Authors Adam Glass Ben Shelley Philip McCall
License CC-BY-4.0
Comment on Propofol and survival: an updated meta-analysis of
randomized clinical trials
Glass, A., McCall, P., & Shelley, B. (2023). Comment on Propofol and survival: an updated meta-analysis of
randomized clinical trials. Critical Care, 27(1), [281]. https://doi.org/10.1186/s13054-023-04550-2
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Download date:13. Oct. 2023
Glass et al. Critical Care (2023) 27:281 Critical Care
https://doi.org/10.1186/s13054-023-04550-2
COMMENT Open Access
Comment on Propofol and survival:
an updated meta‑analysis of randomized clinical
trials
Adam Glass1*, Philip McCall2 and Ben Shelley2
Dear Editor, On closer analysis of the Likhvantsev et al. study, the
We wish to add further comment to the recent publica- mortality rate in both groups is very high and a signifi-
tion by Kotani et al. [1]. Firstly, we would like to thank the cant outlier in the meta-analysis. The study included 900
authors for undertaking a thorough and detailed meta- patients undergoing elective coronary artery bypass
analysis on a clinically important topic suggesting propo- grafting (CABG) with “patients who had a recent or ongo-
fol is associated with increased mortality (RR 1.10, 95% ing myocardial infarction” excluded. The study authors
CI 1.01–1.20, p = 0.03). We would, however, like to add to comment that their “1-year mortality was extremely high
the comments of Benavides-Zora et al.[2] and Hansel [3] in this cohort of patients” and their “hypotheses to explain
regarding the meta-analysis. these findings was that patients’ adherence to cardiologic
medication was extremely poor after hospital discharge”.
Mortality outlier study In comparison, the crude one-year mortality for “all car-
As already highlighted by Benavides-Zora et al. [2] and diac surgery” in the UK is 3.78% [5]. This study is one of
Hansel [3], there is an error in the data extraction regard- only two out of 252 studies included in the meta-analysis
ing the mortality rate from the manuscript by Likhvant- demonstrating increased mortality in a propofol group.
sev et al. [4]. The corrected one-year mortality rate in With such a markedly high mortality rate, this study is a
this study is 52/292 (17.8%) in the sevoflurane group and clear outlier and has the potential to influence the meta-
81/326 (24.8%) in the propofol group, rather than 52/450 analysis results, in addition to the data extraction error.
(11.6%) and 81/450 (18%), respectively, as detailed in the
Kotani et al. meta-analysis. As detailed by Hansel, this Study not included in the analysis
artificially inflates the estimated risk ratio of the study in Further investigation of the 900-patient study by Likh-
the meta-analysis. vantsev et al. [4] shows that two authors (Likhvantsev and
Landoni) went on to perform a 5400-patient randomized
control trial comparing maintenance of anaesthesia in
patients undergoing elective CABG with volatile anaes-
This comment refers to the article available online at https://doi.org/10.1186/ thetic (2709 patients) to total intravenous anaesthetic
s13054-023-04431-8. (TIVA, 2691 patients) [6]. This later paper demonstrated
*Correspondence: no significant mortality difference at 1 year (relative risk,
Adam Glass
0.94; 95% [CI] 0.69 to 1.29; p = 0.71). Mortality rates in
aglass01@doctors.org.uk
1
Wellcome‑Wolfson Institute for Experimental Medicine, Queen’s this study were 2.8% in the volatile group and 3.0% in the
University Belfast, Belfast, UK TIVA group, markedly different to the 17.8% and 24.8%
2
Academic Unit of Anaesthesia, Pain and Critical Care, University
reported in the previous 900 patient study of Likhvantsev
of Glasgow, Glasgow, UK
et al. and more in keeping with contemporary reports [4].
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Glass et al. Critical Care (2023) 27:281 Page 2 of 2
We must highlight that whilst the 900-patient study Availability of data and materials
Not applicable.
of Likhvantsev et al. [4] is included in the meta-analysis,
the 5,400-patient study of Landoni et al. [6] is not. This
may be due to the concise literature search strategy used Declarations
in the meta-analysis in which the Landoni et al. paper Ethical approval and consent to participates
does not appear as the intervention was documented Not applicable.
as TIVA and not propofol. In the TIVA group, however, Competing interests
anaesthetic was maintained by a propofol infusion in BS is co-investigator and co-grant holder of VITAL—Volatile vs Total intrave-
2297/2665 (86.9%) patients allowing comparison against nous Anaesthesia for major non-cardiac surgery (ISRCTN62903453).AG and PM
declare that they have no competing interests.
2709 patients with volatile anaesthetic maintenance. It
is therefore surprising that this study was not included
in the meta-analysis given; the detailed data collection Received: 17 June 2023 Accepted: 25 June 2023
methods described, it is mentioned in the discussion sec-
tion and, most surprisingly, that the first author (Land-
oni) is a co-author in this meta-analysis [1].
References
1. Kotani Y, Pruna A, Turi S, Borghi G, Lee TC, Zangrillo A, Landoni G, Pasin L.
Spin Propofol and survival: an updated meta-analysis of randomized clinical
Again, we wish to add to the comment of Benavides- trials. Crit Care. 2023;27(1):139.
Zora et al. [2] in regard to the “spin” of the presentation 2. Benavides-Zora D, Arias-Botero JH. Comment to: Propofol and survival:
an updated meta-analysis of randomized clinical trials. Crit Care.
of results. In Kotani et al.’s discussion of the difference 2023;27(1):198.
between the meta-analysis and the 5400 patient Land- 3. Hansel J. Propofol versus the world: the whole is not always greater than
oni et al. study, they comment, “We hypothesize that the the sum of its parts. Crit Care. 2023;27(1):208.
4. Likhvantsev VV, Landoni G, Levikov DI, Grebenchikov OA, Skripkin YV,
use of propofol in the majority of patients who were ran- Cherpakov RA. Sevoflurane versus total intravenous anesthesia for
domized to the volatile group [crossover between treat- isolated coronary artery bypass surgery with cardiopulmonary bypass: a
ment groups] blunted the detrimental effect of propofol on randomized trial. J Cardiothorac Vasc Anesth. 2016;30(5):1221–7.
5. Research NIfCO. National Adult Cardiac Surgery Audit. 2019.
survival in this trial”. This contradicts a sub-group analy- 6. Landoni G, Lomivorotov VV, Nigro Neto C, Monaco F, Pasyuga VV, Bradic
sis in their paper that showed no difference in mortality N, Lembo R, Gazivoda G, Likhvantsev VV, Lei C, et al. Volatile anesthetics
between groups in studies where propofol was not used versus total intravenous anesthesia for cardiac surgery. N Engl J Med.
2019;380(13):1214–25.
in the comparator arm (RR 1.03, 95% CI 0.94–1.14, p =
0.50).
Publisher’s Note
As Hansel commented, Kotani et al. “stop short of Springer Nature remains neutral with regard to jurisdictional claims in pub-
addressing the elephant in the room” of the impact of the lished maps and institutional affiliations.
900 patient Likhvantsev et al. on the overall meta-analy-
sis results. In addition, we fell that they fail to address the
white elephant in the room of the 5400-patient study of
Landoni et al. which mysteriously does not feature in the
meta-analysis at all.
Summary
In summary, we believe that the readers of Critical Care
should be cautious in their interpretation of the results of
this important meta-analysis and would no doubt appre-
ciate re-analysis without the significantly outlier in mor- Ready to submit your research ? Choose BMC and benefit from:
tality of the Likhvantsev et al. study and including the
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