ARDS is considered to be present in the setting of bilateral infiltrates on a chest radiograph, a PaO2/FiO2 (The ratio of the partial pressure of oxygen in arterial blood to the percentage inhaled oxygen concentration ) <200, and a left atrial filling pressure <18 mm Hg or no clinical or radiologic evidence of elevated left atrial pressure.
MEDICAL TREATMENT :
Medical Care: No treatment for ARDS is definitive. The cornerstone of management is impeccable intensive care. Early anticipatory management may avoid late complications and poor outcome. Treat the primary cause (eg, sepsis, pneumonia) if possible. As much as possible, minimizing the risk of multiple organ failure and VILI is essential.
Critical aspects are maintaining nutrition and being cognizant of the risk of numerous complications in critically ill children, including sepsis, fluid overload, inappropriate levels of sedation, and neuromuscular blocking agents. Many of the therapies and strategies proposed for ARDS are founded on rational physiologic and pathologic principles, but they have not been shown to have unequivocal benefits. Reasons include an incomplete understanding of the pathophysiology of ARDS, the lack of a standardized diagnostic test, and the heterogeneity of the illness and the patient population. Furthermore, an inability to adequately control for other therapies, specifically ventilation modalities, and the fact that most patients die from multiple organ failure or their precipitating illness confound the analysis and interpretation of data from many trials.
Ventilation
Ventilation is the cornerstone of treating the patient with ARDS. Striking a balance between the level of ventilator support necessary to provide a reasonable ventilation and oxygenation while minimizing VILI is one of the most active areas of research in critical care.
Noninvasive ventilation has been used early in ALI and ARDS to avoid endotracheal intubation. Published experience has largely been limited to the adults, and most patients with ARDS require endotracheal intubation for airway control and invasive mechanical ventilation.
Traditional ventilatory strategies are aimed at maintaining normal tidal volumes and normal blood gas values; however, this was associated with a high morbidity and mortality rate. Therefore, many clinicians attempted to use high partial pressures of carbon dioxide (PaCO2), ie, the permissive hypercapnic strategy. Associated with this was the increasing recognition that repetitive opening and closing of alveoli exacerbated lung injury. Hence, a strategy of maintaining an open lung evolved.
The twin goals of permissive hypercapnia and open lung maintenance are achieved, in simple terms, by optimizing PEEP and minimizing delivered tidal volumes.
Hickling et al (1990) gave one of the original descriptions of permissive hypercapnia, reporting an almost 80% reduction in mortality rates. Although subsequent trials showed no benefit in reducing tidal volumes.
Amato et al (1998) reported that their strategy of ventilating at a low tidal volume with an elevated carbon dioxide level and preventing alveolar closure by optimizing PEEP decreased the mortality rate (38% versus 71%, P < .001).
The study by Amato et al was criticized for the high mortality rate in the control arm. However, a multicenter study sponsored by the National Institutes of Health (NIH) confirmed these results. The control group was ventilated with a tidal volume of 12 mL/kg adjusted to maintain a plateau pressure of 45-50 cm H2O. In the study group, tidal volume was reduced to 6 mL/kg and then as low as 4 mL/kg to maintain a plateau pressure <30 cm H2O. The trial was terminated prematurely when an interim analysis showed a markedly reduced mortality rate in the group receiving low tidal volume (31% vs 39.8%, P = .007).
Ranieri et al provided additional information to suggest that low tidal volume may be beneficial. They reported lowered levels of cytokines in BAL fluid and plasma in patients treated with low tidal volume. The authors postulated that decreased levels of cytokines reflect reduced inflammation in organs other than the lungs, leading to a possible survival benefit. Numerous ventilator modes are available; however, little if any data demonstrate the superiority of 1 mode versus another.
Two modes of high-frequency ventilation are high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV).
HFJV is rarely used in pediatric practice, and it is not discussed any further.
