Beta-blocker is used for tachycardia among patients with sepsis. Landiolol, a new beta-blocker with highly selective B1-agonist (ratio of B1:B2 250:1) has recently been approved for use. In a network meta-analysis comparing landiolol with esmolol (B1:B2 ratio 30:1), landiolol was associated with increased 28-day mortality (relative risk [RR], 1.57; 95% CI, 1.08–2.30). This result carried low certainty as there were not as many studies using landiolol and there was no direct comparison between landiolol versus esmolol.
Similarly, landiolol was associated with higher norepinephrine requirements (mean difference [MD], 0.17 ?g/kg/min; 95% CI, 0.02–0.32). Again, there was no direct head-to-head comparison between landiolol versus esmolol.
It is a common scenario in the ICU, and occasionally in the ED, to be asked which pressor you would like to wean first, norepinephrine or vasopressin. This is mostly an “art not science” question, but is there a right answer? Does picking one vs the other to wean first lead to less hypotension?
Bottom Line: This meta-analysis doesn't suggest that either the norepi-first or vasopressin-first strategies for vasopressor wean are associated with an increased incidence of hypotension, although the literature is mixed. Whatever your current practice is, it's probably reasonable to stick with that. See the additional information for my personal approach.
Bottom Line: Hypertonic sodium bicarbonate (8.4%) can be used judiciously as an alternative hyperosmolar therapy in the setting of increased intracranial pressure (ICP) or cerebral edema with impending herniation, particularly in setting of concomitant metabolic acidosis. Two 50 mL ampules of hypertonic sodium bicarbonate is the equivalent of approximately 200 mL of 3% sodium chloride (hypertonic saline).
Diagnostic Errors in the Critically Ill
Etomidate is often a go-to agent for RSI because it is considered relatively hemodynamically neutral. However, lab studies have shown an association with transient adrenal suppression, and some observational studies and meta-analyses have suggested that patients intubated with etomidate face higher risk of cardiovascular collapse and in-hospital mortality than those intubated with ketamine.
The RSI trial was a pragmatic open-label multi-center randomized control trial conducted in 6 EDs and 8 ICUs across the US and compared induction with ketamine 1-2mg/kg versus etomidate 0.2-0.3mg/kg for RSI of critically ill adults (excluding trauma patients). They found no significant difference in overall 28 day hospital mortality across the cohort. They found an increased risk of cardiovascular collapse during intubation in the ketamine group. This increased risk was more pronounced in patients with sepsis or septic shock and patients with APACHE II ?20.
Some details:
Overall - this was a well conducted randomized control trial that - at the very least - suggests that etomidate is likely as safe (if not safer) than ketamine with respect to 28d mortality and peri-intubation cardiovascular collapse, even among patients with critical illness or septic shock.
A crucial part of cardiac arrest management is identification of the underlying rhythm, with key aspects of management diverging depending whether shockable (pulseless ventricular tachycardia/pVT or ventricular fibrillation/VF) or unshockable (pulseless electrical activity/PEA or asystole).
A recent study prospectively evaluated adult atraumatic out-of-hospital-cardiac-arrests (OHCAs) presenting to the ED, to determine what percentage of cases had “Occult VF” – VF found point-of-care echocardiogram but not by ECG. The researchers only included cases with simultaneous ECG and echo assessments for the initial 3 pulse checks. Echo and ECG determinations for the study were adjudicated by research team members.
They found that:
Major limitations:
Bottom Line: Point-of-care echocardiogram continues to have value in the management of cardiac arrest, potentially changing management and affecting post-ROSC decisions. Ensuring high-quality CPR, with appropriate defibrillation and anti-arrhythmic strategies, remains paramount in management of shockable OHCA.
Settings: Secondary analysis of the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial.
