Tuesday, November 1, 2011

Dabigatran Worsens/Does Not Worsen Bleeding

Stroke and Circulation are both Journals under the umbrella of the American Heart Association.  So, when they publish articles that come to contrasting conclusions, I find that entertaining.

Both of these articles are mouse models of bleeding on dagibatran, C57BL/6 or CD-1 mice.  Sadly, they are frighteningly complex in their adjustments and statistical analyses - which means it defeats my ability to concisely summarize the findings and methods.

In short, one of these articles looks at intracranial hemorrhage after collagenase injection for mice receiving several different doses of oral dabigatran, and compare it to controls, warfarin, lepirudin, fondaparinux, and heparin.  It appears, and the author's final conclusion is, that dabigatran is the least harmful of all anticoagulants - about halfway between controls and the other anticoagulants.  They also shoot the mice with lasers in another portion of the study, and dabigatran "wins" that as well.

The other article looks at trying to reverse dabigatran - which, if you recall the human study I posted a few weeks back, was not successful in humans.  However, human trials were all surrogate markers of bleeding as measured by laboratory measurements of clotting.  What entertains me is, in contrast to the other study, these authors have no trouble inducing bleeding and significant ICH formation with dabigatran.  In any event, once the mice were adequately bleeding, the authors compared prothrombin concentrate complexes (specifically, Beriplex), FFP, and FVIIa for treatment of ICH 30 minutes after induced injury with collagenase.  Happily, PCCs, in a dose-dependent manner, attenuated the induced ICH, while the others failed.

So, perhaps this "novel, reversible" anticoagulant has a treatment option for life-threatening bleeding.  Human confirmation, at least case reports, needed.

"Anticoagulation With the Oral Direct Thrombin Inhibitor Dabigatran Does Not Enlarge Hematoma Volume in Experimental Intracerebral Hemorrhage"

"Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated With the Direct Thrombin Inhibitor Dabigatran"

Monday, October 31, 2011

Sodium Polystyrene Sulfonate For Lithium Toxicity

This one is for @drsamko, thanks to his tweet yesterday.  

The most recent of 19 articles in pubmed for the search "sodium polystyrene sulfonate lithium", a retrospective cohort review looking at the use of SPS in the treatment of lithium toxicity.  Given that lithium and potassium are similarly charged cations, multiple animal studies evaluated its use in lithium overdose, but only case reports in humans.  These authors reviewed 9 years of cases at their institutions, two hospitals in Montreal, Canada, for the effect on lithium serum half-life between patients prescribed SPS vs. patients who were not prescribed SPS.

They only looked at chronic overdoses admitted for management - 90 patients, 72 chronic, 48 had data points to properly evaluate the half-life.  36 received "standard treatment" and 12 were prescribed SPS.  The authors don't well-describe the standard treatment group, and don't indicate whether any received hemodialysis - but I get the impression the treatment for chronic toxicity only employs HD on rare occasions of renal failure.  Of the 12 that received SPS, most simply received IV hydration and observation in addition to SPS - and one received hemodialysis due to renal failure.  Half-life of lithium in the controls was 43 hours compared to 20.5 hours in the SPS-receiving group.

SPS isn't totally benign - there was mild hypokalemia in half their treatment population - and in rare cases it causes intestinal necrosis.  And, considering chronic lithium toxicity generally has a benign course, you could go either way.  You can certainly argue that decreased hospital length-of-stay is a significant financial and health benefit and justify giving it, though, so it's worth knowing about.

"Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a retrospective cohort study"

Saturday, October 29, 2011

Novel Ischemia Prediction from CCTA

One of the arguments against CCTA is that it only describes coronary anatomy - and has no demonstrated clinical predictive value regarding whether the observed lesions are flow-limiting or potentially related to anginal symptoms.  This study develops a computational fluid dynamics model that attempts to predict flow through coronary stenoses seen on CCTA.

Korea, Latvia, and California come together to evaluate 103 patients in a multicenter trial in which patients with suspected CAD underwent CCTA, invasive coronary angiography, and fractional flow reserve measurement.  They used only 256 and 64-slice scanners for CCTA, and CAD was quantified as none, mild (0-49%), moderate (50-70%), and severe (>70%).  Patients then underwent invasive coronary angiography where ischemia-related flow-limitation was defined as a fractional flow reserve of < 0.80.  The study group then developed a method of deriving the FFR from CCTA data, and compared it to the actual measurements from invasive coronary angiography using the same threshold value.

