CONCLUSIONPostoperative spirometry is not affected by PEEP and RM during intraoperative ventilation for open abdominal surgery in nonobese patients at a high risk of PPCs, but rather is
Trang 1ORIGINAL ARTICLE
Ventilation with high versus low peep levels during
general anaesthesia for open abdominal surgery does not affect postoperative spirometry
A randomised clinical trial
Tanja A Treschan, Maximilian Schaefer, Johann Kemper, Bea Bastin, Peter Kienbaum,
Benedikt Pannen, Sabrine N Hemmes, Marcelo G de Abreu, Paolo Pelosi and Marcus J Schultz, for the PROVEMNetwork Investigators
BACKGROUNDInvasive mechanical ventilation during
gen-eral anaesthesia for surgery typically causes atelectasis and
impairs postoperative lung function
OBJECTIVE We investigated the effect of intraoperative
ventilation with high positive end-expiratory pressure (PEEP)
and recruitment manoeuvres (RMs) on postoperative
spiro-metry
DESIGNThis was a preplanned, single-centre substudy of
an international multicentre randomised controlled trial, the
PROVHILO trial
SETTING University hospital from November 2011 to
January 2013
PATIENTSNonobese patients scheduled for major
abdomi-nal surgery at a high risk of postoperative pulmonary
com-plications (PPCs)
INTERVENTION Intraoperative low tidal volume ventilation
with PEEP levels of 12 cmH2O and RM (the high PEEP
group) or with PEEP levels of 2 cmH2O or less without RM
(the low PEEP group)
MAIN OUTCOME MEASURES Time-weighted averages
(TWAs) of the forced expiratory volume in 1 s (FEV1)
and the forced vital capacity (FVC) up to postoperative day five
RESULTSThirty-one patients were allocated to the high PEEP group and 32 to the low PEEP group No post-operative spirometry test results were available for 6 patients In both groups, TWA of FEV1 and FVC until postoperative day five were lower than preoperative values Postoperative spirometry test results were not different between the high and low PEEP group; Data are median [interquartile range], TWA FVC 1.8 [1.6 to 2.4] versus 1.7 [1.2 to 2.4] l (P¼ NS) and TWA FEV1 1.2 [1.1
to 2.5] versus 1.2 [0.9 to 1.9] l (P¼ NS) Patients who developed PPCs had lower FEV1 and FVC on postopera-tive day five; 1.1 [0.9 to 1.6] versus 1.6 [1.4 to 1.9] l (P¼ 0.001) and 1.6 [1.2 to 2.6] versus 2.3 [1.7 to 2.6] l (P¼ 0.036), respectively
CONCLUSIONPostoperative spirometry is not affected by PEEP and RM during intraoperative ventilation for open abdominal surgery in nonobese patients at a high risk of PPCs, but rather is associated with the development of PPCs
TRIAL REGISTRATIONClinicalTrials.gov NCT01441791 Published online 16 March 2017
From the Department of Anesthesiology, Du¨sseldorf University Hospital, Medical Faculty of Heinrich-Heine University, Du¨sseldorf, Germany (TAT, MS, JK, BB, PK, BP), The Department of Anesthesiology, The Academic Medical Center, Amsterdam, The Netherlands (SNH), The Department of Anesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Dresden, Germany (MGA), The Department of Surgical Sciences and Integrated Diagnostics, IRCCS San Martino IST, University of Genoa, Genoa, Italy (PP) and the Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), and the Department of Intensive Care, The Academic Medical Center, Amsterdam, The Netherlands (MJS) for the PROVE Network Investigators
Correspondence to Tanja A Treschan, MD, CLiPS – Clinical Trials – Patient–centred Studies, Department of Anesthesiology, Du¨sseldorf University Hospital, Moorenstrasse 5, 40225 Du¨sseldorf, Germany
E-mail: tanja.treschan@med.uni-duesseldorf.de
*PROVE network = the PROtective VEntilation Network (www.provenet.eu).
Trang 2Copyright © European Society of Anaesthesiology Unauthorized reproduction of this article is prohibited.