Participants:
1368 patients who survived on day 28 after enrollment, and were retrospectively assigned different subtypes:
Low risk, barriers to care. Younger patients with few comorbidities, less severe disease,
Unhealthy baseline with severe illness: Previously healthy with severe illness and complex needs after discharge, barriers to care.
Multimorbidity. Older patients with more comorbidities and are frequently readmitted.
Low functional status: Poor functional status. Older patients with high prevalence of frailty at discharge and high functional needs who are often discharged to a facility.
Unhealthy baseline with severe illness: Existing poor health with severe illness and complex needs after discharge. Older patients with severe comorbidities, more severe illness, high functional needs, prolonged hospital stay,
Outcome measurement:
A) 90-day mortality,
B) 6-month and 12-month EuroQol 5D five level score
Study Results:
A) 90-day mortality:
Unhealthy baseline with severe illness (37.6%) > low functional status (45.5%) > multimorbidity (17.4%) > unhealthy baseline, severe illness (13.2%) > Low risk (5.1%).
B) 6-month EuroQol 5D-Five Level: lower score, lower functional outcomes)
Unhealthy baseline with severe illness (0.53) > unhealthy baseline, severe illness (0.68) > low functional status (0.69) > multimorbidity (0.78) > Low risk (0.80).
Discussion:
a) The framework, readily available to clinicians provides good prognostic tools for mortality.
b) Although there was prediction of poor functional outcomes at 6-month and 12-month, the differences between subtypes in their EuroQoL 5D-5L did not seem to correspond to 90-day mortality. Low functional status group had 2nd-highest rate of mortality, but only 3rd in their EuroQoL 5D-3L score. Thus, there needs to be more studies in these nuances.
Conclusion:
Sepsis survivor subtypes—assigned using only three routinely available discharge variables—are strongly associated with 3-month mortality and long-term disability and HRQOL up to 12 months
Recall that MAP = (cardiac output) x (systemic vascular resistance)
Consequently, a patient can be normotensive due to increased SVR despite a very low cardiac output and shock. In fact, normotensive shock may have worse outcomes compared to patients with isolated hypotension.
Take home points:
Yet another study (this time ED focused) has shown benefits to patients and hospital systems when implementing a Phenobarbital-based treatment algorithm. Shorter ED LOS, fewer admissions, and treatment with phenobarbital alone was independently associated with discharge when compared to mixed treatment regimens. Higher age and heart rate, as well as treatment with benzodiazepines alone were independently associated with hospitalization.
Cautions/contraindications include: pregnancy, cirrhosis with history of hepatic encephalopathy (consider dose reduction in hepatic dysfunction), acute intermittent porphyria, and prior chronic phenobarbital use.
Phenobarbital has a long half life (one of its benefits in AWS) and works synergistically with benzodiazepines, so should be used preferentially as monotherapy in patients where the diagnosis is relatively certain and who have not received high doses of benzos. Once the diagnosis is made, go with phenobarbital and stick with it.
PulmCrit has an excellent in-depth article on this and also see Dr. Flint's pearl describing another centers experience in a hospital-wide rollout (links below).
Perintubation hypotension is a major problem, and can precipitate hemodynamic collapse and cardiac arrest for a multitude of reasons. To prevent this, many different strategies have been explored (some of which work and some of which don't), including empiric IV fluid boluses, additional resuscitation before intubation, switching or dose-reducing induction agents and much more. But we know pressors like norepinephrine raise blood pressure effectively, so should we just put everybody on a norepinephrine drip before we intubate them?
Probably not. The EPITUBE trial included 210 patients at a single-institution undergoing cardiac surgery, and randomized them to empirically starting a norepinephrine infusion before induction vs just rescue ephedrine when needed (fairly standard anesthesia practice). For the empiric norepinephrine group, they started at 0.06 ug/kg/min, and once the drip was up and running, they titrated for a MAP of 65-80 (which could include stopping the norepi if that the patient remained above 80 despite downtitration)
The incidence of severe hypotension (MAP < 55) did not differ between the groups, although fewer empiric norepinephrine patients had a MAP < 65 at any point (which was a secondary outcome). Naturally, the differences between this practice setting (the cardiac surgery OR) and the emergency department should be noted and are not addressed by this study.
