British Journal of Anaesthesia, ▪ (▪): 1e2 (2018)

CORRESPONDENCE

Hyperoxia is a modifiable anaesthetic risk factor that varies in the

practice of individual anaesthetists
A. K. Staehr-Rye1,2,*, T. Kurth3, F. T. Scheffenbichler1, L. S. Rasmussen4 and
M. Eikermann1,5
1
Department of Anaesthesia, Critical Care, Pain Medicine, Massachusetts General Hospital, 55 Fruit Street,
Boston, MA 02114, USA, 2Department of Anaesthesiology, Herlev and Gentofte Hospital, University of


Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark, 3Institute of Public Health, Charite
Universitatzmedizin Berlin, Germany, 4Department of Anaesthesia, Centre of Head and Orthopaedics,
Rigshospitalet, University of Copenhagen, Denmark and 5Klinik fur Anaesthesie und Intensivmedizin,
Universitaetsklinikum Essen, Essen, Germany
*Corresponding author. E-mail: akstaehr1@hotmail.com

We thank Acka1 and de Jonge and colleagues2 for their in-
terest in our study analysing the association between intra-
operative inspiratory oxygen fraction and risk of respiratory
complications.3 We agree with both that for cause and effect
relationships, more targeted research is needed. We do not
follow the arguments of Acka that the results are probably
caused by an epiphenomenon triggering high FIO2 rather than
an effect of high FIO2. Acka mentions that patients receiving
the highest FIO2 were different from the patients receiving
lower FIO2 in terms of several characteristics such as comor-
bidities, volatile anaesthetic dose, duration of surgery, pro-
cedural severity, etc. That is correct. We anticipated that a
high FIO2 would be used in the sickest patients, and in the
primary analysis we therefore adjusted for several covariates
including procedural risks, comorbidities, and anaesthesia-
related risk factors. In a subgroup analysis, we included
adjustment for minutes with hypotension and oxygenation
(ratio of PaO2 and FIO2) as additional potential confounding
factors, and this did not change the results. These analyses
show that the association between FIO2 and respiratory
complications is robust and not an epiphenomenon of a high
FIO2 requirement. When analysing blood gas samples in
approximately 6000 patients, we saw that >30% of the pa-
tients in the high FIO2 group had in fact a PaO2 above 40
kPadthis hyperoxia indicates that these patients did not need
this high FIO2.
Acka assumes that the concentration of FIO2 is mainly
driven by patient and procedural characteristics and not by
the preference of the anaesthetist. Additional data show that
this assumption does not hold true. To quantify the distribu-
tion of inter-provider variability in utilization of high FIO2, we
plotted the proportion of cases where the individual anaes-
thesia provider administered high FIO2 defined as median FIO2
>0.63 (upper quintile), a statistical approach we have reported
before.4e6 The data show that the median FIO2 varied widely
across practitioners within our cohort. A small number of
anaesthesia providers consistently used lower FIO2, whilst
another group regularly used higher FIO2. Similar distributions
were observed before and after propensity-matched adjust-
ment using covariates that can influence FIO2 (including pro-
cedure duration, procedural severity score, diagnosis of
chronic obstructive pulmonary disorder before surgery,
admission status, PEEP, tidal volume, surgical service, body
mass index, weight, and minimum alveolar concentration of
inhaled anaesthetics) suggesting that this variability is
driven more by individual preference than by patient or
procedure characteristics. That is concerning because
harmful effects of high FIO2 have been detected in a number
of studies.6e8
De Jonge and colleagues are concerned about suboptimal
confounder control. Our statistical analyses have been a priori
defined and all sensitivity analyses have been clearly indi-
cated. Our rationale for confounding control is strictly based
on clinical knowledge, and we have not used data mining for
any aspect of the analysis. We are not concerned about
collinearity; we exclude any collinearity related bias by

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1
 2 - Correspondence
analysing the condition index and the variance decomposition
matrix. Our methods follow modern causal inference princi-
ples, and we have conducted several sensitivity analyses to
evaluate the robustness of our findings. With the availability of
large datasets, powerful statistical analysis tools are currently
applied in many fields of medicine.9 We have taken a careful
look at our data and have conducted additional analyses as
suggested by the reviewers of our manuscript. For instance,
we modified the categorization of the outcome and our results
did not change. Overall, our results are very robust and we
have no reason to believe that confounding or misclassifica-
tion is driving our results.
We have carefully tried to isolate the impact of intra-
operative FIO2 on postoperative outcomes in the context of
many other factors that might also be related to that risk.10,11
The study was conducted on a large sample of diverse pa-
tients undergoing surgery and represents the typical patient
undergoing surgery at our institutions (i.e. there is no re-
striction of range of predictor classes). We observed a sub-
stantial variability in treatment, which is needed to make
meaningful comparisons in observational research. It is not
possible to explain why a high FIO2 was used and this natu-
rally leads to some speculation and interesting hypotheses
that should be tested in future research. Finally, the charac-
teristics of the groups being compared have a reasonable
amount of overlap. Thus, we are convinced that our study has
generated important new information for researchers and
clinicians alike.
In summary, our data demonstrate that hyperoxia is an
anaesthetic risk factor that varies in the practice of individual
anaesthetists. As this factor is potentially modifiable, we
encourage other groups to focus research on this factor. We
believe that our data provide evidence for avoiding the
routine use of high FIO2dwe should rather titrate the con-
centration of this drug that has desirable and unwarranted
effects.
Declaration of interest
None declared.
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