[version 1; peer review: 2 approved with reservations]
No competing interests were disclosed.
Septic shock is a life-threatening condition characterized by systemic inflammation and organ dysfunction, with fluid resuscitation being a cornerstone of management. However, indiscriminate fluid administration can lead to fluid overload and worsen outcomes. Extravascular lung water (EVLW) estimation by lung ultrasound has emerged as a promising tool for guiding fluid therapy in septic shock, allowing clinicians to assess pulmonary edema and tailor resuscitation strategies accordingly.
This prospective observational study aims to evaluate the utility of EVLW estimation by lung ultrasound in guiding fluid resuscitation therapy in adult patients with septic shock admitted to a rural tertiary care teaching hospital. Eligible patients admitted to the intensive care unit (ICU) will undergo baseline demographic and clinical assessments, including lung ultrasound, to quantify EVLW using B-line analysis. Fluid resuscitation therapy will be initiated based on EVLW findings, with subsequent adjustments guided by repeat lung ultrasound examinations at 6, 12, 24, and 48 hours post-initiation. Outcome measures include changes in mean PaO2/FiO2 ratios, respiratory parameters, renal function, fluid balance, and mortality rates.
We anticipate that EVLW-guided fluid resuscitation therapy will lead to more precise and tailored management of septic shock, potentially reducing the incidence of fluid overload, ARDS, and renal dysfunction. By optimizing fluid management strategies based on individual patient characteristics and responses, we aim to improve clinical outcomes and enhance the delivery of care for patients with septic shock.
Septic shock remains a leading cause of mortality and morbidity worldwide, particularly in critically ill patients admitted to intensive care units (ICUs).
However, indiscriminate fluid administration can lead to complications such as fluid overload and pulmonary edema, which are associated with worse outcomes in patients with septic shock.
Lung ultrasound has emerged as a valuable tool for assessing extravascular lung water (EVLW), providing a non-invasive means of detecting pulmonary edema and guiding fluid management in patients with septic shock.
Despite growing evidence supporting the utility of lung ultrasound in assessing EVLW and guiding fluid therapy, more research needs to be conducted to evaluate its implementation in resource-limited settings, particularly in rural tertiary care hospitals.
This study aims to evaluate the utility of extravascular lung water (EVLW) estimation by lung ultrasound in guiding fluid resuscitation therapy in adult patients with septic shock admitted to a rural tertiary care teaching hospital.
To quantify extravascular lung water (EVLW) using lung ultrasound by counting the number of B-lines in patients with septic shock. To determine the optimal dose and timing of fluid resuscitation therapy (FRT) based on the presence and severity of extravascular lung water (EVLW) detected by lung ultrasound.
To assess changes in mean PaO
2/FiO
2 ratios at various time points following initiation of fluid resuscitation therapy. To monitor lung parameters such as pulmonary edema and ARDS. To evaluate renal parameters, including serum creatinine levels and urine output in response to fluid resuscitation therapy.
This study will employ an observational prospective cross-sectional design to assess the utility of extravascular lung water (EVLW) estimation by lung ultrasound in guiding fluid resuscitation therapy in adult patients with septic shock.
The study population will consist of adult patients admitted to the intensive care unit (ICU) of Acharya Vinoba Bhave Rural Hospital (AVBRH) with a diagnosis of septic shock. Patients meeting the inclusion criteria and not meeting the exclusion criteria will be eligible for enrollment in the study.
Adult patients (age ≥ 18 years) Diagnosed with septic shock Admitted to the ICU at AVBRH
Patients aged below 18 years Pregnant women Active bleeding, acute respiratory distress syndrome (ARDS), or chronic lung diseases Left ventricular ejection fraction less than 50% Diagnosed with cardiogenic shock
The study will be conducted at Acharya Vinoba Bhave Rural Hospital (AVBRH), a tertiary care teaching hospital in Wardha District. AVBRH serves as a major healthcare facility for rural residents in central India. The study will specifically take place within the ICU of AVBRH, where critically ill patients, including those with septic shock, receive specialized care and management.
The data collection process for this study will involve systematic and standardized procedures to ensure the accuracy and reliability of the collected data. Trained research personnel will be responsible for conducting the data collection activities under the supervision of the principal investigator. At the outset, eligible patients meeting the inclusion criteria will be identified upon admission to the intensive care unit (ICU) at Acharya Vinoba Bhave Rural Hospital (AVBRH). Patients who fulfill the study criteria will be approached for participation, and informed consent will be obtained from the patient or their legally authorized representative.
Once consent is obtained, baseline demographic information, including age, sex, BMI, and past medical history, will be recorded. Clinical parameters such as blood pressure, heart rate, respiratory rate, and temperature will also be documented. Additionally, relevant comorbidities and risk factors will be noted for each participant. The primary outcome measure, extravascular lung water (EVLW), will be assessed using lung ultrasound by counting the number of B-lines. Trained ultrasound operators will perform the lung ultrasound examinations according to standardized protocols. The presence and severity of pulmonary edema will be determined based on the number of B-lines observed between rib spaces.
Following the initial assessment, fluid resuscitation therapy (FRT) will be initiated based on the presence and severity of EVLW detected by lung ultrasound. The type and dose of fluid therapy will be recorded, along with any adverse events or complications associated with the intervention. Subsequent lung ultrasound examinations will be conducted at predetermined time points (6, 12, 24, and 48 hours post-FRT initiation) to monitor changes in EVLW and assess treatment response. Clinical parameters, laboratory values (including serum creatinine levels and urine output), and vital signs will also be recorded each time.
Data integrity and quality will be ensured throughout the study period through regular monitoring and validation checks. The research team will promptly address and resolve any discrepancies or missing data. Confidentiality of patient information will be maintained at all times, with data stored securely in compliance with regulatory guidelines.
