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Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children

  1. Louise Rose1,*,
  2. Marcus J Schultz2,
  3. Chris R Cardwell3,
  4. Philippe Jouvet4,
  5. Danny F McAuley5,6,
  6. Bronagh Blackwood7

Editorial Group: Cochrane Anaesthesia Group

Published Online: 6 JUN 2013

Assessed as up-to-date: 29 AUG 2012

DOI: 10.1002/14651858.CD009235.pub2


How to Cite

Rose L, Schultz MJ, Cardwell CR, Jouvet P, McAuley DF, Blackwood B. Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD009235. DOI: 10.1002/14651858.CD009235.pub2.

Author Information

  1. 1

    University of Toronto, Lawrence S. Bloomberg Faculty of Nursing, Toronto, ON, Canada

  2. 2

    Academic Medical Center, University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam, Netherlands

  3. 3

    Queen's University Belfast, Centre for Public Health, Belfast, Northern Ireland, UK

  4. 4

    Sainte-Justine Hospital, University of Montreal, Department of Pediatrics, Montreal, Quebec, Canada

  5. 5

    Queen's University of Belfast, Centre for Infection and Immunity, Belfast, Northern Ireland, UK

  6. 6

    Royal Victoria Hospital, Regional Intensive Care Unit, Belfast, UK

  7. 7

    Queen's University Belfast, School of Medicine, Dentistry & Biomedical Sciences, Belfast, Northern Ireland, UK

*Louise Rose, Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, 155 College St, Toronto, ON, M5T 1P8, Canada. louise.rose@utoronto.ca.

Publication History

  1. Publication Status: New
  2. Published Online: 6 JUN 2013

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Characteristics of included studies [ordered by study ID]
Davis 1989

MethodsSingle centre randomized controlled trial


Participants40 adult patients (intervention 22; control 18) ventilated for longer than 24 hours for acute respiratory failure due to pulmonary parenchymal and airway pathology. Respiratory failure was defined as PaO2 <8 kPa on 40% FiO2 or a PaCO2 >6. Patients with muscular weakness, asthma and respiratory centre depression due to head injury or overdose were excluded. Patients were randomized when fulfilled the following weaning criteria: haemodynamic stability, vital capacity >10ml/kg, respiratory rate <30/minute, PaO2>9kPa on not more than 40% FiO2 and 10 cmH2O of PEEP and a normal PaCO2.

Setting: South Africa, respiratory ICU.


InterventionsIntervention: Mandatory minute volume set at 75% of the ventilator minute volume prior to commencing weaning. Achieved by decreasing frequency to an appropriate reference value while maintaining the same tidal volume as the reference point.Weaning was considered complete after 4 hours of spontaneous breathing.

Control: Weaning commenced by decreasing the ventilator rate by two breaths per minute at 3-4 hourly intervals between 06:00 and 18:00 hours, to a rate of 4 breaths per minute. Following a 3-4 hour period of stability at this rate the ventilator was switched from IMV to CPAP. If initial weaning criteria were violated, the ventilator rate was returned to the previous setting. Weaning was considered complete after 4 hours of spontaneous breathing.


OutcomesWeaning success

Duration of successful wean

Frequency of arterial blood gas sampling

Number of ventilator adjustments


NotesDuration of weaning success: time from randomization to 4 hours of independent spontaneous breathing.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported.

Allocation concealment (selection bias)Unclear riskNot reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskAssumed as high risk due to the nature of the intervention

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Dongelmans 2009

MethodsSingle centre randomized controlled trial


Participants128 adults (intervention 64:control 64) ≥18 years of age after uncomplicated coronary artery bypass grafting without a history of pulmonary disease or haemodynamic instability. Excluded patients comprised those with pulmonary disease or history of pulmonary surgery, intraaortic balloon pump on admission to ICU, receiving inotropes and/pr vasopressors at a rate higher than usual (upper limits in milligrams per hour: dopamine 20, norepinephrine 0.5, dobutamine 25, and epinephrine at any rate).

Setting: The Netherlands, 28 bed ICU of academic medical centre. Staffing comprised 140 nurses, 8 full-time intensivists, 8 ICU fellows, and 10 residents of other specialties.


InterventionsIntervention: Adaptive Support Ventilation with the minute ventilation was set at 100% of the theoretical value based on predicted body weight, FiO2 of 50%, PEEP of 10 cmH2O (maintained constant for 4 hours after which it was set to 5cmH2O until extubation), maximum airway pressure of 35 cmH2O equivalent to an absolute Pinsp limit of 25cmH2O, flow trigger 2 L/s. Arterial blood gas (ABG) analysis was performed 30 minutes after connection to the ventilator. If the PaCO2 was <3.5 kPa or >5.5 kPa, minute ventilation was decreased or increased by 10%. Any modification of ventilator settings was followed after 30 minutes by an ABG. Extubation criteria included: responsive and cooperative, urine output >0.5 mL/kg/hr, chest drainage <100 mL last hour, no uncontrolled arrhythmia, rectal temperature >36.0C, respiratory frequency of 10-20 breaths/min without machine-controlled breaths, FiO2 40% and Pinsp 5-10 cmH2O for 30 minutes.

Control: Pressure Control Ventilation with VT of 6-8 mL/kg predicted body weight, respiratory rate of 12-15 breaths/min, FiO2, PEEP and flow trigger at same settings as ASV group. Respiratory rate was increased or decreased to satisfy ASV PaCO2 criteria on ABG taken 30 minutes after ventilation commenced. Any modification of ventilator settings was followed after 30 minutes by an ABG. When patients breathed spontaneously, the mode was switched to PSV set at 10 cmH2O, support was decreased to 5-10 cmH2O depending on VT. Extubation criteria were the same as ASV group.


OutcomesPrimary endpoint was time to tracheal extubation. Secondary endpoints were the duration of assisted ventilation as the proportion of the total duration of ventilation of MV and switches from controlled ventilation to assisted ventilation. Also studied ASV with respect to VT, airway pressures, respiratory rate, and ABG results.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAllocation in random order (author communication).

Allocation concealment (selection bias)Low riskOpaque, sealed envelopes used.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot possible due to nature of intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Hendrix 2006

MethodsSingle centre randomized controlled trial


Participants20 consecutive male adult patients undergoing coronary artery bypass grafting. Patients with a history of respiratory disease or FEV1 ≤ 70% were excluded from the study.

Setting: Germany, university hospital, cardiac surgery ICU.


InterventionsIntervention: After surgery, patients were admitted to the ICU and ventilated with the Siemens 300A/Automode ventilator set to pressure regulated volume control with VT of 10 mL/kg body weight, I:E time of 1:1, upper pressure limit of 30 cmH2O and Automode function on. Patients weaned and extubated according to standard criteria. After initial FiO2 weaning per protocol, all ventilator changes were automated (ventilator mode changes automatically from PRVC to VS when patient triggers the ventilator).

Control: Ventilated with conventional Siemens 300 ventilator using same ventilator settings as intervention group with the exception of Automode activation. Patients weaned and extubated according to same standard criteria as intervention group. When patients became fully alert, the ventilator mode was changed to CPAP with 10 cmH2O pressure support by the ICU nurse or physician).


