As hospital volumes increase and ED patient boarding becomes more commonplace, emergency physicians may find themselves managing critically ill patients beyond the initial resuscitation.

The benefit of glucocorticoids in critically ill patients with septic shock has remained a topic of controversy for decades due to conflicting studies, including the 2002 Annane trial and the 2008 CORTICUS trial, which had opposing results when it came to the mortality benefit of steroids.

The results of the eagerly-awaited ADRENAL trial, a multicenter randomized controlled trial investigating the benefit of steroids in septic shock, were released earlier this month:

• 3658 patients from 69 different medical and surgical ICUs
• Adults with septic shock requiring mechanical ventilation (including noninvasive) and vasopressors/inotropes for at least 4 hours
• Continuous infusion hydrocortisone 200mg/day vs placebo for 7 days or until ICU discharge, if shorter
• No mortality benefit at 90 days (primary outcome) or at 28 days (secondary outcome)
• Other secondary outcomes:
  • Hydrocortisone group = Shorter ICU LOS, shorter duration of shock, shorter duration of initial mechanical ventilation, fewer # of patients receiving a blood transfusion
  • No difference in: mortality at 28 days, hospital LOS, recurrence of shock, total vent-free days, mean volume of blood transfused in patients receiving blood products, use of renal replacement therapy, development of new bacteremia/fungemia

Take Home Points:

1. Administration of standard daily dose hydrocortisone by infusion does not seem to affect mortality in septic shock.

2. Emergency providers should continue to consider stress-dose steroids in patients with shock and a high risk of adrenal insufficiency (e.g., chronic steroid therapy, genetic disorders, infectious adrenalitis, etc).  

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Septic Cardiomyopathy

• Cardiac dysfunction is common in patients with sepsis.
• Though mulitiple definitions exist, sepsis cardiomyopathy (SCM) is generally defined as an "acute syndrome of cardiac dysfunction that is unrelated to ischemia in patients with sepsis".
• Depending on the study, the incidence of SCM ranges anwywhere from 7% to 70%.
• Risk factors for SCM include:
  • Male
  • Younger age
  • High lactate at admission
  • History of heart failure
• The best approach to treating patients with SCM is to maximize your treatment of sepsis.
• Dobutamine is no longer routinely recommended for SCM based solely on measurements of ScvO2.

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Although the data is limited, current published rates of in-hospital, non-operating room peri-intubation cardiac arrest (PICA) range from 2 to 6%.^1,2,3

Several risk factors associated with PICA have been identified and include:

• Preintubation hemodynamic instability (shock index ≥ 1 or systolic blood pressure < 90mmHg)^1,2,3
• Elevated Body Mass Index (and increased risk with every 10kg body weight)¹
• Use of succinylcholine as paralytic³
• Intubation occurring within one hour of nursing shift change³

Other common findings:

• Most PICA occurs within 10 minutes of rapid sequence induction (RSI)^1,2
• PEA is the initial recorded rhythm 80-100% of the time.^1,2,3
• Even if ROSC obtained, PICA is associated with higher rates of in-hospital mortality compared to patients requiring emergent intubation who do not experience cardiac arrest.^1,2,3

Bottom Line:  Endotracheal intubation is one of the riskiest procedures we regularly perform as emergency physicians.

• Resuscitate hypotensive patients prior to or concomitantly with RSI and/or have a vasopressor at the ready in patients with higher risk of cardiovascular collapse.
• Consider use of vecuronium or rocuronium, rather than succinylcholine, in patients who require a paralytic for intubation but are at higher risk of hyperkalemia or have an unknown history. 

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Sedating The Critically Ill Patient

• Sedating critically ill ED patients can be challenging.
• Excessive sedation is associated with a prolonged duration of mechanical ventilation, ICU LOS, and may increase mortality.
• Important pearls to consider when managing these patients include:
  • Prioritize pain management first - may reduce the need for sedative medications
  • When possible, target a calm and interactive patient shortly after intubation - consider adding a atypical antipyschotic with propofol or dexmedetomodine
  • Use a validated tool (i.e., RASS) to dose opioids and sedative medications
  • Avoid continuous infusions of benzodiazepines

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Severe acute respiratory failure among patients with PCP pneumonia, especially among those newly diagnosed with AIDS, remains a disease of high morbidity and mortality. Among those requiring mechanical ventilator support, the mortality rate has been reported between 50-70%.

According to ELSO guidelines, pharmacologic immunosuppression (specifically neurtrophil <400/mL) is a relative contraindication. Furthermore, a status predicting poor outcome despite ECMO should also be considered a relative contraindication.

