Hypercapnic Acidosis Associated With Increased Mortality Risk in Acute Cerebral Injury

Graph on screen in ICU
Graph on screen in ICU
Hypercapnic acidosis may be associated with increased mortality in mechanically ventilated patients with acute cerebral injury.

In mechanically ventilated adult patients with acute cerebral injury, hypercapnic acidosis is associated with a greater in-hospital mortality risk than compensated hypercapnia acidosis or normocapnia, according to study findings published in JAMA Neurology.

An Australian and New Zealand database was used to retrospectively review mechanically ventilated adult patients who were admitted to 167 intensive care units (ICUs) for acute cerebral injury. The diagnosis used for cerebral injury required an admission diagnosis of cardiac arrest, traumatic brain injury, or stroke.

Investigators categorized patients as having normocapnia and normal pH (n=13,052), compensated hypercapnia (n=1338), and hypercapnic acidosis (n=16,352). In-hospital mortality comprised the primary outcome, and investigators also examined the association between hypercapnic or hypercapnia acidosis and ICU mortality, ICU and hospital stay duration, and survival to discharge.

In the crude analysis, in-hospital mortality rates were higher among patients with hypercapnic acidosis vs normocapnia/normal pH and compensated hypercapnia (50.3% vs 27.7% and 29.9%, respectively).

After adjustment, the independent risk for in-hospital mortality was greater among patients with hypercapnic acidosis vs normocapnia/normal pH, particularly for patients with cardiac arrest (odds ratio [OR], 1.51; 95% CI, 1.34-1.71), stroke (OR, 1.43; 95% CI, 1.27-1.6), and traumatic brain injury (OR, 1.22; 95% CI, 1.06-1.42; P <.001).

Conversely, Cox proportional hazards analysis demonstrated no difference between the compensated hypercapnia and normocapnia/normal pH groups in terms of in-hospital mortality among those with traumatic brain injury (HR, 0.85; 95% CI, 0.6-1.21; P =.07). In addition, increasing partial pressure of carbon dioxide was associated with an increased odds of adjusted in-hospital mortality rates among those with hypercapnic acidosis, yet no similar association was found among those with compensated hypercapnia.

Related Articles

Because of the study’s retrospective design, the investigators of this analysis were unable to assess whether patients with acute cerebral injury had pre-ICU renal compensation, which may have contributed to mortality rates. Also, the investigators were unable to evaluate patient measurements of cerebral blood flow or intracranial pressures, which may have elucidated further insight into the mechanisms driving the increased mortality rates.

The investigators explain that prolonged acidosis in the first 24 hours of admission to the ICU “is likely to represent significant exposure to this mechanism for neuronal influx of calcium ions and higher levels of consequent injury caused by the excitotoxic action of glutamate release triggered by high intracellular levels of calcium 2.”


Tiruvoipati R, Pilcher D, Botha J, et al. Association of hypercapnia and hypercapnic acidosis with clinical outcomes in mechanically ventilated patients with cerebral injury [published online March 19, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.0123