Ventilation Strategy During General Anesthesia for Orthopedic Surgery: A Quality Improvement Project
Phase: NA
Conditions: Orthopedic Surgery, Ventilation
Sponsor: The Cleveland Clinic

 
 
 
 
 
 
Ventilation Strategy during General Anesthesia 
for Orthopedic Surgery  
 
 
Alparslan Turan, M.D and Colleagues 
 
Version 1, September 6, 2017 
Version 2, December 18, 2017 
Version 3, March 5, 2018 
Version 4, March 20, 2018 
Version 5, August 13, 2018 
Version 6, April 30, 2019 
Version 7, August 20, 2020 
 
 
 
 
 
 
Collaboration between the Departments of OUTCOMES RESEARCH, 
General Anesthesiology, and Orthopedic Surgery. 
 
 

 
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Version 7, August 20, 2020 
Summary of changes 
 
 
Version 7 (August 20, 2020) 
 
Explanation about the meaning of the primary outcome was added in 
measurement and data collection (page 10): The diagnostic criteria of acute lung 
injury (ALI) has traditionally relied on clinical findings and PaO2/FIO2 ratio14. 
PaO2/FIO2 ratio describes the severity of lung injury (e.g. PaO2/FIO2 ≤300 for ALI 
and ≤200 for acute respiratory distress syndrome). Recently, SaO2/FIO2 has been 
accepted as a surrogate for PaO2/ FiO2 ratio on the diagnosis of adults with acute 
lung injury and ARDS.15,16,17 Noticeable, previous work demonstrated that a 
PaO2/FiO2 decrease of 10% from baseline was clinically meaningful of lung injury. 
18, 19, 20 Therefore, we decide to use SaO2/FIO2 ratio because: 1) it avoids invasive 
blood sampling, 2) there is evidence that SaO2/FIO2 is a reliable substitute for 
PaO2/FIO2 with good sensitivity and specificity in diagnosing lung injury, including 
ALI and ARDS,17,21,22 and 3) a 10% difference on SaO2/FIO2 between groups may 
be indicative of differences the level of lung injury induced by the ventilatory 
strategy.  
 
 
Version 6 (April 30, 2019) 
• 
Exploratory objective has been added: estimated blood loss and perioperative 
transfusions (Objectives and Hypotheses section, page 5 and page 11. 
Version 5, August 13, 2018 
 
• 
Exploratory objective has been added: time from extubation to first oxygen 
saturation on ambient air breathing (Objectives and Hypotheses section, page 5 
and page 11) 
• 
Tidal volume will be calculated according predicted body weight and not ideal body 
weight (Study procedures section, page 7)  
• 
Patients excluded from the study will be register: (Measurements and Data 
collection section, page 9) 
• 
Respiratory parameters related to intubation and extubation procedures will be 
excluded from the analysis. (Measurements and Data collection section, page 9) 
• 
We restricted our primary outcome, the time-weighted average SaO2/FIO2 ratio in 
the post-anesthesia care unit (PACU) to the first postoperative hour. 
(Measurements and Data collection section, page 9) 

 
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Version 7, August 20, 2020 
• 
The secondary outcome will be the oxygenation in ward, defined as  the overall of 
SaO2/FIO2  instead the time-weighted average (TWA) SaO2/FIO2  (Measurements 
and Data collection section, page 11) 
• 
We eliminated pulmonary collapse and hypoxemia from the composite of serious 
postoperative pulmonary complications. (Measurements and Data collection 
section, Table 4, page 10) 
 
Version 4, March 20, 2018.  
• 
Minors were excluded 
 
Version 3, March 5, 2018. 
• 
The protocol was revised as research project instead of quality improvement project. 
• 
An Information Sheet as an alternative to written consent with a drop out option (last 
paragraph) was added. 
 
