UMEM Educational Pearls - Critical Care

Historically, guideline recommendations have been to use a transfusion threshold of hemoglobin < 7 g/dL for patients unless they are a) undergoing orthopedic surgery or b) have cardiovascular disease (CVD).  

Applefeld et al conducted a meta-analysis in 2018 which suggested that restrictive (i.e. lower hemoglobin trigger, typically 7-8) transfusion targets lead to worse outcomes in CVD patients than liberal (i.e. higher hemoglobin trigger, typically 9-10) targets, and those authors have updated this analysis to include data from newer trials.  Interestingly, the conclusion remains similar: that when you look at the larger studies on restrictive vs liberal transfusion targets, CVD plays an important role, as patients with CVD tend to do better with liberal targets, and patients without CVD tend to do better with restrictive targets.  Of note, CVD is variably defined in these studies, and sometimes limited only to active Acute Coronary Syndromes, and other times refers to all patients with acute or chronic CVD.  However, according to their analysis, the aggregated data suggests that we should continue having higher transfusion targets in patients with CVD, and perhaps even more in the 9-10 range, as opposed to the goals of 7 or 8 which are common.

Bottom Line: We will likely continue to see different transfusion targets recommended for patients with cardiovascular disease (CVD), and may even see guideline and blood bank recommendations raise the target for these patients more into the 9-10 range, or expand this group to include chronic CVD.  This would mean a substantial increase in recommended RBC transfusions, and as emergency physicians it is important for us to monitor these recommendations, especially since transfusions are not harmless and raising hemoglobin thresholds could lead to complications that are difficult to measure in the literature.

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Title: Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study

Settings: Retrospective observational study from a combination of Abbott Northwestern Hospital and 15 others as part of the Mayo Health system.

Participants: Patients between 2012 – 2020 who were treated for PE. Patients were propensity-matched according to the probability of a patient receiving a reduced- dose of alteplase.

Outcome measurement

  • Primary outcome: all-cause and PE-related mortality or hemorrhage within 7 days of alteplase administration.
  • Secondary outcomes: shock index at 8 hours after alteplase administration, LOS.

Study Results:

  • A total of 284 patients were included in the retrospective analysis; 98 were treated with the full-dose and 186 with the reduced-dose alteplase regimen.
  • Primary outcome was similar in both groups:
    • 7-day all-cause (5.6% in full- dose vs. 8% in reduced-dose, p = 0.45) 
    • PE-related (4% in full-dose vs. 4.2% in reduced-dose, p = 0.93)
  • All other secondary outcomes were similar between both groups
  • overall rates of hemorrhagic complications were significantly lower in the reduced-dose group than in the full-dose group (13% vs. 24.5%, respectively, p = 0.014).
  • Major intracranial hemorrhage was higher, but not statistically significant, for full-dose group: 1.3% in reduced-dose vs. 7.1% in full-dose for major, (p = 0.067)


  • Overall, there was more risk for full-dose. However, this is a retrospective study so whether it will be factored into clinical practice remains to be seen.
  • The PERT team at UMMC still recommends full dose for hemodynamic unstable patients. Perhaps for those with somewhat instability, a half dose should be considered?
  • There is still not enough data regarding the newer ones, as UMMS hospitals are starting to use TNK more frequently nowadays.


In this retrospective, Propensity-score matching study, the full-dose regimen but is associated with a lower risk of bleeding.

