Month: December 2013

The Shock Index is a Shockingly Poor Predictor of Peri-Intubation Arrest

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.
This retrospective analysis of 410 patients undergoing RSI is a helpful reminder of how a statistically significant association does not implicitly translate into a clinically useful one.

The authors of this paper attempted to identify factors that would predict peri-intubation cardiac arrest using a cohort of patients requiring emergent intubation in a large urban emergency department. Specifically does the Shock Index accurately predict those who will suffer post-intubation cardiac arrest? The Shock Index (HR/systolic BP) is essentially an attempt to quantify a patient’s volume status and cardiac reserve into simple ratio. These same authors have examined this score’s ability to predict peri-intubation hypotension in the past and found similar predictive capabilities.

Given the pedigree of the authors (Dr. Alan Jones and company) it is no surprise their chart review methods were next to flawless. Using standardized data collection forms, a single trained extractor identified patients who underwent ED intubations over a one year period. To ensure inter-observer reliability, 10% of this data was randomly audited by a second extractor blinded to the trials hypothesis. Backwards stepwise regression was utilized to determine what factors were independently associated with peri-intubation cardiac arrest (defined as cardiac arrest up to 60 minutes after intubation).

In this cohort, the rate of cardiac arrest after intubation was 4.2%, or 17 patients. 10 out of these 17 events occurred within 10 minutes of the intubation and, in 15 of the 17 events the initial arresting rhythm was PEA.  As one would expect, patients who experienced peri-intubation cardiac arrest had faster a heart rate, lower blood pressure and more frequent incidence of pre-RSI hypotension. The only two metrics that were found to be independently associated with cardiac arrest were the patient’s body weight and pre-intubation Shock Index. The Shock index was found to have an odds ratio of 1.16 with a confidence interval ranging from 1.003 to 1.3. Put in another manner, it was found to have an AOC of 0.73, rendering it essentially clinically useless.

Given these test characteristics, if we were to use a Shock Index of 0.88 (as suggested by the authors) to determine who is at risk for peri-intubation arrest than we would be left unprepared for an unacceptable quantity of patient who will decompensate during the procedure. This should be inherently obvious, as a formula that incorporates only heart rate and systolic blood pressure is incapable of encapsulating all the many reasons a patient may code peri-intubation. Not to mention that this study does not tell us whether the patients whom the Shock Index identifies as “at risk” will actually benefit from our added vigilance and pre-intubation hemodynamic optimization. Or does the Shock Index merely highlights a spectrum of the more critically ill patients who will inevitably deteriorate despite our clairvoyant best efforts?

Tachycardic, hypotensive patients are at increased peril for peri-intubation arrest. Sicker patients, older patients, and patients with poor cardiac reserve are all at higher risk. Most importantly, the Shock Index does not accurately predict who will and will not arrest after intubation. Similar to tools meant to predict difficult airways (not accurate enough to depend on clinically), we must be prepared for peri-intubation arrest in the majority of the patients requiring emergent intubation. Once a patient reaches the critical juncture of requiring intubation, we should be aware of all the perils this procedure involves and plan accordingly.

“Incidence and Factors Associated with Cardiac Arrest Complicating Emergency Airway Management”
www.ncbi.nlm.nih.gov/pubmed/23911630

Remember: Tamiflu is Still Junk

It’s that season of the year again, and with the fatalities from the H1N1 strain returning to the news folks are clamoring for Tamiflu (oseltamivir).

And, there’s still no evidence it has any protective effect at reducing complications from seasonal influenza.  In these two studies, a systematic review and a meta-analysis, some small reductions in symptom duration in mild illness were outweighed by drug adverse events such as nausea, vomiting, and diarrhea.  There is no evidence of any decrease in severe complications of influenza.

Unfortunately, the heterogeneity of trials, irregularities in baseline characteristics, and incomplete peer review all impair knowledge translation of this relatively expensive outpatient medication.  You’re all hopefully aware of the BMJ’s ongoing open data campaign regarding Tamiflu.  The last update from July seemed to indicate independent access to higher-quality trial data had finally been achieved.  If there is a durable, beneficial effect attributable to osletamivir, perhaps we will soon know.  Given the lack of transparency to date, I’m not optimistic.

