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Critical Care Medicine Mar 2020Epinephrine is frequently used as an inotropic and vasopressor agent in critically ill patients requiring hemodynamic support. Data from observational trials suggested... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Epinephrine is frequently used as an inotropic and vasopressor agent in critically ill patients requiring hemodynamic support. Data from observational trials suggested that epinephrine use is associated with a worse outcome as compared with other adrenergic and nonadrenergic vasoactive drugs. We performed a systematic review and meta-analysis of randomized controlled trials to investigate the effect of epinephrine administration on outcome of critically ill patients.
DATA SOURCES
PubMed, EMBASE, and Cochrane central register were searched by two independent investigators up to March 2019.
STUDY SELECTION
Inclusion criteria were: administration of epinephrine as IV continuous infusion, patients admitted to an ICU or undergoing major surgery, and randomized controlled trials. Studies on epinephrine administration as bolus (e.g., during cardiopulmonary resuscitation), were excluded. The primary outcome was mortality at the longest follow-up available.
DATA EXTRACTION
Two independent investigators examined and extracted data from eligible trials.
DATA SYNTHESIS
A total of 5,249 studies were assessed, with a total of 12 studies (1,227 patients) finally included in the meta-analysis. The majority of the trials were performed in the setting of septic shock, and the most frequent comparator was a combination of norepinephrine plus dobutamine. We found no difference in all-cause mortality at the longest follow-up available (197/579 [34.0%] in the epinephrine group vs 219/648 [33.8%] in the control group; risk ratio = 0.95; 95% CI, 0.82-1.10; p = 0.49; I = 0%). No differences in the need for renal replacement therapy, occurrence rate of myocardial ischemia, occurrence rate of arrhythmias, and length of ICU stay were observed.
CONCLUSIONS
Current randomized evidence showed that continuous IV administration of epinephrine as inotropic/vasopressor agent is not associated with a worse outcome in critically ill patients.
Topics: Cardiovascular Diseases; Critical Illness; Dobutamine; Drug Therapy, Combination; Epinephrine; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Norepinephrine; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Shock, Septic; Vasoconstrictor Agents
PubMed: 31789701
DOI: 10.1097/CCM.0000000000004127 -
BMC Neurology Nov 2019Myasthenia gravis associated takotsubo syndrome is a rare condition. This study aimed to explore its typical presentation, investigations and treatment through a...
BACKGROUND
Myasthenia gravis associated takotsubo syndrome is a rare condition. This study aimed to explore its typical presentation, investigations and treatment through a systematic review of previously reported cases.
METHODS
Databases and reference lists of the selected articles were searched for case reports on Myasthenia gravis associated takotsubo syndrome. CARE guidelines were used for the quality assessment of the selected articles.
RESULTS
Sixteen cases were selected out of 580 search results. Western Pacific, American and European regions contributed to 88% of the cases. Females were most affected (81%). Features of both myasthenia gravis and takotsubo syndrome were the common clinical presentations. All cases had a myasthenic crisis. Half of the cases had no prior diagnosis of myasthenia gravis. Pyridostigmine and prednisolone were useful for myasthenia gravis while dobutamine was most commonly used for takotsubo syndrome. All cases survived except four (25%).
CONCLUSIONS
Myasthenia gravis associated takotsubo syndrome via a myasthenic crisis is rare but life-threatening. Therefore, predisposition due to emotional and physical triggers needs to be avoided for its prevention. The rare entity should be suspected even in patients without a prior diagnosis of Myasthenia gravis.
Topics: Adult; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Precipitating Factors; Takotsubo Cardiomyopathy
PubMed: 31718587
DOI: 10.1186/s12883-019-1523-z -
Critical Care (London, England) May 2019Catecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Catecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin, vasopressin V1A agonist, and even Ca sensitizer were increasingly used by physicians. The aim of this study is to compare the efficacy of such different kinds of vasoactive medications on mortality among patients with septic shock.
METHODS
Relevant randomized controlled trials were identified by searching PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to February 22, 2018. A network meta-analysis was performed to evaluate the effect of different types of vasoactive medications. The primary outcome was 28-day mortality. Intensive care unit (ICU) mortality, hospital and ICU length of stay (LOS), and adverse events were also assessed.
