Anaphylaxis: An Interesting Diagnostic Test...

Hi everyone,

Today, we had noon rounds on the topic of drug reactions, allergies and anaphylaxis. 

We recently chatted about Anaphylaxis at Morning Report last week, but I wanted to include an interesting diagnostic pearl. The following test is actually available at LHSC and is recommended by the allergists when you see a patient whom you are treating as anaphylaxis, but perhaps are not sure that this is the definitive diagnosis.

Confirming the Diagnosis: The Role of Tryptase measurement?

Elevated levels of total tryptase in the serum can be useful to help distinguish anaphylaxis from other conditions on the DDx (i.e. vasovagal episode, MI, benign flushing, carcinoid syndrome, etc—as these other disorders are normally not associated with an elevation of total tryptase).

An increase in tryptase indicates that mast cell activation has occurred.

Bottom Line: some hospitals allow you to order tryptase levels; collection of tryptase measurements should be done if the diagnosis of anaphylaxis is being considered. Elevations in tryptase correlate with hypotension and support the diagnosis of anaphylaxis, however; normal levels do not exclude anaphylaxis (especially in food-induced reactions). The specificity and sensitivity of tryptase elevations have not been elucidated. Try to collect the sample within 1-3 hours of the event. Generally, large elevations of the tryptase level persist for several hours after the onset of the query anaphylaxis.

Thank you all for a great first block!

-Jade

Approach to Hyponatremia- Summary!

Hi Team,

We recently reviewed Hyponatremia (Na<135 mmol/L).

A few key points to keep in mind:

THE ISSUE: hyponatremia is a disorder of WATER balance, not sodium. In virtually all patients, this results from the intake (oral or IV) and subsequent retention of water. Normally, patients can handle a “water load” via renal excretion, as the dilutional fall in serum osmolality suppresses the release of ADH, thus, allowing excretion of the excess water in the form of a dilute urine. The maximum attainable urine volume in normal people on a regular diet is >10 L/day. This provides us with an enormous range of protection against the development of hyponatremia since the daily fluid intake in most healthy individuals is <2-2.5 L/day

DON’T FORGET THE HORMONES THAT GOVERN WATER AND SODIUM HOMEOSTASIS:

-Antidiuretic Hormone (ADH): synthesized in the hypothalamus, secreted to the posterior pituitary where it is stored and subsequently released. Stimulus for secretion include:

1) High Plasma Osmolality

2) Low intra-vascular volume/volume depletion

ADH increases water permeability in the collecting tubules of the kidney (via aqua-porin 2 channels), increasing water absorption and thus increasing urine osmolality but decreasing serum osmolality

-Aldosterone: regulated by intra-vascular volume via the renin-angiotensin system (RAS) and also regulated by sodium levels and hyperkalemia. Aldosterone stimulates the Na-K+ exchange pump in the distal tubule, to increase sodium reabsorption and decrease urine sodium.

THE APPROACH

-Determine Osmolality & Exclude “Pseudo-hyponatremia” Causes

1) ISO-OSMOLAR HYPONATREMIA

·       “Pseudo-hyponatremia”: sodium may be falsely elevated in the setting of paraproteinemia (elevated plasma proteins) and hypertriglyceridemia. This occurs, because sodium is only present in the aqueous portion of the blood, whereas, protein and lipids are present in the non-aqueous portion. The lab analyzer measures sodium over the entire blood volumes—and not just the aqueous portion. Thus, with a higher proportion of protein and triglycerides, the sodium value is divided over a larger total blood volume, creating a hyponatremic value

·          -Theoretical concern that utilizing glycine or sorbital flushing during a TURP can cause hyponatremia

2) HYPEROSMOLAR HYPONATREMIA

·        Hyperglycemia: for every glucose value increase of 10 mmol/L above the level of 10 mmol/L, add 3 mmol/L to the Na value; high serum osmolesà increase water absorption in the intravascular spaceà dilutes the Na *(this is a true hypoNa); once the glucose is corrected, the Na will naturally move back towards it’s baseline value

3) HYPOOSMOLAR HYPONATREMIA

·       Assess volume status: Hypovolemia, Euvolemia, Hypervolemia

·       The volume status governs your differential diagnosis (DDx)

Hypovolemic: renal loss (diuretics, hypoadrenalism, Bartter’s, hypomagnesemia), GI loss (N/V/Diarrhea), 3^rd spacing, blood loss, skin loss (sweat, burns).

·       Exam: tachycardia, hypotension, orthostatic VS, dry MM, poor skin turgor;

·       Investigations: elevated Urea:Cr ratio;

·       Decrease in intravascular volume à Increases ADHà  Increases urine osmolality (>100, often higher)

·       Decrease in intravascular volume à  Increases aldosterone à decreases urine Na (<20)

·       Treatment: NS infusion. Can consider hypertonic saline + furosemide (More water loss relative to Na loss) if severe- but use caution!

