Friday, February 27, 2015

Is “atypical coverage” really important in community acquired pneumonia?

In this study the inclusion of atypical coverage was not associated with reduced mortality but did result in shortened time to clinical stability.

Thursday, February 26, 2015

Occult bacteremia

These are the people who get sent home from the ER then have to be called back because their blood cultures turn positive. In this study from a single institution it appeared to be a benign entity:

This is a retrospective cohort study (September 2010 to September 2012), in adult patients discharged from the ED in whom blood cultures turned positive. Patients were evaluated according to a preestablished protocol.

We recorded 4025 cases of significant BSI in the ED and 113 patients with adult occult BSI. In other words, the incidence of occult BSI in the ED was 2.8 per 100 episodes. The predominant microorganisms were gram-negative bacteria (57%); Escherichia coli was the most common (41%), followed by gram-positive bacteria (29%), anaerobes (6.9%), polymicrobial (6.1%), and yeasts (0.8%). The most frequent suspected origin was urinary tract infection (53%), and most infections were community acquired (63.7%). Of the 105 patients that we were able to trace, 54 (42.5%) were asymptomatic and were receiving adequate antibiotic treatment at the time of the call, and 65 (51.2%) had persistent fever or were not receiving adequate antibiotic treatment.

Occult BSI is relatively common in patients in the adult ED. Despite the need for readmission of a fairly high proportion of patients, occult BSI behaves as a relatively benign entity.

Tuesday, February 24, 2015

When is permanent pacing indicated for AV block?

I'm working through MKSAP 16's section on cardiovascular disease. As much as I hate to be immodest, it's a content area I think I know just a little something about, particularly in the area of electrophysiology. I was drawn to their statement on permanent pacing after acute MI (AMI). Sprinkled throughout MKSAP are sets of high value care recommendations for various specialties, apparently their own version of Choosing Wisely.

The pacing recommendation, which is to wait several days after the occurrence of AV block (AVB) before inserting a permanent pacemaker (PPM) in order to see if the block persisted, struck me as awfully simplistic. Pacing recommendations for AVB have strong underpinnings in physiology which have withstood evidence based scrutiny. The relevant electrophysiology, far more often than not, can be assessed at the bedside via simple electrocardiography. Well, maybe I should qualify that by saying it's true provided adequate skill in interpretation of the ECG is brought to the bedside.

Things have changed through the years. Clinical skills in this area have deteriorated, in part because AVB complicating AMI is much less common in today's reperfusion era than it once was. The question of what to do with AVB after AMI seldom comes up anymore. Before the reperfusion era it was routine. The guiding principle back then was that, at least in acute anterior MI, when the block was subjunctional, that is true type II block, permanent pacing was indicated no matter how transient the block. (Caveat: the atypical situation of block arising in the common bundle of His is a nuanced topic, beyond the scope of this post).

So what about the current guidelines? The STEMI guidelines refer this topic to the device therapy guidelines which say in part:

1. Permanent ventricular pacing is indicated for persistent second-degree AV block in the His-Purkinje system with alternating bundle-branch block or third-degree AV block within or below the His Purkinje system after ST-segment elevation MI. (Level of Evidence: B) (79,126 –129,131)

2. Permanent ventricular pacing is indicated for transient advanced second- or third-degree infranodal AV block and associated bundle-branch block. If the site of block is uncertain, an electrophysiological study may be necessary. (Level of Evidence: B) (126,127) 

For patients in general with acquired AVB the guidelines include the following, listed under the class IIa category:

4. Permanent pacemaker implantation is reasonable for asymptomatic type II second-degree AV block with a narrow QRS.

When type II second-degree AV block occurs with a wide QRS, including isolated right bundle-branch block, pacing becomes a Class I recommendation. (See Section 2.1.3, “Chronic Bifascicular Block.”) (Level of Evidence: B) (70,76,80,85)

The recommendation summary is much more extensive but this small sample illustrates the complexity of decision making and the reliance on assessment of the anatomic site of block via electrocardiography (bedside electrophysiology). When it comes to pacing decisions post MI there's considerably more to it than the MKSAP recommendations would indicate.

