journal club and critical appraisal checklist intensive recruitment versus moderate recruitment strategy in postop cardiac surgery patients to avaoid postop pulmonary complications

1. JOURNAL CLUB
DR. YOGESH RATHOD
CHRISTIAN MEDICAL COLLEGE, VELLORE.

3. Effect of Intensive vs Moderate Alveolar Recruitment
Strategies Added to Lung-Protective Ventilation on
Postoperative Pulmonary Complications
A Randomized Clinical Trial
JOURNAL CLUB

4. AUTHORS
• Alcino Costa Leme, RRT, PhD; Ludhmila Abrahao Hajjar,MD, PhD; et al.
• Trial Registration clinicaltrials.gov Identifier: NCT01502332

5. Key Question
• Is there any extra benefit to applying more intensive alveolar
recruitment strategies for high-risk surgical patients already receiving
perioperative small tidal volumes and protective lung ventilation?

6. • Findings An intensive recruitment strategy compared with a
moderate recruitment strategy to treat patients with hypoxemia after
cardiac surgery resulted in significantly lower severity of pulmonary
complications during the hospital stay. The strategy caused a
consistent shift to lower scores that favored use of an intensive
recruitment strategy.
• Meaning A more intensive alveolar recruitment strategy applied
postoperatively may reduce the severity of pulmonary complications
in patients with hypoxemia after cardiac surgery.

7. • Importance Perioperative LPV has been recommended to reduce
pulmonary complications after cardiac surgery. The protective role of a
small VT has been established, whereas the added protection afforded by
alveolar recruiting strategies remains controversial.
• Objective To determine whether an intensive alveolar recruitment
strategy could reduce postoperative pulmonary complications, when
added to a protective ventilation with small VT.
• Design, Setting, and Participants Randomized clinical trial of patients
with hypoxemia after cardiac surgery at a single ICU in Brazil (December
2011-2014).

8. • Interventions Intensive recruitment strategy (n=157) or moderate
recruitment strategy (n=163) plus protective ventilation with small VT.
• Main Outcomes and Measures Severity of postop pulmonary
complications computed until hospital discharge, analyzed with a
common odds ratio (OR) to detect ordinal shift in distribution of
pulmonary complication severity score (0-to-5 scale, 0, no
complications; 5, death). Prespecified secondary outcomes were
length of stay in the ICU and hospital, incidence of barotrauma, and
hospital mortality.

9. Introduction
• Postoperative pulmonary complications are common after cardiac surgery,
often increasing postoperative morbidity and mortality.
• The complications may result in increased resources utilization, delayed
mobilization, prolonged need of supplemental oxygen or mechanical
ventilation and a longer hospital stay.
• Recent studies have shown that intraoperative lung-protective ventilation may
reduce postoperative pulmonary complications.
• This clinical trial evaluated the specific role of a more intensive alveolar
recruitment strategy for reducing the severity of pulmonary complications.

10. Methods
• Study Design
• This was a single-center, randomized clinical trial performed at the
Heart Institute (Incor) from the University of São Paulo in Brazil.
Patients were enrolled between December 2011 and February 2014.

11. Flow of Study Patients With Hypoxemia After Cardiac SurgeryBMI indicates body mass index, calculated as weight in kilograms divided by height
in meters squared; LVEF, left ventricular ejection fraction; Pao2, partial pressure of arterial blood oxygen; Fio2, fraction of inspired oxygen.

12. • Participants
• INCLUSION CRITERIA
• elective cardiac surgery(CABG surgery, valve surgery, or both, with or without CPB)
and
• had hypoxemia in ICU. [P:F ratio of less than 250 mm Hg]
• EXCLUSION CRITERIA
• <18 years or >80 years;
• had previous lung disease [FEV1:FVC] <70%);
• had previous cardiac surgery or neuromuscular disease;
• had a mean PA pressure >35 mm Hg;
• had LVEF of <35%;
• BMI <20 or >40
• needed emergency surgery or ventricular assist device;
• needed more than 2 μg/kg/min of norepinephrine;
• had refractory hypotension or arrhythmia at entry;
• had pneumothorax or air leak syndrome at entry;
• or were enrolled in another study.

