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Intensive Care Medicine Jun 2018We set out to summarize the current knowledge on vasoactive drugs and their use in the management of shock to inform physicians' practices. (Review)
Review
PURPOSE
We set out to summarize the current knowledge on vasoactive drugs and their use in the management of shock to inform physicians' practices.
METHODS
This is a narrative review by a multidisciplinary, multinational-from six continents-panel of experts including physicians, a pharmacist, trialists, and scientists.
RESULTS AND CONCLUSIONS
Vasoactive drugs are an essential part of shock management. Catecholamines are the most commonly used vasoactive agents in the intensive care unit, and among them norepinephrine is the first-line therapy in most clinical conditions. Inotropes are indicated when myocardial function is depressed and dobutamine remains the first-line therapy. Vasoactive drugs have a narrow therapeutic spectrum and expose the patients to potentially lethal complications. Thus, these agents require precise therapeutic targets, close monitoring with titration to the minimal efficacious dose and should be weaned as promptly as possible. Moreover, the use of vasoactive drugs in shock requires an individualized approach. Vasopressin and possibly angiotensin II may be useful owing to their norepinephrine-sparing effects.
Topics: Cardiotonic Agents; Dobutamine; Humans; Intensive Care Units; Norepinephrine; Shock; Shock, Septic; Vasoconstrictor Agents
PubMed: 29868972
DOI: 10.1007/s00134-018-5242-5 -
The New England Journal of Medicine Oct 2014Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.
METHODS
In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.
RESULTS
Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.
CONCLUSIONS
In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).
Topics: Adult; Aged; Combined Modality Therapy; Critical Illness; Dobutamine; Emergency Service, Hospital; Erythrocyte Transfusion; Female; Fluid Therapy; Humans; Length of Stay; Male; Middle Aged; Renal Replacement Therapy; Respiration, Artificial; Shock, Septic; Survival Analysis; Vasoconstrictor Agents
PubMed: 25272316
DOI: 10.1056/NEJMoa1404380 -
Circulation May 2023Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness.
METHODS
EMPA-VISION (Assessment of Cardiac Energy Metabolism, Function and Physiology in Patients With Heart Failure Taking Empagliflozin) is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction ≤40%; New York Heart Association class ≥II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≥125 pg/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction ≥50%; New York Heart Association class ≥II; NT-proBNP ≥125 pg/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr/ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated.
RESULTS
Empagliflozin treatment did not change cardiac energetics (ie, PCr/ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin - placebo], -0.25 [95% CI, -0.58 to 0.09]; =0.14) or HFpEF (adjusted mean treatment difference, -0.16 [95% CI, -0.60 to 0.29]; =0.47]. Likewise, there were no changes in PCr/ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, -0.13 [95% CI, -0.35 to 0.09]; =0.23) or HFpEF (adjusted mean treatment difference, -0.22 [95% CI, -0.66 to 0.23]; =0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed.
CONCLUSIONS
In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT03332212.
Topics: Humans; Heart Failure; Stroke Volume; Ventricular Function, Left; Prospective Studies; Dobutamine; Energy Metabolism; Adenosine Triphosphate
PubMed: 37070436
DOI: 10.1161/CIRCULATIONAHA.122.062021 -
Veterinary Anaesthesia and Analgesia Nov 2022To determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with...
OBJECTIVE
To determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan.
STUDY DESIGN
Balanced, randomized crossover trial.
ANIMALS
A total of eight healthy Beagle dogs.
METHODS
Each dog was anaesthetized with isoflurane (end-tidal isoflurane 1.3%) and five treatments: dexmedetomidine hydrochloride (2.5 μg kg) bolus followed by 0.9% saline infusion (DEX-S); dexmedetomidine and vatinoxan hydrochloride (100 μg kg) bolus followed by an infusion of 0.9% saline (DEX-VAT-S), dobutamine (DEX-VAT-D), norepinephrine (DEX-VAT-N) or phenylephrine (DEX-VAT-P). The dexmedetomidine and vatinoxan boluses were administered at baseline (T0) and the treatment infusion was started after 15 minutes (T15) if mean arterial pressure (MAP) was < 90 mmHg. The treatment infusion rate was adjusted every 5 minutes as required. Systemic haemodynamics were recorded at T0 and 10 (T10) and 45 (T45) minutes. A repeated measures analysis of covariance model was used.
RESULTS
Most dogs had a MAP < 70 mmHg at T0 before treatment. Treatments DEX-S and DEX-VAT all significantly increased MAP at T10, but systemic vascular resistance index (SVRI) was significantly higher and cardiac index (CI) lower after DEX-S than after DEX-VAT. CI did not significantly differ between DEX-S and DEX-VAT-S at T45, while SVRI remained higher with DEX-S. Normotension was achieved by all vasoactive infusions in every dog, whereas MAP was below baseline with DEX-VAT-S, and higher than baseline with DEX-S at T45. Median infusion rates were 3.75, 0.25 and 0.5 μg kg minute for dobutamine, norepinephrine and phenylephrine, respectively. Dobutamine and norepinephrine increased CI (mean ± standard deviation, 3.35 ± 0.70 and 3.97 ± 1.24 L minute m, respectively) and decreased SVRI, whereas phenylephrine had the opposite effect (CI 2.13 ± 0.45 L minute m).
