Trends in the use of physostigmine for anticholinergic overdose

Here's a new study from the Division of Emergency Medicine at Washington University, drawing on a large toxicology database, looking at the treatment of patients with anticholinergic toxicity. From the paper:

The anticholinergic toxidrome is well described and relatively common. Despite controversy, studies have shown that physostigmine is relatively safe and effective in reversing this toxidrome. We would expect toxicologists would be liberal in its use. We retrospectively analyzed data in the Toxicology Investigators Consortium (ToxIC) registry, representing data from medical toxicologists in multiple institutions nationwide, searching for patients who exhibited an anticholinergic toxidrome, determining what treatment(s) they received, and classifying the treatments as physostigmine, benzodiazepines, physostigmine and benzodiazepines, antipsychotics, or no definitive treatment. The causal agents of the toxidrome were as reported by the treating toxicologist. Eight hundred fifteen consecutive patients with anticholinergic toxidromes were analyzed. Benzodiazepines alone were given in 28.7 %, 12.4 % were given physostigmine alone, 8.8 % received both physostigmine and benzodiazepines, 2.7 % were given antipsychotics, and 47.4 % were given no definitive treatment. In patients who received only physostigmine, there was a significant difference in the rate of intubation (1.9 vs. 8.4 %, OR 0.21, 95 % CI 0.05-0.87) versus other treatment groups. Physostigmine was given at varying rates based on causative agent with use in agents with mixed or unknown effects (15.1 %) being significantly lower than those with primarily anticholinergic effects (26.6 %) (p less than 0.001). Patients with anticholinergic toxicity were more likely to receive benzodiazepines than physostigmine. Those patients who received only physostigmine had a significantly lower rate of intubation. Physostigmine was more likely to be used with agents exerting primarily anticholinergic toxicity than in those agents with multiple actions.

Physostigmine is making a comeback for this indication. It appears to be safe and very effective (markedly reduces the intubation rate) for patients with a pure anticholinergic toxidrome. Conservative use reported in the article for patients with a mixed toxidrome probably reflects hesitancy to use it in cases of TCA overdose where physostigmine carries a risk of adverse cardiac effects and seizures. I previously blogged this topic here.

Phlegmasia dolens (cerulea and alba)

A nice mini-lecture from Mayo EMBlog.

Percutaneous closure of a patent foramen ovale to correct hypoxemia

Here is a case discussion and brief review.

Peripheral neuropathy: diagnosis and management

A concise review from Mayo Clinic Proceedings.

Parasitology resource

Visit this site for the parasitology case of the week!

Panic disorder and coronary heart disease

A recent systematic review suggests a link:

Method. Relevant studies were retrieved from Medline, EMBASE, SCOPUS and PsycINFO without restrictions from inception to January 2015 supplemented with hand-searching. We included studies that reported hazard ratios (HR) or sufficient data to calculate the risk ratio and 95% confidence interval (CI) which were pooled using a random-effects model. Studies utilizing self-reported CHD were ineligible. Twelve studies were included comprising 1 131 612 persons and 58 111 incident CHD cases.

Results. PD was associated with the primary incident CHD endpoint [adjusted HR (aHR) 1.47, 95% CI 1.24–1.74, p less than 0.00001] even after excluding angina (aHR 1.49, 95% CI 1.22–1.81, p less than 0.00001). High to moderate quality evidence suggested an association with incident major adverse cardiac events (MACE; aHR 1.40, 95% CI 1.16–1.69, p = 0.0004) and myocardial infarction (aHR 1.36, 95% CI 1.12–1.66, p = 0.002). The risk for CHD was significant after excluding depression (aHR 1.64, 95% CI 1.45–1.85) and after depression adjustment (aHR 1.38, 95% CI 1.03–1.87). Age, sex, length of follow-up, socioeconomic status and diabetes were sources of heterogeneity in the primary endpoint.

The quest for open access point of care resources: can we have a free Up to Date?

Should physicians have to pay for information resources? Many physicians, among the most vocal being the pharmascolds, have maintained that they should. Recently, though, there has been a large and growing push for open access to clinical look up resources at the point of care. This was the subject of an essay and a related editorial from a recent issue of PLOS Medicine.

