Ryan Radecki

More Futility for Mechanical CPR

A few weeks ago we reported on the use of the LUCAS-2 for crushing the thorax, resulting in significant internal injuries. None of these injuries were judged to have contributed to any patient’s demise – but, still, concerning. This could be more forgivable if there were other advantages, say, survival.

Unfortunately, yet again, mechanical CPR fails to demonstrate superiority.

This is the PARAMEDIC trial, from the Lancet, a cluster-randomized trial aiming to demonstrate the superiority of the LUCAS-2 device as compared to manual CPR. Based on a deployment of 143 available LUCAS devices, these authors compared 1,652 patients randomized to attempt device deployment compared with 2,819 in a control group. There were no important differences in the baseline characteristics of the two groups, and other measures of initial treatment were similar. And, in the end, there was no difference between initial return of circulation, event survival, 30-day survival, 3-month survival, or 12-month survival (all dismal).

The mildly interesting aspect to this trial is that it was not directly a test of the LUCAS device – but, rather, a pragmatic trial comparing deployment with LUCAS as an option with deployment without. Thus, 638 patients in the clusters randomized to include the LUCAS device received manual compressions. However, on multiple causal effect analyses, no advantage was detected from cases in which the LUCAS device was used, nor was a selection bias apparent.

In the absence of efficacy data, use of mechanical devices is defended primarily on the basis of convenience – freeing up hands for other tasks. However, this argument fails in the face of these data – as it does not appear the handsfree advantage, when available, results in improved patient outcomes.

“Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61941-3/fulltext

Thanksgiving & Christmas, the Least Depressing Holidays

For Labor Day, I referenced an article regarding the temporal patterns of pediatric traumatic injury – showing Labor Day, above all, was the most dangerous of holidays.

However, conversely, Thanksgiving may have one of the lowest rates of self-injury of all the major holidays. These authors reviewed the rates of calls to poison control for suspected suicide attempts and found, compared with control days, essentially only New Year’s Day had consistently, and statistically, increased incidence of suicide attempts by poison. In contrast, Independence Day, Thanksgiving, and Christmas were consistently, and statistically, lower than the control days. Other major holidays were, essentially, a wash.

So, enjoy the protective effect against self-harm of this holiday season!

“Variation in Suicide Occurrence by Day and during Major American Holidays”
http://www.ncbi.nlm.nih.gov/pubmed/24462023

Bronchiolitis, Simplified

There are new guidelines from the American Academy of Pediatrics, just in time for the 2014-15 bronchiolitis season looming on the horizon – as if we don’t have enough to worry about with influenza and various West African hemorrhagic fevers.

But, the good news – these guidelines substantially reduce the things you have to remember to do for bronchiolitis. Specifically, the only evidence-supported intervention you have is: supportive care.

Ineffective, or of inadequate risk/benefit, treatments:

A trial of bronchodilators, such as albuterol or salbutamol.
Nebulized epinephrine.
Nebulized hypertonic saline, except possibly those requiring hospitalization.
Systemic or inhaled corticosteroids.
Chest physiotherapy.

… which basically covers everything.

And, not inconsistent with a recent trial regarding the misleading clinical weight of pulse oximetry, the guidelines state it is reasonable not to perform continuous oximetry on infants and children with bronchiolitis, and set 90% as an acceptable oxygen saturation. Finally, the authors also state routine chest radiography should be avoided, as abnormalities are common in bronchiolitis – thus leading to ineffective, and harmful, antibiotic administration.

Simply put – do no harm!

“Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis”
http://pediatrics.aappublications.org/content/early/2014/10/21/peds.2014-2742.full.pdf+html

A Brave New Kayexalate Free World

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

There may soon come a time when we witness the death of the much maligned cation-exchange resin, Kayexalate Unfortunately not for the reasons we hoped. We will not see the use of sodium polystyrene sulfonate fade from use in the modern Emergency Department because of our tireless efforts to remind our Internal Medicine colleagues of its lack of efficacy. Rather its clinically irrelevant place in the management of acute hyperkalemia will now be replaced by a brand new shiny cation-exchange resin that our Nephrologist consultants can use to delay the 3 am dialysis treatment our patient with a potassium of 9 mmol/L desperately requires.

