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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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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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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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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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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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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Lung Protective Ventilator Settings Still Underutilized

• It's been over 10 years since the publication of the ARDSnet trial, which demonstrated an 8.8% absolute reduction in short-term mortality for patients with ARDS ventilated with "lung protective" settings (tidal volume 6 ml/kg, plateau pressure < 30 cm H20).
• A recent study in the BMJ evaluated the association of these settings with 2-yr survival in patients with acute lung injury.
• The study, carried out in 13 ICUs from 4 academic hospitals in Baltimore, found some surprising results:
  • In patients whose ventilator settings were 100% compliant with lung protective settings, there was an 8% absolute reduction in mortality.
  • For each increase of 1 ml/kg above recommended tidal volume there was an 18% relative increase in mortality.
  • 37% of patients never received lung protective ventilation.
• Take home point: lung protective settings appear to confer not only short-term but also long-term mortality benefit for patients with acute lung injury, yet remain underutilized even in major academic centers.

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Steroids and Septic Shock

• Do low-dose steroids improve mortality or shock reversal in patients with septic shock?
• A recent systematic review published in the Journal of Emergency Medicine found:
  • A statistically significant improvement in shock reversal (RR 1.17)
  • A favorable, but not statistically significant, mortality benefit for patients with refractory septic shock (RR 0.92; CI 0.79-1.07)
• Most guidelines recommend against steroids for septic patients that are responding to fluid resuscitation and vasopressor therapy.
• Updated guidelines from the Surviving Sepsis Campaign (soon to be published) will continue to recommend low-dose IV corticosteroids (200 mg over 24hrs) for those who are refractory to fluids/vasopressors.

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Anaphylaxis

• The incidence of anaphylaxis appears to be rising.
• Recall that death can occur anywhere from 5 to 30 minutes after allergen exposure.
• A few important pearls in management:
  • Epinephrine is the drug of choice and should be given intramuscularly (not subcutaneous) in the mid-anterolateral thigh.
  • Be aggressive with IV fluids, as up to 35% of circulating volume can be extravasated within 10-15 minutes of symptom onset.
  • Get an ECG ASAP! Mast cells are located around the coronary arteries.  The release of mediators can induce vasospasm and precipitate an acute coronary syndrome.

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Acute Kidney Injury and Tumor Lysis Syndrome

• Tumor lysis syndrome (TLS) is characterized by hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia.
• Acute kidney injury in TLS increases patient mortality and can be caused by an obstructive uropathy from calcium phosphate crystalluria or uric acid crystal precipitation.
• Fluid resuscitation remains the primary treatment for TLS.
• Urine alkalinization, however, is no longer recommended, as it can result in calcium phosphate crystal precipitation. 
• Recombinant urate oxidase rapidly decreases uric acid levels and should be given to patients at high-risk for TLS and those with pre-existing kidney disease and high uric acid levels.

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Use the Measured Sodium Concentration!

• During a recent shift, a question arose regarding whether to use the measured or corrected sodium to calculate the anion gap in a critically ill patient with DKA.
• Recall that the anion gap provides an estimation of unmeasured anions - in this case acetoacetate and beta-hydroxybutyrate.
• Glucose is electrically neutral and therefore does not affect the anion gap.
• When calculating the anion gap in a patient with DKA, use the actual (measured) serum Na, rather than the corrected value.

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Severe UGIB

• Differentiating between upper and lower GIB can be challenging. 
• A recent review evaluated the accuracy of historical features, symptoms, signs, and lab values in distinguishing between UGIB and LGIB. 
• Features with the highest likelihood for identifying UGIB included:
  • Melenic stool on exam (LR 25)
  • A prior history of UGIB (LR 6.2)
  • Serum urea:creatinine ratio > 30 (LR 7.5)
• Features that increased the likelihood of severe UGIB (defined as requiring blood transfusion, need for urgent endoscopy, surgery, or interventional radiology) included:
  • Heart rate > 100 bpm (LR 4.9)
  • Hemoglobin < 8 g/dL (LR 6.2)
  • History of cirrhosis or cancer (LR 3.7)
• For patients with an UGIB, the Blatchford Score can be used to determine the need for urgent intervention.  Those with a Blatchford Score of 0 have a low likelihood for severe UGIB and may not need emergent intervention.

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Balloon Tamponade for Variceal Bleeding

• Despite advances in pharmacology and endoscopy, placement of a balloon tamponade device is occasionally required to stabilize a patient with acute variceal bleeding.
• Currently, there are 3 devices available: the Linton-Nachlas (gastric balloon only), the Blakemore (gastric and esophageal balloons), and the Minnesota (gastric and esophageal balloons) tubes.
• The tube should initially be passed at least to the 50-cm mark and preferably to the maximum depth allowed by the length of the tube.
• Once the gastric balloon is inflated and correct position confirmed, traction must be applied to keep the gastric balloon engaged in the cardia and fundus of the stomach.
• An overhead pulley system is the preferred method to deliver traction.  If you don't have weights for the pulley system, a 1-liter bag of crystalloid provides the desired 1.0 kg of traction.

