Vasopressor Choice and Timing in Vasodilatory Shock

General Reanimatology

Septic shock, as the most severe form of sepsis, is characterized by high mortality reaching 40% despite the use of the most modern standards of diagnosis and treatment. In the thanatogenesis of septic shock, vasoplegia plays a leading role, respectively, and therapy of the condition under discussion involves the use of vasoconstrictors, along with the standard prescription of infusion therapy, antibiotics and symptomatic treatment. The choice of a specific vasoactive drug is a difficult task for a practicing anesthetist, as along with undoubtedly positive properties, vasoconstrictors each have their own spectrum of undesirable side effects, which, of course, must be taken into account when determining treatment tactics.The aim of review: A comprehensive assessment of the multifactorial effect of various vasoconstrictors on the patient to determine the criteria for choosing the optimal drug (or a combination of drugs) in septic shock.The search was carried out using PubMed and Scopu...

Clinical and Experimental Emergency Medicine

Journal of Pediatric Critical Care

Mean Arterial Pressure (MAP)-Central venous pressure (CVP) (MM of Hg) Term Newborn 120 to 180 55 Up To 1 year 120 to 180 60 Up To 2 years 120 t0 160 65 Up To 7 years 100 t0 140 65 Up To 15 years 90 to 140 65 ABSTRACT Severe sepsis and septic shock are complications of infection leading to high morbidity and mortality. Hemodynamic outcomes are considered surrogate markers for survival-an ultimate goal of treatment strategies. The goal of vasoactive agents is to improve arterial blood pressure (age related norms) without associated adverse effects. Early initiation of a vasoactive agent in fl uid-refractory septic shock has a signifi cant role in the outcome; initiation within an hour of presentation is recommended and is associated with favorable outcomes. The choice of the correct vasoactive agent in a given scenario has a pivotal role on the desired outcome as well as the duration to achieve it. Cardiac dysfunction is a well recognized complication of septic shock, occurring in about 60% of the patients. So ionotropes may play a role in septic shock patients with associated myocardial dysfunction and signs of organ hypoperfusion despite achieving adequate preload and mean arterial pressure. In children presentation of septic shock is more complex, predominantly vasoconstricted with low cardiac output. Sometimes they can have deranged myocardial contractility and SVR problems requiring combination of inotropes and vasopressors. Hence the choice of inotrope remains empirical. Vasoactive therapy should be guided by clinical end points.

Research, Society and Development

Refractory shock is characterized by hemodynamic instability unresponsive to norepinephrine with a high mortality rate. As there are still doubts regarding the pharmacological benefit of the vasopressin addition, this retrospective study aimed to assess the profile of vasopressin use in the intensive care unit of a university hospital in Paraná, Brazil. The information collected was obtained through the analysis of electronic medical records. 73 patients with refractory shock, mainly of septic etiology (61.6%), were included. The dose (μg/Kg/minute) and duration of norepinephrine, upon finding refractoriness, was 35.6% infusion < 1, 34, 3% of 1-1.9, 30.1% > 2 and mean time of 1.5 days. High mortality (80.8%) was observed, with a mean hospital stay of 8.2 days. Median survival after vasopressin infusion was 4.5 days until the unfavorable outcome. Still, 80.5% of patients used other adjuvant therapy, 71.2% being corticotherapy and 9.6% dobutamine. Due to the great variability, i...

Critical Care Nursing Clinics of North America, 2014

The authors recommend close monitoring and aggressive titration of vasopressors to maximize both vasopressor treatment and weaning in patients with sepsis. The rationale for mean arterial pressure (MAP) greater than or equal to 65 mm Hg is based on the physiologic concept of autoregulation of blood flow, the body's attempt to withhold or divert blood flow to the most critical organs. Close monitoring includes narrow alarm parameters for MAP and heart rate to minimize adverse events and facilitate rapid attainment of MAP greater than or equal to 65 mm Hg and subsequent discontinuance of vasopressor therapy. Implementation of a weaning protocol inclusive of narrow monitor alarm parameters will decrease the total time and dose of vasopressor therapy, thereby ensuring adequate tissue perfusion with minimal adverse events.