Version 2, December 18, 2017  
• 
A paragraph explaining why this project is eligible for waiver informed consent was 
added (page 8) 
 

 
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Version 7, August 20, 2020 
December 18, 2017 Summary of changes:  
- 
A paragraph explaining why this project is eligible for waiver informed consent 
was added (page 8) 
 
Background 
Anesthesia and mechanical ventilation cause pathophysiological respiratory and 
ventilatory changes that can lead to pulmonary complications. Postoperative pulmonary 
complications are common after anesthesia, and cause substantial morbidity and 
mortality1 that worsen clinical outcomes. Pulmonary complications also augment the cost 
of a surgery 2-12-fold.2 The Cleveland Clinic Perioperative Health Documentation System 
database indicates that postoperative pulmonary complications occur after 5-10% of all 
surgeries, and that those complications are associated with in-hospital mortality, 
prolonged hospitalization, 30-day readmission, and higher overall cost.3,4 Because they 
cause so much morbidity and impose such a substantial burden on health-care systems, 
pulmonary complications have become a key quality and safety metric for United States 
hospitals.5 
The twin — and potentially contradictory — goals of mechanical ventilation are 
adequate gas exchange and prevention of iatrogenic lung injury. Two key ventilator 
settings are tidal volume and positive end-expiratory pressure (PEEP). Traditionally 
generous tidal volumes (i.e., 10-12 ml/kg of predicted body weight – PBW) were routine 
as high volumes prevents atelectasis and improve oxygenation. But relatively recently, 
restricted tidal volumes (i.e., 4-8 ml/kg PBW) were proven beneficial in critical care 
patients with acute respiratory distress syndrome/acute lung injury who were ventilated 
for days.1 Restricted tidal volumes have since been inconsistently adapted for operating 
room use — despite lack of evidence that lower volumes reduce pulmonary risk or 
improve outcomes in surgical patients who rarely have serious pre-existing lung disease 
and are usually ventilated for only a few hours.  
Restricted intraoperative tidal volumes improve breathing mechanics and reduce 
the risk of postoperative reintubation after cardiac surgery.6 Lower tidal volumes also 
prevent alveolar inflammation and coagulation in healthy surgical patients.7 On the other 
hand, low tidal volumes promote atelectasis which is an important cause of postoperative 
lung injury, and promotes pneumonia and respiratory failure. It remains unknown whether 
restricted tidal volumes are preferable during surgery, or whether lower volumes might 
actually worsen outcomes.   
There is similarly ongoing debate about the optimal level of intraoperative PEEP. 
Generous PEEP reduces atelectasis, but also increases intrathoracic pressure and thus 
promotes hypotension and a consequent reduction in coronary blood flow.8 Generous 
PEEP reduces lung injury in patients with acute respiratory distress syndrome. The 
IMPROVE study by Futier et al. is the most recent and largest relevant trial.9 In this 

 
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multicenter randomized trial of 400 patients, protective lung ventilation (tidal volume 6-
8 ml/kg PBW and 6-8 cm H2O PEEP) was compared with conventional ventilation (tidal 
volume 10-12 ml/kg PBW and no PEEP) in patients having major abdominal surgery who 
were at intermediate-to-high risk of postoperative complications. There were fewer 
pulmonary and extra-pulmonary complications in patients assigned to protective 
ventilation.  
In contrast, the PROVHILO trial compared the effects of high (12 cm H2O) vs low 
(<2 cm H2O) PEEP during open abdominal surgery and found no difference in postop 
pulmonary complications. Furthermore, patients assigned to high PEEP had more 
intraoperative hypotension requiring treatment.10 The PROVHILO results are consistent 
with a systematic review by Briel et al. that included 2,299 patient from three trials 
(ALVEOLI, LOVS, and EXPRESS) in which PEEP did not influence in-hospital mortality 
in non-ARDS patients, leading the authors to conclude that high PEEP may be harmful in 
patients without ARDS.11 Because existing results conflict, there is no consensus 
whatsoever on the optimal level of PEEP during elective surgery.  
A consequence of limited and conflicting literature about optimal ventilation 
strategy is that ventilator settings in our institution vary widely amongst practitioners and 
patients. For example, between 2007-2016 at the Main Campus, 18% of patients were 
ventilated with tidal volumes exceeding 10 mL/kg PBW. Patients presenting for 
orthopedic surgeries are typically elderly, and often debilitated. Comorbidities are 
common, including cardiac and pulmonary disease, thus putting orthopedic patients at 
special risk for postoperative pulmonary complications. Curiously, no substantive trials of 
ventilator management in orthopedic patients have been published.  
As part of developing a care pathway for Cleveland Clinic orthopedic surgical 
patients, we thus propose a research project to evaluate commonly used ventilator 
settings. Both the anesthesia and surgical teams have agreed to the proposed project, 
and representatives are designated co-investigators. While the results will presumably be 
published, our primary goal is to test the potential clinical consequences of switching to a 
standardized ventilation strategy in this unique patient population. We will use a non-
randomized alternating intervention cohort approach, restricted to the physically distinct 
orthopedic surgery unit (H operating rooms 32-37) on the Main Campus.  
 