Enter sodium zirconium cyclosilicate (ZS-9), a highly selective cation-exchanger that entraps potassium in the intestinal tract in exchange for sodium and hydrogen. Makers of this medication, ZS Pharma, claim it entraps 10 times as much potassium as the tried and (not-so-)true Kayexalate A recent article published in the NEJM examines its efficacy in patients presenting with hyperkalemia. Authors, Packham et al, randomized 753 patients presenting with mild hyperkalemia (5.0 to 6.5 mmol/L) to either 1.25g, 2.5g, 5g, 10g, or placebo every 8 hours for 48 hours. Only the patients who responded to ZS-9 during the initial phase and were normokalemic after 48 hours were then randomized to either once daily ZS-9 at the original dose they were randomized to or placebo. Unfortunately none of the patients who truly concern us were included in this trial. Authors excluded patients if they were receiving dialysis, had diabetic ketoacidosis, had a potassium level of more than 6.5 mmol/L, or a cardiac arrhythmia that required immediate treatment. These are often the patients in which we are asked to perform a trial of Kayexalate therapy in place of definitive dialysis.

For the initial phase of the trial, the authors found a statistically significant difference in their primary endpoint, the between-group difference in the exponential rate of change in the mean serum potassium level during the first 48 hours of treatment, between patients receiving the 2.5g, 5g, and 10g dose when compared to placebo. At 48 hours, the absolute mean reductions in the 2.5g, 5g, and 10g group were 0.46 mmol/L, 0.54 mmol/L, and 0.73 mmol/L respectively. These differences were statistically significant when compared with a mean reduction of 0.25 mmol/L that was seen in the placebo group. The overall reduction in potassium seemed to be mildly correlated with the extent of hyperkalemia at presentation, but authors only presented the results of this analysis in the group who was administered the 10g dose of ZS-9 (1.1 mmol/L > 5.5 mmol/L, 1.0 mmol/L 5.4 to 5.5 mmol/L, and 0.6 mmol/L < 5.3 mmol/L or less). Additionally patients who received the 5g and 10g doses of ZS-9 during the 15-day maintenance phase, had significantly fewer repeat episodes of hyperkalemia. A second study just published in JAMA by Kosiborod et al also examining the utility of ZS-9 in the acute management of mild hyperkalemia (5.0 to 6.5 mmol/L) confirms these findings. Though in this trial, patients in the first 48 hours were not randomized, but rather all were given a 10g dose every 8 hours, the mean absolute change in serum potassium was comparable to the change observed in the 10g group in the Packham et al trial( −0.7 mmol/L at 24 hours and −1.1 mmol/L at 48 hours). Likewise the severity dependent response was also observed in this second trial.

Although statistically a success, ZS-9 adds very little to the acute management of clinically relevant hyperkalemia. Even the high doses of ZS-9 reduced the potassium level on average by 0.73 mmol/L at 48-hours, nowhere near the efficacy that would allow us to comfortably hold dialysis overnight in the acutely hyperkalemic patient. Interestingly these results are not dissimilar to what Scherr et al discovered in their 1961 investigation into the effects of Kayexalate on serum potassium. In this non-randomized, non-blinded trial the cation-exchange resin lowered patients potassium by a mean of 1.0 mmol/L over the first 24-hours. Furthermore unlike the Scherr cohort neither of these studies examined oliguric patients or those with a history of ESRD on dialysis. The very patients which most frequently require emergent dialysis for acutely elevated levels of serum potassium.

Neither of these trials possessed the statistical power to definitively assess safety. Though no obvious concerns were demonstrated in this cohort, the rates of intestinal necrosis observed in patients given Kayexalate are far too infrequent to detect if ZS-9 causes similar effects with such a small sample size. While none of the patients in either of these trial experienced a fatal arrhythmia related to their hyperkalemia, the authors’ inclusion and exclusion criteria insured these types of events would be highly unlikely. On a side note, ED nurses will be happy to see that rate of diarrhea following the administration of ZS-9 at 1.9% is far less than what is commonly seen in patients given Kayexalate.

The editorial published alongside the Packham et al paper in the NEJM is entitled, “A New Era in the Management of Hypoerkalemia”. Though ZS-9 may play a role in the long-term management of patients at risk for hyperkalemia, for the acute management of hyperkalemia it seems we will still be arguing with our consultants over the administration of an ineffective exchange resin as a replacement for the definitive dialysis they require. A new era indeed…

“Sodium Zirconium Cyclosilicate in Hyperkalemia” http://www.nejm.org/doi/full/10.1056/NEJMoa1411487

“Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia The HARMONIZE Randomized Clinical Trial” http://jama.jamanetwork.com/article.aspx?articleid=1936753

Social Media in Medicine – Useless!

Or, might it be how you use it that matters?