Monday, February 23, 2015

Opiate withdrawal: usually benign but not always

The main problem is when opiate withdrawal is precipitated (such as with naloxone) in a narcotic tolerant patient. Here is a case report and review.

Sunday, February 22, 2015

PVCs can help in the diagnosis of myocardial ischemic syndromes

Here is a case presented at Dr. Smith's ECG blog and a link to several more. As Barney Marriott was fond of saying, PVCs pay diagnostic dividends. Know them!

Saturday, February 21, 2015

Admission HgbA1C to help determine discharge diabetes regimen

From a study in Diabetes Care:

RESEARCH DESIGN AND METHODS This was a prospective, multicenter open-label study aimed to determine the safety and efficacy of a hospital discharge algorithm based on admission HbA1c. Patients with HbA1c less than 7% (53.0 mmol/mol) were discharged on their preadmission diabetes therapy, HbA1c between 7 and 9% (53.0–74.9 mmol/mol) were discharged on a preadmission regimen plus glargine at 50% of hospital daily dose, and HbA1c greater than 9% were discharged on oral antidiabetes agents (OADs) plus glargine or basal bolus regimen at 80% of inpatient dose. The primary outcome was HbA1c concentration at 12 weeks after hospital discharge.

RESULTS A total of 224 patients were discharged on OAD (36%), combination of OAD and glargine (27%), basal bolus (24%), glargine alone (9%), and diet (4%). The admission HbA1c was 8.7 ± 2.5% (71.6 mmol/mol) and decreased to 7.3 ± 1.5% (56 mmol/mol) at 12 weeks of follow-up (P less than 0.001). The change of HbA1c from baseline at 12 weeks after discharge was −0.1 ± 0.6, −0.8 ± 1.0, and −3.2 ± 2.4 in patients with HbA1c less than 7%, 7–9%, and greater than 9%, respectively (P less than 0.001). Hypoglycemia (less than 70 mg/dL) was reported in 22% of patients discharged on OAD only, 30% on OAD plus glargine, 44% on basal bolus, and 25% on glargine alone and was similar in patients with admission HbA1c less than or equal to 7% (26%) compared with those with HbA1c greater than

CONCLUSIONS Measurement of HbA1c on admission is beneficial in tailoring treatment regimens at discharge in general medicine and surgery patients with type 2 diabetes.

From commentary in the ACP Hospitalist Weekly:

Measuring HbA1c at admission can help with tailoring a postdischarge treatment regimen for type 2 diabetes patients, the study authors concluded. The observed rate of hypoglycemia was acceptable, which should reassure any hospital clinicians who avoid intensifying outpatient regimens out of fear of hypoglycemia, the authors noted. The findings also support recent guidelines recommending insulin treatment during hospitalization, but resumption of oral medications at discharge for patients with acceptable control. Improving postdischarge glucose control could potentially reduce revisits to the emergency department or hospital, the authors suggested.
Measuring HbA1c at admission can help with tailoring a postdischarge treatment regimen for type 2 diabetes patients, the study authors concluded. The observed rate of hypoglycemia was acceptable, which should reassure any hospital clinicians who avoid intensifying outpatient regimens out of fear of hypoglycemia, the authors noted. The findings also support recent guidelines recommending insulin treatment during hospitalization, but resumption of oral medications at discharge for patients with acceptable control. Improving postdischarge glucose control could potentially reduce revisits to the emergency department or hospital, the authors suggested.

It's important to note that patients in the study had telephone contacts every 2 weeks in the 2 months after discharge and follow-up visits at 1 and 3 months, which could have contributed to their improved glycemic control.
It's important to note that patients in the study had telephone contacts every 2 weeks in the 2 months after discharge and follow-up visits at 1 and 3 months, which could have contributed to their improved glycemic control.

