Trial Information

Postoperative Pulmonary Complications in Major (Abdominal) Surgery: a Multicenter Study

INTRODUCTION Pulmonary Postoperative Complications (PPCs) are among the most common causes
of adverse events in the perioperative period and can determine a significant increase of
mortality risk in hospitalization time.

Incidence of PPCs varies from 2% to 19%, according to the population under examination and
the criteria used to define pulmonary complications. There is no univocal definition of
PPCs. Usually physicians associate atelectasis, respiratory insufficiency, pneumonia,
bronchospasm, necessity of tracheal reintubation. Moreover, the evaluation of risk factors
is becoming increasingly difficult. Many aspects linked to the patient's conditions and
postoperative anesthesiologic management have been demonstrated to influence the risk of
developing PPCs. (with the endorsement of European Society of Anesthesiology) proposed a
risk index based on seven perioperative parameters to predict PPCs probability.

Furthermore, patients who survive after pulmonary complications will still suffer from
functional reductions and are at risk of having a decrease in medium and long-term survival.

PRIMARY END POINT To determine the actual incidence of respiratory postoperative
complications in patients undergoing general anesthesia for major abdominal surgery (general
surgery, urology, gynecology).

Respiratory complications are: pneumonia, respiratory insufficiency 8,9, pleural effusion,
pneumothorax, atelectasia, ab ingestis pneumonia, necessity of oxygen supply, non invasive
mechanical ventilation (NIMV) or tracheal reintubation.

SECONDARY END POINTS

To determine:

- postoperative incidence of necessity of tracheal reintubation

- duration of mechanical ventilatory support

- postoperative incidence of infections

- postoperative incidence of PostOperative Residual Curarization (PORC)

- postoperative incidence of cardiovascular complications

- postoperative outcome (30, 60 days and one year later)

- time of hospital stay, hospital mortality

- necessity of admission to ICU and ICU length of stay

Duration of the clinical phase: hospitalization (data collection: two hours after discharge
from the operating room, then from the first, up to the fifth postoperative day) Duration
of follow-up after hospitalization (follow up period): 30 days - 60 days - 1 year.

RECRUITMENT AND MONITORING PROCEDURES All patients scheduled for elective major abdominal
surgery, urologic surgery or major gynecological surgery under general anaesthesia will be
enrolled in this study.

Patients will be enrolled over a 15 days period, after that, if the sample would be too
small, another 15 days enrollment period will be repeated.

During the preoperative evaluation, the anesthesiologist will expose the study protocol to
all patients who will match the inclusion criteria. The informed consent will be obtained.

Patients will be monitored in the postoperative period and will receive, standard
postoperative care, as directed by the clinical teams and if indicated, antibiotics,
diuretics, oxygen therapy and every therapy according to the underlying disease. Medical and
nursing staff will monitor peripheral oxygen saturation in the origin ward.

In every center a researcher will evaluate the enrolled patients daily, checking for
peripheral oxygen saturation, arterial pressure, heart rate, respiratory rate, body
temperature and pain assessment (NRS scale).

Patient's clinical status until the hospital discharge will be reported on case report forms
(CRFs). Every intraoperative parameter (like drugs used, the need of blood transfusion,
fluid management and fluid balance at the end of surgery) will be recorded.

Treatments and therapy will be continued according to clinicians decision and will be
recorded in the CRF.

The decision to start an oxygen therapy or a ventilatory support (invasive or non-invasive)
or to admit the patient to the ICU will be taken by clinicians of every single participating
center according to their guidelines.

Every device used, with oxygen flow values, FiO2, PEEP and ventilation mode
(assisted/mechanical) will be noted in the CRF.

Antibiotic therapy and any pathogen responsible for pneumonia will be noted on the CRF.

Anesthesiologist will evaluate all the patients two hours after their return in the ward,
and from the first to the fifth postoperative day. Anesthesiologists will be also on-call by
the attending physician or the nursing staff every time patient's clinical conditions will
need it.

Every patient will be followed (and will be enrolled in the study) until hospital discharge.
Date of discharge will be noted in the CRF.

Moreover every enrolled patient will be followed-up at 30, 60 days and a year after hospital
discharge, to verify the patients health status and to evaluate the incidence of
re-hospitalization and mortality.

DATA COLLECTION:

A form divided in three sections (pre/intra/postoperative period) will be used for data
collection. Data will be collected on paper support and then entered in an electronic CRF.

Data will be anonymous. Every patient will be identified by a six number code: first three
(from left to right) identify the participating center, the others identify the sequential
number of enrollment.

