Hypothermia as an inotrope

This small study supports the hypothesis that therapeutic hypothermia can have positive inotropic effects in patients with cardiogenic shock of ischaemic or non-ischaemic origin.

Cooling resulted in a temperature-dependent decrease in heart rate and temperature-dependent increases in stroke volume index, cardiac index, mean arterial pressure, and cardiac power output. These changes reversed when the patients were rewarmed.

The authors summarise as follows:

In summary, our studies demonstrate that moderate hypothermia is feasible and safe also for patients in cardiogenic shock.

Improved cardiac performance may contribute to the considerable decrease of mortality for survivors of cardiac arrest, and the use of hypothermia can be recommended for patients with a clear indication for cooling and poor cardiac performance.

Moreover, hypothermia might be considered as a positive inotropic intervention during cardiogenic shock.

Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II)
Resuscitation. 2013 Mar;84(3):319-25.
Abstract

Decatecholaminization in septic shock

A subset of patients from the 2008 Vasopressin and Septic Shock Trial (VASST) trial had invasive haemodynamic monitoring measurements from pulmonary artery catheters. These data have now been analysed, revealing that vasopressin was associated with a lower heart rate compared with norepinephrine (noradrenaline) alone, without significant difference in cardiac index or stroke volume index. However, there was significantly greater use of inotropic drugs in the vasopressin group compared with the norepinephrine group.

Tachycardia and high quantities of catecholamine infusion are both associated with mortality in sepsis. The authors discuss:

“The idea of decatecholaminization, reducing both endogenous and exogenous adrenergic stimulation, is now believed to be an important treatment strategy, and the use of beta-blockers in septic shock is being considered. The early use of vasopressin or specific V1a receptor agonists in early septic shock may be another possible treatment.”

This interesting post-hoc analysis may help further define the patients in whom vasopressin is to be considered, by those clinicians who are using it in septic shock. For those that aren’t, I wouldn’t worry about it.

The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock
Chest. 2012 Sep;142(3):593-605
Click for abstract

New STEMI guidelines

Primary percutaneous coronary intervention or fibrinolysis for STEMI? What if you don’t have PCI at your hospital?

The new 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction is out and you can get the summary here.

Here’s what they say about initial reperfusion therapy:

Onset of Myocardial Infarction: Recommendations
Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-Treatment Goals

Class I

1. All communities should create and maintain a regional system of STEMI care that includes assessment and continuous quality improvement of emergency medical services and hospital-based activities. Performance can be facilitated by participating in programs such as Mission: Lifeline and the Door-to-Balloon Alliance.(Level of Evidence: B)

2. Performance of a 12-lead electrocardiogram (ECG) by emergency medical services personnel at the site of first medical contact (FMC) is recommended in patients with symptoms consistent with STEMI.(Level of Evidence: B)

3. Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours. (Level of Evidence: A)

4. Primary PCI is the recommended method of reper- fusion when it can be performed in a timely fashion by experienced operators. (Level of Evidence: A)

5. Emergency medical services transport directly to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI, with an ideal FMC-to-device time system goal of 90 minutes or less.(Level of Evidence: B)

6. Immediate transfer to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI who initially arrive at or are transported to a non–PCI-capable hospital, with an FMC-to-device time system goal of 120 minutes or less.(Level of Evidence: B)

7. In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non–PCI-capable hospitals when the anticipated FMC-to-device time at a PCI-capable hospital exceeds 120 minutes because of unavoidable delays.(Level of Evidence: B)

8. When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival.(Level of Evidence: B)

Class IIa

1. Reperfusion therapy is reasonable for patients with STEMI and symptom onset within the prior 12 to 24 hours who have clinical and/or ECG evidence of ongoing ischemia. Primary PCI is the preferred strategy in this population. (Level of Evidence: B)

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Circulation. 2012 Dec 17. [Epub ahead of print]

Echo for cardiac arrest outcome prediction

A meta-analysis of studies evaluation transthoracic echo as a means of predicting return of spontaneous circulation in cardiac arrest (ROSC) provides some likelihood ratios to what we already know: absence of sonographic cardiac activity means a very low chance of ROSC.