 

 
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Objectives and Hypotheses 
Our objective is to determine the optimal intraoperative ventilation strategy among 
the chosen tidal volume and PEEP levels, and standardize it in an enhanced recovery 
pathway for orthopedic surgical patients. In particular, we propose to determine which 
combination of intraoperative tidal volume and positive end-expiratory pressure is best 
for patients having elective orthopedic surgery.  
Primary objective: 
Evaluate the effects of various ventilation strategies, tidal volume at 6 versus 10 
ml/kg of PBW and PEEP at 5 versus 8 cmH20, on oxygenation in the postoperative care 
unit, defined by the SaO2/FIO2 ratio, a validated measure of acute lung injury.12   
Secondary objective: 
To evaluate the effects of various ventilation strategies on: 
1. A composite of serious postoperative pulmonary complications;  
2. Oxygenation in surgical wards, defined by the SaO2/FIO2 ratio; 
3. Postoperative duration of hospitalization.  
 
Exploratory objective: 
1. Time from extubation to first oxygen saturation on ambient air breathing 
2. Intraoperative estimated blood loss and perioperative transfusions. 

 
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Methods 
We propose a non-randomized alternating intervention cohort study in which all 
orthopedic surgery operating rooms will alternate amongst four designated ventilation 
settings which include two tidal volumes and two PEEP levels (Table 1). At the end of the 
four-week sequence, the entire sequence will be repeated 26 times over a 2-year period. 
Thus, ventilator settings will not be randomized on a per-patient basis, or even among 
study weeks.  
Ventilation parameters will be designated at the beginning of each study week. 
However, clinicians will be free to adjust to whatever ventilation settings they believe is 
optimal in individual patients to ensure oxygenation and patient safety. We anticipate that 
approximately 2,500 patients will be included in the study.   
Subject selection 
This research study will be restricted to the operating rooms 32-37 which are 
primarily used for orthopedic surgery. The participating cohort will thus exactly represent 
those who will benefit from the proposed enhanced recovery pathway. Operating rooms 
32-37 constitute a physically distinct unit that is normally staffed by a small group of 
anesthesiologists and surgeons. Typically, about 150-200 cases with general anesthesia 
are performed each month in these operating rooms.  
We request a waived consent because: 1) obtaining individual consent would be 
nearly impossible for the number of patients required; 2) the interventions we propose are 
well within national and local standards-of-care and used routinely at the Cleveland Clinic; 
3) the interventions are low risk; 4) clinicians are free to modify ventilation parameters as 
they see fit in individual patients. From a practical perspective, this unfunded research 
project will not be feasible except as an alternating intervention trial with waived consent. 
Inclusion criteria: 
1. Patient  age ≥ 18 years old; 
2. Surgery in orthopedic operating rooms 32-37; 
3. General anesthesia with endotracheal intubation. 
 
Exclusion criteria: 
1. Non-orthopedic procedures; 
2. Intubation before induction of anesthesia. 
 

