R E S E A R C H Open Access
Early fluid bolus in adults with sepsis in the
emergency department: a systematic
review, meta-analysis and narrative
, Steven A. Frost
, Deborah Hatcher
, Amith Shetty
, Jann Foster
and Stephen McNally
Background: Early intravenous fluids for patients with sepsis presenting with hypoperfusion or shock in the
emergency department remains one of the key recommendations of the Surviving Sepsis Campaign guidelines to
reduce mortality. However, compliance with the recommendation remains poor. While several interventions have
been implemented to improve early fluid administration as part of sepsis protocols, the extent to which they have
improved compliance with fluid resuscitation is unknown. The factors associated with the lack of compliance are
also poorly understood.
Methods: We conducted a systematic review, meta-analysis and narrative review to investigate the effectiveness of
interventions in emergency departments in improving compliance with early fluid administration and examine the
non-interventional facilitators and barriers that may influence appropriate fluid administration in adults with sepsis.
We searched MEDLINE Ovid/PubMed, Ovid EMBASE, CINAHL, and SCOPUS databases for studies of any design to
April 2021. We synthesised results from the studies reporting effectiveness of interventions in a meta-analysis and
conducted a narrative synthesis of studies reporting non-interventional factors.
Results: We included 31 studies out of the 825 unique articles identified in the systematic review of which 21 were
included in the meta-analysis and 11 in the narrative synthesis. In meta-analysis, interventions were associated with
a 47% improvement in the rate of compliance [(Random Effects (RE) Relative Risk (RR) = 1.47, 95% Confidence
Interval (CI), 1.25–1.74, p-value < 0.01)]; an average 24 min reduction in the time to fluids [RE mean difference = −
24.11(95% CI −14.09 to −34.14 min, pvalue < 0.01)], and patients receiving an additional 575 mL fluids [RE mean
difference = 575.40 (95% CI 202.28–1353.08, pvalue < 0.01)]. The compliance rate of early fluid administration
reported in the studies included in the narrative synthesis is 48% [RR = 0.48 (95% CI 0.24–0.72)].
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* Correspondence: firstname.lastname@example.org
Western Sydney University, School of Nursing and Midwifery, Locked bag
1797, Penrith, NSW 2751, Australia
Department of Emergency, Westmead Hospital, Sydney, Australia
Full list of author information is available at the end of the article
Kabil et al. BMC Emergency Medicine (2022) 22:3
Conclusion: Performance improvement interventions improve compliance and time and volume of fluids administered
to patients with sepsis in the emergency department. While patient-related factors such as advanced age, co-morbidities,
cryptic shock were associated with poor compliance, important organisational factors such as inexperience of clinicians,
overcrowding and inter-hospital transfers were also identified. A comprehensive understanding of the facilitators and
barriers to early fluid administration is essential to design quality improvement projects.
PROSPERO Registration ID: CRD42021225417.
Keywords: Sepsis, Fluid therapy, Barriers, Facilitators, Compliance
Sepsis is defined as a dysregulated immune response to
infection, which if deteriorating to septic shock results
in high mortality and morbidity . It is a medical emer-
gency now recognised as a global health priority [2,3].
One of the key determinants of mortality is tissue hypo-
perfusion, which leads to multi-organ failure . There-
fore, restoration of cardiac output with early intravenous
fluid bolus remains a mainstay of treatment in patients
with septic shock . In their landmark study, Rivers
et.al  showed that early management of sepsis with
appropriate fluids within the first 6 hours of presentation
resulted in a 16% reduction in the risk of mortality.
The Surviving Sepsis Campaign has since provided
several recommendations for sepsis management with
goals to be achieved within the first 3 and 6 h . The
recommendations include administration of 30 mL/kg of
intravenous fluid bolus for patients with hypotension;
administration of antibiotics; obtaining blood culture
and lactate . Implementation of these guidelines over
the last decades has resulted in an overall 16.7% decrease
in mortality . However, the Surviving Sepsis Guide-
lines have been revised periodically with ongoing
changes to recommended time of initiation and comple-
tion of bundles varying from 6-h in 2005 to 1-h in 2018
 with the latest change to 3-h bundles in 2021 .
