Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 1/2016

Open Access 01-12-2016 | Original research

Early goal-directed resuscitation for patients with severe sepsis and septic shock: a meta-analysis and trial sequential analysis

Authors: Li-bing Jiang, Mao Zhang, Shou-yin Jiang, Yue-feng MA

Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Issue 1/2016

Login to get access

Abstract

Background

The aim of this study was to explore whether early goal-directed therapy (EGDT) was associated with a lower mortality rate in comparison to usual care in patients with severe sepsis and septic shock.

Methods

PubMed, EMBASE, Cochrane library and a Chinese database (SinoMed) were searched systematically to identify randomized controlled trials (RCTs) comparing standard EGDT with usual care in resuscitation of patients with severe sepsis and septic shock and the search time could date back to the publication of the study by Rivers in 2001. The study selection, data extraction and methodological evaluation were performed by two investigators independently. The primary outcome was all-cause mortality. The present meta-analysis had been registered in PROSPERO (CRD42015017667).

Results

Our meta-analysis identified 6 studies and enrolling 4336 patients. There was no significant difference in mortality between the two groups, and the pooled odds ratio (OR) was 0.83 (95 % confident interval, CI, 0.64–1.08) with significant heterogeneity (p = 0.02, I2 = 64 %). However, the pooled OR of 3 multicenter RCTs was 1.03 (95 % CI, 0.89–1.21) with no heterogeneity (p = 0.78, I2 = 0 %). The effects of EGDT on length of stay in the emergency department and intensive care unit were uncertain, and there was no effect of EGDT on hospital length of stay. There were no differences of mechanical ventilation rate and renal replacement therapy rate between the two groups, and patients in the EGDT group were more admitted in ICU than patients in the control group. During the early 6-h intervention period, patients in the EGDT group received more intravenous fluids, had a higher vasopressor usage rate, higher dobutamine usage rate and higher blood transfusion rate, than patients in the control group. Finally, there was no difference in the incidence of adverse events between the two groups, and the pooled OR was 1.06 (95%CI 0.80–1.39) with moderate heterogeneity (I2 = 62 %, p = 0.07).

Discussion

Our meta-analysis showed that the application of EGDT was not associated with lower mortality rate currently. However it does not mean that it is useless of EGDT in patients with sever sepsis and septic shock. On the contrary, there was no difference in mortality rate between the two groups may be due to the improvement of therapeutic strategies in these patients. And the results may be related to the different compliance rate of EGDT resuscitation bundle.

