Author Archives: Cathy

“Outcomes associated with corticosteroid dosage in critically ill patients with acute exacerbations of chronic obstructive pulmonary disease,” AJRCCM, 2016

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“Outcomes associated with corticosteroid dosage in critically ill patients with acute exacerbations of chronic obstructive pulmonary disease,” AJRCCM, 2016, University of Colorado

Question: Is high-dose or low-dose systemic corticosteroid therapy better for intensive care unit (ICU) patients with acute exacerbations of COPD (AE-COPD)?

 Study Type: Retrospective cohort study using a large national quality and health care use database.

Study Population: Patients >40 years of age admitted to an ICU and treated with systemic corticosteroids by hospital day 2 for AE-COPD.  Patients excluded if steroid dose >1g/day methylpred, OSH tx, re-admission within 30 days of a prior discharge, solid organ transplant, or presence of pulmonary embolism, pneumothorax, shock, or antifungal therapy.

Study Groups: Patients divided into high-dose corticosteroids (>240 mg/day methylpred) and lower-dose corticosteroids (≤240 mg/day methylpred, i.e., 60 mg Q6 hrs or less).

Primary Outcome: In-hospital mortality

Results: 17,239 patients included in analysis.  After propensity score matching, there was no difference in the primary outcome between groups.  Patients in the lower-dose group had better clinical outcomes (less time on mechanical ventilation, less time in the ICU, less time in the hospital) and less steroid-related complications (decreased insulin requirements and fewer fungal infections).

Caveats: Retrospective design, association ≠ causation, and potential for unmeasured confounding.

Take-home Point: High-dose systemic corticosteroid therapy does not improve outcomes for critically ill patients with AE-COPD and is associated with a higher rate of steroid-related complications.

The third international consensus definitions for sepsis and septic shock (sepsis-3)

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“The third international consensus definitions for sepsis and septic shock (sepsis-3),” JAMA 315: 801, 2016, SCCM sepsis definitions task force

Intro:

  • initial definitions of sepsis, severe sepsis, and septic shock from 1991; defined severe sepsis as sepsis complicated by organ dysfx which could progress to septic shock, defined as hypotension despite adequate fluid resuscitation; revisited in 2001
  • the definitions of sepsis, severe sepsis, and septic shock have remained largely unchanged for more than 2 decades

Process of developing new definitions:

  • recognizing the need to reexamine current definitions, the euro society of critical care medicine and the society of critical care medicine convened a task force (TF) of 19 experts in critical care, ID, surgery, and pulmonology (no EM) in jan 2014
  • existing definitions were revisited in light of an enhanced appreciation of the pathobiology and the availability of large EMR databases and pt cohorts
  • expert consensus process forged agreement on updated definitions and the criteria to be tested in the clinical arena
  • the agreement between potential clinical criteria and the ability of the criteria to predict outcomes (eg ICU admission, mortality) were then tested in multiple large EMR databases
  • systematic lit review/metaanalysis and delphi consensus methods were also used for the definition and clinical criteria describing septic shock
  • when compiled, the TF recommendations were circulated to major international societies and other relevant bodies for peer review and endorsing (a total of 31 endorsing societies) (again, no EM)

 Challenges and opportunities:

  • because no gold standard diagnostic tests exist for sepsis, the TF sought definitions and supporting clinical criteria that were clear and fulfilled multiple domains of usefulness and validity
  • the original conceptualization of sepsis as infection + ³2 SIRS criteria focused solely on inflammatory excess; sepsis is now recognized to involve early activation of both pro- and anti-inflammatory responses, along with major modifications in nonimmunologic pathways such as cardiovascular, neuronal, autonomic, hormonal, bioenergetic, metabolic, and coagulation, all of which have prognostic significance; a broader perspective also emphasizes the significant biological and clinical heterogeneity in affected individuals
  • the current ³2 SIRS criteria to identify sepsis was unanimously considered by the TF to be unhelpful
  • the “sequential organ failure assessment” (SOFA) score looks at severity of organ dysfx via the following variables: P/F ratio (resp), platelets (coag), bili (liver), BP (cardiovascular), GCS (neuro), creat and UO (renal); a higher SOFA score is associated with increased mortality, but outside the critical care community the score is not well known + cumbersome to use
  • multiple definitions for septic shock are currently in use resulting in significant heterogeneity in reported mortality
  • the public needs an understandable definition of sepsis and health care providers require improved clinical prompts and diagnostic approaches to facilitate earlier identification and an accurate quantification of the burden of sepsis

