UMEM Educational Pearls - By Feras Khan

How does it present?

  • Fever, cough, sore throat, runny nose, muscle aches, headaches, fatigue, diarrhea (in children especially)

Who cares…I got my vaccine! Does the vaccine work this year?

  • There has been some antigenic drift this year in the influenza A (H3N2) type virus.
  • 52% are anti-genically different than the H3N2 vaccine virus.
  • So the vaccine is less effective this year but it can give some cross-protection (in addition to protection against the other strains used in the vaccine)
  • CDC recommends still getting the vaccine  (
  • 91% of samples reported to the CDC have been influenza A this year

Can I test for this?

  • Rapid influenza diagnostic tests check for antigen detection
  • Pooled sensitivity of 62%; specificity of 98%
  • False negatives are common
  • Good technique during sample collection is important

The CDC is recommending treatment...wait I thought we were done with Tamiflu?

  • Benefits: shortens the duration of symptoms (day or less), reduces the risk of complications, reduces the risk of death among hospitalized patients
  • Risks: side effects (see below)
  • A recent Cochrane review revealed that treatment did not really help reduce complications and most of the data on anti-viral agents is biased (Roche funded) and hotly debated

Who is at risk/who deserves consideration for treatment?

  • Hospitalized patients with influenza 
  • Old people (>65)
  • Children
  • Pregnant women
  • Chronic medical conditions (asthma, COPD, diabetes, or heart disease)
  • American Indians and Alaskan natives
  • Chronic immunosuppression
  • Institutional outbreaks (nursing homes, correctional facilities)

Pearls of treatment

  • Treat as early as possible (<48hours from symptom onset)
  • 5 days of treatment; twice daily dosing. Wt based for children. Renally dosed.
  • Oseltamivir: used for more severe influenza cases
  • Zanamivir: 7 years or older; IV Zanamivir is currently in Phase III clinical trials

What are the side effects of anti-viral agents?

  • Don’t use zanamivir in patients w/ pulmonary disease
  • Transient neuropsychiatric events for oseltamivir
  • Nausea, vomiting, diarrhea are common both both


Show References

Tips for the inpatient management of community acquired pneumonia

How do I know if my patient needs ICU admission?
  • The best scoring system is the Pneumonia Severity Index (PSI) for deciding on ICU admission and inpatient treatment. You can also use the CURB-65 score or the SMART-COP score but these are less sensitive.
  • In general, PSI score of 4 or 5 tends to require ICU admission
Do I still need to treat within 4 hours?
  • No, not really. Just try to do it as fast as you reasonably can do without over-treating
What do I use for general inpatient treatment?
  • Beta-lactam plus a macrolide or a quinolone alone. These work pretty well, cure rate around 90% or so
What about ICU admission treatment?
  • You can stick with a beta-lactam plus a macrolide or quinolone in some cases but should be aware of certain issues
  • Consider influenza now that we have entered the flu season
  • Consider Staph aureus coverage for patients with influenza or those on chronic glucosteroids. Use linezolid or vancomycin for this.
  • Consider P. aeruginosa coverage in patients with COPD or bronchiectasis.
How long do I treat for?
  • This can vary based on clinician preference but there is good data to support treating for around 5-7 days
  • Longer treatment for Staph aureus or gram negative bacilli.   
What if there is no response?
  • Consider correct dosage of medications, possible antibiotic resistance, empyema, noninfectious cause etc. 


Show References

Category: Critical Care

Title: Choosing Wisely in the ICU

Keywords: choosing wisely, icu, critical care (PubMed Search)

Posted: 10/21/2014 by Feras Khan, MD (Updated: 7/10/2020)
Click here to contact Feras Khan, MD

Choosing Wisely in the ICU

  • There is a general overuse of medical tests and treatments
  • This wastes healthcare resources
  • The Choosing Wisely Campaign was developed to have providers of different specialties choose medical services that should be questioned

The Critical Care Societies Collaborative came up with this list for ICU providers

1.     Don’t order diagnostic tests at regular intervals (such as every day) but rather in response to specific clinical questions. Do you really need a daily INR check or CBC check in all ICU patients? Really?

