Authors: Jie Weng, Zhe Xu, Jiaze Song, Chen Liu, Haijuan Jin, Qianhui Cheng, Xiaoming Zhou, Dongyuan He, Jingwen Yang, Jiaying Lin, Liang Wang, Chan Chen, Zhiyi Wang
Categories: Research, Fluid resuscitation, Heart failure, ICU admission, Invasive ventilation, Mortality, Sepsis, Sepsis-induced hypoperfusion
Source: BMC Medicine
To determine the optimal fluid resuscitation volume in septic patients with acutely decompensated heart failure (ADHF).
Septic patients with ADHF were identified from a tertiary urban medical center. The generalized additive models were used to explore the association between fluid resuscitation volume and endpoints, and the initial 3 h fluid resuscitation volume was divided into four groups according to this < 10 mL/kg group, ≥ 10 to ≤ 15 mL/kg group, > 15 to ≤ 20 mL/kg group, and > 20 mL/kg group. Logistic and Cox regression models were employed to explore the association between resuscitation volume and primary endpoint, in-hospital mortality, as well as secondary endpoints including 30-day mortality, 1-year mortality, invasive ventilation, and ICU admission.
A total of 598 septic patients with a well-documented history of HF were enrolled in the study; 405 patients (68.8%) had sepsis-induced hypoperfusion. Patients with NYHA functional class III and IV were 494 (83.9%) and 22 (3.74%), respectively. Resuscitation volumes above 20 mL/kg (OR 3.19, 95% CI 1.31–8.15) or below 10 mL/kg (OR 2.33, 95% CI 1.14–5.20) significantly increased the risk of in-hospital mortality in septic patients, while resuscitation volumes between 15 and 20 mL/kg were not associated with the risk of in-hospital death in septic patients (OR 1.79, 95% CI 0.68–4.81). In the multivariable Cox models, the effect of resuscitation volume on 30-day and 1-year mortality in septic patients was similar to the effect on in-hospital mortality. Resuscitation volume exceeds 15 mL/kg significantly increased the risk of tracheal intubation, while fluid resuscitation volume was not associated with ICU admission in the septic patients. In septic patients with hypoperfusion, these fluid resuscitation volumes have similar effects on patient outcomes. This association was consistent across the three subgroups with worsened cardiac function, as well as in sensitivity analyses.
Our study observed that an initial fluid resuscitation volume of 10–15 mL/kg in the first 3 h was optimal for early resuscitation in septic patients with ADHF, particularly those with worsened cardiac function. These results need to be confirmed in randomized controlled trials with larger sample sizes.
The online version contains supplementary material available at 10.1186/s12916-024-03715-2.
Keywords: Sepsis, Sepsis-induced hypoperfusion, Heart failure, Fluid resuscitation, Mortality, Invasive ventilation, ICU admission
Sepsis, a life-threatening syndrome resulting from a dysregulated host response to infection, continues to be a significant global health concern [1, 2]. Timely and appropriate fluid resuscitation is a cornerstone of sepsis management [3]. According to the latest guidelines from the Surviving Sepsis Campaign (SSC), it is still recommended to administer an initial intravenous (IV) 30 mL/kg crystalloid bolus within 3 h for septic patients with hypotension, indiscriminate of comorbidities [1, 4–6]. However, it is important to note that this recommendation is primarily based on several early observational studies [6–10]. Despite being endorsed in the SSC guidelines, it is considered a weak recommendation with low-quality evidence [11].
The lack of consideration in this standard fluid resuscitation dose for the heterogeneity among patient populations, particularly those with heart failure (HF) [6], is a significant concern. This one-size-fits-all fluid resuscitation strategy fails to acknowledge the complexities associated with specific comorbidities [12, 13]. Patients with HF may respond differently to excessive fluid resuscitation due to compromised cardiac function, potentially leading to an increased risk of further deterioration.
