Drug-Induced Thrombocytopenia

• Thrombocytopenia is common in critically ill patients and is associated with increased mortality.
• Up to 25% of critically ill patients will develop thrombocytopenia as a result of a medication, termed drug-induced thrombocytopenia (DIT)
• Antibiotcs are a common, yet infrequently recognized, cause of DIT.
• Antibiotics reported to cause DIT include linezolid, vancomycin, trimethoprim/sulfamethoxazole, and the beta-lactams.
• In fact, piperacillin/tazobactam has been associated with DIT more frequently than any other penicillin. 

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ICU Acquired Weakness

• ICU acquired weakness (ICU-aw) is a general term that refers to the weakness that develops in critically ill patients during the course of their illness - especially in patients with sepsis and those receiving mechanical ventilation.
• ICU-aw is an very common complication of critical illness that can develop within hours and has been shown to increase the duration of mechanical ventilation and ICU/hospital LOS.  Observational studies have also reported an association with mortality.
• Risk factors associated with ICU-aw include medications (neuromuscular blocking agents, corticosteroids), hyperglycemia and immobility.
• For the critically ill ED patient, current recommendations suggest limiting the administration of neuromuscular blocking agents and corticosteroids, when possible.

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Drug-Drug Interactions in the Critically Ill

• Critically Ill ED patients are at risk for drug-drug interactions (DDIs) due to altered organ function, polypharmacy, and altered drug kinetics.
• DDIs involving the cytochrome isoenzyme CYP3A4 are of particular importance.
• CYP3A4 inhibitors, such as macrolides and azoles (fluconazole, voriconazole), can cause serious DDIs when given concomitantly with meds that are a subtrate for CYP3A4 - midazolam, cyclosporine, tacrolimus, diltiazem, amiodarone.
• Pay particular attention to your transplant patients, as administration of an azole can result in significant cyclosporine or tacrolimus toxicity.

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Asthma, Peak Pressures, and the Ventilator

• In previous pearls, we have highlighted ventilator settings for the asthmatic, along with the differences between peak and plateau pressure measurements.
• When ventilating the asthmatic, pay attention to the ventilator settings placed by your respiratory therapist.
• In general, the respiratory therapist will set the ventilator to stop delivering tidal volumes when the peak pressure exceeds 40-60 cm H₂O.
• For asthmatics, this practice can result in very low tidal volumes.
• Thus, peak pressure limits must be set higher.
• As you know, high peak pressures have not been shown to be injurious, provided that the plateau pressure remains < 30 cm H₂O

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Pre-existing acidosis and mechanical ventilation

• Not surprisingly, many critically ill ED patients often develop a metabolic acidosis.
• To compensate, patients hyperventilate, thereby producing a respiratory alkalosis.
• When these patients require intubation and mechanical ventilation, be sure to provide the same level of respiratory compensation when setting the ventilator. 
• Failing to provide a rate sufficient to compensate for the pre-intubation acidosis leads to a rapid drop in pH, bradycardia and eventually asystole.
• In general, rates can be increased to about 30-35 breaths per minute, after which auto-PEEP becomes problematic.

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Hypotension after intubation and initiation of mechanical ventilation

• Approximately 25-30% of patients develop hypotension after intubation and initiation of mechanical ventilation (MV).
• Although the literature is not robust, risk factors for hypotension after initiation of MV include:
  • hypotension prior to intubation
  • tachycardia prior to intubation
  • obesity
  • high intrathoracic pressure (COPD)
  • excess catecholamine states (ETOH withdrawal, cocaine intoxication) with rapid relaxation during RSI
• In addition to administering isotonic intravenous fluids (IVFs) while preparing for intubation, consider having a vasopressor medication, such as phenylephrine, available if IVFs alone prove insufficient at maintaining blood pressure.

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Platelet Transfusions in the Critically Ill

• Recommendations for the transfusion of platelets in the critically ill patient is primarily extrapolated from the oncology literature; literature that is predominantly observational and expert opinion.
• Nevertheless, indications for the transfusion of platelets in a critically ill ED patient include:
  • active bleeding with a plt count < 50 x 10⁹/L
  • plt count < 10 x 10⁹/L (high risk of spontaneous bleeding)
  • prior to an invasive procedure when the plt count is < 50 x 10⁹/L
• Importantly, the decision to transfuse platelets should also take into account the clinical setting (ie. a uremic patient with active bleeding)

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Postcardiac Arrest Syndrome: Controlled Reoxygenation

• In previous pearls, Dr. Marcolini has highlighted the poscardiac arrest syndrome (PCAS), comprised of brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating disease.
• Not surprisingly, postcardiac arrest brain injury is a major cause of morbidity and mortality, accounting for > 60% of deaths in some studies.
• In addition to therapeutic hypothermia, consider "controlled reoxygenation" in order to optimize neurologic outcome.
• Animal data has demonstrated that too much oxygen may worsen neuronal damage during the initial resuscitation phase.
• Take Home Points:
  • Use a minimum amount of F_iO₂ to maintain S_pO₂ of 94-96%
  • Avoid unnecessary arterial hyperoxia