2.     Don’t transfuse red blood cells in hemodynamically stable, non-bleeding ICU patients with a hemoglobin concentration greater than 7 g/dl. See last week’s Pearl!

3.     Don’t use parental nutrition in adequately nourished critically ill patients within the first seven days of an ICU stay. TPN is the Cinnamon Toast Crunch of fungi.

4.     Don’t deeply sedate mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation. Use as little as possible when you can.

5.     Don’t continue life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort. Engage families early in the hospital stay regarding aggressive life-sustaining treatments. Get palliative care involved in the ED!

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Category: Critical Care

Title: Massive Transfusion Protocols

Keywords: massive transfusion, bleeding (PubMed Search)

Posted: 9/23/2014 by Feras Khan, MD (Updated: 7/10/2020)
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What is a massive transfusion?

  • Can be institution dependent but usually means greater than 10 Units of blood products transfused within 24hrs.
  • Most hospitals have this as a protocol that a physician can order to notify the blood bank that a large volume of blood products may be required rapidly.

When would I use this?


-Systolic Blood pressure < 100

-Unable to obtain blood pressure


-Penetrating torso trauma

-Positive FAST

-External blood loss

-Plans to go to the OR

How do I give it?

  • The transfusion ratio is usually 1:1:1 or 2:1:1
  • Give 1 unit PRBC, then 1 U FFP, and alternate until 6 units of each have been given and then 1 bag of apheresis platelets (6 equivalent units). Can repeat as needed.

Does this apply for just traumatic bleeding?

  • Although this data was based on soldiers in the recent Iraq Wars, it has been used for medical patients as well.
  • Therefore, consider using in upper GI bleeds, post-partum hemorrhage, etc.

Are there other agents I can use?

  • There is some data to give tranexamic acid early (less than three hours from injury) in trauma patients who are hypotensive and are having severe bleeding.

What am I trying to do with this protocol?

  • Control hemorrhage
  • Use the best products possible
  • Prevent hypothermia
  • Prevent hemodilution
  • Treat coagulopathy

Show References

Category: Critical Care

Title: Enteral Nutrition in Critical Care

Keywords: immunonutrition, enteral feeding (PubMed Search)

Posted: 8/26/2014 by Feras Khan, MD (Updated: 7/10/2020)
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  • Artificial nutrition is a staple of critical care
  • Patients who are unable to eat, require enteral nutrition (preferred over parental nutrition)
  • There are some formulas that are called "immunonutrition" which try to alter the inflammatory response seen in critical illness
  • They may contain omega-3 fatty acids and essential amino acids such as arginine or glutamine, and anti-oxidants.


  • A recent trial (MetaPlus) was designed to see if immunonutrition could decrease the development of infections in the critically ill
  • Compared to regular high protein formulas, there was no difference in mortality, duration of ventilation, or hospital length of stay

What to do

  • Immuno-nutrition formulas cannot be routinely recommended
  • Use regular high protein formulas
  • Start within 48 hours of identifying a need


Show References

Category: Critical Care

Title: I just gave IM Epi for anaphylaxis, how long do I need to observe the patient?

Keywords: epinephrine, im, anaphylaxis, allergic reaction, observation (PubMed Search)

Posted: 7/29/2014 by Feras Khan, MD
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Observation after giving IM Epi for allergic reactions or anaphylaxis


  • Common practice is to observe patients who receive epinephrine for allergic reactions or anaphylaxis for several hours post-administration
  • This can be from 4-24 hours depending on the institution
  • This is to monitor for a biphasic reaction


  • Do we need to observe these patients?
  • And if so, for how long?


