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Running head: FLUID RESUSCITATION
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Fluid Resuscitation for Sepsis: Integrated Review
Autumn Teal
HCM 440 – Healthcare Research & Evaluation
Southern New Hampshire University
April 26, 2020
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Abstract
Aim: The aim of this integrative review is to conduct a review of the literature using a
systematic approach for current research and synthesize these research studies of albumin
resuscitation compared to saline resuscitation in critical care patients with sepsis to validate a
program Critical Care Center for Patient Innovation at Tennessee Memorial Hospital.
Background: Fluid resuscitation is the primary treatment for patients with septic shock and
sepsis. However, only few studies have described the current initial fluid resuscitation practice.
Design and Data Sources: Systemic literature searches from healthcare evidence-based
databases, CINAHL, MEDLINE, and Cochrane Database of Systemic Review for previously
published peer-reviewed studies throughout the years 2011-2019. The inclusion of healthcare
evidence-based databases was integrated. Articles published beyond 2011 were excluded from
database searches.
Review Method: A five-stage integrative review method was used to review and synthesize
current knowledge. This method consisted of developing a problem formulation using a PICO
format, “In critical care patients, how does albumin resuscitation compared to saline resuscitation
affect sepsis?”
Results: Six papers were included in this research dated between 2011 to 2019. According to the
synthesis, the use of albumin containing products versus saline fluid resuscitation did not show a
reduction in mortality among patients.
Conclusion: The use of albumin-containing fluids compared to normal saline for resuscitation in
patients diagnosed with sepsis of any severity did not demonstrate significant advantage. Due to
the cost-effectiveness of albumin, crystalloids should be the first choice for fluid resuscitation in
septic patients.
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Keywords: fluid resuscitation, saline, albumin, sepsis, crystalloids, colloids
Introduction
Background. The problem being addressed in this integrated review is the significance of
mortality rates based on albumin or saline fluid resuscitation in patients diagnosed with sepsis.
The primary treatment and management of patients diagnosed with sepsis is the resuscitation of
fluids. The ideal volume and composition of the resuscitation fluids are currently unknown
(Carlsen & Perner, 2011). The estimated number of patients per year diagnosed with severe
sepsis tops 750,000 in the United States and reaches up to 19 million worldwide. Sepsis presents
with a short-term mortality rate of 20%-30% and exceeds up to 50% when shock is present in the
body. Sepsis death rates continue to rise in the United States and is the leading cause of death
among hospitalized patients in non-coronary intensive care units (Jiang, et al., 2014). However,
early administration of fluid resuscitation interventions is key in the management of sepsis.
Nevertheless, the appropriate use of fluid therapy remains controversial. Therefore, the question
arises, in critical care patients, how does albumin resuscitation compared to saline resuscitation
affect sepsis? The independent variable (IV) in the study is the use of albumin-containing fluids
and the dependent variable (DV) would be how this affects patients diagnosed with sepsis. The
aim of this integrative review is to conduct a review of the literature using a systematic approach
for current research and synthesize these research studies of albumin resuscitation compared to
saline resuscitation in critical care patients with sepsis to validate a Critical Care Center for
Patient Innovation program at Tennessee Memorial Hospital.
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Literature Review
Design and Data Sources. Systemic literature searches were performed from CINAHL,
MEDLINE, and Cochrane Database of Systemic Review databases from 2011 to 2019 for
previously published peer-reviewed studies. These databases were chosen for the searching of
evidence-based scholarly-reviewed articles to validate credible and reliable studies. CINAHL
database provides the top nursing and allied health literature available including nursing journals
and publications from the National League for Nursing and the American Nurses Association.
Literature covers a wide variety of topics from biomedicine to allied health disciplines.
