Despite ongoing research and efforts to improve our care of patients with ARDS, it remains an entity with high morbidity and mortality. Early recognition of the disease process and appropriate management by emergency physicians can have profound effects on the patient's course, especially in centers where ICU boarding continues to be an issue.

Recognition of ARDS (Berlin criteria)

• Acute in onset
• Bilateral infiltrates on chest imaging not due to cardiac failure/volume overload
• PaO2 : FiO2 < 300 despite PEEP of at least 5cmH2O 
• This is the standard ED patient who gets intubated with multifocal pneumonia and has continued hypoxemia

*An ABG should be obtained in the ED if physicians are unable to wean down FiO2 from high settings, if oxygenation by pulse ox is marginal, or if the patient is in a shock state.

Tenets of ARDS Management:

• Low tidal volume ventilation (6-8ml/kg ideal body weight*)
• Maintain plateau pressures (Pplat) < 30 cmH2O
• Driving pressure (Pplat – PEEP) < 15 cmH2O
• Goal PaO2 > 55-60 
• Permissive hypercapnia to pH >7.2

*IBW Males = 50 + 2.3 x [Height (in) - 60]   /  IBW Females = 45.5 + 2.3 x [Height (in) - 60]

Strategies for Refractory Hypoxemia in the ED:  You can't prone the patient, but what else can you do? 

1. Escalate PEEP in stepwise fashion

• ex: 2cmH20 every 10 minutes
• can use ARDSnet PEEP/FiO2 table as guide

2. Recruitment maneuvers

• "20 of PEEP for 20 seconds" or "30 for 30"
• if patient is "PEEP responsive," leave PEEP on a higher setting than when you started (ex: 10 instead of 5, 16 instead of 10)
• Risk of barotrauma with higher PEEPs and hypotension in underresuscitated or hemodynamically unstable patients due to decreased venous return

3. Appropriate sedation and neuromuscular blockade

• promotes patient synchrony with lung protective settings
• can result in improved oxygenation by itself

4. Inhaled pulmonary vasodilators (inhaled prostaglandins, nitric oxide) if known or suspected right heart failure or pulmonary hypertension

Bottom Line: Emergency physicians are the first line of defense against ARDS. Early recognition of the disease process and appropriate management is important to improve outcomes AND to help ICU physicians triage which patients need to be emergently proned or even who should potentially be referred for ECMO. 

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Does This Patient Have Pericardial Tamponade?

• Echocardiography is critical for the identification of a pericardial effusion and rapid diagnosis of pericardial tamponade.
• Common echocardiography findings that suggest tamponade include diastolic right ventricular collapse, systolic right atrial collapse, a plethoric IVC with minimal respiratory variation, and potentially exaggerated respiratory cycle changes in mitral and triscupid inflow velocities.
• Of these, systolic right atrial collapse is the earliest echocardiographic sign of tamponade, with a sensitivity ranging from 50% to 100%.
• Of the 4 standard echo views, systolic right atrial collapse can best be viewed in the apical 4-chamber and subxiphoid views.

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Neutropenic enterocolitis can occur in immunosuppressed patients, classically those being treated for malignancy (hematologic much more commonly than solid tumor). When involving the cecum specifically, it is known as "typhlitis."

It should be considered in any febrile neutropenic patients with abdominal pain or other symptoms of GI discomfort (diarrhea, vomiting, lower GI bleeding), and can be confirmed with CT imaging.

A recent study found that invasive fungal disease, most often candidemia, occurred in 20% of febrile neutropenic patients with CT-confirmed enteritis, a rate that increased to 30% if the patient was in septic shock.

Take Home: 

1. Have a lower threshold for abdominal CT imaging in your patients with febrile neutropenia and abdominal pain/GI symptoms, especially if they are critically ill.

2. Consider addition of IV antifungal therapy if they are hemodynamically unstable with enterocolitis on CT.

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Management of Acute Variceal Bleeding

• Patients with an acute UGIB secondary to esophageal or gastric varices frequently present in extremis.
• The initial resuscitation of patients with a variceal bleed should focus on the administration of antibiotics, packed red blood cells (PRBC), vasoactive agents, and emergent endoscopy.
• Antibiotics have been shown to reduce recurrent bleeding and mortality. A third-generation cephalosporin (e.g., ceftriaxone) is commonly recommended as the initial antibiotic of choice.
• Utilize a restrictive PRBC transfusion strategy to target a Hb between 7 to 8 g/dL.
• Vasoactive agents (e.g., octreotide) reduce portal pressure through splanchnic vasoconstriction and have been shown to reduce acute bleeding and the need for transfusion.

