Review And Update On Inotropes And Vasopressors PdfBy Ned C. In and pdf 12.05.2021 at 05:04 7 min read
File Name: review and update on inotropes and vasopressors .zip
Shock is a life-threatening, generalized state of circulatory failure resulting in the inability to deliver oxygen in peripheral tissues to meet their demands. More specifically, the state of shock is the result of one of the four following mechanisms.
- Current use and advances in vasopressors and inotropes support in shock
- Inotropes, vasopressors and other vasoactive agents
- Vasopressor therapy in critically ill patients with shock
- Review and update on inotropes and vasopressors: Evidence-based use in cardiovascular diseases
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education. He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. This site uses Akismet to reduce spam. Learn how your comment data is processed.
Current use and advances in vasopressors and inotropes support in shock
Shock is a life-threatening, generalized state of circulatory failure resulting in the inability to deliver oxygen in peripheral tissues to meet their demands. More specifically, the state of shock is the result of one of the four following mechanisms. The first one is the decrease of the venous return due to the loss of the circulating volume hemorrhagic shock 3. The second one is the inability of the heart to function as a pump due to the loss of contractility or abnormal electrical activity such as arrhythmias cardiogenic shock 4.
The third one is obstruction due to pulmonary embolism, tension pneumothorax and cardiac tamponade obstructive shock 1. The fourth one is loss of vascular tone due to maldistribution of blood septic, anaphylactic and neurogenic shock 5 - 7. As far as the shocked patient is concerned, the earlier the diagnosis, the better the outcome; it is of crucial importance to identify early the presence of the state of shock 8.
The skin decreased tissue perfusion , the kidneys decreased urine output and the brain impaired mental status are the most easily accessible organs to assess the state of shock. It should be noted that the Expert Panel Recommendations on circulatory shock and hemodynamic monitoring suggest that the determination of the type of shock leads to the most appropriate therapeutic interventions, improving survival rates 1. The main priority in shock is to maintain the hemodynamics of the patient until the cause of shock can be identified.
This is mainly achieved with fluid resuscitation, inotropic and vasopressor therapy 2 , 9. The purpose of this review is to address both the current use of vasopressors and inotropes support in shock thereby, offering a concise review of the pathophysiology behind shock alongside a helpful clinical reference tool for the emergency physician as well as to describe recent advances both experimental and clinical that could hold a critical role for the near future regarding patient management.
The physiological basis for their actions, apart from its direct effect on cardiac myocyte excitation and contraction, is characterized by changes in the homeostasis of the microvascular flow, alterations of the metabolic rate through the production of metabolically active molecules and alterations in the state of activation of immune cells Vasopressors are a heterogeneous class of drugs with powerful and immediate hemodynamic effects that increase the tone of the vascular system vasotonus and, therefore, mean arterial pressure MAP.
Restoration of adequate pressure is the criterion of their effectiveness; however, blood pressure BP does not always equate to blood flow. The relative potency of various vasopressors on cardiac heart rate and contractility and peripheral vasculature tone depends on receptor distribution and their corresponding affinity for them. Vasopressors can be classified according to their adrenergic and non-adrenergic actions Adrenergic agents include norepinephrine, phenylephrine, epinephrine, dopamine, dobutamine and isoproterenol.
Non-adrenergic agents include angiotensin II and nitric oxide NO inhibitors. Many drugs have both vasopressor and inotropic effects Vasopressors and inotropes act on alpha adrenergic, beta adrenergic, dopamine, calcium sensitizers and angiotensin receptors 11 , Alpha-1 adrenergic receptors are located in vascular walls and induce significant vasoconstriction. Alpha-1 adrenergic receptors are, also, located in the heart and can increase the duration of contraction without increasing chronotropy, that is the HR Beta-2 adrenergic receptors in vessels induce vasodilation Dopamine receptors are present in the cerebral, coronary, mesenteric and renal vascular beds.
When stimulated, they induce vasodilation. Dopamine receptor subtypes are responsible for norepinephrine release which causes vasoconstriction Some of these drugs increase the sensitivity of the myocardial contractile apparatus to calcium, leading to increase in inotropy and vasodilation 12 , Less frequent causes of cardiogenic shock secondary to AMI are mechanical complications, such as acquired ventricular septal defect, free wall rupture and papillary muscle rupture or dysfunction with subsequent acute ischemic mitral regurgitation.
Furthermore, acute right ventricular infarction might cause cardiogenic shock The SHOCK trial, one of the most popular trials regarding cardiogenic shock, suggested that early revascularization in AMI patients coronary artery bypass grafting, CABG or percutaneous coronary intervention, PCI , was accompanied by a lower rate of mortality when compared to the initial patient medical stabilization 4.
