• Necrotizing enterocolitis with predilection for cecum.
• Occurs in the immunosuppressed, especially when neutropenic (<500 PMNs)
• Typically a polymicrobial infection; gram positive cocci, gram negative rods, anaerobes, and/or fungal. 
• Classically, right lower quadrant pain but can present with diffuse abdominal pain and peritoneal signs.
• CT scan with IV and PO contrast is diagnostic (see below)
• Treatment:
  • Culture and begin broad spectrum antibiotics (cover anaerobes) and antifungals (if suspected) 
  • Aggressive resuscitation
  • Surgical consult for GI perforation or clinical deterioration
• High mortality (40-50%)

TIP: Suspect when abdominal pain presents 10-14 after chemotherapy (when PMNs are lowest).

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Acute Liver Failure (ALF)

• ALF is defined as sudden and severe liver failure in a patient without preexisting liver disease.
• The clinical presentation can include altered mental status, coagulopathy, MODS, & cerebral edema.
• In the US, the most common cause of ALF is drug-induced (e.g. acetaminophen).
• Important components of the ED management of patients with ALF include:
  • Monitoring and correcting hypoglycemia (may need infusion of D20)
  • Monitoring and maintaining a normal sodium concentration
  • Volume resuscitation with isotonic crystalloids or colloids
  • Prophylactic administration of broad spectrum antibiotics (given high incidence of sepsis)
  • Consideration for continuous veno-venous hemodiafiltration (CVVHD) for severe elevations in ammonia and acidosis (even if renal function is normal)
  • Transfer to center capable of liver transplantation

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Although oral metronidazole is indicated for mild to moderate Clostridium difficile associated diarrhea, oral vancomycin should be considered first-line therapy in critically-ill patients with moderate to severe disease. Vancomycin dosing should begin at 125mg PO q6 and increased to 250mg q6 if poor enteral absorption exists. Consider adding metronidazole IV if either reduced enteral absorption or severe disease exists. 

Recently, fidaxomicin has been shown to be non-inferior to oral vancomycin in the treatment of mild to moderate C. difficile. While promising, the study population was not critically-ill and extrapolation should be avoided.

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Gastrointestinal Changes of Obesity that Complicate Critical Illness

• Obesity predisposes patients to several gastrointestinal abnormalities that can cause, or complicate, critical illness.
• Important abnormalities to keep in mind when managing a critically ill obese patient include:
  • Increased intra-abdominal pressure which predisposes to abdominal compartment syndrome
  • Increased incidence of nonalcoholic fatty liver disease which may lead to prolonged drug metabolism
  • Increased incidence of cholelithiasis which may result in pancreatitis or cholangitis

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A mortality benefit from combination antimicrobial therapy has not been clearly demonstrated in sepsis. However, when only the most severely-ill patients (i.e., septic shock) are considered in subgroup analysis, there appears to be a mortality benefit to using two antimicrobials against a suspected organism.

Combination antimicrobial therapy may reduce mortality through three mechanisms.

1. Increased probability that the causative organism will respond to at least one drug. 
2. Preventing emergence of antimicrobial resistance.
3. Two antimicrobials may act synergistically.

Always obtain appropriate cultures before initiating therapy. Although identification and susceptibility of the organism may take some time, eventually narrowing antimicrobial therapy to monotherapy in the ICU is still recommended. 

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Combination Antimicrobial Therapy for Gram (+) Bacteremia

• Bacteremia is a major cause of morbidity and mortality in the critically ill patient.
• S.aureus remains a common isolate in patients with either hospital-acquired or community-acquired bacteremia.
• In cases of suspected endocarditis due to S.aureus, traditional teaching has been to give an aminoglycoside (i.e. gentamicin) in combination with vancomycin or an antistaphylococcal penicillin.
• Importantly, there is no strong evidence to support this combination in patients with suspected S.aureus bacteremia.
• Furthermore, patients receiving the aminoglycoside combination have higher rates of renal impairment without any added clinical benefit.

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Vancomycin is often started empirically for gram-positive and MRSA coverage. Although effective and generally well-tolerated, emerging resistance and side-effect profiles limit its use in some patients. Two alternatives are Linezolid and Daptomycin.

