Ryan Radecki

The Latest Myth: Contrast-Induced Nephropathy?

Here’s the simple explanation for why none of our observed treatments to prevent contrast-induced nephropathy – acetylcysteine, hydration, sodium bicarbonate – reliably work: CIN is a myth.

There’s a lot of observational literature evaluating the incidence of mild acute-kidney injury after iodinated contrast exposure – either CT scans or vascular procedures – and every study shows some increase in serum creatinine in a small, but significant, proportion of patients. But, as this study suggests, is this just random effects, a confounder from co-occurring medical illness, or true dose-dependent renal injury?

This study, although retrospective, is almost precisely how I would have addressed the question. This is a single-center review of ten years of patients receiving CT scans. There were 116,694 contrast-enhanced scans and 40,446 non-contrast scans for whom before-and-after serum creatinine values were available. These CT scan events were compared by both risk-stratification as well as propensity score-matched subsets, as well as a counterfactual set of patients who had both independent contrast-enhanced and non-contrast CTs in their records. With every adjusted and unadjusted analysis, regardless of baseline renal insufficiency, there was no evidence of an excess of CIN following the contrast-enhanced events.

This is retrospective, so it’s hard to say whether there are undetected confounders – other comorbid illnesses, diagnosis disparities – that influenced these results despite the large numbers analyzed. However, it is absolutely reasonable to move forward with a prospective study design based on the hypothesis that intravenous contrast-enhanced CT scans do not increase risk of AKI. These results are not yet generalizable, however, to other interventional procedures in which higher volumes of contrast might be used.

This article was also covered by James Roberts in Emergency Medical News.

Addendum: Joel Topf argues this and related work is junk science at Precious Bodily Fluids.

“Intravenous Contrast Material-induced Nephropathy: Casual or Coincident Phenomenon”
http://www.ncbi.nlm.nih.gov/pubmed/23360742

HIAT-2 for Prognosticating Outcomes After Endovascular Interventions in Stroke: Proving Once Again Sick People are Sick

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

Since the publication of IMS-3, SYNTHESIS and MR RESCUE in the NEJM earlier this year, proponents of endovascular interventions for acute ischemic stroke have hypothesized why these trials were universally negative. Among the various explanations, one of the most prominent was that the trial designs selected the wrong patients. In order to fully highlight the benefits of endovascular therapy it must be performed on large vessel occlusions with ischemic but viable brain tissue down stream. The authors of a recently published study in STROKE have suggested a solution for this very problem. With the publication of their derivation and validation cohorts of the second generation of the HIAT score, HIAT-2 score, they postulate this decision rule will help predict which patients will benefit from endovascular interventions. The second revision of the HIAT score incorporates the original 3 factors, age, NIHSS and blood glucose at presentation in addition to the ASPECT score of the initial non-contrast CT. As opposed to the initial iteration of HIAT (1 point allotted for each of the 3 factors), HIAT-2 is a 10-point scale (10 being most severe) with age, ASPECT score, NIHSS and blood glucose level relatively weighted in descending order of influence.

The score was retrospectively derived and validated from two prospectively gathered databases of patients who underwent endovascular treatment for acute ischemic stroke. Older patients, with increased NIHSS and more ischemic changes on their initial CT fared far worse than their younger less critically presenting counterparts. In patients with a HIAT-2 scores of 5 or greater, 80% had a mRS of >4 at 90 days. A HIAT-2 score of >7 resulted in 100% of patients having a mRS of >4 at 90 days. The authors conclude that since patients with a high HIAT-2 score had poor 90-day outcomes, endovascular interventions should be limited to patients with a HIAT-2 score of 5 or less.

Never mind that the HIAT-2 score is only moderately capable of identifying those with a poor outcome after endovascular intervention (AOC is only 0.73), the more egregious logical fallacy committed by these authors was to conclude that the HIAT-2 score will differentiate those who will benefit from an endovascular intervention from those who will not. HIAT-2 does nothing of the sort. It is merely a predictor of prognosis at 90 days. Older patients, with more severe strokes at presentation (both clinically and radiologically) will have a worse prognosis no matter what interventions are performed. Interestingly, if the HIAT-2 score is utilized as proposed by its authors, it would exclude the patients who were originally hypothesized to benefit from these endovascular interventions. Patients with symptoms severe enough (usually NIHSS 10 or greater) to be large vessel occlusions are the types of strokes, which lend themselves to endovascular interventions. These are the types of infarcts the HIAT-2 score would exclude from endovascular treatment options.