Wednesday, February 18, 2015

Monitoring the limb lead voltage may help track improvement in acute decompensated heart failure

Especially lead aVR. It performed better than proBNP in this study. Small numbers, but interesting. 

Boerhaave's syndrome

Here is a case report and concise review.

From the paper:

Boerhaave's syndrome is readily suspected in a patient with a history of overindulgence in food or drinks who, after severe or repeated vomiting, experiences excruciating chest pain and develops subcutaneous emphysema [3]. However, up to one-third of patients have atypical symptoms or are admitted with severe respiratory distress and/or shock. The differential diagnosis of Boerhaave's syndrome includes a variety of acute thoracic and abdominal conditions including myocardial infarction, pulmonary embolus, dissecting aorta, ruptured aortic aneurysm, perforated peptic ulcer, Mallory-Weiss syndrome, pancreatitis, pneumonia, and spontaneous pneumothorax [4].

Tuesday, February 17, 2015

Early repolarization syndrome: the latest channelopathy

Traditionally the electrocardiographic early repolarization pattern has been considered benign. The last decade, however, has raised awareness of a subset of patients with this pattern who are at risk for sudden cardiac death. With advances in our understanding this subset has emerged as a new channelopathy. Distinguishing characteristics which differentiate the malignant variety (now termed early repolarization syndrome, ERS) from benign early repolarization (which is fairly common in the general population) are now better defined. This free full text review summarizes the latest evidence, provides some illustrative tracings and discusses an algorithm for evaluation.

Cardiac sarcoid versus ARVD

The distinction can be difficult even when the accepted ARVD criteria are applied. Based on the Hopkins experience there are some clues though:

Conclusions—The 2010 diagnostic criteria for ARVD/C have limited discrimination in distinguishing between ARVD/C and CS. Despite the overlay in clinical presentation, older age of symptom onset, presence of cardiovascular comorbidities, nonfamilial pattern of disease, PR interval prolongation, high-grade atrioventricular block, significant left ventricular dysfunction, myocardial delayed enhancement of the septum, and mediastinal lymphadenopathy should raise the suspicion for CS.

Monday, February 16, 2015

Discharge summary quality for heart failure hospitalizations

The conclusion from recent findings:

Even at the highest performing hospital, discharge summary quality is insufficient in terms of timeliness, transmission, and content. Improvements in all aspects of discharge summary quality are necessary to enable the discharge summary to serve as an effective transitional care tool.

Elements that were missing in almost all discharge summaries were discharge weight and discharge volume status. Discharging patients “too wet” has previously been cited as a driver of recurrent heart failure hospitalizations.

Cauda equina syndrome

This is a diagnosis you want to make early. Here's a very helpful review.

A post at Academic Life in Emergency Medicine, which cites the review, has a lot of pearls. It notes this regarding the medicolegal risk:

About 84% of the plaintiff verdicts involved a situation where the patient experienced permanent bowel or bladder dysfunction. Plaintiffs were more likely to win in cases when deficits developed after presentation, specifically when CES was initially missed. When patients present with incontinence, the plaintiff only won 16% of the cases [2].

Hence the importance of carefully documenting the patient's findings on initial presentation.

Sunday, February 15, 2015

Cerebral vein and sinus thrombosis: plain language summary

Free full text from Circulation.

A series of patients with primary pulmonary coccidioidomycosis

In this series of patients seen at the Mayo Clinic in Arizona several points are noteworthy:

It accounts for 15%–29% of community-acquired pneumonia in Arizona.

Symptom and radiographic resolution is slow, a matter of weeks.

It has seen a dramatic increase in Arizona. From the article:

The incidence of infection in this coccidioidomycosis-endemic area has considerably increased from 5.3 cases per 100,000 population in 1998 to 42.6 cases per 100,000 population in 2011.