Limited literature exists regarding fluid resuscitation in septic patients with comorbid HF. However, the available evidence tends to support guideline recommendations [14, 15]. Despite the inclination to align with the recommended 30 mL/kg resuscitation volume in sepsis guidelines, there is still a critical gap in understanding whether this approach is suitable for the heterogeneous population of patients with varying degrees of HF [16]. Real-world clinical practice shows that septic patients with HF often receive less fluid resuscitation or experience delays in achieving the recommended 30 mL/kg target [6, 16–18]. These deviations from guidelines may have different impacts on patient outcomes, highlighting clinicians’ concerns regarding fluid resuscitation in this population.
In the case of a septic patient with HF, there is a significant amount of uncertainty regarding the appropriate amount of fluid resuscitation and its tolerability. Our study aims to address this knowledge gap by examining the relationship between initial fluid resuscitation volumes and mortality rates in septic patients with HF. Our study specifically examines the impact of early fluid dosing in septic patients with ADHF, a scenario that presents unique challenges compared to stable chronic HF. While the overall prevalence of HF in sepsis is well-documented, the acute decompensation superimposed on sepsis is less studied, and our work aims to fill this gap. By focusing on this distinct subset of patients, we aim to provide more nuanced insights into fluid management strategies that could potentially improve clinical outcomes.
This retrospective cohort study was conducted at a tertiary urban medical center with approximately 175,000 annual hospital admissions. The study spanned from June 1, 2015, to December 31, 2022. This study followed the guidelines outlined in the Reporting of studies Conducted using observational Routinely collected health Data (RECORD) statement and received approval from the Institutional Review Board.
Participants who met the following eligibility criteria were (1) ≥ 18 years old, (2) diagnosed with sepsis, and (3) had a documented history of pre-existing HF. The definition of sepsis was based on the criteria set forth by the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) as the presence of infection or suspected infection, accompanied by an acute increase in the total Sequential Organ Failure Assessment (SOFA) score of at least 2 points [19]. The New York Heart Association (NYHA) classification was ascertained through medical record review within the last year prior to the onset of sepsis, allowing for an assessment of heart function that is proximate to the patient’s condition at the time of sepsis diagnosis. Exclusion criteria consisted of patients (1) with age < 18 years, (2) without signs of infection, (3) had multiple hospitalizations, (4) whose hospital length of stay < 1 day, (5) without a documented HF diagnosis, (6) with indeterminate NYHA classification, (7) who were diagnosed with HF only during the current hospitalization, (8) diagnosed with sepsis after being hospitalized for more than 7 days, (9) transferred from other medical facilities who had already undergone fluid resuscitation, (10) requiring endotracheal intubation prior to fluid resuscitation, and (11) for whom height and weight measurements were unavailable. All included patients were hospitalized; for patients with multiple hospital admissions for sepsis, only their initial admission was considered for analysis.
The study systematically collected the following variables from the electronic medical records (EMR): age upon admission, gender, height, actual body weight (ABW), NYHA functional classification, ejection fraction (EF), source of infection, underlying comorbidities, Charlson comorbidity index, admission type, vital signs, SOFA score, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score at the time of sepsis diagnosis, time of antibiotic initiation, vasopressor use, fluid resuscitation volumes at 3, 6, 12, 24, 48, and 72 h following sepsis diagnosis, urine output at 1, 2, and 3 days, as well as laboratory test results. The initial recorded values of ABW and height within 24 h of admission were considered for definition. The ideal body weight (IBW) was calculated using the Devine formula as follows [20]:
For patients whose ABW ≥ 1.3 times of their IBW, IBW was further adjusted as [21]:
Sepsis-induced hypoperfusion was defined as the presence of sepsis accompanied by either hypotension (systolic blood pressure ≤ 90 mm Hg or mean arterial pressure (MAP) ≤ 65 mm Hg, or a drop of > 40 mm Hg from baseline) or elevated serum lactate levels (≥ 4 mmol/L), regardless of blood pressure [22]. Vasopressors administered in the presence of sepsis-induced hypoperfusion were categorized as septic shock. Acute renal dysfunction (AKD) was identified based on the criteria established by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [23]. The fluids supplied by the pre-admission emergency medical service (EMS) were excluded from the analysis as they were not recorded in the EMR of the hospital. Maintaining fluid volume is also not included in the calculation of fluid resuscitation volume. Only crystalloid fluids administered as bolus doses within the first 6 h after the diagnosis of sepsis were included in the calculation of resuscitation volume [15]. The specific volume of fluid resuscitation at each time point (3 h, 6 h, etc.) was determined based on the timestamps of administered intravenous fluids recorded in the nursing notes, which indicated the initiation and completion of fluid resuscitation. Fluid resuscitation was calculated per kilogram of body weight (mL/kg) based on IBW in this study.