Results/recommendations:

Definition of sepsis:

  • sepsis is defined as life-threatening organ dysfx caused by a dysregulated host response to infection
  • under this definition (“life-threatening organ dysfx”), the term “severe sepsis” becomes superfluous

Clinical criteria to identify pts with sepsis:

  • the TF evaluated which clinical criteria best identified pts most likely to have sepsis; this objective was achieved by interrogating large datasets of hospitalized pts with presumed infection, assessing agreement among existing scores of inflammation (SIRS) or organ dysfx (SOFA), and delineating their correlation with subsequent outcomes; in addition, multivariable regression was used to explore the performance of 21 bedside and lab criteria proposed by the 2001 TF
  • the EMR included 150,000 pts with suspected infection (from 12 hosps within the univ of pittsburgh system); two outcomes – ICU stay ³3 days and mortality – were used to assess predictive validity
  • for ICU pts, a change in SOFA score ³2 from baseline was superior to SIRS criteria; the TF recommends the use of SOFA score ³2 from baseline to identify life-threatening organ dysfx and, thus, sepsis
  • for non-ICU pts, the TF found that 2 or more of the following clinical variables – altered mental status, syst BP £100, and RR ³22 – offered good predictive validity; this new measure is termed qSOFA (for quick SOFA) and provides simple bedside criteria to identify life-threatening organ dysfx and, thus, sepsis; the TF recommends that qSOFA criteria be used to prompt clinicians to further investigate organ dysfx, to initiate or escalate therapy as appropriate, and to consider referral to critical care specialists
  • thus, for ER pts, the TF recommends the following for identification of pts with sepsis: ³2 of the qSOFA criteria: altered MS, syst BP £100, RR ³22

Definition of septic shock:

  • septic shock is a subset of sepsis in which underlying circulatory and cellular metabolic abnormalities are profound enough to substantially increase mortality

Clinical criteria to identify septic shock:

  • 3 variables were identified to test in cohort studies – MAP <65, lactate >2, and need for vasopressor(s) to maintain MAP ³65 after volume resuscitation
  • the first database interrogated was the surviving sepsis campaign’s international multicenter registry; a total of 20,000 septic pts; the mortality for septic pts with all 3 variables was >40%
  • these same 3 variables were then used to interrogate 2 unrelated large EMR datasets – univ of pittsburgh (12 hosps, 6,000 pts) and kaiser (20 hosps, 54,000 pts); the mortality for septic pts with all 3 variables was 35-55%
  • thus, the TF recommends the following criteria for identification of pts with septic shock: MAP <65, lactate >2, and need for vasopressor(s) to maintain MAP ³65 after volume resuscitation

Controversies – lactate levels:

  • because lactate offered no meaningful change in the predictive validity beyond ³2 of the qSOFA criteria in the identification of pts with sepsis, the TF could not justify adding the complexity/cost of lactates alongside these simple bedside criteria
  • the TF recommendations should not, however, constrain the monitoring of lactate as an indicator of illness severity or as a guide to therapeutic response
  • some TF members suggested that elevated lactate represents an important marker of “covert shock” in the absence of hypotension

Implications:

  • simple clinical criteria (qSOFA) that identify pts with sepsis (ie pts with evidence of infection who are likely to have a prolonged ICU course +/- death) have been developed and validated
  • there is potential conflict with current organ dysfx scoring systems, early warning scores, ongoing research studies, and pathway developments

“Editorial: new definitions for sepsis and septic shock: continuing evolution but with much still to be done,” wake forest

  • the TF assessed the predictive validity of SOFA, SIRS, and qSOFA in a primary cohort that included 150,000 pts with suspected sepsis and a confirmatory analysis that included 700,000 pt encounters at 156 US and non-US hosps
  • for identifying pts with sepsis: the investigators found that in the ICU the best predictive value was found with change in SOFA score >2 from baseline; in non-ICU settings, the best predictive value was found with the qSOFA score
  • for identifying pts with septic shock: the TF conducted a systematic review and metaanalysis of 92 studies informing a delphi process that created the new definition, then tested the variables identified by the delphi process in cohort studies using datasets from the surviving sepsis registry, univ of pittsburgh hosps, and kaiser hosps
  • according to the new recommendations:
    • sepsis is now identified by evidence of infection + life-threatening organ dysfx, clinically characterized by an acute change in the SOFA score ³2 from baseline (ICU pts) or ³2 of the 3 clinical variables of the qSOFA score (nonICU pts)
    • septic shock is now identified by MAP <65, lactate >2, and the need for vasopressor(s) to maintain MAP >65 after volume resuscitation
  • there is no longer any mention of the SIRS criteria (HR >90, RR >20, T >38° or <36°, WBC >12K or bands >10%)
  • there remain concerns with the quality of the information used to generate the updated criteria
  • regarding the new qSOFA score: because this score was retrospectively derived from databases that had substantial gaps in clinical info for pts treated outside ICUs, qSOFA will require prospective real-world validation before it should enter routine clinical practice