OutcomesTime to extubation

Postoperative function of the cardiovascular system (cardiac index and mixed venous saturation)

Use of analgesic and sedative drugs

Adverse events including arrhythmias and blood loss

Pulmonary function testing five days postoperatively


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSequence generation described as "eligible patients were randomized in blocks of two prior to undergoing CABG. Only one single Automode ventilator was available for use. Thus, two patients undergoing surgery on the same day were randomized either to the Siemens 300 A/Automode ventilator (group A) or to the conventional Siemens 300 ventilator (group B) using slips of paper in a box technique which was our procedure to randomize patients. Once the Automode ventilator was again ready for use, two more patients could again be randomized".

It is unclear whether the 2 patients were randomly selected from the total number of CABG patients undergoing surgery that day (no response from author regarding clarification of this issue).

Allocation concealment (selection bias)Unclear riskIt is unclear if the writing on the slips of paper were visible to the person selecting them (no response from author regarding clarification of this issue).

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot possible to blind personnel.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Jouvet 2011

MethodsSingle centre pilot randomized controlled trial


Participants30 children (intervention 15; control 15) between 2 years and 18 years with body weight ≥ 15 kg admitted for any reason, except cardiac surgery and mechanically ventilated for at least 12 hours. Children were included if the Evita XL ventilator with SmartCare/PS™ was available and if they fulfilled the following weaning criteria during the screening periods (Monday to Friday mornings): patient able to breath spontaneously, no vasopressor or inotrope medication (other than digoxin or low dose dopamine (< 5 μg/kg/min)), FiO2 ≤ 60% in order to obtain oxygen saturation by pulse oxymetry ≥ 95%, positive end expiratory pressure (PEEP) ≤ 8 cmH2O, plateau pressure ≤ 25 cmH2O, PaCO2 < 70 mmHg on the most recent blood gas, endotracheal tube leak ≤ 20%. Patients were excluded if: they had severe chronic respiratory insufficiency due to neurological, neuromuscular or lung diseases prior to PICU admission, primary pulmonary hypertension or cyanotic congenital heart disease with unrepaired or palliated right to left intracardiac shunt, children with extubation anticipated on the day of inclusion, not expected to survive, with a decision to withdraw care or with no parental consent.

Setting: Canada, PICU.


InterventionsIntervention: After passing a pressure support test, patients were weaned with SmartCare/PS™. PEEP was adjusted using a written protocol; if the child's clinical status deteriorated, ventilation mode was switched back to Assist Control. The decision to extubate was made by the attending clinician.

Control: Physicians weaned according to their discretion in the absence of formal guidelines, including modification of ventilator mode if required. The decision to extubate was made by the attending clinician.


OutcomesTime from randomization to first extubation

Weaning failure defined as resumption of mechanical ventilation within 48 hours after extubation

Total duration of mechanical ventilation

Length of ICU stay

Length of hospital stay


NotesPilot study included 30 patients corresponding to 10% of the sample size needed for a multicentre RCT.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk30 sealed enveloped contained either control or Smartcare group sheet of paper (15 each) in a random manner and numbered from 1 to 30.

Allocation concealment (selection bias)Low riskOpaque envelopes used.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding of personnel not possible.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Kirakli 2011

MethodsSingle centre randomized controlled trial


Participants97 COPD patients (intervention 49; control 48) with a confirmed diagnosis according to the Global Initiative for COPD criteria. Patients were excluded if they had severe cardiac or neurologic disease, sepsis, mechanical ventilation for < 24 hours, and those with a tracheostomy. Patients receiving non-invasive ventilation prior to intubation were not enrolled as care for these patients was managed by non-intensivist pulmonary physicians.

Setting: Turkey, 30 bed respiratory ICU of an education and research hospital specializing in pulmonary diseases and thoracic surgery.


InterventionsIntervention: Adaptive Support Ventilation with minute ventilation set at 100 mL/kg ideal body weight (IBW). Minute ventilation was decreased to 50 mL/kg IBW after 1 hour and to 30 mL/kg after 2 hours if patient was hemodynamically stable, had normal mental status and no signs of anxiety, somnolence or dyspnoea. Patients underwent a 2 hour trial of spontaneous breathing at 30 mL/kg prior to extubation.

Intervention: Initial pressure support (above PEEP) was set at 15 cmH2O. Pressure support was evaluated at least every 30 minutes and titrated to keep the respiratory rate ≤ 35 breaths/min and gradually decreased to 7 cmH2O by 2 cmH2O intervals. In patients achieving 7 cmH2O pressure support, a 2-hour trial of spontaneous breathing was performed before extubation.


OutcomesWeaning duration defined as time from randomization to spontaneous breathing

Weaning success defined as independence from mechanical ventilation (invasive or noninvasive) for ≥ 48 hours after extubation

Respiratory parameters at the end of the weaning period

Duration of ventilation defined as the time from the initiation of ventilator support to the permanent cessation of any form of ventilatory support (invasive or noninvasive)

ICU length of stay


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskUsed an online randomization website (author communication).

Allocation concealment (selection bias)Low riskOpaque, sealed envelopes (author communication).

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition, no missing outcome data (though discrepancies of reported data in sections of published manuscript resolved with author).

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot possible due to nature of intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

States "weaning and extubation performed by pulmonary and critical care physicians who were not aware of the study". Clarification by the author as to the meaning of this statement provided as "The physicians were aware of the modes and which protocol they were going to use for that individual patient so that they could set the ventilator parameters but they were not aware of the hypothesis and the aim of the study".

Lellouche 2006

MethodsMulti-centre randomized controlled trial


Participants147 adult patients (intervention 74: control 70) ventilated for ≥ 24 hours using an assisted mode screened for eligibility before usual criteria for weaning were present. Inclusion criteria were: pulse oximetry >90% with FiO2 ≤ 50% and PEEP ≤ 8 cmH2O, no need for epinephrine or norepinephrine at a rate > 1 mg/h, body temperature between 36 to 39 C, and a stable neurological status with little or no sedation. Eligibility criteria included absence of: a do-not-resuscitate order, expected poor short-term prognosis, tracheostomy, and cardiac arrest with poor neurological prognosis.

Setting: 5 teaching hospital medical-surgical ICUs in 4 countries in Europe (Belgium, Spain, France, Switzerland).


InterventionsIntervention: SmartCare/PS™.

Control: Weaning according to local practice (guidelines [weaning protocols] were available in 4/5 ICUs). Ventilator settings were chosen by the physician in charge of the patient. Weaning comprised once daily or more screening for criteria to decide for a SBT (T-piece or PSV ± PEEP). SBT could be performed as soon as criteria were present; after passing a SBT standard extubation criteria were used.


OutcomesTime to successful extubation defined as the time from inclusion until successful extubation (followed by 72 hours without ventilator support)

Total duration of ventilation

Duration of ventilatory support until first extubation

Length of ICU stay

Length of hospital stay

Number of complications in the ICU

Number of cases of nosocomial pneumonia

ICU mortality

Hospital mortality


NotesProportion and time to satisfying extubation criteria not reported for usual care arm.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated by blocks of six.