Treatment criteria are controversial. Again, from the article:

Although the Infectious Diseases Society of America treatment guidelines acknowledge differences of expert opinion regarding the need to treat primary coccidioidomycosis (23), the guidelines suggest identifying characteristics to facilitate diagnosis of moderate to severe infection in patients who might benefit from treatment (23). These guidelines recommend possible antifungal treatment for patients with symptoms lasting greater than 2 months, night sweats greater than 3 weeks, weight loss of greater than 10%, inability to work, serologic complement fixation titer greater than 1:16, bilateral infiltrates or involvement of at least one half of 1 lung, or prominent or persistent hilar adenopathy (23).

Thursday, February 12, 2015

Dr. Richard Baron debates Dr. Charles Cutler and defends MOC before the Philadelphia County Medical Society

Yes, the same Richard Baron who just two months later sent out the “We're sorry. We got it wrong” email to ABIM diplomats. You can watch the debate here. I was not aware of this video until just the other day, following ABIM's announcement, from some of the comments on social media. It gave me a better understanding of what's going on and dampened my initial optimism about ABIM's February 3 announcement. Dr. Cutler's description of how our money is being spent by the board was shocking.

What was of particular interest to me was Dr. Baron's vigorous defense of MOC including the changes that went into effect in 2014. He claimed to have years of demonstrated need and evidential support to back up the changes. There was nothing tentative or circumspect in his arguments. He came across as one who had firmly made up his mind. How then do you get from there to “we got it wrong” in just two months? My skepticism concerning the February 3 announcement is heightened.

Coronary subclavian steal: an increasingly recognized entity

From a recent review:

Coronary subclavian steal syndrome (CSSS) is the reversal of blood flow in an internal mammary artery bypass graft that results in coronary ischemia. CSSS is an uncommon but treatable cause of coronary ischemia. In this review, we highlight the historical background and epidemiology of CSSS, common clinical presentations, diagnosis of CSSS and management strategies for relieving ischemia…

Recent findings: Most commonly, CSSS results from atherosclerotic stenosis of the subclavian artery and occurs in 2.5–4.5% of patients referred for coronary artery bypass grafting (CABG). All patients referred for CABG should have bilateral noninvasive brachial blood pressures checked to screen for the underlying subclavian stenosis. A review of 98 case reports with 128 patients demonstrated a diverse clinical presentation of CSSS, including acute myocardial infarction, unstable angina and acute systolic heart failure. Resolution of CSSS symptoms has been reported with both surgical and percutaneous revascularization. Long-term patency with either revascularization strategy is excellent. Percutaneous revascularization is largely considered the first-line therapy for CSSS and can be safely performed prior to CABG to prevent CSSS.

Summary: CSSS should be suspected in patients presenting with angina, heart failure or myocardial infarction after CABG. Successful amelioration of CSSS symptoms can be safely and effectively performed via percutaneous revascularization.

Diabetic ketoalkalosis


That was the topic of this paper in the Southern Medical Journal. Diabetic ketoalkalosis (DKALK) refers to a complex acid base disorder in which diabetic ketoacidosis (DKA) coexists with a separate process causing metabolic alkalosis. This results in a rise in the delta ratio (DR, or delta gap/delta bicarb) to greater than 1.2 when, in simple DKA it should be around 1.0. Put another way, the coexisting metabolic alkalosis prevents the bicarb from falling as much as would be expected from the rise in the anion gap. It's a misnomer, of course, because the ketosis does not cause the alkalosis; the alkalosis is a separate process. The alkalosis is believed due to vomiting and counter regulatory responses to volume loss. The DR could be incalculable if the metabolic alkalosis is severe enough that the bicarb (and pH) are normal.

Don't forget that the opposite can occur. A DR less than 0.8 suggests a second process causing metabolic acidosis such as lactic acidosis.

Wednesday, February 11, 2015

A success story in community health promotion

From a new study in JAMA:

Conclusions and Relevance Sustained, community-wide programs targeting cardiovascular risk factors and behavior changes to improve a Maine county’s population health were associated with reductions in hospitalization and mortality rates over 40 years, compared with the rest of the state. Further studies are needed to assess the generalizability of such programs to other US county populations, especially rural ones, and to other parts of the world.

