Background:

• Antibiotics are prescribed commonly for URIs including acute bronchitis and community acquired pneumonia.
• Antibiotic prescriptions for non-bacterial causes of URIs lead to antibiotic overuse, which can lead to antibiotic resistance and risk of Clostridium difficile.
• Procalcitonin is a biomarker for bacterial infections and is released in response to bacterial toxins during infections.
• Several algorithms using procalcitonin have been developed to help guide antibiotic treatment of URIs based on blood levels and to aid discontinuing antibiotics when procalcitonin levels have returned to normal, leading to decreased use and length of antibiotic treatment courses.

Clinical Question:

• Does measurement of procalcitonin lead to shorter antibiotic exposure without increasing mortality and treatment failure?

Meta-analysis:

• 14 trials; 2004-11; 4211 patients with a variety of URI severity and type including CAP and COPD exacerbations.
• Inpatient and outpatient settings
• Compared to regular antibiotic treatment without procalcitonin level guidance.
• Primary outcomes: All cause mortality and treatment failure within 30 days.

Conclusions:

• No increase in all-cause mortality using procalcitonin algorithms versus standard therapy in any clinical setting or type of URI (5.7% vs. 6.3%, respectively).
• Treatment failure was LOWER for procalcitonin guided patients in the ED [OR 0.76 (95% CI, 0.61-0.95)].
• Lower antibiotic exposure due to lower prescription rate in COPD exacerbations and bronchitis.

Limitations:

•  Non-blinded to outcome assessment.
•  Adherence to algorithms was variable.
• Immunosuppressed patients and children were excluded.

Bottom Line:

• Another tool to help aid clinical decision making regarding antibiotic treatment
• Test is around $25-30 and takes about 1 hour to run
• Low levels may indicate a non-bacterial cause of infection.

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Peri-Intubation Cardiac Arrest

• Emergency intubation is a common critical care procedure that carries the risk of life-threatening complications.
• Although cardiac arrest (CA) is an established complication, there is scant literature on the actual incidence ad factors associated with CA in the peri-intubation period.
• In a recent retrospective analysis from Carolinas Medical Center, investigators found:
  • Peri-intubation CA occurred in 4.2% of patients and was associated with a 14-fold increase in hospital mortality.
  • A pre-RSI shock index > 0.9 was indepedently associated with CA.
  • Obese patients had a higher incidence of CA; odds of CA increased 1.37 times for every 10 kg increase in weight.
• Take Home Point: Peri-intubation CA may be more common than previously thought and, not suprisingly, is associated with an increased risk of in-hospital death.

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Necrotizing Pneumonia
 

Necrotizing pneumonia is a rare, but potentially deadly complication of bacterial pneumonia.

It is characterized by the finding of pneumonic consolidation with multiple areas of necrosis within the lung parenchyma. Necrotic foci may coalesce, resulting in a localized lung abscess, or pulmonary gangrene if involving an entire lobe.

Most common pathogens: S. aureus, S. pneumoniae, and Klebsiella pneumonia.  
Others include S. epidermidis, E. coli, Acinetobacter baumannii, H. influenzae and Pseudomonas.

Contrast-enhanced chest CT is the diagnostic test of choice and is also helpful in evaluating  for parenchymal complications. 

Empiric antibiotic therapy should include:

• Broad spectrum coverage for commonly implicated pathogens (vancomycin, pseudomonal-dose piperacillin/tazobactam)
• PLUS either clindamycin or metronidazole to cover possibly involved anaerobes

Consider an early surgical evaluation for the patient with necrotizing pneumonia complicated by septic shock, empyema, bronchopleural fistula, or hemoptysis. 

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UEDVT comprise 10% of all DVTs (majority are lower extremity), but incidence of UEDVT is rising; UEDVTs are categorized into distal (veins distal to axillary vein) or proximal (from superior vena cava to axillary vein)

Compared to lower extremity DVT, UEDVTs have lower:

• mortality
• risk of pulmonary embolism
• rates of recurrence

75% of UEDVT are secondary (indwelling catheters, pacemakers, malignancy, etc.) and 25% are primary in nature; #1 primary cause of UEDVT is Paget – Schroetter disease

Up to 25% of patients with primary UEDVTs are eventually found to have an underlying malignancy; patients with idiopathic UEDVT should be referred for cancer workup

Treatment includes removal of the catheter (if no longer needed) and:

• anticoagulation (minimum of 3 months)
• consideration of thrombolytics, including catheter-directed administration
• mechanical thrombolysis (clot aspiration, fragmentation, etc.)
• surgical thrombectomy / venous bypass

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Background

• Stroke is common in the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke.
• Aspirin reduces the risk of recurrent stroke by 12% or so.
• Thus far there is a trend toward no benefit from dual anti-platelet treatment.

