Ace844

52 Precepts EMS Students and Providers Should Consider Regularly

Also, since you were championing it's use, I am surprised you didn't post this. For those who are interested heres a MNEMONIC for AC use: Charcoal, Substances Poorly Absorbed by Activated CHARCOAL C austics and corrosives H eavy metals (arsenic, iron, lead, lithium, mercury) A lcohols (ethanol, methanol, isopropyl) and glycols (ethylene glycol) R apid onset or absorption of cyanide and strychnine C hlorine and iodine O thers insoluble in water (substances in tablet form) A liphatic and poorly absorbed hydrocarbons (petroleum distillates) L axatives, sodium, magnesium, potassium

Since I posted some of these in other threads, here's another..

Ahhh...THE CHESTPAIN!!!!...

Breathe via laryngoscopy and ET tube, or DIE....I'll take breathe every time thank you.... ACE

"Stcommodore," While your perusing the threads and learning, here's something else for you to look at and compare with the literature... Oh and by the way because your going to need it to prophalax the migraine your going to get.... have one or more of these to: Now on to the charts:

"Peppermintpatty," Here's a decent decision tree which should help you in your practice in the future. This is something you should print and keep for future reference. It was made by a group of people whose JOB AND ACADEMIC LIFE is spent in this specialty.... Hope This Helps, ACE844

"firefighter523," Here's something you should print and post at your station and or give to your boss. It was made by a group of people whose JOB AND ACADEMIC LIFE is spent in this specialty.... Hope This Helps, ACE844

[fade:20711d095b]WHO KNEW?!?!!?!?! [/[/fade:20711d095b]b]

Hello Everyone, While doing some research and posting info for another thread I ran across this which i thought you all may be interested in reading. Out Here, ACE844 (Panel clarifies warnings for CHF medication July 19 @ 2005) Scios and the US Food and Drug Administration notified health care professionals on July 13, 2005, about the recommendations of an expert panel of cardiology and heart failure clinicians with regard to Natrecor (nesiritide). Recent questions raised about worsened renal function and mortality prompted the formation of the panel, which provided a consensus statement on each issue, provided advice on the ongoing and planned clinical development program, made recommendations about the appropriate use of the drug, and recommended an educational campaign to ensure that clinicians understand when the use of Natrecor is appropriate and when it is not. In a letter addressed to health care professionals, California-based biopharmaceutical company Scios noted that the panel, led by Dr Eugene Braunwald, Distinguished Hersey Professor of Medicine, Harvard Medical School, reviewed the available data, including review of the original 2001 Natrecor product labeling that has described these risks. They endorsed the company's plan to conduct several clinical trials, including a large trial of clinical outcomes to further assess the benefits and risks of Natrecor. The panel also strongly encouraged Scios and investigators to continue enrollment of patients in current Natrecor trials (eg, Follow-up Serial Infusion of Nesiritide [FUSION] II) and in the planned Natrecor trials. The panel also made recommendations about the appropriate use of Natrecor and encouraged the manufacturer to engage in a campaign to further educate clinicians about the drug. The panel made the following specific recommendations: The use of Natrecor should be strictly limited to patients presenting to the hospital with acutely decompensated congestive heart failure (CHF) who have dyspnea at rest, as were the patients in the largest trial that led to approval of the drug (VMAC). Physicians considering the use of nesiritide should consider its efficacy in reducing dyspnea, the possible risks of the drug, and the availability of alternate therapies to relieve the symptoms of CHF. Nesiritide should not be used to replace diuretics. Furthermore, because sufficient evidence is not currently available to demonstrate benefit for the applications listed below, nesiritide should not be used: For intermittent outpatient infusion For scheduled repetitive use To improve renal function To enhance diuresis Scios should immediately undertake a proactive educational program to inform physicians regarding the conditions and circumstances in which nesiritide should and should not be used, as described above. Sponsor-supported communications, including review articles of nesiritide, should reflect the above recommendations. Scios should ensure that current and future marketing and sales activities related to nesiritide are consistent with this educational program. Natrecor is indicated for the intravenous treatment of patients with acutely decompensated CHF who have dyspnea at rest or with minimal activity. In this population, the use of Natrecor reduced pulmonary capillary wedge pressure and improved dyspnea. The recommended dose of Natrecor is an intravenous bolus of 2 mcg/kg followed by a continuous infusion of 0.01 mcg/kg/min. Consistent with the clinical trials supporting its approval, the commercial use of Natrecor in clinical practice (noninvestigational) should be strictly limited to patients with acutely decompensated heart failure with a clinical presentation severe enough to warrant hospitalization. Natrecor should be administered in a clinical setting where blood pressure can be closely monitored. The drug should not be initiated at a dose higher than the recommended dose. The prescribing information for Natrecor reflects data from 10 clinical trials including 941 patients with CHF (NYHA class II-III, 61%; class IV, 36%; mean age, 60 years; women, 28%). There were 5 randomized, multicenter, placebo- or active-controlled studies in which 772 patients with decompensated CHF received continuous infusions of Natrecor at doses ranging from 0.01 to 0.03 mcg/kg/min. Of these patients, the majority (70%) received the Natrecor infusion for at least 24 hours; 48% received Natrecor for 24 to 48 hours, and 22% received Natrecor for greater than 48 hours. All of the patients participating in each of these trials required hospitalization for acutely decompensated heart failure. The study trials permitted entry at any point during the treatment course of acutely decompensated CHF, demonstrating that the use of Natrecor is safe and effective in a broad range of hospitalized patients. For example, the studies included patients in whom the study drug (either Natrecor or control) was started as the first intravenous vasoactive therapy before or after intravenous diuretics, as replacement therapy for patients not sufficiently responsive to another intravenous vasoactive therapy, or as add-on therapy in patients refractory to dobutamine or dopamine. The VMAC trial, the largest relied on for the approval of the drug, was a randomized, double-blind study of 489 patients who required hospitalization for management of shortness of breath at rest or with minimal activity (eg, talking, eating, or bathing) due to acutely decompensated CHF. Patients with acute coronary syndrome, preserved systolic function, arrhythmia, and renal insufficiency were not excluded. The study compared the effects of Natrecor, placebo, and intravenous nitroglycerin when added to background therapy (intravenous and oral diuretics, nonintravenous cardiac medications, dobutamine, and dopamine). VMAC was designed to show primary efficacy comparisons between Natrecor and placebo. The nitroglycerin arm was included to show the relative safety and tolerability of Natrecor in comparison with a commonly used intravenous vasodilator. The primary end points of VMAC were the change from baseline in patients' dyspnea and the change from baseline in pulmonary capillary wedge pressure (PCWP), evaluated after 3 hours. Patients receiving Natrecor reported greater improvement in dyspnea at 3 hours than patients receiving placebo plus standard care (P = .034). Natrecor led to a significant reduction in PCWP compared with placebo at 3 hours, when added to standard care (P < .001). There was a significant reduction in mean PCWP, relative to placebo, within 15 minutes of starting the Natrecor infusion, with most of the effect observed at 3 hours being achieved within the first 60 minutes of the infusion. In its letter to health care professionals, Scios acknowledged that Natrecor is sometimes administered via intermittent and scheduled infusions to treat severely ill patients with CHF, particularly in the outpatient setting. Although a clinical development program is currently underway in this setting (FUSION II trial), Scios does not recommend Natrecor for this use at this time. According to Scios, the only controlled clinical trial to assess the use of Natrecor for serial infusions in the outpatient setting is FUSION I. FUSION I was a pilot study (n = 210) and was not powered to adequately assess the effectiveness or safety of serial infusions of Natrecor. The size of the study, its design, and its findings provide an inadequate basis to recommend the routine use of intermittent, serial, or scheduled repetitive infusions of Natrecor. In certain instances, Natrecor is also being used to replace diuretics, to improve renal function, or to enhance diuresis. To date, adequate clinical data that demonstrate clinically relevant diuretic properties or positive renal effects of Natrecor do not exist. The manufacturer does not recommend such use. Moreover, it is important to understand that clinical trial data show that the use of Natrecor was associated with a dose-dependent increase in serum creatinine. In VMAC, the serum creatinine level rose by more than 0.5 mg/dL above baseline in at least 1 blood draw in 7% of patients in the control groups and 8% in the nesiritide groups by 5 days, and by 21% and 28% respectively, by 30 days. Most of these increases occurred days after discontinuation of the drug. Natrecor may cause hypotension. If hypotension occurs during the administration of Natrecor, the dose should be reduced or discontinued, and blood pressure should be monitored closely. At the recommended dose of Natrecor, the incidence of symptomatic hypotension (4%) was similar to that of intravenous nitroglycerin (5%). Asymptomatic hypotension occurred in 8% of patients treated with either drug. The mean duration of symptomatic hypotension was longer with Natrecor than intravenous nitroglycerin (2.2 vs 0.7 hours, respectively). Higher doses of Natrecor increased the risk of hypotension and elevated creatinine. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with Natrecor may be associated with azotemia. Other adverse events reported at a rate of at least 5% during the first 24 hours of infusion with either Natrecor plus standard care or intravenous nitroglycerin plus standard care therapy, respectively, included the following: ventricular tachycardia (3%, 5%), nonsustained ventricular tachycardia (3%, 5%), headache (8%, 20%), abdominal pain (1%, 5%), and nausea (4%, 6%). Natrecor should not be used in patients with systolic blood pressure <90 mm Hg or as primary therapy in patients with cardiogenic shock. Natrecor is not recommended for patients for whom vasodilating agents are not appropriate and should be avoided in patients with low cardiac filling pressures. In the 7 Natrecor clinical trials that collected mortality data through 30 days, 5.3% in the Natrecor treatment group died, compared with 4.3% in the group treated with other standard medications. In the 4 clinical trials in which mortality was collected through 180 days, 21.7% in the Natrecor treatment group died compared with 21.5% in the group treated with other standard medications. There are insufficient numbers of deaths to identify or exclude, with confidence, a moderate excess of risk to survival after treatment with Natrecor. For more information about the use of Natrecor, call the Scios Medical Information department at 1-877-4-NATRECOR (1-877-462-8732) or visit www.natrecor.com.

Does anyone else want here want to throw this guy a life jacket or help him out, or perhaps sell him one of the below...???? [marq=left:dc9091265b]***NOTE:when reading the picture please ignore the 'BITCH' comment...I don't know how to edit that out of the photo...my apologies if this offends someones senseabilities******[/marq:dc9091265b]

:shock: Perhaps that was all they had access to..... It was Denmark Afterall... :wink: :wink: 8) :shock: 8)

For all of you who are interested in learning more about this I'd like to direct you to this thread here:: Teaching Points:::: Intubation-RSI In addition to doing a further search on 'the city' as well. Hope This Helps, ACE844

Hello Everyone, Since we discuss this alot here I thought that perhaps I would make this teaching post and allow some of you all to benefit alittle from the wisdom of Ron Walls MD, whose bokk is highly recommened here by ALL OF US WHO HAVE IT, and it is in the EMTCITY Book Club. If for whatever reason you can't get it, or are to lazy to, here's just a small taste of what you've been missing. LIKE IT, LOVE IT, KNOW IT READ IT, MEMORIZE IT, READ IT AGAIN!!!! Enjoy, ACE844

{Said tongue in cheek in my worst DR Phil type PC whiny dribble voice} "Paramedicmike," Don't you know know its not nice or PC, or POLITE to say to someone's face anymore that they lied, and it's obvious and we all know it!!! SHEESH, now his psychotherepy bills are going to be through the roof. We can't go around offending people who are willing to blatantly lie to us all, ya know!?!? I mean what is this world coming to? SIGH...SHRUG... ACE844 8) 8)

