Permissive hypercapnia for the prevention of morbidity and mortality in mechanically ventilated newborn infants.
BACKGROUND
Experimental animal data and uncontrolled, observational studies in human infants have suggested that hyperventilation and hypocapnia may be associated with increased pulmonary and neurodevelopmental morbidity. Protective ventilatory strategies allowing higher levels of arterial CO2 (permissive hypercapnia) are now widely used in adult critical care. The aggressive pursuit of normocapnia in ventilated newborn infants may contribute to the already present burden of lung disease. However, the safe or ideal range for PCO2 in this vulnerable population has not been established.


OBJECTIVE
To assess whether, in mechanically ventilated neonates, a strategy of permissive hypercapnia improves short and long term outcomes (esp. mortality, duration of respiratory support, incidence of chronic lung disease and neurodevelopmental outcome).


METHODS
Standard strategies of the Cochrane Neonatal Review Group were used. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, CINAHL, and Current Contents. Searches were also made of previous reviews including cross-referencing, abstracts, and conference and symposia proceedings published in Pediatric Research.


METHODS
All randomised controlled trials in which a strategy of permissive hypercapnia was compared with conventional strategies aimed at achieving normocapnia (or lower levels of hypercapnia) in newborn infants who are mechanically ventilated were eligible.


METHODS
Standard methods of the Cochrane Neonatal Review Group were used. Trials identified by the search strategy were independently reviewed by each author and assessed for eligibility and trial quality. Data were extracted separately. Differences were compared and resolved. Additional information was requested from trial authors. Only published data were available for review. Results are expressed as relative risk and risk difference for dichotomous outcomes, and weighted mean difference for continuous variables.


RESULTS
Two trials involving 269 newborn infants were included. Meta-analysis of combined data was possible for three outcomes. There was no evidence that permissive hypercapnia reduced the incidence of death or chronic lung disease at 36 weeks (RR 0.94, 95% CI 0.78, 1.15), intraventricular haemorrhage grade 3 or 4 (RR 0.84, 95% CI 0.54, 1.31) or periventricular leukomalacia (RR 1.02, 95% CI 0.49, 2.12). There were no differences in any other reported outcomes when the strategy of permissive hypercapnia/minimal ventilation was compared to routine ventilation in newborn infants. Long term neurodevelopmental outcomes were not reported. One trial reported that permissive hypercapnia reduced the incidence of chronic lung disease in the 501 to 750 gram subgroup.


CONCLUSIONS
This review does not demonstrate any significant overall benefit of a permissive hypercapnia/minimal ventilation strategy compared to a routine ventilation strategy. At present, therefore, these ventilation strategies cannot be recommended to reduce mortality, or pulmonary and neurodevelopmental morbidity. Ventilatory strategies which target high levels of PCO2 (> 55 mmHg) should only be undertaken in the context of well-designed controlled clinical trials. These trials should aim to establish the safe, or ideal, range for CO2 in ventilated newborns, and examine the role of protective ventilatory techniques in achieving this target.
Woodgate
P G
PG
Department of Neonatology, Mater Mother's Hospital, Raymond Terrace, South Brisbane, Brisbane, Queensland, Australia, 4101. PWOODGAT@mater.org.au
Davies
M W
MW
D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control; D002245:Carbon Dioxide / Q000097:blood*; D002543:Cerebral Hemorrhage / Q000517:prevention & control; D002908:Chronic Disease; D006801:Humans; D007226:Infant Mortality; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000517:prevention & control; D008171:Lung Diseases / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012119:Respiration; D012121:Respiration, Artificial; D012178:Retinopathy of Prematurity / Q000517:prevention & control
D002245:Carbon Dioxide