“The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.”
http://www.ncbi.nlm.nih.gov/pubmed/23565231

“Effectiveness of oseltamivir in adults: a meta-analysis of published and unpublished clinical trials.”
http://www.ncbi.nlm.nih.gov/pubmed/22997224

The Great Chocolate Question

Continuing our mini-Christmas sabbatical from serious business, yet again Science has asked an important question.  And, yet again Science has the answer – chocolates don’t survive very long on medical wards.

In the BMJ’s annual Christmas collection, this “covert” observational study evaluated the median time Cadbury Roses and Nestle Quality Street chocolates survived from their arrival on the wards.  The boxes were opened within an average of 12 minutes, and were half-consumed within 2 hours.  Roses appeared to be preferred to Quality Street, based on median survival time.

Important science; previously known as Sweet Consumption of Famished Faculty – a Limited Observational Trial; SCOFF-A LOT.

“The survival time of chocolates on hospital wards: covert observational study”
http://www.bmj.com/content/347/bmj.f7198

Biphasic anaphylactic reactions – How long should we observe?

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

ED Nurse: “You want to watch that allergic reaction for 6 hours? Seems like a long time.”
ED MD: “Yeah, I know but I want to make sure they don’t have a biphasic anaphylactic response.”
ED Nurse: “When does that usually happen?”
ED MD: “Well, uh . . . I’m not sure . . . hey did anyone see that 90 year old with dizziness yet? I should go see her now.”

If this conversation seems familiar, you’re not alone. We’ve all been taught that patients with allergic reactions have a risk of recurrent reaction. What we fear, is an anaphylactic episode that improves, the patient goes home and then has recurrent anaphylaxis and dies. As a result, many of us have been taught that if the patient resolves, you watch them for 4-6 hours and if they remain okay, they can go home.

However, when you look at the literature, it shows that the biphasic reaction can be delayed. It can occur anywhere from 5 minutes up to 3-4 days out. So what is the optimal duration of observation?

Enter this retrospective, chart review from the University of British Columbia. The researchers found 2,819 patients with allergic reactions at two institutions (496 classified as anaphylaxis) and the scoured databases for representations within 7 days. They further separated out those patients with clinically important biphasic reactions. Overall, there were five patients (0.18%) who had clinically important biphasic anaphylactic responses in seven days. Of these, two had immediate biphasic anaphylaxis during their initial Emergency Department visit and three experienced a delayed response up to six days out of their initial visit. Two of the biphasic reactions were in patients initially presenting with anaphylaxis (0.40%) and three were in patients presenting with simple allergic reactions (0.13%).  There were no deaths identified.

The study has the typical limitations of any retrospective chart review. One major concern is that patients presented to EDs other than the original two sites. The researchers did, however, check the regional database for representations and checked the provincial database for mortality.

Although the study isn’t perfect, it suggests that the biphasic response may be lower than previously thought. Prior studies have shown biphasic reaction rates ranging from 3 – 20% (Tole 2007). As a result, some authors have recommended observation for up to 24 hours after an anaphylactic reaction. The truth is that there are no consistent recommendations about observation. The authors conclude that,

“although extended observation would be justified in patients with severe or protracted anaphylaxis, the added costs and resource use involved in routine prolonged monitoring of patients whose symptoms have resolved may worsen ED crowding while likely adding little to individual patient safety.”

While it’s hard to recommend changing practice based on a retrospective study, this is the largest study done on the subject and offers very reassuring numbers. The bottom line is that clinically important biphasic reactions are rare (less than 1%) and can occur days after the initial reaction. There is no 100% safe observation period. After symptom relief, and decision for discharge, patients should be given epinephrine auto injectors and taught how to use them. Any potential inciting allergens should be removed and follow up should be arranged with an allergist. With a clinically important biphasic response rate < 0.5%, extended observation seems to be unnecessary.
References
Grunau BE et al. Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients with Allergic Reactions or Anaphylaxis. Ann of EM 2013. ePub http://dx.doi.org/10.1016/j.annemergmed.2013.10.017

Tole JW, Lieberman P. Biphasic Anaphylaxis: Review of Incidence, Clinical Predictors and Observation Recommendations. Immunol Allergy Clin N Am 2007; 27: 309-26.
http://www.ncbi.nlm.nih.gov/pubmed/17493505

God Bless Us, Everyone

So says Tiny Tim, from the Dickensian Christmas fable – or, more familiarly, from the Disney production on the same theme.