As the open access movement has grown increasing numbers of research articles are available free of charge on line. In addition, not only these but all Medline indexed articles can be searched for free via Pubmed, with free access to the abstracts of those journals that are not open. This, then, makes it possible for everyone to do free searching and retrieval according to the original standards of evidence based medicine. But optimal use of Pubmed requires special skills and, as I have said before, is too time consuming for most clinicians. That is one of the main barriers to the practice of evidence based medicine. The founders of EBM realized early on that the solution was to develop secondary sources, which are pre-processed summaries of clinical topics that doctors could access at the point of care. The problem is that those that have been developed, at least those widely regarded to be good, are expensive. Therein, according to the articles, lies the problem: the open access movement, for all its accomplishments, has yet to deliver pre-processed content of the type doctors need at the point of care.

It's not that it hasn't been tried. The essay cites some attempts that have failed. I can think of others not mentioned, or only given passing mention. Scientific American Medicine, for example, originated as the first continually updating paper textbook of medicine, was offered on line for free to physicians who registered with WebMD. Free access went away after a couple of years. Merck Medicus once offered free access portals to Access Medicine, MD Consult and more but they didn't last.

We still have eMedicine though it has gone through a few iterations. It remains free access and, though I have not found it as helpful as Up to Date in the past, it has improved over time.

Conspicuously absent from both papers was any mention of the open access initiatives in social media such as FOAM and BLITTER.

Conclusions and reflections:

The availability of free on line secondary source point of care information is limited.

High quality POC reference sources are largely subscription based.

Efforts on the part of the open community to build free resources have been of limited success.

Free high quality resources have mainly been available through industry support but they have not been sustainable.

There appears to be a sharp divide between pharmascolds and the open access community over whether clinicians should have to pay for access to information. Over the past decade and a half the pharmascolds have largely won the battle against industry support.

Efforts by the social media community show promise but are early in development.

The new CHEST guidelines for antithrombotic therapy

This go round the update is being handled a bit differently it would seem, by releasing one section at a time.  As of now only the section on VTE treatment has been posted, and the full text can be accessed here.  The rest of the guidelines, e.g. those for antiplatelet therapy and VTE prevention, will, I'm guessing, be posted later, a section at a time.

Retired Doc has already written a nice summary post which you can access here.

For my own take, I'll highlight the major changes and comment on some other points of particular interest.  In this edition as in previous ones the authors are true to the first principle of evidence based medicine (EBM) which is that the ultimate decision maker for treatment is the patient, providing he or she wants to be, as opposed to some pathway, core measure or central controlling authority.  This is illustrated by phrases throughout the paper, often used after their recommendation statements, to the effect that the patient may choose this over that treatment.  The document is well referenced and the recommendations seem based on careful consideration of the evidence.  Those good things being said, the paper is also a masterpiece of obfuscation, examples of which I will point out along the way.  Although there is some sense to be made of it (as I try to provide in plain language below) the process of doing so was very difficult.  The guideline is worth reading in the original text but do so when you are rested, fed and have plenty of time.


The 2012 definitions for duration of therapy are maintained.

Somewhere along the line, in 2012 I believe, the guideline authors changed the category definitions for VTE treatment duration.  They have now been around for a while but, I believe, still confuse clinicians.  The old classification seemed pretty straightforward:  short term (3 months, mainly for patients with transient risk factors), usual (6 months, appropriate for most patients with spontaneous events) and indefinite (potentially for the rest of the patient's life, for those with especially high risk of recurrence).   But the current classification turns that all around.  “Long term” is now defined as 3 months of treatment.  The middle category, “longer, time limited” is defined as 6-12 months.  The third category, termed “extended,” could be any time of longer than 3 months but without a scheduled stop date.  At the risk of pushing this to absurdity extended treatment could be as little as 3 months and one day, meaning that the order of this listing is not necessarily in order of treatment duration though it is implicit in the discussions in the paper that “extended” usually means longer than a year.


So what are the recommended durations of treatment for various clinical circumstances?

For VTE (for purposes of this post that means DVT and/or PE) not associated with active cancer and associated with a transient risk factor, surgical or otherwise, the guideline calls for 3 months treatment.  The strength of the statement (we recommend versus we suggest) varies with bleeding risk but the guideline always prefers 3 months over longer time limited or extended. 

