaining skill competency: survey of pediatric emergency department directors. Pediatr Emerg Care 2008; 24: pp. 294-299

2. Pacheco, G. S., Mendelson, J., & Gaspers, M. (2018). Pediatric Ventilator Management in the Emergency Department.  Emergency Medicine Clinics of North America, 36(2), 401–413.  https://doi.org/10.1016/j.emc.2017.12.008

3. Rimensberger, Peter C., Ira M. Cheifetz, and Martin C. J. Kneyber. “The Top Ten Unknowns in Paediatric Mechanical Ventilation.” Intensive Care Medicine 44, no. 3 (2018): 366–70. https://doi.org/10.1007/s00134-017-4847-4

4. Kneyber, Martin C. J., Daniele de Luca, Edoardo Calderini, Pierre-Henri Jarreau, Etienne Javouhey, Jesus Lopez-Herce, Jürg Hammer, et al. “Recommendations for Mechanical Ventilation of Critically Ill Children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC).” Intensive Care Medicine 43, no. 12 (December 2017): 1764–80. https://doi.org/10.1007/s00134-017-4920-z.

5. Wells et al. The accuracy of the Broselow tape as a weight estimation tool and a drug-dosing guide – A systematic review and meta-analysis. Resuscitation. 2017 Dec;121:9-33.

6. Singer, BD. Corbridge, TC. "Pressure modes of invasive mechanical ventilation" Southern Medical Journal"  104, no. 10 October 2011, pp 701-709 

7. Singer, BD. Corbridge, TC. "Basic Mecahnical Ventilation" Southern Medical Journal"  102, no. 12 December 2009 , pp pp 1238-1245 

8. de Jager P, Burgerhof JG, van Heerde M, et al: Tidal volume and mortality in mechanically ventilated children: A systematic review and meta-analysis of observational studies*. Crit Care Med 2014; 42:2461–2472

9.  Rimensberger PC, Cheifetz IM. Ventilatory support in children with pediatric acute respiratory distress syndrome: proceedings from the pediatric acute lung injury consensus conference. Pediatr Crit Care Med.(2015) 16(5 Suppl. 1):S51–60. 10.1097

10. Chameides L, Samson RA, Schexnayder SM, Hazinski MF (Eds).Pediatric Advanced Life Support Provider Manual, , American Heart Association, Dallas 2012.

11. Semple-Hess, J., & Campwala, R. (2014). Pediatric submersion injuries: emergency care and resuscitation.  Pediatric Emergency Medicine Practice, 11(6), 1–21

12. Kneyber, Martin C. J. “Mechanical Ventilation for Pediatric Acute Respiratory Distress Syndrome: Few Known Knowns, Many Unknown Unknowns.” Pediatric Critical Care Medicine: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 17, no. 10 (2016): 1000–1001.

13. Rampa S, Allareddy V, Asad R, et al. Outcomes of invasive mechanical ventilation in children and adolescents hospitalized due to status asthmaticus in United States: a population based study. J Asthma 2015; 52:423.

14. Rubin, Bruce K., and Vladimir Pohanka. “Beyond the Guidelines: Fatal and near-Fatal Asthma.” Paediatric Respiratory Reviews 13, no. 2 (June 2012): 106–11. https://doi.org/10.1016/j.prrv.2011.05.003.

15. Cox, R. G., G. A. Barker, and D. J. Bohn. “Efficacy, Results, and Complications of Mechanical Ventilation in Children with Status Asthmaticus.” Pediatric Pulmonology 11, no. 2 (1991): 120–26