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      Health economic evaluations of sepsis interventions in critically ill adult patients: a systematic review

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          Abstract

          Background

          Sepsis is a global health priority. Interventions to reduce the burden of sepsis need to be both effective and cost-effective. We performed a systematic review of the literature on health economic evaluations of sepsis treatments in critically ill adult patients and summarised the evidence for cost-effectiveness.

          Methods

          We systematically searched MEDLINE, Embase, and the Cochrane Library using thesaurus (e.g. MeSH) and free-text terms related to sepsis and economic evaluations. We included all articles that reported, in any language, an economic evaluation of an intervention for the management of sepsis in critically ill adult patients. Data extracted included study details, intervention details, economic evaluation methodology, and outcomes. Included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.

          Results

          We identified 50 records representing 46 economic evaluations for a variety of interventions including antibiotics ( n = 5), fluid therapy ( n = 2), early goal-directed therapy and other resuscitation protocols ( n = 8), immunoglobulins ( n = 2), and interventions no longer in clinical use such as monoclonal antibodies ( n = 7) and drotrecogin alfa ( n = 13). Twelve (26%) evaluations were of excellent reporting quality. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (lower costs and higher effectiveness) for early goal-directed therapy, albumin, and a multifaceted sepsis education program to dominated (higher costs and lower effectiveness) for polymerase chain reaction assays (LightCycler SeptiFast testing MGRADE®, SepsiTest™, and IRIDICA BAC BSI assay). ICERs varied widely across evaluations, particularly in subgroup analyses.

          Conclusions

          There is wide variation in the cost-effectiveness of sepsis interventions. There remain important gaps in the literature, with no economic evaluations identified for several interventions routinely used in sepsis. Given the high economic and social burden of sepsis, high-quality economic evaluations are needed to increase our understanding of the cost-effectiveness of these interventions in routine clinical practice and to inform decision makers.

          Trial registration

          PROSPERO CRD42018095980

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          Most cited references48

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          Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review.

          The benefit of corticosteroids in severe sepsis and septic shock remains controversial. We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P = .05; I(2) = 53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P = .02; I(2) = 4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P < .001; I(2) = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P = .50; I(2) = 0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P = .92; I(2) = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P = .58; I(2) = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P < .001; I(2) = 0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P < .001; I(2) = 0%). Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.
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            Severe sepsis and septic shock.

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              Fluid resuscitation in sepsis: a systematic review and network meta-analysis.

              Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. To examine the effect of different resuscitative fluids on mortality in patients with sepsis. MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014. Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied. Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed. 14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence). These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect. Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality. The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.
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                Author and article information

                Contributors
                lisa.higgins@monash.edu
                Journal
                J Intensive Care
                J Intensive Care
                Journal of Intensive Care
                BioMed Central (London )
                2052-0492
                8 January 2020
                8 January 2020
                2020
                : 8
                : 5
                Affiliations
                [1 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, , Monash University, ; 553 St Kilda Rd, Melbourne, Victoria 3004 Australia
                [2 ]ISNI 0000 0004 0432 511X, GRID grid.1623.6, Department of Intensive Care and Hyperbaric Medicine, , The Alfred, ; Melbourne, Victoria Australia
                [3 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, Centre for Health Economics, , Monash University, ; Melbourne, Victoria Australia
                Author information
                http://orcid.org/0000-0001-8295-7559
                Article
                412
                10.1186/s40560-019-0412-2
                6950865
                31908779
                d115ee49-105c-4089-8f79-09d22485de63
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                History
                : 14 August 2019
                : 31 October 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 579709
                Award ID: 1142215
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                sepsis,septic shock,cost-effectiveness,economic evaluation,systematic review

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