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Current Cardiology Reviews 2019The management of patients with shock is extremely challenging because of the myriad of possible clinical presentations in cardiogenic shock, septic shock and... (Review)
Review
The management of patients with shock is extremely challenging because of the myriad of possible clinical presentations in cardiogenic shock, septic shock and hypovolemic shock and the limitations of contemporary therapeutic options. The treatment of shock includes the administration of endogenous catecholamines (epinephrine, norepinephrine, and dopamine) as well as various vasopressor agents that have shown efficacy in the treatment of the various types of shock. In addition to the endogenous catecholamines, dobutamine, isoproterenol, phenylephrine, and milrinone have served as the mainstays of shock therapy for several decades. Recently, experimental studies have suggested that newer agents such as vasopressin, selepressin, calcium-sensitizing agents like levosimendan, cardiac-specific myosin activators like omecamtiv mecarbil (OM), istaroxime, and natriuretic peptides like nesiritide can enhance shock therapy, especially when shock presents a more complex clinical picture than normal. However, their ability to improve clinical outcomes remains to be proven. It is the purpose of this review to describe the mechanism of action, dosage requirements, advantages and disadvantages, and specific indications and contraindications for the use of each of these catecholamines and vasopressors, as well as to elucidate the most important clinical trials that serve as the basis of contemporary shock therapy.
Topics: Humans; Shock; Shock, Cardiogenic; Shock, Septic; Vasoconstrictor Agents
PubMed: 30543176
DOI: 10.2174/1573403X15666181212125024 -
EBioMedicine Dec 2022Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response.... (Review)
Review
Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response. Each aspect should be considered in all patients and, when relevant, managed at the same time. Infection control is applicable to all patients with sepsis and will include antibiotic therapy and often surgical intervention to remove an infectious source. Haemodynamic support involves fluid administration in all patients and vasoactive agents in patients with associated circulatory shock. Noradrenaline is the first choice vasopressor agent; inotropic agents, usually dobutamine, may be added in case of myocardial depression. No interventions directed at individual components of the host response to sepsis have yet been shown to improve outcomes, but glucocorticoids and vasopressin have a global impact on the response and can thus be considered in this category. A move toward more personalized treatment is needed across all three arms of sepsis management.
Topics: Humans; Shock, Septic; Sepsis; Vasoconstrictor Agents; Hemodynamics; Anti-Bacterial Agents
PubMed: 36470828
DOI: 10.1016/j.ebiom.2022.104318 -
The New England Journal of Medicine Feb 2023Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.
METHODS
In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed.
RESULTS
A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups.
CONCLUSIONS
Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).
Topics: Humans; Fluid Therapy; Sepsis; Hypotension; Time Factors; Treatment Outcome; Vasoconstrictor Agents
PubMed: 36688507
DOI: 10.1056/NEJMoa2212663 -
Internal and Emergency Medicine Sep 2021Early management of sepsis and septic shock is crucial for patients' prognosis. As the Emergency Department (ED) is the place where the first medical contact for septic... (Review)
Review
Early management of sepsis and septic shock is crucial for patients' prognosis. As the Emergency Department (ED) is the place where the first medical contact for septic patients is likely to occur, emergency physicians play an essential role in the early phases of patient management, which consists of accurate initial diagnosis, resuscitation, and early antibiotic treatment. Since the issuing of the Surviving Sepsis Campaign guidelines in 2016, several studies have been published on different aspects of sepsis management, adding a substantial amount of new information on the pathophysiology and treatment of sepsis and septic shock. In light of this emerging evidence, the present narrative review provides a comprehensive account of the recent advances in septic patient management in the ED.
Topics: Anti-Bacterial Agents; Disease Management; Emergency Service, Hospital; Fluid Therapy; Humans; Monitoring, Physiologic; Resuscitation; Sepsis; Shock, Septic; Vasoconstrictor Agents
PubMed: 33890208
DOI: 10.1007/s11739-021-02735-7 -
The New England Journal of Medicine Mar 2010Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other.
METHODS
In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events.
RESULTS
The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses).
CONCLUSIONS
Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)
Topics: Aged; Arrhythmias, Cardiac; Combined Modality Therapy; Dopamine; Female; Fluid Therapy; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Norepinephrine; Shock; Vasoconstrictor Agents
PubMed: 20200382
DOI: 10.1056/NEJMoa0907118 -
Emergency Medicine Australasia : EMA Apr 2020Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of...
OBJECTIVE
Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of vasoconstrictive medications. Recent studies have suggested that vasopressor administration via peripheral intravenous catheters (PiVCs) may be a feasible and safe alternative. This systematic review evaluates the safety of delivering vasopressor medications via PiVCs.
METHODS
We performed a systematic review to assess the frequency of complications associated with the delivery of vasopressors via PiVCs. A literature search for prospective and retrospective studies of vasopressor infusions in adults was performed. We included studies of continuous infusions of vasopressor medications (noradrenaline, adrenaline, metaraminol, phenylephrine, dopamine and vasopressin) delivered via a PiVCs that included at least 20 patients. Data on patient factors, cannulation approach, monitoring protocols, vasopressor dosing and dilutions and adverse events were collected and summarised.