13. Study Protocol
• All postoperative patients were admitted to the ICU; received volume-controlled ventilation; and had a
VT of 6 mL/kg of predicted body weight (PBW), FIO2 of 0.60, and PEEP of 5 cm H2O. After confirming
entry or exclusion criteria, patients were randomly assigned to 1 of 2 strategies: lung-protective
ventilation plus intensive alveolar recruitment strategy or lung-protective ventilation plus moderate
alveolar recruitment strategy
• In the intensive strategy group, patients received 3 cycles of lung inflation (60 seconds each), consisting
of PEEP of 30 cm H2O, pressure-controlled ventilation, driving pressure of 15 cm H2O, respiratory rate
of 15/min, inspiratory time of 1.5 seconds, and FIO2 of 0.40. During the intervals (60 seconds) among
inflation cycles and subsequently, patients received assist-controlled or pressure-controlled ventilation,
with driving pressures adjusted to obtain a VT of 6 mL/kg of PBW, inspiratory time of 1 second, PEEP of
13 cm H2O, and minimum respiratory rate to maintain PaCO2 between 35 and 45 mm Hg.
• In the moderate strategy group, patients received 3 sustainedinflations (30 seconds each) under
continuous positive airway pressure (CPAP) mode at 20 cm H2O and FIO2 of0.60. During the intervals
(60 seconds) among sustained insufflations and subsequently, patients received assist or
controlvolume-controlled ventilation (decelerating-flow waveform), VT of6mL/kg of PBW, inspiratory
time of 1 second,PEEPof 8 cm H2O, FIO2 of 0.60, and minimum respiratory rate adjusted to maintain
PaCO2 between 35 and 45mmHg.

14. • After 4 hours under the randomized ventilation strategy, patients
received a second recruiting maneuver (right after the second
pressure volume curve)and were subsequently weaned from
mechanical ventilation according to the institutional protocol
(progressively reduced levels of pressure support, until a minimum of
5 cm H2O), with the exception of PEEP, which was maintained
constant until patient extubation, at the level defined by
randomization.
• Both groups received similar care and physical therapy in the
postoperative period.

15. Data Collection and Outcomes Measurements
• The primary outcome was the severity of postoperative pulmonary
complications during hospital stay, scored on an ordinal scale ranging
from 0 to 5.
• The prespecified secondary outcomes were length of ICU stay, length
of hospital stay, hospital mortality, and incidence of barotrauma.

16. SCORE OF
POSTOPERATIVE
PULMONARY
COMPLICATIONS

17. Severity of Postoperative Pulmonary ComplicationsEach postoperative pulmonary complication, the worst each patient experienced
throughout his/her hospital stay, was graded from 0 to 5. Grade 0 represents no symptoms or signals; grade 1, one of the following:
dry cough, abnormal lung findings and temperature 37.5°C or higher with normal chest radiograph, or dyspnea without other
documented cause; grade 2, two of the following: productive cough, bronchospasm, hypoxemia (Spo2 ≤ 90%) at room air, atelectasis
with gross radiological confirmation (concordance of 2 independent experts) plus either temperature higher than 37.5°C, or
abnormal lung findings, hypercarbia (Paco2>50 mm Hg) requiring treatment; grade 3, one of the following: pleural effusion resulting
in thoracentesis, pneumonia, pneumothorax, extended noninvasive ventilation, or reintubation lasting less than 48 hours; grade 4,
reintubation or invasive mechanical ventilation for 48 hours or more; and grade 5, death before hospital discharge.

18. Statistical Analysis
• The study was designed to have a 90% power to detect a difference in the incidence of
major (grade ≥3) pulmonary complications between the moderate (expected incidence
of 30%) and intensive recruitment strategy (expected incidence of 15%, based on low-
range estimates of effect size for this population), at a 2-sided α error of 5%.
• Study generated the sample size of 322 patients, rounded to 320.
• An independent data and safety monitoring committee performed a blinded and planned
interim analysis after enrollment of 50% of patients (n = 160) to evaluate adverse events.
The committee recommended that the study should be continued.
• We compared the baseline characteristics, follow-up measures, and clinical outcomes on
an intention-to-treat basis according to randomized study strategy. Continuous variables
were compared using t tests or repeated analysis of variance measures. The scores of
pulmonary complications were analyzed through Mann-Whitney U tests and
multivariable ordinal logistic regression by estimating the common odds ratio for a shift
in the direction of a better outcome on the modified scale of pulmonary complications.

