It’s a hot summer day. A 40s M with a hx of psychiatric illness smokes crack and becomes agitated and incoherent in the street. EMS and the cops are called. In order to bring the EDP to medical attention, PD subdues the pt physically and cuffs him. The patient is transported on his stomach to the hospital. On arrival to the hospital, he is violent and uncooperative. How do we proceed?
This is a bread-and-butter EM case that is both simple and complicated, like much of medicine.
There are two inter-related issues here – chf and tachyarrhythmia.
It’s not a slam-dunk that the pt is in chf. She is tachypneic, hypoxic, with some crackles and a hx of chf. The cxr doesn’t look so bad (as a matter of fact, it’s very similar to her cxr from a few months ago); she doesn’t have typical signs of right heart failure or an S3; and her BP is not high nor is she diaphoretic (typical of patients in acute pulmonary edema, usually with diastolic failure). However, chf is the most likely diagnosis given all the findings. You can treat her empirically for failure and see what happens. You can also send a bnp and do a bedside sono on her heart / lungs.
The patient has a narrow-complex rhythm at a rate of 150. If you stood there and watch the cardiac monitor, there is little variation in the HR, which means that it’s not sinus tachycardia (where the HR tends to vary). The main treatments for aflutter are beta blockers (bb) and calcium-channel blockers (ccb). Alternatives to bb and ccb include electricity, digoxin, procainamide, etc.
A common maneuver is to give adenosine. If it’s an re-entry svt, it may break. If it’s sinus tach, nothing will happen to the rhythm. If it’s aflutter, you may see it slow down and then speed back up again.
There is no clear benefit to rate-control or rhythm-control in a typical ER patient with rapid afib / aflutter. It is not life-saving or heart-saving, though this is debatable. It’s also a long discussion that I would rather skip for now.
If a patient is in acute pulmonary edema, treating the tachyarrhythmia is more important. A rapidly pumping heart makes the failure worse. Think of a clogged sink. If you crank up the faucet, there is more water backing up. If you turn down the faucet, the water level won’t be as bad.
Administration of a bb or ccb in a patient with acute pulmonary edema is potentially hazardous since the drugs are negative inotropes (including diltiazem). If you know your patient has diastolic failure (HFpEf), it’s less of a risk. If your patient has an Ef of 20% to begin with, the bb / ccb may make things a whole lot worse.
Computers make medicine more difficult in virtually every way, but one area of universal benefit is access to medical records. I looked up the patient, and her Ef was good in her last echo a few months ago. Of course, you can do a bedside echo, but that takes a little longer.
BNP is generally a waste of time because most patients have slam-dunk chf. If there’s uncertainty, then bnp can be helpful. This pt’s bnp was over 4000. The patient was given asa, lasix, and her rapid aflutter was controlled with iv diltiazem. She did not make trops and made an unremarkable recovery in the ccu.
A typical aflutter response to adenosine. The flutter waves aren’t always obvious.
An 80s F presents to the ED with shortness of breath x one day. There is no cough or chest pain. Her medical problems include asthma-copd, cabg-mi-chf, dvt, and diabetes. Her VS are HR 148, RR 28, BP 104/70, T 98.0. Her room air oxygen sat is 80. On exam, the patient is not in distress. She has mild bibasilar crackles on exam, no S3, no murmurs, no JVD, and no lower extremity edema. A cxr and an ekg are done. What do we do next?
Send a beta. Cannonballs in the chest usually means choriocarcinoma, but many types of mets can look like this. His beta was nearly 10k.
There are multiple hypodense lesions on the head ct, likely to be caused by masses and edema. There is no herniation.
Although head CTs are commonly done in the ED for a first seizure, they are generally not needed. Indications for head CT are debatable, and include focal seizure, patients with low CD4 counts, abnormal neuro exam, recent head trauma, anti-coagulation, and age < 6 months old (correction: 6 months, not 6 years). I scan everyone with a history of lung or breast cancer, and all show metastatic cns disease. “Cachexia” isn’t on anyone’s CT list, but it’s an obvious reason for concern. Typically, the work-up will result in un-diagnosed cancer (or aids).
A first-time seizure does not require anti-seizure medication. A first-time seizure due to cns brain lesions should get anti-seizure meds, because the seizures are likely to recur. The benefits greatly outweigh the risks.