HFOV may be thought of as the ultimate in high-PEEP low-tidal-volume strategy. Because of the extremely small tidal volumes used, HFOV minimizes repetitive opening and closing and possibly reduces VILI, if the lung is recruited sufficiently. Because of the extremely high respiratory rates, carbon dioxide can be maintained at satisfactory levels. Randomized controlled trials have been done to compare HFOV with conventional mechanical ventilation in pediatric and neonatal practice, with generally encouraging results. Although initial studies in neonates show no benefit, the strategy was less than optimal. Recruiting (or opening) the atelectatic areas of the lung is critical to maintaining lung volume at the FRC. Optimal lung volume is gauged with clinical assessment, monitoring of arterial oxygen saturation, ABGs, and lung inflation on chest radiography.
Airway pressureโrelease ventilation (APRV) is a relatively new mode of ventilation that allows for spontaneous ventilation with mean airway pressures similar to that achieved with HFOV. Case studies report the successful use of APRV in ARDS; however, data are insufficient to compare it with conventional or HFOV.
As an adjunct to ventilator management, prone positioning has been advanced as a means to improve oxygenation in patients with severe ARDS. By turning patients prone, V/Q matching is thought to be optimized by reducing atelectasis in dependent areas of the lung. Many trials have shown improved oxygenation with prone positioning, however, a recent multicenter trial of 102 patients demonstrated no significant difference in clinical outcomes, including ventilator-free days. The study population had a mortality rate of only 8%, suggesting that prone positioning may still have a role in extremely ill patients with ARDS. Although no consensus exists regarding how to incorporate prone positioning into the care of a child with ARDS, it should still be attempted in a patient with profound hypoxemia.
Steroid therapy
The use of steroids is reported as a therapy for ARDS. A number of reported trials demonstrated no benefit with large doses of steroids administered as a short course in the early phases of ARDS. However, many investigators contend that on-going or late-stage ARDS is partly an inflammatory condition. Hence, by virtue of their anti-inflammatory properties, steroids may be beneficial when used in the fibroproliferative phase.
In 1998, Meduri et al reported their randomized double-blind placebo-controlled trial in adults with ARDS who were not improving, as defined by lack of improvement in lung injury score by day 7 of respiratory failure. Patients received methylprednisolone or placebo for 32 days. Those with no response were given the alternative treatment on day 10. Those receiving steroids had reduced lung injury and multiorgan dysfunction scores, and they were extubated more frequently than those given placebo. The hospital mortality rate significantly decreased (12% vs 62%). Rates of infection did not differ between the groups. Similar data in the pediatric population are not available. Many centers begin steroid therapy on days 7-10 of mechanical ventilation. Use of steroids for the fibroproliferative phase of ARDS in the pediatric population is extrapolated from this study.
To the authors' knowledge, no study has been performed to examine the potential role of inhaled steroids in ARDS.
Steroids may be indicated as part of the treatment for the underlying etiology of ARDS, eg, ARDS secondary to Pneumocystis jiroveci infection.
A subgroup of patients with ARDS with marked eosinophilia in their peripheral blood or bronchoalveolar fluid may benefit from steroid therapy.
Steroid use may contribute to prolonged weakness after ARDS. Care should be taken to minimize concomitant neuromuscular blockade.
Surfactant treatment
One of the key events in the progression of ARDS is a reduction in both volume and function of surfactant. In addition, surfactant inhibitors may be present in the alveolus. Based on positive results of many clinical trials of IRDS, a number of studies have been conducted to examine the role of surfactant in ARDS.
Administration of exogenous surfactant has many theoretical benefits, as demonstrated in vitro. These include the prevention of alveolar collapse, maintenance of pulmonary compliance, optimization of oxygenation, enhancement of ciliary function, enhancement of bacterial killing, and downregulation of the inflammatory response.
Studies of various surfactants and different modes of delivery in adults have not yielded a consensus regarding the efficacy of surfactant in ARDS. In vitro data and extrapolated data from neonatal in vivo studies suggest that animal-derived surfactant may be superior to synthetic surfactant. In addition, inhalation may be inefficient as a means of delivery.
A growing body of literature supports the use of surfactant for severe pediatric ARDS. A retrospective chart review of 19 patients showed improvement in oxygenation index and hypoxemia score but no change in other outcome measures. Prospective studies from the late 1990s to early 2000 involving porcine or bovine surfactant showed variable outcomes ranging from improvement in only oxygenation to shortened ventilation and PICU stay.
