A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators

Angus, Derek C.; Barnato, Amber E.; Bell, Derek; Bellomo, Rinaldo; Chong, Cher‐Rin; Coats, Timothy J; Davies, Andrew R.; Delaney, Anthony; Harrison, David A; Holdgate, Anna; Howe, Belinda; Huang, David T.; Iwashyna, Theodore J.; Kellum, John A.; Peake, Sandra; Pike, Francis; Reade, Michael C.; Rowan, Kathy; Singer, Mervyn; Webb, Steven A R; Weissfeld, Lisa A.; Yealy, Donald M.; Young, John

doi:10.1007/s00134-015-3822-1

Cited by 318 publications

(224 citation statements)

References 21 publications

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“…This excluded the early period of critical illness when arguably the oxygen supply-demand balance may be most deranged. The recent early goal-directed trials in sepsis (ProCESS, ARISE, and PROMISE), which included the use of red cell transfusions when the Hb was below 100 g/L and ScVO 2 below 70 %, found no outcome benefit overall [11], but relatively few patients triggered the blood transfusion part of the algorithm. It also seems unlikely that many patients had Hb below 70 g/L during the intervention period.…”

Section: Physiological Arguments Against a Blanket Restrictive Hb Trimentioning

confidence: 99%

Should blood transfusion be individualised? We are not sure

Docherty

Walsh

2015

Intensive Care Med

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Section: Physiological Arguments Against a Blanket Restrictive Hb Trimentioning

confidence: 99%

Should blood transfusion be individualised? We are not sure

Docherty

Walsh

2015

Intensive Care Med

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“…Nevertheless, a meta-analysis of early goal-directed therapy for patients with septic shock including the ARISE, the Pro-CESS, and the ProMISe trials with a total of 4200 patients could not find benefit of therapeutic schedules based on the Surviving Sepsis Guidelines bundles when compared to what was valued as usual care [18].…”

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confidence: 99%

Focus on acute circulatory failure

Bakker

2016

Intensive Care Med

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A task force of the European Society of Intensive Care Medicine published the results of a consensus conference on the definition, diagnosis, monitoring, and treatment of circulatory failure [1]. Circulatory failure was defined as a life-threatening, generalized form of acute circulatory failure with inadequate oxygen utilization by the cells resulting in cellular dysfunction as a result of dysoxia, i.e., the loss of the physiological independence of oxygen delivery and oxygen consumption associated with increased lactate levels.However, the interpretation of increased lactate levels may not be as straightforward as suggested. In many cases lactate levels remain elevated after initial resuscitation. Ospina-Tascón et al. [2] showed that under these circumstances, the use of the venous-arterial CO 2 to arterial-venous O 2 content difference ratio as a surrogate of the respiratory quotient could reveal an increased lactate level as a result of persisting anaerobic metabolism. Increased lactate with an abnormal ratio (suggesting anaerobic metabolism) was associated with an excess mortality of almost 30 % compared to APACHE II expected mortality. Therefore, early resolution of tissue hypoperfusion and oxygen delivery-dependent oxygen consumption might prevent excess mortality. As shown by Gu et al. [3] in their meta-analysis of four studies, the use of early therapy aimed at decreasing lactate levels in patients with sepsis is associated with a significant improvement in mortality [risk ratio 0.65 (95 % CI 0.26-1.95)].Frequently abnormalities in skin perfusion are present in circulatory failure. Coudroy et al. [4] showed that skin mottling was present in 49 % of septic shock patients. Prolonged mottling (more than 6 h) was associated with a 40 % mortality. Similarly, Ait-Oufella et al. [5] showed that persistent abnormal capillary refill time (CRT) after initial resuscitation was related to mortality in septic shock patients. Although these data confirm similar studies in circulatory failure, the effect of using skin perfusion as a goal of therapy on outcome is not yet clear [6].Fluid resuscitation is an important intervention to improve tissue perfusion. In this regard the results of the FENICE study [7] on the use of fluid challenges in intensive care are remarkable. From this study in 2213 patients admitted to 311 ICUs in 46 countries, it was clear that the use of a fluid bolus was mainly aimed at restoring blood pressure. In the majority of cases, central venous pressure (CVP) was used to predict fluid responsiveness and monitor effectiveness. This is most likely based on the misconception of the original Starling experiments where CVP was the dependent variable on venous return and cardiac function instead of an independent variable of preload [8]. The goal of fluid resuscitation should not be an increase in CVP but rather an increase in stressed volume resulting in an increase in mean systemic filling pressure (MSFP) and a rise in the pressure for venous return (Pvr = MSFP − CVP) thus increasing cardiac ou...