When we find a cns brain lesion causing edema and seizure, the patient is typically given steroids to reduce edema. There’s nothing wrong with that, but the steroids may get you a few unkind words from the oncologist because steroids are contra-indicated in the face of primary cns lymphoma. The concern is that cns lymphoma is sensitive to steroids and may alter diagnosis and treatment. If you’re relatively sure that the cns lesions are metastatic disease, there’s no problem with steroids.
A patient with cns lesions and a first-time seizure should be admitted.
A chest CT is done on this patient. How do you make the diagnosis?
Whenever you see a slow, wide QRS ekg; think hyperkalemia, regardless of the underlying rhythm. The ddx includes (1) heart disease – ischemia, cardiomyopathy / scarring, carditis, (2) medications – digoxin, tricyclic antidepressants (TCAs), other meds that affect the sodium channels, beta-blockers (bb) / calcium channel blockers (ccb), and (3) hyperkalemia.
The most common causes I see are hyperkalemia or beta-blocker / ccb. You can check a potassium quickly with a bedside test (e.g. i-stat). Arguably, it’s the most dangerous ddx on the list. I see this ekg all the time. The unusual feature of this case is the patient’s red-herring complaint of chest pain. Patient usually come in with weakness, dizzy, or dyspnea.
Most everything can be ruled out by h&p. It’s unusual to see this kind of ekg due to acute coronary syndrome (acs). Most brady-arrhythmias in acs are related to inferior wall stemi, which is not present on this ekg. The ekg is also not consistent with TCAs – if you see this ekg in a TCA overdose, they are typically tachycardic, hypotensive, and comatose. The patient’s medication list did not include digoxin or a beta-blocker, but she was on a ccb. It’s unusual for this to be due to a ccb unless it’s an intentional overdose.
Her i-stat K was over 7.0. She received iv calcium, insulin, dextrose, and a nebulized albuterol treatment. Repeat ekg is shown. Her creatinine was bumped to 2.0 from a baseline of 1.2. She was admitted and had an unremarkable recovery. See the repeat ekg a hour later. And yes, we did this at follow-up.
Swallowing a little anti-freeze is harmless. You know the guy is ok, but do you work him up anyway? The main goal here is make sure the story is accurate. It was a sip, it was not intentional, it was anti-freeze, and the patient feels ok.
Toxic alcohols are only toxic when ingested in significant quantities per body weight. An adult can drink more ethylene glycol without getting sick compare to a child or toddler. Thus, the approach to an accidental anti-freeze ingestion is different in a child. In addition, little kids don’t come in with this scenario (siphoning), and glycols are somewhat sweet and tasty. With little exception, all children should be “worked up”, i.e., get labs and be observed.
The lab tests needed are a basic chemistry, a serum osmolarity, and a serum ethanol (sic) measurement. Don’t bother sending an ethylene glycol level on everyone, it’s a waste. For the physical, look in the mouth, see if there are any burns. Look over the vital signs. In the early stages of a bad ethylene glycol ingestion, patients are not all that sick, they are just intoxicated (by an alcohol). When the toxic metabolites kick in, patients are sick (mostly lethargy / coma) and it’s not subtle. All of the sick patients I’ve seen come in one variety – a young-ish, healthy person is brought in for coma / lethargy and has an unexplained anion gap because someone poisoned them. It is not a suicidal modus operandi in the Bronx.
If BOTH the anion gap and the osmolar gap are normal, the patient did not ingest a significant amount of ethylene glycol and can be discharged. Patients with ethylene glycol poisoning may present with only an osmolar gap or only an anion gap.
Toxic alcohols all have unique characteristics. For ethylene glycol – it’s brain, kidney, heart that are affected. Look for hypocalcemia and crystals in the urine (urine glow is unreliable). Treatment is either ethanol or fomepizole + hemodialysis. Fomepizole is costly but much easier to administer. Thiamine / pyridoxine may be helpful.
I sent labs on the guy even though I knew he’s fine. I did it so we can talk about ethylene glycol. It meant the guy sat around the ED for an hour or two. The labs were normal and the patient was discharged.
A 30s M accidentally swallows some anti-freeze when he was siphoning it from a bottle. What do we need to know in a history and physical? What work-up is needed?
And yes, this is a tylenol overdose.
Is a viable alternative sedative/hypnotic agent for procedural sedation in the ED?