A recent multicenter randomized double-blind placebo-controlled trial (Wilson, 2005) of Calfactant demonstrated a significant reduction in mortality, with an absolute risk reduction of 17%. This reduction was most pronounced in patients younger than 12 months, who had a corresponding absolute risk reduction of 33%. Significant improvement was also demonstrated in the oxygenation index, in ventilator-free days, and in rates of failure with conventional mechanical ventilation. One confounding factor was that the placebo group had more immunocompromised patients than the treatment group.
Data from a cost-effectiveness study of Infasurf suggested that the use of exogenous surfactant may be cost-effective in an American healthcare setting. The expense of the surfactant was offset by early PICU discharge. Mortality benefits and ventilator-free days were not factored into the model.
Nitric oxide (NO) therapy
NO is a potent vasodilator, first described in 1989. Its use as a specific pulmonary vasodilator was first described almost a decade ago in neonates with persistent pulmonary hypertension. Subsequent trials confirmed the efficacy of inhaled NO (iNO) in this population, in whom iNO decreased the use of extracorporeal membrane oxygenation (ECMO).
iNO is a selective pulmonary vasodilator, as it rapidly binds to hemoglobin and is inactivated before reaching the systemic circulation. It may have a number of attractive properties in patients with ARDS. By reducing hypoxic pulmonary vasoconstriction (HPV), iNO may reduce right-sided pulmonary pressures. This, in turn, lessens the degree of leftward septal shift, which improves cardiac output. Oxygenation benefits that occur while iNO diffuses to only relatively well-aerated parts of the lung lessen any local HPV. Other benefits may include decreased pulmonary edema while pulmonary pressures are reduced.
Despite the potential benefits, no study has shown lasting advantage associated with iNO. Although many studies demonstrated improvement in surrogate measures (eg, oxygenation, degree of ventilator support), no differences are noted in primary outcome measures (eg, mortality, ventilator-free days, time to extubation). Reasons for this lack of clinical benefit are unclear. The fact that ARDS tends to be a heterogeneous lung disease in contrast to persistent pulmonary hypertension of the newborn may be part of the explanation. As an alternative, the fact that most patients with ARDS die from sepsis, multiorgan failure, or their primary illness may imply that no survival benefit is observed with improved oxygenation and decreased ventilator support. Another confounder is that patients with ARDS are heterogeneous.
A recent multicenter study of the use of iNO (dose of 10 ppm) in children with acute hypoxic respiratory failure was reported. Although oxygenation acutely improved in the group treated with iNO, this change did not translate into a survival benefit. However, data from a post-hoc analysis suggested that patients with severe respiratory failure (oxygenation index >25) or immunocompromise may have benefited from the use of iNO. However, this analysis has been criticized.
In summary, although a number of trials have shown an improvement in various physiologic indices, these results have not translated to tangible benefits, such as decreased mortality rates. A recent review by the Cochrane database confirmed this assessment. According to this review, iNO has no effect on mortality and only transiently improves oxygenation in both children and adults.
Liquid ventilation
Perfluorocarbons (PFCs) have a number of attractive properties that facilitate their use in liquid ventilation. Because PFCs are chemically and biologically inert, with a high vapor pressure that ensures rapid evaporation when exposed to the atmosphere, both oxygen and carbon dioxide dissolve easily in PFC liquid.
Perceived advantages of PFCs in ARDS include an ability to maintain open lung, and repetitive opening and closing of the alveoli are minimized. Authors have called this liquid PEEP or "PEEP in a bottle."
In addition, a lavage effect may clear the alveoli and small airways of debris and inflammatory mediators, reducing ongoing inflammation.
PFCs are also thought to have intrinsic anti-inflammatory actions.
By flowing preferentially to dependent areas of the lung where alveolar collapse is maximal, intra-alveolar pressure is increased; hence, perfusion to these areas is decreased, which may improve V/Q matching.
Two types of liquid ventilation have been described: partial liquid ventilation (PLV), in which a volume of liquid equal to the FRC is instilled and total liquid ventilation (TLV) with a conventional ventilator. In contrast to PLV, TLV requires that the lung is filled completely with PFC and that the patient is ventilated with a specially designed liquid ventilator. For logistical reasons and because no data suggest that TLV is superior to PLV, PLV has been used more widely than TLV.