Trial

• Randomized, double blind, placebo-controlled trial conducted in China.
• 5170 patients were randomized to either combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75mg per day for 90 days, plus aspirin 75 mg per day for 21 days) or to placebo plus aspirin.
• Primary outcome was stroke during 90 days of follow-up using intention to treat analysis

Results

• Stroke occurred in 8.2% of patients in the aspirin-clopidogrel group as compared with 11.7% in the aspirin group (Hazard ratio 0.68; 95% confidence interval, 0.57-0.81; p<0.001). Rates of hemorrhage were similar in both groups (0.3%).
• Relative risk reduction of stroke at 90 days by 32%.

Conclusions

• Patients with acute TIA or minor stroke may benefit from combination therapy with no increased risk of hemorrhage

Bottom Line:

• 41,561 patients were screened in order to find 5170 appropriate patients! 
• Patients with major stroke, who are risk for hemorrhage, and have isolated sensory TIAs, were excluded.
• The trial was conducted in China, so the results may not apply in other countries (A similar trial, the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) study is being done in North America).
• Decision to treat should be made with neurology assistance.  

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Clostridium Difficile Associated Diarrhea and The Elderly Patient

• Infectious diseases remain the leading cause of mortality in the elderly.
• An infection that is increasing in prevlance among elderly patients is Clostridium difficile-associated diarrhea (CDAD).
• Mortality rates are up to 3.5 times higher in elderly patients with CDAD compared to younger patients.
• Antimicrobial therapy within the previous 6 weeks is the strongest risk factor for CDAD.
• Though any antibiotic may cause CDAD, clindamycin, fluoroquinolones, and cephalosporins have the highest risk.
• Importantly, the diarrhea may not always bloody.
• Metronidazole remains the treatment of choice for uncomplicated infections.

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Bad brain, good lungs.... Right?

A recent retrospective study reviewed the incidence of acute respiratory distress syndrome (ARDS) in patients presenting with spontaneous intracerebral hemorrhage over a 10-year period.  After reviewing 1,665 patients, the authors found that:

• The development of ARDS occurred in approximately 27% of patients with spontaneous ICH (similiar to previous literature).
• The incidence ARDS after spontaneous ICH was similiar to other "high-risk" conditions such as sepsis, trauma, & aspiration.
• Modifiable risk factors include: high tidal volume ventilation, higher total fluid balance, & transfusion of PRBCs/FFP.
   

It's of particular importance to note that high tidal volume ventilation (>8cc/kg) was the single greatest modifiable factor for the development of ARDS.

Bottom line:  Try and use lung-protective ventilation strategies (6-8cc/kg ideal body weight) and avoid excessive volume resuscitation in your critically-ill patients whenever possible.  Even in cases of isolated intracerebral hemorrhage - where the patient's lungs may appear to be completely normal - traditional tidal volume settings may be harmful.

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Question

Elderly patient who originally presented for severe pancreatitis now intubated for worsening hypoxemia. CXR is shown below, what's the diagnosis?  

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HIV, ART, and the ICU

• Though survival has dramatically improved for patients with HIV, there has been no decrease in the quantity of ICU admissions for this select patient population.
• One of the most common reasons for ICU admission is now adverse effects of antiretroviral therapy (ART).
• When managing a critically ill HIV patient in the ED or ICU, consider the following effects of ART as an etiology:
  • Lactic acidosis
    • Seen with nucleoside reverse transcriptase inhibitors (NRTIs): greatest risk with didanosine, stavudine, and zidovudine
    • Presentation: fatigue, malaise, vomiting, abdominal pain, hepatomegaly
    • Lactate often > 10 mmol/L
  • Abacavir hypersensitivity
    • Usually within first 6 weeks of drug initiation
    • Presentation: rash, fever, shortness of breath, vomiting, abdominal pain
    • Can rapidly progress to cardiovascular collapse

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COPD treatment guidelines (e.g., GOLD) recommend 10-14 days of steroid therapy following a COPD exacerbation to prevent recurrences; the supporting data is weak.

A recent noninferiority trial (here) compared patients with a severe COPD exacerbation who received either a 5-day course (n=156) or 14-day course (n=155) of prednisone 40mg.

The results were:

• No significant reduction in time until the next exacerbation (primary end-point)
• No significant difference in mortality, incidence of mechanical ventilation, FEV1, or dyspnea scores (secondary end-points)

What you need to know:

• This was a non-inferiority trial, which has limitations
• All subjects received broad-spectrum antibiotics and an initial dose of IV steroid
• Surprisingly, there were no differences between groups with respect to steroid complications (e.g., hyperglycemia, hypertension, etc.)

Bottom-line: 5 days of prednisone may be as effective as 14-days for COPD exacerbations.