Introduction
Invasive mechanical ventilation during general
anaesthe-sia for surgery typically results in atelectasis as well as
reduced lung volume due to a cephalad shift of the
diaphragm and a decreased muscle tone after induction
of anesthesia.1 In particular, in patients undergoing
abdominal surgery, the risk of atelectasis increases the
closer the incision is to the diaphragm.2,3 Although
intraoperative atelectasis impairs intraoperative
oxygen-ation,4more importantly, atelectasis often continues into
the postoperative period, changing the mechanics of
regional lung aeration and impairing the postoperative
recovery of pulmonary function.5Accordingly, atelectasis
could predispose to the development of postoperative
pulmonary complications (PPCs), including hypoxemia
and pneumonia,2with an increased risk of postoperative
morbidity and mortality.6
Postoperative regeneration of pulmonary function could
depend, at least in part, on the intraoperative ventilation
strategy Indeed, a significantly greater reduction in
peri-operative and postperi-operative lung volumes is seen with
general anaesthesia as compared with spinal anesthesia,7
and with controlled rather than with assisted modes of
ventilation.8 Furthermore, so-called ‘protective
intrao-perative ventilation’ that uses a combination of low tidal
volumes and positive end-expiratory pressure (PEEP)
and recruitment manoeuvres (RMs) could prevent the
development of PPCs.9 – 12 However, the protective
role of PEEP in preventing PPCs was challenged
recently.13,14
Despite protective intraoperative ventilation, PPCs occur
in up to 39% of patients.9,10,13 Risk scores, using
pre-operative characteristics, for the development of PPCs
and early recognition of patients who develop PPCs could
contribute to an improved patient outcome.15,16As with
preoperative spirometry to predict PPCs,17,18
postopera-tive spirometry could be a useful tool to monitor
post-operative recovery of lung function.7,9Therefore, in this
substudy of the international multicentre, randomised
controlled ‘PROtective Ventilation using HIgh versus
LOw PEEP’ (PROVHILO) trial,13,19 in which
intrao-perative ventilation with a high level of PEEP
(12 cmH2O) and RMs was compared with a low level
of PEEP (2 cmH2O) without RMs during general
anaesthesia for planned open abdominal surgery in
non-obese patients at risk of PPCs, we tested the hypothesis
that postoperative spirometry results would be modified
by the intraoperative level of PEEP In addition, we
compared postoperative spirometry test results in
patients who did and who did not develop PPCs
Materials and methods
Ethical approval and informed consent
This was a preplanned substudy of the recently
pub-lished PROVHILO trial.13,19This single-centre substudy
was performed at the Du¨sseldorf University Hospital,
Du¨sseldorf, Germany Patients at our institution were included from November 2011 until January 2013 The original trial was approved by the Institutional Review Boards of the Academic Medical Center (AMC), Amster-dam, The Netherlands, and on 5 July 2011 by the Medizinischen Fakulta¨t der Heinrich–Heine Universita¨t Du¨sseldorf, Du¨sseldorf, Germany (Study number 3664, chairperson Prof Kro¨ncke), and registered at Clinical-Trials.gov NCT01441791 The latter additionally approved this substudy as an amendment Participants had to give written informed consent prior to participa-tion for any procedure related to the original trial and this substudy
Design of the original trial
In the PROVHILO trial, nonobese patients with an intermediate or high risk of PPCs according to the Assess Respiratory Risk in Surgical Patients in Catalonia (ARIS-CAT) score15,16 and who were scheduled for open abdominal surgery under general anaesthesia were ran-domly assigned to intraoperative ventilation with high levels of PEEP and RMs (12 cmH2O; the ‘high PEEP group’) or ventilation with lower levels of PEEP without RMs (<2 cmH2O; the ‘low PEEP group’) In the high PEEP group, patients received RMs at the following times: after intubation at the start of ventilation; before tracheal extubation; after each accidental disconnection from the ventilator RMs were performed as follows: peak inspiratory pressure limit is set at 45 cmH2O; tidal volume
is set at 8 ml kg1predicted body weight (PBW), respir-atory rate at 6 to 8 breaths min1 (or lowest respiratory rate that the anaesthesia ventilator allows), and PEEP is set at 12 cmH2O; inspiratory to expiratory (I:E) ratio is set
at 1 : 2; tidal volumes are increased in steps of 4 ml kg1 PBW until a plateau pressure of 30 to 35 cmH2O is attained; three breaths are administered with a plateau pressure of 30 to 35 cmH2O; peak inspiratory pressure limit, respiratory rate, I:E ratio, and tidal volume are reset
to the settings preceding each recruitment manoeuver
FiO2remained unchanged during RMs
Patients were excluded for the following reasons: a planned laparoscopic abdominal procedure, pregnancy,
a BMI more than 40 kg m2, severe cardiac or pulmonary
or other comorbidities, and if they were participating in other interventional studies This substudy had no additional exclusion criteria
In both arms of the trial, patients were ventilated with a tidal volume of 8 ml kg1PBW, FiO2was 0.4 or higher to maintain SpO2 at least 92%, the respiratory rate was adjusted to maintain end-tidal CO2 between 4.67 and 6.0 kPa; and the I:E ratio was 1 : 2 Patients, and post-operative investigators who assessed whether or not a patient developed one or more PPCs, were blind to the intraoperative ventilation strategy As recommended by the protocol and according to institutional routine, in this