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PRBC Transfusions in Neurocritical Care

• Historically, neurocritical care textbooks have favored a more liberal PRBC transfusion strategy, as the brain is very sensitive to decreases in oxygen delivery.
• Despite these recommendations, limited studies have failed to show a mortality benefit to PRBC transfusion in critically ill patients with neurologic illness.
• Postulated reasons for the lack of morbidity or mortality benefit center around the injured brain's response to attempts to increase oxygen delivery through transfusion.
  • TBI: PET studies have shown an overall lower level of metabolic activity along with a lower oxygen extraction and loss of autoregulation
  • SAH: transfusion may increase the risk of vasospasm in SAH and worsen flow
• Although the evidence is not overwhelming, current recommendations from SCCM-Eastern Society for the Surgery of Trauma recommend a restrictive PRBC transfusion threshold (Hgb < 7 gm/dL) even in neurocritical care patients.

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PRBC Transfusion Threshold for Patients with Cardiac Disease

• As previously discussed, the PRBC transfusion threshold for the general population of critically ill patients is a Hgb < 7 gm/dL.
• Traditional teaching has been to maintain a Hgb > 10 gm/dL in patients with a history of CAD.
• This threshold stems from a 1950s cohort of Jehovah's Witness patients, and several observational studies, that demonstrated increased perioperative mortality in patients whose Hgb was < 10 gm/dL.
• Recent studies, however, have found that patients with a history of CAD tolerate lower Hgb levels without increases in morbidity or mortality.  In fact, current cardiovascular surgery guidelines favor a conservative Hgb threshold (7 gm/dL) for patients with CAD.
• Importantly, the Hgb threshold of < 7 gm/dL for PRBC transfusion applies to patients with simply a history of CAD and not to patients with evidence of an acute coronary syndrome (STEMI, NSTEMI, unstable angina).  Guidelines continue to recommend a Hgb > 10 gm/dL for patients with ACS.

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Type B Lactic Acidosis

• In the critically ill, patients may often have elevated lactate levels without ongoing tissue hypoperfusion.
• In these patients it is important to consider the causes of what is referred to as "Type B Lactic Acidosis".
• Pertinent to critically ill ED patients, consider the following:
  • Type B1 - related to underlying disease
    • renal faiilure
    • hepatic failure
    • malignancy
    • HIV
  • Type B2 - effects of drugs/toxins
    • acetaminophen
    • alcohols
    • beta-adrenergic agents: epinephrine
    • cocaine, methamphetamine
    • propofol
    • salicylates
    • valproic acid
    • metformin
  • Type B3 - inborn errors of metabolism

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Ventilator Pearls for H1N1 Influenza Virus

• As the spring/summer travel season begins, it is predicted that we will see additional cases of H1N1
• The most common presentation requiring ICU admission to date has been a viral pneumonitis
• As highlighted in previous pearls, the hallmark of disease has been refractory hypoxemia requiring mechanical ventilation in about 85% of patients.
• Current recommendations for H1N1 respiratory failure:
  • Consider early intubation
  • Noninvasive ventilation has been unsuccessful in most and should generally be avoided
  • Low tidal volume settings (6 ml/kg) with PEEP based on F_iO₂ to maintain S_pO₂ > 88% and plateau pressure < 35 cm H₂O
  • Although there is no proven mortality benefit to rescue therapies such as recruitment maneuvers, neuromuscular blockade, and prone ventilation, these can be considered in discussion with your intensivist.

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Warfarin and ICH

• Warfarin causes approximately 10-15% of all intracerebral hemorrhages (ICH)
• Many warfarin-related ICHs occur with INRs in the therapeutic range
• Patients with warfarin-related ICH have higher mortality and typically suffer worse neurologic outcome
• The primary pitfall in treating patients with warfarin-related ICH is the failure to rapidly normalize the INR
• Do not delay treatment while awaiting the results of coagulation labs
• Patients should receive IV vitamin K via slow infusion and FFP
• Prothrombin Complex Concentrate (PCC) is gaining popularity but much of the supporting literature uses agents not available in the US
• Similarly, there is no significant evidence that recombinant factor VIIa improves outcomes in patients with warfarin-related ICH

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Ventilating the Patient with Traumatic Brain Injury

• Many patients with acute TBI will require intubation and mechanical ventilation for a variety of reasons.
• Ventilating the patient with TBI becomes a balancing act between maintaining adequate cerebral perfusion and minimizing lung injury.
• Some pearls to consider:
  • Avoid hypoxia: although guidelines recommend a P_aO₂ > 60 mm Hg, most suggest a higher P_aO₂ (> 80 mm Hg) be initially targeted.
  • Avoid hypercapnia:  many patients will develop hypercapnia when ventilated using the low tidal volume strategy (6 ml/kg) of the ARDSnet trial; titrate TVs to maintain a P_aCO₂ between 32-35 mm Hg.
  • PEEP: the application of PEEP remains controversial in patients with TBI given the theoretical risk of increasing ICP through reductions in venous return; if PEEP is applied pay close attention to the cerebral perfusion pressure to ensure it remains > 60 mm Hg.

