Atrial Fibrillation: Resources & a few Papers

Hi team,

We recently discussed atrial fibrillation, which is a common medical problem you will encounter both in the in-patient and out patient setting. Here are a couple of resources, including papers and guidelines that serve as references on this topic.

AFFIRM trial- A Comparison of Rate Control and Rhythm Control in patients with Atrial Fibrillation

CHEST (abstract)-Predictive Value of the HAS-BLED and ATRIA Bleeding Scores for the Risk of Serious Bleeding in a “Real-World” Population With Atrial Fibrillation Receiving Anticoagulant Therapy

2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)

Acute Kidney Injury (AKI)- the kidneys are sort of a big deal.

The kidneys play a crucial role in BP regulation, hormone synthesis (i.e. EPO, Vitamin D), electrolyte homeostasis, acid-base balance and fluid balance. Here are a few other reminders as per our discussion on AKI this week.

Acute Kidney Injury (AKI): a rise in serum Cr 1.5x or more the baseline value within 48h

Rapidly Progressive Glomerulonephritis (RPGN): Cr rises within days to weeks. Can be insidious in nature and patients can present quite unwell. 

Major Approach to the patient with AKI: Pre-renal, Renal, & Post-renal

Clues regarding Chronic Kidney Disease (CKD)

·       GFR <60 for three months or more and/or evidence of kidney damage (albuminuria, urine sediment abnormalities or findings on renal imaging or biopsy

·       Renal U/S: small, echogenic kidneys (most consistent with CKD) –progressive loss of renal parenchyma and increased interstitial fibrosis over time *(keep in mind that the kidneys are NOT small in DM, amyloidosis acromegaly, HIV nephropathy), Anemia, Volume Overload, Electrolyte-Acid Base imbalance (i.e. hyperkalemia), Metabolic Acidosis, Ca/PO4 abnormalities (decrease in Vit D synthesis d/t reduction in function or amt of 1-alpha hydroxylase—increase PO4 d/t decreased filtration, decrease in Ca, increases PTHà renal osteodystrophy)

Always keep in mind URGENT or ACUTE indications for dialysis ("AEIOU"): acidosis (resistant to medical therapy), electrolytes abnormalities resistant to medical therapy (i.e. hyperkalemia), intoxication (ASA, Li, methanol), Overload (fluid overload resistance to medical tx); Uremia (pericarditis, encephalopathy)

Always keep RPGN on your list...

RPGN: a clinical syndrome characterized by features of glomerular disease in the urine (i.e. dysmorphic RBCs in the urine), and progressive loss of renal function over a short time period (i.e. days, weeks, months). Clinically, they can present with fatigue, edema, oliguria. The presentation may be insidious. Initial investigations reveal dysmorphic RBCs, hematuria, variable proteinuria, and elevation of Cr (usually >264). 

Morphologically, there are crescent formations evident; these are non-specific markers of a response due to severe injury to the glomerular capillary wall. Left unrecognized and un-treated, these patients can undergo rapid progression to end-stage renal disease (ESRD).

Approach to RPGN

1.Vasculitis (pauci-immune): ANCA +ve

• C-ANCA, with granulomas: Granulomatosis with polyangiitis (GPA, formerly called Wegener's) 
• P-ANCA: Microscopic polyangiitis (MPA) or churg-strauss

2.Anti-Glomerular Basement Membrane (GBM) Antibody Disease (linear)

• Anti-GBM Antibody
• Pulmonary hemorrhage: more in keeping with Goodpasture's
• No pulmonary hemorrhage: more in keeping with Anti-GBM disease 

3.Immune Complex/Complement Mediated (granular)

• Clinical history & order Complement levels
• low C3: DDx- IBE, HCV, SLE, Cryoglobulinemia, post-strep GN (PSGN), MPGN
• normal C3: DDx- IgA, Fibrillary, HSP

4. Double Antibody Positive Disease

• Pauci-immune, but ANCA-negative
• Immune Complex, but do not fit onto the list above

Investigations:

Labs: Cr urea (*compare to previous), lytes, extended lytes, CBC, UA, urine Cr, Urine lytes, peripheral smear

 Etiology: ANA, anti-ds DNA, ENA, P-ANCA, C-ANCA, anti-GBM Ab, C3, C4, CK, uric acid, ASO titre, HBV/HCV serology, RF, cryoglobulinemia, quantitative Ig, SPEP, UPEP, urine eosinophils

Initial Management

• Recognition is key! Call Nephrology consult in
• Pulse steroids: Methylprednisolone 1g IV daily x 3 days, followed by prednisone PO (i.e. 1mg/kg PO daily) for a few months, then a taper
• Immunosuppressants: often start Cyclophosphamide 2 mg/kg/d; duration R/A by nephrology
• +/- Plasmapharesis (PLEX): removes circulating antibodies (i.e. anti-GBM Antibodies) and other mediators of inflammation (i.e. complement)
• Initiated if pulmonary hemorrhage!
• Long term: careful follow-up, with bone health preventative measures given the long-term steroid use (i.e. Vitamin D, CaCO3, Bisphosphonate)
• Immunosuppressive therapy, consider PJP Prophylaxis with Septra DS 1 tab PO M/W/F

·  Clinical Practice Guidelines (KDIGO): Acute Kidney Injury

Meningitis Recap & The role of steroids in Bacterial Meningitis...

