The Effect of Preemptive APRV on Patients With High Risk for ARDS
Condition: Acute Respiratory Distress Syndrome; Intensive Care Unit
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome
Study type: Interventional

Summary: 
      Airway pressure release ventilation (APRV) is a mode of mechanical ventilation that
      alternates between two levels of continuous positive airway pressure (CPAP) support and
      allows spontaneous respiratory effort at either CPAP level. It is considered as an
      alternative, life-saving modality in patients with acute respiratory distress syndrome (ARDS)
      that struggle for oxygenation. Compared to the classical ventilation, APRV has been shown to
      provide lower peak pressure, better oxygenation, less circulatory loss, and better gas
      exchange without deteriorating the hemodynamic condition of the ARDS patient. This mode is
      believed to help to achieve the target of opening consolidated lung areas (recruitment) and
      to prevent repeated opening-closing of alveoli (decruitment). However, there is still
      insufficient and limited proof to support this hypothesis.

      Recently, it has been proposed that early use of protective mechanical ventilation with APRV
      could be used preemptively to prevent development of ARDS in high risk patients. In that
      study, APRV prevented clinical and histological lung injury by protecting alveolar epithelial
      integrity, preserving surfactant and alveolar stability, and reducing pulmonary edema.

      The primary purpose of the present study was to investigate whether early use of APRV as a
      lung-protecting strategy was superior to the conventional methods in a patient population
      with high risk of acute respiratory distress syndrome (ARDS).
    

Detailed description: 
      This study was planned as a single-centered, prospective, and randomised-controlled study in
      a general intensive care unit with 18 bed capacity. The majority of the general patient
      population is made up of trauma and post-operative patients. The local ethics committee
      reviewed and approved the study protocol (protocol number: 2016/175) prior to the start of
      the investigation. Enrollment for the study was performed between May 2016-October 2018.
      Written informed consent was obtained from each patient's relatives.

      Study design and sample:

      The study included patients who required invasive mechanical ventilation but was not
      initially diagnosed with ARDS 9, had a LIPS (Lung Injury Prediction Score) of > 7 10, and
      have been staying in the ICU for more than 24 hours. Patient demographic properties, sedation
      requirements, inotrope/vasopressor levels, ARDS development status during follow-up,
      mechanical ventilation times, length of ICU stay, arterial blood gas results, mean airway
      pressure (Pmean), peak airway pressure (Ppeak) and tidal volume (Vt) in addition to the
      mode-specific mechanical ventilation parameters were recorded. Exclusion criteria were
      pregnancy, intracranial hypertension (suspected or confirmed by measurement with external
      ventricular drainage catheter), severe chronic obstructive pulmonary disease or type II
      respiratory failure, confirmed bronchopleural fistula, documented barotrauma, history of
      pneumonectomy, and age below 18 or above 85 years. Consecutive eligible patients were
      enrolled block randomization with a 1:1 allocation, randomly assigned to APRV or P-SIMV+PS
      groups using opaque, sealed envelopes.

      Ventilator Settings:

      All mechanical ventilation settings were made by intensivists, or trained residents on the
      night shifts. Prior to randomization, all patients were treated with VC-SIMV mode. Patients
      admitted during the day were ventilated in VC-SIMV mode until the main investigators
      evaluated the patient (1-2 hours), and patient admitted in the evening-night shift were
      ventilated in VC-SIMV mode until the main investigators took over the shift in the morning
      (maximum 16 hours). Assignment to groups was performed after calculation of LIPS score.
      Microprocessor-controlled mechanical ventilators (Galileo GOLD; Hamilton Medical AG, Bonaduz,
      Switzerland) and heated humidifiers were used as a standard in all patients. In both groups,
      mechanical ventilation targets were determined as maintaining plateau airway pressure
      (Pplateu) < 30 cmH2O and PaO2 between 60-100 mmHg or SO2>88%. In both groups, arterial blood
      gas measurement was performed at least twice a day. Oxygenation and respiratory mechanics
      were evaluated by comparing P-SIMV+PS and APRV groups at baseline and on days 1, 2, 3, and 7.
      Patients were followed until transfer to CPAP/T-tube and extubation, or a maximum of 28 days.
      During this period, follow-up was terminated once at extubation, exitus, discharge from ICU
      or ARDS occurred.

      P-SIMV+PS group:

      The reason behind using P-SIMV+PS as a conventional mode was that it is a pressure controlled
      mode like APRV. Pressure level was adjusted in order to get a Vt of 6-8 ml.kg-1.PBW-1
      (predicted body weight). Optimal PEEP between 5-10 cmH2O was applied to all patients by
      titrating according to O2 requirement. Respiratory rate was adjusted as 12-15 breaths.min-1,
      and inspiratory time was initially adjusted to approximately 1.5 seconds. The I:E ratio was
      adjusted by either changing inspiratory time, respiratory rate, or both. Inspiratory
      triggering sensitivity was adjusted as 2 L.min-1, and was tittered by reaching the minimum
      level in the absence of automatic triggering.

