Protocol-directed Weaning From Mechanical Ventilation in Neurological Patients: a Controlled Trial
Phase: NA
Conditions: Neurological Diseases or Conditions
Sponsor: Hospital General Universitario de Castellón

Weaning From Mechanical Ventilation in Neurological Patients 
NCT03128086 
Date: March 3, 2017
INTRODUCTION
A  high  percentage  of  patients  with  acute  neurological  disease  require  invasive
mechanical ventilation (MV) to isolate the airway, to provide adequate oxygenation and to
prevent aspiration of gastric content (1-3). During weaning from MV, a spontaneous breathing
trial (SBT) is realized before extubation in order to assess patient's capacity to breath (4-6),
and  reducing the  risk  of extubation failure.  The  extubation failure  is  associated  with  a
prolonged length of stay in the intensive care unit (ICU) and in the hospital, as well as, more
risk of infections and higher mortality (7). In neurological patients, a successful SBT can not
predict exactly the success of extubation (8-10). It is necessary both the assessment of muscle
strength and the ability to keep the airway clearance capacity to ensure success of extubation
(8-15).
The results obtained with the application of weaning protocols in neurological patients
are not conclusive (16), with the exception of one clinical trial (17). A meta-analysis concluded
that the establishment of weaning protocols in subjects in a medical-surgical unit reduced the
duration of MV by 25%, weaning time by 78% and ICU stay by 10%.  These results support the
use of weaning protocols in patients undergoing MV (18).
In this study we try to demonstrate that the use of a protocol-directed weaning in
neurological patients will reduce the rate of extubation failure and associated complications.
The primary objective is to reduce the failure rate of extubation. As secondary objectives we
are going to analyse the incidence of infections, need for tracheostomy, duration of MV, length
of ICU and hospital stay, and mortality at ICU, hospital and 90 days.
MATERIAL AND METHODS
A prospective interventionist no randomized  study will be conducted in a medical-
surgical ICU. Patients 18 years or older with acute medical or surgical neurological disease
[acute ischaemic or haemorrhagic stroke, acute subarachnoid haemorrhage, traumatic brain
trauma, metabolic encephalopathy (toxic, infectious as encephalitis or meningitis), scheduled
neurosurgical surgery with a prolonged MV, and status epileptics], will be included. Exclusion
Criteria: scheduled neurosurgical surgery (duration of MV <24 hours), neuromuscular disease,
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spinal  cord  injury,  tracheostomized,  inability  to  be  evaluated,  severe  multiple  traumatic
injuries evaluated by the Injury Severity Score (19), direct extubation and self-extubation,
patients who died during their ICU stay (without a trail of weaning), and patients transferred
to another hospital. 
At ICU admission, the following variables will be collected: age, sex, body mass index,
comorbidities, prognosis severity scale by Simplified Acute Physiological Score (SAPS) 3,
Organ failure by Sequential Organ Failure Assessment (SOFA) (at ICU admission and 5 days
after admission), reason for MV, the level of consciousness by Glasgow Coma Scale (GCS) at the
time  of  intubation  and  where  it  was  performed.  During  the  ICU  stay,  all  neurological
treatments  and  procedures  such  as  treatment  of  intracranial  hypertension  (manitol  or
hypertonic  saline,  hyperventilation,  decompressed  craniotomy),  cranial  tomography  (CT)
scanner, external ventricular drainage, intracranial pressure sensor, cerebral arteriography,
will  be  collected.  The  infectious  complications  (ventilator-associated  pneumonia,
tracheobronchitis, urinary tract infection, bacteraemia,) will be registered during the ICU stay. 
To be included into study, subject  undergoing mechanical ventilation will meet the
following conditions:  no  or  minimal  sedation (propofol≤1mg/kg/h o  midazolam≤0,1mg/
kg/h), with spontaneous ventilatory stimulus, absence of intracranial hypertension, Glasgow
Coma  Score  (GCS)>  9  (motor>  4  points),  noradrenaline  ≤ 0,2mcgr/kg/min,  (fraction  of
inspired  oxygen)FiO2  ≤ 0.5  (positive  end-expiratory  pressure)  PEEP  of  5cmH20,  no
intervention scheduled in the next 48 hours, maximal inspiratory pressure (MIP)< -20cmH20
(20), occlusion pressure (P0.1) >6mmHg with support pressure of 7cmH20 and 0 cmH20 of
positive end-expiratory pressure (Z-PEEP). 