CONCLUSIONS AND CLINICAL RELEVANCE
Hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine.
Topics: Dogs; Animals; Isoflurane; Dexmedetomidine; Dobutamine; Anesthetics, Inhalation; Phenylephrine; Norepinephrine; Saline Solution; Blood Pressure; Hypotension; Dog Diseases
PubMed: 36058821
DOI: 10.1016/j.vaa.2022.07.007 -
Anaesthesiology Intensive Therapy 2022Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior...
INTRODUCTION
Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior mesenteric blood flow to different vasopressors with and without dobutamine.
MATERIAL AND METHODS
Thirty New Zealand rabbits were included and randomly allocated to 5 groups: group A - sham group; group B - norepinephrine; group C - norepinephrine plus dobutamine; group D - vasopressin; and group E - vasopressin plus dobutamine. Mean arterial pressure (MAP) target was greater than 60 mmHg. Endotoxic shock was induced by intra-venous injection of lipopolysaccharide (LPS) in four of the five groups. Aortic blood flow (Qao), superior mesenteric artery flow (QSMA) and lactate were measured after LPS injection. Enterocyte damage was evaluated by measurements of serum citrulline and intestinal fatty acid-binding protein (I-FABP) after 4 h.
RESULTS
The largest reduction in Qao occurred in group D (64 ± 17.3 to 38 ± 7.5 mL min-1; P = 0.04). QSMA also declined significantly in groups D and E and remained lower than in the other groups over 4 h (group D - baseline: 65 ± 31; 1 h: 37 ± 10; 2 h: 38 ± 10; 3 h: 46 ± 26; and 4 h: 48 ± 15 mL min-1; P < 0.005; group E - baseline: 73 ± 14; 1 h: 28 ± 4.0; 2 h: 37 ± 6.4; 3 h: 40 ± 11; and 4 h: 48 ± 11; P < 0.005; all in mL min-1). Serum citrulline was significantly lower in groups D (P = 0.014) and E (P = 0.019) in comparison to group A. The fluid administration regimen was similar in all groups.
CONCLUSIONS
Vasopressin seems to negatively impact gut enterocyte function during endotoxic shock despite the association of an inodilator and adequate fluid replacement.
Topics: Animals; Citrulline; Dobutamine; Hemodynamics; Humans; Lipopolysaccharides; Norepinephrine; Rabbits; Shock, Septic; Vasoconstrictor Agents; Vasopressins
PubMed: 35792110
DOI: 10.5114/ait.2022.117264 -
British Journal of Clinical Pharmacology Feb 2020To describe the pharmacokinetics (PK) and concentration-related effects of dobutamine in critically ill neonates in the first days of life, using nonlinear mixed effects...
AIMS
To describe the pharmacokinetics (PK) and concentration-related effects of dobutamine in critically ill neonates in the first days of life, using nonlinear mixed effects modelling.
METHODS
Dosing, plasma concentration and haemodynamic monitoring data from a dose-escalation study were analysed with a simultaneous population PK and pharmacodynamic model. Neonates receiving continuous infusion of dobutamine 5-20 μg kg min were included. Left ventricular ejection fraction (LVEF) and cardiac output of right and left ventricle (RVO, LVO) were measured on echocardiography; heart rate (HR), mean arterial pressure (MAP), peripheral arterial oxygen saturation and cerebral regional oxygen saturation were recorded from patient monitors.
RESULTS
Twenty-eight neonates with median (range) gestational age of 30.4 (22.7-41.0) weeks and birth weight (BW) of 1618 (465-4380) g were included. PK data were adequately described by 1-compartmental linear structural model. Dobutamine clearance (CL) was described by allometric scaling on BW with sigmoidal maturation function of postmenstrual age (PMA). The final population PK model parameter mean typical value (standard error) estimates, standardised to median BW of 1618 g, were 41.2 (44.5) L h for CL and 5.29 (0.821) L for volume of distribution, which shared a common between subject variability of 29% (17.2%). The relationship between dobutamine concentration and RVO/LVEF was described by linear model, between concentration and LVO/HR/MAP/cerebral fractional tissue oxygen extraction by sigmoidal E model.
CONCLUSION
In the postnatal transitional period, PK of dobutamine was described by a 1-compartmental linear model, CL related to BW and PMA. A concentration-response relationship with haemodynamic variables has been established.
