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Journal of Cardiovascular Pharmacology... May 2015This paper summarizes the pharmacologic properties of vasoactive medications used in the treatment of shock, including the inotropes and vasopressors. The clinical... (Review)
Review
This paper summarizes the pharmacologic properties of vasoactive medications used in the treatment of shock, including the inotropes and vasopressors. The clinical application of these therapies is discussed and recent studies describing their use and associated outcomes are also reported. Comprehension of hemodynamic principles and adrenergic and non-adrenergic receptor mechanisms are salient to the appropriate therapeutic utility of vasoactive medications for shock. Vasoactive medications can be classified based on their direct effects on vascular tone (vasoconstriction or vasodilation) and on the heart (presence or absence of positive inotropic effects). This classification highlights key similarities and differences with respect to pharmacology and hemodynamic effects. Vasopressors include pure vasoconstrictors (phenylephrine and vasopressin) and inoconstrictors (dopamine, norepinephrine, and epinephrine). Each of these medications acts as vasopressors to increase mean arterial pressure by augmenting vascular tone. Inotropes include inodilators (dobutamine and milrinone) and the aforementioned inoconstrictors. These medications act as inotropes by enhancing cardiac output through enhanced contractility. The inodilators also reduce afterload from systemic vasodilation. The relative hemodynamic effect of each agent varies depending on the dose administered, but is particularly apparent with dopamine. Recent large-scale clinical trials have evaluated vasopressors and determined that norepinephrine may be preferred as a first-line therapy for a broad range of shock states, most notably septic shock. Consequently, careful selection of vasoactive medications based on desired pharmacologic effects that are matched to the patient's underlying pathophysiology of shock may optimize hemodynamics while reducing the potential for adverse effects.
Topics: Cardiotonic Agents; Dobutamine; Hemodynamics; Humans; Intensive Care Units; Milrinone; Receptors, Adrenergic; Shock; Vasoconstrictor Agents
PubMed: 25432872
DOI: 10.1177/1074248414559838 -
Current Opinion in Critical Care Aug 2019Data and interventional trials regarding vasopressor and inotrope use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of... (Review)
Review
PURPOSE OF REVIEW
Data and interventional trials regarding vasopressor and inotrope use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of solid evidence regarding their effectiveness in improving outcomes. In this article, we review the current use of vasopressor and inotrope agents during cardiogenic shock.
RECENT FINDINGS
Two recent Cochrane analyses concluded that there was not sufficient evidence to prove that any one vasopressor or inotrope was superior to another in terms of mortality. A recent RCT and a meta-analysis on individual data suggested that norepinephrine may be preferred over epinephrine in patients with cardiogenic shock . For inotrope agents, when norepinephrine fails to restore perfusion, dobutamine represents the first-line agent. Levosimendan is a calcium sensitizer agent, which improves acute hemodynamics, albeit with uncertain effects on mortality.
SUMMARY
When blood pressure needs to be restored, norepinephrine is a reasonable first-line agent. Dobutamine is the first-line inotrope agent wheraes levosimendan can be used as a second-line agent or preferentially in patients previously treated with beta-blockers. Current information regarding comparative effective outcomes is nonetheless sparse and their use should be limited as a temporary bridge to recovery, mechanical circulatory support or heart transplantation.
Topics: Cardiotonic Agents; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Shock, Cardiogenic; Vasoconstrictor Agents
PubMed: 31166204
DOI: 10.1097/MCC.0000000000000632 -
Current Opinion in Critical Care Aug 2021To discuss the use of vasopressors and inotropes in cardiogenic shock. (Review)
Review
PURPOSE OF REVIEW
To discuss the use of vasopressors and inotropes in cardiogenic shock.
RECENT FINDINGS
The classic form or cardiogenic shock requires administration of inotropic and/or vasopressor agents to try to improve the impaired tissue perfusion. Among vasopressors various alpha-adrenergic agents, vasopressin derivatives and angiotensin can be used. The first-line therapy remains norepinephrine as it is associated with minimal adverse effects and appears to be associated by the best outcome in network meta-analyses. On the contrary, epinephrine is associated with an increased incidence of refractory shock and observational studies suggest an increased risk of death. Vasopressin may be an excellent alternative in tachycardiac patients or in the presence of pulmonary hypertension. Concerning inotropic agents, dobutamine is the first-line agent but levosimendan is an excellent alternative or additional agent in cases not responding to dobutamine. The impact on outcome of inotropic agents remains controversial.
SUMMARY
Recent studies have refined the position of the various vasopressor and inotropic agents. Norepinephrine is recommended as first-line vasopressor agent by various guidelines. Among inotropic agents, selection between the agents should be individualized and based on the hemodynamic response.
Topics: Cardiotonic Agents; Cardiovascular Agents; Dobutamine; Humans; Shock; Shock, Cardiogenic; Vasoconstrictor Agents
PubMed: 33797431
DOI: 10.1097/MCC.0000000000000822 -
Nature Medicine Nov 2018Sepsis is the third leading cause of death worldwide and the main cause of mortality in hospitals, but the best treatment strategy remains uncertain. In particular,...
Sepsis is the third leading cause of death worldwide and the main cause of mortality in hospitals, but the best treatment strategy remains uncertain. In particular, evidence suggests that current practices in the administration of intravenous fluids and vasopressors are suboptimal and likely induce harm in a proportion of patients. To tackle this sequential decision-making problem, we developed a reinforcement learning agent, the Artificial Intelligence (AI) Clinician, which extracted implicit knowledge from an amount of patient data that exceeds by many-fold the life-time experience of human clinicians and learned optimal treatment by analyzing a myriad of (mostly suboptimal) treatment decisions. We demonstrate that the value of the AI Clinician's selected treatment is on average reliably higher than human clinicians. In a large validation cohort independent of the training data, mortality was lowest in patients for whom clinicians' actual doses matched the AI decisions. Our model provides individualized and clinically interpretable treatment decisions for sepsis that could improve patient outcomes.
