Does my patient have COPD?

We are often faced with many patients who are given a label of obstructive airway disease based on a history of smoking and wheezing. But in many instances patients with these features do not have obstructive airway disease. Dr. Straus and colleagues identified 4 elements on history and physical examination that were significantly associated with a diagnosis of obstructive airway disease:

1. Smoking at least 40 pack-years (LR + 8.3)

2. Self-reported history of chronic obstructive airway disease (LR + 7.3)

3. Maximum larygeal height less than 4cm (LR + 2.8)

4. Age at least 45 yrs (LR + 1.3)

The presence of all 4 of these elements has a LR + 220, rulling in a diagnosis of obstructive airway disease.

Click on the following link to see the abstract: http://http//jama.ama-assn.org/content/283/14/1853.abstract

Adrenal Insufficiency

The clinical presentation of adrenal insufficiency is variable and depends on whether the onset is acute (leading to adrenal crisis) or chornic, with symptoms that are often vague and insidious. The key to making the diagnosis of adrenal insufficiency is a high level of clinical suspicion. The signs and symptoms of adrenal insufficiency depend upon the rate and extent of loss of adrenal function, whether mineralocorticoid production is preserved, and the degree of stress. The following is a list of key clinical features of primary adrenal insufficiency:

• weakness


• fatigue


• anorexia


• orthostatic hypotension


• nausea


• vomiting

The following is a list of key laboratory abnormalities of primary adrenal insufficiency:

• hyponatremia


• hyperkalemia


• hypoglycemia


• lymphocytosis


• eosinophilia


• hypercalcemia (rarely)

Patients with Headache

Headaches are a very common medical complaint. In assessing patients with headaches, we must determine who has a serious cause of a headache and who requires neuroimaging. A Rational Clinical Exam article from JAMA entitled "Does this patient with headache have a migraine or need neuroimaging?" helps to outline an approach to headache. After a systemic review of the literature, the best predictors of a migraine were summarized by the mnemonic POUNDing: Pulsation, duration of 4-72 hOurs, Unilateral, Nausea, Disabling). If a patient meets 4 out of the 5 criteria, the likelihood ratio (LR) for definite or possible migraines is 24. For neuroimaging, several clinical features were found on pooled analysis to predict the presence of a serious intracranial abnormality: cluster-type headache (LR 10.7), abnormal findings on neurological examination (LR 5.3), undefined headache (LR 3.8), headache with aura (LR 3.2), headache aggrevated by exertion or valsalva (LR 2.3), and headache with vomiting (LR 1.*). It should be noted that no clinical features were useful in ruling out significant pathologic conditions. To see the full Rational Clinical Exam article click here http://jama.ama-assn.org/content/296/10/1274.full.pdf+html?sid=80cae855-c34e-401a-a365-34f964dfe247

Dabigatran for anticoagulation in Afib

Dabigatran is an oral, direct thrombin inhibitor. Its efficacy and safety relative to warfarin was evaluated in the RE-LY trial, at 2 doses. It was the first randomized trial to demonstrate that an alternative oral anticoagulant is superior to adjusted-dose warfarin. Over 18,000 patients with non-valvular atrial fibrillation and at least 1 stroke risk factor were were randomly assigned to receive oral dabigatran at one of two doses (110 or 150 mg) twice daily, or adjusted dose warfarin (INR 2-3). The primary study outcome was stroke or systemic embolism. After a median follow-up 2 years, rates of the primary outcome were 1.69%/yr in the warfarin group, compared with 1.53%/yr in the group that received 110 mg of dabigatran (P<0.001), and 1.11%/yr in the group that received 150 mg of dabigatran (P<0.001). The rate of major bleeding was higher in the warfarin group, compared to the lower dose dabigatran group. This study concluded that in patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. To see the full article click here http://www.nejm.org/doi/full/10.1056/NEJMoa0905561#t=article

Clubbing

Today in morning report we discussed a patient, who among other problems, was clubbed.