 
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Study procedures 
Four combinations of PEEP and tidal volume (Vt) will be used in patients having 
orthopedic surgery with general anesthesia, endotracheal intubation, and mechanical 
ventilation. Designated tidal volumes and PEEP levels were selected on the basis of 
previous studies12 and after discussion with Clinic orthopedic anesthesiologists. All are 
well within the range of ventilator setting commonly used in orthopedic patients at the 
Clinic. The following suggested ventilatory parameters will be suggested during each 
study month: 
 
Table 1. Tidal volume and PEEP settings 
 
Week 
Tidal volume (ml /predicted body weight) 
PEEP (cm H2O) 
1 
6 
5 
2 
6 
8 
3 
10 
5 
4 
10 
8 
 
As usual, predicted body weight (PBW) will be used to determine tidal volume, and charts 
will be provided in each orthopedic operating room. To calculate PBW we’ll use the 
formula which was used by ARDS network trial39 as following: 
Male 
50 + 0.91(centimeters of height – 152.4); 
Female 
45.5 + 0.91(centimeters of height – 152.4). 
Inspired oxygen concentration will be at least 50%, per Clinic routine. However, 
enough oxygen will always be given to maintain oxygen saturation (as determined by 
pulse oximetry) ≥ 95%. The respiratory rate will be adjusted to maintain an end-tidal partial 
carbon dioxide partial pressure between 35 and 45 mmHg, with a default inspired-to-
expired ratio of 1:2.   
Recruitment maneuvers are designed to re-expand atelectasis and are considered 
good clinical practice. Typically, a recruitment maneuver would be to maintain a constant 
airway pressure of  40-45 cmH2O for  40 seconds13. Clinicians will be asked to perform a 
recruitment maneuver after induction of anesthesia at a FIO2 of 50%, and shortly before 
extubation. Intraoperative driving pressure Driving pressure, plateau pressure minus 
positive end-expiratory pressure (Pplat – PEEP), will be kept less than 15 cmH2O by 
adjusting tidal volume and PEEP as necessary.  
There will be no other restriction on anesthetic management. Clinicians will thus 
be free to use any combination of drugs they care to for general anesthesia. There will 
also be no restriction on peripheral nerve blocks or postoperative analgesic management.  

 
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Measurements and Data collection 
All data will be obtained from the Cleveland Clinic Perioperative Health 
Documentation System (PHDS) and the Clinic’s Electronic Medical Record (EMR). 
Demographic and morphometric characteristics will be recorded including age, sex, race, 
weight, height, and body mass index. We will also consider risk factors which may 
increase chance of pulmonary complications including American Society of 
Anesthesiologists physical status, preoperative comorbidities, smoking history. 
Types of surgery will be characterized from ICD-9 codes using AHRQ Clinical 
Classifications Software. Routine anesthetic variables recorded in PHDS include use of 
regional anesthesia, patient position, anesthetic agent, tidal volume, PEEP, ventilation 
frequency, minute volume, airway pressures, inspired oxygen fraction, expired carbon 
dioxide partial pressure, SaO2, blood pressure, transfused blood products, iv fluid types 
and volumes given during surgery, vasoactive medication needs, and duration of surgery.  
We will register in redcap database all patients excluded from the study due to: 
- 
Patients decision 
- 
Anesthesiology decision 
- 
Surgeon decision 
Other Respiratory parameters related to intubation and extubation procedures will be 
excluded from the analysis. Thus we will exclude the tidal volume and PEEP values within 
15 minutes from the after intubation and before extubation.  
Baseline Patient/Surgery Characteristics  
1. Age 
2. Gender 
3. Race 
4. BMI  
5. ASA status 
6. Charlson score  
7. Smoking status  
8. Medical history 
a. Obstructive sleep apnea  
b. COPD 
c. Asthma 
9. Intraoperative risk factors: 
a. Duration of surgery  
b. Total dose of muscle relaxants   
c. Intraoperative crystalloids 
d. Intraoperative blood products transfused  
10.  Surgery characteristics: 
a. Surgery type 
b. Anesthesia type 
11.  Mechanical ventilation parameters: 
a. PEEP 
b. Tidal volume 