For VTE not associated with active cancer and not associated with a transient risk factor, the order of preference for duration is extended preferred over 3 months which in turn is preferred over longer time limited (see the one exception below).  It is really difficult to make sense of this when, in plain language, it says “potentially for the rest of your life” is choice number 1, 3 months is choice number 2 and 6-12 months is choice number 3.  That is, the descending order of preference does not equal the descending order of duration!  The exception is that if the bleeding risk is high (I'll explain how the guideline defines that later) 3 months of treatment is the preference over the other two options.

To add to the confusion (and perhaps the entertainment value) of the guideline check out this statement from section 9 regarding the decision making process for patients who are potential candidates for extended (as opposed to 3 month) treatment:

Patient sex and D-dimer level measured a month after stopping anticoagulant therapy may influence the decision to stop or extend anticoagulant therapy..

But a month after stopping, well, you've already stopped!  It's almost comical when you think about it.  The plain language version would be stop treatment, wait a while, then run a test to see if you should stop.  What they really must have meant was stop treatment, wait a while, then run a test to see if you should have stopped.  It seems the authors didn't say what they really meant, perhaps because that would have sounded as though they were recommending you put the patient at undue risk.  But I do think there is a basis for this.  The body of the paper cites evidence.  I will appeal to pathophysiology and attempt to explain it this way.  While the patient is systemically anticoagulated the coagulation system is held at bay.  Once you stop, there are certain higher risk patients who will reactivate their coagulation systems in a subclinical manner, with the process simmering beneath the surface.  Such patients, identified by an elevated D dimer, would be considered poised to clot again soon.  So, in certain circumstances, the D dimer may be a useful decision tool.  But what is gender specific about it, as implied in the indented text above?  More from the guideline on that:

..patient sex and D-dimer level measured about 1 month after stopping anticoagulant therapy can help to further stratify the risk of recurrent VTE. 66-69  Men have about a 75% higher (1.75-fold) risk of recurrence compared with women, whereas patients with a positive D-dimer result have about double the risk of recurrence compared with those with a negative D-dimer, and the predictive value of these two factors appears to be additive. The risk of recurrence in women with a negative posttreatment D dimer appears to be similar to the risk that we have estimated for patients with a proximal DVT or PE that was provoked by a minor transient risk factor (approximately 15% recurrence at 5 years); consequently, the argument for extended anticoagulation in these women is not strong, suggesting that D-dimer testing will often influence a woman’s decision. The risk of recurrence in men with a negative D-dimer is not much less than the overall risk of recurrence that we have estimated for patients with an unprovoked proximal DVT or PE (approximately 25% compared with approximately 30% recurrence at 5 years); consequently, the argument for extended anticoagulation in these men is still substantial, suggesting that D-dimer testing will often not influence a male’s decision.

For patients without active cancer who have had two or more spontaneous events the recommendations are the same as for patients with a single spontaneous (ie no transient risk factor) event.

For patients with active cancer extended therapy is favored for all, although the strength of the recommendation varies with bleeding risk. 

No special consideration is given for other high risk situations (eg thrombophilia, clots in unusual places).

Finally, the guideline says that if systemic anticoagulation is stopped for any reason aspirin, absent a contraindication, is considered better than nothing, making the special point that aspirin is not an acceptable alternative for extended systemic anticoagulation.


Choice of anticoagulant:  it's complicated.

The recommendation summary is simple enough but there are many nuances.  In general, for VTE in non-cancer patients the order of preference of agents is a NOAC over warfarin.  The authors give no order of preference among the NOACs.  Concerning initiation of treatment:

Initial parenteral anticoagulation is given before dabigatran and edoxaban, is not given before rivaroxaban and apixaban, and is overlapped with VKA therapy.

There are exceptions to be noted, mainly in unstable patients, for the recommendation not to start with parenteral anticoagulants before administration of some of the NOACs listed above.

For VTE patients with active cancer LMWH is recommend over all the others for initial and long term treatment and, by implication, extended treatment.  There is no order of preference for any of the ones after LMWH (orals). 

Now for the nuances that apply to certain special situations, from table 6:

If the patient has liver disease sufficiently severe to alter the coag tests LMWH is indicated for all phases of treatment.  Two reasons are stated for this, one being that NOACs are contraindicated if the INR is raised by liver disease, and the other being that warfarin is difficult to control in such circumstances and its monitoring is confounded since when the INR is altered by liver disease it is not a reliable indicator of antithrombotic effect.