Eur J Anaesthesiol 2017; 34:534–543
Trang 3substudy, extubation was undertaken without suctioning
of the trachea Patients received additional oxygen as
deemed necessary by the attending anaesthesiologist and
were typically positioned supine with heads elevated to a
maximum of 308 when extubated
The primary endpoint of the PROVHILO trial was a
composite of PPCs within the first five postoperative
days These PPCs consisted of an unexpected need for
supplementary oxygen, severe hypoxemia,
bronchos-pasm, suspected pulmonary infection, a pulmonary
infil-trate, aspiration pneumonitis, development of ARDS,
atelectasis, pleural effusion, pulmonary oedema caused
by cardiac failure or pneumothorax The definition of
every complication is presented in the online
Supple-ment Table 1, http://links.lww.com/EJA/A115
Design of the present substudy
Preoperative and postoperative spirometry on
postopera-tive days 1, 3 and 5 was performed after detailed
instruc-tions to participating patients Patients were requested to
rate their pain, while at rest in the supine position with
308 upper body elevation, on a numeric rating scale of 0 to
10 (from 0, no pain, to 10, maximum pain) Spirometric
testing was only performed if pain scores at rest were 3 or
less; otherwise, analgesia was optimised before
spiro-metric measurements According to institutional
proto-col, a continuous infusion of ropivacaine 0.2% through a
thoracic epidural catheter was used for analgesia
Additional bolus doses and rate adjustments were made
by the pain service according to the patients’ needs For
patients without epidural catheters, piritramid was
admi-nistered intravenously as bolus doses or by
patient-con-trolled analgesia pumps Spirometry was performed in
accordance with the American Thoracic Society’s
stan-dards20using a single pneumotachograph (SpiroPro,
Jae-ger, Wu¨rzburg, Germany) with the patient in the supine
position with 308 upper body elevation Each
measure-ment was performed three times at each timepoint and
the best value was selected for inclusion in the analysis
The postoperative investigators who performed the
spirometry were blind as to the intraoperative ventilation
strategy
The primary endpoints of this substudy were the
post-operative time-weighted averages (TWAs) of both the
forced expiratory volume in 1 s (FEV1) and the forced
vital capacity (FVC), up to postoperative day 5 TWAs
were calculated for each patient as the area under the
curve for FVC and FEV1 measurements divided by the
follow-up duration in hours
Power calculation
We intended to include all the participants within our
centre from the original trial into this substudy
Con-sequently, the number of patients who could be included
was restricted to the recruitment period of the original
trial An a priori sample-size estimate indicated that a
minimum of 57 patients per group would provide an 80% chance of detecting a 20% difference in the TWAs of FVC and FEV1 from a presumed postoperative TWA
of FVC of 1.6 0.5 l with a corresponding TWA of FEV1
of 1.2 0.4 l, with an alpha error level of 2.5% for com-bined outcomes On the same basis, a minimum of 25 patients per group would provide an 80% chance of detecting a 30% difference
Analysis plan
We first compared results of postoperative spirometric measurements between patients ventilated with high PEEP with RM to those ventilated with low PEEP without RM Then, postoperative spirometry results were compared between patients who developed PPCs and those who did not
In two posthoc analyses, we evaluated whether intrao-perative pulmonary compliance or the site of the surgical incision in combination with high PEEP and RM or low PEEP without RM influenced outcomes in our substudy Therefore, we first compared spirometric results in patients with an intraoperative pulmonary compliance more than 50 ml cm1 H2O (high compliance) to those with a compliance 50 ml cm1H2O or less (low compli-ance) The cut-off was based on the median intraopera-tive pulmonary compliance in all substudy patients We then further subdivided the spirometric results of patients with high or low compliance by ventilation strategy, that is low PEEP without RM versus high PEEP with RM Secondly, we compared postoperative spiro-metry results of patients who had the incision closer to the diaphragm (i.e upper abdominal surgery) with those with the incision at a distance from the diaphragm (i.e lower abdominal surgery) and also further subdivided these spirometric results by ventilation strategy, that is low PEEP without RM or high PEEP with RM
Statistical analysis
Data are presented as absolute values, means with stan-dard deviation or medians with interquartile range, as appropriate Analyses were performed on an intention-to-treat basis We used the Kolmogorow –Smirnow test to test the distribution of data and the two-tailed Fishers’ exact test, Student’s t-test or Mann–Whitney U tests
as appropriate for comparison between groups For analysis within groups, the Wilcoxon rank-sum test was performed
The IBM SPSS Statistics Versions 21 and 22 (IBM Deutschland GmbH, Ehningen, Germany) were used
To take account of two primary endpoints, FEV1 and FVC, a Bonferroni-corrected P value less than 0.025 was considered to be statistically significant for the two primary outcomes TWA of FEV1 and FVC For second-ary outcomes, which were exploratory, P value less than 0.05 was considered to be statistically significant
Trang 4Copyright © European Society of Anaesthesiology Unauthorized reproduction of this article is prohibited.
