ORIGINAL ARTICLE
High Frequency Oscillatory Ventilation in Children: Experience of a Medical Center in Taiwan Ching-Chia Wang, Wei-Lun Wu, En-Ting Wu, Hung-Chieh Chou, Frank Leigh Lu* Background/Purpose: Data about the effectiveness of high frequency oscillatory ventilation (HFOV) in children with respiratory failure are limited. This study investigated the efficacy and prognostic factors of this treatment. Methods: Children between 2 months and 18 years of age who received HFOV between January 2000 and September 2006 in a tertiary care center were enrolled in this retrospective study. Results: Thirty-six HFOV treatments were given to 33 patients (twice in one patient and three times in another patient) at a mean age of 5.4 ± 5.0 years. HFOV was used as a rescue after conventional mechanical ventilation (CMV) for 4.4 ± 4.2 days. The mean duration of HFOV was 7.6 ± 7.9 days. The most common indication for HFOV was oxygenation failure, which was due to pneumonia with acute respiratory distress syndrome in 15 (45.5%), severe lobar pneumonia in nine (27.3%), pulmonary hemorrhage in eight (24.2%) and pneumothorax in one (3%). PaCO2 was significantly improved 4 hours after HFOV and the PaO2/FiO2 ratio increased significantly 12 hours later. The oxygenation index and alveolar-arterial oxygen difference P(A–a)O2, however, did not change markedly. Four (12%) patients needed further extracorporeal life support and two of these survived. The overall survival rate was 45.5%. Patients with heavier body weight (p < 0.05) and of the male gender (p < 0.05) had a higher risk of mortality. Conclusion: As a relatively late rescue therapy after failure of CMV, HFOV may improve PaCO2 and PaO2/FiO2 in children with respiratory failure. However, it carries an increased mortality rate in patients with heavier body weight and male gender. [J Formos Med Assoc 2008;107(4):311–315] Key Words: acute respiratory distress syndrome, children, high frequency oscillatory ventilation
High frequency oscillatory ventilation (HFOV) is an alternative mode of mechanical ventilation that has been used to treat pediatric patients with respiratory failure, especially in neonates.1–3 HFOV can safely provide higher levels of mean airway pressure (Paw) to patients than conventional mechanical ventilation (CMV). HFOV can deliver small tidal volumes at extremely fast respiratory rates, thus avoiding dangerous large alveolar pressure and volume excursions. These characteristics
suggest that HFOV is an excellent alternative to achieve protective ventilation goals.4–6 Although previous studies have suggested the potential benefits of HFOV in children with respiratory failure, the data are limited and the prognostic factors remain to be established.7–12 This study investigated the use of HFOV in children aged from 2 months to 18 years with respiratory failure, and analyzed the factors that may affect survival.
©2008 Elsevier & Formosan Medical Association .
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Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Received: July 17, 2007 Revised: October 24, 2007 Accepted: January 15, 2008
J Formos Med Assoc | 2008 • Vol 107 • No 4
*Correspondence to: Dr Frank Lu, Department of Pediatrics, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan. E-mail:
[email protected]
311
C.C. Wang, et al
Methods Data were retrieved by retrospective chart review of patients who had used HFOV between January 2000 and September 2006 in the pediatric intensive care unit of National Taiwan University Hospital, which is a 13-bed unit in a tertiary medical center. Patients were excluded from the study if they were younger than 2 months or older than 18 years of age. The data collected included demographic information and the parameters during HFOV usage, which included gender, age at the time of HFOV usage, duration of HFOV, duration of CMV prior to HFOV, indications for HFOV, underlying diseases, hemodynamic data, extracorporeal membrane oxygenation treatment after HFOV, and outcome. All patients with respiratory failure initially received CMV, and HFOV was used as a rescue treatment. The indication for HFOV was failure of CMV at high settings. In all of the patients, HFOV was initiated under the following conditions: intractable hypoxia with PaO2/FiO2 < 200 and a plateau pressure > 30 cmH2O, severe airleak syndrome, or persistent hypercapnea with PaCO2 > 90 mmHg.