The authors report a pooled negative LR of 0.18 (95% CI = 0.10 to 0.31), and a positive likelihood ratio of 4.26 (95% CI = 2.63 to 6.92).

They conclude that focused transthoracic echo is a fairly effective (although not definitive) test for predicting death if no cardiac activity is noted during resuscitation, and recommend interpreting the echo in the light of the test characteristics and the clinical pre-test probability, as one should do for all imaging investigations:

“An elderly patient with an unwitnessed cardiac arrest already has very poor odds for survival. Confirmation of asystole on echo lowers those pretest odds by a factor of 5.6 and therefore might lead to termination of resuscitation. However, in the case of a 50-year-old rescued from drowning, detection of cardiac contractility on echo would increase his already fair odds of survival by a factor of 4.3, prompting continued aggressive resuscitation.”

Only five relatively small studies contributed to the findings. A more definitive answer to this question should be provided in the future by the multi-centre REASON 1 trial.

Objectives:  The objective was to determine if focused transthoracic echocardiography (echo) can be used during resuscitation to predict the outcome of cardiac arrest.

Methods:  A literature search of diagnostic accuracy studies was conducted using MEDLINE via PubMed, EMBASE, CINAHL, and Cochrane Library databases. A hand search of references was performed and experts in the field were contacted. Studies were included for further appraisal and analysis only if the selection criteria and reference standards were met. The eligible studies were appraised and scored by two independent reviewers using a modified quality assessment tool for diagnostic accuracy studies (QUADAS) to select the papers included in the meta-analysis.

Results:  The initial search returned 2,538 unique papers, 11 of which were determined to be relevant after screening criteria were applied by two independent researchers. One additional study was identified after the initial search, totaling 12 studies to be included in our final analysis. The total number of patients in these studies was 568, all of whom had echo during resuscitation efforts to determine the presence or absence of kinetic cardiac activity and were followed up to determine return of spontaneous circulation (ROSC). Meta-analysis of the data showed that as a predictor of ROSC during cardiac arrest, echo had a pooled sensitivity of 91.6% (95% confidence interval [CI] = 84.6% to 96.1%), and specificity was 80.0% (95% CI = 76.1% to 83.6%). The positive likelihood ratio for ROSC was 4.26 (95% CI = 2.63 to 6.92), and negative likelihood ratio was 0.18 (95% CI = 0.10 to 0.31). Heterogeneity of the results (sensitivity) was nonsignificant (Cochran’s Q: χ(2) = 10.63, p = 0.16, and I(2) = 34.1%).

Conclusions:  Echocardiography performed during cardiac arrest that demonstrates an absence of cardiac activity harbors a significantly lower (but not zero) likelihood that a patient will experience ROSC. In selected patients with a higher likelihood of survival from cardiac arrest at presentation, based on established predictors of survival, echo should not be the sole basis for the decision to cease resuscitative efforts. Echo should continue to be used only as an adjunct to clinical assessment in predicting the outcome of resuscitation for cardiac arrest.

Bedside Focused Echocardiography as Predictor of Survival in Cardiac Arrest Patients: A Systematic Review
Acad Emerg Med. 2012 Oct;19(10):1119-1126

Echocardiography in Pulmonary Embolism

I had great fun joining in a Google Hangout with the Ultrasound Podcast guys and some real masters of emergency/critical care ultrasound. You can watch it here:

Is diastolic worse than systolic dysfunction in sepsis?

Septic myocardial dysfunction is a well recognised contributor to shock in sepsis but for many of us we assume this to be gross systolic impairment. Interestingly a recent study highlights that patients with severe sepsis and septic shock frequently have diastolic dysfunction¹. They found that diastolic dysfunction was the strongest independent predictor of early mortality, even after adjusting for the APACHE-II score and other predictors of mortality.

In this study, 9.1% of severe sepsis/septic shock patients had isolated systolic dysfunction, 14.1% had combined systolic and diastolic dysfunction, and 38% had isolated diastolic dysfunction.

