Respiratory syncytial virus (RSV) is the cause of approximately 75,000 to 125,000 hospitalizations of pediatric patients each year in the United States1 and is the major cause of bronchiolitis and pneumonia in children younger than 2 years of age. The occurrence of annual outbreaks and the high incidence of infection during the first months of life are unique among human viruses. RSV is a medium-sized, membrane-bound RNA virus that develops in the cytoplasm of infected cells and matures by budding from the plasma membrane. “The virus is unstable in the environment (surviving only a few hours on environmental surfaces) and is readily inactivated with soap and water and disinfectants.”2

The first signs of infection in an infant with RSV are rhinorrhea and pharyngitis; cough may appear simultaneously but more often after an interval of 1 to 3 days, at which time there may also be sneezing and a low-grade fever. After a few days, these clinical manifestations may develop into respiratory distress, particularly dyspnea and tachypnea. Chest x-ray will show signs of hyperinflation with areas of consolidations. The virus can be diagnosed by immunofluorescent assay the same day, which will assist in the implementation of a treatment plan.

Background

From October 2007 through April 2008, Children’s Hospital of Orange County (CHOC) admitted 471 patients with the diagnosis of RSV bronchiolitis or RSV pneumonia. Of those patients, 30 were placed on mechanical ventilation, three received inhaled nitric oxide, and two were placed on extracorporeal membrane oxygenation (ECMO).3 This means that 7% of our children did not respond to the “conventional” treatment plan and required a higher level of care. The severity of the infection and the clinical signs and symptoms of these patients are important factors to consider regarding the progression of their disease process. Patients with more critical RSV symptoms (eg, apnea) and comorbidity (eg, bronchopulmonary dysplasia [BPD]/congenital heart disease [CHD}, among others) are usually hospitalized and treatment is directed at relieving the airway obstruction and associated hypoxemia. Which brings us to the question: How do we ventilate these critically ill children?

Mechanical Support for RSV

By understanding the pathophysiology of RSV, which is characterized by edema and inflammation with airway hyperactivity, we can strive for a mechanical ventilation plan to overcome the complex process of this deadly disease. With advancement in mechanical ventilation technology, the choice of which mode of ventilation to utilize is complex. To complement these advances are monitoring devices (capnography, pulse oximetry, etc) that assist the bedside-care provider in making decisions on ventilator management. Conventional modes of mechanical ventilation, volume-controlled or pressure-controlled, are still the principal modes used in all age groups. Thus, the choice of mode of ventilation is strictly up to the individual institution, and more study needs to be done to determine the best way to ventilate these patients.

RSV Facts from the CDC

Clinical features

  • Most common cause of bronchiolitis and pneumonia among infants and children under 1 year of age.
  • Begins most frequently with fever, runny nose, cough, and sometimes wheezing.

The Virus

  • Negative-sense, enveloped RNA virus.
  • Virion is variable in shape and size, unstable in the environment.

Epidemiology

  • Spread from respiratory secretions through close contact with infected persons or contact with contaminated surfaces or objects.
  • Infection can occur when infectious material contacts mucous membranes of the eyes, mouth, or nose.

Diagnosis

  • Virus isolation.
  • Detection of viral antigens.
  • Detection of viral RNA.
  • Demonstration of a rise in serum antibodies.
  • Combination of above approaches.

Treatment

  • Mild disease does not require specific treatment other than the treatment of symptoms.
  • Severe disease may require oxygen therapy and sometimes mechanical ventilation.
  • Ribavirin aerosol can be used in cases of severe disease.

Prevention

  • Good infection-control practices.
  • RSV-IGIV and an anti-RSV humanized murine monoclonal antibody.
  • Frequent handwashing and not sharing items such as cups, glasses, and utensils with persons who have RSV illness.
  • In a hospital setting, strict attention to contact precautions, such as handwashing and wearing gowns and gloves.

From: Respiratory Syncytial Virus. [removed]www.cdc.gov/ncidod/dvrd/rev/respiratory/rsvfeat.htm[/removed]

We must remember that one of the major purposes of mechanical ventilation is to rest the respiratory muscles and allow them to recover from fatigue. Patients with RSV need to be adequately sedated to decrease their metabolic demand and appropriately ventilated to assist their recovery. At CHOC, we use the decelerating waveform produced by pressure regulated volume control (PRVC) mode to reduce peak inspiratory pressure, total respiratory resistance, work of inspiration, ratio of dead space to tidal volume (VD/VT), and alveolar-arterial gradient for oxygen (A-a)Po2. In addition, the decelerating waveform increases static and kinetic compliances and Pao2 with no significant changes in Paco2. These observations, along with the additive effect of inhaled nitric oxide (iNO), as indicated, allow us to reach our goal of appropriately managing patients with hypoxemic respiratory failure. The reason for this approach was the rising A-ado2 and the assumed ventilation–perfusion mismatch typically present in severe RSV pneumonia.