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Historically, there has been very limited data regarding the epidemiology of OHCA in pregnant females. Two recently-published studies tried to shed some light on the issue.

Both Maurin et al.¹ and Lipowicz et al.² looked at all-cause out-of-hospital maternal cardiac arrest (MCA) data in terms of numbers and management, in Paris and Toronto respectively, from 2009/2010 to 2014. Collectively, they found: 

• MCA was relatively rare: 0.8 MCA per 1000 OHCA (Maurin) and 1.71 MCA per 100,000 pregnant females (Lipowicz)
• Low incidence of bystander CPR in witnessed MCA (33% and 0%)
• Adherence to PMCS guidelines was poor 
• Maternal survival was lower than what has been previously quoted for in-hospital CA: 12.5 and 16.7% compared to 40-50%^3,4

A few reminders from the 2015 AHA guidelines for the management of cardiac arrest in pregnancy: 

• Hand location for chest compressions should be in the center of the chest as for nonpregnant patients (previous recommendations had been to shift upward to accommodate for the gravid uterus but there is no data to support this).

• Chest compressions should be performed with the patient supine, using manual lateral uterine displacement for aortocaval decompression. Left lateral tilt position is no longer recommended due to poorer quality of cardiac compressions, the lack of full aortocaval decompression, and further complication of other procedures such as airway management.

• IV or IO access should be obtained above the diaphragm, to ensure no interference to flow to the heart by the gravid uterus.

• Rate and depth of chest compressions, ACLS drugs and doses, and defibrillation all remain the same as in nonpregnant OHCA patients.
  • NB: As opposed to nonpregnant patients periarrest, oxygen saturation in the pregnant female should be maintained at 95% or greater, or PaO2 > 70mmHg, to ensure appropriate oxygen delivery to the fetus. The goal PCO2 is ~28-32 mmHg, to facilitate fetal CO2 removal.⁶  

• If advanced airway is pursued, the most experienced provider should perform intubation due to the higher intrinsic difficulties, more rapid decompensation, and propensity for airway trauma and bleeding in the pregnant female.

• Perimortem c-section should occur within the first 5 minutes of cardiac arrest / arrival to the ED in ongoing arrest. 

Bottom Line: Although maternal cardiac arrest is relatively rare, survival in OHCA is lower than perhaps previously thought. Areas to improve include public education on the importance of bystander CPR in pregnant females, and appropriate physician adherence to PMCS recommendations, with decreased on-scene time by EMS in order to decrease time to PMCS. 

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Respiratory Complications of ICIs

• Acute respiratory failure (ARF) is the leading cause of ICU admission for immunocompromised patients.
• While infectious etiologies remain the most common cause of ARF in these patients, there is an increasing prevalence of non-infectious, treatment-related causes.
• Immune check-point inhibitors (ICIs) are now used with increasing frequency, and can cause severe pulmonary toxicity in approximately 6% of patients.
• Pearls for ICI pulmonary toxicity include:
  • Acute pneumonitis is the most common presentation
  • Median time of onset of approximately 4 months after treatment initiation
  • Symptoms include dry cough, hypoxemia, and infiltrates not c/w CHF, infection, or progression of malignancy
  • Treatment is to DC the ICI and initiate steroids

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--Late awakening (>48h after sedation held) was common (78/402) in patients with cardiac arrest in prospective cohort study

--Poor prognostic signs of discontinuous (10-49% suppression) EEG and absent brain stem reflexes were independently associated with late awakening. Use of midazolam also associated with late awakening

--Late awakeners had good functional outcome when compared to early awakeners

DON'T NEUROPROGNOSTIC EARLY (OR IN ED)!

And traditional poor prognostic signs may not be as poor as previously thought!

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Critically Ill Renal Transplant Patients

• Renal transplant patients are at high risk of critical illness from a variety of etiologies.
• Sepsis is the most common reason for critical illness and ICU admission.  
• Due to their immunosuppression, renal transplant patients are at risk of a multitude of infections.
• Notwithstanding, acute bacterial pyelonephritis of the transplant is the most frequent cuase of sepsis, followed by bacterial pneumonia.
• Be sure to consider these two etiologies when faced with a critically ill, septic renal transplant patient.

