Author Archives: Mac Walter

Academic Half Day 11/18/2022: Managing Respiratory Failure in the ICU Part 2

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Mechanical Ventilation in Severe Asthma

The effects of ventilatory pattern on hyperinflation, airway pressures, and circulation in mechanical ventilation of patients with severe air-flow obstruction – Am Rev Respir Dis 1987

  • Initial case series mentioned by Dr. Corbridge that described the relationship between minute ventilation, tidal volume, and inspiratory time on pulmonary hyperinflation in states of severe airflow obstruction

Mechanical ventilation for severe asthma – CHEST 2015

  • Helpful review of how to manage the ventilator in severe asthma

Management of life-threatening asthma – CHEST 2022

  • New CHEST review which provides more details on pharmacotherapies

Advanced Topics in ARDS and Ventilator Management

Acute Respiratory Distress Syndrome – Nat Rev Dis Primers 2019

  • Nice review which summarizes a lot of what we know about ARDS pathobiology

Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy – Am J Respir Crit Care Med 2013

  • Important study which found that < 50% of autopsy specimens from patients who met Berlin Criteria for ARDS had diffuse alveolar damage on pathology. Pneumonia was the most common alternative finding

New Insights into Clinical and Mechanistic Heterogeneity of the Acute Respiratory Distress Syndrome: Summary of the Aspen Lung Conference 2021 – Am J Respir Cell Mol Bio 2022

  • Summary of discussions from Aspen Lung Conference. Provides a nice review of ARDS phenotyping including hypo and hyperinflammatory  phenotypes and implications for clinical trial design

The “baby lung” became an adult – Intensive Care Med 2016

  • Easy to ready summary of “baby lung” concept in ARDS

Driving pressure and survival in the acute respiratory distress syndrome – N Engl J Med 2015

  • Re-analysis of ARDS clinical trials which found that driving pressure was strongly associated with survival and that interventions which lowered delta P were associated with improved outcomes

Fifty Years of Research in ARDS. Spontaneous Breathing during Mechanical Ventilation. Risks, Mechanisms, and Management – Am J Respir Crit Care Med 2017 

  • Nice summary of potential risks and benefits of spontaneous breathing during ARDS. Discusses transpulmonary pressure and pendelluft

Setting PEEP in ARDS

Fifty Years of Research in ARDS. Setting Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome – Am J Respir Crit Care Med 2017

  • Part of 50 years of research in ARDS series (worth reading entire series). Review several approaches to setting PEEP including driving pressure, PV curves, and esophageal pressure monitoring

Liberation from Mechanical ventilation

Summary of ACCP/ATS Liberation from IMV guidelines on this blog 

Two foundational vent liberation trials to know:

A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group – N Engl J Med 1995

  • Landmark weaning trial which found T-piece was superior to weaning by pressure support or IMV

Comparison of three methods of gradual withdrawal from ventilator support during weaning from mechanical ventilation – Am J Respir Crit Care Med 1994

  • Using the specific weaning protocols in the trial, a progressive reduction in pressure support was superior to weaning by T-piece or SIMV

Journal Club

Early Active Mobilization during Mechanical Ventilation in the ICU – N Engl J Med 2022

  • In mechanically ventilated patients, an intervention to achieve the highest possible level of mobilization that was deemed safe during daily therapy did not improve outcomes and was associated with more adverse events compared to usual care

Anaglesia and Sedation in the ICU

2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU,

 

 

 

Academic Half Day 7/21/2022: Acute Hypoxemic Respiratory Failure and ARDS References

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Ventilatory Dyssynchrony

Patient-ventilator Interactions: Implications or Clinical Management – AJRCCM 2013

  • Evergreen review of trigger, flow, and cycle dyssynchronies including recognition and management

Alveolar Gas Equation

Teaching an intuitive derivation of the clinical alveolar equations: mass balance as a fundamental physiological principle – Adv Physiol Educ 2020

  • In-depth derivation of alveolar gas equation for those interested in a deep dive