More from Cardiobrief.

Mechanisms of diabetic cardiomyopathy

From a recent review:

Core tip: Diabetic patients develop a cardiomyopathy that is independent of vascular disease, and is thought to develop as a direct result of the prolonged hyperglycaemia. Animal models of diabetes can help us understand the cellular mechanisms that lead ultimately to contractile dysfunction of diabetic cardiomyopathy. The streptozotocin rat model of type 1 diabetes has slowed Ca2+ transients and twitch force kinetics, with reduced myofilament Ca2+ sensitivity. Myocytes are decreased in volume in diabetic hearts, with reduced and disrupted F-actin, and type 1 collagen is increased. Together, these changes all contribute to the reduced contractility of diabetic cardiomyopathy.

Monday, February 09, 2015

Chloramphenicol 50 years later

Nowadays, with rising antimicrobial resistance outpacing the antibiotic pipeline, we increasingly have to consider pulling old drugs off the shelf. What about chloramphenicol? From a recent systematic review and meta-analysis:

Results Sixty-six RCTs fulfilled the inclusion criteria, and these included 9711 patients. We found a higher mortality with chloramphenicol for respiratory tract infections [risk ratio (RR) 1.40, 95% CI 1.00–1.97] and meningitis (RR 1.27, 95% CI 1.00–1.60), both without heterogeneity. The point estimate was similar for enteric fever, without statistical significance. No statistically significant difference was found between chloramphenicol and other antibiotics regarding treatment failure, except for enteric fever (RR 1.46, 95% CI 1.07–2.00, without heterogeneity). This difference derived mainly from studies comparing chloramphenicol with fluoroquinolones (RR 1.85, 95% CI 1.07–3.2). There were no statistically significant differences between chloramphenicol and other antibiotics in terms of adverse events, including haematological events, except for anaemia, which occurred more frequently with chloramphenicol (RR 2.80, 95% CI 1.65–4.75, I2 = 0%), and gastrointestinal side effects, which were less frequent with chloramphenicol (RR 0.67, 95% CI 0.46–0.99, I2 = 0%). Many of the studies included were sponsored by pharmaceutical companies marketing the comparator drug to chloramphenicol, and this might have influenced the results.
Conclusions Chloramphenicol cannot be recommended as a first-line treatment for respiratory tract infections, meningitis or enteric fever as alternatives are probably more effective. Chloramphenicol is as safe as treatment alternatives for short antibiotic courses.

Historically, the safety concern with chloramphenicol has been its hematologic toxicity. This study mitigates that concern somewhat but also found that newer agents tend to be more effective for its old indications.

Via Hospital Medicine Virtual Journal Club.

The fragmented or notched QRS

---was associated with a worse prognosis in patients with systolic heart failure and a narrow QRS complex in this study.

Sunday, February 08, 2015

Antiviral drugs for this year’s seasonal influenza

From the Medical Letter via JAMA.

From the article:

In patients with mild illness caused by a susceptible strain of influenza, starting treatment with a neuraminidase inhibitor within 48 hours after the onset of illness can decrease the duration of fever and symptoms and may also reduce the risk of complications such as pneumonia.3 In hospitalized and critically ill patients, observational studies indicate that these drugs can decrease the risk of death when started soon after symptom onset; the results of some studies suggest that treatment within 4-5 days after symptoms appear may still have some benefit.4- 6 The usual duration of treatment with a neuraminidase inhibitor is 5 days, but a prolonged treatment course (eg, 10 days) is often used for critically ill or immunocompromised patients, in whom viral replication may be protracted.

Cardiovascular risk after a diagnosis of giant cell arteritis

It is increased, both in the long and the short term.

Saturday, February 07, 2015

Changes to Maintenance of Certification (MOC)

The American Board of Internal Medicine's February 3 announcement came during a very busy week in hospital medicine for me and I have just now had time to process it. There is a lot to unpack. The announcement, which contains an apology and an acknowledgment that they “got it wrong,” is a welcome development but it raises many questions. Below is my very preliminary take.

