Types:
- Uniphasic anaphylaxis: occuring immediately after exposure to allergen, resolves over minutes to hours and does not recur
- Biphasic anaphylaxis: occuring after apparent resolution of symptoms typically 8 hours after the first reaction. Occur in up to 23% of adults and up to 11% of children with anaphylaxis

Treatment:
1. First line: IM epinephrine 1:1000 solution
   - vasoconstrictor effects on hypotension and peripheral vasodilation; bronchodilator effects on upper respiratory obstruction
   - NO absolute contraindication for use in anaphylaxis
   - Dosage: Adult: 0.3 - 0.5mg; Peds: 0.01mg/kg (max 0.3mg)
   - can be repeated every 5-15 minutes
2. Adjunctive therapy:
   - H1 Blocker: diphenhydramine 1-2mg/kg up to 50mg IV
   - H2 Blocker: ranitidine 1-2mg/kg
   - Corticosteroid: 1-2 mg/kg for prevention of biphasic reactions
   - Bronchodilator: Albuterol for bronchospasm
   - Glucagon: for refractory hypotension or if patient is on beta blocker
          - Dosage: Adult: 1-5 mg; Peds 20-30microgm/kg
          - Dose may be repeated or followed by infusion of 5-15 mg/min
   - place patient in recumbent position if tolerated with lower extremities elevated
   - supplemental O2
   - IV fluids for hypotension

Fatalities: typically seen with peanut or treenut ingestions from cardiopulmonary arrest. Associated with delayed or inappropriate epinephrine dosing

Disposition:
   - Mild reaction with symptom resolution: observe for 4-6 hrs (ACEP, AAP)
   - Recurrent symptoms or incomplete resolution: admit

Reference:
1. World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis, Feb 2011
2. Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel Oct 2010

Patients that experience altered mental status (specifically lethargy) and are on valproic acid - check a serum ammonia level regardless if it is an overdose or just therapeutically on VPA.

If the ammonia is elevated in combination with the mental status change consider administration of L-carnitine either po or IV. It will lower the ammonia and improve the mental status  within hours.

High risk patients for hyperammonia who therapeutically take VPA are certain pediatric patients that experience malnutrition, have seizure disorder and are on multiple seizure medications.

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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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Question

36 year-old female presents with left knee-pain following a motor vehicle crash (XRs are shown). What's the diagnosis AND what is the first test that should be performed to assess for vascular injury?

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Pulmonary P waves (S1Q3T3 pattern + clockwise rotation) are specific for PE, but not sensitive.
This study examines if an ECG can discriminate between ACS vs. PE
- 40 patients with PE & 87 patients with ACS 
- All had negative T waves in the precordial leads (V1-V4) on the admission ECG
The PE group had negative T waves commonly present in leads II, III, aVF, V1, V2, but less frequent in leads I, aVL, and V5 to V6 (p <0.05).
The ACS group had negative T waves in leads III and V1 in 1% compared with 88% of patients with PE (p <0.001).
Sensitivity, specificity, positive predictive value, and negative predictive value for Dx of PE were 88%, 99%, 97%, and 95%, respectively.
Negative T waves in both leads III and V1 may suggest PE can be differentiated from ACS in patients with negative T waves in the precordial leads.

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The Analysis of Synovial Fluid Analysis

When trying to diagnosis a septic joint, it is common to order the following labs on the synovial fluid:

• Synovial WBC count
• Glucose
• Protein
• Gram Stain
• Culture

Unfortunately, there is no value of glucose or protein that has enough sensitivity and specificity to make the tests diagnostically helpful.  Gram stains are only postive in culture positive septic joints in approximately 50% of the cases.  Cultures take too long to be helpful in the ED.  The synovial WBC count can be helpful if very high, but a low value does not ensure that the patient does not have a septic joint.

The one test that has been shown to have a Positive Likelihood ratio of Infinity is a synovial lactate level >10.  A synovial lactate should be sent on all synovial fluid as a level of 10 and greater makes the diagnosis of septic arthritis, regardless of the gram stain or synovial WBC level.