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The Rapid Ultrasound in Shock (RUSH) Exam

• Evaluating the ED patient with undifferentiated shock can be challenging.
• Ultrasound can be an invaluable tool in helping to differentiate between hypvolemic, cardiogenic and obstructive shock.
• The RUSH exam essentially focuses on the evaluation of the "pump", the "tank" and the "pipes".
• The pump: exclude pericardial effusion, global estimate of LV EF, and determine if RV strain is present.
• The tank: evaluate the IVC/jugular veins for volume status, look for fluid in the thorax/peritoneum, and exclude pulmonary edema or pneumothorax.
• The pipes: look for a ruptured AAA or aortic dissection and DVT.

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Defining Acute Kidney Injury (AKI)

• In the pearl from 1/5/10, I highlighted the association of AKI with increased morbidity and mortality in the critically ill along with the avoidance of nephrotoxic medications.
• Currently, two sets of criteria (RIFLE and AKIN) can be used to identify patients with AKI
• According to AKIN, the current diagnostic criteria for AKI is:
  • an absolute increase in serum creatinine > 0.3 mg/dL OR
  • a > 50% increase in serum creatinine from patient baseline OR
  • urine output < 0.5 ml/kg/hr for > 6 hours
• For the critically ill ED patient, the most common causes of AKI include sepsis, hypovolemia, medications, trauma, rhabdomyolysis, obstruction and abdominal compartment syndrome

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AKI and the Critically Ill

• Acute kidney injury (AKI) is an abrupt reduction in kidney function causing disturbances in electrolytes, fluids, and acid-base balance.
• AKI occurs in up to 67% of critically ill patients and is associated with a substantial increase in morbidity and mortality.
• AKI in the critically ill is often multifactorial and most commonly due to sepsis, hypovolemia, medications, and hemodynamic instability.
• Medications account for up to 20% of AKI in the critically ill.
• Common medications that cause, or exacerbate AKI, in the critically ill include:
  • NSAIDS
  • Antibiotics (aminoglycosides, amphotericin, acyclovir)
  • ACE-inhibitors
  • Radiocontrast dye
• Take Home Point:  AKI is common in our critically ill ED patients and, whenever possible, avoid nephrotoxic medications that can result in additional injury.

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Appropriate Antimicrobial Therapy for Sepsis

• In previous pearls, we have discussed the importance of early antimicrobial administration for patients with sepsis.
• In patients with septic shock, current guidelines recommend empiric antimicrobial therapy be initiated within 1 hour.
• Equally as important as early administration is the selection of appropriate antimicrobial therapy (i.e. choosing an antibiotic that is effective against the presumed or identified pathogen).
• In one of the most recent studies, investigators found a 5-fold reduction in survival (52% vs. 10.3%) between patients who received appropriate antibiotics compared to those who received antibiotics that were ineffective against the identified pathogen.
• In fact, choosing the right antibiotic is one of the strongest factors associated with patient outcome in sepsis.
• When selecting empiric antimicrobial therapy for patients with septic shock consider patient history, co-morbidities, the clinical site of infection, and local resistance data.

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Early Recognition of Shock

• Early recognition, and thus early treatment, of shock is crucial in reducing morbidity and mortality in the critically ill ED patient.
• Traditionally, the diagnosis of shock has been based on vital sign abnormalities such as tachycardia, tachypnea, oliguria, etc.
• Vital sign abnormalities have been shown to be insensitive markers of shock in the critically ill.
• The Shock Index, although clearly not 100% sensitive, can assist in the detection of shock compared to heart rate and blood pressure alone.
• Shock Index is simply heart rate divided by systolic blood pressure.
• Values greater than 0.9 are abnormal and suggest markedly impaired cardiac output.

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Spinal Epidural Abscess Pitfalls

• The classic triad of back pain, fever, and neurologic deficits are found in < 15% of patients at the time of presentation
• Up to 75% will be afebrile
• Up to 67% will have a normal initial neurologic exam
• < 40% have a WBC greater than 12,000 cells/mm³
• < 33% will have an abnormality on plain film in the first 7-10 days

Take Home Point: In the patient with risk factors for spinal epidural abscess (IVDU, DM, indwelling catheters, etc) do not exclude the diagnosis based upon the absence of a fever, a normal WBC count, and a normal neurologic exam.