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Dyspnea in the Intubated Patient

• Dyspnea may occur in up to 50% of intubated patients and has been associated with prolonged mechanical ventilation.
• A number of assessment tools are available to detect dyspnea in the intubated patient.
• Regardless of the tool used, once dyspnea is diagnosed, consider the following;
  • When possible, reduce nonrespiratory stimuli of the respiratory drive (i.e., fever, acidosis, anemia)
  • Minimize respiratory impedance (i.e., bronchodilators, thoracentesis for pleural effusion)
  • Optimize ventilator settings (i.e., change modes if applicable, increase inspiratory flow, increase PEEP)
  • Pharmacologic treatment (i.e., opioids, benzodiazepines)

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The European Society of Intensive Care Medicine (ESICM) recently released a review with recommendations from an expert panel for the use of IV fluids in the resuscitation of patients with acute circulatory dysfunction, especially in settings where invasive monitoring methods and ultrasound may not be available.

Points made by the panel include: 

• Circulatory dysfunction should be identified not only by HR and BP, but by other indicators of poor perfusion: altered mentation, decreased urine output, and skin abnormalities (poor skin turgor, mottling, delayed capillary refill)

• The absence of arterial hypotension does not preclude hypovolemia

• The lack of an increase in MAP (especially in patients with decreased vascular tone) does not exclude positive response to IVF

• The purpose of IVF administration is to improve tissue perfusion by increasing cardiac output

• Fluid "loading" as the rapid administration of large volumes of fluid to treat overt hypovolemia, while a fluid "challenge" is a test of fluid responsiveness

• In elderly patients or those with arteriosclerosis or chronic arterial hypertension, a low pulse pressure (e.g. less than 40 mmHg) indicates that stroke volume is low. PP = SBP - DBP

Recommendations from the panel include:

• The early measurement of lactate to incorporate in the assessment of perfusion

• The use of crystalloids as initial resuscitation fluid (unless blood products are indicated)

• When overt hypovolemia is unclear, the use of a fluid challenge of 150-350mL IVF within 15 minutes to help assess fluid responsiveness

• Avoidance of using jugular venous distension alone as a guide for resuscitation

• Avoidance of using acute urine output response alone as a guide for resuscitation, as renal response to fluids can be delayed

• A recommendation against using CVP as a target for resuscitation; if CVP is being measured, a rapid increase with IVF should suggest poor fluid tolerance

• Individualizing fluid resuscitation to the patient's current presentation, underlying comorbidities, and response to fluids

Bottom Line: Utilize all the information you have about your patient to determine whether or not they require IVF, and reevaluate their physical and biochemical (lactate) response to fluids to ensure appropriate IVF administration and avoid volume overload. 

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Noninvasive Ventilation in De-Novo Respiratory Failure

• Noninvasive ventilation (NIV) is a primary therapy for patients with acute hypercapnic respiratory failure, especially those with an acute COPD exacerbation.
• Notwithstanding its benefits in COPD and acute cardiogenic pulmonary edema, NIV should be used cautiously in patients with "de-novo" respiratory failure.
• Many patients with de-novo respiratory failure will meet criteria for ARDS and have a high rate of intubation (30% - 60%).
• The use of NIV with delayed intubation in this patient population has been associated with increased mortality. 

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Hyperoxia has been repeatedly demonstrated to be detrimental in a variety of patients, including those with myocardial infarction, cardiac arrest, stroke, traumatic brain injury, and requiring mechanical ventilation,^1-4 and the data that hyperoxia is harmful continues to mount:

• Systematic review and meta-analysis of 16,000 patients admitted to hospital with sepsis, trauma, MI, stroke, emergency surgery, cardiac arrest: liberal oxygenation strategy (supplemental O2 for average SpO2 96%, range 94-100%) associated with increased in-hospital and 30-day mortality compared to conservative strategy.⁵

• ED patients requiring mechanical ventilation admitted to ICU: hyperoxia defined as PaO@ >120mmHg. Patients with hyperoxia in the ED had higher mortality than not only normoxic but hypoxic patients (30% v 19% v 13% respectively), and longer vent days and ICU/hospital LOS.⁶

• ICU patients, majority respiratory failure, 60% requiring mechanical ventilation; hyperoxia defined as PaO2 >100mmHg. Just ONE episode of hyperoxia an independent risk factor for ICU mortality (OR 3.80, 95% CI 1.08-16.01, p=0.047).⁷

Bottom Line: Avoid hyperoxia in your ED patients, both relatively stable and critically ill. Remove or turn down supplemental O2 added by well-meaning pre-hospital providers and nurses, and wean down ventilator settings (often FiO2). A target SpO2 of >92% (>88% in COPD patients) or PaO2 >55-60 is reasonable in the majority of patients.⁸

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A few (out of 10) tips for the care of sick patients with liver failure:

• Use of albumin is indicated to improve outcomes in spontaneous bacterial peritonitis (SBP), large-volume paracentesis, and hepatorenal syndrome (HRS).