Renal impairment with clearance below 30 is considered a contraindication to all NOACs for treatment of VTE in the guideline even though the product labeling of some of them allows usage with such reduction in renal function.

Dabigatran is not recommend if the patient has CAD, dyspepsia or prior history or GI bleeding (even if remote).

Similarly rivaroxaban and edoxaban are not recommend if there has been GI bleeding.

If there is concern for poor compliance, warfarin is favored over the NOACs, since it can be detected in the lab and its consequences are not immediate.

Unfractionated heparin is favored for initial treatment if thrombolytics are used or are being considered.

I checked Up to Date regarding the choice of anticoagulant and found that it is more conservative, favoring the traditional approach over starting with a NOAC.


Distal leg DVT.

The recommendations for distal leg DVT are essentially the same as those for proximal DVT except for the acknowledgment that clinical judgment will dictate withholding treatment in some patients.  The guideline “suggests” such a strategy of withholding treatment if there are not severe symptoms or risk factors for recurrence.  In such patients serial imaging is recommended. 



Catheter directed (regional) thrombolysis is not recommended.

The authors imply that it is worthy of consideration in certain circumstances but come short of making even a soft recommendation:

Patients who are most likely to benefit from CDT (see text), who attach a high value to prevention of PTS, and a lower value to the initial complexity, cost, and risk of bleeding with CDT, are likely to choose CDT over anticoagulation alone.

An exception to this non-recommendation is “impending venous gangrene.”  Another exceptional situation, May Thurner syndrome, is not addressed.

(Note: this applies to both upper and lower extremity DVT).


The guideline finds no indication for IVC filter insertion in any patient who can be anticoagulated.

---which is another way of saying that they would recommend an IVC filter only for patients with acute VTE and an absolute contraindication to anticoagulation.  Acknowledging low level data in favor of combined anticoagulation and IVC filter insertion in patients whose PE is severe or unstable (variously defined) the guideline makes this statement:

However, because it is uncertain if there is benefit to placement of an IVC filter in anticoagulated patients with severe PE (eg, with hypotension), and this is done by some experts, our recommendation against insertion of an IVC filter in patients with acute PE who are anticoagulated may not apply to this select subgroup of patients.

Thus the guideline gives little support for IVC filter insertion in any but the strictest indications, which may be important in light of the current FDA Safety Communication on filters and the resulting flurry of legal actions.


What about compression stockings?

Although the guideline authors acknowledge that they may be useful to control leg swelling they are no longer recommended for the singular purpose of prevention of post thrombotic syndrome.


Some small pulmonary artery filling defects may not need to be treated at all.

How is this determined?  Here's the recommendation:

In patients with subsegmental PE (no involvement of more proximal pulmonary arteries) and no proximal DVT in the legs who have a (i) low risk for recurrent VTE (see text), we suggest clinical surveillance over anticoagulation (Grade 2C), and (ii) high risk for recurrent VTE (see text), we suggest anticoagulation over clinical surveillance..

As simple as this sounds it requires some elaboration.  Unanswered questions include: 1)  are they talking about a single subsegmental defect or can treatment be withheld in some cases of more than one?  2)  Is the recommendation based on the idea of a false positive (non VTE filling defect), or that such low clot burdens, even if real, don't require treatment, or both?  The discussion in the body of the paper talks around these issues but is not definitive on either one.  Suffice it to say the recommendations leave much to clinical judgment and patient preference.  Despite such ambiguity in the text here is my take:


The text contradicts itself on whether treatment can ever be withheld in real subsegmental PEs however tiny the clot burden.  However, from the explanatory text it can be inferred that all filling defects judged to be “real” should be treated since such a determination is a risk factor for progression.

Subject to variations based on bleeding risk, patient preference and other clinical judgment factors, for treatment to be withheld ALL the following conditions must be met:

The defect is single.

The CT angio leaves doubt about whether the filling defects really represent PE (ie false positive is likely).

The filling defect is distally situated in a subsegmental branch.

The patient is asymptomatic (usually meaning that the discovery of the filling defect was incidental).

Clinical pretest probability is low or intermediate.

The D dimer is normal or minimally elevated and the elevation is otherwise explained.

The patient is not hospitalized already.

The patient has no recent history of immobility.

The patient does not have active cancer.

The patient has good cardiopulmonary reserve.