RESULTS
A total of 43 trials with 5767 patients assessing 17 treatment modalities were included. Treatments ranking based on surface under the cumulative ranking curve values from largest to smallest were NE/DB 85.9%, TP 75.1%, NE/EP 74.6%, PI 74.1%, EP 72.5%, VP 66.1%, NE 59.8%, PE 53.0%, DA 42.1%, DX 38.2%, SP 27.0%, PA 24.3%, EX 22.8%, LE 21.5%, and DB 13.3% for 28-day mortality. Treatments ranking for ICU mortality were TP/NE 86.4%, TP 80.3%, TP/DB/NE 65.7%, VP/NE 62.8%, NE 57.4%, VP 56.5%, PE 48.4%, DA 33.0%, PA 27.5%, LE 22.1%, and DB 9.9%. The incidence of myocardial infarction was reported with NE/EP 3.33% (n = 1 of 30), followed by EP 3.11% (n = 5 of 161), and then VP 3.10% (n = 19 of 613), NE 3.03% (n = 43 of 1417), DA 2.21% (n = 19 of 858), NE/DB 2.01% (n = 4 of 199), LE 1.16% (n = 3 of 258), and PA 0.39% (n = 1 of 257). The incidence of arrhythmia was reported with DA 26.01% (n = 258 of 992), followed by EP 22.98% (n = 37 of 161), and then NE/DB 20.60% (n = 41 of 199), NE/EP 20.0% (n = 6 of 30), NE 8.33% (n = 127 of 1525), LE 5.81% (n = 15 of 258), PA 2.33% (n = 6 of 257), and VP 1.67% (n = 10 of 600).
CONCLUSIONS
The use of norepinephrine plus dobutamine was associated with lower 28-day mortality for septic shock, especially among patients with lower cardiac output.
Topics: Catecholamines; Dopamine; Humans; Mortality; Norepinephrine; Odds Ratio; Randomized Controlled Trials as Topic; Shock, Septic; Terlipressin; Vasopressins
PubMed: 31088524
DOI: 10.1186/s13054-019-2427-4 -
Frontiers in Cardiovascular Medicine 2019Exercise testing has become a diagnostic standard in the evaluation and management of heart disease. While different methods of exercise and pharmacological stress...
Hemodynamic Changes During Physiological and Pharmacological Stress Testing in Healthy Subjects, Aortic Stenosis and Aortic Coarctation Patients-A Systematic Review and Meta-Analysis.
Exercise testing has become a diagnostic standard in the evaluation and management of heart disease. While different methods of exercise and pharmacological stress testing exist, only little is known about their comparability. We aimed to assess hemodynamic changes during dynamic exercise, isometric exercise, and dobutamine stress testing at different stress intensities in healthy subjects and patients with aortic stenosis (AS) and aortic coarctation (CoA). A systematic literature search (PROSPERO 2017:CRD42017078608) in MEDLINE of interventional trials was conducted to identify eligible studies providing evidence of changes in hemodynamic parameters under different stress conditions acquired by MRI or echocardiography. A random effects model was used to estimate pooled mean changes in hemodynamics. One hundred and twenty-eight study arms with a total of 3,139 stress-examinations were included. In healthy subjects/(where available) in AS, pooled mean changes (95% CIs) during light dynamic stress were 31.78 (27.82-35.74) bpm in heart rate (HR) and 6.59 (2.58-10.61) ml in stroke volume (SV). Changes during light pharmacological stress were 13.71 (7.87-19.56)/14.0 (9.82-18.18) bpm in HR, and 5.47 (0.3-10.63)/8.0 (3.82-12.18) ml in SV. Changes during light isometric stress were 18.44 (10.74-26.14)/5.0 (-1.17-11.17) bpm in HR and -4.17 (-14.37-6.03)/-4.0 (-16.43-8.43) ml in SV. Changes during moderate dynamic stress were 49.57 (40.03-59.1)/46.45 (42.63-50.27) bpm in HR and 11.64 (5.87-17.42) ml in SV. During moderate pharmacological stress, changes in HR were 42.83 (36.94-48.72)/18.66 (2.38-34.93) bpm and in SV 6.29 (-2.0-14.58)/13.11 (7.99-18.23) ml. During high intensity dynamic stress changes in HR were 89.31 (81.46-97.17)/55.32 (47.31-63.33) bpm and in SV 21.31 (13.42-29.21)/-0.96 (-5.27-3.35) ml. During high pharmacological stress, changes in HR were 53.58 (36.53-70.64)/42.52 (32.77-52.28) bpm, and in SV 0.98 (-9.32-11.27)/14.06 (-1.62-29.74) ml. HR increase and age were inversely correlated at high stress intensities. In CoA, evidence was limited to single studies. This systematic review and meta-analysis presents pooled hemodynamic changes under light, moderate and high intensity exercise and pharmacological stress, while considering the potential influence of age. Despite limited availability of comparative studies, the reference values presented in this review allow estimation of the expected individual range of a circulatory response in healthy individuals and patients with AS and may contribute to future study planning and patient-specific models even when stress testing is contraindicated.
