The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Monica S Vavilala - One of the best experts on this subject based on the ideXlab platform.
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translational approach towards determining the role of cerebral autoregulation in outcome after traumatic brain injury
Experimental Neurology, 2019Co-Authors: William M Armstead, Monica S VavilalaAbstract:Abstract Cerebral autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, cerebral autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of Vasoactive Agents to increase mean arterial pressure (MAP) and thereby limit impairment of cerebral autoregulation and neurological deficits. However, current Vasoactive Agent choice used to elevate MAP to increase CPP after TBI is variable. Vasoactive Agents, such as phenylephrine, dopamine, norepinephrine, and epinephrine, clinically have not sufficiently been compared regarding effect on CPP, autoregulation, and survival after TBI. The cerebral effects of these clinically commonly used Vasoactive Agents are incompletely understood. This review will describe translational studies using a more human like animal model (the pig) of TBI to identify better therapeutic strategies to improve outcome post injury. These studies also investigated the role of age and sex in outcome and mechanism(s) involved in improvement of outcome in the setting of TBI. Additionally, this review considers use of inhaled nitric oxide as a novel neuroprotective strategy in treatment of TBI.
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cerebral perfusion pressure directed therapy modulates cardiac dysfunction after traumatic brain injury to influence cerebral autoregulation in pigs
Neurocritical Care, 2019Co-Authors: William M Armstead, Monica S VavilalaAbstract:BACKGROUND: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with cerebral ischemia, impaired cerebral autoregulation, and poor outcomes. Normalization of CPP and limitation of cerebral autoregulation impairment is a key therapeutic goal. However, some Vasoactive Agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by Vasoactive Agent choice to normalize CPP and prevent impairment of cerebral autoregulation after injury. METHODS: TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP. RESULTS: Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe. CONCLUSIONS: These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects cerebral autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.
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dopamine protects cerebral autoregulation and prevents hippocampal necrosis after traumatic brain injury via block of erk mapk in juvenile pigs
Brain Research, 2017Co-Authors: Victor Curvello, Monica S Vavilala, Hugh Hekierski, Philip Pastor, William M ArmsteadAbstract:Traumatic brain injury (TBI) contributes to morbidity in children, and more boys experience TBI. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of Vasoactive Agents to increase mean arterial pressure (MAP). In prior studies of newborn and juvenile pigs, Vasoactive Agent choice influenced outcome after TBI as a function of age and sex, with none protecting cerebral autoregulation in both ages and sexes. Dopamine (DA) prevents impairment of cerebral autoregulation in male and female newborn pigs via inhibition of upregulation of ERK mitogen activated protein kinase (MAPK) after fluid percussion injury (FPI). We investigated whether DA protects autoregulation and limits histopathology after FPI in juvenile pigs and the role of ERK in that outcome. Results show that DA protects autoregulation in both male and female juvenile pigs after FPI. Papaverine induced dilation was unchanged by FPI and DA. DA blunted ERK MAPK and prevented loss of neurons in CA1 and CA3 hippocampus of males and females after FPI. These data indicate that DA protects autoregulation and limits hippocampal neuronal cell necrosis via block of ERK after FPI in male and female juvenile pigs. Of the Vasoactive Agents prior investigated, including norepinephrine, epinephrine, and phenylephrine, DA is the only one demonstrated to improve outcome after TBI in both sexes and ages. These data suggest that DA should be considered as a first line treatment to protect cerebral autoregulation and promote cerebral outcomes in pediatric TBI irrespective of age and sex.
William M Armstead - One of the best experts on this subject based on the ideXlab platform.
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translational approach towards determining the role of cerebral autoregulation in outcome after traumatic brain injury
Experimental Neurology, 2019Co-Authors: William M Armstead, Monica S VavilalaAbstract:Abstract Cerebral autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, cerebral autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of Vasoactive Agents to increase mean arterial pressure (MAP) and thereby limit impairment of cerebral autoregulation and neurological deficits. However, current Vasoactive Agent choice used to elevate MAP to increase CPP after TBI is variable. Vasoactive Agents, such as phenylephrine, dopamine, norepinephrine, and epinephrine, clinically have not sufficiently been compared regarding effect on CPP, autoregulation, and survival after TBI. The cerebral effects of these clinically commonly used Vasoactive Agents are incompletely understood. This review will describe translational studies using a more human like animal model (the pig) of TBI to identify better therapeutic strategies to improve outcome post injury. These studies also investigated the role of age and sex in outcome and mechanism(s) involved in improvement of outcome in the setting of TBI. Additionally, this review considers use of inhaled nitric oxide as a novel neuroprotective strategy in treatment of TBI.
