Proton pump inhibitors increase risk of acute kidney injury

lanzoprazole3 out of 5 stars

Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. Antoniou T et al. CMAJ Open 2015;Apr;3:E166-E171.

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Previous studies have suggested that use of proton pump inhibitors (PPIs) increases risk of acute interstitial nephritis, especially in elderly patients. Using information from  several large computerized databases containing medical information about patients in Ontario, Canada, the authors carried out a population-based cohort study of patients in Ontario aged 66 years and older who were newly prescribed  PPIs, compared with matched controls. Patients were followed for 120 days. The main outcome was hospital admission for acute kidney injury (AKI); the secondary outcome was admission for acute interstitial nephritis.

Of the approximately 290,000 patients who started PPIs during the course of the study (April 2002 through November 2011), 1787 were admitted with AKI during the 120 days of follow-up. This constituted a hazard ratio 2.5-3.0 times controls. There was no significant different in hazard ratios among specific individual PPIs.

The limitations inherent in extracting data from a computerized database — adequately discussed by the authors — makes it somewhat unclear how to apply these results to the prescribing of PPIs. But it is important for clinicians to be aware of the association between PPIs and AKI. This is not appreciated by many practitioners. It is not unusual for a patient on PPIs admitted for interstitial nephritis to be discharged on the same medicine.

Other potential adverse effects of PPIs include: increased risk of Clostridium difficule colitis, community-acquired pneumonia, and osteoporosis and bone fractures.

Poisonous birds: what’s new

3 out of 5 stars

Poisonous birds: A timely review. Ligabue-Braun R, Carlini CR. Toxicon 2015 Mar 31;99:102-108.


It was just over two decades ago that Dumbacher et al published their landmark paper describing the presence of the alkaloid batrachotoxin (BTX, “frog poison”) in the skin and feathers of three species of Pitohui bird in New Guinea. This toxin binds to voltage-gated sodium channels maintaining them in the open position. This action causes depolarization of nerves and myocardial cells. This may serve the bird by acting as a “chemical defense” against large predators, or as a means of parasite control.

Since BTX is present at relatively low levels, human exposure can cause numbness, sneezing, burning, nausea and a bitter taste, but is usually not fatal.

The 1992 paper by Dumbacher et al was one of the first description of toxicity in a bird. Since then, researchers have described toxicity in several other avian species:

European migratory quails (Coturnix coturnix coturnix): Consuming these quail can cause rhabdomyolysis in certain individuals who may be deficient in a specific muscle enzyme. This syndrome is called coturnism. Neither the enzyme nor a causative toxin has been identified as yet.

Some scholars believe that the following biblical passage (Numbers 11:31-33) describes an epidemic of coturnism:

Now a wind went out from the Lord and drove quail in from the sea. It scattered them up to two cubits deep all around the camp, as far as a day’s walk in any direction. All that day and night and all the next day the people went out and gathered quail. No one gathered less than ten homers. Then they spread them out all around the camp. But while the meat was still between their teeth and before it could be consumed, the anger of the Lord burned against the people, and he struck them with a severe plague.

Spur-winged gooseThe flesh of this goose contains the toxin catharidin, which the bird acquires by eating specific blister beetles.

Hoopoes: Bacteria in the glands of these birds produce”obnoxious volatile compounds.”

This paper is a quick, fascinating survey of a topic that is relatively new. Recommended for those interested in toxicology and evolutionary development.

27 fatalities from laboratory-confirmed exposure to PMMA (“Dr. Death”)

4 out of 5 stars

Deaths from exposure to paramethoxymethamphetamine in Alberta and British Columbia, Canada: a case series. Nicol JJE et al. CMAJ Open. 2015 Jan 13;3(1):E83-9

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From June 2011 through April 2012, 27 deaths in the Canadian provinces of Albert and British Columbia were attributed to the hallucinogenic stimulant para-methoxy-N-methylamphetamine (PMMA) as the primary toxic agent based postmortem examination and toxicology results. PMMA is so dangerous that it is known on the street as “Death” and “Dr. Death.” This paper constitutes a retrospective review of those cases based on records from the Chief Medical Examiner and Coroners Service of those respective provinces.

in all cases laboratory results confirmed exposure to PMMA. In cases where details were known, all decedents believed they were consuming MDMA (ecstasy). All subjects tested positive for multiple other stimulants, including PMA, MDA, amphetamine, and cocaine.