Importantly, the authors point out that although diastolic dysfunction is associated with age, hypertension, diabetes mellitus, and ischaemic heart disease, diastolic dysfunction is a stronger independent predictor of mortality than age and the other co-morbidities. However, a limitation of the study acknowledged by the authors is that it did not include follow-up echocardiography examinations, so we do not know whether sepsis was responsible for a transient diastolic dysfunction or whether the observed diastolic dysfunction was a pre-existing condition.

Both troponin and NT-ProBNP elevations also predicted mortality.

Want to know how to measure diastolic dysfunction? These authors measured mitral annular early-diastolic peak velocity, or the e’-wave (called ‘e prime’). It is a way of seeing how fast myocardial tissue relaxes in diastole, and if its peak velocity is slow (in this case < 8cm/s) there is diastolic dysfunction. We measure speed using Doppler, and in this case we’re looking at the speed of heart tissue (as opposed to the blood cells within the heart chambers) so we do ‘Tissue Doppler Imaging’, or TDI. You need an echo machine with pulsed-wave Doppler, and you need to be able to get an apical view. This is explained really nicely here² but if you don’t have the time or the echopassion to read a whole article on TDI watch this one minute video (BY emergency physicians FOR emergency physicians!) on diastology, where TDI measurement of e’ is shown from 45 seconds into the video.

For reference, there is some more detail on diastolic function measurements at the Echobasics site.

If you think you can cope with any more of this level of awesomeness and want these geniuses to talk to you from your smartphone in the ED then get the free One Minute Ultrasound app for Android or Apple devices.

AIMS: Systolic dysfunction in septic shock is well recognized and, paradoxically, predicts better outcome. In contrast, diastolic dysfunction is often ignored and its role in determining early mortality from sepsis has not been adequately investigated.

METHODS AND RESULTS: A cohort of 262 intensive care unit patients with severe sepsis or septic shock underwent two echocardiography examinations early in the course of their disease. All clinical, laboratory, and survival data were prospectively collected. Ninety-five (36%) patients died in the hospital. Reduced mitral annular e’-wave was the strongest predictor of mortality, even after adjusting for the APACHE-II score, low urine output, low left ventricular stroke volume index, and lowest oxygen saturation, the other independent predictors of mortality (Cox’s proportional hazards: Wald = 21.5, 16.3, 9.91, 7.0 and 6.6, P< 0.0001, <0.0001, 0.002, 0.008, and 0.010, respectively). Patients with systolic dysfunction only (left ventricular ejection fraction ≤50%), diastolic dysfunction only (e’-wave <8 cm/s), or combined systolic and diastolic dysfunction (9.1, 40.4, and 14.1% of the patients, respectively) had higher mortality than those with no diastolic or systolic dysfunction (hazard ratio = 2.9, 6.0, 6.2, P= 0.035, <0.0001, <0.0001, respectively) and had significantly higher serum levels of high-sensitivity troponin-T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). High-sensitivity troponin-T was only minimally elevated, whereas serum levels of NT-proBNP were markedly elevated [median (inter-quartile range): 0.07 (0.02-0.17) ng/mL and 5762 (1001-15 962) pg/mL, respectively], though both predicted mortality even after adjusting for highest creatinine levels (Wald = 5.8, 21.4 and 2.3, P= 0.015, <0.001 and 0.13).

CONCLUSION: Diastolic dysfunction is common and is a major predictor of mortality in severe sepsis and septic shock.

1. Diastolic dysfunction and mortality in severe sepsis and septic shock
Eur Heart J. 2012 Apr;33(7):895-903

2. A clinician’s guide to tissue Doppler imaging
Circulation. 2006 Mar 14;113(10):e396-8 Free Full Text

T waves in V1-V3 were not associated with badness

This long term follow up study showed that T-wave inversions in right precordial leads are not associated with adverse outcome.

Background-: T-wave inversion in right precordial leads V1 to V3 is a relatively common finding in a 12-lead ECG of children and adolescents and is infrequently found also in healthy adults. However, this ECG pattern can also be the first presentation of arrhythmogenic right ventricular cardiomyopathy. The prevalence and prognostic significance of T-wave inversions in the middle-aged general population are not well known.

