British Journal of Anaesthesia, 132 (3): 616e618 (2024)

CORRESPONDENCE

Intraoperative hypotension and postoperative outcomes. Comment

on Br J Anaesth 2023; 131: 823e831
Daniel Patricio1,* , Sebastian Boelefahr2 and Sean Coeckelenbergh3,4
1

Libre de Bruxelles,
Department of Anesthesia and Perioperative Medicine, St Pierre University Hospital, Universite
Brussels, Belgium, 2Department of Anesthesiology and Intensive Care, Klinikum Aschaffenburg-Alzenau, Frankfurt
University and Wuerzburg University, Aschaffenburg, Germany, 3Department of Anesthesiology and Intensive Care,
^ pitaux Universitaires Paris-Saclay, Universite
Ho
Paris-Saclay, Ho
^ pital Paul-Brousse, Assistance Publique Ho
^ pitaux de
Paris, Villejuif, France and 4Outcomes Research Consortium, Cleveland, OH, USA
*Corresponding author. E-mail: daniel.patricio@stpierre-bru.be

Keywords: cardiac output; hypotension; mean arterial pressure; patient outcome; personalised medicine

EditordWe read with great interest the meta-analysis by
D’Amico and colleagues1 regarding the potential difference
in impact between intraoperative ‘permissive’ and ‘targeted’
arterial blood pressure management on postoperative
morbidity and mortality.1 Their meta-analysis was challen-
ging to design, and we would like to elaborate on some
choices that the authors had to make to conduct such a study.
The meta-analysis reported that there was no difference in
mortality between permitting hypotension (i.e. mean arterial
pressure [MAP] 45e59 mm Hg) and targeting normotension
(i.e. MAP 60e100 mm Hg), and that permissive arterial pres-
sure management that allows hypotension was associated
with reduced incidence of arrhythmias and hospital length of
stay. The authors state that their work could be useful for
future guidelines. We find this concerning, as the message
could be interpreted as providing evidence for the safety of
perioperative hypotension. We would like to caution that such
a message is unwarranted given several important limitations
in this study.
Can we assimilate cardiopulmonary bypass with
human physiology?
There is heterogeneity in the patient populations included in
their surgical procedures and the definitions of the intra-
operative period. Six of the 10 trials include cardiac surgery
patients whereas the other four focus on noncardiac surgery.
The studies consist of predominantly older patients, except for
DOI of original article: 10.1016/j.bja.2023.08.026.
one that includes young trauma patients with active bleeding
(Table 1). Moreover, the cardiac surgery studies only compare
blood pressure management during cardiopulmonary bypass
(CPB). Pump flow rate, which can be an even more important
factor than perfusion pressure, is not considered. Is it valid to
make conclusions when mixing cardiac and noncardiac sur-
gical populations? CPB-induced vasoplegia requires the use of
various vasoactive agents at high doses, which are rarely used
outside of cardiac surgery. Induction of anaesthesia and
weaning from CPB represent two high-risk periods for hypo-
tension in cardiac surgery. Although a sensitivity analysis and
subanalyses were done for each population, they ultimately
provide a general conclusion based on these heterogeneous
studies.
Is it valid to consider targets and not actual
values?
Another important point is that their study compares arterial
pressure targets and not the actual values of arterial pressures
achieved. Yet compliance to arterial pressure targets is often
suboptimal, even during randomised controlled trials. For
example, compared with closed-loop vasopressor therapy,
patients undergoing abdominal surgery were only within their
MAP target 70% of the time, whereas those who benefited from
closed-loop vasopressor management had their MAP within
target for 94% of case time.2 Although closed-loop systems are
not available in most operating rooms, this study indicates
that compliance to protocols can be poor and that studies that
are analysed as intention-to-treat might show no difference
simply because the protocol was poorly applied. The

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616
Table 1 Key differences between the included studies in D’Amico and colleagues’1 meta-analysis. Data values are presented as mean (SD) for actual MAP and mean for bypass flow rate.
CPB, cardiopulmonary bypass; HES, hydroxyethyl starch; NA, not applicable; NS, not significant; SD, standard deviation.

Study Patient Patient population Age (yr) Target MAP Actual MAP Bypass flow rate MAP treatment Fluid strategy
number (mm Hg) (mm Hg) (L min¡1 m¡2