Clubbing is the enlargement of the terminal segments of the fingers and/or toes that results from the proliferation of the connective tissue between the nail matrix and the distal phalanx. It develops in the context of a number of neoplastic, infectious, inflammatory and vascular conditions.

Features on physical exam that make clubbing more likely include changes in nail-fold angles, as well as changes in the shape, depth, and width of the terminal phalanges.

1) Phalangeal Depth - This ratio compares the depth of the distal phalanges to the inerphalangeal areas. Normally, this is less than 1. Once this ratio exceeds 1, clubbing is more likely.

2) Nail Fold angles - Two angles are commonly discussed: the profile angle and hyponychial angle.

a) The profile angle can be estimated by the angle the nail projects from the nail fold. normally this is about 160 degrees but exceeds 180 degrees when the finger is clubbed.

b)The hyponychial angle compares two lines, (1), from the DIP joint to the nail fold and (2), from the nail fold to the point where the nail meets the finger tips. This angle is should not exceed 190 degrees normally and if it does, clubbing is likely present.

3) Nail bed squishiness - Palpation of the nail bed in clubbed fingers tends to be spongier than a normal nail with the sensation that the nail is floating.

Check out the JAMA rational clinical exam series here for an evidence based review.

Grade 4 Left Ventricles

Today in morning report, we discussed a patient presenting with complications related to their grade-4 left ventricle. Much of our discussion focused on the management of these patients. Specifically, what about device therapy? Here is a summary:



Device Therapy
This really came to the forefront with the MADIT-2 trial where patients with a history of MI and severe LV dysfunction (grade 3 or worse) after optimal medical therapy had prophylactic ICDs placed. This showed improved survival. The SCD-HeFT trial looked at amiodarone vs. ICDs and again, device therapy appeared superior. Cost effective analysis has been favourable, but controversial. Check out this editorial for another look.


The MADIT-CRT trial looked at relatively asymptomatic patients (NYHA class 1 and 2) with depressed LV function (less than 30%) and prolonged QRS durations and found that CRT decreased rates of CHF exacerbations.

Recently, results of the RAFT trial were presented in NEJM and found that "among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure." More adverse events were noted, however.

All in all, this is a rapidly progressing area in medicine and it may not be too long until we find ourselves here!

Toxic Epidermal Necrolysis

Today in Morning Report, we discussed the case of toxic epidermal necrolysis likely secondary to allopurinol use.

Allopurinol and its metabolite, oxipurinol (alloxanthine), decrease the production of uric acid by inhibiting the action of xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Indications are most commonly for disorders of hyperuricemia (urate nephropathy, tumor lysis sydrome prophylaxis, and gout). When used for gout, most would agree that >3 flares/year (or tophaceous deposition) would merit its use. Incidentally discovered hyperuricemia is not an on-label indication.

With regards to the side-effect profile, the biggest concern, as seen in our patient, is toxic epidermal necrolysis. This is a very rare, but acute and potentially fatal skin reaction in which there is sheet-like skin and mucosal loss. It exists in a spectrum with Stevens-Johnson Sydrome and is mainly differentiated by the degree of epidermal involvement.

Treatment is mostly supportive but begins with the discontinuation of the offending drug. Wound care is very important to prevent excess fluid loss and secondary infections. In severe cases, consultation with a burn unit may be appropriate. Adjunct treatment with corticosteroids, cyclosporin, cyclophosphamide and IVIg have been trialed with variable success.

TEN is reviewed nicely at this link, check it out for a summary on the diagnosis and treatment.

Hyperkalemia

Last week, a patient with hyperkalemia was discussed in morning report.

Causes of hyperkalemia always come down to renal handling of potassium. Dietary (or iatrogenic!) intake of potassium may play a role, but most clinical scenarios revolve around limitations in excretion.

Management options include:
1) Stop the exogenous potassium - this seems simple but is embarassing when missed.