19. Results
• Study Population
• A total of 4483 patients were screened for eligibility. After checking the inclusion-exclusion criteria, and after
excluding those with absence of consent, we ultimately enrolled and randomized 320 patients: 163 assigned to
the moderate and 157 to the intensive recruitment strategy. All patients completed the study and were followed
up until death or hospital discharge.
• Primary Outcome
• The pulmonary complications score was a mean 1.8 (95% CI, 1.7-2.0) and a median 1.7 (IQR, 1.0-2.0) for the
intensive recruitment strategy group vs a mean 2.1 (95% CI, 2.0 to 2.3) and median 2.0 (IQR, 1.5-3.0) for the
moderate strategy group. The severity and occurrence of postoperative pulmonary complications, computed
during whole hospital stay, was reduced in the intensive recruitment strategy group compared with those in the
moderate strategy group with a shift in the distribution of the primary outcome scores in favor of the intensive
recruitment strategy, with a common odds ratio for lower scores of 1.86 (95% CI, 1.22 to 2.83; P = .003;)
• Prespecified Secondary Outcomes
• The mean number of days patients in the moderate recruitment strategy group spent in the hospital was 12.4
(median, 9 days) vs 10.9 (median, 8 days) in the intensive group (absolute difference, −1.5 days; 95% CI, −3.1 to
−0.3; P = .04, log-rank test;). The mean number of days patients in the moderate recruitment strategy groups
spent in the ICU was 4.8 days vs 3.8 days in the intensive group (absolute difference, −1.0 day; 95% CI, −1.6 to
−0.2; P = .01, log-rank test). Hospital mortality (absolute difference, −2.4%; 95% CI, −7.1% to 2.2%; P = .27) and
barotrauma incidence (absolute difference, −0.6%; 95% CI, −1.8% to 0.6%; P = .51) were not significantly different
between study groups.

21. Discussion
• Among patients with hypoxemia after cardiac surgery, the use of an intensive alveolar recruitment strategy
compared with a moderate recruitment strategy resulted in less severe pulmonary complications during the
hospital stay.
• Patients in the intensive alveolar recruitment strategy group also had shorter hospital and shorter ICU
lengths of stay but no difference in hospital mortality or incidence of barotrauma than did patients in the
moderate alveolar recruitment strategy group.
• Physiological parameters explored in post hoc analysis indicated a faster recovery of lung function after the
first recruitment maneuver was applied in the ICU, resulting in physiological benefits that lasted through
extubation and beyond.
• Further lung function benefits were observed in the next days following extubation, resulting in a
significantly lower use of supplemental oxygen and lower use of extended noninvasive mechanical
ventilation.

22. • This is the first study to show a significant effect of lung recruitment maneuvers on clinical
outcomes, which objectively resulted in modest reductions in ICU and hospital length of stay with
no difference in in-hospital mortality or the occurrence of barotrauma.
• This is especially noteworthy considering that the control group was also receiving protective lung
ventilation with low VT and moderate PEEP levels. Thus, the major difference between treatment
groups was the intensity of lung recruitment.
• The moderate recruitment strategy used in this study was similar to the lung-protective strategy
applied intraop in the recent Intraop Protective Ventilation in Abdominal Surgery (IMPROVE) trial.
• Enrolling patients undergoing abdominal surgery, the IMPROVE trial had already demonstrated a
76% reduction in postoperative pulmonary complications (grade ≥3) compared with a control
group receiving nonprotective ventilation (0 PEEP and median VT, 11 mL/kg of PBW). Thus, the
present study suggests that a step further in postoperative lung protection is possible.
• Patients in the intensive recruitment strategy group showed greater reversal of atelectasis
(suggested by electrical impedance tomography maps), with a better respiratory-system
compliance and lower driving-pressure applied to the inflamed lung.
• After several hours, they also showed a better lung inflation profile (suggested by the enhanced
P-V loops), and, subsequently, a better gas-exchange during the weaning time, as well as along
the subsequent days. This long-lasting improvement in lung function prevented pulmonary
complications and the need of more intensive therapies, allowing the patients to be discharged
earlier from the ICU and hospital.

