UMEM Educational Pearls - Critical Care

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) or DIHS (Drug-Induced Hypersensitivity Syndrome) is a potentially life-threatening adverse drug-reaction.

Incidence is 1/1,000 to 1/10,00 drug exposures. It occurs 2-6 weeks after the drug is first introduced, distinguishing it from other adverse drug-reactions which typically occur sooner.

The syndrome classically includes:

• Severe skin eruptions (typically morbilliform or erythrodermic eruptions)
• Hematologic abnormalities (eosinophilia or atypical lymphocytosis)
• Organ involvement; e.g., hepatic (most common), pneumonitis, renal failure, etc.
• Fevers
• Arthralgia
• Lymphadenopathy

The most commonly implicated drugs are anticonvulsants (e.g., carbamazepine, phenobarbital, and phenytoin), sulfonamides, and allopurinol. 

Recovery is typically complete after discontinuing the offending drug; systemic steroids may promote resolution of the illness.

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VV-ECMO for Refractory Hypoxemia

• In the absence of significant cardiac disease, patients with refractory hypoxic respiratory failure should be considered for venovenous extracorporeal membrane oxygenation (VV-ECMO).
• Though indications vary slightly among organizations, the Extracorporeal Life Support Organization states that ECMO is indicated when the P_aO₂/F_iO₂ is < 80 mm Hg on F_iO₂ > 90% or safe plateau pressures (< 30 cm H₂O) cannot be maintained.
• A few pearls when initiating VV-ECMO:
  • Fluids are often needed in the first few hours after initiation of ECMO
  • Reduce tidal volumes to maintain plateau pressures < 25 cm H₂O
  • Decrease F_iO₂ to maintain oxygen saturations > 88%
  • Use a hemoglobin threshold of 7-8 g/dL for blood transfusion

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Management of patients with severe traumatic brain injury (TBI) typically involves the use of invasive intra-parenchymal pressure monitors. Although use of these monitors is recommended by TBI management guidelines, good quality evidence of benefit is lacking.

A recently published study evaluated the outcomes of TBI patients using a management protocol incorporating either an intracranial pressure (ICP) monitor compared to use of the clinical exam PLUS serial neuroimaging; a total of 324 patients were prospectively randomized into either group.

The primary study outcome was a composite of survival, impaired consciousness, and functional status at both three and six months.

The results of the study did not show a significant difference in the:

• Primary outcome  
• Median length of ICU stay
• Distribution of serious adverse events

Bottom line: This study suggests that clinical exam PLUS serial neuroimaging may perform as well as invasive intra-parenchymal monitors for guiding therapy in TBI patients.

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Ultrasound-Guided Pericardiocentesis

• Though emergent pericardiocentesis is a relatively rare procedure in the ED, it is a critical intervention in patients with effusion and life-threatening instability/PEA arrest.
• Ultrasound-guided pericardiocentesis is preferred over the traditional "blind" approach, as it allows the provider to choose an optimal position and is associated with fewer complications.
• A few pearls when using ultrasound for emergent pericardiocentesis:
  • Consider placing an NGT for abdominal decompression.
  • Don't mistake the epicardial fat pad for an effusion; fat pads don't change size and usually move in concert with the ventricle.
  • The apical 4-chamber view tends to be the most common probe position, as the largest collection of fluid is usually around the apex.
  • If you are unsure about your needle location, inject 5-ml of agitated saline to confirm you are in the pericardial space.

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• Serum total tryptase measurements may be useful for confirmation of venom or drug induced anaphylaxis (not as useful for food induced)
• Can send serial tryptase levels at the time of presentation, 1-2 hours later, and at resolution
• This is NOT helpful for confirmation at the time of the episode, as it takes several hours to perform

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Managing Critically Ill Patients with AKI

• Acute kidney injury (AKI) occurs in almost 50% of hospitalized patients and is an independent risk factor for mortality. 
• Updated guidelines have recently been published on the management of patients with AKI.
• Pearls for the management of patients with, or at risk of, AKI include:
  • Optimize volume status and perfusion pressure
    • Crystalloids preferred over colloids
    • Consider vasopressors to maintain MAP > 65 mm Hg
  • Avoid nephrotoxic drugs
  • Control co-factors
    • Monitor intra-abdominal pressure
    • Avoid hyperglycemia - target glucose < 150 mg/dL

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A low-tidal volume (or protective) strategy of mechanical ventilation (i.e., tidal volume of 6-8cc/kg of ideal body weight) has previously been demonstrated to be beneficial in patients with acute respiratory distress syndrome (ARDS).

A meta-analysis was recently performed to determine whether this strategy of mechanical ventilation is also beneficial for patients without lung injury prior to initiation of mechanical ventilation.