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           -Muscle rigidity has been described as a side-effect of fentanyl, specifically activation of expiratory muscles 

           -Excessive expiratory muscle use acts as “anti-PEEP,” causing lung derecruitment and hypoxemia

           -End-expiratory lung volume (EELV) has been used as a surrogate for lung recruitment


          -Small, two center, observational study (46 patients with ARDS)

          -50% of  patients had a significant increase in EELV after administration of neuromuscular blockade (NMB)

          -Statistically significant correlation between a higher dosage of fentanyl and a greater increase in EELV after NMB


          -NMB can improve lung recruitment for a subset of patients with ARDS, particularly in patients with significant expiratory muscle use (this can be seen on your physical exam of your intubated ED boarding patient)

          -Although this was not the main point of this study, consider fentanyl-associated “anti-PEEP,” particularly in patients receiving fentanyl whose hypoxemia and/or ventilator mechanics are disproportionate to their imaging

                    -This can be assessed with NMB (but ensure the patient will have adequate minute ventilation first)

                    -Naloxone has also been shown to reverse fentanyl-associated rigidity, but obviously would induce patient discomfort/withdrawal

*Of note, because this was an observational trial, it is possible that the patients with increased work of breathing were simply given more fentanyl. Regardless, these findings are consistent with previously documented physiologic side effects of fentanyl.

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Moderate to High-Risk Pulmonary Embolism

In stable patients, call your local PE Response Team (PERT) for advice. The UMMC PERT team is available for any patient in the region and can be contacted through Maryland Access Center.

UMMC PERT stratifies by BOVA (with lactate criteria), CTA imaging, and patient physiology/history. For the consult, we will use the patients most recent vitals, their ROOM AIR sat if available, presence of RV dysfunction on echo/CTA, recent lactate, troponin, BNP, bedside/formal echo, and HPI.

Broad management recommendations for moderate or high-risk patients

  • Presence of signs and symptoms of RV failure are usually the most concerning findings (cor pulmonale, RV:LV ratio > 1, hypoxia, etc)
  • Fluid should only be given to optimize preload, usually guided by bedside echo. Start with aliquots of 250mL or 500mL. Fluid-restrictive strategy is usually preferred.
  • First line pressor is norepinephrine. Epinephrine should be used for evidence of ventricular dysfunction
  • We recommend inhaled vasodilators should be used in persistent hypoxemia or evidence of RV dysfunction. (This can be done via high-flow nasal cannula. Author editorial: every ED in America with HFNC should have the ability to do this. This alone can save a life.)
  • Recommended SPO2 goal is >90% in absence of other lung pathology. AVOID positive pressure ventilation if at all possible.
  • If intubation is necessary, optimize pressors, inotropes, and bronchodilation beforehand and have code drugs ready!
  • Anticoagulation with unfractionated heparin in high risk patients. Our typical recommendation is 48-72 hours of unfractionated heparin in moderate risk patients as well, but DOACs are also an option. DOACs are not recommended in high risk patients currently.
  • In hemodynamically unstable or coding patients without rapid access to VA-ECMO, we usually recommend thrombolytics in all patients with high suspicion for PE and without absolute contraindications (see below - PERT team can help guide this decision if there is time).
  • See Pearl from 8/23/2023 for excellent summary of fibrinolytics and CPR in PE.
  • IMPORTANT: While a patient may not be a candidate for therapy at the moment, it is important to clarify with PERT if they WOULD BE if they experience a degradation in circulating biomarkers or physiology (most patients would). Please pass this along to your admitting teams as well!
  • Typical recommendations are for anticoagulation and repeat echocardiography in 48-72 hours to detect any worsening in RV function. 
  • When in doubt, call your local PERT team!

PERT Acceptance for Transfer to UMMC/CCRU

  • The primary decision will be whether this patient is a candidate for mechanical therapy (catheter-based or VA-ECMO). We are also evaluating for enrollment in the HI-PEITHO trial (see below). For patients who are candidates for mechanical therapy, the CCRU attending may bring on the entire PERT team: Cardiac Surgery, MICU, and Interventional Radiology (day 1-7 each month) or Vascular Surgery (day 8 or after each month).

See below for more information.


