Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College

Dr. Merkler reports no financial relationships relevant to this field of study.

SYNOPSIS: In this multicenter retrospective study, hypercapnic acidosis was associated with worse clinical outcomes in mechanically ventilated patients with acute brain injury.

SOURCE: Tiruvoipati R, Pilcher D, Botha J, et al. Association of hypercapnia and hypercapnic acidosis with clinical outcomes in mechanically ventilated patients with cerebral injury. JAMA Neurol 2018;75:818-826.

Acute brain injury is becoming increasingly common worldwide. Methods to reduce secondary brain injury following acute cerebral injury remain elusive. Prior studies regarding the association between hypercapnia and clinical outcomes in patients with acute brain injury have revealed conflicting results.^1,2 Establishing the role of hypercapnia in patients with acute brain injury may provide a useful laboratory measure for prognostication; in addition, it may provide a novel target to reduce secondary brain injury and improve clinical outcomes.

In this multicenter retrospective study, investigators evaluated the association between hypercapnia and mortality among mechanically ventilated patients with acute brain injury. The study included all patients with acute brain injury, including stroke, traumatic brain injury, and cardiac arrest, who were mechanically ventilated. Patients were classified into three categories based on arterial pH and arterial carbon dioxide (pCO₂): 1) normocapnia and normal pH; 2) compensated hypercapnia; and 3) hypercapnic acidosis. Patients were classified into these groups based on their worst pH/pCO₂ in the first 24 hours of ICU admission. Patients with other acid-base abnormalities were excluded (including metabolic acidosis). The primary outcome was in-hospital mortality. Multivariate logistic regression and Cox proportional hazard regression models were used to adjust for demographics, illness severity, Glasgow Coma Scale (GCS) score, and type of acute brain injury.

A total of 30,742 patients were included in the study: 11,785 had cardiac arrest, 9,507 had traumatic brain injury, and 9,477 had stroke. Out of the 30,742 patients, 13,052 had normocapnia and normal pH, 1,338 had compensated hypercapnia, and 16,352 had hypercapnic acidosis. Compared to patients with normocapnia and normal pH, patients with hypercapnic acidosis were older and had more medical comorbidities, had higher severity illness scores (based on APACHE III scores), and had lower GCS scores. In multivariable analyses, patients with hypercapnic acidosis had an increased risk of in-hospital death compared to patients with normocapnia and normal pH levels. Although the association was present in all three diagnosis categories (stroke, traumatic brain injury, cardiac arrest), the association was more robust in patients with cardiac arrest (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.34-1.71) than stroke (OR, 1.43; 95% CI, 1.27-1.6) and traumatic brain injury (OR, 1.22; 95% CI, 1.06-1.42). Among patients with hypercapnic acidosis, the adjusted odds of in-hospital mortality appeared to rise with increasing levels of pCO₂, but this trend was not present among patients with compensated hypercapnia.

COMMENTARY

This multicenter retrospective study demonstrates that hypercapnic acidosis is associated with an increased risk of in-hospital mortality among mechanically ventilated patients with acute brain injury. Although the authors performed multiple sensitivity analyses to try to account for illness severity in their models, it certainly is plausible that other risk factors for mortality existed, for which the models remained unaccounted. As the primary outcome was in-hospital mortality, the effect of acute hypercapnia on long-term mortality and functional status is uncertain.

Overall, this study indicates that hypercapnic acidosis is associated with in-hospital mortality. However, it remains uncertain whether avoidance of hypercapnic acidosis will reduce secondary brain injury and improve long-term outcomes or whether the presence of hypercapnic acidosis is merely a marker of overall brain injury.

REFERENCES

1. Westermaier T, Stetter C, Kunze E, et al. Controlled transient hypercapnia: A novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage? J Neurosurg 2014;121:1056-1062.
2. Davis DP, Idris AH, Sise MJ, et al. Early ventilation and outcome in patients with moderate to severe traumatic brain injury. Crit Care Med 2006;34:1202-1208.