Results
Substudy patients and occurrence of postoperative
pulmonary complication
All 63 patients enrolled in the PROVHILO trial in
Du¨sseldorf participated in this substudy; 31 and 32
patients were randomised to the high and the low PEEP
group, respectively (Fig 1) One patient in the high
PEEP group received ventilation with a PEEP of
5 cmH2O for 3 out of 4 hours by mistake; PEEP of
12 cmH2O was thus only applied for the last hour
Accord-ing to the intention-to-treat analysis, this patient
remained in the high PEEP group Six patients were
excluded from the analysis because postoperative
spiro-metry results could not be obtained, leaving 27 in the
high PEEP group and 30 in the low PEEP group for the
final analysis (Fig 1)
The occurrence of PPC in the substudy was high (24/
57¼ 42%) but comparable to that found in the original
trial (346/880¼ 39%, Chi-squared P ¼ 0.677) A
compari-son between characteristics of patients enrolled in the
original trial and patients in the substudy is provided in
the online supplement (Supplement Table S2, http://
links.lww.com/EJA/A115)
Among patients participating in the substudy, baseline characteristics, including preoperative spirometry results, did not differ between the two randomisation groups ventilated with high or low PEEP (Table 1) The level
of PEEP and peak inspiratory pressure levels were different between the randomisation groups, as was the pulmonary compliance during intraoperative ventilation (Supplement Table S3, http://links.lww.com/EJA/A115)
PPC did not differ between the randomisation groups (Supplement Table S4, http://links.lww.com/EJA/A115)
Postoperatively, the ratio between FEV1/FVC remained within the normal range in the majority of patients [TWA FEV1/FVC¼ 76 (68 to 80)%]
Association between intraoperative ventilation strategy and spirometry results
Spirometry results were unaffected by the intraoperative ventilation strategy: TWA of FVC and FEV1 were not different between the high and low PEEP group [TWA
Fig 1
63 patients underwent randomisation
31 patients were assigned to
high PEEP with RM
1 patient received treatment
other than that allocated
32 patients were assigned to low PEEP without RM
0 patients received treatment other than that allocated
Missing postoperative lung function tests n = 4
27 patients available for
the primary analysis
30 patients available for the primary analysis
Missing postoperative lung function tests n = 2
63 patients underwent preoperative lung function tests
CONSORT diagram of patients Reasons for missing postoperative spirometry were open abdominal wounds (n¼ 2), continued mechanical
ventilation (n ¼ 1) and uncontrolled pain (n ¼ 1) in patients ventilated with high PEEP and continued mechanical ventilation (n ¼ 2) in the low PEEP
group.
Eur J Anaesthesiol 2017; 34:534–543
Trang 5Table 1 Baseline characteristics of patients
Male sex – n/N 30 (53%) 13 (48%) 17 (56%) 0.600 Age (years), median [IQR] 57 [44 to 69] 55 [44 to 68] 59 [44 to 69] 0.876 BMI (kg m2), mean (SD) 27 5 26 6 25 5 0.510 Body weight (kg), mean (SD) 77 17 77 16 75 18 0.850 ARISCAT score – median [IQR] 41 [38 to 50] 41 [38 to 51] 41 [34 to 50] 0.462 Intermediate (26 to 44) – % (n/N) 39/57 (68%) 19/27 (70%) 20/30 (67%)
High (>44) – % (n/N) 18/57 (32%) 8/27 (30%) 10/30 (33%)
Smoking status – n/N
Never 26/57 (46%) 13 (48%) 13 (43%) 0.935 Former 11/57 (19%) 5 (19%) 6 (20%)
Current 20/57 (35%) 9 (33%) 11 (37%)
Alcohol status (past 2 weeks) – % (n/N)
None 39/57 (69%) 17 (63%) 22 (73%) 0.492
0 to 2 units of alcohol 15/57 (26%) 9 (33%) 6 (20%)
>2 units of alcohol 3/57 (5%) 1 (4%) 2 (7%)
ASA physical status classification system – % (n/N)
1 10/56 (18%) 5/27 (19%) 5/29 (17%) 0.768
2 26/56 (46%) 12/27 (44%) 14/29 (48%)
3 19/56 (34%) 10/27 (37%) 9/29 (31%)
5
New York Heart Association Classification – % (n/N)
I 46/50 (92%) 21/23 (91%) 25/27 (93%) 0.632
II 4/50 (8%) 2/23 (9%) 2/27 (7%)
Functional status – % (n/N)
Nondependent 54/57 (95%) 25/27 (93%) 29/30 (97%) 0.599 Partially dependent 3/57 (5%9 2/27 (7%) 1/30 (3%)
Totally dependent 0/57 0/28 0/30
History of active cancer – n/N 31/52 (60%) 12/23 (52%) 19/29 (56%) 0.400 History of chronic renal failure – % (n/N) 2/57 (4%) 1/27 (4%) 1/30 (3%) 1.0
COPD – % (n/N) 1/57 (2%) 0/27 1/30 (3%) 1.0
With inhalation therapy 1/56 (2%) 0/27 1/29 (3%) 1.0
