Intern Report 6.9

Case Presentation by Dr. Eugene Rozen

CC:

Suicide attempt by pill ingestion

HPI

History is provided by the patient and her parents.

This is a 15-year-old female that arrived via ambulance to the emergency department at Children’s Hospital of Michigan 2½  hours after intentionally ingesting an unknown quantity of aspirin and acetaminophen in a suicide attempt. She denies taking any other pills of any kind. She denies having ingested any alcohol or recreational drug. At presentation she is complaining of abdominal discomfort with nausea, and has had several episodes of non-bloody, non-bilious vomiting. She denies headache, dizziness, alterations in vision, tinnitus, LOC, dyspnea, chest pain, or palpitations.

ROS

General: Malaise

Neurologic: No dizziness or headaches

HEENT: No changes in vision or tinnitus

Respiratory: No dyspnea

Cardiovascular: No chest pain or palpitations

Gastrointestinal: Negative except as stated in HPI

Musculoskeletal: No weakness, no trauma

Genitourinary: No dysuria, no hematuria

Integumentary: No rashes

Psychiatric: Initially wanted to commit suicide but presently denies suicidal ideation and regrets what she has done

Physical Exam

Vitals: T 36.5ºC, HR 108, RR 24, BP 109/80, O­2 Sat 100% ORA

General: In NAD on stretcher.

Head: Normocephalic, atraumatic

Eyes: PERRL 5mm, Non-icteric, non-injected, EOMI

ENT: TM intact, No rhinorrhea, no nasal flaring, no pharyngeal erythema

Respiratory: Tachypneic with clear, bilateral air entry and no retractions

Cardiovascular: Tachycardic. Regular rhythm, S1, S2 with no murmur.  Radial and pedal pulses are strong and symmetric

Abdomen: Soft, non-tender, non-distended. BS normal in 4 quadrants.

Musculoskeletal: Full passive range of motion in all joints. No tenderness or swelling.

Neurologic: No focal deficits, cranial nerves intact.

Psych: Awake, alert and interactive.

Ancillary Studies

APAP @ 4 hours: 40

ASA @ 4 hours: 55 mg/dL

UDS: Negative except APAP, aspirin

ABG: pH 7.43, pCO2 27.6, Bicarb 19.1, pO2 100 (RA)

CBC: w 18.5 (85%N, 10%L 5%M); h/h 13.4/39.4; p 340

BMP:

136

103

11

108

4.3

18

0.72

ALT 65, AST 45

UA: Clear, Yellow, pH 6.0, SG 1.023, Blood 1+, Bac 2+, RBC 5-10, otherwise normal

UhCG: negative

ECG: Sinus tachycardia, otherwise normal

CXR: No acute cardiopulmonary process

Questions:

1. Which of the following is most representative of an ABG in a patient with moderate ASA toxicity?

a)  pH 7.34 pCO2 33 HCO3 16

b)  pH 7.38 pCO2 30 HCO3 20

c)  pH 7.32 pCO2 52 HCO3 27

d)  pH 7.29 pCO2 52 HCO3 16

2. Which of the following is an absolute indication for hemodialysis in acute ASA toxicity?

a)  pH >7.45 on ABG

b)  Salicylate level of 65mg/dL

c)  Hyperventilation

d)  New crackles on lung auscultation

3. Which of  the following  is true regarding acute and chronic salicylate ingestion?

a)  Chronic ingestion carries a significantly lower mortality than acute ingestion

b)  Hemodialysis is indicated at a higher ASA level in chronic ingestion than in acute ingestion

c)  ASA toxicity may present in a nearly therapeutic level of ASA in chronic ingestions

d)  Chronic aspirin ingestion is common in children

Answers

1. B

The metabolic manifestations of ASA ingestion are mixed metabolic acidosis and respiratory alkalosis. Although they reciprocate, they are actually independent processes. Answer choice B shows a primary metabolic acidosis. When compensation is calculated (either by Winter’s formula, HCO3+15, or the comparing the pCO2 and after-decimal digits of the pH) this option shows a superimposed respiratory alkalosis. Option A is incompletely compensated metabolic acidosis, Option C is respiratory acidosis and Option D is mixed respiratory and metabolic acidosis.

2. D

Hemodialysis is a therapeutic measure taken either in the presence of symptoms indicating severe toxicity or in patients who have failed other treatments. The absolute indications in acute toxicity are a salicylate level >75mg/dL, pulmonary edema, central nervous system symptoms, renal failure, severe acidosis and increasing salicylate levels despite other treatments.

An alkalotic pH may be from bicarbonate therapy or from hyperventilation, but in either event it is likely a good sign, as severe toxicity is associated with acidosis. Hyperventilation is a symptom seen in mild toxicity that can be treated with more conservative therapy. In chronic salicylate toxicity, a serum level >50mg/dL is an absolute indication for hemodialysis.

3. C

Even in acute ingestion, ASA levels do not actually correlate with severity of disease and toxicity may persist at nearly therapeutic levels. Chronic toxicity may be difficult to identify because its symptoms mimic cardiopulmonary conditions, there may not be a history of ingestion and serum levels may even be within normal levels.

Chronic ingestion has a 25% mortality compared to 1% with acute. Hemodialysis is indicated at 50mg/dL in chronic ingestion, compared to 100mg/dL for acute. Before the association was made between Reye’s syndrome and aspirin, children would actually commonly present with chronic ingestion toxicity when treated for fevers or colds. This would be a self-propagating cycle since the symptoms of ASA toxicity may resemble the conditions the aspirin was meant to treat. These days, young children do not commonly receive ASA for fevers/viral syndromes and their presentations are usually due to acute ingestions.

Discussion

Aspirin overdose is a physiology-heavy topic. The patient described in the case did not need the level of intervention that will be discussed below, but I realized during that shift and in researching this topic that she could have been critically ill and I would have been unprepared to treat her properly. I’ve made this discussion rather dense in the way of basic science, but I think that an understanding of the pathophysiology in this case makes the clinical portion logical and largely self-evident.

Salicylism

Salicylates are derived from the bark of trees from the genus Salix (as in salicylate) and Spiraea (as in aspirin) and have been used for millennia to treat pain, fevers, and inflammation. Near the end of the 19th century, the Friedrich Bayer Dye company developed a chemical synthesis for acetylsalicylic acid from Spiraea bark extracts by a reaction similar to the one for converting morphine into heroin (a product developed by the same company). Bayer AG, as it is now known, patented acetylsalicylic acid as Aspirin and began selling it in 1899. It’s other wonder drug, Heroin, continues to sell like hotcakes.