Allocation concealment (selection bias)Low riskRandomization was centralized, concealed and generated by electronic mail system.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition reported, analysis according to ITT, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding of personnel not possible.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Petter 2003

MethodsSingle centre randomized controlled trial


Participants34 adult patients (18 intervention; 16 control) undergoing elective cardiac surgery under cardiopulmonary bypass. Preoperative exclusion criteria were age >80 years, preoperative left ventricle ejection fraction < 30%, COPD requiring bronchodilator therapy, significant hepatic disease, renal failure, history of seizure and stroke. After enrolment, patients presenting with any condition hindering rapid extubation were excluded. Specific postoperative exclusion criteria were: severe postoperative haemorrhage, surgical complication requiring reoperation, postoperative cardiac failure requiring large dose inotropes, refractory hypoxaemia, and neurological complication precluding patient collaboration.

Setting: Switzerland, surgical ICU.


InterventionsIntervention: Adaptive support ventilation with initial settings at the default value and peak pressure less than 25 cmH2O. ABG analysis was performed 10 minutes after connection to the ventilator. If PaCO2 was ≤ 38 mmHg or ≥ 50 mmHg, the % minute volume was decreased or increased by 20% (phase 1). All subsequent changes to ventilator settings were assessed after 10 minutes via ABG analysis. Phase 1 ended with recovery of spontaneous breathing (no controlled breaths for 20 minutes). Phase 2 ended when PS had decreased to 10 cmH2O (within 2 cmH2O for 20 minutes). ABGs and clinical criteria for weaning failure were assessed. Phase 3 comprised manual setting of PS to 5 cmH2O for 10 minutes, if no contraindications were present, the patient was extubated.

Control: reflected current standard of care. Initial settings were SIMV, VT of 8 mL/kg IBW, respiratory rate of 12 breaths/min. ABG management was identical to ASV group. When patients breathed spontaneously for ≥ 6 breaths/min, PS 10cmH2O was set manually. After 20 minutes, ABG and clinical criteria were assessed. If weaning was stopped if not tolerated, and patient reassessed after 20 minutes for further reduction of PS. Phase 3 performed same as ASV group.


OutcomesDuration of tracheal intubation

Mechanical ventilation transitions from controlled to assisted ventilation

Number of ventilator setting changes performed by health care workers

Number of alarms

Amount of sedative and analgesic administered


NotesUnderpowered study as identified by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA study nurse not involved in the study wrote the assignment (ASV versus control equal number of each) on cards. She shuffled the cards, put them in sealed envelopes, and numbered the envelopes. Hence the sequence of allocation was defined by the shuffling of the cards, but unknown to the investigators (author communication).

Allocation concealment (selection bias)Low riskOpaque envelopes used (author communication).

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition reported, analysis according to ITT, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskPersonnel not blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Rose 2008

MethodsSingle centre randomized controlled trial


Participants102 adult patients (51 intervention: 51 control) requiring > 24 hours of mechanical ventilation on a mandatory ventilator mode. Patients tolerating PSV within 24 hours of ventilation were excluded. Other eligibility criteria included: PEEP ≤ 8 cmH2O, PaO2/FiO2 ratio >150 or SaO2 ≥ 90% with FiO2 ≤ 0.5, plateau pressure ≤ 30 cmH2O, haemodynamic stability, peripheral body temperature 36-39 C, stable neurological status with GCS >4, and no anticipated (within 2 hours) for transport or surgery).Final study inclusion criterion was completion of 30 minute SBT to determine tolerance of pressure support.

Exclusion criteria: no SmartCare/PS™ enabled ventilator available, CNS disorder with anticipated poor outcome.

Setting: Australia, 390 bed acute tertiary referral hospital with 100,000 admissions/annum, 24 bed mixed medical/surgical/trauma ICU. Nurse:patient ratio 1:1, 9 intensivists providing twice daily structured rounds supported by 26 hospital medical officers (registrars and residents).


InterventionsIntervention: SmartCare/PS™. Extubation remained at the discretion of the attending clinician.

Control: clinicians instructed to wean PS and PEEP according to usual local practice in the absence of formal guidelines. Clinicians were instructed to wean PS as able with no constraints as to the frequency or size of PS adjustment while maintaining patients in the same zone of comfort as described for SmartCare/PS™. Extubation remained at the discretion of the attending clinician.


OutcomesTime to separation defined as time in hours from randomization to separation potential

Total duration of weaning defined as time from randomization to successful extubation

Time from intubation to first extubation

Time from intubation to successful extubation

ICU length of stay

Hospital length of stay

ICU mortality

Reintubation

Post-extubation NIV


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated block randomization.

Allocation concealment (selection bias)Low riskSequential opaque envelopes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition reported, analysis according to ITT, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskPersonnel not blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation). Outcome assessor was independent from those managing care.

Roth 2001

MethodsSingle centre randomized controlled trial


Participants40 consecutive adult patients (intervention 20: control 20) with healthy lungs who underwent brain surgery. Included patients were those who required controlled ventilation and who were expected to show spontaneous breathing efforts during the 1st 24 hours after ICU admission. Patients with central depression of breathing drive expected to last > 24 hours as well as patients with mechanical or neural damage making spontaneous breathing efforts impossible were excluded.

Setting: Germany, university hospital, 18 bed ICU.


InterventionsIntervention: Automode on Siemens Servo ventilator 300. Initial stabilisation period on PCV for 20 minutes after ICU admission. Automode was activated by automatically switching from PCV to PSV in cases of repeated triggering of the ventilator and back in cases of apnoea of more than 12 seconds. Patients were considered ready for extubation when there was stable spontaneous breathing without switching back to controlled ventilation.

Control: SIMV with an initial stabilisation period on PCV for 20 minutes after ICU admission. Mandatory frequency was initially reduced by 2 breaths/min if the ventilator indicated triggering by the patient. Mandatory frequency was further decreased in cases of stability and/or an increase in minute ventilation over the pre-set alarms. If MV dropped below the pre-set alarms, the mandatory rate was increased again. Adjustments were made by the nurses, supervised by the physicians. Manual switching to PSV was done in cases of stable spontaneous breathing. Alarm levels for MV were set to 8-% and 120% of values measured in the stabilisation phase.

In both groups, pressure levels were adjusted within a range of 10-15 cmH2O to reach a VT of 10 mL/kg body weight. Respiratory rate adjusted to reach normoventilation. I:E ratio set to 1:2, FiO2 0.35-40 (PaO2 90 mmHg), PEEP 5 cmH2O. PSV was adjusted to the same inspiratory pressure used during PCV. PS, PEEP and FiO2 were kept constant until extubation. Patients were considered ready for extubation when there was stable spontaneous breathing without the need for mandatory background frequency.


OutcomesTotal weaning time

Number of manipulations

Respiratory and circulatory parameters measured at randomization (T0), 20 minutes after the 1st spontaneous breathing activity (T20), 2 hours after T20 (T140), before extubation (Tex), and 1 hour after extubation (Tpost)

Variability of ventilation (range of PaCO2 levels)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported.

Allocation concealment (selection bias)Unclear riskNot reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot possible to blind personnel.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Schaedler 2012

MethodsSingle centre (multiple ICU) randomized controlled trial


Participants300 adult patients (Intervention 150; Control 150) who at 09:00 AM, were ventilated for longer than 9 hours since ICU admission. Exclusion criteria comprised: cerebral surgery/trauma, age <18 years, do-not-resuscitate order, duration of ventilation > 24 hours, patients already enrolled in the study.