Bottom line: There isn't good evidence to support empirically starting all patients on a norepinephrine infusion prior to intubation as a method to prevent perintubation hypotension. You should always have rapid access to vasopressors when intubating, and should continue to tailor your therapy to the individual patient, but probably don't start just putting everyone on norepinephrine before you intubate them.
The emergency department serves many critically ill patients that require airway management and mechanical ventilation. Most of these patients go on to require ICU care. However, some patients require only brief intubation and should be appropriate candidates considered for emergency physician-driven extubation. Early extubation can minimize the risks associated with mechanical ventilation for patients such as ventilator associated pneumonia (VAP), ventilator induced lung injury (VILI), and others. Additionally, in setting of high levels of ED boarding and limited ICU resources, extubating appropriate candidates in the ED can reduce boarding times and improve patient flow.
Who?
Screening Checklist
Testing
Prepare - depending on institution, may require consultation with the hospital intensivist
Perform - see this video courtesy of Respiratory Skills - LSC on performing extubation
Pitfalls in Lactate Interpretation
Last month, Mark Sutherland posted an overview of a new article investigating the use of personalized MAP targets in resuscitation for septic shock (1). Now, the authors of ANDROMEDA-SHOCK-2 (2) suggest a new multimodal approach to personalize resuscitation in septic shock that largely operates outside of the traditional focus on MAP and lactate.
In 2019, the ANDROMEDA-SHOCK Trial (3) suggested that capillary refill time (CRT) may be a better resuscitation in septic shock than lactate. Now, the same group is suggesting that a stepwise algorithm to guide resuscitation may provide more optimal and “personalized” results when compared to usual care for patients with abnormal CRT:
Tier 1: If CRT is abnormal, assess pulse pressure (PP) and DBP:
Tier 2: If CRT remains abnormal despite the above, use POCUS to assess for cardiac dysfunction.
The authors found that at 6 hours, following the protocol resulted in increased use of dobutamine, lower fluid balance, and similar CVP and MAP with lower lactate levels and CRT. They reported an improvement in their composite hierarchical outcome at 28 days, primarily driven by a shorter duration of organ support (vasoactives, mechanical ventilation, renal replacement therapy) and among sicker patients. No difference in mortality was observed between groups.
Food for Thought:
Study Details:
We have all been there – an ED patient with circulatory shock requiring vasoactive medications and, therefore, an arterial line for accurate and close monitoring of the MAP and appropriate titration of the infusions. But does it save lives?
The recently published NEJM article by Muller et al. takes a look at noninvasive BP monitoring (NIBP) by cuff versus early arterial catheterization in patients with hypotension and evidence of tissue hypoperfusion:
Bottom Line: This trial indicates that in appropriately-selected patients with shock, such as those not on high doses of vasopressors, with BMI < 40 and an ability to consistently obtain NIBP measurements, early arterial line placement in the ED for vasopressor titration is unlikely to improve outcomes. It is important to note other potential indications for arterial line placement (severe hypoxia, inability to obtain reliable SpO2 with need for ABG monitoring, cardiac arrest, pain related to NIBP cuff monitoring, intracranial hemorrhage, etcetera) may still make arterial line placement in the ED prudent and better for overall patient care.
*France refers to norepi by the tartrate formulation dose, US refers to the base norepi dose (ratio is 2:1 tartrate: base).
Settings: this is a meta-analysis of 17 observational studies about boarding of critically ill patients in US Emergency Departments. All studies were from urban, academic centers.
Participants:
Outcome measurement: all cause mortality, as reported by the authors of the original studies.