Bias in Pulse Oximetry

Racial bias and reproducibility in pulse oximetry among medical and surgical inpatients in general care in the Veterans Health Administration 2013-19: multicenter, retrospective cohort study – BMJ 2022

  • Recently published large retrospective study that found occult hypoxemia (SaO2 <88% with SpO2 ≥92%) more common in Black vs White patient

Non-invasive Ventilation in the ICU

Philips Respironics V60 User Manual 

  • Critically important to know how to use the devices available to you
  • Page 4-7 reviews trigger, target, and cycle for the different modes available on the V60

ATS/ERS Guidelines on use of NIV for Acute Respiratory Failure – ERJ 2017

  • Consensus guidelines on use of NIV in respiratory failure. A nice summary of the literature on the use of NIV in the pre-intubation and post-extubation setting

Liberation from Mechanical Ventilation in Critically Ill Adults: An Official ATS/ACCP Clinical Practice Guideline – AJRCCM 2017

  • Summary of 3 important guidelines from the ATS/ACCP on evidence-based liberation from mechanical ventilation in critically ill adults. References to the parent documents are provided in this summary

Journal Club: PROSEVA

Prone positioning in severe acute respiratory distress syndrome – NEJM, 2013

  • Landmark RCT which found prone positioning for 16 hrs/day associated with a significant mortality benefit for patients with severe ARDS

Prone position-induced improvement in gas exchange does not predict improved survival in the acute respiratory distress syndrome – AJRCCM 2014

  • Retrospective analysis of PROSEVA data which found that did not find an association between the improvement in gas exchange and survival – suggesting perhaps that proning mechanism of benefit is largely through limiting VILI

Evidence-based ARDS Care

An OfficialAmerican Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome – AJRCCM 2017

  • Evidence-based multi-society guidelines on mechanical ventilation in ARDS. Only LTVV + Pplt < 30 cmH20 and prone positioning for > 12hrs/day in severe ARDS receive strong recommendations FOR

Formal guidelines: management of acute respiratory distress syndrome – Annals Intensive Care 2019

  • More recent guidelines from Société de Réanimation de Langue Française. Their approach:

Fig. 1

High-impact PCCM Article Summaries: Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis (The WATERFALL Trial)

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De-Madaria et al. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis: The WATERFALL Trial. NEJM 2022

Question: Does aggressive fluid resuscitation compared to moderate fluid resuscitation improve clinical outcomes in patients with acute pancreatitis?

 

Why ask it: How to administer intravenous fluids (IVF) for patients with acute pancreatitis remains a source of debate. Early IVF may improve pancreatic microcirculatory hypoperfusion and help prevent pancreatic necrosis. However, excessive IVF can contribute to complications including respiratory failure and abdominal compartment syndrome.

 

Intervention: 249 patients in 8 countries presenting to the emergency department with mild acute pancreatitis randomized to aggressive or moderate fluid resuscitation protocols (see comment for important exclusion criteria and details of intervention).

 

Results (all written as aggressive IVF group vs moderate IVF group):

  • Development of moderately severe or severe acute pancreatitis (primary outcome)
    • 1% vs 17.3% (adjusted RR 1.3; [95% CI, 0.78 – 2.18], p=0.32)
  • Fluid overload during hospitalization (primary safety outcome)
    • 5% vs 6.3% (adjusted RR 2.85; [95% CI, 1.36 – 5.94])
  • No signal of benefit with aggressive IVF across a range of secondary outcomes (select secondary outcomes listed below)
    • Necrotizing pancreatitis
      • 9% vs 7.1% (adjusted RR 1.95; [95% CI, 0.87 – 4.38])
    • Local complications
      • 5% vs 16.5% (adjusted RR 1.28; [95% CI, 0.74 – 2.22])
    • Any organ failure
      • 4% vs 3.9% (adjusted RR 1.23; [95% CI, 0.47 – 3.23])
    • Respiratory failure
      • 4% vs 2.4% (adjusted RR 2.19; [0.63 – 7.64])
    • ICU admission
      • 6% vs 1.6% (adjusted RR 2.71; [95% CI, 0.64 – 11.51])
    • Death
      • 3% vs 0.8% (adjusted RR 3.05; [95% CI, 0.32 – 28.76]
  • The trial was halted by the DSMB at the first interim analysis due to worse safety outcomes in the aggressive IVF group
  • Similar results in prespecified subgroup analyses of patients with SIRS at baseline and those with baseline hypovolemia