The primary endpoint was the in-hospital mortality, established by the survival situation of the patient upon their discharge from the hospital. The secondary endpoints were 30-day mortality, 1-year mortality, the need for invasive ventilation within 72 h after fluid bolus, and ICU admission.
Data distribution determined whether continuous variables were described using mean and standard deviation or median and interquartile range. Comparisons were carried out using either t-test or Mann–Whitney test based on the respective data distribution. Counts and percentages were used to present categorical variables, which were then compared using either the chi-square test or Fisher’s exact test.
In septic patients with HF, both excessive and inadequate fluid resuscitation were associated with adverse outcomes, indicating a non-linear relationship between fluid volume and mortality. To address this non-linearity, we employed a generalized additive model [24], a multivariate regression approach capable of accommodating such complexities. After adjusting for age, gender, Charlson index, vasopressor use, antibiotic initiation time, and APACHE-II score, we utilized this model to estimate the relationship between fluid resuscitation volume and mortality, providing a foundation for exploring the optimal fluid resuscitation range. According to the curve graph depicting the fluid resuscitation volume and mortality, we categorized the initial 3 h resuscitation volume into four groups.
Risk of in-hospital mortality, invasive ventilation, and ICU admission were estimated using logistic regression models, covariates included for age, gender, Charlson index, vasopressor use, antibiotic initiation time, and APACHE-II score. The effect of varying fluid resuscitation volumes on 1-year mortality was assessed using the Kaplan–Meier method and log-rank test. To analyze outcomes as a time to 30-day and 1-year mortality, Cox proportional-hazards (PH) models were performed while adjusting for the same baseline covariates mentioned above, without violating the PH assumption. Correlation analysis was employed to address multicollinearity among variables within the regression model.
Several predefined subgroup analyses were conducted by restricting the analysis to patients with varying degrees of HF: (1) NYHA class III and IV; (2) EF below 50%; and (3) brain natriuretic peptide (BNP) levels exceeding 4000. These subgroup analyses were specifically focused on the cohort of patients with septic-induced hypoperfusion. Additionally, a sensitivity analysis was performed by repeating the logistic and Cox regression models mentioned above, but using SOFA scores as the baseline measure of disease severity. This analysis was conducted for all septic patients, septic-induced hypotensive patients, and the subgroup of patients.
All analyses were conducted using R package (version 3.4.3) with P < 0.05 indicating statistical significance.
Following a rigorous selection process, 598 septic patients who had a well-documented history of HF were included as participants (Fig. 1). The majority of patients (494, 83.9%) were classified as NYHA functional class III, with a smaller cohort in class IV (22, 3.74%). Approximately 38.4% of patients exhibited an EF less than 50%. Sepsis-induced hypoperfusion was prevalent in 405 (68.8%) patients, primarily originating from pulmonary infections, which accounted for 269 (45.7%) cases. Fluid resuscitation was administered with an average volume of 7.3 ± 7.9 mL/kg (431 ± 462 mL) within the first 3 h, 9.1 ± 8.9 mL/kg (533 ± 518 mL) within the initial 6 h, and 10.7 ± 10.6 mL/kg (624 ± 614 mL) within the first 12 h. Notably, 247 (41.9%) patients did not receive fluid therapy during the initial 3 h, 215 (36.5%) during the first 6 h, and 196 (33.3%) within the first 12 h. Among the entire cohort, 153 (26.0%) patients required mechanical ventilation support. The in-hospital mortality, 30-day mortality, and 1-year mortality were 147 (25.0%), 129 (21.9%), and 157 (26.7%), respectively. Detailed baseline characteristics are presented in Additional file Table S1.