Little convincing data are available to assess the use of PFC liquid ventilation in ARDS. Investigators from 2 uncontrolled trials (1 in adults and 1 in pediatric patients) described its use in conjunction with extracorporeal life support (ECLS) (Hirschl, 1998; Fedora, 1999). A randomized trial in 1998 did not demonstrate a difference in outcome in a group treated with PLV compared with a group treated with CMV (Davies, 2004).
Other pharmacologic therapy: Although they have shown promise in animal and small-scale human studies, many pharmaceutical agents have not demonstrated an unequivocal benefit in large trials. These agents include systemic pulmonary vasodilators, pentoxifylline, various antioxidants, ketoconazole, anticytokines, and antiproteases. Their use is not discussed further.
Surgical Care:
Chest-tube placement: In the event of a pneumothorax, placement of a chest tube is usually mandatory.
Extracorporeal life support
ECLS has been used since the 1970s to improve oxygenation and/or ventilation in critically ill patients with severe ARDS.
A number of modalities have been reported, including ECMO, which may consist of an arterial and venous cannula (AV-ECMO) or 2 venous cannulae (VV-ECMO).
Extracorporeal carbon dioxide removal (ECCO2R) has been used, most commonly in Europe.
The rationale of ECCO2R is similar to that for ECMO, which is to allow the lung to rest while carbon dioxide is removed and excessive hypercarbia is prevented. Limited data are available concerning this modality in the pediatric population.
Extracorporeal membrane oxygenation
A large randomized study of the efficacy of ECMO in adults with severe ARDS was published in 1979. Zapol et al did not demonstrate a benefit with ECMO, reporting a mortality rate of >90% in both control and ECMO groups.
Anecdotal reports and case series are numerous. They suggest that ECMO may be of benefit in children with severe ARDS unresponsive to maximal conventional therapy.
In 1996, Green et al reported data from a pediatric study. Although they concluded that ECMO was associated with improved survival, their study had a number of limitations. It was not a controlled trial; instead, it was a retrospective collection of data from a large number of PICUs. Furthermore, conventional therapy was not uniform. An attempt at a definitive, randomized controlled trial was terminated when the overall mortality rate in pediatric ARDS decreased to such a degree that sufficient numbers of patients could not be recruited.
Numerous studies from the United Kingdom showed that the use of ECMO in neonates with respiratory failure was associated with improved outcomes (Brown, 2004; Petrou, 2004; Bennett, 2001). With pediatric ECMO, the survival rate is approximately 50%. This is markedly less than the reported survival rate of 80% in neonates treated with ECMO. Reasons for this disparity may include the heterogeneity of illness leading to respiratory failure in the pediatric population, relatively limited experience with pediatric versus neonatal ECMO, or a reluctance to commence ECMO that leads to delays that further exacerbate lung damage.
The question of who should receive ECMO remains uncertain. Candidates should have severe lung disease that progresses despite maximal conventional medical therapy. The disease process leading to respiratory failure should have a reasonable potential for reversibility and recovery. Objective indicators include an alveolar-arterial (A-a) gradient >450 mm Hg or ventilator peak pressures >40 cm H2O. Exclusion criteria include cerebral hemorrhage, preexisting chronic lung disease, congenital or acquired immunodeficiency, congenital anomalies, or other organ failure associated with poor outcomes. Ventilation for >10 days before ECMO is a relative contraindication.
Why ECMO may confer a survival benefit is unclear. Possibilities include the ability to rest the lung by reducing excess stretch (ie, high pressures) and reducing repetitive opening and closing (ie, high ventilator rates). Oxygen toxicity may be minimized. Fluid balance can be optimized with aggressive diuresis or with renal replacement therapy.
DIET :
Diet: The thinking regarding the role of nutrition in patients with ARDS has taken a paradigm shift.
As attention was being given to the role of adequate nutrition in the critically ill patient, bacterial overgrowth in the GI tract due to antibiotic use and the late introduction of feeds was postulated to contribute to bacterial translocation across the bowel wall. Hence, the standard practice of introducing early enteral feeds when possible has expanded.