Euvolemic: Non-SIADH (Low solute diet, Hypothyroidism, Adrenal Insufficiency, Psychogenic Polydipsia) versus SIADH causes (Physiological-pain, nausea, stress, anxiety; Cancer-SCLC, duodenum, thyoma, pancreatic, lymphoma; Lung- cancer, TB, pneumonia, abscess, empyema; CNS- skull fracture, SDH, SAH, meningitis, mass/neoplasm, GBS, acute intermittent porphyria; Drugs-opioids (i.e. morphine), carbamazepine, SSRIs, TCAs, vincristine, oxytocin, general anesthetic)

·       Exam: euvolemic

·       SIADH: diagnosis requires a cause available, a clinically euvolemic patient, High Urine Na (>40), high urine osmolality (>100, but, usually >300), usually a high specific gravity. Need to rule out AI, hypothyroidism, PP, and diuretic use

·        Increases ADHà  Increases urine osmolality (>100, but usually, >300)

·        Increase ADHà  Increases intravascular volume à Decreases aldosterone à Increases urine Na (>40)

·       Treatment: Free Water Restriction <1 L/day; for SIADH, may consider Demeclocycline (tetracycline that inhibits action of ADH); NS may be needed, but, tx the underlying cause

In Psychogenic Polydipsia: the primary problem is an increase in intravascular volume d/t water intoxication:

 Increase in Intravascular volume à Decreases ADHà Decreases Urine Osmolality (<100)

 Increase in Intravascular volume à Decreases Aldosterone à increases urine Na (>20)

Hypervolemic: CHF, GI protein losing enteropathy, cirrhosis, nephrotic syndrome, malnutrition (can decrease albumin, effecting oncotic pressure)

·       On exam: elevated JVP, Crackles, edema, ascites

·       Investigations: pulmonary edema on CXR;

·       Actual Decrease in intravascular volume à Increases ADHà Increases urine osmolality (>100, often higher)

·       Actual Decrease in intravascular volume à increases aldosterone à Decrease in urine Na (<20)

·       Treatment: sodium & Free Water restrict (<1L/d). Treat the underlying cause. May need Lasix.

NOTE: urine osmolality & urine Na levels are the same in hypovolemia and hypervolemia; the only way to tell the difference is with clinical exam

TREATMENT GUIDELINES: Correction Rate should correct 0.5 mmol/h or 12 mmol/24h to reduce the risk of Osmotic Demylination Syndrome (formerly known as Central Pontine Myelinolysis). Note that these correction rules are not perfect, but are merely a guideline and help you conceptualize your rate of correction.

Steps & Example: Patient with a sodium of 119 mmol/L that you want to raise to 123 mmol/L over a defined time period with plans to re-assess the electrolytes and rate of infusion of IV fluid

STEPS

1.Calculation of Na deficit per liter= Na goal – Current Sodium (i.e. 123-119= 4 mmol/L

2.Calculation of Total Body Water (L)= 0.5 (female) x weight (kg); use 0.6 for men

i.e. 60 kg x0.5= 30 L TBW

3.Calculate Total Sodium Deficit per liter for Initial Therapy= sodium deficit/L x TBW (L)i.e. 4 mmol/L x 30 L= 120 mmol

4. Calculate the Total Amount of IVF to be given: i.e. for NS (1L= 154 mmol Na); 1L/154 mmol= x/120 mmol = 0.779 = ~ 800mL of 0.9 NS

5. Calculate the Infusion Rate: 800 mL/desired time (i.e. 6h)= 133.3 mL/h for 6h then reassess

Recall Concentrations: D5W (dextrose 5% in water)=0 mmol/L; ½ NS (0.45 NaCL)= 77 mmol/L; Ringer’s Lactate= 130 mmol/L; NS= 154; Hypertonic (3%)= 513 mmol/L

What if the patient was seizing and this was an acute drop in Na?

-Give HYPERTONIC saline! Slow, once in the moderate range of 125-129

RISK FACTORS FOR OSMOTIC DEMYLINATION SYNDROME?

3 MAJOR RF: serum [Na+] at presentation, duration of hyponatremia, & rate of correction

·          More common if presenting Na 120 or less

·         More common in chronic cases, or even >2-3 days

·         More common with elevation of Na >10 mmol in a 24h period and >18 in 48h

Prevention is key!

NOTE: if you over-correct, consider Desmopressin (ADH): 2 mcg IV or SC q6h, or therapeutically lower the Na with IVF (i.e. 5% dextrose in water (D5W), 6 ml/kg lean BW, infuse over 2h, which should lower the Na by 2 mmol/L) 

Acute Pancreatitis- consideration of feeds in patients with protracted hospital stay

Hi Team,

We recently discussed approach to Acute Pancreatitis.

One point that I thought was interesting to discuss a bit further is the role of nutrition in patients that have a prolonged course of complicated pancreatitis (i.e. those in the ICU).

For those who have a normal course of acute pancreatitis, we keep them NPO initially to provide bowel rest and subsequently advance the diet in a few days once the nausea, vomiting and pain have settled. We typically would start a clear fluid diet at that point and advance as tolerated.

In patients with prolonged and protracted courses of pancreatitis, consideration of nasogastric (NG) or nasojejunal (NJ) tube feeds should be considered.