Fig. 1 Flowchart of patient selection
Additional file Table S2 and Table 1 provide a comprehensive overview of the demographic and clinical profiles of septic patients and those with sepsis-induced hypoperfusion, respectively, in relation to hospital survival outcomes. In general, individuals in the mortality group exhibited a higher NYHA functional class, a lower EF, and elevated BNP levels. However, when stratified by mortality alone, the initial volume of fluid resuscitation was comparable between the two groups.
Additional file Fig. S1 presents an S-shaped curve illustrating the correlation between fluid resuscitation volume and in-hospital mortality among the overall septic patients (P < 0.001). In contrast, among sepsis-induced hypoperfusion patients, a U-shaped relationship (P < 0.001) is evident, with the lowest mortality rates observed when fluid resuscitation volumes range from 10 to 15 mL/kg (500–1000 mL) within the initial 3 h (Fig. 2). It is worth noting that among patients experiencing hypoperfusion, 64 individuals (15.8%) did not receive fluid resuscitation within the initial 3 h, and 32 patients (7.9%) still had not received fluid therapy within the first 6 h.
Fig. 2 Association between fluid resuscitation volume and in-hospital mortality among hypotensive patients with HF. A, C, E, and G represent the relationship between the resuscitation volume (in mL) at 3 h, 6 h, 12 h, and 24 h, respectively, and in-hospital. B, D, F, and H represent the relationship between the resuscitation volume (in mL/kg) at 3 h, 6 h, 12 h, and 24 h, respectively, and in-hospital mortality
Subsequently, patient fluid volumes ranged from < 10 mL/kg, ≥ 10 to ≤ 15 mL/kg, > 15 to ≤ 20 mL/kg, and > 20 mL/kg based on 3-h resuscitation volume and in-hospital mortality curves. Among these four groups, the in-hospital mortality rates for hypoperfusion patients were 94 (23.6%), 11 (13.9%), 16 (30.8%), and 26 (43.3%), respectively (Table 2).
In unadjusted models, resuscitation volumes above 15 mL/kg was associated with a higher risk of in-hospital mortality compared to 10–15 mL/kg resuscitation volumes, for all septic patients and specifically within the hypotensive patient subset. Resuscitation volumes below 10 mL/kg in hypotensive patients were also linked to an elevated risk of in-hospital mortality. In the multivariable adjusted logistic regression models, fluid resuscitation between 15 and 20 mL/kg is no longer associated with in-hospital mortality (OR 1.79, 95% CI 0.68 to 4.81), while above 20 mL/kg (OR 3.19, 95% CI 1.31 to 8.15) or below 10 mL/kg (OR 2.33, 95% CI 1.14 to 5.20) still increased the risk of in-hospital mortality in all septic patients after adjusting for APACHE-II, age, gender, Charlson index, vasopressor use, antibiotic initiation time, lactate, and BNP. Similar results were observed in the hypotensive patient subset (Table 3).
In the hypotensive subgroup, the 30-day mortality rate was 24.7% and the 1-year mortality rate was 29.1%. Similar to the in-hospital mortality, Additional file Fig. S2 shows that there is an S-shaped association between the volume of early fluid resuscitation and the 30-day mortality rate in septic patients. On the other hand, Additional file Fig. S3 demonstrates a U-shaped correlation between the volume of early fluid resuscitation and the 30-day mortality rate in the hypotensive subgroup. In the unadjusted Cox model, resuscitation volumes above 15 mL/kg or below 10 mL/kg were all associated with a higher likelihood 30-day mortality rate. In the multivariable Cox models, resuscitation volumes below 10 mL/kg (HR 2.07, 95% CI 1.11 to 3.88) and above 20 mL/kg (HR 3.19, 95% CI 1.31 to 8.15) continued to show correlations with the 30-day mortality rate in both septic patients and the hypotensive subgroup (HR 2.31, 95% CI 1.07 to 5.32 and HR 3.26, 95% CI 1.32 to 8.43, respectively). However, resuscitation between 15 and 20 mL/kg did not have a statistically significant association with the 30-day mortality rate (Table 4). The relationship between the volume of early fluid resuscitation and the 1-year mortality rate is shown in Additional file Fig. S4 and summarized in Additional file Table S3. The results closely align with those observed for the 30-day mortality rate.
