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Cheryl L Holmes

Publications and source records attributed to Cheryl L Holmes.

10 recordsLinked to original sources
PubMed2005

Vasoactive drugs in the intensive care unit.

PURPOSE OF THE REVIEW: Vasoactive drugs are the mainstay of hemodynamic management of vasodilatory shock when fluids fail to restore tissue perfusion. In this review, studies published during the past year that increase our understanding of the use of vasoactive drugs in the intensive care unit are discussed. RECENT FINDINGS: In septic shock, there is no benefit in increasing mean arterial pressure from 65 to 85 mmHg. Norepinephrine did not worsen renal function. Epinephrine induced visceral hypoperfusion and hyperlactatemia, and worsened organ function and survival compared with norepinephrine and vasopressin. There are a number of reports of the safety and efficacy of vasopressin but it is not currently recommended as first line therapy, and if used, should be given as a continuous low dose infusion. Terlipressin is showing promise but decreases cardiac output. Metaraminol is being investigated as an alternative to norepinephrine. Dopamine may improve splanchnic flow mainly by increasing cardiac output. Dobutamine improves oxygen delivery and may improve mesenteric blood flow. SUMMARY: Over the last 40 years, there have been few controlled clinical trials to guide clinicians on the use of vasoactive drugs of treating shock states. It is not known whether the currently favored combination of norepinephrine and dobutamine is superior to traditional therapy with dopamine. Epinephrine is not recommended as the first-line therapy. The role of vasopressin and terlipressin remains unknown. Three large ongoing clinical trials will be completed soon and the results should clarify the role of these various agents.

Dobutamine↗
PubMed2004

Vasopressin.

Vasopressin is a hormone that is essential for both osmotic and cardiovascular homeostasis. A deficiency of vasopressin exists in some shock states and replacement of physiological levels of vasopressin can restore vascular tone. Vasopressin is therefore emerging as a rational therapy for vasodilatory shock. In this article we review the rationale and summarize the evidence for using vasopressin in vasodilatory shock states, such as septic shock. We then highlight the areas of uncertainty in using vasopressin for septic shock and summarize the reasons for clinical equipoise. We close by suggesting that further randomized controlled trials of vasopressin in septic shock are required before vasopressin is used routinely for management of septic shock.

Journal Article↗
PubMed2004

Vasopressin in the ICU.

PURPOSE OF THE REVIEW: Vasopressin is one of the most important endogenously released stress hormones during shock. In this review, studies published in the past year that add to our understanding of the use of vasopressin in the ICU are discussed. RECENT FINDINGS: Endogenous vasopressin levels are inappropriately low in adults with severe sepsis but not in children with meningococcal septic shock. Vasopressin but not norepinephrine improved renal blood flow and oxygen delivery and prolonged survival in animal models of septic shock. In human vasodilatory shock, the combination of low-dose vasopressin and norepinephrine was found to be safe and effective. In humans, vasopressin can cause gastrointestinal hypoperfusion and ischemic skin lesions. In hypodynamic animal models of sepsis vasopressin compromised oxygen delivery and decreased systemic and gut blood flow.High-dose bolus vasopressin appeared promising in animal studies of hemorrhagic shock and cardiopulmonary arrest and in a large, randomized clinical trial of vasopressin versus epinephrine in human cardiopulmonary arrest with asystole. However, poor neurologic outcomes raised controversy in introducing vasopressin into CPR guidelines. SUMMARY: There is growing evidence that vasopressin infusion in septic shock is safe and effective. Several studies published this year support the hypothesis that vasopressin should be used as a continuous low-dose infusion (between 0.01 and 0.04 U/min in adults) and not titrated as a single vasopressor agent. However, multiple studies highlight the clinical equipoise that exists regarding the use of vasopressin in vasodilatory shock. Guidelines on management of septic shock recommend "cautious use of vasopressin pending further studies."

Animals↗
PubMed2003

Science review: Vasopressin and the cardiovascular system part 1--receptor physiology.