The conclusions from this article depend what takeaways you're looking for.  On one hand, the FFR-CT method was pretty decent - 87.9% sensitive and 82.2% specific regarding their definition of ischemia-causing lesions.  The other real takeaway is that CCTA has abysmal performance at the threshold typically used in the CCTA studies of >50% stenosis.  Their calculated +LR for CCTA stenoses >50% was only 1.51 in the setting of a specificity of 39.6%.  To me, another nail in the coffin showing CCTA is the d-Dimer of CAD, leading to a ton of unnecessary testing.

Considering it took them 5(!) hours to generate the FFR-CT measurement based on Newtonian fluid and Navier-Stokes equations on a parallel supercomputer, I don't think we'll be seeing this anytime soon - but hope is out there for the future.

"Cardiac Imaging Diagnosis of Ischemia-Causing Coronary Stenoses by Noninvasive Fractional Flow Reserve Computed From Coronary Computed Tomographic Angiograms"

Friday, October 28, 2011

Soft Drinks & Youth Aggression

This is not an EM article - but it was too bizarre to pass up.  Apparently, the use of soft drinks and junk food is a validated legal strategy for justifying homicide (e.g., the 'Twinkie Defense') - and this study finds an association to support it.

2,725 Boston high-school students surveyed regarding non-diet soft drink use and violence towards peers, dates, children, or firearm use.  Attempting to control for other factors, they eventually find statistically significant associations between youths who drink >5 cans of soft drinks in a week and increased alcohol use, increased tobacco use, as well as all categories of violence.  In fact, with all four categories of violence, the incidence of each increased in a dose-dependent manner with soft drink consumption.

This is, of course, an observed association, not necessarily a causal relationship, although the authors speculate on how sugars and caffeine might incite aggression.  If you are the parent of a high-school student, it isn't necessarily going to prevent violence to deny them access to non-diet soft drinks - but, if your high-school student is a heavy soft drink consumer, look out!

"The ‘Twinkie Defense’: the relationship between carbonated non-diet soft drinks and violence perpetration among Boston high school students."

Wednesday, October 26, 2011

Do/Don't Scan the Trauma Patient

In a study attempting to build consensus, they discovered philosophical differences between the trauma team and the emergency physician.

This is a prospective observational study in which 701 blunt trauma activations at LAC-USC were enrolled, with the EP and the trauma team each giving an opinion on which CT studies were necessary.  The authors then reviewed which scans were obtained, sorted out the scans that were undesired by one or both physicians, and determined whether any injuries would be missed.

Bafflingly, 7% of the 2,804 scans obtained during the study period were deemed unnecessary by both the emergency physician and the trauma attending - yet were still performed.  The remaining 794 undesired scans were desired by the trauma team but not the emergency physician.  Their question - would anything of significance been missed if the scans had been more selectively ordered?

The answer is - yes and no.  The trauma surgeon authors state yes, and justify that by saying that many of the abnormalities missed on CT required closer monitoring - just because none of the missed injuries deteriorated during the study period does not mean they were not significant.  The emergency physician authors point to a 56% reduction in pan-scanning, the benefits of radiation and cost reductions, and hang their hats on the fact that none of the hypothetically missed injuries changed management.

So, who is right?  Both, and neither, of course.  Emergency physicians and trauma teams should work on developing evidence-based clinical decision rules to support selective scanning in blunt trauma - and then try this study again to see if they can generate results they can agree on.

Definitely a fun read.

As far as medical literature goes, of course.

"Selective Use of Computed Tomography Compared With Routine Whole Body Imaging in Patients With Blunt Trauma."

Tuesday, October 25, 2011

ECMO For Influenza

Not many institutions in the U.S. are set up for ECMO in adults, particularly in the Emergency Department, but there are several small datasets out there indicating it should be a significant part of our arsenal for selected patients.  This is a review of ECMO's use in H1N1 influenza-associated ARDS in England during the "Swine Flu" pandemic.

The authors retrospectively reviewed 80 patients with H1N1 from prospectively collected cohort data, all of whom required critical care for ARDS and were referred for ECMO in the United Kingdom.  Through some data calisthenics, these 80 patients were compared to matching subgroups of patients out of 1,756 in the H1N1 critical care cohort.  Of the 80 patients referred for ECMO, only 69 actually received it.  However, when compared to these 80 patients in an intention-to-treat analysis, there was a significant survival advantage associated with referral to ECMO - approximately 24% mortality in the ECMO-referral group compared to 46-52% in the matched controls, depending on which method they used to identify matched controls.

