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Prehospital EtCO2 and mortality in suspected severe traumatic brain injury patients

Article

Auteur: Alba Badell

Date: 22.07.2024

The authors' point? Targeting EtCO2 levels of 35–45 mmHg seems reasonable during prehospital care as lower levels are associated with a significant increase in 30-day mortality.

Prehospital EtCO2 and mortality in suspected severe traumatic brain injury patients

Clinical question

What is the association between prehospital end-tidal carbon dioxide (EtCO2) levels and mortality in patients with suspected severe traumatic brain injury (TBI)?

Clinical background

  • TBI is a leading global cause of mortality and morbidity. Prehospital treatment including endotracheal intubation and ventilation plays a crucial role in patient outcomes, as patients with severe TBI are at significant risk of secondary brain injury even before reaching the hospital.
  • As ventilation affects arterial partial pressure of carbon dioxide (PaCO2) levels and therefore cerebral blood flow, Hypercapnia may result in cerebral vasodilation and increased intracranial pressure, whereas hypocapnia might produce cerebral vasoconstriction and decreased cerebral blood flow, potentially aggravating TBI.
  • Recommendations for "normoventilation" and evidence supporting this practice are weak, with conflicting research findings on the association between CO2 levels and TBI outcomes.
  • As blood gas analyses are not generally available during prehospital care, prehospital providers usually use EtCO2 values to guide ventilation. 
  • Targeting EtCO2 values below the normal range, which is typically ≤ 35 mmHg in protocols, may increase the risk of hypocarbia.
  • This study aimed to investigate the association between prehospital EtCO2 levels and mortality (Bossers SM, Mansvelder F, Loer SA, et al. Association between prehospital end-tidal carbon dioxide levels and mortality in patients with suspected severe traumatic brain injury. Intensive Care Med. 2023;49(5):491-504. doi:10.1007/s00134-023-07012-z1​), utilizing data from the BRAIN-PROTECT cohort study in the Netherlands.

Design and settings

BRAIN-PROTECT is a multicenter prospective observational study focusing on the prehospital treatment of patients with severe TBI in the Netherlands.

The study included four Dutch physician-staffed helicopter emergency medical services (HEMS) and nine trauma centers. From February 2012 to December 2017, data was collected from patients with suspected severe TBI treated by participating HEMS services.

Outcomes

Primary All-cause mortality at 30 days
Secondary Functional neurologic outcome at discharge assessed using the Glasgow Outcome Scale (GOS)

Patients

  • Patients included in the study had trauma mechanisms or clinical findings suggestive of severe TBI and presented with a prehospital Glasgow Coma Scale (GCS) score of 8 or lower.
  • After prehospital care by the HEMS, patients were transferred to one of the nine participating trauma centers.  
  • Data collection included patient and trauma characteristics, injuries, vital parameters, prehospital treatments, and interventions.
  • Sample size of the study was based on the ability to detect an absolute 5% reduction in mortality with 80% power.

Inclusion criteria Suspected severe TBI rather than confirmed TBI
Prehospital GCS score of 8 or lower
Transferral to one of the nine participating trauma centers after prehospital care
Exclusion criteria Transferral to a non-participating trauma center (no follow-up data)
Prehospital traumatic cardiopulmonary resuscitation
No prehospital advanced airway management

Intervention

After advanced airway management, patients were usually mechanically ventilated or manually ventilated with a self-inflating bag, depending on the availability of a mechanical ventilator in the ambulance, the distance to the hospital, and the preference of the treating physician.

Measurements

The following measurements and parameters were utilized in various analyses, including logistic regression, Cox proportional hazards regression, and subgroup analyses, to investigate associations between prehospital EtCO2 levels and outcomes such as 30-day mortality and survival time up to 1 year after trauma.

Prehospital EtCO2 level Recorded at three timepoints:
1. After HEMS arrival
2. After initial stabilization and airway management
3. Before arriving at the emergency department

Only values from the second and third timepoints were considered as most patients did not undergo advanced airway management before HEMS arrival.
Vital parameters Systolic blood pressure
Heart rate
Oxygen saturation (measured at the same time as EtCO2)
Injury severity Injury severity score
First GCS score
Additional analyses First, second, lowest, and highest EtCO2 values per patient
EtCO2 categorized into:
1. Hypocapnia (< 35 mmHg)
2. Normocapnia (35–44 mmHg)
3. Hypercapnia (≥ 45 mmHg)
Subgroup analyses Confirmed TBI: head abbreviated injury score (HAIS) ≥ 3
Isolated TBI: HAIS ≥ 3, all other AIS ≤ 2
Symptoms of intracerebral herniation: Abnormal pupils, signs of elevated intracranial pressure on initial CT scan