  • 2 urban Canadian EDs
  • 5 year period
  • Primary outcome was the amount of patients with a clinically important biphasic reaction
  • Secondary outcome was mortality


  • 2819 encounters: 496 anaphylactic + 2323 allergic reactions
  • 5 clinically important biphasic reactions (0.18%; 95% CI 0% to 0.17%)
  • No fatalities
  • Biphasic reactions tended to happen several hours (>24hrs) after ED discharge


  • If patients did not return to an ED in the region, then they would not be identified as a possible biphasic reaction

What to do?

  • You can probably discharge most patients whose symptoms have resolved without a prolonged observation period (<4hrs)
  • Patients with ongoing anaphylaxis and allergic reaction, should be observed longer or admitted
  • Biphasic reactions are very rare

Show References

Category: Critical Care

Title: Risk of infection from blood transfusions

Keywords: blood, anemia, infection, blood transfusions (PubMed Search)

Posted: 7/1/2014 by Feras Khan, MD (Updated: 7/10/2020)
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Risk of infection from Blood transfusions

  • We are already moving to decreasing transfusions in general for most of our hospital patients
  • But now there is evidence that more transfusions can lead to an increase in nosocomial infections

JAMA Meta-Analysis

  • 18 randomized trials with 7,593 patients
  • All tested higher vs lower transfusion thresholds in a variety of inpatient settings
  • Hospital-acquired infections were the outcome

What they found

  • Absolute risk for nosocomial infection was 17% among patients with a higher hemoglobin target compared to 12% with a lower target
  • NNT to avoid an infection was 38 using a restrictive transfusion strategy

Bottom Line

  • Potential cost savings to the healthcare industry with less transfusions
  • For most patients, a hemoglobin > 7 g/dL is just fine



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Category: Critical Care

Title: How Do I Emergently Reverse Dabigatran?

Keywords: bleeding, coagulopathy, dabigatran, PCC, (PubMed Search)

Posted: 6/3/2014 by Feras Khan, MD (Updated: 7/10/2020)
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Emergent reversal of Dabigatran

What is it:

Direct thrombin inhibitor used for stroke prevention in non-valvular atrial fibrillation

When do I worry about reversal:

Patients can have clinically important bleeding (GI hemorrhage, or Intracranial bleeding) or need reversal for emergent surgery

Patients with renal failure can have a prolonged medication effect

What can I do:

1.     Activated charcoal: good for recent overdose or recent ingestion (within 2 hours)

2.     Hemodialysis:  around 60-65% can be removed within 2-4 hrs; putting in a dialysis line can be…bloody

3.     FFP: in rat studies, has been shown to reduce the volume of intracranial hemorrhage. Unknown in humans. No good evidence of use based on coagulation mechanisms. Still worth a try though. 

4.     Recombinant activated factor VII: Has been shown to correct the bleeding time in animal studies. Probably the best bet in severe bleeding

5.     Pro-thrombin complex concentrate: has been shown to decrease the bleeding time in animal studies

How do I monitor effect?

No great way here. Check aPTT and thrombin time (TT). At supra-therapeutic doses there is no good test. 

Coming attractions: Dabigatran-fab for emergent reversal (see previous pearl:

Show References

Category: Critical Care

Title: High Flow Nasal Cannula

Keywords: HFNC, vapotherm, high flow, nasal cannula, hypoxemia (PubMed Search)

Posted: 5/7/2014 by Feras Khan, MD (Updated: 7/10/2020)
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High Flow Nasal Cannula

What is it?

