AUTHOR INFORMATION

Section 1 of 11

Authored by Andrew Feng, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Critical Care, Hasbro Children's Hospital

Coauthored by Dale Steele, MD, Assistant Professor, Department of Emergency Medicine, Division of Pediatric Emergency Medicine, Brown University School of Medicine and Hasbro Children's Hospital

Andrew Feng, MD, is a member of the following medical societies: Society of Critical Care Medicine

Edited by Garry Wilkes, MD, Director, Emergency Medicine, Adjunct Associate Professor, Edith Cowan University, Department of Emergency Medicine, Bunbury Health Service; Robert Konop, PharmD, Director, Clinical Account Management, Ancillary Care Management, Inc; Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Division of Emergency Medicine, Children's Hospital of Boston

Author's Email:	Andrew Feng, MD
Editor's Email:	Garry Wilkes, MD

eMedicine Journal, May 17 2006, VOLUME 7, Number 5

INTRODUCTION

Section 2 of 11

Background: Although originally described in adults, acute respiratory distress syndrome (ARDS) occurs in children of all ages; hence, the change from "adult" to "acute" respiratory distress syndrome. The syndromes of acute lung injury (ALI) and ARDS usually do not manifest in the typical time frame for emergency department (ED) treatment. However, effective early recognition and treatment of bacteremia, shock, and respiratory failure may prevent or ameliorate the cascade of host responses that result in ARDS as well as comorbidities.

Recognizing that patients who have been resuscitated from circulatory failure may have a period of relative stability followed by deterioration secondary to ARDS or other components of the multiple organ failure syndrome (MOFS) is important for the emergency physician. This recognition should allow informed decision making of the need for transport or ongoing critical care.

Pathophysiology: ALI and ARDS are characterized by progressive hypoxemia. According to the 1994 American-European Consensus Conference on ARDS, ALI is defined by the following:

• Acute onset

• Arterial oxygen tension/fractional concentration of inspired oxygen ratio (PaO₂/FiO₂) of <300 (regardless of positive end-expiratory pressure [PEEP] levels)

• Acute-onset bilateral infiltrates on chest radiograph

• Noncardiogenic pulmonary edema

ARDS is defined by all of the above and PaO₂/FiO₂ of <200.

The syndrome follows a direct pulmonary or systemic insult resulting in injury to the alveolar-capillary unit. Several diseases can cause ALI/ARDS, more commonly following pneumonia, aspiration, and sepsis.

The course of ARDS can be divided into 3 pathologic stages as follows: exudative, proliferative, and fibrotic.

• Exudative: Injury to lung endothelial cells and alveolar epithelial cells occurs and results in air spaces filled with exudate and fluid and the development of microvascular thrombi leading to capillary occlusion.

• Proliferative: This stage occurs between the first and third week after the initial insult. Type II pneumocytes, fibroblasts, and myofibroblasts proliferate, resulting in widening of the alveolar septa and conversion of intra-alveolar hemorrhagic exudate into cellular granulation tissue.

• Fibrotic: If the patient survives for 3 weeks, the lungs exhibit remodeling and fibrosis.

Patients presenting in the ED will typically be confined to the exudative stage.

Pulmonary mechanics

Involvement is nonhomogeneous, with patchy and transient airway collapse occurring primarily in dependent portions of the lung. In these areas, functional residual capacity (FRC) is reduced and the closing capacity is above FRC. Thus, airway closure occurs during normal tidal breathing, leading to alveolar collapse, ventilation/perfusion (V/Q) mismatch, and progressive hypoxemia. During early stages, pulmonary resistance is near normal, as is anatomic dead space; thus, the initial problem usually is one of oxygenation rather than ventilation.

Effectively, the lung may be conceptualized as small rather than stiff. Although the total lung compliance is reduced, as little as 25% of the lung may be participating in gas exchange. Those areas that remain viable for gas exchange are normally compliant and subject to overdistension when subject to excessive inflating pressures.

Frequency:

• In the US: Approximately 1-4% of patients admitted to pediatric intensive care units (PICU) have established ARDS.

• Internationally: ARDS is observed in all locations where medical care allows patients to survive acute insults of a primary pulmonary or systemic nature.

Mortality/Morbidity:

• Mortality rates have varied between 20-75% among several studies, but they are difficult to interpret because of inconsistent diagnostic criteria. In a recent prospective multicenter study, Flori et al examined the epidemiology and risk factors associated with ALI/ARDS; the following findings were noted:
  
  
  • Of patients admitted to the PICU, 72% required intubation at the onset of ALI.
    