Topics: Cardiac Output; Dobutamine; Gestational Age; Humans; Infant; Infant, Newborn; Stroke Volume; Ventricular Function, Left
PubMed: 31657867
DOI: 10.1111/bcp.14146 -
Revista Brasileira de Terapia Intensiva 2017Dobutamine is the inotrope most commonly used in septic shock patients to increase cardiac output and correct hypoperfusion. Although some experimental and clinical... (Review)
Review
Dobutamine is the inotrope most commonly used in septic shock patients to increase cardiac output and correct hypoperfusion. Although some experimental and clinical studies have shown that dobutamine can improve systemic and regional hemodynamics, other research has found that its effects are heterogenous and unpredictable. In this review, we analyze the pharmacodynamic properties of dobutamine and its physiologic effects. Our goal is to show that the effects of dobutamine might differ between healthy subjects, in experimental and clinical cardiac failure, in animal models and in patients with septic shock. We discuss evidence supporting the claim that dobutamine, in septic shock, frequently behaves as a chronotropic and vasodilatory drug, without evidence of inotropic action. Since the side effects are very common, and the therapeutic benefits are unclear, we suggest that dobutamine should be used cautiously in septic shock. Before a definitive therapeutic decision, the efficacy and tolerance of dobutamine should be assessed during a brief time with close monitoring of its positive and negative side effects.
Topics: Animals; Cardiac Output; Cardiotonic Agents; Dobutamine; Drug Monitoring; Hemodynamics; Humans; Shock, Septic
PubMed: 29340539
DOI: 10.5935/0103-507X.20170068 -
JACC. Clinical Electrophysiology Dec 2020
Topics: Atrial Fibrillation; Catheter Ablation; Dobutamine; Humans; Isoproterenol; Pulmonary Veins
PubMed: 33334451
DOI: 10.1016/j.jacep.2020.08.037 -
International Journal of Molecular... Jul 2021The occurrence and prevalence of heart failure remain high in the United States as well as globally. One person dies every 30 s from heart disease. Recognizing the... (Review)
Review
The occurrence and prevalence of heart failure remain high in the United States as well as globally. One person dies every 30 s from heart disease. Recognizing the importance of heart failure, clinicians and scientists have sought better therapeutic strategies and even cures for end-stage heart failure. This exploration has resulted in many failed clinical trials testing novel classes of pharmaceutical drugs and even gene therapy. As a result, along the way, there have been paradigm shifts toward and away from differing therapeutic approaches. The continued prevalence of death from heart failure, however, clearly demonstrates that the heart is not simply a pump and instead forces us to consider the complexity of simplicity in the pathophysiology of heart failure and reinforces the need to discover new therapeutic approaches.
Topics: Adenosine Triphosphatases; Adrenergic beta-1 Receptor Agonists; Adrenergic beta-Antagonists; Animals; Antioxidants; Ca(2+) Mg(2+)-ATPase; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiotonic Agents; Dobutamine; Heart Failure; Humans; Myocardial Contraction; Sarcoplasmic Reticulum
PubMed: 34299010
DOI: 10.3390/ijms22147392 -
BMC Pharmacology & Toxicology Nov 2020To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry.
METHODS
We conducted a single-center, prospective randomized study in 16 healthy subjects each receiving an infusion of dobutamine sufficient to increase heart rate by 30 bpm followed by a 60 min infusion of 10 μg/kg/min landiolol.
RESULTS
Dobutamine-induced increases in heart rate were stable for at least 20 min before a 60 min landiolol- infusion was started. The dobutamine effects were rapidly antagonized by landiolol within 16 min. A further slight decrease in heart rate during 20-60 min of the landiolol infusion occurred as well. Upon termination of landiolol infusion, heart rate and blood pressure recovered rapidly in response to the persisting dobutamine infusion but did not return to the maximum values before landiolol infusion. The pharmacokinetic parameters of landiolol in presence of dobutamine showed a short half-life (3.5 min) and a low distribution volume (0.3 l/kg). No serious adverse events were observed.
CONCLUSION
Landiolol can antagonize the dobutamine-induced increases in heart rate and blood pressure in a fast way. A rapid bradycardic effect until steady-state plasma levels is followed by a slow heart rate reduction. The latter can be attributed to an early desensitization to dobutamine. Consequently, after termination of landiolol, the heart rate did not achieve maximum pre-landiolol values. The pharmacokinetics of landiolol during dobutamine infusion are similar when compared to short- and long-term data in Caucasian subjects. Landiolol in the given dose can thus serve as an antagonist of dobutamine-induced cardiac effects.
TRIAL REGISTRATION
Registration number 2010-023311-34 at the EU Clinical Trials Register, registration date 2010-12-21.
Topics: Adrenergic beta-Antagonists; Adult; Blood Pressure; Cardiotonic Agents; Cross-Over Studies; Dobutamine; Double-Blind Method; Female; Healthy Volunteers; Heart Rate; Humans; Infusions, Intravenous; Male; Morpholines; Prospective Studies; Urea; Young Adult
PubMed: 33239108
DOI: 10.1186/s40360-020-00462-x