Since the information about these cases came from the coroner and medical examiner — not from medical records — there is limited clinical information available about these victims, 17 of whom died in hospital. However, some of the details presented here are fascinating:

  • The median initial temperature recorded at hospital was 39.4oC (102.9oF) [highest initial temperature, 43.8oC (110.8oF)]
  • Sixteen of the seventeen patients who survived to arrival at hospital had findings consistent with serotonin syndrome, according to the Hunter criteria. (For more on the Hunter Criteria for the diagnosis of serotonin syndrome, click here.)
  • End-organ dysfunction seen in the patients who survived to hospital included renal failure, rhabdomyolysis, hepatic injury, coagulopathy, cardiac ischemia, and dysrhythmias.

The authors point out that PMMA is similar in structure to MDMA (ecstasy), and that its major pharmacological mechanism is enhancing serotonin release. Given that, the Hunter Criteria for serotonin syndrome includes some specific neuromuscular findings, and I have doubts if much reliable information to this point would be available in records from the coroner or medical examiner.

The online version of this article has links to the alerts issued for health care professionals at the time of these deaths, as well as well as the FAQ information sheet issued by local poison centers to educate the public and the media.

All in all, a very well done article, made much more valuable by the laboratory confirmation of PMMA exposure in all cases. And thanks to the authors for including TPR in their list of references.
Related posts:

Hallucinogenic stimulant PMMA found in “Superman” pills that killed 4 in Britain

Epidemic of PMMA-associated deaths in Norway

Meet “Dr. Death”: PMMA and PMA

Potent stimulant PMMA associated with ecstasy deaths





Predicting delirium tremens in patients with alcohol withdrawal seizures

delirium_tremens_label_22 out of 5 stars

Clinical predictors for delirium tremens in patients with alcohol withdrawal seizures. Kim DW et al. Am J Emerg Med 2015 Feb 23 [Epub ahead of print]


Being able to predict which patients with alcohol withdrawal seizures will go on to develop delirium tremens (DTs) may lead to improved clinical outcomes and decreased morbidity and mortality.  The goal of this retrospective Korean study was to identify clinical and laboratory findings in emergency department (ED) patients with seizures attributed to alcohol withdrawal and would predict progression to delirium tremens.

ED patients presenting to 4 tertiary referral centers with seizures over a 22 month period were identified retrospectively. Patients with seizure etiology other than alcohol withdrawal were excluded. Eligible patients were observed for a minimum of 48 hours. Diagnosis of DTs was made according to the definition in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV.)

The authors identified 97 eligible patients with alcohol withdrawal seizures. Thirty-four (35%) of these went on to be diagnosed with delirium tremens. High blood homocysteine levels and low platelet count were independent risk factors for progression to delirium tremens.

Unfortunately, these results will, in my opinion, turn out to be less than clinically useful. For one thing, homocysteine levels are not readily available at most institutions, and are unlikely to be so in the foreseeable future. Secondly, making multiple comparisons (the authors analyze 24 clinical and laboratory factors) means that some apparent distinguishing characteristics will just appear by chance. Finally, even given these limitations, the factors the authors identify are that good, despite using cutoffs that were not predetermined. A platelet count of 137,000/μL was only 73% sensitive, and a homocysteine level of 14.5 micromoles per liter was only 81% sensitive. These population numbers are not good enough to be helpful in the individual patient.
Related posts:

Surely the NEJM could do a better review of delirium tremens

Risk of completed suicide after initial hospitalization for deliberate overdose

3.5 out of 5 stars

Risk of Suicide Following Deliberate Self-poisoning. Finkelstein Y et al. JAMA Psychiatry 2015 Apr 1 [Epub ahead of print]


The authors primary objective was to determine the risk of subsequent successful suicide in patients discharged from hospital after a first suicide attempt. They used multiple healthcare databases to identify patients hospitalized for first suicide attempt in Ontario, Canada from April 2002 through December 2010. Subjects identified were followed through the end of 2011. For each subject a control patient without history of self-poisoningt was selected, matched for age, gender, and calendar year.