2) Stop offending drugs - this is not the right time for any potassium sparing diuretics or ACE inhibitors

3) Shift the Potassium - This does not equal excretion and is only a temporary fix. Classically, a high glucose load (1 amp of D50W) with an intravenous insulin chaser (1o units iv) is the mainstay cocktail. Other options include intravenous sodium bicarbonate and inhaled beta agonists (8 puffs with aerochamber). Interestingly, beta agonists may be more efficacious than previously believed (see the article below).

4) Dump the Potassium - at the end of the day, you need to rid the body of the excess. A number of options exist. High dose furosemide (assuming this is not oliguric renal failure) is an effective way to mobilize potassium. Potassium binders are often used (kayexalate) but are slow and have other side effects (colonic necrosis!). Finally, hyperkalemia refractory to medical management is an indication for hemodialysis.

Check out CMAJ for a very recent review.

Aches and Pains

Today we discussed an interesting case of a man with fevers and progressive muscle pain and weakness. Among the many things on the differential diagnosis was Giant Cell Arteritis.

GCA (formerly known as temporal arteritis) should be considered in patients with new headaches, abrupt onset of visual disturbances, symptoms of polymyalgia rheumatica, jaw claudication, unexplained fever or anemia, high erythrocyte sedimentation rate and/or high serum C-reactive protein.

A temporal artery biopsy is part of the workup but can be negative in some patients who have the disease (7-13% will have a negative unilateral biopsy but a postive bilateral biopsy).

The treatment for GCA are glucocorticoids. Prednisone at 1mg/kg is the commonest initial therapy with tapering initiated after 4 weeks (providing a normalized ESR).

Here is a link to a NEJM review on the topic and here is a look at the topic in the JAMA rationale clinical exam.

Vertigo

Today in morning report, we discussed an approach to a patient with vertigo.

Vertigo is defined an illusory or hallucinatory sense of movement of the body. When approaching a patient with this problem, the history is quite important as patients often label "dizziness" in many ways. Once true vertigo is confirmed, a common approach to it involves dividing peripheral from central problems. Here are some contrasting points:

-Direction of nystagmus - Peripheral: Unidirectional, Central: Bidirectional or Unidirectional
-Purely horizontal nystagmus with no torsional component - Peripheral: Rare, Central: Common
-Vertical or purely Torsional nystagmus - Peripheral: Rare, Central: May be present
-Visual Fixation - Peripheral: inhibits nystagmus, Central: no effect
-Tinnitus - Peripheral: often present, Central: usually absent
-Associated central abnormalities - Peripheral: None, Central: Common

Finally, the Dix-Hallpike manuevers can help prove that the vertiginous symptoms are positional. This is thought to be secondary to a malpositioned canalith errantly stimulating the nerves in the vestibular apparatus. The Epley manuevers are designed to reposition the canalith. Here is a link to a short article explaining how to perform this.

Finally, here is a review looking at the approach to a chronically dizzy patient.

Meet me at the club

Today in Morning Report, we discussed a variety of cases. Among them was an interesting case of a patient who experienced a syncopal event and on initial assessment, was found to be hypoxic with a normal chest radiograph. Causes of hypoxia can include:

1)Respiratory Hypoxia - This refers a situation when respiratory failure leads to hypoxemia.
Most commonly, this is caused by ventilation-perfusion mismatch (ventilation to areas of the lung that are not perfused) as can occur with a PE. Hypoventilation can also be a cause of hypoxia, but this is classically associated with increases to the PaCO2. A third cause is shunting of blood away from parts of the lung that are oxygen rich (perfusion to diseased lung) as can occur in pneumonia or atelectasis.

2) Hypoxia Secondary to High Altitude - The available oxygen for respiration is a consequence of the atmospheric pressure. Recall that the pAO2 = FI02(Patm-PH2O) - (PaCO2/RQ)*. As the atmospheric pressure drops, so does the quantity of oxygen available at the alveolus for inspiration.