As several physician-historians have done before, this short piece explores the malady afflicting Tiny Tim in the context of industrial London.  Because Dickens tended to very accurately portray phenotypic manifestations of illness – Pickwickian Joe, the epileptic Monks, the dwarf Jenny Wren – the character depictions give realistic insights into the travails of the working poor.  Was it cerebral palsy?  Simple malnutrition?  Or something more exotic like renal tubular acidosis?

Regardless the diagnosis, the treatment of the time would have been the same:  cod liver oil.

May your Christmas be merrier than that.

“Environmental Factors in Tiny Tim’s Near-Fatal Illness”
http://archpedi.jamanetwork.com/article.aspx?articleID=1107722

Uninjured Children are Uninjured, and Other Tautologies

In America’s culture wars (e.g., War on Drugs, War on Women, War on Christmas, etc.), few rise to the magnitude of the Emergency Physician vs. the consultant surgeon.  The disagreement in necessity of CT radiography for minor trauma is well-documented, and even surgeons themselves admit to possibly overdoing it in their valorous quest for zero-miss.

This study has the conclusion we’d like to see – but not the evidence needed to fully support it.  These authors from Denver performed a retrospective review of 174 pediatric trauma team activations, specifically evaluating the incidence of CT-identified injuries for four categories of patients.  The cohort these authors focus on for their conclusions are those with no apparent injury and no abnormal vital signs, but were imaged (presumably, considering this is retrospective) based on “mechanism of injury”.  Of the 66 patients who received any kind of CT imaging in the absence of objective indications, zero serious injuries were identified.

However, this MOI-indicated CT group was not exactly uninjured – over a third had a long bone fracture, and 9% had a skull fracture.  In a group of children whose average age is 7, of whom half have a significant injury, it is hard to quibble retrospectively with the indications for each CT individually – even if all were ultimately negative.  There is an obvious hint of truth that, yes, if MOI is the overriding justification for CT, it will result in an embarrassingly low incidence of true injury.  In the end, this study only shows us we need to continue advancing our development of clinical evaluation instruments to improve yield and cost-effective care.

“Mechanism of injury alone is not justified as the sole indication for computed tomographic imaging in blunt pediatric trauma”

Follow the Money

The sun is coming up – in 2014 the Sunshine Act will further illuminate just how much money is being hemorrhaged in healthcare to support the profit motives of pharmaceutical and device providers.  However, increased transparency has become more prevalent – including a few companies posting grant award registries to their websites.  These 14 companies, and their distribution of funds in 2010, are the focus of this brief report in JAMA.

Considering this is just a subset of a little more than half the top drug companies in sales from 2010, the numbers are more than a little staggering: $657M distributed, with over $100M from Roche/Genentech alone.  Medical communication companies received 26%, followed by academic medical centers with 21%, then disease-targeted advocacy organizations with 15%.  But, this report focuses only on the MCCs – considering their role in knowledge translation to the average clinician and consumer.

The largest beneficiary/offender?  Medscape/WebMD.  $20M in grant awards from just this subset of 14 drug companies – suggesting pharmaceutical corporation “donations” represent a significant portion of their $500M annual revenue.  It might be most appropriate to label every news post on their site as “sponsored content” or “special advertising section”.  This brief report further evaluates the privacy policies of these MCCs, and determines physician behavior collected by their sites is likely redistributed for profit back to various industry players.

Pharmaceutical and device manufacturers are not charities.  Executives from these companies, despite what their public relations department would have you believe, are not sitting in strategy meetings discussing altruistic giving for the good of health.  These financial outlays are investments in marketshare and mindshare, and ought to be viewed for what they are – corrupting influences contributing to the degradation of cost-effective care.

“Medical Communication Companies and Industry Grants”

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.

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