Intensive Care Medicine, 2016

In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock. Methods: We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60-65 mmHg) versus a higher (75-80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups. Results: A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The betweengroup separation in MAP was 9 mmHg (95 % CI 7-11). In the lower and higher MAP groups, we observed deviations on 12 versus 8 % of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36 %, p = 0.07) and hospital mortality (30 versus 33 %, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60 %, p = 0.03) but not in younger patients.

Journal of Clinical Medicine

Background: Vasopressors are frequently utilized for blood pressure stabilization in patients with cardiogenic shock (CS), although with a questionable benefit. Obtaining central venous access is time consuming and may be associated with serious complications. Hence, we thought to evaluate whether the administration of vasopressors through a peripheral venous catheter (PVC) is a safe and effective alternative for the management of patients with CS presenting to the intensive cardiovascular care unit (ICCU). Methods: A prospective single-center study was conducted to compare the safety and outcomes of vasopressors administered via a PVC vs. a central venous catheter (CVC) in patients presenting with CS over a 12-month period. Results: A total of 1100 patients were included; of them, 139 (12.6%) required a vasopressor treatment due to shock, with 108 (78%) treated via a PVC and 31 (22%) treated via a CVC according to the discretion of the treating physician. The duration of the vasopr...

Journal of Thoracic Disease

Critical Care, 2010

The research papers on shock that have been published in Critical Care throughout 2009 are related to four major subjects: fi rst, alterations of heart function and, second, the role of the sympathetic central nervous system during sepsis; third, the impact of hemodynamic support using vasopressin or its synthetic analog terlipressin, and diff erent types of fl uid resuscitation; as well as, fourth, experimental studies on the treatment of acute respiratory distress syndrome. The present review summarizes the key results of these studies together with a brief discussion in the context of the relevant scientifi c and clinical background published both in this and other journals.

Intensive Care Medicine, 2010

Purpose: To delineate some of the characteristics of septic vascular hypotension, to assess the most commonly cited and reported underlying mechanisms of vascular hyporesponsiveness to vasoconstrictors in sepsis, and to briefly outline current therapeutic strategies and possible future approaches. Methods: Source data were obtained from a PubMed search of the medical literature with the following MeSH terms: Muscle, smooth, vascular/ physiopathology; hypotension/etiology; shock/physiopathology; vasodilation/physiology; shock/therapy; vasoconstrictor agents. Results: Nitric oxide (NO) and peroxynitrite are crucial components implicated in vasoplegia and vascular hyporeactivity. Vascular ATP-sensitive and calcium-activated potassium channels are activated during shock and participate in hypotension. In addition, shock state is characterized by inappropriately low plasma glucocorticoid and vasopressin concentrations, a dysfunction and desensitization of alpha-receptors, and an inactivation of catecholamines by oxidation. Numerous other mechanisms have been individualized in animal models, the great majority of which involve NO: MEK1/2-ERK1/2 pathway, H 2 S, hyperglycemia, and cytoskeleton dysregulation associated with decreased actin expression. Conclusions: Many therapeutic approaches have proven their efficiency in animal models, especially therapies directed against one particular compound, but have otherwise failed when used in human shock. Nevertheless, high doses of catecholamines, vasopressin and terlipressin, hydrocortisone, activated protein C, and non-specific shock treatment have demonstrated a partial efficiency in reversing sepsis-induced hypotension.

Critical Care, 2018

Background: Vasopressin (AVP) is commonly added to norepinephrine (NE) to reverse shock in patients with sepsis. However, there are no data to support the appropriate strategy of vasopressor tapering in patients on concomitant NE and AVP who are recovering from septic shock. Therefore, the objective of this study was to evaluate the incidence of hypotension while tapering vasopressors in patients on concomitant NE and AVP recovering from septic shock. Methods: Patients with septic shock receiving concomitant NE and AVP were randomly assigned to taper NE first (NE group) or AVP first (AVP group). The primary end point was the incidence of hypotension within one hour of tapering of the first vasopressor. We also evaluated the association between serum copeptin levels and the occurrence of hypotension. Results: The study was stopped early due to a significant difference in the incidence of hypotension after 38 and 40 patients were enrolled in the NE group and the AVP group, respectively. There were 26 patients (68.4%) in the NE group versus 9 patients (22.5%) in the AVP group who developed hypotension after tapering the first vasopressor (p < 0.001). There was a similar finding during the subsequent tapering of the second vasopressor (64.5% in the NE vs 25.0% in the AVP group, p = 0.020). Finally, NE tapering was significantly associated with hypotension during the study period (hazard ratio, 2.221; 95% confidence interval, 1.106-4.460; p = 0.025). The serum copeptin level was lower in patients in whom hypotension developed during tapering of AVP than it was in those without hypotension. Conclusions: Tapering NE rather than AVP may be associated with a higher incidence of hypotension in patients recovering from septic shock who are on concomitant NE and AVP. However, further studies with larger sample sizes are required to better determine the appropriate strategy for vasopressor tapering.

