Hall Principles of Critical Care 2015 – Chapter 44: Noninvasive Ventilation

Most likely to benefit – COPD or hypercapnic acute cardiogenic pulmonary edema

Caution in severely hypoxemic patients

  • Delay in endotracheal intubation should not occur because of NIPPV
  • Favorable response is usually apparent in the first 2 hours
  • Key is appropriately selecting the right patients for NIPPV

COPD

2004 Cochrane database review showed decrease in mortality, decreased intubation, and faster clinical improvement associated with NIPPV.

Dangers of inadequate ventilation

  • Transdiaphragmatic pressure generation is high -> risk of respiratory muscle fatigue

Acute cardiogenic pulmonary edema

Decreases work of breathing and improves cardiovascular function

Cardiovascular function

  • Decreases LV afterload
  • Reduces RV and LV preload

3CPO study showed that in patients with clinical dx of CPE (RR > 30, pH < 7.35, CXR w/ edema) randomized to NIPPV or standard oxygen tx had improved physiologic outcomes with NIPPV, but no difference in intubation rates and 7 and 30 day mortality.

  • Crossover – There was a high incidence of crossover (~15%) from the standard oxygen group. This could make argument that higher rates of intubation could have happened in standard oxygen group.
  • Sick patients excluded – Severely ill patients w/ need for lifesaving intervention were excluded.
  • CPAP vs. PSV+PEEP – Similar outcomes (re: intubation, mortality, clinical changes) between the two modes of NIPPV.

Hypoxemic respiratory failure

Difference between CPAP and PSV+PEEP

CPAP

  • Early benefit with dyspnea and oxygenation
  • But, no difference with ETI, mortality, or ICU LOS
  • CPAP alone not recommended in mild to severe ARDS

PSV+PEEP

  • Multiple RCTs (Martin 2000, Ferrer 2003) found benefits regarding intubation and mortality. Though importantly these studies had heterogenous patient populations with ARDS from multiple etiologies.
  • Despite some benefit seen in the studies above, there have been high rates of NIPPV failure in PNA and severe hypoxemia patients (Meduri 1996, Jolliet 2001, Domenighetti 2002, Antonelli 2001).

 

Frat Crit Care Med 2018 – Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With Noninvasive Oxygenation Strategy

Article Citation

Frat JP, Ragot S, Coudroy R, et al. Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy. Crit Care Med. 2018;46(2):208-215.

What We Already Know About the Topic

Per the FLORALI study, patients managed with HFNC appear to have better mortality outcomes than those managed with combination of HFNC and non-invasive ventilation (NIV). Furthermore, the LUNG SAFE study showed that hypoxemic patients failing NIV had higher mortality rate than those invasively ventilated. This introduces the topic of the optimal pre-intubation (i.e. noninvasive ventilation) strategy in ICU patients.

Why This Study is Important

Helps to guide the airway management for hypoxemic respiratory failure patients. Further, the increased work on patient self-induced lung injury (P-SILI) has shown that large swings in transpulmonary pressure may help characterize patients who do not do well in acute respiratory failure.

Purpose (PICO format)

In a post hoc analysis of a randomized controlled trial, ICU patients with acute respiratory failure were randomized to receive standard oxygen, HFNC, or NIV with measured outcomes of early and late predictors of intubation as well as 90 day mortality.

Site

23 centers in France and Belgium

Methods

This analysis a post hoc look at a randomized controlled trial of ICU patients. Acute respiratory failure was defined as RR > 25 bpm, PaO2/FiO2 < 300 mm Hg and a PaCO < 45 mm Hg. Data collection was at baseline and at 1 hour post-randomization to specific oxygen strategy. Intubation criteria were predetermined and were 1) worsening respiratory failure via > 2 of criteria: RR > 40, no improvement in signs of respiratory muscle workload, copious secretions, pH < 7.35, or SpO2 < 90% for 5 min; 2) HD instability; or 3) Deterioration of mental status.

Outcome Measures

Identify early factors associated with intubation–at baseline and 1 hour after initiation of each treatment. Secondary outcome was to identify factors associated with mortality at 90 days.