Not a big stretch to interpret this as a positive treatment association for ECMO in H1N1-associated ARDS.  But, I'd still get your flu shot.

"Referral to an Extracorporeal Membrane Oxygenation Center and Mortality Among Patients With Severe 2009 Influenza A(H1N1)"

Sunday, October 23, 2011

EMS Blood Pressures Aren't Unreliable

Ever since a trauma patient billed as normotensive with stable vital signs rolled off the elevator with CPR in progress having "just lost pulses", I've been somewhat skeptical of my prehospital report, including vital signs.  This study, at least, supports a position that, barring untruthfulness, EMS providers vital signs are usually not clinically significantly different than vital signs obtained on arrival to the Emergency Department - even if observed techniques for EMS providers weren't perfect.

The first phase study looked at 100 patients arriving in the Emergency Department.  BP measurements were obtained within 5 minutes of arrival, and compared to the reported measurement from EMS.  There was approximately a 17mmHg +/- spread to the systolic pressures measured by EMS compared to the first BP in the Emergency Department.

The second phase of the study had observers riding with EMS and documenting the technique at which they used to find vital signs - and then having the research assistants performing the same measurement in the field as well.    In this phase, EMS providers systolic pressure was only a 10.1mmgHg +/- spread away from the research assistant - despite having ideal technique deficiencies and a terminal digit preference for numbers ending in zero.

The article concludes that EMS providers measurements had poor agreement with subsequent measurements, and that the differences were clinically significant.  However, based on the distribution of error in their Bland-Altman plots, I disagree that assessment, as most of the variability occurred throughout a range of inconsequential systolic pressures between 120 and 170.  They unfortunately had very few patients with clinically important hypo- or hypertension, so the question really remains unanswered whether EMS measurements at the clinically important extremes are reliable.

I do find it rather entertaining that their methods included a "specially trained research assistant" to measure blood pressure, referred to in the title as an "expert".  You can be an "expert" in anything nowadays, apparently.

"Agreement between emergency medical services and expert blood pressure measurements."

Saturday, October 22, 2011

A Third of TPA Patients Do Not Have Stroke

...but they almost all do well!  Only 5.1% of patients without stroke who receive TPA end up with intracerebral hemorrhage - so it's OK that we give TPA to a ton of patients without a confirmed diagnosis of stroke, right?

This is a retrospective Finnish registry study of 1,104 consecutive TPA patients enrolled in a prospective cohort.  Of these, 119 had basilar artery occlusion, which is angiographically proven prior to treatment, and are excluded from their analysis, and a couple others were excluded for other reasons.  This left 985 patients who were initially diagnosed with ischemic stroke, and, eventually, 14 of those patients were diagnosed as a stroke mimic such as migrane, epilepsy, or a demyelinating disorder.  The authors then go on to say that stroke mimics such as these accounted for a mere 1.4% of all TPA patients, and none of them had ICH.

But, this isn't exactly a true reading of their data.  The authors also state that 275 of their patients had "neuroimaging negative ischemic stroke", which is to say, their follow-up MRI detected no sign of infarct.  Now, there is a false-negative rate on DWI MRI for stroke, but it's in the range of 5% for acute infarcts, and generally involves small lacunar, small cortical, and some posterior circulation strokes.  Not only that, it's reasonable to suggest that around 40% of TIAs actually have DWI or FLAIR sequence abnormalities as well.

So, some of their "neuroimaging negative ischemic stroke" group probably does have ischemic stroke with false negative MRI - but not 30% of the study population.  And, some of their neuroimaging positive group is likely false positive from TIA as well.  These numbers for stroke mimics are also far below other reported case series, which have estimated 10-30% incidence, depending on whether TIAs are included.

I absolutely cannot fathom this line of reasoning and distortion Neurology is developing in justify recklessly pushing TPA onto a larger population.

"Stroke Mimics and Intravenous Thrombolysis"

Thursday, October 20, 2011

Preventing Mechanical Ventilation in Newborns

This is lovely article regarding the treatment of respiratory distress in newborns.  It is not a new concept to use surfactant in clinically indicated situations to improve ventilation in the newborn in distress - however, the typical treatment involves endotracheal intubation and mechanical ventilation prior to application.  This is a randomized, controlled trial of surfactant administration prior to mechanical ventilation.

This involves 220 preterm infants in Germany who were selected for the trial, essentially, if they were on CPAP requiring more than 30% inspired O2.  In the intervention group, patients received intratracheal surfactant if stable on CPAP and 30% O2.  Outcome measures were the portion of patients mechanically ventilated at any time or at day 2 or 3 after birth.  Minimal differences between groups, although the control group was a few grams lighter at birth.