In situations of feeding intolerance, efforts to optimize enteral nutrition include the placing of a transpyloric tube (duodenal or jejunal), administering continuous drip feeds, and administering promotility agents (metoclopramide or erythromycin).
Recent researchers concluded that administration of a formula supplemented with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants is associated with a reduction in pulmonary neutrophil recruitment, improved gas exchange, decreased requirement for mechanical ventilation, reduced length of ICU stay, and a reduction of new organ failures.
In some patients with limited pulmonary reserve, high-energy loads may lead to respiratory failure because of marked carbon dioxide production.
Intravenous fat emulsions have been associated with worsening pulmonary mechanics in some patients with ARDS. Published evidence is not currently conclusive and limited to animal data and findings in small case series. Caution should be used if parenteral nutrition is required during the early stages of ARDS.
DRUG TREATMENT :
1. ADRENAL CORTICOSTEROIDS :
- METHYL PREDNISOLONE : (Medrol, Solu-Medrol) -- Mechanism of action in ARDS unknown. By virtue of anti-inflammatory effects, host fibrotic response presumably dampened, allowing for salvage of viable lung tissue. DOSES AS FOLLOWING : ( SAME IN ADULTS & CHILDREN )
Days 1-14: 2 mg/kg IV loading dose then 2 mg/kg/d IV divided q6h until enteral feeding established, then change to same dose administered PO
Tapering schedule:
Days 15-21: 1 mg/kg/d
Days 22-28: 0.5 mg/kg/d
Days 29-30: 0.25 mg/kg/d
Days 31-32: 0.125 mg/kg/d, then stop
If patient extubated before day 14, therapy is advanced to day 15 (1 mg/kg/d) and tapered according to the schedule
2. SURFACTANTS : Exogenous surfactant can be helpful in treating airspace disease (eg, RDS). If administered under carefully controlled conditions, surfactant may also be helpful in other conditions (eg, meconium aspiration syndrome [MAS]), though it is not yet approved for this indication. After inhaled administration, surface tension is reduced, and alveoli are stabilized, decreasing the work of breathing and increasing lung compliance.
- CALFACTANT(Infasurf) -- Natural calf lung extract containing phospholipids, fatty acids, and surfactant-associated proteins B (260 mcg/mL) and C (390 mcg/mL).
Endotracheal instillation of 80 mL/m2 of Infasurf delivered in 4 equal aliquots in rotating positions (ie, right side down, head down; right side down, head up; left side down, head down; left side down, head up); children hand ventilated during administration for 10-20 min with FiO2 of 1 by using peak pressures and rates that approximated previous ventilator settings
Further Inpatient Care:
Prevention of the numerous complications associated with intensive care is paramount. Have a high index of suspicion for nosocomial infections, specifically line-related bacteremia and ventilator-associated pneumonia. Continue aggressive nutrition to maintain anabolism or at least to prevent catabolism. Use neuromuscular blockers judiciously, especially in conjunction with steroids, to minimize the risk of myopathy and long-term weakness.
Meticulous attention to fluid balance is essential because excess body water may further increase ventilator requirements because of increased parenchymal water and chest-wall edema, which decrease pulmonary and total chest compliance. Furthermore, alveolar water may reduce oxygen diffusion across the alveolar membrane. Judicious use of diuretics may be necessary, as is early renal replacement therapy (eg, hemofiltration, hemodialysis, peritoneal dialysis) if renal failure leads to difficulties in maintaining fluid balance. Routine use of renal-dose dopamine is not recommended.
Critically ill children may require sedation and pharmacological paralysis. Hence, it may be necessary to prevent joint contractures. Early occupational/physical therapy is essential in preventing these complications.
Many institutions, as part of their standard of care for children treated with HFOV, require that earplugs be placed to reduce both discomfort and the risk of permanent hearing loss resulting from HFOV.
Placement of a semipermanent line (eg, as a peripherally inserted central catheter [PICC] line) may help reduce nosocomial infections in at-risk children by allowing the removal of large-caliber central venous catheters.
Bronchodilators may be beneficial in cases of ARDS complicated by reactive airway disease.
All children should receive prophylaxis for stress ulcers.
Many predictors of extubation success have been published; however, clinicians often use clinical judgment to determine a patients' readiness for extubation.