SBP, HRS, and Albumin

• Spontaneous bacterial peritonitis (SBP) is the most common infection in patients with end-stage liver disease (ESLD).
• In critically ill patients, SBP can precipitate type 1 hepatorenal syndrome (HRS), which, if not treated, carries a mortality > 90%.
• Infusion of albumin at 1.5 g/kg at the time of SBP diagnosis (and a second dose of 1 g/kg on day 3) has been shown to significantly decrease the incidence of type 1 HRS and decrease mortality.
• In your next critically ill patient wth ESLD, strongly consider giving albumin at the time of SBP diagnosis.

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Cuff Pressures and the Prevention of VAP

• As highlighted in a recent pearl, ventilator-associated pneumonia (VAP) is the second most common nosocomial infection in the US and is associated with increases in ICU length of stay and mortality.
• With increasing ED lengths of stay for many critically ill patients receiving mechanical ventilation, measures to prevent VAP should be initiated in the ED.
• In addition to elevating the head of the bed to 30-45 degrees, another low cost intervention is the measurement of endotracheal tube cuff pressures.
• Cuff pressures below 20 cm H₂O increase the risk of VAP.
• Measure cuff pressure within 4 hours of inflation and maintain between 20-30 cm H₂O.

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Transferring Multidrug-Resistant Organisms

• Hospital-associated infections are a major cause of morbidity and mortality, especially among the critically ill.
• Worldwide, the emergence of multidrug-resistant (MDR) bacteria has caused significant problems.
• A recent study from the University of Maryland examined the impact of environmental contamination on the rate of transfer of MDR bacteria to healthcare workers clothing.
• Two important findings from this study of ICU patients were:
  • Up to 8% of healthcare workers entered a patient's room with MDR bacteria on their hands
  • Almost 5% of healthcare workers had MDR bacteria (most notably Acinetobacter) on their hands upon exiting the room despite using gloves and a gown
• Take Home Point: Be sure to use hand hygiene upon entering and exiting a patient's room who is colonized with MDR bacteria!

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High-Frequency Oscillatory Ventilation for ARDS?

• High-frequency oscillatory ventilation (HFOV) is increasingly utilized for adult patients with ARDS who remain hypoxemic despite optimal settings of conventional mechanical ventilation (CMV).
• HFOV maintains a constant mean airway pressure and delivers very small tidal volumes (1-3 ml/kg) at very high respiratory rates (frequency range up to 10 Hz).
• Potential advantages to HFOV over CMV include greater alveolar recruitment, prevention of atelectrauma, and limiting excess alveolar distension (i.e. volutrauma).
• Studies on HFOV in adults are not as numerous as those in neonates.  As a result, optimal timing for initiation of HFOV is unclear.
• Nevertheless, some recommend considering HFOV for patients who persistently need an F_iO₂ > 60% with at least 10 cm H₂O of PEEP on CMV.
• Due to the ventilator settings, patients receiving HFOV often require significant sedation and often neuromuscular blockade.  

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Preventing VAP in the Intubated ED Patient

• Ventilator-associated pneumonia (VAP) occurs in 9-27% of patients receiving mechanical ventilation (MV).
• VAP increases the duration of MV and increases the ICU length of stay.
• VAP is primarily caused by aspiration of oropharyngeal secretions either during intubation or while receiving MV.
• While there are many interventions that may potentially reduce the incidence of VAP (aspiration of subglottic secretions, selective digestive decontamination, monitoring endotracheal cuff pressure), a simple, no cost intervention is patient positioning.
• Placing intubated patients in the semirecumbent position is associated with a lower risk of VAP.

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Ice-Cold Crystalloid for Therapeutic Hypothermia

• Therapeutic hypothermia (TH) is a critical component in the care of patients with ROSC from out-of-hospital cardiac arrest.
• Despite recent guidelines, initiation of TH in the ED for appropriate patients remains less than optimal.
• Reported barriers to the induction of TH in the ED include lack of familiarity, lack of collaboration with the ICU, access to special equipment, and the logistics of cooling.
• A recent analysis of studies on the use of ice-cold crystalloids (ICC) found that an infusion of 4⁰ C fluid is a safe, effective, inexpensive, and readily available method for inducing TH.
• Importantly, no study reported any significant hemodynamic complication (i.e. CHF) from the use of ICC.
• Lastly, once the target temperature has been reached, ICC alone cannot maintain TH.  Additional methods, such as surface cooling blankets or ice packs, should be used.

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