Salicylate toxicity

Salicylate toxicity is not a common phenomenon in internal medicine, but it is important to recognize it because the management is specific.

A couple of general principles to remember in overdoses and toxidromes:

(1) Assess ABCs early and frequently. Patients can change.
(2) There is no such thing as too much IV access. Patients with toxic ingestions can seize, become hypotensive and do other unpredictable things. You will never be sorry that you asked for two IVs.
(3) Always call POISON CONTROL.
(4) Consider multiple ingestions.
(5) Think about general principles of overdose management, including decontamination.
(6) The patient may need additional monitoring, possibly in the intensive care unit setting. This is particularly true if the level of consciousness if depressed or if there is significant hypotension. Again, remember that patients change and a patient who does not need ICU at one moment may later on.

Salicylate toxicity comes in two forms:
(1) Acute overdoses - often intentional, with self-harm of suicidal intent.
(2) Chronic overdoses - from regular high dose ASA use.

The presentation can be variable and non-specific, although there are some cardinal features.

• Tachycardia, hyperventilation, fever
• Altered level of consciousness - related to direct toxicity, hypoglycemia, cerebral edema.
• Nausea, vomiting
• Platelet dysfunction
• Pulmonary edema (especially with chronic toxicity, more common in the elderly)
• Tinnitus (especially with chronic toxicity)

**The combination of an anion gap metabolic acidosis and a primary respiratory alkalosis (beyond compensation for the metabolic acidosis) should trigger the diagnosis of salicylate toxicity**

Specific Management Guidelines
(1) Alkalanize the urine. This is done by running a sodium bicarbonate infusion, targeting a urine pH of 7.5-8.5. In general, start the infusion at 150-200mL/hr and increase according to your urine pH.
(2) Potassium replacement. For any patient with urine output and a serum potassium <5, consider replacement. Similarly to patients with diabetic ketoacidosis, the total body potassium may be low despite a normal measured serum potassium because of intracellular shift related to acidosis. With alkalanization, you may see a precipitous drop in the serum K.
(3) Nephrology consultation +/- hemodialysis - Consider in patients with severe toxicity, acute renal failure, pulmonary edema. If you are not sure, involve nephrology.
(4) Consider ICU consultation. Consider endotracheal intubation if necessary from the perspective of airway protection. However, mechanical ventilation may not be as effective as the patient's own respiratory drive in correcting their metabolic acidosis.

Bacterial Meningitis

Today we discussed the approach to the diagnosis and management of bacterial meningitis.


For a good general review of bacterial meningitis, read the NEJM review by van de Beek et al. The Infectious Diseases Society of America also provides Clinical Practice Guidelines.

I've focused the discussion here on a few evidence based points that were discussed this morning.

(1) Pre-treatment with antibiotics prior to lumbar puncture may cause the culture to become negative, but should not change the biochemical properties of the CSF. This was shown in a study published by Schaad et al comparing ceftriaxone to cefuroxime where repeat lumbar punctures were done at 24 hours post initiation of antibiotics and were found to be unchanged in terms of WBC count, protein and glucose. Based partly on this data, guidelines recommend that if the patient requires a CT scan prior to LP, antibiotics should be given after blood cultures have been drawn, but prior to CT or lumbar puncture.

(2) Concurrent administration of dexamethasone with or prior to the first dose of antibiotics reduces mortality. This difference was shown in a 2002 study published in the NEJM. In this study of a combined group of patients with both streptococcus pneumoniae and with neisseria meningitidis, although the difference was largely evident in the s. pneumoniae group. The dose of dexamethasone used was 10 mg Q6H and this is the current standard of care.

(3) As shown in this brief report, re-insertion of the stylet post lumbar puncture decreases the risk of post-LP headache.

(4) Which patients need a CT brain prior to lumbar puncture? Although the vast majority of CTs done in these patients are normal, the IDSA guidelines recommend CT for anyone with an altered LOC, focal neurologic deficits, papilledema, an immunocompromised state, history of CNS disease or new onset seizure. I've linked the NEJM article supporting these guidelines here.

Physical Exam - Aortic Stenosis

To determine if a systolic murmur is related to aortic stenosis, consider the following predictive factors:

The following factors are SENSITIVE (help to rule OUT aortic stenosis)
No systolic murmur
No radiation of murmur to right clavicle

The following are SPECIFIC (help to rule IN aortic stenosis)
Pulsus parvus
Plusus tardus
Decreased S2
Brachioradial delay
Apical carotid delay
Mid-late peaking murmur

Two very good evidence based evaluations supporting this are the JAMA Rational Clinical Exam Series paper on systolic murmurs and the JGIM paper on aortic stenosis. Both come from Toronto clinicians, and are linked here and here.

Mesothelioma

Today we discussed the evaluation of a new pleural effusion in the context of a history of smoking and possible occupational asbestos exposure. The approach to pleural effusions is reviewed here.

One interesting disease that was brought up today was malignant mesothelioma. Although most commonly found as a pleural based malignancy, mesothelioma is probably best described as a cancer of serosal surfaces and can rarely present as peritoneal disease with ascites or pericardial disease.

The incidence of malignant mesothelioma is expected to rise until at least 2020, an epidemiologic phenomenon that lags behind known exposure to asbestos. In fact, in parts of the developing world, asbestos is an ongoing exposure, and therefore mesothelioma may be an ongoing problem for many years.

The diagnosis of mesothelioma can be difficult, and the sensitivity of cytology of pleural or ascitic fluid is quite variable, ranging from 33-84%, often necessitating needle or thorascopic biopsy. The disease usually presents at an advanced stage when large effusions have reached the point of symptoms, and median survival is less than one year from the time of diagnosis. Management is typically palliative, and may include local management such as pleurodesis or chronic drainage, or systemic therapy. Occasionally surgery is required to manage complications of locally advanced disease.

A good NEJM review is available.

Welcome to "The Pulse", a blog of educational activities at TGH. This blog was started by Isaac Bogoch last year and will be continued onwards this year. All errors, omissions and mis-representations are his.

Today at morning report, we discussed the approach to a patient with an altered level of consciousness. The facilitator provided a framework for the differential diagnosis:

1. Neurologic causes - including stroke, CNS infections, dementing illnesses such as Lewy Body dementia, normal pressure hydrocephalus and others.

2. Metabolic causes - including electrolyte abnormalities (think sodium and calcium!), endocrinopathies (e.g. thyroid disease).

3. Medications - overdose, intoxication, withdrawal. Also consider over-the-counter and alternative therapies.

4. Major medical illness. Both liver and kidney dysfunction can present with altered level of consciousness.

5. Psychiatric illness. Depression can present in atypical ways, particularly in the elderly.

We also talked about the basics of the workup and management of stroke. A good general review article on stroke can be found in the New England Journal of Medicine 2007, Vol 357 (6), pp 572-579. A link to the abstract is found here

I would encourage you to consult the Canadian Stroke Network best practice guidelines on stroke management, linked here. Although practice guidelines often represent a combination of evidence and expert opinion, they can be helpful resources and can direct you to the peer-reviewed literature.

Hope you are all enjoying the first week. Let me know how I can help make this a great experience for you!

Shannon