Definitions of RV dysfunction

  • TTE - RV/LV ratio >0.9, sPAP >30, RV end diastolic diameter >30mm, RV dilation, or free wall hypokinesis
  • CTA - RV/LV ratio > 1

Absolute Contraindications to Fibrinolytic Therapy in Pulmonary Embolism

UMMC Relative Exclusion Criteria for VA ECMO for PE

  • Age > 75
  • Known metastatic cancer
  • Cirrhosis
  • O2 dependent COPD/ lung disease
  • Severe dementia/ nursing home dependence

HI-PEITHO (NCT04790370) “is a prospective, multicenter RCT comparing Ultrasound-facilitated catheter-directed therapy (USCDT) and best medical therapy (BMT; systemic anticoagulation) with BMT alone in patients with acute intermediate–high-risk PE.”

Inclusion Criteria

  • Two or more of
    • HR >100
    • SBP<110
    • RR>20 or SPO2<90% RA
  • RV:LV > 1.0 on CTA
  • Troponin elevated

Category: Critical Care

Title: Keeping Dead Patients on the Vent -- Can We Use Mechanical Ventilation during CPR?

Keywords: cardiac arrest, OHCA, airway, mechanical ventilation, resuscitation, bag-valve mask, manual ventilation (PubMed Search)

Posted: 4/10/2024 by Kami Windsor, MD
Click here to contact Kami Windsor, MD

In cardiac arrest, avoidance of excessive ventilation is key to achieving HQ-CPR and minimizing decreases in venous return to the heart. The controversy regarding BVM vs definitive airway and OHCA outcomes continues, but data indicates that mechanical ventilation during CPR carries no more variability in airway peak pressures and tidal volume delivery than BVM ventilation [1], with the AHA suggestion to keep in-hospital cardiac arrest patients with COVID-19 on the ventilator during the pandemic [2]. 

So, can we automate this part of CPR?

Two recent studies looked at mechanical ventilation (MV) compared to bagged ventilation (BV) in intubated patients with out-of-hospital-cardiac arrest (OHCA).  

Shin et al.'s pilot RCT evaluated 60 intubated patients, randomizing half to MV and half to BV, finding no difference in the primary outcome of ROSC or sustained ROSC, or ABG values, despite significantly lower tidal volumes and minute ventilation in the MV group [3]. 

Malinverni et al. retrospectively compared MV and BV OHCA patients from the Belgian Cardiac Arrest Registry, finding that MV was associated with increased ROSC although not with improved neurologic outcomes. Of note, patients across the airway spectrum were included (mask, supraglottic, intubated), and the mechanical ventilation was a bilevel pressure mode called Cardiopulmonary Ventilation (CPV) specific to their ventilators, specifically for use during cardiac arrest [4]. 

Bottom Line: Larger randomized trials will be necessary to get a definitive answer as to how mechanical ventilation affects outcomes in OHCA, but in instances where the cause of arrest is not primarily pulmonary (severe asthma, pneumothorax) and the ED is short-staffed or prolonged resuscitations are likely (such as in accidental hypothermic arrests), it is probably reasonable to keep patients on the ventilator:

  • in a control mode
  • with a target tidal volume of 6ml/kg,
  • a PEEP of 5-8cmH2O (depending on habitus)
  • and an FiO2 of 100% while still in arrest.
  • Set the trigger to “off” to avoid additional breaths triggered by chest compressions
  • Pressure alarms may need adjustment to allow asynchronous breath delivery during chest compressions

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Category: Critical Care

Title: It's only a little fluid - does it matter what kind I choose?

Keywords: IV Fluid, balanced solutions (PubMed Search)

Posted: 4/3/2024 by Mark Sutherland, MD (Updated: 5/24/2024)
Click here to contact Mark Sutherland, MD

Multiple studies have suggested differences in patient outcomes with balanced solutions (e.g. plasmalyte) vs unbalanced solutions (e.g. normal saline) when large volumes are administered.  But what about when giving smaller volumes of fluid?  Does it matter which one you choose?

A recent study by Raes et al in the Journal of Nephrology looked at urine and serum effects of administering 1L of normal saline, vs 1L of plasmalyte, to ICU patients needing a fluid bolus.  Chloride levels, strong ion difference (SID), and base excess were all significantly different between the two groups.  There was no difference in blood pressure or need for vasopressors.  As best I can tell, other clinically significant differences such as kidney injury were unfortunately not reported.