Finally, in the IMS-3 trial though the HIAT-2 score was not specifically measured, age, NIHSS and the ASPECT score were all recorded. 31% of the cohort was younger than 65, over half the cohort was ASPECT 8,9, or 10 and greater than 80% had a NIHSS at presentation of 19 or less. No benefit of endovascular treatment over tPA was seen in any of the subgroups that are the most heavily weighted components of the HIAT-2 score.

The HIAT-2 score would require prospective validation before it can be used clinically, but I argue that in its current form, HIAT-2 is unable to answer the question for which it was conceived. At present the best evidence we have demonstrates endovascular interventions are no better than tPA (and some would argue tPA is no better than placebo). More high quality trials are needed to identify if there is a subgroup of patients who may benefit from endovascular interventions but pseudoscience and logical fallacies do nothing to augment the knowledge we have gained so far.

“Optimizing Prediction Scores for Poor Outcome After Intra-Arterial Therapy in Anterior Circulation Acute Ischemic Stroke”
www.ncbi.nlm.nih.gov/pubmed/23929748

HIAT-2 for Prognosticating Outcomes After Endovascular Interventions in Stroke: Proving Once Again Sick People are Sick

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

“Optimizing Prediction Scores for Poor Outcome After Intra-Arterial Therapy in Anterior Circulation Acute Ischemic Stroke”
www.ncbi.nlm.nih.gov/pubmed/23929748

Sepsis, NHAMCS, and Non-Truths

“… our results provide a worrisome view of the quality of care of septic patients in U.S. EDs.”

Crikey.

This is serious business. Tell me more.

“Our data suggest that many emergency department patients (31%) with sepsis do not receive antibiotics until they arrive on the inpatient unit.”

This is somewhat concerning data. Of course, some patients can have sepsis from viremia, and would not warrant antibiotics – but, I think most admitted patients with SIRS and a suspected infectious source ought to receive treatment.

But, unfortunately, for this study, the question is less the quality of ED care, and more the quality of the data source. The National Hospital Ambulatory Medical Care Survey is a lovely data set, whose quality is only increasing as coding and structured data become more prevalent – but a retrospective analysis of these data is not appropriate substrate to make sweeping generalizations regarding the care in the Emergency Department.

From the ~400 Emergency Departments providing yearly data to NHAMCS, 0.32% of patients met their definition of sepsis. That meant these data reflect a sample of 1,141 patients, and the admitted limitation of “studies relying on NHAMCS data are vulnerable to errors of omission in data collection.” These authors lack information regarding previously administered antibiotics from transferred patients, and admit some patients – those spending <1 hour in the ED – may simply have left the ED before antibiotic administration could be completed.

Quite simply, it’s (mostly) garbage in and (mostly) garbage out.

The authors also attempt an assessment of antibiotic appropriateness from this retrospective chart abstraction. It is so egregiously flawed it doesn’t even warrant comment.

“Sepsis Visits and Antibiotic Utilization in U.S. Emergency Departments”
http://www.ncbi.nlm.nih.gov/pubmed/24201179

Total Fever Illiteracy

If you weren’t already aware, the American Academy of Pediatrics recently published a policy statement concerning the use of antipyretics to reduce temperature in a febrile child.

Don’t do it.

The available evidence is treatment of fever may ultimately attenuate the body’s natural immune defenses, while parents inadvertently place their children at risk by using inappropriate dosages. The only goal of antipyretic use is to improve overall patient comfort.

And, as this study shows, we have a long, long way to go in educating our patients.

This is a survey of 100 patients – 54 from a private clinic and 46 from a county clinic – and, within the bounds of the small sample, there is essentially no difference in the perception of fever. Nearly 75% failed to correctly identify the temperature range constituting fever (>38°C). 93% thought high fever results in brain damage. 89% would give antipyretics to a comfortable child with temperature >38°C, and 86% would go ahead and schedule a clinic visit. Equally surprising (or not), 59% would dose a comfortable child with temperature 37.4-37.8°C with antipyretics, and 38% would schedule a clinic visit.

