Clinical trial NCT01701908: Postoperative Pulmonary Complications in Major Abdominal Surgery
Official title: Postoperative Pulmonary Complications in Major Abdominal Surgery: a Multicenter Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postoperative Pulmonary Complications
Keywords: PPCs
abdominal surgery
postoperative infections
postoperative residual curarization
tracheal re-intubation
mortality
ICU stay
Lead sponsor: University of Udine
Sponsor class: OTHER
First posted: 2012-10-05
Enrollment: 1542
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1500 patients undergoing elective major abdominal surgery, urologic surgery or major gynecological surgery under general anaesthesia.

Brief summary: Incidence of Postoperative Pulmonary Complications (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 to reintubate. Moreover the evaluation of risk factors has become difficult.

The endpoint of this study is to determine the actual incidence of respiratory postoperative complications in patients undergoing general anesthesia for major abdominal surgery (general surgery, gynecology, urology).

This is an observational, descriptive, prospective, multicentric study. Investigators are going to enroll all the patients matching the inclusion criteria and follow them until discharge (clinical phase). Then they will be followed up until one year later.

Detailed description: 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 elective general anesthesia for major abdominal surgery (general surgery, urology, gynecology).

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

SECONDARY END POINTS

To determine:

* postoperative pulmonary complications rate in general, gynecology and urology
* length of hospital stay
* unplanned postoperative Intensive care unit (ICU) admission and ICU length of stay
* postoperative incidence of tracheal reintubation
* postoperative incidence of infections
* postoperative incidence of PostOperative Residual Curarization (PORC)
* postoperative incidence of cardiovascular complications
* postoperative mortality (in-hospital, 30, 60 days and one year later)

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 and on the day of hospital discharge) 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..

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.

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; history of alcohol abuse; 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. 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 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 and analyzed with SPSS.

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 18 years
* Ability to provide informed consent
* Elective surgery
* Laparotomic or laparoscopic major abdominal surgery
* Major urological surgery (performed under general anesthesia)
* Major gynecological surgery (performed under general anesthesia)

Exclusion Criteria:

* Patients undergoing urgent or emergent surgery
* Patients undergoing: vascular, thoracic ,cardiac surgery, neurosurgery, obstetrics procedures and transplantation surgery
* Patients with chronic neuro-muscular junction disorders
* Immunocompromised or immunodepressed patients
* Patients with chronic or acute respiratory disease (acute respiratory infection, bronchial asthma, chronic obstructive pulmonary disease, sleep apnea syndrome)
* Patients with preoperative mechanical ventilation
* Patients with preoperative SpO2 \<90%, PaO2 \<60 mmHg (FiO2 0.21), or a PaO2/FiO2 ratio \<300, or PaCO2 \>45 mmHg.

Primary outcomes:
measure: Postoperative pulmonary complications rate
timeFrame: From surgery to hospital discharge (an average of 10 days)
Secondary outcomes:
measure: Postoperative pulmonary complications rate in general, gynecology and urology
timeFrame: From surgery to hospital discharge (an average of 10 days)
measure: Mortality rate after surgery
timeFrame: Up to 1 year after surgery
measure: Length of hospital stay
timeFrame: From surgery to hospital discharge (an average of 10 days)
measure: Unplanned postoperative Intensive care unit (ICU) admission
timeFrame: From surgery to hospital discharge (an average of 10 days)
measure: Intensive care unit length of stay
timeFrame: From surgery to hospital discharge (an average of 10 days)
measure: Postoperative incidence of tracheal re-intubation
timeFrame: From surgery to hospital discharge (an average of 10 days)
measure: Postoperative incidence of infections
timeFrame: From surgery to hospital discharge (an average of 10 days)
measure: Postoperative incidence of cardiovascular complications
timeFrame: From surgery to hospital discharge (an average of 10 days)
measure: Postoperative incidence of PostOperative Residual Curarization (PORC)
timeFrame: Up to 3 hours after extubation
Other outcomes:
Locations:
city: Ostia
country: Italy
facility: Ospedale Grassi
state: Rome
city: Candiolo
country: Italy
facility: Istituto di Candiolo
state: Torino
city: Montebelluna
country: Italy
facility: S. Valentino Hospital
state: Treviso
city: Udine
country: Italy
facility: AO Santa Maria della Misericordia
state: UD
city: Bussolengo
country: Italy
facility: University of Verona
state: Verona
city: Ancona
country: Italy
facility: Ospedali Riuniti
city: Asti
country: Italy
facility: Cardinal Massaia Hospital
city: Aviano
country: Italy
facility: Irccs Cro
city: Bari
country: Italy
facility: Policlinico di Bari Ospedale Giovanni XXIII
city: Benevento
country: Italy
facility: Ospedale Rummo
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Bologna
country: Italy
facility: S.Orsola-Malpighi Hospital
city: Brescia
country: Italy
facility: Spedali Civili
city: Camaiore
country: Italy
facility: Ospedale Versilia
city: Como
country: Italy
facility: ASST Lariana
city: Cremona
country: Italy
facility: ASST Cremona
city: Cuneo
country: Italy
facility: ASO S Croce e Carle
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria
city: Firenze
country: Italy
facility: Mugello Hospital
city: Firenze
country: Italy
facility: S. Maria Nuova Hospital
city: Foggia
country: Italy
facility: University of Foggia
city: Frosinone
country: Italy
facility: Presidio Ospedaliero Sora
city: Genova
country: Italy
facility: IRCCS San Martino
city: Lecce
country: Italy
facility: Fazzi Hospital
city: Macerata
country: Italy
facility: Ospedale Provinciale di Macerata
city: Milano
country: Italy
facility: IRCCS S. Raffaele, Milano
city: Milan
country: Italy
facility: IRCCS Fondazione Istituto Nazionale dei Tumori
city: Naples
country: Italy
facility: Azienda Ospedaliero Universitaria Vanvitelli
city: Naples
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Naples
country: Italy
facility: Ospedale Monaldi
city: Napoli
country: Italy
facility: Federico II Hospital
city: Pisa
country: Italy
facility: Nuovo Santa Chiara Hospital
city: Potenza
country: Italy
facility: Irccs Cro
city: Reggio Emilia
country: Italy
facility: Azienda USL IRCCS
city: Rome
country: Italy
facility: Umberto I, "Sapienza", University of Rome
city: Rome
country: Italy
facility: Catholic University Hospital A. Gemelli
city: Rome
country: Italy
facility: Campus Bio-medico Foundation
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Trento
country: Italy
facility: Ospedale S Chiara
city: Vicenza
country: Italy
facility: OC San Bortolo
Study officials:
affiliation: University of Udine
name: Giorgio Della Rocca, Professor
role: PRINCIPAL_INVESTIGATOR
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