Bottom Line: When giving small (e.g. 1L) volumes of IVF, there ARE real physiologic differences seen between balanced and unbalanced solutions.  Whether these differences translate to patient-oriented or clinically significant outcomes remains unclear.

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Bag-Valve-Mask Ventilation During OHCA

  • Current OHCA resuscitation guidelines recommend a 30:2 strategy of CPR with BVM ventilations.
  • Idris and colleagues performed a secondary analysis of the Resuscitation Outcomes Consortium CCC clinical trial to determine the incidence of BVM ventilation during a 30:2 CPR strategy and assess the association of detectable ventilations with patient outcomes.
  • In 1,976 patients, the authors found that only 40% of patients had detectable ventilations (> 250 ml) in more than half of CPR pauses.
  • For those patients with detectable ventilations in more than 50% of pauses, there was an association with increased survival to hospital admission, increased survival to hospital discharge, and increased survival with favorable neurologic outcome.
  • The current study highlights the importance of proper BVM ventilation during OHCA resuscitation and the opportunity to improve performance of this vital skill.

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Category: Critical Care

Title: Which Vasopressor Should You Use to Manage Shock After Cardiac Arrest?

Keywords: ROSC, OHCA, cardiac arrest, shock, vasopressors, norepinephrine, noradrenaline, epinephrine, adrenalin (PubMed Search)

Posted: 3/19/2024 by Kami Windsor, MD
Click here to contact Kami Windsor, MD

Post-arrest shock is a common entity after ROSC. There is support for the use of continuous norepinephrine infusion over epinephrine to treat shock after ROSC, due to concerns about increased myocardial oxygen demand and associations with higher rates of rearrest [1,2] and mortality [2,3] with the use of epinephrine compared to norepinephrine, and increased refractory shock with use of epinephrine infusion after acute MI [4].

An article in this month’s AJEM compared norepinephrine and epinephrine infusions to treat shock in the first 6 hours post-ROSC in OHCA [5].  With a study population of 221 patients, they found no difference in the primary outcome of incidence of tachyarrhythmias, but did find that in-hospital mortality and rearrest rates were higher in the epinephrine group. 

Bottom Line: Absent definitive evidence, norepinephrine should probably be the first pressor you reach for to manage post-arrest shock, especially if there is strong suspicion for acute myocardial infarction.

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Background: There is no clear guidelines regarding whether norepinephrine or epinephrine would be the preferred agent to maintain hemodynamic stability after cardiac arrest. In recent years, there has been more opinions about the use of norepinephrine in this situation.

Settings: retrospective multi-site cohort study of adult patients who presented to emergency departments at Mayo Clinic hospitals in Minnesota, Florida, Arizona with out-of-hospital-cardiac arrest (OHCA). Study period was May 5th, 2018, to January 31st, 2022

Participants: 18 years of age and older

Outcome measurement: tachycardia, rate of re-arrest during hospitalization, in-hospital mortality.

Multivariate logistic regressions were performed.

Study Results:

  • The study included 221 patients, 151 patients received norepinephrine infusion vs. 70 patients received epinephrine infusion.
  • The maximum dose of epinephrine = 0.28 mcg/kg/min vs. 0.15 mcg/kg/min for norepinephrine.
  • The Odds for clinically significant tachyarrhythmia was the same between both groups (OR 1.34, 95% CI 0.6802.62, P=0.40).
  • Epinephrine infusion was associated with higher odds of in-hospital mortality (OR 6.21, 95% CI 2.37–16.25, P <0.001)
  • Epinephrine infusion was associated with higher odds of re-arrest ( OR 5.77, 95% CI 2.74–12.18, P < 0.001)


It was retrospective study that uses electronic health records. Thus, other important factors from the pre-hospital settings might not be accurate.