"GA," "TECHmedic," great post, very sucinct and well said. "GAmedic," I posted this study here because although I was initially skeptical of this machine, now having seen it work a few times in 'real time' I have started to come around. There are numerous posts here on CHF, cardiac phys, etc... feel free to do a search and read some of them. Clinicians must continually integrate vast amounts of medical information with their skills in clinical decision making. They must be thorough yet efficient in gathering data and use strategies that promote maximal diagnostic proficiency while limiting time and performing maximal benefical intervention. These unique skills are neither adequately taught nor measured in medical schools, professional medical programms, and residencies. Emergency physicians, and other clinicians (READ PARAMEDICS AND EMS PROVIDERS) have become some of the most facile and rapid decision-makers in medicine. This is likely due to the nature of their specialty. Emergency physicians, and other clinicians (READ PARAMEDICS AND EMS PROVIDERS) are bombarded by diagnostic and management decisions throughout a clinical shift. Many pertain directly to diagnosing and managing a patient’s problem. Others relate to managing the scene, other agencies and providers, the clinical environment, and tranpsort destinations and decisions and interventions. As well as the risk-benefit ratios of all of the aforementioned as they apply to the patient. By better understanding the decision-making process of emergency provider, improved decision-making strategies can be developed and taught. Both an adequate knowledge base of medical information and a repertoire of decision-making skills are necessary to diagnose and manage medical problems. Expert emergency care providers have learned to recognize disease and injury patterns and have developed sets of heuristics (rules of thumb) to make rapid decisions. When patient presentations do not fit an existing pattern or heuristic, EMS providers move between several levels of clinical decision making depending on their clinical experience, the clinical situation, and time constraints. Most errors in mental functioning affecting patient care can be traced to defects in one or more of these levels of clinical decision making. Mental effort saved through improved decision making provides a “cognitive reserve” for emergency physicians, and other clinicians (READ PARAMEDICS AND EMS PROVIDERS) to control their hectic environment with decreased occupational stress and potential burnout. With greater reserve, emergency care providers are better able to consider patients’ values and expand their knowledge base. In closing; please as 'AZCEP, TECHmedic, Ridryder," have written please take all of the time and space you need to explain your rationale and previous posts here. WE await your futher posts and explanations, and please peruse this post as well: Panel clarifies warnings for CHF medication. Out Here, ACE844 P.S. Here's some more information; first a MNEMONICthen more info. about DOBUTAMINE: Non-Cardiogenic Pulmonary Edema, Causes of PONS P hosgene, paraquat, phenothiazines O pioids/organophosphates N itrous dioxide S alicylates (Dobutamine: Drug information Copyright 1978-2006 Lexi-Comp @ Inc. All rights reserved.) PHARMACOLOGIC CATEGORY Adrenergic Agonist Agent DOSING: ADULTS — Cardiac decompensation: I.V. infusion: 2.5-20 mcg/kg/minute; maximum: 40 mcg/kg/minute, titrate to desired response; see table. I.V. Infusion Guidelines To deliver 2.5 mcg/kg/minute: Using 500 mcg/mL solution1; infuse at 0.005 mL/kg/minute. Using 1000 mcg/mL solution2; infuse at 0.0025 mL/kg/minute. To deliver 5 mcg/kg/minute: Using 500 mcg/mL solution1; infuse at 0.01 mL/kg/minute. Using 1000 mcg/mL solution2; infuse at 0.005 mL/kg/minute. To deliver 7.5 mcg/kg/minute: Using 500 mcg/mL solution1; infuse at 0.015 mL/kg/minute. Using 1000 mcg/mL solution2; infuse at 0.0075 mL/kg/minute. To deliver 10 mcg/kg/minute: Using 500 mcg/mL solution1; infuse at 0.02 mL/kg/minute. Using 1000 mcg/mL solution2; infuse at 0.01 mL/kg/minute. To deliver 12.5 mcg/kg/minute: Using 500 mcg/mL solution1; infuse at 0.025 mL/kg/minute. Using 1000 mcg/mL solution2; infuse at 0.0125 mL/kg/minute. To deliver 15 mcg/kg/minute: Using 500 mcg/mL solution1; infuse at 0.03 mL/kg/minute. Using 1000 mcg/mL solution2; infuse at 0.015 mL/kg/minute. 1500 mg/L or 250 mg per 500 mL of diluent. 21000 mg/L or 250 mg per 250 mL of diluent. DOSING: PEDIATRIC — Cardiac decompensation: Refer to adult dosing. (For additional information see "Dobutamine: Pediatric drug information") DOSING: ELDERLY — Refer to adult dosing. DOSAGE FORMS Infusion, as hydrochloride [premixed in dextrose]: 1 mg/mL (250 mL, 500 mL); 2 mg/mL (250 mL); 4 mg/mL (250 mL) Injection, solution, as hydrochloride: 12.5 mg/mL (20 mL, 40 mL, 100 mL) [contains sodium bisulfite] DOSAGE FORMS: CONCISE Infusion [premixed in dextrose]: 1 mg/mL (250 mL, 500 mL); 2 mg/mL (250 mL); 4 mg/mL (250 mL) Injection, solution: 12.5 mg/mL (20 mL, 40 mL, 100 mL) GENERIC EQUIVALENT AVAILABLE — Yes ADMINISTRATION — Use infusion device to control rate of flow; administer into large vein. Do not administer through same I.V. line as heparin, hydrocortisone sodium succinate, cefazolin, or penicillin. (show formula) COMPATIBILITY — Stable in D5LR, D51/2NS, D5NS, D5W, D10W, LR, 1/2NS, NS, mannitol 20%; not stable in sodium bicarbonate 5%; variable stability (consult detailed reference) in peritoneal dialysis solutions Y-site administration: Compatible: Amifostine, amiodarone, atracurium, aztreonam, bretylium, calcium chloride, calcium gluconate, ciprofloxacin, cisatracurium, cladribine, clarithromycin, diazepam, diltiazem, docetaxel, dopamine, dopamine with lidocaine, dopamine with nitroglycerin, dopamine with sodium nitroprusside, doxorubicin liposome, enalaprilat, epinephrine, etoposide, famotidine, fentanyl, fluconazole, gatifloxacin, gemcitabine, granisetron, haloperidol, hydromorphone, inamrinone, insulin (regular), labetalol, levofloxacin, lidocaine, lidocaine with nitroglycerin, lidocaine with sodium nitroprusside, linezolid, lorazepam, magnesium sulfate, meperidine, milrinone, morphine, nicardipine, nitroglycerin, nitroglycerin with sodium nitroprusside, norepinephrine, pancuronium, potassium chloride, propofol, ranitidine, remifentanil, sodium nitroprusside, streptokinase, tacrolimus, theophylline, thiotepa, tolazoline, vecuronium, verapamil, zidovudine. Incompatible: Acyclovir, alatrofloxacin, alteplase, aminophylline, amphotericin B cholesteryl sulfate complex, cefepime, foscarnet, indomethacin, phytonadione, piperacillin/tazobactam, thiopental, warfarin. Variable (consult detailed reference): Furosemide, heparin, midazolam Compatibility in syringe: Compatible: Heparin, ranitidine. Incompatible: Doxapram Compatibility when admixed: Compatible: Amiodarone, atracurium, atropine, dopamine, enalaprilat, epinephrine, flumazenil, hydralazine, isoproterenol, lidocaine, meperidine, meropenem, metaraminol, morphine, nitroglycerin, norepinephrine, phentolamine, phenylephrine, procainamide, propranolol, ranitidine. Incompatible: Acyclovir, alteplase, aminophylline, bumetanide, calcium gluconate, diazepam, digoxin, floxacillin, furosemide, insulin (regular), magnesium sulfate, phenytoin, potassium phosphates, sodium bicarbonate. Variable (consult detailed reference): Bretylium, calcium chloride, heparin, nitroglycerin with sodium nitroprusside, potassium chloride, verapamil USE — Short-term management of patients with cardiac decompensation USE - UNLABELED / INVESTIGATIONAL — Positive inotropic agent for use in myocardial dysfunction of sepsis ADVERSE REACTIONS SIGNIFICANT — Incidence of adverse events is not always reported. Cardiovascular: Increased heart rate, increased blood pressure, increased ventricular ectopic activity, hypotension, premature ventricular beats (5%, dose related), anginal pain (1% to 3%), nonspecific chest pain (1% to 3%), palpitation (1% to 3%) Central nervous system: Fever (1% to 3%), headache (1% to 3%), paresthesia Endocrine & metabolic: Slight decrease in serum potassium Gastrointestinal: Nausea (1% to 3%) Hematologic: Thrombocytopenia (isolated cases) Local: Phlebitis, local inflammatory changes and pain from infiltration, cutaneous necrosis (isolated cases) Neuromuscular & skeletal: Mild leg cramps Respiratory: Dyspnea (1% to 3%) CONTRAINDICATIONS — Hypersensitivity to dobutamine or sulfites (some contain sodium metabisulfate), or any component of the formulation; idiopathic hypertrophic subaortic stenosis (IHSS) WARNINGS / PRECAUTIONS — May increase heart rate. Patients with atrial fibrillation may experience an increase in ventricular response. An increase in blood pressure is more common, but occasionally a patient may become hypotensive. May exacerbate ventricular ectopy. If needed, correct hypovolemia first to optimize hemodynamics. Ineffective in the presence of mechanical obstruction such as severe aortic stenosis. Use caution post-MI (can increase myocardial oxygen demand). Use cautiously in the elderly starting at lower end of the dosage range. DRUG INTERACTIONS Beta-blockers (nonselective ones) may increase hypertensive effect; avoid concurrent use. (For additional information: Launch Lexi-Interact™ Drug Interactions Program ) Cocaine may cause malignant arrhythmias; avoid concurrent use. Guanethidine can increase the pressor response; be aware of the patient's drug regimen. MAO inhibitors potentiate hypertension and hypertensive crisis; avoid concurrent use. Methyldopa can increase the pressor response; be aware of patient's drug regimen. Reserpine increases the pressor response; be aware of patient's drug regimen. TCAs increase the pressor response; be aware of patient's drug regimen. PREGNANCY RISK FACTOR — B (show table) LACTATION — Excretion in breast milk unknown MONITORING PARAMETERS — Blood pressure, ECG, heart rate, CVP, RAP, MAP, urine output; if pulmonary artery catheter is in place, monitor CI, PCWP, and SVR; also monitor serum potassium TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include fatigue, nervousness, tachycardia, hypertension, and arrhythmias. Reduce rate of administration or discontinue infusion until condition stabilizes. CANADIAN BRAND NAMES — Dobutrex® INTERNATIONAL BRAND NAMES — Butamine® (IL); Cardiject® (ID, TH); Cloridrato de Dobutamina® (BR); DBL Dobutamine® (TH); Dobucor® (ES); Dobuject® (CZ, FI, ID, IL, MX, PL, SG, TH); Dobutamin Fresenius® (DE); Dobutamin Giulni® (SI); Dobutamin Hexal® (DE, HU, PL, RU); Dobutamin Liquid Fresenius® (CH); Dobutamin Nycomed® (AT); Dobutamin Ratiopharm® (DE); Dobutamin Solvay® (AT, DE, HU); Dobutamin-Guilini® (AT, RO, RU); Dobutamina Abbott® (ES); Dobutamina Bioindustria Lim® (IT); Dobutamina Clorhidrato® (CL); Dobutamina DBL® (IT); Dobutamina Duncan® (AR); Dobutamina Fabra® (AR); Dobutamina Gray® (AR); Dobutamina Inibsa® (ES); Dobutamina Richet® (AR); Dobutamina Rovi® (ES); Dobutamina® (CL); Dobutamine Abbott® (TH); Dobutamine Antigen® (TH); Dobutamine Faulding® (BE); Dobutamine Hcl Abbott® (ID); Dobutamine Hydrochloride® (AU, NZ, TR); Dobutamine Solvay® (TH); Dobutamine® (ID, PL, TR); Dobutamin® (BG, CZ, NO); Dobutam® (IL); Dobutrex® (AU, BE, BR, CA, CH, CL, CZ, DK, ES, FI, FR, GB, HK, HR, HU, ID, IE, IN, IT, MX, NL, NO, NZ, PL, RO, RU, SE, TH, TR, YU, ZA); Duvig® (AR); E.M.C.® (AR); Inotop® (AT, SI); Inotrop® (ID); Miozac® (IT); Oxiken® (MX); Posiject® (GB, IE, ZA) MECHANISM OF ACTION — Stimulates beta1-adrenergic receptors, causing increased contractility and heart rate, with little effect on beta2- or alpha-receptors PHARMACODYNAMICS / KINETICS Onset of action: I.V.: 1-10 minutes Peak effect: 10-20 minutes Metabolism: In tissues and hepatically to inactive metabolites Half-life elimination: 2 minutes Excretion: Urine (as metabolites) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Bax, JJ, Poldermans, D, Elhendy, A, et al. Improvement of Left Ventricular Ejection Fraction, Heart Failure Symptoms and Prognosis After Revascularization in Patients With Chronic Coronary Artery Disease and Viable Myocardium Detected by Dobutamine Stress Echocardiography. J Am Coll Cardiol 1999; 34:163. 2. Leier, CV, Webel, J, Bush, CA. The Cardiovascular Effects of the Continuous Infusion of Dobutamine in Patients With Severe Cardiac Failure. Circulation 1977; 56:468. 3. Patel, MB, Kaplan, IV, Patni, RN, et al. Sustained Improvement in Flow-Mediated Vasodilation After Short-Term Administration of Dobutamine in Patients With Severe Congestive Heart Failure. Circulation 1999; 99:60. 4. Paulman, PM, Cantral, K, Meade, JG, et al. Dobutamine Overdose. JAMA 1990; 264:2386. 5. Practice Parameters for Hemodynamic Support of Sepsis in Adult Patients in Sepsis. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Crit Care Med 1999; 27(3):639-60. Available at: http://www.sccm.org/pdf/Hemodynamic%20Support.pdf. Accessed August 13, 2003. 6. Rich, MN, Woods, WL, Davila-Roman, VG, et al. A Randomized Comparison of Intravenous Amrinone Versus Dobutamine in Older Patients With Decompensated Congestive Heart Failure. J Am Geriatr Soc 1995; 43:271. 7. Rivers, E, Nguyen, B, Havstad, S, et al. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. N Engl J Med 2001; 345:1368 Dobutamine — Dobutamine (Dobutrex®) is not a vasopressor but rather is an inotrope that causes vasodilation. Dobutamine's predominant beta-1 adrenergic receptor effect increases inotropy and chronotropy and reduces left ventricular filling pressure. In patients with heart failure this results in a reduction in cardiac sympathetic activity [26]. However, minimal alpha- and beta-2 adrenergic receptor effects result in overall vasodilation, complemented by reflex vasodilation to the increased CO. The net effect is increased CO, with decreased SVR with or without a small reduction in blood pressure. Dobutamine is most frequently used in severe, medically refractory heart failure and cardiogenic shock and should not be routinely used in sepsis because of the risk of hypotension. Dobutamine does not selectively vasodilate the renal vascular bed, as does dopamine at low doses. (See "Inotropic agents in heart failure due to systolic dysfunction"). Next Here's a pic of a CHF Assessment and Pharm management Algorythmn: Now, Let's See what you've got.... ACE844

