Girardis M, Busani S, Damiani E et al. JAMA 2016; 136 (15): 1583-1589
AIM OF STUDY
To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units.
DESIGN & LOCATION
Single centre, open-label randomised clinical trial conducted from March 2010 to October 2012 at Modena University Hospital (Italy)
METHODOLOGY
All patients aged 18 yrs or older, during the study period, were considered for inclusion if their expected length of stay was greater than 72 hrs
PRIMARY OUTCOME
ICU mortality.
SECONDARY OUTCOMES
New onset respiratory, cardiovascular, liver and renal failure occurring more than 48 hrs after ICU admission. Need for reoperation in surgical patients, and bloodstream, respiratory and surgical site infections. Hospital mortality and ventilation free hours were outcomes looked at that were not pre-specified.
STATISTICS
Baseline mortality for patients at this unit for patients staying over 3 days had already been established at 23%. Sample size was calculated at 660 (2-sided alpha =0.05 and power of 80%). Baseline and outcome variables were compared with Mann- Whitney and Chi- squared tests. The effect of conservative oxygen therapy on the time to death was assessed using Kaplan-Meier Analysis and the log-rank test.
RESULTS
A total of 434 patients (median age, 64 years; 188 [43.3%] women) received conventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis. Daily time-weighted PaO2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median PaO2, 102mmHg [IQR, 88-116]) vs the conservative group (median PaO2, 87mmHg [IQR, 79-97]). Mortality was lower in the conservative oxygen therapy group. The conservative group had fewer episodes of shock, liver failure, and bacteraemia.
CONCLUSIONS/DISCUSSION
Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicentre trial is needed to evaluate the potential benefit of this approach.
STATED LIMITATIONS FROM STUDY
Enrolment to the study was terminated early after just 480 of the planned 660 patients were recruited (the primary outcome measure was comparatively rare compared to the modest sample size (25 out of 500). They performed an unplanned interim analysis. Baseline groups weren’t appropriately matched at the time of randomisation (age, illness severity and organ failures). They also decided to modify the intention to treat design of their primary analysis by choosing to exclude patients post randomisation.
DISCUSSION FROM JOURNAL CLUB MEETING
We discussed how their control group (standard practice on their unit) (FiO2 >0.4 allowing a PaO2 of up to 20kPa and SpO2 of 97-100%) doesn’t really reflect our standard practice in the UK, which is much more closely represented by the parameters set in their study group (lowest FiO2 possible to keep PaO2 between 9.33 and 13.33kPa and SpO2 94-98%) As well as discussing this study – along with its not insignificant limitations – we also widened the discussion to the appropriate use of oxygen in other environments and other clinical situations within the scope of our clinical practice. Including discussing Oxygen Therapy in Suspected Acute Myocardial Infarction Hofmann. NEJM. 2017. DOI: 10.1056/NEJMoa1706222 (this paper has been critically reviewed at http://www.thebottomline.org.uk/summaries/icm/deto2x-ami/) Giving enough oxygen, but no more, would appear to be prudent given the current evidence available. Clearly more work is required in this area.
Summary by Dr C Jeganathan. Journal Club 21 September 2017.
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