The Value of Critical Care Ultrasound and Noninvasive Cardiac Output Monitoring in Guiding Fluid Resuscitation for Septic Shock in the Emergency Department
Phase: NA
Conditions: Septic Shock
Sponsor: Mai Xiaowei

Clinical research protocol
Project name: The value of critical care ultrasound and
noninvasive cardiac output monitoring in guiding fluid resuscitation
for septic shock in the emergency department
leading unit:Guangzhou Panyu Central Hospital, Guangzhou,
Guangdong, China
project leader:Xiaowei Mai
Department: Emergency Department
Research period: July 2025 to July 2025
Version No.: V1.0
Version Date: May 22, 2023

1
object name
The value of critical care ultrasound and non-invasive cardiac output
monitoring in fluid resuscitation for emergency department patients with
septic shock.
goal of study
This study
explores the value
of critical
care ultrasound and
non-invasive cardiac output monitoring in fluid resuscitation for emergency
department patients with septic shock, providing evidence for optimizing
hemodynamic management of septic shock, improving patient prognosis, and
guiding clinical selection ofappropriate monitoring modalities.
research design
Subjects were recruited from patients with septic shock admitted to the
Emergency Department of Guangzhou
Panyu
District
Central Hospital
between July 2023 to luly 2025. Demographic data of patients, including
gender, age, and underlying diseases, were collected, along with mean
arterial pressure, baseline lactate levels, and vital signs at enrollment.
Records were made of the total fluid volume administered within the first 6
hours after patients were randomized into groups, the achievement of
resuscitation targets, blood lactate levels, blood pressure, and the incidence of
complications such as pulmonary edema and renal injury. Additionally, the
use of vasoactive agents (e.g.,
dopamine,
epinephrine/norepinephrine),
mechanical ventilation support, and antibiotics was documented. Patients
were followed up to record the duration of emergency department stay, total
hospital stay, 28-day mortality, and adverse events occurring during the study
period (e.g., severe arrhythmias, anaphylactic shock).
Total number of
cases studied
60 cases (30 cases in each group)

2
caseselection
Inclusion criteria:
(1) diagnosis of septic shock in accordance with the Surviving Sepsis
Campaign International; (2) receipt of initial fluid resuscitation in the
emergency department with a hospital stay ofat least 6 hours; (3) age ≥18
years; (4) provision ofinformed consent.
excluded criteria:
(1) contraindications to rapid fluid administration (e.g., end-stage renal
disease, end-stage heart failure, acute pulmonary edema); (2) inability to
comply with treatment, such as patients with severe trauma, burns, cancer
undergoing chemotherapy, pregnant or lactating women, and those with
mental illness; (3) withdrawal from treatment or transfer to another facility
within 24 hours ofadmission.
Treatment plan
Both groups were managed according to the 2021 Surviving Sepsis
Campaign (SSC) International Guidelines for septic shock resuscitation,
including: (1) early antimicrobial therapy, (2) vasopressor support (with
norepinephrine as first-line), and (3) organ function support. The key
difference between groups lay in the fluid resuscitation monitoring approach
(critical care ultrasound vs. noninvasive cardiac output monitoring)
efficacy evaluation
The main efficacy indicators: emergency department length of stay, total
hospital stay.
Secondary efficacy indicators: regarding total fluid volume within the first 6
hours of resuscitation, early resuscitation efficacy (time to achieve mean
arterial pressure ≥65 mmHg, lactate reduction ≥20% from baseline, or lactate
clearance ≥10%), complication rates (including pulmonary edema, renal
injury, and acute respiratory distress syndrome).