Inclusion criteria

ICU patients with acute respiratory failure

Exclusion criteria

Severe neutropenia, acute-on-chronic respiratory failure, cardiogenic pulmonary edema, shock, or altered consciousness

Results

Of the 310 patients included, most of them had moderate hypoxemia (i.e. PaO2/FiO2 ratio between 101 and 200 mm Hg). 94 patients received standard oxygen (mean gas flow ~13LPM). 106 patients received HFNC (mean gas flow 48 LPM). 110 patients were treated with NIV (mean expired tidal volume 8.7 mL/kg). 45% of the population needed intubation. For each group, independent factors predictive of intubation were as follows: standard oxygen patients – RR > 30 bpm, HFNC patients – increased HR at one hour after intiation, NIV patients – both PaO2/FiO2 ratio at one hour < 200 mm Hg and expired TV  at one hour > 9 mL/kg.

In terms of 90 day mortality, factors significantly associated were the following: standard oxygen or HFNC – SAPS II score, NIV – TV > 9 mL/kg of PBW one hour post oxygen strategy implementation.

Limitations

Tempting to extrapolate these data findings to emergency department patients; though, would have caution as these are different substrates.

Conclusions of the Authors of the Study

Finding the significant factors predictive of intubation and mortality can help physicians decide airway management strategies early in the acute respiratory failure process.

Take Home Points for Us

Pay attention to certain variables like RR, HR, and expired tidal volumes when managing tenuous acute respiratory failure patients in the ICU. Realize that these variables may represent crucial pathophysiological changes portending worsened prognosis (i.e. large expired TV may represent swings in transpulmonary pressure and the resultant baro-/atelectatrauma of ARDS).

Chua Ann Intensive Care 2011 – Sodium bicarb in DKA

Citation

Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis – a systematic review. Ann Intensive Care. 2011;1(1):23.

What We Already Know About the Topic

DKA is either a absolute or relative deficiency of insulin. Ketones are generated with the liver’s metabolism of free fatty acids. Accumulation of anions occurs through various mechanisms with severe dehydration as clinical manifestation. Sulphate, urate and phosphate are accumulated.

Metabolic acidemia has prompted some physicians to administer bicarbonate given the thought process that a base is required to reverse an acidosis.

The concern is that side effects of bicarbonate (namely intracellular worsening of acidosis) outweigh the potential benefits in acidemia.

Why is This Study Important?

Looked not only at important outcomes like mortality and hospitalization, but also looked at physiolgical data like acidosis or ketosis resolution.

Purpose (PICO format)

Adult and pediatric patients with DKA treated with bicarb or no bicarb for emergent treatment; outcomes were mortality and hospitalization duration.

Site

Multiple centers

Methods

Systematic search by two investigators identified 508 potentially relevant citations. Any disagreements were adjudicated by a third independent investigator.

Outcome Measures

Primary outcomes of length of hospitalization and mortality. Secondary outcomes of resolution of acidosis, ketosis, potassium balance, tissue oxygenation, CSF acidosis, neurologic deterioration, and hemodynamic parameters.

Inclusion Criteria

Adult and pediatric patients with DKA and treated with bicarbonate were reviewed for inclusion

Exclusion Criteria

No review articles

No commentaries/letters/editorials

Articles not related to cerebral edema, bicarb, or acid/base in DKA

Results

Of the 508 potentially relevant articles, 44 were selected and reviewed. There was only one double-blinded RCT and two nonblinded RCTs; the majority of studies were case-controlled studies.

No apparent impact on LOS; also, no published study in bicarb in DKA was able to comment on mortality–though, most studies excluded the severely ill DKA (i.e. severe metabolic acidemia).

The studies that seemed to see physiological benefit in RCTs found improved pH and bicarb levels at 2h; however, 24h later, there was no difference.

Paradoxical worsening of ketonemia; specifically, slower decline in the ketonemia in the first hour of bicarbonate infusion.

Variable results on the potassium or rate of decline in blood lactate. Furthermore, there was a variable, non-statistically significant difference in CSF pH and bicarb levels within 24 hours in bicarb and control groups.

A small number of the analyzed studies included outcomes like neurologic performance or hemodynamics but found no significant differences.