Conclusions

The current evidence does not support the significant advantage of Early goal-directed therapy (EGDT) in the resuscitation of patients with severe sepsis and septic shock.
Appendix
Available only for authorised users
Literature
1.
Jawad I, Lukšić I, Rafnsson SB. Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Glob Health. 2012;2:010404.CrossRefPubMedPubMedCentral
2.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.CrossRefPubMed
3.
Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41:1167–74.CrossRefPubMed
4.
The Australasian Resuscitation in Sepsis Evaluation (ARISE) Investigators, Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD) Management Committee. The outcome of sepsis and septic shock presenting to the emergency departments of Australia and New Zealand. Crit Care Resusc. 2007;9:8–18.
5.
Quenot JP, Binquet C, Kara F, Martinet O, Ganster F, Navellou JC, et al. The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study. Crit Care. 2013;17:R65.CrossRefPubMedPubMedCentral
6.
Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–93.CrossRefPubMed
7.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–77.CrossRefPubMed
8.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.CrossRefPubMed
9.
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296–327.CrossRefPubMed
10.
Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32(3):858–73.CrossRefPubMed
11.
Micek ST, Roubinian N, Heuring T, Bode M, Williams J, Harrison C, et al. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med. 2006;34:2707–13.CrossRefPubMed
12.
Nguyen HB, Corbett SW, Steele R, Banta J, Clark RT, Hayes SR, et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med. 2007;35:1105–12.
13.
Trzeciak S, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, et al. Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest. 2006;129:225–32.CrossRefPubMed
14.
Shapiro NI, Howell MD, Talmor D, Lahey D, Ngo L, Buras J, et al. Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol. Crit Care Med. 2006;34:1025–32.
15.
Kortgen A, Niederprum P, Bauer M. Implementation of an evidence-based “standard operating procedure” and outcome in septic shock. Crit Care Med. 2006;34:943–9.CrossRefPubMed
16.
El Solh AA, Akinnusi ME, Alsawalha LN, Pineda LA. Outcome of septic shock in older adults after implementation of the sepsis “bundle”. J Am Geriatr Soc. 2008;56:272–8.CrossRefPubMed
17.
Sebat F, Johnson D, Musthafa AA, Watnik M, Moore S, Henry K, et al. A multidisciplinary community hospital program for early and rapid resuscitation of shock in nontrauma patients. Chest. 2005;127:1729–43.
18.
Jones AE, Focht A, Horton JM, Kline JA. Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock. Chest. 2007;132:425–32.CrossRefPubMedPubMedCentral
19.
Girardis M, Rinaldi L, Donno L, Marietta M, Codeluppi M, Marchegiano P, et al. Sopravvivere alla Sepsi Group of the Modena-University Hospital: Effects on management and outcome of severe sepsis and septic shock patients admitted to the intensive care unit after implementation of a sepsis program: a pilot study. Crit Care. 2009;13:R143.
20.
Castellanos-Ortega A, Suberviola B, García-Astudillo LA, Holanda MS, Ortiz F, Llorca J, et al. Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study. Crit Care Med. 2010;38:1036–43.
21.
Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015;43(1):3–12.CrossRefPubMed
22.
Ferrer R, Artigas A, Levy MM, Blanco J, González-Díaz G, Garnacho-Montero J, et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299:2294–303.
23.
Shin HJ, Kang HL, Hwang SO, Kim H, Shin TY, Sang CK, et al. The efficacy of early goal-directed therapy in septic shock patients in the emergency department: severe sepsis campaign. Korean J Critic Care Med. 2010; 25(2):61-70.
24.
Pestaña D, Espinosa E, Sangüesa-Molina JR, Ramos R, Pérez-Fernández E, Duque M, et al. Compliance with a sepsis bundle and its effect on intensive care unit mortality in surgical septic shock patients. J Trauma. 2010;69:1282–7.
25.
Miller 3rd RR, Dong L, Nelson NC, Brown SM, Kuttler KG, Probst DR, et al. Intermountain Healthcare Intensive Medicine Clinical Program: Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med. 2013;188:77–82.
26.
Heppner HJ, Singler K, Kwetkat A, Popp S, Esslinger AS, Bahrmann P, et al. Do clinical guidelines improve management of sepsis in critically ill elderly patients? A before-and-after study of the implementation of a sepsis protocol. Wien Klin Wochenschr. 2012;124:692–8.
27.
Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-h and 24-h sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Crit Care. 2005;9:R764–70.CrossRefPubMedPubMedCentral
28.
Lefrant JY, Muller L, Raillard A, Jung B, Beaudroit L, Favier L, et al. Reduction of the severe sepsis or septic shock associated mortality by reinforcement of the recommendations bundle: a multicenter study. Ann Fr Anesth Reanim. 2010;29:621–8.
29.
Cardoso T, Carneiro AH, Ribeiro O, Teixeira-Pinto A, Costa-Pereira A. Reducing mortality in severe sepsis with the implementation of a core 6-h bundle: results from the Portuguese community-acquired sepsis study (SACiUCI study). Crit Care. 2010;14:R83.CrossRefPubMedPubMedCentral
30.
Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496–506.CrossRefPubMed
31.
Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301–11.CrossRefPubMed
32.
Gu WJ, Wang F, Bakker J, Tang L, Liu JC. The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials. Crit Care. 2014;18(5):570.CrossRefPubMedPubMedCentral
33.
