Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial

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Abstract

Background

Administration of dexmedetomidine has been reported to improve inflammatory response in animals. We explored the effects of administering dexmedetomidine on the levels of C-reactive protein (CRP) and procalcitonin, and thus on inflammation, in patients with sepsis enrolled in a randomized clinical trial.

Methods

The DESIRE trial was a multicenter randomized clinical trial in which adult patients with sepsis were sedated with (DEX group) or without (non-DEX group) dexmedetomidine while on mechanical ventilators. As a prespecified sub-analysis, we compared CRP and procalcitonin levels during the first 14 days of treatment between the two groups. The 14-day mortality rate, albumin level, and the number of patients with disseminated intravascular coagulation (DIC) were also assessed. We used generalized linear models to estimate the differences in these outcomes between groups. We also used the Kaplan-Meier method to estimate the 14-day mortality rate and the log-rank test to assess between-group differences.

Results

Our study comprised 201 patients: 100 in the DEX group and 101 in the non-DEX group. CRP and procalcitonin levels were lower in the DEX vs. non-DEX group during the 14-day treatment period [CRP—range, 5.6–20.3 vs. 8.3–21.1 mg/dL ( P = 0.03); procalcitonin—range, 1.2–37.4 vs. 1.7–52.9 ng/mL ( P = 0.04)]. Albumin levels were higher in the DEX group (range, 2.3–2.6 g/dL) than in the non-DEX group (range, 2.1–2.7 g/dL; P = 0.01). The percentage of patients with DIC did not significantly differ between the groups (range, 21–59% and 17–56% for the DEX and non-DEX groups, respectively; P = 0.49). The 14-day mortality rates in the DEX and non-DEX groups were 13 and 21%, respectively ( P = 0.16).

Conclusion

Sedation using dexmedetomidine reduced inflammation in patients with sepsis requiring mechanical ventilation.

Trial registration

ClinicalTrials.gov, NCT01760967. Registered on 4 January 2013.

Related collections

Most cited references 22

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The late phase of sepsis is characterized by an increased microbiological burden and death rate

Gordon Otto, Maik Sossdorf, Ralf A. Claus … (2011)

Introduction Recent models capturing the pathophysiology of sepsis and ex-vivo data from patients are speculating about immunosuppression in the so-called late phase of sepsis. Clinical data regarding survival and microbiological burden are missing. The aim of this study was to determine the clinical significance of the 'late phase' of sepsis with respect to overall survival and occurrence of microbiological findings. Methods In a retrospective trial, 16,041 patient charts from a university intensive care unit were screened, and 999 patients with severe sepsis or septic shock were identified. Three phases were established according to the mortality peaks which were separated by two distinct nadirs: phase I (days 1 to 5), phase II (days 6 to 15) and phase III (days 16 to 150). Patients were analyzed for outcome, SOFA scores, procalcitonin levels, antimicrobial treatment, dialysis, mechanical ventilation and results of blood cultures during their hospital stay. Results Out of 999 enrolled patients, 308 died during the course of sepsis presenting a characteristic mortality rate (30.8%) with three distinct mortality peaks (at days 2, 7 and 17). Overall 36.7% of all deaths occurred in the early phase (phase I) and 63.3% during the later phases (phase II + III). In total 2,117 blood cultures were drawn. In phase I, 882 blood cultures were drawn, representing a sampling rate of 88% with a positive rate of 14.9%. In phase II, 461 samples were taken, indicating a sampling rate of 52% and a positive rate of 11.3%. Within phase III, 524 samples were obtained representing a sampling rate of 66% with a positive rate of 15.3%, which was significantly higher compared to the positive rate of phase II and similar to phase I. In particular, the rate of typically opportunistic bacteria increased significantly from 9% in phase I up to 18% in phase III. The same is true for Candida spp. (phase I 13%, phase III 30%). Conclusions The later phase of sepsis is associated with a significant re-increase of positive blood culture results, especially regarding opportunistic bacteria and fungi. These observations warrant further studies focusing on the underlying mechanisms resulting in this outcome burden in the later phase of sepsis.

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Hypoalbuminemia.