Limitations

Most of the studies included in this systematic review excluded critically ill/severe metabolic acidemia DKA cases. The pH threshold for bicarbonate administration varied between < 7.00 to < 7.20. Dosages varied with more recent dosing strategies 120-150 mmol for adults. More recent studies were preferentially using slow infusions of half-isotonic or isotonic preparations (approx 1%) or small intermittent boluses.

Conclusions of the Authors of the Study

Data heterogenous and without clear signal for benefit in bicarbonate administration for DKA; potential for worsening ketonemia and requirements for potassium. However, there could be a transient improvement in acidosis without clinical outcome changes.

Take Home Points for Us

The potential for worsening ketonemia and potassium requirements seems minor; furthermore, bicarb’s transient improvement in acidosis bears no clinically relevant outcome. The minor, transient improvement in pH could be useful in severe acidemia as a brief temporizing measure in rare situations but remains unproven.

Farkas – Submassive PE after PEITHO long-term follow up

Long-term PEITHO Follow Up -> Thrombolytics Don’t Affect Long-Term Morbidity. Therefore, Lysis Goal is Avoiding PEA Arrest.

Original PEITHO -> Submassive PE with lysis (specifically, loaded with heparin then lysed) via tenectaplase found reduction in hemodynamic collapse, but increase in ICH. Overall, non-significant trend towards reduced all-cause mortality with lysis.

  • Therefore, the point of lysing was to avoid hemodynamic collapse as well as decrease pulmonary hypertension.
  • But, new work coming out showing that lysis perhaps without effect on pulmonary hypertension.

Konstantinides 2017 – Thrombolysis did not cause long-term improved functional status, nor improvements in pulmonary hypertension.

Question: If there appears to be no improvement with lysis in submassive PE from standpoint of pulmonary hypertension or functional status, why do it?

Answer: Long-term PEITHO data showing us pulmonary hypertension isn’t the issue; we lyse to avoid PEA arrest.


Dosing Lytics -> Highly Variable Over Different Studies.

Theme remains increased dose with increased risk of bleeding. There’s indication that 100 mg alteplase is too much per Sharifi 2016.

MOPETT – 50 mg

Aykan – 25 mg over 8h in massive PE

Catheter-directed lysis studies – They’ve suggested that can do slow infusion of 25 mg alteplase at 1 mg/hr


How to Administer Lytics

Combining lytics with heparin

  • 2% ICH rates in PEITHO <- Reflects the full-dose tenectaplase and loading dose of heparin

Controlled thrombolysis

  • Slow-loading -> 24 mg infused over 24 hours

How to Risk Stratify the Individual Patient -> Chatterjee 2017

ICH risk factors in lysis for PE

  • CVA or intracranial pathology
  • Age
  • Vascular disease (MI or peripheral vascular disease)
  • Coagulopathy

Identifying Those at Risk for “Clot-Throwing” Death <- I.e That Group That’s Not Stereotypically RV Dilatation, IVC Plethora, Syncope

Trying to find those who look fine, but are at risk of throwing clot/PEA death.

Predicated on studies saying certain factors associated with badness -> Jimenez 2014

  • Proximal DVT is independent risk factor for poor outcomes
  • Troponin I > 0.05 ng/ml
  • BNP > 100
  • Echo w/ RV dysfunction
  • sPESI > 0 points
  • “Immobilization” (defined as bed rest w/ bathroom privileges for preceding 1 month)

 

Scott – Thrombolysis in submassive PE

Difference in Guidelines

ACEP – not enough data for full-dose lytics for submassive PE

AHA – reasonable to consider it; however, there’s been some new studies since AHA guidelines

ESC, ACCP – recommend against lytics in submassive PE -> recommend rescue lysis if pt progresses to massive

 

Need to identify who will progress to decompensation


Risk Scores

  • PESI/sPESI/msPESI
    • Does not require a lot of labs
    • Identifies whom you can send home -> good way to find peeps you can send home with AC
    • From the ICU, you need a test with specificity -> need to identify who is going to die
  • ESC 2014 Guidelines -> how to generally risk stratify
    • If you only have either one of lab or imaging evidence of RV strain = IM-low risk
    • But, if you have more than of lab or  imaging evidence of RV strain = IM-high riks
    • Was not validated
  • BOVA score -> identifies step-wise increase in short-term risk
    • Systolic hypotension
    • Troponinemia
    • RV dysfunction on imaging
    • Increased HR

