Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial
Abstract
Purpose Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin's effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock.Methods In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20-160 µg/h with maximum infusion rate of 4 mg/day) or NE (4-30 µg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population.Results Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55-1.56]; p = 0.80). Change in SOFA score on day 7 was similar between the two groups: - 7 (IQR - 11 to 3) in the terlipressin group and - 6 (IQR - 10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p < 0.001).Conclusions In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events.Trial registration This trial is registered at ClinicalTrials.gov: ID NCT01697410.
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The largest terlipressin study in 617 septic shock patients found 28-day mortality of 40% with terlipressin versus 38% with norepinephrine and no differences in SOFA score at day 7 or vasopressor-free days.
“The 28-day mortality in the two groups was 40% for terlipressin and 38% for norepinephrine (OR 0.93; 95% CI 0.55–1.56, p = 0.80), and there were no differences in SOFA score at day 7 or vasopressor free days.”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [367]
In the largest terlipressin study, more patients receiving terlipressin had serious adverse events, including digital ischaemia and diarrhea.
“More patients who received terlipressin had serious adverse events; 33 of 260 (12%) patients experienced digital ischaemia after receiving terlipressin, versus only one patient who received norepinephrine (p < 0.0001); diarrhea was also more common in the terlipressin group (2.7% versus 0.35%, p = 0.037).”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [367]
There were three cases of mesenteric ischaemia in the terlipressin group versus one in the norepinephrine group.
“There were three cases of mesenteric ischaemia in the terlipressin group versus one in the norepinephrine group.”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [367]
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References 30 · Cited by 127
- Authors
- Liu, Z.-M., Chen, J., Kou, Q., Lin, Q., Huang, X., Tang, Z., Kang, Y., Li, K., Zhou, L., Song, Q., Sun, T., Zhao, L., Wang, X., He, X., Wang, C., Wu, B., Lin, J., Yuan, S., Gu, Q., Qian, K., Shi, X., Feng, Y., Lin, A., He, X., Study Group of investigators, Guan, X.-D., Liu, Z.-M., Chen, J., Lin, A., Zeng, J., Huang, Y., Kou, Q., Liu, E., Lin, Q., Liu, J., Huang, X., Zhang, X., Tang, Z., Pan, Y., Kang, Y., Chen, Y., Li, K., Cheng, J., Zhou, L., Qiang, X., Song, Q., Wang, L., Sun, T., Zhao, L., Zhong, J., Wang, X., Chen, H., He, X., Wu, Q., Wang, C., Zeng, J., Wu, B., Luo, J., Lin, J., Fu, Z., Yuan, S., Gu, Q., Liu, N., Qian, K., Shi, X., Feng, Y., Gui, S., & Guan, X.-D.
- Affiliations
- Sun Yat-sen University (CN)
- ORCID
- He, Xiaoshun
- Venue
- Intensive Care Medicine
- Published
- 2018-07-03
- Volume
- 44
- Issue
- 11
- Pages
- 1816-1825
- ISSN
- 0342-4642 (ISSN-L)
- 1432-1238
- OpenAlex
- W2810109598
- Cited by
- 127
- References
- 30
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 12 · 2023: 16 · 2022: 20 · 2021: 15 · 2020: 18 · 2019: 23 · 2018: 1
- FWCI
- 11.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Intensive Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sun Yat-sen University Clinical Research Program 5010 (2007015)
- Major Science and Technology Project of GuangDong province (2012A080204018)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- terlipressin, norepinephrine, septic shock, vasopressor therapy, 28-day mortality, SOFA score, adverse events, vasopressor-free days, vasopressin analogue, catecholamines, intensive care unit patients, fluid resuscitation, sepsis treatment
- MeSH terms
- Terlipressin, Adult, Aged, China, Critical Care, Double-Blind Method, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Norepinephrine, Shock, Septic, Vasoconstrictor Agents, Survival Rate, Treatment Outcome
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