Scienze mediche

Curriculum Vitae
Parte I - Informazioni generali
Nome e Cognome Luigi Tritapepe
Data di nascita 06 marzo 1959
Luogo di nascita Roma
Cittadinanza Italiana
residenza fissa via del Pigneto 110 D, 00176 Roma
Numero di telefono cellulare 3391748348
E-mail luigi.tritapepe@uniroma1.it, luigitritapepe@gmail.com
Lingue parlate italiano, inglese (upper intermediate level at British Council School)
Parte II - Educazione
Tipo: Laurea in Medicina e Chirurgia
Anno: 1985
Università di laurea: Università degli Studi “La Sapienza” di Roma
Voto di laurea 110/110 e lode
Post-laurea
specialità: Anestesia e Rianimazione
Anno 1988
Università di specializzazione: Università degli Studi “La Sapienza” di Roma
voto di specializzazione 70/70 e lode
Parte III - Incarichi accademici
Risultato idoneo nella VALUTAZIONE COMPARATIVA PER LA COPERTURA DI N. 1 POSTO DI PROFESSORE UNIVERSITARIO DI RUOLO FASCIA
DEGLI ASSOCIATI PER IL SETTORE SCIENTIFICO-DISCIPLINARE F21 X PRESSO LA FACOLTA' DI MEDICINA E CHIRURGIA DELL'UNIVERSITA'
DI ROMA “TOR VERGATA”
(Bandita con D.R. del 20/04/01 il cui avviso è stato pubblicato sulla G.U. n. 34 del 27/04/01).
01/01/2005 Chiamata in ruolo come Professore Associato non confermato per il settore scientifico disciplinare MED/41 “Anestesiologia” presso la 1^ Facoltà di
Medicina e Chirurgia dell'Università degli Studi “La Sapienza”
01/01/2008 nominato Professore Associato Confermato per il settore scientifico disciplinare MED/41 “Anestesiologia” presso la 1^ Facoltà di Medicina e Chirurgia
dell'Università degli Studi “La Sapienza”
04/01/2014 Risultato idoneo in prima fascia per il settore scientifico disciplinare all'abilitazione nazionale ANVUR 2012 06/L1 (id. 2983)
Papers 103
Libri [scientifico] 14
Impact Factor totale 352,73
Citazioni totali 1385
H index 22
Reviewer delle seguenti riviste:
Critical Care Medicine, Intensive Care Medicine, Minerva Anestesiologica, Medical Science Monitor, American Journal of Respiratory and Critical Care Medicine,
Perfusion, International Journal of Cardiology, Journal of anesthesiology

Progetti di Ricerca Piccoli : 262 progetti finanziati da 4.000 a 5.000 euro

Approximately 230 million surgical procedures are carried out worldwide each year. After surgery more than seven million patients develop complications with one million deaths.1 Estimates of postoperative mortality range from 1 to 4% depending on the population sampled and the type of surgical procedure. However, it is clear that mortality and morbidity following surgery is greater in high-risk cohorts, where patients have pre-existing medical conditions, are elderly or undergoing a major abdominal procedure, for example surgery to gastrointestinal tract. The lasting impact of postoperative morbidity should not be underestimated, since complications following surgery are associated with reduced long-term survival. Some of the most common postoperative complications affect the respiratory tract. The published incidence of postoperative pulmonary complications ranges from 9 to 40%, depending on the definition used. Major abdominal surgery is associated with significant adverse changes in respiratory function. Anaesthesia can cause reduced vital capacity, hypoxaemia and impair central respiratory drive, while surgical manipulation can restrict ventilation, damage the respiratory muscles and cause atelectasis. These factors interact with pre-existing respiratory disease and postoperative pain to create a significant risk of pneumonia and respiratory failure, which may result in death. Continuous positive airway pressure (CPAP) is a non-invasive method of supporting the respiratory function. The patient breathes through a pressurized circuit against a threshold resistor that maintains a pre-set positive airway pressure during both inspiration and expiration. It is delivered via a facemask, helmet or nasal device by experienced nurses with minimal physician supervision. CPAP is often provided in specialist areas of a hospital such as the intensive care unit due to the benefit of increased staff numbers.

