Table 2. Summary of harms of permissive hypercapnia for CNS.

BBB: blood-brain barrier; pH: potential of hydrogen; VLBW: very low birth weight

Study	Year	Model	Effects on CNS	CO2
Ding et al. [20]	2020	Rat	Hypercapnia-induced IL-1β overproduction in the hypoxemic blood may decrease tight junctional protein expression in cerebrovascular endothelial cells via the IL-1R1/p-IRAK-1 pathway, further disrupting the BBB integrity, and eventually resulting in increased BBB permeability.	Exposed to 5% CO2
Kaiser et al. [21]	2005	Human	The autoregulatory slope increases with increasing PaCO2, suggesting that autoregulation in ventilated VLBW infants during the first week of life may be associated with increased vulnerability to brain injury.	PCO2 >45 mmHg
Ding et al. [22]	2018	Rat	Hypercapnia-induced IL-1β overproduction via activating the NLRP3 inflammasome by hypoxia-activated microglia may augment neuroinflammation, increase neuronal cell death, and contribute to the pathogenesis of cognitive impairments.	Exposed to CO2 concentrations of 5% of the gas mixture to maintain pH at 7.20-7.25
Tiruvoipati et al. [23]	2018	Human	Hypercapnic acidosis was associated with an increased risk of hospital mortality in patients with cerebral injury. Hypercapnia, when compensated to a normal pH during the first 24 hours of intensive care unit admission, may not be harmful in mechanically ventilated patients with cerebral injuries.	PCO2 >45 mmHg
Ding et al. [25]	2020	Rat	Hypercapnia promotes microglial pyroptosis via inhibiting mitophagy in hypoxemic adult rats.	Exposed to 5% CO2 to maintain the pH of arterial blood at 7.20-7.25
Wang et al. [26]	2015	Human	The presence of intraoperative hypercapnia appears to be associated with the development of postoperative delirium in geriatric patients after orthopedic surgery.	Not mentioned