Principal investigator: Rafael Fernandez Fernandez*
Hospital Sant Joan de Dèu-Fundació Althaia Manresa.
Coordinator: Maria del Mar Fernandez Fernandez.
Hospital Universitari Mútua de Terrassa.
Collaborator investigators: ANNEX 1
* Fundació Althaia Xarxa Assistencial
Address: C/ Dr Joan Soler, 1. Manresa, Spain.
Telf: +34 619835178.
E-mail:
1.- INTRODUCTION:
To avoid complications, patients should be weaned from mechanical ventilation as soon as possible. However, it is difficult to predict whether weaning will be successful, even when criteria such as minute ventilation, negative inspiratory force, inspiratory pressure/maximal inspiratory pressure ratio, and work of breathing are taken into account.1, 2, 3,4 Spontaneous breathing trials are used to assess readiness for disconnection from mechanical ventilation, but it is difficult to choose the best time to perform these trials, although an international consensus panel stated several minimum conditions.5,6 Nevertheless, these criteria are far from ideal; extubation failure is common, and 5% to 20% of patients require reintubation.7,8 Moreover, the rates of intensive care unit (ICU) and hospital mortality are higher in patients who need reintubation.9,10
Attempts to ascertain the effects of different approaches to spontaneous breathing trials (e.g., using different durations and different levels of patient effort) on weaning outcome have yielded inconclusive results.11 Very demanding tests may better identify patients who will be successfully weaned, but can induce fatigue in very sick patients and thereby preclude extubation. The impact of periextubation respiratory muscle fatigue on weaning is unclear. The incidence of respiratory muscle weakness in critically ill patients varies widely depending on case-mix; treatment with steroids and muscle relaxants favor weakness, and early mobilization of mechanically ventilated patients may mitigate weakness.12
Respiratory muscles can develop high-frequency or low-frequency contractile fatigue (also known as short-lasting and long-lasting fatigue, respectively). Patients can recover from high-frequency fatigue in 10 to 15 minutes; however, low-frequency fatigue can persist for more than 24 hours, suggesting that the diaphragm could need more than 24h to recover after an overwhelming effort.13 More relevant factors for weaning failure are worse pulmonary mechanics, poor nutritional status, duration of sedative and muscle relaxant administration, humidification of respiratory secretions, early physiotherapy, and ventilatory mode.
Given that most ICU patients have some degree of weakness, the increased work of breathing caused by the endotracheal tube during spontaneous breathing trials may be excessive for some patients, and a period of rest after a spontaneous breathing trial and before extubation may be advisable.7,8,9,15
Most studies extubated patients immediately after successful spontaneous breathing trials, but some studies reconnected patients to the ventilator for variable intervals before proceeding to extubation. In one study by Ely et al.,9 respiratory therapists performed spontaneous breathing trials and then reconnected patients to mechanical ventilation, reporting to attending physicians about weanability; this protocol inadvertently enabled patients to rest for some hours before extubation. In two other studies, investigators reconnected patients to the ventilator for up to 25 minutes to see whether minute ventilation was a predictor of extubation outcome after successful spontaneous breathing trials7,8.
We hypothesized that resting after the effort of SBT would reduce extubation failure and reintubation.
Suitability of the teams, ICUs and hospitals: This study will be performed in different Spanish ICUs that have been participated in other studies about mechanical ventilation. The principal investigator and the coordinator hadve a wideextensive research experience in investigation the field.
2. OBJECTIVE:
Primary objective: reduction of extubation failure rate and reduction of the reintubation rate.
Secondary objectives: ICU mortality, hospital mortality, ICU length of stay and hospital length of stay.
3. STUDY DESIGN:
A multicenter randomiszed and controlled multicenter trial hasve been designed. Patients will be randomized to divide those patients who alter after succeeding passing a spontaneous breathing trial (SBT) to (a) be extubated as usual or (b) being reconnecteding to mechanical ventilation with the same ventilatory parameters for an hour and after being extubated without a new SBT.
For Due to the study technical characteristics of the study, it cannot be blinded; therefore, so the study investigators will be excluded of from clinical decisions.
4. STUDY POPULATION:
Inclusion criteria
We will screened patients deemed ready for an SBT spontaneous breathing trial after at least 12 hours of mechanical ventilation. The SBT could can be done withbe T-tube, pressure support, or continuous positive airway pressure (CPAP).
