UMEM Educational Pearls - By Mike Winters

Daptomycin and MRSA

• Several new antibiotics are approved for the treatment of infections due to MRSA: linezolid, daptomycin, and tigecycline.
• Although most are familiar with linezolid, it seems that both daptomycin and tigecycline are being used more frequently.
• A few pearls on daptomycin:
  • administered IV once daily
  • dose needs to be adjusted in patients with renal failure
  • exerts its effect through a calcium-dependent binding to the bacterial membrane resulting in cell death
• Importantly, daptomycin is inactivated by pulmonary surfactant and therefore should not be given in patients with suspected MRSA pneumonia.

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Complications of Resuscitation

• CPR, defibrillation, endotracheal intubation, and cannulation of peripheral and central veins are common procedures during resuscitation of cardiac arrest patients
• Although not obvious immediately, complications from these procedures can develop and manifest several hours after successful return of spontaneous circulation
• Not surprisingly, the most common complications are rib and sternal fractures
• Additional complications to recall include:
  • tracheal mucosal lesions (almost 20%)
  • retropharyngeal bleeding
  • liver/spleen injuries
  • rhabdomyolysis (post-defibrillation)
  • air embolism (central venous access)
  • gastric rupture (very rare; due to continuous air insufflation into the stomach)

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The Supraclavicular Subclavian Central Venous Cathetherization

• Central venous catheters (CVCs) are routinely placed in critically ill ED patients.
• The literature has clearly demonstrated that CVCs placed in the subclavian vein have lower risks of infection and thrombosis when compared to the femoral and internal jugular vein routes.
• Although we routinely teach the infraclavicular approach, don't forget the subclavian vein can also be cannulated via the supraclavicular approach.
• Some pearls on the supraclavicular approach:
  • Identify the clavisternomastoid angle: formed by the lateral head of the sternocleidomastoid muscle (SCM) and the clavicle
  • Insert the needle 1 cm lateral to the lateral head of the SCM and 1 cm posterior to the clavicle
  • Direct the needle at a 45-degree angle aimed at the contralateral nipple
  • The right side is preferred due to a more direct route to the SVC and a lower pleural dome (decreasing the incidence of pneumothorax)
  • Place the patient in Trendelenburg position and aim the bevel of the needle downward

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Pulse Pressure Variation and Volume Responsiveness

• Assessing volume status in the critically ill is extremely challenging, as up to 50% of patients do not respond to a fluid challenge (i.e. increase their stroke volume/cardiac output with additional IVFs).
• As highlighted in previous pearls, traditional measurements such as blood pressure, heart rate, and urine output are extremely variable and inaccurate in determining volume status.
• Pulse pressure variation is an emerging method of volume assessment that, to date, seems even better than ultrasound measurements of the IVC.
• To calculate PPV, print out a tracing from an arterial line that captures both inspiration and expiration use the following formula:
  • ΔPP = 100 × (PPmax - PPmin)/[(PPmax + PPmin)/2]
• Values > 13% indicate that the patient is likely on the ascending portion of their Starling Curve and will augment their cardiac output with additional IVFs.
• Note that arrhythmias and spontaneous breathing can affect measurements, thus patients should be mechanically ventilated and well sedated when measuring PPV.

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High Frequency Oscillatory Ventilation (HFOV)

• Although traditionally used in neonates, HFOV is becoming increasingly popular for select adult patients with ALI/ARDS.
• Benefits of HFOV include:
  • use of smaller tidal volumes than conventional ventilation
  • maintains alveoli open at a relatively constant airway pressure thereby preventing atelectrauma
  • improves ventilation/perfusion
• Indications for use of HFOV are when:
  • conventional ventilator settings require an F_iO₂ > 70% and PEEP > 14 cm H₂O OR
  • pH < 7.25 despite higher tidal volumes and plateau pressures > 30 cm H₂O
• Key variables, along with suggested initial settings, for HFOV include:
  • Frequency: 4 - 7 Hertz
  • Amplitude: 70 - 90 cm H₂O
  • Mean airway pressure: 5 cm H₂O greater than last plateau pressure measured on conventional setting
  • Bias flow: 40 L/min
  • Inspiratory time: 33%
  • F_iO₂: 100%

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Airway Pressure Release Ventilation (APRV)

• As emergency physicians manage mechanically ventilated patients for longer periods of time, it is important to be familiar with newer, alternative modes of ventilation
• APRV is an open-lung ventilation strategy designed to provide oxygenation benefits while augmenting ventilation for patients with low compliance lung disease
• APRV has been described as CPAP with brief, regular, intermittent releases in airway pressure - essentially cycling between two CPAP levels
• The degree of ventilatory support is determined by the duration at each of the 2 CPAP levels and the distending pressure
• The 5 major parameters of APRV, along with suggested initial settings include:
  • P_high (high pressure): set at desired plateau pressure
  • T_high (time spent at the high pressure): 4-6 seconds
  • P_low (low pressure): 0 cm H₂O
  • T_low (time spent at the low pressure): 0.6-0.8 seconds
  • F_iO₂: 100%
• The pressure gradient between P_high and P_low, T_low, and the patient's spontaneous minute ventilation are the primary determinants of alveolar ventilation
• When using APRV, be sure to optimize intravascular volume to offset the decrease in venous return that results from prolonged positive intrathoracic pressure