    

  • The mortality rate was 22%.
    
    

  • Poor prognostic indicators were associated independently with (1) the initial severity of hypoxemia, measured by the PaO₂/FiO₂ ratio; (2) the presence of nonpulmonary organ system failure, especially with 2 or more organ systems; and (3) the presence of central nervous system dysfunction.
    
    

  • Higher mortality rates occurred in patients with near-drowning, heart disease, and sepsis.

Age: In one series, the ages of children with ARDS ranged from 2 months to 21 years, similar to the overall distribution of the PICU population.

CLINICAL

Section 3 of 11

History: Histories at the time of initial presentation offer little with regards to diagnosis of ALI/ARDS except for alerting the clinician to risks for development of lung injury such as exposure to gaseous fumes or hydrocarbon ingestion and potential aspiration. The time to develop hypoxemia severe enough for ALI/ARDS criteria is also dependent on the time of onset of the triggering disease or injury. ALI/ARDS may further be masked by preexisting medical problems including reactive airway disease and bronchopulmonary dysplasia. Exacerbation of such underlying chronic lung diseases can lead to severe wheezing as the chief complaint.

• Establishing ALI/ARDS criteria is highly variable and is dependent of the onset of illness/insult.

• In most patients, ARDS developed within 72 hours after the onset of the associated acute disease and many (42%) within 24 hours.

• In those with infectious pneumonia, the onset is often gradual.

Physical: Patients who present with a short history of symptoms are unlikely to meet ALI/ARDS criteria. As their lungs undergo changes during the first exudative stage of the disease, patients may become hypoxic out of proportion to the underlying disease. They may also become tachypneic but not significantly dyspneic, ie, comfortably tachypneic.

• The evolution of clinical signs depends on the type, acuity, and severity of the initial insult. However, often a latent period occurs in which the patient exhibits little respiratory distress, except for hyperventilation and hypoxia, with normal auscultation and normal or mildly abnormal chest radiograph findings.

• Over a period of hours to days, hypoxemia worsens, and the patient appears dyspneic and more tachypneic.

• Chest examination reveals diffuse rales.

• Supplemental oxygen may maintain adequate oxygenation, but often fails to improve the clinical appearance.

Causes:

• ARDS is a clinical syndrome for which no specific marker exists. However, several have been identified to be associated with ARDS including tumor necrosis factor-a (TNF-a), interleukin-b (IL-b), interleukin 10 (IL-10), and more recently, soluble intercellular adhesion molecule 1 (sICAM-1). One of the most common diseases associated with ARDS is sepsis and/or septic shock. Other more common etiologies include infectious pneumonia, aspiration pneumonia, aspiration of gastric contents and other noxious substances (eg, hydrocarbons), inhalational injury (eg, thermal injury, noxious gases), and barotrauma/volutrauma secondary to mechanical ventilation.

• Failure of other organ systems commonly results in ARDS.

• Most near-drowning victims aspirate at least some water. Both fresh and saltwater aspiration results in pulmonary edema. If near-drowning occurs in stagnant or contaminated water, the risk of bacterial pneumonia is high. However, neither corticosteroids nor prophylactic antibiotics are beneficial.

DIFFERENTIALS

Section 4 of 11

Congestive Heart Failure and Pulmonary Edema
Pediatrics, Bronchiolitis
Pediatrics, Pneumonia
Pneumonia, Aspiration
Pneumonia, Bacterial
Pneumonia, Empyema and Abscess
Pneumonia, Immunocompromised
Pneumonia, Mycoplasma
Pneumonia, Viral
Pneumothorax, Iatrogenic, Spontaneous and Pneumomediastinum
Pneumothorax, Tension and Traumatic
Pulmonary Embolism

Other Problems to be Considered:

Oxygen toxicity
Ventilator-induced lung injury
Decreased capillary oncotic pressure
Neurogenic pulmonary edema
Postobstructive pulmonary edema (due to increased negative interstitial pressure)
Fat embolism

WORKUP

Section 5 of 11

Lab Studies:

• Suggested laboratory tests would include blood gas, CBC with differential, and electrolyte panel with BUN and creatinine. An arterial blood gas may be the most appropriate laboratory test to obtain and would be necessary if calculating the Pa₂/FiO₂ ratio for ALI/ARDS criteria. However, given the time course of the disease process, Pa₂/FiO₂ criteria is less likely to be met during the early disease course in the ED setting. A CBC may indicate an infectious etiology as well as uncover significant anemia, which will further compromise oxygen-carrying capacity. An electrolyte panel may also screen intravascular volume status, anion gap acidosis, and other potential comorbidities. Additional laboratory tests would be indicated pending specific concerns toward individual patients.