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“…In this issue of Intensive Care Medicine, Peake and colleagues [11] report a systematic review with metaanalysis of five RCTs [1,[8][9][10][11][12] showing no difference in mortality between ED-initiated EGDT versus usual care groups. However, the ED-initiated EGDT group had significantly more use of vasopressors and duration of stay in the ICU.…”

mentioning

confidence: 99%

“…However, the ED-initiated EGDT group had significantly more use of vasopressors and duration of stay in the ICU. Peake and colleagues [11] also reviewed six RCTs of non-ED-initiated EGDT, again finding no difference in mortality between EGDT versus usual care. The systematic review adheres to current standards for the conduct and reporting of a systematic review [13,14], including a pre-experimentally published protocol, a comprehensive search strategy, adequate conventional cumulative meta-analyses, relevant sensitivity and subgroup analyses, and adequate assessment of risk of bias.…”

mentioning

confidence: 99%

“…Thus, Rivers' improved process of care (early recognition and intervention) that is now an integrated part of sepsis bundles and guidelines around the globe has ironically led to lower mortality rates Fig. 1 Trial sequential analysis of all-cause mortality (five trials [1,[8][9][10][11]). The upper and lower red boundaries are trial sequential monitoring boundaries for benefit and harm.…”

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Early goal-directed therapy: from discovery through enthusiasm to equipoise?

2015

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The original Rivers trial [1] of early goal-directed therapy (EGDT) discovered that a process of EGDT that guided fluids, vasopressors, inotropic agents and transfusions in the first 6 h of sepsis dramatically reduced mortality (relative risk reduction, RRR of 42 %) compared to usual care in an emergency department (ED) setting. That discovery ushered in an exciting era of early identification, resuscitation and monitoring of patients with sepsis. Since 2003, EGDT has been recommended in international sepsis guidelines [2][3][4], and implementation in routine care has been associated with benefits [5]. Likewise, many observers suggested that prompt recognition and treatment of sepsis may partly explain declining mortality from sepsis [6,7].Some have suggested that EGDT as described in Rivers' trial may not apply to the intensive care setting, because it was a single-centre trial conducted in the emergency department, the control mortality rate was higher than expected, and baseline central venous oxygen saturation (ScvO 2 ) was remarkably low (about 50 %)-an observation thought to be rare in septic ICU patients. Accordingly, many argued that there was clinical equipoise about the role of EGDT in ICU patients with sepsis, and several subsequent multicentre RCTs [8-10] did not find survival benefits from EGDT (mortality was actually slightly higher in EGDT than the usual care group in ProMISe).In this issue of Intensive Care Medicine, Peake and colleagues [11] report a systematic review with metaanalysis of five RCTs [1,[8][9][10][11][12] showing no difference in mortality between ED-initiated EGDT versus usual care groups. However, the ED-initiated EGDT group had significantly more use of vasopressors and duration of stay in the ICU. Peake and colleagues [11] also reviewed six RCTs of non-ED-initiated EGDT, again finding no difference in mortality between EGDT versus usual care. The systematic review adheres to current standards for the conduct and reporting of a systematic review [13,14], including a pre-experimentally published protocol, a comprehensive search strategy, adequate conventional cumulative meta-analyses, relevant sensitivity and subgroup analyses, and adequate assessment of risk of bias. Conventional cumulative meta-analyses are at risk of producing random errors because of sparse data and repetitive testing of accumulating data [15][16][17]. The risk of random errors can be assessed by trial sequential analysis (TSA), where trial sequential monitoring boundaries are applied to the conventional meta-analysis. The underlying assumption of TSA is that significance testing and calculation of the 95 % confidence interval are performed each time a new trial result is published or available. TSA depends on the accrued information

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A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators

Abstract: EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

Cited by 318 publications

References 21 publications

Should blood transfusion be individualised? We are not sure

Should blood transfusion be individualised? We are not sure

Focus on acute circulatory failure

Early goal-directed therapy: from discovery through enthusiasm to equipoise?

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