PubMed: 31024935
DOI: 10.3389/fcvm.2019.00043 -
Journal of Interventional Cardiology Dec 2018The aim of our systematic review was to investigate the efficacy of coronary sinus (CS) reducer device in patients with refractory angina.
OBJECTIVES
The aim of our systematic review was to investigate the efficacy of coronary sinus (CS) reducer device in patients with refractory angina.
BACKGROUND
The CS reducer device provides a therapeutic option for patients with coronary artery disease who are not suitable for revascularization.
METHODS
Two independent investigators (GB and GT) systematically searched the Medline and Cochrane library databases for studies describing the efficacy and safety of the CS reducer in patients with refractory angina from January 1, 2000 until May 12, 2018 using the following terms: "coronary sinus (reducer OR reducing) device." Efficacy was defined as ≥1 unit improvement in the Canadian cardiovascular society (CCS) score.
RESULTS
Our search strategy provided six studies (five observational studies and one randomized clinical trial) with 196 patients. The CS reducer device was effective in 146/186 (78.5%) patients. CCS score improved from 3.2 at baseline to 1.9 after 8.6 months of follow-up. The efficacy of CS reducer device was also demonstrated as an improvement in Seattle Angina Questionnaire score, dobutamine echocardiography, thalium single-photon emission computed tomography perfusion studies, 6-min-walk test and myocardial perfusion reserve index. Implantation failed in 4 of 196 (2%) patients and 5 patients (2.5%) had a complication during 30-day follow-up.
CONCLUSIONS
The CS reducer is a promising treatment option for patients with refractory angina who are not candidates for revascularization. However, larger randomized control trials with long-term follow-up are needed to elucidate its role.
Topics: Aged; Angina Pectoris; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Coronary Sinus; Endovascular Procedures; Female; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 30191622
DOI: 10.1111/joic.12560 -
Anatolian Journal of Cardiology Jun 2018
Topics: Aged; Cardiotonic Agents; Coronary Angiography; Diagnosis, Differential; Dobutamine; Electrocardiography; Female; Humans; Takotsubo Cardiomyopathy
PubMed: 29848925
DOI: 10.14744/AnatolJCardiol.2018.78642 -
The Cochrane Database of Systematic... Jan 2018Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery are life-threatening conditions. While there is a broad body of evidence for the treatment of people with acute coronary syndrome under stable haemodynamic conditions, the treatment strategies for people who become haemodynamically unstable or develop CS remain less clear. We have therefore summarised here the evidence on the treatment of people with CS or LCOS with different inotropic agents and vasodilative drugs. This is the first update of a Cochrane review originally published in 2014.