MEDLINE is a bibliographic database of life sciences and biomedical information. It includes
academic journals covering medicine, nursing, pharmacy, dentistry, veterinary medicine, and
healthcare. Cochrane Database of Systemic Review is a library consisting of collections of
databases in medicine and other healthcare specialties. Initial key word searches included fluid
resuscitation, sepsis, saline, albumin-containing solutions, and crystalloids. Further restriction of
key words and MeSH terms included meta-analysis, systematic-review, sepsis, albumin, and
resuscitation yielded considerable results with reliable and expedient information. Utilizing
MeSH terms such as albumin and resuscitation and sepsis produced relevant research articles to
include those specific key words in correlation with the PICO being addressed. Inclusion criteria
for this integrated review were journals and articles that were peer reviewed with information on
fluid resuscitation for sepsis patients and published between 2011 and 2019. Exclusions
consisted of any articles beyond the year 2011 in order to narrow the search. Journal and articles
that did not contain information on sepsis patients or did not have supportive data were also
excluded. All articles were evaluated for highest level of evidence (LOE).
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Methodology Analysis
Review method. A five-stage integrative review method was used. This method consisted of (a)
problem formulation was developed using a PICO format, in critical care patients, how does
albumin resuscitation compared to saline resuscitation affect sepsis, (b) searches of these
evidence-based databases, CINAHL, MEDLINE, and Cochrane Library by using the key words
fluid resuscitation, sepsis, saline, albumin-containing solutions, and crystalloids and MeSH terms
included meta-analysis, systematic-review, sepsis, albumin, and resuscitation (c) evaluation of
data, (d) data analysis and interpretation, and (e) presentation of results in an evidence table by
the identification and evaluation of what was used to review and synthesize current knowledge.
Focus of this review on fluid resuscitation in sepsis was narrowed towards articles less than eight
years old with a focus on systematic reviews and meta-analysis for highest level of evidence
(LOE). Any and all articles from blogs, books, and Google or Google Scholar were excluded due
to lack of credibility and reliability. The dependent and independent variable search terms lead to
the majority of articles and journals chosen being systematic reviews and meta-analysis. These
findings indicate that the articles contain high level of evidence (LOE) and reliability.
Synthesis and Interpretation
Results. Using standard process for conducting an integrative review, six peer-reviewed research
studies published in refereed journals were analyzed and synthesized. According to the synthesis
of these studies, the use of albumin-containing products versus normal saline resuscitation
therapy demonstrated no significant advantage in patients with any severity of sepsis.
The research strategies used to gather information consisted of predominantly randomized
controlled trials (RCTs) with secondary data such as systematic reviews and meta-analysis in
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quantitative research methods. These studies followed a logical manner with a clear and evident
link beginning with the purpose of the study following through. These sources were objective
with no bias noted in the research studies reviewed, with the exception of Annals of Internal
Medicine and The American Journal of Emergency Medicine. The risk of bias for individual
studies and quality of evidence were assessed and was found within the limitations. These trials
were heterogenous in case mix, fluids evaluated, and duration of fluid exposure. Imprecise
estimates for several comparisons in this network meta-analysis contribute to low confidence in
most estimates of effect (Rochwerg, et al., 2014).
Data was collected in numerous ways however randomized trials was leading. Carlsen & Perner
(2011) consisted of a prospective cohort study of all patients with sepsis or septic shock admitted
in six intensive care units during a three-month period. Patients were divided into two groups
according to the overall median volume of resuscitation fluid administered during the first
twenty-four hours after the diagnosis. Jiang, et al., (2014) consisted of fifteen eligible
randomized controlled trials for analysis. Several predefined subgroup analyses were performed
according to patient age (adult or pediatric), type of resuscitation fluid (crystalloids or gelofusine
or starch), concentration of albumin (4% to 5% solution or 20% to 25% solution), follow-up
interval (intensive care unit mortality, hospital mortality, 28/30 day mortality and ninety day
mortality), disease severity (sepsis, sever sepsis, septic shock), and definition of sepsis. Despite
the subgrouping of this particular study, there was no significant effect of albumin-containing
fluids on mortality in patients with sepsis of any severity. While the difference in mortality
between groups did not reach statistical significance, these findings indicate that 4% to 5%
albumin may be safer than 20% to 25% albumin for fluid resuscitation in patients diagnosed with
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sepsis of any severity. Conclusive to this, further studies are implausible to change the existing
conclusion.