These changes have provoked debates among clinicians
with some resistance to implementing these guidelines
. Concerns regarding fluid volume overload associated
with injudicious use of intravenous fluids  have also
resulted in some advocating for a conservative approach
to fluid resuscitation while others show benefit from
early administration of fluid bolus . However, it is
important to note that these studies do not contradict
the importance of early fluid administration but warn
against unwarranted cumulative administration of intra-
venous fluids beyond the initial resuscitation phase.
These clinical concerns and controversies are of particu-
lar relevance in settings like ED with time pressures and
constant competing priorities.
Prompt recognition and management of sepsis in the
emergency department remains an ongoing challenge.
Compliance with critical interventions such as intravenous
fluid bolus is reported to be poor . Recently an
increasing number of studies [13,14]haveexaminedthe
facilitators and barriers to the implementation of the
Surviving Sepsis Campaign interventions with a subset of
them analysing the time taken to initiate the first intraven-
ous fluid bolus. However, the results of these studies have
not been systematically identified and reported to sum-
marise the overall benefit of the interventions to facilitate
the timely administration of fluids in sepsis patients pre-
senting to the emergency department. Therefore, we have
undertaken a systematic review with meta-analysis and
narrative synthesis [15,16] to summarize the published
literature investigating factors associated with early initi-
ation of intravenous fluid bolus in patients presenting to
the emergency department with sepsis.
This systematic review has two aims: (1) to describe
the effectiveness of interventions implemented in the
emergency department to improve compliance with
early fluid bolus initiation, including time to, and the
total volume of fluids administered by conducting a
meta-analysis; and (2) to examine the non-interventional
factors that may be barriers or facilitators to appropriate
fluid administration using narrative synthesis.
This systematic review has been conducted based on a
priori protocol published in PROSPERO (ID:
CRD42021225417), and planned, conducted and reported
in accordance with the PRISMA statement . We
sought to conduct a mixed-method systematic review.
However, the search results yielded only one qualitative
study  that met the inclusion criteria. Therefore, a sys-
tematic review and meta-analysis of quantitative studies
was conducted with a narrative synthesis of potential facil-
itators and barriers to appropriate fluid administration
among adult septic patients presenting to the emergency
This review includes studies with experimental or quasi-
experimental design that included adult patients (age >
17 years) presenting to the emergency department with
sepsis, systemic inflammatory response syndrome (SIRS),
Kabil et al. BMC Emergency Medicine (2022) 22:3 Page 2 of 11
severe sepsis, septic shock or a combination of any of
these. Study designs included randomised controlled tri-
als, before and after studies, prospective and retrospect-
ive cohort studies, case-control studies and analytical
cross-sectional studies. Studies published before 2001
were excluded as the concept of early goal-directed ther-
apy for sepsis was introduced in 2001. Studies conducted
in settings other than the emergency department were
excluded. The search was not restricted for language,
however, only articles that were available in English were
reviewed. We did not restrict studies if factors improving
or increasing the time to first fluid bolus, were not re-
ported as their main objectives, however all included
studies provided data based upon either of these two
For aim (1), any intervention or strategies imple-
mented that influence early intravenous fluid bolus such
as educational programs, sepsis alerts and sepsis
protocols were included. Studies reporting the rate of
compliance with intravenous fluid resuscitation, time to
first fluid bolus, and volume of fluids administered were
included. Studies with well-defined intervention and
control groups were included in the meta-analysis. We
did not impose restrictions based on the number of in-
terventions implemented. For aim (2), studies exploring
the influence of non-interventional factors such as over-
crowding and inter-hospital transfers on compliance
with early fluid bolus initiation were included in the
Data sources and search strategy
The search strategy (Additional file 1) was developed in
collaboration with two expert librarians and the search
results were reviewed and verified. We systematically
searched the electronic databases MEDLINE Ovid/
PubMed, Ovid EMBASE, CINAHL, SCOPUS from in-
ception through April 2021. The JBI and COCHRANE
libraries were searched for related systematic reviews.
Trove, ProQuest Dissertations, Google Scholar were
used for grey-literature search. Reference lists from
eligible studies were manually searched to identify add-
After removing duplicates, two investigators (GK and
SM) independently screened all identified titles and
abstracts using COVIDENCE software for systematic
reviews  and conflicts were resolved by a third inves-
tigator (SF). Articles not meeting the inclusion criteria
were excluded, and the remaining were evaluated in full
text. Disagreements were reconciled through discussion
and consensus with all the investigators. Studies with in-
terventions or strategies implemented that influence the
compliance or time of administration and volume of
intravenous fluid bolus were included in the meta-
analysis. Studies reporting non-interventional factors
were included in the narrative synthesis.