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cerebral perfusion pressure directed therapy modulates cardiac dysfunction after traumatic brain injury to influence cerebral autoregulation in pigs
Neurocritical Care, 2019Co-Authors: William M Armstead, Monica S VavilalaAbstract:BACKGROUND: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with cerebral ischemia, impaired cerebral autoregulation, and poor outcomes. Normalization of CPP and limitation of cerebral autoregulation impairment is a key therapeutic goal. However, some Vasoactive Agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by Vasoactive Agent choice to normalize CPP and prevent impairment of cerebral autoregulation after injury. METHODS: TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP. RESULTS: Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe. CONCLUSIONS: These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects cerebral autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.
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dopamine protects cerebral autoregulation and prevents hippocampal necrosis after traumatic brain injury via block of erk mapk in juvenile pigs
Brain Research, 2017Co-Authors: Victor Curvello, Monica S Vavilala, Hugh Hekierski, Philip Pastor, William M ArmsteadAbstract:Traumatic brain injury (TBI) contributes to morbidity in children, and more boys experience TBI. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of Vasoactive Agents to increase mean arterial pressure (MAP). In prior studies of newborn and juvenile pigs, Vasoactive Agent choice influenced outcome after TBI as a function of age and sex, with none protecting cerebral autoregulation in both ages and sexes. Dopamine (DA) prevents impairment of cerebral autoregulation in male and female newborn pigs via inhibition of upregulation of ERK mitogen activated protein kinase (MAPK) after fluid percussion injury (FPI). We investigated whether DA protects autoregulation and limits histopathology after FPI in juvenile pigs and the role of ERK in that outcome. Results show that DA protects autoregulation in both male and female juvenile pigs after FPI. Papaverine induced dilation was unchanged by FPI and DA. DA blunted ERK MAPK and prevented loss of neurons in CA1 and CA3 hippocampus of males and females after FPI. These data indicate that DA protects autoregulation and limits hippocampal neuronal cell necrosis via block of ERK after FPI in male and female juvenile pigs. Of the Vasoactive Agents prior investigated, including norepinephrine, epinephrine, and phenylephrine, DA is the only one demonstrated to improve outcome after TBI in both sexes and ages. These data suggest that DA should be considered as a first line treatment to protect cerebral autoregulation and promote cerebral outcomes in pediatric TBI irrespective of age and sex.
Gretchen Sacha - One of the best experts on this subject based on the ideXlab platform.
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Vasoactive Agent use in septic shock beyond first line recommendations
Pharmacotherapy, 2019Co-Authors: Gretchen Sacha, Seth R. Bauer, Ishaq LatAbstract:Septic shock is a life-threatening disorder associated with high mortality rates requiring rapid identification and intervention. Vasoactive Agents are often required to maintain goal hemodynamics and preserve tissue perfusion. However, guidance regarding the proper administration of adjunct Agents for the management of septic shock is limited in patients who are refractory to norepinephrine. This review summarizes vasopressor Agents and describes the nuanced application of these Agents in patients with septic shock, specifically focusing on clinical scenarios with limited guidance including patients who are nonresponsive to first-line Agents and individuals with mixed shock states, tachyarrhythmias, obesity, valvular abnormalities, or other comorbid conditions.
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Vasoactive Agent Use in Septic Shock: Beyond First‐Line Recommendations
Pharmacotherapy, 2019Co-Authors: Gretchen Sacha, Seth R. Bauer, Ishaq LatAbstract:Septic shock is a life-threatening disorder associated with high mortality rates requiring rapid identification and intervention. Vasoactive Agents are often required to maintain goal hemodynamics and preserve tissue perfusion. However, guidance regarding the proper administration of adjunct Agents for the management of septic shock is limited in patients who are refractory to norepinephrine. This review summarizes vasopressor Agents and describes the nuanced application of these Agents in patients with septic shock, specifically focusing on clinical scenarios with limited guidance including patients who are nonresponsive to first-line Agents and individuals with mixed shock states, tachyarrhythmias, obesity, valvular abnormalities, or other comorbid conditions.