Angelo Gatta, Alberto Verardo, Massimo Bolognesi (2012)

Hypoalbuminemia is frequently observed in hospitalized patients and it can be associated with several different diseases, including cirrhosis, malnutrition, nephrotic syndrome and sepsis. Regardless of its cause, hypoalbuminemia has a strong predictive value on mortality and morbidity. Over the years, the rationale for the use of albumin has been extensively debated and the indications for human serum albumin supplementation have changed. As the knowledge of the pathophysiological mechanisms of the pertinent diseases has increased, the indications for intravenous albumin supplementation have progressively decreased. The purpose of this brief article is to review the causes of hypoalbuminemia and the current indications for intravenous administration of albumin. Based on the available data and considering the costs, albumin supplementation should be limited to well-defined clinical scenarios and to include patients with cirrhosis and spontaneous bacterial peritonitis, patients with cirrhosis undergoing large volume paracentesis, the treatment of type 1 hepatorenal syndrome, fluid resuscitation of patients with sepsis, and therapeutic plasmapheresis with exchange of large volumes of plasma. While albumin supplementation is accepted also in other clinical situations such as burns, nephrotic syndrome, hemorrhagic shock and prevention of hepatorenal syndrome, within these contexts it does not represent a first-choice treatment nor is its use supported by widely accepted guidelines.

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Treating patients with severe sepsis.

A P Wheeler, G R Bernard (1999)

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Author and article information

Contributors

Takeshi Morimoto:

ORCID: http://orcid.org/0000-0002-6844-739X

morimoto@kuhp.kyoto-u.ac.jp

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 10 August 2020

Publication date PMC-release: 10 August 2020

Publication date Collection: 2020

Volume: 24

Electronic Location Identifier: 493

Affiliations

[1 ]GRID grid.272264.7, ISNI 0000 0000 9142 153X, Education and Training Center for Students and Professionals in Healthcare, , Hyogo College of Medicine, ; Nishinomiya, Japan

[2 ]GRID grid.412857.d, ISNI 0000 0004 1763 1087, Department of Emergency and Critical Care Medicine, , Wakayama Medical University, ; Wakayama, Japan

[3 ]GRID grid.69566.3a, ISNI 0000 0001 2248 6943, Division of Emergency and Critical Care Medicine, , Tohoku University Graduate School of Medicine, ; Sendai, Japan

[4 ]Osaka Prefectural Nakakawachi Emergency and Critical Care Center, Higashiosaka, Japan

[5 ]GRID grid.272264.7, ISNI 0000 0000 9142 153X, Department of Clinical Epidemiology, , Hyogo College of Medicine, ; Nishinomiya, Japan

Author information

Takeshi Morimoto http://orcid.org/0000-0002-6844-739X

Article

Publisher ID: 3207

DOI: 10.1186/s13054-020-03207-8

PMC ID: 7416813

PubMed ID: 32778146

SO-VID: 454525e5-971e-4346-ab65-0f8b3c260665

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 8 February 2020

Date accepted : 27 July 2020

Funding

Funded by: Hospira

Award ID: NA

Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;

Award ID: JP17K09252

Award ID: JP25860484

Award ID: JP15K21535

Award ID: JP17689022

Award ID: JP21659130

Award ID: JP22390103

Award ID: JP23659256

Award ID: JP26293159

Award Recipient : Yoshinori Ohta Takeshi Morimoto

Funded by: Japan Society for the Promotion of Science (JP)

Award ID: JP20K07839

Award Recipient : Yoshinori Ohta

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: dexmedetomidine,inflammation,sepsis,c-reactive protein,procalcitonin

Data availability:

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: dexmedetomidine, inflammation, sepsis, c-reactive protein, procalcitonin

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Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial

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Abstract

Background

Methods

Results

Conclusion

Trial registration

Related collections

Irish Journal of Paramedicine

Most cited references 22

The late phase of sepsis is characterized by an increased microbiological burden and death rate

Hypoalbuminemia.

Treating patients with severe sepsis.

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Contributors

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Affiliations

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Article

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Funding

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Cited by 23

Most referenced authors 935