Setting: Germany, academic tertiary hospital, 3 ICUs serving all surgical disciplines (10 bed cardiovascular ICU, 10 bed interdisciplinary ICU and 8 bed surgical ICU). ICUs staffed with a 1:2 nurse:patient ratio. During daytime a board certified physician was responsible for medical care + 1 resident for 3 shifts per day and 1 consultant on-call. Daily ward round carried out by 2-3 experienced intensivists, one resident, one consultant microbiologist and 1-2 nurses.


InterventionsIn both study arms, haemodynamically stable patients (maximal continuous infusion of epinephrine or norepinephrine of 0.01 mg/kg/h) were assessed with a 30 minute pressure support test initiated by the responsible physician or during study visits if clinically indicated. Patients were switched from PCV to PSV with PS between 15 to 30 cmH2O and identical settings of FiO2 and PEEP. Patients passed the PS test if remained clinically stable, spontaneous breaths were <35 per minute, VT ≥ 6 mL/kg predicted body weight with allowed PS, SpO2 ≥ 90%. Patients successfully passing the PS test were then weaned according to the allocated group.

Intervention: SmartCare/PS™ via Evita XL ventilators with night rest and automatic tube compensation turned off and using a heat and moisture exchange filter. Readiness for extubation was identified by SmartCare/PS™. Extubation or end of ventilator therapy for tracheostomized patients occurred when the following criteria were satisfied: PaO2/FiO2 >200, patient awake and cooperative, sufficient airway protection or GCS >8, effective cough, and no surgical indication.

Control: Standardized weaning protocol. Adjustment of PS at least 3 times per day by 2 or 3 cmH2O with the aim of maintaining the spontaneous breath rate ≤ 35 and good clinical adaptation. PS was increased if the spontaneous breath rate was >35 for longer than 3 minutes. A daily SBT lasting 30 minutes was commenced when PS ≤ 12 cmH2O, PEEP ≤ 5 cmH2O and FiO2 ≤ 0.5. Patients were deemed to have passed the SBT if the spontaneous breath rate remained below 35, SpO2 ≥ 90%, patient remained clinically stable (no diaphoresis, agitation or decreased level of consciousness). If a patient failed the SBT the test was reinitiated at least once during the next 24 hours. The same criteria were used for extubation/discontinuation of ventilation as used in the intervention arm.

Analgesia was maintained by a continuous infusion of sufentanil (range 0.1 to 0.4 μg/kg/h). Sedation was achieved via continuous infusion of propofol (max 4 mg/kg/h) for 24 hours after inclusion. Thereafter bolus doses of midazolam were used to maintain a Ramsay score of 2.


OutcomesOverall ventilation time during ICU stay considering any time the patient required invasive or noninvasive ventilation during the 28 day study period

Time in zone of respiratory comfort

Number of ventilator manipulations

Length of ICU stay

Length of hospital stay

28 day mortality

90 day mortality


NotesStudy sponsored by Dräger Medical via a restricted research grant. Sponsor had no role in the study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskElectronically generated and locally maintained randomization schedule.

Allocation concealment (selection bias)Low riskAllocation was concealed.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition reported, analysis according to ITT, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot possible to blind personnel.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Stahl 2009

MethodsRandomized controlled trial


Participants60 adult patients (Intervention 30; Control 30) who were mechanically ventilated via an endotracheal tube or tracheostomy for at least 24 hours, breathing spontaneously, Ramsay sedation score ≤ 3, PaO2 >75mmHg or SaO2 >90% with FiO2 ≤ 0.5, 18-80 years of age, body weight 35-200kg. Exclusion criteria comprised: PEEP > 10cmH2O, haemodynamic instability with a need for catecholamines, rectal temperature >39°C, haemoglobin <7g/dL, and pH <7.2.


InterventionsIntervention: SmartCare/PS™

Control: physician-directed weaning using no strict protocol but recommending PS should be gradually reduced in single steps of no more than 15 cmH2O.

Extubation criteria: respiratory rate <30 breaths/min, PaO2 >75mmHg or SaO2 >90%, sufficient airway protection, haemodynamic stability.


OutcomesDuration of ventilator weaning (time from switching controlled to assisted breathing (CPAP/ASB mode) until extubation or disconnection (if tracheostomy).

Total duration of mechanical ventilation (intubation to successful extubation)

Length of ICU stay

Reintubation within 48 hours

Physician workload (frequency of PS, FiO2 and PEEP setting changes/hour)

Nursing workload (frequency of alarms indicating "clean CO2 cuvette)/hour)

ICU and hospital mortality


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomization list generated using RITA version 1.13a. Stratified randomization with age and duration of mechanical ventilation prior to weaning.

Allocation concealment (selection bias)Low riskOpaque sealed envelopes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll a priori outcomes reported. Analysis according to ITT.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasUnclear riskSample size calculation states: based on 80% power to detect a 2 days difference in weaning time, α 0.05 requires 54 patients in each group. Unplanned interim analysis was undertaken because of low recruitment after 1 year: sample size and significance levels were recalculated as N = 60. After the 60th patient the trial was stopped for futility.

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants, staff and research personnel were unblinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation). Communication with authors: outcome assessors were independent from those managing patient care.

Strickland 1993

MethodsSingle centre pilot randomized controlled trial


Participants17 patients (9 computer; 7 physician weaning group) judged ready to wean by his/her attending physician and meeting the following criteria: pH ≥ 7.30 and ≤ 7.50, PaCO2 ≥30 and ≤ 50 mmHg, SaO2 ≥ 90% while on SIMV with a rate of 6-10, VT of 10-15 mL/kg, PS 20 cmH2O and FiO2 ≤ 0.4, negative inspiratory force ≤ - 20 cmH2O, forced vital capacity ≥ 10 mL/kg, stable haemodynamics and renal function, parenteral or enteral feeding, no ileus, normal electrolytes, infection controlled with antibiotics with oral temperature ≤ 37.7C. Post operative patients were excluded unless had been on ventilator for ≥ 3 days. Patients requiring PEEP had to be weaned of (PEEP) prior to entering the study.

Setting: United States, 3 pulmonary physicians were involved in patient care either in a consultative or attending role.


InterventionsIntervention: modification of Puritan Bennett 7200 to allow direct control of the ventilator settings by an external PC-compatible computer that monitored the patient and ventilator data through the serial digital outputs of the pulse oximeter and ventilator. Weaning started at SIMV rate 6, PS 20 cmH2O, FiO2 ≤ 0.4, and VT 10-15 mL/kg. The computer sampled respiratory rate and SpO2 every 5 minutes, and calculated a moving average of VT using the average of the last 5 time 1 minute VT samples. To proceed with weaning the respiratory rate had to be ≥ 8 and ≤ 30 and VT ≥ 5 mL/kg (ideal body weight based on height). The system alarmed if SpO2 was <90% but no weaning changes were made by the computer based on SpO2. The computer decreased the SIMV rate by 2 every hour until a rate of 2 was reached. The computer then decreased the PS by 2 cmH2O every hour as long as the VT and respiratory rate limits were met. The weaning process was complete when the SIMV rate was 2 and the PS 5 cmH2O. If the 5-minute samples of respiratory rate or VT were not within acceptable limits, the computer increased the level of ventilator support.