 
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Primary outcome 
The primary outcome will be time-weighted average SaO2/FIO2 ratio in the post-
anesthesia care unit (PACU) during the first postoperative hour. SaO2 is monitored 
continuously in the PACU by pulse oximetry. FIO2 will be estimated from the type of device 
and the oxygen flow rate, using the following conversion table (Table 3). We will assume 
that the FIO2 remains at the same level until the time of next record. 
The diagnostic criteria of acute lung injury (ALI) has traditionally relied on clinical 
findings and PaO2/FIO2 ratio14. PaO2/FIO2 ratio describes the severity of lung injury (e.g. 
PaO2/FIO2 ≤300 for ALI and ≤200 for acute respiratory distress syndrome). Recently, 
SaO2/FIO2 has been accepted as a surrogate for PaO2/ FiO2 ratio on the diagnosis of 
adults with acute lung injury and ARDS.15,16,17 Noticeable, previous work demonstrated 
that a PaO2/FiO2 decrease of 10% from baseline was clinically meaningful of lung injury. 
18, 19, 20 Therefore, we decide to use SaO2/FIO2 ratio because: 1) it avoids invasive blood 
sampling, 2) there is evidence that SaO2/FIO2 is a reliable substitute for PaO2/FIO2 with 
good sensitivity and specificity in diagnosing lung injury, including ALI and ARDS,17,21,22 
and 3) a 10% difference on SaO2/FIO2 between groups may be indicative of differences 
the level of lung injury induced by the ventilatory strategy.  
 
Table 3. Estimation of FIO2  
 
 

 
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Secondary Outcomes 
1. Composite of serious postoperative pulmonary complications  
Postoperative diagnoses will be collected from electronic medical records of patients. 
Individual chart reviews (blinded to ventilation management) will confirm that terms of the 
composite are met will be performed. Our composite of postoperative pulmonary 
complications is defined as the presence of at least one of the following ICD-10 codes 
(Table 4) that were not present on admission:  
Table 4. Secondary Outcome: Composite of Pulmonary complications (ICD-10 codes) 
   
Respiratory complications 
997.31….J95851 
997.32…..J9589 
997.39…..J95859, J9588, J9589 
Pulmonary infection, Pneumonia 
481………J13, J181 
482………J150 
483………J157, J160, J168 
484………B250 
485………J180 
486………J189 
Respiratory failure and distress 
518.3……….J82 
518.51………J95821, J9600 
518.52………J952, J953 
518.53………J95822, J9620 
518.81………J9600, J9690 
518.84………J9620 
Tracheitis and Bronchitis 
466……...J209 
464………J040 
Pulmonary edema 
518.4…….J810 
Pneumothorax and air leak   
512……….J930,  
512.84……J9382 
Pleural effusion 
511.9……..J918 
Atelectasis 
518.0……..J9811, J9819 
ARDS 
518.5…….. J80 
518.82…… J80 
Acute COPD exacerbation  
Acute asthma exacerbation  
491.21……J441 
493.92……J45901 
Other 
continuous 
invasive 
mechanical 
ventilation 
xxxxxx……Z99.11 
Re-intubation 
Defined by: Re-intubation surrogate search 
• 
Intubation note 
• 
Propofol bolus >100 mg  
• 
Etomidate 
• 
Muscle relaxant 
Transfusion-related acute lung injury  
518.7……..J9584 
Pulmonary embolism   
Respiratory acidosis  
415.1……..I2699 
276.2……..E872 
 

 
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2. Oxygenation in ward, defined as SaO2/FIO2 ratio 
Oxygen administration and SaO2 are normally recorded at 4-hour intervals on surgical 
wards. The overall of SaO2/FIO2 will be compared among different ventilation strategies.  
3. Length of postoperative hospital stay 
 
Exploratory outcome: 
- 
Time from extubation to first oxygen saturation on ambient air breathing.  
- 
As exploratory outcome, the time between extubation and the first saturation 
while breathing ambient air, can be related to underlying oxygen deficits and 
postoperative pulmonary complications.23,24 
 