We recently discussed meningitis and an approach to the work-up and management of patients with meningitis. Here are a few key points:

Major causes of Community-Acquired bacterial meningitis in adults in developed nations: Streptococcus pneumonia, Neisseria meningitidis. In those >50 years, or those with immune deficiencies, consider Listeria monocytogenes.

Mortality is higher for S. pneumonia meningitis (9-26%) versus N. meningitidis (3-13%).

How good are our physical exam approaches?

Kernig’s sign: patient laying supine, with hips flexed >90; 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: both of these signs are specific, but both have a low sensitivity! These two tests were initially developed to assess patients with late, end-stage meningitis (i.e. caused by TB)

·          

        Jolt Accentuation of headache: patient turns their head horizontally at a frequency of 2-3 rotations per second. Worsening heachache = +ve sign, sensitivity 97%, specificity 60%

o NOTE: evaluated in a single study of 34 patients!

When to order a CT head prior to performing a Lumbar Puncture (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

o   Evidence; those without findings on hx or physical to suggest increase ICP, can safely undergo an LP without a prior head CT

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

§  Age >60

§  History of CNS disease, 

§  New onset seizures within 1 week

§  Focal neurological deficits/abnormalities

§  Papillodema

§  Obtunded/AMS

§  Immuno-compromised state (i.e. HIV infection, immune-suppressive therapy, solid organ/hematopoietic stem cell transplantation)

CT and/or performing a Lumbar Puncture: Should NOT delay empiric antibiotic therapy

• Ensure the patient is hemodynamically stable, protecting their airway, etc. 
• Draw blood cultures and administer empiric antibiotics, consider dexamethasone 0.15 mg/kg IV q6h (see Cochrane review link below)
• Cochrane Review (2010): summarized that the meta-analysis, although not demonstrating evidence of optimal strength, they recommended a 4 day regimen of dexamethasone (0.6 mg/kg daily) given before or with the first dose of antibiotics. This may reduce sequelae (i.e. hearing loss)

• Droplet precautions: H. influenza & N. meningiditis x24h of Abx
• Empiric Antibiotics “CVA”

o   Give Dexamethasone for acute bacterial meningitis 15-20 minutes before 1^st dose of Antiobiotics if suspicion for S. pneumonia (0.15 mg/kg or 10 mg IV q6h x4 days)à ? reduce mortality, ? reduce sequelae (i.e. hearing loss)

o   Ceftriaxone 2g IV q12h (or Cefotaxmine)

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

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

NOTE: If concern for HSV encephalitis, add acyclovir 10 mg/kg IV q8h

NOTE: IF culture comes back with N. meningididisà prophylaxis to household and those who have had intimate contact; Healthcare workers should receive prophylaxis if they have had direct contact with respiratory secretions.

Resources: Papers & Links

Infectious Disease Society of America (IDSA)- Guidelines on Meningitis

Corticosteroids for acute bacterial meningitis (Review). Cochrane Review (2010).

JAMA

Approach to Anemia: Recap!

Anemia: a reduction in one or more of the major RBC measurements obtained as part of the CBC (i.e. Hemoglobin concentration, hematocrit, or RBC count)

·      

Always consider the patient's volume status: concentrations (i.e. hemoglobin, hematocrit, RBC count) are all dependent on red blood cell mass (RCM) and plasma volume. Thus, the values of all three masses will be reduced if the RCM is decreased and/or the plasma volume is increased. 

Examples:

• Acute UGIB: a 70 kg adult with a UGIB from a peptic ulcer, with 750 mL hematemesis (i.e. 15% normal total blood volume) within the last 30 minutesà likely to have postural hypotension due to acute volume depletion, but he/she will have normal hemoglobin (Hb) & hematocrit (Hct). Over the next 48 hours, most of the total blood volume deficit will be repaired by movement of fluid from extra-vascular into the intra-vascular spaceà only during these later times will the Hb and Hct reflect blood loss!!
• Pregnancy: in the third trimester (T3), the RBC mass and plasma volume are expanded by 25 and 50% respectively, resulting in reductions in Hb, Hct and RBC count
• Volume depletion: initial Hb may appear normal, due to hemoconcentration

Special Populations to consider in Anemia: Altitude (higher values), Smokers (carboxy-hemoglobin & polycythemia), ethnic differences (lower Hb values in African Americans vs Caucasians), Chronic Disease, Athletes

RBC lifespan: Erythropoiesis in the BM (influence: cytokines, erythroid specific growth factors, EPO); mature RBCs circulate for 110-120 daysà then they are removed from the circulation via macrophages

·      

    Under steady-state conditions: Rate of RBC production= rate of RBC loss

APPROACH & CAUSES: Kinetic (mechanistic) vs Morphological (MCV)

·        Morphological Approach

Microcytic Anemia: MCV<80 fl; most commonly iron (Fe) deficiency, thalassemia minor, ACD. Think "TAILS"...