Linezolid

• 600 mg IV every 12 hours
• No renal dosing
• Better lung penetration in pneumonia (compared to Vancomycin)
• Side effects: Serotonin Syndrome (w/ concurrent MAOIs), hypersensitivity reaction, and myelosuppresssion

Daptomycin

• 4 mg/kg IV once daily (skin/subcutaneous tissues infection), 6 mg/kg IV once daily (bacteremia or endocarditis), or 6-8mg/kg IV once daily (bacteremia with intravascular line)
• Renally dosed by altering administration frequency; no change in dose.
• NEVER use for pneumonia; pulmonary surfactant binds and inactivates drug.
• Side effects: Reversible rhabdomyolysis (requires weekly CPK levels)

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Emergency Medicine physicians are gaining experience with non-invasive ventilation (i.e., Bi-level ventilation and continuous positive-pressure ventilation) in managing respiratory distress and failure. Although NIV is commonly used across a variety of pathologies, the best data exists for use with COPD exacerbation and cardiogenic pulmonary edema (CHF, not an acute MI) 

Although other indications for NIV have been studied, the data is less robust (eg., smaller study size, weak control groups, etc.). If there are no contraindications, however, many experts still support a trial of NIV in the following populations:

• Asthma
• Severe community acquired pneumonia
• Acute lung injury / Acute Respiratory Distress Syndrome
• Chest trauma (lung contusion, rib fractures, flail chest,etc)
• Immunosuppression with acute respiratory failure
• Neuromuscular respiratory failure (eg., Myesthenia Gravis)
• Cystic Fibrosis
• Pneumocystis Jiroveci Pneumonia
• “Do not intubate” status

Failure to clinically improve during a NIV trial should prompt invasive mechanical ventilation.

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Aspiration Pneumonitis and Pneumonia

• Aspiration of low pH gastric fluid or food matter is common in critically ill patients and often underdiagnosed.
• Patients with aspiration initially develop a pneumonitis that, in some, can be complicated by bacterial pneumonia.  Up to 33% develop severe ALI/ARDS, with an associated 30% mortality rate.
• Aspiration pneumonitis presents with hypoxia and a CXR demonstrating infiltrates in the dependent portion of the lungs.  Often, the degree of respiratory distress is worse than the CXR appearance.
• Since it is challenging to differentiate aspiration pneumonia from aspiration pneumonitis, current recommendations suggest initiating empiric antibiotics with agents that have adequate Gram-negative coverage.  Routine coverage against anaerobic bacteria is not currently recommended, except in patients with severe periodontal disease and those with a lung abscess on CXR or CT.
• Despite the initial inflammatory response, steroids are not indicated for patients with aspiration.

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Many changes in pulmonary physiology occur during pregnancy. These changes are generally well tolerated but can become problematic when pathologic states arise.

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The Severely Hypoxemic ED Patient

• Most define hypoxemia as a P_aO₂ < 60 mm Hg.
• Perhaps a better definition of hypoxemia is a P_aO₂ that is associated with continued tissue hypoxia (rising lactate, low S_cvO₂), the need for vasopressor medications, or severe metabolic acidosis.
• For ED patients that remain hypoxemic despite increased F_iO₂ and high levels of PEEP, consider the following rescue therapies:
  • Recruitment maneuvers - brief periods of high PEEP (35-50 cm H₂O) or pressure-controlled breaths to reopen collapsed alveoli
  • High-frequency oscillatory ventilation - employs a high airway pressure to recruit closed alveolar segments
  • Prone positioning - believed to improve oxygenation through a redistribution of ventilation and perfusion
  • Extracorporeal membrane oxygenation

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Hemodynamic Monitoring in the Ventilated Patient