• The onset of capillary congestion and changes in the alveolar epithelium during the initial exudative stage leads to significant V/Q mismatching and intrapulmonary shunting. During this stage of ARDS, oxygen diffusion is impeded much greater than carbon dioxide diffusion, which is attributed to the much greater solubility of carbon dioxide. Therefore, hypoxemia tends to be a predominant laboratory finding with either a normal or low PCO₂.

• Arterial blood gas measurements reveal hypoxemia refractory to supplemental oxygen.

• The radiologic findings in ARDS are nonspecific (see Image 1, Image 3). Radiographic findings immediately after the inciting event may be entirely normal or may show only the primary disease process.

• Subsequently, progressive bilateral interstitial and alveolar infiltrates develop without cardiomegaly (see Image 2, Images 4-6).

• CT in ARDS, while not a routine part of the evaluation of children with ARDS, reveals most of the infiltrates in the dependent regions of the lung.

TREATMENT

Section 6 of 11

Prehospital Care: Since the eventual severity of acute respiratory distress syndrome (ARDS) relates to the severity of the inciting event, prehospital care is likely to have the most impact by early recognition of associated risk factors and aggressive treatment to reversing respiratory and circulatory failure, potentially averting the onset of ARDS.

Emergency Department Care: Children who ultimately develop ARDS more typically present in the emergency department (ED) without many of the signs and symptoms that fulfill the diagnostic criteria. However, early recognition of these signs and symptoms as well as recognition of the more common risk factors for developing ALI/ARDS can impact the decision to initiate varying treatments for respiratory distress. When patients present in the ED with increased work of breathing secondary to worsening lung compliance, increasing mean airway pressure and instituting other alveoli-recruiting maneuvers may offer the most benefit in addition to administering supplemental oxygen. This can be achieved either invasively (ie, with tracheal intubation and mechanical ventilation) or noninvasively. Provided that the patient continues to have good respiratory effort and adequate oxygenation, noninvasive positive airway pressure support may be all that is required in the ED setting.

Continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP) therapies via nasal mask or face mask have been successful in maintaining adequate oxygenation and ventilation in some patients who present with impending acute respiratory failure and who otherwise would require tracheal intubation. The main benefits of CPAP and BiPAP include improvement of oxygenation and work of breathing without the expense of inducing and maintaining sedation for intubation, since CPAP and BiPAP are relatively well tolerated by patients. Patients are also able to continue regulating their own minute ventilation.

More recently, Vapotherm (Vapotherm; Stevensville, MD) has become an option for delivering positive airway pressure and supplemental oxygen noninvasively, especially as a substitute for nasal CPAP in infants. Very few studies have been performed using this device. Based on personal experience, advantages of using the Vapotherm device or a similar high-flow, humidified nasal cannula device include easy set-up, easy access to the patient’s mouth, and better visualization of the patient’s face. Disadvantages include not being able to titrate, regulate, and measure pressures as precisely as with CPAP and BiPAP.

In the event that a patient requires intubation for acute lung injury, it may be prudent to use a cuffed endotracheal tube regardless of the age of the patient. Traditionally, children younger than 8 years are intubated with uncuffed tubes. However, various lung conditions, such as ALI/ARDS, worsen lung compliance. Therefore, cuffed tubes are often required to effectively inflate the lungs. Otherwise, excessive air may leak around the endotracheal tube resulting in inadequate oxygenation and ventilation.

• Once intubated, the following steps should be taken to minimize further lung injury:

• Peak inspiratory pressure (PIP): PIPs or plateau pressures generally should be maintained ideally no more than 30 cm H₂O. Because this may be difficult with volume-control ventilation, patients are alternatively managed with pressure-control ventilation. However, no data support pressure-control ventilation as being superior to volume-control ventilation. When using the latter, the National Institutes of Health (NIH) ARDS Network protocols include a target tidal volume of less than or equal to 6 mL/kg.