OBJECTIVES
To assess efficacy and safety of cardiac care with positive inotropic agents and vasodilator strategies in people with CS or LCOS due to AMI, HF or cardiac surgery.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in June 2017. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials in people with myocardial infarction, heart failure or cardiac surgery complicated by cardiogenic shock or LCOS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified 13 eligible studies with 2001 participants (mean or median age range 58 to 73 years) and two ongoing studies. We categorised studies into eight comparisons, all against cardiac care and additional other active drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo, epinephrine versus norepinephrine-dobutamine, amrinone versus dobutamine, dopexamine versus dopamine, enoximone versus dopamine and nitric oxide versus placebo.All trials were published in peer-reviewed journals, and analysis was done by the intention-to-treat (ITT) principle. Twelve of 13 trials were small with few included participants. Acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements emerged in five of 13 trials. In general, confidence in the results of analysed studies was reduced due to serious study limitations, very serious imprecision or indirectness. Domains of concern, which show a high risk of more than 50%, include performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events.Levosimendan may reduce short-term mortality compared to a therapy with dobutamine (RR 0.60, 95% CI 0.37 to 0.95; 6 studies; 1776 participants; low-quality evidence; NNT: 16 (patients with moderate risk), NNT: 5 (patients with CS)). This initial short-term survival benefit with levosimendan vs. dobutamine is not confirmed on long-term follow up. There is uncertainty (due to lack of statistical power) as to the effect of levosimendan compared to therapy with placebo (RR 0.48, 95% CI 0.12 to 1.94; 2 studies; 55 participants, very low-quality evidence) or enoximone (RR 0.50, 95% CI 0.22 to 1.14; 1 study; 32 participants, very low-quality evidence).All comparisons comparing other positive inotropic, inodilative or vasodilative drugs presented uncertainty on their effect on short-term mortality with very low-quality evidence and based on only one RCT. These single studies compared epinephrine with norepinephrine-dobutamine (RR 1.25, 95% CI 0.41 to 3.77; 30 participants), amrinone with dobutamine (RR 0.33, 95% CI 0.04 to 2.85; 30 participants), dopexamine with dopamine (no in-hospital deaths from 70 participants), enoximone with dobutamine (two deaths from 40 participants) and nitric oxide with placebo (one death from three participants).
AUTHORS' CONCLUSIONS
Apart from low quality of evidence data suggesting a short-term mortality benefit of levosimendan compared with dobutamine, at present there are no robust and convincing data to support a distinct inotropic or vasodilator drug-based therapy as a superior solution to reduce mortality in haemodynamically unstable people with cardiogenic shock or LCOS.Considering the limited evidence derived from the present data due to a generally high risk of bias and imprecision, it should be emphasised that there remains a great need for large, well-designed randomised trials on this topic to close the gap between daily practice in critical care medicine and the available evidence. It seems to be useful to apply the concept of 'early goal-directed therapy' in cardiogenic shock and LCOS with early haemodynamic stabilisation within predefined timelines. Future clinical trials should therefore investigate whether such a therapeutic concept would influence survival rates much more than looking for the 'best' drug for haemodynamic support.
Topics: Aged; Cardiac Output, Low; Cardiotonic Agents; Cause of Death; Dobutamine; Enoximone; Humans; Hydrazones; Middle Aged; Myocardial Infarction; Nitric Oxide; Pyridazines; Randomized Controlled Trials as Topic; Shock, Cardiogenic; Simendan; Vasodilator Agents
PubMed: 29376560
DOI: 10.1002/14651858.CD009669.pub3 -
World Journal For Pediatric &... Jan 2018Inotropes are frequently being used in children undergoing heart surgery to prevent or treat low cardiac output syndrome (LCOS). There is only limited evidence that... (Review)
Review
INTRODUCTION
Inotropes are frequently being used in children undergoing heart surgery to prevent or treat low cardiac output syndrome (LCOS). There is only limited evidence that inotropes actually positively influence postoperative outcome. Our aim was to describe the current international practice variation in the use of inotropes following congenital heart surgery.
METHODS
We developed an online survey regarding the postoperative use of inotropes. We sent an invitation to all 197 registered members of the Pediatric Cardiac Intensive Care Society (PCICS) to participate in the survey. We also performed a systematic review of the literature.
RESULTS
Ninety-eight people (50%) responded, representing 62 international centers. Milrinone is routinely used perioperatively by 90 respondents (97%). Adrenaline/epinephrine is routinely used by 43%, dopamine by 36%, dobutamine by 11%, and levosimendan by 6%. Steroids are used routinely by 54% before initiating cardiopulmonary bypass. Vasopressin is used by 44% of respondents. The development of LCOS is monitored with lactate in 99% of respondents, physical examination (98%), intermittent mixed venous saturation (76%), continuous mixed venous saturation (13%), echocardiography (53%), core-peripheral temperature gap (29%), near-infrared spectrometry (25%), and 4% use cardiac output monitors (PiCCO, USCOM). To improve cardiac output, 42% add/increase milrinone, 37% add adrenaline, and 15% add dopamine. Rescue therapy is titrated individually, based on the patients' pathophysiology. A systematic review of the literature failed to show compelling evidence with regard to the benefit of inotropes.