The findings of several trials have demonstrated the efficacy of CPAP as a preventative treatment for high-risk patients following abdominal surgery by reducing the incidence postoperative pulmonary complications. This is supported by evidence from systematic review (figure 1).
However, the current evidence base for postoperative CPAP has a number of limitations. Firstly, all of the previous randomised trials have been relatively small (n<250) and therefore lacking in statistical power for patient centered outcomes. Whilst the results of these trials suggest that postoperative CPAP is efficacious, there has yet to be a large multi-centre trial to evaluate clinical effectiveness. Secondly, whilst the several trials of CPAP in the abdominal surgery population have shown encouraging results, there has been limited translation to clinical practice. A robust evidence base is needed to justify the changes needed in the perioperative care pathway, and as a result the preventive use of CPAP after major abdominal surgery has not been introduced into routine practice in most healthcare systems. There is a clear need for a major randomized trial to provide definitive evidence to address this uncertainty.
Current evidence suggests that the routine use of postoperative CPAP is an efficacious preventative treatment that can reduce postoperative respiratory complications. However, evidence of clinical effectiveness is lacking. In particular postoperative CPAP needs to be studied in the context of routine clinical care with reference to patient-centred outcomes. We propose a large, pragmatic, international multi-centre trial to confirm the clinical effectiveness of CPAP administered as routine for four hours immediately following major abdominal surgery, compared to usual clinical care.

TRIAL OBJECTIVES

5.1 Primary Objective
To determine whether postoperative continuous positive airway pressure (CPAP) reduces the incidence of pneumonia, re-intubation or death following major elective intra-peritoneal surgery compared to usual care in patients aged 50 years and over.

5.2 Primary outcome measure
Composite endpoint of pneumonia, endotracheal re-intubation or death within 30 days of the end of surgery (Appendix 1).

5.3 Secondary objectives
To determine whether routine postoperative CPAP reduces other forms of postoperative morbidity, mortality, or improves quality of life.

5.4 Secondary outcome measures
• Postoperative infection within 30 days of surgery
• Mechanical ventilation (invasive or non-invasive) within 30 days of surgery
• 30-day re-admission
• Days in critical care
• Duration of hospital stay
• All-cause mortality at 180 days following surgery
• Quality adjusted life years (QALY) at 180 days following surgery

5.5 Tertiary objectives
To determine the safety and tolerability of routine postoperative CPAP.

5.6 Tertiary outcome measures
The following pre-defined adverse events will be used as safety endpoints to quantify harm associated with during CPAP (Appendix 1):
• Interface intolerance due to excessive air leaks
• Skin lesions at the site of skin-interface contact
• Claustrophobia
• CO2 re-breathing

• Facial pain
• Oro-nasal dryness
• Other harm assessed as probably or definitely related to CPAP

6. METHODOLOGY

6.1 Study design
International, multi-centre randomised controlled trial with open study group allocation.

6.2 Inclusion criteria
• Patients aged 50 years or over undergoing major, open, intra-peritoneal surgery.

6.3 Exclusion criteria
• Inability or refusal to provide informed consent
• Anticipated requirement for invasive or non-invasive mechanical ventilation for at least four hours after surgery as part of routine care
• Pregnancy or obstetric surgery
• Previous enrollment in PRISM trial
• Participation in a clinical trial of a treatment with a similar biological mechanism or related primary outcome measure
 
STUDY PROCEDURES

7.1 Recruitment and screening
Patients will be identified and approached by a member of the research team before surgery. Potential participants will be screened by research staff at the site having been identified from pre-admission clinic lists, operating theatre lists and by communication with the relevant nursing and medical staff. Wherever possible, the patient will be approached at least 24 hours prior to surgery to allow time for any questions. However, by the nature of the inclusion criteria for this trial, many patients will arrive in hospital on the morning of surgery. Provided that all reasonable efforts have been made to identify a potential participant 24 hours in advance of surgery, they will still be eligible for recruitment within a shorter time frame if this has not proved possible. Written informed consent must be obtained before surgery.