Vasopressin is emerging as a rational therapy for vasodilatory shock states. Unlike other vasoconstrictor agents, vasopressin also has vasodilatory properties. The goal of the present review is to explore the vascular actions of vasopressin. In part 1 of the review we discuss structure, signaling pathways, and tissue distributions of the classic vasopressin receptors, namely V1 vascular, V2 renal, V3 pituitary and oxytocin receptors, and the P2 class of purinoreceptors. Knowledge of the function and distribution of vasopressin receptors is key to understanding the seemingly contradictory actions of vasopressin on the vascular system. In part 2 of the review we discuss the effects of vasopressin on vascular smooth muscle and the heart, and we summarize clinical studies of vasopressin in shock states.

Humans↗
PubMed2003

Science Review: Vasopressin and the cardiovascular system part 2 - clinical physiology.

Vasopressin is emerging as a rational therapy for vasodilatory shock states. In part 1 of the review we discussed the structure and function of the various vasopressin receptors. In part 2 we discuss vascular smooth muscle contraction pathways with an emphasis on the effects of vasopressin on ATP-sensitive K+ channels, nitric oxide pathways, and interaction with adrenergic agents. We explore the complex and contradictory studies of vasopressin on cardiac inotropy and coronary vascular tone. Finally, we summarize the clinical studies of vasopressin in shock states, which to date have been relatively small and have focused on physiologic outcomes. Because of potential adverse effects of vasopressin, clinical use of vasopressin in vasodilatory shock should await a randomized controlled trial of the effect of vasopressin's effect on outcomes such as organ failure and mortality.

Animals↗
PubMed2003

The evaluation and management of shock.

Shock is an emergency that requires continuous bedside evaluation, resuscitation, and re-evaluation. The initial bedside examination allows the clinician to determine whether the patient exhibits a clinical picture that is consistent with hypovolemic, cardiogenic, or vasodilatory shock. The primary survey dictates urgent initial resuscitation that usually consists of intubation, ventilation, and volume support. Vasoactive therapy is started when the patient is well volume-resuscitated and consists of inotropic support for cardiogenic shock and pressor therapy for vasodilatory shock. The secondary survey is helpful in revealing the cause of shock and necessary to institute early definitive therapy. Early shock has a hemodynamic component, which is often easily reversed. Septic shock and prolonged shock from any cause has an inflammatory component, which is not easily reversed and leads to multiple-system organ failure (MSOF) and death. Success in treatment of shock depends on early recognition of shock and the rapid tempo of resuscitation of its hemodynamic component to prevent or minimize the inflammatory component.

Critical Illness↗
PubMed2003

Bad medicine: low-dose dopamine in the ICU.

Low-dose dopamine administration (ie, doses < 5 microg/kg/min) has been advocated for 30 years as therapy in oliguric patients on the basis of its action on dopaminergic renal receptors. Recently, a large, multicenter, randomized, controlled trial has demonstrated that low-dose dopamine administered to critically ill patients who are at risk of renal failure does not confer clinically significant protection from renal dysfunction. In this review, we present the best evidence and summarize the effects of low-dose dopamine infusion in critically ill patients. We review the history and physiology of low-dose dopamine administration and discuss the reasons why dopamine is not clinically effective in the critically ill. In addition to the lack of renal efficacy, we present evidence that low-dose dopamine administration worsens splanchnic oxygenation, impairs GI function, impairs the endocrine and immunologic systems, and blunts ventilatory drive. We conclude that there is no justification for the use of low-dose dopamine administration in the critically ill.

Animals↗
PubMed2003

Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy.

Genetic epidemiologic studies suggest a strong genetic influence on the outcome from sepsis, and genetics may explain the wide variation in the individual response to infection that has long puzzled clinicians. Several candidate genes have been identified as important in the inflammatory response and investigated in case-controlled studies, including the tumor necrosis factor (TNF)-alpha and TNF-beta genes, positioned next to each other within the cluster of human leukocyte antigen class III genes on chromosome 6. Other candidate genes for sepsis and septic shock include the interleukin (IL)-1 receptor antagonist gene, the heat shock protein gene, the IL-6 gene, the IL-10 gene, the CD-14 gene, the Toll-like receptor (TLR)-4 gene, and the TLR-2 gene, to name a few. In this review, we summarize the evidence for a genetic susceptibility to development of sepsis and death from sepsis, discuss design of clinical genetics studies relevant to the study of complex disorders, consider the candidate genes likely to be involved in the pathogenesis of sepsis, and discuss the potential for targeted therapy of sepsis and septic shock based on genetic variability.

Acute-Phase Proteins↗