Data extraction and quality assessment
Studies selected for retrieval were assessed by two
independent reviewers (GK and SM) for methodological
validity using standardised critical appraisal instruments
from JBI SUMARI . The results of the critical
appraisal are presented as a table (Additional file 2). All
studies regardless of their methodological quality were
extracted and synthesised where possible.
The study characteristics data of all included studies
was extracted using the standardised Joanna Briggs Insti-
tute data extraction tool in JBI SUMARI with details
about the study population, study methods and out-
comes of significance to the review objective (Additional
file 3). The information included in data extraction for
studies included in the meta-analysis are presented in
Table 1. The primary outcome of interest was the time
to and volume of initial fluid bolus administration or the
rates of compliance with the internationally accepted
Surviving Sepsis Campaign guidelines.
The meta package V4.17–0 in R statistical language
was used to conduct the meta-analysis. We
summarised the effectiveness of the interventions on
compliance, time to administration and volume adminis-
tered in a meta-analysis. We grouped the studies based
Table 1 Data Extraction Information for Studies included in the
S. No Information
2 Year of publication
3 Study design
4 Emergency department type
5 Number of patients enrolled in the control group
6 Number of patients in the intervention group
7 Number compliant with early intravenous fluid bolus in control
8 Number complaint with early intravenous fluid bolus in
9 Time to administration of first fluid bolus in control group
10 Time to administration of first fluid bolus in intervention group
11 Volume of fluids received by patients in control group
12 Volume of fluids received by patients in intervention group
13 Whether or not the studied intervention had any improvement
in compliance with time and volume of initial fluid bolus
14 Number of interventions implemented
Kabil et al. BMC Emergency Medicine (2022) 22:3 Page 3 of 11
on outcomes reported as compliance rate. We have
reported both the random-effects model (DerSimonian-
Laird estimator) and fixed-effects model (Mantel-
Haenszel estimator). For continuous variables (time to
fluids and volume), the mean and standard deviations
(SD) or the median and interquartile range (IQR) were
presented. For meta-analysis of these continuous out-
comes, if only median and IQR were reported, mean
and SD were derived using the method suggested by
Luo and Shi [23–26]. Heterogeneity between studies
was assessed using an I
statistic and a p-value < 0.1
was chosen to represent evidence of statistical hetero-
geneity. Publication bias was assessed by inspection of
funnel plots and asymmetry was assessed using the re-
gression test suggested by Egger (a p-value < 0.1 was
considered as evidence of funnel plot asymmetry) .
The narrative synthesis was undertaken using the
Guidance for Systematic Reviews [28,29]. We identified
factors such as overcrowding, inter-hospital transfer and
failure to recognise sepsis reported in the studies that
were not suitable for a meta-analytical approach. To syn-
thesise all these factors, we tabulated the data from these
studies and used textual description of the identified fac-
tors. We then regrouped the factors based on whether
they were found to be barriers, facilitators or factors that
had no influence on the early initiation of intravenous
fluid bolus in sepsis along with any additional recom-
mendations reported in the studies (Table 2).
Assessing temporal trend
To examine any potential impact of the changes to the
Surviving Sepsis Guidelines over the years, cumulative
meta-analysis  was performed using the year the
studies were commenced reflecting the guideline
changes during the study period. In addition, meta re-
gression was done using the year studies commenced as
The process of identifying studies to be included in the
review at various stages are presented as a PRISMA
flow-diagram in Fig. 1. The initial electronic search from
databases identified 925 potential articles, of which 100
articles were identified as duplicates. Titles and abstracts
of 825 articles were screened for eligibility, of which 172
articles were retained for full-text review. After applying
the inclusion and exclusion criteria, 31 articles were
retained. Twenty-one of these studies [33,41–60]included
interventions and reported the effectiveness of these inter-
ventions and were subsequently included in a meta-
analysis. Eleven studies that reported non-interventional
factors are presented as a narrative synthesis. One of
the eleven studies reported both intervention and explored
the non-interventional factors impacting the compliance
using a survey and has therefore been included in both the
meta-analysis and the narrative synthesis. Among the stud-
ies included in the meta-analysis, we observed variations in
the definitions used to define sepsis and septic shock in-
cluding Sepsis 2 definition, Sepsis 3 definition, International
Classification of Diseases (ICD) Codes 9 and 10 (see
Additional file 3). Of the studies included in the analysis of
time to first fluid bolus, most studies used time of arrival at
triage as the time zero while two studies [54,59], have used
time of diagnosis of sepsis as part of the intervention as the
time zero (see Additional file 3).