With systemic steroids 1/56 (2%) 1/27 (4%) 0/29 0.482 Diabetes mellitus – % (n/N) 6/57 (11%) 4/27 (15%) 2/30 (7%) 0.408 With oral medication 1/4 (25%) 1/3 (33%) 0/1
With insulin therapy 3/4 (75%) 2/3 (67%) 1/1 (100%)
Use of systemic steroids – % (n/N) 5/56 (9%) 3/27 (11%) 2/29 (7%) 0.664 Use of statins – % (n/N) 3/57 (5%) 2/27 (7%) 1/30 (3%) 0.599 Preoperative transfusion – % (n/N) 0/57 0/27 0/30 1.0
Preoperative tests
Haemoglobin (g l1) 129 (22) 128 (23) 131 (21) 0.620 Creatinine (mmol/l) median [IQR] 61 [46 to 61] 61 [46 to 61] 51 [46 to 61] 0.952 Urea, mmol/l, median [IQR] 4.3 [2.6 to 5.6] 4.3 [3.6 to 5.7] 4.5 [3.8 to 5.2] 0.527 White blood cells ( 10 9 l 1 ) median [IQR] 7.2 [5.6 to 9.6] 7.6 [6.2 to 10.2] 7.0 [5.5 to 8.5] 0.275 Preoperative SpO 2 – %, median [IQR] 97 [96 to 98.5] 97 [96 to 99] 96 [96 to 98] 0.145 Abnormalities on chest radiograph – % (n/N) 1/36 (3%) 1/17 (5%) 0/19 0.563 Peri-operative variables
Duration of surgery a (min), mean (SD) 309 (161) 326 (132) 295 (184) 0.473 Surgical procedure – % (n/N)
Antibiotic prophylaxis – % (n/N) 57/57 (100%) 27/27 (100%) 30/30 (100%) 1.0
Type of anaesthesia – % (n/N)
Total intravenous 3/57 1/27 2/30 1.0
Mixed (volatile and intravenous) 54/57 26/27 28/30
Epidural – % (n/N) 42/57 19/27 23/30
thoracic 42/42 (100%) 19/19 (100%) 23/23 (100%) 0.764
Eur J Anaesthesiol 2017; 34:534–543
Trang 6Copyright © European Society of Anaesthesiology Unauthorized reproduction of this article is prohibited.
FVC¼ 1.8 (1.6 to 2.4) versus 1.7 (1.2 – 2.4) l (P ¼ 0.792)
and TWA FEV1¼ 1.2 (1.1 to 2.5) versus 1.2 (0.9 to 1.9)] l
(P¼ 0.497) There were also no differences in FVC or
FEV1 between randomisation groups on individual
post-operative days (Fig 2)
Association between the occurrence of postoperative
pulmonary complication and spirometry results
In patients who developed PPCs, FEV1 and FVC values
on postoperative day 5 were about 30% lower than
patients who did not develop PPCs (Fig 3) Compared
with patients who did not develop PPCs, patients who
developed PPCs had longer surgery (supplement Table
5, http://links.lww.com/EJA/A115), received higher tidal
volumes, higher minute ventilation volumes and more
intravenous fluids during surgery (supplement Table 6,
http://links.lww.com/EJA/A115)
Posthoc analyses
Association between intraoperative pulmonary compliance
and spirometry results
On the first postoperative day, spirometry results were
about 40% higher in patients with high pulmonary
com-pliance, but unaffected by PEEP and RM (Fig 4a, b)
Patients with high intraoperative pulmonary compliance
were not different from those with a low compliance
(supplement Table 7, http://links.lww.com/EJA/A115), but more frequently received intraoperative ventilation with high PEEP (supplement Table 8, http://links.lww
com/EJA/A115), but incidence of PPCs was not different (supplement Table 9, http://links.lww.com/EJA/A115)
Association between location of incision and spirometry results
Patients who had upper abdominal surgery were current smokers more frequently and had a longer duration of surgery than patients who had lower abdominal surgery (supplement Table 10, http://links.lww.com/EJA/A115) and received more fluids and transfusions (supplement Table 11, http://links.lww.com/EJA/A115) The inci-dence of PPCs, however, was not different (supplement Table 12, http://links.lww.com/EJA/A115) Postoperative spirometry showed no differences between the high and low PEEP groups, neither in patients who had upper abdominal surgery nor in patients who had lower abdomi-nal surgery (Fig 4c, d)
Discussion
The results of this substudy of a larger randomised controlled trial comparing high with low PEEP during intraoperative ventilation in nonobese patients at risk of PPCs and scheduled for open abdominal surgery can be
Table 1 (continued )
Preoperative spirometry- median [IQR]
FVC (l) 3.7 (2.9 to 4.5) 3.6 (2.7 to 4.6) 3.7 (3.1 to 4.5) 0.587
FEV1 (l) 2.7 (2.1 to 3.3) 2.6 (2.0 to 3.0) 2.8 (2.3 to 3.6) 0.274
FEV1/FVC (%) 73 (69 to 80) 73 (68 to 80) 77 (72 to 79) 0.243
Data are presented as means (SD) Median [IQR] or n/N and proportion %; Calculated as weight (kg)/ height (m) 2 ¼ kg/m 2 ASA, American Society of Anesthesiology;
COPD, chronic obstructive pulmonary disease; FVC, forced vital capacity, FEV1, forced expiratory volume in 1 s; Inhalation therapy for COPD, inhaled bronchodilators
