Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials

Nagendran, Myura; Russell, James A.; Walley, Keith R.; Brett, Stephen; Perkins, Gavin D.; Hajjar, Ludhmila Abrahão; Mason, Alexina J.; Ashby, Deborah; Gordon, Anthony

doi:10.1007/s00134-019-05620-2

Cited by 103 publications

(72 citation statements)

References 38 publications

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“…This meta-analysis underlined the additional risk of digital ischaemia [51]. In a recent meta-analysis of individual patients data from randomized studies (1453 septic shock patients) [52], no difference in mortality was found between vasopressin and norepinephrine. Furthermore, vasopressin use was not associated with more undesirable effect, but safety profiles were different: vasopressin led to more digital ischaemia, but fewer arrhythmias.…”

Section: Vasopressin Analogues: Terlipressin and Selepressinmentioning

confidence: 91%

Vasopressin and its analogues in shock states: a review

Demiselle

Fage

Radermacher

et al. 2020

Ann. Intensive Care

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Activation of arginine-vasopressin is one of the hormonal responses to face vasodilation-related hypotension. Released from the post-pituitary gland, vasopressin induces vasoconstriction through the activation of V1a receptors located on vascular smooth muscle cells. Due to its non-selective receptor affinity arginine-vasopressin also activates V2 (located on renal tubular cells of collecting ducts) and V1b (located in the anterior pituitary and in the pancreas) receptors, thereby potentially promoting undesired side effects such as anti-diuresis, procoagulant properties due to release of the von Willebrand's factor and platelet activation. Finally, it also cross-activates oxytocin receptors. During septic shock, vasopressin plasma levels were reported to be lower than expected, and a hypersensitivity to its vasopressor effect is reported in such situation. Terlipressin and selepressin are synthetic vasopressin analogues with a higher affinity for the V1 receptor, and, hence, potentially less side effects. In this narrative review, we present the current knowledge of the rationale, benefits and risks of vasopressin use in the setting of septic shock and vasoplegic shock following cardiac surgery. Clearly, vasopressin administration allows reducing norepinephrine requirements, but so far, no improvement of survival was reported and side effects are frequent, particularly ischaemic events. Finally, we will discuss the current indications for vasopressin and its agonists in the setting of septic shock, and the remaining unresolved questions.

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Section: Vasopressin Analogues: Terlipressin and Selepressinmentioning

confidence: 91%

Vasopressin and its analogues in shock states: a review

Demiselle

Fage

Radermacher

et al. 2020

Ann. Intensive Care

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“…The use of noradrenalin as compared to vasopressin (the endogenous hormone arginine-vasopressin, which is shorter acting than terlipressin) will likely result in more episodes of atrial fibrillation as observed in a recent IPDMA [14]. Also, in this analysis, more episodes of digital ischemia were observed with vasopressin as compared to noradrenalin.…”

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confidence: 71%

Focus on blood pressure targets and vasopressors in critically ill patients

2019

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For patients in shock, decisions on blood pressure targets are an ongoing task for the clinicians at the bedside in critical care settings. In general, there are only limited amount of data from studies with lower risk of bias to support the clinicians in these decisions. However, in recent years, large cohort studies and randomised clinical trials (RCTs) have given us somewhat better data to support better care.What blood pressure target is chosen will likely have important clinical implications, not only because different blood pressure targets may affect organ perfusion differently, but also because they require different dosing and choices of vasopressor agents. A delicate balance likely exists between the consequences of hypotension-induced hypoperfusion, on one side, and on the other side, the consequences of the interventions given, mainly vasopressors and their dosages and the duration of administration.In a large registry study from 110 ICUs in the US, hypotension-as time-weighted averages-in patients with sepsis was associated with increased risk of myocardial injury, acute kidney injury and death [1]. For the two latter outcomes, the odds for worse outcome increased with decreasing mean arterial pressures (MAP) from 85 mmHg. This does not mean that we should apply 85 mmHg as the target for vasopressor therapy, because observational data cannot prove causality and any timedependent interactions with interventions and any other physiological markers are very difficult to control for in such analyses [2][3][4]. In addition, registry data often contain few or no data on important clinical markers, in this case the simple markers of peripheral perfusion, which likely interacts with any effects of hypotension on mortality [5,6]. Importantly, a recent individual patient data meta-analysis (IPDMA) of two RCTs [7, 8] of lower vs. higher blood pressure targets in ICU patients with shock suggested that no sub-groups were harmed from lower MAP targets [9]. If anything, two sub-groups of patients were harmed from a higher MAP target being patients with more than 6 h of vasopressor exposure before randomization and those aged 65 years or above. Taken together, clinical equipoise exists [10], and more RCTs on blood pressure targets in shock patients are underway, including the large 65-trial on permissive hypotension in patients aged above 65-year who have shock (ISRCTN10580502). The results of the 65-trial should be presented soon as enrolment has ended. Uncertainty may remain regarding the need to individualize blood pressure targets based on habitual blood pressure levels or the trajectory of critical illness, e.g., the phases of resuscitation, stabilization and recovery.The choice of vasopressor to obtain the blood pressure target is also likely to matter. A recent multicenter, blinded RCT of the longer-acting vasopressin-analogue terlipressin, which has higher affinity for the V 1a receptor, showed no effect on the primary outcome 28-day mortality as compared with noradrenalin in patients with septic shock (Tabl...

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“…In a Chinese randomised clinical trial of 617 patients with septic shock, no difference in mortality between patients receiving terlipressin versus norepinephrine was observed; however, patients in the terlipressin group experienced more serious adverse events [15]. In a recent individual patient data meta-analysis of four RCTs, the use of vasopressin in patients with septic shock reduced arrhythmias, on the expense of a small increase in the risk of digital ischemia compared to norepinephrine [16].…”

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confidence: 99%

Focus on sepsis

2019

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Compliance with ethical standards Conflicts of interest WA is the methods Chair of the adult and children Surviving Sepsis Campaign Guidelines. MHM is a methodologist in the adult Surviving Sepsis Campaign guideline and a panel member of the children Surviving Sepsis Campaign guideline. MHM and MS-H are on the Editorial Board for ICM and declares no competing interests. All authors are active researchers within the field of sepsis.

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Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials

Cited by 103 publications

References 38 publications

Vasopressin and its analogues in shock states: a review

Vasopressin and its analogues in shock states: a review

Focus on blood pressure targets and vasopressors in critically ill patients

Focus on sepsis

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