Carbon dioxide levels in neonates: what are safe parameters?

Abstract There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5–64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0–7.3 kPa: 45.0–54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. Impact There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5–7 kPa was inferred following systematic review.

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Asthma and Cystic Fibrosis

Cognitive and Behavioral Abnormalities of Pediatric Diseases ◽

10.1093/oso/9780195342680.003.0059 ◽

2010 ◽

Author(s):

Robert Hilt ◽

Alison Leary

Keyword(s):

Carbon Dioxide ◽

Cystic Fibrosis ◽

Motor Development ◽

Very Low Birth Weight ◽

Permissive Hypercapnia ◽

Low Birth Weight Infants ◽

Respiratory Problems ◽

Systemic Hypoxia ◽

Carbon Dioxide Levels ◽

Carbon Dioxide Co2

Asthma and cystic fibrosis (CF) are examples of childhood pulmonary illnesses with significant psychological impacts. These disorders have in common an induced difficulty with a primal drive, the drive to breathe. Acute impairment with the drive to breathe is highly anxiety provoking, and chronic impairment is life-altering. Pulmonary illnesses like asthma and CF can have direct impacts on brain functioning through systemic hypoxia (low blood oxygen [O2] level) or hypercapnia (high blood carbon dioxide [CO2] level) due to poor respiratory gas exchange. With chronic respiratory problems in children, hypoxia is the more clinically pertinent issue in that hypoxia seems to produce developmental impacts. Studies that have looked at the outcomes of pulmonary hypoxia have found associations with adverse effects even from oxygen levels that were just slightly below the normal range (Bass et al. 2004). A drop of only 4% O2 saturation from baseline is associated with attentiondeficit hyperactivity (ADHD)-like symptoms. Persistent oxygen saturation levels that are even lower than this have been associated with decreased IQ and delays in motor development (Bass et al. 2004). Negative neurobehavioral effects of the hypercapnia side of impaired respiratory status are less well documented. In fact, hypercapnia, besides triggering an increase in cerebral blood flow and driving a sense of air hunger particularly in people with trait anxiety, seems to have no lasting neurocognitive impact (Wan et al. 2008). Research on the use of intentional ‘‘permissive’’ hypercapnia when using mechanical ventilation assistance (allowing higher blood carbon dioxide levels to minimize barotrauma from the assist device) has shown no common neurocognitive complications from this strategy. There are even suggestions of some improved neurocognitive outcomes for neonates managed in this manner (Miller and Carlo 2007). These results are tempered by a higher reported frequency of intraventricular hemorrhage in hypercapnic very-low-birth-weight infants, and there is at least one case report of subarachnoid hemorrhage in a child ventilated with permissive hypercapnia for an asthma episode (Edmunds and Harrison 2003; Kaiser et al. 2006). The severe hypercapnia of complete respiratory failure goes hand in hand with hypoxia, so the effects of each in that potentially fatal scenario are difficult to separate.

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Association of maternal diabetes mellitus with preterm infant outcomes: a systematic review and meta-analysis

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2020-320054 ◽

2020 ◽

pp. fetalneonatal-2020-320054

Author(s):

Abdul Razak ◽

Maheer Faden

Keyword(s):

Systematic Review ◽

Hospital Mortality ◽

Preterm Infant ◽

Preterm Infants ◽

Meta Analysis ◽

Periventricular Leukomalacia ◽

Intraventricular Haemorrhage ◽

Maternal Diabetes ◽

Infant Outcomes ◽

Meta Analyses

ContextThe association between maternal diabetes and outcomes of infants who are born preterm is unclear.ObjectiveTo perform a systematic review and meta-analysis of clinical studies exploring the association between maternal diabetes and preterm infant outcomes.MethodsMedline, PubMed and Cumulative Index of Nursing and Allied Health Literature databases were searched without language restriction from 1 January 2000 until 19 August 2019. Studies examining preterm infants <37 weeks gestational age and reporting prespecified outcomes of this review based on maternal diabetes as primary exposure variable were included.ResultsOf 7956 records identified through database searches, 9 studies were included in the study. No significant association was found between maternal diabetes and in-hospital mortality (adjusted RR (aRR) 0.90 (95% CI 0.73 to 1.11); 6 studies; participants=1 191 226; I2=83%). Similarly, no significant association was found between maternal diabetes and bronchopulmonary dysplasia (aRR 1.00 (95% CI 0.92 to 1.07); 4 studies; participants=107 902; I2=0%), intraventricular haemorrhage or cystic periventricular leukomalacia (aRR 0.91 (95% CI 0.80 to 1.03); 3 studies; participants=115 050; I2=0%), necrotising enterocolitis (aRR 1.13 (95% CI 0.90 to 1.42); 5 studies; participants=142 579; I2=56%) and retinopathy of prematurity (ROP) (aRR 1.17 (95% CI 0.85 to 1.61); 5 studies; participants=126 672; I2=84). A sensitivity analysis where low risk of bias studies were included in the meta-analyses showed similar results; however, the heterogeneity was lower for in-hospital mortality and ROP.ConclusionMaternal diabetes was not associated with in-hospital mortality and severe neonatal morbidities in preterm infants. Future studies should explore the association between the severity of maternal diabetes with preterm infant outcomes.