(Heart & Lung: The Journal of Acute and Critical Care Volume 35 @ Issue 3 , May-June 2006, Pages 178-189 doi:10.1016/j.hrtlng.2005.08.003 Copyright © 2006 Mosby, Inc. All rights reserved. Issues in pulmonary nursing Functional recovery after neuromuscular blockade in mechanically ventilated critically ill patients Janet G. Whetstone Foster PhD, RN, CNS, CCRNa, and Angela P. Clark PhD, RN, CS, FAAN, FAHAb aTexas Woman’s University, Houston, Texas bThe University of Texas at Austin, Austin, Texas. Available online 18 May 2006) Background An estimated 24% to 70% of individuals have prolonged paralysis or severe weakness after receiving neuromuscular blocking agents (NMBAs) when therapy is terminated. Objectives The purposes of this study were to (1) evaluate the relationship between recovery of neuromuscular transmission (NMT) and functional muscle activity after NMBA administration; (2) evaluate the relationship between delayed recovery of NMT or muscle activity and functional performance; and (3) determine the predictors of delayed recovery of NMT, muscle activity, and functional performance. Methods This was a multisite study using a prospective, nonexperimental, descriptive design with convenience sampling techniques. Instruments used included a five-point muscle score, Actigraph, and peripheral nerve stimulator. Results Key findings were as follows: (1) NMT returned promptly, whereas muscle activity remained severely depressed; (2) only two subjects (5%) recovered functional performance within 24 hours; (3) degree of muscle weakness immediately after neuromuscular blockade was associated with prolonged time to extubation and mobility; and (4) predictors of delayed recovery included cumulative dose of aminosteroid NMBAs, age, and renal function. Conclusion Prolonged recovery of muscle activity and extreme weakness may occur despite brisk recovery of NMT after neuromuscular blockade. Neuromuscular blocking agents (NMBAs) are most commonly administered to critically ill patients to decrease the work of breathing and facilitate mechanical ventilation for acute lung injury, and for management of intracranial pressure, control of muscle spasms associated with tetanus, drug overdose, seizures, and preservation of delicate reconstructive surgery.1 NMBAs paralyze all skeletal muscle with little effect on smooth, cardiac, or ocular muscles. An undesirable effect of the drugs recognized for more than two decades is prolonged paralysis and severe weakness after termination of NMBA therapy.1, 2 and 3 Spontaneous resumption of voluntary movement, according to previous studies, should occur in less than 4 hours after concluding therapy with NMBAs.4 However, there are reports of patients remaining paralyzed or acutely weak for hours, days, and even months. Persistent paralysis or severe weakness after termination of NMBAs has been estimated as high as 24% to 70%.5, 6 and 7 Background Numerous terms have been used to describe the prolonged neuromuscular complications of NMBAs including acute quadriplegic myopathy syndrome (AQMS), floppy man syndrome, critical illness polyneuropathy (CIP), and acute myopathy.1, 8 and 9 Regardless of the term used, profound immobility results, causing exaggerated skeletal muscle atrophy and functional alterations in every major organ system. Health care costs increase exponentially when patients remain paralyzed or significantly weak, because this perpetuates ventilator dependence and costly related care, prolonged use of intensive and acute care services, and comprehensive physical and pulmonary rehabilitation. Two patterns of weakness after discontinuation of NMBAs have been identified. One is prolonged recovery time of 50% to 100% longer than predicted determined by pharmacologic parameters such as duration of action and accumulation of metabolites, generally lasting a period of hours. The second pattern, AQMS, is devastating diffuse weakness persisting for days or weeks long after termination of NMBAs and is characterized by abnormal electromyography and muscle biopsy findings, along with slight elevations in serum creatine phosphokinase.1 Cranial nerve function and sensation remain intact. Monitoring the neuromuscular twitch response with a peripheral nerve stimulator during NMBA therapy for medication titration is recommended, which should limit drug overdosage and prevent prolonged drug effects.1 Lower cumulative doses of NMBAs and faster recovery of neuromuscular transmission (NMT) have been demonstrated when doses are titrated according to peripheral nerve monitoring, but no improvement in functional muscle activity has been reported.4 Moreover, the muscle response to peripheral nerve stimulation is merely a twitch and therefore severe muscle weakness is often present even when NMT recovers. No studies have evaluated the relationship between return of NMT and resumption of functional muscle activity. The purposes of this study were to (1) evaluate the relationship between recovery of NMT and functional muscle activity when peripheral nerve monitoring is performed during NMBA administration; (2) evaluate the relationship between delayed recovery of NMT or muscle activity and functional performance; and (3) determine the predictors of delayed recovery of NMT, muscle activity, and functional performance. The nervous system The two principal divisions of the nervous system include the central nervous system (CNS) and peripheral nervous system (PNS). The CNS consists of the brain and spinal cord, whereas the PNS is composed of the sense organs and nerves. Twelve pairs of cranial nerves and 31 pairs of spinal nerves link the brain, spinal cord, sense organs, and muscles, facilitating communication between the CNS and PNS. The PNS is further subdivided into the autonomic division, which is concerned with internal regulatory mechanisms and functions involuntarily, and the somatic division, which includes the sense organs, sensory neurons, and motor neurons and controls responses to external stimuli.10 Voluntary movement involves neuronal structures in both the CNS and PNS through the upper and lower motor neurons. The upper motor neuron originates in the motor cortex of the brain, with the nerve axons forming the corticospinal tract of the spinal cord. Here, the neurons synapse with the lower motor neurons of the spinal cord that directly innervate skeletal muscle. Voluntary muscle activity and coordination is achieved through complex neuronal interaction and coordination between the premotor cortex, primary motor cortex, basal ganglia, and cerebellum in the brain, corticospinal tracts in the brain stem and spinal cord, and terminating at the motor neuron endplate as it connects to the skeletal muscle.10 NMBAs primarily affect the PNS at the synaptic cleft between the motor neuron and muscle fiber, rendering diminished or absent muscle activity. The reticular activating system in the brain stem is responsible for maintaining consciousness and determines state of alertness. In contrast with NMBAs, sedatives, hypnotics, anxiolytics, and narcotic analgesics used in conjunction with NMBAs alter motor responses to external stimuli through depressing effects on the reticular activating system, basal ganglia, and other structures in the brain in the CNS.11 Neuromuscular blocking agents NMBAs exert their primary effects at the neuromuscular junction (NMJ) of the motor neuron of striated muscles by interfering with the release or the action of the neurotransmitter, acetylcholine.12 Nondepolarizing agents, used most commonly in the critically ill, prevent NMT by competing with acetylcholine at the receptor sites on the postsynaptic terminal. This prevents activation of acetylcholine, which in turn, prevents depolarization, contraction, and muscle movement.10 Two classes of nondepolarizing agents are used clinically, the aminosteroid derivatives and the benzylisoquinolinium derivatives. The most commonly used aminosteroid derivatives in the intensive care unit (ICU) include pancuronium and vecuronium.13 and 14 Of the benzylisoquinolinium compounds, atracurium and cisatracurium are used most often.13 Although the effects on the NMJ are similar among agents in the two groups of nondepolarizing agents, metabolism and elimination processes differ. The aminosteroids are eliminated through both renal and hepatic pathways. Metabolism of pancuronium and vecuronium produce active metabolites, which have approximately 80% of the neuromuscular blocking effects of the parent drugs.15 Atracurium and cisatracurium, in contrast, are largely cleared by a process called Hofmann degradation, a mechanism in which the drugs are nearly spontaneously reduced to less complex compounds at physiologic pH and temperature to two molecules, laudanosine and acrylate, and that is independent of organ function and enzyme action.16 However, when the benzylisoquinolinium compounds are substituted for aminosteroid derivatives for patients with compromised renal or hepatic function, prolonged paralysis, and persistent weakness have been reported.1 and 17 Medications and conditions that potentiate paralysis or weakness Residual effects of NMBAs have been associated with duration of NMBA administration, concomitant use of aminoglycosides and corticosteroids, renal failure, and electrolyte and acid-base imbalance.1, 18, 19, 20, 21 and 22 Short-term delay in recovery of neuromuscular activity, evident in hours to days after termination of NMBAs, most likely results from slow return of NMT. This may be attributed to prolonged blockade at the NMJ resulting from accumulation of NMBAs or metabolites, or excess dose or duration of NMBA infusion. Aminoglycosides and several other medications act synergistically with NMBAs, interfering with impulse transmission at the NMJ and may cause delayed recovery Table I.21 Table I. Drugs and conditions that potentiate neuromuscular blocking agents17 and 19 Aminoglycosides Amikacin Gentamicin Neomycin Streptomycin Tobramycin Other antibiotics Clindamycin Kanamycin Polymixin A,B,E Lincomycine Tetracyclines Vancomycin Procaine Other drugs Beta-blocking agents Calcium channel blockers Cyclosporine Dantrolene Diuretics Magnesium sulfate Nitroglycerin Procainamide Quinidine Trimethaphan Sedatives/psychotropics Benzodiazepines Etomidate Droperidol Ketamine Lithium carbonate Midazolam Local anesthetics Bupivacaine Lidocaine Mepivicaine Prilocaine Volatile inhalational anesthetics Enflurane Halothane Isoflurane Electrolytes/acid-base Acidosis Hypocalcemia Hypokalemia Hypermagnesemia Hypothermia Renal failure, possibly because aminosteroid NMBAs depend largely on renal excretion, has been associated with prolonged paralysis and persistent weakness. High concentrations of metabolites of vecuronium and pancuronium have been reported in patients with renal failure who exhibit residual drug effects.20 Continued circulation of the metabolites prolongs exposure of nerve receptors to neuromuscular blockade and may account for prolonged paralysis.20 Acid-base and electrolyte abnormalities may cause failure of transmitter release, interfere with receptor/transmitter union, or disrupt ion channels, hindering impulse spread throughout the NMJ.18 The second pattern of neuromuscular dysfunction, weakness that persists for weeks to months, has been linked with steroid use and the development of a myopathic process.22 Corticosteroids do not directly interfere with impulse transmission at the neuronal portion of the NMJ. Instead, corticosteroids cause direct muscle tissue damage. Atrophy, necrosis, architectural disarray, myosin loss with degeneration of fibers, lipid accumulation, and multiple metabolic alterations can occur.1 and 23 These structural and functional variations account for disruption in muscle function. The molecular structure of aminosteroidal compounds, vecuronium and pancuronium, is similar to that of corticosteroids. Concurrent administration of corticosteroids and vecuronium or pancuronium may precipitate muscle fiber degeneration, resulting in AQMS.1 Methods This was a multisite study using a prospective, nonexperimental design. Data collection took place over a 20-month period in four critical care units in three large metropolitan medical center facilities. The study was approved by the institutional review boards at the designated institutions, and informed consent was obtained from the patient’s next of kin before enrollment into the study. A convenience sampling technique was used. On notification of the primary investigator at the time NMBAs were initiated, subjects were screened for eligibility criteria and entered into the study if the family consented. Subject eligibility included age 18 years or older, endotracheal intubation, supported by mechanical ventilation, and receiving NMBAs as a continuous infusion for more than 24 hours. Demographic information was collected from the medical record, and Acute Physiology and Chronic Health Evaluation scores (APACHE III) were calculated. Medications administered in the ICU and results of laboratory tests, including serum electrolytes, renal and liver function tests, and arterial blood gases, were recorded. Exclusion criteria included a diagnosis of underlying neuromuscular disease, brain injury, spinal cord injury, history of previous sensitivity to NMBAs, and pregnancy. Subjects hospitalized for traumatic injury were screened for brain injury before initiation of NMBAs, because injury to upper motor neurons or depressed level of consciousness could explain delayed recovery of muscle activity. Physical examinations were conducted to assess for movement of extremities and response to verbal commands. Subjects with Glasgow coma scores below 10/15 were excluded; only compromised verbal scores as the result of intubation were acceptable. Data were collected by the primary investigator with the assistance of designated critical care nurses who received initial and ongoing training. The training was provided by the primary investigator and included data-collection procedures, subject eligibility, and validation of proper application of the instruments. Recovery data were calculated from the time NMBAs were discontinued and included time to recovery of muscle activity, functional performance, endotracheal extubation, mobility, and NMT. Recovery of muscle activity was measured with two instruments: (1) a widely used five-point scoring system that evaluates the force of primary muscle groups against gravity and resistance24 and (2) actigraphy, which senses and records movement detection and vigor over time. The number of hours within the first 24-hour time frame after discontinuance of NMBAs to achieve the best muscle activity score was entered as the muscle activity recovery time. Table II shows scoring criteria. Table II. Muscle scoring system (Medical Research Council, 1976)22 No movement or contraction = 0 Palpable contraction, no movement observed = 1 Movement at the joint with gravity eliminated = 2 Able to move the joint against gravity = 3 Able to move the joint against resistance, less than normal = 4 Fully normal strength = 5 The Actigraph selected for this study was the Actiwatch,™ (Minimitter Company Inc., Sun River, OR), which is a wrist-worn, coin battery-operated device weighing approximately 3 ounces. The sensor uses a piezoelectric element that senses movement and translates it to an electrical signal, which is continuously sampled by a microprocessor and stored in memory.25 Validity, reliability, and sensitivity have been well established in the laboratory25 and in clinical research to discriminate between sedentary and nonsedentary activities.26 Three Actigraph measurements were recorded: total average activity counts over the first 24 hours after termination of NMBAs, average activity counts within the first 4 hours, and average activity counts within the 20- to 24-hour interval after NMBAs were discontinued. Functional performance, defined as volitional movement necessary for activities such as repositioning, suctioning, and communication gestures commonly used by intubated patients, was determined through direct observation by the primary investigator 20 to 24 hours after NMBA termination. The 24-hour time frame for measurement was selected because it allows for reasonable recovery time from neuromuscular blockade based on pharmacologic parameters while minimizing the effects of prolonged bedrest and immobilization. Time to extubation and time to mobility, defined as ambulation or transfer to a chair, was calculated in number of days after NMBA termination and was determined by retrospective medical record review. NMT was measured with a peripheral nerve stimulator, the Microstim Plus P/N 7100 (Neurotechnology, Inc. Kerrville, TX). The instrument has been calibrated against a standardized delivery of milliamperes at the National Bureau of Standards, Washington, DC, to ensure instrument sensitivity and accuracy in the delivery of stimulating current indicated by the milliamperes selector dial. The ulnar nerve and adductor pollicis muscle were used to test the train-of-four (TOF) response to peripheral nerve stimulation in most instances, with a few subjects’ clinical condition necessitating use of the facial nerve and orbicularis oculi muscle for testing. At the conclusion of NMBA administration, the TOF response was measured hourly until four twitches resumed. All of the subjects’ medications from admission to the ICU to 24 hours after discontinuing NMBAs were assessed. Drugs known to act synergistically with NMBAs on the NMJ were recorded. Corticosteroids, sedatives, and other drugs that may influence recovery from neuromuscular blockade were recorded. Table III shows a list of medications for each subject. Table III. Medications received by subjects that may potentiate the affect of continous neuromuscular blocking agent infusion Study ID Drugs that potentiate NMBAs Sedatives Corticosteroids 1 Mannitol, magnesium Propofol,† morphine, lorazepam, pentobarbital 2 Mannitol, tobramycin, magnesium, vancomycin, furosemide, nicardipine Propofol, morphine, lorazepam, fentanyl 3 Nicardipine, magnesium, labetolol, magnesium, diamox Propofol, lorazepam, haloperidol 4 Magnesium, tobramycin Propofol, lorazepam, haloperidol Hydrocortisone 5 Pancuronium⁎ Lorazepam, morphine, general anesthesia 6 Mannitol, esmolol, rocuronium⁎ Propofol, morphine 7 Rocuronium,⁎ furosemide, magnesium, clindamycin, vancomycin Propofol, lorazepam, haloperidol, fentanyl, morphine 8 Rocuronium,⁎ magnesium, clindamycin, mannitol Propofol, morphine, lorazepam, pentobarbital 9 Nimodipine, labetolol, tobramycin, rocuronium⁎ Propofol, morphine 10 Methylprednisolone 11 12 Furosemide, clindamycin, rocuronium,⁎ cisatracurium,⁎ vancomycin, midazolam Propofol, lorazepam, morphine, fentanyl Methylprednisolone 13 Lorazepam, morphine 14 Magnesium, labetolol Lorazepam, morphine 15 Furosemide, rocuronium,⁎ vancomycin, midazolam, nicardipine, magnesium, labetolol, nitroglycerin, cyclosporine Propofol, morphine, lorazepam Prednisone, hydrocortisone 16 Magnesium Morphine, lorazepam 17 Mannitol, magnesium, gentamycin Morphine, lorazepam 18 Furosemide, clindamycin, vancomycin, vecuronium,⁎ magnesium, midazolam Propofol, lorazepam, morphine 19 Lorazepam, morphine 20 Vancomycin, magnesium, furosemide, midazolam Propofol, morphine, lorazepam Methylprednisolone 21 Magnesium, vancomycin Lorazepam, propofol 22 23 Vancomycin, furosemide, magnesium, midazolam Lorazepam, morphine, propofol, fentanyl 24 Vancomycin Lorazepam, propofol 25 Vecuronium, pancuronium,⁎ midazolam, magnesium, gentamycin, labetolol, gentamycin Morphine, lorazepam, propofol, midazolam, haloperidol 26 Vancomycin, gentamycin, magnesium, labetolol, metaprolol Morphine, lorazepam 27 Magnesium, labetolol Morphine, lorazepam 28 Propofol, lorazepam, haloperidol 29 Magnesium, clindamycin, vecuronium,⁎ metoprolol Propofol, morphine, lorazepam 30 Magnesium, calcium Morphine, lorazepam 31 Diltiazem, vecuronium,⁎ metoprolol Propofol, morphine, lorazepam Methylprednisolone NMBA, Neuromuscular blocking agent. ⁎ Bolus doses administered before continuous infusion. † Propofol is a sedative-hypnotic agent used for induction and maintenance of anesthesia or sedation. Data analysis Statistical analyses included descriptive statistics, chi-square analysis, bivariate analysis, Spearman rho correlation, and linear regression analysis. Linear regression analysis was run using five separate analyses with all indices of recovery except time to return of muscle score serving as dependent variables. All baseline data and TOF responses were entered and stored on a PC data-collection program for subsequent analysis, using SPSS 10.0 Software (SPSS Inc., 1999).27 Stored data in the Actigraph were downloaded to an IBM-compatible microcomputer (IBM, Armonk, NY) for interpretation and analysis. Results Thirty-seven subjects were entered into the study; however, subject mortality left 31 subjects remaining for analysis. Four subjects expired while receiving NMBAs; thus, there were no recovery data for analysis, and two subjects failed eligibility criteria after enrollment. The sample was composed of white non-Hispanic (41.9%), Hispanic (35.4%), and black non-Hispanic (22.5%). A summary of the subjects’ gender, age, and medical diagnoses is shown in Table IV. The median APACHE score was 52.59 (M = 54.63, standard deviation [sD] = 20.24, range 83). Length of hospital stay ranged from 9 to 120 days, with a median of 37 days (M = 42.67, SD = 27.92). Range of ICU length of stay was 7 to 60 days, with a median of 26 days (M = 29.06, SD = 16.76). Subjects had one to six medical diagnoses. Subjects received from one to nine medications known to potentiate blockade (n = 27, median 4, M = 3.8, SD = 2.0). The number of sedatives, which could reduce the level of consciousness and thereby influence activity, ranged from 2 to 5 (n = 30, median 3, M = 2.83, SD = .95), with 20 subjects receiving propofol, primarily during NMBA administration. Nine subjects received propofol for 1 day only, six subjects received propofol for 2 days, three subjects received propofol for 3 days, one subject received propofol for 5 days, and one subject received propofol for 8 days concurrently with NMBAs. Two subjects had propofol initiated during the 4 hours immediately after termination of NMBAs, but it was discontinued before the 20- to 24-hour period. In addition, two other subjects had propofol initiated during the 20- to 24-hour period after NMBAs were discontinued. Six subjects received corticosteroids. Table IV. Subject age, race, and medical diagnoses Age (y) Medical diagnoses M 25 SDH, SAH, craniotomy, pneumonia M 26 MVA, skull frx, DAI M 87 HTN, Lt basal ganglia, SAH MVA, cardiac tamponade, pericardial window, frx rt acetabulum, M 40 ARDS, ARF MVA, fetal demise, hysterectomy, nephrectomy, splenectomy, multiple F 29 frx M 24 