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Antibiotic Dosing in the Critically Ill Septic Patient

• Current international guidelines recommend that intravenous antibiotics begin within one hour for those with severe sepsis and septic shock.
• Equally as important as choosing the right antimicrobial is choosing the correct dose at the right dosing schedule.
• In fact, there is evidence to suggest improved outcomes in patients given continous antimicrobial infusions (over hours) rather than intermittent bolus dosing (over minutes).
• An important cause of underdosing in critically ill patients, especially those with sepsis, is hypoalbuminemia.
• It is believed that by increasing the unbound fraction, hypoalbuminemia promotes more extensive distribution and greater renal clearance, thereby increasing the risk of underdosing.
• Take Home Point: Critically ill septic patients with hypoalbuminemia require higher dosages, or alternative regimens, to ensure appropriate antimicrobial coverage.

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Internal Jugular CVC Placement and Posterior Wall Penetration

• For a variety of reasons, many critically ill ED patients require central venous access.
• Ultrasound guidance, especially with catheters placed in the internal jugular (IJ), has become standard practice in many EDs.
• Ultrasound guidance is associated with higher success rates, reduced insertion attempts, and reduced placement failures.
• Importantly, ultrasound allows you to visualize the carotid artery which often either partially overlies or even sits direclty under the IJ.
• Recent literature, however, suggests that posterior wall penetration of the IJ, even with ultrasound guidance, may be much more common than previously thought.
• Take Home Point: Even when using ultrasound, maintain strict visualization of the needle in the IJ lumen and recognize that posterior wall penetration (into the carotid) can easily occur.

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Dexmedetomidine and the Critically Ill

• Dexmedetomidine is a newer sedative agent that is being used with increasing frequency in the critically ill
• A few pieces of information regarding dexmedetomidine:
  • highly selective alpha-2 agonist
  • produces dose-dependent sedation and anxiolysis while maintaining arousability at deep levels of sedation (hypercapnic arousal is preserved)
  • onset of action is approximately 15 minutes with peak concentration achieved in about 1 hour
  • metabolized via the liver
  • no known active or toxic metabolites
  • loading dose of 1 mcg/kg over 10 minutes followed by 0.2 - 0.7 mcg/kg/hr
• Primary side effect is bradycardia at excessive doses
• Cost is an issue when compared to propofol and midazolam

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Lorazepam Infusions

• There is some literature that propofol may be better for sedation in the mechanically ventilated patient, yet many emergency physicians still do not have access to the medication
• Lorazepam infusions are frequently used in many EDs for sedation of the mechanically ventilated patient
• Patients receiving continuous infusions of lorazepam are at risk for propylene glycol toxicity
• Propylene glycol toxicity primarily causes a metabolic acidosis and acute tubular necrosis
• Critically ill patients with renal or hepatic dysfunction are at increased risk of toxicity
• Monitoring propylene glycol levels are impractical
• Rather, check the osmol gap: a gap > 10 - 15 reflects significany propylene glycol accumulation
• Hemodialysis effectively removes propylene glycol

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The Cuff Leak Test

• As many of us have undoubtedly experienced, we are now extubating patients in the ED due to prolonged lengths of stay
• Critical to extubation is determining whether laryngeal edema may be present
• Laryngeal edema, resulting in airway obstruction, is one of the most common causes of respiratory distress following extubation
• Although shown to have moderate accuracy, many use the 'cuff leak test' to determine the iikelihood of laryngeal edema
• In most studies, performance of the cuff leak test is as follows:
  • take the average of 6 serial measurements of expired tidal volume with the ETT cuff inflated
  • take the average of 6 serial measurements of expired tidal volume with the ETT cuff deflated
  • a difference of < 110 ml between averages strongly suggests the presence of laryngeal edema
• Take Home Point: patients with a cuff leak test < 110 ml are likely to have laryngeal edema and are at high risk of airway obstruction post-extubation.  It is best not to extubate these patients in the ED.