• Norepinephrine remains the vasopressor of choice for nonhemorrhagic shock. Use vasopressin or terlipressin (outside the U.S.) in AKI due to HRS to maintain a target MAP and for splanchnic vasoconstriction.

• INR does not correctly reflect coagulation performance. Platelet count and fibrinogen are the best predictors of bleeding, and thromboelastography (via TEG/ROTEM) can reduce blood products administered for hemorrhage without affecting mortality.

• If a nasogastric tube is indicated (administration of lactulose, decompression of SBO, etcetera), presence of [non-recently banded] esophageal varices is not a contraindication.

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Identifying Critically Ill Cancer Patients in the ED

• Immunosuppressed patients with malignancy are at high risk of complications and rapid decompensation.
• Select pearls in identifying ED patients with cancer that are at high risk of critical illness include:
  • Patients with profound neutropenia (< 100/mm³) are at high risk for fungal infections (i.e., aspergillosis)
  • Hypoxemia that requires oxygen is a predictor of later ICU admission.
  • Patients with bilateral infiltrates on CXR are at high risk of decompensation. Consider ICU admission.
  • Patients with promyelocytic leukemias are at high risk of DIC. Patients with this complication should be admitted to the ICU.

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The most recent AHA guidelines for goal blood pressure after return of spontaneous circulation (ROSC) post-cardiac arrest recommend a definite mean arterial pressure (MAP) goal of > 65 mmHg.¹ There is no definitive data to recommend a higher specific goal, but there is some evidence to indicate that maintaining higher MAPs may be associated with better neurologic outcomes.²

A recently published prospective, observational, multicenter cohort study looked at neurologic outcomes corresponding to different MAPs maintained in the initial 6 hours post-cardiac arrest.³

Findings: 

1. Compared to lower blood pressures (MAPs 70-90 mmHg), the cohort with MAPs > 90 mmHg had:

• a higher rate of good neurologic function at hospital discharge (42 vs.15%, p < 0.001)
• a higher rate of survival to 72 hours (86 vs. 74%, p=0.01) and hospital discharge (57 vs 28%, p < 0.001)

2. The association between MAP > 90 mmHg and good neurologic outcome was stronger among patients with a previous diagnosis of hypertension, and persisted regardless of initial rhythm, use of vasopressors, or whether the cardiac arrest occured in or out of hospital.

3. There was a dose-response increase in probability of good neurologic outcome among all MAP ranges above 90 mmHg, with MAP >110 mmHg having the strongest association with good neurologic outcome at hospital discharge.

Note: The results of a separate trial, the Neuroprotect post-CA trial, comparing MAPs 85-100 mmHg to the currently recommended MAP goal of >65 mmHg, are pending.⁴

Bottom Line: As per current AHA guidelines, actively avoid hypotension, and consider use of vasopressor if needed to maintain MAPs > 90 mmHg in your comatose patients post-cardiac arrest, especially those with a preexisting diagnosis of hypertension.

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We know that high flow nasal cannula is an option in the management of acute hypoxic respiratory failure without hypercapnea. A newer iteration of high flow, "high velocity nasal insufflation" (HVNI), may be up-and-coming.

According to its makers (Vapotherm), it is reported to work mainly by using smaller bore nasal cannulae that deliver the same flows at higher velocities, thereby more rapidly and repeatedly clearing dead space, facilitating gas exchange and potentially offering ventilatory support. 

In an industry-sponsored non-inferiority study published earlier this year:

• 204 adult patients in 5 EDs
• Any acute respiratory failure deemed by the treating physician to require non-invasive positive pressure ventilation (NPPV)
• Patients randomized to either NPPV (bilevel positive airway pressure) or HVNI
• Rate of HVNI treatment failure (26%) and intubation @ 72 hours (7%) fell within predefined noninferiority margins
• Rates of PCO2 clearance were similar between HVNI and NPPV groups
• The study was not powered to detect differences between different etiologies for respiratory failure
• Authors concluded that HVNI is noninferior to NPPV for all-comer respiratory failure.