3
Safety evaluation index: 28-day mortality.
statistical method
This study adopted a prospective randomized controlled design, and the
sample size was estimated using PASS 15.0 software. Based on the
difference in 6-hour fluid resuscitation volume between the two groups in the
pilot study (mean difference 1261 mL, standard deviation 3155 mL), α=0.05
(bilateral) was set β=0.2, Calculated to require 27 cases per group,
considering a 20% dropout rate, 60 cases were ultimately included. Use SPSS
26.0 to generate block random sequences (block size 4), and allocate
concepts through sealed envelopes. The normality of the measurement data
was confirmed by Shapiro Wilk test, and those that conform to the normal
distribution were expressed as mean ± standard deviation. Independent
sample t-test was used for inter group comparison; non normally distributed
individuals are represented by the median (interquartile range) and Mann
Whitney U test is used. The categorical data is presented in terms of the
number of cases (%), and the comparison between groups is conducted using
the chi square test or Fishers exact test (when the theoretical frequency is less
than 5). The main outcome (28 day mortality rate) was plotted using Kaplan
Meier survival curve, and inter group differences were analyzed using log
rank test, and HR (95% CI) was calculated. Secondary outcomes (such as
fluid dosage, MAP, etc.) report mean difference (MD) or relative risk (RR)
and their 95% confidence intervals. All tests are bilateral, and P<0.05 is
considered statistically
significant. Perform
Bonferroni correction
on
secondary outcomes (α=0.05/6 ≈0.008). Multivariate Cox regression was
used to adjust for confounding factors such as age and baseline lactate, and
sensitivity analysis included protocol set (PP) and intention to treat (ITT)
analyses. The statistical software used is R 4.3.1 (R Foundation) and SPSS
26.0 (IBM).

4
Research period
July 2023 to luly 2025

5
(1)Research background
Septic shock represents the severe phase of infection-induced systemic inflammatory
response syndrome (SIRS), characterized by a complex pathophysiological mechanism. It is
primarily manifested as vasodilation, capillary leakage, and myocardial depression triggered
by SIRS, with persistent hypotension, tissue hypoperfusion, and multiple organ dysfunction
resulting from insufficient effective circulating blood volume as the main clinical features.
With a mortality rate exceeding 40%, it ranks among the common critical illnesses in the
emergency department. International guidelines for the management of septic shock
highlight that early goal-directed fluid resuscitation is the cornerstone of septic shock
treatment. It aims to alleviate the systemic damage caused by shock by rapidly restoring
effective circulating blood volume and increasing tissue oxygen delivery, thereby improving
prognosis and enhancing quality of life. Consequently, fluid resuscitation holds an
irreplaceable role in the management of septic shock, and the first 6 hours after shock
recognition, in particular, is designated as the "golden resuscitation period" . However, both
excessive and insufficient fluid resuscitation may exacerbate the condition and elevate the
risk of complications such as pulmonary edema, acute respiratory distress syndrome
(ARDS), and acute kidney injury (AKI). Thus, how to rapidly and accurately assess a
patients volume status and cardiac function in the emergency department, formulate
individualized fluid resuscitation strategies, achieve precise volume management, and avoid
over-resuscitation or under-resuscitation has become an urgent clinical challenge.
Traditional fluid resuscitation strategies rely predominantly on static parameters such as
central venous pressure (CVP), mean arterial pressure (MAP), and urine output for guidance.
However, these indices have inherent limitations in assessing volume responsiveness and
predicting fluid resuscitation efficacy, failing to accurately and dynamically reflect a patients
volume status or cardiac preload responsiveness. In recent years, with advances in
hemodynamic monitoring technologies, dynamic evaluation of volume responsiveness has
emerged as a key strategy for optimizing fluid resuscitation and improving patient outcomes.

6
Critical care ultrasound, for instance, enables rapid bedside assessment of cardiopulmonary
function by real-time visualization of indices including inferior vena cava variability,
ventricular wall motion, volume responsiveness, and lung water content, thereby providing
visual evidence to guide early fluid resuscitation. Non-invasive cardiac output monitoring,
conversely, dynamically tracks circulatory function through quantification of parameters
such as cardiac output and stroke volume variability, offering objective data to evaluate
resuscitation efficacy. Accordingly, critical care ultrasound and non-invasive cardiac output
monitoring have increasingly
become valuable
clinical adjuncts
in guiding
fluid
resuscitation for patients with septic shock in the emergency department.
(2) research objective
1. Main Objective: This study explores the value of critical care ultrasound and
non-invasive cardiac output monitoring in fluid resuscitation for emergency department
patients with septic shock, providing evidence for optimizing hemodynamic management of
septic shock, improving patient prognosis, and guiding clinical selection of appropriate
monitoring modalities.
2.Secondary purpose: This study aims to explore the value of critical care ultrasound
and non-invasive cardiac output monitoring in fluid resuscitation for emergency department
patients with septic shock, to inform optimized hemodynamic management, improve
prognosis, and guide clinical selection ofmonitoring modalities.
(3) Research Design Types, Principles, and Test Procedures
1. Research Design
Subjects were recruited from patients with septic shock admitted to the Emergency
Department of Guangzhou Panyu District Central Hospital between July 2023 to luly
2025. Demographic data ofpatients, including gender, age, and underlying diseases, were
collected, along with mean arterial pressure, baseline lactate levels, and vital signs at
enrollment. Records were made of the total fluid volume administered within the first 6
hours after patients were randomized into groups, the achievement ofresuscitation targets,