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Coagulopathy from Acute Liver Failure

• ALF is defined as
  • absence of chronic liver disease
  • acute elevation in AST/ALT accompanied by INR > 1.5
  • any degree of mental status change (encephalopathy)
  • illness less than 26 weeks duration
• The most common cause is acetaminophen toxicity
• Regarding the coagulopathy that develops with ALF:
  • FFP transfusion is not encouraged, as the volume may exacerbate cerebral edema and it has been shown to be ineffective for improving INR elevations
  • The prophylactic transfusion of platelets for extreme thrombocytopenia is also not recommended for similar reasons

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The Maintenance Phase of Therapeutic Hypothermia

Therapeutic hypothermia (TH) has become standard in the care of patients with return of spontaneous circulation from cardiac arrest.  Although the optimal duration of TH is unknown, current literature supports 12-24 hours of cooling to 32-34^oC.  As many of our critically ill patients remain in the ED for seemingly endless lengths of stay, it is likely that most emergency physicians will be managing patients with TH during the maintenance phase of cooling.  Some pearls regarding the maintenance phase:

• Metabolic and hemodynamic homeostasis is critical
• Target volume-cycled mechanical ventilation to maintain a normal pH
• Maintain a MAP > 65 mm Hg
• Maintain blood glucose between 120 - 160 mg/dL
• Frequently check and aggressively replete potassium, magnesium, and phospate

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Acute Hyponatremia and the Critically Ill

• I just left a busy ED shift during which we had a patient with altered mental status and a serum Na of 115 mmol/L.
• Recall that severe hyponatremia may present with lethargy, disorientation, agitation, nausea/vomiting, altered mental status, abnormal respirations, and seizures.
• For severe, symptomatic hyponatremia, the treatment of choice is 3% hypertonic saline
• At a rate of 100 ml/hr, the serum Na should rise approximately 2 mmol/L per hour.
• In general, the duration of treatment with hypertonic saline is based upon sign and sypmtom improvement.
• For those with more longstanding hyponatremia, serum Na should not be increased by more than 12 mmol in the first 24 hours.

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Transient Hypotension and Mortality in Sepsis

• Not surprisingly, septic ED patients with persistent hypotension despite fluid resuscitation have increased mortality.
• What about the more common scenario of septic ED patients who have a transient drop in their BP?
• Recent evidence suggests that ED patients with sepsis who have non-sustained decrease in their BP (SBP < 100 mm Hg) have a 3-fold increased risk of in-hospital mortality compared with those who maintain arterial pressure.
• Take Home Point: Any drop in BP in a septic patient, even if it responds to fluids, portends a higher mortality.  Be vigilant and aggressively resuscitate these patients.

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Heparin for Maintaining Arteral Catheter Patency ?

• Arterial catheter placement is common in many critically ill ED patients.
• Typically, a heparin solution is used in arterial catheters based on the belief that it helps to maintain catheter patency.
• In one of the most recent studies (referenced below), the use of a heparinized solution did not improve the functionality, or increase the duration of patency, of arterial catheters when compared to a saline solution.
• As the incidence of heparin-induced thrombocytopenia (HIT) continues to increase, it is worth noting that the routine use of heparin to maintain arterial catheter patency is not well supported by the literature.

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NICE-SUGAR and Glucose Control in the Critically Ill

• Hypergycemia is associated with increased morbidity and mortality in hetergeneous populations of critically ill patients.
• Over the past few years there has been great interest in aggressively controlling glucose through the use of continuous insulin infusions.
• Results of recent trials and meta-analyses, however, question the benefit of tight glucose control and highlight the marked increase in severe hypoglycemia rates.
• Recently, the results of the NICE-SUGAR study were published, the largest trial to date (6000 patients)evaluating intensive vs. conventional glucose control in the critically ill.
• Investigators found an INCREASED mortality among adults randomized to intensive glucose control
• Given the lack of benefit, potential harm, risks of severe hypoglycemia, and resource utilization, intensive glucose control should not be a therapy routinely implemented in the ED.

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Platelet Transfusions and the Critically Ill

• Current literature suggests that platelets are given too frequently and inappropriately
• Recall that approximately 50% of platelet transfusions fail to increase counts
• In addition, bacterial contamination of units is a special concern, with sepsis occurring 10x more frequently than with PRBCs
• In general, platelet transfusions in nonbleeding patients can be withheld untl the count reaches 10 x 10³/mm³
• A transfusion trigger of 50 x 10³/mm³ should be used for invasive procedures

Ultrasound of the IVC for Volume Assessment

• In a recent pearl, I discussed that a 15% variation in IVC collapsibility could be used as a marker of hypovolemia
• As a follow up and since % variation is sometimes difficult to calculate at the bedside, consider the following numbers:
  • The normal diameter of the IVC is 1.6 - 1.75 cm
  • Patients with hypovolemia typically have an IVC diameter < 0.8 - 1.0 cm
  • In general, the IVC diameter should increase 1 mm for every 100 ml of isotonic fluid

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New Perspectives on Clostridium difficile

• In the past 5 years, C.difficile infection rates have doubled and the overall disease severity appears to be worsening.
• Particularly concerning is the increase in community acquired infections in young patients without antibiotic or nosocomial exposure.
• These epidemiologic changes are likely due to a new strain of C.difficile characterized by increased virulence and quinolone resistance.
• Importantly, the efficacy of metronidazole has waned in recent years.  In fact, > 25% of patients with moderate to severe disease do not respond to metronidazole therapy.
• As a result, vancomycin has become first-line therapy for any critically ill patient with C.difficile.

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