Mechanism of Toxicity

The pharmacological mechanism of acetylsalicylic acid (ASA) is irreversible inhibition of cyclooxygenase 1 and 2 (blocking the synthesis of prostaglandins, prostacyclins and thromboxanes), disruption of the kallikrein-kinin system (inhibiting polymorphonucleocyte chemotaxis and granulocyte adherence to damaged endothelium), and inhibition of interleukin-1 (a macrophage-derived mediator that causes pyrexia). Together these functions, primarily its effects on prostaglandins and thromboxanes, serve to decrease pain, fever, inflammation and thrombosis.

 6.9-0

At low doses, the inhibition of these physiologic functions causes ASA’s common adverse effects, erosive gastritis, GI bleeding, and impaired hemostasis. At higher levels, ASA can interfere with cellular respiration, which is the principal method by which it induces toxicity, referred to as Salicylism.

6.9-1

Within the mitochondria, a proton gradient created by the tricarboxylic acid cycle and the electron transport chain between the intermembrane space and the mitochondrial matrix powers ATP synthesis (figure 1), this is called oxidative phosphorylation. Aspirin interferes with this cycle by buffering and transporting the protons across this membrane, thereby decreasing the potential of the gradient. When this happens, the reactions of the TCA cycle and the ETC are rendered futile, since a lesser amount of ATP is produced. This activates alternative pathways for ATP generation: anaerobic glycolysis and fatty acid oxidation. The upregulation of these two processes induces lactic acidemia and the formation of ketone bodies, respectively. The relative inefficiency of anaerobic glycolysis, which creates approximately 2 ATP molecules per glucose compared to aerobic cellular respiration, which creates approximately 32 ATP molecules per glucose, may deplete glucose stores, resulting in clinical hypoglycemia. Aspirin at high concentrations or prolonged exposure can also induce apoptosis via increased membrane permeability of mitochondria, but this is a complex process and less relevant for clinical medicine.

ASA’s toxic manifestations are dose dependent and begin in the hair cell of the ear. ASA, possibly through a mechanism similar to its effect on mitochondria, can affect the voltage-dependent membrane capacitance of outer hair cells. Through mechanisms that are beyond the scope of this discussion, tinnitus and reversible hearing loss result. These are often present in acute aspirin toxicity, but are also features of chronic ASA use. With chronic toxicity, ASA may also induce the synthesis of prestin, a membrane protein that alters the piezoelectric qualities of the hair cells, leading to hearing deficits.

At slightly higher doses, ASA begins to affect the brainstem. Most sources  state that this is due to “direct stimulation” of the respiratory center in the medulla. The putative mechanism is that the locally diminished ATP and resulting acidic environment stimulates tachypnea, as would hypoxia and hypercarbia. The result of the tachypnea is a respiratory alkalosis and one of the early objective findings in these patients. The renal response to respiratory alkalosis is elimination of bicarbonate which complicates the toxicity at higher levels.

At these higher levels, the effect on the mitochondria can become systemic with accumulation of lactic acid and ketone bodies. The renal elimination of bicarbonate as a compensatory response to the primary respiratory alkalosis causes a decrease in the acid-buffering ability of the blood. An additional contribution to the systemic acidosis is made by the kidneys.  ASA can result in renal damage through its inhibition of prostaglandins which normally serve to vasodilate the intrarenal vasculature. The resultant hypoxic damage can cause the kidneys to not only have diminished capacity for acid-base compensation, but to also retain inorganic acids (phosphoric and sulfuric), which are the primary mechanism by which the nephron excretes hydrogen atoms.  The kidney’s ability to handle acidosis is further diminished by the inhibitory effect of ASA on alpha-ketoglutate dehydrogenase, a TCA enzyme involved in renal ammoniagenesis, a secondary mechanism of renal acid buffering. This effect is compounded by prerenal azotemia caused by volume losses in the form of vomiting and insensible losses from tachypnea and diaphoresis. The metabolic derangement seen in ASA-intoxicated patients is mixed respiratory alkalosis and metabolic alkalosis with a wide anion gap.

As the plasma levels of ASA increase further, central nervous system and pulmonary cell abnormalities result, which in turn cause edema of these tissues. These mechanisms are not fully understood but may result from both direct cellular damage and alteration in hemodynamics leading to vasoconstriction.

Principles of Treatment

There is no antidote to aspirin and the approach to management relies on managing symptoms supportively and decreasing absorption of ASA until elimination of ASA from the serum and tissues, the mainstay of therapy, is successful. The theoretical basis of the latter two will be discussed here, and supportive treatments  specific to ASA intoxication will be discussed in the Clinical Approach section.

Decreasing absorption is generally of little value. Until recently, gastric lavage and induced emesis were used to cleanse the stomach of ASA but it has been commonly accepted that these treatments are not benign and that the risks posed by their implementation are not justified by the marginal benefit they produce.6.9-2J Activated charcoal (and its DIY alternative, burnt toast) remains controversial. The mechanism of action of activated carbon is that is has an enormous surface area (1 gram may have a surface area equal to 500-1,500m2) and a chemical milieu that promotes the non-covalent adsorption of many small organic molecules including aspirin and the salicylates (figure 2). When given orally, it can bind ASA, precluding its systemic absorption via the small intestine.  It works best when given early, but ASA may come in extended release formulations and is known to not only delay gastric emptying and cause pylorospasm, but also to form gastric concretions which cannot be rapidly broken down by digestion. The result of these combined factors is that a large acute ingestion may take up to 12 hours to be fully absorbed and reach peak plasma levels – compared to 1-2 hours in regular 6.9-00doses – and that administration of activated charcoal later in the patient’s presentation may still be beneficial.

Elimination of ASA in mild-moderate toxicity relies on the concept of ion trapping. Acetylsalicylic acid and its main bioactive metabolite, salicylic acid, are weak acids with pKa 3.5, and 3.0, respectively. So long as they are un-ionized, i.e. protonated and uncharged, their passage through cellular membranes is facilitated. This includes peripheral tissues, the blood brain barrier, and the cellular membranes that line the nephrons. If they can pass through these cellular barriers they are more likely to cause toxicity to the tissues, most importantly the brain, and more likely to be reabsorbed in the nephrons, prolonging their time in the body.

The basis of ion trapping is that a deprotonated weak acid (its conjugate base) is a charged molecule (ion) and as such is considerably more polar; causing it to form aqueous complexes and impeding passage through non-polar cellular membranes. It is essentially trapped in the extracellular fluid which keeps it from exerting its toxic effects on the tissues and keeps it in the nephron lumen from which it is ultimately excreted with the urine.