3)Hypoxia Secondary to Right-to-Left Extrapulmonary Shunting - A portion of arterial blood bypasses the lung and, as such, is not oxygenated.

4) Anemic Hypoxia - The bulk of oxygen is carried in the blood by hemoglobin. If the concentration of hemoglobin is too low, the ability to carry oxygen in the blood is compromised.

5) Carbon Monoxide (CO) Intoxication - Carboxyhemoglobin (COHb) does not readily dissociate oxygen and this leads to tissue hypoxia.

6) Circulatory Hypoxia - With decreases in effective circulation, more oxygen content is extracted at the tissue level. This leads to poorer oxygen content in the venous return to the heart and subsequent hypoxia.

* PAtm = Atmospheric Pressure, PH2O= Water vapour Pressure, PaCO2 = Arterial Carbon Dioxide pressure, FIO2 = fractional inspired O2 content, RQ=respiratory quotient.

Variceal Hemorrhage

Today we discussed the case of an elderly man who presented with an upper GI bleed in the setting of known cirrhosis. A variceal bleed was suspected.

Management of an upper GI bleed is a common scenario faced in our hospital's Emergency Department. Keep the following questions in mind:

1) Is my patient stable (ABCs, IV access -large bore, and on the monitor)?
2) Do they need fluid?
3) Do they need blood?
4) Are they coagulopathic?
5) What management can I initiate now (acid suppression, octreotide)?
6) Do I need to call Gastroenterology now?

Here is a link to a recent review on the management of variceal bleeds in the setting of cirrhosis.

Finally, here is a link for a review on the natural history and consequences of Hepatitis B.

Atrial Fibrillation

Today we discussed a case of a critically ill patient who had atrial fibrillation with rapid ventricular response and hypotension.

From a management perspective, this can be a difficult situation as many of the agents we use to rate control patients (beta-blockers and CCBs) also have a negative inotropic effect. Amiodarone can be used intravenously but also drops blood pressure in this formulation. Alternative therapies (digoxin) may avoid this, but also seem to be less effective. D/C cardioversion may bring the patient back to sinus rhythm, but will not keep them there if the underlying issue has not been assessed.

Remember that if critical illness is driving the rhythm, aggressive therapy to the underlying cause is what counts.

If you are looking for some light reading, here are the AHA guidelines on atrial fibrillation.

Finally, this is the link for the article I mentioned comparing diltiazem to digoxin or amiodarone for rate control in atrial fibrillation.

Aortic Stenosis

Today in Morning report we discussed a case of chest pain was attributed to aortic stenosis. Much of our discussion centred on the physical exam findings.

Here is a link to a previous posting that summarizes this for you.

Medical management of aortic stenosis is limited as no drug has been shown to significantly change outcomes. If the stenotic lesion is severe enough, and the patient is symptomatic, valve replacement procedures should be considered (open vs. percutaneous). Read a NEJM review here, that summarizes surgical indications.

Find the JAMA rationale clinical exam article on systolic murmurs here, and review a bedside prediction rule here.

Fever after International Travel

Yesterday we discussed the classic case of fever in a returning traveler.

There are many diagnostic approaches to take in this situation but a careful travel history is often the key to the diagnosis. Never forget that when people travel, the may do riskier things then is typical for them (or that they may care to admit) both in the environment or with other people. Point is: you need to ask and you need to look.

Inquire about chemoprophylaxis, vaccines and sick contacts and take a minute to check out the country's information on the CDC website.

An oldie but goodie review from NEJM can be found here and does a nice job with the differential diagnosis.

Rashes and bleeds

In Morning Report today, we ran through a number of cases. I wanted to highlight a couple of points:

Upper GI Bleeding

Discussion surrounding the medical management of upper GI bleeding focused on the role and dose of acid suppression medication. Specifically, does intravenous pantoprazole change outcomes as compared to an oral equivalent. The administration of high-dose intravenous proton-pump inhibitors while the patient is awaiting endoscopy does not appear to have an effect on the outcome, even though its use may be associated with a significant down-staging of endoscopic lesions. Whether this is cost-effective is still controversial. There is a recent NEJM review on the topic that I would encourage you to read.