Control: weaning progressed through SIMV rate and PS reduction as judged appropriate by the patient's physician.


OutcomesWeaning success

Time to wean

Number of ABG samples

Number of minutes per hour respiratory rate and VT were outside acceptable limits


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number table.

Allocation concealment (selection bias)Low riskSealed envelopes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition reported, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible to blind personnel.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Sulzer 2001

MethodsSingle centre randomized controlled trial


Participants36 adults undergoing elective coronary artery bypass grafting under cardiopulmonary bypass. preoperative exclusion criteria comprised: age > 75 years, poor myocardial function (preoperative ejection fraction < 30%), COPD requiring bronchodilator therapy, significant hepatic disease, renal failure, history of seizure or stroke. Postoperative exclusion criteria comprised: severe postoperative haemorrhage, repeat operation, postoperative myocardial ischaemia, refractory hypoxaemia, neurologic complication.

Setting: Switzerland, university hospital, surgical ICU.


InterventionsIntervention: Adaptive support ventilation with initial settings at minute ventilation set at 100%, FiO2 100%, PEEP 4 cmH2O and peak pressure less than 25 cmH2O. ABG analysis was performed 10 minutes after connection to the ventilator. If PaCO2 was ≤ 38 mmHg or ≥ 50 mmHg, the % minute volume was decreased or increased by 20% (phase 1). All subsequent changes to ventilator settings were assessed after 10 minutes via ABG analysis. Phase 1 lasted until patients breathed spontaneous at ≥ 6 breaths per minute for 20 minutes. Weaning progressed after ABG was checked and clinical criteria of poor tolerance were ruled out. Continuation of weaning composed of 2 phases lasting at least 20 minutes each. In Phase 2 minute ventilation was lowered by 50%. If ABGs and clinical criteria indicated poor tolerance, phase 1 was reinstated. If ABGs and clinical criteria were satisfactory, weaning progressed to Phase 3. In Phase 3 minute ventilation was lowered by another 50%. At the end of Phase 3, if the patient achieved extubation criteria, pulmonary physiotherapy was performed, followed by extubation.

Control: reflected current standard of care. Initial settings (Phase 1) were SIMV, VT of 7 mL/kg, respiratory rate of 12 breaths/min. ABG performed after 10 minutes, respiratory rate was lowered or increased to satisfy same criteria as ASV group. When patients breathed spontaneously for ≥ 6 breaths/min for 20 minutes, weaning could progress to Phase 2, according to the criteria defined for the ASV group. The ventilator was set to PSV of 10cmH2O. ABG and clinical criteria were assessed. If indicating poor tolerance, phase 1 was reinstated, if ABG and clinical criteria were complied with, weaning progressed to Phase 3 in which PS was reduced to 5 cmH2O. At the end of Phase 3 patients were assessed for extubation according to the same criteria as the ASV group.


OutcomesDuration of mechanical ventilation (Phases 1, 2 and 3)

Amount of sedative and analgesic drugs administered


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA study nurse not involved in the study wrote the assignment (ASV versus control equal number of each) on cards. She shuffled the cards, put them in sealed envelopes, and numbered the envelopes. Hence the sequence of allocation was defined by the shuffling of the cards, but unknown to the investigators (author communication).

Allocation concealment (selection bias)Low riskSealed opaque envelopes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition reported, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding of personnel not possible.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Taniguchi 2009

MethodsSingle centre randomized controlled trial.


Participants106 (53 in each group) postoperative adults (over 18 years), receiving mechanical ventilation after cardiac, thoracic, abdominal or orthopaedic surgery. Excluded patients included neurological surgery and patients with previous pulmonary disease or haemodynamic instability during weaning.

Setting: Brazil, adult ICU.


InterventionsIntervention: mandatory rate ventilation (MRV) automatic, computerised weaning, ventilated with Taema-Horus Ventilator. Initial ventilation was the same as the control group except that to obtain a RR of 15 breaths per minute, the target RR was set at 15 and the minimum RR as 15. When the patient commenced breathing spontaneously the ventilator mode was switched to PSV to achieve a VT ≥ 8 mL/kg with PS maximum of 25 cmH2O, target RR of 15 with minimum RR of 8, FiO2 to achieve an SpO2 of 95%, PEEP 5 cmH2O. The MRV mode then commenced automatic reduction of PS.

Control: manual weaning guided by ICU staff comprising PCV targeting a VT of 8 mL/kg, with a RR of 15 breaths per minute, FiO2 to achieve an SpO2 of 95%, PEEP of 5 cmH2O. When the patient started breathing spontaneously the ventilator mode was switched to PSV set to achieve VT of 8 mL/kg, RR/VT less than 80 L, FiO2 to achieve an SpO2 of 95%, PEEP 5 cmH2O. PSV was reduced every 30 minutes keeping RR/VT < 80 and VT ≥ 8 mL/kg. PSV could be reassessed and possibly decreased every 30 minutes aiming to make the manual weaning as close as possible to the automatic algorithm.

Patients in both arms were extubated if meeting the following criteria: PSV from 5 - 7 cmH2O, PEEP 5 cmH2O, FiO2 40%, SpO2 >95%, haemodynamically stable, adequate mental status, capable of protecting airway, RR/VT < 80L.


OutcomesDuration of the weaning process from the moment the patient started to breathe spontaneously until successful extubation

levels of PS, VT, RR, FiO2, SpO2, PEEP and RR/VT required during the weaning process

Need for reintubation

Need for NIV


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomly drew folded slips of paper from large envelope.

Allocation concealment (selection bias)Low riskSlips of paper drawn from opaque envelope.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition reported, analysis according to ITT, no missing outcome data.

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported.

Other biasLow riskNo other sources of bias detected.

Blinding of participants and personnel (performance bias)
All outcomes
High riskUnable to blind personnel.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

Walkey 2011

MethodsSingle centre randomized controlled trial


Participants33 adult patients (15 intervention; 18 control) receiving mechanical ventilation via an endotracheal tube for >48 hours.

Setting: USA, medical ICU.


InterventionsIntervention: SmartCare/PS™.

Control: weaning according to usual care.


OutcomesDuration of weaning assessed as the time from the initiation of weaning (randomization) to the time of successful extubation (defined as 48 hours free of mechanical ventilation)

Hospital mortality

Complications (death during wean, ventilator-associated pneumonia during wean, self extubation, reintubation)


NotesThis trial was terminated early due to slow recruitment.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskOnline random number generator.

Allocation concealment (selection bias)Low riskOpaque envelopes used.

Incomplete outcome data (attrition bias)
All outcomes
High riskStudy terminated early due to slow recruitment. Limited reporting of outcome data.

Selective reporting (reporting bias)Unclear riskStudy terminated early due to slow recruitment. Limited reporting of outcome data.

Other biasUnclear riskStudy terminated early due to slow recruitment.

Blinding of participants and personnel (performance bias)
All outcomes
High riskNot possible due to nature of intervention.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAssumed as low risk due to the objective nature of outcomes (weaning commencement/extubation).

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

East 1999Not evaluating a closed loop automated system.

Jiang 2006Quasi-randomized trial. Allocation sequence generated according to case record number (odd and even).

