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Three Part Question

In [patients with acute exacerbation of COPD] does [pre hospital high flow oxygen] affect [mortality]?

Clinical Scenario

67 year old life long smoker, known COPD, on long term home oxygen and home nebuliser therapy, was brought into the emergency department by ambulance. He received 100% oxygen in the ambulance and was put on 4 litre/min oxygen by triage nurse in A&E. On assessment by the emergency doctor the patient was found to be in decompensated type 2 respiratory failure. You wonder whether it was appropriate for this patient to receive 100% oxygen in the ambulance and whether this would affect his outcome.

Search Strategy

MEDLINE 1950 to date using Dialogue Datastar. In addition, the National Institute of Clinical Excellence was searched for relevant guidelines
"((((chronic) AND (lung ADJ disease) AND (obstructive)) OR (emphysema) OR (bronchitis) OR (coad) OR (copd)) AND (acute OR exacerbation)) AND (((high ADJ flow) OR (high ADJ concentration)) AND (oxygen)) AND (mortality OR outcome OR death)"

Search Outcome

4 papers were found using the above search strategy of which 2 were relevant. A furthur 8 papers were found by scanning the references of the above papers. Altogether 6 papers were deemed relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Denniston, O'Brien, Stableforth 2002 UK	Retrospective study with 97 consecutive patients with a final diagnosis of acute exacerbation of COPD made by a respiratory physician	Meta analysis	Higher frequency of severe respiratory acidosis and mortality in patients receiving Fio2 >0.28	(8/57)14% in- hospital mortality in patients administered FiO2 >0.28 versus (1/44)2% in those administered FiO2 <0.28	Small study (n=97) English language search only
Durrington, Flubacher, Ramsay, Howard, Harrison 2005 UK	Retrospective audit with 108 episodes of acute admissions with exacerbation of COPD. A second audit was conducted one year later with 103 episodes of acute exacerbation of COPD	Meta analysis	High Concentration oxygen (FiO2>0.28)causes significant (p<0.01) acidosis, inappropriately high PaO2 and PaCO2 compared to intial low concentration oxygen (FiO2=<0.28) therapy.	For FiO2>0.28, mean pH 7.20, PaCO2 11.70 and PaO2 18.90	No clear definition of 'complications' and no direct relationship between high concentration oxygen and mortality
			Significantly increased complication rate during admission (p<0.01) in those COPD patients receiving high concentration oxygen compared to low concentration oxygen, particularly when ambulance journeys exceeded 30 mins.	Complication ensued in only 19.4% (12.3-26.5) of those whose ambulance journey was <30mins and who received only low concentration oxygen, compared to 60.0% (51.1-68.9) in those whose journey was =>30 mins and had received high concentration oxygen in ambulance (p<0.05)
Plant, Owen, Elliot 2000 UK	One year prospective prevalence study with 983 patients with COPD admitted with acute exacerbations	Meta analysis	Hypercapnic patients with higher PaO2 was associated with worse acidosis. A proportion had been made acidotic by injudicious oxygen therapy and were able to rapidly correct their pH once FiO2 was reduced. The only variable that was significantly different between acidotic patients who normalised their pH and those who did not was the initial PaO2	454 patients (46.7%, 95% CI) were hypercapnic and 199 patients (20.4%, 95% CI) were acidotic of whom 40 (20.1%, 95% CI) normalised their pH on arrival to the ward. For hypercapnic patients a higher paO2 was asoociated with worse acidosis (r=-0.214, p<0.01)	Acidosis was associated with subsequent ITU admission but there was no association between acidosis and mortality
Jeffrey, Warren, Flenley 1992 UK	Prospective study with 95 patients with acute exacerbation of COPD admitted with 139 episodes of acute hypercapnic Type 2 respiratory failure	Meta analysis	Arterial pH during admission is an important prognostic factor for survival. Mortality was greater for episodes where pH was below 7.26	Death occurred in 10 of the 39 episodes in which the lowest recored pH was less than or equal to 7.26 compared with 7 of the 100 episodes in which pH was greater than 7.26 (p<0.001)	No direct relation between intial PaO2 and mortality
Murphy, Driscoll, O'Driscoll 2001 UK	Systematic review (Medline 1966-2000 for articles on oxygen therapy and CO2 retention)	Systematic review	High concentration oxygen causes more CO2 retention and more acidosis than low concentration oxygen. The degree to which this occurs has not been quantified. It does not happen to every patient and there is only indirect evidence linking excessive oxygen therapy to an increased risk of death or requirement for mechanical ventilation	8 different studies involving different concentration of oxygen therapy to patient with acute exacerbations of COPD and subsequent outcome in respect of rise in paCO2, fall in pH and mortality.	Study effects were not summarised by meta analysis
National Institute of Clinical Excellence 2004 UK	Guidelines on management of chronic obstructive pulmonary disease in adults in primary and secondary care	Systematic review	Grade D recommendations	During transfer to hospital it is not desirable to exceed an oxygen saturation of 93%. Oxygen therapy should be commenced at 40% and titrated upwards if the saturation fall below 90% and downwards if the patient becomes drowsy or if it exceeds 93-94%

Comment(s)

The fourth paper establishes a direct relationship between high flow oxygen and mortality in patient with acute exacerbation of COPD. The sixth paper establishes a relationship between high flow oxygen with longer ambulance journey time and the development of acidosis, hypercapnia and subsequent complications. The first and second papers describe a relationship between high flow oxygen and acidosis, and acidosis and mortality respectively. Therefore the two results combined together establish an indirect relationship between high flow oxygen and mortality. The latest NICE guideline clearly states the acceptable oxygen saturation for patients with acute exacerbation of COPD while transfer to hospital and the recommends starting oxygen therapy at no more than 40%. A randomised double blinded controlled trial of different oxygen concentrations administered to patients with acute exacerbation of COPD is impossible for ethical reasons.

Clinical Bottom Line

Pre Hospital high flow oxygen does affect mortality in patients with acute exacerbation of COPD. Latest guidelines (NICE 2004) should be followed on oxygen administration to patients with acute exacerbation of COPD. Ambulance and Paramedic protocols should be reviewed for correctly identifying patients with COPD and administering the recommended level of oxygen while transfer to hospital.

References

1. Alaistair KO Denniston, Christine O'Brien and David Stableforth The use of oxygen in acute exacerbations of chronic obstructive pulmonary disease: a prospective audit of pre-hospital and hospital emergency management Clinical Medicine 2002;2:449-51
2. H J Durrington, M Flubacher, C F Ramsay, L S G E Howard and B D W Harrison Initial oxygen management in patients with an acute exacerbation of chronic obstructive pulmonary disease Q J Med 2005;98:499-504
3. PK Plant, JL Owen, MW Elliot One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration Thorax 2000;55:550-554
4. Andrew A Jeffrey, Patricia M Warren, David C Flenley Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management Thorax 1992;47:34-40
5. R Murphy, P Driscoll and R O'Driscoll Emergency oxygen therapy for COPD patients Emerg Med J 2001;18:333-339
6. National Institute of Clinical Excellence Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care NICE February 2004