7.2 Informed consent
It is the responsibility of the Principal Investigator (PI) at each site, or persons delegated by the PI to obtain written informed consent from each subject prior to participation in this trial. This process will include provision of a patient information sheet accompanied by the relevant consent form, and an explanation of the aims, methods, anticipated benefits and potential hazards of the trial. The PI or designee will explain to all potential participants that they are free to refuse to enter the trial or to withdraw at any time during the trial, for any reason. If new safety information results in significant changes in the risk/benefit assessment, the patient information sheet and consent form will be reviewed and updated if necessary. However, given the short duration of the intervention period, it is most unlikely that new safety information would come to light during the intervention period of an individual patient. Patients who lack capacity to give or withhold informed consent will not be recruited. Patients who are not entered into this trial should be recorded (including reason not entered) on the patient-screening log in the PRISM Investigator Site File.

7.3 Randomisation
Randomisation will occur after the participant has provided informed consent but before the surgical procedure is due to start. Participants will be centrally allocated to treatment groups (1:1) by a computer generated dynamic procedure (minimisation) with a random component. Minimisation will be performed on trial centre and surgical
procedure category. Each participant will be allocated with 80% probability to the group that minimises between group differences in these factors among all participants recruited to the trial to date, and to the alternative group with 20% probability. To enter a patient into the PRISM trial, research staff at the site will log on to a secure web-based randomisation and data entry platform hosted by Queen Mary University of London and complete the patient’s details to obtain a unique patient identification number and allocation to a treatment group.

7.4 Trial Intervention
The trial intervention period will commence immediately after the completion of surgery and continue for at least four hours. After four hours, CPAP will be continued or discontinued at the clinician’s discretion.

Intervention group
The trial intervention is defined as CPAP for at least four hours, with minimal interruption, started immediately after the patient has left the operating room following surgery. Administration of CPAP will only take place under the direct supervision of appropriately trained staff in an adequately equipped clinical area. The monitoring of patients receiving CPAP will be in accordance with local hospital policy or guidelines for the use of CPAP. Alterations to the administered dose will be recorded along with the reason for this change. Clinicians may choose from a range of CPAP machines to deliver the intervention. However, the minimum airway pressure should be 5cmH2O. Nasal high flow oxygen is not considered CPAP. It is foreseeable that some patients in the intervention group will not receive CPAP or fail to complete the minimum four hours of CPAP, for example due to unplanned invasive or non-invasive ventilation after surgery or because the patient is unable to tolerate the CPAP mask. These situations will be managed as protocol deviations and follow-up data will still be collected. Please see section 7.9 for further details.
Usual care group
Patients in the usual care group will be managed by clinical staff according to local policy and guidelines. It is considered good practice for postoperative patients to receive oxygen via a facemask or nasal cannulae. However, this may vary according
to local policy. It is foreseeable that some patients in the usual care group could receive CPAP as part of usual care. This will be managed as a protocol deviation and follow-up data will still be collected. Please see section 7.9 for further details.
7.5 Intervention Algorithm
This algorithm illustrates the steps for delivering postoperative CPAP to patients in the intervention group. Patients in the usual care group will receive postoperative care according to local guidelines. Further details are listed in the CPAP SOP.

7.6 Procedures to minimise bias
PRISM is a pragmatic clinical effectiveness trial of a treatment algorithm. It is not possible to conceal treatment allocation from all staff in trials of this type. However, procedures will be put in place to minimise the possibility of bias arising because research staff become aware of trial group allocation. Patients will be followed up for complications by a member of research staff who is unaware of trial group allocation. Complications will then be verified by the local PI or designee who will also be unaware of trial group allocation. The local principal investigator may nominate a senior clinician to assist with this task if he/she becomes aware of the trial group allocation of any individual patient. Research staff will be asked to confirm whether these procedures have been complied with. The decision to admit a trial participant to a critical care unit will be made by clinical staff and this decision must not be affected by trial group allocation.