and/or steroids’ SpO2, oxyhaemoglobin saturation measured by pulse oximeter; kg, kilogram; m, meters; n, number of patients; N, total patients a Duration of surgery is the
time between skin incision and closure of the incision.
Fig 2
6.0 litres
litres
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
6.0
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
Results of spirometry for patients ventilated with high or low PEEP (a) Forced vital capacity (FVC), and (b) Forced expiratory volume in 1 s (FEV1) in
patients ventilated with high (black bars) and low PEEP (grey bars) during intraoperative ventilation On postoperative day 1, spirometric results were
significantly lower than preoperative values (P < 0.001 in both groups) Compared with day 3, spirometric values increased significantly by day 5
(P ¼ 0.001 for FVC and P ¼ 0.005 for FEV in both groups) Differences between PEEP groups are nonsignificant Data are presented as median
(thick line across box), interquartile ranges (ends of boxes), 90% range (whiskers) and outliers (standalone data points).
Eur J Anaesthesiol 2017; 34:534–543
Trang 7summarised as follows: In patients ventilated with a tidal
volume of 8 ml kg1 PBW, postoperative spirometry
results are no different between patients receiving
venti-lation with high PEEP and RM and patients receiving
ventilation with low PEEP without RM: postoperative
spirometry results are abnormal up to postoperative day 5:
occurrence of PPCs seems to be associated with a change
in postoperative spirometry results on postoperative
day 5
To our knowledge, this is one of the largest prospective
randomised controlled studies investigating the
associ-ation between postoperative spirometry changes in
patients undergoing major abdominal surgery and at risk
of developing PPCs
This substudy stopped when the PROVHILO trial
com-pleted recruitment, so we did not recruit the total number
of patients required according to the sample size
calcu-lation, and we had less than 80% power to show a 20%
statistically significant difference between the two
groups A comparison of the median TWAs of the two
treatment groups, high PEEP with RM versus low PEEP
without RM, suggests no difference between FEV1 and a
difference of only 6% in FVC The latter would not be
considered to be of clinical relevance We calculated a
potential effect size based on the means and standard
deviation of each treatment group FVC TWA in the high
PEEP group was 1.89 0.99 versus 1.95 0.68 in the low
PEEP group FEV1 TWA in the high PEEP groups was
1.46 0.8 versus 1.29 0.5 I in the low PEEP group
Thus, dCohen effect size for FVC TWA would be 0.07
[95% confidence interval, 95% CI -0.4 to 0.59] and 0.24
[95% CI -0.7 to 0.27] Our initial hypothesis and sample
size calculation was built on a much stronger effect size of
0.5, which we consider to be clinically relevant
However, we detected significant differences in spiro-metric test results between patients who developed PPCs and those who did not Although this might not seem to
be a surprising result, to our knowledge, postoperative spirometry is not used commonly as a tool to detect or predict PPC It is important to note that our study was not designed to show a direct or timely correlation between spirometric results and the development of PPCs Further studies are needed to determine, whether spiro-metric results could predict or indicate the development
of PPCs at an early stage such that this would allow the initiation of preventive or early therapeutic measures Postoperative spirometry per se might be a useful as a tool
to detect PPCs However, technical and practical reasons limit its utility as a postoperative monitor For instance, pain needs to be adequately controlled and patients need
to be fully awake and compliant
In this substudy and preplanned analysis, we had a unique opportunity to determine the effect of two differ-ent levels of PEEP and RM during intraoperative vdiffer-enti- venti-lation on postoperative lung function test results Its prospective design, the completeness of follow-up and the fact that occurrence of PPCs was scored by assessors who were blind to the intraoperative ventilation strategy helped reduce bias In addition, the definition of PPCs was defined a priori and the patients were similar with regard to their clinical characteristics and type of surgery Lastly, all patients were ventilated with tidal volumes of