HFOV was performed using SensorMedics 3100A or 3100B (Yorba Linda, CA, USA) according to body weight. All patients were sedated with continuous intravenous infusion of midazolam, and some were also paralyzed with neuromuscular blocking agents. PaO2/FiO2 ratio, alveolar-arterial oxygen difference P(A–a)O2, and oxygenation index (OI) were recorded.
Statistical analysis Data were presented as mean ± standard error. All statistical analyses were performed with SPSS version 14 (SPSS Inc., Chicago, IL, USA), using logistic regression, Student’s t test and χ2 test. A value of p < 0.05 was considered statistically significant.
Results From January 2000 to September 2006, 33 patients (20 male, 13 female) who had failed CMV underwent HFOV rescue therapy in the pediatric intensive care unit. The Table compares the clinical profiles of survivors and non-survivors, including characteristics and severity of respiratory failure.
Table. Comparison between survivors and non-survivors* Survivors (n = 15)
Non-survivors (n = 18)
p
Age (mo)
36 (4–144)
120 (24–216)
NS
Body weight (kg)
13 (4.5–48)
28.2 (12.4–44)
< 0.05
Male/female ratio Underlying diseases Hematologic/oncologic diseases Congenital heart diseases Autoimmune diseases Liver/gastrointestinal diseases OI before HFOV P(A–a)O2 before HFOV
6/9 8 (24.2) 4 (12.1) 1 (3) 2 (6.1) 1 (3)
14/4 17 (51.5) 11 (33.3) 2 (6.1) 2 (6.1) 2 (6.1)
< 0.05 NS NS NS NS NS
17.8 (12.3–23.3)
18.3 (11.6–24.9)
NS
402.3 (224.4–580.2)
476.6 (355.6–597.6)
NS
Duration of CMV before HFOV (d)
2 (1–10)
1.5 (1–2)
NS
Duration of HFOV (d)
7 (1–25)
4.5 (3–6)
NS
62 (15–172)
41.5 (32–51)
NS
Duration of hospital stay (d)
*Data are presented as median (range) or n (%). OI = oxygenation index; HFOV = high frequency oscillatory ventilation; P(A–a)O2 = alveolar-arterial oxygen difference; CMV = conventional mechanical ventilation; NS = not significant.
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PaCO2 (mmHg)
120 100 80 60 40 20 0 −4
−2 2 Time (hr)
4
Figure 1. Mean changes in PaCO2 after application of high frequency oscillatory ventilation in 33 patients. 200 PaO2/FiO2
The mean age of the 33 patients at the time of HFOV was 5.4 ± 5.0 years (range, 2 months to 18 years). Mean body weight was 22.58 ± 22.5 kg (range, 4.1–114 kg). Twenty-five patients had underlying disease, including hematologic or oncologic diseases (n = 15, 45.5%), autoimmune disease (n = 4, 12.1%), congenital heart disease (n = 3, 9.1%), and fulminant hepatitis or congenital gastrointestinal anomaly (n = 3, 9.1%). The remaining eight patients had primary pulmonary infectious diseases. Three patients had pneumococcal pneumonia. Two had viral pneumonia and the other three had pneumonia without a definite pathogen. A total of 36 treatment courses of HFOV were given to the 33 patients (twice in one patient due to underlying immunodeficiency and three times in another patient with bronchiectasis during the same infection course). The most common clinical indication for HFOV was oxygenation failure (33 treatments, 91.7%), which was attributed to lobar pneumonia with acute respiratory distress syndrome (ARDS) in 15 (45.5%) patients, pulmonary hemorrhage in eight (24.2%), severe lobar pneumonia in nine (27.3%), and pneumothorax with subcutaneous emphysema in one (3%). Hypercapnia was the indication for three treatments only. The mean duration of CMV prior to HFOV was 4.4 ± 4.2 days. Immediately before the initiation of HFOV, the mean PaO2/FiO2 ratio was 63 ± 8.3 mmHg, mean P(A–a)O2 was 512 ± 149 mmHg, and mean OI was 18.5 ± 16.3. The mean duration of HFOV was 7.6 ± 7.9 days. Figures 1 and 2 show the mean changes in PaCO2 and PaO2/FiO2 ratio after the use of HFOV. A significant improvement in PaCO2 was observed 4 hours after HFOV (p < 0.05) and the PaO2/FiO2 ratio was increased 12 hours after HFOV (p < 0.05) (Figure 2). However, the OI and P(A–a)O2 did not change markedly after HFOV. The mean hospital stay was 63.6 ± 57.2 days. The survival rate was 45.5% and most deaths were caused by persistent intractable hypoxia followed by bradycardia and hypotension. For the 15 survivors, seven had primary lung disease and eight had underlying diseases. For the 18 deaths, 17 patients (94.4%) had underlying diseases. Four patients received further
150 100 50 0 −4
−2
2
12
Time (hr) Figure 2. Mean changes in PaO2/FiO2 after application of high frequency oscillatory ventilation in 33 patients.