Pulmonary morning report

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Patient in her 60s, former smoker 40py, with abnormal LDCT imaging. Some dyspnea but thought to be related to significant weight gain during pandemic.

Special shoutout to Dr. Agrawal’s Youtube channel and MIPs!

The case had a small endobronchial lesion on CT. We reviewed the differential for endobronchial lesions:

 

And focused on trahceobronchial tumors, which are rare, 0.6% of pulmonary tumors. (With a fun jeopardy matching series of slides, not captured in this post.)

DIPNECH – associated with bronchial carcinoid, consider in asthma patient with endobronchial abnormality.

Thanks for a great review and a fun interactive session, Dr. Rowe!

Timothy Rowe, MD, Pulmonary and Critical Care

Prevalence of pulmonary embolism among patients hospitalized for syncope

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“Prevalence of pulmonary embolism among patients hospitalized for syncope,” NEJM, 2016, Italy

Question: What is the prevalence of pulmonary embolism in patients hospitalized for a first episode of syncope?

Study Type: Multicenter cross-sectional study at 11 hospitals in Italy

Study Population: Patients admitted for syncope were eligible. Exclusion criteria included pregnancy, previous episodes of syncope, and use of anticoagulation.

Study Groups: Enrolled patients had a simplified dichotomized Wells score calculated and a D-dimer drawn. Patients with a Wells score ≤4 and a negative D-dimer were considered to have PE excluded. Patients with a Wells score >4, a positive D-dimer, or both underwent further evaluation for PE with either a PE-CT or V/Q scan

Primary Outcome: Presence of a pulmonary embolism on either PE-CT or V/Q scan.

 Results: Of 2,584 patients who visited the ED for syncope, 717 were admitted, and 560 (22% of all patients) were included in the study.  The median age of the cohort was 80. 330 patients (60%) had a PE excluded by a low-risk Wells score and a negative D-dimer.  PE was identified in 97 of the remaining 230 patients (17% of the study cohort).  Of patients diagnosed with a PE, 45% had a RR>20, 33% had a HR >100, 40% had clinical signs of DVT, and 20% had active cancer.  17 patients with a PE (18%) had a small thrombus burden identified by either a subsegmental PE on CT-PE or a perfusion defect of 1-25% on V/Q scan.

Caveats: No information on outcomes of patients discharged from the ED, normal diagnostic testing for PE risk stratification (troponin, BNP, echo) not included, age-adjusted D-dimer not used, no outcomes information for patients diagnosed with a PE, concern regarding generalizability (the study cohort was elderly and the prevalence of PE in Europe is different than in the United States).

Take-home Point: A diagnosis of pulmonary embolism should be considered in patients admitted to the hospital with a first episode of syncope.

Commentary: There is concern that this article will be used to justify indiscriminate testing for PE in patients with syncope (one educational blog review of this article is entitled “The Impending Pulmonary Embolism Apocalypse”).  My thoughts on what this trial should and should not do:

  1. This trial should remind clinicians of the important Christopher study (JAMA 2006) which showed that a clinical decision score (a dichotomized Wells score) combined with D-dimer testing can exclude PE and avoid unnecessary CT scans with a low miss rate (<0.5%) in a large number of patients. Interns and residents not familiar with this article should give it a read. 
  1. This trial should also remind clinicians that pulmonary embolism is a potential cause of syncope and that especially in older patients with concerning signs/symptoms, a diagnostic evaluation for VTE should be considered. Of patients diagnosed with PE in this trial, 45% were tachypneic, 33% were tachycardic, 40% had signs of DVT, and 40% had a high risk Wells score on presentation all in a cohort in which 20% had active cancer. Considering the diagnosis of VTE in this group seems like a reasonable thing to do.  It is notable that 25% of patients who were diagnosed with a PE did not have clinical manifestations of VTE. 
  1. The prevalence of 17% found in this study should not be generalized to practice in theUS. Multiple studies have found the prevalence of PE in Europe to be consistently higher than in the United States (around 25-30% for Europe vs. <10% in the US).  The patients in this trial were also elderly and likely a higher risk cohort than other syncope populations.  The striking difference between the prevalence of 17% found in this trial and the very low prevalence found in the studies they cite (<3%) likely in part reflect their rigorous testing and unique patient cohort.
  2. Identification should not be conflated with causation. 18% of patients had a small thrombus burden identified on either CT or V/Q scanning. It is not clear from the trial if these small clots were the cause of syncope or if identifying and treating them impacts patient outcomes.  ​

Levosimendan for the prevention of acute organ dysfunction in sepsis

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“Levosimendan for the prevention of acute organ dysfunction in sepsis,” NEJM, 2016, UK

Background: Levosimendan is a calcium-sensitizing drug marketed under the trade name Simdax that is approved in Europe and South American for use in acute decompensated heart failure. It increases cardiac contractility through calcium sensitization of troponin C and vasodilates by opening potassium channels in vascular smooth muscle cells. It is felt to only minimally increase myocardial oxygen demand. Small trials have suggested that it may improve organ perfusion and hemodynamics in sepsis.

Question: Does the addition of levosimendan to standard care in patients with septic shock reduce the severity of organ dysfunction?

Study Type: Multicenter, randomized, double-blind, placebo-controlled trial in 34 ICUs in the UK.

Study Population: Adult patients who required vasopressor support for ≥4hrs for septic shock were eligible for the trial. Exclusion criteria included >24 hrs of vasopressor support prior to enrollment, ESRD, Child-Pugh C liver disease, history of torsades, DNR, weight >125kg, and pregnancy.

Study Groups: Patients randomized to levosimendan or placebo for 24 hours. Additional inotropic medications were allowed if felt necessary by the treating clinician. Orion Pharmaceuticals provided the study drug but was not otherwise involved in the trial.

Primary Outcome: Mean daily SOFA score while in the ICU for a maximum of 28 days.

Results: 516 patients were randomized. The majority of screened patients were excluded because they were outside the 24hr window since meeting inclusion criteria. Notable baseline characteristics: Caucasian (93%), recent surgery (37%), APACE II (25), lung as primary source of infection (39%), beta-blockers at baseline (19%), mechanical ventilation (81%), dobutamine (9%). There was no difference in the mean SOFA score during ICU stay (6.68 +/-3.96 in the levosimendan group and 6.06 +/- 3.89 in the placebo group). Patients given levosimendan required more norepinephrine, were less likely to be liberated from mechanical ventilation, and more likely to experience SVT. Levosimendan did not improve outcomes in any of the pre-specified subgroups including patients with low cardiac output, impaired O2 delivery to tissue, and those on high-dose vasopressors. There was no difference in any mortality measure. Of note, cardiac index was similar throughout the trial in both groups (largely between 3.1-3.5 L/min/m2).

Caveats: Mostly Caucasian patients, does not answer the question of whether levosimendan may be helpful in the initial resuscitation of septic shock (median time from shock to randomization in this trial was 16 hrs), does not answer the question of whether a supranormal cardiac index is helpful in septic shock (both groups had a similar CI and very few patients in the intervention arm would have fit into the “cardiac index” arm of the 1995 NEJM trial we reviewed where CI goal was >4.5), does not answer the question of whether an inotrope is helpful in septic shock as the addition of levosimendan was offset in part by increased dobutamine use in the control arm, cardiac index was only measured in a subset of patients (30%) and measured using a variety of methods (PiCCO, esophageal Doppler, PAC) raising questions about generalizability and accuracy, more dobutamine use in the standard care arm then is seen at NMH.

Take-home Point: The addition of levosimendan to standard care in patients with septic shock does not improve outcomes and may be harmful.