If the Henderson-Hasselbach equation is applied to ASA at a pH of 7.1, an acidotic serum value typical of salicylate toxicity, the concentration of the ionized conjugate base is roughly 4,000 times that of the unionized acid (i.e. for every uncharged molecule, there are 4,000 ionized molecules). At a pH of 7.5, a therapeutic target value discussed later, that ratio increases to nearly 8,000. For salicylic acid, whose toxic effects are comparable to ASA’s, these values are 12,500 and 31,600, more than a 2.5-fold increase. At a pH of 8.0, the ASA ratio is increased to 30,000:1 and the salicylic acid ration is increased to 100,000:1. Having a larger fraction of the molecules in the ionized form decreases the exposure of CNS cells to the toxins and speeds the toxins’ elimination.

It is not always the case that the patient’s condition permits the time necessary for this detoxification. This elimination may also be disrupted in patients with renal impairment which, inconveniently, is a known adverse effect of chronic ASA ingestion. In these cases extracorporeal hemodialysis may be a therapeutic necessity.

Clinical Approach

6.9-3The pathophysiology of ASA toxicity provides a logical framework for understanding its clinical manifestations. Evaluation of the patient can vary depending on the acuity of disease, and if the clinical situation permits it, a history should be attained that can elucidate the quantity of ingestion and the time course. The presence of comorbidities may hint at the possibility of chronic toxicity, which will affect treatment. As with the evaluation of other toxidromes, the clinician should make an effort to elicit the presence of coingestants.

Figure 3 shows the clinical manifestations of acute ASA toxicity and the serum concentrations at which they occur. It should be understood that chronic toxicity results in a more insidious onset and generally lower serum concentrations for a given symptom.

The common alterations in vital signs will be hyperthermia and tachypnea, although hyperpnea (increased depth, rather than frequency, of respirations) may be a more common finding in mild toxicity. Vomiting, hyperventilation and diaphoresis can cause hypovolemia, which may manifest with tachycardia. Hypotension is a more troubling finding and associated with more severe toxicity.

Early symptoms, as elaborated in the preceding section, are tinnitus, hearing deficits and hyperventilation. The patient may otherwise appear mildly distressed and report a history of nausea and vomiting. Symptoms of hyperpyrexia, dehydration, vomiting may initially be managed supportively in the emergency department, but the presence of pulmonary involvement and CNS effects, which may include confusion, agitation, delirium, lethargy, convulsions and coma warrant a considerably more aggressive approach to therapy as well as specialist consultations.

Managing aspirin toxicity is an intensive process in which treatments go hand in hand with lab results, and they will be discussed together. Any patient who presents with salicylism needs to have a serum aspirin level, which can be done by gas chromatography/mass spectrometry, nuclear magnetic resonance, infrared spectroscopy, enzyme specific assays or fluorescence polarization immunoassay. For immediate verification of suspicions, collect a urine specimen and add it to a solution of ferric chloride, mercuric nitrate, and hydrochloric acid, commonly known as the (largely unavailable) Trinder Reagent or Trinder spot test, to detect ASA levels greater than 30mg/dL colorimetrically with very high sensitivity. These ASA levels should be monitored regularly and are an endpoint to treatment. It is critical to recognize that complications of ASA ingestion can manifest in the face of  decreasing and even near-therapeutic levels. The initial salicylate level may be misleading since absorption can be delayed, as discussed.

Acute toxicity begins to manifest at 30-50mg/dL with dose dependent increases in severity of intoxication from there on. A concentration of 100mg/dL in acute ingestion is an absolute indication for hemodialysis. At a serum concentration of 500mg/dL, ASA is uniformly lethal. The information obtained in the anamnesis is important when evaluating the ASA level because chronic ingestion has not only a higher mortality (25% vs. 1% for acute) but manifests complications at lower serum levels. In a chronically intoxicated patient, 50mg/dL is an indication for hemodialysis.

The patient’s acid base status should be regularly assessed with blood gas analysis and pH measurements of the urine. The goal of ion trapping is to administer bicarbonate solution titrated to a urine pH exceeding 7.5 while avoiding a serum pH greater than 7.55. Bicarbonate is given initially as a 1-2mEq/kg bolus and then is added to D5W at 150mEq/L (3 ampules in 1 liter) and administered at 1.5-2 times the normal maintenance requirements (calculated using the 100/50/20 rule or the 4/2/1 rule in children). Forced diuresis should be avoided in attempting to eliminate ASA, and acetazolamide should not be used to alkalinize the urine.

Patients with toxicity are likely to have multiple metabolic derangements and a full electrolyte panel should be drawn initially and as treatment progresses. Vomiting, respiratory alkalosis, ASA-induced renal tubular damage, and inhibition of the electron transport chain (needed for active ion transport) all contribute to a fall in potassium. Hypokalemia should be managed early and aggressively because the renal secretion of H+ and urine alkalization cannot properly work without adequate serum potassium.

The uncoupled oxidative phosphorylation causes a hypermetabolic state that can deplete glucose which should be regularly checked and supplemented as needed. After initial correction with dextrose bolus, maintenance fluids must contain 5% dextrose with bicarbonate. BUN and creatinine levels should be analyzed as renal failure is an absolute indication for hemodialysis and renal impairment should prompt consideration of the possibility.

Patients with severe ASA toxicity can be critically ill, and terminal complications must be identified. The three most ominous features in these patients are hypoventilation, brain edema and pulmonary edema. Most patients with ASA toxicity will present with some measure of hyperventilation. Although this is an independent pathologic process rather than a compensatory physiologic process for metabolic acidosis, it nonetheless provides some measure of serum alkalization which can balance the serum pH  and trap salicylate anions. A hyperventilating patient may pose a concern for “tiring out” and being unable to sustain a respiratory effort, tempting the possibility of intubation. This becomes even more tempting if there is pulmonary edema, especially if there is a degree of hypoxia. The intubation of these patients should be avoided at all costs. The period of apnea needed during RSI, limitations of mechanical ventilation that result in relative hypoventilation, and ventilator asynchrony can all exacerbate acidemia and cause bad outcomes. Non-invasive oxygenation and non-invasive ventilation are alternatives that should be tried first. If intubated, patients must be put on hemodialysis. The best outcomes for intubation and mechanical ventilation are in those patients that are hypoventilating, in whom a high minute ventilation would be beneficial.

Hemodialysis is the last measure that can be taken in the critically ill patients. The indications for hemodialysis are an ASA level of 50mg/dL in chronic ingestions or 75 mg/dL in acute ingestions, CNS symptoms, pulmonary edema, renal or hepatic failure, severe metabolic abnormalities, rising salicylate levels during treatment, and failure of other therapies.

References:

1)  Rosen’s Emergency Medicine – Concepts and Clinical Practice, 7th Edition

2)  Goldfrank’s Manual of Toxicologic Emergencies

3)  Katzung’s Basic and Clinical Pharmacology, 12th edition

4)  Katzung’s Basic and Clinical Pharmacology

5)  Am J Physiol. 1985 Feb;248(2 Pt 2):H225-31.