Bottom Line: 

The availability of a nasal cannula that helps with CO2 clearance would be great, and an option for patients who can't tolerate the face-mask of NPPV would be even better.

HVNI requires more investigation with better studies and external validation before it can really be considered noninferior to NPPV, but it certainly is interesting. 

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Sedating Mechanically Ventilated Patients

• Providing appropriate analgesia and sedation to mechanically ventilated patients is of paramount importance.
• In a recent systematic review and meta-analysis, Stephens et al. assessed the impact of deep sedation within the first 48 hours of initiation of mechanical ventilation.
• In 9 studies that included over 4,500 patients, deep sedation within the first 48 hours of initiation of mechanical ventilation was associated with increased mortality, increased ICU LOS, and increased frequency of delirium.
• Take Home Points
  • When possible, target lighter levels of sedation in mechanically ventiilated patients.
  • Though no universally accepted definition of light sedation exists, most studies use a RASS of -2 to +1

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The recently published BICAR-ICU study looked at the use of bicarb in critically ill patients with severe metabolic acidemia...

• Multicenter, open-label, RCT, 26 French ICUs
• Adult patients with pH < 7.2 not secondary to hypercapnia, serum bicarb < 20 not due to bicarb wasting process 
• SOFA score > 4 or lactate > 2
• No bicarb versus 4.2% sodium bicarb infusion titrated to pH >7.3
• Primary outcome: Composite measure of 28-mortality and presence of any organ failure at 7 days post-randomization
• Secondary outcomes: Need for/length of life support measures (renal-replacement, vasopressors, mechanical ventilation), SOFA score after enrollment, electrolyte effects, occurrence of ICU-acquired infections, and ICU length of stay
• Major findings:
  • No difference in primary outcome overall
  • No difference in pressor-free days, days off RRT, dialysis dependence at ICU discharge, ICU LOS
  • Bicarb group had less need for RRT during ICU stay (35 vs 52%, p=0.0009)
  • In patients with AKI and AKIN score 2-3*, the bicarbonate group had a decrease in both 28-day mortality (46 vs 63%, p=0.0166) and presence of any organ failure at day 7 (66 vs 82%, p=0.0142)
• Limitations:
  • Unblinded
  • A quarter of the control group actually received bicarb
  • No data regarding vent settings, ABGs to r/o ventilation effects on pH
  • 4.2% is not a standard concentration of bicarb used in the U.S.

Bottom Line: 

Consider administration of sodium bicarbonate for your critically ill ED patients with severe metabolic acidosis and AKI, especially if acidosis &/or renal function is not improved with usual initial measures (such as IVF, etc).

*Acute Kidney Injury Network Staging Criteria

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Does Lactated Ringer's Raise Serum Lactate?

• Intravenous fluid administration is a cornerstone of resuscitation and the treatment of many critically ill ED patients.
• Recent publications have suggested that balanced crystalloid solutions may be better than 0.9% normal saline (NS) for select conditions.
• Lactated Ringer's (LR) is a common balanced crystalloid solution often used for fluid resuscitation in critically ill patients.
• AS LR contains approximately 28 mmol/L of sodium lactate, the question of whether LR elevates serum lacate is frequently asked.
• In a recent small, randomized, double-blind, controlled trial, investigators randomized healthy volunteers to receive 30 ml/kg of either 0.9% NS or LR. The authors report no statistical difference in the mean serum lactate when comparing LR to 0.9% NS.

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Critical Post-Arrest Interventions

• Critical interventions to optimize neurologic outcome in the post-cardiac arrest patient include optimizing hemodynamics, preventing lung injury, maintaining normal O2 and CO2 tensions, targeted temperature management, and treating the underlying cause of the arrest.
• Current guidelines recommend the following:
  • Target MAP > 70 mm Hg with IVFs, vasopressors, and inotropes.
  • Use a low tidal volume strategy of 6 to 8 ml/kg predicted body weight.
  • Decrease FiO2 to maintain SpO2 94% to 97%.
  • Adjust RR to maintain PaCO2 35 to 45 mm Hg
  • Initiate TTM with the goal temperature between 32 to 36^o C

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