Azau and 300 Cardiac surgery 76 vs 76 50 vs 75 60 (6) vs 79 (6) 2.5 vs 2.6 Norepinephrine 12 ml kg
1 saline after
colleagues, 2014 with CPB P<0.0001 induction
Gold and 248 Cardiac surgery 66 vs 65 50 vs 80 59 (5) vs 82 (8) 1.9 vs 1.9 Phenylephrine and Not indicated
colleagues, 1995 with CPB P¼0.001 norepinephrine
Kandler and 90 Cardiac surgery 76 vs 77 < 60 vs > 60 47 (5) vs 61 (4) 2.6 vs 2.6 Norepinephrine or Not indicated
colleagues, 2019 with CPB P<0.001 nitroprusside
Siepe and 133 Cardiac surgery 65 vs 69 60 vs 80 65 (8) vs 84 (11) Not indicated Norepinephrine or Not indicated
colleagues, 2011 with CPB P<0.001 urapidil
Vedel and 197 Cardiac surgery 65 vs 70 40 vs 70 45 (5) vs 67 (5) 2.7 vs 2.7 Phenylephrine up to 2 Not indicated
colleagues, 2018 with CPB NS mg followed by
norepinephrine
Sirvinskas and 122 Cardiac surgery 74 vs 75 45 vs 70 54 (2) vs 75 (4.3) Not indicated Norepinephrine Volume corrected using
colleagues, 2012 with CPB NS HES 500e1000 ml;
furosemide if urine
output <0.5 ml kg
1 h
1
Wanner and 451 Major noncardiac 69 vs 70 75 vs 60 Mean (SD) MAP not NA Treatment of reversible Not indicated
colleagues, 2021 surgery in reported causes before
patients with administration of
cardiovascular ephedrine,
risk norepinephrine, or
both
Carrick and 168 Trauma patients 28 vs 32 50 vs 65 66 (12) vs 70 (14) NA Titration of Discretion of the
colleagues, 2016 NS phenylephrine, anaesthesiologist
nitroglycerine or
urapidil
Marcucci and 7490 Noncardiac surgery 70 vs 70 60e79 vs >80 Mean (SD) MAP not NA Discretion of the Not indicated
colleagues, 2023 with history of reported anaesthesiologist
hypertension
Hu and colleagues, 298 Non-cardiothoracic 73 vs 72 60e70 vs 90e100 Mean (SD) MAP not NA Phenylephrine 10 ml kg
1 h
1 of lactated
2021 surgery in older reported Ringer’s solution þ blood

Correspondence
patients loss correction in a 1:1
ratio using Gelofusine þ
hospital transfusion
guidelines

-
617
 618 - Correspondence
noncardiac surgery studies, which are dominated by the
Perioperative Ischemic Evaluation-3 (POISE-3) study,3 might be
particularly impacted by poor protocol compliance as they
either show no difference in achieved arterial pressure targets
or do not report data on average intraoperative arterial pres-
sure values (Table 1). D’Amico and colleagues1 do include a
sensitivity analysis, which could help solve this problem by
removing studies where patients had blood pressure values
that did not respect the 60 mm Hg limit, but it is unclear which
studies were included in this sensitivity analysis. If it included
only studies that have MAP values above and below the 60 mm
Hg limit (Gold, Kandler, Sirvinskas and Vedel), only cardiac
populations were included in the sensitivity analysis, which
again, limits this conclusion to this population and exclusively
during CPB.
Can heterogeneous therapies offer a clear
message?
The interventions for arterial pressure management in this
meta-analysis, just like the study populations, are extremely
heterogeneous (Table 1). Arterial pressure is directly related to
systemic vascular resistance and cardiac output, but modi-
fying each component has different effects. Increasing sys-
temic vascular resistance, for example with norepinephrine,
can have negative consequences such as increased cardiac (or
CPB pump flow rate) afterload. However, optimising cardiac
output by increasing preload can increase MAP without the
potentially negative impact of excessive systemic vascular
resistance. Overzealous and inadequate fluid therapy each
have their own consequences.4 Focusing on MAP targets
without considering cardiac output clouds any answer ob-
tained. Future meta-analyses should include homogeneous
studies that apply the same intervention in the same popu-
lation.
Is the Perioperative Ischemic Evaluation-3 trial the
right trial for this meta-analysis?
Other concerns relate directly to the POISE-3 trial.3 In this trial,
the hypertension-avoidance group (i.e. the group with the
lowest arterial pressure target) had an MAP target between 60
and 79 mm Hg, whereas the hypotension-avoidance group
targeted an MAP above 80 mm Hg. As D’Amico and colleagues1
define ‘permissive management’ as a hypotensive MAP
between 45 and 59 mm Hg, both POISE-3 groups actually fit this
definition of ‘targeted management’. This situation is also
found in the trial of Hu and colleagues5 (Table 1). Furthermore,
the study intervention of the POISE-3 trial focuses on the
entire perioperative period, which includes much more than
the intraoperative period. Including this large multifaceted
study that focuses on perioperative arterial pressure man-
agement, and not solely on intraoperative arterial pressure,
and the groups of which do not even fit the predefined blood
pressure targets, is problematic.
In their conclusion, D’Amico and colleagues1 suggest that
their meta-analysis could help establish future guidelines. We
wonder what they would hope to convey with this study. In
our perspective, this analysis does not offer the required level
of evidence to allow a return of the concept of permissive
hypotension into contemporary perioperative medicine.
Acknowledgements
The authors would like to thank Edgard Engelman (EW Data
Analysis, Brussels, Belgium) for his statistical advice.
References
1. D’Amico F, Fominskiy EV, Turi S, et al. Intraoperative hy-
potension and postoperative outcomes: a meta-analysis of
randomised trials. Br J Anaesth 2023; 131: 823e31
2. Joosten A, Chirnoaga D, Van der Linden P, et al. Automated
closed-loop versus manually controlled norepinephrine
infusion in patients undergoing intermediate- to high-risk
abdominal surgery: a randomised controlled trial. Br J
Anaesth 2021; 126: 210e8
3. Marcucci M, Painter TW, Conen D, et al. Hypotension-avoid-
ance versus hypertension-avoidance strategies in noncardiac
surgery: an international randomized controlled trial. Ann
Intern Med 2023; 176: 605e14
4. Bellamy MC. Wet, dry or something else? Br J Anaesth 2006;
97: 755e7
5. Hu A-M, Qiu Y, Zhang P, et al. Higher versus lower mean
arterial pressure target management in older patients
having non-cardiothoracic surgery: a prospective random-
ized controlled trial. J Clin Anesth 2021; 69, 110150
doi: 10.1016/j.bja.2023.11.048