This is a brief report from the journal Circulation, regarding a self-assessment of their social media strategy. The editors of the journal performed a prospective, block-randomization of published articles to either social media promotion on Facebook and Twitter, or no promotion, and compared 30-day website page views for each article. 121 articles were randomized to social media and 122 to control, and were generally evenly balanced between article types.

And, the answer – unfortunately, for their 3-person associate editor team – is: no difference. Articles posted to social media received an average of 409 pageviews within 30-days, compared with 392 to those with no promotion. Thus, the journal of Circulation declares social media dead – and ultimately generalizes their failures to all cardiovascular journals via their Conclusions section.

So, we should all stop blogging and tweeting? Or, is journal self-promotion futile? And, are page views the best measure of the effectiveness of knowledge translation? Or, is there more nuance and heterogeneity between online strategies, rendering this Circulation data of only passing curiosity? I tend to believe the latter – but, certainly, it’s an interesting publication I hope inspires other journals to perform their own, similarly rigorous studies.

[Note: if my blog entries receive as many (or more!) pageviews as Circulation articles, does this mean my impact factor is higher than Circulation’s 14.98?]

“A Randomized Trial of Social Media from Circulation”
http://circ.ahajournals.org/content/early/2014/11/17/CIRCULATIONAHA.114.013509.abstract

(Don’t) Dive! Dive! For Carbon Monoxide Poisoning

It is, again, the time of year when the temperatures drop precipitously – and, so, it is again the time of year to expand the differential for atraumatic headache to include carbon monoxide poisoning. With records already being broken in Southern states unused to such temperatures in November, this message comes earlier than usual.

And, as a reminder, there is essentially no usable evidence describing the use of hyperbaric oxygen therapy for acute CO poisoning.

The most recent Cochrane Review, from 2011, covers six studies regarding the efficacy of HBOT as compared to normobaric oxygen therapy. And, regrettably, all have serious methodologic flaws and potential for bias. Four of these trials are absolutely negative, with trivial differences in outcomes between the two arms. Two trials favor HBOT – a 60-patient trial published by Thom in 1995, and the seminal 152-patient trial presented by Weaver in the NEJM in 2002. All told, the pooled effect of HBOT on short-term neurologic sequelae provides a protective effect with an OR of 0.78 – but with a confidence interval crossing unity (0.54 to 1.12).

Thus, these data neither support nor refute the utility of HBOT for treatment acute carbon monoxide poisoning – and provide no insight into appropriate patient selection. What is most likely, given these results, is there is a cohort of patients for whom some benefit is observed. Probably the most reasonable patients to select for treatment include those with the most severe poisoning and who can receive treatment immediately – but, otherwise, expect extraordinarily low-yield resource utilization to attempt treatment in the remainder.

“Hyperbaric oxygen for carbon monoxide poisoning (Review)”
http://www.ncbi.nlm.nih.gov/pubmed/21491385

Ketamine For You! And You and You and You!

Over the last decade, ketamine has shifted from pariah status to celebrity, increasingly popular for procedural sedation, delayed-sequence intubation, treatment of intracranial hypertension, and even status epilepticus. There is also a smattering of trials demonstrating its use for inpatient post-operative patients as an opiate-sparing mechanism – but how well does it work in the Emergency Department?

These authors from Brown evaluated use of ketamine for adjunctive pain control in a small, three-arm prospective, blinded comparison between “usual care”, and two doses of ketamine. Patients with severe acute pain received 0.1 mg/kg of morphine up to 10mg, followed either by placebo injection, 0.15 mg/kg ketamine, or 0.3 mg/kg ketamine. Patients were then followed for need of rescue medication.

With only 20 patients in each group, the potential for type I and type II errors are substantial. All groups derived substantial pain relief from treatment. Patients in the two ketamine groups, however, derived a greater degree of relief – and required a lower gross amount of rescue analgesia. The authors eke only a few “statistically significant” p-values out of their tiny samples, but, regardless, the underlying differences likely appropriately reflect an expected acute analgesic effect from ketamine.

Unfortunately, the largest limitation of the small sample concerns the incidence of adverse events. The largest dose of ketamine, 0.3 mg/kg, had clearly distressing effects – half the patients felt dizzy – while both ketamine groups included a handful of patients with nausea, vomiting, and confusion. On the flip side, two patients in the standard-care group suffered possible morphine-related hypotension and respiratory depression as a result of rescue analgesia.

Ketamine may have a role in acute analgesia in the Emergency Department. However, appropriate dosing and ideal patient selection remain unclear.