7.7 Data Collection

Data will be collected before and after the trial intervention.

Randomisation data
• Checklist to ensure the patient meets the eligibility criteria
• Surgical procedure category
• Centre ID

Baseline data
• Full name
• Gender
• Age/DOB
• ASA grade
• Planned surgical procedure
• Diagnosis of chronic lung disease
• Diagnosis of ischaemic heart disease
• Diagnosis of diabetes
• Diagnosis of stroke
• Diagnosis of heart failure
• Diagnosis of cirrhosis
• Preoperative haemoglobin
• Preoperative creatinine
• Quality of life according to EQ-5D
• Height
• Weight
• NHS number or corresponding patient identifier for database follow-up
• Residential postcode or corresponding patient identifier for database follow-up

Intraoperative period
• Surgical procedure category
• Open or laparoscopic technique
• Anaesthetic technique (general, spinal, regional)
• Mechanical ventilation Y/N
o Duration
o Maximum PEEP
o Maximum Vt
• Extubated at the end of surgery Y/N

24 hours postoperative
• Patient received CPAP within 12 hours of surgery? (Y/N)
o Total duration of CPAP within 12 hours of surgery
o CPAP started within 1 hour of patient leaving operating room? (Y/N)
o Starting CPAP airway pressure
o Delivery method (mask, nasal, helmet)
o Maximum airway pressure
• Additional research staff present to help deliver CPAP (Y/N)
• Were tools used to monitor CPAP and inspiratory oxygen fraction? (Y/N)
• Adverse events during CPAP
o Excessive air leaks (Y/N)
o Pain (mild/moderate/severe)
o Cutaneous pressure sore/area (Waterlow grade I-IV12)
o Claustrophobia (mild/moderate/severe)
o Oronasal dryness (mild/moderate/severe)
o Hypercapnia (mild/moderate/severe and peak PCO2)
o Haemodynamic instability (Y/N)

Clinical outcomes within 30 days of randomisation
• Pneumonia (date & time)
• Re-intubation (date & time)
• Death (date)
• Mechanical ventilation (date & time)
• Quality of life according to EQ5D

Health economic outcomes
• Duration of primary hospital stay (not including re-admission)
• Days in critical care during the first 30 days after index surgical procedure

Clinical outcomes within 180 days of randomisation
• Death (date)
• Quality of life according to EQ5D

7.8 Predefined protocol deviations
• Failure to administer CPAP to patients in the intervention group. This includes patients that unexpectedly remain intubated after surgery
• Starting CPAP at a dose other than 5cmH2O
• Administration of CPAP to a patient in usual care group.
• Administration of CPAP for less than 4 hours or with significant interruption for a patient in the intervention group. Brief interruptions to CPAP to adjust mask, for oral care or routine nursing care are considered part of the intervention. However, if the interruption is prolonged this should be consider a protocol deviation.
7.9 Follow-up procedures
To minimise bias, follow-up data will be collected by an investigator who is unaware of the study group allocation. Investigators will review a participant’s medical record (paper or electronic) and contact participants on the telephone to conduct brief interviews at 30 days and 180 days after surgery.
7.10 Withdrawal of participants
All study participants are free to withdraw from the study at any time. All randomised patients will be included in the final analysis on an intention to treat basis, unless a participant specifically asks for their data not to be included.

7.11 Self-assessment of blinding by research staff
Research staff will complete a self-assessment to allow us to report the effectiveness of blinding procedures during the trial. They will grade themselves as one of the following options:
• Suitably blinded
• May have known study group allocation
• Definitely knew study group allocation

7.12 End of study definition
The end of the study is defined as the point when the last patient has completed 180-day telephone follow-up. An interim analysis will be performed at a pre-defined point by the data monitoring and ethics committee (DMEC). Early termination of the study on safety grounds will be addressed via the DMEC. They will report any concerns to the Chief Investigator, who will inform the Sponsor and take appropriate action, which may include stopping the trial, to address concerns about participant safety. The Research Ethics Committee will be informed in writing if the trial is suspended or terminated early.