Mark Estrellado MD, PGY3
Given the regularity of noninvasive and minimally invasive procedures that emergency physicians must perform on a daily basis, proficiency in the art of procedural sedation remains an indispensable component of their already broad repertoire of skills. And while every discussion on the topic of procedural sedation most often begins with the description of the “ideal sedative” as an inexpensive agent that is easily administered, has a rapid and predictable onset and dissipation of effect without prolonged accumulation despite repeated dosing, and is free of adverse side effects and drug interactions, no such agent exists. Instead, the ED physician’s current armamentarium consists of a handful of agents–namely benzodiazepines, opioids, propofol, ketamine, and etomidate–each of which have proven useful when taking into account each individual patient’s comorbidities and when utilized in the appropriate setting.3 Nevertheless, the issue of respiratory depression remains a constant concern, and this is where dexmedetomidine has garnered increasing attention over the last two decades as a potential addition to the current set of sedation agents.
Unlike its other sedative counterparts, dexmedetomidine exerts its effects primarily via presynaptic α-2 agonism resulting in lower levels of norepinephrine, and consequently, decreased sympathetic drive.1-2 This manifests in profound analgesia and sedation with decreased heart rate and blood pressure. Associated respiratory depression is virtually nonexistent, with maintenance of both rate and depth of ventilation.4 Given its respiratory profile, dexmedetomidine was originally used as a short-term sedative for mechanically vented critically ill patients.5 More recently, however, there seems to be a growing trend towards expanding its use for sedation and analgesia in adult and pediatric patients undergoing small, minimally invasive surgical and diagnostic procedures.
While evidence in the current literature is still modest at best, several experimental and observational studies suggest that dexmedetomidine may be just as efficacious, if not superior when compared to other sedative agents. Several case reports highlight the successful use of dexmedetomidine during airway surgical procedures (e.g. microlaryngeal surgery, bronchoscopy, laryngoscopy), where dexmedetomidine was either the sole anesthetic agent or supplemented with small doses of fentanyl and topical lidocaine. Recovery times in these reports were not prolonged compared to conventional anesthetics.6-7
A randomized, double-blind study compared dexmedetomidine with midazolam for intravenous sedation during dental surgery under local anesthesia. The study concluded that sedation with dexmedetomidine was comparable to midazolam, but also provided more “predictability” as it was associated with less “restlessness” and “disinhibition among patients.” While the majority of patients in the study did rate dexmedetomidine’s analgesic effect as satisfactory, however, researchers found its amnestic effects to be unreliable.8-10
In 56 patients undergoing endarterectomy with regional anesthesia, dexmedetomidine proved an acceptable alternative to sedation using midazolam and fentanyl, without showing superiority to conventional sedation techniques used during awake carotid endarterectomy.11
In another study by Kaygusus et al., the combination of dexmedetomidine with a small dose of fentanyl was used safely and effectively when compared to the standard propofol regimen used during extracorporeal shockwave lithotripsy.12
In the pediatric setting, dexmedetomidine has been garnering popularity as an alternative to propofol among nonanesthesiologists for sedation of children during diagnostic CT and MRI imaging. Comparative studies have seen an association between using higher doses of dexmedetomidine and higher rates of completion of imaging without the need to administer another sedative. One study found that utilizing higher doses of dexmedetomidine even resulted in shorter recovery times, which the authors attributed to the lower use of barbiturates for rescue sedation.13-14
Nevertheless, several controversies surrounding dexmedetomidine’s efficacy and safety profile have hindered its universal acceptance. Despite a growing number of positive studies, dexmedetomidine’s effectiveness as a sedative agent has not been uniformly successful, particularly for invasive procedures. For instance, in a prospective study where dexmedetomidine was used as the sole agent during cardiac catheterization in pediatric patients, investigators found that, not only did dexmedetomidine have a longer time of onset, but also more than half of the subjects required additional propofol boluses in order to facilitate successful cannulae placement.15 Concerns have also arisen regarding dexmedetomidine’s hemodynamic effects, especially when used in higher doses. As a case in point, in a randomized, single-blind study comparing the use of dexmedetomidine and fentanyl versus midazolam and meperidine for outpatient colonoscopies, Jalowiecki et al. reported a higher incidence of hypotension and bradycardia in the dexmedetomidine group, prompting the investigators to terminate the study prematurely.16 Given these issues, the addition of a second agent–ketamine–in conjunction with dexmedetomidine has been proposed by some as a more preferable alternative. An NMDA receptor antagonist, ketamine causes dose dependent direct stimulation of the CNS that leads to increased sympathetic nervous system outflow, manifesting as increases in systemic and pulmonary blood pressure, heart rate, and cardiac output without producing any significant respiratory depression.17 As such, ketamine may complement the limitations of dexmedetomidine as a sole anesthetic agent.