MVA, CHI, SAH, ICH, multiple frxs F 45 AMI, ARDS, aspiration pneumonia M 18 MVA, CHI, pulmonary contusion, acute respiratory failure, ARF M 40 SAH F 43 Asthma, pneumonia M 18 MVA, pulmonary contusion, ARF, acute respiratory failure M 48 pneumonia, ARDS M 19 MVA, ARDS MVA, exploratory laparotomy, splenectomy, ARDS, subtotal M 50 pancreatectomy M 36 S/P renal transplant, ACDF, ARDS, pneumonia M 49 MVA-pedestrian, frx pelvis, frx rt femur, pneumothorax M 18 Fall, SDH, epidural hematoma M 43 ETOH withdrawal, cirrhosis, ARDS M 19 MVA, pelvic frxs F 33 Pneumonia, sepsis, ARF, pneumothorax, hepatic insufficiency F 41 Hemoptysis, metastatic lung cancer, S/P TB F 34 Lupus, CRF, bleeding rt femoral artery M 48 Cirrhosis, esophageal varices, UGI bleed, ARDS, sepsis, DIC F 34 DM, CHF, pleural effusion M 20 PE, multiple gunshot wounds, lobectomy, cholecystectomy M 41 MVA, frx C5-C4, fixation and stabilization M 18 MVA, rib frxs, liver laceration M 54 Hemoptysis, S/P TB F 23 MVA, femur rt femur, pulmonary embolism, ARDS M 43 MVA, pelvic frx, lt tibia/fibula frx F 34 Nephritis, Lupus, ICH, pulmonary hemorrhage SDH, Subdural hemorrhage; SAH, subarachnoid hemorrhage; MVA, motor vehicle accident; frx, fracture; DAI, diffuse axonal injury; HTN, hypertension; lt, left; rt, right; ARDS, acute respiratory distress syndrome; ARF, acute renal failure; CHI, closed head injury; ICH, intracerebral hemorrhage; AMI, acute myocardial infarction; S/P, status post; ACDF, anterior cervical disc fusion; ETOH, alcohol; TB, tuberculosis; CRF, chronic renal failure; UGI, upper gastrointestinal; DIC, disseminated intravascular coagulation; DM, diabetes mellitus; CHF, congestive heart failure; PE, pulmonary embolism; C5-C4, cervical vertebrae. Three different NMBAs were used, including pancuronium in 19 subjects (61%), cisatracurium in 8 subjects (26%), and vecuronium in 4 subjects (13%). The median cumulative dose of each drug administered was pancuronium 300 mg (range 897 mg, interquartile range 327, M = 325, SD = 214), cisatracurium 1113 mg (range 4938 mg, interquartile range 3392, M = 1934, SD = 1829), and vecuronium 119 mg (range 233 mg, interquartile range 214, M = 127, SD = 103). The median duration of NMBA administration was 3 days (range 27 days, interquartile range 3.5, M = 5.55, SD = 6.5). NMT returned promptly after NMBAs were discontinued in all subjects (median = 1 hour, M = 4.55, SD = 7.97). Muscle activity remained depressed by all measures. Muscle activity scores ranged from 0 to 5, with 10 of 31 subjects scoring 0 and only 3 subjects scoring 5 (Fig 1). Median recovery time for best scores was 12 hours (M = 12.96, SD = 9.67). Actigraphy counts were low at three intervals after NMBAs were discontinued: within 4 hours (median = 7.7 counts per minute, M = 18.25, SD = 36.7); 20 to 24 hours (median = 5.5, M = 13.25, SD = 28.6); and over the 24-hour period (median = 8.34, M = 9.09, SD = 4.73) (Fig 2). Although the median activity count was lower during the 20- to 24-hour period than in the first 4 hours after stopping NMBAs, a runs test of differences in median scores determined this was not statistically significant (P = .661). These values represent sharply depressed activity compared with actigraphy counts reported in the literature (35–80, M = 66). Thus, in satisfying the first aim of the study, these results indicate there was no relationship between recovery of NMT and functional muscle activity (Fig 3, Fig 4, Fig 5 and Fig 6). (23K) Fig 1. Dispersion of muscle activity scores within 24 hours after NMBAs. 0 = 32%; 1 = 10%; 2 = 13%; 3 = 29%; 4 = 3%; 5 = 10%. No movement or contraction = 0. Palpable contraction, no movement observed = 1. Movement at the joint with gravity eliminated = 2. Able to move the joint against gravity = 3. Able to move the joint against resistance, less than normal = 4. Fully normal strength = 5. NMBA, neuromuscular blocking agents. (22K) Fig 2. Comparison of actigraphy counts at three intervals after NMBAs. NMBA, neuromuscular blocking agents. (19K) Fig 3. Four-hour post-NMBA actigraphy counts and NMT. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR, hours. (21K) Fig 4. Twenty- to 24-hour post-NMBA actigraphy counts and NMT recovery. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR,. (21K) Fig 5. Average 24-hour post-NMBA actigraphy counts and NMT recovery. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR,. (22K) Fig 6. Five-point muscle activity score recovery time and NMT recovery. NMBA, neuromuscular blocking agents; NMT, neuromuscular transmission; TOF, train-of-four; HR,. The second aim of the study was to evaluate the relationship between delayed recovery of NMT or muscle activity and return of functional performance. Because only two subjects (5%) recovered functional performance within 24 hours, the results were not conducive to statistical analysis. However, an assessment of the relationship between short-term muscle weakness and long-term measures of recovery, time to extubation, and time to mobility (ambulation or chair transfer) was undertaken using chi-square analysis. Median time to extubation and initial mobility was 11 and 12.9 days, respectively. Actigraphy counts for the 2-day average was associated with time to extubation (χ2 = 5.98, df = 1, P = .014) and time to mobility (χ2 = 3.81, df = 1, P = .051). Also, muscle activity score recovery time was associated with time to mobility (χ2 = 5.07, df = 1, P = .024). These findings indicate that muscle weakness immediately after neuromuscular blockade influences functional performance (extubation and mobility) long after termination of NMBAs. The third study aim was to identify predictors of delayed recovery and return of functional performance. Bivariate analyses identified several variables associated with depressed muscle activity. First, severity of illness was a factor, with APACHE score showing a relationship with actigraphy counts during the first 4 hours after NMBAs were stopped (n = 20, rs = −.556, P = .011). Second, altered renal function was associated with persistent muscle weakness. There was an inverse relationship between blood urea nitrogen (BUN) and actigraphy counts at 4 hours (n = 20, rs = −.732, P = .000) and creatinine 20 to 24 hours (n = 21, rs = −.462, P = .035) after terminating NMBAs, indicating that higher values in BUN and creatinine were associated with lower activity levels. Third, because a large number of subjects received propofol for a period of time during NMBA administration (mostly 1–2 days), a relationship between propofol use and muscle weakness was explored. There was an association between actigraphy counts and concurrent propofol use within 4 hours of terminating NMBAs (χ2 = 6.19, df = 2, P = .045), at the 20- to 24-hour interval (χ2 = 7.64, df = 2, P = .022) and the 2-day average actigraphy count (χ2 = 7.23, df = 2, P = .027). However, missing data spread unevenly across the actigraphy count categories and propofol use accounted for 2 degrees of freedom in the analysis and confounded the results. Furthermore, actigraphy counts for one of two subjects who received propofol during the first 4 hours after NMBAs were 165, the highest overall for all data-collection points; actigraphy data were missing for the second subject during this time frame. Actigraphy counts for the two subjects who received propofol during the 20- to 24-hour time period were 20.88, one of the two highest levels of activity during this interval, and .49. After bivariate analyses, linear regression analysis was performed to determine the predictors of NMT and muscle activity recovery. Five separate analyses were performed with all indices of recovery except muscle score recovery time serving as dependent variables, including NMT recovery time, two determinations of actigraphy counts, time to mobility, and time to extubation. Too few subjects scored higher than 0 on the muscle score; thus, regression analysis was not plausible. When NMT recovery time was entered into the analysis as the dependent variable, all independent variables were derived from the literature, because no associations were extrapolated from bivariate analyses of the other variables. Age, APACHE score, duration of NMBA infusion, cumulative dose of NMBA, BUN, and medications synergistic with NMBAs were entered stepwise into the model. Initial analysis of collinearity diagnostics showed BUN and creatinine were highly correlated, along with cumulative dose of NMBAs among the three agents. Therefore, only BUN was entered. Cumulative dose of pancuronium and vecuronium were collapsed and entered as one variable because they are both aminosteroid compounds with like dosing units, and cisatracurium was eliminated because only four subjects received the drug and the dosing unit differs from the other two drugs. A summary of the model indicated that no NMBA properties were associated with NMT recovery and that age was the only predictor variable (R2 = .509, F = 16.594, P = .001). For the second analysis, actigraphy count at 4 hours after discontinuing NMBAs was entered into the regression model as the dependent variable, because bivariate analysis showed a relationship between APACHE score and BUN and actigraphy counts at the 4-hour interval. These variables, along with age, duration and cumulative dose of NMBA, synergistic drugs, and TOF recovery time were entered into the model as independent variables. The only predictor for muscle activity recovery at this interval was BUN (R2 = .313, F = 5.93, P = .030). Actigraphy counts at the 20- to 24-hour endpoint were entered as the dependent variable for the next regression analysis. Both cumulative dose of NMBA and creatinine level were found on bivariate analysis to be associated with actigraphy counts at this interval and were entered into the model as independent variables along with age, APACHE score, duration of NMBA therapy, synergistic drugs, and TOF recovery time. Cumulative dose of NMBA was the only predictor variable (R2 = .311, F = 6.309, P = .025). In evaluating the long-term recovery variables time to extubation and time to mobility, data were available on relatively few subjects achieving extubation (n = 12) or mobility (n = 8). Thus, statistical analysis was not reportable. In summary, there were two predictors of delayed muscle activity recovery, cumulative dose of aminosteroid NMBAs and impaired renal function, and one predictor of NMT recovery, age. There was no association between prolonged paralysis or weakness and steroid or aminoglycoside use, electrolyte or acid-base imbalance, or duration of NMBA therapy as reported in the literature. Discussion The study demonstrated severe depression in muscle activity during the first 24 hours after termination of neuromuscular blockade, which persisted for days to weeks in some cases, resulting in prolonged mechanical ventilation and delayed mobility. NMT returned promptly, which may provide further support for the hypothesis that there are two types of skeletal muscle weakness syndromes after neuromuscular blockade: “prolonged recovery” (short-term) and AQMS (long-term). It is possible, however, that there may be other explanations for the episodes of severe weakness observed in this study. For example, CIP and critical illness myopathy (CIM) are syndromes associated with severe weakness in critically ill patients. It has been hypothesized that a process of microcirculatory impairment induced by inflammatory mediators causes damage to motor neuron integrity.28 CIP and CIM are most frequently identified in patients with sepsis, acute organ dysfunction, and adult respiratory distress syndrome.28 Two subjects in the current study were diagnosed with sepsis, three with acute failure of one or two organs, and nine with ARDS. It is possible that many of these subjects developed CIP and/or CIM, which could explain severe weakness independent of NMBAs. However, without electrophysiology studies and muscle biopsies for confirmation, the presence of CIP or CIM is uncertain. The benefits of peripheral nerve monitoring to guide medication titration and facilitate rapid recovery of NMT were clearly demonstrated. Appropriate dosing holds several advantages. First, direct costs of the drugs are reduced when dosing is carefully titrated to patient response and smaller quantities are given. Second, NMT must be restored before muscle movement is possible. Minimizing delay in resuming NMT allows initiation of muscle recovery and prevents complications of unnecessary immobility. Preventing complications is an important responsibility of nurses, which contributes to better overall patient outcomes and reduces costly iatrogenesis. The results of five separate regression analyses determined that age, renal function, and cumulative dose of aminosteroid compounds were the best predictors of recovery of NMT and muscle activity after neuromuscular blockade. This underscores the importance of physiologic monitoring and assessment performed by critical care nurses, who must consider the factors associated with persistent weakness when caring for patients receiving NMBAs. Vigilant assessment and monitoring of physiologic function and response to NMBAs, with careful adjustments in dose, will contribute to improved recovery and avert complications of neuromuscular blockade. Because many medications, treatments, and patient conditions alter renal function, particularly in older patients, nurses play a critical role in preserving normal function and assessing for signs of renal compromise. Knowledge of delayed muscle activity recovery is useful in determining the needs of patients who remain immobile, for example, measures to preserve pulmonary function, continued use of therapeutic beds to maintain skin integrity, medications and devices to prevent deep vein thrombosis, and analgesia and nonpharmacologic comfort measures. Limitations There were several limitations to the study. Missing data for measures of time to extubation and mobility because of a prolonged internal disaster at one of the facilities during data collection limited multiple analyses concerning these variables. Second, measurement of muscle strength by the 5-point scale is only useful in conscious, aware patients, and actigraphy has limited published use in critically ill patients. However, there was strong agreement between the two instruments in evaluating muscle weakness. Third, CNS-depressing effects of various sedatives and narcotics could have explained delays in recovery of muscle activity. The half-life of midazolam, lorazepam, haloperidol, and propofol ranges from 3 to 11, 8 to 15, 18 to 54, and 26 to 32 hours, respectively.11 However, no published reports were found describing delayed recovery after any of these medications that mimic the prolonged recovery effects of NMBAs. In contrast, benzodiazepines sometimes induce paradoxic agitation with excessive muscle activity, rather than severe weakness and inactivity.29 In addition, relative rapid awakening from propofol is reported, although slightly longer when infusions exceed 12 hours.30 Because only two subjects received propofol during the first 4 hours and two other subjects received propofol during the 20- to 24-hour period after termination of NMBAs, with two of those four time frames reflecting some of the higher actigraphy counts, propofol does not explain the overall delay in recovery of muscle activity. Controlled studies comparing muscle recovery times for patients receiving NMBAs and sedation versus sedation alone are needed. Conclusion Delays in time to recover muscle activity and extreme muscle weakness may occur despite prompt recovery of NMT. With ongoing advances in mechanical ventilation and other technology, especially with an aging population and comorbidity, predictably there will be a continued need for temporary, chemically induced paralysis and heavy sedation. Continued use of PNS and careful NMBA titration according to patient TOF response are warranted to minimize the cumulative dose and facilitate prompt recovery whenever possible. Clinicians should consider patient factors such as age and severity of illness when administering NMBAs and adjust the dose according to patient TOF response and goals of therapy. Targeted assessment of renal function during NMBA administration is recommended to anticipate dose reduction. Preventing prolonged effects of neuromuscular blockade that complicate recovery allows the individual to channel restorative processes toward recuperation from his or her underlying illness or injury. This facilitates earlier resumption of normal activities and roles, contributing to quality of life for persons with critical illness and injury. Averting the cascade of events associated with prolonged immobility helps to reduce length of stay, decrease consumption of resources, and shrink the astronomic costs of care associated with prolonged immobility. Continued investigation of problems relative to recovery from neuromuscular blockade is indicated. Prospective, randomized, controlled trials are needed to evaluate benefits and muscle recovery for NMBAs and sedatives versus sedatives alone, because of the potentially confounding effects of sedatives and hypnotics on muscle activity in the current study. References 1 M. Murray, J. Cowen, H. DeBlock, B. Erstad, A. Gray and A. Tescher et al., Clinical guidelines for sustained neuromuscular blockade in the adult critically ill patient, Crit Care Med 30 (2002), pp. 142–156. Abstract-MEDLINE | Abstract-EMBASE | Full Text via CrossRef 2 I.A. MacFarlane and F.D. Rosenthal, Severe myopathy after status asthmaticus, Lancet 2 (1977), p. 615. Abstract 3 J.W. Hoyt, Persistent paralysis in the intensive care unit. A clinical conundrum, Crit Care Med 2 (1994), p. 1. 4 M. Rudis, E. Angus, E. Peterson, J. Popovich, R. Hyzy and B. Zarowitz, Vecuronium (V) dosing by peripheral nerve stimulation (PNS) reduces paralytic dosing requirements and recovery times in critically ill medical patients a prospective, randomized controlled evaluation, Crit Care Med 24 (1996) (1 Suppl), p. A71. 5 J. Douglass, M. Tuxen and C. Horne, Acute myopathy following treatment of severe life threatening asthma, Am Rev Respir Dis 141 (1990), p. A397. 6 J. Hanschen-Flaschen, J. Cowen and E. Raps, Neuromuscular blockade in the intensive care unit more than we bargained for, Am Rev Respir Dis 147 (1993), pp. 234–236. 7 N. Latronic, F. Fenzi and D. Recupero, Critical illness myopathy and neuropathy, Lancet 347 (1996), pp. 1579–1582. 8 W.C. Bowman, Physiology and pharmacology of neuromuscular blocking transmission, with special reference to the possible consequences of prolonged blockade, Intensive Care Med 19 (1993), pp. S45–S53. Abstract-MEDLINE | Abstract-EMBASE | Full Text via CrossRef 9 D.W. Zochdne, D. Ramsay and S. Shelley, Acute necrotizing myopathy of intensive care electrophysiological studies, Muscle Nerve 17 (1994), pp. 285–292. 10 C. Ghez, The control of movement. In: E.R. Kandel, J.H. Schwartz and T.M. Jessel, Editors, Principles of neural science (4th edition), McGraw-Hill, Health Professions Division, New York (2000), pp. 533–547. 11 B.K.J. Wagner and D.A. O’Hara, Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of critically ill patients, Clin Pharmacokinet 33 (1997), pp. 426–453. Abstract-MEDLINE | Abstract-EMBASE 12 D.G. Silverman and F.G. Standaert, Mechanisms of neuromuscular block. In: D.G. Standaert, Editor, Neuromuscular block in perioperative and intensive care, JB Lippincott, Philadelphia (1994), pp. 11–22. 13 J. Foster, S. Kish and C. Keenan, A national survey of critical care nurses’ practices related to administration of neuromuscular blocking agents, Am J Crit Care 10 (2001), pp. 139–145. Abstract-MEDLINE 14 T.J. Gan, R. Madan and R. Alexander, Duration of action of vecuronium after intubating dose of rapacuronium, vecuronium, or succinylcholine, Anesth Analg 92 (2001) (5), pp. 1199–1202. Abstract-EMBASE | Abstract-Elsevier BIOBASE | Abstract-MEDLINE | Full Text via CrossRef 15 J.E. Caldwell, J. Szenohradszky and V. Segredo, The pharmacodynamics and pharmacokinetics of the metabolite 3-desacetylvecuronium (ORG7268) and its parent compound vecuronium in human volunteers, J Pharmacol Exp Ther 270 (1994) (3), pp. 1216–1222. Abstract-MEDLINE | Abstract-EMBASE 16 M.L. Buck and M.D. Reed, Use of nondepolarizing agents in mechanically ventilated patients, Clin Pharmacol 10 (1991), pp. 32–48. Abstract-MEDLINE | Abstract-EMBASE 17 J.W. Leatherman, W.C. Fluegel, W.S. David, S.F. Davies and C. Iber, Muscle weakness in mechanically ventilated patients with severe asthma, Am J Respir Care Med 153 (1996), pp. 1686–1690. Abstract-MEDLINE | Abstract-EMBASE 18 T. Torda, The nature of gentamicin-induced neuromuscular block, Br J Anesth 52 (1980), pp. 325–328. 19 J. Viby-Mogensen, Interaction of other drugs with muscle relaxants, Semin Anesth 4 (1985), pp. 52–64. 20 V. Segredo, J.E. Caldwell, M.A. Matthay, M.L. Sharma and L.D. Gruenke, Pharmacokinetics of vecuronium after long-term administration (abstract), Anesth Analg 70 (1990), pp. S1–S450. 21 D.G. Silverman and R.K. Mirakhur, Effects of patient status and condition on nondepolarizing relaxants. In: D.G. Standaert, Editor, Neuromuscular block in perioperative and intensive care, JB Lippincott, Philadelphia (1994), pp. 11–22. 22 J.L. Gooch, M.P. Suchyta, J.M. Balbierz, J.H. Petajan and T.P. Clemmer, Prolonged paralysis after treatment with neuromuscular blocking agents, Crit Care Med 19 (1991) (9), pp. 1125–1131. Abstract-MEDLINE | Abstract-EMBASE 23 B.A. Kakulas and F.L. Mastaglia, Drug-induced, toxic and nutritional myopathies. In: F.L. Mastaglia and L.W. Detchant, Editors, Skeletal muscle pathology, Churchill Livingstone, Edinburgh (1992), pp. 511–540. 24 Medical Research Council, Aids to the examination of the peripheral nervous system, Her Majesty’s Stationary Office, London (1976). 25 W.W. Tryon, Activity measurement in psychology and medicine, Plenum Press, New York (1991). 26 S.M. Patterson, D.S. Krantz, L.C. Montgomery, P.A. Deuster, S.M. Hedges and L.E. Nebel, Automated physical activity monitoring validation and comparison with physiological and self-report measures, Psychopathology 30 (1993), pp. 296–305. Abstract-MEDLINE | Abstract-EMBASE 27 Statistical Package for the Social Sciences. SPSS base 10.0 applications guide, SPSS, Inc, Chicago (1999). 28 S. Bercker, S. Weber-Carstens and M. Deja et al., Critical illness polyneuropathy and myopathy in patients with acute respiratory distress syndrome, Crit Care Med 33 (2005) (4), pp. 711–715. Abstract-MEDLINE | Abstract-EMBASE 29 J. Jacobi, G.L. Fraser and D.B. Coursin et al., Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult, Crit Care Med 30 (2002), pp. 119–140. 30 S.D. Kowalski and C.A. Rayfield, A post hoc descriptive study of patients receiving propofol, Am J Crit Care 8 (1999), pp. 507–513. Abstract-MEDLINE