What is the immediate impact?
For me, two items are significant:

Effective immediately, ABIM is suspending the Practice Assessment, Patient Voice and Patient Safety requirements for at least two years.

That is a great relief for me as I trudge through. Now I can focus on the learning activity, which is the important part. I get points for MKSAP, which I love doing and would have done anyway.

Within the next six months, ABIM will change the language used to publicly report a diplomate's MOC status on its website from “meeting MOC requirements” to “participating in MOC.”

That is in response to the problem I addressed here:

So what am I talking about? Well, for the grandfathered internists who choose not to perform the “voluntary” recertification activities the Board is coming as close to de-certifying them as they can without actually taking the certification away and having to say “Sorry. We lied.”
How does it work? It's in the way they report your certification status. Go to their website and look up the name of a grandfathered colleague (this portion of the site is open to the public). Those not participating are designated as Certified but right under that it says Meeting Maintenance of Certification Requirements: No.
What will the public think? What will credentialing bodies think? While this will confuse some people it comes across loud and clear to most as nominally certified but not really certified.

While I am thankful they softened the language they have not fully addressed the problem, which is that in a round about way they went back on their promise of lifetime certification with voluntary maintenance.

ABIM's announcement is a positive step but is it enough?
For the practice assessment and patient safety modules, perhaps the most troublesome aspect of MOC, all they did was call a moratorium. Nobody knows what they will do with this in two years. These exercises were fundamentally flawed but ABIM did not acknowledge that. All they admitted was that they launched programs that weren't ready and that docs did not find meaningful. That leads to the question of what these programs will look like once ABIM deems them “ready.” What about the apology? Does it represent appeasement or is it genuine contrition? I will take a wait and see attitude. The move by ABIM was a first step but only that. Vigorous debate of the issues surrounding MOC needs to move forward.

Despite ABIM's pledge to freeze MOC fees the accusations of financial impropriety were not addressed.
These have been nicely summarized in a series of posts over at Dr. Wes. Whether the conflicts are real or only perceived they need to be addressed by the board in a manner that will restore the credibility of their leadership. I have yet to see movement in that direction.

Questions linger about CME.
In a recent post about the MOC discussion medical journalist Larry Husten said this:

As I said, CME can play a key role in MOC, but only when the doctors pay for it themselves. To start, every effort should be taken to remove industry’s role from CME.

In his thinking that would rule out most accredited category I offerings because, as he correctly implied in the same post, most of it is funded, to one degree or another, by industry.

A very vocal group of physicians agree with Mr. Husten. But if the ABIM leaders really mean what they said in the February 3 announcement it would appear that they disagree because they say that going forward they plan to recognize “most forms of ACCME-approved Continuing Medical Education.”

But one part of ABIM's statement on CME is concerning, from the FAQ page:

We are absolutely interested in finding ways to recognize meaningful clinical work that you do in your practices to earn CME points, and we're particularly interested in recognizing CME activities for which there is evidence that they drive learning and/or change practice. Many forms of “passive” CME do not meet this standard.

This implies that we're headed back to the practice improvement modules and, even worse, that the learning points may be tied to those activities. And what kind of evidential support are they looking for? I know of no robust evidence that ties any form of CME, inside or outside of MOC, to meaningful outcomes. We all know intuitively that knowledge helps drive better patient care but the idea that these processes with all their layers of complexity can be measured in a meaningful way strikes me as naive.

Glycemic effects of various classes of antihypertensive drugs

From a recent review:

Core tip: Hypertension is a major contributor to the development and progression of cardiovascular disease. Increased blood pressure often coexists with insulin resistance. The various antihypertensive drugs have different effect on glucose metabolism. Indeed, angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis. Calcium channel blockers are considered to have neutral metabolic effects. On the other hand, diuretics and β-blockers have an overall disadvantageous effect on glucose metabolism. As a result the metabolic effects of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment.