5)  Mol Cell Biochem. 1992 Sep 8;114(1-2):3-8.

6)  Annals of Emergency Medicine Volume 41, Issue 4 , Pages 583-584, April 2003

7)   http://wichita.kumc.edu/hastings/

8)   https://wikispaces.psu.edu/download/attachments/46924786/image-1.jpg

9)   Journal of Physiology (1995), 485.3, pp.739-752

10) http://www.ata.org/

 

Intern Report 6.8

Case Presentation by Dr. Alexandra Weissman

Chief Complaint:

I’m coughing up blood.

History of Presenting Illness:

The patient is a 22 y/o M with no previous medical problems who has been experiencing lightheadedness, headaches, occasional nausea and vomiting, fatigue, cough, anorexia, and 10 pound weight loss for the past 2 months. The patient was taking Motrin daily for headache.  In October, the patient presented to his PCP’s office initially with these complaints and was found to have nephrotic range pronteinuria of 4.8 on 24 hour urine collection, as well as hypertension of 180s/100s. At this time he was told to follow up with a Nephrologist, however he decided to rest at home and felt somewhat better. However, over the past month the patient has had progressive fatigue and a chronic cough, and in the past two weeks the patient developed hemoptysis, exertional shortness of breath, paroxysmal nocturnal dyspnea, bilateral flank pain, night sweats, fever/chills, nausea and emesis with black clots, anorexia, and non-bloody/non-mucoid diarrhea. The patient also noted intermittent periorbital edema. The patient denies any recent travel, rashes, joint pain, known sick contacts, hematuria, dysuria, or polyuria. The patient has continued to take Motrin multiple times daily for pain. Two weeks ago, the patient presented to the ED with the above complaints and was diagnosed with atypical pneumonia and discharged home with azithromycin. The patient did not improve and returned on 12/24/12 with the same complaints.  The patient denies recent travel inside or outside the country or known sick contacts.

Family Medical History:  HTN

Social History:

Positive for tobacco use and occasional marijuana use, denies other illicit drug use or alcohol use.

Allergies:

NKDA

Review of Systems:

Constitutional:  Fever, Chills, Sweats, Weakness, Decreased activity.

Eye:  Negative.

Ear/Nose/Mouth/Throat:  Negative.

Respiratory:  Shortness of breath, Cough, Sputum production, Hemoptysis, Wheezing.

Cardiovascular:  Tachycardia, No peripheral edema, No syncope. Bilateral pleuritic chest pain.

Gastrointestinal:  Nausea, Vomiting, Diarrhea.  Abdominal pain: Right, The pain is mild.

Genitourinary:  No dysuria, No hematuria, No change in urine stream, No urethral discharge, No lesions.

Hematology/Lymphatics:  No bruising tendency, No bleeding tendency, No swollen lymph nodes.

Endocrine:  No excessive thirst, No polyuria, No excessive hunger.

Immunologic:  Recurrent fevers, Recurrent infections.

Musculoskeletal:  Back, hands and legs cramp up. No back pain, No neck pain, No joint pain.

Integumentary:  No rash, No breakdown, No skin lesion.

Neurologic:  Negative, No confusion, No numbness, No tingling, No headache.

Psychiatric:  Negative.

Physical Exam:

Vital Signs: Blood pressure 154/101, pulse 103, respiratory rate 22, temperature 35.9, and pulse ox 97% on room air.

General:  Alert and oriented, Mild distress, Rigors, Restless.

Eye:  Pupils are equal, round and reactive to light, Extraocular movements are intact.

HENT:  Normocephalic, Atraumatic, Oral mucosa is moist, No sinus tenderness, No nasal discharge, No oral ulcers .

Respiratory:  Breath sounds are equal, Using accessory muscles, RR calculated to be around 40. Auscultation revealed minimal crackles in the lung bases, no wheezes. Dullness to percussion bilateral lower lung fields, left greater than right. Egophony bilaterally at the bases. Crackles heard in the dependent left lung when patient is in the lateral decubitus position, no crackles when patient upright.

Cardiovascular:  Regular rhythm, S1 auscultated, S2 auscultated, No rub, No murmur, Good pulses equal in all extremities, No edema, Tachycardic.

Gastrointestinal:  Soft, Non-distended, Normal bowel sounds, Mild tenderness in the abdomen, mostly in the right middle abdomen. No rebound, No guarding. Positive bowel sounds. No masses appreciated.

Genitourinary:  CVA tenderness bilaterally.

Lymphatics:  No lymphadenopathy.

Musculoskeletal: No tenderness.  No swelling.  No deformity.

Integumentary:  Warm, Intact, No rash.

Neurologic:  Alert, Oriented, No focal defects.

Psychiatric:  Cooperative, Appropriate mood & affect.

Workup:

Electrolytes: 138/3.9|101/17|92/11 anion gap is 20, calcium < 5, phosphorus 7.4

CBC: 10.5/9.2/27.7/349.

INR is 0.97. PTT is 30.8. PT 10.1

Urinalysis: SG 1.025, pH 6, Glucose/Ketones/Leuk Est/Nitrites/Bili/Urobili are negative, 2+ blood, 2+ protein, 2-5 RBC, < 5 WBC, < 5 Epithelial Cells, No casts/crystals/mucus/bacteria/sperm/Trich

12-lead ECG: normal sinus rhythm with a rate of 101 beats per minute.  The axis is normal.  The PR, QRS, and QT intervals are normal.  R-wave progression is normal.  There is no ST elevation or depression.  There are inverted T waves in the lateral precordial leads.  Voltage consistent with LVH, otherwise this is a normal ECG.

 

6.8-1

IMPRESSION:

Rapidly progressing central interstitial pattern.  The differential diagnosis includes atypical pneumonia, atypical pulmonary edema, viral pneumonia, TB, Goodpasture’s disease, lupus vasculitis, Wegener’s granulomatosis, or microscopic polyangiitis.

EXAM:

Ultrasound – Renals – Complete

IMPRESSION:

1.  Mildly echogenic kidneys raise suspicion for medical renal disease.

2.  No hydronephrosis or renal calculus.

3.  Small left pleural effusion.

ED Course:

Initially, given history and physical examination, it was suspected that the patient had HTN and bronchitis refractory to outpatient therapy. However, upon examination of the labs and imaging studies, the differential widened to renal failure of unknown duration with bronchitis vs. nephrotic syndrome vs. pulmonary-renal syndrome (Goodpasture vs. Wegener). The patient was initially admitted to the internal medicine service for renal failure and bronchitis, however he went into respiratory failure requiring intubation while still in the ED. ICU was consulted regarding the patient, and a bronchoscopy was performed in the ED that did not demonstrate an active source of bleeding or tracheobronchal abnormality. Fluid obtained during bronchoscopy was sent for cytology and culture.