CONCLUSIONS
Despite the lack of sufficient evidence, milrinone is used by the vast majority of caregivers following congenital heart surgery.
Topics: Animals; Cardiac Output; Cardiac Output, Low; Cardiac Surgical Procedures; Cardiotonic Agents; Europe; Health Care Surveys; Heart Defects, Congenital; Humans; Pediatrics; Postoperative Care; United States
PubMed: 29092664
DOI: 10.1177/2150135117731725 -
BMC Cardiovascular Disorders Aug 2017The presence of left ventricular contractile reserve (LVCR) during stress echo (SE) may provide favorable response to cardiac resynchronization therapy (CRT) in heart... (Meta-Analysis)
Meta-Analysis Review
Left ventricular contractile reserve by stress echocardiography as a predictor of response to cardiac resynchronization therapy in heart failure: a systematic review and meta-analysis.
BACKGROUND
The presence of left ventricular contractile reserve (LVCR) during stress echo (SE) may provide favorable response to cardiac resynchronization therapy (CRT) in heart failure patients. The aim of the study was to perform a meta-analysis of available SE data in this set of patients.
METHODS
From a Pubmed and Advance Google Scholar database web based search scan up to December 2016, we initially identified 5906 records. From this initial set, we removed that did not include SE and duplicate studies. We assessed for eligibility 71 full-text articles assessed for eligibility, and 60 of them did not meet the inclusion criteria as follow: 1) heart failure patients with NYHA class III and IV, depressed ejection fraction (EF <35%) and QRS duration ≥120 ms at study entry; 2) SE with assessment of LVCR; 3) Follow-up data. LVCR during SE was identified as reduction in wall motion score index and/or an increase in EF.
RESULTS
Eleven studies with 861 patients (mean age 67 ± 9 years, ejection fraction 25 ± 6%) were included in the meta-analysis. The type of stress was either exercise (n = 2) or dobutamine (n = 9), the latter with low-dose (10 mcg) in two, intermediate-dose (20 mcg) in five, and high-dose (40 mcg) protocol in two studies. LVCR was detected in 555 patients (63%) and CRT-response was present in 584 (66%). The overall odds ratio for LVCR to predict a favorable CRT response was 2.06 (95%, CI 1.70-2-43), Z score: 11.055, p < 0.001.
CONCLUSION
The presence of LVCR during SE with either dobutamine or exercise is associated with a greater chance of response to CRT. This parameter is now ready to be tested in a prospective multicenter trial to select patients more likely to benefit from CRT.
Topics: Aged; Aged, 80 and over; Cardiac Resynchronization Therapy; Cardiotonic Agents; Dobutamine; Echocardiography, Stress; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Odds Ratio; Predictive Value of Tests; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left
PubMed: 28814264
DOI: 10.1186/s12872-017-0657-4 -
European Journal of Heart Failure Jul 2017To perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization... (Meta-Analysis)
Meta-Analysis Review
AIM
To perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure.
METHODS AND RESULTS
We searched MEDLINE/PubMed and Cochrane for all papers published up to 26 April 2016, supplemented by manual searches of reference lists from retrieved articles. The search strategy yielded nine observational studies that met our eligibility criteria with a total of 767 patients of which 757 provided data for this analysis. Contractile reserve after dobutamine infusion was present in 496 patients (66%). During follow-up 474 patients (63%) qualified as CRT responders. The presence of contractile reserve was associated with a higher chance of CRT response (odds ratio 4.42, 95% confidence interval 2.15-9.07, P < 0.001) using a random-effects model. There was evidence of publication bias. Imputation of missing studies attenuated the association to some extent, but the positive association between contractile reserve and CRT response remained with an odds ratio of 2.42 (95% confidence interval 1.17-5.05, P = 0.018).
CONCLUSION
The presence of global contractile reserve at baseline, as assessed by dobutamine stress echocardiography, is associated with a higher chance of CRT response in patients with heart failure.
Topics: Cardiac Resynchronization Therapy; Echocardiography, Stress; Heart Failure; Myocardial Contraction; Prognosis; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling
PubMed: 28233406
DOI: 10.1002/ejhf.768