UMEM Educational Pearls - By Mark Sutherland

Intubation and mechanical ventilation of brain injured patients, which is extremely common in the Emergency Department, can be very challenging and subject to significant practice variation.  It is often said that brain injured patients “can't take a joke”, meaning that they are less tolerant to hemodynamic and metabolic perturbations, and these perturbations tend to be associated with very large swings in their clinical outcomes.  For example, hypo/hyperglycemia, hypo/hypernatremia, hypo/hypertension, hypo/hyperoxia, hypo/hypercapnea, etc are all extremely important to avoid.  This is probably the one patient population where “euboxia” (the notion that we obsess too much about making all the numbers pretty in the EMR) is probably not as applicable.  As such, there is at least good physiologic rationale, and now increasing empirical evidence, that ventilating these patients very thoughtfully is extremely important and likely to have meaningful impact on patient-oriented outcomes (mortality, neurologic outcome, etc).

The VENTIBRAIN study was a prospective observation trial of 2,095 intubated patients in 26 countries who had TBI, ICH (including SAH), or acute ischemic stroke.  Interestingly, they found that patients with lower tidal volume (TV) per predicted body weight had higher mortality (although the majority of their TVs were well controlled and in a fairly tight range), which is contrary to conventional thinking in pulmonary pathologies like ARDS.  They also found that higher driving pressure (DP) was associated with higher mortality, which agrees with data from other conditions.  PEEP and FiO2 had U-shaped curves, but FiO2 in particular tended to favor lower FIO2, also similar to current thinking for ICU patients in general.  

Take Home Points:

1. Although most brain injury patients have relatively normal pulmonary function, lung compliance, ventilator waveforms, etc, their ventilatory parameters (TV, PEEP, DP, pCO2/pH, oxygenation, etc) should be carefully monitored and a deliberate strategy to manage these parameters is essential.  Haphazard ventilatory strategies in these patients are clearly associated with poorer patient-oriented outcomes.
2. It's possible (although not definitively proven) that aggressively low TVs in these patients may lead to hypercapnea - which we know is poorly tolerated in brain injured patients - and worse outcomes.  The role of classic “permissive hypercapnea” (ala ARDS management, goal pH > 7.2) in these patients is unclear, and one should probably be more judicious in letting these patients get overly acidotic or hypercapneic, as opposed to other pathologies like ARDS where this is probably more allowable.  
3. Despite the paradoxical finding with low TVs, high driving pressure remains an important predictor of mortality in essentially all critical patient populations.   Care should be taken to minimize DP (guidelines say < 15 cm H2O, but goal should be minimum achievable value while meeting pCO2/pH targets).  DP/PEEP titrations should be carried out regularly when feasible (not all providers are comfortable with this practice, but it is safe and easy to learn, see references below).
4. Hypoxia and hyperoxia are both extremely dangerous for this population.  The minimum FiO2 needed to achieve a pulse oximetry reading of around 90-96% (exact numbers vary slightly by guideline and any underlying pulmonary pathology) should be used.  Be very wary of the pulse ox sitting constantly at 100% in these patients.

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Post-Intensive Care Syndrome (PICS) is an increasingly recognized phenomenon of impairment of physical, cognitive, and/or mental health after intensive care admission.  Even more recently, similar deficits in caregivers of patients admitted to the ICU, often called Post-Intensive Care Syndrome Family (PICS-F) is increasingly recognized.  A study recently published by Watland et al in Critical Care Medicine looking at reducing PICS-F through a “caregiver pathway” got me wondering if there's any literature out there about reducing PICS-F via interventions in the emergency department.  Patients' treatment course in the ED is a highly stressful and uncertain time for both the patient and family members, so it stands to reason this is an impactful period where intervention may help, and even in patients where their condition is too advanced for us to make a medical difference, our actions could have a positive impact on long term outcomes for the family members.