Thalassemias: decrease synthesis of alpha or beta globin chains of Hb, leading to destruction of RBCs & erythroid precursors

• MCV is usually quite low (<70), normal Fe, more narrow RDW then Fe deficiency
• Thalassemia index: MCV/RBC; <13 suggests Thalassemia, >13 Fe deficiency
•  Target cells, basophilic stipling
• Order Hb Electrophoresis

Anemia of chronic inflammation: impaired Fe utilization and reduction in EPO responsiveness due to hepcidin and cytokine increase in the setting of autoimmune diseae, chronic infection, inflammation, malignancy, etc

• High/Normal Ferritin, TIBC low, Fe low

Iron Deficiency: you always must determine how and where the iron is being lost. Considerations include chronic GI bleeding, menstrual loss (i.e. menorrhagia), reduced supply (cases of malnutrition, poor absorption, high gastric pH), increased demand (i.e. pregnancy)

• Low ferritin, increase in TIBC (transferrin), low Fe

·       Lead Poisoning

      

      Sideroblastic: defective heme biosynthesis within RBC precursors

•       Causes: hereditary, idiopathic (MDS), Reversible (EtOH, lead, isoniazid). Fe increased, ferritin increased, normal TIBC. Smear may show basophilic stippling and ringed sideroblasts.
• 
  

Normocytic Anemia: MCV 80-100 fL

Acute Blood Loss: GI, GU, pelvis/abdomen, skin, CNS

Decreased Production

• Primary BM disorder: Bone marrow (BM) suppression from drugs (Chemotherpay), MM, Myelodysplasia, Myeloproliferative disorders, lymphoma, mets, infections (i.e. TB)
•  Decreased EPO: CKD
• Anemia of Chronic Disease

Sequestration: Splenomegaly

Increased Destruction

• Immune: AI hemolytic anemia (Warm & Cold agglutinins)
•  Non-immune

o   RBC membrane: spherocytosis

o   RBC enzyme: G6PD, pyruvate kinase deficiency

o   RBC HB: Sickle Cell Anemia

o   MAHA: DIC, HUS/TTP, HTN (malignant), drugs

o   Blood: toxins, infections (malaria)

Mixed Picture: combined microcytic and macrocytic

Macrocytic Anemia: MCV> 100 fL (femtoliters)

·       Reticultocytosis

·       Impaired DNA synthesis: Vitamin B12 and Folate deficiency

•        Low folate: malnutrition (EtOH, anorexic, elderly), decrease in absorption (celiac), impaired metabolism (MTX, TMP, hydroxyurea)
•       Low Vitamin B12: this vitamin is found in foods of animal origin. Normally, vitamin B12 binds intrinsic factor (IF), which is secreted from gastric parietal cells; absorption of vitamin B12 occurs in the terminal ileum (TI)
•  Malnutrition (vegans, EtOH), pernicious anemia (AI disease against gastric parietal cells), dec abs (celiac, Crohn’s), bacterial overgrowth

·       EtOH use/abuse

·       Liver disease

·       Hypothyroidism

·         Drugs: Chemo (hydroxyurea, MTX, azathioprine), AEDs (phenytoin), Abx (TMP-SMX)

·         MDS, Acute Leukemia

·       Paroxysmal Nocturnal Hemoglobinuria (PNH)

Clinical

 Symptoms: more profound with a more rapid onset vs. a slow evolution of anemia.  Symptoms are due to decreased O2 delivery to tissues +/- hypovolemia. Reduction in O2 deliveryà fatigue, exertional dyspnea, increased cardiac demand (may have angina, bounding pulses, palpitations), CHF, confusion, arrhythmia

-Inquire about GIB (hematemesis, hematochezia, melena), Gyne (menorrhagia); constitutional symptoms, chronic infections, rheumatological conditions, diet, meds (NSAIDs, ASA, anticoagulation), FHx (thalassemia), fatigue

- Ethnicity: thalassemias & other hemoglobinopathies—more common in Mediterranean, Middle East, sub-Saharan Africa & SE Asia

-Acute bleed: volume depletion can cause fatigue, muscle cramps, dizziness, lethargy, syncope, persistent hypotension, shock and death

Physical Exam Signs

•  VS: postural drop, hypotensive, tachycardia
• Pallor (mucous membranes, palmer creases, conjunctiva), jaundice (Bili>40) tachycardia, orthostatic hypotension; LAD, consider DRE with FOBT, HSM, Bone pain
• Nail changes, atrophic glossitis; petechiae, ecchymoses

Diagnostic Work-up

• CBC (always track down and compare to recent previous CBC), peripheral smear
• Reticulocytes
• Fe studies: Fe, Ferritin, TIBC (transferrin), % saturation
•  Hemolysis evaluation (smear- fragments/spherocytes), increase LDH, indirect bilirubin and reduction in haptoglobin. A  combination of increased LDH & reduced Haptoglobin= 90% SPECIFIC for hemolysis
• Intravascular hemolysis: plasma & urinary Hb, urinary hemosiderin (? PNH)
• May need to consider bone marrow aspirate and biopsy, SPEP & UPEP (if ? Multiple Myeloma)