7
blood lactate levels, blood pressure, and the incidence of complications such as pulmonary
edema and renal injury. Additionally, the use of vasoactive agents (e.g., dopamine,
epinephrine/norepinephrine),
mechanical
ventilation
support,
and
antibiotics
was
documented. Patients were followed up to record the duration of emergency department stay,
total hospital stay, 28-day mortality, and adverse events occurring during the study period
(e.g., severe arrhythmias, anaphylactic shock).
After patients met the inclusion criteria and signed the informed consent form, random
numbers were generated using SPSS 26.0 statistical software to randomly assign 73 participants
to the critical care ultrasound group and the non-invasive cardiac output group. The generated
random allocation table was prepared
in
duplicate, which were
sealed
and
stored by the
statistician and research coordinator
respectively to prevent premature
disclosure of group
allocation information.
In the critical care ultrasound group, patients underwent immediate bedside assessment
using a Philips EPIQ 5 color Doppler ultrasound
system equipped with both phased-array
(1 .5-4.0 MHz) and convex-array (2 .0-5.0 MHz) transducers. The initial ultrasound evaluation
was completed within
10
minutes
of enrollment
and
included comprehensive hemodynamic
monitoring: inferior vena cava diameter (IVC) and collapsibility index (IVC-CI) for volume
status assessment, left ventricular ejection fraction (LVEF) and end-diastolic volume (LVEDV)
for cardiac function evaluation, ventricular wall motion analysis, along with pulmonary B-line
quantification to assess pulmonary
edema.
This protocol
ensured real-time,
comprehensive
evaluation
of both
cardiac
function
and
fluid
status
to
guide
resuscitation.
Ultrasound
reassessment was performed every 1-2 hours to dynamically adjust both the volume and rate of
fluid administration until predefined resuscitation targets were achieved.
In the noninvasive cardiac output monitoring group, continuous hemodynamic assessment
was performed using the NICOM system based on thoracic bioreactance technology. Following
the manufacturers standard operating procedures, four electrode pads were placed at bilateral
subclavicular areas and the left subcostal region. Monitoring commenced immediately after

8
enrollment, with baseline parameters recorded after signal stabilization (≤5 minutes), including
cardiac output (CO), stroke volume (SV), stroke volume variation (SVV), and systemic vascular
resistance ( SVR) . The
system
automatically updated these parameters every
3 0
seconds
and
displayed them in real-time on the monitor screen. Fluid resuscitation was dynamically adjusted
according to these continuous measurements until achieving the predefined therapeutic targets.
(4) caseselection
1. Inclusion criteria:
(1) diagnosis of septic shock in accordance with the Surviving Sepsis Campaign
International; (2) receipt of initial fluid resuscitation in the emergency department with a
hospital stay ofat least 6 hours; (3) age ≥18 years; (4) provision ofinformed consent.
2. excluded criteria:
(1) contraindications to rapid fluid administration (e.g., end-stage renal disease,
end-stage heart failure, acute pulmonary edema); (2) inability to comply with treatment,
such as patients with severe trauma, burns, cancer undergoing chemotherapy, pregnant or
lactating women, and those with mental illness; (3) withdrawal from treatment or transfer to
another facility within 24 hours ofadmission.
3. Elimination criteria
Subjects who have been enrolled in the study but meet one ofthe following criteria
should be excluded:
( 1 ) After inclusion, those who did not meet the inclusion criteria or met the exclusion
criteria were found.
( 2 ) Those who have not used test drugs / interventions.
4. Standard for suspension ofresearch
( 1 ) Ifthe following conditions occur during the experiment: cardiac arrest, intestinal
perforation, intracranial and other serious complications; ( 2 ) the need for rescue is not
suitable for experimental related operators; ( 3 ) The competent physician believes that the
clinical condition is not suitable for continuing the experiment; ( 4 ) Ifthe clinical symptoms