The short answer is no, to this author's knowledge and based on my review of the literature, there is no good evidence for reducing PICS-F by ED interventions (hint, hint: if anyone's looking for a good area to study…)  Based on evidence from the critical care realm, the following are probably reasonable approaches that would translate well to the ED:

1. Recognize, especially when you have a patient who likely has a very poor prognosis, that for our critical patients it is important to treat the family, as well as the patient.  
2. Update the family early and often.  Uncertainty is a key contributor to PICS-F.  
3. Consider developing a brochure for family of critically ill patients at your facility.  Basic information such as where to park, how to get into the hospital, where their loved one may go after the ED, where they can get food, what visiting hours are allowed, whom to contact with questions, etc seem exceptionally simple to us but are often early points of stress for family.  
4. Consider screening family members for PICS-F (probably better left to the ICU, but could be considered for longer ED stays or if patient prognosis is extremely poor).  There are multiple validated screening tools available.
5. Consider encouraging patient (if they are able) or family to keep a diary.  ICU diaries have been shown to decrease incidence of both PICS and PICS-F.  See also icu-diary.org
6. If feasible, consider follow up with family members at high risk of PICS-F.  Could be done as a joint venture between the ED and inpatient services or as a hospital-wide initiative.  
7. Engage ancillary services such as pastoral care, palliative care, integrative medicine, and others early and often to foster a multi-disciplinary approach.  Also, make sure to communicate well with your nursing team, who are at the bedside and often more in tune with family signs of future PICS-F.

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In out of hospital cardiac arrest (OHCA), does it matter if you choose an intraosseous (IO) vs intravenous (IV) approach to getting access and giving meds?

No, according to a recent study by Couper et al, just published in NEJM.  No significant difference in any clinically meaningful outcome including survival, neurologically intact discharge, etc.  Technically the IV group had slightly higher rates of ROSC, which just met statistical significance, and to be fair that group did trend very slightly towards better outcomes in some categories, but really well within the range expected by statistical noise.  

Interestingly, the median time from EMS arrival to access being established was the same in both groups (12 minutes), which I think raises some face validity questions.  Furthermore, of course, previous trials have raised questions as to whether ACLS meds even work or impact outcomes anyways, so naturally if they don't, the method by which they are given isn't likely to matter either.

Bottom Line: This large, well conducted trial continues to support the notion that either an IV-focused, or IO-focused approach to access and medication delivery in OHCA is reasonable.  You and your prehospital colleagues can likely continue to make this decision based on personal comfort, local protocols, and patient/case circumstances.  At the very least, this continues to support the notion that if an IV is proving challenging, pursuing an IO instead is a very appropriate thing to do.

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Airway management in the pre-hospital setting is a matter of much controversy, and overall I will defer to my EMS colleagues, but several previous studies have failed to show a benefit to endotracheal intubation in the field as opposed to alternate approaches like a supraglottic airway.  Another nod in this direction has recently come out, with Battaglini et al performing a post-hoc analysis of one of the larger studies in the history of cardiac arrest, TTM-2, looking specifically at outcomes stratified by pre-hospital airway management strategy.  

Do patients who undergo endotracheal intubation in the field do better than those who get a supraglottic airway?

No, they don't.  TTM-2 included 1900 patients, of whom 1702 had enough data to be included in this re-analysis.  28% got supraglottic airways, and 72% got endotracheal intubation.  The groups were reasonably well matched on most characteristics, and if anything most well-known prognostic factors favored the endotracheal intubation group (very slightly).  It should be noted that several outcome metrics, including modified Rankin scale, did show slight signs of benefit for the endotracheal intubation group, even sometimes in a statistically significant fashion, but fell out when a multi-regression analysis, which was the primary endpoint, was done.  

Bottom Line: In pre-hospital cardiac arrest, there remains limited data to support the notion that endotracheal intubation results in better outcomes than supraglottic airway placement.  You should defer to your local protocols and continue to work with your paramedics and EMS directors as evidence continues to evolve.  For now, I don't think there's sufficient data to suggest that a given patient should be intubated vs undergoing supraglottic airway placement, and it is probably best to defer to the judgement, training, and protocols of your folks on scene.

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The CLOVERS trial (NEJM 2023) examined one of the eternal questions of critical care, liberal vs restrictive fluid management in sepsis… and found no difference.  But there are criticism of CLOVERS, and while some other trials agreed with this result, there are also signals in the literature that restrictive fluid strategies are beneficial.  Furthermore, we know that these trials suffer from issues of  heterogeneity, and often lump together very different patients.