• Peak end-expiratory pressure (PEEP): Starting PEEP levels are typically 5 cm H₂O for normally compliant lungs. However, for poorly compliant lungs due to ALI/ARDS, PEEP levels can be increased aggressively to optimize oxygenation by increasing the mean airway pressure without increasing PIP (see above). Patients may require more deep sedation +/- paralysis for PEEP significantly greater than 10 cm H₂O. Furthermore, if it becomes clear that escalating PEEP levels significantly greater than 10 cm H₂O will be required to maintain adequate oxygenation, or despite “high” PEEP levels, oxygenation remains poor, changing to high-frequency oscillatory ventilation (HFOV) should be considered (see below).

• Inspiratory time (IT): Increasing IT may increase the mean airway pressure and thus improve oxygenation. In volume-control ventilation, this may also decrease PIP as long as I:E remains less than or equal to 1:1 or as long as no evidence of air-trapping is present.

• Respiratory rate (RR): RR normally should be set ideally to maintain normal arterial pH. However, RR should not be increased at the expense of exacerbating lung injury. Since relative hypercarbia has no significant deleterious effects beyond the context of intracranial hypertension, “permissive hypercapnia” is a common approach. However, severe acidemia may diminish other organ system functions. Therefore, other methods to avoid extreme acidosis such as administering NaHCO₃ and THAM may be used instead of increasing RR.

• FiO₂: During the acute period, 100% FiO₂ is typically administered to the patient, especially if the patient is hypoxic upon presentation. Although excessively high oxygen concentrations can result in increased oxygen free radicals production and subsequently lead to barotrauma independently, several hours of high oxygen concentration exposure is required for significant barotrauma effect. This time period would most likely exceed the duration of the patient’s stay in the ED and, therefore, FiO₂ weaning need not be addressed in most situations.

• High-frequency oscillatory ventilation (HFOV): Although less likely to be observed during the ALI phase or earlier ARDS phases, lung compliance may be already severely compromised, and excessive PIP and/or PEEP settings may be needed just to meet adequate oxygenation needs. HFOV may provide superior lung protection in this scenario. However, this should be initiated in an ICU setting, since set-up would be more practical given nursing support needs, equipment and space, more invasive monitoring and vascular access, and anticipation for other potential complications that are beyond the scope of this discussion. Regardless of the patient’s mechanical ventilation needs, an expedient transfer to the PICU may be prudent.

• The need for pediatric critical care resources should be anticipated early.

Consultations: Consult a pediatric intensivist.

MEDICATION

Section 7 of 11

No specific drug therapy for ARDS exists, and many drugs relating to ARDS therapy will not be indicated during the early ED intervention period beyond supportive care. However, as a sequela to intubation and mechanical ventilation, high mean airway pressures for poor oxygenation may compromise cardiac output and may require fluid resuscitation and the initiation of vasoactive agents.

Corticosteroids have been used empirically and in numerous clinical trials. Early use of steroids has not yielded any significant impact on attenuation or survival outcome, except for patients at risk for fat embolism and patients with AIDS and Pneumocystis carinii pneumonia. Late use of steroids was demonstrated by Meduri et al to attenuate ARDS and improve survival.

Inhaled nitric oxide has produced short-term physiologic improvements in ventilation-perfusion matching and intrapulmonary shunting; however, no randomized clinical studies have documented improved patient outcome. Of prognostic value, a poor early response to inhaled nitric oxide is associated with death.

Drug Category: Vasoactive agents -- To increase cardiac output and improve hypotension induced by elevated mean airway pressures from mechanical ventilation. Increases in pulmonary vascular resistance may also be seen in ARDS, which may result in increased right ventricular work. Adequate cardiac output depends on the ability of the right ventricle to increase stroke work. Dobutamine or inamrinone (formerly amrinone) may be chosen in this context because they increase cardiac output without producing significant pulmonary vasoconstriction.

