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During our GU board review this week, I got to thinking about kidney stones and the frustrating stepwise approach to the patient with equivocal flank pain and a working diagnosis of nephrolithiasis. Most cases are easy since renal colic is common and presents so characteristically, but there are some patients with equivocal presentations. These patients with mushy histories, maybe some mild flank pain, maybe not, possible dysuria, and subjective fevers present diagnostic challenges. Is this an episode of renal colic, renal colic with obstruction and superinfection, pyelonephritis, or something else in the back or belly? This is when the first groan happens because the realization is the that the patient is possibly going to need 2 CT scans: one without IV contrast and then another one with. But maybe that’s not necessary because pyelo can be seen on a non-contrasted CT right? Something about fat stranding? Maybe we can just get away with the single scan, and if we don’t see the stone, we’ll find something to hang a weak diagnosis of pyelo on.

A quick review of nephrolithiasis. The most general approach to these patients is pain control followed by urinalysis. As was mentioned at conference, pain control is best achieved with combination therapy using an NSAID such as ketorolac and narcotic such as morphine (PMID: 16953530). If the clinical presentation is correct and urinalysis shows blood, imaging is not necessary. Here’s the first problem: the “classic” finding of hematuria can be absent up to 15% of the time (PMID: 7747369).

In cases which the diagnosis is not as clear, non-contrasted CT scan of the abdomen is indicated and proves to be a very good test for nearly all renal stones except for those secondary to HIV protease inhibitors such as indinavir (PMID: 9230000). So that’s great because unless we are dealing with that specific situation, the non-contrasted CT scan should certainly find the stone. But invariably that sometimes doesn’t happen, which brings up the second problem: what now?

At this point the arrow starts to point further down the differential and a diagnosis of pyelonephritis comes to mind given the patient’s bloody urine, positive leukocyte esterase, and mild flank tenderness. While pyelo is a clinical diagnosis supported by a characteristic urine, often muddled histories and unconvincing exams can leave the diagnosis in doubt. Non-contrasted CT scans can show an enlarged kidney or perinephric fat stranding indicative of a pyelo, but they can also be normal in the setting of pyelo. Thus in the patient with an unclear diagnosis based on urine and history and non-diagnostic CT scan, a contrasted CT scan should be pursued as the next step(PMID: 16937102, 15486235). Besides giving a much better image of the kidney in cases where the diagnosis is in doubt, a contrasted scan will highlight vascular diseases or renal infarcts whose presentations mimic that of renal colic and would not be seen on a non-contrasted scan. These are rare entities but can be missed easily. Bottom line: slog through getting 2 CT scans when kidney stones are not seen on the initial non-contrasted CT and the clinical picture is not a slam dunk for pyelo - the correct imaging for pyelo should be with IV contrast.

Today’s simulation led to a discussion of the optimal therapy for treatment of the acutely dyspneic, diaphoretic, tachycardic, hypertensive distressed patient with acute pulmonary edema. After discussing the routine medical therapies — nitro SL, nitro gtt, ACE inhibitors, and furosemide — the discussion turned to the role of non-invasive ventilation (NIV).

It is no longer thought to be controversial that a trial of NIV is a crucial intervention for patients presenting with acute pulmonary edema prior to committing to endotracheal intubation (assuming that the patient has the mental status to tolerate NIV). The controversy lies in which modality of NIV to use — continuous positive airway pressure (CPAP) vs. bilevel non-invasive positive pressure ventilation (NIPPV), commonly referred to by the proprietary name BiPAP®.

Theoretically, it seems that BiPAP would be superior to CPAP since in addition to the basal positive pressure of CPAP which helps to stent open alveoli prone to collapse due to the weighty edema filling the lungs, there is an augmentation with positive pressure during inhalation to reduce the work of breathing. It would seem to follow that BiPAP would likely be superior to CPAP in reducing rates of intubation and possibly even mortality, while both modalities would be superior to just oxygen alone as they prevent derecruitment of alveoli.

Numerous trials have studied whether NIV is superior to oxygen alone when used to augment medical therapy for APE. Recent meta-analyses in JAMA (PMID: 16380593) and Critical Care (PMID: 16646987 and 16569254) have concluded that both CPAP and BiPAP are effective in the treatment of acute pulmonary edema with respect to the endpoints of mortality and subsequent need for intubation. However, all three meta-analyses find that BiPAP is not superior to CPAP with respect to either of these two endpoints.