Topics: Administration, Intravenous; Artificial Intelligence; Clinical Decision-Making; Cohort Studies; Critical Care; Female; Humans; Learning; Male; Sepsis; Software; Vasoconstrictor Agents
PubMed: 30349085
DOI: 10.1038/s41591-018-0213-5 -
Chest Nov 2023This review discusses the rationale for vasopressin use, summarizes the results of clinical trials evaluating vasopressin, and focuses on the timing of vasopressin... (Review)
Review
TOPIC IMPORTANCE
This review discusses the rationale for vasopressin use, summarizes the results of clinical trials evaluating vasopressin, and focuses on the timing of vasopressin initiation to provide clinicians guidance for optimal adjunctive vasopressin initiation in patients with septic shock.
REVIEW FINDINGS
Patients with septic shock require vasoactive agents to restore adequate tissue perfusion. After norepinephrine, vasopressin is the suggested second-line adjunctive agent in patients with persistent inadequate mean arterial pressure. Vasopressin use in practice is heterogeneous likely because of inconsistent clinical trial findings, the lack of specific recommendations for when it should be used, and the high drug acquisition cost. Despite these limitations, vasopressin has demonstrated price inelastic demand, and its use in the United States has continued to increase. However, questions remain regarding optimal vasopressin use in patients with septic shock, particularly regarding patient selection and the timing of vasopressin initiation.
SUMMARY
Experimental studies evaluating the initiation timing of vasopressin in patients with septic shock are limited, and recent observational studies have revealed an association between vasopressin initiation at lower norepinephrine-equivalent doses or lower lactate concentrations and lower mortality.
Topics: Humans; United States; Vasoconstrictor Agents; Shock, Septic; Vasopressins; Norepinephrine; Arterial Pressure
PubMed: 37479058
DOI: 10.1016/j.chest.2023.07.009 -
Expert Review of Clinical Pharmacology Aug 2022Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors... (Review)
Review
INTRODUCTION
Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB), and hydroxocobalamin can be added to maintain blood pressure.
AREAS COVERED
VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP.
EXPERT OPINION
Evidence supporting additional vasopressor agents in catecholamine-resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor, is used in VS to maintain adequate MAP. MB and/or hydroxocobalamin, vitamin C, thiamine, and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given.
Topics: Angiotensin II; Ascorbic Acid; Cardiotonic Agents; Catecholamines; Cytomegalovirus Infections; Dobutamine; Humans; Hydroxocobalamin; Methylene Blue; Milrinone; Shock; Shock, Septic; Thiamine; Vasoconstrictor Agents; Vasopressins
PubMed: 35920615
DOI: 10.1080/17512433.2022.2110067 -
Intensive Care Medicine Oct 2020ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.
PURPOSE
ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.
METHODS
In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.
RESULTS
Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02).
CONCLUSION
Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.
Topics: Adult; Australia; Humans; Hypotension; Intensive Care Units; Midodrine; Vasoconstrictor Agents
PubMed: 32885276
DOI: 10.1007/s00134-020-06216-x -
Archives of Disease in Childhood. Fetal... Jul 2021In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary... (Review)
Review
In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary shunts (patent ductus arteriosus and patent foramen value) allow for right-to-left shunting and hypoxaemia. Systemic hypotension can occur in newborns with PPHN due to variety of reasons, such as enhanced peripheral vasodilation, impaired left ventricular function and decreased preload. Systemic hypotension can lead to end organ injury from poor perfusion and hypoxaemia in the newborn with PPHN. Thus, it must be managed swiftly. However, not all newborns with PPHN and systemic hypotension can be managed the same way. Individualised approach based on physiology and echocardiographic findings are necessary to improve perfusion to essential organs. Here we present a review of the physiology and mechanisms of systemic hypotension in PPHN, which can then guide treatment.
Topics: Blood Pressure Monitors; Extracorporeal Membrane Oxygenation; Fluid Therapy; Hemodynamics; Humans; Hypotension; Infant, Newborn; Persistent Fetal Circulation Syndrome; Practice Guidelines as Topic; Vasoconstrictor Agents
PubMed: 33478959
DOI: 10.1136/archdischild-2020-319705 -
Critical Care (London, England) Jan 2023Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line... (Review)
Review
Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.
Topics: Humans; Norepinephrine; Shock, Septic; Shock; Vasoconstrictor Agents; Vasopressins; Critical Care
PubMed: 36670410
DOI: 10.1186/s13054-023-04322-y -
Clinics in Liver Disease May 2022Hepatorenal syndrome (HRS) is defined as a functional renal failure without major histologic changes in individuals with severe liver disease and it is associated with a... (Review)
Review
Hepatorenal syndrome (HRS) is defined as a functional renal failure without major histologic changes in individuals with severe liver disease and it is associated with a high mortality rate. Renal hypoperfusion due to marked vasoconstriction as a result of complex circulatory dysfunction has been suggested to be the cornerstone of HRS. Splanchnic and peripheral arterial vasodilation and cirrhotic cardiomyopathy result in effective arterial hypovolemia and compensatory activation of vasoconstrictor mechanisms. The efficacy of current therapeutic strategies targeting this circulatory dysfunction is limited. Increasing evidence suggests a substantial role of systemic inflammation in HRS via either vascular or direct renal effects. Here we summarize the current understanding of HRS pathophysiology.
Topics: Female; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Male; Vasoconstrictor Agents; Vasodilation
PubMed: 35487603
DOI: 10.1016/j.cld.2022.01.013