RESULTS
Seven studies were identified that fulfilled the inclusion criteria, including 1382 patients. No study fulfilled all of the validity criteria. Noradrenaline was the most commonly administered agent (n = 702 episodes of administration), followed by phenylephrine (n = 546), dopamine (n = 108), metaraminol (n = 74) and vasopressin and adrenaline (<5 patients). Mean duration of infusion was 22 h (95% confidence interval [CI] 8-36 h). Extravasation occurred in 3.4% (95% CI 2.5-4.7%) of patients. There were no reported episodes of tissue necrosis or limb ischaemia. All extravasation events were successfully managed conservatively or with vasodilatory medications.
CONCLUSIONS
Reports of the administration of vasopressors via PiVCs, when given for a limited duration, under close observation, suggest that extravasation is uncommon and is unlikely to lead to major complications.
Topics: Adult; Catheterization, Peripheral; Humans; Hypotension; Prospective Studies; Retrospective Studies; Vasoconstrictor Agents
PubMed: 31698544
DOI: 10.1111/1742-6723.13406 -
Revista Portuguesa de Cardiologia :... Dec 2016Cardiogenic shock is characterized by a decrease in myocardial contractility, and presents a high mortality rate. Inotropic and vasopressor agents have been recommended... (Review)
Review
Cardiogenic shock is characterized by a decrease in myocardial contractility, and presents a high mortality rate. Inotropic and vasopressor agents have been recommended and used for several years in the treatment of patients in shock, but they remain controversial. Despite its beneficial effect on myocardial contractility, the side effects of inotropic therapy (arrhythmias and increased myocardial oxygen consumption) may be associated with increased mortality. The pharmacodynamics of different inotropic agents suggest benefits in specific situations, but these differences have not been reflected in reduced mortality in most studies, making it difficult to formulate recommendations. This review integrates data from different studies on the use of inotropes and vasopressors in patients with cardiogenic shock, proposing a therapeutic scheme for the pharmacological treatment of patients in cardiogenic shock according to the patient's hemodynamic profile.
Topics: Cardiotonic Agents; Hemodynamics; Humans; Myocardial Contraction; Shock, Cardiogenic; Vasoconstrictor Agents
PubMed: 27836218
DOI: 10.1016/j.repc.2016.08.004 -
Journal of the American Heart... Aug 2023Cardiogenic shock is characterized by tissue hypoxia caused by circulatory failure arising from inadequate cardiac output. In addition to treating the pathologic process... (Review)
Review
Cardiogenic shock is characterized by tissue hypoxia caused by circulatory failure arising from inadequate cardiac output. In addition to treating the pathologic process causing impaired cardiac function, prompt hemodynamic support is essential to reduce the risk of developing multiorgan dysfunction and to preserve cellular metabolism. Pharmacologic therapy with the use of vasopressors and inotropes is a key component of this treatment strategy, improving perfusion by increasing cardiac output, altering systemic vascular resistance, or both, while allowing time and hemodynamic stability to treat the underlying disease process implicated in the development of cardiogenic shock. Despite the use of mechanical circulatory support recently garnering significant interest, pharmacologic hemodynamic support remains a cornerstone of cardiogenic shock management, with over 90% of patients receiving at least 1 vasoactive agent. This review aims to describe the pharmacology and hemodynamic effects of current pharmacotherapies and provide a practical approach to their use, while highlighting important future research directions.
Topics: Humans; Shock, Cardiogenic; Vasoconstrictor Agents; Hemodynamics; Vascular Resistance; Perfusion
PubMed: 37489740
DOI: 10.1161/JAHA.123.029787 -
Critical Care (London, England) Feb 2018Vasoplegia is a ubiquitous phenomenon in all advanced shock states, including septic, cardiogenic, hemorrhagic, and anaphylactic shock. Its pathophysiology is complex,... (Review)
Review
Vasoplegia is a ubiquitous phenomenon in all advanced shock states, including septic, cardiogenic, hemorrhagic, and anaphylactic shock. Its pathophysiology is complex, involving various mechanisms in vascular smooth muscle cells such as G protein-coupled receptor desensitization (adrenoceptors, vasopressin 1 receptors, angiotensin type 1 receptors), alteration of second messenger pathways, critical illness-related corticosteroid insufficiency, and increased production of nitric oxide. This review, based on a critical appraisal of the literature, discusses the main current treatments and future approaches. Our improved understanding of these mechanisms is progressively changing our therapeutic approach to vasoplegia from a standardized to a personalized multimodal treatment with the prescription of several vasopressors. While norepinephrine is confirmed as first line therapy for the treatment of vasoplegia, the latest Surviving Sepsis Campaign guidelines also consider that the best therapeutic management of vascular hyporesponsiveness to vasopressors could be a combination of multiple vasopressors, including norepinephrine and early prescription of vasopressin. This new approach is seemingly justified by the need to limit adrenoceptor desensitization as well as sympathetic overactivation given its subsequent deleterious impacts on hemodynamics and inflammation. Finally, based on new pathophysiological data, two potential drugs, selepressin and angiotensin II, are currently being evaluated.
Topics: Adrenal Cortex Hormones; Adrenergic alpha-Agonists; Humans; Norepinephrine; Shock; Vasoconstrictor Agents; Vasoplegia
PubMed: 29486781
DOI: 10.1186/s13054-018-1967-3 -
The Western Journal of Emergency... Feb 2021Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.
METHODS
We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.
RESULTS
We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.
CONCLUSION
In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.
Topics: Humans; Intensive Care Units; Length of Stay; Norepinephrine; Shock, Septic; Vasoconstrictor Agents
PubMed: 33856300
DOI: 10.5811/westjem.2020.10.47825