Permissive hypercapnia for the prevention of morbidity and mortality in mechanically ventilated newborn infants

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Abstract
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. 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). 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. 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. 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. 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. 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. 在使用機械式呼吸器的新生兒，以容許較高之二氧化碳之方式來預防罹病與死亡的情況 在實驗性動物資料，以及未採取對照的人體嬰兒之觀察性研究，都認為過度換氣與血液之二氧化碳濃度過低可能與肺部與神經發展方面的罹病情況增加有關。採取保護性措施的呼吸器使用方法，來允許動脈中的二氧化碳維持在較高之濃度(容許較高之二氧化碳)，目前已經廣泛地被使用在成年人的重症照護上。在使用呼吸器的新生兒，若是要積極地追求二氧化碳的濃度正常，可能會讓原本就已經存在的肺部疾病負擔加重。然而，在這易受傷害的族群中，卻還沒有針對二氧化碳的分壓(PCO2)而建立起安全或是理想的範圍。 在實驗性動物資料，以及未採取對照的人體嬰兒之觀察性研究，都認為過度換氣與血液之二氧化碳濃度過低可能與肺部與神經發展方面的罹病情況增加有關。採取保護性措施的呼吸器使用方法，來允許動脈中的二氧化碳維持在較高之濃度(容許較高之二氧化碳)，目前已經廣泛地被使用在成年人的重症照護上。在使用呼吸器的新生兒，若是要積極地追求二氧化碳的濃度正常，可能會讓原本就已經存在的肺部疾病負擔加重。然而，在這易受傷害的族群中，卻還沒有針對二氧化碳的分壓(PCO2)而建立起安全或是理想的範圍。 在使用機械式呼吸器的新生兒身上，要評估容許較高之二氧化碳的策略是否能夠改善短期與長期的預後(尤其是針對死亡率、呼吸輔助的時間長度、發生慢性肺部疾病的比例，以及神經發展方面的預後)。 在接受了機械式呼吸器的新生兒身上，將容許較高之二氧化碳的策略與傳統的策略(達到正常或是只有些微高之二氧化碳濃度)進行了比較，這些試驗都是合格的。 我們使用的是the Cochrane Neonatal Review Group的標準方法。這些由研究策略所確認出來的試驗，都是經由每1位作者獨立地檢查過，並且針對合格度與試驗的品質來加以評估。這些資料都是分開進行擷取的。差異會拿來比較，然後予以解決。我們還跟試驗的作者們索取過更多的資訊。只有已經發表過的資料，才能夠被用於回顧當中。這些結果在針對二元性的資料方面，是用相對風險(RR)與風險差異(RD)的方式來表達，在針對連續性的變異數方面，則是用加權平均差(WMD)來表達。...