On the other hand, the patient population came from multiple hospitals with varying practices so the patient population is more generalizable.


Although the rate of tachyarrhythmia was not different between patients receiving norepinephrine vs. epinephrine after ROSC. This study would add more data to the current literature that norepinephrine might be more beneficial for patients with post-cardiac arrest shock.

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Category: Critical Care

Title: GCS less than/equal to 8? Don't be in a rush to intubate!

Keywords: poisoning, intoxication, altered mental status, GCS, endotracheal intubation (PubMed Search)

Posted: 2/20/2024 by Kami Windsor, MD
Click here to contact Kami Windsor, MD

Background: Acutely intoxicated / poisoned patients are commonly encountered in the ED, with the classic teaching that a GCS < 9 is an indication to intubate for airway protection. But we’ve probably all had a patient who was borderline, or who we thought was still protecting their airway pretty well despite a lower GCS. Are we risking our patient’s health and our careers by holding off on intubation? Maybe not. 

The NICO trial, a multicenter, randomized controlled trial, looked at patients presenting by EMS with GCS <9 due to suspected poisoning, without immediate indication for intubation (defined by signs of respiratory distress with hypoxia, clinical suspicion of any brain injury, seizure, or shock with systolic BP <90 mmHg). They found that withholding intubation with close monitoring, compared to the standard practice of intubating at the EMS or ED physician’s discretion, resulted in: 

  • No deaths in either group
  • Fewer intubations (18.1% vs 59.6%; AR difference 41.5%, 95% CI -54.1 to -30.9)
  • Fewer intubation-associated adverse events (6% vs. 14.7%; 95% CI -16.6 to -0.7)
  • Decreased incidence of pneumonia (6.9% vs 14.7%; 95% CI -15.9 to 0.3)
  • Fewer ICU admissions (39.7% vs. 66.1%) and decreased hospital and ICU LOS

Comparing the patients who were intubated in each group, there was no significant difference between groups in:

  • Rate of intubation-associated adverse events or first-pass failure
  • Median ICU or hospital length of stay


  • French study – EMS setup there is different from ours in the US
  • Median GCS = 6, study population skewed young and male (mean age 33yo, 62% male) 
  • Mostly alcohol or benzodiazepine intoxication
  • Unblinded study

Bottom Line: Without clear indication for intubation such as respiratory distress or accompanying head bleed, etcetera, intubation for mental status alone shouldn't be dogma in acute intoxication. Close monitoring will identify need for intubation, without apparent worsened outcomes due to a watchful waiting approach.

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PEEP in the Ventilated COPD Patient?

  • Patients with acute respiratory failure secondary to COPD often have dynamic hyperinflation and intrinsic PEEP (PEEPi).
  • Both dynamic hyperinflation and PEEPi adversely effect pulmonary mechanics, markedly increase the work of breathing, impair respiratory muscle function, and can result in hemodynamic compromise.
  • It has traditionally been felt that the application of external PEEP in the intubated COPD patient may worsen hyperinflation.
  • Importantly, external PEEP has been shown to improve ventilator synchrony and decrease the work of breathing.
  • PEEPi is measured using an end-expiratory hold maneuver in a passive, relaxed patient.
  • External PEEP can then be set to approximately 70% of PEEPi, followed by frequent monitoring of plateau pressures in a volume-cycled ventilation mode.

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Category: Critical Care

Title: Empiric antibiotics for sepsis and associated AKI -- avoid vanc-and-zosyn right?

Keywords: sepsis, antibiotics, AKI, ACORN, zosyn, piperacillin-tazobactam, cefepime (PubMed Search)

Posted: 1/31/2024 by Kami Windsor, MD (Updated: 5/24/2024)
Click here to contact Kami Windsor, MD

Background: For better or worse, the combination of “vanc-and-zosyn” has long been a go-to empiric regimen for the treatment of septic shock. Piperacillin-tazobactam is known to cause decreased creatinine secretion into the urine leading to an increased serum creatinine without any actual physiologic harm to the kidney, but the results of previous studies have led researchers to posit an increase in actual AKI with the vanc and zosyn combo. This concern has led to some physicians choosing cefepime for anti-pseudomonal gram-negative coverage instead, despite its known potential for neurotoxicity and cefepime-associated encephalopathy.