Protocol study (study group). The subject will be connected to MV in a pressure support
ventilation (PSV) mode, which will be gradually reduced (until a level de pressure support of
10 cmH20 above 5 cmH20 of PEEP). After, the subject will be disconnected from the ventilator
and a SBT will begin through the connexion of the subject to a T-tube and a source of oxygen
(21).  Haemodynamic  parameters  [systolic  blood  pressure  (SBP),  heart  rate  (HR)],  and
respiratory parameters [respiratory rate (RR), partial pressure of carbon dioxide (paCO2),
partial pressure of oxygen to fraction of inspired oxygen ratio (paO2/FiO2), and pH through
blood  gas  analysis  and  saturation  of  oxyhemoglobin  (SaO2)  by  pulse  oximetry],  and
neurological parameters (means by GCS) will be collected during final period of pressure
support ventilation (before disconnection) and at onset (5 minutes) and final (between 30 to
120 minutes) of SBT (22). A once daily SBT will be established in all the subjects until they
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were  extubated.  A  failure  SBT will  be  considered  with more  than 2  criteria:  paO2<50-
60mmHg with FiO2 ≤ 0.5 (or SaO2 <90%), paCO2 > 50 mmHg, pH <7.35, RR > 35bpm, HR >
140 bpm, SBP > 180mmHg, cardiac arrhythmias during SBT, dyspnea, and increased use of
accessory muscles (6). If the SBT fails, the subject will reconnect to MV. A successful SBT is
defined  as  absence  of  whatever  of  variables  above  defined.  Airway  clearance  capacity.
Otherwise, if the SBT is successful, the ability to maintain airway will be analysed by the
following variables: Number of aspirations of secretions/8-h nursing shift (No pass-0, 1 pass-
1, 2 passes-2, ≥ 3 passes-3), cough capacity (strong -0, mild-1, weak-2, absent-3), appearance
of secretions [viscosity (liquid-0, frothy-1, thick-2, dry-3) and colour of secretions (clear- 0,
brown- 1, yellow-2, green-3), and finally, the presence of gag reflex (strong- 0, moderate- 1,
weak- 2, absent- 3). A score ≤8 was considered as adequate to keep the permeability of airway
(4). Then the subject will be extubated and connected to venturi mask with FiO2 of 0.4. In case
of extubation failure, the patient will be reintubated. The use of non-invasive ventilation is not
considered in this study (neither prevention of extubation failure nor in case of extubation
failure).
Conventional weaning (control group). Subjects in the control group will receive weaning
from MV according to the usual procedure, by reducing level of PSV. Then a SBT will be
performed through a T-tube (the same parameters as protocol study will be collected) and
subsequent extubation of the patient if there is a successful SBT. The criteria for SBT and for
extubation failure are the same than in the study group. In case of extubation failure, non-
invasive ventilation will be not considered, but it left to the discretion of the attending
physician.
STATISTIC ANALYSIS. Based upon previous results (10), the authors considered that the need
for an intubation could be reduced by 13% (6) [26% in the control group vs. 13% in the study
group]. The estimated sample size was 109 patients in each group (confidence interval [1-α] =
95% (P=0.05) and power [1-β] = 80%). A comparative analysis was conducted by using the
Student's t-test or the Mann-Whitney test for a comparison of the quantitative variables for
the parametric and non-parametric characteristics, respectively. For the qualitative variables,
we used the Chi-Square statistic or Fisher's exact test. A statistical significance was reached if
P<0.05.  The  cumulative  probability  of  survival  was  compared  by  using  a  Kaplan-Meier
estimation of survival and a Log-Rank Test to compare both of the groups. Intention-to-treat
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analysis will be realized. The data will be analysed with the aid of the statistical package SPSS
22.0. 
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