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Original Article Indian Pediatrics 2005; 42:645-651 |
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Predictors of Fatality in Neonates Requiring Mechanical Ventilation |
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N.B. Mathur, Pankaj Garg and T.K. Mishra* From Departments of Pediatrics and Biochemistry *,Maulana Azad Medical College, New Delhi-110 002, India. Correspondence to Dr. N.B. Mathur, D-5, MS Apartments, Tilak Lane, New Delhi-110 001, India. E-mail: [email protected] Manuscript received: July 1, 2003, Initial review
completed: September 3, 2003,
A large number of neonates in neonatal intensive care unit require mechanical ventilation. These mechanically ventilated neonates have a high fatality(1-4). For reduction in fatality in this group of neonates, identification of risk factors is important. Earlier reports on fatality in mechanically ventilated neonates are simple correlation studies done in an uncontrolled way. Lower levels of serum Vitamin A are associated with poor outcome in neonates with severe respiratory failure(5). There is a paucity of reports on risk factors associated with fatality in mechanically ventilated neonates using multiple regression analysis to establish risk factors for fatality with adjustment for potential confounders. The present study was therefore designed to evaluate the risk factors associated with fatality in mechanically ventilated neonates using multiple regression analysis. Subjects and Methods The study was conducted on neonates admitted to the Referral Neonatal Unit of Lok Nayak Hospital, New Delhi between March 2001-December 2001. The unit caters to neonates referred from hospitals of Delhi and surrounding states or born at home and transported to the hospital directly by the relatives. All 163 neonates consecutively put on mechanical ventilator were enrolled in the study. Eighty neonates who required ventilation for surgical malformations and terminally ill neonates in multi-organ dysfunction (evidence of disseminated intra vascular coagulation along with altered renal hepatic or neurologic dysfunction) were excluded from the study. Eighty-three neonates thus finally constituted the study population. The mechanical ventilator used was pressure-limited time-cycled ventilator with facility for on line measurement of volumes and pulmonary mechanics. (Drager Babylog 8000 plus and Infant Star 500 star Sync with Star Trac). Only one neonate had received antenatal steroids. All neonates were continuously monitored electronically for temperature, pulse, respiration and oxygen saturation. The indications for neonatal mechanical ventilation were (i) PaO2 <50 mm of Hg or SaO2 <85% with FiO2 requirement more than 70%, (ii) PaCO2 >55 mm of Hg with pH <7.2 or PaCO2 >60 mm of Hg and (iii) Intractable apneic spell. Observations at the time of initiation of mechanical ventilation included (i) Arterial blood gas analysis done half hour after initiation of mechanical ventilation, (ii) Initial pulmonary pressures: peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), mean airway pressure (MAP), (iii) pulmonary compliance, pulmonary resistance, (iv) tidal volume, minute ventilation, initial pulmonary pressures, pulmonary mechanics and pulmonary volumes were displayed on the ventilator. Oxygen saturation was monitored and maintained between 92 and 95%, (v) Oxygen indices (PaO2/PAO2 or the a/A ratio, AaDO2, Oxygenation index), (vi) Duration of mechanical ventilation, and (vii) Serum carotenoid levels measured by spectro-photometric method(6,7). The continuous variables were analyzed using student ‘t’ test and proportions by Chi square test or Fischer test. Probability of 5% was considered significant. Man Whitney U test statistics was used where standard deviations were more than half of mean, where negative values are absurd. The factors found to be of statistical significance on univariate analysis were subsequently subjected to a stepwise multiple logistic regression analysis (backward model) using computer software SPSS to evaluate the independent factors associated with fatality in mechanically ventilated neonates. Results Eighty-three neonates were enrolled for the study. Causes of respiratory insufficiency requiring mechanical ventilation included apnea in 32 (38.6%), pneumonia in 28 (33.7%), meconium aspiration syndrome in 14 (16.9%), Hyaline membrane disease in 7 (8.4%) and congenital heart disease in 2 (2.4%). Forty six neonates were home delivered and 52 were males. At admission, 72 neonates were unstable with respect to temperature, oxygen saturation, perfusion and blood sugar. Complications of mechanical ventilation included pulmonary air leaks in 13 and pneumonia in 20 neonates. Retinopathy of prematurity was present in none. Out of 83 mechanically ventilated neonates enrolled for the study, 62 (74%) died. Factors significantly different in non-survivors were weight, gestational age, fraction of inspired oxygen, peak inspiratory pressure, compliance, AaDO2, a/A, oxygenation index (OI) and serum carotenoid levels (Table I). Weight (<2000 grams), gestational age (<34 weeks), pH <7.3, duration of mechanical ventilation <72 hours, fraction of inspired oxygen (>60%), compliance (<1 mL/mm of Hg), a/A <0.25, AaDO2 >250, oxygenation index >10 and serum carotenoid levels <100 µg/dL were significantly associated with fatality in neonates requiring mechanical ventilation (Table II). However, sex, age at initiation of ventilation, PaO2, PaCO2, base excess, PIP, PEEP, MAP, minute volume, tidal volume and resistance were not associated with fatality. Table I Descriptive Statistics of the Survivors and Non-survivors
Table II Correlation of Variables with Outcome in Mechanically Ventilated Neonates.