Current literature regarding the use of a dexmedetomidine-ketamine combination is severely limited at present, but the preliminary findings show some promise. A prospective randomized trial by Tosun et al. compared dexmedetomidine-ketamine to propofol-ketamine for pediatric patients with acyanotic congenital heart disease undergoing cardiac catheterization found that sedation was effective in both regimens without any clinically significant differences in hemodynamic stability or respiratory status between the two.18 However, the dexmedetomidine-ketamine group required more supplemental boluses of ketamine. Koruk et al. conducted a similar prospective investigation comparing dexmedetomidine-ketamine versus midazolam-ketamine during extracorporeal shockwave lithotripsy for pediatric patients, again showing that sedation was equally effective in both groups, with the incidence of nausea and vomiting significantly lower in the dexmedetomidine-ketamine group.19 Additional evidence regarding the potential utility of the dexmedetomidine-ketamine combination comes by way of small retrospective case series and anecdotal case reports, several of which attest to the achievement of a satisfactory level of sedation even in patients with significant comorbid conditions–e.g. obstructive sleep apnea, pulmonary hypertension–with minimal adverse effects observed.20-27
Overall, while the existing data is still insufficient to make any definitive conclusions at this time, the potential for the dexmedetomidine-ketamine combination to be a viable sedative/hypnotic alternative for procedural sedation is undeniable. From a theoretical standpoint, the two agents have the capacity to complement each other’s limitations. When used in tandem, dexmedetomidine may limit the tachycardia, hypertension, and “emergence phenomenon” commonly associated with ketamine. Conversely, ketamine may counteract the bradycardia and hypotension seen with dexmedetomidine and may help achieve a more rapid time of onset of sedation compared to dexmedetomidine alone. Ultimately, more large randomized-control trials must be conducted with direct comparisons to other commonly used regimens in order to gain a better sense of the impact, if any, that dexmedetomidine-ketamine will have in the practice of procedural sedation in the ED.
1) Scholz J, Tonner PH. α2-Adrenoceptor anesthesia: a new paradigm. Curr Opin Anaesthesiol 2000;13:437-42.
2) Chiu TH, Chen MJ, Yang YR, Yang JJ, Tang FL. Action of dexmedetomidine on rat locus coerleus neurons: intracellular recording in vitro. Eur J Pharmacol 1995;285:261-8.
3) Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30:119–141
4) Bhana N, Goa KL, McClellan K. Dexmedetomidine. Drugs 2000;59: 263-8.
5) Dyck JB, Shafer SL. Dexmedetomidine pharmacokinetics and pharmacodynamics. Anaesthetic Pharmacology Review. 1993;1:238–245.
6) Jense RJ, Souter K, Davis J, Romig C, Panneerselvam A, Maronian N. Dexmedetomidine sedation for laryngeal framework surgery. Ann Otol Thinol Laryngol. 2008;117:659–664.
7) Ohata H, Tanemura E, Dohi S. Use of high-dose dexmedetomidine infusion for anesthesia and sedation in a patient for microlaryngeal surgery maintained with spontaneous breathing. Masui. 2008;57:428–432.
8) Ogawa S, Seino H, Ito H, Yamazaki S, Ganzberg S, Kawaai H. Intravenous sedation with low-dose dexmedetomidine: its potential for use in dentistry. Anesth Prog. 2008;55:82–88.
9) Cheung CW, Ying CLA, Chiu WK, Wong GTC, Ng KFJ, Irwin MG. A comparison of dexmedetomidine and midazolam for sedation in third molar surgery. Anaesthesia. 2007;62:1132–1138.
10) Ustun Y, Gunduz M, Erdogan O, Benlidayi ME. Dexmedetomidine versus midazolam in outpatient third molar surgery. J Oral Maxillofac Surg. 2006;64:1353–1358.