The data insertion will be done by the investigators of every participating center, using
personal username and password.

Data will be sent to the coordinator center where the data cleaning will be completed and
statistical analysis will be performed with this timing:

after the 15 days enrolment period; after 4 months from the beginning of the study (30 days
postoperative follow up); after 6 months from the beginning of the study (60 days
postoperative follow up); after 16 months from the beginning of the study (1 year
postoperative follow up) Every center will store its own paper CRF.

In the preoperative section will be recorded the patient's data about:

age, weight, height, sex; comorbidities (neurological, cardiovascular, metabolic, renal,
muscular-skeletal) respiratory history positive for: previous pleuro-parenchymal diseases in
the 30 days before surgery, previous chest, pleural or lung surgery, presence of pleural
effusion; history of cigarettes smoking: active smoker (number of cigarettes), ex-smoker or
not smoker; history of alcohol abuse (active potus, previous or abstinent); active cancer
(excluding the diagnosis for surgery); SpO2, PaO2, PaO2/FiO2, PaCO2 when available; white
cell number, hemoglobin and preoperative creatinine; ASA class; presence of nasogastric tube
before surgery; presence of urinary catheter before surgery; blood products transfusion
before surgery.

In the intraoperative section will be recorded the patient's data about:

type of surgery; type of anaesthesia (TIVA, balanced); type of analgesia (intravenous,
epidural, perineural block); preoperative antibiotic prophylaxis; blood products
transfusion; intraoperative fluid management (crystalloids Vs colloids, mL/Kg/h); type of
ventilation (PCV/VCV); ventilation parameters (TV, Pins, PEEP, RR, FiO2); recruitment
maneuvers (yes/no) (manuals, pressure controlled); intraoperative ventilatory problems (
(SpO2 < 90%, PaO2/FiO2 < 300, PaCO2 > 45 mmHg, increase of airways pressure over than 30
cmH2O, bronchospasm, needs of TV> 10 mL/Kg); hemorrhage or need of blood products
transfusion; cardiovascular problems (hypotension, tachycardia, bradycardia, arrhythmia) and
use of cardio/vasoactive drugs;

- length of surgery;

- use of qualitative or quantitative (TOF Watch) neuromuscular transmission monitoring
systems use of neostigmine or sugammadex

- Final TOF ratio

In the postoperative section will be recorded the following data:

pain score at discharge from the operating room and up to the fifth postoperative day; needs
of blood products transfusion in the postoperative period; stay of nasogastric tube;

- stay of urinary catheter;

- postoperative respiratory complications;

- postoperative non-respiratory complications (cardiovascular, renal, surgical,
infections)

- needs of re-intubation in the postoperative period;

- needs of ventilatory support (non invasive ventilation, invasive ventilation) in the
postoperative period; needs of ICU admission (planned, unplanned, cause, length of ICU
stay); length of hospital stay; 30, 60 days and 1 year mortality (specify the cause).

STATISTICAL PLANS

Investigators are going to enroll 1500 patients undergoing elective major abdominal surgery,
in a period of 15 days. Investigator decided to enroll all the patients in a limited period
of time (as in LAS VEGAS [for more information...see www.euroanaesthesia.org., European
Society of Anesthesiology (ESA) Clinical Trial Network]) and, if the sample size will not be
sufficient, it will be possible to add 15 extra days. On the basis of works published by
Squadrone et. al.[11] (16%), Lawrence et.al. [17] (4,5%), Hall et. al. [18] (15%), Mitchell
et.al. [19] (11%) and Canet et. al. (7,2%) [10], the hypothesis was that the incidence of
primary outcome (PaO2 /FiO2≤ 300) will be 7%.

The sample size has been calculated using alpha = 0,05 (2-tailed test) and CI of 95%.

The result of this calculation is a sample size of 1422. Investigators decided to enroll
1500 patients because this way our population will be heterogeneous and because of possible
deviations from the protocol.

The statistic analysis will include:

- descriptive statistics of all the collected data (average, median, standard deviation,
interquartile range, minimum and maximum for the continuous variables; relative and
absolute frequency for the qualitative variables

- interdependence between two or more variables (if present)

- Statistic comparison between continuous variables, using t-Student test (if the
variable has a normal distribution) or non-parametric tests.

- Comparison between qualitative variables, using Chi-square test

- Odds ratio

- Logistic regression

- The study will include the possibility to perform non-planned analyses, if useful.

The data will be saved on an electronic support, using the Softwares Epi info 2002 (CDC),
SPSS11.0 (SPSS) and STATA 9.0 (STATA), when appropriate.