9
and other auxiliary examinations are inconsistent with the relevant non-invasive examination
results; ( 5 ) Someone did not agree to continue the experiment during the experiment.
5 .Drop-out / exit criteria
Expulsion / withdrawal criteria: (
1 ) the competent physician believes that the clinical
condition is not suitable for the continuation ofthe experiment; ( 2 ) Ifthe clinical symptoms and
other auxiliary examinations are inconsistent with the relevant non-invasive examination results;
( 3 ) Someone did not agree to continue the experiment during the experiment.
(5)research method
Subjects were recruited from patients with septic shock admitted to the Emergency
Department of Guangzhou Panyu District Central Hospital between December 2022 and
January 2026. Demographic data ofpatients, including gender, age, and underlying diseases,
were collected, along with mean arterial pressure, baseline lactate levels, and vital signs at
enrollment. Records were made of the total fluid volume administered within the first 6
hours after patients were randomized into groups, the achievement of resuscitation targets,
blood lactate levels, blood pressure, and the incidence of complications such as pulmonary
edema and renal injury. Additionally, the use of vasoactive agents (e.g., dopamine,
epinephrine/norepinephrine),
mechanical
ventilation
support,
and
antibiotics
was
documented. Patients were followed up to record the duration of Emergency Department
stay, total hospital stay, 28-day mortality, and adverse events occurring during the study
period (e.g., severe arrhythmias, anaphylactic shock).
(6) Observation items and detection time points
1.
Demographic data of patients, including gender, age, and underlying diseases, were
collected, along with mean arterial pressure, baseline lactate levels, and vital signs at
enrollment.
2.
Records were made ofthe total fluid volume administered within the first 6 hours after
patients were randomized into groups, the achievement of resuscitation targets, blood

10
lactate levels, blood pressure, and the incidence of complications such as pulmonary
edema and renal injury.
3.
Document the use ofvasoactive agents (e.g., dopamine, epinephrine/norepinephrine),
mechanical ventilation support, and antibiotics.
4.
Record the duration of Emergency Department stay, total hospital stay, 28-day
mortality, and adverse events occurring during the study period (e.g., severe
arrhythmias, anaphylactic shock).
(7) standards for efficacy appraisal
The primary outcome was 28-day mortality
Secondary outcomes included the efficacy of initial resuscitation, duration ofhospital
stay, incidence ofcomplications, and other relevant parameters.
(8) Observation of adverse events
Observation of adverse events: Clinicians should evaluate the fluid resuscitation of
children at any time during the experiment. If the clinical symptoms and other auxiliary
examinations ( such as heart rate, liver size, mental state, X-ray, blood gas analysis, etc. ) If
they are inconsistent with the relevant non-invasive examinations, the experiment should be
terminated immediately and the superior physician should be found in time to assist.
(9)Data security monitoring
Clinical research will develop a corresponding data security monitoring plan based on
the size ofthe risk. All adverse events were recorded in detail, properly handled and tracked
until they were properly resolved or stable. Serious adverse events and unexpected events
were reported to the ethics committee, competent authorities, sponsors and drug supervision
and management departments in a timely manner according to the regulations. The main
researchers regularly conduct a cumulative review of all adverse events, and if necessary,
convene a meeting of researchers to assess the risks and benefits ofthe study; research that
is greater than the minimum risk will arrange independent data monitors to monitor the
research data, and high-risk research will establish an independent data security supervisory