Exclusion criteria:
Age <18 y, tracheostomy, excessive respiratory secretions (requiring >2 suctionings in the last 8 h), lack of cooperation, do-not-resuscitate or do-not-reintubate orders, out-of-protocol extubation, participation in other trials. We will also excluded patients in whom postextubation noninvasive ventilation was is recommended (mainly due to hypercapnia during the spontaneous breathing trial).
A successful spontaneous breathing trial was is defined by international guidelines6 as correct gas exchange (SpO2 85%–90%; PaO2 50–60 mmHg; pH> 7.32; increase in PaCO2 10 mmHg from basal); hemodynamic stability (heart rate < 120–140 beats/min; systolic blood pressure <180–200 mmHg and > 90 mmHg without vasopressors), and stable ventilatory pattern (respiratory rate <30–35 breaths/min and <150% from basal).
We will classifyied patients in two different populations according to their risk of extubation failure (high risk or low risk). Patients who meet any of the following criteria will beere considered high risk: age > 65 y, congestive heart failure as the reason for intubation, chronic obstructive pulmonary disease, APACHE II >12 on extubation day, body mass index >30, ineffective cough or copious respiratory secretions (>2 suctionings in the 8 h before extubation), > 1 failed SBT, > 1 comorbidity, and problems related with the upper airway (including intubation for >7 days). This is an important point because patients without extubation failure risk criteria have an extubation failure rate of 10% but if any of the previous factors is present this rate increases up tod as far as 30%.
Study protocol:
When the attending physician considers a patient is ready for weaning, informed consent will be asked to the same patient or to their authorized representatives will be asked to provide informed consent. The patient will be allocated in the high or low risk group for extubation failure in accordance to the criteria mentioned above. Then an opaque randomization opaque envelope will be opened and the instructions will be followed, the patient will be extubated (Control group) or reconnected to the ventilator for one hour with the same ventilatory parameters as before SBT, being extubated after this time without a new SBT (Rest group).
Each participating hospital will use its own weaning and physiotherapy protocols, so practices such as pre-oxygenation before extubation, suctioning secretions before and/or during cuff deflation, administering additional doses of bronchodilators, and supplying oxygen after extubation are not protocolized.
ECG, SpO2, respiratory frequency and arterial pressure will be continuously monitoreding. Blood analysis and respiratory physiotherapy (secretions mobilization …) would will be in accordance of each hospital protocol.
We do n’ot recommend the use of noninvasive ventilation in extubation failure even though it is not but we do not forbid itden.
Extubation failure criteria:
Extubation failure was will be defined as the appearance of two or more of the following criteria within 48 h: respiratory acidosis (arterial pH<7.32 with PaCO2 >45 mmHg), clinical signs of increased work of breathing (nasal flaring; vigorous activity of the sternomastoid muscles; tracheal tug; recession of the suprasternal, supraclavicular, and intercostal spaces; paradoxical motion of the abdomen; or paradoxical pulse), respiratory rate >35 breaths/min, SpO2 < 90% or PaO2 <60 mmHg with FiO2 ≥0.5, worsening level of consciousness (GCS ≤13), or out-of-control delirium.
Each participating hospital’s protocol will determined how extubation failure will be treated and whether rescue noninvasive mechanical ventilation will be employed. Reintubation will remain at the discretion of attending physicians. Successful Eextubation successful is will be defined as the maintenance of normal respiratory pattern without ventilatory support within for 48h after extubation. If the patient presentsed respiratory distress or needs to be reintubated after this 48h postextubation, we will consider that the cause for the reintubation is not related with the previous process. We will follow these patients until hospital discharge.
5. TREATMENT ASSIGNMENT:
The estimation of the sample size has been performed based on our experience, we expected a 25% extubation failure rate in the Control group, and we aimed to detect a 10% decrease (40% relative reduction) in the Rest group. This objective requiresd a sample of 219 patients in each group for an alpha error of 5% and a power (1-β) of 80%. Taking into account Estimating 5%missing cases, of 5% the total number of patients to be recruited is 462.
Randomization: Randomization was will be achieved via computerized random-number table in blocks of 4 for each hospital; allocation was will be concealed through numbered opaque envelopes categorized in high and low risk extubation failure patients.
6.- STATISTICAL ANALYSIS
Qualitative variables will be compared using Chi2 chi-square or Fisher’s exact tests. Normally distributed quantitative variables will be expressed as means with standard deviations and compared with Student’s t-test for independent samples. Non-normally distributed quantitative variables will be expressed as medians with 25% and 75% percentiles and will be compared with the Mann-Whitney U-test.