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.CrossRefPubMedPubMedCentral
34.
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55.
35.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250–6.CrossRefPubMed
36.
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. Oxford: The Cochrane Collaboration; 2011.
37.
Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials. BMJ. 2011;343:d5928.
38.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefPubMed
39.
40.
41.
42.
Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61:763–9.CrossRefPubMed
43.
Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Med Res Methodol. 2009;9:86.CrossRefPubMedPubMedCentral
44.
Jiang L, Jiang S, Zhang M, Zheng Z, Ma Y. Albumin versus other fluids for fluid resuscitation in patients with sepsis: a meta-analysis. PLoS One. 2014;9(12):e114666.CrossRefPubMedPubMedCentral
45.
Wang XZ, Lü CJ, Gao FQ, Li XH, Yan WF, Ning FY. Efficacy of goal-directed therapy in the treatment of septic shock. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2006;18:661–4.PubMed
46.
Early Goal-Directed Therapy Collaborative Group of Zhejiang Province. The effect of early goal-directed therapy on treatment of critical patients with severe sepsis/septic shock: a multi-center, prospective, randomized, controlled study. ZhongguoWei Zhong Bing Ji Jiu Yi Xue. 2010;22:331–4.
47.
Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012;40:754–61.CrossRefPubMed
48.
Muck A, Adams BD. ACP journal club. Early goal-directed therapy did not reduce mortality more than usual care in early septic shock. Ann Intern Med. 2015;162(6):JC4.CrossRefPubMed
49.
Zhu Y, Tao RJ, Shi W, Tong JJ, Lu YM. A study of rate of compliance with sepsis bundle in patients with severe sepsis and septic shock in emergency department. Chin Crit Care Med. 2011;23:138–41.
50.
Nguyen HB, Lynch EL, Mou JA, Lyon K, Wittlake WA, Corbett SW. The utility of a quality improvement bundle in bridging the gap between research and standard care in the management of severe sepsis and septic shock in the emergency department. Acad Emerg Med. 2007;14:1079–86.CrossRefPubMed
51.
Na S, Kuan WS, Mahadevan M, Li CH, Shrikhande P, Ray S, et al. Implementation of early goal-directed therapy and the surviving sepsis campaign resuscitation bundle in Asia. Int J Qual Health Care. 2012;24(5):452–62.CrossRefPubMed
52.
Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, et al. Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ. 2011;342:d3245.CrossRefPubMedPubMedCentral
53.
Yin M, Meng XK, Zheng XY, Xiong LH, Zhou D, Zhang XH, et al. The implementation of early goal-directed therapy of patients with severe sepsis and septic shock in China: a multi-center study. The ninth army emergency medicine academic conference proceedings. 2011. p. 161–4.
54.
Zhao L, Xiao B, Liu CL, Wang XY, Li B, Du XX. Establishment and application of the number of outpatient and emergence visits and discharged patients prediction linear regression model. Chinese Medical Record. 2014;11:39–40.
55.
Wira CR, Dodge K, Sather J, Dziura J. Meta-analysis of protocolized goal-directed hemodynamic optimization for the management of severe sepsis and septic shock in the emergency department. West J Emerg Med. 2014;15:51–9.CrossRefPubMedPubMedCentral
56.
Chamberlain DJ, Willis EM, Bersten AB. The severe sepsis bundles as processes of care: a meta-analysis. Aust Crit Care. 2011;24:229–43.CrossRefPubMed
57.
Barochia AV, Cui X, Vitberg D, Suffredini AF, O’Grady NP, Banks SM, et al. Bundled care for septic shock: analysis of clinical trials. Crit Care Med. 2010;38:668–78.CrossRefPubMedPubMedCentral
58.
59.
Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303:739–46.CrossRefPubMedPubMedCentral
60.
Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;182:752–61.CrossRefPubMed
61.
Legrand M, Dupuis C, Simon C, Gayat E, Mateo J, Lukaszewicz AC, et al. Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Crit Care. 2013;17:R278.CrossRefPubMedPubMedCentral
62.
63.
Saugel B, Trepte CJ, Heckel K, Wagner JY, Reuter DA. Hemodynamic Management of Septic Shock: Is It Time for “Individualized Goal-Directed Hemodynamic Therapy” and for Specifically Targeting the Microcirculation? Shock. 2015;43(6):522–9.CrossRefPubMed
Metadata
Title
Early goal-directed resuscitation for patients with severe sepsis and septic shock: a meta-analysis and trial sequential analysis
Authors
Li-bing Jiang
Mao Zhang
Shou-yin Jiang
Yue-feng MA
Publication date
01-12-2016
Publisher
BioMed Central
DOI
https://doi.org/10.1186/s13049-016-0214-7

Other articles of this Issue 1/2016

Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 1/2016 Go to the issue

Original research

Physician staffed helicopter emergency medical service case identification - a before and after study in children

Original research

Which score should be used for posttraumatic multiple organ failure? - Comparison of the MODS, Denver- and SOFA- Scores

Original research

Impact of Cushing’s sign in the prehospital setting on predicting the need for immediate neurosurgical intervention in trauma patients: a nationwide retrospective observational study

Original research

Head computed tomographic measurement as a predictor of outcome in patients with subdural hematoma with cerebral edema

Original research

Continuous venovenous hemofiltration decreases mortality and ameliorates acute lung injury in canine model of severe salt water drowning

Original research

An exploration of the views of paramedics regarding airway management