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Hydroxyethyl starch (HES) is a colloid used for volume resuscitation in critically-ill patients.

Previous studies (click here) have compared crystalloids to HES during fluid resuscitation and have demonstrated that HES has an increased cost with more adverse effects. Adverse effects may include:

• Coagulopathy
• Acute kidney injury
• Increased mortality

In the United States, the Federal Drug Administration published a warning on June 24^th 2013 with respect to the use of HES in critically ill adult patients. Specifically, it warned about the use of HES in patients,

• with sepsis
• with pre-existing kidney injury
• admitted to the ICU
• undergoing heart surgery with cardiopulmonary bypass

If a decision to use HES is made, the FDA warning advises to:

• discontinue use of HES at the first sign of renal injury or coagulopathy
• continue to monitor renal function for at least 90 days (all patients)

Bottom line: With an increased cost and evidence of harm compared to crystalloids, it appears the indications for use of HES are rapidly declining.

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CVP and Fluid Responsiveness

• Central venous pressure (CVP) has been used over the last 50 years to assess volume status and fluid responsiveness in critically ill patients.
• Despite widespread practice habit, CVP has not been shown to reliably predict fluid responsiveness in the critically ill.
• In a recent updated meta-analysis, Marik et al reviewed 43 studies, totaling over 1800 patients.
  • 57% of patients were fluid responders
  • The mean CVP was 8.2 mm Hg for fluid responders and 9.5 mm Hg for non-responders
  • For studies performed in ICU patients, the correlation coefficient for CVP and change in cardiac index was just 0.28.
• Bottom line: Current literature does not support the use of CVP as a reliable marker of fluid responsiveness.

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Keep Immune Thrombocytopenic Purpura (ITP) in your differential for patients with thrombocytopenia and evidence of bleeding. Although ITP has classically been described in children, it can occur in adults; especially between 3^rd- 4^th decade.

Thrombocytopenia leads to the extravasation of blood from capillaries, leading to skin bruising, mucus membrane petechial bleeding, and intracranial hemorrhage.

ITP occurs from production of auto-antibodies which bind to circulating platelets. This leads to irreversible uptake by macrophages in the spleen. Causes of antibody production include:

• Medication exposure
• Infection (usually viral), including HIV and hepatitis
• Immune disorders (e.g., lupus)
• Pregnancy
• Idiopathic

Suspect ITP in patients with isolated thrombocytopenia on a CBC without other blood-line abnormalities. Abnormality in other blood-line warrants consideration of another diagnosis (e.g., leukemia).

ITP cannot be cured; treatments include:

• Steroid to suppress antibody production (first-line therapy)
• Intravenous immunoglobulin (IVIG)
• IV Rho immunoglobulin (for Rh+ patients only)
• Rituximab +/- dexamethasone
• Splenectomy (rare cases of massive hemorrhage refractory to pharmacologic treatment)

Rhabdomyolysis in the Critically Ill

• Rhabdomyolysis can be disastrous in the critically ill patient, resulting in metabolic acidosis, life-threatening hyperkalemia, acute kidney injury, and acute renal failure (ARF).  In fact, mortality can be as high as 60% for those that develop ARF secondary to rhabdomyolysis.
• Although creatine kinase (CK) is a sensitive marker of muscle injury and used for diagnosis, it is actually the presence of myoglobinuria that results in ARF.
• Current guidelines recommend treatment when the CK level is > 5000 U/L.
• The mainstay of treatment remains aggressive fluid resuscitation with crystalloids.
• The administration of bicarbonate to alkalinize the urine, diuretics to increase urine output, and osmotic agents (mannitol) to augment urine output remain controversial and are not supported by current literature.

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Therapeutic hypothermia (TH) following out-of-hospital cardiac arrest (OHCA) has increasingly been utilized since it was first described. TH following in-hospital cardiac arrest (IHCA), on the other hand, is not as commonplace or consistent despite a recommendation by the American Heart Association (AHA).

A recent prospective multi-center cohort-study demonstrated that of 67,498 patients with return of spontaneous circulation (ROSC) following IHCA only 2.0% of patients had TH initiated; of those 44.3% did not even achieve the target temperature (32-34 Celsius). 

The factors found to be most associated with instituting TH were:

• Younger patients
• Admission to non-ICU units
• Arrests occurring Monday through Friday (as compared to weekends)
• Arrests within teaching hospitals (as compared to non-teaching institutions)

Bottom-line: Hospitals should consider instituting and adhering to local TH protocols for in-house cardiac arrests.