Catheter-Directed Lysis

ULTIMA 2014 – RCT of 59 pts <- the only RCT on catheter-directed lysis

  • Submassive via RV:LV ratio on TTE echo
  • Primary outcome – improvement in RV:LV ratio in 24 hours
    • Statistically significant result
    • However, when you followed up at 90 days, there was no difference in RV:LV ratio
  • Questionable part of this trial was that there was zero death and zero hemodynamic  decompensation at 90 days
  • *The only RCT for catheter-directed lysis*
  • Seems that most of the data shows that catheter-directed lysis is safe
  • Efficacy data is questionable

Half-Dose Lysis

MOPETT 2013 Sharifi – diagnosed intermediate risk via CT and counting number of lobes involved

  • 50 mg with 10 mg bolus then the rest over remaining 2 hours
  • Primary outcome was echo PASP over 40 mm Hg and/or recurrent PE
    • Found sig better PA pressures both at 48 hours and when followed up at 2 years

Commentary: Not sure what to do with echo-findings of R sided pressures

  • Also, until you have a right heart cath, it’s weird to call someone pulmonary HTN
  • Did have mortality similar to other registries
  • Odd that half-dose isn’t mentioned as much as catheter-directed lysis; only mentioned in the ESC Guidelines…not the others

Conclusions

  • Currently, if you give routine lytics in submassive PE, you are going against current guidelines
  • The trick is going to be identifying a higher risk subgroup of submassive PE <- i.e. calculating a BOVA score. This may tip the risk-benefit balance in favor of lytics.
  • Lower risk therapies like catether-directed lysis or half-dose lytics may also tip the risk-benefit balance in favor of the intervention.

 

Hennessey Stanford 2018 – Post-cardiac surgery codes

Brief Overview

  • Higher incidence of reversible causes
  • Higher survival rate for post-cardiac surgery patients
  • AHA algorithm for the post-cardiac surgery within the first ~10 days

First steps:

Hold compressions

Code cart

Maintain finger on pulse

Check your chest tubes


Recs for epi in cardiac arrest in post-cardiac surgery

  • European Society Cardiology guidelines
  • Some addressed in AHA
  • Mostly based off expert opinion
  • Don’t give full code-dose epi -> b/c there’s high likelihood for re-sternotomy or restoring sinus rhythm via defib -> can give 100 mcg (i.e. one full stick of push dose epi)
  • Also in the Duning Ann Thorac Surg 2017 -> 50 mcg – 300 mcg
  • Caution with too much epinephrine in these post-cardiac surgery pts -> increases O2 consumption and demand -> can also cause severe hypertension which causes bleeding
    • Can counteract with vasodilator prn

Approach to external cardiac massage/compressions is different in the post-cardiac surgery patient

  • Deviates from ACLS normal cardiac arrest algorithm
  • Can attempt defib or pacing prior to initiating compressions
    • Provided that can be done in less than one minute
    • Prior to compressions, you can do three stacked shocks <- defib first prior to the ACLS algorithm
  • Asynch pace (i.e. DDD mode or aka “emergency” mode) -> careful if the pacer is in AAI mode and getting amio or something blocking the node <- need to be able to pace the ventricles (i.e. hit up that DDD mode but really all you really need is the V-wires to be working)

HOW-TO -> it’s all about the rhythm

Vfib or pulseless vtach

  • Instead of ext cardiac massage, should try to defib (if available within the first minute); also, can administer three stacked shocks prior to external cardiac massage
  • Amiodarone 300 mg via CVC
  • Eventually c/w resternotomy

Asystole or profound bradycardia

  • DDD pacing at max output if available within 1 min
  • Atropine 3mg <- took out of the European guidelines; still in there for the American STS guidelines
  • Eventually c/w resternotomy