During the study period, approximately patients with septic shock are expected to participate. The sample size calculation was based on a previously reported prevalence of sepsis and septic shock, which was found to be 42.6%. This is an estimated sample size of approximately 44 participants. The study will include patients diagnosed with septic shock admitted to the Intensive Care Unit (ICU) at the research site, adhering to predefined inclusion criteria to ensure relevance to the research objectives and sample homogeneity.
This study’s statistical methods encompass descriptive and inferential techniques to comprehensively analyze the collected data about extravascular lung water (EVLW) estimation and fluid resuscitation therapy (FRT) in patients with septic shock. Descriptive statistics will be employed initially to summarize baseline characteristics of the study population, encompassing demographic variables, clinical parameters, and comorbidities. Continuous variables such as age, BMI, and laboratory values will be summarized using measures of central tendency (mean, median) and dispersion (standard deviation, interquartile range). In contrast, categorical variables like sex and comorbidities will be presented as frequencies and percentages. Inferential statistics will then be applied, including repeated measures analysis of variance (ANOVA) to assess changes in mean PaO 2/FiO 2 ratios and other continuous variables over multiple time points post-FRT initiation. Chi-square analysis will be utilized to compare categorical variables such as ICU mortality rates and requirements for renal replacement therapy between different patient groups based on EVLW levels. Additionally, correlation analysis will explore associations between EVLW measured by lung ultrasound and relevant variables like serum creatinine levels and urine output. In contrast, survival analysis techniques such as Kaplan-Meier curves and Cox proportional hazards models may evaluate the association between EVLW and long-term outcomes. Regression analysis will further investigate predictors of outcomes such as fluid overload or the need for renal replacement therapy. A significance level of p < 0.05 will be considered statistically significant for all analyses, and results will be interpreted alongside measures of effect size and confidence intervals to ensure robust conclusions. Analysis will be conducted using appropriate software packages such as R Studio to facilitate accurate and reliable interpretation of findings.
The Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol (Reference number: DMIHER (DU)/IEC/2022/297. Date: 21-07-2022). Before commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives.
After the completion of the study, we will publish it in an indexed journal or conference.
The study has not yet started. After the publication of the protocol, we will start recruiting for the study.
Septic shock remains a significant cause of morbidity and mortality in critically ill patients, necessitating timely and effective management strategies. This study protocol outlines the investigation of extravascular lung water (EVLW) estimation by lung ultrasound as a guide to fluid resuscitation therapy (FRT) in adult patients with septic shock. The rationale for utilizing lung ultrasound lies in its non-invasive nature, bedside availability, and ability to provide real-time assessment of pulmonary edema, a common complication in septic shock.
The primary objective of this study is to determine EVLW through lung ultrasound, with subsequent adjustment of FRT based on these findings. This approach aligns with personalized medicine, wherein treatment decisions are tailored to patient-specific characteristics and responses.
Several methodological considerations warrant discussion. The observational prospective cross-sectional design enables the evaluation of EVLW-guided FRT in real-world clinical settings, enhancing the generalizability of study findings. However, this design may be susceptible to confounding factors and biases inherent to observational studies. To mitigate these risks, rigorous data collection protocols, standardized procedures for EVLW assessment, and statistical adjustments for potential confounders will be employed.
Limitations of this study include the potential for selection bias, given its single-center nature and reliance on patients admitted to a rural tertiary care teaching hospital. Additionally, while lung ultrasound offers valuable insights into pulmonary fluid status, its interpretation may be operator-dependent, necessitating rigorous training and quality assurance measures. Furthermore, the impact of EVLW-guided FRT on long-term outcomes such as ICU mortality and organ dysfunction warrants further investigation through prospective longitudinal studies.
No data are associated with this article.
I read your protocol with interest.
Pay attention to exclude diastolic dysfunction as one of your criteria is EF > 50%.
Sometime pneumonia can increase "local" B-lines and further in ARDS diffuse B-lines in hypovolemic patients and this need hemodynamic monitoring.
I do not understand why you exclude Pregnant women as we previously found that: Lung Ultrasound Pattern Is Normal during the Last Gestational Weeks: An Observational Pilot Study. Gynecol Obstet Invest. 2017;82(4):398-403. doi: 10.1159/000448140. Epub 2016 Oct 5. PMID: 27701165.
Please state that in the discussion.
I will be happy to read the revised version of this protocol.
Good Luck
Is the study design appropriate for the research question?
Yes
Is the rationale for, and objectives of, the study clearly described?
Yes
Are sufficient details of the methods provided to allow replication by others?
Yes
Are the datasets clearly presented in a useable and accessible format?
Yes
Reviewer Expertise:
lung ultrasound, diaphragm ultrasound, cardiac ultrasound, fluid management, airway management
We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above.
The current study protocol aims to assess pulmonary edema by USG estimation of extra vascular lung water. The fluid therapy would be titrated as per the EVLW findings at 6, 12, 24 and 48 hours.
The study protocol is well written with good rationale and outcomes defined. However, there are methodological issues. The major comment is the method of performing the USG should be described step by step with images . The definition of pulmonary edema or fluid overload clinically as well as by USG (even if for study purposes) should be clearly defined. Counting of B lines is mentioned but not defined clearly.
Is the study design appropriate for the research question?
Partly
Is the rationale for, and objectives of, the study clearly described?
Yes
Are sufficient details of the methods provided to allow replication by others?
Partly
Are the datasets clearly presented in a useable and accessible format?
Not applicable
Reviewer Expertise:
Sepsis, septic shock; fluid therapy; resuscitation; USG studies ; fluid responsiveness
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.