That said, there are several case reports now of successful use of ECMO in AIDS patients, particularly those suffering with PCP pneumonia.

In a case report and literature review published in BMJ in Aug 2017, 11 cases of ECMO (including 1 VA) in AIDS patients were described.

• 7 survived to hospital discharge (including 1 VA)
• 2 survived to decannulation, but ultimately died in hospital
• 2 died on ECMO
• Length of ECMO runs in survivors varied between 4 days (VA) to 31 days

Bottom Line: HIV/AIDS is not an absolute contraindication to VV ECMO therapy in ARDS and may be particularly useful in the treatment of severe PCP pneumonia. Initiation of ECMO in this patient population should be considered on an individual case by case basis. 

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Background:

We are all familiar with the Surviving Sepsis Campaign recommendation (& CMS core measure) for an initial 30ml/kg bolus of IV crystalloid within the first 3 hours for our patients with septic shock. There is minimal data, however, on how much IVF we should be giving our patients with BMIs ≥30.

A recent study in obese patients with septic shock retrospectively stratified the total fluids administered at 3 hours into 3 different weight categories, to categorize patients as having received 30mL per kg of ___ body weight, whether actual (ABW), adjusted (AjdBW), or ideal (IBW**).

AdjBW = (ABW – IBW) *40% + IBW

They found:

• Most patients received fluids based on actual body weight, BUT
• Patients at highest BMIs received ABW fluids less often
• 30ml/kg dosing according to adjusted body weight was associated with improved mortality compared to IVF per actual or ideal body weight.

Bottom Line:

• If the 30ml/kg IVF bolus seems clinically appropriate for your obese patient, consider administering according to Adjusted Body Weight first.
• As always, reevaluate your septic shock patients frequently to determine if additional fluids are necessary, and go to vasopressors early if they are not fluid responsive.

**IBW calculated using Devine’s formula for men and women:

• Males:  IBW = 50 + 2.3*(# inches over 5 feet)
• Females: IBW = 45.5 + 2.3*(# inches over 5 feet)

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Mechanical Ventilation in Shock

• Emergency physicians and intensivists routinely resuscitate patients in shock.
• For patients who manifest signs of persistent shock (i.e., rising lactate), consider intubation and mechanical ventilation, even in the absence of acute respiratory failure.
• The respiratory muscles are avid consumers of oxygen.  In fact, up to 50% of available O2 can be used by the respiratory muscles to perform the work of breathing.
• Initiation of mechanical ventilation can reduce oxygen consumption and allow oxygen to be shunted to other vital organs.

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Should that patient be admitted to the floor? 

Several studies have evaluated factors associated with upgrade in admitted patients from the floor to an ICU within 24 or 48 hours. Elevated lactate, tachypnea, and "after-hours" admissions have been repeatedly identified as some of the risk factors for decompensation. 

Two recent studies tried again to identify predictors of eventual ICU requirement...

Best predictors of subsequent upgrade:

• Hypercapnia*
• Tachypnea (in sepsis patients)*
• Hypoxemia (in pneumonia patients)
• Nighttime admission
• Initial lactate ≥ 4

The most common reasons for upgrade:

1. Respiratory failure
2. Hemodynamic instability

Effect on mortality? 

Despite a more stable initial presentation, mortality of patients who decompensated on the floor (25%) matched that of patients initially admitted to the ICU.

*One of the studies noted that although respiratory rate was demonstrated to be the most important vital sign, it was missing in 42% of the study population, while PCO2 was only obtained in 39% of patients.

Bottom Line: 

• Make sure to physically reassess patients you've stabilized/improved in the ED with current vital signs (including an accurate respiratory rate!) before okaying their admission/transfer to the floor. 
• If you get a blood gas, make sure to pay attention to the PCO2 and address any abnormalities appropriately.

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Core Temp <32 degrees leads to impaired shivering and confers increased risk for malignant ventricular dysrhythmias. Core Temp <28 degrees substantially increases risk of cardiac arrest. 

If in cardiac arrest:

• VA ECMO. Rewarming rate ~6 degrees per hour.
• Cardio Pulmonary Bypass. Rewarming Rate ~9 degrees per hour.
• Consider transfer to center with ECMO or CPB capabilities
• Consider up to 3 defibrillation attempts for shockable rhythm
• Consider with holding epi until core temp >30 degrees and doubling interval between doses (q6-10 minutes) until core temp >35 (European Resuscitation Council recs – note this differs from AHA guidelines/recommendations)

If perfusing rhythm:

• Institute active external rewarming (warm environment, forced-air heating blankets, arctic sun, warm parenteral fluids). Rewarming Rate ~ 0.1-3.4 degrees per hour.
• Consider minimally invasive rewarming with TTM cooling/rewarming catheter (Alsius/Zoll) via femoral vessel. Rewarming Rate ~3.5 degrees per hour.
• Hemodialysis or CRRT can be considered if intravascular rewarming device unavailable. Rewarming rate 2-4 degrees per hour.
• Avoid IJ or SC central lines, rewarming catheters, and HD catheters -- myocardial irritation with wire/catheter may precipitate ventricular dysrhythmia.