Conclusion: In patients with mild acute pancreatitis, aggressive IVF did not improve clinical outcomes and was associated with more fluid overload compared to moderate IVF.

Comments:

  • Acute pancreatitis pathobiology
    • Intra-acinar activation of trypsin causes autodigestive injury to the vascular endothelium, interstitium, and acinar cells with a resulting inflammatory response
    • Acute pancreatitis and sepsis share similar pathobiology including microcirculatory dysfunction, dysregulated inflammatory and coagulation cascades, and the potential for systemic and end-organ complications
  • Central goals of IVF in acute pancreatitis are the correction of hypovolemia and restoration of perfusion to the pancreatic microcirculation
  • WATERFALL was a multi-center, open-label, parallel-group, controlled superiority trial conducted at 18 centers in 4 countries (India, Italy, Mexico, Spain)
  • Many exclusion criteria
    • Moderately severe or severe disease per the Revised Atlanta Classification
    • NYHA CHF II – IV
    • Uncontrolled HTN
    • Hyper or hyponatremia
    • Hyperkalemia
    • Hypercalcemia
    • Life expectancy < 1 year
    • Chronic pancreatitis
    • Chronic renal failure
    • Decompensated cirrhosis
  • Details of interventions (Lactated Ringers used for all)
    • Aggressive-resuscitation group
      • Enrollment
        • Bolus 20 mL/kg, then infusion 3 mL/kg/hr
      • Hour 3 (“safety checkpoint”)
        • Physical assessment to evaluate for signs of volume overload
        • If present, decrease or stop infusion
      • Hours 12, 24, 48, and 72 (“goal-directed therapy checkpoints”)
        • Hypovolemia
          • Bolus 20 mL/kg, then infusion 3mL/kg/hr
          • Additional boluses of 20 mL/kg if low UOP or SBP
        • Normovolemia
          • Infusion 1.5 mL/kg/hr
          • Stop after 48 hrs if oral feeding tolerated for > 8 hrs
        • Suspicion of fluid overload
          • Decrease or stop infusion
          • Infusion stopped after 48 hrs if oral feeding tolerated for > 8hr
    • Moderate-resuscitation group
      • Enrollment
        • 1.5 mL/kg/hr without bolus in pts without hypovolemia
        • If hypovolemia present, bolus 10 ml/kg over 2 hrs then start infusion
      • Hour 3
        • Physical assessment to evaluate for signs of volume overload
        • If present, decrease or stop infusion
      • Hours 12, 24, 48, and 72
        • Hypovolemia
          • Bolus 10 mL/kg, then infusion 1.5 mL/kg/hr
          • Additional boluses of 10 ml/kg if low UOP or SBP
        • Normovolemia
          • Infusion 1.5 mL/kg/hr
          • Stop after 20 hrs if oral feeding tolerated for > 8 hrs
        • Suspicion of fluid overload
          • Decrease or stop infusion
          • Infusion stopped after 20 hrs if oral feeding tolerated for > 8hr
    • Oral feeding started at 12 hrs in both groups if minimal abd pain per the PAN-PROMISE SCORE
    • Fluid overload identified by at least 2 of the following: symptoms, physical signs, and imaging evidence of hypervolemia
  • Notable patient characteristics
    • Age: ~57
    • Gallstone pancreatitis: 61%
    • CAD: 1%
    • Median BiSPAP score: 1
    • 2 or more SIRS: 26%
  • Results of intervention (all written as aggressive IVF group vs moderate IVF group)
    • Median cumulative IVF
      • 12 hrs: 3.4 L vs 1.5 L
      • 24 hrs: 5.4 L vs 3.3 L
      • 48 hours: 7.8 L vs 5.5 L
      • 72 hours: 8.3 L vs 6.6L