There is evidence that enteral feeding in this group of patients can be beneficial (more so than parenteral feeds) with respect to lowering the rate of hospital acquired infections, decreasing the incidence of surgical intervention and reducing the length of hospital stay. There may be a theoretical benefit to NJ versus NG feeds, as NJ feeds bypass the need for pancreatic secretion.

Article: "Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis", Marik, P.E. et al, BMJ 2004

 http://www.bmj.com/content/328/7453/1407.reprint

Some key points on Meningitis...

Hi everyone,

We recently covered our approach to meningitis, and I wanted to highlight some of the discussion points.

Epidemiology: Major causes of Community-Acquired bacterial meningitis in adults in developed nations include Streptococcus pneumoniae (gram positive diplococci) & Neisseria meningitidis (gram negative diplococci). In those >50 years, or those with immune deficiencies consider Listeria monocytogenes (gram positive rods & cocco-bacilli).

History: Classic triad includes fever, nuchal rigidity, & altered mental status (AMS). In patients with meningitis, 99% of patients have 1 of the 3 components. Fever is the most sensitive of the triad. Thus, if the patient does not have fever, neck stiffness or AMS on examà meningitis is virtually ruled out! Other things to inquire about include nausea, vomiting, photophobia, headache, lethargy, recent URTI, inner ear infection (i.e. OM), sinus infection, or mastoiditis. Focal neurological deficits (i.e. cranial nerve palsies) typically occur later in the course. Inquire about dermatological manifestations (i.e. N. meningiditis can cause petechiae, palpable purpura). Ask about arthralgia or any active joints.

Physical Exam Pearls-Review of Meningeal Signs:

Kernig’s sign: patient laying supine, with hips flexed >90 degrees; extension of knees from this position elicits resistance or pain in low back or posterior thigh

Brudzinksi’s sign: passive neck flexion in the supine patient results in flexion of the knees and hips

NOTE: these signs are specific, but have a low sensitivity! 

Article: Thomas K, et al. The diagnostic accuracy of Kernig’s sign, Brudzinski’s sign, and nuchal rigidity in adults with suspected meningitis. Clin Infect Dis 2002; 35: 46-52. 

Link:

http://cid.oxfordjournals.org/content/35/1/46.full.pdf+html

Jolt Accentuation of headache: patient turns their head horizontally at a frequency of 2-3 rotations per second. Worsening h/a = +ve sign, sensitivity 97%, specificity 60%. Note that this was only evaluated in a single study, which had an N of 34 patients!

CT head prior to LP

CT head: may demonstrate structural abnormalities (ICH, brain abscess, tumor); risk of herniation in performing an LP when the patient has a mass/increased ICP. Evidence suggests that those without findings on history or physical to suggest increase ICP, can safely undergo an LP without a prior head CT

2004 IDSA Guidelines: A CT head is indicated before LP if 1 or more of:

Age >60, history of CNS disease, new onset seizures within 1 week, focal neurological deficits/abnormalities, papilledema, obtunded/AMS, & immune-compromised state (i.e. HIV infection, immune-suppressive therapy, solid organ/hematopoietic stem cell transplantation)

Article:  

Hasbun R, et al. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001; 345: 1727-33

http://www.nejm.org/doi/pdf/10.1056/NEJMoa010399

Lumbar Puncture Pearls

If LP is delayed (i.e. d/t CT head), draw blood cultures and administer empiric antibiotics, consider dexamethasone 0.15 mg/kg IV q6h. Appreciate that administration of antibiotics will reduce the yield of the gram stain (untreated cases: gram stain is 60-80% sensitive, versus 40-60% in cases of partially treated meningitis).

Mortality: Higher for S. pneumoniae meningitis (19-26%) versus N. meningididis (3-13%)

Management: ABC, IV, O2, Intubation is severe deterioration in LOC and not protecting the airway

-Droplet precautions: H. influenza & N. meningiditis , until 24h of Abx therapy has been given

-Empiric Antibiotics “CVA”

-Give Dexamethasone for acute bacterial meningitis 15-20 minutes before 1^st dose of Abx if suspicion for S. pneumoniae (0.15 mg/kg or 10 mg IV q6h x4 days)à some literature to suggest it may reduce mortality and reduce adverse sequelae (i.e. sensorineural hearing loss) in meningitis, specifically S. pneumoniae

-Ceftriaxone 2g IV q12h (or Cefotaxmine)

- Vancomycin 1-1.5 g IV q12h: to cover resistant S. pneumoniae (penicillin-resistant Pneumococci coverage until sensitivities are known!)

-Ampicilin 2g IV q4h if: age >50, immune-compromised (to cover Listeria)

-If concern for HSV encephalitis: acyclovir 10 mg/kg IV q8h

NOTE: If culture comes back with N. meningiditisà prophylaxis to household and intimate contact. Prophylaxis for health care workers only if they were in direct contact with respiratory secretions *(should have been on droplet!)

More information on use of corticosteroid administration:

Article:  Assiri M, et al. Corticosteroid administration and outcome of adolescents and adults with acute bacterial meningitis: a meta-analysis. Mayo Clin Proc 2009; 84: 403-9.

http://www.mayoclinicproceedings.org/article/S0025-6196(11)60558-2/abstract