Jorda et al recently published in Critical Care a posthoc re-analysis of CLOVERS looking specifically at patients with advanced CKD (eGFR < 30).  This is a challenging group of patients to manage.  On the one hand their renal function is already marginal, so the last thing we want to do is potentially deprive starved kidneys of necessary intravascular volume, but on the flip side their septic shock puts them at high risk of full blown renal failure (transient or permanent) and they're thus at very high risk of fluid overload with aggressive resuscitative fluids and potentially limited ability to clear those fluids renally in the next few days.  So how did these patients do in CLOVERS?

They did significantly better with the restrictive fluid strategy (mortality 22% vs 39%, HR CI 0.29-0.85).  They also had more pressor free days and vent free days.  

Bottom Line (my opinion): While a restrictive vs liberal fluid strategy in septic shock remains a bit up for debate, the evidence continues to slowly tip towards restrictive fluids (i.e. earlier pressors) as the preferred approach.  In patients with advanced CKD (eGFR < 30), there is probably now sufficient evidence to favor vasopressors over IV fluid administration when resuscitating septic shock.

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Magnesium is known to relax smooth muscles.  Interestingly, there is also some literature using it as part of Rapid Sequence Intubation (RSI) pre-treatment in general, in hopes that this or other mechanisms might allow it to improve intubating conditions.  Zouche et al recently published an RCT looking at giving IV magnesium as part of RSI pretreatment in cases where neuromuscular blockade (NMB) is not going to be given (e.g. scenarios where it is contraindicated).  IV Magnesium Sulfate, 50 mg/kg in 100 mL of saline given 15 minutes before induction, significantly improved intubating conditions in those getting sedation but not NMB (95% vs 39%).  

In 2013, Park et al did an RCT giving magnesium to all RSIs, even with the use of rocuronium in those patients, arguing that magnesium is also known to potentiate the effects of non-depolarizing NMB agents.  They also found better intubating conditions in the magnesium patients.

In both trials, magnesium was associated with lower heart rates and less hypertension in the peri-intubation and immediate post-intubation periods (of note: high dose magnesium is known to be associated with lower blood pressures, and can induce overt hypotension).  Neither study was really powered for more important measures like first pass success, mortality, or important side effects like peri-intubation hypotension.

Bottom Line: These are two small trials, and while more abundant literature should probably be obtained before we change our practice, one could consider giving magnesium sulfate, 50 mg/kg in 100 mL saline, prior to intubation in an attempt to improve intubating conditions.  In my opinion, this is probably worth considering in the rare circumstance that your patient has a true contraindication to neuromuscular blockade, but I probably wouldn't start doing this in standard RSI where you're going to be giving NMB until more literature confirms the safety of this approach.  Also, I would avoid this in situations where the patient is already hypotensive or at high risk of peri-intubation hypotension.  This may be worth considering in the very rare patient you're not necessarily going to give NMB to right away (maybe awake fiberoptic intubations?) who are also very low risk for hypotension.

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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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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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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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For the folks who have been in practice for a while, you may be aware of the roller-coaster evidence base looking at steroids for pneumonia.  Once thought to be beneficial and clearly indicated, of late steroids for pneumonia have fallen out of favor.  Hamad et al have published an excellent (and brief) review in Clinical Infectious Diseases which suggests the pendulum might be swinging back in favor of giving steroids to patients with pneumonia.  It's a ~5 minute read, so I recommend glancing through it yourself, but below are my two cents (solely my opinion) on where we are with steroids for pneumonia.