11) McCutcheon CA, Orme RM, Scott DA, Davies MJ, McGlade DP. A comparison of dexmedetomidine versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy performed under regional anesthesia. Anesth Analg. 2006;102:668–675.
12) Kaygusuz K, Gokce G, Gursoy S, Ayan S, Mimaroglu C, Gultekin Y. A comparison of sedation with dexmedetomidine or propofol during shockwave lithotripsy: a randomized controlled trial. Anesth Analg. 2008;106:114–119.
13) Mason KP, Zurakowski D, Zgleszewski SE, et al. High dose dexmedetomidine as the sole sedative for pediatric MRI. Pediatr Anesth. 2008;18:403–411.
14) Koroglu A, Demirbilek S, Teksan H, Sagir O, But AK, Ersoy OM. Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results. Br J Anaesth. 2005;94:821–824.
15) Munro HM, Tirotta CF, Felix DE, et al. Initial experience with dexmedetomidine for diagnostic and interventional cardiac catheterization in children. Pediatr Anesth. 2007;17:109–112.
16) Jalowiecki P, Rudner R, Gonciarz M, Kawecki P, Petelenz M, Dziurdzik P. Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy. Anesthesiology 2005;103:269-75.
17) J Albanèse, S Arnaud, M Rey, L Thomachot, B Alliez, C Martin Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology: 1997, 87(6);1328-34
18) Tosun Z, Akin A, Guler G, et al: Dexmedetomidine-ketamine and propofol-ketamine combinations for anesthesia in spontaneously breathing pediatric patients undergoing cardiac catheterization. J Cardiothor Vasc Anesth 2006; 20:515–519
19) Koruk S, Mizrak A, Gul R, et al: Dexmedetomidine-ketamine and midazolam-ketamine combinations for sedation in pediatric patients undergoing extracorporeal shock wave lithotripsy: A randomized prospective study. J Anesth2010; 24:858–863
20) Bozdogan N, Sener M, Caliskan E, et al: A combination of ketamine and dexmedetomidine sedation with caudal anesthesia during incarcerated inguinal hernia repair in three high-risk infants. Pediatr Anesth 2008; 18:1009–1011
21) Barton KP, Munoz R, Morell VO, et al: Dexmedetomidine as the primary sedative during invasive procedures in infants and toddlers with congenital heart disease. Pediatr Crit Care Med 2008; 9:612–615
22) Luscri N, Tobias JD: Monitored anesthesia care with a combination of ketamine and dexmedetomidine during magnetic resonance imaging in three children with trisomy 21 and obstructive sleep apnea. Pediatr Anesth 2006; 16:782–786
23) Iravani M, Wald SH: Dexmedetomidine and ketamine for fiberoptic intubation in a child with severe mandibular hypoplasia. J Clin Anesth 2008; 20:455–457
24) Mahmoud M, Tyler T, Sadhasivam S: Dexmedetomidine and ketamine for large anterior mediastinal mass biopsy.Pediatr Anesth 2008; 18:1011–1013
25) Munro HM, Felix DE, Nykanen DG: Dexmedetomidine/ketamine for diagnostic cardiac catheterization in a child with idiopathic pulmonary hypertension. J Clin Anesth 2009; 21:435–438
26) Rozmiarek A, Corridore M, Tobias JD: Dexmedetomidine-ketamine sedation during bone marrow aspirate and biopsy in a patient with duchenne muscular dystrophy. Saudi J Anaesth 2011; 5:219–222
27) Corridore M, Phillips A, Rabe A, et al: Dexmedetomidine-ketamine sedation in a child with a mediastinal mass.World J Pediatr Cong Heart Surg (in press)28)
28) Shukry M, Miller J: Update on dexmedetomidine: use in nonintubated patients requiring sedation for surgical procedures. Therapeutics and Clinical Risk Management 2010; 6:111-121
29) Gerlach A, Dasta J: Dexmedetomidine: An Updated Review. Annals of Pharmacotherapy 2007; 41:245-253
30) Tobias J: Dexmedetomidine and Ketamine: An Effective Alternative for Procedural Sedation? Pediatric Crit Care Med 2012; 13(4):423-27
BNP: Data, Diagnosis and Applications
M Lamberta PGY-3
What are the Biomarkers?