 
Data analysis  
Control for confounding variables 
Given that this study will not be randomized, we will control for observed potential 
confounding variable (Table 5) using the inverse propensity score weighting method. To 
estimate the propensity score, we will first fit a multinomial logistic regression model with 
the four treatments of different ventilation strategies as outcome. For each patient, the 
probability of receiving each treatment given the observed confounding variables is 
estimated and the weight is calculated as inverse of the propensity score. To be 
conservative, we stabilized the weights further by truncating at 99th percentile. The 
success of the control for confounding will be assessed by pairwise comparisons among 
four groups on potential confounders using absolute standardized difference (ASD), 
defined as the absolute difference in means or proportions divided by the pooled standard 
deviation. Any confounding variables with an ASD > 0.10 will be adjusted for in all 
analyses. 
 
 
 

 
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Table 5. List of potential confounders 
Demographics 
Age 
 
Sex 
 
Race 
Baseline characteristics 
BMI 
 
ASA status 
 
Charlson score 
 
Smoking status 
Comorbidity 
Obstructive sleep apnea  
 
COPD 
 
Asthma 
Intraoperative risk factors 
Duration of surgery  
 
Total dose of muscle relaxants   
 
Intraoperative crystalloids 
 
Intraoperative blood products transfused  
 
 
Primary analysis 
Linear regression will be used to assess the effect of tidal volume (2 levels), PEEP 
(2 levels) and their interaction on the time-weighted average SaO2/FIO2ratio during first 
postoperative hour in PACU, including propensity score weights and adjusting for 
unbalanced confounders as appropriate. If interaction effect is not significant (P>0.10), 
treatment effect estimates will be summarized using mean difference comparing tidal 
volume of 10 vs. 8 and PEEP of 8 vs. 5. If interaction is significant, the effects of each 
intervention will be assessed within levels of the other intervention. Moreover, we will use 
time-weighted average SaO2/FIO2 value as outcomes and assess the effect of ventilation 
on it as a sensitivity analysis. With an overall alpha of 0.05 for the primary analysis, the 
significance criterion will be 0.25 for each treatment effect without significant interaction 
(i.e. 0.05/2, Bonferroni correction) before adjusting for interim analysis. 
 

 
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Secondary analysis  
We will use logistic regression model to assess the effect of tidal volume level, PEEP 
level and their interaction on the binary outcome of postoperative pulmonary complication. 
The effect on the lowest SaO2/FIO2 at ward will be assessed using linear regression. 
Finally, we will evaluate the length of hospital stay using a Cox proportional hazard 
regression model. The length of stay will be analyzed as time from operation to live 
discharge from hospital, where patients who died before hospital discharge will be 
considered as never having the event and will be assigned a censoring time using the 
observed longest duration among those discharged alive.    
Interim analyses 
At each quarter of the maximum enrollment, we will conduct an interim analysis to assess 
for efficacy and futility of tidal volume and PEEP and SaO2/FIO2. The interim analysis will 
use the gamma spending function with parameters -4 for alpha (efficacy) and -1 for beta 
(futility). Boundaries for efficacy (futility in parentheses) at each stage are P<0.0008 
(P>0.9056), P<0.0024 (P>0.4969), P<0.0072 (P>0.1249), and P<0.0215 (P>0.0215), 
respectively. 
 
Sample size estimation 
Based on literature and a preliminary query of PHDS database and Epic EMR system, 
we assume that the mean TWA SaO2/FIO2 is 330 with a standard deviation of 100. After 
accounting for 3 interim analyses and 1 final analysis, a maximum N=2,500 in total 
patients (i.e., 625 for each of the 4 groups for assessing each main effect) will be needed 
to have 90% power at the 0.025 significance level to detect main effects of 15 or more in 
PaO2/FIO2 for tidal volume and PEEP (high versus low).  
The table below provides the probability of stopping the study for possible true underlying 
treatment effects: Null (no effect), Alternative (20 increase in SaO2/FIO2), half-way 
between the null and alternative, and 1.5 times the alternative effect. For example, if the 
alternative hypothesis were true, the cumulative probability of crossing either efficacy or 
futility boundary at the 1st, 2nd, 3rd and 4th looks would be 0.086, 0.392, 0.778 and 1 
respectively. 