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If you have a patient who meets (or has had close exposure to someone meeting) the clinical case definition of pertussis (a cough lasting at least 2 weeks with one of the following: paroxysms of coughing, inspiratory “whoop,” or post-tussive vomiting) here are some important points to keep in mind:

Vaccination

• Be wary that children younger than 7 might not be “up to date” for pertussis vaccination.
  • The recommended schedule is four primary doses of DTap at 2, 4, 6 and 15-18 months, and a fifth DTap booster at 4- 6 years old. ACIP now recommends kids 7 and older get a Tdap booster if their immunizations were previously incomplete.

Testing

• The available testing modalities for routine surveillance are culture and/or PCR (from a posterior nasopharyngeal swab or aspirate) and serologic testing.
  • Serologic results are not currently accepted as laboratory confirmation for purposes of national surveillance, but may be more useful for testing patients in the convalescent stage.

Treatment

• The CDC recommends treatment of clinical or confirmed cases with one of these regimens:
  • Azithromycin daily x 5 days
  • Clarithromycin BID x 7 days
  • Erythromycin QID x 14 days
  • Trimethoprim/sulfamethoxazole (Bactrim) BID x 14 days if resistance or allergy to macrolides
    • However, a 2011-updated Cochrane review showed that short-term antibiotics (azithromycin for 3-5 days, or clarithromycin or erythromycin for 7 days) were as effective as long-term (erythromycin for 10-14 days)  (RR 1.01) (95% CI  0.98-1.04). Trimethoprim/sulfamethoxazole for seven days was also effective.
• Insufficient evidence to decide whether there is clear benefit for treating healthy contacts, but the CDC does recommend prophylactic treatment of close contacts and family members.

References:

Altunaiji SM, Kukuruzovic RH, Curtis NC, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004404. DOI: 10.1002/14651858.CD004404.pub3

http://www.cdc.gov/vaccines/pubs/surv-manual/chpt10-pertussis.html

Femoral venous access is typically limited to the acute resuscitation of critically-ill patients. Several practice-guidelines recommend avoiding the femoral site, or removal once admitted to the ICU, because of the risk of catheter-related bloodstream infection (CRBI) and deep-vein thrombosis (DVT).

A recent systematic review and meta-analysis (including two randomized-control trials and eight cohort-studies) evaluated the risk of CRBI and DVT for catheters placed in either the internal jugular, subclavian, or femoral-venous sites. No difference in the rate of CRBI or DVT was found between the three sites, although the DVT data was less robust (i.e., contained heterogeneous data).

The authors hypothesized that improvements in sterility during central-line placement (e.g., full-barrier precautions), improved nursing care (e.g., central-line site care), and ultrasound guidance may have led to a reduction in femoral site complications. 

Although a prospective randomized-control trial is necessary to confirm these results, this meta-analysis challenges the traditional teaching that femoral central-access should be avoided.

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Placement of central-lines through the subclavian (SC) route has several advantages over other sites of venous cannulation:

•    Lower rates of infection

•    Lower rates of deep vein thrombosis

Placing a central-line through the "blind" SC approach increases the risk of non-compressible vessel injury and pneumothorax as compared to other approaches (e.g. internal jugular).

Ultrasound can help place central-lines in the SC vein while reducing the risk of complications; this video demonstrates the technique: http://ultrarounds.com/Ultrarounds/Subclavian_Ultrasound.html

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Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy (typically asymmetric) that occurs in the absence of pressure overload or storage/infiltrative disease.

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Apologies for the long pearl, I did not want to split this into 3 parts)

Disruptions in sleep and circadian rhythms (from travel across time zones and jet lag) are known to alter cognitive functions. Mood and complex mental performance tasks deteriorate faster than do simpler mental performance tasks.

An athlete’s circadian rhythms are believed to be optimal for performance in the early evening (reaction time to light and sound in the fastest). Interestingly, the evening is the time of day when most world records have been broken. However, activities that require fine motor control and accuracy (hand steadiness and balance) are best in the morning.

In the normal population, travel effects are seen in inattention and an increase in errors and injuries in the workplace.

Athletes who perform in international competitions immediately after time zone transitions demonstrate a decline in performance involving complex mental activities, with an associated feeling of lethargy and a general loss of motivation.

British Olympic athletes demonstrated a decrease in leg and back strength in addition to reaction time when traveling westward across 4 time zones. In the NFL, west coast teams consistently beat east coast teams in evening games.