The studies included in the meta-analysis were analysed
based on data reported for three specific outcome
measures: (1) compliance with early fluid bolus adminis-
tration within the protocol recommended time; (2) time
to administration of initial fluid bolus; and (3) volume of
fluids administered within the protocol recommended
Compliance with early fluid bolus administration
Fifteen studies enrolling 1538 patients in the interven-
tion group and 1969 patients in the control group inves-
tigated the effectiveness of the interventions on the rate
of compliance with the initiation of 20-30 mL/Kg of
intravenous fluid bolus within 3–6 h of presenting at tri-
age in the emergency department. Individual study and
summary estimates of the comparison of rates of com-
pliance during the intervention and control period are
presented in Fig. 2. A random effects summary meta-
analysis estimated a 47% improvement in the rate of
compliance with early fluid bolus initiation during the
intervention period compared to the control period
(Random Effects (RE) Relative Risk (RR) = 1.47, 95%
Confidence Interval (CI), 1.25–1.74, p-value < 0.01).
Time to initiation of first fluid bolus
Eleven studies evaluated the impact of the interventions
on the time of initiation of the first intravenous fluid
bolus (Fig. 3). A total of 940 patients were enrolled in
the intervention group and 1256 patients in the control
group. The pooled (RE) estimate of the mean difference
in time was −24.11 min (95% CI −14.09 to −34.14 min,
p-value < 0.01), indicating an average 24 min reduction
in the time to fluid resuscitation between the interven-
tion and control groups.
Volume of fluids administered
Six studies with 537 patients in the control group
and 544 patients in the intervention group were eval-
uated for the difference in the volume of fluids ad-
ministered to patients who received the intervention
(Fig. 4). The pooled (RE) effect size was a mean of
Kabil et al. BMC Emergency Medicine (2022) 22:3 Page 4 of 11
575.40 mL (95% CI 202.28–1353.08 mL, pvalue <
0.01), indicating that patients received an average
additional 575 mL within the protocol recommended
time as a result of the interventions.
All studies included in the three outcome groups of
meta-analysis were assessed for publication bias using
visual inspection of the funnel plots (Additional file 4).
Table 2 Narrative Synthesis with description of factors influencing early initiation of fluid bolus in sepsis
Barriers identified Compliance Rate Factors that had no
32 Near patient
Underestimating the severity of
sepsis; incomplete triage data
hindering prompt diagnosis; first
assessment done by very junior
53% 100% completion of triage
vital signs; review by
middle grade doctors
within first 30 min; training
nurses and doctors.
317 Care by board-
nurses with > 3
Patients with cryptic shock,
higher serum lactate levels or
without hyperthermia; care by
junior resident doctors
256 (80.8%) Overcrowding; sex-
based differences of
the treating physician
Interventions focussing on
the identified barriers
770 ED overcrowding 81.9% Multidisciplinary response
team; effective bed
626 Difficulty recognising sepsis;
clinical reliance on development
48% Pre-hospital sepsis
195 Survey response to why IV fluid
challenge was not achieved: 41%
unsure; 59% didn’t think it was
needed. Knowledge, attitude and
27% (Control group)
193 Interhospital transfers from
regional hospitals; inadequacy of
emergency trained physicians in
rural hospitals; clinical
deterioration of patient during
Use of telemedicine
ED patients in
earlier stages of
Emphasis on treatment in
patients with and without
organ failure in sepsis
2913 Time of presentation of patients
to ED (between 07:00–19:00 less
likely to receive fluids within 1 h
compared to presenting after-
hours); overcrowding, increased
occupancy rate and patient
hours in ED
Appropriate staffing and
patient flow in ED
487 Correctness of exact
sepsis- SIRS, severe
sepsis, recognised or
130 Advanced age; cardiac co-
morbidities; delay in sepsis rec-
ognition; ED overcrowding;
25 (19%) received
Mean time to
10 ± 27 min
with simple guidelines,
electronic alerts; qSOFA
5631 Patients without an ICD sepsis
diagnosis code despite similar
baseline organ dysfunction
10.6% for patients
without a sepsis
19.6% for patients
with a diagnosis
Education and quality
Kabil et al. BMC Emergency Medicine (2022) 22:3 Page 5 of 11
Among the included studies, except for the volume of
fluids studies, there was no evidence of significant publi-
cation bias on visualisation of the funnel plots.