The ACORN trial: The recently published ACORN trial compared cefepime to piperacillin-tazobactam in adult patients presenting to the ED or medical ICU with sepsis or suspected serious infection. The primary outcome was a composite of highest stage of AKI or death at 14 days.

  • Single-center, unblinded, pragmatic, randomized control trial
  • 2500 patients, approx. 20% with chronic kidney disease
  • Approximately 77% received vancomycin as well
  • ~20% antibiotic crossover in each group


  • No difference between groups in the primary outcome, or in major adverse kidney events, even in subgroup that also received vancomycin
  • No difference in hospital length of stay, vasopressor days, ventilator days
  • Slightly higher incidence of delirium or coma in the cefepime group 

Bottom Line:  Good antibiotic stewardship would probably decrease the frequency of vanc-and-zosyn administration, but concern for renal dysfunction alone shouldn’t guide the choice between cefepime or piperacillin-tazobactam, even in those with CKD, and even in those patients also receiving vancomycin.

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Hot of the press from the Society of Critical Care Medicine (But most of us would know it already)

Settings: This is a prospective observational population-based study design with non-contemporaneous, nonrandomized clinical trial direct (unadjusted) head- to-head evaluations
Propensity score–matched comparisons of non-shockable cardiac arrest (NS-OHCA) patient survivor using conventional CPR (C-CPR) vs. C-CPR plus Automated Head/thorax up positioning-CPR (AHUP-CPR).

Participants: patients with non-traumatic, non-shockable out of hospital cardiac arrest (NS-OHCA).

Outcome measurement: primary outcome = survival, secondary outcome = survival with good neurologic outcome (Cerebral Performance Category score of 1–2 or modified Rankin Score less than or equal to 3).

Study Results:
•    There was a total of 380 AHUP-CPR vs. 1852 C-CPR patients. After 1:1 matching, there were 353 AHUP-CPR patients and 353 C-CPR patients.
•    In unadjusted analysis
o    AHUP-CPR was associated with higher odds of survival (Odds ratio 2.46, 95% CI 1.55-3.92) and higher odds of survival with good neurologic function (Odds ratio 3.09 (95% CI 1.64-5.81)
•    In matched groups
o    AHUP-CPR was associated with higher odds of survival (Odds ratio 2.84, 95% CI 1.35-5.96) and higher odds of survival with good neurologic function [Odds ratio 3.87 (95% CI 11.27-11.78]

•    There was no difference in rates of ROSC between groups.  The authors argued that there was “neuroprotective effects” for the AHUP-CPR group.
•    Although randomized controlled trials are usually required before clinical interventions are adopted, the aurthors argued that it would be difficult to randomize OHCA patients, and that the risk vs benefits may facilitate early adoption of this strategy.
•    AHUP-CPR should be used first by well-trained clinicians to ensure its benefits.

OHCA patients with NS presentations will have a much higher likelihood of surviving with good neurologic function when chest compressions are augmented by expedient application of the noninvasive tools to elevated head and thorax used in this study.