      APRV group:

      Standard initial settings were Thigh / Tlow: 4/0.8 secods, Phigh: taking Pplateau value (if
      patient is paralyzed) or Pmean in the previous conventional method as reference, Pplateau <
      30 cmH20 and target Vt 6-8 ml.kg-1.PBW-1. Plow was always set to 0 cmH2O. T-low was adjusted
      according to PCO2 value in blood gas measurement, by evaluating expiratory flow curve (gas
      flow wave form), and to get a release duration of 10-14.cycle-1. Tlow range was adjusted as
      0.4-1.2 seconds. When needed, Thigh was gradually increased to 12-15 seconds by increments of
      1-2 seconds. In case of hypoxemia, the problem was generally solved by increasing Phigh and
      FiO2, and as an additional strategy, Thigh was increased. In case of hypercapnia, sedation
      was lowered to allow spontaneous breaths. In order to increase the number of releases and
      thus, increase the minute-ventilation, Thigh was shortened and Phigh was increased 12,13.

      Weaning Process:

      Weaning was performed according to the European Respiratory Society Weaning Task Force
      recommendations in both groups 14. In APRV group, Phigh was reduced by 2-3 cmH2O and Thigh
      increased by 0.5-2.0 sec during weaning as the patient tolerated it. Tlow was kept constant
      at the same time. Before transfer to CPAP, Phigh was kept at approximately 14-16 cm H2O or
      lower, and Thigh was increased up to level of 10-12 sec. In P-SIMV+PS group, respiratory rate
      was reduced by 2 breaths.min-1, and PS level was reduced by decrements of 2-4 cmH2O. In both
      groups, spontaneous breathing trial was attempted for 30-60 minutes with T-tube when CPAP was
      5-10 cmH2O, and patients were extubated afterwards. For patients with tolerance, the same
      trial was repeated the next day. Total MV time was defined as the time passed from intubation
      to the last successful extubation. Patients who required tracheotomy during follow-up were
      recorded.

      Medical and Supportive Treatments:

      Preferred medications for those patients requiring sedation was midazolam infused at loading
      dose: 0.5 to 5 mg every 1 to 5 minutes (if needed), followed by 1 to 8 mg.hour-1 or 0.01 to
      0.1 mg.kg-1.hour-1 continuous infusion; titrate infusion rate to clinical effect; for
      analgesia, fentanyl infused at 1-2 mcg.kg-1.hr-1 i.v. The sedation goal was a Richmond
      Agitation Sedation Scale score of - 2 to 0 15. According to our clinic's sedation policy,
      Richmond Agitation Sedation Scale was assessed hourly by the nursing staff, and medication
      doses were titrated by the respiratory therapists according to target spontaneous respiration
      level. Evaluation of whether patients received sedation and the number of days which they
      received sedation were recorded. Sedation doses were not evaluated. None of the patients
      received neuromuscular blocker. Fluid management, antibiotic strategy, glucose control and
      enteral nutrition were also standardized between the two groups according to the ICU
      protocols.

      Statistical Analysis On the primary outcome of developing ARDS in the light of P/F ratio
      8[Clinically defined ALI/ARDS developed in the CMV group (mean [SE] PaO2/FIO2 [P/F] ratio,
      242.96 [S.E. 24.82]), and this was prevented with APRV (P/F ratio, 478.00 [S.E.41.38]; P <
      .05 vs CMV)], power analysis using the Gpower computer program11 indicated that a total
      sample of 58 people would be needed to detect large effects (d: 0.888) with 90% power using a
      t test between means with 2-tailed alpha at .05.

      All data were analyzed using IBM SPSS V23 (Chicago, USA). The Shapiro Wilk test was used to
      determine whether the data were normally distributed. Comparisons of data that were not
      normally distributed were made with the Kruskal Wallis test and the Mann Whitney U test.
      Categorical data were analyzed with the Pearson chi-square test. The groups were compared
      with regard to laboratory parameters measured on days 1, 2, 3, and 7. Non-normally
      distributed data were presented as median (min-max), while normally distributed data were
      presented as mean ± standard deviation. Categorical data were expressed as frequency and
      percentage. Values of p < .05 were considered significant.

      Study Endpoint The primary endpoint of the study was to determine whether APRV mode was
      protective against ARDS compared to the conventional mode in patients with high risk of ARDS
      as determined by LIPS score. The secondary endpoint was to determine whether this mode
      provided any improvement in oxygenation, airway pressures, sedation and inotrope
      requirements, mechanical ventilation time and length of ICU/hospital stay.
    

Intervention name(s): Mechanical Ventilation Mode (airway pressure release ventilation )
Intervention type(s): Device
Intervention description(s): Airway pressure release ventilation (APRV) is a mode of mechanical ventilation that alternates between two levels of continuous positive airway pressure (CPAP) support and allows spontaneous respiratory effort at either CPAP level. It is considered as an alternative, life-saving modality in patients with acute respiratory distress syndrome (ARDS) that struggle for oxygenation.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: a randomized controlled trial
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: APRV; Intensive Care Unit