DVT is ruled out by lower extremity ultrasound (the upper extremity should also be evaluated if there are risk factors such as lines).

Again this is just my attempt to make sense of the text of this portion of the guideline, which is in places ambiguous and self contradictory.  However one interprets this portion it is suggested between the lines that the authors are concerned about an emerging problem of over treatment of small filling defects, a problem that would nearly cease to exist if clinicians relied on the best evidence and chose VQ over CT scanning as the initial imaging modality to assess for PE.

A prospective observational cohort study is underway to help answer the question.


Some patients with acute PE can be treated at home.

---meaning that they can be sent straight home from the ER or sent home after only very brief (a day or so) hospitalization.  The last edition of the guidelines said that some PE patients can be sent home after a very short stay.  The current ones take it a step further to say some patients can have their entire treatment outside the hospital.  In order to be eligible the following conditions are specified in the text, all of which must be met:

1) clinically stable with good cardiopulmonary reserve; (2) no contraindications such as recent bleeding, severe renal or liver disease, or severe thrombocytopenia (ie,less than 70,000/mm 3);  (3) expected to be compliant with treatment; and (4) the patient feels well enough to be treated at home.

Note that risk scores (eg PESI), biomarkers and other clinical indicators for RV dysfunction are not included explicitly in these criteria although criterion #1 would imply that there has been some assessment of RV function and in the text the authors say that elevated biomarkers or other indicators of RV dysfunction should discourage outpatient treatment.


As in the previous edition of the guidelines, it is suggested that hypotensive PE be treated with systemic thrombolytic therapy.

---but not generally normotensive PE even when the latter is associated with RV dysfunction (aka submassive PE).  The guideline suggests that if patients with submassive PE not initially treated with thrombolysis subsequently deteriorate, even short of developing hypotension, that lysis may then be indicated.


Catheter delivered regional thrombolysis for hypotensive PE is only suggested in certain circumstances.

These are stated in the guideline thusly:

..acute PE associated with hypotension and who have (i) a high bleeding risk, (ii) failed systemic thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours)..

What about anticoagulant failure?

From the guideline text:

In patients who have recurrent VTE on VKA therapy (in the therapeutic range) or on dabigatran, rivaroxaban, apixaban, or edoxaban (and are believed to be compliant), we suggest switching to treatment with LMWH at least temporarily (Grade 2C)…

In patients who have recurrent VTE on long-term LMWH (and are believed to be compliant), we suggest increasing the dose of LMWH by about one-quarter to one-third (Grade 2C).

How is bleeding risk assessed?

Many of the recommendations and suggestions above vary with bleeding risk.  Low risk is defined as no risk factors, moderate risk is defined as 1, and 2 or more mean high.  The factors are age over 65, prior bleeding, cancer, renal failure, liver failure, thrombocytopenia, prior stroke, DM, anemia, antiplatelet therapy, poor anticoagulant control, comorbidities causing reduced functional capacity, recent surgery, frequent falls, alcohol abuse and use of nsaids. 

Surgical complications and the obesity paradox

From a recent paper:

Methods

A single-centre prospective analysis of postoperative complications in 4293 patients undergoing general surgery was conducted, with a median follow-up time of 6.3 years. We analyzed the impact of bodyweight on postoperative morbidity and mortality, using univariate and multivariate regression models.

Results

The obese had more concomitant diseases, increased risk of wound infection, greater intraoperative blood loss and a longer operation time. Being underweight was associated with a higher risk of complications, although not significant in adjusted analysis. Multivariate regression analysis demonstrated that underweight patients had worse outcome (HR 2.1; 95 % CI 1.4-3.0), whereas being overweight (HR 0.6; 95 % CI 0.5–0.8) or obese (HR 0.7; 95 % CI 0.6–0.9) was associated with improved survival.

Conclusion

Obesity alone is a significant risk factor for wound infection, more surgical blood loss and a longer operation time. Being obese is associated with improved long-term survival, validating the obesity paradox. We also found that complication and mortality rates are significantly worse for underweight patients. Our findings suggest that a tendency to regard obesity as a major risk factor in general surgery is not justified. It is the underweight patient who is most at risk of major postoperative complications, including long-term mortality.

How much oxygen should we give in COPD exacerbations?

Here is a great summary post at Emergency Medicine Blog.