Results

Patients included 1776 out of 2589 patients with suspected severe traumatic brain injury
Patient characteristics Majority male
Median age: 45 years [23, 65]
Initial GCS: 4
Outcome at 30 days 66.8% of patients alive
40.6% recovered with moderate or good recovery at discharge (GOS 4–5)
EtCO2 measurements Total of 2649 measurements available
Moderate correlation between measurements at two time points
Weak correlation between last EtCO2 measurement and first in-hospital PaCO2
Ventilation after airway management Most patients mechanically ventilated (61.4%)
35.4% manually ventilated with a self-inflating bag
Association between EtCO2 and mortality L-shaped association observed
Marked increase in mortality with EtCO2 levels below 35 mmHg
No evident increase in mortality for high EtCO2 level
Hypocapnia vs. normocapnia Hypocapnia is associated with approximately 90% increased odds of mortality (OR 1.89) compared to normocapnia (p < 0.001)
Hypercapnia vs. normocapnia No significant association between hypercapnia and mortality was observed (p = 0.212)
Subgroup analyses EtCO2 values < 35 mmHg associated with increased mortality in patients with confirmed TBI and isolated TBI

Consistent results found in survival analyses and after multiple imputation

Primary outcome

  • An L-shaped association was observed between EtCO2 levels and 30-day mortality in patients with severe TBI. 
  • Lower EtCO2 values (< 35 mmHg) were associated with a significant increase in mortality within 30 days after sustaining severe TBI.
  • An association between low EtCO2 values and mortality was observed across all subgroups, including patients with isolated TBI and signs of cerebral herniation.
  • Higher EtCO2 values (> 45 mmHg) did not show a significant association with increased mortality. 
  • Maintaining EtCO2 levels within a "safe zone" of 35–45 mmHg could be a reasonable target for prehospital ventilation in patients with severe TBI.

Secondary outcome

At discharge, 40.6% of the patients who survived the initial injury had a functional neurologic outcome categorized as moderate or good recovery (GOS score of 4 or 5).

Conclusions

  • A safe zone of 35–45 mmHg for end-tidal CO2 guidance seems reasonable during prehospital care. 
  • In particular, EtCO2 of less than 35 mmHg was associated with significantly increased mortality. 

Clinical highlights

  • Mortality significantly increased with EtCO2 values below 35 mmHg (hypocapnia).
  • EtCO2 levels within a range of 35–45 mmHg were associated with lower and constant mortality rates.
  • These findings challenge current prehospital ventilation practices and emphasize the importance of monitoring and managing EtCO2 levels to improve outcomes in patients with severe TBI.
  • The study focused on 30-day mortality as a primary endpoint; however, other clinically relevant outcomes like neurological recovery were not fully addressed due to incomplete data.

How to incorporate these findings into my daily work with Hamilton Medical technology?

Hamilton Medical ventilators offer a range of features to support effective monitoring of end-tidal CO2, such as the ventilation mode INTELLiVENT-ASV and time-based or volumetric capnography. With these tools, healthcare professionals can measure and maintain EtCO2 levels within the recommended range of 35–45 mmHg for patients with severe traumatic brain injury (TBI). 

The incorporation of time-based and volumetric capnography allows for continuous and accurate monitoring of EtCO2 levels, ensuring precise ventilation management. Being able to observe SBCO2 (single breath of CO2) helps identify ventilation/perfusion changes, lung heterogeneity, etc.

In addition, INTELLiVENT-ASV offers an automated solution that optimizes ventilation parameters by continuously adjusting them breath by breath. EtCO2 is thus kept within the target range, minimizing the risk of hypo- or hypercapnia while promoting better patient outcomes as concluded in this paper.

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Association between prehospital end-tidal carbon dioxide levels and mortality in patients with suspected severe traumatic brain injury.

Bossers SM, Mansvelder F, Loer SA, et al. Association between prehospital end-tidal carbon dioxide levels and mortality in patients with suspected severe traumatic brain injury. Intensive Care Med. 2023;49(5):491-504. doi:10.1007/s00134-023-07012-z



PURPOSE

Severe traumatic brain injury is a leading cause of mortality and morbidity, and these patients are frequently intubated in the prehospital setting. Cerebral perfusion and intracranial pressure are influenced by the arterial partial pressure of CO2 and derangements might induce further brain damage. We investigated which lower and upper limits of prehospital end-tidal CO2 levels are associated with increased mortality in patients with severe traumatic brain injury.

METHODS

The BRAIN-PROTECT study is an observational multicenter study. Patients with severe traumatic brain injury, treated by Dutch Helicopter Emergency Medical Services between February 2012 and December 2017, were included. Follow-up continued for 1 year after inclusion. End-tidal CO2 levels were measured during prehospital care and their association with 30-day mortality was analyzed with multivariable logistic regression.

RESULTS

A total of 1776 patients were eligible for analysis. An L-shaped association between end-tidal CO2 levels and 30-day mortality was observed (p = 0.01), with a sharp increase in mortality with values below 35 mmHg. End-tidal CO2 values between 35 and 45 mmHg were associated with better survival rates compared to < 35 mmHg. No association between hypercapnia and mortality was observed. The odds ratio for the association between hypocapnia (< 35 mmHg) and mortality was 1.89 (95% CI 1.53-2.34, p < 0.001) and for hypercapnia (≥ 45 mmHg) 0.83 (0.62-1.11, p = 0.212).

CONCLUSION

A safe zone of 35-45 mmHg for end-tidal CO2 guidance seems reasonable during prehospital care. Particularly, end-tidal partial pressures of less than 35 mmHg were associated with a significantly increased mortality.