All three articles make mention of a 1997 comparison study of BiPAP and CPAP by Mehta, et al. published in Critical Care Medicine (PMID: 9142026) which was terminated after interim analysis indicated that the patients randomized to the BiPAP arm of the study suffered greater myocardial infarction rates than those receiving CPAP (71% vs 31%). The articles mention that subsequent studies have failed to show this disparity and that the numbers in this trial we very small. Despite these assurances, none of the authors’ conclusions recommend a strategy of BiPAP over CPAP in lieu of the fact that the “physiological benefits [of BiPAP] did not translate into primary outcomes.” (JAMA). The JAMA article goes on to conclude that

the question of whether one technique offers advantage over the other and what subset of patients would benefit more with either one of these techniques remains unresolved.

The first of the Critical Care articles concludes that CPAP should be the NIV of choice because “from a practical point of view CPAP has been shown to be cheaper and easier to use” while the second recommends whichever modality is available.

ACEP also weighed in on this controversy in early 2007 when it published its Clinical Policy on patients presenting to the ED with acute heart failure syndromes. ACEP recommends the use of CPAP as a level B recommendation and downgrades the use of BiPAP to a level C recommendation citing the possible increase in myocardial infarction in conjunction with the lack of observed benefit over CPAP in the two main endpoints, mortality and reduction in the need for intubation.

Bottom line: It’s the smart and safe move to favor CPAP over BiPAP unless and until BiPAP is shown unequivocally to be more effective than CPAP with similar safety profile.

During cardiology conference one of the senior cardiology fellows mentioned that we have seen several cases of patients presenting with new right bundle branch block in the setting of acute MI who had complete arterial occlusion requiring coronary reperfusion (PCI or thrombolytics). While the traditional teaching is that new left bundle branch block in the setting of a clinical presentation suggestive of myocardial infarction mandates immediate reperfusion therapy, the point was made that a new RBBB may also suggest significant myocardial infarct territory, and coronary reperfusion in this setting should be considered.

This reminded me of a conversation I had a few years ago about guidelines for coronary reperfusion in the setting of ACS. The gist of that conversation was that only 1 of the major societies that issues these guidelines suggests consideration of a new RBBB for immediate reperfusion — ACEP.

I pulled the major guidelines to determine why they differed on this issue, and more importantly, why ACEP felt it necessary to broaden the indication for coronary reperfusion to include new RBBB. The first thing to note is that ACEP certainly does not enthusiastically endorse reperfusion therapy in the setting of RBBB given that it is given only a level C recommendation (based on preliminary, inconclusive, or conflicting evidence or expert opinion). Here is their rationale as quoted from the ACEP Clinical Policy:

…only 6 of the 9 trials included in the FTT analysis included BBB as an entry criteria and none of these studies made a distinction from right, left, or atypical, and from new or old. There were only 2,146 (4%) patients with BBB out of a total of 58,600 patients. In this undifferentiated group of BBB, mortality was 18.7% in the fibrinolytic treated patients versus 23.6% in controls…Due to the relatively small number of these patients included in the FTT report, it suggests that these patients with undifferentiated BBB most likely had symptoms strongly suggestive of AMI in order to be enrolled in these clinical trials. Studies since the FTT report have failed to clarify this issue, and it has become commonplace for clinical trials in AMI to either exclude all BBB patients or to include only patients with new or presumably new LBBB as one of the entry criteria.

In essence, ACEP concludes that the FTT analysis (PMID: 7905143) reviewed trials in which the BBB included was undifferentiated, and given that those patients did better with reperfusion therapy and that more recent trials exclude patients with RBBB, evidence is inconclusive to support excluding patients with new RBBB from consideration for reperfusion therapy. Given the acknowledged evidentiary weakness of the this claim, it is given a level C recommendation.

Reviewing the AHA/ACC Practice Guidelines and the European Society of Cardiology Guidelines, there is consensus recommendations on the use of reperfusion therapy for new LBBB or ECG-demonstrated STEMI. The AHA/ACC guidelines do not ever mention the case of new RBBB, and while the ESC guidelines mention the same shortcomings (patients with undifferentiated BBB) in the data reviewed in the FTT analysis, they stop short of recommending consideration of reperfusion therapy for new RBBB (at least in the text, although there is an ambiguous chart on page 38).

The bottom line is that ACEP has put this into a clinical policy which may hold medicolegal weight, although in clinical practice the entire controversy may be moot. This is because unlike in a LBBB, it is still possible to decipher true, ischemic ST elevations in the setting of a RBBB. Thus patients with new RBBB resulting from complete occlusion of a coronary vessel will have ST elevations that should be interpretable despite the right bundle and therefore qualify for reperfusion based on that well-accepted criteria.