8 ml kg1PBW; thus, we were able to assess the effect of PEEP and RMs on postoperative lung function
FVC and FEV1 decreased by more than 50% compared with preoperative values in both randomisation groups This restrictive ventilatory pattern has long been recog-nised after upper abdominal surgery and results from
Fig 3
6.0
(a) FVC
P < 0.05
FEV1 (b)
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
6.0
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
P < 0.05
Results of spirometry of patients with or without postoperative pulmonary complications (a) Forced vital capacity (FVC), and (b) Forced expiratory volume in 1 s (FEV1) in patients with (grey bars) or without (black bars) postoperative pulmonary complications On postoperative day 5, spirometric results were significantly lower in patients who developed postoperative pulmonary complications Data are presented as median (thick line across box), interquartile ranges (ends of boxes), 90% range (whiskers) and outliers (standalone data points).
Trang 8Copyright © European Society of Anaesthesiology Unauthorized reproduction of this article is prohibited.
reduced ventilatory muscle activity, diaphragmatic
dys-function and decreased lung compliance and is also
influenced by pain levels.21 Although we found
intrao-perative dynamic lung compliance to be significantly
higher in the high PEEP group, this did not protect
against a decline in postoperative lung function These
findings are consistent with the overall results of the
PROVHILO trial, in which the occurrence of PPCs
was high, but not different between patients who
received high PEEP or low PEEP during intraoperative
ventilation.13
The results of the present study support the information that came from two preceding trials of intraoperative ventilation.9,22 In an Italian single-centre, randomised controlled trial of patients scheduled for open abdominal surgery lasting more than 2 h, the FVC and FEV1 on postoperative day 1 were also approximately 50% lower than preoperative values.9However, in that trial, recov-ery of lung function was better in patients ventilated with
a lung-protective ventilation strategy (a PEEP of
10 cmH2O, a low tidal volume of 7 ml kg1 PBW and RM) compared with patients ventilated with a
Fig 4
6.0 litres litres
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
6.0
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
6.0 litres litres
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
6.0
4.0
2.0
0.0 PRE DAY 1 DAY 3 DAY 5
Low High Low High Low High Low High
UpperLower UpperLower UpperLower UpperLower UpperLower UpperLower UpperLower UpperLower
Low High Low High Low High Low High
Results of spirometry in patients with high or low pulmonary compliance and upper or lower abdominal surgery, ventilated with high or low PEEP (a)
Forced vital capacity (FVC), and (b) Forced expiratory volume in 1 s (FEV1) for patients with high or low pulmonary compliance ventilated with high or
low PEEP Patients with low (50 ml cm 1 H 2 O) or high (>50 ml cm1H 2 O) dynamic pulmonary compliance (as indicated by the brackets labelled
‘high’ or ‘low’ in the figures) were ventilated with high PEEP (black bars) or low PEEP (grey bars) On postoperative day 1, patients with high
intraoperative pulmonary compliance had higher FVC (P ¼ 0.021) and FEV1 (P ¼ 0.016) than patients with low intraoperative pulmonary compliance.
Time-weighted average of FVC and FEV1 did not differ between patients with high or low intraoperative pulmonary compliance Data are presented
as median (thick line across box), interquartile ranges (ends of boxes), 90% range (whiskers) and outliers (standalone data points) (c) Forced vital
capacity (FVC), and (d) Forced expiratory volume in 1 s (FEV1) for patients with upper or lower abdominal surgery ventilated with high or low PEEP.
Patients undergoing upper or lower abdominal surgery (indicated by brackets labelled ‘upper’ or ‘lower’ in the figures) were ventilated with high
PEEP (black bars) or low PEEP (grey bars) On postoperative day 1, patients with lower abdominal surgery had higher FVC (P ¼ 0.011) and FEV1
(P ¼ 0.018) than patients with upper abdominal surgery Time-weighted average of FVC and FEV1 did not differ between patients with upper or
lower abdominal surgery Data are presented as median (thick line across box), interquartile ranges (ends of boxes), 90% range (whiskers) and
outliers (standalone data points).