 
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Table 1. Expected Cumulative Stopping Probabilities. 
 
 
Human Subjects 
The project we propose is primarily for research and cost reduction, although the results 
may be interesting enough to publish. Specifically, we seek to determine which 
combination of tidal volume and PEEP should be specified in the enhanced recovery 
pathway being developed for orthopedic surgical patients.  
We will use a non-randomized alternating treatment design in which various tidal volumes 
and PEEP levels will be used for successive weeks in a designated physically distinct 
surgical unit. The two tidal volumes and two PEEP levels we propose to use are generally 
thought to be safe in perioperative use, and are well within the range of current practice 
at the Clinic. The protocol includes safeguards to prevent excessive peak airway pressure 
and assure adequate ventilation. Importantly, clinicians will be free to provide whatever 
ventilation they believe might be necessary in individual patients. An Information Sheet 
will be used as alternative to written consent. 
 
Significance 
Postoperative pulmonary complications are common, occurring in about 5% of surgical 
patients. Pulmonary complications increase morbidity, mortality, length of hospital stay, 
and healthcare costs. Because so many orthopedic surgeries are performed at the 
Cleveland Clinic, reducing PACU time and pulmonary complications will improve clinical 
outcomes and reduce healthcare costs. Our research project will provide strong clinical 
evidence for selecting an optimal ventilation strategy for an enhanced care pathway in 
patients having elective orthopedic surgeries with mechanical ventilation. 
 
 
Effect  
Expected 
Stopping Stage 
Stopping Probabilities 
Stage 1 
Stage 2 
Stage 3 
Stage 4 
Null 
2.47 
0.095 
0.538 
0.898 
1.000 
½ Null, Alt 
2.96 
0.069 
0.315 
0.652 
1.000 
Alternative 
2.74 
0.086 
0.392 
0.778 
1.000 
Alt X 1.5 
1.89 
0.295 
0.830 
0.987 
1.000 

 
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References 
1. 
Serpa Neto A, Hemmes SN, Barbas CS, et al. Incidence of mortality and morbidity 
related to postoperative lung injury in patients who have undergone abdominal or 
thoracic surgery: a systematic review and meta-analysis. Lancet Respir Med. 
2014;2(12):1007-1015. 
2. 
Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ. 
Determinants of long-term survival after major surgery and the adverse effect of 
postoperative complications. Ann Surg. 2005;242(3):326-341; discussion 341-323. 
3. 
Dimick JB, Chen SL, Taheri PA, Henderson WG, Khuri SF, Campbell DA, Jr. 
Hospital costs associated with surgical complications: a report from the private-
sector National Surgical Quality Improvement Program. J Am Coll Surg. 
2004;199(4):531-537. 
4. 
Sabate S, Mazo V, Canet J. Predicting postoperative pulmonary complications: 
implications for outcomes and costs. Curr Opin Anaesthesiol. 2014;27(2):201-209. 
5. 
Shander A, Fleisher LA, Barie PS, Bigatello LM, Sladen RN, Watson CB. Clinical 
and economic burden of postoperative pulmonary complications: patient safety 
summit on definition, risk-reducing interventions, and preventive strategies. Crit 
Care Med. 2011;39(9):2163-2172. 
6. 
Sundar S, Novack V, Jervis K, et al. Influence of low tidal volume ventilation on 
time to extubation in cardiac surgical patients. Anesthesiology. 2011;114(5):1102-
1110. 
7. 
Choi G, Wolthuis EK, Bresser P, et al. Mechanical ventilation with lower tidal 
volumes and positive end-expiratory pressure prevents alveolar coagulation in 
patients without lung injury. Anesthesiology. 2006;105(4):689-695. 
8. 
Luecke T, Pelosi P. Clinical review: Positive end-expiratory pressure and cardiac 
output. Crit Care. 2005;9(6):607-621. 
9. 
Futier E, Constantin JM, Paugam-Burtz C, et al. A trial of intraoperative low-tidal-
volume ventilation in abdominal surgery. N Engl J Med. 2013;369(5):428-437. 
10. 
Prove Network Investigators for the Clinical Trial Network of the European Society 
of Anaesthesiology, Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High 
versus low positive end-expiratory pressure during general anaesthesia for open 
abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. 
Lancet. 2014;384(9942):495-503. 
11. 
Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure 
in patients with acute lung injury and acute respiratory distress syndrome: 
systematic review and meta-analysis. Jama. 2010;303(9):865-873. 
12. 
Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of Pao2/FIO2 From 
Spo2/FIO2 Among Patients With Acute Respiratory Distress Syndrome. Chest. 
2016;150(2):307-313. 
13. 
Valente Barbas CS. Lung recruitment maneuvers in acute respiratory distress 
syndrome and facilitating resolution. Crit Care Med. 2003;31(4 Suppl):S265-271. 
14. 
Bernard GR, Artigas A, Brigham KL, et al. Report of the American-European 
consensus conference on ARDS: definitions, mechanisms, relevant outcomes and 