There is a new article in JAMA published this week that attempts to make estimates for the risk of development of malignancy in patients as a result of a single coronary artery CT scan (CTCA) for evaluation of possible coronary artery disease. The is an especially prescient article for emergency medicine physicians given the large number of chest pain complaints that present to EDs and also specifically at our institution since we have now started to perform this test (not to mention that one of the co-authors of the paper is based at our medical center).

Briefly, the paper uses statistical risk modeling (called the Monte Carlo method, more about that later) to make estimates about the risk of development of malignancy as correlated with the level of radiation exposure from each of 4 different type of CTCAs and the age of the patient when the scan was done. Unsurprisingly, the risk of cancer development increased the earlier that the scan was done, but somewhat surprisingly the curve was quite concerning for patients dosed with radiation early in life. Particulary concerning were young females (20 years old) who had twice the RR and thrice the RR of their 40-year old and 60-year old counterparts, respectively, for the development of cancer during their lifetime.

Regarding the statistics, what is interesting is the Monte Carlo method was used for statistical modeling. This is the same mathematical modeling used for risk modeling in the insurance and financial industries, and the results bear striking resemblance. Much as the power of interest compounded over time is the great wealth creator, it seems that the effect of early radiation compounded over time is similarly potent for causing malignancy in later life.

This study is certainly limited in that it studied no real patients and simply extrapolated data from mathematical models. Further the authors did not compare this test with others that may employ similar or slightly lesser amounts of radiation. That being said, it should give pause that all the imaging that is ordered is not without risk, and even if that risk is small for the individual, the population-based risk — given the fantastic numbers in question — is not small indeed.

Ordinarily I like to write a conference follow up on the same day as conference to review clinical information or research relevant to the topics that were covered that day. Yesterday, however, I was working overnight and just didn’t have the time to put anything together. As fate would have it, I saw something during that very shift that was very apropos to our cardiology board review. There is no better way to learn something in medicine that to review it and then see it clinically, which is what happened in this case.

As you may recall, I mentioned numerous times during the board review that a new left bundle branch block in patients with no prior EKG and symptoms of acute coronary syndrome should be treated as an STEMI and receive treatment with thrombolytics or mobilization of the cath lab (owing to journal club yesterday, I’ll say either-or since we all seemed to agree that doing both is not yet supported by the evidence).

Well, at the end of my shift, a 58 yo smoker with DM and HTN happened to come in with chest pain and SOB for the last 75 minutes upon awaking. The pain was in the left chest without radiation, pressure-like. Vital signs were HR 120, BP 176/98, O2 sat 100% on RA, RR 18. The initial EKG while having pain was:

Note the LBBB with the wide QRS, notched R waves in I, V5, V6 with deep S waves in the early precordium V1-V3. The patient denied prior history of heart disease or myocardial infarction and had never been to this facility before. At this point, the patient was moved into the Resus area and the cardiac cath team was called. Aspirin, beta-blocker, and nitro were administered. Shortly thereafter, the patient reported being pain-free. A repeat EKG was obtained:

Whoa!?! What is going on here? Where’s the bundle? Is this the same patient? If it is, this would seem to be reassuring since the pain is now gone and the left bundle has resolved. Just get two sets and stress or even send for follow up as an outpatient, right?

Actually no. This is what is known as having “dynamic EKG changes” and is very concerning and would seem to indicate that the LBBB is indeed new and is related to a dynamic lesion in the heart. Presumably, the pain and LBBB resolved because the 100% stenosis auto-lysed (or maybe with the help of the aspirin) and the patient’s underlying, native rhythm can be seen on the second EKG. So this is worrisome and indicates that this patient should be evaluated urgently for a critical lesion. In this case, the cath was performed and the patient was found to have a single-vessel coronary disease with 60-70% stenosis in the LCx. Again, presumably no 100% lesion was found in any vessel owing to the pre-cath lysis of the clot which was causing the LBBB.

So in summary, new LBBB is bad and should be treated with the same urgency as an STEMI. It also highlights the importance of the repeat EKG. No matter how tedious it may seem, you can’t see dynamic EKG changes without repeats.

We had a resident feedback session today after conference that was constructive. I discussed most of the issues that came up with the residency leadership and will provide updates as they are available. For more information, see my email from this date as I don’t want to post that information online.

That’s it. No clinical review this week. See you in 2 weeks for our first conference of the academic year.

Thanks to everyone who stuck it out through conference today with us running late and starving because the food was delayed. I’m glad that we had time to get all the talks in, especially the seniors who provided some useful insights about our IRB. I wanted to follow up on some points that came up today in conference:

Use of cholestyramine in decontamination after digoxin overdose: Cholestyramine does have an effect on reducing absorption of digoxin from the gut but its role has largely been limited by the overwhelmingly more effective activated charcoal so it has been relegated to being used as an adjunct. (As with almost all tox, the studies are old, small, or just case reports: PMID 3358884, 3341874, 1841076) Bottom line: reach for the activated charcoal first.