Overall, 33% of all intervention infants required mechanical intervention vs. 73% of the control group.

Simple takeaway - surfactant isn't just useful after intubation, but may also prevent mechanical ventilation.

"Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial"

Wednesday, October 19, 2011

Ultrasound In Undifferentiated Infant Vomiting

Is there anything ultrasound can't do?  Trauma, vascular access, undifferentiated abdominal pain - and another nice case report for vomiting in children.

These authors are using ultrasound in the projectile-vomiting infant looking at the pylorus, and, after finding a normal pylorus, they scan the rest of the abdomen.  Lo and behold, they identify intussusception.  I am not entirely certain I would be able to well-identify the pylorus, but I can definitely see potentially noting the intussusception.  The authors include several nice images as teaching points.

As the barriers to routine ultrasound use in the ER decrease, hopefully we will all become more facile with using it in many more clinical situations.

"Use of Emergency Ultrasound in the Diagnostic Evaluation of an Infant With Vomiting"

Monday, October 17, 2011

Hypertonic Saline In Cardiac Arrest

There is a physiologic phenomenon observed in animal studies that a small increase in plasma osmolarity using hypertonic saline increases microperfusion, including myocardial and cerebral blood flow.  Therefore, in theory, hypertonic saline administration during resuscitation from cardiac arrest should be efficacious in improving survival and neurologic outcome.

These authors conduct a randomized prospective trial in which they prove that 100 patients in each arm is not enough to make valid claims about a secondary endpoint for which the study was not designed to evaluate.  There is no difference between groups in mortality - and not even non-significant trends - but a small, significant, absolute difference in neurologic impairment, 4.9% without neurologic impairment in the control group and 13% in the intervention group.

So, another study suggesting further study is needed.  If anything, it demonstrates how impossibly hard it is to evaluate treatments in the heterogenous population of out-of-hospital cardiac arrest, and to ensure internal and external validity.

"Randomised study of hypertonic saline infusion during resuscitation from
out-of-hospital cardiac arrest."

Sunday, October 16, 2011

Stroke After-Care Is Far More Important

Somewhere in the rush to but up billboards and focus the medical establishment on experimental revascularization interventions for acute stroke (e.g., time is brain), we've overlooked what truly matters - follow-up care after the ischemic event.  This is a lovely study that reminds us of what we probably knew once, but have forgotten - that even in the absence of acute therapy, simple protocols to prevent fever, prevent hyperglycemia, and prevent aspiration pneumonia lead to profound differences in the number of patients with zero or minimal disability after stroke.

This is a prospective interventional study in which acute stroke units in New South Wales Australia were randomized to either no protocolized intervention, or an intervention with nursing protocols named above.  At the end of the three-year intervention period, 42% of the control group had mRS 0 or 1 at 90 days, and 58% of the intervention group had mRS 0 or 1 at 90 days.  There were small differences in the type of stroke, education level, and prior ability to work that probably favored the intervention group, but the differences at baseline were far smaller than the magnitude of the treatment effect.  In short, a basic nursing protocol intervention improved outcomes more than any other intervention for acute stroke.

"Implementation of evidence-based treatment protocols to manage fever, hyperglycemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial."

Friday, October 14, 2011

Yes, Let MONA Fade Away

These authors make a brief argument regarding the inappropriateness of the commonly taught acronym of "MONA" for the initial treatment of acute coronary syndrome.  It is probably the case that well-read Emergency Physicians have since moved on, but it bears repeating.

 - Morphine, which has been associated with worsened outcomes in CRUSADE, but the results are confounded by other factors.  Narcotics are still probably reasonable for nitrate-resistant pain.
 - Oxygen, in which hyperoxia is associated with coronary vasoconstriction, exacerbates reperfusion injury and infarct size.  It is currently recommended that oxygen only be used for patients who are hypoxic.
 - Nitrates, suitable for the relief of anginal symptoms in selected patients.
 - Aspirin, the only element of MONA proven to be strongly beneficial.

And, presumably, future trials will involve the use of newer anti-platelet and other agents in the inital treatment of ACS.

The market is ripe for a replacement acronym!

"Initial treatment of acute coronary syndromes.  Is there a future for MONA acronym after the 2010 guidelines?"