 Questions:

1. Which of the following drugs is not known to cause Acute Interstitial Nephritis?

a) Acetaminophen

b) Cephalosporins

c) NSAIDS

d) Penicillins

2. What dangerous complication should you think of in a person presenting with nephrotic syndrome?

a) Myocardial infarction

b) Pulmonary embolism

c) Pneumonia

d) All of the above

3. From and emergency medicine perspective, what is the mainstay of treatment for nephrotic syndrome in an otherwise stable patient?

a) Cyclophosphamide

b) Corticosteroids

c) High-protein diet and follow up with a Nephrologist

d) Oral anticoagulation and supportive treatment

 

DISCUSSION:

Differential Diagnoses (diseases paired with the lab tests that are classically diagnostic)

NSAID-induced AIN – +/- urine eosinophils

Tuberculosis – 3 AFB sputum cultures, Quantiferon gold test

Pneumonia – urine Streptococcal antigen, sputum culture

Legionella – Legionella urine antigen

HIV – ELISA HIV test and Western blot

Goodpasture Syndrome – anti-glomerular basement membrane antibody

Wegener Granulomatosis – ANCA, anti-myeloperoxidase antibody, anti-serine protease 3 antibody

Microscopic Polyangiitis – ANCA, RBC urinary casts, normal C3 and C4

SLE – ANA, dsDNA, anti-Sm, anti-RNP

Sjogren’s syndrome – anti-Ro, anti-La

Scleroderma – Scl-70, anti-Ro, anti-La, anti-RNP

Mixed Connective Tissue Disorders – anti-Ro, anti-La, anti-RNP

Rheumatoid Arthritis – RF, anti-CCP

Churg-Strauss – pANCA (anti-MPO Ab), eosinophilia, RBC urinary casts, RF

Heroin or HIV induced FSGS

Hepatitis B or C induced nephrotic syndrome

Endocarditis

Hospital Course:

The patient was admitted to the ICU for a total stay of 20 days before being stabilized for transfer to the general medical floor. A thorough workup for autoimmune etiologies, infectious etiologies, and toxic etiologies was performed. UDS and SDS were negative.  Urinalysis demonstrated no dysmorphic RBC or RBC casts, with few WBC and WBC casts, and rare tubular cells – these results pointed away from a glomerulonephritis and toward a nephrotic syndrome. Testing for urine eosinophils was negative, however this does not rule out NSAID-induced AIN. All serologic testing for autoimmune disorders was negative including cANCA, pANCA, ENA profile (ANA, dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, Scl-70, anti-Jo-1), RF, anti-myeloperoxidase Ab, anti-serine proteinase-3 Ab, C3, C4, IgG and IgG subtypes 1-4, and immunofluroescence assay. ESR and CRP were elevated, however these are nonspecific markers for inflammation. There was initially concern for Tuberculosis since the patient had hemoptysis, weight loss, chronic cough, and sweats, however 3 AFB sputum cultures and Quantiferon Gold testing was negative for Tuberculosis. There was also concern for new-onset HIV, however the patient was found to be HIV negative.  Urine Legionella antigen, urine Streptococcal antigen were negative and ASO were negative. Sputum cultures and BAL cultures with gram stain were negative bacteria, fungi, HSV 1 and 2, Influenza A and B, Parainfluenza 1/2/3, Herpes Zoster, Adenovirus, RSV, Pneumocystis jiroveci, or Chlamydia. Hepatitis B and C were negative as well. TTE did not demonstrate vegetations and blood cultures were negative, therefore endocarditis was highly unlikely.

The patient had at least a 3 month history of elevated creatinine, hypertension, and regular NSAID use. Nephrology concluded that the most likely cause of the patient’s nephrotic syndrome was interstitial nephritis from NSAID use. A renal biopsy was not performed since the patient was considered to have chronic renal disease at the time of presentation and Nephrology stated that renal biopsy would only reveal nonspecific histological findings of focal segmental glomerulosclerolsis at this time. The patient was placed on high dose IV steroids, which he responded to well. The chronic cough likely resulted from pulmonary congestion secondary to hypoalbuminemia and renal failure. Although the initial physical exams did not demonstrate edema, periorbital edema is a common finding in nephrotic syndrome, and in children is often one of the first signs of the disease. Low oncotic pressure in the intravascular space secondary to hypoalbuminemia creates a gradient for water to move to the extravascular space, resulting in peripheral edema. Chronic edema affects the gastrointestinal tract as well, causing defective absorption and often resulting in diarrhea and chronic malnutrition.

Answers:

1. A – Acetaminophen is not known to cause AIN. Many drugs are implicated in the development of AIN, most commonly NSAIDS, penicillins, diuretics, cephalosporins, rifampin, anticoagulants, and proton-pump inhibitors. AIN can also result from infection with HIV, tuberculosis, bacterial, fungal, protozoan, and rickettsial infections as well as in association with autimmune states such as SLE, Scleroderma, Sjogren’s Syndrome, sarcoidosis, and essential cryoglobinemia. The pathophysiology of drug-induced AIN involves both the humoral and cellular immune systems. Antibodies directed at the drug can be found on the tubular basement membrane, and biopsy reveals a mixture of T cells, eosinophils, plasma cells, and monocytes. Effacement of the podocyte processes is a common histological finding in NSAID-induced AIN.

2. D – Nephrotic syndrome is associated with venous thromboembolism including pulmonary embolism and deep venous thrombosis, myocardial infarction, and pneumonia. In nephrotic syndrome, a prothrombotic state emerges due to to the loss of antithrombin III and plasminogen secondary to renal losses of these proteins. At the same time, the liver is induced to make more proteins, including clotting factors, in response to hypoalbuminemia from renal losses of albumin. As for myocardial infarction, the increased hepatic synthesis of proteins also results in increased synthesis of lipoproteins, which results in accelerated atherosclerosis and hyperlipidemia. The increased synthesis of lipids results in lipiduria, which is why oval fat bodies and fatty casts are typical urine sediment findings in nephrotic syndrome. Lastly, it is hypothesized that the increased renal losses of proteins including immune globulins combined with the malnourished low protein state predisposes the body to infection in nephrotic syndrome.

3. B – In addition to treating the underlying infection or removing the offending drug, corticosteroids are the mainstay of treatment for nephrotic syndrome of autoimmune, infectious, drug-induced, or idiopathic etiology. Corticosteroids reduce the inflammatory response via inhibition of inflammatory mediator gene transcription and thus also diminish proteinuria. They are particularly effective for Minimal Change Disease in children. However, there are steroid resistant forms of nephrotic syndrome that do require more cytotoxic agents such as cyclophosphamide or cyclosporine.  Other medications given for supportive therapy are diuretics for associated edema, ACE-inhibitors for their anti-hypertensive and renal protective benefits, low salt and 1-2g/kg protein diet.