Natriuretic Peptide (NP) assays gained approval by the FDA around the year 2000 for the evaluation of undifferentiated dyspnea and suspected ADHF. The first commercially available test detected the biologically active hormone BNP, but many more recent assays also detect the inert Amino-terminal cleavage product of the BNP prohormone: N-Terminal proBNP (NT-proBNP). (Table 1) Both biomarkers are comparable in their diagnostic accuracy demonstrated by Receiver Operating Characteristic (ROC) curves.
From 1999 to 2000, Maisel et al. recruited 1,586 participants in the first large multinational randomized control trial (RCT) to evaluate BNP for the diagnosis of heart failure in ED patients presenting with acute dyspnea.. The Breathing Not Properly (BNP) study analyzed a subgroup from this cohort to conclude that adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. This trial supported BNP as a good rule-out test for Acute Decompensated Heart Failure (ADHF) with a sensitivity of 90% for BNP < 100 pg/mL when compared to the gold standard: blinded assessment of two independent cardiologists. The authors also argued that BNP ruled-in 14 of the 19 patients that were erroneously diagnosed by clinicians as “CHF improbable,” thereby reducing false negatives from 2% to 0.6%. The improved sensitivity, however, inevitably reduced specificity to near 74% for a cut-off of BNP ≥100 pg/mL.  Furthermore, a secondary analysis pointed out the limited application of this biomarker as clinical judgment seemed to outperform BNP assay when applied to the dyspneic patient at the extremes of pretest probability ie greater than 95% or less than 5% certainty of ADHF.  Therefore, a higher rule-in threshold (BNP > 500 pg/mL improved specificity of this assay but also opened up a “gray-zone” in the interpretation of BNP where the test could neither rule-in nor rule-out with good certainty.
By the mid-2000s, the rule-out and rule-in cut-offs for CHF began to gain modest support by professional organizations including ACEP.  Wang et al. contributed to JAMA’s Rational Clinical Examination series by conducting a meta-analysis of these preceding data in addition to 20 smaller studies on BNP to determine Likelihood ratios for BNP. The meta-analysis calculated a negative likelihood ratio (LR-) near 0.9 (cut-off <100 pg/mL) again promoting BNP as a strong test to rule-out ADHF. Yet, comparing BNP to patient history “significant for heart failure” (LR+ 5.8) or “interstitial edema” on chest X-Ray (LR+ 12), BNP stood as an equivocal test to rule-in HF with LR+ 2.7 (≥100 pg/mL).
In the later 2000s, large RCTs would similarly establish the accuracy of NT-proBNP in ADHF. The PRIDE (N-Terminal Pro-BNP Investigation of Dyspnea in the Emergency Department) constructed ROC curves to conclude that adding NT-proBNP to the evaluation of patients with dyspnea was superior to clinician-estimated likelihood of CHF alone with area under the curve (AUC) measuring 0.90 for clinician alone versus 0.94 for clinician+NT-proBNP, (p = 0.006). The Canadian IMPROVE-CHF study affirmed similarly that adding NT-proBNP to clinical judgment alone increased the AUC from 0.83 to 0.90. 
Despite showing statistical differences in diagnostic accuracy through Receiver-Operator Characteristic Curves, the application of natriuretic peptides did not appear to add much to clinical judgement at the extremes of pre-test probability, so many began to apply it to patients who were considered intermediate pretest probability (21% to 79%) or under circumstances of competing diagnoses ie COPD vs PNA vs CHF. Steinhart et al. attempted to better stratify these “intermediate probability” patients by deriving an algebraic model that capitalized on increased positive likelihood ratios at higher absolute levels of NT-proBNP. In a validation study, this model appeared to correctly reclassify 44% of the “intermediate” patients to either low risk or high risk. The strength of this approach is that it provides for practical application of NT-proBNP as a continuous variable rather than just relying on discrete cut-offs, it accounts for age-adjusted variability, and it prompts the clinician to appropriately consider pre-test probability before interpreting the test result. The weakness lies in the fact that it requires math (yet, an excel model is available for download here), and it does not appear to approve diagnostic accuracy in a majority of cases. In this study, the model helped to correctly reclassify 10% of the study participants. [8,9]
When NPs came to the scene 15 years ago the hope was that it would be the “super-hero” for the bewildered clinician in the diagnosis of dyspnea, but subsequent trials and meta-analyses gave BNP the persona of more of a “yes-man” supporting what the clinician already knew and equivocating just as much for cases of “intermediate probability.” The literature of the last 15 years has elucidated NP test characteristics, confounding variables (Tables 1 and 2), and interpretation, but application of the test still appears rather heterogeneous by anecdote as either a rule-in, rule-out, adjudicator, or prognosticator.