Eur J Anaesthesiol 2017; 34:534–543
Trang 9conventional ventilation strategy (no PEEP, a tidal
volume of 9 ml kg1 PBW, without RM).9In a German
single-centre, randomised controlled trial of patients
undergoing upper abdominal surgery, in which all
patients received a similar level of PEEP and the same
RM, postoperative changes in spirometry results were not
different in patients ventilated with 6 ml kg1PBW
ver-sus 12 ml kg1PBW.22On the basis of the results of these
two preceding trials and the results from the present
study, we suggest that postoperative spirometry changes,
specifically in the time course of lung function recovery,
might be affected by a combination of the two parameters
‘size of intraoperative tidal volume’ along with ‘PEEP’
and ‘RM’, but not solely by changes either in ‘tidal
volume’ or ‘PEEP’ alone
Since publication of the Italian trial mentioned above,
two other randomised trials of intraoperative ventilation
have been published.10,11 In both trials, patients were
randomly assigned to lung-protective ventilation with
low tidal volumes and high PEEP or conventional
venti-lation with high tidal volume and no PEEP Both trials
found fewer pulmonary complications with
lung-protec-tive ventilation The results from the original trial of this
substudy, the PROVHILO trial,13 suggest that high
levels of PEEP with RM do not protect against
devel-opment of PPCs in patients ventilated with low tidal
volumes
Accordingly, a differentiated algorithm for protective
intraoperative mechanical ventilation has recently been
proposed.23In nonobese patients without acute
respirat-ory distress syndrome undergoing open abdominal
surgery, mechanical ventilation should be performed
with tidal volumes of 6 to 8 ml kg1PBW combined with
a low PEEP of 2 cmH2O or less If hypoxemia develops
and hypotension, hypoventilation or other causes have
been excluded, inspiratory oxygen fraction should be
increased first, followed by increase of PEEP and
recruit-ment manoeuvers.23
Of note, high PEEP with RM failed to affect
postopera-tive spirometry results in two subgroups of patients in
which more benefit of high PEEP could be expected, that
is in patients with a lower pulmonary compliance during
intraoperative ventilation and patients who underwent
upper abdominal surgery
Our study was restricted to patients at risk of PPCs who
were scheduled to undergo open abdominal surgery The
majority of patients in our substudy received thoracic
epidural anaesthesia both intraoperatively and
postopera-tively Therefore, the results could be different in other
patient groups We detected differences in spirometric
test results between patients who developed PPCs and
those who did not However, our study was not designed
to show a direct or timely correlation between spirometric
results and the development of PPCs Further studies are
needed to determine whether spirometric results could
predict or indicate the development of PPCs at an early stage, and whether this would allow preventive or early therapeutic measures to be initiated However, even though postoperative spirometry per se might prove to
be useful as a tool to detect PPCs, technical and practical reasons could limit its utility: postoperative pain needs to be adequately controlled, and patients need to be fully awake and compliant Another limita-tion of our study relates to intra-abdominal pressure Intra-abdominal pressure in the postoperative period could interfere with lung function and hence spiro-metry results We did not measure intra-abdominal pressure, and thus cannot evaluate, whether this influ-enced our results
With the knowledge of our results, the question may arise
as to whether patient management during the emergence phase of anaesthesia could influence lung function to such an extent that the consequences of several hours of intraoperative ventilation become negligible We do not know whether extending the application of PEEP into the postoperative period, or prohibiting use of 100% oxygen during extubation would have changed our results Other trials suggest that if there is an effect due to how the emergence phase of anaesthesia is man-aged, this would only have minor consequences.24,25 Interestingly, as part of a protective ventilation strategy, the beneficial effect of RMs might also be questioned.26 The focus of our study was to compare the effects of several hours of ventilation using high levels of PEEP along with RMs with similar periods of ventilation with-out PEEP and RMs
In conclusion, postoperative spirometry test results are not affected by the PEEP level during intraoperative ventilation during anaesthesia for open abdominal surgery in patients at high risk of PPC Spirometry test results on postoperative day five are associated with the development of PPCs during this time period
Acknowledgements relating to this article
Assistance with the study: we thank Renate Babian for her assist-ance with the study.
Financial support and sponsorship: this work was supported by the Department of Anesthesiology, Du¨sseldorf University Hospital, Du¨sseldorf, Germany.
Conflicts of interest: none.
Presentation: none.
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