“Low-dose Ketamine Improves Pain Relief in Patients Receiving Intravenous Opioids for Acute Pain in the Emergency Department: Results of a Randomized, Double-blind, Clinical Trial”
http://www.ncbi.nlm.nih.gov/pubmed/25377395

Bayesian Statistics: We’re Dumb as Rocks

A guest post by Justin Mazzillo, a community doc in New Hampshire.

Physicians are often required to interpret medical literature to make critical decisions on patient care. Given that it is often in a hectic and hurried environment a strong foundation of evidence-based medicine is paramount. Unfortunately, this study from JAMA showed that physicians at all levels of training have anything but that.

This group surveyed a mix of medical students, interns, residents, fellows, attending physicians and one retired physician. They were asked to answer the following question:

“If a test to detect a disease whose prevalence is 1/1000 has a false positive rate of 5%, what is the chance that a person found to have a positive result actually has the disease, assuming you know nothing about the person’s symptoms or signs?”

Unfortunately three-quarters of the subjects got the answer wrong. The results were consistent across all levels of training. The most commonly given answer was almost as far from correct as possible.

I’ve withheld the answer for those who want to try out the questions themselves, and I know all the dedicated EMLoN readers will fare much better.

“Medicine’s Uncomfortable Relationship With Math: Calculating Positive Predictive Value”
http://archinte.jamanetwork.com/article.aspx?articleid=1861033

[I gave this same test to our residency program – and the results were almost identical. A few sample “answers” below. -Ryan]

Laundry Detergent is Delicious Candy

Children, rumor has it, are curious, persistent, and nefarious creatures. Furthermore, the entire natural environment must first be tasted. Thus, age-old cautionary guidance regarding home safety for children to prevent exposure to potentially hazardous materials.

So, naturally, laundry detergent would be kept safely out of reach of children – particularly the pre-packaged pod systems, which are candy-like and perfect for oral consumption – correct?

Nope!

According to this data from the National Poison Data System, in just a single year, there were 17,230 calls for pediatric exposure to laundry detergent pods in just two years, between January 2012 and December 2013. The majority – 79.7% of cases – were secondary to ingestion. 4.4% of patients with an ingestion were judged to necessitate hospitalization, including 102 requiring intubation. One death was reported – but the autopsy showed intracranial bleeding of uncertain/unlikely relation to the ingestion of detergent.

The authors specifically call out Procter & Gamble, maker of Tide Pods, for failure to place adequate warning labels or safety latches on their packaging – although, frankly, the ultimate responsibility lay with parents. Keep cleaning supplies safely out of reach!

“Pediatric Exposure to Laundry Detergent Pods”
http://pediatrics.aappublications.org/content/early/2014/11/05/peds.2014-0057.abstract

It’s a Patient Hand-Off Miracle

Transitions of care – more frequent now in medicine than ever before – are fertile opportunities for error and miscommunication. Most institutions have developed, at least, informal protocols to exchange patient information during hand-off. But, certainly, everyone has some anecdotal tale of missed information leading to a near-miss or actual patient harms.

This study tells the story of I-PASS, a handoff bundle implemented and measured as an error prevention strategy by a pre- and post-intervention study design. Across 9 pediatric residency training programs, residents were observed for six months for time spent in hand-offs, time spent in patient care, and a variety of classifications of preventable and non-preventable errors. Then, the I-PASS bundle was introduced – a structured sign-out mnemonic, a 2-hour workshop on communication skills, a 1-hour role-playing and simulation intervention, a faculty development program, direct-observation tools, and a culture-change campaign with a logo, posters, and other promotional activities.

Following the intervention, residents were, again, observed for six-months. And, in general, preventable medical errors decreased a small absolute amount, along with a larger absolute decrease in near misses. 2 of 9 hospitals had increases in medical errors after the interventions, and the bulk of the effect size was a result of improvements at two hospitals whose baseline error rate was double that of the other 7 facilities.

The authors, then, are very excited about their I-PASS bundle. But, as they note at the end of their discussion: “Although bundling appears to have been effective in this instance, it prevents us from determining which elements of the intervention were most essential.” And, on face validity, this is obvious – the structured sign-out sheet was only one of many quality improvement interventions occurring simultaneously. A decisive change in culture will trump the minor components of implementation anytime.

The final takeaway: if your institutional audit reveals handoff-related errors are pervasive and troublesome, and if reductions in such errors are prioritized and supported with the correct resources, you will probably see a reduction. The I-PASS tool itself is not important, but the principles demonstrated here probably are.

“Changes in Medical Errors after Implementation of a Handoff Program”
http://www.ncbi.nlm.nih.gov/pubmed/25372088