Ma 2010Quasi-randomized trial. Study subjects separated into two clinical trial groups according to their sequence of ICU admittance.

Maloney 2007Not evaluating a closed loop automated system.

McKinley 2001Reporting data on a subset of trauma patients from the East 1999 study. Not evaluating a closed loop automated system.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Burns 2013

MethodsMulti-centre pilot randomized controlled trial.

Participants92 mixed ICU population (adults).

InterventionsIntervention: Smartcare/PS.

Control: written protocol for weaning and sedation.

OutcomesProtocol feasibility, acceptability and compliance

Duration of weaning

Duration of mechanical ventilation

Length of ICU stay

Length of hospital stay

Mortality

NotesStudy published in March 2013. Awaiting data for inclusion.

Domingo 2010

MethodsSingle centre parallel group allocation.

ParticipantsPost cardiac surgery patients.

InterventionsIntervention: adaptive support ventilation.

Control: standard protocol using T Piece weaning.

OutcomesDuration of weaning

Duration of tracheal intubation

Length of ICU stay

Length of hospital stay

Reintubation

Rates of ventilator associated pneumonia and pneumothorax

NotesUnable to contact authors to confirm randomization methods. Available in abstract form only.

Lellouche 2009b

MethodsSingle centre pilot randomized controlled trial.

Participants28 adult patients receiving mechanical ventilation after cardiac surgery.

InterventionsIntervention: Automated systems with an algorithm embedded into a computer connected to a pulse oximeter providing recommendations for PEEP and FiO2.

Control: usual written protocol for PEEP and FiO2 adjustment based on SpO2 value.

OutcomesTime to wean PEEP and FiO2.

NotesAvailable in abstract form only.

Lellouche 2013

MethodsSingle centre randomized controlled trial.

Participants60 adult patients receiving mechanical ventilation after cardiac surgery.

InterventionsIntervention: Intellivent.

Control: written protocol.

OutcomesPercentage of time within the predefined zones of optimal, acceptable and not acceptable ventilation.

NotesStudy published in March 2013. Awaiting data for inclusion.

Ramet 2002

MethodsSingle centre pilot randomized controlled trial

Participants18 infants (aged > 2 weeks confirmed through author communication) receiving mechanical ventilation with pressure regulated volume control (PRVC).

InterventionsIntervention: Automode (Siemens Servo 300) with automated switching from PRVC to volume support ventilation (VSV).

Control: manual (clinician) switching from PRVC to VSV.

OutcomesDays of ventilation

Randomization to extubation in hours

Randomization to switching to VSV in hours

Comfort score on extubation

NotesAvailable in abstract form only.

 
Characteristics of ongoing studies [ordered by study ID]
Agarwal/Srinivusan 2010

Trial name or titleAdaptive Support Ventilation in Acute Respiratory Distress Syndrome (ARDS)

MethodsRandomized controlled trial in a single respiratory ICU

ParticipantsAdults with acute respiratory distress syndrome

InterventionsIntervention: ASV. Patients will be stabilized on assist control ventilation for 1 hour to determine the adequate minute ventilation.

Control: assist control mode ventilation using low tidal volume strategy of 6ml/kg with FiO2/PEEP as per ARDSnet table to achieve a saturation between 88-95% with the lowest possible FiO2 to maintain plateau pressures < 30 cm H2O and pH > 7.3 with option to reduce tidal volume to 4 ml/kg and increase respiratory rate to 35/ min to achieve the above said goals.Weaning as per standard protocol of spontaneous breathing trial of 30 minutes once recognized as eligible as per statement of the sixth International consensus conference on weaning.

OutcomesDuration of mechanical ventilation

Duration of ICU stay

Duration of hospital stay

Mortality

Ease of use of ventilator mode

Frequency of blood gas analysis

Starting dateJanuary 2010

Contact informationRitesh Agarwal Respiratory intensive care unit, PGIMER Chandigarh, India; Ph: 9914209825 ext 2756825 riteshpgi@gmail.com

NotesNCT01165528

Alander/Kontiokari 2009

Trial name or titleNeurally Adjusted Ventilatory Assist (NAVA) in Pediatric Patients

MethodsRandomized controlled trial

ParticipantsAll children from term newborn (37+0 gestational week) to 16 years old needing ventilatory care at least 30 minutes. Exclusion criteria are: any condition that prevents feeding tube positioning. Critical ventilatory or perfusion problems

InterventionsIntervention: NAVA.

Control: pressure controlled ventilation for newborns; older children will be treated with pressure regulated volume controlled (PRVC) ventilation.

OutcomesDuration of mechanical ventilation

Amount of sedative medication needed

Starting dateSeptember 2009

Contact informationTero Kontiokari University of Oulu, +358 40 757 4423 tero.kontiokari@oulu.fi Merja Ålander +358 44582 5148 merja.alander@oulu.fi

NotesNCT01056939

Beale 2004

Trial name or titleComparison of an automated weaning programme and a standard clinical weaning protocol for weaning critically ill patients: a randomized controlled trial

MethodsRandomized controlled trial

ParticipantsAdults ≥18 years with suspected or proven infection, presence of a systemic response to the infection within the 48-hour period immediately preceding enrolment into the study, have or have had one or more sepsis-induced organ failures within the 48-hour period immediately preceding enrolment into the study with an expected length of stay in the ICU >3 days

InterventionsIntervention: Smartcare/PS.

Control: weaning from mechanical ventilation using the standard protocol.

OutcomesTime from the initiation of weaning to successful separation of the patient from the ventilator, defined as no longer needing mechanical ventilation for a minimum period of 48 hours

Mortality (28-day, ICU and hospital, six-months)

Infectious complications (e.g. pneumonia, wound infection, abscesses)

APACHE II

Organ failure-free days

LOS in ICU

LOS in hospital (intervention until discharge)

Duration of antibiotic treatment (antibiotics days)

Duration of ventilation (ventilator days)

Duration of renal support

Starting dateDec 1 2004

Contact informationRichard Beale, Adult ICU East Wing St Thomas' Hospital Lambeth Palace Rd, London, United Kingdom, +44 (0)20 7188 3038, Richard.Beale@gstt.nhs.uk

NotesISRCTN82559457

Bosma 2010

Trial name or titleComparison of Weaning on Pressure Support vs. Proportional Assist Ventilation: a Pilot Study

MethodsRandomized controlled trial

ParticipantsMechanically ventilated patients >=18 years who are ready to begin weaning according to prespecified eligibility criteria, and tolerate 30 minutes of pressure support ventilation, but are not ready for extubation, defined as an f/Vt >105 after 2 minutes of CPAP or failing a spontaneous breathing trial on PSV 5 cmH2O

InterventionsIntervention: weaning with PAV+.

Control: weaning using pressure support.

OutcomesDuration of weaning: (1) randomization to successfully passing a spontaneous breathing trial; and (2) randomization to successful extubation

Number of ventilator free days (alive and free of mechanical ventilation 28 days post-randomization

Change in asynchrony index from baseline

Change in sedative drug administration from baseline

Delirium

Starting dateMarch 2009

Contact informationKarenJ.Bosma@lhsc.on.ca

TraceyC.Bentall@lhsc.on.ca

Notes

Fernandez 2010

Trial name or titleProportional Assist Ventilation (PAV) in Early Stage of Critically Ill Patients

MethodsRandomized controlled trial

ParticipantsAdults 18 years of age or older with an anticipated duration of mechanical ventilation > 24 hours

InterventionsIntervention: ventilatory support performed by PAV at 80% assistance (PB 840-plus) FiO2 and PEEP according to routine practice.