  • High flow nasal cannula has been used in pediatrics for some time now
  • It can be used in adults as well
  • It is a simple nasal cannula setup with larger cannula sizes in both nares
  • It is heated, humidified oxygen
  • You can control your oxygen level and flow of oxygen


  • Small amount of PEEP provided to the patient (estimated 5-7 cm H20)
  • Improves oxygenation (more reliable oxygenation than a non-rebreather face mask)
  • Can provide some alveolar recruitment
  • Increases FRC (functional residual capacity)
  • Pharyngeal dead space washout

Who to use it on

  • Acute hypoxemic respiratory failure
  • Pre-intubation (can place before and during intubation in patients who have low oxygen saturation)
  • Post-extubation
  • Palliative care (DNI patients)

How to set it

  • Flow rates: 0-60 L/min
  • Spontaneously breathing patient with mild-moderate hypoxemia/respiratory distress:

            -15-30 L per minute

            -100% oxygen (wean as tolerated)

            -temp 35-40 C

            -when weaning decrease oxygen prior to flow

Bottom line: No evidence that it reduces intubation rates in patients with hypoxemic respiratory failure but may improve oxygenation issues while deciding on treatment options

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Category: Critical Care

Title: How low should you go? MAP Goals in Septic Shock

Keywords: map, sepsis, septic shock, hypertension (PubMed Search)

Posted: 4/7/2014 by Feras Khan, MD (Emailed: 4/8/2014) (Updated: 4/8/2014)
Click here to contact Feras Khan, MD

How low should you go? MAP Goals in Septic Shock


  • Since Rivers’ Early-Goal Directed Therapy, a MAP of 65 mm Hg was been the standard goal for blood pressure in septic shock
  • Some studies have suggested a higher target may be better for patients with hypertension
  • Potentially less renal failure with a higher target

The Trial:

  • 776 adult patients in France; Multi-center; randomized; non-blinded
  • All patients had septic shock and on vasopressors
  • MAP was maintained for 5 days or when the patient was weaned off pressors
  • Primary outcome: Mortality at Day 28
  • High target 65-70 mm Hg vs Low target 80-85 mm Hg


  • No significant difference in mortality at 28 days: 36.6%  (high target) vs 34% (low target) (95 %CI; 0.84 to 1.38; P=0.57)
  • No significant difference at 90 days: 43.8% (high target) vs 42.3% (low target) (95% CI; 0.83 to 1.30; P=0.74)
  • Incidence of newly diagnosed atrial fibrillation was higher in the high-target group
  • Patients with chronic hypertension: those in the higher target group required less renal-replacement therapy
  • Significant percentage of patients in the high target group did not meet goal MAP BUT the trial mirrored actual clinical practice and allowed clinicians the ability to limit blood pressure and differences in actual MAP attained in both groups was significantly different

Bottom Line:

  • A MAP goal of 65 is just fine in most patients
  • Patients with chronic hypertension and atherosclerosis seem to benefit (less need for renal-replacement therapies) with a higher MAP: so aim higher in these patients or monitor renal function and increase MAP goals accordingly


Show References

Category: Critical Care

Title: Lung Ultrasound in Pulmonary Edema

Keywords: lung ultrasound, pulmonary edema, B-lines (PubMed Search)

Posted: 3/11/2014 by Feras Khan, MD
Click here to contact Feras Khan, MD

  • “B-Lines” can be seen in patients with pulmonary edema (see attached image below)
  • A “B-line” is a reverberation artifact defined by Lichtenstein as having several properties:

1.     A comet-tail artifact

2.     Arising from the pleural line

3.     Well defined

4.     Hyperechoic

5.     Long (does not fade)

6.     Erases A lines

7.     Moves with lung sliding


  • A large amount of B-lines is pathologic
  • These artifacts are also called “comet-tails” due to their appearance
  • One or two B-lines can be seen in dependent lung zones in normal lungs
  • AIS (Alveolar interstitial syndrome) describes a group of conditions including pulmonary edema, interstitial pneumonia, and pulmonary fibrosis that show similar findings on lung ultrasonography
  • The most common presentation of this syndrome is from cardiogenic pulmonary edema and is characterized by B-lines in multiple lung zones
  •  B lines correspond with interlobular septal thickening on CT scans, which represent pulmonary vascular congestion 