Take Home Points (OPINION ALERT):

1) When you have a condition present that you consider an indication for steroids (e.g. severe COVID-19 for sure; septic shock, s. pneumo infection, and ARDS depending on how you feel about the existing literature) --> strongly consider giving steroids unless there's a contraindication

2) When you have an undifferentiated patient who MAY have one of these conditions (e.g. pneumonia with COVID pending, patient potentially in ARDS or high risk of going into ARDS, etc) who is very sick --> it is reasonable to give steroids (if no contraindication) or not give steroids.  My tendency is to lean towards giving steroids in these cases, but do be aware that society guidelines recommend against steroids here (although debatable if they just haven't caught up to more recent literature)

3) When you have an undifferentiated patient who may have one of these conditions, but is NOT very sick --> I do not think there is significant enough evidence to support empiric steroids

4) Factors that might push you one way or another:

• Severity of disease (more severe favors giving steroids),
• Pathogen (COVID-19 and s. pneumo favor steroids),
• What formulation of steroids you have availabile.  Some of these studies used continuous hydrocortisone infusions, for example, which most hospitals don't routinely do.
• Comorbidities (uncontrolled diabetes, wound healing issues, risk for opportunistic infections might argue against giving steroids)

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When patients fail simple respiratory support therapies like nasal cannula or non-rebreather, it is often a point of debate whether to move next to High Flow Nasal Cannula (HFNC) or Noninvasive Positive Pressure Ventilation (NIPPV).  This study randomized patients in acute respiratory failure (ARF) to CPAP, a form of NIPPV, vs HFNC.  They looked at all comers in ARF, and primary outcome was need for intubation.  Importantly, they excluded asthma/COPD exacerbation, for which BiPAP is typically considered the first line therapy due to improved CO2 clearance.

They found a significantly lower number of patients required intubation in the CPAP (28.9%) group than the HFNC (42.6%) group (p=0.006).  They hypothesized that the enhanced PEEP improved oxygenation (hypoxia being a common trigger for moving to intubation), but as opposed to BiPAP,  the lack of additional driving pressure limited tidal volumes and Patient Self-Inflicted Lung Injury (P-SILI), which is a known mechanism of ARDS and mortality.  They use this argument to explain why trials like FLORALI, pitting HFNC vs BiPAP, tend to not find an advantage for the NIPPV arm.  While this rationale makes sense, it should be noted that the study does not directly investigate if this was the reason for the difference, and for what its worth the inverse argument that using driving pressure to reduce respiratory rate, hypercarbia, and work of breathing (other very common indications for intubation) would also theoretically reduce intubations.  Furthermore, it's not clear why reducing P-SILI, which tends to cause mortality on a much longer duration, would improve the short-term outcome of need for intubation.

Bottom Line: This study demonstrated a benefit to CPAP over HFNC in terms of decreasing need for intubation amongst non-asthma/non-COPD patients with acute respiratory failure, and offered a physiologic rationale but one that requires further verification and discussion.  While it may be reasonable to choose CPAP instead of HFNC in marginal patients at risk of intubation (but stable enough to trial noninvasive support first), in my opinion more studies are likely needed before a wholesale change in practice.  The study also does not take into consideration the enhanced comfort and compliance we tend to see with HFNC over NIPPV, which should be considered as well.  

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Central Venous Catheter (CVC; aka central line) placement is a common procedure in both the ED and ICU, and while overall quite safe, does carry some risk.  In particular, many of us regularly are confronted with the challenge of placing a line in a patient with profound thrombocytopenia, which can result in significant bleeding.  In these cases, should we give platelets before we place the line?

Van Baarle et al published a randomized study in NEJM comparing an empiric 1u platelet transfusion vs no transfusion in patients with a platelet count of 10,000-50,000, prior to line placement.  The study included both HD and non-HD (e.g. TLC) lines, from all three major access sites, in patients in their ICU or hematology ward.  They found statistically fewer serious bleeding events in the transfusion group (4.8%) vs no transfusion group (11.9%).  The study wasn't powered to look at more patient oriented outcomes like mortality, but I'm sure we can all agree less bleeding is probably a good thing.  Also importantly, this study did not evaluate the risks/benefits of delaying line placement to obtain platelets when the line is urgently needed, so I would not recommend extending this to conclude platelets must be given before line placement if the line is needed for something highly time-sensitive (e.g. only available access to infuse pressors in a hypotensive patient).  

Bottom Line: It is probably beneficial and appropriate to provide prophylactic platelet transfusion prior to CVC placement in patients with a platelet count less than 50,000, assuming circumstances allow.  

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Ability to move the head and neck freely can be clutch in endotracheal intubation, so in patients such as certain trauma patients who may have c-spine instability and need to be immobilized, it's all the more important to choose the optimal intubation approach to maximize success and minimize head movement.