This is the reason why revascularization is considered the definitive treatment of patients with shock after AMI. The mechanical augmentation of cardiac function with intra-aortic balloon pump or left ventricular assisted devices LVADs should only be used as a temporary solution until definitive revascularization treatment Vasopressors are administered to raise BP and restore end-organ perfusion Inotropes are used as they increase myocardial contractility, thereby, increasing CO.
Often this kind of agents increase HR; subsequently, the increased myocardial oxygen consumption worsens the condition of the patient. Along with the positive inotropic properties, these drugs manifest peripheral vasoconstrictive and vasodilatory effects In general, vasopressor agents and inotropes should be used in clinical practice at the lowest doses and the shortest period possible. However, data from the Acute Decompensated Heart Failure National Registry revealed an increase in mortality due to the manifested precipitating myocardial ischemia and tachyarrhythmias Milrinone is a phosphodiesterase inhibitor that prevents the degradation of cyclic adenosine monophosphate cAMP.
It improves hemodynamics acutely; however, a concern exists regarding its long-term safety, as it has been correlated with new-onset atrial fibrillation and flutter and sustained hypotension. This is the rationale behind the use of milrinone only for patients with refractory cardiogenic shock The recommended doses are 0. Levosimendan is a calcium-sensitizing agent, which exerts positive inotropic effects on the heart by increasing the cardiac contractile apparatus sensitivity to calcium.
The SURVIVE randomized clinical trial that compared the efficacy between levosimendan and dobutamine in a total number of 1, patients revealed that levosimendan did not reduce the all-cause mortality compared to dobutamine alongside manifesting more peripheral vasodilating effects than dobutamine The recommended dose is 0. It also increases pulmonary vascular resistance and right ventricular afterload. It is rarely used in acute decompensated heart failure because it increases the myocardial oxygen demand leading to ischemia Norepinephrine increases systemic BP, pulse pressure, peripheral vascular resistance and SV.
In response to norepinephrine therapy, the CO is unchanged or decreased, and there is a compensatory vagal reflex that slows the HR. It is widely used as a first-line agent to increase BP and it is preferred rather than dopamine The recommended starting dose is from 0.
Dopamine is a catecholamine that is dose-dependent. At low doses, it causes vasodilation, especially in splanchnic and renal artery beds. At high doses, it promotes peripheral arterial and venous vasoconstriction. The SOAP II Investigators suggested that the patients with cardiogenic shock treated with dopamine had a higher day mortality rate compared to those treated with norepinephrine One of the leading causes of mortality in the world is trauma.
The main reason of death in these patients is uncontrolled hemorrhage The first step in the management of the hemorrhage is to control bleeding along with fluid volume resuscitation in order to maintain adequate end-organ perfusion.
However, an excessive amount of fluid administration can worsen hemorrhage. This vicious cycle is achieved due to the hemodilution of the coagulation factors leading to coagulopathy or due to hypothermia which precipitates coagulopathy as well The use of vasopressors in hemorrhagic shock has been a controversial issue for a long period.
On the contrary, vasopressors induce arteriolar vasoconstriction with subsequent alterations of the microcirculation leading to tissue hypoxia A retrospective study suggested that early vasopressor infusion in trauma patients increased the mortality rate independently of the trauma severity. The leading cause was low arterial pressure, increased fluid requirements and increased serum creatinine In the early stages of compensated hemorrhagic shock, the arterial pressure is maintained at adequate levels because of the compensatory sympathetic mechanisms that are activated, promoting venous and arterial vasoconstriction.
When this mechanism becomes overwhelmed, the sympathetic system is not activated anymore and, subsequently, peripheral vascular resistance is reduced Excessive NO production promotes vasodilation leading to vasoplegia Even though vasoplegia describes excessive vasodilation, the term vascular hyporesponsiveness to vasopressors describes better the vascular state in shock In this case, the use of vasopressors may be helpful.
Norepinephrine is the main first-line agent that is used due to its sympathomimetic properties. Inotropic support with dobutamine or epinephrine should be administered in the case of myocardial dysfunction which could be suspected if the patient does not respond in adequate fluid infusion and norepinephrine administration It should be noted that vasopressors should be administered along with adequate fluids because norepinephrine alone could lead to detrimental effects Sepsis is a life-threatening dysfunction of the vital organs caused by the inability of the host to respond to an infection.