  • B-mode is used with the micro-convex (cardiac) probe scanning in at least 8 lung zones
  • Quantify the number of B-lines in each zone
  • A lung zone is considered to be “positive” when three or more B-lines are present in a longitudinal plane between two ribs
  • Two or more regions bilaterally are required to be defined as AIS
  • Bilateral diffuse B-lines have a specificity of 95% and a sensitivity of 97% for the diagnosis of pulmonary edema

Show References


Fig6.1BLINESFINAL.jpg (55 Kb)

Category: Critical Care

Title: How to warm your frozen patient

Keywords: accidental hypothermia, rewarming, ecmo, artic sun (PubMed Search)

Posted: 2/11/2014 by Feras Khan, MD (Updated: 7/10/2020)
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A 50yo man found dow in the snow was brought into our ER last week in cardiac arrest with a bladder temperature of 21° C. Let’s warm him up!

  • Passive external warming (good for mild hypothermia > 34° C):  remove all wet clothing, use warm blankets, hot chocolate.
  • Active external rewarming (Used for temp between 30-34° C): Radiant heat, electric blankets, Bair-Hugger. Disadvantages: “core temperature after drop” theory: drop in core temp because of peripheral vasodilatation. Therefore, focus on warming the chest and torso area.  May not occur with certain warming techniques.
  • Active core rewarming (<30 °C, above techniques and several other options):
  1. Heated humidified oxygen via mechanical ventilation at 42-46°
  2. IV normal saline warmed to 41-43° C
  3. Cardio-pulmonary bypass: 1-2° C increase every 5 minutes
  4. ECMO (best option in cardiac arrest): Up to 4-6° C/hr. VV or VA ECMO. Provides Cardio-pulmonary support. Can continue CPR while placing a cannula.
  5. CVVH: less costly, more available, 1-4°C/hr. Case reports only. 
  6. Artic Sun; external rewarming pads: used in hypothermia protocols. Easy to use. Case reports only.
  • Other methods (use if other methods are unavailable):
  1. Pleural irrigation: one chest tube in the mid-clavicular line w saline at 42° and another chest tube in the post-axillary line and connected to a pleurovac.
  2. Peritoneal lavage: 8 Fr catheter into the peritoneum using a standard paracentesis method. Use 40-45° C dialysate.
  3. Gastric, bladder, colonic irrigations

We were able to get ROSC with CPR and ACLS and then used Artic Sun to re-warm successfully.

Other tips/tricks:

  • Continue CPR while rewarming (This is debatable: monitor ECG for new rhythms)
  • How warm is “warm and dead”? Probably around 32°C
  • How fast to rewarm?  Would warm quickly in cardiac arrest and then 1-2° C/hr thereafter; (No good evidence here)
  • Arrhythmias corrected by rewarming (bradycardia etc); no need for pacing
  • Up to three defibrillations for V. fib/V. tach; hold if no benefit
  • Can give epinephrine per ACLS protocol but would be cautious with further dosing
  • Pressors: can use epinephrine drip cautiously for hypotension
  • Cisaturacurium for paralysis w/ sedation to prevent shivering
  • Rule out hypoglycemia, adrenal insufficiency, hypothyroidism, sepsis if patient does not rewarm as expected!
  • Avoid IJ lines or irritating the myocardium with a guidewire.
  • K>12 mmol /L: consider termination of CPR


nejm_hypothermia2012.pdf (581 Kb)

Determination of Brain Death

  • With the recent media spotlight on brain death (irreversible end of brain activity) due to a few recent cases, it would be helpful to review the definition.
  • Rule out alternative causes including hypothermia, drug-induced coma, metabolic abnormalities, or severe electrolyte disturbances.
  • A clear irreversible cause must be known based on history and diagnostic studies.