Considerable statistical heterogeneity was found in stud-
ies reporting compliance and volume of fluids adminis-
tered in the meta-analysis with I
values of 90 and 94%
respectively with pvalues < 0.01 and substantial hetero-
geneity found in the studies analysing time to fluids
58%, p value < 0.01). No statistically significant regres-
sion co-efficients were found using the mortality as a co-
variate in studies reporting compliance and volume of
fluids, however in studies reporting time to fluids, mor-
tality explained 45.4% of the heterogeneity (R
QE = 7.25, p value < 0.404). Using the number of inter-
ventions used as a covariate, with more than one inter-
vention treated as a bundle of interventions, in the
studies reporting the volumes of fluids administered,
75.4% of the heterogeneity was accounted for with the
number of interventions (R
75.4%, QE = 11.8, p value
0.008). However, the heterogeneity in the studies analys-
ing time to fluids and compliance could not be explained
using the number of interventions. Key results of the
meta regression are presented in Additional file 5.
The results of the cumulative meta-analysis are pre-
sented in Additional file 6. Visual exploration of tem-
poral trends based on the year the studies commenced
reflecting the changes to the guidelines used in the stud-
ies did not show a significant relationship with the com-
pliance with early fluid bolus administration, time to
administration of fluids and volume of fluids adminis-
tered. Meta-regression performed using year of study as
a covariate did not show significant regression co-
efficients (see Additional file 5).
Of the eleven studies included in the narrative synthesis,
eight studies reported the proportion of patients with
sepsis who received early intravenous fluid bolus in the
emergency department with a total of 13,026 patients in-
cluded in the studies. The pooled estimate is 0.48 (95%
CI 0.24–0.72), indicating that the average compliance of
patients who received early fluid bolus is 48%. Most of
these studies were conducted as retrospective chart ana-
lysis or audit. The factors identified as barriers and facili-
tators are summarised in Table 2.
Identifiable barriers to early fluid bolus initiation in sepsis
Barriers to the early initiation of intravenous fluids was
reported in eight out of the eleven studies. The patient-
related factors reported were presentation with cryptic
Fig. 1 PRISMA flowchart of study inclusion
Fig. 2 Association between intervention and compliance with early
initiation of intravenous fluid bolus
Fig. 3 Association between intervention and time of initiation of
first intravenous fluid bolus administration
Fig. 4 Association between intervention and volume of fluids
administered within the protocol recommended time
Kabil et al. BMC Emergency Medicine (2022) 22:3 Page 6 of 11
shock, those with higher serum lactate level, patients
without hyperthermia on presentation, and those who
have an advanced age, and cardiac co-morbidities [30,
31]. Most studies have reported non-patient related fac-
tors as barriers. Improper diagnosis of sepsis such as
underestimating the severity of sepsis, difficulty and
delay in recognising sepsis, and clinical reliance on de-
velopment of hypotension to begin treatment have been
repeatedly reported [32,34,38]. Experience of the treat-
ing healthcare professional has been identified as an
inhibiting factor when inexperienced junior physicians
and those without emergency training care for patients
during the initial hours [30,31,34]. Assessment errors
such as incomplete triage vital signs data and incorrect
allocation of sepsis specific International Classification
of Diseases (ICD) codes are reported to cause delays in
commencing fluids [30,39]. In contrast, Morr et al., re-
port that correctness of the classification of sepsis and
its severity had no impact on early initiation of fluid
bolus . Three studies have reported that overcrowd-
ing in the emergency department and its associated fac-
tors such as increased occupancy rate, increased patient
hours and patients presenting between 0700 and 1900 h
was strongly associated with delays in initiating fluid
bolus [36,38,61]. However, the retrospective study by
Kang et al., shows that over-crowding had no impact on
the compliance rate . Other reported factors include
delays caused due to inter-hospital transfers from re-
gional to referral centres associated with natural disease
progression enroute  and knowledge, attitude and
behavioural barriers of the healthcare professionals .