Additional file Figs. S5 and S6 demonstrate a clear linear correlation between the volume of fluid resuscitation and the need for invasive ventilation in septic patients as well as in the subgroup of hypotensive patients (P < 0.05). In the hypotensive subgroup, invasive ventilation accounted for 128 cases, which is equivalent to 31.6% of the total. Both unadjusted and adjusted logistic regression models consistently showed that resuscitation volumes above 20 mL/kg significantly increased the risk of endotracheal intubation (Additional file Table S4).
In the unadjusted logistic regression model, there appears to be a correlation between fluid resuscitation volume and ICU admission. However, after adjusting for multiple variables, the initial fluid resuscitation volume is no longer associated with ICU admission, either in all septic patients or the hypotensive subgroup (Additional file Table S5).
Subsequently, subgroup analysis was conducted on sepsis-induced hypotensive patients based on NYHA classification, HFrEF, and BNP levels. The subgroups consisted of NYHA class III and IV, HFrEF (< 50%), and BNP > 4000. The results consistently supported the previously drawn conclusions regarding the effect of initial fluid resuscitation volume on various outcomes in these subgroups (Table 5). The Kaplan–Meier curves for each subgroup showed that the optimal resuscitation group had the lowest mortality rate, which was significantly different from the other resuscitation volume groups (Fig. 3). It is important to note that there was no significant difference in fluid resuscitation volume related to mechanical ventilation in the HFrEF < 50% subgroup (Table 5). However, the rate of mechanical ventilation in this specific subgroup was 39%.
Fig. 3 One-year Kaplan–Meier survival curves in the four fluid resuscitation groups. A represents the NYHA classification III and IV subset; B represents the HFrEF (< 50%) subset; C represents the BNP > 4000 subset
In the sensitivity analysis, the impact of various initial fluid resuscitation volumes on in-hospital mortality, 30-day mortality, 1-year mortality, mechanical ventilation, and ICU admission remained consistently in line with the previous findings. Additionally, the results within the subgroup of patients showed similar trends (Additional file Tables S6–S11).
Fluid resuscitation is a cornerstone of sepsis management, yet determining the optimal fluid volume for individual patients, especially those with HF, presents a formidable challenge [25, 26]. Our results suggest that the traditional “one-size-fits-all” approach to fluid resuscitation in sepsis may not be appropriate for patients with ADHD. The high BNP levels and the prevalent use of diuretics observed in our study population are indicative of a more active HF process, which may respond differently to fluid management strategies.
Our data indicate that an initial fluid resuscitation volume of 10–15 mL/kg within the first 3 h may be optimal for patients with sepsis and ADHD, particularly in those with worsened cardiac function. This finding is significant as it suggests a tailored approach to fluid management that takes into account the acute changes in cardiac status that can occur in the context of sepsis. It is important to note that for fluid volumes within 15–20 mL/kg, there were no statistically significant differences in in-hospital mortality, 30-day, and 1-year mortality rates compared to the 10–15 mL/kg range. However, it is crucial to acknowledge that this higher range significantly increases the risk of endotracheal intubation. Subgroup analysis revealed that patients classified as NYHA III and IV experienced the greatest benefits from fluid resuscitation within the 10–15 mL/kg range. This range notably outperformed other ranges in terms of reducing mortality rates, as well as intubation rates. Our analysis found no significant association between fluid volume and ICU admission, suggesting that clinicians may lean towards ICU admission for such patients regardless of the administered fluid volume.