Friday, February 06, 2015

Hemochromatosis: a treatable cardiomyopathy

From a recent review:
The average survival is less than a year in untreated patients with severe cardiac impairment. However, if treated early and aggressively, the survival rate approaches that of the regular heart failure population.

Thursday, February 05, 2015

The physiology and clinical importance of hyperinflation in COPD

This open access full text review examines the physiology and mechanism of dyspnea due to hyperinflation in COPD.

Monday, February 02, 2015

Magnesium and cardiovascular disease

The cardiovascular effects of magnesium are multiple and complex. Here is a recent free full text review.

From the conclusion of the review:

Mg2+ has vasodilatory, anti-inflammatory, anti-ischemic, and antiarrhythmic properties (Fig. 3). It is a critically important nutrient and a potentially useful therapeutic agent in cardiovascular medicine. Several experimental, epidemiological, and clinical studies have established the role of Mg2+ in the pathogenesis of cardiovascular disorders. Currently, the use of Mg2+ is limited mostly for the prevention and/or treatment of cardiac arrhythmias. We believe that adequate Mg2+ intake should be a part of the heart healthy diet. However, there is a compelling need for several well-designed cohort studies to determine the interrelationship among dietary Mg2+ intake, serum (or intracellular) Mg2+ concentration, and CVD, and to provide concrete evidence on the risks and/or benefits of taking Mg2+ supplements. Future basic science research should be focused on gaining a better understanding of the metabolic effects of Mg2+ intake in health and disease. Lastly, larger well-designed, randomized controlled trials are needed to widen the therapeutic scope of this inexpensive nutrient.

Sunday, February 01, 2015

Methotrexate overdose

From the Journal of Toxicology:

Objective. Limited reported data have reports effects after acute ingestion of methotrexate. Treatment recommendations do not differentiate between exposure routes. Our objective was to determine the frequency of significant toxicity effects and use of therapy after methotrexate ingestion in adults. Methods. We performed a retrospective study on adult cases reported to 6 poison centers over 6 years (2000–2005) which exceed 180,000 exposures/year.. No patient in the series received dialysis or died. The mean dose ingested for all patients was 24mg (range 2.5–100mg) and the mean dose for suicidal ingestions was 47.5mg (12.5–100mg). The most common clinical effects were abdominal pain, oral irritation, throat irritation, nausea, dizziness, and headache. Nine patients received folinic acid and 3 patients received sodium bicarbonate. No patient developed renal failure, bone marrow suppression, seizure, or coma. No patient died or received dialysis. Conclusion. In our series of patients from 6 poison centers over six years, 63 cases of acute adult methotrexate ingestions were reported. Methotrexate toxicity from ingestion in adults was uncommon and rarely toxic...

Methotrexate has been used in parenteral form as a chemotherapeutic agent for decades. In recent years, the oral form has been used for the treatment of rheumatologic conditions with both increased frequency and dosage [8]. Parenteral methotrexate toxicity has been examined, and several effects such as renal failure, respiratory failure, myelosuppression, and neurologic disruption have been described [1, 9]. Recent case reports have described fatal overdose of methotrexate ingestions, although no data from a large series of acute ingestions has been reviewed until now [4].

While several antidotes have been postulated for methotrexate toxicity, folinic acid (leucovorin) has been shown to be the most effective and has few known complications [10]. We found that the use of methotrexate-specific treatments was uncommon, possibly suggesting that physicians were unfamiliar with this rarely used drug or the physicians were not concerned the patients were ill and need it...

Based on these findings, supportive care and observational therapy without methotrexate-specific treatment should be considered in acute ingestions. Patients can be monitored for development of renal insufficiency, neurologic effects, or bone marrow suppression. Based on the clinical effects and followup, the measurements and reexaminations could be done as an inpatient or outpatient. A large, prospective study to evaluate this treatment approach is warranted.