Intraoperative Positive End-Expiratory Pressure Setting Guided By Esophageal Pressure Measurement in Patients Undergoing Laparoscopic Gynecologic Surgery
Phase: NA
Conditions: Positive-Pressure Respiration/Methods, Esophagus/Physiopathology, Pleura/Physiopathology, Gynecologic Surgical Procedures, Laparoscopy, Humans, Female
Sponsor: Mahidol University

 
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Official Title: Intraoperative Positive End-Expiratory Pressure Setting Guided by 
Esophageal 
Pressure 
Measurement 
in 
Patients 
Undergoing 
Laparoscopic Gynecologic Surgery  
Brief Title: 
Intraoperative PEEP Setting During Laparoscopic Gynecologic 
Surgery  
 
Principal Investigator: Annop Piriyapatsom, MD 
Affiliation:  
Department of Anesthesiology, Faculty of Medicine Siriraj 
Hospital, Mahidol University, Thailand   
 
NCT Number: N/A 
 
Updated: August 17, 2017 
 
 
 
 

 
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Intraoperative Positive End-Expiratory Pressure Setting Guided By Esophageal 
Pressure Measurement in Patients Undergoing Laparoscopic Gynecologic Surgery  
 
Introduction  
 
Nowadays, laparoscopic surgery has been substantially performed worldwide. It 
is considered as minimally invasive procedure with numerous advantages compared with 
open surgery including less postoperative pain, faster recovery, shorter length of hospital 
stay and less overall medical cost(1). The creation of pneumoperitoneum (PP) during 
laparoscopic surgery, however, can have significant effects on the respiratory system. 
The rise in intraabdominal pressure (IAP) causes cephalic displacement and stiffness of 
the diaphragm resulting in a decrease in the compliance of the respiratory system (CRS) 
and of the chest wall (CCW)(2-4) as well as an increase in pleural pressure (Ppl) likely due to 
thoracoabdominal transmission of IAP. Combine with a decrease in respiratory muscle 
tone following general anesthesia(5), the vital capacity and the functional residual capacity 
(FRC) are declined(2). There also atelectasis formation resulted from airway closure 
(compressive atelectasis) and absorption of gas trapped distal to occluded airways 
(absorption atelectasis)(6). All of these changes potentially lead to an increase in dead 
space ventilation as well as shunt and subsequently impair oxygenation(5). This 
pathophysiology may put patients at risk of postoperative pulmonary complications 
(PPCs) such as respiratory infection, respiratory failure, reintubation or prolonged 
mechanical ventilation and possibly increase mortality(7, 8).  
Therefore, intraoperative mechanical ventilation has an important role in respiratory 
management during laparoscopic surgery(9). Setting of positive end-expiratory pressure 

 
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(PEEP) has been shown to attenuate the derangement of respiratory mechanics and the 
impairment in oxygenation caused by PP(10-15). In addition, the application of PEEP as a 
part of intraoperative protective mechanical ventilation may be associated with a decrease 
in PPCs following laparoscopic surgery(16). Nevertheless, there is no consensus on the 
optimal PEEP level and the best method to set PEEP during laparoscopic surgery(9). In 
patients with acute respiratory distress syndrome (ARDS), Talmor et al(17) demonstrated 
that mechanical ventilation with PEEP set according to Ppl measured by using esophageal 
balloon catheter significantly had beneficial effects in terms of oxygenation, CRS and 
possible mortality. With PEEP set according to this method, the transpulmonary pressure 
(PTP), which is the difference between the pressure inside alveoli or PEEP and the 
pressure outside or Ppl, is constantly maintained positive during expiration. Consequently, 
it helps to prevent the formation of atelectasis as well as to recruit the collapsed alveoli 
and, thus, to improve oxygenation. To date, there is limited data regarding the use of 
esophageal balloon catheter to set PEEP in mechanically ventilated patients undergoing 
laparoscopic surgery. Therefore, the aim of this study is to determine whether PEEP 
titration guided by Ppl measurement during laparoscopic surgery would improve 
pulmonary function in term of oxygenation as well as other parameters such as 
compliance and alveolar dead space. 
  