Commentary: For me, an odd hypothesis to think that levosimendan would provide much physiologic benefit in this patient group: resuscitated septic patients who had been on vasopressors for a median of 16 hours and had adequate DO2 (as assessed by a median ScVO2 of 75 at the time of enrollment) especially as another inotrope was allowed in both arms. I would have been more interested in a protocol focused on early resuscitation, perhaps specifically in patients with a low ScVO2 or known cardiac dysfunction comparing levosimendan to placebo (without additional dobutamine) or a three-armed trial with levosimendan vs dobutamine vs placebo (as levosimendan’s ability to only minimally raise myocardial O2 demand offers some potential advantages over dobutamine). In any case, this trial, and others strongly suggest that a supranormal DO2 (or attempts to achieve one) are of little benefit in patients with sepsis. This trial is also a good reminder to take systematic reviews of small trials with a big grain of salt (see “Levosimendan reduces mortality in patients with severe sepsis and septic shock: a meta-analysis of randomized trials,” J Critical Care, 2015).

Bilateral pneumonectomies and ECMO support

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I read with fascination these case reports about bilateral pneumonectomies with ECMO support – came up during Lung Rescue discussion.

From Cypel et al

https://www.sciencedirect.com/science/article/pii/S0022522316316233 – Cypel et al, a CF patient who had shock from Pseudomonas bacteremia who had this done to get source control, after pneumonectomies, she had dramatic improvement. Had this configuration:

https://www.sciencedirect.com/science/article/pii/S1053249819316298?via%3Dihub – Barac et al, another young CF patient with Bulkholderia, with bilateral pneumonectomies to clear his infection prior to transplant. With this layout:

Figure 1

Really interesting to read about these cases. A more recent case: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780122/ – severe COVID respiratory failure on ECMO with persistent COVID and Stenotrophomonas, interestingly had a PFO that was used for shunting to offload the left ventricle (they suggest atrial septostomy could be performed in those who don’t have a PFO).

Azithromycin for acute exacerbations of asthma: The AZALEA randomized clinical trial

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“Azithromycin for acute exacerbations of asthma: The AZALEA randomized clinical trial,” JAMA IM, 2016, United Kingdom

Question: Does azithromycin improve outcomes for patients with acute asthma exacerbations?

Study Type: Multicenter, double-blind, placebo-controlled randomized trial

Study Population: Adults with a documented history of asthma who required IV or oral steroids for an acute asthma exacerbation were eligible.  Notable exclusion criteria included the use of oral or intravenous corticosteroids within the previous 28 days and need for intensive care unit admission.

Study Groups: Patients were randomized to receive azithromycin 500mg daily or placebo for 3 days.

Primary Outcome: Diary card summary symptom score at day 10

Results: Of the 4,500 patients screened, 45% were excluded because they had already received antibiotics.  199 patients were randomized.  Asthma symptom scores measured at day 10 did not differ between the two groups. Similarly, the addition of azithromycin did not improve quality-of-life scores, lung function measurements, or time to 50% reduction in symptom score.

Caveats: Study did not meet enrollment goal and was underpowered, investigators enrolled a select group of patients that treating clinicians felt would not benefit from antibiotic therapy (the 55% of patients not excluded for already receiving abx) perhaps skewing the trial toward a negative result.

 Take-home Point: Azithromycin does not improve outcomes for patients with acute asthma exacerbations.  The trial also shows that abx are still widely prescribed for asthma exacerbations despite not being supported by guidelines or evidence.

Impact of thrombolytic therapy on the long-term outcome of intermediate-risk pulmonary embolism

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“Impact of thrombolytic therapy on the long-term outcome of intermediate-risk pulmonary embolism” JACC, 2017, Europe

Question: Does thrombolytic therapy for submassive PE impact long-term outcomes?

Study Type:  Long-term follow-up of a multicenter, double-blind, placebo-controlled trial

Study Population: Study focused on a subset of patients from the PEITHO trial (NEJM, 2012). In PEITHO, 1,006 adults with confirmed PE + RV dysfunction (on either TTE or CT) + elevated troponin I or T were randomized to heparin +/- a single weight-based intravenous bolus of tenecteplase.  After a protocol amendment, consent was obtained from a subset of these patients to obtain 2-year survival data and prospectively conduct long-term clinical and echocardiographic follow-up.