The search identified 65,784 patients discharged from hospital or the emergency department after a first suicide attempt. These patients were followed for a median of 5.3 years. Of these, 976 committed suicide and were over 40 times more likely to do so than controls. Overdose was the method in 41% of subjects who ultimately killed themselves. The median time from initial self-poisoning to completed suicide was 585 days.

Given the immensity of the problem, the (relatively) small percentage of patients who went on to kill themselves during the follow-up period, and the length of time from first attempt to completed suicide, I have my doubts that much can done to approach this problem as a public health issue. However, these results lead to some important considerations for medical toxicologists, emergency medicine practitioners, and psychiatrists. I sometimes find it astounding how often patients who have attempted self-harm with their own particularly dangerous psychiatric medication — drugs such as tricyclics, venlafaxine, and bupropion — are discharged from hospital on that same medication.  Certainly any patient who presents with a suicide attempt should have a thorough re-evaluation of his or her drug regimen by a psychiatrist and psychiatric pharmacologist to determine which medications are dangerous, which are essential, and which could be replaced by less risky alternatives.


Less is more: fatal C. difficile colitis after empiric antibiotics

Aspiration pneumonitis

Aspiration pneumonitis

4 out of 5 stars

Antibiotics “Just-In-Case” in a Patient With Aspiration Pneumonitis. Joundi RA et al. JAMA Intern Med 2015 Apr 1;175:489-490


This very brief but very important case report contains more key points than most papers 10 times as long. The case describes a 50-year-old man with cerebral palsy and a known seizure disorder who had several witnessed tonic-clonic seizure episodes treated with a benzodiazepine. Subsequent chest x-ray revealed multiple bibasilar opacities consistent with aspiration.

The patient was started on piperacillin-tazobactam. Although he showed significant clinical improvement on the second hospital day, the antibiotics were continued for a full 7-day course because of the “possibility” of aspiration pneumonia.

The patient was discharged in good condition after 10 days in hospital, but returned a week later with diarrhea, shock, and an increased white blood cell count. Work-up revealed Clostridium difficile colitis. Despite medical treatment, he succumbed to the infection on hospital day 18.

In their cogent discussion, the authors point out the differences between aspiration pneumonitis and aspiration pneumonia:

Aspiration pneumonitis is an acute chemical caustic lung injury that begins abruptly — often after a witnessed seizure — and generally improves within 48 hours. Treatment generally consists of supportive care without antibiotics. In approximately 1 in 4 of these patients bacterial infection will supervene and be manifest by clinical worsening 2 – 7 days after the episode of aspiration. Empiric prophylactic antibiotics have not been shown to provide benefit in routine cases, may select for resistant organisms, and subject the patient to risk of an adverse event, such as in this case.

Aspiration pneumonia is a bacterial lung infection in which symptoms begin gradually, often without a witnessed episode of aspiration.

The authors conclude:

Because patients with aspiration pneumonitis are often critically ill, withholding antimicrobial therapy can be challenging. In those with witnessed aspiration events, there should be the necessary confidence to forego antibiotic therapy for the first 48 hours while continuing supportive management. Lack of expected improvement within 48 hours or recurrence of fever and worsening respiratory status 2 or more days following the aspiration event suggests the development of pneumonia that warrants initiation of antimicrobial therapy.

Possible exceptions to this approach include patients with conditions that predispose to bacterial colonization of gastric contents. These include patients with small bowel obstruction, gastroparesis, and those who use antacids, H2-blockers, or proton-pump inhibitors. In these cases, early antibiotic treatment may be justified.

As the White Rabbit said, “Don’t just do something, stand there!“:


[Chest x-ray showing aspiration pneumonitis used under Creative Commons license]