- Ruling-in low-probability: BNP as a rule-in test to diagnose patients who are being treated erroneously for other conditions ie a 65-year-old patient with a history of COPD but no current diagnosis of HF. Rosen even suggests “we abandon the routine obtaining of a BNP level for patients deemed to be having a CHF flare-up, and instead consider it in all dyspnea patients that we don’t believe are having CHF.”  This implies a sentiment of screening. In an older population, where prevalence is higher, it may be a good consideration.
- Ruling-out high-probability: As expenditures for heart failure continue to soar, the use of BNP, in concert with other clinical signs and adjunct studies, may have significant application for ruling-out ADHF in known HF patients. This may lead to scoring protocol or institutional decision rules to help identify ED patients who are safe for outpatient management.
- Adjudicating intermediate risk: Likely BNP will continue to find application case-by-case by the ED clinician who is interested in detecting the presence of heart strain whether it will change management or not. Interpretation of BNP should be considered after establishing pre-test probability for the patient, with the knowledge of confounding variables, and can employ tools to interpret the test like that proposed by Steinhart et al. (available for download here). That said, the same cases of intermediate probability will more likely represent the complex and sicker patients requiring longer hospital stays and extended work-ups and more than half the time the knowledge of BNP will unlikely help to narrow the diagnosis. 
- Prognosticating: Elevated BNP almost always suggests a poor prognosis whether it is used to stratify ADHF, NSTEMI, or PE, but prognosis is often more accurately reflected—and more easily assessed—by patient hemodynamics and renal perfusion. [11,12,13] There is no strong evidence that BNP will consistently help an admitting team in their management, but there is still ongoing research discerning how BNP may help in response-guided therapy and discharge planning.
- Outcomes: Only a handful of randomized controlled trials have measured changes in outcomes for clinicians who use natriuretic peptide assays in the ED. Meta-analyses of these trials have shows trends towards decreased cost and length of stay, but no reproducible significant difference in these outcomes or in regards to therapy or mortality. [14,15]
- Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161-167.
- McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 2002;106:416–22
- Schwam E. B-type natriuretic peptide for diagnosis of heart failure in emergency department patients: a critical appraisal. Acad Emerg Med. 2004;11:(6)686-91.
- Silvers SM, Howell JM, Kosowsky JM, Rokos IC, Jagoda AS. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute heart failure syndromes. Ann Emerg Med 2007;49:627–69. (BNP Clinical Policy) http://www.acep.org/workarea/DownloadAsset.aspx?id=8778
- Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency department have congestive heart failure? JAMA 2005;294:1944–56
- Januzzi JL Jr, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Am J Cardiol. 2005;95:948-954.
- Moe GW, Howlett J, Januzzi JL, Zowall H, for the Canadian Multicenter Improved Management of Patients With Congestive Heart Failure (IMPROVE-CHF) Study Investigators. N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure: primary results of the Canadian prospective randomized multicenter IMPROVE-CHF study. Circulation 2007;115:3103–10
- Emergency Medicine Journal Club. Does BNP Augment Acue Decompensated CHF ED Management. WUSM-St. Louis. Journal Club November, 2009. http://emed.wustl.edu/education/EmergencyMedicineJournalClub/Archive/November2009.aspx
- Steinhart B, Thorpe KE, Bayoumi AM, Moe G, Januzzi JL, Mazer CD. Improving the diagnosis of acute heart failure using a validated prediction model. J Am Coll Cardiol 2009;54:1515–21.
- Carpenter CR, Keim SM, Worster A, Rosen P, BEEM (Best Evidence in Emergency Medicine). BRAIN NATRIURETIC PEPTIDE IN THE EVALUATION OF EMERGENCY DEPARTMENT DYSPNEA: IS THERE A ROLE? The Journal of Emergency Medicine. 2012;42(2):197-205.
- Heeschen C, Hamm CW, Mitrovic V, et al. N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes. Circulation. 2004 Nov 16. 110(20):3206-12.
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