My take

  • The trial asks an important and clinically relevant question. As noted in the 2018 American Gastroenterological Association Guidelines on Initial Management of Acute Pancreatitis, there is a paucity of high-quality evidence to inform how and when to administer IVF for patients with acute pancreatitis
  • The intensity of bedside reassessment in the trial (structured safety and goal-directed therapy checks at hours 3, 12, 24, 48, and 72) exceeds what is provided for many hospitalized patients in a real-world setting. The trial therefore likely underestimates the harm associated with aggressive IVF in less monitored settings.
  • By design, the patients in this trial were not that sick. They had minimal co-morbidities and they could not have any organ failures or local/systemic complications related to their acute pancreatitis at the time of enrollment. The results are therefore not generalizable to the care of critically ill patients with acute pancreatitis. Patients who present with severe disease (who may have more pronounced hypovolemia and be at higher risk of progression to necrotizing pancreatitis) may uniquely benefit from IVF. Conversely, those with chronic pulmonary, cardiac, and renal disease are at higher risk of developing clinically significant complications from aggressive IVF. A tough balance.
  • The trial aimed to enroll 744 patients to detect a 10% difference between groups in the development of moderately severe or severe acute pancreatitis assuming an incidence of 35%. Given the lower-than-expected incidence of moderately severe or severe acute pancreatitis during the trial (20% overall) and the early trial termination at an enrollment of 249 patients, the study is underpowered to detect differences in the primary outcome
  • This trial does not inform a safe lower limit for IVF in acute pancreatitis. Do patients really need an infusion of 1.5 mL/kg/hr at days 2 and 3? My guess is no but this trial doesn’t answer that.
  • My simplified view is that we should approach IVF resuscitation in acute pancreatitis much like we do with sepsis (they share many similarities as noted above). IVF in both settings is probably of most benefit when given early and in patients with more severe disease. For the floor patients we evaluate for MICU transfer (worsening disease or organ dysfunction several days into their hospital stay), ongoing high-volume maintenance fluids are likely of little benefit.
  • As in sepsis care, there is not one perfect marker to guide resuscitation in acute pancreatitis. IVF should be guided by serial reassessment of intravascular volume, perfusion pressure, and tissue oxygenation using all of the imperfect tools at our disposal rather than a one-size-fits-all protocol.

 

 

Chylothorax Review

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A review from Amy Ludwig’s AM Report.  Answer to follow in comments

High-impact PCCM Article Summaries: Restriction of Intravenous Fluid in Patients with Septic Shock

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Meyhoff et al. Restriction of Intravenous Fluid in Patients with Septic Shock: The CLASSIC Trial. NEJM 2022

Question: Does a restrictive fluid strategy improve 90-day mortality in ICU patients with septic shock?

 

Why ask it: When to administer intravenous fluids (IVF) to patients with sepsis and septic shock remains a source of debate. Restrictive resuscitation may improve outcomes by avoiding the harms associated with unnecessary fluid loading. However, the safety and efficacy of this approach has not been studied in a large, randomized trial.

Intervention: 1,554 ICU patients in 8 European countries who developed septic shock within 12 hours of screening randomized to a restrictive or standard fluid strategy (see comment for details) for the duration of their ICU stay. Septic shock was defined as suspected or confirmed infection + lactate  ≥ 2 + ongoing vasopressor or inotrope use + ≥ 1L IVF administered in the 24 hours prior to screening.