Drug Name	Dobutamine (Dobutrex) -- Sympathomimetic amine with stronger beta than alpha effects. Produces systemic vasodilation and increases the inotropic state. Vasopressors augment the coronary and cerebral blood flow during the low-flow state associated with shock. Sympathomimetic amines with both alpha- and beta-adrenergic effects are indicated in cardiogenic shock. Dopamine and dobutamine are the drugs of choice to improve cardiac contractility, with dopamine the preferred agent in hypotensive patients. Higher dosages may cause an increase in heart rate, exacerbating myocardial ischemia.
Adult Dose	Begin infusion at 2.5 mcg/kg/min IV; titrate to desired effect
Pediatric Dose	Begin infusion at 5 mcg/kg/min IV; titrate to desired effect
Contraindications	Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis and atrial fibrillation or flutter
Interactions	Beta-adrenergic blockers antagonize effects; general anesthetics may increase toxicity; coadministration with diuretics may result in hypovolemia and decreased filling pressures
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Although unusual in children, following a myocardial infarction, use with extreme caution; hypovolemic state should be initiated before using this drug; arrhythmias

Drug Name	Milrinone (Primacor) -- Positive inotrope and vasodilator with little chronotropic activity in a non–receptor-mediated mechanism. Induces peripheral vasodilation and provides inotropic support. Different in mode of action from either cardiac glycosides (digoxin) or catecholamines.
Adult Dose	50 mcg/kg (0.05 mg/kg) loading dose IV followed by a continuous infusion at 0.375-0.75 mcg/kg/min
Pediatric Dose	50-75 mcg/kg (0.05-0.075 mg/kg) loading dose IV followed by a continuous infusion at 0.25-0.75 mcg/kg/min
Contraindications	Documented hypersensitivity
Interactions	Coadministration with diuretics may result in hypovolemia and decrease in filling pressure; milrinone precipitates in presence of furosemide
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor fluids, electrolyte changes, and renal function during therapy; excessive diuresis may increase potassium loss and predispose digitalized patients to arrhythmias; important to correct hypokalemia with potassium supplementation prior to treatment; patients showing excessive decreases in blood pressure should have infusion rates slowed or stopped; previous vigorous diuretic therapy has caused significant decreases in cardiac filling pressure, cautiously administer milrinone and monitor blood pressure, heart rate, and clinical symptomatology

Drug Name	Dopamine (Intropin) -- Naturally occurring endogenous catecholamine that stimulates beta1-and alpha1-adrenergic and dopaminergic receptors in a dose-dependent fashion; stimulates release of norepinephrine. In low doses (2-5 mcg/kg/min), acts on dopaminergic receptors in renal and splanchnic vascular beds, causing vasodilatation in these beds. In midrange doses (5-15 mcg/kg/min), acts on beta-adrenergic receptors to increase heart rate and contractility. In high doses (15-20 mcg/kg/min), acts on alpha-adrenergic receptors to increase systemic vascular resistance and raise BP. After initiating therapy, increase dose by 1-4 mcg/kg/min q10-30min until optimal response is obtained. More than 50% of patients are satisfactorily maintained on doses less than 20 mcg/kg/min.
Adult Dose	Begin infusion at 2-5 mcg/kg/min IV; not to exceed 50 mcg/kg/min
Pediatric Dose	Begin infusion at 5 mcg/kg/min IV and titrate to desired effect
Contraindications	Documented hypersensitivity; pheochromocytoma or ventricular fibrillation
Interactions	Catechol-o-methyltransferase (COMT) inhibitors may prolong effects of dopamine; beta-adrenergic blockers may antagonize peripheral vasoconstriction caused by high doses of dopamine; butyrophenones (eg, haloperidol) and phenothiazines can suppress dopaminergic renal and mesenteric vasodilation induced with low-dose dopamine infusion; concurrent administration of diuretic agents with low-dose dopamine may produce additive effects on urine flow; hypotension and bradycardia may occur with phenytoin; dopamine may decrease effects of phenytoin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during infusion; prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia; patients who have received MAO inhibitors within 2 or 3 wk prior to administration of dopamine should receive initial doses no greater than 1/10 initial dose; ventricular arrhythmias and hypertension may occur when administering dopamine to patients receiving cyclopropane or halogenated hydrocarbon anesthetics

Drug Name	Epinephrine (Adrenalin) -- Used for hypotension refractory to dopamine. Alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects. Adrenergic receptor activity tends to be dose-related: lower doses predominantly activate beta receptors; higher doses predominantly activate alpha receptors.
Adult Dose	Begin infusion at 1 mcg/min IV; not typically a first-line agent
Pediatric Dose	Begin infusion at 0.02-0.05 mcg/kg/min IV and titrate to desired effect
Contraindications	Documented hypersensitivity; narrow- or shallow-angle glaucoma; aphakia
Interactions	Increases toxicity of beta- and alpha-blocking agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in cardiac arrhythmias

Drug Category: Anti-inflammatory -- Primarily used as an anti-inflammatory in this disease process.