Clinical Examination

  • Patient should be unresponsive to verbal or noxious stimulation, with the exception of spinally mediated responses.
  • Absence of brainstem Reflexes
  1.             No pupillary response
  2.             Absent corneal reflex
  3.             Absent gag and cough reflex
  4.             Absent cervico-ocular reflex (Doll’s Eyes Maneuver)
  5.             Absent vestibulo-ocular reflex (Cold Calorics)
  • Apnea Testing  (disconnecting the ventilator and evaluating respiratory drive)

If apnea testing cannot be performed due to instability, hypoxia, or cardiac arrhythmias, then a confirmatory test should be performed (from highest to lowest sensitivity):

  •  Angiography (lack of intracranial flow)
  •   EEG
  •   Transcranial Doppler
  •   Technetium-99 brain scan
  •   Somatosensory evoked potentials

There is state to state variation on who can perform the test and how many separate examinations need to be performed before brain death can be legally declared.

For a great review on some of the pitfalls in making the diagnosis and difficulties with the examination, please see the attached article. 


Show References


pitfalls_in_brain_death,_wijdicks.pdf (93 Kb)

Category: Critical Care

Title: Hepatic Encephalopathy (HE)

Keywords: Hepatic encephalopathy, HE, liver failure, cirrhosis (PubMed Search)

Posted: 12/17/2013 by Feras Khan, MD (Updated: 7/10/2020)
Click here to contact Feras Khan, MD

Hepatic Encephalopathy (HE)

Pathogenesis: Several theories exist that include accumulation of ammonia from the gut because of impaired hepatic clearance that can lead to accumulation of glutamine in brain astrocytes leading to swelling in patients with hepatic insufficiency from acute liver failure or cirrhosis.

Clinical Features:

  • Impaired mental status
  • impaired neuromotor function (hyperreflexia, hypertonicity, asterixis)
  • Subtle signs include personality changes, decreased energy level, and impaired sleep-wake cycle

Diagnostic tests: Ammonia levels are routinely drawn but must be drawn correctly without the use of a tourniquet, transported on ice, and analyzed within 20 minutes to get an accurate result. Severity of HE does not correlate with increasing levels.


1.     Airway protection as needed

2.     Correct precipitating factors (GI bleed, infection-SBP, hypovolemia, renal failure)

3.     Consider neuro-imaging if new focal neurologic findings are found on exam

4.     Correct electrolyte imbalances

5.     Lactulose by mouth (PO/Naso-gastric tube or Rectally)

a.     10-30 g every 1-2 hours until bowel movement or lactulose enema (300 mL in 1 L water)

b.     Facilitates conversion of NH3 to NH4+, decreases survival of urease-producing bacteria in the gut

6.     Rifaximin 550 mg by mouth BID (minimally absorbed antibiotic with broad-spectrum activity)

7.     Do not limit protein intake acutely

8.     TIPS reduction in certain patients with recurrent HE

9.     Transplant referral as needed

10.  Consider other causes if patient does not improve within 24-48hrs. 

Show References

Category: Critical Care

Title: Ottawa Rules for Subarachnoid Hemmorhage (SAH)

Keywords: subarachnoid hemmorhage, sah (PubMed Search)

Posted: 11/19/2013 by Feras Khan, MD (Updated: 7/10/2020)
Click here to contact Feras Khan, MD

Ottawa Rules for Subarachnoid Hemmorhage (SAH)


  • Headache is a common reason for ER visits
  • 1-3% of headaches are SAH
  • Misdiagnosis of SAH can be fatal
  • Lumbar puncture can be a painful/time-consuming procedure
  • Goal is to design a decision rule to help guide the clinician


  • Multi-center study at ten Canadian emergency departments.
  • 2131 adults with a headache peaking within 1 hour and no neurologic deficits
  • Non-traumatic headaches only; GCS of 15 required
  • SAH defined as: 1. CT evidence of SAH; 2. Xanthochromia in CSF; or 3. RBCs in the final tube of CSF, WITH positive angiography findings.


