Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial

Liu, Zimeng; Chen, Juan; Kou, Qiuye; Lin, Qinhan; Huang, Xiaobo; Tang, Zhanhong; Kang, Yan; Li, Ke; Zhou, Lei; Song, Qing; Sun, Tongwen; Zhao, Ling; Wang, Xue; He, Xiangjiu; Wang, Chunting; Wu, Benquan; Lin, Jiandong; Yuan, Shiying; Gu, Qin; Qian, Kun; Shi, Xianqing; Feng, Yang; Lin, Ang; He, Xiaoshun; Guan, Xiangdong

doi:10.1007/s00134-018-5267-9

Cited by 90 publications

(80 citation statements)

References 28 publications

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“…Of the included studies, four of the six (66.7%) studies (Morelli et al, 2008;Morelli et al, 2009;Chen et al, 2017;Liu, 2018) obtained high scores (>3) assessed by the modified Jadad scale. Only one study (Liu, 2018) reported allocation concealment. Two of the six studies (Albanese, 2005;Choudhury et al, 2017) didn't report blinding method.…”

Section: Quality Assessmentmentioning

confidence: 98%

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Terlipressin Versus Norepinephrine for Septic Shock: A Systematic Review and Meta-Analysis

Huang

Guo

et al. 2019

Front. Pharmacol.

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Purpose: The meta-analysis aims to evaluate the efficacy and safety of terlipressin compared with norepinephrine for septic shock. Materials and Methods:The relevant studies from MEDLINE, Cochrane Library, Embase were searched by two independent investigators. A variety of keywords were used to search the studies. Stata software (version 11.0, Stata Corp LP, College Station, TX, USA) was used for statistical analysis.Results: A total of six studies were identified and incorporated into the meta-analysis. The results showed that there was no difference for 28-day mortality (RR = 0.99, 95% CI = [0.85,1.15], P = 0.849), AE (RR = 2.54, 95% CI = [0.58,11.08], P = 0.214), and MAP (SMD = -0.10, 95% CI = [-0.35,0.14], P = 0.405), OI, urinary output, Scr, total bilirubin, ALT, and AST between TP group and NE group. While TP could decrease HR at 24 and 48 h compared with NE.Conclusions: Current results suggest that terlipressin showed no added survival benefit for septic shock when compared with norepinephrine, while terlipressin could decrease heart rate in the late phase of septic shock compared with norepinephrine without further liver and kidney injury.Systematic Review Registration: PROSPERO (ID: CRD42019128743). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019128743.

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Section: Quality Assessmentmentioning

confidence: 98%

“…All hypotheses were tested at the alpha = 0.05 level. Liu et al, 2017;Choudhury et al, 2017;Liu, 2018) with 756 participants were included ( Figure 1). The characteristics of the six studies are listed in Table 1.…”

Section: Data Synthesismentioning

confidence: 99%

Terlipressin Versus Norepinephrine for Septic Shock: A Systematic Review and Meta-Analysis

Huang

Guo

et al. 2019

Front. Pharmacol.

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“…Fourteen articles were excluded for the following reasons: animal studies (n = 6), paediatric subjects (n = 2), case report (n = 3), and outcome irrelevant (n = 3). Finally, 9 articles (850 patients) were included in the analysis [12,[18][19][20][21][22][23][24][25].…”

Section: Literature Searchmentioning

confidence: 99%

Terlipressin for the treatment of septic shock in adults: a systematic review and meta-analysis

et al. 2020

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Background: Catecholamines are the first-line vasopressors used in patients with septic shock. However, the search for novel drug candidates is still of great importance due to the development of adrenergic hyposensitivity accompanied by a decrease in catecholamine activity. Terlipressin (TP) is a synthetic vasopressin analogue used in the management of patients with septic shock. In the current study, we aimed to compare the effects of TP and catecholamine infusion in treating septic shock patients. Methods: A systematic review and meta-analysis was conducted by searching articles published in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials between inception and July 2018. We only selected randomized controlled trials evaluating the use of TP and catecholamine in adult patients with septic shock. The primary outcome was overall mortality. The secondary outcomes were the ICU length of stay, haemodynamic changes, tissue perfusion, renal function, and adverse events. Results: A total of 9 studies with 850 participants were included in the analysis. Overall, no significant difference in mortality was observed between the TP and catecholamine groups (risk ratio(RR), 0.85 (0.70 to 1.03); P = 0.09). In patients < 60 years old, the mortality rate was lower in the TP group than in the catecholamine group (RR, 0.66 (0.50 to 0.86); P = 0.002). There was no significant difference in the ICU length of stay (mean difference, MD), − 0.28 days; 95% confidence interval (CI), − 1.25 to 0.69; P = 0.58). Additionally, TP improved renal function. The creatinine level was decreased in patients who received TP therapy compared to catecholamine-treated participants (standard mean difference, SMD), − 0.65; 95% CI, − 1.09 to − 0.22; P = 0.003). No significant difference was found regarding the total adverse events (Odds Ratio(OR), 1.48(0.51 to 4.24); P = 0.47), whereas peripheral ischaemia was more common in the TP group (OR, 8.65(1.48 to 50.59); P = 0.02). Conclusion: The use of TP was associated with reduced mortality in septic shock patients less than 60 years old. TP may also improve renal function and cause more peripheral ischaemia. PROSPERO registry: CRD42016035872.

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“…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 (Table 1) [11]. More serious adverse events were observed with terlipressin; more specifically, there were more patients with digital ischemia in the vasopressinanalogue group [11].…”

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confidence: 98%

“…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 (Table 1) [11]. More serious adverse events were observed with terlipressin; more specifically, there were more patients with digital ischemia in the vasopressinanalogue group [11]. The accompanying editorial comment warned that care should be taken if this vasopressor is used [12].…”

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confidence: 99%

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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Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial

Abstract: This trial is registered at ClinicalTrials.gov: ID NCT01697410.

Cited by 90 publications

References 28 publications

Terlipressin Versus Norepinephrine for Septic Shock: A Systematic Review and Meta-Analysis

Terlipressin Versus Norepinephrine for Septic Shock: A Systematic Review and Meta-Analysis

Terlipressin for the treatment of septic shock in adults: a systematic review and meta-analysis

Focus on blood pressure targets and vasopressors in critically ill patients

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