Drug Name	Methylprednisolone (Solu-Medrol) -- Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. For late-onset treatment, "refractory ARDS" defined as 7 days of mechanical ventilation without significant improvement. Based on protocol by Meduri et al.
Adult Dose	Loading dose of 2 mg/kg, followed by 2 mg/kg/d divided q6h from day 1 to day 14; 1 mg/kg/d from day 15 to day 21; 0.5 mg/kg/d from day 22 to day 28; 0.25 mg/kg/d on days 29 and 30; 0.125 mg/kg/d on days 31 and 32 For patients extubated prior to day 14, treatment advanced to "day 15"
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections; administration of live or live-attenuated vaccine in patients receiving immunosuppressive doses of corticosteroids
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics; grapefruit juice increases prednisolone concentrations; methylprednisolone and cyclosporine mutually inhibit one another, resulting in increased plasma levels of each drug
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Peptic ulcer disease, ocular herpes simplex, untreated systemic infections, tuberculosis

FOLLOW-UP

Section 8 of 11

Further Inpatient Care:

• Noninvasive positive pressure ventilation and/or endotracheal intubation with mechanical ventilation is usually required in patients with clinical and radiographic evidence suggestive of worsening lung disease with a fraction of inspired oxygen (FiO₂) of greater than 50%.

• No gas exchange occurs in collapsed or fluid-filled alveoli. A nearly linear increase in FRC develops as PEEP is increased over a range from 0-15 mm Hg with recruitment of terminal airways and alveoli and improved oxygenation.

• A physiologic approach to ventilating patients with ARDS includes the use of optimal PEEP to minimize FiO₂ while maintaining oxygen delivery, small tidal volumes, and extended inspiratory times to allow more uniform ventilation. Permissive hypercapnia may allow reductions in rate and peak inspiratory pressure (PIP), thereby limiting further barotrauma and volutrauma.

• Prophylactic application of PEEP has not been shown to improve outcome. As PEEP is increased, cardiac output may fall and volume expansion and/or inotropic/pressor agents may be required.

• Other techniques include high-frequency oscillatory ventilation and high-frequency jet ventilation.

• Adjuncts to mechanical ventilation

• Surfactant dysfunction has been documented in ARDS and has led to investigational use of exogenous surfactant. A recent randomized, controlled multicenter study by Willson et al using a natural exogenous surfactant (calfactant) demonstrated significant improvement in oxygenation, as measured by oxygenation index and decreased mortality rate. However, earlier clinical trials in adults with sepsis-induced ARDS did not effect overall survival.

• Inhaled nitric oxide often acutely improves oxygenation and, in the short-term, allows weaning of FiO₂ and ventilatory parameters. However, not all patients respond and not all have a sustained response. An association exists between improvement with inhaled nitric oxide and improved clinical outcome.

• Extracorporeal membrane oxygenation (ECMO) is used in some institutions as a rescue therapy for children with failure to respond to conventional ventilation. Matched cohort analysis has suggested a lower mortality rate in patients treated with ECMO.

Transfer:

• Intrahospital transfers: Patients transferred from the ED to the PICU must be accompanied by providers competent to secure and manage the patient's airway. This team often includes a physician, a nurse, and a respiratory therapist.

• Interhospital transfers: Ideally, a dedicated pediatric transport team transfers the patient to a PICU via ground, rotor, or fixed wing transport.

Complications:

• Complications of treatment

• Oxygen toxicity

• Ventilator-induced lung injury

• Pulmonary barotrauma is common, with air leaks occurring in nearly one half of patients.

• Death from refractory respiratory failure is relatively uncommon.

• The major causes of death are sepsis or failure of other major organs, such as the heart, brain, and liver.

• During the proliferative stage, diffuse interstitial fibrosis may develop.

Prognosis:

• Relatively few long-term survivors of pediatric ARDS have been studied.

• Because lung growth is not complete until age 8 years, the effect on young children may be worse than in older children or adults.

Patient Education:

• For excellent patient education resources, visit eMedicine’s Lung and Airway Center and Bacterial and Viral Infections Center. Also, see eMedicine’s patient education articles Acute Respiratory Distress Syndrome and Severe Acute Respiratory Syndrome (SARS).