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Hypotension Risk Based on Vasoactive Agent Discontinuation Order in Patients in the Recovery Phase of Septic Shock
Pharmacotherapy, 2018Co-Authors: Gretchen Sacha, Simon W. Lam, Abhijit Duggal, Heather Torbic, Anita Reddy, Seth R. BauerAbstract:Study objectives Patients with septic shock often require Vasoactive Agents for hemodynamic support; however, the optimal approach to discontinuing these Agents once patients reach the recovery phase is currently unknown. The objective of this evaluation was to compare the incidence of hypotension within 24 hours based on the discontinuation order of norepinephrine (NE) and vasopressin (AVP) in patients in the recovery phase of septic shock. Design Retrospective cohort study. Setting The medical, surgical, and neurosciences intensive care units (ICUs) at a large tertiary care academic medical center. Patients A total of 585 adults in the recovery phase of septic shock who received fixed-dose AVP for at least 6 hours as an adjunct to NE between September 2011 and August 2015 were included. Of these patients, 155 had AVP discontinued first, and 430 had NE discontinued first. Measurements and main results Hypotension was evaluated during the 24-hour period after discontinuation of the first Vasoactive Agent and was defined as mean arterial pressure less than 60 mm Hg with one or more of the following interventions: increased remaining Vasoactive Agent dose by 25%, reinstitution of the discontinued Agent, or administration of at least 1 L of fluid bolus. Time to hypotension was evaluated with survival analysis, and risk of hypotension was evaluated with multivariable Cox proportional hazards regression. No significant difference between groups was noted in the incidence of hypotension within 24 hours (55% in the AVP discontinued first group vs 50% in the NE discontinued first group, p=0.28) or ICU mortality (45.2% vs 40.0%, p=0.26). After adjustment for baseline factors with multivariable Cox proportional hazards regression, having AVP discontinued first was independently associated with an increased risk of hypotension with a time-varying effect that decreased over time (HR(t) = e[1.16-0.08*t] , p Conclusion In patients recovering from septic shock treated with concomitant AVP and NE, no significant difference was noted in the incidence of hypotension based on discontinuation order of these Agents.
Yoen Young Chuah - One of the best experts on this subject based on the ideXlab platform.
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short term Vasoactive Agent treatment driven by physicians preference in acute esophageal variceal bleeding in a tertiary center
PeerJ, 2019Co-Authors: Yoen Young Chuah, Pingi Hsu, Weilun Tsai, Fengwoei Tsay, Wenchi Chen, Kung Hung Lin, Yeong Yeh Lee, Huaymin WangAbstract:Background Vasoactive drugs are frequently used in combination with endoscopic variceal ligation (EVL) in treatment of acute esophageal variceal bleeding (EVB). The aim of study was to assess physicians' preference of Vasoactive Agents in acute EVB, their reasons of preference and efficacy and safety of these short course regimens. Methods Cirrhotic patients with suspected EVB were screened (n = 352). Eligible patients were assigned based on the physician's preference to either somatostatin (group S) or terlipressin (group T) followed by EVL. In group S, intravenous bolus (250 µg) of somatostatin followed by 250 µg/hour was continued for three days. In group T, 2 mg bolus injection of terlipressin was followed by 1 mg infusion every 6 h for three days. Results A total of 150 patients were enrolled; 41 in group S and 109 in group T. Reasons for physician preference was convenience in administration (77.1%) for group T and good safety profile (73.2%) for group S. Very early rebleeding within 49-120 h occurred in one patient in groups S and T (p = 0.469). Four patients in group S and 14 patients in group T have variceal rebleeding episodes within 6-42 d (p = 0.781). Overall treatment-related adverse effects were compatible in groups S and T (p = 0.878), but the total cost of terlipressin and somatostatin differed i.e., USD 621.32 and USD 496.43 respectively. Conclusions Terlipressin is the preferred Vasoactive Agent by physicians in our institution for acute EVB. Convenience in administration and safety profile are main considerations of physicians. Safety and hemostatic effects did not differ significantly between short-course somatostatin or terlipressin, although terlipressin is more expensive.
Martin Westphal - One of the best experts on this subject based on the ideXlab platform.
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terlipressin a promising Vasoactive Agent in hemodynamic support of septic shock
Expert Opinion on Pharmacotherapy, 2009Co-Authors: Andrea Morelli, Christian Ertmer, P Pietropaoli, Martin WestphalAbstract:Background: At present, terlipressin is predominantly used for the management of bleeding gastric and esophageal varices, as well as hepato-renal syndrome secondary to liver cirrhosis. Owing to its high and relatively selective affinity to vascular V1 receptors, terlipressin is also increasingly used as an adjunct vasopressor Agent in the management of vasodilatory hyperdynamic septic shock. Objective: This review article aims to summarize the available knowledge related to hemodynamic support with terlipressin in septic shock. Methods: For literature search, PubMed and specific keywords from the MeSH Database were used. Results/conclusions: Terlipressin represents an effective pressor Agent in patients with catecholamine-unresponsive septic shock. However, caution should be exercised, as terlipressin may contribute dose-dependently to vasoconstriction and a reflectory decrease in cardiac output. Additional studies are needed to clarify: i) the optimal time of therapy institution; ii) the efficacy and the...