Did you read the entire thread? Please refrence my earlier posts where this is explained. Thanks, ACE844

If this wasn't an MCI-Disaster situation, than what would you call it? Please explain your above statement further, Thanks, ACE844

(American Heart Journal Volume 151 @ Issue 6 , June 2006, Pages 1255.e1-1255.e5 doi:10.1016/j.ahj.2006.03.014 Copyright © 2006 Elsevier Inc. All rights reserved. Clinical Investigation Feasibility and benefit of prehospital diagnosis, triage, and therapy by paramedics only in patients who are candidates for primary angioplasty for acute myocardial infarction Arnoud W.J. van 't Hof MD, PhD, a, b, , Saman Rasoul MDa, b, Henri van de Wetering Ma-ANPa, b, Nicolette Ernst MD, PhDa, b, Harry Suryapranata MD, PhDa, b, Jan C.A. Hoorntje MD, PhDa, b, Jan-Henk E. Dambrink MD, PhDa, b, Marcel Gosselink MD, PhDa, b, Felix Zijlstra MD, PhDa, b, Jan Paul Ottervanger MD, PhDa, b, Menko-Jan de Boer MD, PhDa, b and on behalf of the On-TIME study groupa aIsala Klinieken, Zwolle, The Netherlands bAmbulance dienst regio IJssel Vecht, The Netherlands Received 13 October 2005; accepted 20 March 2006. Available online 15 June 2006.) Background Despite data showing that time to treatment is very important in ST-elevation myocardial infarct patients, unacceptable long delays to reperfusion remain present in daily life practice. We sought to evaluate the feasibility and effect of improving logistics by early infarct diagnosis in the ambulance and immediate triage to a percutaneous coronary intervention (PCI) center performed by paramedics only without interference of a physician. Methods In the On-TIME study, 209 patients were included after prehospital infarct diagnosis and triage in the ambulance (ambulance group, n = 209). Infarct diagnosis was made by highly trained paramedics with the help of a computerized electrocardiographic algorithm. The accuracy of diagnosis, time to treatment, left ventricular function, and clinical outcome were compared with the patients who were diagnosed and triaged at a referral non-PCI center (referred group, n = 258). Left ventricular function was assessed before discharge using a nuclear technique. Results Acute myocardial infarction was accurately diagnosed in 95% of patients in the ambulance group, as compared with 99% in the referred group (P = .01). The percentage of patients in whom pharmacologic pretreatment (heparin, aspirin, tirofiban, or placebo) was initiated in the ambulance within 90 minutes after the onset of symptoms was 59% in the ambulance group versus 43% in the referred group (P < .01). A left ventricular ejection fraction of <40% was present in 25% in the ambulance group, as compared with 38% in the referred group (P = .013). After multivariate analysis, ambulance triage was independently associated with a left ventricular ejection fraction >40% and a favorable long-term clinical outcome. Conclusions Early, prehospital infarct diagnosis, triage, and therapy in the ambulance with direct transportation to the nearest PCI center, performed by trained paramedics only, is feasible in 95% of patients. Ambulance triage resulted in earlier diagnosis and initiation of therapy and was independently associated with a better left ventricular function and clinical outcome, as compared with triage and transportation from a referral non-PCI center. Article Outline Background Patients and methods Statistical analysis Results Univariate and multivariate analysis Discussion Prehospital care Mechanism of benefit Limitations Conclusion Appendix A. The On-TIME study group References Background Primary coronary angioplasty has been shown to be a very effective reperfusion modality in patients with acute myocardial infarction (MI),1 and 2 even when additional transport is necessary to a percutaneous coronary intervention (PCI) center.3 However, time to reperfusion is often considerably longer when the data from registries are reported instead of the data from randomized trials. In a large registry in the United States, only 5% of patients had a door-to-balloon time <60 minutes.4 Although door-to-balloon times decreased from 90 to 70 minutes in the most recent Euro Heart Survey analysis on acute coronary syndromes,5 many patients still have unacceptable long times to treatment. Some of the delay might be prevented by prehospital infarct diagnosis and triage, selecting patients who are candidates for primary angioplasty who can immediately be transported to a PCI center. However, it is unclear whether this can be reliably performed by paramedics without interference of a physician. This study evaluates the feasibility and benefit of prehospital infarct diagnosis and triage in the ambulance by paramedics only and compares outcome with triage at a referral non-PCI center. Patients and methods The design, inclusion and exclusion criteria, and main findings of the On-TIME study have been described previously.6 In this study, 209 patients were included after prehospital infarct diagnosis and triage in the ambulance (ambulance group, n = 209). The accuracy of diagnosis, time to treatment, the quality of reperfusion, left ventricular function, and clinical outcome was compared with the patients who were diagnosed and triaged at a referral non-PCI center (referred group, n = 258). The presence of an ambulance equipped with 12-lead electrocardiogram (ECG) diagnostic facilities determined whether a patient was transported to a non-PCI center first or immediately referred to the PCI center. Emergency transportation was performed after a telephone call, done either by the ambulance driver (ambulance group) or the referring physician (referred group), with the aim to prepare the arrival of the patient directly at the catheterization laboratory. Recruitment and randomization in the ambulance was initiated only after a period of training in prehospital infarct diagnosis and care for at least 6 months. All paramedics had at least 2 years of training at a (cardiac) intensive care unit and work strictly according to board certified protocols. Computer diagnosis in the ambulance was made based upon a fixed algorithm, which has been previously described.7 and 8 Before transportation, all patients received 500 mg of aspirin, 5000 IU of unfractionated heparin intravenously, and study medication (tirofiban or placebo). Post PCI, all patients were treated with Clopidogrel (300 mg loading dose followed by 75 mg daily for 1 month), aspirin, β-blockade, statin, and angiotensin-converting enzyme inhibition. Time from symptom onset to diagnosis was defined as the time from the onset of symptoms to the time of the diagnostic ECG, either made in the ambulance or at the non-PCI center. Total ischemic time was defined as the time from symptom onset to first balloon inflation. All angiographic and electrocardiographic parameters were analyzed by an independent core laboratory (Diagram BV, Zwolle, The Netherlands) and scored by observers who were unaware of randomization and outcome data. A correct infarct diagnosis was defined as prolonged chest pain with typical evolutionary electrocardiographic changes, coupled with an unstable coronary lesion on the angiogram and a rise in creatine kinase of >3 times the upper limit of normal. Prevented MI was defined as a correct infarct diagnosis without a rise in creatine kinase of >3 times the upper limit of normal. A false-positive infarct diagnosis was made in those patients who did not meet the criteria for a correct or prevented MI. Left ventricular ejection fraction (LVEF) was assessed in the patients recruited in the Zwolle area only and was measured with a radionuclide technique before discharge, as previously described.1 The data on LVEF were gathered by a specialist in nuclear medicine, who was blinded to the clinical data. Clinical outcome, being the incidence of death or recurrent MI, was assessed at 1-year follow-up. Statistical analysis Statistical analysis was performed with the SPSS 10.0 statistical package (SPSS, Chicago, IL). All noncontinuous angiographic variables were analyzed using the χ2 or Fisher exact test. Continuous variables were analyzed using analysis of variance or Mann-Whitney U test. The continuous variables time from symptom onset to diagnosis and total ischemic time were dichotomized, based upon the median value (94 minutes and 188 minutes, respectively). Key outcome parameters were the percentage of patients with a correct infarct diagnosis, LVEF before discharge, and the 1-year incidence of death or recurrent MI. Risk stratification was based upon the previously described TIMI risk criteria.9 To assess independent predictors of left ventricular function and clinical outcome, multivariate analysis was performed using stepwise logistic regression. All parameters that were significantly different between the groups (sex and distance to the PCI center) and all baseline characteristics associated with left ventricular function or clinical outcome with a P ≤ .10 were entered into the model. The cutoff value of 40% for determination of a poor left ventricular function was based upon a value less than the 25% percentile (38%). Results A correct infarct diagnosis was present in 95% of patients triaged by ambulance personnel, as compared with 99% triaged at a referral center (P = .01). The 14 patients with a false-positive infarct diagnosis either had severe aortic stenosis (n = 3), left ventricular hypertrophy with strain (n = 1), previous MI with persistent ST elevation (n = 2), atrial fibrillation with early repolarization (n= 2), pericarditis (n = 2), gastrointestinal disease (n = 2), or others (n = 2). Baseline characteristics of the ambulance and the referred group are described in Table I and were not significantly different, except for sex and distance to the PCI center (45 vs 24 km, P < .001). The percentage of patients who were diagnosed within 90 minutes or underwent balloon inflation within 3 hours after the onset of symptoms was significantly higher in patients after triage in the ambulance (Table I). Both initial perfusion of the infarct-related vessel and final myocardial perfusion as assessed by the myocardial blush grade was better in the patients triaged in the ambulance (Table I). Table I. Baseline, electrocardiographic and angiographic characteristics Referred (n = 258) Ambulance (n = 209) P Baseline Age (y ± SD) 62 ± 11 61 ± 11 .88 Male sex 77% 85% .03 Diabetes 9% 13% .17 Hypertension 29% 26% .37 Smoking⁎ 66% 64% .68 Anterior MI 46% 46% .90 Previous MI 10% 7% .24 Previous CABG 1.6% 2.4% .52 Previous PCI 4.3% 5.8% .46 Killip class >1† 16% 19% .39 TIMI risk score >3‡ 42% 46% .38 SO to diagnosis <90 min 43% 59% .001 Ischemic time <3 h 29% 52% .001 Electrocardiographic Cum ST elevation (mm) 10 ± 7 11 ± 8 0.24 Cum ST deviation (mm) 15 ± 9 15 ± 9 0.81 Angiographic Single-vessel disease 41% 49% .11 Pre PCI TIMI 2, 3 35% 44% .04 Post PCI TIMI 3 91% 91% .97 MBG 3 47% 59% .02 CABG, Coronary artery bypass grafting; Cuon, cumulative; MBG, myocardial blush grade as previously defined10; SO, symptom onset. ⁎ Current or previous smoking. † Defined as systolic blood pressure <100 mm Hg or heart rate >100 per minute. ‡ TIMI risk score as described by Morrow et al.8 Prevented MI was present in 15% in the ambulance group and in 10% in the referred group (P = .08). Left ventricular ejection fraction was measured before discharge in 318 (75%) of the 426 patients with a confirmed diagnosis of acute MI, recruited in the Zwolle area. The LVEF was 46% ± 10% in the ambulance group, as compared with 44% ± 11% in the referred group (P = .17). An LVEF <40% was present in 25% in the ambulance group, as compared with 38% in the referred group (P = .013). Univariate and multivariate analysis Left ventricular function. Univariate predictors of a poor left ventricular function were male sex, anterior infarct location, the presence of diabetes, an initial heart rate >100 beat/min, a TIMI risk score >2, and nonambulance triage. After multivariate analysis, only male sex, anterior infarct location, and nonambulance triage were independently associated with a poor left ventricular function (Table II). Table II. Predictors of Left Ventricular Function and Clinical Outcome Variables OR 95% CI P Left Ventricular Ejection Fraction < 40% Univariate Male gender 1.8 0.9-3.6 .08 Diabetes 2.1 1.0-4.4 .04 Anterior infarct location 6.3 3.7-10.8 <.01 Heart rate > 100/min 3.1 1.0-9.3 .03 TIMI risk score > 2 5.9 3.2-10.8 <.01 Distance < 41 km .8 0.5-1.4 .54 Ambulance triage .5 0.3-0.8 .01 Single vessel disease 1.0 0.7-1.8 .71 Multivariate Male gender 2.6 1.2-5.5 .02 Anterior infarct location 3.7 1.6-8.9 <.01 Ambulance triage 0.4 0.2-0.8 .01 Death or recurrent myocardial infarction at 1-y follow-up Univariate Age (per y) 1.05 1.0-1.1 .02 Male gender 1.8 0.6-5.2 .29 Hypertension 2.7 1.3-5.5 .01 Anterior infarct location 1.9 0.9-3.2 .08 Heart rate > 100/min 3.0 1.2-7.9 .03 TIMI risk score > 2 2.2 1.1-4.5 .03 Single vessel disease 0.4 0.2-0.9 .03 Distance < 41 km 0.7 0.3-1.4 .29 Ambulance triage 0.3 0.1-0.7 .01 Multivariate Ambulance triage 0.3 0.1-0.9 .03 Hypertension 2.5 1.1-5.5 .03 Single vessel disease 0.4 0.2-1.0 .05 Anterior infarct location 2.3 1.0-5.3 .05 Clinical outcome. At 30-day follow-up, 1.0% of patients with a correct diagnosis of acute MI had died in the ambulance group, as compared with 3.2% in the referred patients (P = .2). At 1-year follow-up, total mortality and the combined incidence of death or recurrent MI was significantly lower in the ambulance group (2.1% vs 6.0%, P = .04 and 3.6% vs 10.5%, P = .006, respectively). After multivariate analysis, ambulance triage remained an independent predictor of survival free from death or MI at 1-year follow-up (Table II). Discussion This study showed that correct infarct diagnosis, triage, and therapy can be performed by highly trained paramedics only, without interference of a physician, in 95% of patients. Furthermore, it shows that ambulance triage is an independent predictor of an LVEF >40% and a favorable clinical outcome, as compared with triage at a referral non-PCI center. The mechanism of the beneficial effect seems to be the combination of earlier diagnosis, earlier initiation of pharmacologic pretreatment, and a better initial and final myocardial perfusion. It showed that further streamlining of logistics, in which an unnecessary visit of a non-PCI center is prevented, saves time and is associated with a better left ventricular function and clinical outcome. Prehospital care The most recent version of the American College of Cardiology/American Heart Association guidelines for the treatment of patients with ST-elevation acute MI state that primary angioplasty is the preferred reperfusion strategy if it can be performed within 90 minutes after first patient contact.11 However, it was recently shown that only 5% of transferred patients in the United States have a door-to-balloon time <90 minutes.4 In addition, in Europe, every day door-to-balloon times are considerably longer than those reported in randomized controlled trials.12 This long delay prevents further development of primary angioplasty programs and is often stated as an excuse for treating the patients with thrombolysis or a combined pharmacoinvasive strategy, which, so far, has not been supported by evidence from randomized controlled trials. Many obstacles have been associated with the lack of development of a prehospital diagnosis and care program of patients with an acute MI. The fear of a false-positive infarct identification when diagnosis is made without interference of a physician is one of them. This study shows that the combination of trained paramedics, together with a validated computerized ECG algorithm, results in a correct diagnosis in 95% of cases. Mechanism of benefit It is unlikely that the reduced total ischemic time alone may sufficiently explain the beneficial effect on left ventricular function. The moment of time saving is important: saving 30 minutes in the very early phase of MI is expected to result in a larger benefit, as compared with saving 30 minutes later on, the so-called golden hour of reperfusion therapy.13 and 14 Most patients triaged in the ambulance were diagnosed within 90 minutes and treated within 180 minutes after the onset of symptoms. This very early diagnosis and therapy is probably related to the better myocardial blush grade after PCI in this group.15 In addition, a prehospital diagnosis gives the opportunity for early initiation of antithrombotic and antiplatelet pretreatment during transportation. Agents such as aspirin, heparin, and glycoprotein IIb/IIIa blockers have shown to improve initial patency of the infarct-related vessel.16 and 17 The very early initiation of these agents in the ambulance group might explain the higher initial patency rate in this group, resulting in a higher rate of prevented MI and might contribute to the better left ventricular function and clinical outcome of these patients. This study confirms previous findings from our group, which showed that extra transportation delay is associated with a worsening of the LVEF.18 The difference in outcome cannot be explained by a difference in medication after discharge, as shown in Table III. Table III. Medication at 30-day follow-up Referred (n = 239) (%) Ambulance (n = 202) (%) P Aspirin 93 89 .17 Oral anticoagulation 10 10 .90 β-Blocker 89 84 .13 Calcium antagonist 6 4 .24 Nitrates 17 15 .51 ACE inhibitor 53 57 .43 Statin 88 85 .33 Clopidogrel⁎ 81 76 .19 ACE, angiotensin-converting enzyme. ⁎ Use at discharge. Limitations This study is a post hoc analysis of patients recruited in the On-TIME trial and not a randomized comparison between prehospital triage in the ambulance versus triage at the referral center; however, randomization would be unethical because this would deliberately prolong time to treatment in 1 arm. The presence of an ambulance equipped with 12-lead ECG diagnostic facilities determined whether a patient was transported to a non-PCI center first or immediately referred to the PCI center. Inclusion and exclusion criteria were the same for both study groups. However, multivariate analysis might correct differences in baseline characteristics between the groups, but this statistical correction might not overcome the problem of undetectable confounders and is less reliable in a relatively small-sized trial with a low incidence of the outcome parameter of interest. Left ventricular ejection fraction was routinely performed at discharge in the patients recruited in the Zwolle area only (prespecified LVEF substudy). Patient characteristics of these Zwolle patients, however, did not differ significantly from the patients recruited at other PCI centers. Conclusion Prehospital infarct diagnosis, triage, and therapy in the ambulance is feasible without physician interference when performed by highly trained paramedics using a validated computerized ECG software in 95% of patients. In addition, ambulance triage was an independent predictor of a left ventricular function >40% and was independently associated with a favorable clinical outcome. Therefore, all efforts should be made to implement prehospital infarct diagnosis, triage, and therapy in the care of patients with an acute MI and to further improve cooperation with ambulance personnel in this regard. References 1 F. Zijlstra, M.J. de Boer and J.C.A. Hoorntje et al., A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction, N Engl J Med 328 (1993), pp. 680–684. Abstract-MEDLINE | Abstract-EMBASE | Full Text via CrossRef 2 E.C. Keeley, J.A. Boura and C.L. Grines, Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials, Lancet 361 (2003), pp. 13–20. SummaryPlus | Full Text + Links | PDF (409 K) | Full Text via CrossRef 3 M. Dalby, A. Bouzamondo and P. Lechat et al., Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis, Circulation 108 (2003), pp. 1809–1814. Abstract-MEDLINE | Abstract-Elsevier BIOBASE | Full Text via CrossRef 4 B.K. Nallamothu, E.R. Bates and J. Herrin et al., NRMI Investigators. Times to treatment in transfer patients undergoing primary percutaneous coronary intervention in the United States: National Registry of Myocardial Infarction (NRMI)–3/4 analysis, Circulation 111 (2005), pp. 761–767. Abstract-MEDLINE | Abstract-EMBASE | Abstract-Elsevier BIOBASE | Full Text via CrossRef 5 S. Behar, Main findings of the EHS-ACS II. Results of the Euro Heart Survey in Acute Coronary Syndromes 2 Presented at the meeting of the European Society of Cardiology, Stockholm (2005). 6 A.W.J. van 't Hof, N. Ernst and M.J. de Boer et al., On-TIME study group. Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial, Eur Heart J 25 (2004), pp. 837–846. Abstract-EMBASE | Abstract-MEDLINE 7 E.W. Grijseels, M.J. Bouten and T. Lenderink et al., Pre-hospital thrombolytic therapy with either alteplase or streptokinase. Practical applications, complications and long-term results in 529 patients, Eur Heart J 16 (1995), pp. 1833–1838. Abstract-EMBASE | Abstract-MEDLINE 8 M.N.S.K.J. Ernst, M.J. de Boer and A.W.J. van 't Hof et al., Prehospital triage for angiography-guided therapy for acute myocardial infarction, Neth Heart J 12 (2004), pp. 51–56. 9 D.A. Morrow, E.M. Antman and A. Charlesworth et al., TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: an intravenous nPA for treatment of infarcting myocardium early II trial substudy, Circulation 102 (2000), pp. 2031–2037. Abstract-MEDLINE | Abstract-EMBASE | Abstract-Elsevier BIOBASE 10 A.W.J. Van 't Hof, A. Liem, H. Suryapranata and on behalf of the Zwolle myocardial infarction study group, Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade, Circulation 97 (1998), pp. 2302–2306. Abstract-Elsevier BIOBASE | Abstract-MEDLINE 11 E.M. Antman, D.T. Anbe and P.W. Armstrong et al., ACC/AHA Guidelines for the management of patients with ST-elevation myocardial infarction—executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction), J Am Coll Cardiol 44 (2004), pp. 671–719. SummaryPlus | Full Text + Links | PDF (1089 K) 12 D. Hasdai, S. Behar and L. Wallentin et al., A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS), Eur Heart J 23 (2002), pp. 1190–1201. Abstract-EMBASE | Abstract-MEDLINE 13 Fibrinolytic Therapy Trialists (FTT) collaborative group, Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients, Lancet 343 (1994), pp. 311–322. 14 G. De Luca, H. Suryapranata and J.P. Ottervanger et al., Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts, Circulation 109 (2004), pp. 1223–1225. Abstract-Elsevier BIOBASE | Abstract-EMBASE | Abstract-MEDLINE | Full Text via CrossRef 15 G. De Luca, A.W.J. van 't Hof and M.J. de Boer et al., Time-to-treatment significantly affects the extent of ST-segment resolution and myocardial blush in patients with acute myocardial infarction treated by primary angioplasty, Eur Heart J 25 (2004), pp. 1009–1013. Abstract-EMBASE | Abstract-MEDLINE 16 F. Zijlstra, N. Ernst and M.J. de Boer et al., Influence of prehospital administration of aspirin and heparin on initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction, J Am Coll Cardiol 39 (2002), pp. 1733–1737. SummaryPlus | Full Text + Links | PDF (81 K) 17 G. Montalescot, M. Borentain and L. Payot et al., Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis, JAMA 292 (2004), pp. 362–366. Abstract-Elsevier BIOBASE | Abstract-EMBASE | Abstract-MEDLINE | Full Text via CrossRef 18 A.L. Liem, A.W.J. van 't Hof and J.C.A. Hoorntje et al., Influence of treatment delay on infarct size and clinical outcome in patients with acute myocardial infarction treated with primary angioplasty, J Am Coll Cardiol 32 (1998), pp. 629–633. SummaryPlus | Full Text + Links | PDF (64 K) Appendix A. The On-TIME study group Steering committee MJ de Boer, E Boersma, AJ van Boven, R Buirma (Nonvoting member), J Dille, AWJ van 't Hof, and RJ de Winter. Ambulance coordinators F Hollak (Ambulance Dienst Regio IJssel Vecht), F de Pooter (Ambulance Dienst Regio Noord West Veluwe). Referral center coordinators T Bouwmeester (Winschoten), R Brons (Meppel), R Dijkgraaf (Harderwijk), W Jap (Apeldoorn), MJ de Leeuw (Assen), A Mosterd (Amersfoort), C Oei (Heerenveen), and J Saelman (Hoogeveen). PCI center coordinators The Netherlands: JM ten Berg (Nieuwegein), AJ van Boven (Groningen), JHE Dambrink (Zwolle), and RJ de Winter (Amsterdam). Italy: S Petronio (Pisa).