23. • Contrasting the results presented in the present trial, a recent multicenter study
by Hemmes et al (Protective Ventilation During General Anesthesia for Open
Abdominal Surgery [PROVHILO]) showed no benefit from a more intensive
alveolar recruitment strategy involving patients undergoing abdominal surgery.
• Variations in study methods might explain the different outcomes. For instance,
100% of patients in this present study were extubated at low FIO2 (≤0.40)
compared with only half of patients in the PROVHILO study. Thus, it is possible
that a greater reabsorption of atelectasis promoted by higher intra-alveolar
FIO2 may have abrogated the effects of that ventilation strategy.
• Second, the maneuvers used in the present trial transiently reached inspiratory
pressures of 45 cm H2O, likely more effective to reverse atelectasis, whereas the
PROVHILO study did not use pressures greater than 35 cm H2O.
• Third, the population in this study had higher chances of developing atelectasis,
presenting higher body mass indexes (28 vs 25.5; calculated as weight in
kilograms divided by height in meters squared), more frequent extracorporeal
support and more open-chest surgeries with direct lung contact. Considering the
lower VT used in this study (6.1 mL/kg of PBW) compared with approximately 7.2
mL/kg of PBW in their study, all such differences may have converged to amplify
the relative importance of recruiting maneuvers.

24. • In contrast with some of previous investigations, the lung recruitment
performed in this study was not done intraoperatively or after
extubation. Although such procedures might have enhanced the benefits of
an intensive recruitment strategy, it is otherwise possible that the selective
application of recruitment strategy, only at the postoperative phase, offers
a good compromise between safety and efficacy. Possibly, this lung-rescue
procedure replaced or avoided the intraoperative recruitment strategy
application in the context of bleeding and reduced peripheral vascular
tonus, a situation that might decrease protocol adhesion or promote
frequent hypotension. By performing the procedure in the ICU,
hemodynamic optimization might be easier, and ventilator disconnections
during transportation could be counterbalanced.

25. Adverse Effects and Resource Utilization
• A larger decrease in arterial blood pressure was observed in the intensive recruitment strategy group,
although blood pressure never decreased to less than 60 mm Hg and was limited to the duration of the
recruitment maneuver. Five minutes later, there were no significant differences in arterial pressure between
groups, despite the higher PEEP in the intensive group. This fast recovery is consistent with clinical studies
showing improved right ventricular function after the maneuver and also with experimental studies in which
a short recruiting maneuver (<1 minute) was applied, under pressure-controlled modes. Pilot studies at our
institution had also suggested that the key elements for such good hemodynamic tolerance were a negative
leg-raising test and a high-enough mean arterial blood pressure beforehand. Both were strictly optimized
before starting the maneuvers.
• Although ICU and hospital costs have not been directly measured, differences in procedures or differences in
resources utilization were not identified between groups during the mechanical ventilation period. The only
observable difference was the settings on the mechanical ventilator, along with the 1-hour shorter (P = .15)
mechanical ventilation period in the intensive recruitment strategy group. It is possible that the clinician’s
awareness of better lung function was related to a faster sequence of weaning steps.
• In contrast, the utilization of resources after extubation was higher in the moderate recruitment strategy
group, with more frequent use of supplemental oxygen, noninvasive ventilation, and modestly longer ICU
and hospital length of stay.

26. Limitations
• This study has several important limitations.
• The criteria for defining postoperative pulmonary complication may influence the results. This study used
the definition elaborated by Kroenke et al, which was also used in some recent trials. To try to achieve
unbiased application, objective definitions were further preestablished: hypoxemia, need of noninvasive
ventilation, and radiographic abnormalities (requiring concordance of 2 independent observers). In
addition, death was included as a maximum complication, increasing its reliance on clinical outcomes.
Within this context, post hoc analysis demonstrated a higher rate of major pulmonary complications
(pulmonary scores ≥3) was observed in the control (moderate) group (26%), compared with previous trials
(≤22%). Contributing to this difference, however, was the strict inclusion criteria (PaO2/FIO2 <250 at PEEP ≥5
cm H2O), which may have selected patients with higher probability of response to PEEP and recruitment
maneuvers. This predictive enrichment was part of the study design, increasing the power of the study but
decreasing generalizability. Also, because of the particular injury of cardiopulmonary bypass patients with
more inflamed lungs were probably selected. Most patients in the present study developed at least some
minor pulmonary complication, although at a systematically lower frequency in the intensive recruitment
strategy group.
• The single-center nature of this study limits the generalizability of findings to a broader population. The large
population studied and the consistent physiologic analysis, add some robustness to results. In addition,
other important factors, such as fluid balance and analgesia after ICU arrival, were not extensively
measured. Counterbalancing this, the chances of systematic biases were low because the investigators were
not responsible for daily prescriptions (eg, oxygen therapy, fluids, drugs) and, after extubation, the clinical
staff was blinded to randomization and allocation, especially so in the ward.