Despite best efforts of research and data collection methods, gaps and inconsistences were
present throughout this review process with indications of observable limitations. Rochwerg, et
al., (2014) trials consisted of heterogenous trials, fluids assessed, extent of exposure, and risk of
bias. These factors have the potential to alter conclusions. Liu, et al., (2019) meta-analysis
comprised of potential limitations. Subgroup and sensitivity analyses were of difficulty to
perform due to lack of data. Patients that were included in this meta-analysis presented with
varying levels of secondary trauma such as acute pancreatitis which resulted in heterogeneity.
There was potential for partial recovery of identified research studies, introducing bias. Carlsen
& Perner (2011) impedes strong conclusions regarding the effects of fluid resuscitation for septic
patients. Gaps for this study includes the lack of timing and rate of fluid infusion assessment by
clinicians. The majority of patients in this research method were given broad-spectrum
antibiotics before the absolute diagnosis, but those who had not received them did not present
with an inferior outcome. Despite the limitations and gaps present, this study was solely
observational in design. Delaney, et al., (2011) consisted of a meta-analysis that presented with
non-optimal methodological quality. The results of this analysis differ from those of previous
meta-analyses of albumin in patients with sepsis or severe sepsis. This method focused on a
specific population rather than heterogenous populations such as others. Jiang, et al., (2014)
meta-analysis presented with heterogeneity between different studies and the methodological
quality of all studies included in this research was adaptable.
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Ethical Concerns
Ethical concerns. There were no present concerns of ethics in the creation and implementation in
any of these reviewed studies. The ethics committee of Copenhagen and the Danish Data
Protection Agency approved the study of Carlsen & Perner, (2011). All other studies were
deemed ethical and declared no conflict of interest.
Conclusion
Strengths. The strength of these reviews is included in a precise clinical question that is limited
to patients with sepsis rather than critically ill patients as a whole. The strength lies in the focus
of resuscitation rather than the maintenance of fluid therapy. Studies consisted of inclusions of
patients in intensive care units and comprised of follow-up with the National Patient Registry
using national patient identification numbers.
Limitations. The patterns of limitations varied between studies reviewed based on population,
study size, demographics and control or subgroups being most prevalent. Despite the present
gaps and inconsistencies in each study, they were efficient in concluding the result of albumin-
containing products versus saline in fluid resuscitation not demonstrating an increase in mortality
rates in patients with sepsis.
Validity and Reliability. The results of all studies reviewed deemed reliable and valid as
indication of highest level of evidence (LOE). All studies presented with strong level I of
evidence excluding Carlsen & Perner, (2011), which consists of LOE II. Studies revealed reliable
as confirmation of strong sources, authors, and year published. Studies supported each other with
aligning evidence and outcomes in relation to albumin versus saline resuscitation in patients with
sepsis.
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Implications. The implications of this research reveal that there is no advantage to administering
albumin versus saline in the reduction of mortality in sepsis patients. Based off of these
conclusions, a sepsis patient can be treated with either available intervention. Factors such as
population, demographic, or available access have no determination in which product is
administered. However, if economic burden is present, the use of crystalloids should be of first
choice due to the cost of albumin-containing products.
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References:
Carlsen, S., & Perner, A. (2011). Initial Fluid Resuscitation of Patients with Septic Shock in the
Intensive Care Unit. ACTA Anaesthesiologica Scandinavica, 394–400. doi:
10.1111/j.1399-6576.2011.02399.x
Delaney, A. P., Dan, A. P., McCaffrey, J. P., & Finfer, S. P. (2011). The Role of Albumin as a
Resuscitation Fluid for Patients with Sepsis: A Systematic Review and Meta-Analysis.