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End-expiratory Occlusion Test

• Volume expansion is a cornerstone of resuscitation for circulatory failure.
• As discussed in previous pearls, only 50% of unstable critically ill patients respond to fluid therapy.  For the 50% that don't respond, additional fluids may increase morbidity and mortality.
• In recent years, there has been tremendous focus on dynamic markers of fluid responsiveness, including respirophasic changes in IVC diameter, passive leg raising, and pulse pressure variation (PPV).
• An additional dynamic marker of fluid responsiveness is the end-expiratory occlusion test.
• Unlike PPV, this test can be performed on patients with spontaneous breathing activity and those with cardiac arrhythmias.
• Recent literature indicates that a 5% increase in cardiac output during a 15-second end-expiratory occlusion test predicts a positive response to a 500 ml saline infusion.

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The Macklin Effect

Pneumomediastinum (click here for image) may be caused by many things:

1. Esophageal perforation (e.g., complication from EGD)
2. Tracheal / Bronchial injury (e.g., trauma, complication of bronchoscopy, etc.)
3. Abdominal viscus perforation with translocation of air across the diaphragmatic hiatus
4. Air may reach mediastinum along the fascial planes of the neck.
5. Alveolar rupture, also known as the "Macklin Effect"

The "Macklin Effect" is typically a self-limiting condition leading to spontaneous pneumomediastinum and massive subcutaneous emphysema after the following:

1. Alveolar rupture from increased alveolar pressure (e.g., asthma, blunt trauma, positive pressure ventilation, etc.)
2. Air released from alveoli dissects along broncho-vascular sheaths and enters mediastinum
3. Air may subsequently track elsewhere (e.g., cervical subcutaneous tissues, face, epidural space, peritoneum, etc.)

Pneumomediastinum secondary to the Macklin effect frequently leads to an extensive workup to search for other causes of mediastinal air. Although, no consensus exists regarding the appropriate workup, the patient's history should guide the workup to avoid unnecessary imaging, needless dietary restriction, unjustified antibiotic administration, and prolonged hospitalization.

Treatment of spontaneous pneumomediastinum includes:

• Supplemental oxygen and observation for airway obstruction secondary to air expansion within the neck
• Avoiding positive airway pressure, if possible
• Avoiding routine chest tubes (unless significant pneumothorax is present)
• Administering prophylactic antibiotics are typically unnecessary
• Ordering imaging as needed

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Monitoring Hyperosmolar Therapy

• Hyperosmolar therapy (mannitol or hypertonic saline) is commonly used in the treatment of neurocritical care paitents with elevated ICP.
• When administering mannitol, guidelines recommend monitoring serum sodium and serum osmolarity.  Though targets remain controversial, most strive for a serum sodium of 150-160 mEq/L and a serum osmolarity between 300 - 320 mOsm/L.
• Unfortunately, serum osmolarity is a poor method to monitor mannitol therapy.
• Instead of serum osmolarity, follow the osmolar gap.  It is more representative of serum mannitol levels and clearance.  If the osmolar gap falls to normal, the patient has cleared mannitol and may be redosed if clinically indicated. 

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Fluid boluses are often administered to patients in shock as a first-line intervention to increase cardiac output. Previous literature states, however, that only 50% of patients in shock will respond to a fluid bolus. 

Several validated techniques exist to distinguish which patients will respond to a fluid bolus and which will not; one method is the passive leg raise (PLR) maneuver  (more on PLR here). A drawback to PLR is that it requires direct measurement of cardiac output, either by invasive hemodynamic monitoring or using advanced bedside ultrasound techniques.

Another technique to quantify changes in cardiac output is through measurement of end-tidal CO2 (ETCO2). The benefits of measuring ETCO2 is that it can be continuously measured and can be performed non-invasively on mechanically ventilated patients.

A 5% or greater increase in end-tidal CO2 (ETCO2) following a PLR maneuver has been found to be a good predictor of fluid responsiveness with reliability similar to invasive measures.

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Neuromuscular Blocking Agents in the Critically Ill

• NMBAs are used in critically ill patients for RSI, patient-ventilator asynchrony, reducing intra-abdominal pressure, reducing intracranial pressure, and preventing shivering during therapeutic hypothermia.
• There are a number of alterations in critical illness that affect the action of NMBAs
  • Electrolyte abnormalities
    • Hypercalcemia: decreases duration of blockade
    • Hypermagnesemia: prolongs duration of blockade
  • Acidosis: can enhance effect of nondepolarizing agents
  • Hepatic dysfunction: prolongs effects of vecuronium and rocuronium
• In addition, there are a number of medications that may interact with NMBAs
  • Increased resistance: phenytoin and carbamazepine
  • Prolongs effect: clindamycin and vancomycin
• Key complications of NMBAs in the critically ill include:
  • ICU-aquired weakness (controversial)
  • DVT: NMBAs are one of the strongest predictors for ICU-related DVT
  • Corneal abrasions: prevalence up to 60%

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