Factors improving early fluid bolus administration in sepsis
Three studies reported factors identified to improve
early fluid bolus administration. Access to near patient
lactate testing , treatment commenced in the earlier
stages of sepsis without organ failure  and care pro-
vided by emergency trained physicians and nurses with
more than 3 years of clinical experience  have been
found to be associated with improved compliance with
early fluid bolus administration.
Recommendations for future practice
Nine studies have suggested recommendations to
improve compliance with early fluid administration. All
nine studies recommend interventions specifically
targeting the identified barriers which include 100%
completion of triage vital signs data , pre-hospital
sepsis screening , use of telemedicine , and use
of assessment tools like qSOFA .Two studies have
recommended appropriate staffing and bed flow to man-
age overcrowding [36,61]. Quality improvement projects
involving multidisciplinary teams and electronic alerts
along with professional development on sepsis
management for nurses and physicians have also been
suggested by five studies [30,31,38,39,61].
Our systematic review, meta-analysis and narrative syn-
thesis have identified a number of factors associated with
the early initiation of intravenous fluid bolus in patients
presenting with sepsis to the emergency department.
Overall, interventions aimed at improving the manage-
ment of sepsis in the emergency department increased
compliance with early fluid bolus administration by 47%,
reduced the time to fluid administration by an average
24 min, and increased the volume of fluids given by 575
mL. Importantly, this improvement was seen across a
variety of emergency departments, worldwide. However,
we found that it was uncommon for studies to
specifically explore barriers to the implementation of in-
terventions that improve the management of sepsis in
the emergency department.
Our findings are consistent with a previous meta-
analysis reporting improved compliance with the entire
surviving sepsis bundle across various settings . Most
of the studies included in this meta-analysis analysed
fluid administration as part of assessing the outcomes of
the entire surviving sepsis bundle. Several of these stud-
ies showed that the proportion of improvement with
fluid bolus administration was still lower compared with
the other components of the surviving sepsis bundle
such as antibiotics administration and lactate measure-
ment [41–49]. Quality improvement programs specific-
ally tailored for each element of the surviving sepsis
bundle and targeting their approach towards fluid ad-
ministration would be necessary to improve compliance
with individual elements of the bundle. An understand-
ing of factors that specifically influence compliance with
early fluid administration is necessary to design suitable
performance improvement measures.
The interventions implemented varied from educa-
tional, to process change measures such as a multidiscip-
linary sepsis program. We did not investigate the
association between the interventions as single/bundled.
However, meta regression showed interventions imple-
mented as a bundle had a significant impact on the vol-
ume of fluids received by patients. However, this effect
was not observed in the studies reporting the rate of
compliance and time to initial fluids. Regardless of the
type and number of interventions, the overall improve-
ment in early fluid bolus indicates that a general increase
in awareness and focus on fluid management in sepsis
management improves performance. Although the
guideline changes over the years have not shown signifi-
cant impact on the compliance with early fluid bolus,
time to fluid bolus administration, and the volume of
fluids administered in this study, the impact the
Kabil et al. BMC Emergency Medicine (2022) 22:3 Page 7 of 11
frequently changing guidelines could have on clinical
practice variations and clinician decision-making cannot
be disregarded warranting further qualitative research.
Though all the studies that were meta-analysed have
analysed the effectiveness of the interventions, only one
study  reported the factors associated with initiation
of an early fluid bolus. Consideration of the factors influ-
encing the interventions is a key strategy to developing
sustainable interventions in the clinical settings .
According to the results from the narrative synthesis,
the baseline compliance with early fluid bolus adminis-
tration is considerably low at 48%. This is congruent
with the compliance rates for fluid resuscitation reported
in studies conducted in other settings such as the wards
and intensive care units with less than half the patients
receiving fluids within the protocol recommended time
[64,65].Only a few studies have reported the barriers
and facilitators specific to initial fluid bolus administra-
tion and we have included those in the narrative synthe-
sis. While some of the barriers reported are similar to
those reported regarding barriers to the implementation
of the entire surviving sepsis bundle  such as insuffi-
cient sepsis training and knowledge , our analysis
has found factors specifically impacting initial fluid bolus
administration. These include patient-related factors
such as advanced age and cardiac co-morbidities
supporting recommendations for cautious fluid adminis-
tration in patients within such subgroups [65,67,68].