11
committee to monitor the accumulated security data and effectiveness data to make
recommendations on whether the research will continue.
(10)Statistical processing
This study adopted a prospective randomized controlled design, and the sample size
was estimated using PASS 15.0 software. Based on the difference in 6-hour fluid
resuscitation volume between the two groups in the pilot study (mean difference 1261 mL,
standard deviation 3155 mL), α=0.05 (bilateral) was set β=0.2, Calculated to require 27
cases per group, considering a 20% dropout rate, 60 cases were ultimately included. Use
SPSS 26.0 to generate block random sequences (block size 4), and allocate concepts through
sealed envelopes. The normality of the measurement data was confirmed by Shapiro Wilk
test, and those that conform to the normal distribution were expressed as mean ± standard
deviation. Independent sample t-test was used for inter group comparison; non normally
distributed individuals are represented by the median (interquartile range) and Mann
Whitney U test is used. The categorical data is presented in terms ofthe number ofcases (%),
and the comparison between groups is conducted using the chi square test or Fishers exact
test (when the theoretical frequency is less than 5). The main outcome (28 day mortality rate)
was plotted using Kaplan Meier survival curve, and inter group differences were analyzed
using log rank test, and HR (95% CI) was calculated. Secondary outcomes (such as fluid
dosage, MAP, etc.) report mean difference (MD) or relative risk (RR) and their 95%
confidence intervals. All tests are bilateral, and P<0.05 is considered statistically significant.
Perform Bonferroni correction on secondary outcomes (α=0.05/6 ≈0.008). Multivariate Cox
regression was used to adjust for confounding factors such as age and baseline lactate, and
sensitivity analysis included protocol set (PP) and intention to treat (ITT) analyses. The
statistical software used is R 4.3.1 (R Foundation) and SPSS 26.0 (IBM).
(11) Ethics in clinical research
Clinical research will follow the World Medical Congress Helsinki Declaration and
other relevant provisions. Before the study began, the clinical study was carried out after the

12
ethics committee approved the test plan. Before each subject is selected for this study, the
researcher has the responsibility to fully and comprehensively introduce the purpose,
procedure and possible risks ofthis study to the subjects or their agents, and to sign a written
informed consent form. The subjects should be informed that they have the right to
withdraw from the study at any time. Informed consent should be retained as a clinical
research document for review. The personal privacy and data confidentiality ofthe subjects
will be protected during the study.
(12)Research progress
From June 2023 to june 2023 : Preparation stage for the experiment: ①
Prepare
relevant instruments and equipment, as well as equipment maintenance, testing, and
parameter calibration; ②Recruitment and training of staff, clear division of labor and job
responsibilities, and familiarity with the experimental process; ③
Complete the pre
experiment.
From july 2023 to july 2025 : Recruit research subjects and conduct clinical trials. ①
Recruit research subjects and implement interventions in groups according to the
randomization plan; ②Record the relevant data of the experiment and follow up on the
prognosis for 28 days.
From July 2025 to December 2025 : Organize research data and conduct statistical
analysis; Writing and submitting research papers.Summarize research results and write a
project summary report.
（13）Reference
[1] Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of Global Incidence and
Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit
Care Med. 2016; 193(3):259-272. doi:10. 1164/rccm.201504-0781OC.
[2] Vincent JL, Marshall JC, Namendys-Silva SA, et al. Assessment of the worldwide
burden of critical illness: the intensive care over nations (ICON) audit. Lancet Respir Med.
2014;2(5):380-386. doi:10. 1016/S2213-2600(14)70061-X.

12
[3] Jawad I, Lukšić I, Rafnsson SB. Assessing available information on the burden of sepsis:

13
global estimates of incidence, prevalence and mortality. J Glob Health. 2012;2(1):010404.
doi:10.7189/jogh.02.010404.
[4] Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international
guidelines for management of sepsis and septic shock 2021. Intensive Care Med.
2021;47(11):1181-1247. doi:10.1007/s00134-021-06506-y
[5] Oh W, Takkavatakarn K, Kittrell H, Shawwa K, Gomez H, Sawant AS, Tandon P,
Kumar G, Sterling M, Hofer I, Chan L, Oropello J, Kohli-Seth R, Charney AW, Kraft M,
Kovatch P, Kellum JA, Nadkarni GN, Sakhuja A. Personalized Fluid Management in
Patients with Sepsis and AKI: A Policy Tree Approach. medRxiv [Preprint]. 2025 Jan
23:2024.08.06.24311556. doi: 10. 1101/2024.08.06.24311556. PMID: 39148835; PMCID:
PMC11326317.
[6] Morton Hamer MJ, Faught SK. Is Early Goal-Directed Therapy or Standard Therapy
More Effective in Decreasing Mortality Among Patients With Sepsis? Ann Emerg Med.
2018 Jan;71(1):37-39. doi: 10. 1016/j.annemergmed.2017.06.006. Epub 2017 Jul 14. PMID:
28712609.
[7] Musikatavorn K, Plitawanon P, Lumlertgul S, et al. Randomized Controlled Trial of
Ultrasound-guided Fluid Resuscitation of Sepsis-Induced Hypoperfusion and Septic
Shock.
West
J
Emerg
Med.
2021;22(2):369-378.
Published
2021
Feb
10.
doi:10.5811/westjem.2020.11.48571
[8] Verras C, Ventoulis I, Bezati S, Matsiras D, Parissis J, Polyzogopoulou E. Point of Care
Ultrasonography for the Septic Patient in the Emergency Department: A Literature
Review. J Clin Med. 2023; 12(3):1105. Published 2023 Jan 31. doi:10.3390/jcm12031105
[9] Lee JY, Kim JY, Choi CH, Kim HS, Lee KC, Kwak HJ. The ability of stroke volume
variation measured by a noninvasive cardiac output monitor to predict fluid responsiveness
in mechanically ventilated
children. Pediatr
Cardiol. 2014
Feb;35(2):289-94. doi:
10.1007/s00246-013-0772-7. Epub 2013 Aug 21. PMID: 23963186.
[10] Awadhare P, Patel R, McCallin T, Mainali K, Jackson K, Starke H, Bhalala U.
Non-invasive Cardiac Output Monitoring and Assessment of Fluid Responsiveness in
Children With Shock in the Emergency Department. Front Pediatr. 2022 Apr 7;10:857106.
doi: 10.3389/fped.2022.857106. PMID: 35463892; PMCID: PMC9021702.
[11] World Medical Association. World Medical Association Declaration of Helsinki:
ethical principles for medical research involving human subjects. JAMA. 2013 Nov
27;310(20):2191-4. doi: 10. 1001/jama.2013.281053. PMID: 24141714.
[12] Nguyen HB, Rivers EP, Havstad S, Knoblich B, Ressler JA, Muzzin AM, Tomlanovich
MC. Critical care in the emergency department: A physiologic assessment and outcome
evaluation.
Acad
Emerg
Med.
2000
Dec;7(12):1354-61.
doi:
10. 1111/j.1553-2712.2000.tb00492.x. PMID: 11099425.

14
[13] Feissel M, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena
cava diameter as a guide to fluid therapy. Intensive Care Med. 2004 Sep;30(9):1834-7. doi:
10.1007/s00134-004-2233-5. Epub 2004 Mar 25. PMID: 15045170.
[14] Mukherjee M, Rudski LG, Addetia K, Afilalo J, D'Alto M, Freed BH, Friend LB,
Gargani L, Grapsa J, Hassoun PM, Hua L, Kim J, Mercurio V, Saggar R, Vonk-Noordegraaf
A. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults and
Special Considerations in Pulmonary Hypertension: Recommendations from the American
Society of Echocardiography. J Am Soc Echocardiogr. 2025 Mar;38(3):141-186. doi:
10. 1016/j.echo.2025.01.006. Erratum in: J Am Soc Echocardiogr. 2025 Jul;38(7):641. doi:
10. 1016/j.echo.2025.05.001. PMID: 40044341.
[15] Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment
of the right heart in adults: a report from the American Society of Echocardiography
endorsed by the European Association of Echocardiography, a registered branch of the
European Society of Cardiology, and the Canadian Society ofEchocardiography. J Am Soc
Echocardiogr. 2010;23(7):685-788. doi:10. 1016/j.echo.2010.05.010
[16] Lichtenstein DA, Mezière GA. Relevance of lung ultrasound in the diagnosis of acute
respiratory failure: the BLUE protocol [published correction appears in Chest. 2013
Aug;144(2):721]. Chest. 2008; 134(1):117-125. doi:10.1378/chest.07-2800
[17] Iwakura K, Onishi T. A practical guide to the lung ultrasound for the assessment of
congestive
heart
failure.
J
Echocardiogr.
2021; 19(4):195-204.
doi:10.1007/s12574-021-00528-7
[18] Bentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT. Will This
Hemodynamically Unstable Patient Respond to a Bolus ofIntravenous Fluids? JAMA. 2016
Sep 27;316(12):1298-309. doi: 10. 1001/jama.2016.12310. PMID: 27673307.
[19] Monnet X, Marik P, Teboul JL. Passive leg raising for predicting fluid responsiveness:
a systematic review and meta-analysis. Intensive Care Med. 2016 Dec;42(12):1935-1947.
doi: 10.1007/s00134-015-4134-1. Epub 2016 Jan 29. PMID: 26825952.
[20] Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical
analysis of the evidence. Chest. 2002 Jun;121(6):2000-8. doi: 10.1378/chest.121.6.2000.
PMID: 12065368.
[21] Oord M, Olgers TJ, Doff-Holman M, Harms MP, Ligtenberg JJ, Ter Maaten JC.
Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild
sepsis in the emergency department: a pilot study. BMJ Open. 2017 Jan 27;7(1):e013465.
doi: 10. 1136/bmjopen-2016-013465. PMID: 28132006; PMCID: PMC5278240.
[22] Chukwulebe SB, Gaieski DF, Bhardwaj A, Mulugeta-Gordon L, Shofer FS, Dean AJ.
Early hemodynamic assessment using NICOM in patients at risk of developing Sepsis
immediately after emergency department triage. Scand J Trauma Resusc Emerg Med.