All pulseless cardiac arrests

  • No epi; no vaso <- reduce epi dose to 100 mcg pre-arrest
  • Take the pacing wires out with PEA <- need to make sure it is not fine vfib
  • Rapid re-sternotomy if no response to initial therapies (<5 min)
  • Lidocaine evidence decent for post-cardiac surgery patients

CODE with a IABP

  • Pause the IABP to make sure you’re actually pulseless

 

Topf – Non-gap metabolic acidosis and RTA

Non-anion gap acidosis

  • Non-anion gap metabolic acidosis -> All hinges on the balance between Chloride and Bicarbonate anions
  • Can either occur 1) via exogenous acid (H+) which pulls (HCO3-)  down or 2) Loss of (HCO3) from fistulae or diarrhea or etc
    • For Topf’s lecture on non-anion gap metabolic acidosis, we use the model #2/loss of (HCO3-)
    • Can lose (HCO3-) from GI tract, from renals, or from the addition of chloride/”chloride intoxication”
    • Chloride intoxication options: HCl, chloride gas, early renal failure, dilutional acidosis

Renal tubular acidoses

  • Fail to absorb the bicarb initially filtered by the kidney, RTA 2
  • Fail of kidney to synthesize new bicarb to replace the lost bicarb from metabolism, RTA 1
  • Stow the hydrogen ions from ammonia, RTA 4
    • The last two mechanisms seem linked (in my own analysis)…

Screen Shot 2018-01-03 at 15.20.43.png

Screen Shot 2018-01-03 at 15.21.55.png

Screen Shot 2018-01-03 at 15.23.33.png

*Main role of the kidney in bicarb management is reabsorptionits job is reabsorb thousands of millimoles of the filtered bicarb -> see above image, 3,456 mmol/day

*Ancillary/side-job is the synthesize a small amount of bicarb to replace bicarb that’s lost in the daily acid load -> see image above, 50-100 mmol/day

Screen Shot 2018-01-03 at 15.11.03.png

  • Commentary on the ancillary job of synthesizing small amount of bicarb:
    • Key point is that body uses either ammonium or a titratable acid (like dihydrogen phosphate, H2PO4-) to collect the H+ that’s excreted when the bicarb is synthesized

RTA 2

  • Acetazolamide
  • Multiple myeloma
  • Lead toxicity
  • Mercury poisoning
  • Wilson’s disease
  • Hyperparathyroidism

Consequences of loss of more bicarb in the urine -> K+ is lost to maintain electroneutrality (?)

Also, consequences of bone disease -> bone buffers the acidosis


RTA 1 -> Occurs b/c of failure at any of the following steps for urinary acidification (i.e. failure to produce new bicarb)

  • Consequences are bone buffering
  • Renal stones -> 2/2 increased urinary pH and hypercalciuria

Screen Shot 2018-01-03 at 15.34.05.png

  • RTA 1: Voltage-dependent -> Problem with the Na+ transporter (?)
    • Only distal RTA that has hyperkalemia
    • Differentiate from RTA 4 by response to fludrocortisone
  • RTA 1: H+ secretion problem
    • Most common cause of distal RTA
    • Lithium
    • Pyelonephritis
    • Sickle cell
    • Also, Wilson’s, Multiple Myeloma like the RTA 2
  • RTA 1: Gradient defect
    • Usually from Amphotericin B

RTA 4

  • Problem with the NH3 which is needed excrete excess H+ as NH4+ ion -> ammonium in urine means there’s no RTA <- i.e. if there’s no urine anion gap (or, it’s neg), then you’re secreting NH4+ in the urine/you don’t have RTA 4.

How to diagnose the etiology of non-gap metabolic acidosis -> get that urine anion gap!

Look for H+ clearance via looking for urinary ammonium (NH4+)

  • Do this via urinary anion gap
  • Normal/negative urinary anion gap means there’s ammonium in the urine = you’ve r/o RTA 4

Screen Shot 2018-01-03 at 15.46.39.png

Screen Shot 2018-01-03 at 15.48.09.png

Check out Joel Topf’s excellent renal blog, Precious Bodily Fluids

Jagoda – Stroke care

STROKE CARE UPDATES GRAND ROUNDS – Dr. Jagoda

QUESTION 1: Do the benefits of TPA outweigh the risks of symptomatic ICH (sICH)?