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IVC POCUS is often misapplied in attempts to assess volume status and/or volume “responsiveness.” Here are some important concepts to understand when using IVC POCUS to guide management:

  1. IVC measurement is not a reliable predictor of fluid responsiveness
  2. Venodilation and obstructive pathology can decrease and increase (respectively) IVC size without any change in actual blood volume or “volume status”
  3. IVC size/variation is affected by multiple factors including spontaneous breathing vs. mechanical ventilation (AND actual ventilator settings), and degree of respiratory effort (in both spontaneous and mechanically ventilated patients) so there are no true “cut off” points that determine volume responsiveness
  4. Attempting to maximize cardiac output/oxygen delivery (macrocirculation) through IVF can actually cause venous congestion and worsen microcirculation and organ function
  5. Some patients with a plethoric IVC (tamponade or tension pneumothorax) may actually benefit from IVF in the acute setting
  6. Examine the entire IVC (cephalad and distal portion) and in the short and long axis (the IVC is actually elliptoid, rather than a true cylinder)
  7. Interpret IVC size in relation to RA/RV function (pts with chronically elevated RA pressures may have a chronically dilated IVC)

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Many of us in the endovascular resuscitation space were eagerly awaiting some clarity on REBOA from this trial. Unfortunately, this is not the definitive trial that either confirms or denies the utility of REBOA in trauma. 

Unfortunately, even this well-designed trial suffered from major problems, most notably enrollment issues (ITT: of the 46 in the REBOA group, only 19 actually got REBOA!!) and matching issues (Brain AIS was significantly higher in the REBOA group versus standard practice [3 vs 0] & initial systolic pressure was lower in the REBOA group, both of which are known risk factors for poor outcome in REBOA). 

This trial's failure to provide a definitive benefit or the nail-in-the-coffin is frustrating to say the least. Until that day, we will continue to be selective of the "right" patient and to put in femoral arterial lines early and often.

Zaf Qasim has an excellent talk on EMRAP about this study, as does St. Emlyn's.

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As is well known, fluid resuscitation strategy ("liberal" vs “restrictive”) in sepsis is a controversial topic.  An RCT in NEJM called CLOVERS that looked at this and found no difference was recently re-analyzed to answer the following question… should my choice of strategy change if the patient presents with an Acute Kidney Injury (AKI)?  

For the most part, the answer is no.  In the group with AKI, the restrictive group did slightly, but non-statistically-significantly, better.  Interestingly, in the group without AKI, the relationship reversed, and in fact of the 4 groups (AKI vs no AKI, Restrictive vs Liberal), the no AKI but liberal strategy group did best (liberal vs restrictive in the no AKI group almost reached statistical significance in favor of the liberal strategy, but not quite).

Bottom Line: In septic patients presenting with an AKI, we don't know whether liberal or restrictive strategy is better, but either is probably reasonable.  In patients presenting without an AKI, it may be more ok to lean more towards liberal fluid resuscitation than in non-AKI patients*.  

*There are several important caveats here: 1) they didn't closely evaluate for potential side effects of over-resuscitation such as hypoxia or pulmonary edema (the primary outcome was need for renal replacement therapy), 2) as mentioned above, this trended towards but did not reach statistical significance, 3) this is one small study which did a subgroup secondary-analysis of a larger trial.

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Acute-On-Chronic Liver Failure

  • Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of liver function in a patient with cirrhosis that is associated with organ failure and has high short-term mortality.
  • Key extrahepatic organ failures in ACLF include the renal, CNS, respiratory, circulatory, and coagulation systems.
  • With respect to CNS failure in ACLF:
    • Hepatic encephalopathy (HE) is the most common manifestation
    • A normal ammonia level makes HE unlikely
    • Benzodiazepines should be avoided
    • Primary triggers for HE include infection, GIB, and aggressive diuresis
    • Treatment of HE primarily consists of lactulose and rifaximin

Show References

Bottom line: In the 2023 updated Clinical Practice Guideline, the American Burn Association recommends 2ml/kg/%TBSA (for burns >20% TBSA)as initial starting point for fluid administration in the first 48 hours, guided by clinical factors with consideration of supplemental albumin to limit fluid administration. Fresh frozen plasma should be considered in the context of a clinical trial.  Vitamin C and advanced hemodynamic monitoring are not recommended as they have not demonstrated improved outcomes.