Intern Report 6.7

Case Presentation by Dr. Katherine Schulman

A little background:

27-year-old African American male seen as follows:

DRH ED:  7/15/2012: ( Time 0 )

C/C:  “My eyes are irritated.”

HPI:  bilateral eye irritation starting a month prior, mild photophobia, markedly injected, greenish discharge

Final Impression/Diagnosis:  Bilateral Conjunctivitis, discharged with Gentamicin ophthalmic solution, f/u w/ Kresge.

DRH ED:  7/22/2012: ( Time +7 Days )

C/C:  “My eyes still hurts.”

HPI:  Pt reports that he never did f/u with Kresge, but has been using the eye drops prescribed.  He states his eyes have gotten progressively more red, with increasing discharge, increasing photophobia, blurry vision, and foreign body sensation bilaterally.

Final Impression/Diagnosis: bilateral conjunctivitis, with evidence of pseudomembrane formation over the left eye.  Ophthalmology consulted and spoken with on phone.  They recommended atropine for symptomatic relief, erythromycin ointment, and artificial tears.  f/u w/ Kresge.

Pt did f/u w/ Kresge on 7/27/12 ( Time +12 Days ):  pt continued on medications as started in the ED, including Pataday (Olopatadine – is a mast cell stabilizer and a histamine H1 antagonist) drops for symptomatic allergy relief.

Final Impression/diagnosis:  Keratoconjunctivitis OU suspected.  Pt advised to f/u within a week (which he did not, next visit as described in case).

CASE:  10/30/2012 ( Time +107 Days )

C/C and HPI:  27-year-old African American male presents to Kresge Eye Institute, last seen in July.  Pt c/o blurry vision, eye discharge -yellow, injection, photophobia, and decreased visual acuity bilaterally for 4 months.

ROS:

Constitutional:  denies fevers, chills;

Eye:  redness, tearing, discharge, foreign body sensation, blurry vision;

ENT:  denies oral lesions;  Head:  denies HA;

GI: denies N/V/D;

GU:  denies dysuria, discharge;

Musculoskeletal:  denies joint pain/swelling, muscle aches;

Skin:  denies rash

Past Medical History: none

Past Surgical History: none

Medications: Only ophthalmic medications as in the previous months

Allergies: No known drug allergies

Family History: Hypertension

Primary care physician: None

Social History: Positive for tobacco and alcohol use.  Denies illicit drug use.

Physical Exam: (Kresge Eye Institute, thus only focused eye exam done)

Eye:

General:  sclera injected bilaterally, mucopurulent discharge, swelling to upper lids

Visual Acuity:  OD 20/30, OS 20/30

Pupils:  dim light 3mm -> bright light 2mm OD & OS

Confrontation:  Full to finger count OD & OS

Motility:  EOMI OD & OS

Slit Lamp Exam:

Eyelids – meibomian gland plugging and mattering OD & OS

Conjunctiva:  numerous, giant papillae and follicles OD & OS, 2+ injection OD,  1+ injection OS

Anterior Chamber:  deep and quiet OD & OS

Iris:  round and reactive OD & OS

Lens:  WNL OD & OS

247374_P1

Picture A

1.  Considering simply the duration of his ophthalmic complaints, which of the following should be considered on the list of differentials (please choose 2 below):

A).  Allergic Conjunctivitis

B).  Corneal Abrasion

C).  Chlamydial Inclusion Conjunctivitis

D).  Gonococcal Infective Conjunctivitis

2.  What is the most likely diagnosis in this patient?

A).  Allergic Conjunctivitis

B).  Corneal Abrasion

C).  Chlamydial Inclusion Conjunctivitis

D).  Gonococcal Infection

3.  What is the most appropriate treatment for this patient?

A).  Tetracycline 250mg QID x 14 days

B).  Ciprofloxacin 500mg PO BID x 10 days

C).  Vancomycin 15-20mg/kg IV QID plus Clindamycin 600mg IV TID x 5 days

D).  Erythromycin ophthalmic ointment BID x 21 days

 

Case Discussion:

1.    Considering simply the duration of his ophthalmic complaints, which of the following should be considered high on the list of differentials (please choose 2 options below):

A).  Allergic Conjunctivitis

B).  Corneal Abrasion

C).  Chlamydial Inclusion Conjunctivitis

D).  Gonococcal Infective Conjunctivitis

 

ANSWERS: 

1)         A, C

2)         C

3)         A

This patient has had ophthalmic symptoms for 4 months now.

Allergic Conjunctivitis:  Symptoms may be present for days, weeks, or months, as long as the offending agent is present.   Symptoms include:  itchy/ watery eyes and injected sclera.  TX: antihistamines, avoidance of stimuli, OTC lubricating/allergy relief eye drops, warm compresses.

Corneal Abrasion:  Injury to the superficial epithelial layer of the cornea heals fairly quickly – in days usually 24-48 hours, but certainly not weeks, nor months.  TX:  Erythromycin ophthalmic ointment QID x 10 days.  In contact lens users – d/c use of contacts and use topical antibiotic solutions with antipseudomonal coverage, such as: gentamicin, levofloxacin, etc.

Chlamydial Inclusion Conjunctivitis:  As described in the case above.  Can occur unilaterally or bilaterally in sexually active young people.  If not treated properly, inclusion conjunctivitis runs a course of 3-9 months or longer.  Details of disease and treatment are discussed below.

Gonococcal Infective Conjunctivitis:  Marked by profuse purulent (not mucopurulent) exudates and progresses quickly.  Exposure can lead to full ocular perforation and blindness within 24-48 hours.   Remember, every baby gets prophylactic treatment preferably with erythromycin ointment.

Other Common Conditions:

Blepharitis:  Inflammation of the eyelids.  Most often bilateral and symmetrical.  Patients often complain of a ‘gritty’ sensation.  Blepharitis is quite often chronic in nature, which can be managed with good eye hygiene/cleansing scrub and warm compresses.

Viral Conjunctivitis:  The most common!  Usually caused by adenovirus, following URIs and is quite contagious.  Patients present with redness, tearing, mild mucous discharge, and itchy/irritated eyes.  Often starts in one eye, but can easily spread without good hygiene.   Symptoms are self-limiting and don’t generally last longer than 4 weeks.  Care is supportive, with emphasis on good hand-eye hygiene.

**KRESGE EYE INSTIT ** UTES FINAL IMPRESSION:  Chlamydial conjunctivitis, bilateral papillary reaction worse on upper lids with mucopurulent discharge, multiple infiltrates with pannus formation.  Patient given a prescription for Tetracycline 250mg QID x 14 days.  Swab sent to lab – positive.