Individualized fluid management in sepsis improves outcomes in patients with septic shock [11, 27]. The recommendation of 30 mL/kg fluid resuscitation originates from the early goal-directed therapy (EGDT) trial conducted by Rivers et al. in 2001 [28]. Subsequently, both the Surviving Sepsis Campaign (SSC) [1, 4] and Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) have endorsed this approach. From 2014 to 2015, three independent, government-funded, multicenter randomized controlled trials were early septic shock in the USA (ProCESS) [7], sepsis resuscitation assessment in Australia (ARISE) [29], and sepsis programmed management in the UK (ProMISe) [9]. The average fluid volume administered to patients prior to randomization in these studies was also around 30 mL/kg, which led to the adoption of 30 mL/kg fluid resuscitation volume in routine clinical practice. However, there has been significant debate regarding the optimal fluid volume for sepsis management [30–32]. Increasing evidence suggests that the fluid administration during the EGDT era, which followed a permissive intravenous fluid strategy, resulted in suboptimal treatment outcomes [10, 33, 34]. This has raised persistent questions about the appropriateness of the 30 mL/kg fluid resuscitation volume [35]. Additionally, the guidelines do not mention a specific rehydration scheme for septic patients at risk of volume overload, and there is no randomized controlled study for reference. Individualized fluid resuscitation may be necessary for patients at risk of volume overload, as the fixed fluid rehydration amount of 30 mL/kg may not be suitable for all sepsis subgroups [12]. The CLOVERS trial demonstrated that early administration of vasopressors to reduce fluid resuscitation volumes did not decrease the 90-day mortality rate in patients with septic hypotension [34]. In line with these findings, our study emphasizes the importance of tailored fluid management strategies in sepsis, particularly for patients with comorbid heart failure, where the optimal initial fluid resuscitation volume of 10–15 mL/kg within the first 3 h may offer the best clinical outcomes.
Although some studies have shown that the resuscitation protocol of 30 mL/kg for patients with HF does not increase adverse outcomes [15, 16, 36], there is concern in practice that fluid administration at this volume may worsen the condition of these patients [6, 12, 17, 37]. Consequently, compliance with the SSC standard protocol is less likely [12, 16]. Studies have indicated that patients with HF often do not adhere to the 30 mL/kg rehydration protocol, and non-compliance with the rapid infusion protocol has been shown not to increase the mortality rate [6, 12, 16–18]. This suggests that it may be unreasonable to provide a one-size-fits-all rehydration volume of 30 mL/kg for patients with HF [12]. However, there is currently no research exploring the optimal initial fluid resuscitation volume range for septic patients with HF. Instead, studies have primarily compared different outcomes using a 30 mL/kg threshold.
The administration of fluids to septic patients with HF requires a careful balance to avoid both inadequate resuscitation and fluid overload, which are both associated with negative outcomes in septic shock. Our study suggests that administering 10–15 mL/kg of fluid within the first 3 h can help mitigate the risks of under-resuscitation and over-resuscitation. Powell et al. found that administering a 30 mL/kg intravenous infusion within the first 6 h to patients with septic shock and pre-existing HF (HFrEF < 40%) can lead to a decrease in in-hospital mortality [37], which may be similar to our study where patients received 10–15 mL/kg intravenous infusion within 3 h. Although the SSC [1, 4] and SEP-1 guidelines recommend initial fluid resuscitation based on body weight, it is unclear whether this is actual weight, predicted weight, or ideal weight (although the latest 2021 guidelines mention ideal weight, the original source could not be found). Even when following these guidelines, estimating patient weight is often necessary in cases of septic shock, and the empirical administration of 30 mL/kg of fluid may not be reliable. In our study, the decision to use IBW was made to standardize fluid resuscitation volumes across a diverse patient population, including those with varying degrees of obesity and underweight conditions. By using IBW, we aimed to minimize the risk of fluid overload, which is a significant concern in critically ill patients, especially those with HF.
Our optimal liquid volume range was 10–15 mL/kg, which is inconsistent with previous studies [15, 16, 36]. This discrepancy may be attributed to the predominantly severe HF patients in our study cohort. As the severity of HF escalates, the volume of fluid resuscitation required tends to decrease. Therefore, our recommended fluid volume ranges are particularly applicable to patients with severe HF. For patients with milder HF, fluid requirements may exceed 15 mL/kg. Unfortunately, a precise estimate for this subgroup could not be determined due to the limited sample size. Although the 15–20 mL/kg fluid resuscitation range did not statistically differentiate in-hospital mortality in the NYHA III and IV subgroups and the BNP > 4000 subgroup, it significantly increased the rate of tracheal intubation. In the HFrEF < 50 subgroup, our study did not find a correlation between fluid volume and intubation, which may be due to the inherently high intubation rate within this subgroup and the limited sample size that did not show statistical significance.