Critical Care Medicine, 39(2), 386–391. doi: 10.1097/CCM.0b013e3181ffe217
Jiang, L., Jiang, S., Zhang, M., Zheng, Z., & Ma, Y. (2014). Albumin Versus Other Fluids for
Fluid Resuscitation in Patients with Sepsis: A Meta-Analysis. PloS One, 1–21. doi:
0.1371/journal.pone.0114666
Liu, C., Lu, G., Wang, D., Lei, Y., Mao, Z., Hu, P., … Zhou, F. (2019). Balanced Crystalloids
Versus Normal Saline for Fluid Resuscitation in Critically Ill Patients: A Systematic
Review and Meta-Analysis with Trial Sequential Analysis. The American Journal of
Emergency Medicine, 37(11), 2072–2078. doi: 10.1016/j.ajem.2019.02.045
Rochwerg, B. H., Alhazzani, W. J., Sindi, A. undefined, Heels-Ansdell , D. undefined, Thabane,
L. undefined, Fox-Robichaud, A. undefined, … Annane, D. undefined. (2014). Fluid
Resuscitation in Sepsis: A Systematic Review and Meta-Analysis. Annals of Internal
Medicine, 1–11. doi: 10.7326/M14-0178
Seccombe, A., McCluskey, L., Moorey, H., Lasserson, D., & Sapey, E. (2019). Assessing Fluid
Resuscitation in Adults with Sepsis Who Are Not Mechanically Ventilated: A Systematic
Review of Diagnostic Test Accuracy Studies. Journal of General Internal Medicine,
1874–1883. doi: 10.1007/s11606-019-05073-9
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Appendix A
Table 1. Summary Evidence Table Report Citation Design Method Sample Data Collection Data Analysis Validity and
Reliability Carlsen & Perner (2011)
To evaluate the current initial fluid resuscitation practice in patients with septic shock in the intensive care unit (ICU) and patient characteristics and outcome associated with fluid volume.
Prospective cohort and observational study.
Patients with septic shock admitted in six ICUs during a 3- month period.
One-page case report form by the clinician of the patient in the specific ICU and entered into an Excel data sheet by a single research nurse.
Although more severely shocked patients received higher volumes of crystalloids, colloids, and blood products, mortality did not differ between groups.
Level II LOE. Strong size of patient groups.
Delaney, et al. (2011)
To assess whether resuscitation with albumin-containing solutions, compared to other fluids, is associated with lower mortality in patients with sepsis.
Prospective randomized clinical trials with quantitative data synthesis.
Eight studies including patients with sepsis and nine studies of patients with sepsis as a subgroup.
Two reviewers independently extracted data onto data forms designed specifically for the study; data was checked for accuracy by a third reviewer.
Evidence suggests albumin reduces mortality when used as a resuscitation fluid for patients with sepsis.
Level I LOE. Systematic review and meta-analysis with strong reliability.
Jiang, et al. (2014)
To evaluate whether the use of albumin-containing fluids for resuscitation in
Fifteen randomized controlled trials.
Patients with sepsis of any severity.
Extraction of all relevant data was conducted by two authors independently.
The present meta-analysis did not demonstrate significant
Level I LOE. A meta-analysis with strong reliability.
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patients with sepsis was associated with a decreased mortality rate.
Methodological quality.
advantage of using albumin- containing fluids for resuscitation in patients with sepsis of any severity.
Liu, et al. (2019).
To compare the efficacy and safety of balanced crystalloids with normal saline.
Nine randomized controlled trials were identified. Methodological quality of included trials was assessed by two reviewers according to the Cochrane Risk of Bias Tool.
Critically ill patients over the age of 18 requiring fluid resuscitation.
Two independent reviewers performed the data extraction using a standardized form.
Among critically ill patients receiving crystalloid fluid therapy, the use of a balanced crystalloid compared with normal saline did not reduce the risk of mortality.
Level I LOE. A systematic review and meta-analysis. Low risk of publication bias. Limited sample size, >18 years.
Rochwerg, et al. (2014).
To examine the effect of different resuscitative fluids on mortality in patients with sepsis.
14 studies (18,916 patients) with 15 direct comparisons.
Adult patients with sepsis or septic shock.
Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias and quality of evidence were assessed.
Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with
Level I LOE. A systematic review and network meta- analysis. Risk of bias. Imprecise estimates.
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reduced mortality.
Seccombe, et al. (2019)
To assess studies of diagnostic tests that identify the need for fluid resuscitation in adults with sepsis, as defined by the presence of fluid responsiveness.
594 patients within 14 studies. Reported using PRISMA guidelines.
Adults with sepsis without intensive care organ support, who would be appropriate for admission to an acute medical unit.
Data was extracted using a piloted, standardized form, following translation of non-English language articles if required.
Evidence to support fluid assessment in awake adults is lacking.
Level I LOE. A systematic review with high reliability. Median sample size and primarily single- centre.