27. Conclusions
• Among patients with hypoxemia after cardiac surgery, the use of an
intensive alveolar recruitment strategy compared with a moderate
recruitment strategy resulted in less severe pulmonary complications
during the hospital stay.

28. CRITICAL APPRAISAL CHECKLIST
• Screening Questions
• The first two questions are screening questions and if the answer to
either of these is no then the study may be of limited usefulness.
• Q1. Did the study ask a clearly focused question?
• YES
• Q2. Was this an RCT and was it appropriately so?
• YES

29. Methodology
• Questions 3 to 7 are intended to assess the methodology of the study. The final published report of the study which includes the
results has very little detail on the methodology so you will also have to read the published report of the study protocol to answer
these questions.
• Q3. Were participants appropriately allocated to intervention and control groups?
YES
• How were participants allocated to the intervention and control groups? Was the process truly random?
RANDOMISATION & YES
• Was stratification used?
NO
• How was the randomisation schedule generated and how were participants allocated to intervention and control groups?
PATIENT SELECTION AND ALLOCATION WAS RANDOMISED, OPERATOR OF INTERVENTION COULD NOT HAVE BEEN BLINDED BUT
ANALYSERS WERE BLINDED.
• (d) Are the groups well balanced? Are any differences reported between the groups at entry to the trial?
NO & NO
• (e) Are there any differences that may confound the result?
PROBABLY (LIKE FLUID BALANCE OR ANALGESIA)

30. • Q4. Were participants, staff and study personnel “blind” to participants study group?
EXCEPT INTERVENTION OPERATORS ALL WERE BLINDED
• Consider:
• Blinding is not always possible YES
• If every effort was made to achieve blinding YES
• Does it matter in this study i.e. could there be observer bias? NO
• Q5. Were all patients accounted for? YES
• Was there a CONSORT diagram and were all the participants accounted for? YES
• Were the reasons for withdrawal given? NO WITHDRAWLS
• Did participants have the option to cross-over from their allocated treatment at
randomisation to the other treatment? NO
• Were all participants followed up in each study group? i.e. was there loss to follow up?
YES & NO
• Were all the participant’s outcomes analysed by the groups to which they were originally
allocated? i.e. was an intention to treat analysis used? YES & NO

31. • Q6. Were the participants in all groups followed up and the data
collected in the same way? YES
• Q7. Did the study have enough participants to minimise the play of
chance? i.e. is there a power calculation? YES & YES

32. • Results
• The results of an RCT should be scrutinised in a similar way to the methods. Q8 and Q9 prompt us
to ask questions about how meaningful the results presented actually are.
• Q8. How are the results presented and what is the main result?
EXPLAINED
• Are the results presented as a proportion of people experiencing an outcome, such as risks or as a
measurement such as mean or median survival curves and hazards? YES
• How large is the size of this result and how meaningful is it? NOT LARGE ENOUGH BUT
MEANINGFUL
• How would you sum up the results of the trial in one sentence?
THE SEVERITY AND OCCURRENCE OF POSTOPERATIVE PULMONARY COMPLICATIONS & HOSPITAL
STAY WAS REDUCED IN THE INTENSIVE RECRUITMENT STRATEGY GROUP COMPARED WITH THOSE
IN THE MODERATE STRATEGY GROUP WITHOUT ANY DIFFERENCE IN INCIDENCE OF BAROTRAUMA
AND HOSPITAL MORTALITY.
• Q9. How precise are these results?
• Is a confidence interval reported? YES
• Is a p-value reported? YES

33. Relevance
• Once we have assessed the quality of the methodology and considered the
importance of the results, we should think about how the results could be
applied to our local population and whether a change in practice seems
justified.
• Q10. Were all important outcomes considered so the results can be applied? YES
• Were the people included in the trial similar to your population? NO
• What was the comparator and was it suitable? SPSS VERSION 19.0 & SUITABLE
• Was the study and follow-up of an appropriate duration for the disease state and
intervention under review? NO
• Does the setting of the trial differ from your local setting? YES
• Could the same treatment be provided in your local setting? YES
• Do the benefits of this treatment outweigh the risks/costs? YES
• Should policy or practice change as a result of the evidence contained within this
trial? RIGHT QUESTION!!!!