Big picture:

NNT for TPA <3hrs is 1:3 for a benefit (MRS improved 1 pt)

  • Critics dismiss 1-point move as sig outcome, but it is a large QOL change.

NNT for TPA within 4.5 hrs is 1:6

Best outcomes are within 90min. Mortality increases after 4.5 hours.


NINDS-1 (1995)

  • Significant benefit (i.e. MRS 0/1 from 26 -36 %, OR 1.7) but hemorrhage rate 0.6 vs 6.4% in TPA group

Data re-analysis – 2004

  • Still found data for benefit

Clarified RF for bleeding risk (0 RF risk 1.8%, 1 RF is 4.9%, >1 RF risk is 21%)

  • sICH RF: NIHSS >20, Age >70, Ischemic changes on CT, Glucose >300
  • Can/should use THRIVE score to estimate bleeding risk (on MDcalc)

SITS-MOST Study: Validated practical application of rt-TPA in community setting with improved outcomes. 4.6% sICH.


ECASS-3 expanded TPA window to 4.5 hours w/ a dichotomous variable of MRS 0/1 or 2+. Increased ICH risk, but benefit is preserved.

  • 52% vs 45% w/ MRS 0/1 (CI low end is 1.02 for OR)
  • sICH 2.4% vs 0.2. No mortality difference. All ICH was 27% vs 17%.

GWTG Stroke program analysis

  • Validated 90 minute cut-off associated w/ decrease mortality vs 90-180
  • sICH 4-5%

Sinai sICH rate around 4% overall, but we need to be giving patients more individualized sICH risks than 6.8% for everyone.

Updated exclusion criteria includes more folks (see last two pages for summary).

  • Example: Glucose >400 removed, glucose <50 not contra if sx persist post correction

QUESTION 2: Does neurothrombectomy offer benefit? Yes

Initial studies with Mercy device did not demonstrate benefit

Newer devices (Solitaire, Stentreiver) with much better outcomes: NNT 2.6


AHA revised their endovascular treatment guidelines in 2015


DAWN Trial just published in NEJM, Nogueira et al

  • Thrombectomy 6-24hrs (ie out of TPA window) for occlusion of ICA or MCA
  • Functional indep 49% vs 13% std of care (NNT 2.8 for functional indep)
  • sICH 6% vs 3% w/ no mortality diff

Levitt Stanford 2018 – PEEP, proning, paralysis

LEVITT ON PEEP

3 RCTs on ARDSnet protocol/standard vs. higher PEEP

  • Lower PEEP (i.e. PEEP of 5 means FiO2 30%)
  • There was no mortality benefit nor change in duration of mechanical ventilation
  • Higher peep arm -> Improved P/F ratio, compliance, but higher mean airway pressures and higher plateau pressures
  • Briel meta analysis in 2010 looking at the three trials
    • Found when you look at mod ARDS -> benefit w/ higher PEEP arm
      • But, then the opposite trend was occurring with the mild ARDS (“ALI” during that era)
      • Discordant effects depending on the severity of illness
    • Take home: if you have real ARDS, you should be on “higher” PEEP

Driving pressure -> Amato 2015

  • Plat-PEEP=driving pressure
  • This one found that increasing PEEP did not (in-and-of-itself) improve mortality

ART trial JAMA 2017 -> Recruitment maneuver to max compliance

  • Lower 6mo mortality in control arm/non-recruited group (“low PEEP”) <- but had higher driving pressures than recruitment arm?? I didn’t know this
  • Recruitment arm/intervention showed high PEEP with best compliance was harmful maybe b/c higher mean airway pressures
  • Harm from intervention??
    • Was the real harm from the hypoxia or hypoventilation in the recruitment maneuver <- pts became unstable during this recruitment
    • Recruitment maneuver was long time -> something like 60 secs

Dreyfuss rat study on transpulmonary pressures -> high vol = ARDS and die…is it the tidal vol or the high transpulmonary pressures that lead to death and ARDS?