 
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Material and Method 
Patient population  
This randomized controlled trial includes patients with age of equal or more than 
18 years old undergoing laparoscopic gynecologic surgery with anticipated surgical 
duration of more than 2 hours. Patients with the American Society of Anesthesiologists 
(ASA) physical status of equal or more than 3, those with significant cardiovascular or 
respiratory diseases, those with significant pathological lesion in pharynx and esophagus 
that preclude placement of esophageal balloon catheter, those with contraindications for 
PEEP titration such as increased intracranial pressure or unstable hemodynamic, those 
with arrhythmias, those who refuse to provide written informed consent, and those 
undergoing surgery with duration of less than 2 hours are excluded from the study. 
Informed consent is obtained from all included patients.  
Study protocol  
Prior to induction of general anesthesia, standard monitoring including non-
invasive blood pressure measurement, pulse oxymetry, electrocardiogram, capnometry 
and peripheral nerve stimulator (TOF-Watch, Organon, Ireland), which is applied to the 
temporal branch of facial nerve and recorded response of the orbicularis oculi, as well as 
non-invasive cardiac output measurement with the pulse wave transit time technology 
(Vismo, Nihon Kohden, Janpan) are applied to all patients. General anesthesia is induced 
with 1.5-2 mg/kg of propofol, 2 mcg/kg of fentanyl and 0.6 mg/kg of rocuronium and 
then trachea is intubated with proper size of endotracheal cuff tube. After induction and 
intubation, arterial catheter is inserted at radial artery for repeated arterial blood gas 
sampling. Anesthesia is maintained with 1 minimal alveolar concentration (MAC) of 

 
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desflurane and supplemental doses of morphine and rocuronium as required. Train-of-
four (TOF) stimulation with peripheral nerve stimulator is kept between 1 and 2 twitches 
to facilitate relaxation. In case of hemodynamic instability, fluid as well as inotropes and 
vasopressors are administered according to discretion of anesthesia staff. The surgery is 
initially started in the lithotomy position and then in the 45-degree Trendelenburg 
position at the initiation of PP. PP is created by intraabdominal insufflation of carbon 
dioxide (CO2) and IAP is maintained at 12 to 15 mm Hg during PP. At the end of the 
surgery, reversal of paralysis with 0.2 mg of sugammadex is administered and extubation 
is carried out after fulfilled criteria of extubation and TOF ratio monitoring of more than 
90%. All patients are then transferred to the recovery room and monitored for 1.5 hours 
prior to transfer to ward. 
For management of mechanical ventilation, all patients are ventilated by an 
anesthetic machine (Aespire View, Datex-Ohmeda Inc., Wisconsin, USA) with preset 
tidal volume of 8 mL/kg of predicted body weight, inspiratory to expiratory time ratio of 
1:2 with 45% inspiratory pause, respiratory rate adjusted to maintain end-tidal carbon 
dioxide (EtCO2) between 35 and 45 mm Hg, fraction of inspired oxygen (FiO2) of 0.40 in 
one liter per minute of the mixture of oxygen and air which can be adjusted to maintain 
peripheral oxygen saturation (SpO2) of equal or more than 95% and PEEP set according 
to the study groups. All included patients are randomly allocated into 2 groups, the 
control group (Group C) and the intervention group (Group E), by computer-generated 
block-of-four randomization. In the Group E, the 5-French, latex-free adult esophageal 
balloon catheter (CooperSurgical Inc., Connecticut, USA) is inserted after induction and 
intubation and connected to the pressure transducer system (TruWave, Edwards 