Choi et al recently published a study in Anesthesia looking at:

-Video laryngoscopy with a standard geometry Mac blade

vs

-Fiberoptic intubation

as the initial method for intubating patients in c-collars about to undergo spinal surgery.  This is an interesting contrast between two extremes, as standard geometry is the most "traditional" approach, whereas fiberoptic is kind of the opposite end of the spectrum, jumping to a more advanced method which might be more flexible (no pun intended) but also introduces new complexities.  

All outcomes actually favored standard geometry VL over fiberoptic, including first pass success (98% vs 91%), time to intubation (50s vs 81s) and need for additional airway maneuvers (18% vs 56%).  There was no difference in complication rates, although a bigger study might be needed to find rare complications (this study had 330 patients).  

In my opinion, it's unfortunate they didn't include hyperangulated VL, as it would be interesting to see how this approach compares.  Personally I think of hyperangulated VL in these patients as a nice blend of the two methods, bringing the familiarity and speed of typical VL intubation, but often requiring less neck movement like fiberoptic.

Bottom Line: This study does not support a fiberoptic first approach to intubating patients with cervical spine instability.  In fact, it may cause harm.

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The classic teaching is that patients with acute pancreatitis should be aggressively hydrated with IV fluids.  But as we increasingly question heavy handed fluid strategies in other areas such as sepsis, should we look at pancreatitis management too?

Li et al did a systematic review of the literature on aggressive fluid resuscitation (the exact protocol/definition varied per study, but we're mostly talking 15-20 mL/kg boluses followed by 3-5 mL/kg/hr infusion) vs less aggressive fluid resuscitation (mostly 10 mL/kg boluses followed by 1.5 mL/kg/hr infusion).  They found that aggressive resuscitation worsened mortality in severe pancreatitis (RR 2.45) and trended towards worse mortality in non-severe pancreatitis (RR 2.26, but CI crossed 1).  Aggressive was associated with more complications in both severe and non-severe pancreatitis pancreatitis.

Multiple society guidelines still call for aggressive IVF resuscitation for acute pancreatitis, but probably need to be updated given mounting evidence that this is harmful.  More recent guidelines suggest "goal-directed therapy", but no one is completely sure what that means.  

Bottom Line:  In acute pancreatitis, a more conservative empiric IVF resuscitation is probably better than the clasically taught aggressive approach.  Whether even less fluids would be better or worse is not known, but for now it's probably best to stick to a 10 mL/kg bolus and 1-2 mL/kg/hr infusion when ordering fluids for these patients unless you have another indication.

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When managing a hypotensive patient who may have some element of cardiogenic shock, it has long been debated whether it is better to start an inodilator like dobutamine, and use a true vasopressor like norepinephrine to offset the vasodilation, or start an inopressor like epinephrine.  Currently, this is largely a practice pattern issue, with different providers and specialties tending to make different choices (in my anecdotal experience, medical intensivists tend to do norepi+dobutamine, whereas cardiac surgeons and intensivists tend to use epi).  

Banothu et al recently studied this question in children with "cold" septic shock (they do not specify how this was defined) and found quicker time to resolution of shock with norepi+dobutamine vs epinephrine.  It should be noted that this was a secondary outcome, was a small study, was in children (who I'm told are not just little adults), and no difference in mortality or patient oriented outcomes was found.  However, this is a good opportunity to review what is known on this topic:

-A small RCT in Lancet 2007 by Annane et al found no difference

-A very small RCT in Acta Pharmacologica Sinica 2002 by Zhou et al suggested norepi-dobutamine has favorable effects on gastric mucosa and tissue oxygenation relative to epi or dopamine

-A small RCT in Intensive Care Medicine 1997 similarly suggested that oxygenation in the splanchnic circulation may be better with norepi+dobut than epi.