More about Chlamydial Inclusion Conjunctivitis:

Chlamydial conjunctivitis is a sexually transmitted disease, and it occurs most commonly in sexually active young adults. The disease is generally transmitted through hand-to-eye or orogenital spread of infected genital secretions. The incubation period can take up to 14 days.  An estimated 1 in 300 patients with genital Chlamydia develop conjunctivitis.

This is more commonly a unilateral eye infection, though it can be seen bilaterally as in the case above.

Patients may present with many of the following symptoms:  photophobia, foreign body sensation, decreased visual acuity/blurry vision, swollen lids, injected sclera, tearing, mucopurulent discharge.  Patients often awake in the morning with significant crusting of lashes and eyelids temporarily stuck together from the drying of the mucopurulent discharge.

The clinical findings seen in Chlamydial Conjunctivitis may also resemble other forms of infectious conjunctivitis.  Infected individuals often have preauricular adenopathy.  On closer exam through slit lamp:  a follicular reaction is the key feature of a chlamydial conjunctivitis, often involving the bulbar conjunctiva and semilunar folds, and papillary hypertrophy.  Take a look at the huge follicles in the pictures below.

6.7-b

Picture B

A diagnosis can be made based on the signs, symptoms, and the clinical suspicion.  A culture may be taken to confirm, but start oral antibiotic treatment immediately with high clinical suspicion.

Treatment:

Topical antibiotics are generally ineffective, and thus systemic antibiotics are the mainstay of treatment.  The following are used:  tetracycline, doxycycline, erythromycin, azithromycin.  A course of 2-3 weeks of oral antibiotics is warranted.

References:

Mandel, Douglas, Bennett:  Microbial Conjunctivitis:  Principles of Infectious Diseases, ed. 7  2009 (Ch) 110.

Sharma R, Brunette DD:  Ophthalmology: Rosen’s Emergency Medicine.  7th edition.  2010.  Ch 69:  859-876.

Root, Timothy.  Eye Infections.  Ophthobook.  Retrieved Jan 3rd, 2013 from ophthobook.com

 

 

Intern Report 6.6

Case Presentation by Dr. Brian Holowecky

Chief Complaint: 

Headache

History of Present Illness:

A 13-year-old obese woman with a past medical history of chronic headaches presents to the emergency department for five days of a headache that is associated with nausea and vomiting. The headache started in the frontal region and now involves the entire head. The pain was initially improved by acetaminophen and ibuprofen, but now is persistent despite these medications. According to mom, the patient is confused, is walking into walls, is vomiting all day, and has new onset right sided weakness in the upper and lower extremities. The patient complains of tingling in her right hand and reports weakness in her right foot. She also reports photophobia, dizziness, and an unsteady gait. There is no history of trauma, international travel, or dental problems. She is pre- enarchal. She also is complaining of severe intermittent sore throat and chest discomfort x3 weeks. “It feels like something is getting stuck in my throat.” She has been treated by her pediatrician for GERD x 3 weeks. One day prior to admission she was dx’d by pediatrician with viral etiology of sore throat with a negative Rapid Strep Test.

Review of Systems:

General: Vomiting, difficulty sleeping, nausea

HEENT: sore throat, congestion, blurry vision twice in past 7 days. No toothache

Cardiac: No chest pain or palpitations

Lungs: Cough x 1 week

Abd: Denies blood in stool, diarrhea

G/U: No blood in urine. No dysuria, hematuria, nocturia

Skin: Some bruises from softball practice.

Neuro: Headaches x 6 months

Heme/Immunologic: No allergies, no bleeding

Past Medical History:

Chronic migraines, seasonal allergies, GERD

Family History:

Mom – Schizophrenia vs Borderline Personality Disorder, depression, agoraphobia

Brother – “Hole in his heart at birth that went away.”

Father – No medical problems.

Paternal Grandfather – Wilson’s Disease

Social History:

Pt lives at home with mom, dad, brother and dog. Older sister who doesn’t live at home has pet pythons. Patient plays competitive softball and is usually very active. Father is a truck driver who delivers loads between the Ohio River Valley and the American Southwest. Pt occasionally rides with him on trips. The family extensively gardens.

Physical Exam:

Vitals: Temp 38.2 HR 125 RR 20 BP 144/83 saturation 99%

General: Obese adolescent girl appears in moderate distress. Confused/Anxious

HEENT: Bilateral Papilledema. No conjunctival hemorrhages. No photophobia. No sinus

tenderness to percussion. Oropharynx clear of lesions with normal healthy dentition.

Neck: Supple. No lymphadenopathy. No masses. No meningismus.

Lungs: Lungs CTAB. No retractions. Breathing non-labored.

Cardio: Regular rate and rhythm. No systolic murmur.

Abdomen: Soft. Epigastric/LUQ tenderness. No guarding or rebound. No organomegaly.

Musculoskeletal: R side weakness upper and lower extremity. Weakness appears more

proximal. No clonus. No babinski.

Neuro: Right sided facial weakness with decreased nasolabial folds without forehead sparing. Slight R tongue deviation. EOMI. PERRL. Other cranial nerves intact. Right Upper

Extremity 2-3/5 strength. Right lower extremity 3/5 strength. Left upper/lower

extremities 5/5. Diffuse symmetical hyporeflexia 1+. Sensation intact. Abnormal gait

– favoring the right side.

ED Course:

Patient was referred from outside hospital for suspicious lesions on head CT.  IV access was obtained. Blood work sent. Patient sent to CT for confirmation.  Also blood cultures, UA, CXR, urine electrolytes.  Consult was placed to neurosurgery and infectious disease.

CBC – 13.57/11/32/411

Electrolytes – 129/4.0|97/21|8/0.67

AST/ALT – 12/13

INR – 1.2

ESR/CRP – 56/227 (elevated)

CXR – No acute process.

UA – ketonuria, proteinuria.  No other abnormalities.

Urine electrolytes WNL

The patient was started on dexamethasone secondary to her neurological findings.  She was empirically treated with ceftriaxone, vancomycin, metronidazole, and bactrim.

6.6-1

Figure 1. Head CT

6.6-2
Figure 2. Abdominal CT

Later in her extensive hospital course, this patient was found to have hilar lymphadenopathy an esophagomediastinal fistula.  Plasma serology came back positive for histoplasmodium. 

6.6-3
Figure 2b. Esophogram.

There is extravasation of contrast on the right side proximally to the third rib.  Contrast is seen collecting in a small featureless structure just to the right and superior to the actual fistula/or leak. The esophagus is displaced to the left likely due to fluid collection, abscess, lymphadenopathy or a combination of the above.

