Tag Archives: ARDS

“Quantifying unintended exposure to high tidal volumes from breath-stacking dyssynchrony in ARDS: the BREATHE criteria,” Intensive Care Medicine, 2016, USA

Note: I am focusing on only one aspect of this paper, see the comments section for more details

Question: Using novel diagnostic criteria, how often does breath-stacking dyssynchrony (BSD) occur in pts with ARDS?

Study Type: Prospective observational study at 2 US hospitals

Study Population: Adult pts with ARDS placed on mechanical ventilation within the previous 24 hours were eligible provided they were ventilated in the assist-control mode. Exclusion criteria included chronic mechanical ventilation, neuromuscular disease compromising spontaneous ventilation, and impending withdrawal of full supportive care

Study Groups: Airflow and pressure were continuously recorded for 72 hours, coded by an analog-digital converter, and read directly into an analysis program. The flow-time waveform was integrated to calculate cumulative tidal volume change over consecutive machine inspiratory cycles. BSD was identified using the BREATHE criteria (consecutive inspiratory cycles + expiratory times <1 sec + expiratory volume between inspiratory cycles at least 2mL/kg PBW less than first inspiratory cycle volume + •120% set inspiratory time {for pressure-targeted breaths} + BSD TV •2mL/Kg PBW above intended TV) (essentially saying the pt inspires twice before fully exhaling the first breath). Medication administration and ventilator management were directed by the ICU team who were blinded to study analysis.

Primary Outcome: BSD as measured by the BREATHE criteria

Results: 33 pts were enrolled. Notable pt characteristics: mean age (57), shock (91%), pneumonia (83%), duration of MV prior to enrollment (16 hrs), death before discharge or day 28 (27%). Vent characteristics: VC+ (volume-targeted pressure control) (79%), VC (typical volume-cycled ventilation with a set flow rate) (21%), set TV (6 mL/kg PBW), RR (25), PEEP (10), FiO2 (50%), P/F (107). 1,841 hrs were recorded and 2,166,076 breaths were analyzed (80% without neuromuscular blockage). Observed BSD frequency was 27 (7-59) breaths/hr, peak hourly BSD frequency was 170 (55-394) breaths/hr. BSD frequency was sustained for more than 60 breaths/hr during 18% (1-37) of hrs recorded without NMB. TV during BSD was 11.3 (9.7-13.3) mL/kg PBW. Peak airway pressure minimally increased with BSD.

Caveats: Small sample size, 743 hours not recorded or included for various reasons, does not establish any connection between BSD and outcomes including ventilator-induced lung injury.

Take-home Point: Among pts with ARDS ventilated in assist-control mode, breath-stacking dyssynchrony occurs and exposes pts to potentially injurious tidal volume.

Commentary

• The BREATHE criteria are fine, but for residents easier to just remember that BSD is “inspiratory flow triggered before complete expiration” (i.e., the pt is triggering a 2nd breath before fully exhaling the first).

• I have purposely ignored one of the main aspects of this study: comparing the BREATHE criteria to other methods of measuring BSD. Unless you are really into reading about ventilator dyssynchrony, this part of the paper is less interesting than the more basic message that BSD occurs (sometimes quite often) in AC modes.

• This paper is a nice reminder that when you are setting a tidal volume in either VC or VC+, this does not guarantee that this is the volume your pt will receive before exhaling. You may think your pt is receiving “lung-protective ventilation,” but frequent episodes of BSD may cause your pt to receive very large TVs (in the above study, an average Vt of 11 mL/kg PBW). These results highlight the importance of looking at ventilator waveforms in your pts and frequently evaluating synchrony.

• Whether decreasing BSD improves outcomes remains to be seen. This is one of the proposed mechanisms by which early neuromuscular blockade may improve outcomes in ARDS but more studies are needed to prove this connection.

“Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department, the LIPS-A randomized clinical trial” JAMA, 2016, USA

Question: Does aspirin prevent the development of ARDS in at-risk patients?

Study Type:  Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial at 16 medical centers across the United States

Study Population: Adults presenting to the emergency department with a Lung Injury Prediction score ≥ 4 were eligible (see commentary for more regarding LIPS).  Numerous exclusions included ARDS on presentation, chronic use of antiplatelet therapy, admission for elective surgery, chronic tracheostomy, presentation due to CHF, active peptic ulcer disease, bleeding disorders, and severe chronic liver disease.  Randomization had to occur within 12 hours of presentation.

Study Groups: Patients were randomized to either placebo or daily ASA given as a 325mg loading dose within 24 hours of presentation followed by 81mg daily up to hospital day 7, discharge, or death.  Clinicians were encouraged to use the Checklist for Lung Injury Prevention to guide clinical care.

Primary Outcome: Development of ARDS requiring mechanical ventilation within 7 days of hospital admission

Results: 390 patients included in intention-to-treat analysis. Notable patient characteristics: median age (67), Caucasian (72%), suspected sepsis (78%), non-cardiogenic shock (21%), possible PNA (61%), ventilated on day of randomization (17%), median LIPS (≈5.75).  ASA did not decrease the development of ARDS (10.3% in ASA group, 8.7% in placebo group, P=0.53). ASA did not significantly impact any secondary outcome measures.  There was no difference in adverse events between groups

Caveats: Generalizability a concern as 95% of the 7,673 patients screened were excluded (with prior antiplatelet use, inability to consent with 12 hours, and suspected active bleeding being the most common reasons for exclusions), delay between consent and medication administration (median delay 12.7 hours), development of ARDS occurred almost half as frequently as anticipated.

Take-home Point: Among at-risk patients presenting to the emergency department, daily ASA use did not decrease the development of ARDS at 7 days.

Commentary

–       I chose to review this study because it is important for residents to be aware of the increasing focus on ARDS prevention.  Indeed, the NHLBI-funded ARDS clinical trial network is named PETAL (Prevention and Early Treatment of Acute Lung Injury).  This refocusing of ARDS clinical trials is based on the observation that ARDS incidence has decreased (suggesting perhaps that through early abx, thoughtful IVF, less injurious ventilator strategies, and restrictive transfusion thresholds we have shown that ARDS prevention is possible) and the hypothesis that so many therapeutic trials in ARDS have been negative because therapies have been initiated AFTER significant alveolar-capillary injury has already occurred.

–       The Lung Injury Prediction Score has been found to have an AUC for the prediction for ARDS of 0.8 (see attached AJRCCM article).  LIPS variables include shock, aspiration, sepsis, PNA, high-risk surgery, high-risk trauma, EtOH abuse, obesity, low albumin, chemotherapy, FIO2>0.35, RR>30, SpO2<95%, pH <7.35, DM.  At a cut-off of 4, LIPS has a sensitivity of 69% and specificity of 78% for the development of ARDS.  Based on the AJRCCM data, with a LIPS of 6 (roughly the average of pts in the JAMA trial), you would expect roughly 15% to develop ARDS.

–       ASA was chosen given the known pathogenic role of platelet activation and aggregation in the development of ARDS, the anti-inflammatory effects of ASA, and encouraging pre-clinical data.