To identify factors independently related with postextubation respiratory failure and to control for confounding variables, we will construct a multivariable logistic regression model including the variables age, APACHE II score, reason for mechanical ventilation.
7. ETHICAL ASPECTS:
- This study protocol follows the principles outlined in the Declaration of Helsinki.
- Written informed consent will asked to the pPatients or to his/her family or to the legal representatives will be asked to provide informed consent.
- The ethics committees of at each hospital have to approve the study.
- The study data will be anonymous in accordance to the Spanish Law of Personal Data protection (LOPD).
When we have the approval of the first ethicsal committee the study will be registered in “ClinicalTrials.gov”.
References:
1.- MacIntyre NR, Cook DJ, Ely EW Jr, Epstein SK, Fink JB, Heffner JE, Hess D, Hubmayer RD, Scheinhorn DJ. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine. Chest 2001; 120(6 Suppl): 375S-95S.
2.- Ely EW, Meade MO, Haponik EF, Kollef MH, Cook DJ, Guyatt GH, Stoller JK. Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: evidence-based clinical practice guidelines. Chest 2001; 120(6 Suppl):454S-63S.
3.- MacIntyre N. Discontinuing mechanical ventilatory support. Chest 2007; 132: 1049-56.
4.- Frutos-Vivar F, Esteban A, Apezteguia C, González M, Arabi Y, Restrepo MI, Gordo F, Santos C, Alhashemi JA, Pérez F, Peñuelas O, Anzueto A. Outcome of reintubated patients after scheduled extubation. J Crit Care 2011; 26: 502-9.
5.- Esteban A, Alía I, Tobin MJ, Gil A, Gordo F, Vallverdú I, Blanch L, Bonet A, Vázquez A, de Pablo R, Torres A, de La Cal MA, Macías S. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1999; 159: 512-8.
6.- Esteban A, Alía I, Gordo F, Fernández R, Solsona JF, Vallverdú I, Macías S, Allegue JM, Blanco J, Carriedo D, León M, de la Cal MA, Taboada F, Gonzalez de Velasco J, Palazón E, Carrizosa F, Tomás R, Suarez J, Goldwasser RS. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1997; 156: 459-65.
7.- Martinez A, Seymour C, Nam M. Minute ventilation recovery time: a predictor of extubation outcome. Chest 2003; 123: 1214-21.
8.- Hernandez G, Fernandez R, Luzon E, Cuena R, Montejo JC. The early phase of the minute ventilation recovery curve predicts extubation failure better than the minute ventilation recovery time. Chest 2007; 131: 1315-22.
9.- Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335: 1864-9.
10.- Ferrer M, Sellarés J, Valencia M, Carrillo A, Gonzalez G, Badia JR, Nicolas JM, Torres A. Non-invasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomised controlled trial. Lancet 2009; 374: 1082-8.
- INFORMED CONSENT
- CRF
STUDY INFORMATION TO THE PATIENT OR PATIENT’S FAMILY
STUDY: RECONNECTION TO MECHANICAL VENTILATION FOR ONE HOUR AFTER A SUCCESSFUL SPONTANEOUS BREATHING TRIAL REDUCES REINTUBATION IN CRITICALLY ILL PATIENTS: A MULTICENTER RANDOMIZED CONTROLLED TRIAL
Promoter: Dr. Rafael Fernández Fernández, Intensive Care Department Chief, Hospital Sant Joan de Dèu (Fundació Althaia Xarxa Assistencial de Manresa) and principal study investigator.
A study in mechanical ventilated patients (with invasive mechanical ventilation) is being carriedying out in several Intensive Care Units in Spain when the patients is considereding ready to breathe spontaneously. After a successfully spontaneous breathing test we are testing if a period of rest before removeing the tube could be advisableis beneficial.
After a prolonged intubation time, when the respiratory assistance (the ventilator and the tracheal tube) is removed, it is possible that the patient don´t might not breathe comfortably and will need a new tube, reintubation,; this is what we called respiratory and extubation failure.
Trying to avoid this extubation failure, we usually perform a spontaneous breathing trial (SBT), which that it means that the patient breathes through the tube without the ventilatory machine or with less ventilatory support. If patient doesn’t complain and feels well, we remove the tube. This trial could identify those patients who are tired or fatigued, and we had have to reconnected them to the mechanical ventilatorion. Nevertheless, some patients (10%-20%) who are able to successfully complete this test but after the extubation they show respiratory distress after the extubation.