Results:

  • Death within 90 days (primary outcome)
    • 42.3% in the restrictive fluid group vs 42.1% in the standard-fluid group (adjusted absolute difference, 0.1 percentage points [95% CI, -4.7 to 4.9], p=0.96)
  • No difference in serious adverse events, serious adverse reactions, number of days alive without life support, or number of days alive and out of the hospital
  • Results were robust to a sensitivity analysis
  • There was no heterogeneity in the effect of the intervention across a range of pre-specified subgroups

Conclusion: In ICU patients with septic shock, a restrictive fluid strategy did not improve 90-day mortality compared to a standard fluid strategy

Comment:

  • Worth being aware of some the arguments in favor of restrictive resuscitation (an incomplete list):
  • CLASSIC was an international, stratified, parallel-group, open-label RCT conducted in both university and community ICUs
  • Notable patient characteristics
    • Median age: ~ 70 years
    • Male: 59%
    • Comorbidities
      • Ischemic heart disease or heart failure: 17%
      • Long-term dialysis: 1%
    • Median time from ICU admission to randomization: ~3 hours
    • Source of admission
      • ED or prehospital: 39%
      • Hospital ward: 37%
    • Source of infection
      • GI: 38%
      • Pulmonary: 27%
    • Median volume of IVF in the 24 hours prior to randomization: ~3L
    • Use of respiratory support: 51%
  • Details of interventions
    • Restrictive-fluid group: Indications for 250-500 mL crystalloid bolus:
      • Severe hypoperfusion
        • Lactate  ≥ 4
        • MAP < 50 mmHg despite vasopressors
        • Mottling of skin beyond the edge of the kneecap
        • Urine output < 0.1 mL/kg/hr during the first 2 hours after randomization
      • Replace documented fluid loss
      • Correct dehydration or electrolyte deficiencies because of limited enteral access
      • Ensure a total daily fluid intake of 1L
    • Standard-fluid group: No upper limit on the amount of IVF that could be given for any of the following:
      • Improvement in hemodynamic factors in response to IVF
      • Replace fluid losses or correct electrolyte deficiencies
      • Need for maintenance fluids
  • Results of intervention (all written as restrictive-fluid vs standard-fluid group)
    • Median IVF volume (Ls)
      • Day 1: 0.5 vs 1.3
      • Day 5: 1.5 vs 3.1
      • Day 90: 1.8 vs 3.8
    • Median total fluid volume (Ls)
      • Day 1: 1.8 vs 2.7
      • Day 5: 8.9 vs 10.8
      • Day 90: 10.4 vs 12.8
    • Median cumulative fluid balance (Ls)
      • Day 1: 0.7 vs 1.3
      • Day 5: 1.7 vs 2.4
      • Day 90: 1.7 vs 2.4
  • My take
    • CLASSIC is a rigorous, large RCT with very few patients lost to follow-up, a robust primary outcome, and a diverse range of study sites that increase its external validity. The intervention produced a durable difference in management in that patients in the standard-fluid group received more fluid at every time point. Yes, the trial was open label, there were some protocol violations, and the trial was powered for an eyebrow-raising 7% difference in mortality, but I do not think these limitations detract from the study’s major findings.
    • Some, including the editorial, have raised concerns about the standard-fluid arm of this trial – noting that this approach was too “restrictive” to be viewed as usual practice and thus biased the trial towards a negative result. As just one comparison, in the PROCESS trial of early goal-directed therapy for sepsis, the protocol-based standard therapy arm received a mean of 8L of IVF between 0 and 72 hours and the usual care arm received 7L over that time frame. These differences are worth noting and comparing to your practice, but I think most would agree that the CLASSIC investigators should not have mandated extra IVF beyond what they felt was reflective of standard care.
    • Depending on one’s enthusiasm for restrictive resuscitation, you will hear the results of this trial framed as “look, restrictive resuscitation is safe” or “look, restrictive resuscitation isn’t helpful.”
    • Coupled with the preliminary results of the CLOVERS trial, CLASSIC pours cold water on the idea that restrictive resuscitation is the next innovation in sepsis care and a necessary response to the fluid-happy practice that followed the Rivers trial. We should give IVF when we think it will benefit our patients, with that decision informed by all of the (imperfect) clinical markers at our disposal. Early antibiotics, prompt source control, and frequent bedside reassessment remain the critical components of early sepsis care.