This study has several strengths. Firstly, we utilized a generalized additive model [24], which takes into account the nonlinear relationship between fluid volume and outcomes, allowing for exploration of the optimal fluid volume range. Secondly, we gathered comprehensive data for all outcome events. Thirdly, although this study is retrospective, the inclusion criteria for septic patients strictly adhered to the Sepsis 3.0 definition. This means that even patients treated before 2016 were classified according to the latest definition. The diagnosis of HF was also based on clearly documented NYHA classifications in EMR, with all ambiguous cases excluded. Finally, our study exclusively focused on patients who were considered for standard care and fluid resuscitation management. Patients who were under comfort care or hospice care protocols were not included in this analysis to ensure that our findings reflect the impact of fluid resuscitation in patients who are candidates for aggressive treatment measures, and this research is based on real-world data.
Several limitations should be acknowledged in this study. Firstly, being a retrospective study, there is a possibility of unrecorded data in medical records, making it challenging to fully account for potential biases that could affect the analysis. Secondly, despite our efforts to consider all possible factors, there may still be unadjusted variables that could impact the results [38]. Thirdly, it is difficult to assess the specific reasons behind patients not receiving fluids, whether due to concerns about fluid overload or other valid reasons. Fourthly, our patient population includes individuals from both the emergency department and the wards, and the timing of sepsis recognition by different physicians or the duration of pre-admission sepsis may vary, potentially influencing patient outcomes. Fifthly, when collecting data on fluid volumes, we solely focused on crystalloid solutions administered for resuscitation purposes, excluding maintenance fluids intended for hypoperfusion correction. Sixth, we recognize that the distinction between chronic and acute HF is not always clear-cut, and our study’s findings should be interpreted in the context of a patient population that is likely experiencing an acute exacerbation of their HF. Future research should continue to explore the nuances of fluid management in this complex patient population, with the goal of developing evidence-based guidelines that can improve outcomes for patients with sepsis and HF. Another limitation of our study is the sample size constraint, which limited our ability to perform subgroup analyses for HF categories with EF < 50% as recommended by ACC/AHA guidelines, potentially affecting the generalizability of our findings to more diverse HF populations. Seventh, we have acknowledged the limitations related to the lack of more detailed clinical indicators of acute HF (i.e., pulmonary edema, echo showing cardiogenic shock, peripheral edema/JVP). We recognize that the absence of such data may limit our ability to fully characterize the acute decompensation status of our patients. Finally, our study is its conduct within a single tertiary care center, which may constrain the generalizability of our findings to other healthcare settings or diverse patient populations.
In conclusion, based on the available evidence, it seems that an initial fluid resuscitation volume of 10–15 mL/kg within the first 3 h is considered to be the optimal range for early resuscitation in sepsis-induced hypoperfusion patients with HF, especially in individuals with deteriorated cardiac function. However, it is important to note that further large-scale randomized controlled trials are required to validate and reinforce these findings.
Not applicable.
J.W., Z.X., L.W., C.C. and Z.W. designed the study and drafted the manuscript; J.S. and C.L. helped interpret the results; H.J., Q.C., X.Z., D.H., J.Y. and J.L. had full access and verified all the data in the study; J.W., Z.W. and L.W. helped in the statistical analysis and result interpretation. C.C. and Z.W. take responsibility for the paper as a whole. All authors read and approved the final manuscript.
This study was supported by the National Natural Science Foundation of China, No. 82100074, Natural Science Foundation of Zhejiang Province of China (ZCLY24H0101), and Zhejiang Medicines Health Science and Technology Program (2023RC216, 2023KY904, and 2023KY893).
No datasets were generated or analysed during the current study.
The Ethics Review Committee of the Second Affiliated Hospital of Wenzhou Medical University approved this retrospective study [2021-k-18–01] and waived the requirement for patient informed consent.
Not applicable.
The authors declare no competing interests.
Chan Chen, Email: chenchan99@126.com.
Zhiyi Wang, Email: wzy1063@126.com.
No datasets were generated or analysed during the current study.