Methods and Results-: We evaluated 12-lead ECGs of 10 899 Finnish middle-aged subjects (52% men, mean age 44+/-8.5 years) recorded between 1966 and 1972 for the presence of inverted T waves and followed the subjects for 30+/-11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. T-wave inversions in right precordial leads V1 to V3 were present in 54 (0.5%) of the subjects. In addition, 76 (0.7%) of the subjects had inverted T waves present only in leads other than V1 to V3. Right precordial T-wave inversions did not predict increased mortality (not significant for all end points). However, inverted T waves in leads other than V1 to V3 were associated with an increased risk of cardiac and arrhythmic death (P<0.001 for both).

Conclusions-: T-wave inversions in right precordial leads are relatively rare in the general population, and are not associated with adverse outcome. Increased mortality risk associated with inverted T waves in other leads may reflect the presence of an underlying structural heart disease.

Prevalence and prognostic significance of T-wave inversions in right precordial leads of a 12-lead electrocardiogram in the middle-aged subjects
Circulation. 2012 May 29;125(21):2572-7

Nitrate bolus in acute heart failure

Despite intravenous nitrate boluses being used in original studies demonstrating benefit in acute heart failure^1,2, I regularly meet reluctance from both physicians and nurses in the emergency department to give them.

Their resistance seems to be based on a concern for inducing hypotension, and they prefer to ‘titrate up’ an infusion.

iv nitrate options include nitroglycerin (GTN), and isosorbide dinitrate (ISDN). Studies have used ISDN 4mg every 4 mins, ISDN 3mg every 5 mins, and GTN 2mg every 3 mins³.

There are a number of reasons to avoid starting with a low rate infusion in a sick heart failure patient.

Matthew Reed highlighted cannula size as an important factor⁴:

If a GTN infusion is commenced at a rate of 1 ml/h, a critically unwell patient with a large cannula—for example, a grey cannula (16G) — will have to wait over 6 min for the drug to enter the body. This compares with 1.5 min for a pink cannula (20G) at the same infusion rate. If a large-diameter cannula is chosen for these patients, then a fast initial infusion rate should also be chosen to ensure that the GTN begins to act quickly.

Alistair Steel subsequently pointed out further reasons to avoid slow infusions⁵:

(1) mechanical slack within an infusion device may mean an infusion set at 1 ml/h will take many minutes for the driver to contact and advance the syringe plunger. For this reason, infusions should be purged before patient connection.

(2) the pharmacokinetics of the drug should be considered. At low infusion rates it will take significant time for a steady state to be achieved (a drug such as GTN, with a half-life of 2 min, would require 10 min to achieve steady state). For clinical effects to be seen quickly, a bolus should be given before commencing infusions.

(3) the use of 1 ml/h infusions (8 µg/min using a 0.5% solution) may be excessively cautious – the British National Formulary recommends a therapeutic dose range from 10 to 200 µg/min. Furthermore, there is emerging evidence that, when used for decompensated heart failure, higher doses of GTN are associated with more favourable outcomes.

(4) at low infusion rates any obstruction in the intravenous system will take a proportionally longer time to become apparent, as it will take longer for the pressure to build up and trigger the syringe pump’s high pressure alarm..

Now a recent study confirms such a regimen can be used safely in the elderly. ISDN 3mg bolus treatment was not associated with higher rates of hypotension in the elderly population treated for heart failure in the emergency department. Despite a small study and a retrospective design, this lends support to the practice of iv bolus nitrate therapy for acute heart failure, even in the elderly.

1. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema
Lancet. 1998 Feb 7;351(9100):389-93

2. High-doses intravenous isosorbide dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema
J Am Coll Cardiol. 2000 Sep;36(3):832-7 Free Full Text

3. Managing acute pulmonary oedema with high or standard dose nitrate
Emerg Med J. 2009 May;26(5):357-8

4. Administering a glyceryl trinitrate infusion: big is not always best
Emerg Med J 2007;24:423-424

5. Administering a glyceryl trinitrate infusion: faster is better than slower
Emerg Med J. 2008 Jan;25(1):60

6. Isosorbide dinitrate bolus for heart failure in elderly emergency patients: a retrospective study
Eur J Emerg Med. 2011 Oct;18(5):272-5

Dobutamine for severe heart failure – more harm than good?