Remember, transpulmonary pressure = airway pressure – pleural pressure

  • Group 1 -> ventilated w/ a highTV -> deemed high vol/high pressure rats
    • ARDS and died
    • High transpulmonary pressures…
  • Group 2 -> iron lungs w/ same TV as group 1 ->  b/c iron lung (airway pressure is neg) -> high vol/low pressure rats
    • ARDS and died
    • This group brings up the huge transpulmonary pressures/P-SILI topic I think…
  • Group 3 -> rubber band around chest wall -> low vol/high pressure
    • No ARDS; no die
    • I.e. low transpulmonary pressure
    • Seems like the low transpulm pressure is the thing that matters–potentially more than low TV…

*not sure what year this three-group rat study by Dreyfuss was…


Talmor 2008 looking at transpulmonary pressure-guided vs. ARDSnet low PEEP arm

  • Looked at esophageal pressure-guided transpulmonary pressure and found trend towards decreased mortality
  • The transpulmonary pressure-guided (i.e. esoph balloon) arm, the PEEP was higher
    • Argument is are you just doing the high vs. low PEEP trial…
    • Kicker -> in the esophageal balloon group they started to see positive end-expiratory transpulmonary pressures
  • Looked at the end-expiratory transpulmonary pressure

EPVENT 2 -> mod/sev ARDS

Control is high PEEP arm

Intervention is arm with PEEP titrated to end-expiratory transpulmonary pressure

  • He gave example to first place the balloon in the right spot
    • Test by pushing on the stomach -> should get the same rise in the airway pressure as you get in the esophageal pressure
      • If you’re in the abd; the “esoph pressure” (which is really abd pressure in this case) would rise out of proportion of airway pressure
  • Prelim data showing PEEP is roughly the same in the two arms <- this is important b/c you’re not doing a high-PEEP vs. low-PEEP trial

Random commentary on bladder pressure <- seeming to make argument that could inform what your transpulmonary pressure: using bladder pressure as rough guide in conjunction w/ PEEP measurement

  • If your PEEP is 12 and bladder P is 16; you prob have neg transpulmonary pressure

LEVITT ON PRONING

Recruitment improves compliance -> theorized to improve outcome

  • Multiple trials that showed no benefit -> Guerin 2004, Taccone JAMA 2009
    • But, the Gattinoni meta-analysis of 1,867 pts showed mortality benefit in pts with P/F < 100

  • Recent Guerin PROSEVA Investig NEJM 2013 RCT showed that P/F <150 showed that 16h/day proning w/ mortality benefit (16% vs. 33%) without increase in complications
    • Thought to be 2/2 increasing compliance of the lung?? <- remember, that above analysis of JE Kenny’s diagram shows how driving pressure decreases 2/2 proning (b/c chest wall compliance decreases w/ proning; but, overall compliance of resp system increases?)
  • Problem with proning is that there were three neg trials before this PROSEVA trial showed benefit <- furthermore, the mortality of 16% is super low…signal or random noise/chance??
  • Gave us an example of strong negative inspiratory efforts creating large, neg transpulmonary pressures <- loses the benefit of PEEP

LEVITT ON PARALYSIS

  • Papazian ACURASYS NEJM 2010 -> 340 pts with mod/sev ARDS
    • Group randomized to 48h of Nimbex w/ small benefit of 90-d mortality <- But not statistically significant difference
    • No difference in lung parameters -> other than rate of PTX was lower
    • Low PEEP for both arms of the study
    • Once they adjusted for the P/F ratios, Pplat, and SAPS II there was a significant difference in 90-d mortality with benefit in Nimbex

  • The new ROSE study of the PETAL network will look at Nimbex, but will give both groups high PEEP -> huge sample size of 1,400 pts
    • Physical therapy will do a formal evaluation of neuromuscular weakness
    • We’ll know the answer to NMB after this ROSE trial
    • Levitt’s hunch is that the trial will be negative trial b/c of clinicians excluding pts/biasing selection prior to enrolling pts <- b/c anyone they thought would benefit from paralysis would’ve already gotten it and those thought to not benefit would have already been decided to not get it. Therefore, left over enrollees are diluted…