Study Results:
Discussion:
Conclusion:
Critically ill patients boarding in the U.S. Emergency Departments were associated with a non-statistically signi?cant increase in odds of mortality and hospital length of stay compared to non-boarded patients
The role of sodium bicarbonate in the treatment of severe acidemia has been controversial, with some studies suggesting no benefit, and others indicating that it may help reduce need for renal replacement therapy (RRT) and even improve mortality. The BICARICU-2 Trial was an open-label multicenter RCT conducted in France that evaluated the impact of a bicarb infusion among patients with metabolic acidosis and moderate to severe AKI.
There was no difference in 90 day mortality, but patients in the bicarb group were less likely to be started on RRT (38% vs 47% in the control group) using pre-defined criteria for RRT initiation, and had a 50% lower rate of bloodstream infections. Patients in the bicarb group who were started on RRT met criteria for RRT later than those in the control group (median 31h vs 15.5h).
Study Details:
Patient Population:
Intervention:
RRT Triggers:
This is an actual patient case:
65 y/o pt intubated for hemoptysis and started on nebulized transexamic acid. Overnight, the pt is found to have severe breath stacking/auto-PEEPing and consequently is started on neuromuscular blockade. The pt has no history of asthma or COPD and the ETT is clear without obstruction.
Ventilator waveforms are as shown. What is the issue?
This study surveyed 111 emergency medicine (EM) trainees to identify factors influencing their choice of critical care (CC) fellowship pathways, particularly surgical critical care (SCC). Respondents included 42 fellows and 69 residents, with most pursuing anesthesiology or medicine CC; only 15 intended SCC.
Key determinants of pathway selection were:
Limited exposure to EM-SCC during residency was noted—only 28% had access to such fellowships, and 42% interacted with surgical intensivists, despite 41% envisioning SCC practice.
Intellectual appeal ranked highest for entering CC, above job prospects or lifestyle.
Fellowship components most valued were:
While descriptive, the authors noted many respondents cited the "preliminary surgical year" as a reason that the Surgical Critical Care pathway is less attractive.
The authors conclude that respondents pursued a career in CC for "intellectual appeal and desire for additional expertise" and that improving EM-SCC matriculation requires targeted interventions.
Another month, another study of hemodynamic targets in sepsis… The age-old questions: is a MAP > 65 a good target for everybody, or should we individualize? Should we just give a bolus of fluids to everyone and then move to pressors, or should this strategy change patient to patient?
Huet et al have a preprint that'll appear in Intensive Care Medicine looking at this question in 517 patients. I can't reprint it here due to copyright (follow link below, go to full PDF and scroll to figures at bottom if curious), but basically their algorithm was 1) check if patient is fluid responsive via either echo or swan, 2) give fluid if yes, 3) do something else (pressors) if no.
Importantly the differences were not statistically significant, but they found a strong, nearly significant, trend towards benefit on SOFA score, ICU and hospital LOS in the “personalized therapy” group (also of note, these are dubious as patient oriented outcomes). The sickest patients (by SOFA) showed the most benefit.
Bottom Line: The “personalized hemodynamic therapy” literature continues to show a modest benefit of using tools like echo (e.g. LVOT VTI) to determine if the patient is fluid responsive (or fluid tolerant) and NOT give fluid (instead using pressors) if that is not the case, but for now there's relatively limited support for hyper-personalized approaches like varying MAP goals or otherwise mixing up your strategy. Some day we'll likely find a more nuanced approach, but for now I think a reasonable strategy in critically ill septic patients is to use ultrasound to determine if the patient needs fluid, if yes give fluid and reassess, and if not move to pressors, to maintain a MAP > 65.
A scoping review of literature involving norepinephrine use during cardiac arrest associated with a shockable rhythm found:
-evidence in animal and signal in human trials of improved myocardial and cerebral blood flow
-a suggestion of less re-arrest
There is not enough evidence comparing epinephrine to norepinephrine however this would be an excellent area of research with a theoretical advantage to norepinephrine.
