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Concept: Hypotension

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Background Vasodilatory 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. Methods We 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. Results A 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 Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843 .).

Concepts: Clinical trial, Blood, Hypertension, Blood pressure, Cardiovascular system, Renin-angiotensin system, Vasoconstriction, Hypotension

167

Orthostatic hypotension (OH) is a common cause of transient cerebral hypoperfusion in the population. Cerebral hypoperfusion is widely implicated in cognitive impairment, but whether OH contributes to cognitive decline and dementia is uncertain. We aimed to determine the association between OH and the risk of developing dementia in the general population.

Concepts: Risk, Stroke, Blood pressure, Cognition, The Association, Uncertainty, Orthostatic hypotension, Hypotension

126

It has been suggested that longer-term postsurgical outcome may be adversely affected by less than severe hypotension under anesthesia. However, evidence-based guidelines are unavailable. The present study was designed to develop a method for identifying patients at increased risk of death within 30 days in association with the severity and duration of intraoperative hypotension.

Concepts: Present, Time, Surgery, Hypotension

49

Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials.

Concepts: Blood, Systemic inflammatory response syndrome, Intensive care medicine, Shock, Septic shock, Sepsis, Hypotension, Surviving Sepsis Campaign

45

“Approximately 2 months ago, I had a patient where I accidently administered a wrong dose of fentanyl during a procedure. The patient developed severe hypotension, and the procedure had to be temporarily halted until we could get her blood pressure back up. My attending was close by. He responded quickly. Ultimately, no harm was done. "The reason I believe this happened is that during a procedure I’m sometimes required to administer fentanyl and must dilute it during the procedure. There are two dilutions, either to directly administer by syringe, or for use as an intravenous drip. We do this dilution . . .

Concepts: Patient, Intravenous therapy, Orthostatic hypotension, Hypotension, Hypodermic needle, Dilution, 2004 singles

34

Objective. Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. Approach. We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. Main results. Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. Significance. The presented method is robust to impedance changes, independent of the electrode’s relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

Concepts: Medicine, Electrochemistry, Vagus nerve, Carotid sinus, Vagus nerve stimulation, Electrochemical cell, Hypotension, Baroreflex

28

Selepressin is a new selective vasopressin V1a agonist for treatment of vasodilatory hypotension in shock. Its effect on coronary and aortic blood flow, hemodynamics, and electrocardiogram as an indication of drug safety in healthy dogs were compared with arginine vasopressin (AVP). Eight dogs were fasted, anesthetized, intubated, and ventilated. Following thoracotomy, coronary and aortic blood flows were monitored, left ventricular and peripheral arterial blood pressures were measured, and ECG was recorded. Selepressin or AVP were administered by dose-escalating infusions (1-300, 0.3-100 ng kg min, respectively). Drug formulation analysis and plasma bioanalysis confirmed exposure. For each dose level, hemodynamic parameters, drug potency, and efficacy were determined. Selepressin and AVP induced a similar increase in mean blood pressure (+13-18%), a moderate decrease in aortic blood flow (-40-45%), and a slight decrease in coronary blood flow (-16-22%). These vasopressors displayed similar hemodynamic characteristics, with peripheral vasoconstriction and decreased aortic blood flow being more pronounced than the increase in coronary resistance and decrease in coronary blood flow. Importantly, selepressin bore no relevant coronary ischemic liability, suggesting that V1a receptor agonists are a potential pharmacological target for treatment of vasodilatory hypotension in shock.

Concepts: Pharmacology, Hypertension, Blood pressure, Shock, Receptor antagonist, Agonist, Vasoconstriction, Hypotension

28

Background: Exercise capacity is critical for therapy and prognosis in patients with heart failure (HF). Effect of beta-blockers (BB) on exercise capacity in elderly patients with HF remains unclear. Objectives: To assess contribution of BB to functional capacity and left ventricular (LV) function in the elderly with HF. Design: According to the protocol of CIBISELD study group, elderly patients were treated with BB during 12 weeks. In CPET subgroup, an integral part of the CIBIS ELD study group, patients were performed Doppler echocardiography and cardiopulmonary exercise testing (CPET) before BB therapy and after 12 weeks. Setting: Randomized patients with HF beta blockers naïve. Participants: Thirty patients with HF aged over 65 years were included in CPET subgroup, while 847 incorporated in CIBIS ELD study group. Results: Heart rate (HR) and systolic blood pressure (SBP) after BB significantly decreased at rest (p < 0.001) and during exercise (p< 0.05), with sustained level of peak VO2. Observed changes of resting HR and peak HR were closely correlated (p < 0.001). Significant improvement of LV ejection fraction after BB was obtained (p= 0.003) and symptoms of breathlessness were reduced (p= 0.001). Left ventricular diastolic dysfunction at rest significantly contributed to exercise capacity (p = 0.019). Conclusions: Beta-blockers in elderly patients with HF are related to a significant decrease of HR and SBP, improvement of systolic LV function and sustained exercise tolerance. Resting LV diastolic dysfunction is strongly associated with lower exercise capacity.

Concepts: Myocardial infarction, Hypertension, Cardiology, Ejection fraction, Echocardiography, Blood pressure, Ventricle, Hypotension

27

Catecholamine-resistant hypotension (CRH) is characterised by inadequate response to standard doses of vasopressors, and increased mortality. Our Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) trial compares the efficacy and safety of angiotensin II (ANGII) versus placebo in CRH.

Concepts: Epidemiology, Clinical trial, Randomized controlled trial, Blood pressure, Shock, Vasopressin, Vasoconstriction, Hypotension

27

Recently, high-dose insulin (HDI) and intravenous lipid emulsion (ILE) have emerged as treatment options for severe toxicity from calcium-channel blocker (CCB) and beta blocker (BB).

Concepts: Myocardial infarction, Hypertension, Glucagon, Shock, Hypotension, Cardiogenic shock, Beta blocker, Lipid rescue