132 (6.2%) had SAH

Decision rule including any:

  1. age 40 years or older
  2. neck pain or stiffness
  3. witnessed LOC
  4. onset during exertion

Had 98.5% sensitivity (95% CI, 94.6%-99.6%) and 27.5% specificity (95% CI, 25.6%-29.5%)

Adding “thunder-clap” headache and “limited neck flexion on examination” (inability to touch chin to chest or raise the head 8cm off the bed if supine) resulted in 100% (95% CI, 97.2%-100%) sensitivity.

The rule was then evaluated using a bootstrap analysis on old cohort data to validate the rule.


  • Exciting new rule for SAH that needs to be validated in a new, independent cohort
  • The rule may not decrease the rate of investigation (CT, LP, or both)
  • It may decrease the amount of SAH that are missed on first visit to the ER
  • Limited by narrow criteria for inclusion in the rule/not meant for other causes of headache
  • See the JAMA editorial with the article for a nice discussion of the difficulties with decision making rules.
  • The rule:
    The Ottawa SAH Rule
    • For alert patients older than 15 y with new severe nontraumatic headache reaching maximum intensity within 1 h

    • Not for patients with new neurologic deficits, previous aneurysms, SAH, brain tumors, or history of recurrent headaches (≥3 episodes over the course of ≥6 mo)

    • Investigate if ≥1 high-risk variables present:

    1. Age ≥40 y

    2. Neck pain or stiffness

    3. Witnessed loss of consciousness

    4. Onset during exertion

    5. Thunderclap headache (instantly peaking pain)

    6. Limited neck flexion on examination



Show References


ottawa_editorial.pdf (109 Kb)

Category: Critical Care

Title: TRALI- Transfusion related lung injury

Keywords: TRALI, TACO, Transfusion, acute lung injury (PubMed Search)

Posted: 10/22/2013 by Feras Khan, MD
Click here to contact Feras Khan, MD


  • Acute lung injury that develops within 6 hours after transfusion of 1 or more units of blood or blood components.
  • Increased risk with greater number of transfusions
  • Incidence is 1 in 4000


  • Acute onset
  • Hypoxemia (PaO2/FiO2 < 300 mm Hg)
  • Bilateral pulmonary opacities on chest x-ray
  • Absence of left atrial hypertension


Two-hit hypothesis: first hit is underlying patient factors causing adherence of neutrophils to the pulmonary endothelium; second hit is caused by mediators in the blood transfusion that activate the neutrophils and endothelial cells.


Can be confused or overlap with TACO or transfusion-associated volume/circulatory overload, which presents similarly but has evidence of increased BNP, CVP, pulmonary wedge pressure, and left sided heart pressures. Patients with TACO tend to improve with diuretic treatment

Supportive tests

  • Echocardiogram 
  • BNP (tends to be low)
  • Transient leukopenia


  • Supportive care
  • Lung protective ventilation strategies
  • Fluid restrictive strategy
  • Aspirin (shown to be helpful in animal studies)
  • Pre-washing of stored RBCs prior to transfusion
  • Decrease the amount of transfusions!

Show References

Category: Critical Care

Title: Procalcitonin Algorithms to Guide Antibiotic Therapy in Upper Respiratory Infections (URIs).

Keywords: Procalcitonin, Upper respiratory infections, antibiotics (PubMed Search)

Posted: 9/24/2013 by Feras Khan, MD (Updated: 7/10/2020)
Click here to contact Feras Khan, MD


  • 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?


  • 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.


  • 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.


  •  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.

Show References

Category: Critical Care

Title: Dual Antiplatelet Therapy in Acute TIA and Minor Stroke: CHANCE Trial

Keywords: TIA, Minor Stroke, Antiplatelet therapy (PubMed Search)

Posted: 8/27/2013 by Feras Khan, MD (Updated: 7/10/2020)
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  • 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.


  • 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


  • 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%.


  • 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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