Control: assist-control ventilation, tidal volume, FiO2 and PEEP set according to routine practice.

OutcomesLength of mechanical ventilation

Gas exchange

Short term complications (barotrauma, ARDS, atelectasis and pneumonia)

Weaning success weaning success defined as the composite end-point: time to resume spontaneous ventilation, rate of extubation success, need for noninvasive ventilation (NIV) as rescue therapy, and reintubation rate

Starting dateSept 2010

Contact informationRafael Fernandez +34 93 874 2112 ext 3216 rfernandezf@althaia.cat; Marcos Delgado +34 93 874 2112 ext 3215 mdelgado@althaia.cat Intensive Care Unit. Xarxa assistencial Althaia, Manresa, Catalunya, Spain

NotesNCT01204281

Kirakli 2012

Trial name or titleClosed Loop Ventilation Strategy in Intensive Care Unit (ICU) Patients

MethodsRandomized controlled trial

ParticipantsAdults intubated and mechanically ventilated ICU patients for more than 24 hours. Patients receiving ventilation via tracheostomy will be excluded.

InterventionsIntervention: Adaptive Support Ventilation according to the patients ideal body weight.

Control: Pressure Controlled Ventilation (6-8 ml/kg tidal volume) according to our ICU protocol.

OutcomesDuration of mechanical ventilation

Starting dateApril 2012

Contact informationCenk Kirakli, +905052352024, ckirakli@hotmail.com, Izmir Chest Diseases and Surgery Education and Research Hospital, Intensive Care Unit, Izmir, Yenisehir, Turkey

NotesNCT01472302

Liu/Qui 2010

Trial name or titleEffect of NAVA on Duration of Weaning in Difficult to Wean Patients

MethodsRandomized controlled trial

ParticipantsIntubated patients deemed ready for extubation by the clinical team but who fail the first spontaneous breathing trials (SBT) or weaning attempt.

InterventionsIntervention: Neurally adjusted ventilatory assist (NAVA).

Control: Pressure Support Ventilation weaning.

OutcomesDuration of weaning was defined as time from study enrolment to extubation.

Extubation rate defined as the percentage of patients with successful weaning.

Diaphragmatic function was measured by neuro-ventilatory efficiency (NVE), a ratio of tidal volume to diaphragm electrical activity (Vt/EAdi), and neuro-mechanical efficiency (NME), a ratio of airway pressure to EAdi(Paw/EAdi) during airway occlusion.

Patient ventilator asynchrony (Time delay between neuro inspiration and ventilator delivery. Time delay between neuro expiration and ventilator cycle-off).

Starting dateDecember 2010

Contact informationLing Liu +86-25-83272201 liuling6600@yahoo.com.cn; Haibo Qiu +86-25-83272200 haiboq2000@yahoo.com.cn, Nanjing Zhong-Da Hospital, Nanjing, Jiangsu, China

NotesNCT01280773

 
Comparison 1. Primary analysis: automated closed loop system versus non-automated system

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total duration of weaning by study population141153Mean Difference (IV, Random, 95% CI)-0.38 [-0.62, -0.14]

    1.1 Mixed or medical ICU population
8749Mean Difference (IV, Random, 95% CI)-0.57 [-1.06, -0.08]

    1.2 Surgical ICU population
6404Mean Difference (IV, Random, 95% CI)-0.07 [-0.19, 0.05]

 2 Total duration of weaning by automated system141153Mean Difference (IV, Random, 95% CI)-0.38 [-0.62, -0.14]

    2.1 Smartcare/PS
6669Mean Difference (IV, Random, 95% CI)-0.37 [-0.67, -0.07]

    2.2 ASV
4295Mean Difference (IV, Random, 95% CI)-0.03 [-0.11, 0.05]

    2.3 Other
4189Mean Difference (IV, Random, 95% CI)-0.60 [-1.32, 0.13]

 3 Total duration of weaning by non-automated strategy (control arm)141153Mean Difference (IV, Random, 95% CI)-0.38 [-0.62, -0.14]

    3.1 usual care
5238Mean Difference (IV, Random, 95% CI)-0.46 [-0.83, -0.10]

    3.2 protocolized weaning (non-automated)
9915Mean Difference (IV, Random, 95% CI)-0.33 [-0.63, -0.04]

 4 Secondary outcome 1: time from randomization to first extubation9920Mean Difference (IV, Random, 95% CI)-0.16 [-0.30, -0.01]

 5 Secondary outcome 2: duration of ventilation by study population8763Mean Difference (IV, Random, 95% CI)-0.19 [-0.30, -0.08]

    5.1 Mixed and medical ICU population
5673Mean Difference (IV, Random, 95% CI)-0.16 [-0.31, -0.01]

    5.2 Surgical ICU population
390Mean Difference (IV, Random, 95% CI)-0.22 [-0.38, -0.06]

 6 Secondary outcome 2: duration of ventilation by automated system7743Mean Difference (IV, Random, 95% CI)-0.17 [-0.29, -0.05]

    6.1 Smartcare/PS
4576Mean Difference (IV, Random, 95% CI)-0.17 [-0.33, -0.01]

    6.2 ASV
3167Mean Difference (IV, Random, 95% CI)-0.17 [-0.36, 0.02]

 7 Secondary outcome 2: duration of ventilation by non-automated strategy (control arm)8763Mean Difference (IV, Random, 95% CI)-0.19 [-0.30, -0.08]

    7.1 Usual care
2132Mean Difference (IV, Random, 95% CI)-0.11 [-0.39, 0.17]

    7.2 Protocolized weaning (non-automated)
6631Mean Difference (IV, Random, 95% CI)-0.20 [-0.32, -0.09]

 8 Secondary outcome 3: time from intubation to randomization8500Mean Difference (IV, Random, 95% CI)-0.05 [-0.14, 0.05]

 9 Secondary outcome 5.1: mortality8741Risk Ratio (M-H, Random, 95% CI)1.18 [0.78, 1.78]

    9.1 ICU mortality
4167Risk Ratio (M-H, Random, 95% CI)2.12 [0.29, 15.63]

    9.2 30 day mortality
2397Risk Ratio (M-H, Random, 95% CI)1.14 [0.75, 1.75]

    9.3 Hospital
2177Risk Ratio (M-H, Random, 95% CI)0.66 [0.11, 4.13]

 10 Secondary outcome 6.1: hospital length of stay5609Mean Difference (IV, Random, 95% CI)-0.06 [-0.19, 0.08]

 11 Secondary outcome 6.2: ICU length of stay by ICU population8871Mean Difference (IV, Random, 95% CI)-0.12 [-0.24, -0.00]

    11.1 Mixed or medical ICU population
5673Mean Difference (IV, Random, 95% CI)-0.21 [-0.37, -0.05]

    11.2 Surgical ICU population
3198Mean Difference (IV, Random, 95% CI)-0.01 [-0.10, 0.08]

 12 Secondary outcome 6.2: ICU length of stay by automated system8871Mean Difference (IV, Random, 95% CI)-0.12 [-0.24, -0.00]

