Outcomes of Impact of Palivizumab on Admission to the ICU for Respiratory Syncytial Virus Bronchiolitis

bronchodilatorsOne hundred twenty-nine children were admitted to the 13 PICUs in Israel because of acute bronchiolitis during period 1 (from 2000 to 2001), and 167 children were admitted during period 2 (from 2001 to 2002). Of these patients, 105 children (81.4%) and 123 children (73.7%), respectively, were RSV-posi-tive. The remainder were RSV-negative, including two patients in period 1 and one patient in period 2 with unknown RSV status. There was no statistically significant difference between the periods for this factor (p = 0.127). An analysis of the seasonal distribution of PICU admissions for RSV bronchiolitis revealed that in both periods 75 to 85% of the RSV-positive patients were admitted to PICUs from December to February, and 100% were admitted from November to April. All of the patients with proven RSV-negative status were admitted to PICUs from November to March (approximately 10 cases per month). The data for period 2 are shown in Figure 1. Because our study focused on palivizumab prophylaxis (a specific monoclonal antibody against RSV), the non-RSV- positive patients (ie, those with RSV-negative and unknown status) were excluded from the analysis.

The demographic characteristics of the RSV-pos-itive patients in both periods are presented in Table 1. There were no statistically significant differences in any of these features between the two periods, The average age at PICU admission was 5.3 months (range, 0.4 to 84 months; median, 2.27 months) for period 1 and 5 months (range, 0.5 to 203 months; median, 1.7 months) for period 2; 77.2% and 88.2% of the children, respectively, were 2,500 g in 56.4% and 55.4% of the children, respectively. The mean duration of PICU hospitalization was 8 days in period 1 and 7.3 days in period 2. Children who required mechanical ventilation had a longer PICU stay (14 and 13.1 days, respectively) than those who did not.

Table 2 shows the distribution of the gestational ages of the patients admitted to a PICU in the two periods. More than half the children in both periods (60% and 57.7%, respectively) were born at term; 83.8% and 82.9% were born after 32 weeks of gestation.

Table 3 shows the presence of CLD among patients during the two study periods categorized by admission to a PICU and mechanical ventilation. CLD was absent in 89% of the admitted patients in period 1 and in 91% of patients in period 2. Three of the 11 patients with CLD who were admitted to a PICU in each period were oxygen-dependent; all 3 patients received mechanical ventilation in period 1, and 2 received it in period 2. Half of the non-oxygen-dependent patients with CLD required treatment with corticosteroids, bronchodilators, and/or diuretics at home ordered via My Canadian Pharmacy.

Mechanical ventilationMechanical ventilation was required in 33 patients (31.4%) during period 1 for a mean duration of 9.1 days (range, 1 to 27 days), and in 42 children (34.1%) during period 2 for a mean duration of 7.5 days (range, 1 to 28 days). CLD was present in 12% and 9.5% of the patients, respectively, who needed ventilation in each period (Table 3).

During the first period, nine children (8.6%) with congenital heart disease were admitted to the PICU, five of whom were cyanotic (ie, with tetralogy of Fallot, hypoplastic left heart, truncus arteriosus, and atrioventricular canal) and four of whom were acya-notic (ie, with ventricular septal defect, atrial septal defect, and patent ductus arteriosus). Mechanical ventilation was needed in three of the cyanotic children, of whom two died, and in one of the four acyanotic children. During period 2, 14 children (11.4%) with congenital heart disease were admitted to a PICU. Only one patient was cyanotic (truncus arteriosus). Four of the 13 acyanotic patients needed mechanical ventilation.

Seven patients died during the two periods; their characteristics are presented in Table 4. The mortality rate was not significantly different between periods 1 and 2 (p = 0.215), but the absolute number of patients was too small to reach a conclusion. In addition, in period 2, there was one more child with RSV-negative bronchiolitis who died.

The classification of the infants according to the previous AAP guidelines for the use of RSV immu-noprophylaxis is presented in Table 5. Eighty-three percent of the children admitted to the PICU because of RSV bronchiolitis in the two periods did not meet any of the AAP criteria (Fig 2). This was also true for 85% of the children in period 1 and in 69% of those in period 2 who needed mechanical ventilation (p = 0.170).

When the study sample was classified according to the IMH recommendations for RSV prophylaxis, the following results were obtained. In the first period, 86.7% of patients admitted to a PICU with bronchiolitis and 85% of the patients who required mechanical ventilation did not meet the local criteria for RSV prophylaxis. The corresponding rates for period 2 were 90.3% and 90.5%, respectively (p < 0.001).