Dr. Neto, et al. performed a meta-analysis of 20 studies (total of 2,822 mechanically ventilated patients) comparing a conventional ventilation strategy (average tidal volume was 10.6 cc/kg) to a protective ventilation strategy (average tidal volume was 6.4 cc/kg) of mechanical ventilation.

The authors concluded that patients ventilated with a protective lung-strategy had reductions in:

• Mortality
• Lung injury and ARDS
• Atelectasis
• Pulmonary infections          
• Length of hospital stay

Bottom-line: This meta-analysis supports the notion that a strategy of low-tidal volume ventilation may have benefits for patients without ARDS, however prospective studies are needed.

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Burn Patients and Antibiotic Dosing

• Burn patients have a number of abnormalities in the early postinjury phase that can significantly impact the efficacy of antimicrobial therapy.  These include hypovolemia, hypoalbuminemia, and increasing GFR.
• A few pearls when dosing select antibiotics in burn patients:
  • Aminoglycosides: in the absence of renal impairment, consider more frequent dosing to achieve adequate concentrations.
  • Beta-lactams: typical doses often don't reach effective concentrations; increase the dose, frequency of administration, or duration of infusion.
  • Vancomycin: the typical dose of 1 gm is usually ineffective; use a larger loading dose (15-20 mg/kg).
  • Linezolid: standard doses are usually ineffective; use a higher initial dose.

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Previous pearls have described the increasing evidence against colloid (e.g., hydroxyethyl starch) use during resuscitation. Now it appears that the crystalloid 0.9% normal saline (NS) may be under fire. 

The use of large volumes of NS has been associated with hyperchloremic metabolic acidosis and harm in animal studies. The risk of harm in humans, however, has been less clear. 

Bellomo et al. conducted a prospective observational study in which patients being resuscitated in the control group received NS at the clinicians' discretion; i.e., chloride-liberal strategy. The use of NS was restricted in the intervention group, where other less chloride containing fluids were used for resuscitation (e.g., Ringer's Lactate); i.e., a chloride-restrictive strategy. 

The authors found that when compared to patients in the chloride-liberal group, the chloride-restrictive group had significantly less rise in baseline creatinine, less overall AKI, and a reduced need for renal replacement therapy.

Bottom line: Although this was only an observational study, the liberal use of normal saline during resuscitation may increase the risk of AKI and renal replacement therapy. 

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Serotonin Toxicity in the Critically Ill

• Serotonin toxicity (aka serotonin syndrome) can easily be overlooked and misdiagnosed in many of our critically ill patients.
• Several common ED medications are associated with serotonin toxicity and include tramadol, linezolid, ondansetron, and metoclopramide.
• Clues to the diagnosis include hyperthermia, increased muscle tone, hyperreflexia, dilated pupils and clonus.  Of these, clonus is the most sensitive and specific sign.
• A few important treatment pearls:
  • Avoid physical restraints
  • Consider cyproheptadine: only available in PO form; initial dose is 12 mg
  • Avoid dopamine for those that need vasopressors
  • Avoid bromocriptine and dantrolene

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Delirium in the Critically Ill

• Delirium has been shown to be an independent predictor of mortality and can occur in up to 75% of critically ill patients.
• Whether preventing or treating delirium in the critically ill patient, consider the following:
  • Minimize the use of anticholinergic medications (i.e. diphenhydramine, chlorpromazine)
  • Ensure pain is adequately controlled (avoid meperidine and tramadol)
  • Be careful with sedative medications; consider bolus dosing and daily interruption of continuous infusions
• Additional measures to treat delirious patients include reducing sensory deprivation, promoting normal sleep-wake cycles, early physical rehabilitation, and treating psychosis.

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Question

70 year-old male recently treated for community-acquired pneumonia presents with bloody diarrhea, fever, and severe abdominal pain. Abdominal Xray is shown below. Diagnosis?  

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Thrombotic Thrombocytopenic Purpura (TTP)

• TTP is a true hematologic emergency.  As a result of delays in diagnosis and initiation of treatment, mortality remains around 20%.
• Often, patients present with nonspecific symptoms that include weakness, anorexia, nausea, vomiting, and diarrhea.
• Recall that the textbook pentad is rarely present upon presentation.  In fact, renal failure and neurologic deficits are late findings.
• Plasma exchange remains the treatment of choice for critically ill ED patients with TTP.
• If plasma exchange is not immediately available, consider FFP (15-30 ml/kg) and methylprednisolone (10 mg/kg).

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Intubated patients may occasionally meet certain criteria for extubation while in the Emergency Department. Extubation is not without its risk, however, as up to 30% of patients have respiratory distress secondary to laryngeal and upper airway edema, with some patients requiring re-intubation.