Summary: Burn care has a paucity of high-quality research about some of the fundamental questions for resuscitation. The American Burn Association since 2010 has endorsed fluid volumes for patients with >20% TBSA (i.e. those predicted to develop burn shock) from 2ml/kg/%TBSA to 4ml/kg/%TBSA as a starting point for fluid resuscitation. Further clinical studies since then have demonstrated that lower volumes of fluid targeting urine output and other physiological variables are effective without demonstrating clear improvement in patient centered outcomes.  Further adjuncts such as albumin or fresh frozen plasma have demonstrated reduced fluid administration but no improvement in patient-centered outcomes. While “fluid creep” is increasingly recognized, demonstrating benefits in clinical trials will likely remain elusive as overall practice continues to shift towards less fluids and the adjunctive use of colloid will likely continue to expand. In addition to ABA CPGs and resources, the Joint Trauma System also has several useful resources for burn care.


Category: Critical Care

Title: To Start Or Not To Start Vasopressor????

Keywords: vasopressor, norepinephrine, timing, septic shock (PubMed Search)

Posted: 12/5/2023 by Quincy Tran, MD, PhD (Updated: 5/24/2024)
Click here to contact Quincy Tran, MD, PhD

Settings: systemic review and meta-analysis

Participants: 2 RCTs, 21 observational studies. Fifteen studies were published between 2020-2023.

There was a total of 25721 patients with septic shock

Outcome measurement: Primary outcome was short-term mortality (ICU, hospital, 28-day, 30-day). Secondary outcomes included ICU LOS, Hospital LOS, time to achieve MAP > 65 mm Hg,

Study Results:

Composite outcome of short term mortality

  • 20 studies and 17470 patients. Early initiation of vasopressors was associated with lower odds of short term mortality (OR 0.775, 95% CI 0.673-0.893, P<0.001, I2 = 68%).
  • Early initiation of norepinephrine was associated with lower odds of short term mortality (OR 0.656, 95% CI = 0.544 to 0.790, P <0.001, I2 = 57.2%)
  • Early initiation of vasopressin was also associated with lower odds of short term mortality (OR 0.685, 95% CI 0.558-0.840, P < 0.001, I2= 57%)

 Secondary outcome:

  • Early vasopressor group was associated with lower odds of RRT use (OR 0.796, 95% CI 0.654-0.968, P = 0.022, I2 = 0%)
  • Mean Serum lactate levels at 6 hours was similar in early vasopressor group (Mean Difference 0.218, 95% CI -0.642 to 1.079, P = 0.619).
  • However, mean serum lactate levels at 6 hours was lower in early norepinephrine subgroup (mean difference -0.489, 95% CI -0.863 to -0.115, P = 0.01).


  • This appears to be a hot topic. When our group did this topic in 2020, there were 8 or 9 studies. Since 2020, there has been a significant increase in the number of publications, although most publications were observation studies.
  • Early initiation of norepinephrine may reduce fluid overload, not by reducing fluid input, but by improving host inflammatory response, improving endothelial cell barrier stability.
  • Counter-intuitively, early vasopressor was also found to be associated with lower incidence of arrhythmia, which the authors attributed to shorter duration of vasopressors and lower total dosage.


More and more studies, although a RCT is still necessary, are showing that early initiation of vasopressor within 1-6 hours of septic shock would be more beneficial to patients with septic shock.

Show References

-Initial lactate clearance over 2 hours has been used to measure pt response to resuscitation in sepsis. However, data supporting its prognostic use is lacking.
-Single center, retrospective cohort study in large academic center
-Adult patients (4,775) admitted through ED with suspected infection
-Lactate clearance defined as 10% decrease in 2 to 12 hrs
-Multivariable logistic regression adjusting for age, sex, cirrhosis, ESRD
-Lactate trajectories highly variable
-Lactate clearance was highly confounded by patient comorbidities (particularly cirrhosis)
-24-h change in peak lactate was a better prognostic indicator (but still poor)
-In the ED, caution should be used when using lactate clearance as a single marker for assessment/prognosis, particularly if the pt has other comorbidities such as cirrhosis

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