Consider addition of more invasive rewarming techniques in those with hemodynamic/cadiac instability or without access to VA ECMO/CPB:

• Thoracic lavage. Rewarming rate ~ 3 degrees per hour
• Peritoneal lavage. Rewarming rate ~ 1-3 degrees per hour  
•  

Consider stopping resuscitation efforts if/when:

• K >12- suggests hypoxia before cooling, no reported survivors. Some recommend K of 10 as cutoff in adults.
• Rewarmed to 32 degrees and no signs of life.

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Improving CPR Performance

• High-quality CPR is the cornerstone of successfull resuscitation from cardiac arrest.
• In fact, high-quality CPR is considered the most important intervention for achieving ROSC and good neurologic recovery.
• Pearls for optimizing CPR performance include:
  • Use a team-focused approach
  • Avoid leaning and ensure complete recoil of the chest
  • Target a chest compression fraction of at least 60%
  • Use POCUS, but pay attention to the duration of hands-off time
  • Target ETCO2 of > 20 mm Hg

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Molecular Adsorbent Recirculating System (MARS) is an artificial liver support system colloquially known in the medical field as "dialysis for the liver."  

• Limited data, small studies
• Consistently shown to improve hemodynamics, toxin clearance, and hepatic homeostasis
• No consistent proven mortality benefit
• Only performed by limited number of US hospitals (including the University of Maryland)
• May depend on the acute liver failure subpopulation, but best use currently seems to be for severe acute liver failure due to a potentially reversible/recoverable cause (toxin ingestion, trauma, acute alcoholic hepatitis, etc) or as a bridge to transplant

Take-Home:

1. Consider MARS in your patient with severe acute liver failure due to potentially reversible/recoverable etiology

2. Know if and where MARS is offered near you

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Risk of Pneumocystis pneumonia  (PCP) increases with degree of immunosuppression. If clinical suspicion exists (CD4 <200 with cough, pulmonary infiltrates, hypoxic respiratory failure), it is reasonable to initiate empiric therapy. 

First line treatment is trimethoprim-sulfamethoxazole (TMP-SMX) orally or IV for 21 days.  IV pentamidine has equivalent efficacy to IV TMP-SMX but greater toxicity and is generally reserved for patients with severe PCP who cannot tolerate or are unresponsive to TMP-SMX.

Importantly, adjunctive corticosteroids have been shown to significantly improve outcomes (mortality, need for ICU admission, need for mechanical ventilation) in HIV-infected patients with moderate to severe PCP (defined by pO2 <70 mmHg on Room Air).

·      Ideally steroids should be started BEFORE (or at the same time as) Pneumocystis-specific treatment to prevent/mitigate the sharp deterioration in lung function that occurs in most patients after initiation of PCP treatment. This is thought to be secondary to the intense inflammatory response to lysis of Pneumocystis organisms, which can cause an ARDS-like picture.

·      Recommended dosing schedule: 40mg prednisone twice daily for 5 days,  then 40mg once daily for 5 days, followed by 20mg once daily for the remaining 11 days of treatment.

Bottom Line: In patients with moderate to severe PCP (pO2 <70 mmHg on RA), don’t forget to initiate adjunctive corticosteroids early (at the same time you initiate empiric therapy for PCP). 

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Post-Arrest Tidal Volume Setting

• Most patients with ROSC from out-of-hospital cardiac arrest undergo endotracheal intubation and mechanical ventilation.
• Optimal management of mechanical ventilation for the post-arrest patient is currently not well defined.
• A recent retrospective cohort study sought to determine if a lower tidal volume (Vt) was associated with improved neurocognitive outcome at hospital discharge.
• Of 256 patients included in the study, investigators found:
  • 38% were ventilated with Vt > 8 ml/kg predicted body weight
  • Lower Vt was significantly associated with favorable neurocognitive outcome, decreased duration of mechanical ventilation, and decreased ICU length of stay
• Take Home Pearl: Pay attention to Vt in the post-arrest patient.