To date, no data specifically describe predictive parameters in children with ARDS. Indices used to predict successful extubation include the rapid, shallow breathing index (RSBI); the compliance, resistance, oxygenation, and pressure (CROP) index; and ratio of tidal volume to dead space (Vd/Vt).
Regardless of the method used, all candidates for extubation should have a leak around their endotracheal tube (ie, at a reasonable airway pressure), and they should be able to maintain their own airway (ie, good cough and gag reflex). Patients must not be dependent on suctioning through their endotracheal tube. The level of sedation must not be excessive. If no air leak is present around the endotracheal tube, consider deferring extubation and administering steroids to reduce airway edema.
Once extubated, patients may require further support of their breathing. Options include continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), supplemental oxygen, heliox, or reintubation.
Further Outpatient Care:
Periodic outpatient follow-up may be necessary for those with severe residual lung damage to assess the need for oxygen supplementation and to monitor for the development of restrictive lung disease.
The most common complaint after intensive-care hospitalization for ARDS is muscular weakness, which may persist for weeks following discharge.
Complications:
General complications
Several complications are associated with ARDS, though many of these are due to the precipitating condition that leads to ARDS.
Acute complications include air-leak syndromes, VILI, and multiorgan-system failure, though definitive evidence linking this syndrome to ARDS or ventilator use remains controversial.
Complications arising specifically from ARDS include persisting lung disease and myopathy due to steroids and neuromuscular-blocking agents, the requirement for a tracheostomy.
Pulmonary complications
Numerous pulmonary complications result from ARDS. The most common are the air-leak syndromes, frequently pneumothorax but also pneumomediastinum, pneumopericardium, pneumoperitoneum, and subcutaneous emphysema.
VILI is an entity receiving attention with the publication of reports of landmark trials suggesting that a "kinder, gentler" form of mechanical ventilation improves outcomes in ARDS. VILI most likely has several causes, including excessive lung stretching due to high tidal volumes, repetitive opening and closing of alveoli leading to shear stress, oxygen toxicity, and cytokine release.
Cardiovascular complications
The patient who develops ARDS may also be compromised from a cardiovascular standpoint. Patients with sepsis, trauma, or other multisystem insults may lose their ability to tolerate high airway pressures. This ability leads to decreased preload and cardiac output.
Moreover, hypoxia, hypercarbia, and acidosis may elevate pulmonary artery pressures, increasing right ventricular afterload and leading to increased right ventricular work and leftward movement of the intraventricular septum.
Tension pneumothoraces may further reduce cardiac output.
GI complications: Complications commonly observed in the critically ill population include stress ulcers, liver failure, pancreatitis, and pancreatic insufficiency, leading to glucose intolerance.
Renal complications: Renal failure may result from the primary illness or may occur secondarily as a result of multiorgan system failure.
Endocrine complications
Critically ill children with glucose intolerance occasionally require exogenous insulin.
Adrenal suppression may be a cause of intractable hypotension.
Iatrogenic adrenal suppression may result from steroid therapy.
Infectious complications
Secondary or nosocomial infection is common in critically ill children. The most common sites of infection are the bloodstream and the lungs.
Urinary tract infections due to indwelling bladder catheters sometimes occur.
Organisms that are commonly isolated include gram-positive organisms, gram-negative organisms, and fungi or yeast species.
Neurologic complications
Prolonged use of muscle relaxants, especially in conjunction with steroids, may lead to a myopathy. Critically ill children are at increased risk of seizures, which may be subtle or not apparent because of the effects of sedation or paralysis.
Although essential in the care of a child with ARDS, the use of sedatives, analgesics, and anxiolytics may be suboptimal, their use may be prolonged, or doses may be weaned inappropriately.
Musculoskeletal complications: Immobilization for any length of time may lead to joint contractures.
Patient Education:
Patients with risk factors for critical illness resulting in ARDS, such as immunodeficiency, chronic lung disease, or cardiac disease, should receive appropriate vaccinations, such as influenza vaccine.
Patients should avoid smoking or exposure to smoke.
Pregnancy is not contraindicated in patients who recover from ARDS, provided that their underlying disease (if any) or lung function does not prevent it.