• Consider pulse pressure variation (PPV) as a method to monitor volume responsiveness in your mechanically ventilated ED patients.
• The theory behind PPV:
  • When a positive pressure breath is delivered via the ventilator, pleural pressure rises and causes a decrease in venous return, right heart filling, and right heart output.
  • Simultaneously, the positive pressure breath causes an increase in left heart filling and a decrease in left heart afterload.  This is reflected clinically as an increase in blood pressure.
  • Within a few beats, the decreased right heart output is transmitted to the left heart resulting in a decrease in blood pressure during expiration.
• Patients who are volume depleted can have significant differences in blood pressure between inspiration and expiration - i.e. a large variation in pulse pressure.
• PPV values > 12% have been shown to identify patients who are volume responsive.
• Importantly, PPV works best in vented patients who have no spontaneous respiratory effort, are in sinus rhythm, and receiving 8 ml/kg tidal volumes.

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Acute LV Dysfunction in the Critically Ill

• Approximately one-third of critically ill hospitalized patients develop acute LV dysfunction, most often due to a stress-induced cardiomyopathy.
• In these patients, up to 25% develop an acute dynamic LV outflow tract obstruction.
• Consider acute LV outflow tract obstruction in hypotensive patients with a new systolic ejection murmur in the left parasternal area.
• Aggressive IVFs is central to the management of these patients with LV outflow tract obstruction.

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The optimal hemoglobin concentration during critical illness is unknown. Although a liberal transfusion strategy (Hb 10-12 g/dL) was once believed to be beneficial for hemodynamics, evidence suggests targeting a conservative strategy (Hb 7-9 g/dL) does not increase mortality, while the unnecessary transfusion of blood products can cause harm (transfusion associated lung injury, infection, etc.) in the non-hemorrhaging patient. 

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Valproic Acid in Status Epilepticus

• In previous pearls, we have discussed the treatment of status epilepticus (SE) with first-line (benzodiazepines) and second-line agents (phenytoin/fosphenytoin).
• Refractory SE is defined as the failure to respond to both first- or second-line antiepileptic medications.
• Valproic acid is listed in many algorithms as a third-line agent for treating SE.
• Avoid valproic acid in refractory SE patients who have hepatic disease or dysfunction.
• Although rare, valproic acid can cause a fatal hepatotoxicity in these patients. 

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Dexmedetomidine for Sedation in Acute Neurologic Disease

• Critically Ill patients with acute neurologic disease are managed daily in the ED.
• Due to the need for frequent neurologic assessments, these patients can be challenging should they require sedation.
• Dexmedetomidine, a selective alpha-2 adrenergic receptor agonist, has emerged as an alternative to traditional sedatives (i.e. opioids and benzodiazepines).
• Dexmedetomidine provides sedation and anxiolysis, while producing little effect on level of arousal and cognitive function.  In essence, it reduces discomfort while permitting the patient to arouse for a neurologic examination.
   

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Posterior reversible encephalopathy syndrome (PRES) is a syndrome of visual loss, headache, altered mental status, and seizures, typically with severe hypertension. PRES usually occurs with hypertensive encephalopathy or ecclampsia, although cyclosporin and tacrolimus use have been implicated. 

PRES is due to a combination of endothelial damage, impaired auto-regulation and increased cerebral perfusion pressure. Classic CT and MRI findings are parietal-occipital, cerebellar, or brainstem cortical and subcortical edema. 

Early recognition and symptomatic treatment is key; IV anti-hypertensives (hypertensive encephalopathy), anti-epileptics (seizures), IV magnesium and emergent delivery (ecclampsia), and discontinuing offending medications (cyclosporin and tacrolimus).  

With treatment, partial to complete recovery is normal, although residual neurological and visual deficits may persist.

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Vancomycin Dosing in the Critically Ill Obese Patient

• Obesity related changes to drug metabolism and distribution can significantly impact the critically ill obese patient.
• Many meds can either be underdosed or overdosed depending on which body weight (ideal vs. actual) is used.
• With the increased incidence of MRSA infections, vancomycin is often included in the initial antibiotic selection for most critically ill ED patients.
• Importantly, vancomycin is one of the most studied antibiotics in obese patients.
• Recent guidelines recommend that an initial vancomycin dose of 25-30 mg/kg actual body weight be considered for any critically ill patient, with subsequent dosing dependent upon renal function and trough levels.

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