Given the volume of ambulatory visits for fever – both in the Emergency Department and community Pediatrics – it would seem continued education regarding “fever phobia” has the potential for significant cost savings.

Brain damage, by the way, is not usually a concern until 42°C.

“Fever Literacy and Fever Phobia”
http://www.ncbi.nlm.nih.gov/pubmed/23349363

Stepping Up to Choosing Wisely

ACEP recently published their own “Choosing Wisely” campaign contribution – a list of five changes to Emergency Medicine practice that ought be encouraged in the interests of increasing cost-effective care. While most would agree the ACEP version is reasonable, I think many clinicians hoped for something a little more earth-shattering.

Something like the Pediatric Hospital Medicine list for Choosing Wisely.

These authors specifically looked at the top 10 inpatient diagnoses in terms of volume and aggregate costs, and specifically evaluated components of treatment as candidates for recommendations. And, even speaking as someone who makes an effort to minimize testing – I find these recommendations take an impressive step in terms of aggressive reduction in resource utilization.

The highlights:
Do not order chest radiographs in children with asthma or bronchiolitis.
Do not use bronchodilators in children with bronchiolitis.
Do not use systemic corticosteroids in children under 2 years of age with a lower respiratory tract infection.

How often do you get radiographs in patients with respiratory disease – that get discharged? How about admitted? The authors estimate 60% of admitted patients receive radiographs, with fewer than 2% affecting clinical management.

Or, routine bronchodilator therapy – which, frankly, is ordered for a lot of children simply due to a sense we ought to do something. Both beta-agonist and racemic epinephrine fall under this recommendation, as they’ve not been shown to confer any reliable, clinically meaningful, patient-oriented outcome in bronchiolitis.

Finally – corticosteroids. Young children, even with albuterol-responsive wheezing, showed no benefit when corticosteroids were added. These are not harmless interventions, particularly for growing infants, and seems to pre-dispose some folks to subsequent readmission.

With pediatric respiratory season on the horizon, I challenge all of you to use this document as a tool share with colleagues and consultants to decrease unnecessary testing and therapy.

“Choosing Wisely in Pediatric Hospital Medicine: Five Opportunities for Improved Healthcare Value”
http://www.ncbi.nlm.nih.gov/pubmed/23955837

Man vs Machine: A CPR Battle to the…

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

Presenting the LUCAS 2.0, the latest and greatest in CPR technology! The LUCAS device “provides the same quality for all patients and over time, independent of transport conditions, rescuer fatigue, or variability in the experience level of the caregiver.” Or at least that is what the manufacturer, Physio-Control Inc, will have you believe.

High quality CPR and early defibrillation have been the cornerstones of cardiac arrest management since the AHA published their “Chain of Survival”. Reducing the time off the chest is of utmost importance in the current CPR mantra. So a machine that not only performs consistent high quality CPR, but delivers countershocks without interrupting compressions was sure to show benefit in patient oriented outcomes. What follows is a Paul Bunyan-like contest of man against machine. One in which the makers of the LUCAS device strived to prove modern technology’s superiority over good old fashion manpower. In a delightful twist on the original tale the fancy new mechanical CPR device was found to be no better than traditional CPR.

The trial published in JAMA in November 2013, randomized 2,589 subjects to either traditional CPR following the 2005 European Resuscitation Council guidelines or a mechanical compressions protocol. Patients in the mechanical CPR group received traditional compressions until the device could be deployed, at which point compressions were continued mechanically. Ninety seconds after deployment the device delivered a countershock regardless of the initial rhythm. After which the rhythm was checked every 3-minutes and, if appropriate, a shock was delivered after a 90-second delay.

Despite the obvious advantages the LUCAS device provides, no difference was found in survival at 4-hours, ICU discharge, 1-month, or 6-months. The authors claim victory in a single positive endpoint that reached significance. The number of patients with a CPC score of 1 at 1-month was 2.6% in the traditional CPR vs 4.2% in the mechanical CPR group (p-value of 0.04). This is, of course, just post-hoc dredging of innumerable secondary outcomes, and nothing more than statistical noise. To the authors’ credit, they do not revisit this positive finding.

Despite their claims that the LUCAS device would free up rescuers to do other life sustaining actions, patients in the manual CPR group were defibrillated sooner, intubated faster, transported earlier, and arrived at the hospital in a swifter fashion than those in the mechanical CPR group.