Prior to extubation, Intensivists use a brief “cuff-leak” test (deflation of the endotracheal balloon to assess the presence or absence of an air-leak around the tube) to indirectly screen for the presence of upper airway edema and ultimately the risk of re-intubation. The cuff-leak test is performed by deflating the endotracheal balloon followed by one or more of the following maneuvers:

• Using the ventilator to measure the difference between inspired and expired tidal volumes; if there is a difference in the measured volumes, then air is “leaking” around the endotracheal tube, implying minimal airway edema.
• Auscultation for an air “leak” around the tube during mechanical ventilation; auscultation of a leak implies that air is passing around the tube and minimal airway edema is present.
• Disconnecting the patient from the ventilator and occluding the endotracheal tube during spontaneous breathing; auscultation of a leak implies that there is air passing around the tube and minimal airway edema is present.

Ochoa et al. performed a systematic review to determine the accuracy of the “cuff-leak” test to predict upper airway edema prior to extubation. The authors concluded that a positive cuff-leak test (i.e., absence of an air-leak) indicates an elevated risk of upper airway obstruction and re-intubation. A negative cuff-leak test (i.e., presence of an air-leak), however, does not reliably exclude the presence of upper airway edema or the need for subsequent re-intubation.

Bottom line: No test prior to extubation reliably predicts the absence of upper airway edema. Patients extubated in the Emergency Department require close observation with airway equipment located nearby.

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The Lung Transplant Patient in Your ED

• The number of lung transplant recipients is increasing.  With improved immunosuppressant medications, pts are living longer.  In fact, the 5-yr survival rate is now approximately 60%.
• When evaluating a lung transplant pt who is < 1 yr following transplant, think about acute rejection and infection
• Acute rejection occurs in up to 40% of pts, can present with cough, SOB, malaise, or hypoxia, and is treated with high-dose corticosteroids.
• Infection
  • Bacterial infections usually occur in the early stages following transplant, with Pseudomonas the predominant organism
  • CMV is the most common organism affecting up to 33% of pts during the first year after transplant

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Question

40 year-old male with severe uncontrolled hypertension presents with altered mental status (head CT below). The CXR is from the same patient. What's the connection?

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Right Heart Failure in the Critically Ill

• In its most simplistic form, right heart failure (RHF) is due to either to right ventricular contractile dysfunction or elevated right ventricular afterload.
  • Primary causes of RV contractile dysfunction include: coronary ischemia, sepsis, drug toxicity, and acute pulmonary hypertension
  • Primary causes of increased RV afterload include: LV dysfunction, venous thromboembolism, hypoxic pulmonary vasoconstriction, and lung injury
• Management of the patient with RHF centers on identifying and treating reversible causes, optimizing preload, inotropes, and possible implantation of a right ventricular assist device.
• Importantly, excessive volume loading can worsen RV contractile function, increase RV dilatation, and impair LV output and systemic perfusion.
• Consider early use of inotropic agents, such as dobutamine, in critically ill patients with RHF.

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A Cochrane review of 37 studies concluded that Succinylcholine (SUC) is superior to Rocuronium (ROC) during rapid sequence intubation.

The authors claim that compared to ROC, SUC has a faster onset of action (45 vs. 60 seconds) and overall a shorter duration of action (10 vs. 60 minutes).

Dr. Reuben Strayer wrote a letter to the journal editors and stated that these findings should be interpreted carefully; he highlighted that most of the studies in the review used doses of ROC less than 0.9 mg/kg (most studies used 0.6mg/kg).

Dr. Strayer asserted that ROC’s onset of action is dose dependent; when using doses of 1.2 mg/kg, ROC’s onset is indistinguishable from that of SUC. He also stated another major benefit of ROC is the lack of adverse effects that SUC possesses (hyperkalemia and malignant hyperthermia).

What are your thoughts on this? Go to http://www.facebook.com/Criticalcarenow and take the poll (there are 5 choices). Results will be posted next week.

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AKI and Fluid Balance

• Up to 70% of critically ill patients develop acute kidney injury (AKI), with 5-6% of ICU patients requiring renal replacement therapy (RRT). 
• Maintaining adequate renal perfusion is central to the management of AKI in the critically ill patient.  As such, fluids are frequently administered.
• As we've highlighted in previous pearls, there is mounting evidence to indicate that a positive fluid balance may be detrimental for select critically ill patients.
• Results from a recent publication suggest a positive fluid balance in patients with AKI may be harmful.
  • Bellomo, et al analyzed data from the RENAL trial to determine the association between daily fluid balance and outcomes.
  • Investigators found a 70% reduction in 90-day mortality for critically ill patients who had a negative mean daily fluid balance compared to those that had a positive balance.
  • A negative fluid balance was also associated with decreased ICU length of stay and the need for RRT.
• Take Home Point: Once critically ill patients with AKI are resuscitated, maintaining a slightly negative daily fluid balance may be beneficial.

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