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60 Correlation of Carbon Dioxide Levels as Measured by Arterial, Transcutaneous and End Tidal Methods in Preterm Infants <28 Weeks Gestation

Paediatrics & Child Health ◽

10.1093/pch/9.suppl_a.37a ◽

2004 ◽

Vol 9 (suppl_a) ◽

pp. 37A-37A

Author(s):

L Aliwalas ◽

L Noble ◽

K Nesbitt ◽

S Fallah ◽

V Shah ◽

...

Keyword(s):

Carbon Dioxide ◽

Preterm Infants ◽

Carbon Dioxide Levels ◽

End Tidal

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Association between perinatal hypoxic-ischemia and periventricular leukomalacia in preterm infants: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0184993 ◽

2017 ◽

Vol 12 (9) ◽

pp. e0184993 ◽

Cited By ~ 7

Author(s):

Jichong Huang ◽

Li Zhang ◽

Bingyao Kang ◽

Tingting Zhu ◽

Yafei Li ◽

...

Keyword(s):

Systematic Review ◽

Preterm Infants ◽

Meta Analysis ◽

Periventricular Leukomalacia ◽

Hypoxic Ischemia

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Agreement of Carbon Dioxide Levels Measured by Arterial, Transcutaneous and End Tidal Methods in Preterm Infants ≤28 Weeks Gestation

Journal of Perinatology ◽

10.1038/sj.jp.7211202 ◽

2004 ◽

Vol 25 (1) ◽

pp. 26-29 ◽

Cited By ~ 26

Author(s):

Lucia Liz D Aliwalas ◽

Laura Noble ◽

Karin Nesbitt ◽

Shafagh Fallah ◽

Vibhuti Shah ◽

...

Keyword(s):

Carbon Dioxide ◽

Preterm Infants ◽

Carbon Dioxide Levels ◽

End Tidal

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Venovenous Extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe ARDS: A systematic review and meta-analysis of the literature

10.1101/2021.10.26.21265546 ◽

2021 ◽

Author(s):

Elliott Worku ◽

Daniel Brodie ◽

Ryan Ruiyang Ling ◽

Kollengode Ramanathan ◽

Alain Combes ◽

...

Keyword(s):

Carbon Dioxide ◽

Systematic Review ◽

Acute Respiratory Distress Syndrome ◽

Distress Syndrome ◽

Meta Analysis ◽

Protective Ventilation ◽

Driving Pressure ◽

List Type ◽

Extracorporeal Carbon Dioxide Removal ◽

Ultraprotective Ventilation

AbstractBackgroundA strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS.MethodsMEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 hours of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 hours of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data.ResultsTen studies reporting 421 patients (PaO2:FiO2 141.03mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p<0.001) and a 1.89 ml/kg (95%-CI: 1.75-2.02, p<0.001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy.ConclusionsVenovenous ECCO2R permitted significant reductions in ΔP in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting.Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.Key MessagesWhat is the Key Question?In adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS), can venovenous extracorporeal carbon dioxide removal (ECCO2R) support ultraprotective lung ventilation beyond the current standard for protective ventilation in ARDS?What is the bottom line?Systematic review of available data on venovenous ECCO2R shows that it can reduce driving pressure in ventilated patients with moderate-to-severe ARDS, supporting ultraprotective ventilation. Prospective measurement of mechanical power, and greater emphasis on safety and patient-centred outcomes is needed.Why read on?This is the first systematic review to exclusively address venovenous ECCO2R use in the moderate-to-severe ARDS cohort. We report the degree of lung protection achieved with venovenous ECCO2R devices, along with factors potentially limiting widespread adoption.

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End-tidal carbon dioxide levels during resuscitation and carbon dioxide levels in the immediate neonatal period and intraventricular haemorrhage

European Journal of Pediatrics ◽

10.1007/s00431-019-03543-0 ◽

2019 ◽

Vol 179 (4) ◽

pp. 555-559

Author(s):

Kentaro Tamura ◽

Emma E Williams ◽

Theodore Dassios ◽

Anoop Pahuja ◽

Katie A Hunt ◽

...