extracorporeal life support and only two of them survived. Those who received repeated HFOV usage all died due to uncontrolled infection and ventilation failure. Increased mortality was found in patients with heavier body weight (p < 0.05; OR, 1.1; 95% CI, 1.0–1.2) and of the male gender (p < 0.05; OR, 5.2; 95% CI, 1.2–23.9) in logistic regression. However, the duration of CMV and pre-existing disease before HFOV were not significantly associated with survival.
Discussion This study revealed that HFOV can rescue children from respiratory failure when they fail to improve under CMV. The effects were demonstrated through decreased PaCO2 and increased PaO2/FiO2 ratio after HFOV. Poor prognostic factors identified for HFOV in children were heavier body weight and male gender. Higher mortality rate was noted in patients with underlying diseases than those with primary lung diseases. 313
C.C. Wang, et al
Since HFOV was introduced in 1972, several studies have compared the effectiveness of HFOV and CMV. Although early studies failed to demonstrate that HFOV had substantial advantages over CMV,13–15 recent studies have revealed its use for avoiding excessive lung injury in patients with acute lung injury and ARDS.5,16,17 Courtney et al have shown that very low body weight infants randomly assigned to HFOV are successfully extubated earlier than infants assigned to synchronized intermittent mandatory ventilation.18 However, a significant advantage of HFOV was better demonstrated in the early stage rather than in the late stage of respiratory failure in children.11,19,20 Ben Jaballah et al reported that the survival rate was approximately 80% in a study of 10 children who used HFOV as an early rescue therapy after a median length of 4 hours of CMV.20 HFOV as early rescue therapy minimizes the risk of pulmonary injury by CMV. Suzuki et al demonstrated the importance of minimizing the secondary injuries produced by CMV before instituting HFOV in surfactant-deficient rabbits.21 Previous studies have also shown that the degree of pulmonary inflammation, barotrauma and ventilator-associated lung injury is lower in HFOV patients than in CMV patients.17,22 The survival rate in the current study was lower than that in two previous studies.11,12 This could be related to the timing of HFOV therapy. We did not adopt an early rescue policy for HFOV and this delayed use may account for the worse results in our patients. We also found that older male patients and those with heavier body weight had a higher mortality rate in logistic regression. The mean age of 5 years of our patients was much older than that in previous pediatric studies. In adult patients, the survival rate after HFOV rescue of respiratory failure was only 35–45%.23,24 These findings suggest that older age and heavier body weight may be risk factors for HFOV therapy. We also found that patients with underlying diseases have a significantly higher mortality rate than those with primary lung diseases. The mean OI in this study was > 18 before HFOV, which has been previously suggested as a poor prognostic factor.24,25 Although we did not 314
find that OI before HFOV was a significant prognostic factor, such a high OI at the initiation of HFOV may indicate that some degree of oxygenation failure might be irreversible. Also, the OI after HFOV had a sustained decrease in 20 pediatric patients with acute respiratory failure.12 SleeWijffels et al suggested that an OI > 13 may serve as an indication for HFOV rescue therapy.11 One previous study has even proposed that an initial OI > 20, without a reduction of at least 20% after HFOV for 6 hours, is associated with a high mortality rate.25 Therefore, early rescue HFOV therapy at a lower OI may be important. This study showed a significant decrease in PaCO2 and a trend of increasing PaO2/FiO2 after HFOV use in children with respiratory failure who had failed CMV. Factors associated with increased mortality after HFOV for respiratory failure included heavier body weight and male gender.
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