Of course, this type of outcome data is multifactorial and travel effects likely are only one of many complex factors.

Treatment:

Full adaptation to the new time zone is NOT recommended for short trips (1 – 2 days), only for longer stays (> 3 days).

Nonpharmacologic: 

Preadaptation and bright light therapy: Remember that exposure to light is the primary cue for circadian rhythms. Bright light exposure in the mornings (after eastward travel) will advance the body clock, while exposure in the evenings (after westward travel) will delay it (Level B).

Shifting the sleep schedule 1 - 2 hours towards the destination time zone in the days preceding departure may shorten the duration of jet lag (Level B).

Strategic napping: Napping in the new time zone during typical sleep times in the destination time zone will delay adaptation. Power naps (20 minutes) may be helpful in decreasing daytime sleepiness in those with jet lag (Level B). The best time to nap (in flight or post flight) is nighttime in the destination time zone (Level B).

Pharmacologic:

Melatonin: Cochrane review concludes that it is safe and effective in both treating and preventing jet lag. It is recommended for adults traveling across 5 or more times zones; and may be effective for travel across 2 to 4 time zones. Take melatonin in the morning when traveling westward, and at the local bedtime when traveling eastward (Level B). Doses of 0.5 to 5mg were similarly effective. Melatonin taken in the evening and at higher doses are effective at inducing sleep (Level A).

Sleep aids:  Hypnotic sleep aids reliably induce insomnia secondary to jet lag. Benzodiazepines improve sleep quality but may cause a “hangover” effect the next day, possibly impairing performance.

Ambien (zolpidem) and Lunesta (zopiclone) can be effective while limiting the hangover effect especially in those who have previosly tolerated the medication (Level A). Zolpidem may be more effective than melatonin and placebo at countering jet lag symptoms. Note: the use of both medicines together was not more effective than zolpidem alone but did cause daytime somnolence.

Stimulants: Care should be used in the athlete as most of these medications are banned in competition. There is a potential off label use for Provigil (modafinil) for improving daytime sleepiness associated with jet lag (currently approved for narcolepsy).

Caffeine, while not banned for the World Anti-Doping Agency, is a monitored substance.  It increases daytime alertness and may accelerate entrainment in new time zones when consumed in the morning (later ingestion may interfere with sleep induction) (Level A).

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• small growth of grainy pink/redish tissue that forms on an area of the umbilical stump which is inflamed and produces a sticky mucous dishcarge not allowing normal tissue to grow on top of it
• caused by abnormal tissue healing after the remaining umbilical cord dries up and falls off
• treatment is painless as the granuloma lacks innervation, and requires applying chemical silver nitrate directly to the granumloma to burn the tissue off
• although rare, careful examination of the tissue is needed to enssure the tissue is not intestinal or bladder in origin

There is a growing recognition of patients who have a subtoxic acetaminophen level at the 4-hour mark, but then still go on to have a toxic level later.

This is concerning in that we usually can exclude the chance for toxicity if the 4-hour, post-ingestion level is < 150 mcg/mL following an acute ingestion (plotted on Rumack-Matthew nomogram).

It still is not clear exactly what subset of patients need to have a second level drawn, but a recurring theme seems to be ingestion of acetaminophen in combination with agents that slow GI motility, such as diphenhydramine or opioids. It may be worth ordering a second APAP level (possibly at 8 hours) in patients ingesting these prodcuts.

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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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Question

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Takotsubo cardiomyopathy a.k.a. stress cardiomyopathy is an acute reversible disorder characterized by left ventricular (LV) dysfunction most commonly affecting postmenopausal women

The LV adopts the shape of an octopus trap (“takotsubo”) describing the narrow neck and broad base globular form during systole

Symptoms include precordial chest pain, dyspnea, or heart failure presenting with pulmonary edema mimicking ACS

Mayo Clinic Diagnostic Criteria

 - Suspicion of AMI based on symptoms and STEMI on ECG

 - Transient hypokinesia or akinesia of the middle and apical regions of LV

 - Functional hyperkinesia of the basal region of LV

 - Normal coronary arteries (luminal narrowing <50%)