For all of you people choosing stethscopes, here's an interesting study for you. HTH, ACE844 (American Heart Journal Volume 152 @ Issue 1 , July 2006, Pages 85.e1-85.e7 doi:10.1016/j.ahj.2006.04.013 Copyright © 2006 Mosby, Inc. All rights reserved. Clinical Investigation Effect of teaching and type of stethoscope on cardiac auscultatory performance Kasper Iversen MDa, , , Ane Søgaard Teisner MDb, Morten Dalsgaard MDa, Rasmus Greibe MDb, Hans Bording Timm MDb, Lene Theil Skovgaard MScic, Asbjørn Hróbjartsson MD, MPhil, PhDd, Ø. Copenhagen, S. Copenhagen and K. Copenhagen aClinic of Cardiology, Rigshospitalet, Copenhagen Ø, Denmark bClinic of Cardiology, Amager Hospital, Copenhagen S, Denmark cDepartment of Biostatistics, University of Copenhagen, Copenhagen K, Denmark dThe Nordic Cochrane Center, Rigshospitalet, Copenhagen Ø, Denmark Received 5 December 2005; accepted 13 April 2006. Available online 13 July 2006) Background Auscultation of the heart is a routine procedure. It is not known whether auscultatory skills can be improved by teaching or with the use of an advanced stethoscope. Methods This study was a randomized trial with a 2 × 2 factorial design. Seventy-two house officers were randomized to a simple or an advanced stethoscope and to a 4-hour course in auscultation or no course. The doctors auscultated 20 patients' hearts and categorized findings as normal or as one or more of 5 categories of heart diseases. Patients were selected such that 16 had a known heart disease as well as a corresponding murmur and 4 had no heart disease or murmur. Auscultatory performance was assessed as concordance with echocardiographic findings and interobserver variation. Results Doctors using the advanced stethoscope diagnosed 35% of the patients correctly, as compared with doctors using the simple stethoscope who did 33% of the patients (P = .27). Similarly, 34% of the patients were diagnosed correctly by doctors who had received teaching as compared with 33% of those who were by doctors who had received no teaching (P = .41). The κ values were higher for doctors who had received teaching for aortic stenosis (0.43 vs 0.28, P = .004) and ventricular septum defect (0.07 vs 0.01, P = .003). There was no difference between groups for any other single murmur or for the detection of murmurs as such. Conclusion Heart auscultation findings were in poor accordance with echocardiographic findings and had high interobserver variation. Neither outcome improved to any important extent with the subjects' use of an advanced stethoscope or attending of a course in heart auscultation. Article Outline Methods Observers Randomization Patients Teaching Stethoscopes Study examinations Data analyses Results Effect of teaching Accuracy Agreement Effect of type of stethoscope Accuracy Agreement General auscultatory performance Secondary analysis Discussion Main results κ Values Teaching Stethoscopes Previous studies Limitations Clinical implications Conclusion Acknowledgements References Stethoscopic examination of the heart is a routine procedure. Auscultatory findings hold important prognostic information1, 2 and 3 and often guide clinicians in recommending further treatment and examinations. The reliability of heart auscultation is reflected partly in the ability to detect or exclude underlying heart disease (accuracy) and partly in the level of agreement between observers (precision). Studies on how to improve auscultatory skills are sparse and have focused on the effect of type of stethoscope and teaching. The studies were small and with important methodological problems, however. No randomized clinical trial that investigates whether auscultatory performance is improved by training has been published. The only randomized trial published investigating the effect of type of stethoscope compared an electronic stethoscope with a conventional stethoscope and could not show a clear benefit of using an advanced stethoscope.4 Our primary aim was to investigate the effects of training and type of stethoscope used on both the accuracy and precision of heart auscultation. Secondarily, we wanted to examine auscultatory performance in general. Methods We conducted a randomized trial with a 2 × 2 factorial design. Seventy-two observers were randomized to use 1 of 2 types of stethoscopes and to either teaching or no teaching. All observers performed heart auscultation on the same 20 patients. Observers All house officers from 10 hospitals in Copenhagen County were sent a letter with an invitation to participate. The first 72 doctors who responded were included in the study. All the participating doctors declared that they had no knowledge of any of the patients and any known hearing disability. All observers consented in using the study stethoscope in their clinical work for 4 weeks before the day the study patients were to be examined. The observers were not informed whether they should receive teaching or not until the day the examinations were performed. House officers in Denmark have between 0 and 18 months of postgraduate clinical experience and do not receive any formalized training or teaching in auscultation during this period. Randomization Observers were irreversibly included in the study before randomization. Randomization was conducted in one public session with 3 of the authors present. It was based on a list of computer-generated random numbers. No reallocation or exclusion of observers took place after randomization. Seventy-two observers were allocated to 4 equal-sized groups. Group 1 received a 3M Littmann (Cerritos, CA) Classic II SE stethoscope and did not receive teaching. Group 2 received a 3M Littmann Master Cardiology stethoscope and did not receive teaching. Group 3 received a 3M Littmann Classic II SE stethoscope and received teaching. Group 4 received a 3M Littmann Master Cardiology stethoscope and received teaching. Patients Potentially eligible outpatients were identified from conveniently sampled patient files by 2 investigators (MD and KI). Sixteen patients with charts describing murmurs and significant valve disease or septal defect and 4 with charts describing no murmur and no valve disease or septum defect were recruited. The patients were examined with auscultation and echocardiography within 48 hours before the study by one investigator (KI). The classification of the echocardiographic findings was based on the discretion of the examiner. We included patients with murmurs only if they had a moderate or severe valve defect or a significant septum defect and a murmur concordant with the echocardiographic examination. Similarly, we included patients without murmurs only if they had normal heart valves without color jets showing regurgitation or turbulent flow (minor tricuspidal regurgitation was accepted) and had no audible murmur. Oral informed consent was given by all included patients. All 20 screened patients were included in the study. The local ethical committee approved the study. Teaching The observers randomized to training were taught for 4 hours by a specialist in cardiology (Frank Steensgaard-Hansen) with extensive experience in teaching auscultation. The course consisted of a theoretical introduction to auscultation as well as auscultatory techniques and a description of auscultatory findings, followed by 3 hours of providing examples and training in recognition of digitally recorded murmurs. Stethoscopes We provided the observers with a simple or an advanced membrane-based stethoscope. We chose the 3M Littmann Classic II SE stethoscope, which is one of the cheapest Littmann stethoscopes, as the simple stethoscope. We chose the 3M Littmann Master Cardiology stethoscope, which is an expensive acoustic stethoscope, as the advanced stethoscope. Study examinations All examinations were conducted on the same day. Auscultation was performed while patients were sitting in their beds. Doctors were instructed to restrict each examination to not longer than 2 minutes per patient. The patients were asked not to reveal any clinical information to the examiners. At the end of each examination, the doctors filled up a multiple-choice questionnaire with 5 categories of heart diseases (aortic regurgitation, aortic stenosis, mitral regurgitation, ventricular septal defect, and atrial septal defect) or no heart disease. Observers could place more than one cross in the multiple-choice questionnaire and were told that the patients had one or more of the cited heart diseases or no heart disease. Data analyses Data were manually transferred from the questionnaires to a data sheet and thereafter checked for typing errors. For each single observer, we calculated sensitivity, specificity, and agreement with the echocardiographic findings. Subsequently, these values were compared between the groups of observers, according to either teaching or type of stethoscope (using unpaired t tests), or both (using general linear models). The κ values were calculated for all pairs of doctors within each group (defined either by teaching or by type of stethoscope, or a combination). Because of the interdependence between these values (several κ values for each single observer), P values from traditional tests (test with an assumption of independence between observations) could not be trusted and we therefore used a randomization test to compare groups.5 Primarily planned analysis was the difference between the randomized groups with respect to (1) sensitivity and specificity of the auscultation as well as the number of findings that concurred with the echocardiographic findings and (2) κ values. For secondary analysis, we studied the difference in the total number of positive auscultatory findings and the interaction between type of stethoscope and teaching. Results All 20 patients who were included finished the study. There were 13 men (65%), and the patients' median age was 69 years (range 30-88 years). Seven patients had aortic stenosis, 5 patients had mitral regurgitation, 1 patient had atrial septal defect, 1 patient had aortic regurgitation, 2 patients had aortic stenosis, and 4 patients had no valve disease or septal defect. All the participating doctors auscultated all the patients' hearts (1440 examinations). Effect of teaching Accuracy Although sensitivity was higher among doctors who received teaching for all murmurs, there was no statistically significant difference in any single sensitivity or specificity of auscultation between doctors who received teaching and those who did not (Table I). Similarly, there was no statistically significant difference between the average number of patients who were diagnosed correctly by physicians who had not received teaching (33% of patients) and that of patients who were by physicians who received teaching (34% of patients) (P = .41). Table I. Effect of teaching on accuracy of heart auscultation (sensitivity and specificity) No teaching [mean (95% CI)] Teaching [mean (95% CI)] Difference [mean (95% CI of the difference)] Aortic regurgitation Sensitivity 0.28 (0.21 to 0.34) 0.32 (0.24 to 0.39) 0.04 (−0.06 to 0.14) Specificity 0.93 (0.90 to 0.95) 0.93 (0.91 to 0.95) 0.00 (−0.03 to 0.04) Aortic stenosis Sensitivity 0.42 (0.36 to 0.47) 0.47 (0.43 to 0.51) 0.05 (−0.02 to 0.12) Specificity 0.88 (0.84 to 0.92) 0.92 (0.89 to 0.96) 0.04 (−0.01 to 0.10) Atrial septum defect Sensitivity 0.11 (0.00 to 0.22) 0.17 (0.04 to 0.29) 0.06 (−0.11 to 0.22) Specificity 0.91 (0.89 to 0.94) 0.90 (0.89 to 0.92) −0.01 (−0.04 to 0.02) Mitral regurgitation Sensitivity 0.19 (0.14 to 0.25) 0.20 (0.16 to 0.24) 0.01 (−0.06 to 0.07) Specificity 0.86 (0.82 to 0.92) 0.83 (0.80 to 0.86) −0.03 (−0.08 to 0.02) Ventricular septum defect Sensitivity NA NA NA Specificity 0.92 (0.90 to 0.94) 0.92 (0.90 to 0.93) 0.00 (−0.04 to 0.02) Any murmur Sensitivity 0.71 (0.67 to 0.75) 0.74 (0.71 to 0.77) 0.03 (−0.02 to 0.08) Specificity 0.67 (0.58 to 0.76) 0.56 (0.46 to 0.66) −0.11 (−0.25 to 0.03) NA, Not applicable. Agreement For 2 of the 5 categories of heart diseases, the observers who received teaching agreed more than did those who received no teaching. The mean κ value for aortic stenosis was 0.43 versus 0.28; for ventricular septum defect, it was 0.07 versus 0.01 (Table II). There was no statistically significant difference between the mean κ values for the observers who had been taught and those who had not been taught with respect to the other 3 single murmurs (Table II)—neither was there any statistically significant difference between those with respect to the detection of any murmur—with the mean κ value being 0.14 versus 0.18. Regardless of the statistically significant effect of training on 2 examinations, the size of the effect was small and did not result in observers reaching mean κ values >0.5. Table II. Effect of teaching on interobserver variation in heart auscultation (mean κ values) Murmur No teaching [mean (95% CI)] Teaching [mean (95% CI)] P Aortic regurgitation 0.23 (0.21-0.26) 0.25 (0.23-0.26) .85 Aortic stenosis 0.28 (0.26-0.30) 0.43 (0.41-0.45) .004 Atrial septum defect 0.09 (0.07-0.11) 0.10 (0.08-0.11) .88 Mitral regurgitation 0.12 (0.10-0.14) 0.10 (0.08-0.12) .73 Ventricular septum defect 0.01 (0.00-0.03) 0.07 (0.05-0.09) .003 Any murmur 0.38 (0.37-0.40) 0.39 (0.37-0.40) .95 Pooled 0.15 (0.14-0.16) 0.19 (0.18-0.20) .14 Effect of type of stethoscope Accuracy There was no statistically significant difference between the doctors using either type of stethoscope with respect to either the sensitivity or the specificity of heart auscultation (Table III). There was no statistically significant difference between the average number of patients who were diagnosed correctly by doctors using the simple stethoscope (33% of patients) and that of patients who were by doctors using the advanced stethoscope (35% of patients) (P = .27). Table III. Effect of type of stethoscope on accuracy of heart auscultation (sensitivity and specificity) Littmann Classic [mean (95% CI)] Master Cardiology [mean (95% CI)] Difference [mean (95% CI of the difference)] Aortic regurgitation Sensitivity 0.29 (0.22 to 0.36) 0.31 (0.23 to 0.38) 0.02 (−0.09 to 0.12) Specificity 0.93 (0.91 to 0.95) 0.93 (0.90 to 0.96) 0.00 (−0.04 to 0.03) Aortic stenosis Sensitivity 0.45 (0.40 to 0.49) 0.44 (0.39 to 0.49) −0.01 (−0.08 to 0.06) Specificity 0.90 (0.85 to 0.94) 0.91 (0.88 to 0.94) 0.01 (−0.04 to 0.07) Atrial septum defect Sensitivity 0.17 (0.04 to 0.29) 0.11 (0.01 to 0.22) −0.06 (−0.22 to 0.11) Specificity 0.92 (0.90 to 0.93) 0.90 (0.88 to 0.92) −0.02 (−0.05 to 0.01) Mitral regurgitation Sensitivity 0.21 (0.06 to 0.26) 0.19 (0.14 to 0.23) −0.02 (−0.09 to 0.05) Specificity 0.82 (0.79 to 0.86) 0.87 (0.84 to 0.90) 0.05 (0.00 to 0.10) Ventricular septum defect Sensitivity NA NA NA Specificity 0.91 (0.89 to 0.93) 0.93 (0.91 to 0.94) 0.02 (−0.02 to 0.04) Any murmur Sensitivity 0.73 (0.70 to 0.77) 0.72 (0.68 to 0.76) −0.01 (−0.07 to 0.04) Specificity 0.60 (0.50 to 0.71) 0.63 (0.54 to 0.72) 0.03 (−0.11 to 0.17) Agreement There was no statistically significant difference in the level of agreement between doctors using the simple stethoscope and those using the advanced stethoscope. This was the case both for the 5 single heart diseases and for the detection of any heart disease (Table IV). Table IV. Effect of type of stethoscope on interobserver variation in heart auscultation (κ values) Murmur Littmann Classic [mean (95% CI)] Master Cardiology [mean (95% CI)] P Aortic regurgitation 0.23 (0.20-0.25) 0.24 (0.21-0.26) .88 Aortic stenosis 0.33 (0.31-0.34) 0.38 (0.36-0.40) .35 Atrial septum defect 0.09 (0.06-0.11) 0.07 (0.05-0.09) .76 Mitral regurgitation 0.11 (0.09-0.13) 0.11 (0.09-0.13) .96 Ventricular septum defect 0.02 (0.01-0.04) 0.01 (0.00-0.02) .90 Any murmur 0.39 (0.37-0.41) 0.38 (0.36-0.40) .88 Mean 0.15 (0.14-0.16) 0.16 (0.14-0.18) .68 General auscultatory performance The sensitivity of heart auscultation ranged from 0.11 to 0.47, lowest for atrial septal defect and highest for aortic stenosis. The specificity ranged from 0.82 to 0.93, lowest for mitral regurgitation and highest for aortic regurgitation. The sensitivity ranged from 0.71 to 0.74 and the specificity ranged from 0.56 to 0.67 for detection of any murmur. Mean κ values ranged from 0.01 to 0.43, lowest for recognition of ventricular septal defect and highest for recognition of aortic stenosis. Secondary analysis We found no interaction between type of stethoscope and teaching (data not shown). There was no statistically significant difference between the compared groups with respect to the number of murmurs detected (Table V). Table V. Effect of teaching and type of stethoscope on number of positive auscultatory findings in heart auscultation (mean and 95% CI) Positive auscultatory findings No teaching 12.67 (11.80 to 13.54) Teaching 13.61 (12.82 to 14.40) Difference 0.94 (−0.21 to 2.10) Littmann Classic 13.33 (12.44 to 14.16) Master Cardiology 12.97 (12.15 to 13.80) Difference −0.36 (−1.50 to 0.84) Discussion Main results We did not find that the performance of heart auscultation was importantly improved by the type of stethoscope or by teaching of doctors. A small effect of teaching was however seen on the mean κ values in 2 of 5 examinations and on a nonsignificant trend for the specificity of auscultation. On average, only one third of the patients were diagnosed correctly; in addition, in general, the sensitivity of diagnosing the different heart diseases was low. The sensitivity in detecting any murmur was between 0.71 and 0.74, implying that more than 1 of 4 patients with significant valve disease were considered to have a normal stethoscopic examination—a finding we find rather troubling. κ Values The κ value summarizes agreement beyond chance for binary variables, with 0 corresponding to no agreement beyond chance and 1 corresponding to perfect agreement. κ Values are dependent on the prevalence of the disease; therefore, comparison of κ values between studies with different objectives and different study populations is difficult. Here, we mainly used κ values for internal comparisons to compare agreement for different stethoscopes and levels of clinical experience. According to Landis and Koch,6 κ values <0 indicate poor agreement; between 0.00 and 0.20, slight agreement; between 0.21 and 0.40, fair agreement; between 0.41 and 0.60, moderate agreement; between 0.61 and 0.80, substantial agreement; and between 0.81 and 1.00, excellent or almost perfect agreement. Agreement in our study was between slight and moderate. Aortic stenosis is traditionally the easiest murmur to detect7 and was in our study also the single murmur with the highest agreement rates. Surprisingly, aortic regurgitation, which is a weak diastolic murmur, had higher agreement rates than did mitral regurgitation, which is a murmur that is detected easily.7 The agreement rates for the detection of whether there is a murmur or not were fair for all groups of doctors and independent of type of stethoscope used and of teaching. Teaching The auscultation course lasted only 4 hours and was based on theory and training with recorded heart sound. We chose a relatively short course with only one teaching session partly owing to the practical difficulties in reassembling the same group of doctors twice and partly to ensure that none of the observers knew whether they were allocated to teaching or no teaching before the day of the examinations, which potentially could influence any preparation for the study. It is however possible that a longer auscultation course with more sessions and practical training with real patients would make the weak effect of teaching stronger. Studies on other clinical skills have shown an effect of training on interobserver variation.8 Stethoscopes We compared 2 stethoscopes from the same firm. 3M Littmann Classic II SE is the cheapest Littmann stethoscope recommended for doctors, whereas 3M Littmann Master Cardiology is the most expensive acoustic Littmann stethoscope. The manufacturer claims that 3M Littmann Master Cardiology offers the ultimate performance (http://www.3m.com/us/healthcare/professionals/littmann/jhtml/products.jhtml). We found no difference between doctors using the simple stethoscope and those using the advanced stethoscope in concordance with echocardiographic findings, interobserver variation, or number of murmurs heard. Although we only compared 2 types of stethoscopes, we think that our results suggest that an expensive and advanced stethoscope does not necessarily improve auscultatory performance, at least not in the hands and ears of house officers. Previous studies The effect of type of stethoscope used has been evaluated using comparison of acoustic performance9, 10 and 11 or clinicians' self-reported preferences.12 and 13 The effect of type of stethoscope on precision has been examined in one study with only 12 observers.4 The study compared an acoustic stethoscope with an electronic stethoscope and could not show a significant difference in κ values between the 2 stethoscopes. The effect of teaching and training has been evaluated in only one clinical study, which suggested a beneficial effect of training and teaching on auscultatory accuracy.14 The study was however nonrandomized and included only 10 observers examining the same patients before and after teaching. Other studies used recordings of cardiac murmurs, which do not necessarily correlate well with bedside skills, and showed only minimal or no effect of training on auscultatory performance.15, 16, 17 and 18 Observational studies on the accuracy of heart auscultation are sparse. They indicate that, in general, the sensitivity of cardiologists in detecting relevant valve disease is reasonable; however, several studies found low to moderate sensitivities of heart auscultation.19, 20, 21, 22, 23 and 24 The few published studies on the interobserver variation of the auscultation of the heart reported surprisingly low agreement rates, expressed as chance-corrected agreement rates, or κ values, <0.5.25, 26, 27 and 28 Disregarding the randomization, our study by far included the largest number of observers in an observational study describing the accuracy and precision of auscultation in a clinical setting.14, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36 and 37 Limitations The setting in our study differed somewhat from a normal clinical situation. The patients were selected to ensure a reasonably high proportion of positive findings. As in most agreement studies, the observers had no knowledge of the patients' history or of other clinical signs apart from their auscultatory findings. The doctors could not discuss the findings with colleagues. However, knowledge of the patients' history has previously been shown not to influence observer variation of auscultation of the lungs.38 We have included a relatively high number of observers, compared with the number of patients, in our study. This was done because the study objective was related to the performance of observers and not to effect on patients. A high number of observers therefore gave the study the largest power. The relatively low number of patients participating in the study could of course be a problem regarding the representation of the murmurs. We did however choose patients with common murmurs and typical auscultatory presentation to minimize this problem. The echocardiographic examinations were performed and judged by a single observer. The risk of misclassification was small, however, because all the patients already had a known heart disease and our echocardiographic examination confirmed previous findings. The comparisons between type of stethoscope and teaching are based on groups with only house officers. This was done to ensure a homogenous group of observers. This could make it difficult to extrapolate the results to doctors with other levels of experience. It seems however most logical to measure the effect of teaching among the most inexperienced doctors for whom it seems reasonable to assume that the reliability of their cardiac auscultation would give room for most improvement and not among doctors who have already received years of training and education. It would however be of interest to see if a study with more experienced observers would find similar results regarding the effect of teaching and type of stethoscope used on auscultatory skills. Minor echocardiographic valve defects might not be possible to hear during auscultation. This could reduce the number of patients who obtained the correct auscultatory diagnosis. However, all the valve diseases were judged as moderate or severe and physicians who examined patients before the study heard a murmur that was concordant with the echocardiographic finding. It is possible that a study with a higher number of observers would be able to find a significant difference regarding auscultatory skills between groups of observers. However, even if the results of such a study would be consistent with our results, we think that such a difference would be of limited clinical interest. Clinical implications Our study shows that stethoscopic examinations performed by house officers have low sensitivity and specificity as well as high interobserver variation. We found no beneficial effect of using an advanced and expensive stethoscope, suggesting that it may be rational to use a simple and cheaper one. Neither did we find a clear tendency for the beneficial effect of teaching, although there might have been a tendency for a minor effect on agreement and sensitivity. We find that it would be interesting to examine the effect of more extensive teaching and training. In the clinical situation, stethoscopic findings are integrated with information from clinical history, physical examination, x-ray pictures, and blood tests. Furthermore, house officers will typically consult more experienced physicians when in doubt. A future study on stethoscopic performance could take these factors into account. In the meantime, stethoscopic findings should be interpreted cautiously. Conclusion We found that the sensitivity of stethoscopic examinations in detecting and excluding echocardiographically defined heart valve diseases was only moderate and that observers disagreed considerably. This is troubling because auscultating of the heart is a routine procedure that often guides clinicians in further planning for patients. Neither training nor type of stethoscope improved sensitivity, specificity, or agreement importantly. KI and AH initiated and coordinated the formulation of the primary study hypothesis and designed the protocol. KI, RG, HT, MD, LT, and AT participated in data collection. KI, AH, and LS analyzed the data and wrote the first draft of the paper. All authors interpreted the data and revised the first draft for important intellectual content. All authors approved the final version. KI is the guarantor of the article. 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Mayer et al., Echocardiography in the evaluation of systolic murmurs of unknown cause, Am J Med 108 (2000), pp. 614–620. SummaryPlus | Full Text + Links | PDF (94 K) 20 J.T. Barron, D.L. Manrose and P.R. Liebson et al., Comparison of auscultation with two-dimensional and Doppler echocardiography in patients with suspected mitral valve prolapse, Clin Cardiol 11(1988), p. A30. Abstract-MEDLINE 21 A. Bloch, J. Crittin and A. Jaussi, Should functional cardiac murmurs be diagnosed by auscultation or by Doppler echocardiography?, Clin Cardiol 24 (2001), pp. 767–769. Abstract-EMBASE | Abstract-MEDLINE 22 S. Reichlin, T. Dieterle and C. Camli et al., Initial clinical evaluation of cardiac systolic murmurs in the ED by noncardiologists, Am J Emerg Med 22 (2004), pp. 71–75. SummaryPlus | Full Text + Links | PDF (123 K) 23 C.A. Roldan, B.K. Shively and M.H. Crawford, Value of the cardiovascular physical examination for detecting valvular heart disease in asymptomatic subjects, Am J Cardiol 77 (1996), pp. 1327–1331. SummaryPlus | Full Text + Links | PDF (568 K) 24 E.A. Shry, M.A. Smithers and A.M. Mascette, Auscultation versus echocardiography in a healthy population with precordial murmur, Am J Cardiol 87 (2001), pp. 1428–1430. SummaryPlus | Full Text + Links | PDF (77 K) 25 N. Gadsbøll, P.F. Høilund-Carlsen and G.G. Nielsen et al., Symptoms and signs of heart failure in patients with myocardial infarction: reproducibility and relationship to chest X-ray, radionuclide ventriculography and right heart catheterization, Eur Heart J 10 (1989), pp. 1017–1028. Abstract-EMBASE 26 A.A. Ishmail, S. Wing and J. Ferguson et al., Interobserver agreement by auscultation in the presence of a third heart sound in patients with congestive heart failure, Chest 91 (1987), pp. 870–873. Abstract-MEDLINE 27 C.E. Lok, C.D. Morgan and N. Ranganathan, The accuracy and interobserver agreement in detecting the ‘gallop sounds’ by cardiac auscultation, Chest 114 (1998), pp. 1283–1288. Abstract-MEDLINE | Abstract-EMBASE 28 E.B. Raftery and W.W. Holland, Examination of the heart: an investigation into variation, Am J Epidemiol 85 (1967), pp. 438–444. Abstract-MEDLINE 29 M.V. Cohen and H. Spindola-Franco, Correlation between left ventriculography, auscultation, and M-mode and two-dimensional echocardiography in mitral valve prolapse, Herz 13 (1988), pp. 293–308. Abstract-EMBASE | Abstract-MEDLINE 30 R.J. Dobrow, J.B. Calatayud and S. Abraham et al., A study of physician variation in heart-sound interpretation, Med Ann Dist Columbia 33 (1964), pp. 305–308. Abstract-MEDLINE 31 G. Forssell, R. Jonasson and E. Orinius, Identifying severe aortic valvular stenosis by bedside examination, Acta Med Scand 218 (1985), pp. 397–400. Abstract-EMBASE | Abstract-MEDLINE 32 R.A. Griffiths and M.G. Sheldon, The clinical significance of systolic murmurs in the elderly, Age Ageing 4 (1975), pp. 99–104. Abstract-MEDLINE 33 A.S. Maisel, E.A. Gilpin and L. Klein et al., The murmur of papillary muscle dysfunction in acute myocardial infarction: clinical features and prognostic implications, Am Heart J 112 (1986), pp. 705–711. Abstract 34 P.A. Heidenreich, I. Schnittger and S.L. Hancock et al., A systolic murmur is a common presentation of aortic regurgitation detected by echocardiography, Clin Cardiol 27 (2004), pp. 502–506. Abstract-EMBASE | Abstract-MEDLINE 35 N.J. Lembo, L.J. Dell'Italia and M.H. Crawford et al., Bedside diagnosis of systolic murmurs, N Engl J Med 318 (1988), pp. 1572–1578. Abstract-EMBASE | Abstract-MEDLINE 36 C. Shub, Echocardiography or auscultation? How to evaluate systolic murmurs, Can Fam Physician 49 (2003), pp. 163–167. Abstract-MEDLINE | Abstract-EMBASE 37 I.M. Stewart, Systolic murmurs in 525 healthy young adults, Br Heart J 13 (1951), pp. 561–565. Abstract-MEDLINE 38 T. Gjørup, P.M. Bugge and A.M. Jensen, Interobserver variation in assessment of respiratory signs, Acta Med Scand 216 (1984), pp. 61–66. Abstract-EMBASE The study was supported by unrestricted grants given by Pfizer Denmark, Medicon Denmark, and the Diamond Foundation. None of the grantors had any influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; as well as preparation, review, and approval of the manuscript. Reprint requests: Kasper Iversen, MD, Clinic of Cardiology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.