Questions:

1. Which of the following is an absolute contraindication to performing a LP?

a) Elevated ESR/CRP

b) Intoxication

c) Papilledema

d) Gait disturbance

2. Which finding explains the mechanism of hematogenous spread from a mediastinal lesion to

the formation of brain abscesses?

a) systolic ejection murmur

b) microcytic anemia

c) splenomegaly

d) feculent vomit

3. Which of the following raises the greatest suspicion for a space occupying lesion in the

brain?

a) unilateral distribution

b) not relieved by hydromorphone

c) vomiting in the morning

d) phonophobia

One Step Further:

How is Histoplasma transmitted between hosts?

a) Spores in the arid Southwest USA

b) Fecal/Oral Transmission of endospores

c) Inhalation of microconidia in dust

d) Inhalation of pidgeon feces

 

Explanation/Discussion:

Case Report:

This is a case of an obese adolescent girl from Grand Rapids, MI, who was found to have 2 discrete brain abscesses and a splenic abscess with positive cultures for Viridans Streptococci.  Her serum was positive for histoplasma, which is endemic to the upper Midwest. The nidus of infection is presumed to be from histoplasma lymphadenitis that led to an esophagomediastinal fistula, which then allowed normal flora of the oropharynx to become a disseminated bacterial infection of normal flora in an immunocompetent young girl.

Her social history was uniquely important in her case.  She had multiple classic social history risk factors for a variety of rare and unusual possible pathogens.  Her father being a truck driver in the midwest (histoplasmosis) and traveling to the arid Southwest (cocciodides).  Her sister had exotic pets.  She was a gardener which is a classic history for a patient with a nocardia infection.  Bactrim was added for nocardia coverage.

Hospital Course: Admitted with consult to infectious disease. Patient started on broad-spectrum antibiotics eventually with the addition of Amphotericin B, to her regimen of Vancomycin, Rocephin, Bactrim, Metronidazole.  Complications included Acute Kidney Failure from her antifungal medication, red man syndrome from Vancomycin.

Her neurological symptoms resolved over the course of one week, with persisten bilateral papilledema.  She underwent a head/neck ULS to rule out obstruction as a cause for venous congestion and papilledema, which was normal.

6.6-5

Figure 3.  MR with spectroscopy of brain lesions. 

An MR with spectroscopy was ordered to determine the etiology of the brain lesions.  An MR signal produces resonances that corresond to various excited states of various metabolites and isotopes.  It was used to confirm that the lesions were indeed due to abscesses rather than a neoplasm or other etiology.  There was a large lactate doublet which was interpreted by infectious disease and radiology to be infectious in nature.

Patient underwent an extensive workup that revealed:

–mediastinal lympadenitis

Histoplasma positive serology testing

–esophagomediastinal fistula

–splenic and brain abscesses positive for S. viridans.

Echo revealed no PFO or shunt with bubble study.  There were no lung lesions.

The working diagnosis is histoplasma mediastinal lymphadenitis that caused an erosion leadingto an esophagomediastinal fistula, which lead to bacteremia and hematogenous spread to discrete lesions in the spleen and brain. 

Learning points from this case:

Differential for ring-enhancing lesions on Head CT:

Ring enhancing brain lesions are suggestive of a variety pathologies.  The ring enhancement is usually due to edematous changes.  The rings suggest that the pathology is chronic or resolving as in the case of an abscess, or hematoma.  Multipe infections can lead to ring enhancing lesions most notably

MAGIC DR

M – Metastasis

A – Abscess (toxoplasmosis, cryptococcus, coccidiodes, blastomycosis, neurocysticercosis, nocardia)

G – Glioma

I – Infarct (resolving)

C – Contusion/Hematoma (Resolving)

D – Demyelinating Disease

R – Radiation Necrosis

6.5-7

Figure 4.  Head MRI.

Shows two discrete ring enhancing lesions.  The lesion in the internal capsule on the left side is the likely etiology of her right sided weakness.  The MRI also reveals edematous changes in the optic nerve consistent with papilledema.

6.6-8

Figure 4.  Head MRI (continued)

Hematogenous Spread of Infection

Hematogenous spread of infection is a common source of disseminated bacterial or fugal disease. However, there are only a few mechanisms responsible for the spread of disease from the infracranial region to the brain. The most common mechanism is hematogenous spread through the systemic and pulmonary circulation. However, this invariably leads to pulmonary nodules as some of the bacteria seed the lungs prior to entering the heart, which would have been seen on CT.

The presence of a shunt can explain the lack of pulmonary findings. The most common type of shunt that bypasses the pulmonary circulation is a vegetation that passes from the right atrium to the left atrium through a patent foramen ovale. The most common murmur in patient with a PFO is a midsystolic ejection murmur that is heard best at the upper sternal border. An echo with bubble study can also be used for confirmation.

Answers:

1. C) Papilledema is an absolute contraindication to an LP. Any clinical finding that suggests an acute elevation of intracranial pressure is a contraindication to LP. The risk of performing an LP in a patient with elevated ICP is the potential for a decrease in pressure of the spinal cavity resulting in herniation of the cerebellum and subsequent brainstem impingement.  This can lead to rapid deterioration and death.

Intoxication is not an absolute contraindication to LP.

ESR/CRP elevation is a nonspecific finding. Elevations are due to an increase in inflammation,but do not indicate that the inflammation originates in the nervous system.

Gait Disturbance should raise your suspicion for increased intracranial pressure, especially from hydrocephalus. However, it is not an absolute contraindication to lumbar puncture.

2. A) systolic ejection murmur. May indicate an atrioseptal defect or patent foramen ovale. The presence of a PFO allows for infectious agents to bypass the lungs and enter the systemic circulation.  When there is no shunt, the infectious agent often becomes lodged in the distal pulmonary vasculature causing pulmonary lesions on chest radiography.

Microcytic anemia is not associated with hematogenous spread of bacteria. Macrocytic anemia is associated with splenomegaly due to erthyrocyte sequestration.

Feculent vomit should raise your suspicion for a bowel obstruction.

Splenomegaly may be due to a splenic abscess, but does not explain the mechanism of hematogenous spread to the brain.

3. C) Morning vomiting is a concerning sign of an intracranial lesion. Intracranial pressure is highest in the morning after sleeping through the night in a recumbent position.

Unilateral distribution of a headache is a nonspecific finding. It may be seen in migraine type headaches, cluster headaches, or even tension headaches.

Phonophobia is classically associated with a migraine headache and extracranial tumors of the vestibular system.

Hydromorphone is not indicated for headache treatment.

One step further: C) Inhalation of microconidia in dust. Histoplasma is endemic to the Ohio and Mississippi River valleys. It is spread by inhalation of microconidia in dust contaminated with excreta from bats, starlings, or chickens. It is classically associated with spelunkers and chicken farmers.