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      Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

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          Abstract

          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.

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          Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature.

          : A systematic review of the literature to determine the ability of dynamic changes in arterial waveform-derived variables to predict fluid responsiveness and compare these with static indices of fluid responsiveness. The assessment of a patient's intravascular volume is one of the most difficult tasks in critical care medicine. Conventional static hemodynamic variables have proven unreliable as predictors of volume responsiveness. Dynamic changes in systolic pressure, pulse pressure, and stroke volume in patients undergoing mechanical ventilation have emerged as useful techniques to assess volume responsiveness. : MEDLINE, EMBASE, Cochrane Register of Controlled Trials and citation review of relevant primary and review articles. : Clinical studies that evaluated the association between stroke volume variation, pulse pressure variation, and/or stroke volume variation and the change in stroke volume/cardiac index after a fluid or positive end-expiratory pressure challenge. : Data were abstracted on study design, study size, study setting, patient population, and the correlation coefficient and/or receiver operating characteristic between the baseline systolic pressure variation, stroke volume variation, and/or pulse pressure variation and the change in stroke index/cardiac index after a fluid challenge. When reported, the receiver operating characteristic of the central venous pressure, global end-diastolic volume index, and left ventricular end-diastolic area index were also recorded. Meta-analytic techniques were used to summarize the data. Twenty-nine studies (which enrolled 685 patients) met our inclusion criteria. Overall, 56% of patients responded to a fluid challenge. The pooled correlation coefficients between the baseline pulse pressure variation, stroke volume variation, systolic pressure variation, and the change in stroke/cardiac index were 0.78, 0.72, and 0.72, respectively. The area under the receiver operating characteristic curves were 0.94, 0.84, and 0.86, respectively, compared with 0.55 for the central venous pressure, 0.56 for the global end-diastolic volume index, and 0.64 for the left ventricular end-diastolic area index. The mean threshold values were 12.5 +/- 1.6% for the pulse pressure variation and 11.6 +/- 1.9% for the stroke volume variation. The sensitivity, specificity, and diagnostic odds ratio were 0.89, 0.88, and 59.86 for the pulse pressure variation and 0.82, 0.86, and 27.34 for the stroke volume variation, respectively. : Dynamic changes of arterial waveform-derived variables during mechanical ventilation are highly accurate in predicting volume responsiveness in critically ill patients with an accuracy greater than that of traditional static indices of volume responsiveness. This technique, however, is limited to patients who receive controlled ventilation and who are not breathing spontaneously.
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            Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial.

            It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome. To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit (ICU) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. Patients were randomly allocated to two groups. In the lactate group, treatment was guided by lactate levels with the objective to decrease lactate by 20% or more per 2 hours for the initial 8 hours of ICU stay. In the control group, the treatment team had no knowledge of lactate levels (except for the admission value) during this period. The primary outcome measure was hospital mortality. The lactate group received more fluids and vasodilators. However, there were no significant differences in lactate levels between the groups. In the intention-to-treat population (348 patients), hospital mortality in the control group was 43.5% (77/177) compared with 33.9% (58/171) in the lactate group (P = 0.067). When adjusted for predefined risk factors, hospital mortality was lower in the lactate group (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87; P = 0.006). In the lactate group, Sequential Organ Failure Assessment scores were lower between 9 and 72 hours, inotropes could be stopped earlier, and patients could be weaned from mechanical ventilation and discharged from the ICU earlier. In patients with hyperlactatemia on ICU admission, lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors. As this was consistent with important secondary endpoints, this study suggests that initial lactate monitoring has clinical benefit. Clinical trial registered with www.clinicaltrials.gov (NCT00270673).
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              Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure.

              In mechanically ventilated patients with acute circulatory failure related to sepsis, we investigated whether the respiratory changes in arterial pressure could be related to the effects of volume expansion (VE) on cardiac index (CI). Forty patients instrumented with indwelling systemic and pulmonary artery catheters were studied before and after VE. Maximal and minimal values of pulse pressure (Pp(max) and Pp(min)) and systolic pressure (Ps(max) and Ps(min)) were determined over one respiratory cycle. The respiratory changes in pulse pressure (DeltaPp) were calculated as the difference between Pp(max) and Pp(min) divided by the mean of the two values and were expressed as a percentage. The respiratory changes in systolic pressure (DeltaPs) were calculated using a similar formula. The VE-induced increase in CI was >/= 15% in 16 patients (responders) and < 15% in 24 patients (nonresponders). Before VE, DeltaPp (24 +/- 9 versus 7 +/- 3%, p < 0.001) and DeltaPs (15 +/- 5 versus 6 +/- 3%, p < 0.001) were higher in responders than in nonresponders. Receiver operating characteristic (ROC) curves analysis showed that DeltaPp was a more accurate indicator of fluid responsiveness than DeltaPs. Before VE, a DeltaPp value of 13% allowed discrimination between responders and nonresponders with a sensitivity of 94% and a specificity of 96%. VE-induced changes in CI closely correlated with DeltaPp before volume expansion (r(2) = 0. 85, p < 0.001). VE decreased DeltaPp from 14 +/- 10 to 7 +/- 5% (p < 0.001) and VE-induced changes in DeltaPp correlated with VE-induced changes in CI (r(2) = 0.72, p < 0.001). It was concluded that in mechanically ventilated patients with acute circulatory failure related to sepsis, analysis of DeltaPp is a simple method for predicting and assessing the hemodynamic effects of VE, and that DeltaPp is a more reliable indicator of fluid responsiveness than DeltaPs.
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                Author and article information

                Journal
                Crit Care Res Pract
                Crit Care Res Pract
                CCRP
                Critical Care Research and Practice
                Hindawi Publishing Corporation
                2090-1305
                2090-1313
                2013
                15 September 2013
                : 2013
                : 654708
                Affiliations
                1Intensive Care Unit, Discipline of General Surgery and Trauma, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP), Avenue Eneas de Carvalho Aguiar 255, 4th Floor, 05403-000 São Paulo, SP, Brazil
                2Intensive Care Unit, Emergency Medicine Discipline, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP), Avenue Eneas de Carvalho Aguiar 255, Room 5023, 05403-000 São Paulo, SP, Brazil
                3Intensive Care Experimental Laboratory, Research and Education Institute, Hospital Sirio-Libanes, Rua Cel. Nicolau dos Santos, 69 01308-060 São Paulo, SP, Brazil
                4Intensive Care Unit, Federal University of São Paulo (UNIFESP), Rua Napoleão de Barros 715, 04024002 São Paulo, SP, Brazil
                Author notes
                *Luciano Cesar Pontes Azevedo: luciano.azevedo@ 123456hsl.org.br

                Academic Editor: Ali A. El Solh

                Article
                10.1155/2013/654708
                3787628
                24151551
                38338a49-444f-4f91-b5a2-7bde89842dd9
                Copyright © 2013 Estevão Bassi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 April 2013
                : 26 June 2013
                : 26 June 2013
                Categories
                Review Article

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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