Arterial carbon dioxide tension has a non-linear association with survival after out-of-hospital cardiac arrest: A multicentre observational study

doi:10.1016/j.resuscitation.2021.01.035

Resuscitation

Volume 162, May 2021, Pages 82-90

https://doi.org/10.1016/j.resuscitation.2021.01.035 Get rights and content

Abstract

Purpose

International guidelines recommend targeting normocapnia in mechanically ventilated out-of-hospital cardiac arrest (OHCA) survivors, but the optimal arterial carbon dioxide (PaCO₂) target remains controversial. We hypothesised that the relationship between PaCO₂ and survival is non-linear, and targeting an intermediate level of PaCO₂ compared to a low or high PaCO₂ in the first 24-h of ICU admission is associated with an improved survival to hospital discharge (STHD) and at 12-months.

Methods

We conducted a retrospective multi-centre cohort study of adults with non-traumatic OHCA requiring admission to one of four tertiary hospital intensive care units for mechanical ventilation. A four-knot restricted cubic spline function was used to allow non-linearity between the mean PaCO₂ within the first 24 h of ICU admission after OHCA and survival, and optimal PaCO₂ cut-points were identified from the spline curve to generate corresponding odds ratios.

Results

We analysed 3769 PaCO₂ results within the first 24-h of ICU admission, from 493 patients. PaCO₂ and survival had an inverted U-shape association; normocapnia was associated with significantly improved STHD compared to either hypocapnia (<35 mmHg) (adjusted odds ratio [aOR] 0.45, 95% confidence interval [CI] 0.24−0.83) or hypercapnia (>45 mmHg) (aOR 0.45, 95% CI 0.24−0.84). Of the twelve predictors assessed, PaCO₂ was the third most important predictor, and explained >11% of the variability in survival. The survival benefits of normocapnia extended to 12-months.

Conclusions

Normocapnia within the first 24-h of intensive care admission after OHCA was associated with an improved survival compared to patients with hypocapnia or hypercapnia.

Introduction

Despite advances in post-resuscitation care, hypoxic-ischemic encephalopathy remains a common cause of death after out-of-hospital cardiac arrest (OHCA).¹ Ischemic-reperfusion brain injury involves a number of mechanisms, including inadequate cerebral oxygen delivery and impaired autoregulation of cerebral blood flow.² Cerebral oxygen delivery is determined by cerebral blood flow, which in turn can be affected by numerous factors including arterial carbon dioxide tension (PaCO₂).³

A recent meta-analysis of eight observational studies4, 5, 6, 7, 8, 9, 10, 11 found that both high and low PaCO₂ levels were associated with worse survival outcomes.¹² These findings are consistent with international guidelines that a normal PaCO₂ should be targeted during post-resuscitation care.13, 14 Data from existing randomized-controlled-trials targeting different PaCO₂ levels in adult patients after cardiac arrest are sparse.15, 16 Most of the observational studies are limited by their use of arbitrary cut-points to define an optimal PaCO₂, analysis of PaCO₂ using data from one single time point or over a limited period of time, and assuming PaCO₂ is linearly associated with survival.¹² Analysis assuming a linear association contradicts the results of a meta-analysis and two multi-centre cohort studies in which a non-linear association between PaCO₂ and patient outcome was demonstrated.5, 17

We hypothesised that normocapnia within the first 24 h after OHCA is associated with a better chance of survival compared to hypocapnia or hypercapnia, and aimed to determine the optimal PaCO₂ cut-points for survival after OHCA.