* Data on compliance is not available in 3 cases. Multiple regression analysis was done on data from 80 cases (3 cases for which data on pulmonary compliance was not available were excluded from the regression model). Initially 7 variables found significant on univariate analysis (Gestational age <34 weeks,weight <2000 grams, pH <7.3, S. Carotenoids <100 µg/dL, Compliance <1 mL/cm of water, a/A < 0.25 and FiO2 >60% ) were put in step- wise backward model. On multiple regression analysis, insignificant variables were eliminated to give final results as shown in Table III. Gestational age <34 weeks, serum carotenoids <100 µg/dL and FiO2 requirement >60% were found to be significant independent predictors of fatality in mechanically ventilated neonates. Table III Multiple Logistic Regression Analysis of Variables (n = 80).
Discussion Mechanically ventilated neonates have a high fatality(1-4). The fatality is even higher in the small number of tertiary referral neonatal units receiving out born neonates. Eighty seven per cent neonates in the present study were destabilized at admission with reference to temperature, oxygen saturation, tissue perfusion and blood sugar. The fatality in these neonates would not lower till a proper network of neonatal services in district hospitals linked to regional referral neonatal units is established. Unfortunately there is a paucity of data on mechanical ventilation in out born neonates and the number of units catering to these neonates is grossly inadequate. The present study highlights the identification of FiO2, gestational age and serum carotenoid levels as significant independent predictors of fatality in mechanically ventilated neonates. In the present study low serum carotenoid levels were the most significant risk factors for fatality in mechanically ventilated neonates. b-carotene and other carotenoids are endogenous non-enzymatic lipid phase anti-oxidants. It is already known that low birth weight infants with low serum vitamin A levels are at higher risk of developing chronic lung disease and broncho-pulmonary dysplasia(5). The reference range of serum carotenoids is 50-250 µg/dL in adults(6). Data on reference range of serum carotenoids in neonates is lacking. Retinol has an essential role in the respiratory tract epithelial cell differentiation and integrity (8,9). Deficiency state of vitamin A is characterized by the loss of cilia and the development of squamous metaplasia in the respiratory tract, changes also found in the bronchopulmonary dysplasia(10,11). Studies correlating initial serum carotenoid and serum vitamin A levels with fatality in mechanically ventilated neonates are lacking. Further studies are required to evaluate the effect of vitamin A supplementation in reducing fatality in mechanically ventilated neonates in India. Gestational age and FiO2 requirement were the other independent risk factors for fatality in our study. These parameters available routinely can be identified to predict the risk of fatality in mechanically ventilated neonates. Earlier studies have also identified gestational age <34 weeks as a risk factor for fatality(12-14). FiO2 requirement reflects the severity of respiratory failure. All oxygen indices like OI, AaDO2 and a/A are dependent on it(15). Ortega and coworkers have shown significant association between a/A ratio and adverse outcome(16). Gilbert and Keighley have shown arterial alveolar oxygen tension ratio as a more stable index of gas exchange than the alveolar arterial oxygen tension difference with changing values of inspired oxygen concentration(17). These indices are dependent on FiO2, which thus is a good indicator of prognosis. In conclusion, risk of fatality can be identified in mechanically ventilated neonates. Main limitation of the present study was that all risk factors could not be taken in the regression model because of sample size. There is an urgent need for further studies with larger sample size to identify risk factors before the neonate reaches a critical stage. Newer modalities of mechanical ventilation like high frequency oscillatory ventilation need evaluation using high risk factors as indicator of severity. Further studies are required to evaluate the effect of vitamin A supplementation on the outcome of mechanical ventilation. Contributors: NBM conceived and designed the study, interpreted the data, was involved in finalising the draft and will act as guarantor of the paper; PG and TKM were involved in acquisition and analysis of the data and drafting and final approval of the article. Funding: None. Competing interests: None stated.
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