The authors conclude “CPR with this mechanical device using the presented algorithm can be delivered without major complications but did not result in improved outcomes compared with manual chest compressions.” Given that there were only 7 major adverse events in the mechanical CPR group vs 3 in the tradition CPR group this does seem to be the case. Though I would caution, with the low incidence of adverse events, this trial was not powered to truly assess safety of the mechanical delivered CPR.

“Mechanical Chest Compressions and Simultaneous Defibrillation vs Conventional Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest: The LINC Randomized Trial” www.ncbi.nlm.nih.gov/pubmed/24240611

Man vs Machine: A CPR Battle to the…

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

It’s Silly Season on Flu

We still don’t know whether neuraminidase inhibitors (e.g., oseltamivir [Tamiflu]) are helpful. Roche has prevented access to trial data until just this year, and the results of independent review are still pending. However, that has not stopped plenty of smart, well-meaning folks from taking their claims at face-value and using NAIs to treat influenza.

This is a retrospective registry review of 3 years of children admitted to California ICUs with a laboratory-confirmed diagnosis of influenza. 850 children were identified in the registry, and 784 children had clinical information available for analysis. Of these, 653 received NAIs and 38 (6%) died. Of the remaining 131 untreated patients, 11 (8%) died. Using a multivariate model adjusting for univariate predictors of death, NAI therapy was associated with decreased mortality (OR = 0.36, 95% CI 0.16-0.84).

But, while registry reporting was mandatory for deaths due to influenza, it was only optional for ICU hospitalization – leading to an unknown selection bias in their study cohort. There were also 23 deaths reported prior to hospitalization for whom no data is available. Most patients in the study treated with NAIs were H1N1, while the small remainder comes from the post-pandemic period with a mix of H1N1, other influenza As, and influenza B – and therefore may not be generalizable to a non-pandemic influenza season. A standardized abstraction form was used, but the complete baseline demographics collected are not included in the article; most patients included had significant respiratory comorbidities, and these chronically ill children were far more likely to die regardless of treatment. In summary, with a small sample size, likely missing data from abstraction, and selection bias underlying their cohort, the multivariate analysis upon which they based their final conclusion is junk.

In contrast to the editor’s summary “What this study adds”, which concludes special emphasis on treatment with NAIs may improve survival, I would revise it to say: “No additional practice-changing evidence”.

Now, I can’t say I’m opposed to treatment of hospitalized influenza patients with NAIs – least of all, those in the ICU. While outpatient therapy with NAIs for influenza is almost certainly a waste of money, in severe disease, the cost relative to the entire expenditure shrinks rapidly – the threshold for cost-effectiveness is met even if one patient out of a hundred has a one day reduction in ICU length-of-stay. But, it’s inappropriate to over-sell the meaning in this data to suggest any certainty NAIs are helpful.

“Neuraminidase Inhibitors for Critically Ill Children With Influenza”
http://www.ncbi.nlm.nih.gov/pubmed/24276847

I’ve Got the [Wrong] Answer!

Most of us think we have fair insight into our own medical decision-making. When presented with a difficult case, I think most would presume to present a provisional diagnosis with a decreased level of confidence.

Apparently, nope.

This fascinating insight into decision-making comes from a set of clinical case vignettes distributed to physician volunteers. 118 physicians were recruited via e-mail to complete four structured case presentations – two “easy”, two “difficult”. Physicians were not specifically notified regarding the variable difficulty of the cases involved. They were provided first the history, then the exam, followed by results of general and specific testing, if requested. During each stage of the process, physicians were asked to provide preliminary diagnoses and their level of confidence.

For the two easy cases, the mean confidence level of respondents was a little over 70%. And, final diagnostic accuracy was a little under 50%. For the difficult cases, the mean confidence level of respondents was about 65%. And diagnostic accuracy was … 5%. Almost as confident, almost never right.

Physician characteristics provided few insights regarding behavior, confidence, and accuracy. Increasing years of experience were related to decreased testing and consultation requests – but, for the most part, the only insight: physicians are lacking in insight.

“Physicians’ Diagnostic Accuracy, Confidence, and Resource Requests”
http://www.ncbi.nlm.nih.gov/pubmed/23979070