Thursday, October 13, 2011

High-Sensitivity Troponin For Better Or Worse

The premise of this article seems fine - as we all learned in medical school, the LDH CK-MB Troponin is now our most sensitive and specific assay for myocardial injury, but, we were also taught that it takes a certain amount of time for the assay to turn positive.  Thus, the inpatient rule-out with multiple sets of cardiac enzymes.  These investigators looked a new assay, with a lower detection limit, and hope to prove that it has 100% sensitivity with a single measurement, obviating the need for additional enzymatic testing.

There were two phases - a cohort observational portion and a clinical deployment portion.  The observational phase was intended to verify prior data suggesting 99% sensitivity for the assay and, of their 703 patients, 195 had initial hs-cTnT levels of <3ng/L - and none had acute MI in their 6 month follow-up period (97.8 to 100% sensitivity).  In their clinical deployment phase, they collected 915 patients who received two sets of the hs-cTnT assay, and found that only one patient had a subsequent hs-cTnT rise after an initially undetectable hs-cTnT, giving a sensitivity of 99.8% (99.1-100).

So, they say, there is no longer any realistic need to get multiple sets of cardiac enzymes in a patient if the first level is undetectable.  This is probably true, but whether it reduces inpatient stays and follow-up invasive cardiac testing is another matter.  My guess is that widespread availability of this assay would lead to clinicians ordering troponins on patients they wouldn't have previously ordered them on, and - perhaps you know how this story will probably play out - a story in which use of the d-Dimer assay would decrease chest imaging for pulmonary embolism, but didn't.  Too many clinicians are applying it incorrectly and using its weak positive likelihood ratio to light up patients unnecessarily, and I expect this to lead to more patients being kept for testing, not fewer, as the authors propose.

"Rapid Exclusion of Acute Myocardial Infarction in Patients With Undetectable Troponin Using a High-Sensitivity Assay"

Tuesday, October 11, 2011

Popular Dehydration Scales Fare Poorly In 3rd-World Use

I like the author's use of the word "popular" to describe pediatric clinical dehydration scales.  In case you're not part of the "in crowd", today's "popular" dehydration scales include the World Health Organization scale, the Gorelick scale, and the Clinical Dehydration Scale.

This article is a prospective application of each of the three scales by a healthcare provider upon admission to one of three hospitals in Rwanda.  Children were weighed on admission and then on discharge, and the gain in weight was used as the gold standard for comparison to each standardized dehydration scale.

So, bad news:  each of these dehydration scoring scales is too complicated to hold in working memory, and you'd have to have it posted on a wall.

But, good news:  in the words of the authors, "The WHO scale, Gorelick scale, and CDS did not have an area on the ROC curve statistically different from the reference line."

Which means, you get to save your wall space because the dehydration scales gave false negatives or false positives as frequently as they gave true negatives and true positives.  More research is necessary to derive more accurate clinical assessment of children presenting with possible dehydration.

"Comparing the accuracy of the 3 popular clinical dehydration scales in children with diarrhea."

Monday, October 10, 2011

600mg Is Probably Your Best Clopidogrel Loading Dose

Most STEMI is the result of an acute thrombotic event, so, more thrombotic inhibition is better, right?  Italy, Hungary, Serbia and Belgium band together for ARMYDA-6 to test a randomized, prospective 600mg vs. 300mg clopidogrel loading dose prior to PCI in STEMI.

They didn't look at mortality and only followed 30-day outcomes - probably because they didn't have statistical power from only 201 patients to detect a difference - but their surrogate markers of infarct size, successful PCI, LVEF and 30-day "major cardiovascular events" all favored clopidogrel.  Unfortunately, almost every nonsignificant difference between the two clinical groups favored the 600mg group - younger, less diabetes, fewer prior MIs, higher LVEF at baseline, faster loading and cath lab times, less multivessel disease, more TIMI flow >1 pre-PCI.

That being said, it's consistent with the prior ARMYDA-1 and CURRENT-OASIS studies, and even if this isn't a fabulous study, it's another but of evidence to consider.

"Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segement Elevation Myocardial Infarction"

Saturday, October 8, 2011

Not Long, But Short QT

Another rare channelopathy that I was not previously aware of, but that carries the same risks of sudden death as long-QT syndromes.

This is a longitudinal observational study of the European Short QT Registry - which has a grand total of 53 patients - who were followed for, on average, 5 years.  The diagnosis of short QT does not have a generally accepted definition, but typically means a QTc less than 340 or 360, and the other literature shows a high association with sudden death and QTc less than 340.  In their registry 23% had a HERG gain-of-function mutation identified, and there is also an autosomal dominant inheritance pattern identified.