Insulin and glucose in treatment of bradycardia: Insulin is well known to help shift potassium into cells for temporary treatment of hyperkalemia. Recent data would suggest that high-dose insulin can be therapeutic in both calcium-channel and beta-blocker overdose. The evidence (again, case reports and animal studies: PMID 11386285, 10465243, 8246150, 16990629 — interestingly, almost all the data comes from the same people at Harvard and Carolinas) is stronger for CCBs than for BBs and suggest that insulin is useful in critically-ill patients in whom the suggested first-line therapies have been ineffective (atropine, glucagon, and — for calcium channel blockers — calcium chloride infusion). Bottom line: use insulin for CCB or BB toxicity if your the patient is crumping and nothing else works.

Digoxin: So we heard the sad story of digoxin as is went from the pinnacle of medicine in the 18th century to the low position that it holds in medicine today. So much that Circulation saw fit to publish and article entitled “Contemporary Use of Digoxin in the Management of Cardiovascular Disorders” in 2006 to clarify when this drug should be used. Further, we as new physicians don’t really know how to use this drug at all (and maybe we shouldn’t). In any case, the only time that I ever consider using it is when I want to be elegant in treating patients who present with CHF exacerbation, abysmally low EF, and Afib with RVR. In that case, you want to avoid a BB and CCB for rate control due to the negative inotropy but dig may just be a good choice with some AV refractoriness and a little inotropy in addition to the standard nitrates and diuretics. It takes time, and you definitely don’t want to give it to anyone with renal failure. There are no studies to back this up, but a few review articles that suggest it (PMID: 16735690, 1352657). For what it’s worth, I ran this approach by Dr. Rubinstein who thought it was a waste of time, and instead suggested using amio (although this will depress EF). Bottom line: don’t use dig often, if at all. Always check a dig level on patients taking digoxin.

That’s it for now. See everyone next week.

Thanks to everyone who attended my first Sinai conference. I’d like to provide some follow-up regarding some of the issues that we discussed today:

Antibiotics during COPD exacerbation: Antibiotics are indicated with severe exacerbations and those with increased sputum production as recommended by all major thoracic societies (even the Brits and Canadians!) based on randomized-controlled data. There was a discussion about choice of antibiotic. To date, there have been 11 RCTs comparing different agents in different clinical settings that show statistically significant improvement in the primary outcome measure (LOS, mortality, decreased sputum production) compared to placebo. Though most studies were done a while ago, the most recent study in 2001 (PMID: 11755608) compared ofloxacin in ventilated, non-pneumonia COPD patients who were randomized to 400mg PO vs placebo via NGT (!) (this study was done in Tunisia, might be hard get this study past some IRBs). This study showed a reduction in in-hospital mortality with an impressive ARR of 17.5% which when inverted yields a NNT of 6. Take home message: start an antibiotic (choose your favorite) on your sicker, sputum-ier COPD patients. If they have PNA, treat it.

Use of ipratropium, magnesium, and SQ terb in asthmatics: A side conversation that not everyone may have heard focused on the evidence behind the use of atrovent, mag, and SQ terb in asthmatics. Evidence exists to support the use of atrovent in both adults and children in improving peak flow and ED LOS, although evidence supporting decreased admission rates is not as strong. (PMID: 7699549 & 10103297). Magnesium has been shown to reduce hospital admission only in a subgroup of severe asthma exacerbations and thus cannot be recommended for routine use. The dose in adults is 2g IV and in children is 25 to 100 mg/kg IV. (PMID: 2879458 & 896972). As for SQ terb, I couldn’t find any evidence substantiating it’s use, although lots of people like to recommend it in the literature (I even used it about a month ago - on someone 58 years old - but the BiPap saved that patient from the tube, not the terb). Bottom line: always on the atrovent, maybe on the mag, and no evidence for the terb.

That’s it for now. See you all next week, if not before.

Thanks to all who stopped by our Innovations inEM Education booth at SAEM these past few days. Your input and encouragement were appreciated! The abstract is now online and an MS-Word version of our informational pamphlet is available for download.  

 For those of you who wanted to discuss things further, my email is Nicholas.Genes /at/ mssm.edu.

Other EM journal club websites with analyses of articles:

• Washington University (archives)
• University of Michigan (archives)
• Emory (archives)
• East Virginia Medical School

If you know of more, please share! The idea of putting EM Journal Clubs online, for prompt bedside access, goes back a few years…