Clinician associated issues such as inexperience, relying
on hypotension as a clinical sign to commence fluid
bolus and inaccurate diagnosis including incomplete tri-
age vital signs, warrants educational interventions specif-
ically tailored to knowledge deficits regarding fluid
resuscitation in sepsis. On the other hand, organisational
factors such as over-crowding and inter-hospital trans-
fers require a more systemic approach. Although non-
interventional factors such as treatment by experienced
clinicians and treating patients in earlier stages of sepsis
have been reported to facilitate early fluid bolus, the
overall low rate of compliance from the pooled estimate
in the narrative synthesis suggests that further studies
are required to explore the facilitators and barriers to
early fluid bolus.
Our study has several limitations. All except one 
included study were observational in nature and there-
fore cannot account for casual relationships. In addition,
the effect of other confounding variables such as severity
of illness between the intervention and control group
patients could not be identified from the available data.
The studies have been conducted across different coun-
tries and differing emergency settings including resource
limited settings [36,37]which makes generalisability of
these findings difficult. Substantial heterogeneity among
studies means the pooled results need to be interpreted
with caution. We conducted meta regression to explore
the possible sources for heterogeneity, however, we can-
not account for the influence of unmeasured sources.
Despite our intention to include qualitative research
using a mixed-method approach, lack of qualitative stud-
ies meeting the inclusion criteria prevented us from con-
ducting a mixed-method review. Future qualitative
studies exploring experiences of healthcare workers re-
garding fluid resuscitation in sepsis could provide wider
range of sources. A number of studies exploring surviv-
ing sepsis bundles did not have data relating specifically
to early fluid bolus initiation limiting the number of
studies that could be included in the analysis. Finally, al-
though we conducted an extensive electronic database
search and review using a systematic approach, we can-
not exclude the possibility of missing studies.
Despite the limitations, our study offers a comprehensive
understanding of the factors influencing early fluid bolus
in sepsis. Our findings show that the overall compliance
rate with early fluid bolus administration in adult
patients with sepsis presenting to the emergency depart-
ment is less than optimal. However, performance im-
provement initiatives significantly improve compliance
with early fluid bolus and improves time to and volume
of fluids administered. In this study, we have not only
focussed on the effectiveness of interventions, we have
also explored the facilitators and barriers specifically
impacting early fluid resuscitation. Recognition of spe-
cific factors will assist in designing suitable performance
improvement initiatives incorporating tailored measures
targeting fluid administration rather than a “One size fits
all”approach. Future studies using qualitative approach
are required to further understand subjective factors in-
fluencing early fluid bolus.
ICD: International Classification of Diseases; PRISMA: Preferred Reporting
Items for Systematic Reviews and Meta-Analyses; PROSPERO: The
International Prospective Register of Systematic Reviews; SIRS: Systemic
Inflammatory Response Syndrome; qSOFA: quick Sequential Organ Failure
The online version contains supplementary material available at https://doi.
Additional file 1.
Additional file 2.
Additional file 3.
Additional file 4.
Additional file 5.
Additional file 6.
Kabil et al. BMC Emergency Medicine (2022) 22:3 Page 8 of 11
The authors would like to thank Dr. Christine Taylor for providing assistance
and access to the JBI SUMARI tools. We would like to thank Ms. Linda
Mulheron and Ms. Maya Sebestyen, Librarians, Westmead Hospital for their
assistance and their advice with the development of the search strategy and
review of search results.
This review forms a component of the requirements for the completion of a
Doctor of Philosophy for GK.
GK, SM, SF, DH conceived and designed the study. GK developed and ran
the search strategy; GK, SM and SF screened abstracts and full-text studies;
all authors reviewed full-text study articles included; GK and SM conducted
quality appraisal of included studies; GK and SF extracted data from included
studies; all authors contributed to and approved the final manuscript.
This is a non-funded study.
Availability of data and materials
Ethics approval and consent to participate
Consent for publication
The authors declare that there are no competing interests.
Western Sydney University, School of Nursing and Midwifery, Locked bag
1797, Penrith, NSW 2751, Australia.
Department of Emergency, Westmead
Hospital, Sydney, Australia.
South Western Sydney Nursing and Midwifery
Research, Ingham Institute of Applied Medical Research, Sydney, Australia.
University of New South Wales, Sydney, Australia.
Westmead Institute for
Medical Research, Westmead, Australia.
NSW Ministry of Health, New South
Received: 22 September 2021 Accepted: 2 December 2021
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