(American Heart Journal Volume 152 @ Issue 1 , July 2006, Pages 11-18 doi:10.1016/j.ahj.2005.11.007 Copyright © 2006 Mosby, Inc. All rights reserved. Curriculum in Cardiology The 12-lead electrocardiogram as a predictive tool of mortality after acute myocardial infarction: Current status in an era of revascularization and reperfusion Mircea Petrina MDa, b, , , Shaun G. Goodman MD, MScc, d, e, and Kim A. Eagle MD, FACCa, aUniversity of Michigan Medical Center, Ann Arbor, MI bUniversity of Illinois at Chicago Michael Reese Hospital Program, Chicago, IL cUniversity of Toronto, Toronto, Ontario, Canada dCanadian Heart Research Centre, Toronto, Ontario, Canada eSt Michael's Hospital, Toronto, Ontario, Canada Received 5 April 2005; accepted 11 November 2005. Available online 13 July 2006.) Many recently published studies established the admission electrocardiogram as an excellent source of prognostic information in patients presenting with acute myocardial infarction. Using our search criteria, we identified a large number of articles but selected only the most relevant in each category. The best predictors of increased short-term mortality are ventricular tachycardia (odds ratio [OR] 6.1, 95% CI 4.6-8.3), ST-segment deviations (OR 5.1, 95% CI 4.6-8.3), high-degree atrioventricular block (OR 5.1, 95% CI 2.1-11.9), and long QRS duration (OR 4.2, 95% CI 1.8-10.4). For increased long-term mortality, the best predictors were ST-segment depression (OR 5.7, 95% CI 2.8-11.6), ST-segment elevation (OR 3.3, 95% CI 2.1-5.1), and left bundle-branch block (OR 2.8, 95% CI 1.8-4.3). In addition, our review discusses electrocardiographic markers of poor outcome that were not independent risk factors on multivariate analysis, conflicting findings, and knowledge gaps that can help plan future research efforts. There are multiple studies assessing the predictive power of different electrocardiographic (ECG) parameters in patients presenting with suspected acute myocardial infarction (AMI). The most commonly reported abnormalities are conduction blocks and ST-segment changes. To our knowledge, there are no review articles or meta-analyses published recently on the subject and only a few original studies performed multivariate analysis to assess the potential prognostic value of multiple ECG parameters simultaneously. This review identifies, critically appraises, and summarizes the best available evidence correlating both traditional and more recently studied ECG predictors of mortality after AMI. Methods A MEDLINE search performed with the search terms AMI, mortality, and ECG identified 424 articles. The following inclusion criteria were then applied: admission for AMI, at least 500 patients per study, and modern revascularization era (ie, 1990 to present), resulting in 103 selected articles. When similar studies were found on the same ECG parameter and follow-up length pair, the studies presenting general inclusion criteria and the most robust statistical methods were included in the final revision. The level of statistical significance (P value) for study reports to be considered in our review was .05. The reviewed articles were sorted based on the ECG phase of interest in the normal sequence from cardiac depolarization to repolarization and by the duration of patient follow-up, with short term defined as <6 months and longer term defined as ≥6 months. Whenever available, for each ECG variable included, the estimated prevalence, the impact, and the independence after multivariate analysis were reported. Results Normal presentation ECG Welch et al1 reported in a study of 391 208 patients diagnosed with AMI that normal (odds ratio [OR] 0.59, 95% CI 0.56-0.63) or nonspecific ECG (OR 0.70, 95% CI 0.68-0.72) conferred lower inhospital mortality risk compared with diagnostic ECG defined as ST-segment elevation (STE) or ST-segment depression (STD) or new left bundle-branch block (LBBB). Patients discharged with missed diagnosis, however, had a high mortality rate (10.5%). Normal or nonspecific admission ECG in the setting of AMI is thus protective for short-term mortality, and long-term mortality studies were not identified. Heart rate In a study by Granger et al2 on 11 389 patients enrolled with acute coronary syndrome (ACS) in the GRACE registry, an increased heart rate (HR) was an independent risk factor for higher inhospital mortality (OR 1.2, 95% CI 1.15-1.24). In 2 GUSTO-I substudies of 34 166 patients with St-segment elevation acute myocardial infarction (STEMI, the median HR in patients who died within 30 days was 80 beat/min (vs overall median 74 beat/min)3 and tachycardia (84 vs 60 beat/min)4 was reported as an independent predictor of 30-day mortality (OR 1.49, 95% CI 1.41-1.59). The authors3 also described increased 30-day mortality in patients with bradycardia (OR not reported). In a study on 1807 patients with AMI, Hjalmarson et al5 also reported that a higher admission HR predicted a higher inhospital and 1-year mortality. The total mortality (day 2 to 1 year) was reported to increase with increased HR from 15% (for an admission HR 50-60 beat/min) to 41% (HR >90 beat/min) and 48% (HR ≥110 beat/min). In another study from GRACE by Eagle et al6, 15 007 patients with ACS had higher 6-month mortality with progressive increases in baseline HR; thus, an average increase of 30 beat/min was an independent risk factor for increased mortality (OR 1.3, 95% CI 1.16-1.43). The mortality reported by Hjalmarson et al5 was higher than in the GRACE registry, possibly because of secular trends and different inclusion criteria (only patients with AMI were studied in the former, all ACS in the latter). All studies thus demonstrate a U-shape relation between HR and mortality, both bradycardia and tachycardia being independent predictors of mortality. Atrial fibrillation Newly diagnosed atrial fibrillation (AF) was found to be an independent predictor of inhospital adverse events in a study by Sakata et al7 and in the GRACE registry by Mehta et al8 (OR 1.65, 95% CI 1.3–2.1). The GUSTO-I trial9 of 40 890 patients with AMI reported that AF developed after admission was an independent predictor for 30-day mortality (OR 1.4, 95% CI 1.3-1.5) in contrast to baseline AF, which was not (OR 1.1, 95% CI 0.88-1.30). Behar et al10 found an incidence of 9.9% of paroxysmal AF among 5803 study patients, and it was a significant independent predictor for 1- and 5-year mortality (relative risk [RR] 1.28, 95% CI 1.12-1.46). Sakata et al7 reported both early- and late-onset AF (first or after 24 hours) as independent predictors of 8-year mortality (OR not available). In conclusion, new-onset AF in the setting of AMI is a strong predictor of poor long- and short-term outcome. Sustained monomorphic ventricular tachycardia Mont et al11 reported that sustained monomorphic ventricular tachycardia (SMVT) occurred in 1.9% of 1120 patients in the early phase of AMI (first 48 hours) and predicted an increased inhospital mortality (43% vs 11% without SMVT) even after multivariate adjustment (OR 5.0, 95% CI 1.63-15.3). An analysis of 16 189 patients with AMI from GISSI-3 registry12 assessed the incidence and short-term prognosis of SMVT with later onset (patients surviving the first 48 hours after AMI). The incidence of late-onset SMVT was 1% and predicted higher 6-week mortality (35% vs 5% without SMVT), even after adjustments using a proportional hazards regression model (hazard ratio 6.13, 95% CI 4.56-8.25). A very large ischemic area and mechanical stretching are considered possible causes of early SMVT, whereas after the first 48 hours, the presence of infarct scar tissue is the likely mechanism. In conclusion, both early and late SMVT are thus markers of extensive myocardial damage and independent predictors of short-term mortality. No long-term mortality studies were identified. Atrioventricular conduction blocks Haim et al13 find an incidence of 7.4% of high-degree atrioventricular conduction block (HAVB), defined as second or third degree atrioventricular conduction block, in 5839 patients with non–Q wave acute myocardial infarction (NQMI) from the SPRINT registry. High-degree atrioventricular conduction block conferred higher 24-hour mortality (15.5% vs 4%) and overall inhospital mortality (42% vs 10% without HAVB) and remained independent predictor of inhospital mortality (OR 5.1, 95% CI 2.1-11.9) after multivariate analysis. Similar conclusions were reported also by Berger et al14 in TIMI II trial, by Abidov et al15 in ARGAMI-2 trial, and for 2-year mortality as reported by Archbold et al16 in a study of 1225 patients. On the other hand, Haim et al13 reported no difference in 1-year mortality (8% in all patients) and no significant statistical difference at 5 years (35% vs 27% without HAVB). The difference between the report from Haim et al13 versus the reports from Berger et al,14 Abidov et al,15 and Archbold et al16 can be explained by the use of different selection criteria (Q-wave acute myocardial infarction (QMI) vs STEMI). In conclusion, HAVB has been demonstrated as an independent risk factor for short-term mortality, whereas its influence on long-term mortality is controversial. Bundle-branch blocks Of the 297 832 patients with AMI from the NRMI,17 6.7% presented with LBBB and 6.2% with right bundle-branch block (RBBB). The authors noted that the patients with bundle-branch block (BBB) received less evidence-based treatment (aspirin and β-blockers), whereas they were older and had more comorbidities (including congestive heart failure). The inhospital mortality after multivariate analysis was increased in both patients with LBBB (OR 1.34, 95% CI 1.28-1.39) and patients with RBBB (OR 1.64, 95% CI 1.57-1.71). New-onset BBB, with an overall incidence of 23.6%, was also evaluated in 681 patients from TAMI-9 and GUSTO-I trials, and the authors18 concluded that persistent, rather than transient, BBB remains predictive of higher 30-day mortality (19.4% vs 5.6%). A study of 932 patients with Q-wave anterior AMI and poor ejection fraction by Ricou et al19 and another study of 681 patients with AMI by Moreno et al20 reported that new-onset nontransient RBBB was an independent predictor for both inhospital (22.9% vs 7.9% without RBBB) and 1-year mortality (40.5% vs 12.3% without RBBB) after multivariate analysis (OR not reported). An independent association was not found by Archbold et al16 for 6-month mortality (hazard ratio 1.18, 95% CI 0.63-2.21) in all RBBB in a nonselected population. Three studies on LBBB have reported a higher mortality after multivariate analysis: GRACE registry2 (11 389 patients with ACS) for inhospital (OR 1.6, 95% CI 1.1-2.31), Archbold et al16 (1220 patients with AMI) for 6-month (hazard ratio 2.89, 95% CI 1.63-5.11), and Cannon et al21 et al from TIMI II (1416 patients with unstable angina or (NQMI) for 1-year mortality (OR 2.8, 95% CI 1.81-4.32). In conclusion, both RBBB and LBBB independently predict poor short-term outcome; whereas LBBB is also an independent risk factor for increased long-term mortality, RBBB is not, with the exception when new onset and persistent.19 Q-wave AMI In a multicenter study of 4202 patients, Chow et al22 reported higher inhospital mortality with QMI, and similar reports were provided by Behar et al23 in 580 patients with NQMI representing 14% of total patients with AMI from the SPRINT registry. Birnbaum et al24 reported the presence of abnormal Q waves in at least 2 leads with STE among 38.9% of 2370 patients with AMI, a finding associated with higher age and multiple comorbidities. It independently predicted higher inhospital mortality (OR 1.61, 95% CI 1.04-2.49), similar to reports from GRACE registry2 (OR 1.3, 95% CI 1.1-1.63) in patients with ACS. Both Behar et al23 and Birnbaum et al24 report that QMI was not found to be a predictor of 1-, 5-, or 10-year mortality. In conclusion, the presence of Q waves leads to higher short-term mortality but no independent influence on longer-term outcome. QRS duration Hathaway et al4 determined that QRS duration (QRSD) ≥100 milliseconds (OR 1.08, 95% CI 1.03-1.13) and QRS <50 milliseconds (OR 0.61, 95% CI 0.43-0.86) were independent predictors of 30-day mortality in 34 166 patients with STEMI from GUSTO-I. Brilakis et al25 reported that in patients with non-ST segment elevation myocardial infarction, inhospital, 1-, 3-, and 5-year mortality were higher with a QRSD ≥ 100 milliseconds (16% vs 5%, 25% vs 11%, 34% vs 17%, 48% vs 26%, respectively), whereas patients with STEMI had similar survival curves regardless of their QRSD. After adjustment for age, sex, Killip class, and HR, a QRSD of ≥100 milliseconds remained an independent risk factor for both inhospital (RR 4.22, 95% CI 1.81-10.39) and long-term mortality (RR 1.63, 95% CI 1.11-2.40). The authors suggested that a long QRSD adversely affected survival possibly because of its coexistence with a higher incidence of heart failure, a larger number of stenosed coronaries, an increased arrhythmia risk, or a combination of the previous. In conclusion, a long QRSD is an independent predictor of both short- and long-term outcome. ST-segment elevation The following ST-segment changes present on the baseline ECG in the patients with ACS from GRACE registry2 were independent risk factors for higher inhospital mortality: any ST-segment deviation (OR 1.8, 95% CI 1.33-2.40), anterior STE (OR 1.7, 95% CI 1.3-2.2), and anterior STD (OR 1.5, 95% CI 1.1-1.92). The same findings were reported in a study correlating outcome with the number of leads showing STE in 7755 patients from GISSI-2 registry26 (Figure 1), in a report from GUSTO-IIb27 on 12 142 patients on 30-day mortality in patients with STE (OR 2.59, 95% CI 1.47-2.92), and by Chow et al.22 (10K) Figure 1. A, Inhospital mortality (n = 7755).26 B, Six-month mortality (n = 2719).28 C, Thirty-day mortality (n = 12 142).27 D, One-year mortality (n = 1588).33 Six-month mortality was studied in 2719 patients recruited for in the InTIME II study28 (Figure 1). Patients had maximum STE measured at 90 minutes postthrombolysis and were stratified into 3 risk groups based on the amount of STE and the presence or absence of BBB, showing higher mortality with higher degree of STE. In conclusion, a higher STE confers a higher short-term mortality, but for long-term outcome, only STE of >2 mm associated with BBB was an independent predictor. ST-segment depression In 9461 patients with ACS from PURSUIT,29 the presence of STD conferred higher 30-day mortality (5.1% vs 2.1% no STD), which remained significant after multivariate analysis (OR 1.80, 95% CI 1.40-2.33), and similar findings were reported in GUSTO-IIb27 (OR 2.07, 95% CI 1.82-3.69) and by Mahon et al.30 Birnbaum et al31 reported on 1321 patients (77% males) enrolled in GUSTO-I that patients with a higher sum of STD in the lateral leads (V4-V6) had higher inhospital mortality (OR 2.78, 95% CI 1.26-6.13) after multivariable adjustment. Peterson et al32 examined 16 521 GUSTO-I patients with inferior AMI finding that the sum of STD remained the most significant independent ECG predictor for 30-day mortality (OR not reported). Kaul et al33 assessed the impact of STD on long-term mortality in 1588 patients from the PARAGON-A trial and validated the predictive model on the GUSTO-IIb population. Patients with greater depths of STD (present in at least 2 continuous leads) had higher 1-year mortality rates (Figure 1). In conclusion, both STD and sum of STD remain strong independent predictors of both short- and long-term mortality, possibly stronger than STE. ST-segment resolution Corbalan et al39 reported in a study of 967 patients that early (within 2 hours after thrombolysis) ST-segment resolution (STR) of >50% of the initial deviation is a strong but not independent predictor of inhospital mortality (univariate OR 0.33, 95% CI 0.21-0.50). In study of 2719 patients from the InTIME II trial, Schroeder et al28 reported similar findings for inhospital mortality but states that any level of the sum of STR (low, partial, or complete) independently predicts 6-month mortality compared with no STR (OR not reported). In GUSTO-III trial,34 complete STR at 90 minutes was found to be strong predictor of 30-day and 1-year mortality (Figure 2) (OR not reported). The ISAM trial35 also reports complete early STR as an independent predictor of both short- and long-term mortality (Figure 3). (64K) Figure 2. Early and late ST-segment resolution and mortality by Anderson34 (n = 1741). (3K) Figure 3. Compared mortality in no STR versus complete STR by Schroeder et al37 (n = 1741). Patients from the GISSI-2 trial36 who reached an STR of >50% by 4-hour postthrombolysis had a lower 30-day (RR 0.46, 95% CI 0.37-0.57) and 6-month mortality (RR 0.58, 95% CI 0.48-0.70). Similar results were reported from the INJECT trial37 where the absence of STR (vs complete STR) was a strong independent predictor of 35-day mortality (OR 6.9, 95% CI 3.8-12.5). In the same article from the ISAM35 trial, Kaplan-Meier survival curves for anterior and inferior AMI showed that patients without STR had a significant increased mortality up to 6 years after AMI, similar to findings by French et al.38 In conclusion, a significant STR, regardless whether early or late, improves both long- and short-term survival after AMI. T-wave inversion In a study of 967 patients with new QMI, Corbalan et al39 assessed the presence of early TWI (first 24 hours after thrombolysis) in the infarct-related ECG leads together with other potential predictors for inhospital mortality and found it to be an independent protective factor (OR 0.29, 95% CI 0.11-0.68). In a substudy of 12 142 patients with AMI from GUSTO-IIb,27 the incidence of TWI was 22%; STE, 28%; STD, 35%; and STE with STD, 25%. The multivariate analysis for 30-day and 6-month mortality showed TWI conferring better protection than STE and STD (Figure 4). Herz et al40 used different methods to classify 2853 patients with STEMI based on the presence of negative T waves (NTWs) in patients treated within 2 hours after symptoms onset versus after 2 hours. They reported higher inhospital mortality when patients with NTW were treated after 2 hours compared to no NTW (OR 1.86, 95% CI 1.07-3.25), but not when treated within 2 hours (mortality 0/52 patients). (6K) Figure 4. Thirty-day (A) and six-month mortality ( (n = 12 142).27 In conclusion, TWI is a strong independent negative risk factor for short-term outcome in STEMI (especially when thrombolysis is given within 2 hours of symptoms onset), whereas in NSTEMI, it is an independent risk factor for both short- and long-term poor outcome. Myocardial infarction location In a study on 7755 patients enrolled in GISSI-2, Fresco et al26 found that anterior infarction was an independent risk factor for increased inhospital mortality (OR 2.1, 95% CI 1.5-2.9). Lee et al3 also report higher overall 30-day mortality with anterior versus nonanterior location (OR 1.55, 95% CI 1.43-1.68) in 41 021 patients with STEMI from GUSTO-I study. The lowest 30-day mortality occurred with inferior location versus noninferior (OR 0.67, 95% CI 0.50-0.90) after multivariate analysis. In a report of 2719 patients by Schroeder et al,28 anterior AMI remained an independent risk factor correlating with increased 180-day mortality (OR not reported). In a study on 610 patients enrolled in SPRINT41 with their first non-QMI, 248 (40.6%) had anterior and 327 (53.6%) had inferior or lateral infarction. Inhospital, 1-year, and 5-year mortality were 15% versus 10% (anterior vs inferior or lateral), 12% versus 6%, and 36% versus 22%, respectively. After correction for age, sex, prior hypertension (HTN), diabetes mellitus and angina, and therapy, anterior infarction location was no longer an independent predictor, but small sample size limits the ability to show this effect. The only specific AMI locations for which our search found relevant articles are anterior and inferior, the first location reported as independent risk factor and the latter reported as negative risk factor for short-term mortality. For long-term mortality, the reports are not as well documented, but the trend is similar as for short-term mortality. Discussion The best predictors of increased short-term mortality identified by our review are ventricular tachycardia, ST-segment deviations, high-degree atrioventricular block, and long QRSD. For long-term mortality, ST-segment deviations and LBBB are the most significant independent risk factors. A summary of the independent risk factors for short- and long-term mortality is depicted in Figure 5 and Figure 6. For calculating the OR for each ECG parameter, the referent was the absence of the respective parameter from the admission ECG. In the absence of a true comparison of different OR that requires all parameters to be studied in the same population, a simulated head-to-head comparison is offered based on significant similarities among the studied populations due to consistently applied inclusion criteria. (7K) Figure 5. Short-term mortality overview. AV, Atrioventricular. (4K) Figure 6. Long-term mortality overview. Our review also identified several ECG parameters as markers of mortality, which did not reach independent predictor status after multivariate analysis. High-degree atrioventricular block was an independent predictor of increased short-term but controversial on long-term mortality. ST-segment depression and anterior AMI location were both reported as independent risk factors for short-term but not for long-term mortality. For certain ECG parameters included in our review, we were able to identify possible knowledge gaps that could be addressed in future studies. We did not identify any study to assess the predictive power on long-term mortality of the normal admission ECG and baseline AF. It is possible that other ECG parameters have been researched but were not identified at the time of our literature search; some of them could be of important prognostic value. In conclusion, most of the studied ECG abnormalities that accompanied an AMI presentation, with the exception of TWI and STR, are associated with various levels of increased mortality risk. Their presence should help the clinician identify the patients who are at the highest risk and will benefit most from maximized monitoring and evidence-based therapies. To help further sort out the numerous ECG findings, so far individually researched, a simultaneous analysis on multiple ECG parameters (possibly including novel ones) in a representative population is clearly needed. Limitations The current review article has inherent limitations because of its nature; occasionally, the original studies included have slightly different inclusion criteria, the populations researched had different baseline characteristics and treatment, and secular trends could have affected enrollment and management. The authors attempted to overcome these limitations by providing a comprehensive, focused, and distinctive analysis of highly selected original articles from the modern revascularization era of AMI therapy. The authors thank Dean E. Smith, PhD, University of Michigan, for his timely and broad statistical support. References 1 R.D. Welch, R.J. Zalenski and P.D. 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