TEST QUESTIONS

Section 9 of 11

CME Question 1: A 2-year-old boy is resuscitated after being submerged in the family pool. Six hours after arrival he becomes progressively agitated and dyspneic. Oxygen saturation (SpO₂) is 85% despite oxygen via a nonrebreather mask. Chest examination reveals diffuse rales. Which of the following is the most appropriate treatment?

A: Lasix 1 mg/kg to decrease pulmonary edema fluid from aspiration of hypotonic pool water
B: Methylprednisolone 30 mg/kg IV
C: Intubation with stepwise adjustment of positive end-expiratory pressure (PEEP)
D: Ceftriaxone 50 mg/kg for suspected aspiration pneumonitis
E: Sedation to decrease agitation and air hunger

The correct answer is C: Most aspirated fresh water is rapidly absorbed. Pulmonary edema is likely due to acute respiratory distress syndrome (ARDS). Tracheal intubation with PEEP will improve oxygenation and allow less toxic oxygen concentrations to be delivered. A trial of noninvasive positive pressure ventilation (NIPPV) may be considered, but this is not one of the choices. In addition, preparation for tracheal intubation should be done at the same time as starting a trial on NIPPV.

Corticosteroids have no role in the treatment of ARDS and may increase morbidity. Prophylactic use of antibiotics is likely to select resistant organisms and is not indicated. Agitation is an important early clinical indicator of hypoxia. Oxygenation should be assessed and ventilation controlled prior to use of sedation.

CME Question 2: A 13-month-old child develops sudden onset of upper airway obstruction. He is carried into the ED by a police officer. He is deeply cyanotic and limp but has a palpable radial pulse. A Magill forceps is used to remove a checker from the airway. After brief bag-valve mask ventilation, the child begins to breathe spontaneously. Thirty minutes later, he is more dyspneic with an oxygen saturation (SpO₂) of 80% in mask oxygen. A chest radiograph reveals bilateral pulmonary edema. What is the most likely etiology for his persistent respiratory distress?

A: Acute respiratory distress syndrome (ARDS)
B: Aspiration of gastric contents
C: Cardiogenic pulmonary edema due to acute myocardial failure from hypoxia
D: Acute pulmonary edema due to high negative interstitial pressure associated with acute upper airway obstruction
E: Pneumothorax

The correct answer is D: The time course is too rapid for ARDS. Pneumothorax should be considered but can be excluded after a chest radiograph. Aspiration of gastric contents is possible; however, acute pulmonary edema after relief of severe upper airway obstruction would explain the findings on chest radiograph.

Pearl Question 1 (T/F): Cuffed endotracheal tubes should be considered for some children despite being younger than 8 years.

The correct answer is True: Cuffed endotracheal tubes are commonly used for children younger than 8 years when their lung compliance is known or anticipated to be very poor. Poor lung compliance may result in excessive resistance and impede airflow down the airways. Without a cuff, airflow may be redirected back out around the endotracheal tube through the vocal cords and into the oropharynx, since this would be the path of least resistance.

As a general rule for selecting a cuffed tube size for a child younger than 8 years, a half-size smaller than the appropriate uncuffed tube size is selected.

Pearl Question 2 (T/F): Significantly elevated positive end-expiratory pressure (PEEP) can potentially compromise cardiac output.

The correct answer is True: In children with acute respiratory distress syndrome (ARDS), PEEP improves oxygenation. However, at higher levels, PEEP may result in decreased cardiac output, primarily by decreasing venous return (decreased preload). Volume expansion is often needed to expand preload in order to maintain cardiac output. Once preload/intravascular volume is optimized, vasoactive agents, such as dopamine, are commonly added to improve cardiac output as needed.

Pearl Question 3 (T/F): In acute respiratory distress syndrome (ARDS), mechanical ventilator rates should be increased as high as necessary to maintain normal pCO₂.

The correct answer is False: Utilizing high mechanical ventilator rates to regulate normal pCO₂ can have a negative impact on barotrauma/volutrauma. This may lead to worsening and prolonging ARDS. Respiratory rates typically do not exceed 30 breaths/minute, and other maneuvers, such as administering NaHCO₃ or THAM, are used to maintain arterial pH typically above 7.20 or higher.

Pearl Question 4 (T/F): Acute respiratory distress syndrome (ARDS) results from infectious lung diseases only.