Take Home: There is very limited evidence in either direction when choosing between an inodilator + vasopressor (e.g. norepi + dobutamine) vs single inopressor (e.g. epi) strategy for a hypotensive patient in which inotropy is desired.  There is some weak evidence that norepi + dobutamine may be better for maintaing gut oxygenation and may resolve shock faster.  Personally, I would weakly recommend norepi + dobutamine over epinephrine, but continuing to follow provider preference and go with the agent(s) you're most comfortable with is also very reasonable.  If using the inodilator/vasopressor combination, it is recommended to titrate the vasopressor (e.g. norepi) to MAP and inodilator (e.g. dobutamine) to a measure of cardiac function such as CO/CI.  

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Although extubation has historically been the purview of critical care, as ED lengths of stay continue to worsen, and as we see more and more rapidly reversible respiratory failure (e.g. opioid overdose), it is valuable for ED providers to be facile in extubating patients.  In addition, a longstanding debate in critical care has revolved around the proper device to extubate patients to, specifically: regular nasal cannula (NC) vs high flow nasal cannula (HFNC) vs noninvasive positive pressure ventilation (NIPPV).  Although data are mixed, the literature suggests extubation to HFNC or NIPPV may reduce risk of reintubation, esspecially in patients at a high risk of reintubation, but doesn't show a clear difference between HFNC and NIPPV.  

Hernandez et al recently conducted an RCT in two Spanish ICUs looking at HFNC vs NIPPV upon extubation for high risk patients.  NIPPV was associated with a lower reintubation rate (23%) as opposed to HFNC (39%).  Hospital LOS was also shorted in the NIPPV group, but no other differences were observed.  

It should be noted that this study, and pretty much the entirety of this literature base, is in ICU patients.  In fact, in this study, patients were excluded if they were intubated less than 24 hours.  Generally speaking, patients with shorter intubation tend to be lower risk for reintubation and other post-extubation negative outcomes, so I would use caution extrapolating this too much to the ED.  Unfortunately however, there is very limited literature to guide ED extubation practices.  

Bottom Line:

1) Know how to assess readiness for extubation and consider extubation in the ED if they meet  criteria

2) For patients at higher risk of reintubation (older, sicker, CHF, COPD, obesity, airway issues) who you are considering extubating, you may wish to extubate them to Noninvasive Positive Pressure Ventilation, even though there is little solid literature showing best practices in terms of post-extubation respiratory support in the ED.

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Needless to say, therapeutics for COVID-19 pneumonia have been controversial.  From hydroxychloroquine to ivermectin to remedesivir to steroids to bleach (sorry, but it had to be said...),  it depends on who you ask whether medications make a difference in COVID, how much of a difference, when they should be given, and what the correct dose is. 

Dexamethasone, however, ala the RECOVERY trial, is one of the relatively few therapies supported by the majority of the literature and guidelines, and generally is recommended when respiratory support is required for COVID-19 pneumonia.  Further add to this that steroids for ARDS is a long-running point of critical care controversy (e.g. DEXA-ARDS, Meduri, etc), and all you need to say to an intensivist is "how much steroid should I give this patient?" and you can walk away and come back 10 minutes later to find them having not noticed you had ever left.

Wu et all did a fairly small (n=107) single-centered RCT looking at dexamethasone 6 mg daily vs dexamethasone 20 mg daily for COVID-19 requiring O2.  There are several notable limitations to this study, but in short it did NOT add support to the notion that higher dose dexamethasone is a good thing for COVID-19 pneumonia.  In fact, the 20 mg group trended towards worse outcomes.  Small sample size, single-center, limited follow up, variable use of biologics between the groups, and failure to investigate intermediate doses between 6 and 20 are all significant limitations of this trial. Of note, DEXA-ARDS, which was conducted before COVID (2013-2018), looked at 20 mg x 5 days followed 10 mg x 5 days and DID find a significant benefit, as well as pretty darn good NNT and p values (and was a higher quality trial), so in my opinion it is also not unreasonable to use DEXA-ARDS dosing if the patient meets moderate-severe ARDS (P:F < 200) criteria, even though of course DEXA-ARDS was before COVID and Wu et al slightly contradicts it. 

When faced with a very sick COVID-19 pneumonia patients many intensivists will do either RECOVERY or DEXA-ARDS dexamethasone (with relatively limited basis to choose one vs the other), and some will do Meduri protocol methylprednisolone (1-2 mg/kg/day).  Relatively few nowadays will omit steroids unless there's a contraindication.