 - Absence of recent head injury, ICH, HCOM, myocarditis, or pheochromocytoma

Treatment is symptomatic and determined based on complications during the acute phase; occasionally requiring IABP or ECMO

Prognosis is better than those with ACS, however initial LVEF is similar to those seen with ischemic heart disease 

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A recent paper reviewed 53 articles to assess the utility of vasopressors in cardiac arrest. The authors aimed to determine if vasopressors improved ouctomes in this patient population. Here are their conclusions:

1. Epinephrine is associated with improvement in short term survival outcomes as compared to placebo, but no long-term survival benefit has been demonstrated.
2. Vasopressin is equivalent for use as an initial vasopressor when compared to epinephrine during resuscitation from cardiac arrest.
3. There is a short-term, but no long-term, survival benefit when using high dose vs. standard dose epinephrine during resuscitation from cardiac arrest.
4. There are no alternative vasopressors that provide a long-term survival benefit when compared to epinephrine.

Although these conclusions don't support the use of vasopressors in cardiac arrest, we should not abandon these therapies. Most of the trials were completed before wide-spread recognition of the post-cardiac arrest syndrome, implementation of therapeutic hypothermia protocols, and early cardiac catheterization.

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Henoch-Schonlein Purpura (aka. Anaphylactoid purpura) is a small vessel vasculitis.

Background:

• most commonly diagnosed vasculitide in childhood
• age range 3-15 years, mean age 4yo, mostly <7yo (75% cases)
• more cases in Winter and Spring months
• boys more commonly than girls (2:1)
• IgA-mediated leukoclastic vasculitis

Clinical Features:

• Rash: progresses to petechiae, purpura; occurs on lower extremities and buttocks in dependent areas
• Joints: arthritis/arthralgia mainly of large joints (knees, ankles)
• GI: colicky abdominal pain, may occur with melena (33%) or less likely, hematemesis; ultrasound for intussusception (2-14%)
• Renal: microscopic hematuria with/without proteinuria; usually transient but may lead to progressive renal disease in patients with more severe, persistent symptoms
• Orchitis and/or angioedema may also occur

Etiology:

• unknown
• preceding URI (50%)
• associated with bacteria (Strep pyogenes, Legionella, Mycoplasma), viruses (EBV, CMV, parvovirus), drugs (penicillin, cephalosporins), and insect bites

Diagnosis:

• clinical features
• lab studies that are helpful but nonspecific: high WBC, high ESR, high IgA, normal platelet and coagulation studies

Treatment:

• supportive care, may last up to 4 weeks
• steroids may be helpful but evidence has not shown true benefit
• recurrence happens in 40% of cases

Acute, uncomplicated cystitis (in the non-pregnant female):

·      The drug of choice is SMX/TMP (provided the resistance rate is <20%) X 3 days.

·      An alternative is nitrofurantoin X 5 days.

Acute, uncomplicated pyleonephritis (in the non-pregnanct female) may be treated with:

·      Levofloxacin X 5 days, or ciprofloxacin X 7 days (provided resistance rate is <10%).

·      Alternatively, SMX/TMP may be used X 14 days.

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Crystalloids (i.e., 0.9% saline and lactated ringers) have been used during resuscitation for more than a century. Their invention, however, was more accidental than intentional.

Crystalloids were first used during the European Cholera epidemic of 1831. Hartog Hamburger later modified this solution in 1896 to the solution we know today as "normal" saline. Hamburger's solution was only intended for in vitro study of RBC lysis and was never intended for clinical use.  

Around this time, Sydney Ringer was testing several fluids to use for physiologic studies. Ringer's lab assistant was erroneously substituting tap water for distilled water when preparing these solutions. Ringer later discovered that this tap water contained minerals making the solution "physiologic", isotonic, and safe for human use; Alexis Hartmann later added sodium lactate to create Ringer's Lactate. 

Since the invention of crystalloids, many types of resuscitation fluids have been created and studied (i.e., albumins, gelatins, and starches); all have been shown to be more expensive, with no more benefit, and with possibly more harm when compared to crystalloids. 

The "perfect" resuscitation fluid still alludes us today, but of all of the solutions marketed crystalloids are arguably the best...despite their accidental history.

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