15
2021;29(1):23. Published 2021 Jan 28. doi:10. 1186/s13049-021-00833-1
[23] Zhu G, Zhang K, Fu Y, Hu Z. Accuracy assessment of noninvasive cardiac output
monitoring in the hemodynamic monitoring in critically ill patients. Ann Palliat Med. 2020
Sep;9(5):3506-3512. doi: 10.21037/apm-20-1731. PMID: 33065801.
[24] Min JJ, Lee JH, Hong KY, Choi SJ. Utility of stroke volume variation measured using
non-invasive bioreactance as a predictor of fluid responsiveness in the prone position. J Clin
Monit Comput. 2017 Apr;31(2):397-405. doi: 10.1007/s10877-016-9859-z. Epub 2016 Mar
10. PMID: 26964992.
[25] Oord M, Olgers TJ, Doff-Holman M, Harms MP, Ligtenberg JJ, Ter Maaten JC.
Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild
sepsis in the emergency department: a pilot study. BMJ Open. 2017;7(1):e013465. Published
2017 Jan 27. doi:10. 1136/bmjopen-2016-013465
[26] Cai XE, Ling WT, Cai XT, Yan MK, Zhang YJ, Xu JY. Effect of restrictive fluid
resuscitation on severe acute kidney injury in septic shock: a systematic review and
meta-analysis. BMJ Open. 2025 Feb 16; 15(2):e086367. doi: 10. 1136/bmjopen-2024-086367.
PMID: 39956601; PMCID: PMC11831265.
[27] Shahnoor H, Divi R, Addi Palle LR, Sharma A, Contractor B, Krupanagaram S, Batool
S, Ali N. The Effects ofRestrictive Fluid Resuscitation on the Clinical Outcomes in Patients
with Sepsis or Septic Shock: A Meta-Analysis ofRandomized-Controlled Trials. Cureus.
2023 Sep 20; 15(9):e45620.
doi: 10.7759/cureus.45620.
PMID: 37868575;
PMCID:
PMC10588294.
[28] Toledo-Palacios HA, Pérez-Nieto OR, Reyes-Monge R, Rodríguez-Guevara I, Mark
NM. Sepsis Resuscitation: Time to Embrace a Restrictive Fluid Strategy? J Am Coll Emerg
Physicians Open. 2025 Jan 21;6(2):100040. doi: 10. 1016/j.acepjo.2024.100040. PMID:
39895809; PMCID: PMC11780708.
[29] Reynolds PM, Stefanos S, MacLaren R. Restrictive resuscitation in patients with sepsis
and mortality: A systematic review and meta-analysis with trial sequential analysis.
Pharmacotherapy. 2023 Feb;43(2):104-114. doi: 10. 1002/phar.2764. Epub 2023 Jan 21.
PMID: 36625778; PMCID: PMC10634281.
[30] Devia Jaramillo G, Menendez Ramirez S. USER Protocol as a Guide to Resuscitation
of the Patient with Septic Shock in the Emergency Department. Open Access Emerg Med.
2021; 13:33-43. Published 2021 Feb 12. doi:10.2147/OAEM.S289148
[31] Verras C, Ventoulis I, Bezati S, Matsiras D, Parissis J, Polyzogopoulou E. Point ofCare
Ultrasonography for the Septic Patient in the Emergency Department: A Literature
Review. J Clin Med. 2023; 12(3):1105. Published 2023 Jan 31. doi:10.3390/jcm12031105
[32] Rice JA, Brewer J, Speaks T, Choi C, Lahsaei P, Romito BT. The POCUS Consult:
How Point of Care Ultrasound Helps Guide Medical Decision Making. Int J Gen Med.