The correct answer is False: Although pneumonia is one of the most common causes of ARDS, many systemic diseases commonly result in ARDS.

PICTURES

Section 10 of 11

Caption: Picture 1. An 8-year-old girl with a diagnosis of pneumonia. Chest radiograph on the day of admission.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: X-RAY
Caption: Picture 2. A 14-month-old boy with a diagnosis of exacerbation of bronchopulmonary dysplasia (BPD). Chest radiograph on the day of admission.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: X-RAY
Caption: Picture 3. An 8-year-old girl with pneumonia and impending respiratory failure. Chest radiograph on day 2.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: X-RAY
Caption: Picture 4. A 14-month-old boy with bronchopulmonary dysplasia (BPD) exacerbation and impending respiratory failure. Chest radiograph on day 2 in the morning.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: X-RAY
Caption: Picture 5. A 14-month-old boy with bronchopulmonary dysplasia (BPD) exacerbation and respiratory failure. Chest radiograph on day 2 in the afternoon.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: X-RAY
Caption: Picture 6. A 14-month-old boy with bronchopulmonary dysplasia (BPD) exacerbation, respiratory failure, and severe hypoxemia. Chest radiograph on day 2 in the evening.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: X-RAY

BIBLIOGRAPHY

Section 11 of 11

• Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000 May 4; 342(18): 1301-8[Medline].
• Antonelli M, Conti G, Rocco M, et al: A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998 Aug 13; 339(7): 429-35[Medline].
• Beaufils F, Mercier JC, Farnoux C, et al: Acute respiratory distress syndrome in children. Curr Opin Pediatr 1997 Jun; 9(3): 207-12[Medline].
• Brower RG, Ware LB, Berthiaume Y, Matthay MA: Treatment of ARDS. Chest 2001 Oct; 120(4): 1347-67[Medline].
• Davis SL, Furman DP, Costarino AT Jr: Adult respiratory distress syndrome in children: associated disease, clinical course, and predictors of death. J Pediatr 1993 Jul; 123(1): 35-45[Medline].
• Fackler JC, Arnold JH, Nichols DG: Acute respiratory distress syndrome. In: Rogers M, Williams, Wilkins, eds. Textbook. 1996:197-233.
• Flick R: Mechanical Ventilation: A Physiological Approach to ARDS. March 5, 1998. [Full Text].
• Flori HR, Glidden DV, Rutherford GW, Matthay MA: Pediatric acute lung injury: prospective evaluation of risk factors associated with mortality. Am J Respir Crit Care Med 2005 May 1; 171(9): 995-1001[Medline].
• Flori HR, Pittet JF: Biological markers of acute lung injury: prognostic and pathogenetic significance. New Horiz 1999; 7: 287-311.
• Goldman AP, Tasker RC, Hosiasson S, et al: Early response to inhaled nitric oxide and its relationship to outcome in children with severe hypoxemic respiratory failure. Chest 1997 Sep; 112(3): 752-8[Medline].
• Green TP, Timmons OD, Fackler JC, et al: The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group. Crit Care Med 1996 Feb; 24(2): 323-9[Medline].
• Levitzky MG: Pulmonary Physiology. New York: McGraw-Hill Health Professions Division; 1999:131.
• Meduri GU, Headley AS, Golden E, et al: Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 1998 Jul 8; 280(2): 159-65[Medline].
• Nichols DG, McCloskey JJ, Rogers MC: Adult respiratory distress syndrome. In: Rogers MC, ed. Textbook of Pediatric Intensive Care. Baltimore: Williams & Wilkins; 1992:296.
• Paulson TE, Spear RM, Peterson BM: New concepts in the treatment of children with acute respiratory distress syndrome. J Pediatr 1995 Aug; 127(2): 163-75[Medline].
• Poponick JM, Renston JP, Bennett RP, Emerman CL: Use of a ventilatory support system (BiPAP) for acute respiratory failure in the emergency department. Chest 1999 Jul; 116(1): 166-71[Medline].
• Taylor RW, Zimmerman JL, Dellinger RP: Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. JAMA 2004 Apr 7; 291(13): 1603-9[Medline].
• Willson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA 2005 Jan 26; 293(4): 470-6[Medline].

eMedicine Journals > Emergency Medicine > Pediatric > Pediatrics, Respiratory Distress Syndrome

Please email us with any comments you have on our new chapter format.

Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Test Questions | Pictures | Bibliography