A systematic review and meta-analysis of randomised controlled trials showed dobutamine is not associated with improved mortality in heart failure patients and in the case of severe heart failure there is some suggestion of increased mortality, although this did not reach statistical significance.

The authors do point out that the quality of the reports of the trials reviewed was suboptimal. However, they state:
It should be noted that the results of this study are in accord with large observational studies that have also suggested harm associated with use of dobutamine in patients with severe heart failure. Taken together, this evidence should cause clinicians to reconsider their use of dobutamine in patients with heart failure, particularly those most at risk of the adverse effects, those with underlying ischaemic heart disease.

PURPOSE: Dobutamine is recommended for patients with severe heart failure; however uncertainty exists as to its effect on mortality. This study aims to critically review the literature to evaluate whether dobutamine, compared with placebo or standard care, is associated with lower mortality and a range of secondary outcomes, in patients with severe heart failure.

METHODS: A systematic review and meta-analysis of randomised controlled trials was performed. PubMed, EMBASE, the Cochrane Central Trials Registry, the metaRegister of Controlled Trials and bibliographies of retrieved articles were searched. Randomised trials comparing dobutamine with placebo or standard care, in human, adult patients with severe heart failure, were included if they reported at least one outcome of interest. Data regarding trial validity, methodological processes and clinical outcomes were extracted, and a meta-analysis was performed.

RESULTS: Fourteen studies, with 673 participants, met the inclusion criteria and were included; 13 studies reported mortality. There was minimal heterogeneity (I (2) = 4.5%). The estimate of the odds ratio for mortality for patients with severe heart failure treated with dobutamine compared with standard care or placebo was 1.47 (95% confidence interval 0.98-2.21, p = 0.06).

CONCLUSIONS: This meta-analysis showed that dobutamine is not associated with improved mortality in patients with heart failure, and there is a suggestion of increased mortality associated with its use, although this did not reach the conventional level of statistical significance. Further research to define the role of dobutamine in treatment of severe heart failure should be a priority.

Dobutamine for patients with severe heart failure- a systematic review and meta-analysis of randomised controlled trials
Intensive Care Med. 2012 Mar;38(3):359-67

Enoxaparin beats heparin for PCI

This is of interest to those of us in retrieval medicine, for logistic reasons: an infusion of heparin can be an unnecessary hassle during transport, especially if a subcutaneous injection prior to retrieval is a satisfactory alternative. This systematic review and meta-analysis shows enoxaparin appears to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention. This applies particularly to patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction

OBJECTIVE: To determine the efficacy and safety of enoxaparin compared with unfractionated heparin during percutaneous coronary intervention.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline and Cochrane database of systematic reviews, January 1996 to May 2011.

STUDY SELECTION: Randomised and non-randomised studies comparing enoxaparin with unfractionated heparin during percutaneous coronary intervention and reporting on both mortality (efficacy end point) and major bleeding (safety end point) outcomes.

DATA EXTRACTION: Sample size, characteristics, and outcomes, extracted independently and analysed.

DATA SYNTHESIS: 23 trials representing 30 966 patients were identified, including 10 243 patients (33.1%) undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction, 8750 (28.2%) undergoing secondary percutaneous coronary intervention after fibrinolysis, and 11 973 (38.7%) with non-ST elevation acute coronary syndrome or stable patients scheduled for percutaneous coronary intervention. A total of 13 943 patients (45.0%) received enoxaparin and 17 023 (55.0%) unfractionated heparin. Enoxaparin was associated with significant reductions in death (relative risk 0.66, 95% confidence interval 0.57 to 0.76; P<0.001), the composite of death or myocardial infarction (0.68, 0.57 to 0.81; P<0.001), and complications of myocardial infarction (0.75, 0.6 to 0.85; P<0.001), and a reduction in incidence of major bleeding (0.80, 0.68 to 0.95; P=0.009). In patients who underwent primary percutaneous coronary intervention, the reduction in death (0.52, 0.42 to 0.64; P<0.001) was particularly significant and associated with a reduction in major bleeding (0.72, 0.56 to 0.93; P=0.01).

CONCLUSION: Enoxaparin seems to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention and particularly in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction.

Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis

BMJ. 2012 Feb 3;344:e553

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