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Negative-pressure pulmonary edema (NPPE) is a well-documented entity that occurs after a patient makes strong inspiratory effort against a blocked airway. The negative pressure causes hydrostatic edema that can be life-threatening if not recognized, but if treated quickly and appropriately, usually resolves after 24-48 hours. These patients may have any type of airway obstruction, whether due to edema secondary to infection or allergy, laryngospasm, or traumatic disruption of the airway, such as in attempted hangings.

Management: 

1.     Alleviate or bypass the airway obstruction.

·      Usually via intubation; may require a surgical airway

·      If obstruction in an intubated patient is due to biting on tube or dyssynchrony, add bite-block (if not already in place), sedation, and even paralysis if needed.

2.     Provide positive pressure ventilation and oxygen supplementation.

3.     Use low tidal volume ventilation.

4.     In severe hypoxemia without shock, add a diuretic agent and consider additional measures such as proning and even ECMO if the hypoxemia is refractory to standard therapy.  

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Background: Sedation and analgesia are key components for mechanically ventilated patients. While significant data exists regarding how to manage sedation and analgesia in the ICU setting, very little data exists on management in the ED.

Data: A prospective, single-center, observational study of mechanically-ventilated adult patients used linear regression to identify ED sedation practices and outcomes, with a focus on sedation characteristics using the Richmond Agitation-Sedation Scale (RASS).

Findings:

• 15% of intubated patients had no sedation or analgesia ordered
• 64% of intubated patients were documented as deeply-sedated (RASS -3 to -5)
• Deep sedation was not only associated with more ventilator days, but also increased mortality, with an adjusted OR of 0.77 (95% CI 0.54-0.94) favoring patients with lighter sedation.

Bottom line:  Avoid early deep sedation in your intubated patients as this may be directly associated with increased mortality. Instead, a goal RASS of 0 to -2 should be appropriate for most non-paralyzed, mechanically-ventilated ED patients, extrapoloating from ICU guidelines.

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Hyponatremic Encephalopathy

• Hyponatremic encephalopathy is a true emergency and due to hypoosmolar-induced cerebral edema.
• In contrast to the asymptomatic patient with hyponatremia, treatment of hyponatremic encephalopathy is determined by symptoms and not the duration of hyponatremia.
• Clinical manifestations include nausea, vomiting, headache, confusion, seizures, respiratory failure, and coma.
• Hypertonic saliine is the treatment of choice
  • Administer 2 ml/kg 3% hypertonic saline (100 ml in many cases)
  • This will typically raise serum sodium 2 mEq/L
  • In most cases, a 4-6 mEq/L rise will reverse neurologic symptoms

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Catastrophic Antiphospholipid Syndrome (CAPS):

A life-threatening “thrombotic storm” of multi-organ micro & macro thrombosis in patients with antiphospholipid syndrome (known or unknown).

Triggered circulating antibodies (usually by infection, but can be prompted by malignancy, pregnancy, and lupus itself) cause endothelial disruption and inflammation leading to prothrombotic state, commonly with SIRS response.

Mortality is high at an estimated 40%.

Confirm diagnosis with antiphospholipid antibody titers.

Treat ASAP with unfractionated heparin, corticosteroids, and Hematology consultation for plasma exchange and/or IVIG.

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--RV systolic function is negatively affected by high RV afterload

--High mean airway pressures on the ventilator (particularly in modes such as APRV [airway pressure release ventilation]) can induce RV dysfunction

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Improving Resuscitation Performance

• Resuscitating the critically ill patient can often be quite stressful.
• Stress has been shown to decrease the quality and effectiveness of decisions, decrease the amount of information a person can process, and lead to short-term memory deficits.
• Recently, there has been emphasis on the use of performance-enhancing psychological skills (PEPS) to allow providers to think clearly, maintain situational awareness, recall important information, and perform skills efficiently.
• A recent article highlights 4 key elements of an EM model for PEPS that can be used to improve performance in resuscitations.
  • Breathe - consider tactical breathing
  • Talk - positive instructional or motivational self-talk
  • See - visualize the steps of a procedure before actually performing it
  • Focus - use a trigger word as a prompt to shift attention to a prioritized task

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When surveyed, half of general medicine patients interviewed stated that they would prefer to have a loved one present if they were to develop cardiac arrest and require CPR. So far, studies have demonstrated that…

Allowing family presence during CPR is associated with the following benefits to family members:

• Decreased rates of PTSD-related symptoms
• Decreased scores on anxiety and depression scales
• Decreased incidence of complicated grief
• Decreased incidence of family member regret (at having been present vs absent during CPR)

And is NOT associated with a difference in:

• Survival rate
• Duration of resuscitation efforts
• Type or dose of administered medications
• Number of shocks delivered
• Emotional stress level of medical providers
• Occurrence of medicolegal conflict

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