Rash

Our case of the night focused on an approach to a patient with a rash involving the palms and soles. Involvement of the palms and soles minimizes the differential and includes syphilis, rocky mountain spotted fever, Enteroviral infections including Coxsackievirus and Echovirus, drug reactions and contact dermatitis. You MUST rule out syphilis in this context. Here is a BMJ review on syphilis. Check out some pictures here in CMAJ.

Kiss of the spider

We discussed many interesting topics today. Here's some info on two of them.

Brown recluse spider bites: These spiders belong to the Loxosceles genus and are commonly found in the south, west and midwest US so we don't see cases in Toronto that often. The brown recluse spiders have a brownish colour with a violin like mark on their head, though victims often fail no notice the spider. Bites typically occur on the upper arm, thorax, or inner thigh and happen most commonly indoors. Bites are rare on hands and feet.

The initial brown recluse bite is painless and is followed by a red plaque that can necrose in the next 24-48h and form an eschar over the ensuing days. Systemic symptoms are rare. Treatment consists of general wound care and tetanus prophylaxis. Sometimes Dapsone is used for prevention of wound progression, but there is no evidence from human studies. Here's a good review article from NEJM on Loxosceles and other spider bites.


Treatment of AAA: We touched briefly on the relative advantages of endovascular vs. open repairs for AAA. Remember that aneurysm size is a key factor on deciding how to manage AAA:

- For aneurysms 3 - 4 cm we do survelillance with U/S every 2-3 years
- For aneurysms 4 - 5.4 cm surveillance is more frequent, every 6 mo- 1 year
- At or above 5.5 cm the risk of rupture becomes greater and consideration for repair is recommended, if the aneurysm is > 2x the diameter of the normal aorta repair is also recommended
- Any symptomatic aneurysm should be considered for repair !!!

While short term mortality for endovascular repair is lower, the 2 year outcomes show similar mortality with more complications as compared to surgery. This recent trial and its accompanying editorial give a good overview of the current thinking on the topic.

Cheers

Thrombolysis in PE

Today we discussed a patient who presented with a pulmonary embolism. Indications/Evidence for thrombolysis was discussed.

To Summarize:

In 2002, a paper in NEJM compared Aleplase and Heparin vs Heparin alone and demonstrated that patients in the alteplase arm had improved clinical courses. All patients had submassive PE (and evidence of RV dysfunction or Pulmonary HTN) without arterial hypotension. This was driven by escalation of therapy in the placebo arm, not death.

A 2004 metanalysis demonstrated thrombolytic therapy compared with heparin was associated with a significant reduction in recurrent pulmonary embolism or death (9.4% versus 19.0%) in studies that enrolled patients with hemodynamically unstable PEs.

Two pro and con commentaries were published in Archives of Internal Medicine in 2005 and are good reads.

Finally, a recent NEJM review can be found here.

Overall, this is an area with uncertaintly and more RCT evidence is needed.

Rash and Fever

Today we discussed an approach to a patient presenting with fever and rash who ultimately seemed to have a drug reaction to his antiretroviral medications. We focused our discussion around a differential diagnosis of a rash in this context while touching briefly on immune reonstitution inflammatory syndrome.

Drug hypersensitivity syndromes manifest as part of a triad: fever, rash and end organ involvement (hepatitis, thyroiditis, lymphadenopthy, renal failure). Stopping the offending drug and providing supportive care is the cornerstone of treatment.

With regards to timing of therapy in patients with TB and HIV, here is a NEJM article .

Panhypopituitarism

Today we discussed an a case of hyponatremia that eventually led to the diagnosis of panhypopituitarism.

This can be a very difficult diagnosis to make due to the non-specific symptoms that a patient complains of (as was seen here).