Case Study

High-frequency oscillatory ventilation is our next progressive step in ventilating these children. In 1998, a case report from University Children’s Hospital, Freiburg, Germany, concluded that “the combined therapy of HFV and iNO should be considered in hypoxemic respiratory failure.” In their case report, Hoehn et al4 followed a 7-month-old infant born at 28 weeks of gestation with a mild bronchopulmonary dysplasia. The patient’s respiratory status progressively worsened during the course of hospitalization. The patient regressed from not requiring supplemental oxygen therapy to being intubated and mechanically ventilated due to increased secretions. A course of ribavirin was given to the patient. With oxygenation becoming marginal on conventional mechanical ventilation in pressure control mode and ribavirin therapy, iNO was initiated up to 40 ppm. There was no improvement in oxygenation, however, and iNO was discontinued. At that point, the patient was placed on HFV. After 2 hours of HFV, a second trial of iNO was started. Within minutes, there was markedly improved oxygenation and the oxygen index (OI) was reduced from 24 to 6. The initial iNO of 40 ppm was tapered to levels of 6 within 2 hours. The patient eventually completed the course of mechanical ventilation and was discharged home on day 35.

As this early case report indicates, there is still much to be learned regarding the role of mechanical ventilation and the synergistic effects of combined treatments. With multiple choices in modes of ventilation, the decision of when to initiate HFV ventilation for patients with hypoxemic respiratory failure remains debatable. Thus, ventilator criteria need to be established and protocols developed to provide best practice in the ventilatory management of patients who are diagnosed with RSV.

Conclusion

RSV infections occur as part of an annual outbreak that often lasts 4 to 6 months. Based on our data of 471 patients who were diagnosed with the disease and with comorbidity, the fact that approximately 7% of these patients required mechanical ventilation along with other treatments is significant for this patient population. There are 75,000 to 125,000 occurrences of RSV annually in the United States. Assume that 7% of those patients (5,250 to 8,610) will require mechanical ventilation. The lives of these patients will be dependent on the medical team’s expertise in pediatric critical care units across the nation. Prevention is the key to the development of RSV. Current “prevention options include good infection-control practices, RSV-IGIV [RSV-immune globulin intravenous], and an anti-RSV humanized murine monoclonal antibody. The anti-RSV humanized murine monoclonal antibody or RSV-IGV can be given during the RSV outbreak season to prevent serious complications of infection in some infants and children at high risk for serious RSV disease.”2 Mechanical ventilation with combined treatments is available to treat patients with RSV and varies with the severity of the infection and the clinical signs and symptoms. Having a good understanding of the pathophysiology of RSV will assist clinicians in planning ventilatory goals for treating their patients. Using lung protective strategies requires proactive decisions that must be specific for disease pathophysiology and lung maturity and involves compromises between gas exchange goals and other potential toxicities. Thus, the most important issue is not the specific mode of ventilation or the specific ventilator used, but rather a matching of a ventilatory strategy to the patient’s underlying pathophysiology.

Dan Villareal, MBA, RRT, RCP, is emergency transport RCP, Emergency Transport Department, Children’s Hospital of Orange County, Orange, Calif. For further information, contact [email protected].

References

  1. Panozzo CA, Fowlkes AL, Schneider E, Anderson LJ. Brief Report: Respiratory Syncytial Virus Activity—United States, July 2006–November 2007. MMWR Weekly. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5648a3.htm. Accessed June 15, 2008.
  2. Respiratory Syncytial Virus. National Center for Infectious Diseases. Respiratory and Enteric Virus Branch. Available at: www.cdc.gov/ncidod/dvrd/revb/respiratory/rsvfeat.htm. Accessed June 16, 2008.
  3. Children’s Hospital of Orange County. Health Information Department. 2007.
  4. Hoehn T, Krause M, Krueger M, Hentschel R. Case report: treatment of respiratory failure with inhaled nitric oxide and high-frequency ventilation in an infant with respiratory syncytial virus pneumonia and bronchopulmonary dysplasia. Respiration. 1998;65:477-480.