Septic shock is a subset of sepsis accompanied by circulatory and cellular dysfunction that poses a life-threatening situation Similarly to other emergencies, early sepsis diagnosis and management improves outcomes. Data from recent studies suggested that early initiation of vasopressors could prevent sustained hypotension leading to decreased mortality Fluid therapy is the first-line management of septic shock. Fluid resuscitation should be initiated promptly but with caution because positive fluid balance could lead to higher mortality rates Thus, the use of norepinephrine in the first 2 hours of resuscitation could restrict the amount of fluid administration in the long-term management.
Individualization of the management algorithms for septic shock is considered the most appropriate step by taking into account the diastolic arterial pressure of the patient; the lower the diastolic arterial pressure, the earlier the initiation of vasopressors As suggested by the sepsis surviving campaign SSC , norepinephrine is the first vasopressor that should be administered in a case of septic shock Norepinephrine and its venoconstricting effects move blood from the veins to the circulation increasing the preload which is of critical importance in early stages of septic shock as it can be overfilled during fluid administration The MAP is the target for the resuscitation because it reflects the perfusion of the vital organs.
Increasing MAP with norepinephrine leads to significant increase in the tissue oxygen saturation StO 2 recovery slope a parameter that demonstrates the capacity of microvessels to be recruited in case of tissue hypoxia It has been postulated that an increase in MAP leads to increased peripheral microvascular blood flow. However, MAP is not always the most accurate parameter for the management of septic shock as often in sepsis there is dissociation between macrocirculation and microcirculation depending on the baseline characteristics of the patient i.
Norepinephrine is preferred rather than dopamine as recent studies have shown that the latter is responsible for tachyarrhythmias 44 ; it can be considered as an alternative solution only in highly selected patients with low risk of tachyarrhythmias or absolute bradycardia. A randomized control, double-blind clinical trial suggested that the use of epinephrine approximates the combined use of norepinephrine and dobutamine, but it demonstrated increased lactate levels in the peripheral tissues due to local ischemia Thus, epinephrine is considered as an adjunct agent to norepinephrine if the MAP is not adequately increased.
Vasopressin is an endogenous peptide hormone released by the neurohypophysis promoting non-adrenergic vasoconstriction, especially in sepsis-associated hypotension. In the early phases of shock, the endogenous vasopressin stores become depleted. Vasopressin is used as a catecholamine-sparing agent to reduce the levels of norepinephrine dosage Inotropic support in septic shock patients is used when there is evidence of myocardial dysfunction as suggested by low CO, increased filling pressures and persistent hypoperfusion despite optimal fluid resuscitation and use of vasopressors.
Besides, the dysregulated cardiac contractility is a mixture of altered cellular metabolism and autoregulatory mechanisms in the microvasculature of the heart per se Dobutamine is the first-line inotropic agent in septic patients as suggested by the SSC. Milrinone is recommended only in patients that are chronically beta-blocked or with chronic heart failure whose adrenergic receptors are desensitized Levosimendan is not currently used in septic shock.
Further investigations may shed light upon the use of agents that increase cytoplasmic calcium.
Inotropes, vasopressors and other vasoactive agents
This open-access and indexed, peer-reviewed journal publishes review articles ideal for the busy physician. Vasiliki Bistola ,. Angelos Arfaras-Melainis ,. Eftihia Polyzogopoulou ,. Ignatios Ikonomidis ,.
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Vasopressor therapy in critically ill patients with shock
Vasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation.
Metrics details. Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use. A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines.
Review and update on inotropes and vasopressors: Evidence-based use in cardiovascular diseases
Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Yesin and S. Karakoyun and Y. Patients in the intensive care unit frequently develop low-output syndromes due to cardiac dysfunction, myocardial injury and activation of inflammatory cascades. Pharmacological agents, including vasodilators, inotropes and vasopressors, are frequently used in the critical care setting for the management of unstable cardiac patients.
International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock. Systematic review and meta-analysis. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality.
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Metrics details. Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. A total of physicians from 82 countries responded.
The Portuguese Journal of Cardiology, the official journal of the Portuguese Society of Cardiology, was founded in with the aim of keeping Portuguese cardiologists informed through the publication of scientific articles on areas such as arrhythmology and electrophysiology, cardiovascular surgery, intensive care, coronary artery disease, cardiovascular imaging, hypertension, heart failure and cardiovascular prevention. The Journal is a monthly publication with high standards of quality in terms of scientific content and production. Since it has been published in English as well as Portuguese, which has widened its readership abroad. It is distributed to all members of the Portuguese Societies of Cardiology, Internal Medicine, Pneumology and Cardiothoracic Surgery, as well as to leading non-Portuguese cardiologists and to virtually all cardiology societies worldwide. It has been referred in Medline since The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years.
О принципе Бергофского Сьюзан узнала еще в самом начале своей карьеры.