Bottom Line: It probably remains a good idea to give dexamethasone to your COVID-19 pneumonia patients with hypoxia, but you can probably stick to RECOVERY (see reference below; 6 mg daily x 10 days) dosing as opposed to higher doses.  If they're REALLY sick (P:F < 200), consider DEXA-ARDS (20 mg x 5 days followed by 10 mg x 5 days) dosing.

We previously posted on the COCA trial, which looked at empiric calcium administration in cardiac arrest.  They studied 391 adult Danish cardiac arrest patients.  The immediate and 30 day outcomes showed no benefit, and in fact strongly trended towards calcium being WORSE than placebo.  This article provides the 6 month and 1 year follow up data.  Surprise, surprise... calcium is still not looking good.  

At 6 months survival non-significantly favored the placebo group, and at 1 year it significantly favored the placebo group.  Neurologic outcome for those who survived was also no better, and perhaps slightly worse, in the calcium group. 

Importantly, the trial excluded patients with "traumatic cardiac arrest, known or suspected pregnancy, prior enrollment in the trial, adrenaline prior to possible enrollment, and clinical indication for calcium at the time of randomization."

Bottom Line:  The evidence continues to not support the routine empiric administration of calcium in cardiac arrest.  Patients in whom there is an indication to give calcium (e.g. known ESRD, suspected hyperkalemia, etc) are excluded from these trials, and should likely still receive empiric calcium, but in undifferentiated cardiac arrest you can probably skip the calcium.

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Although it is well-documented that there is no true "maximum" dose of vasopressor medications, further blood pressure support as doses escalate to very high levels tends to be limited.  As such, debate has raged in Critical Care as to when is the "right" time to start a second vasoactive medication.  The VASST trial (Russell et al, NEJM, 2008) is considered to be the landmark trial in this area, and found a trend towards improvement with early addition of vasopressin to norepinephrine, but no statistically significant difference, and may have been underpowered.  

Partly as a result of VASST, the pendulum has tended to swing towards maximizing a single vasoactive before adding a second over the past decade.  The relatively high cost of vasopressin in the US has also driven this for many institutions.  However, more recently a "multi-modal" approach, emphasizing an earlier move to second, or even third, vasoactive medication, is increasingly popular.  Although cost is often prohibitive for angiotensin-2 given controversial benefits, many now advocate for targeting adrenergic receptors (e.g. with norepinephrine or epinephrine), vasopressin receptors (e.g. with vasopressin or terlipressin) and the RAAS system (e.g. with angiotensin 2) simultaneously in patients with refractory shock.  A recent review by Wieruszewski and Khanna in Critical Care (see references) outlines this approach well. 

Bottom Line: When to add a second vasoactive medication (e.g. vasopressin) for patients with refractory shock after a first vasoactive is controversial and not known.  Current practice is trending towards earlier addition of a second (or third) agent, especially if targeting different receptors, but there is limited high-quality evidence to support this approach.  Many practicioners (including this author) still follow VASST and consider vasopressin once doses of around 5-15 micrograms/min (non-weight based) of norepinephrine are reached.

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How to set the correct PEEP remains one of the most controversial topics in critical care.  In fact, just on UMEM Pearls there are 55 hits when one searches for PEEP, including this relatively recent pearl on PEEP Titration.  

A recent Systematic Review and Network Meta-Analysis looked at existing trials on this issue.  They found that:

1) Higher PEEP strategies were associated with a mortality benefit compared to lower PEEP strategies

2) Lung Recruitment Maneuvers were associated with worse mortality in a dose (length of time of the maneuver) dependent fashion.

This fits with recent literature and trends in critical care and bolsters the feeling many intensivists are increasingly having that we may be under-utilizing PEEP in the average patient.  

Bottom Line: As an extremely broad generalization, we would probably benefit the average patient by favoring higher PEEP strategies, and avoiding lung recruitment maneuvers.  Do keep in mind that it is probably best to continue lower PEEP strategies in patient populations at high risk of negative effects of PEEP (e.g. COPD/asthma, right heart failure, volume depleted with hemodynamic instability, bronchopleural fistula) until these groups are specifically studied.

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