16
2021; 14:9789-9806. Published 2021 Dec 15. doi:10.2147/IJGM.S339476
[33] Rice JA, Brewer J, Speaks T, Choi C, Lahsaei P, Romito BT. The POCUS Consult:
How Point of Care Ultrasound Helps Guide Medical Decision Making. Int J Gen Med. 2021
Dec
15;14:9789-9806.
doi:
10.2147/IJGM.S339476.
PMID:
34938102;
PMCID:
PMC8685447.
[34] Vincent JL, De
Backer D.
Circulatory shock. N
Engl J Med.
2013 Oct
31;369(18):1726-34. doi: 10.1056/NEJMra1208943. PMID: 24171518.
[35] Bateman RM, Sharpe MD, Jagger JE,. 36th International Symposium on Intensive Care
and Emergency Medicine : Brussels, Belgium. 15-18 March 2016. Crit Care. 2016 Apr
20;20(Suppl 2):94. doi: 10. 1186/s13054-016-1208-6. Erratum in: Crit Care. 2016 Oct
24;20:347. doi: 10. 1186/s13054-016-1358-6. PMID: 27885969; PMCID: PMC5493079.
[36] Douglas IS, Alapat PM, Corl KA, Exline MC, Forni LG, Holder AL, Kaufman DA,
Khan A, Levy MM, Martin GS, Sahatjian JA, Seeley E, SelfWH, Weingarten JA, Williams
M, Hansell DM. Fluid Response Evaluation in Sepsis Hypotension and Shock: A
Randomized
Clinical
Trial.
Chest.
2020
Oct;158(4):1431-1445.
doi:
10. 1016/j.chest.2020.04.025. Epub 2020 Apr 27. PMID: 32353418; PMCID: PMC9490557.
[37] Chaves RCF, Barbas CSV, Queiroz VNF, Serpa Neto A. Assessment of fluid
responsiveness using pulse pressure variation, stroke volume variation, plethysmographic
variability index, central venous pressure, and inferior vena cava variation in patients
undergoing mechanical ventilation: a systematic review and meta-analysis. Crit Care. 2024
Aug
31;28(1):289.
doi:
10. 1186/s13054-024-05078-9.
PMID:
39217370;
PMCID:
PMC11366151.
[38] Awadhare P, Patel R, McCallin T, Mainali K, Jackson K, Starke H, Bhalala U.
Non-invasive Cardiac Output Monitoring and Assessment of Fluid Responsiveness in
Children With Shock in the Emergency Department. Front Pediatr. 2022 Apr 7;10:857106.
doi: 10.3389/fped.2022.857106. PMID: 35463892; PMCID: PMC9021702.
[39] Permpikul C, Leelayuthachai T. Non-invasive estimated continuous cardiac output
(escCO) during severe sepsis and septic shock resuscitation. J Med Assoc Thai. 2014
Mar;97 Suppl 3:S184-8. PMID: 24772597.
[40] Oord M, Olgers TJ, Doff-Holman M, Harms MP, Ligtenberg JJ, Ter Maaten JC.
Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild
sepsis in the emergency department: a pilot study. BMJ Open. 2017;7(1):e013465. Published
2017 Jan 27. doi:10. 1136/bmjopen-2016-013465