Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

Bassi, Estêvão; Park, Marcelo; Azevedo, Luciano César Pontes

doi:10.1155/2013/654708

Cited by 64 publications

(66 citation statements)

References 71 publications

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“…glucocorticoids, vasopressin, methylene blue, and high-volume hemofiltration, all of which are used as adjunct therapies to maintain blood pressure in patients with vasodilatory shock. 21 Previously, new therapies proved to be disappointing. Notably, the nitric oxide synthase inhibitor 546C88 increased blood pressure in patients with septic shock but was associated with more frequent cardiovascular side effects and increased 28-day mortality.…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin II for the Treatment of Vasodilatory Shock

et al. 2017

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BACKGROUNDVasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODSWe randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTSA total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (−1.75 vs. −1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS 420T h e ne w e ngl a nd jou r na l o f m e dicine S hock is a life-threatening syndrome characterized by decreased organ perfusion that can progress to irreversible organ failure. 1 Vasodilatory shock is the most common type of shock and is characterized by peripheral vasodilation and reduced blood pressure despite preserved cardiac output. 2 Vasodilatory shock requires immediate treatment to ensure organ perfusion through the reestablishment of adequate blood pressure while the underlying cause of shock is identified and treated. 3 Vasopressors are used when intravenous fluid resuscitation alone fails to restore blood pressure. Patients with severe vasodilation who have hypotension despite the use of high doses of vasopressors have a poor prognosis, with 30-day all-cause mortality exceeding 50%. 4,5 Currently, only two classes of vasopressors are available: catecholamines (and other sympathomimetic amines) and vasopressin. 3 Both classes have narrow therapeutic windows owing to substantial toxic effects at high doses. 6 However, when hypotension occurs, human physiology engages a third system, which is represented by hormones in the renin-angiotensin-aldosterone system (RAAS). 7 Previously, modified bovine angiotensin II was shown to elicit consis...

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Section: Discussionmentioning

confidence: 99%

“…21 Previously, new therapies proved to be disappointing. Notably, the nitric oxide synthase inhibitor 546C88 increased blood pressure in patients with septic shock but was associated with more frequent cardiovascular side effects and increased 28-day mortality.…”

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confidence: 99%

Angiotensin II for the Treatment of Vasodilatory Shock

et al. 2017

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“…5,7,8,59,65,66 Norepinephrine doses >0.5 to 1 mg/kg/min are considered high (Table 3), but there is no defined maximum norepinephrine dose for refractory shock. 57,67 Norepinephrine may produce reflex reductions in HR by increasing MAP, although worsening tachycardia can occur at high doses due to B1R stimulation. Norepinephrine is the first-line vasopressor for all forms of shock with severe hypotension, including undifferentiated shock, vasodilatory/septic shock, and cardiogenic shock ( Figure 3).…”

Section: Goals Of Resuscitationmentioning

confidence: 99%

“…2,7,8,17 Epinephrine doses >0.3 to 0.5 mg/kg/min are considered high (Table 3), but there is no defined maximum epinephrine dose for refractory shock (Table 3). 57,67 Dopamine Pharmacologic doses of dopamine activate dopaminergic receptors and exert AR agonist effects via direct activation of B1R and indirect increases in A1R signaling (Table 1). 13 Dopaminergic receptors produce vasodilation in the mesenteric and renal arterioles and inhibit renal tubular sodium reabsorption.…”

Section: Goals Of Resuscitationmentioning

confidence: 99%

Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit

Jentzer

Coons

Link

et al. 2014

J Cardiovasc Pharmacol Ther

142

106

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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.

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“…5,23 Methylene blue prevents vasodilation by inhibiting soluble guanylyl cyclase and nitric oxide synthase activity. The optimal dose is unknown, 66 as well as its effect on morbidity and mortality. 67 Methylene blue (2 mg/kg iv) in persistent shock should only be used during the first 24 hours following cardio-pulmonary bypass.…”

Section: Maintain Perfusion Pressurementioning

confidence: 99%

Shock Management For Cardio-Surgical ICU Patients — The Golden Hours

Hauffe¹,

Krüger²,

Béttex³

et al. 2015

Cardiac Failure Review

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Shock in cardio-surgical intensive care unit (ICU) patients is a serious condition with a high morbidity and mortality.1,2 Prompt identification of the underlying conditions and correct management of the lifethreatening physiological deteriorations are crucial to save the patient's life. In daily practice, however, focusing on the main goal -to provide adequate oxygen delivery thereby preventing further organ damage -is often difficult due to multiple influences, distractions, and pending results. Hence, the setting up of priorities is necessary.In addition, many questions arise on how to optimally treat patients in shock: What blood pressure should we target? What fluid should we use and how much? Which vasoactive drug is best and which inotrope? While discussions about these issues can be very fruitful for experts, they risk confusing younger colleagues and nurses at the bedside. Disputes about controversial therapy opinions might consequently delay adequate resuscitation, putting the patient at risk of an adverse outcome. This review aims to give recommendations for the management during the early phase of shock of cardio-surgical patients hospitalised in the ICU. The focus is on the first 6 hours, which are also called 'the golden hours'. Methods Clinical SettingThe cardio-surgical ICU at the University Hospital Zurich is a 12-bed, high-intensity unit that cares for more than 1,100 patients every year.The majority of these critically ill patients undergo cardiac and/or major vascular surgery, most of them being mechanically ventilated and on inotrope/vasopressor support. The unit is part of a successful heart failure programme that includes extracorporeal life support, ventricular assist devices and a heart transplantation service. In order to optimise the initial resuscitation of patients and to avoid adverse effects of inadequate treatment, the consultants of the unit have agreed on treatment recommendations, which are presented here.They are based on current evidence and complemented by clinical experience in areas of uncertainty. Data ExtractionFor this narrative review, a search of the PubMed database and a review of bibliographies from selected articles were performed to identify original data relating to this topic. Key words used for the search were 'shock', 'cardiac surgery', 'critical care', 'inotropes', 'inotropic therapy', 'circulatory support', 'cardiogenic shock' and 'sepsis'. National and international guidelines were reviewed and integrated, e.g. The 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation, 3 The 2014 ESC/ EACTS guidelines on myocardial revascularization 4 and The Surviving Sepsis Campaign guidelines 5 . Articles were scrutinised regarding their study design, population evaluated, interventions, outcomes, and limitations. Finally, personal recommendations were included and highlighted as such to give a comprehensive overview on this topic. Rationale for an Early Management of ShockShock in patients under...

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Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

Cited by 64 publications

References 71 publications

Angiotensin II for the Treatment of Vasodilatory Shock

Angiotensin II for the Treatment of Vasodilatory Shock

Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit

Shock Management For Cardio-Surgical ICU Patients — The Golden Hours

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