Etiologies incluede;
1) Brain Damage (Traumatic, radiation, SAH, CVA, Surgery)
2) Neoplastic (originating in the pituitary or compression from outside)
3) Infectious
4) Infarction (Sheehan's, apoplexy)
5) Autoimmune
6) Infiltrative (hemochromatosis, histiocytosis)
7) Congenital

Here is a recent review from Lancet that highlights diagnosis and management.

Paraneoplastic Demyelination

First, wow and thank you to Dr. Panisko for flexing his muscles and walking through the differential diagnosis of yesterday's case! We discussed, among other things, an approach to weakness with a focus on demyelinating disease. A paraneoplastic syndrome was the likely conclusion.

You can find an overview on paraneoplastic neurologic disorders here.

Here is a case report of GBS associated with an adenocarcinoma of the gallbladder (only one that I could find).

Finally, here is a review of chronic demyelinating disorders.

Venous Thrombosis

Today we briefly discussed DVTs in morning report. Clinically, these can be a diagnostic challenge but clinical prediction tools are available. Check out an article in JAMA's Rational Clinical Exam series here.

We often separate severity of venous thrombosis on the basis of location (deep vs superficial). Earlier this year, a French study looked into this and found some interesting associations. Here is the link.

Finally, in our patients with COPD exacerbations of unknown cause, this article in CHEST suggests that pulmonary embolism may be the cause.

Thrombocytopenia

Today we discussed an approach to thrombocytopenia. Here is a brief overview.:

Pseudothrombocytopenia:
This is a consequence of platelet clumping as a consequence of the EDTA (lavender top) tube. The presence of this leads to the platelet clumps being miscounted on the automated system. If this is an issue, order the CBC to be drawn in citrate.

Decreased Production:
The bone marrow is unable to produce platelets in sufficient quantity as a consequence of toxicity (meds, chemotherapy, alcohol), infection (viral, TB, histoplasma), replacement (cancer, fibrosis, amyloid, sarcoid), or nutrition (folate and B12 deficiency).

Sequestration:
Think of the spleen as a giant sponge and its easy to see how as hypersplenism can reduce counts. We usually see this as a consequence of portal hypertension but primary hypersplenism is also possible. Typically, counts do not drop below 1/3 of the lower limit of normal (50k) if this is the only problem.

Destruction/Consumption:
This can be broken down into mechanical (high flow over prosthetic valves, malignant HTN), immune (HIT, ITP) or consumptive (TTP, DIC) causes. TTP is a medical emergency and this is why the blood film is so important. You need to ensure that there are no schistocytes (RBC helmets) present. I will blog on TTP as a separate post in the near future. Also, remember that ITP is a diagnosis of exclusion.

Our patient was ultimately diagnosed with ITP. A great overview on diagnosis and treatment can be found here, in the recent consensus guidelines.

Legionnaire's Disease

Today we discussed a case of a pneumonia that did not initially respond to empiric therapy. Supplemental investigations were notable for a positive Legionella urinary antigen.

Legionnaire's Disease was first described after an outbreak in Philadelphia in 1976. It is now being recognized as a more common cause of respiratory infections. It is a difficult to culture organism requiring special growth media (talk to the micro lab if you are thinking about it). Testing can also be done by the rapid urinary antigen assay (only detects L. pneumophilia serotype 1). Interestingly, one study demonstrated persistent urinary antigen positivity months after exposure (in an immunocompromised host).

Overall, empiric therapy for CAP (respiratory fluoroquinolones or a macrolide) should cover Legionella species and there are no RCTs that show one class to be superior to the other.

Here is a recent review.

Hydatid Cysts

Today we discussed a patient with abdominal pain who had a surprising finding on his abdominal imaging.

The differential diagnosis included a hydatid cyst (Echinococcus granulosus).

Information regarding the lifecycle and pathogenesis can be found in this review.

Interestingly, in a hepatic abscess caused by Klebsiella, there is an association with DM and septic endopthalmitis.

Other causes of liver cysts are discussed here.