 
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Version 7, August 20, 2020 
clinical trial coordination. The Consensus Committee. Intensive Care Med. 
1994;20(3):225-232. 
15. 
Chen W-L, Lin W-T, Kung S-C, Lai C-C, Chao C-M: The Value of Oxygenation 
Saturation Index in Predicting the Outcomes of Patients with Acute Respiratory 
Distress Syndrome. J Clin Med 2018; 7:205. 
19.  
Festic, E., et al., SpO2/FiO2 ratio on hospital admission is an indicator of early 
acute respiratory distress syndrome development among patients at risk. J 
Intensive Care Med, 2015. 30(4): p. 209-16. 
17. 
Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB. 
Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute 
lung injury or ARDS. Chest. 2007;132(2):410-417. 
18.  
Douville NJ, Jewell ES, Duggal N, Blank R, Kheterpal S, Engoren MC, Mathis MR: 
Association of Intraoperative Ventilator Management With Postoperative 
Oxygenation, Pulmonary Complications, and Mortality. Anesth Analg 2019. 
19. 
 Villar J, Blanco J, del Campo R, Andaluz-Ojeda D, Diaz-Dominguez FJ, Muriel 
A, Corcoles V, Suarez-Sipmann F, Tarancon C, Gonzalez-Higueras E et al: 
Assessment of PaO(2)/FiO(2) for stratification of patients with moderate and 
severe acute respiratory distress syndrome. BMJ Open 2015, 5(3):e006812. 
20.  
Hovaguimian F, Lysakowski C, Elia N, Tramer MR: Effect of intraoperative high 
inspired oxygen fraction on surgical site infection, postoperative nausea and 
vomiting, and pulmonary function: systematic review and meta-analysis of 
randomized controlled trials. Anesthesiology 2013, 119(2):303-316 
21.  
Bilan N, Dastranji A, Ghalehgolab Behbahani A. Comparison of the spo2/FIO2 
ratio and the pao2/FIO2 ratio in patients with acute lung injury or acute respiratory 
distress syndrome. Journal of cardiovascular and thoracic research. 2015;7(1):28-
31. 
22. 
Khemani RG, Patel NR, Bart RD, 3rd, Newth CJL. Comparison of the pulse 
oximetric saturation/fraction of inspired oxygen ratio and the PaO2/fraction of 
inspired oxygen ratio in children. Chest. 2009;135(3):662-668. 
23. 
Ferrando, C. et al. The accuracy of postoperative, non-invasive Air-Test to 
diagnose atelectasis in healthy patients after surgery: A prospective, diagnostic 
pilot study. BMJ Open 7, 1–9 (2017). 
24. 
Canet, J. et al. Development and validation of a score to predict postoperative 
respiratory failure in a multicentre European cohort. Eur. J. Anaesthesiol. 32, 458–
470 (2015).