Based on their follow-up for events, or for cardiac events recorded by implantable defibrillators, there was a 4.9% incidence of syncope, defibrillator shocks, or nonsustained polymorphic ventricular tachycardia.  Prophylactic treatment involves either the implantable defibrillator or daily hydroquinidine therapy to prolong QT.

Something new to look for on EKGs that you'll probably never see, but will seem really smart if you do.

"Long-term follow-up of patients with short QT syndrome"

Friday, October 7, 2011

Lack of IV Access, Harbinger of Death

Interesting observational study of 56,332 patients picked up in an EMS system in King County, looking at IV access and outcomes.

For reasons they don't look into in this study, they find that IV access is an independent predictor of decreased in-hospital mortality.  Not for the less-acute patients, but for patients of high-acuity, lack of IV access shows a pretty significant trend towards poor outcomes.  They don't look at fluid therapy, medication therapy, etc. as confounding variables - so we don't know what it is specifically about IV access that confers a survival advantage.

They do a brief breakdown of the systolic blood pressure and the percentage of patients receiving IV access, and, as expected, more IVs are attempted at the extremes.  This leads me to believe there are patients who were high acuity, required IV access, but had failed IV access attempts - but there's no data on that either.

This is a study that could end up telling us something, or nothing.  Interesting, nonetheless.

"Intravenous Access During Out-of-Hospital Emergency Care of Noninjured Patients: A Population-Based Outcome Study"

Wednesday, October 5, 2011

C-Collars Cannot Stabilize Unstable Injuries

This is another cautionary anatomic study that demonstrates cervical collars are not adequate immobilization devices - except in patients who already do not need them.

This is a cadaveric spinal immobilization study in which C5/C6 instability was induced, and the Ambu extrication collar, the Aspen collar, and no collar were evaluated for range of bending and rotation during a bed transfer simulation.

The results are pretty straightforward.  Before the instability was induced, patients had minimal neck movement, whether immobilized or not.  After instability was induced, the patients all had significant bending and rotation - nearly the same for the patients in the collars as in no collar at all.

This is consistent with the small amount of prior work done in actual unstable spines; most of the cervical collar data is in healthy volunteers.  The limitations of a cervical collar should be recognized, and patients should have their cervical spine evaluated and cleared or intervened on immediately.

"Cervical collars are insufficient for immobilizing an unstable cervical spine injury."

Tuesday, October 4, 2011

Linezolid Is Superior To Vancomycin For Pneumonia

This is consistent with prior studies and not particularly earthshaking, but if you needed more literature to support switching antibiotics in the case of treatment failure, this would be another one.

This is in pigs, and it's an animal model of MRSA ventilator-associated pneumonia.  Four groups - controls, twice-daily vancomycin, continuous vancomycin infusion, and linezolid.  Treatment was initiated after 12 hours of bacterial inoculation in ventilated pigs.  At the end of their 96 hour treatment period, 75% of controls, 11% of each vancomycin group, and 0% of linezolid pigs were BAL positive for MRSA by culture.  Likewise, pathologic sections also showed decrease inflammation and damage in the linezolid group.

Short story, linezolid is better - but not quite better enough that we can't still start with vancomycin and keep it in reserve.

Sponsored by Pfizer and Eli Lilly.

"Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs"

Sunday, October 2, 2011

N-acetylcysteine Overdose With Anaphylactoid Reaction and Myocardial Infarction

This is another toxicology case that illustrates a point I make (probably too often) to my residents - that every action we take has a risk of harm, whether known or unanticipated.  I'm probably the only attending who cancels their IM ketorolac orders and changes them to PO ibuprofen.  Why?  Because of cases like this.

This is an entirely appropriate therapy - N-acetylcysteine given for hydrocodone-acetaminophen overdose - gone wrong because of a mixing error resulting in 10-fold overdose (126,000mg loading dose!).  Anaphylactoid reactions are known side effects in N-acetylcysteine, and, unfortunately, this patient's reaction was more severe than most, suffering an inferior MI with a peak troponin of 658ng/mL.  He expired 17 hour after the N-acetylcysteine overdose.

I've seen epinephrine given IV instead of SQ more than once (one time resulting in an MI), many medications are tissue toxic if they extravasate, you can get sterile abscess formation from intramuscular injections, etc.  The fewer interventions and the less invasive the interventions, the less risk at which we place our patients.

"Fatal myocardial infarction associated with intravenous N-acetylcysteine error"