EBQ:Titrated Oxygen Therapy for COPD Exacerbation

incomplete Journal Club Article

Austin MA et. al.. "Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial". BMJ. 2010. 341:c5462.
PubMed Full text PDF

Clinical Question

In the prehospital setting, does titrating oxygen saturation of patients with presumed AECOPD to SpO₂ 88-92% compared to high flow oxygen for all decrease prehospital and in-hospital mortality?

Conclusion

Compared to high flow oxygen, titrating supplemental oxygen to a target SpO₂ of 88-92% decreased mortality overall, and decreased hypercapnia and acidosis in patients treated according to protocol.

Major Points

• Patients presenting with dyspnea often receive supplemental oxygen empirically to correct hypoxemia and for symptomatic relief . However, in patients with COPD hyperoxia has been shown to increase the risk of hypercapnia and acidosis, possibly through decreasing respiratory drive and worsening VQ-mismatch by disruption of hypoxic pulmonary vasoconstriction. Furthermore, observational studies have shown an association between high flow oxygen administration and length of stay, ICU admission and mortality.
• In this study, paramedics were randomized to administer either high flow oxygen or oxygen titrated to 88-92% SpO₂ to patients with suspected AECOPD along with standard treatments such as nebulized bronchodilators.

Study Design

• Cluster randomized controlled single centre parallel group trial.
• N=405
  • 214 had confirmed COPD by PFTs in the past 5 years
• Enrolment: June 2006 to July 2007
• Setting: Ambulance service in Hobart, Tasmania, Australia

Population

Patient Demographics

• All patients (n=405)
  • Male: 49%
  • Mean Age: 69
• Confirmed diagnosis of COPD (n=214)
  • Male: 48%
  • Mean Age: 68
  • FEV₁ from most recent PFT: 42.6% predicted
  • Avg Pack years: 45.5

Inclusion Criteria

• Age ≥ 35
• Paramedic diagnosis of AECOPD based upon one or more of:
  • appropriateness of symptoms
  • patient-reported history of COPD
  • >10 pack-year smoking history

Interventions

• Paramedics were randomized to administer one of two treatments:
  • Active arm: Oxygen via nasal prongs to target an SpO2 or 88-92% + bronchodilators administered via nebulizer face mask over NPs driven by compressed air.
  • Control arm: High flow oxygen via non-rebreather at 8-10 L/min + bronchodilators administered via nebulizer with oxygen 6-8L/min

Outcomes

Primary Outcome

Prehospital and in-hospital mortality

• 21/226 (9%) in high flow arm vs. 7/179 (4%) in the titrated oxygen arm. RR 0.42 (95% CI: 0.20 to 0.89) p=0.02

Secondary Outcomes

Incidence of both invasive and non-invasive ventilation

• 19/213 (9%) in high flow arm vs. 13/166 (8%) in the titrated oxygen arm. RR 0.88 (95% CI: 0.45 to 1.72) p=0.7.
  • NIV 9/226 vs 8/179

Subgroup analysis

Confirmed COPD. (Analysis of PFT within last 5 years + medical records by respirologist blinded to treatment allocation)

• Mortality
  • 11/117 (9%) in high flow arm vs. 2/97 (2%) in the titrated oxygen arm. RR 0.22 (95%CI: 0.05 to 0.91) p=0.04
• Mean blood gasses (note the low # of patients who had blood gasses taken)
  • pH: 7.29 (n=19) in high flow arm vs. 7.35 (n=19) in the titrated oxygen arm. Mean difference 0.06. p=0.11
  • paCO2 (mmHg) : 77.8 (n=20) in high flow arm vs. 54.7 (n=20). Mean difference −23.1. p=0.06.

Criticisms & Further Discussion

• Treatment protocol violation occurred in 56% of patients in the titrated oxygen arm based on ambulance records. All violations involved administration of high flow oxygen at some point pre-hospital.
• Very few patients had a blood gas taken within 30 minutes of arrival at hospital. Those who did may represent a subgroup of sicker patients.
• Though hospital staff were instructed to treat according to patient assignment, data regarding whether patients received high flow oxygen in-hospital is largely missing.
• COPD subgroup defined retrospectively. In addition, this group excluded any patients who lacked recent PFTs, likely excluding patients with bona fide AECOPD.
• All patients were admitted to hospital which may not represent the typical disposition of all patients brought to EDs by ambulance for suspected AECOPD.
• Relatively little use of non-invasive ventilation, though this has been shown to improve hypercapnia and other outcomes in AECOPD.
• Nebulized treatments administered differently in each group.
• Single centre study, no blinding post-treatment initiation.

Funding

• Australian College of Ambulance Professionals (ACAP)
• FlaemNuova (equipment)