Professional Documents
Culture Documents
Wright, M and Peidimone, G. RSV Prevention and Therapy: Past. Present and Future. Ped Pulm.
RSV: Manifestations
• Severity of illness depending on age, co-morbidities, environmental
exposure & h/o previous infection
• 2-4 days URI LRTI with cough, wheeze, increased WOB,
cyanosis
• CXR: patchy infiltration/atlectasis, hyperinflation, & peribronchial
thickening
• Apnea: 20% in <6mos hospitalized patients
– Highest incidence in premies and <1mos
– Self-limited, does not recur with subsequent infection
– Prolongs reflex central apnea triggered by peripheral sensorineural
stimulation
Sabogal et al, Effect of RSV on apnea in weanling rats. Pediatr res 2005
RSV: Co-infection
• 165 PICU admissions with RSV bronchiolitis
• 42% mechanically intubated patients in PICU with lower
airway secretions positive for bacteria
• Required longer ventilatory support
• WBC, neutrophil & CRP are non-conclusive
• Organisms: H. influenza, S. aureus, M. catarrhalis, S.
penumoniae, S. pyogens
– Rare: Pseudomonas, B. pertussis, K. pneumoniae, E. coli
Thornburn, K et al. High incidence of pulmonary bacterila co-infection in children with severe respiratory
sysncytial virus (RSV) bronchiolitis. Thorz 2006; 61:611-615
RSV: Treatment
• Supportive care: fluid, nutrition and hydration
• Oxygen supplementation: non-invasive to CMV, to HFOV to
ECMO
• Deep nasal suction
• CPT: administered to mobilize secretions and recruit atelectatic
lungs: not beneficial (Cochrane systemic review)
RSV: Pharm. Interventions
• Bronchiodilators
– Beta-agonists: minimally significant improvement in clinical scores but
not likely to be clinically significant. No statistically significant
improvement in oxygenation, admission rate or LOS (Gadomski and Basale in
Cochrane review). Levoalbuterol may have better anti-inflammatory effect
than racemic epi in animal model, no clinical trial
– Epinephrine: no benefit in in-patient settings but may produce a modest
short-term improvement in out patient
– Anticholinergic: not effective in RSV
RSV: Pharm. Interventions
• Corticosteroids:
– Systemic: not statistically significant in clinical scores, respiratory rate,
oxygen saturation, admission rate and LOS (Patel et al.; Teeratakulpisarn et al.;
Corneli et al.)
– Inhaled: No difference in reduction in wheezing, readmission rate, use
of systemci corticosteroids or use of bronchiodilators (Cochrane review; Ermers
et al.)
– Combination: oral dexamethasone + inhaled racemic epi significantly
less likely to require hospitalization (Plint AC, et al. Epinephrine and dexamethasone in
children with bronchiolitis.. N Engl J med 2009;360:2079-2089)
RSV: Pharm. Interventions
• Antivirals:
– Ribavirin: synthetic nucleoside analog. Inhibits RSV replication in vitro,
not in vivo
» Expensive, difficult to administer, possibly a teratogen
» Controversies in inhaled Ribavirin
» Recommended either alone or in combination with anti-RSV antibodies to treate
infection in select immunocompromised hosts
• Antibiotics: co-infections
– 0.2% in all bronchiolitis
– 40% in intubated patients
– Most common sites of co-infections: UTI, OM
RSV: Pharm. Interventions
• Recombinant Human Deoxyribonuclease (DNAse)
– No demonstrable benefits (Boogaard, R. et al. Recombinant human deoxyribonuclease in
infants with RSV bronchiolitis. Chest 2007;131:788-795)
• Hypertonic saline
– Nebulized HTS could reduced LOS without any adverse effects (ZhangL, et
al. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Databse Syst Rev
2008:(4):CD006458)
– 5% nebulized HTS is safe, superior to current treatment (Khalid A., et al.
Nebulized 5% or 3% hypertonic or 0.9% saline for the treating acute bronchiolitis in infants. J Ped:2010)
RSV: Pharm. Interventions
• Surfactant
– Decrease surface tension; protein components (A & D) gthat bind viral
and bacterial surface markers and facilitate their immune-mediated
elimination. Protein D promote alveolar macrophage production of free
radicals
– Exogenous surfactant decrease ventilation and PICU LOS, improvement
of pulm mechanics and gas exchange (Ventre K. et al. Surfactant therapy for
bronchiolitis in critically ill infants. Cochrane Database Syst Rev. 2006:(3):CD005150)
RSV: Pharm. Interventions
• Heliox
– No improvement in ventilation or oxygenation (Liet et al.)
• Anti-Leukotrienes
– Controversies in using monolukast (leukotrienes antagonist)
RSV: Immnunoprophylaxis
• RSV Immunoglobulin (RSV-IVIG)
– Pooled polyclonal human immunoglobuline, administered monthly
– Decreased hospitalization and LOS of high risk infant: premies and CLD
– Associated with an increase in surgical morbidity and mortality in infants
with CHD
– Interfere with immune response to live virus, delayed MMR until 9mths
– Disadvantages:
» Large volume 15ml’kg, infuse over 4-6 hrs fluid overload
» Transfer of blood born pathogens
RSV: Immnunoprophylaxis
• Palivizumab (Synagis)
– Humanized monoclonal IgG1 abs produced by recombinant DNA: >95%
human with minimally immunogenic, broadly reactive activity to both
subtypes; 15ml/kg IM monthly
– Preventing infection of upper respiratory tract but also limiting
downward spread
– Protection for premies without BPD and acyanotic CHD patients
– Also decrease risk of long term wheezing
– Titers dropped below protective level after first dose and increase after
subsequent dose, still with risk of RSV infection after the first 2 doses
– Low level in nasal mucosa doesn’t prevent infection but reduces
downward spreading
RSV: Immnunoprophylaxis
• Motavizumab (Rezied)
– Second generation IgG1 monoclonal antibody
– 70x higher affinity for the RSV F protein. It inhibits RSV replication in
upper respiratory tract and fully humanized
– Phase III with 26% reduction in hospitalization compared to
palivizumab, 50% reduces in outpatient medical management
– Not yet approved by FDA