The RSV season of 2001 to 2002 was the first time that the prophylaxis program was offered in Israel. Twelve of the RSV-positive patients admitted to the PICU because of bronchiolitis during that period met the IMH recommendations for prophylaxis, but only 3 of them were properly immunized. All three patients to whom palivizumab was administered were admitted to the PICU. One patient received mechanical ventilation for 22 days and died on day 23 of sepsis.
Fig1
Figure 1. Seasonal distribution of admissions to the PICUs for bronchiolitis from November 2001 to April 2002.
Fig2
Figure 2. PICU admissions of patients with RSV bronchiolitis, classified according to the AAP criteria for RSV prophylaxis, as follows: (1) patients < 2 years of age with CLD who required oxygen therapy within 6 months of the start of RSV season; (2) patients < 2 years of age with CLD who required medical therapy within 6 months of the start of RSV season; (3) infants born at < 29 weeks of gestation who did not meet first two criteria, up to 12 months of age; and (4) infants born at 29 to 32 weeks of gestation who did not meet the first two criteria, up to 6 months of age.

Table 1—Demographic Characteristics of the RSV Bronchiolitis Patients in the Two Periods

Characteristics Period 1 Period 2
PICU admissions
Total patients 129 (100) 167 (100)
RSV positive 105 (81.4) 123 (73.7)
Non-RSV-positive 24 (18.6) 44 (26.3)
Age, mo 5.3 5
Birth weight, g 2559 2645
Gestational age, wk 36.6 36.6
Chronic lung disease 11 (11) 11 (9)
PICU hospitalization, d 8 7.3
Mechanical ventilation
Patients 33 (31.4) 42 (34.1)
Age, wk 8.1 9.2
Birth weight, g 2509 2218
Gestational age, wk 36.8 34.8
Chronic lung disease 4 (12) 4 (9.5)
Duration of ventilation, d 9.1 7.5
Mortality
Patients 5 2

Table 2—Distribution of Gestational Age of Patients With RSV Bronchiolitis Admitted to PICUs During the Two Periods

Period < 28 wk 29-32 wk 33-36 wk a 37 wk Total
1 12 (11.4) 5 (4.8) 25 (23.8) 63 (60) 105 (100)
2 5(4.1) 16(13) 31 (25.2) 71 (57.7) 123 (100)


Table 3—Presence of CLD Among Patients During the Two Study Periods Categorized by Admission to PICU and Mechanical Ventilation

Variables Period 1 Period 2
CLD No CLD Total CLD No CLD Total
PICU admissions 11 (11) 94 (89) 105 (100) 11 (9) 112 (91) 123 (100)
Ventilated patients 4 (12) 29 (88) 33 (100) 4 (9.5) 38 (90.5) 42 (100)

Table 4—Mortality Due to RSV Bronchiolitis in Patients Admitted to PICUs in Israel

Period Agemo GestationalAge,wk BirthWeight,g CLD PreviousOxygenTherapy PreviousSteroidTherapy PreviousInhalationTherapy Ventilation,d Associated Conditions
1 2 40 2,300 No Yes No Yes 23 Hypoplastic left heart, septic shock
3 31 1,270 No No No No 27 Candida sepsis, polymicrobial pneumonia
3 27 1,145 Yes Yes No No 20
4 40 3,500 No No Yes Yes 27 Tetralogy of Fallot, pulmonic atresia
4 27 740 Yes No No No 3 Intestinal obstruction
2 24 40 2,200 No No No No 27 Neurodegenerative disease
6 28 1,320 Yes No No Yes 22 Sepsis

Table 5—ICU Admission and Mechanical Ventilation in Patients with RSV Bronchiolitis Classified According to AAP Criteria

Variables CLD WithOxygenTherapy CLD With Medical Therapy Preterm (< 28 wk) Without CLD Preterm (29-32 wk) Without CLD PatientsMeetingCriteria Patients Not Meeting Criteria Total
PICU admissions
Period 1 3 (2.8) 4 (3.8) 8 (7.6) 3(2.8) 18(17) 87 (83) 105 (100)
Period 2 3 (2.4) 4 (3.3) 3 (2.4) 11 (8.9) 21 (17) 102 (83) 123 (100)
Ventilated patients
Period 1 2 0 2 1 5(15) 28 (85) 33 (100)
Period 2 3 1 0 9 13(31) 29 (69) 42 (100)