    12.1 Smartcare/PS
4576Mean Difference (IV, Random, 95% CI)-0.26 [-0.46, -0.07]

    12.2 ASV
4295Mean Difference (IV, Random, 95% CI)-0.02 [-0.10, 0.06]

 13 Secondary outcome 7.1: reintubation11950Risk Ratio (M-H, Random, 95% CI)0.81 [0.61, 1.09]

    13.1 Usual care
4182Risk Ratio (M-H, Random, 95% CI)0.71 [0.27, 1.88]

    13.2 Protocolized weaning (non-automated)
7768Risk Ratio (M-H, Random, 95% CI)0.82 [0.60, 1.13]

 14 Secondary outcome 7.2: self-extubation8774Risk Ratio (M-H, Random, 95% CI)1.35 [0.61, 2.96]

 15 Secondary outcome 7.3: non invasive ventilation8927Risk Ratio (M-H, Random, 95% CI)0.72 [0.50, 1.04]

 16 Secondary outcome 7.3: prolonged mechanical ventilation5622Risk Ratio (M-H, Random, 95% CI)0.58 [0.29, 1.15]

 17 Secondary outcome 7.5: tracheostomy7831Risk Ratio (M-H, Random, 95% CI)0.71 [0.48, 1.04]

 
Comparison 2. Sensitivity analysis: automated closed loop system versus non-automated system, unlogged data duration of weaning

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total duration of weaning by ICU population141153Mean Difference (IV, Random, 95% CI)-0.74 [-1.85, 0.38]

    1.1 Mixed or medical ICU population
8749Mean Difference (IV, Random, 95% CI)-26.85 [-43.81, -9.88]

    1.2 Surgical ICU population
6404Mean Difference (IV, Random, 95% CI)-0.12 [-0.52, 0.28]

 2 Total duration of weaning by automated system141153Mean Difference (IV, Random, 95% CI)-1.73 [-3.54, 0.08]

    2.1 Smartcare/PS
6669Mean Difference (IV, Random, 95% CI)-38.74 [-58.58, -18.90]

    2.2 ASV
4295Mean Difference (IV, Random, 95% CI)-0.31 [-1.18, 0.57]

    2.3 Other
4189Mean Difference (IV, Random, 95% CI)-3.96 [-8.03, 0.12]

 3 Total duration of weaning by non-automated strategy (control arm)141153Mean Difference (IV, Random, 95% CI)-0.64 [-1.69, 0.40]

    3.1 usual care
5238Mean Difference (IV, Random, 95% CI)-7.62 [-13.78, -1.47]

    3.2 protocolized (non-automated)
9915Mean Difference (IV, Random, 95% CI)-0.42 [-1.43, 0.58]

 4 Secondary outcome 1: time from randomization to first extubation9920Mean Difference (IV, Random, 95% CI)-0.57 [-1.55, 0.42]

 5 Secondary outcome 2: total duration of ventilation8763Mean Difference (IV, Random, 95% CI)-1.02 [-2.23, 0.19]

 6 Secondary outcome 3: time from intubation to randomization9533Mean Difference (IV, Random, 95% CI)-0.16 [-0.69, 0.37]

 7 Secondary Outcome 6.1: hospital length of stay5609Mean Difference (IV, Random, 95% CI)-2.49 [-6.30, 1.32]

 8 Secondary outcome 6.2: ICU length of stay8871Mean Difference (IV, Random, 95% CI)-0.15 [-0.52, 0.23]

 
Comparison 3. Sensitivity analysis: automated closed loop system versus non-automated system excluding high risk of bias studies

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total duration of weaning131120Mean Difference (IV, Random, 95% CI)-0.38 [-0.63, -0.13]

 
Summary of findings for the main comparison.

Automated compared with non-automated weaning for critically ill adults and children

Patient or population: critically ill adults and children requiring weaning from mechanical ventilation

Settings: intensive care units

Intervention: automated closed loop control of weaning

Comparison: clinician-led protocolized or non-protocolized usual weaning practices

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Non-automated weaningAutomated weaning

Total duration of weaning defined as study randomization to successful extubation (hours)a Mean 24 hours

b Mean 62.4 hours
Mean 16.3 hours

Mean 42.4 hours
Geometric mean difference
-32% (-19% to -46%)
1153 participants
(14 trials)
⊕⊕⊝⊝
low
We detected substantial heterogeneity explained only in part by differences in study population, automated closed loop system used, and the comparator arm. We also detected a wide confidence interval suggesting imprecision.

Total duration of ventilation defined as intubation or commencement of ventilation in ICU to successful extubation (hours)a Mean 96 hours

b Mean 182.4 hours
Mean 79.7 hours

Mean 151.4 hours
Geometric mean difference

-17% (-8% to -26%)
763 participants
(8 trials)
⊕⊕⊕⊕
high

ICU length of stay (days) a Mean 8 days

b Mean 8 days (survivors)

Mean 7 days (non-survivors)
Mean 7.1 days

Mean 7.1 days (survivors)

Mean 6.2 days (non-survivors)
Geometric mean difference
-11% (0 to -21%)
871 participants
(8 trials)
⊕⊕⊕⊝
moderate
We detected substantial heterogeneity which was explained only in part by differences in study population, automated closed loop system used, and the comparator arm.

Hospital length of stay (days)aMean 17 days

b Mean 17 days (survivors)

Mean 11.5 days (non-survivors)
Mean 16 days

Mean 16 days (survivors)

Mean 10.8 days (non-survivors)
Geometric mean difference
-6% (-17 to 8%)
609 participants
(5 trials)
⊕⊕⊕⊕
high

Mortality (ICU, hospital) (days)a ICU 31%, hospital 37% (adults)

b ICU 15%, hospital 18% (children)
ICU 66%

hospital 24%

(adults)

ICU 32%

hospital 12% (children)
Risk ratio

ICU
2.12 (0.29 to 15.63)

Hospital

0.66 (0.11 to 4.13)
905 participants
(8 trials)
⊕⊕⊕⊝
moderate
We detected moderate heterogeneity and a wide confidence interval that includes both benefit and harm suggesting imprecision

Reintubation ratea11% (adults)

b 10% (children)
9% (adults)

8% (children)
Risk ratio
0.84 (0.63 to 1.12)
950 participants
(11 trials)
⊕⊕⊕⊝
moderate
We detected a wide confidence interval that includes both benefit and harm suggesting imprecision.

*The basis for the assumed risk (e.g. the mean control group risk) is provided in footnotes. The corresponding risk is based on the assumed risk in the comparison group and the relative effect of the intervention.
CI: Confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 a Assumed risk for adults is derived from large international cohort study of mechanical ventilation and weaning by Esteban and colleagues (Esteban 2008). Reported medians are used as an approximation for the means used for illustrative comparisons of all continuous variables.
b Assumed risk for children is derived from international cohort study of mechanical ventilation and weaning by Farias and colleagues (Farias 2004). The mean duration of weaning and ventilation are reported in the paper and have been used in this illustrative comparison. Reported medians for survivors and non-survivors are used as an approximation for the mean ICU and hospital length of stay used for illustrative comparisons.