27 Apr 2018

Monash study reveals insights into brain injury, blood carbon dioxide levels and hospital deaths

Professor Ravi Tiruvoipati
by Anne Crawford

A large multi-centre study has made an important finding about the relationship between hypercapnia (high carbon dioxide or CO2) in the blood of patients with acute brain injury and hospital mortality. CO2 makes your blood more acidic which, if not adjusted, can affect your outcomes for the worse.
Professor Ravindranath Tiruvoipati, Adjunct Clinical Professor at the Peninsula Clinical School, Monash University and Intensive Care Specialist at Frankston Hospital, Peninsula Health, was first author on the paper, published in JAMA Neurology.  

Professor Tiruvoipati looked at data from 30,742 patients with acute cerebral injury admitted to 167 intensive care units in Australia and New Zealand between January 2000 and December 2015 aiming to unravel the complex relationship between blood CO2 (PCO2), blood acidosis (pH) and hospital mortality.

High carbon dioxide levels set in due to several causes in patients who are critically ill.

Many studies have investigated the effects of partial pressure of arterial carbon dioxide (PCO2) and pH in critically ill patients with cerebral injury, showing that high PCO2 or low pH is harmful for patients. However, they all investigated the effects of PCO2 and pH in isolation – PCO2 and pH are interrelated. A high PCO2 can be associated with a low pH (hypercapnic acidosis) or a normal pH (compensated hypercapnia).

The researchers investigated the association of PCO2 and pH in conjunction to differentiate the association of hypercapnic acidosis and compensated hypercapnia in patients with acute cerebral injury caused by cardiac arrest, stroke and traumatic brain injury.

As such, it is the first and largest study relating blood carbon dioxide and pH status to mortality in such patients.

Patients with brain injury admitted to ICU for mechanical ventilation were classified into three groups based on a combination of arterial pH and arterial carbon dioxide levels: those with normal CO2 and pH; high CO2 and normal pH (compensated hypercapnia; and high CO2 and low pH during the first 24 hours of ICU stay.

The study concluded that hypercapnic acidosis in patients during the first 24 hours of ICU was associated with up to 30% increased risk of hospital mortality, compared to those with normal CO2 and pH. However, those with compensated hypercapnia did not have an increase in risk of death compared with those with normal CO2 and pH. Furthermore, in patients with hypercapnic acidosis the risk of hospital mortality increased with increasing PCO2 while in patients with compensated hypercapnia no increased risk of mortality was noted with increasing PCO2.

An editorial on the study, in the same issue of JAMA Neurology, noted that while clinical acute ventilation strategy recommendations specify a range for blood CO2 levels, they do not include a pH target. “In this context, the study by Tiruvoipati et al5 is interesting, specifically regarding the relative importance of hypercapnia with or without acidosis on outcomes after acute brain injury,” the editorial notes.

The editorial also says the finding that “patients with compensated hypercapnia did not have increased mortality risk, but rather the same likelihood of mortality as those with normocapnia and a normal pH” is “potentially important”.  “(It) suggests that any impact of a single value of elevated blood CO2 early after acute brain injury needs to be considered in the context of the patient’s acid-base status (ie, pH value).”

It then discusses the implications of this for clinical ICU practitioners.

Professor Tiruvoipati said, “It is important to interpret PCO2 levels in conjunction with pH when treating patients with cerebral injury. Our study shows that hypercapnic acidosis (high PCO2 and low pH) was associated with increased hospital mortality and should be avoided or actively treated. However, when elevated CO2 is associated with a normal pH it may not be harmful.”

Tiruvoipati R, Pilcher D, Botha J, Buscher H, Simister R, Bailey M. Association of Hypercapnia and Hypercapnic Acidosis With Clinical Outcomes in Mechanically Ventilated Patients With Cerebral Injury. JAMA Neurol. 2018 Mar 19. doi: 10.1001/jamaneurol.2018.0123. [Epub ahead of print]

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