Keyword(s):

Carbon Dioxide ◽

Preterm Infants ◽

Gestational Age ◽

Intraventricular Haemorrhage ◽

Poor Correlation ◽

End Tidal Carbon Dioxide ◽

Severe Group ◽

The Difference ◽

Carbon Dioxide Levels ◽

End Tidal

AbstractAbnormal levels of end-tidal carbon dioxide (EtCO2) during resuscitation in the delivery suite are associated with intraventricular haemorrhage (IVH) development. Our aim was to determine whether carbon dioxide (CO2) levels in the first 3 days after birth reflected abnormal EtCO2 levels in the delivery suite, and hence, a prolonged rather than an early insult resulted in IVH. In addition, we determined if greater EtCO2level fluctuations during resuscitation occurred in infants who developed IVH. EtCO2 levels during delivery suite resuscitation and CO2 levels on the neonatal unit were evaluated in 58 infants (median gestational age 27.3 weeks). Delta EtCO2 was the difference between the highest and lowest level of EtCO2. Thirteen infants developed a grade 3–4 IVH (severe group). There were no significant differences in CO2 levels between those who did and did not develop an IVH (or severe IVH) on the NICU. The delta EtCO2 during resuscitation differed between infants with any IVH (6.2 (5.4–7.5) kPa) or no IVH (3.8 (2.7–4.3) kPA) (p < 0.001) after adjusting for differences in gestational age. Delta EtCO2 levels gave an area under the ROC curve of 0.940 for prediction of IVH.Conclusion: The results emphasize the importance of monitoring EtCO2 levels in the delivery suite. What is Known:• Abnormal levels of carbon dioxide (CO2) in the first few days after birth and abnormal end-tidal CO2levels (EtCO2) levels during resuscitation are associated in preterm infants with the risk of developing intraventricular haemorrhage (IVH). What is New:• There were no significant differences in NICU CO2levels between those who developed an IVH or no IVH.• There was a poor correlation between delivery suite ETCO2levels and NICU CO2levels.• Large fluctuations in EtCO2during resuscitation in the delivery suite were highly predictive of IVH development in preterm infants.

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Risk Factors for Periventricular Leukomalacia in Preterm Infants: A Systematic Review, Meta-analysis, and GRADE-Based Assessment of Certainty of Evidence

Pediatric Neurology ◽

10.1016/j.pediatrneurol.2021.08.003 ◽

2021 ◽

Vol 124 ◽

pp. 51-71 ◽

Cited By ~ 1

Author(s):

Thangaraj Abiramalatha ◽

Tapas Bandyopadhyay ◽

Viraraghavan Vadakkencherry Ramaswamy ◽

Nasreen Banu Shaik ◽

Sivam Thanigainathan ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Preterm Infants ◽

Meta Analysis ◽

Periventricular Leukomalacia

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Neurodevelopmental impairment in necrotising enterocolitis survivors: systematic review and meta-analysis

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2019-317830 ◽

2019 ◽

Vol 105 (4) ◽

pp. 432-439 ◽

Cited By ~ 4

Author(s):

Andreea Matei ◽

Louise Montalva ◽

Alexa Goodbaum ◽

Giuseppe Lauriti ◽

Augusto Zani

Keyword(s):

Systematic Review ◽

Preterm Infants ◽

Meta Analysis ◽

Periventricular Leukomalacia ◽

Intraventricular Haemorrhage ◽

Cochrane Collaboration ◽

Necrotising Enterocolitis ◽

Cerebral Lesions ◽

Neurodevelopmental Impairment ◽

The Impact

AimTo determine (1) the incidence of neurodevelopmental impairment (NDI) in necrotising enterocolitis (NEC), (2) the impact of NEC severity on NDI in these babies and (3) the cerebral lesions found in babies with NEC.MethodsSystematic review: three independent investigators searched for studies reporting infants with NDI and a history of NEC (PubMed, Medline, Cochrane Collaboration, Scopus). Meta-analysis: using RevMan V.5.3, we compared NDI incidence and type of cerebral lesions between NEC infants versus preterm infants and infants with medical vs surgical NEC.ResultsOf 10 674 abstracts screened, 203 full-text articles were examined. In 31 studies (n=2403 infants with NEC), NDI incidence was 40% (IQR 28%–64%) and was higher in infants with surgically treated NEC (43%) compared with medically managed NEC (27%, p<0.00001). The most common NDI in NEC was cerebral palsy (18%). Cerebral lesions: intraventricular haemorrhage (IVH) was more common in NEC babies (26%) compared with preterm infants (18%; p<0.0001). There was no difference in IVH incidence between infants with surgical NEC (25%) and those treated medically (20%; p=0.4). The incidence of periventricular leukomalacia (PVL) was significantly increased in infants with NEC (11%) compared with preterm infants (5%; p<0.00001).ConclusionsThis study shows that a large proportion of NEC survivors has NDI. NEC babies are at higher risk of developing IVH and/or PVL than babies with prematurity alone. The degree of NDI seems to correlate to the severity of gut damage, with a worse status in infants with surgical NEC compared with those with medical NEC.Trial registration numberCRD42019120522.

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