Critical Care Research and Practice, 2013

There is no consensual definition of refractory shock. The use of more than 0.5 mcg/kg/min of norepinephrine or epinephrine to maintain target blood pressure is often used in clinical trials as a threshold. Nearly 6% of critically ill patients will develop refractory shock, which accounts for 18% of deaths in intensive care unit. Mortality rates are usually greater than 50%. The assessment of fluid responsiveness and cardiac function can help to guide therapy, and inotropes may be used if hypoperfusion signs persist after initial resuscitation. Arginine vasopressin is frequently used in refractory shock, although definite evidence to support this practice is still missing. Its associations with corticosteroids improved outcome in observational studies and are therefore promising alternatives. Other rescue therapies such as terlipressin, methylene blue, and high-volume isovolemic hemofiltration await more evidence before use in routine practice.

2019

who served on the dissertation committee. Thank you to all my family, friends, colleagues, and students who have provided encouragement and support. I dedicate this dissertation to my late grandmother Linda R. Sheffield, who taught me to be persistent, determined, and always pursue higher education despite obstacles.

Chest, 2001

Vasopressin is emerging as a rational therapy for the hemodynamic support of septic shock and vasodilatory shock due to systemic inflammatory response syndrome. The goal of this review is to understand the physiology of vasopressin relevant to septic shock in order to maximize its safety and efficacy in clinical trials and in subsequent therapeutic use. Vasopressin is both a vasopressor and an antidiuretic hormone. It also has hemostatic, GI, and thermoregulatory effects, and is an adrenocorticotropic hormone secretagogue. Vasopressin is released from the axonal terminals of magnocellular neurons in the hypothalamus. Vasopressin mediates vasoconstriction via V1-receptor activation on vascular smooth muscle and mediates its antidiuretic effect via V2-receptor activation in the renal collecting duct system. In addition, vasopressin, at low plasma concentrations, mediates vasodilation in coronary, cerebral, and pulmonary arterial circulations. Septic shock causes first a transient early increase in blood vasopressin concentrations that decrease later in septic shock to very low levels compared to other causes of hypotension. Vasopressin infusion of 0.01 to 0.04 U/min in patients with septic shock increases plasma vasopressin levels to those observed in patients with hypotension from other causes, such as cardiogenic shock. Increased vasopressin levels are associated with a lesser need for other vasopressors. Urinary output may increase, and pulmonary vascular resistance may decrease. Infusions of > 0.04 U/min may lead to adverse, likely vasoconstriction-mediated events. Because clinical studies have been relatively small, focused on physiologic end points, and because of potential adverse effects of vasopressin, clinical use of vasopressin should await a randomized controlled trial of its effects on clinical outcomes such as organ failure and mortality.

Chest, 2018

Refractory shock is a lethal manifestation of cardiovascular failure defined by an inadequate hemodynamic response to high doses of vasopressor medications. Approximately 7% of critically ill patients will develop refractory shock, with short-term mortality exceeding 50%. Refractory vasodilatory shock develops from uncontrolled vasodilation and vascular hyporesponsiveness to endogenous vasoconstrictors, causing failure of physiologic vasoregulatory mechanisms. Standard approaches to the initial management of shock include fluid resuscitation and initiation of norepinephrine. When these measures are inadequate to restore BP, vasopressin or epinephrine can be added. Few randomized studies exist to guide clinical management and hemodynamic stabilization in patients who do not respond to this standard approach. Adjunctive therapies, such as hydrocortisone, thiamine, and ascorbic acid, may increase BP in severe shock and should be considered when combination vasopressor therapy is needed...