Risk stratification in normotensive PE

This has been a somewhat controversial area in PE management. Here is a update which incorporates an algorithm from recent guidelines. Free full text.

Neurocysticercosis

Free full text review from Neurohospitalist.

Neurologic complications of infective endocarditis

From Neurohospitalist.

Neurally adjusted ventilatory assist (NAVA) versus pressure support ventilation (PSV)

Here are the results of a recent study:

Conclusion

The total number of asynchronies in NAVA is lower than that in PSV. This finding reflects improved patient-ventilator interaction in NAVA compared with the PSV mode, which is consistent with previous studies. Our study is the first to analyze patient-ventilator asynchronies in NAVA and PSV on such an important duration. The decrease in the number of asynchronies in NAVA is due to reduced ineffective efforts and auto-triggering.

National diet recommendations for fat content were not evidence based

From a systematic review of the literature available before the recommendations:

National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments, respectively, with the ambition of reducing coronary heart disease (CHD) by reducing fat intake. To date, no analysis of the evidence base for these recommendations has been undertaken. The present study examines the evidence from randomised controlled trials (RCTs) available to the US and UK regulatory committees at their respective points of implementation.

Methods

A systematic review and meta-analysis were undertaken of RCTs, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD.

Results

2467 males participated in six dietary trials: five secondary prevention studies and one including healthy participants. There were 370 deaths from all-cause mortality in the intervention and control groups. The risk ratio (RR) from meta-analysis was 0.996 (95% CI 0.865 to 1.147). There were 207 and 216 deaths from CHD in the intervention and control groups, respectively. The RR was 0.989 (95% CI 0.784 to 1.247). There were no differences in all-cause mortality and non-significant differences in CHD mortality, resulting from the dietary interventions. The reductions in mean serum cholesterol levels were significantly higher in the intervention groups; this did not result in significant differences in CHD or all-cause mortality. Government dietary fat recommendations were untested in any trial prior to being introduced.

Conclusions

Dietary recommendations were introduced for 220 million US and 56 million UK citizens by 1983, in the absence of supporting evidence from RCTs.

In the discussion section the authors say:

This undermines the role of serum cholesterol levels as an intermediary to the development of CHD..

Recent findings about the pleiotropic effects of statins have also contributed to the notion that cholesterol doesn't matter, a notion that is mistaken. The cholesterol hypothesis is supported by mechanistic understanding of atherosclerosis, non-statin based lipid lowering trials and strong epidemiologic evidence. That said, the idea that we could impact the epidemic of atherosclerosis by a national diet recommendation to reduce fat content was pretty stupid. I believe one reason for the failure of the early diet trials was the isocaloric substitution of carbohydrate which activated the metabolic syndrome in those who were genetically predisposed.

Mucormycosis

From the Mayo Clinic EMBlog.

Metformin-induced lactic acidosis

A case report and brief review.

Medication safety alerts: why they don't work

Here's a secondary analysis of 26 papers.

Mechanical ventilation notes

Here is a collection of padlet notes from the Emergency Medicine blog.

MDS/MPN overlap syndromes

From a review in Blood:

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) comprise a World Health Organization (WHO) category of hematopoietic stem cell malignancies sharing morphologic and hematologic features of both myelodysplastic syndromes and myeloproliferative neoplasms.1 As characterized by the WHO in 2008, these disorders include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), atypical BCR-ABL1 negative chronic myeloid leukemia (aCML), myelodysplastic/myeloproliferative neoplasm unclassifiable (MDS/MPN-U), and a provisional entity named refractory anemia with ring sideroblasts and thrombocytosis (RARS-T).

Genetics for the internist

Genetics and internal medicine (1& 2) from Ahmad Elshebiny

Myelodysplastic syndromes

A review from Mayo Clinic Proceedings.

Marijuana for glaucoma

From a recent review:

Marijuana has been shown to lower intraocular pressure (IOP) but with limited duration of action and numerous adverse effects. Use of marijuana to lower IOP as a means of glaucoma treatment would require frequent use throughout the day, leading to significant adverse effects, possible progression toward Cannabis Use Disorder (CUD), and/or withdrawal symptoms. The treatment of glaucoma based on the cannabis plant or drugs based on the cannabinoid molecule should be considered carefully before being prescribed. Considerations should include the adverse physical and psychological adverse effects, including substance abuse. Currently, the deleterious effects of marijuana outweigh the benefits of its IOP-lowering capacity in most glaucoma patients.