Primary Outcome: Death from any cause at 2 years

Results: 709 patients included (70% of entire PEITHO cohort). Compared to patients without 24-month follow-up, patients in the study had a lower mean body weight (81.8 kg vs. 84.4 kg) and less prior VTE (25% vs. 32%). Patients in the follow-up cohort had a mean age of 66.6 and 8.2% had active cancer. Overall, treatment with tenecteplase was not associated with any improvement in long-term outcomes. Notable results (tenecteplase % listed first): death from any cause between randomization and 2-year follow-up (20.3% vs. 18%), persistent clinical symptoms (36% vs. 30%), NYHA class III or IV dyspnea (12% vs. 10.9%), 1 or more echo indicators of pulmonary HTN or RV dysfunction (44.1% vs 36.6%), PASP (31.6 vs. 30.7)

Caveats: Only included a subset of the PEITHO cohort, only 40% of included patients had TTE f/u, up to 33% of patients had missing data for various endpoints, outcomes not stratified by submassive risk (i.e., rising troponin, progressive hypoxemia, etc), duration to determine risk of CTEPH may not be long enough to truly identify people who develop the disease.

Take-home Point: Among patients with submassive PE (defined by the presence of RV dysfunction and elevated troponin), systemic thrombolytics does not appear to improve long-term mortality, functional outcomes, or rates of pulmonary hypertension compared to anticoagulation alone.

Commentary

–       Despite the limitations noted above (I am not sure why assessing long-term outcomes was not a pre-specified aim of the study before it started), this is an important article.

–       The PEITHO study remains the highest quality trial of thrombolytics for submassive PE. In that trial, lytics decreased the risk of a composite endpoint of hemodynamic collapse or death within 7 days (3% with lytics vs. 6% with placebo driven almost entirely by a decrease in hemodynamic collapse) at the cost of an increased risk of bleeding including ICH (2% with lytics vs 0.2% with placebo for ICH). Important also to recognize that the inclusion criteria for PEITHO were VERY liberal – all you needed was a +trop and some evidence of RV dysfunction. Many would argue that a large # of PEITHO pts should never have been given lytics at all.

–       Based on very flawed studies (TOPCOAT, MOPPET), many clinicians give lytics for submassive PE with the goal of improving functional status and decreasing the risk of CTEPH. The results of this article should temper enthusiasm for such a strategy as there was no signal in any of the outcomes assessed that lytics was beneficial.

–       This study does not specifically address catheter-directed therapy nor does it help answer whether lytics are beneficial in particularly high-risk patients (rising troponins, mild hypoxemia, relative hypotension, rising lactate, etc.).

–       In summary, there is potentially (likely?) a role for lytics in a very high-risk group of patients with submassive PE but accumulating evidence suggests that when lytics are given to all patients who meet criteria for submassive PE, they increase rates of bleeding and provide little short or long-term benefit.

Quantifying unintended exposure to high tidal volumes from breath-stacking dyssynchrony in ARDS: the BREATHE criteria,

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“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.

 

Grand Rounds: COLDSTER trial

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Thanks to Scott for summarizing this trial today! COLDSTER

Cold Weather Health Risks: A Detailed Guide | Everyday Health

In patients who had COVID 3-8 weeks ago, who have dyspnea or hypoxia and >20% abnormalities on CT, do high vs low dose steroids help and is one dose better than the other?

290 patients -> 160 excluded (82 too mild lung abnormalities)

130 randomized 1:1 -> high dose (40 x1 w then 30mg x1w then 20mgx2w then 10mg x2w) vs low dose (10mg x6w) treatment

Baseline tests, 2, 4 weeks in telephone checkin for adherence, adverse effects, final 6 week checkin – lost 4 in one arm and 5 in another arm

57yo, only 32% female, 73% had at least one comorbidity, all had required hospitalization for acute COVID, 98% having WHO severe disease, 43% received mech vent, 91% had organizing pneumonia patterns on CT

Scored images by lobe and averaged and primary outcome was >90% radiological improvement and they also had numerous subgroups.

There were low rates of ‘complete radiological response’ in both groups 25%-19%. Both groups had improvements in FVC, 6MWT, symptom scores, and overall CT scores.

Both groups had adverse effects including hyperglycemia (though only 30%), hypertension (23-21%), cushinoid habitus (20%). No deaths in either groups, 3 infections in high dose and 1 in low dose group, all treated.

It seems that in these post-acute COVID patients, low steroid dose with 10mg prednisolone performs similarly to high dose steroids to improve symptoms and imaging.

Limitations include the small size and lack of blinding. There haven’t yet been a placebo trial either, so that could be a next step. Also, was this done too soon, as patients may still have been recovering from the original infection? Multi-center would be nice as well, and blinding where able (for example, reviewers of the CT).

Thanks, Dr. Laurenzo!