 
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Lifesciences, Irvine, USA). The proper position of the catheter is in the lower one third of 
the esophagus, which is determined by rising in pressure during positive pressure 
ventilation plus presence of cardiac oscillation recognized on the pressure tracing(18-20). 
The esophageal pressure (Peso) is measured and used as a surrogate of Ppl
(19-21). PEEP is 
titrated to maintain PTP during expiration, which is equal to PEEP minus Peso during 
expiration, between 0 and 5 cm H2O. The conversion factor of 1.36 is used to convert 
mm Hg to cm H2O. In the group C, the esophageal balloon catheter is inserted as in the 
group E for measuring Peso but patients are ventilated with fixed PEEP of 5 cm H2O 
throughout the operation.  
Data collection 
 
In all patients, demographic data including age, weight, height, body mass index 
(BMI), the ASA physical status, comorbid diseases, diagnosis, operation, duration of the 
operation are recorded. After induction and intubation and insertion of the esophageal 
balloon catheter, hemodynamic parameters including blood pressure, heart rate, cardiac 
index and stroke volume index; respiratory mechanics including peak inspiratory 
pressure, plateau pressure (Pplat), PEEP, Peso during inspiration and expiration, and tidal 
volume; and gas exchange parameters including partial pressure of arterial oxygen (PaO2) 
and carbon dioxide (PaCO2), pH, FiO2, SpO2 and EtCO2 are recorded as baseline T0 
parameters. After initiation of PP and position in 45-degree Trendelenburg position, 
PEEP is set according to patient’s group allocation. Hemodynamic parameters, 
respiratory mechanics, gas exchange parameters and IAP are recorded at 15 minutes and 
at one hour after setting of PEEP as T1 and T2 parameters, respectively. Thirty minutes 
after arrival in the recovery room, hemodynamic and gas exchange parameters are 

 
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recorded again as T3 parameters. The CRS is calculated from tidal volume in mL divided 
by difference between Pplat and PEEP in cm H2O and the alveolar dead space to tidal 
volume ratio (VD/VT) is calculated using the formula reported by Hardman et al(22). 
Adverse respiratory events defined as requirement of oxygen supplement after discharge 
from the recovery room, episodes of desaturation (SpO2 of less than 90%), now-onset 
respiratory infection, new infiltration on chest radiograph, or respiratory failure are 
followed up in all patients for 72 hours postoperatively or until discharge from hospital. 
Length of hospital stay as well as other adverse events are also recorded.  
Statistical analysis 
 
The primary endpoint of the study is to determine the difference in oxygenation 
that is PaO2 between the Group E and the Group C. Spadaro et al(15) reported PaO2 of 
127.5±30 mm Hg during PP in patients undergoing laparoscopic abdominal surgery with 
application of PEEP of 5 cm H2O. Meanwhile, PaO2 was reported as high as 142.5±30 
mm Hg(15) to 190.2±11.9 mm Hg(12) during PP with application of PEEP of 10 cm H2O. 
Given that PaO2 in the Group C is equal to that reported by Spadaro et al(15) and 
estimated 20% higher PaO2 in the Group E is clinically relevant, with a power of 0.8 and 
a significance level of 0.05, sample size of 22 subjects per group is required. The 
secondary endpoints are the difference in CRS and VD/VT between the two groups, 
changes in hemodynamic parameters with application of PEEP, proportion of 
thoracoabdominal transmission of IAP as well as adverse respiratory events and length of 
hospital stay in the two groups.   
 
Categorical variables are reported as number with percentage and compared 
between the groups using the chi-squared test or the Fisher’s exact test as appropriated. 

 
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Continuous variables are tested for normal distribution with the Kolmogorov–Smirnov 
test and reported as mean with standard variation (SD) or median with interquartile range 
(IQR) and compared between the groups using the unpaired Student’s t-test or the Mann 
Whitney U test as appropriated. The changes in parameters within the group are analyzed 
using the repeated-measure analysis of variance (ANOVA). For all analyses, a two-tailed 
test is performed and a p value of less than 0.05 is considered statistical significance. The 
statistical analysis is carried out using the IBM SPSS Statistics 21 (IBM Corporation, 
New York, USA). 

 
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