Magnesium levels in hospitalized patients: hyper may be worse than hypo

From a recent huge Mayo Clinic database:

Patients and Methods

All admissions to Mayo Clinic in Rochester, Minnesota, from January 1, 2009, through December 31, 2013 (288,120 patients), were screened. Admission Mg from each unique patient and relevant clinical data were extracted from the institutional electronic database.

Results

After excluding patients aged less than 18 years, those without Mg measurement, and readmission episodes, a total of 65,974 patients were studied. Magnesium levels of 2.1 mg/dL or higher were found in 20,777 patients (31.5%), and levels less than 1.7 mg/dL were noted in 13,320 (20.2%). Hypomagnesemia was common in patients with hematologic/oncological disorders, and hypermagnesemia was common in those with cardiovascular disease. The lowest hospital mortality, assessed by restricted cubic spline and percentage death, occurred in patients with Mg levels between 1.7 and 1.89 mg/dL. An Mg level of less than 1.7 mg/dL was independently associated with an increased risk of hospital mortality after adjusting for all variables except the admission diagnosis; risk for longer hospital stay and being discharged to a care facility were increased in the fully adjusted model. An elevated Mg level of 2.3 mg/dL or higher was a predictor for all adverse outcomes. The magnitude of Mg elevations in patients with levels of 2.3 mg/dL or higher (N=7908) was associated with worse hospital mortality in a dose-response manner. In patients with cardiovascular diseases, Mg levels of 1.5 to 1.69 mg/dL and 2.3 mg/dL or higher both independently predicted poor outcomes including hospital mortality.

Conclusion

Dysmagnesemia in hospitalized patients is common, with hypermagnesemia being most prevalent. Compared with hypomagnesemia, hypermagnesemia is a stronger predictor for poor outcomes. Magnesium supplementation for patients without Mg deficiency should be avoided in the absence of randomized controlled trials documenting a benefit.

Test characteristics of lung ultrasound for the diagnosis of pneumonia

Better than CXR in this study.

The approach to low serum testosterone levels

This is nicely outlined in a recent review.

Laboratory interference after lipid rescue

 Here's another report on this topic:

CASE REPORT:

A 43-year-old female was admitted to the hospital after an unwitnessed ingestion of propranolol, tramadol, zolpidem, and alprazolam. She was intubated and treated with intravenous normal saline, insulin/glucose, and norepinephrine infusions due to hypotension. Two bolus doses and one maintenance dose of 20 % ILE were administered. Beginning approximately 2 h after ILE administration, laboratory assays were unable to be performed due to the presence of lipemia. The patient developed refractory hypotension and was transferred to a tertiary care center. Upon admission to the ICU, the patient received one additional bolus of 20 % ILE. Laboratory assays were again attempted but were unable to be adequately performed due to a pinkish-white discoloration of the patient's blood. Percutaneous femoral extracorporeal membrane oxygenation (ECMO) was initiated, but laboratory interference noted with the arterial blood gas analyzer prevented the analysis of oxygenation. The patient's hemodynamic condition did not improve; she expired 31 h after initial admission.

CASE DISCUSSION:

In one previous report, centrifugation was effective in removing more than 90 % of glycerol-banked triglycerides, thus minimizing lipid interference with laboratory assays. We noted persistent laboratory interference for more than 20 h after ILE administration, despite ultracentrifugation of specimens.

CONCLUSION:

Clinicians should be aware that ILE administration may cause significant and prolonged interference with laboratory assays, which may affect the monitoring of critically ill patients.

Background here.

Life threatening asthma

A collection of resources.

How does stress make you sick?

The Holmes- Rahe Stress Inventory has been around for years. I remember it from one of my college psychology classes. The idea is that if you score over a certain level on this survey chances are you'll get sick in some way, pretty soon. Intuitively it makes sense and there are multiple lines of evidence, some strong and some not so strong, as to various mechanisms. One, according to a recent study, is telomere shortening.

Leprosy in the United States

Case report and brief review.

Serum lactate, anion gap and serum bicarbonate

In this study most patients with elevated lactate had normal anion gaps and bicarbonate levels. The authors argue that the decision to measure lactate should be base on clinical suspicion rather than the results of other blood chemistries.