Section snippets

Study design and setting

This multicentre retrospective cohort study included all patients with OHCA of non-traumatic aetiology¹⁸ transported to one of four adult tertiary intensive care units (ICUs)¹⁹ in Perth, Western Australia, between January 2012 and December 2017. In 2017 the Perth metropolitan area had a population 2.05 million.²⁰ St John Western Australia (SJWA) is the sole provider of emergency medical services in Western Australia. SJWA delivers a single tier of road-based paramedics who provide advanced life

Selection of the study population and its characteristics

Between January 2012 and December 2017, SJWA paramedics attended 8016 patients with non-traumatic OHCA. Of these, 3997 (49.9%) had resuscitation commenced by paramedics and 2812 (70.4%) were transported to a hospital emergency department (954; 33.9% with ROSC). Of the 887 (31.5%) patients who survived to emergency department discharge, 728 (82.1%) were admitted (directly or indirectly) to a tertiary hospital with 502 (69.0%) to the ICU. Nine patients (1.8%) were excluded because two were not

Discussion

This multicentre cohort study found that normocapnia during the first 24-h of ICU admission was associated with a significantly higher odd of survival compared to hypocapnia (<35 mmHg) or hypercapnia (>45 mmHg), and was the third most important predictor of OHCA survival. These results are clinically relevant and require careful consideration.

Our findings are consistent with a recent meta-analysis of eight observational studies including 23,434 patients, in which the relationship between PaCO₂

Conclusions

Compared to hypocapnia (<35 mmHg) and hypercapnia (>45 mmHg), normocapnia (35−45 mmHg) within the first 24-h of ICU admission after OHCA was associated with a significantly greater chance of survival to hospital discharge and at 12 months. Our results support the existing international guidelines, and have important implications on how OHCA patients should be managed within the first 24 h after ICU admission.

Conflict of interest

None.

Funding

Nicole Mckenzie received PhD funding from the Australian Resuscitation Outcomes Consortium – NHMRC Centre of Research Excellence (#1029983) and an Australian Government Research Training Scholarship.

The WA OHCA Registry is funded by St John WA.

Judith Finn is a NHMRC Leadership Fellow, receiving salary and research funding from a NHMRC Investigator grant (#1174838).

Janet Bray received a Heart Foundation Fellowship.

CRediT authorship contribution statement

Nicole Mckenzie: Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Judith Finn: Conceptualization, Supervision, Writing - review & editing. Geoffrey Dobb: Conceptualization, Writing - review & editing. Paul Bailey: Writing - review & editing. Glenn Arendts: Writing - review & editing. Antonio Celenza: Writing - review & editing. Daniel Fatovich: Writing - review & editing. Ian Jenkins: Writing - review & editing. Stephen Ball: Data

Acknowledgments

KMH acknowledges the support of the WA Department of Health and Raine Medical Research Foundation through the Raine Clinical Research Fellowship.

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Citation Excerpt :
Some studies have shown an association between mild hypercapnia and improved outcomes among post-cardiac arrest patients. However, an analysis of 493 patients admitted to ICU after OHCA in Western Australia showed that normocapnia in the first 24 hours was associated with significantly improved survival to hospital discharge compared with hypocapnia or hypercapnia.79 Previous studies have documented an association between low jugular venous oximetry (SjvO2) values and poor outcome among patients with traumatic brain injury.
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A Meta-analysis of the Effect of Unprofessional Early Defibrillation on the Survival Rate of Patients with Out-of-hospital Cardiac Arrest
2022, Chinese General Practice

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Clinical paperArterial carbon dioxide tension has a non-linear association with survival after out-of-hospital cardiac arrest: A multicentre observational study

Abstract

Purpose

Methods

Results

Conclusions

Introduction

Section snippets

Study design and setting

Selection of the study population and its characteristics

Discussion

Conclusions

Conflict of interest

Funding

CRediT authorship contribution statement

Acknowledgments

Resuscitation

Resuscitation

Am J Emerg Med

J Crit Care

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Lancet

Resuscitation

Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort

Intensive Care Med

The brain after cardiac arrest

Semin Neurol

Individualized perfusion targets in hypoxic ischemic brain injury after cardiac arrest

Crit Care

FINNRESUSCI Study Group. Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest: associations with long-term neurologic outcome

Crit Care Med

Associations of arterial carbon dioxide and arterial oxygen concentrations with hospital mortality after resuscitation from cardiac arrest

Crit Care

Clinical paper
Arterial carbon dioxide tension has a non-linear association with survival after out-of-hospital cardiac arrest: A multicentre observational study