Background:In medicine, guidelines are valuable tools that help guide care. However, they are not rigid rules that must be strictly followed. Clinicians often find themselves grappling with the challenge of balancing the demands of meeting Center for Medicaid & Medicare (CMS) requirements while also addressing the unique needs of each individual patient. For those with sepsis, the administration of intravenous fluids (IVF) at the volumes recommended in the Surviving Sepsis Campaign (SSC) requires careful consideration of an individual’s chronic medical conditions and subsequent sensitivity to IVF. The available studies providing insights into clinical practices in these situations are limited in number and quality, leaving clinicians to rely on judgment and anecdotal experiences.
This systematic review and meta-analysis attempts to elucidate whether a more conservative fluid resuscitation approach is warranted in volume sensitive sepsis patients, such as those with congestive heart failure (CHF). Current SSC guidelines recommend fluid resuscitation with at least 30mL/kg IV crystalloid in patients with sepsis induced hypoperfusion or septic shock within the first three hours of resuscitation, regardless of comorbidities.
Article: Vaeli Zadeh A, Wong A, Crawford AC, Collado E, Larned JM. Guideline-based and restricted fluid resuscitation strategy in sepsis patients with heart failure: A systematic review and meta-analysis [published online ahead of print, 2023 Aug 9]. Am J Emerg Med. 2023;73:34-39. PMID: 37597449
Clinical Question: In sepsis patients with CHF, does a restricted volume resuscitation strategy of less than 30mL/kg IV crystalloid initiated within the first three hours of sepsis identification, compared to volume resuscitation with 30 mL/kg IV crystalloid, decrease in-hospital mortality?
What They Did:
Researchers performed a systematic review and meta-analysis.
The study was conducted according to PRISMA guidelines.
The authors searched Embase, PubMed, and Scopus.
Utilized the Newcastle-Ottawa Scale to assess risk.
Utilized Egger’s linear regression and Begg and Mazumdar’s rank correlation test to assess publication bias.
Population:
Inclusion Criteria:
Studies with sepsis patients with a history of HF and in-hospital mortality data on patients that did or did not meet the 30×3 SSC guidelines.
Exclusion Criteria:
Studies that focused on a period longer than 3 h from diagnosis of sepsis.
Studies without a clear timeframe for fluid administration.
Studies without a mortality breakdown for patients.
Studies without IRB approval
Studies older than 2016
Intervention:
Administration of <30 mL/kg IV crystalloid fluids within three hours of sepsis identification.
Comparator:
Administration of at least 30 mL/kg IV crystalloid within three hours of identifying sepsis.
Outcomes:
Primary Outcome: In-hospital mortality.
Secondary Outcomes: Delayed hypotension, increased ICU stay, and other relevant outcomes.
Results:
26,069 studies met initial inclusion criteria.
2,549 studies remained after screening for duplicates,
9 studies remained after screening for irrelevant titles or abstracts
3 studies were removed due to lack of mortality data
2 studies were removed due to lack of a clear timeframe for fluid administration.
4 studies remained, with a total of 571 patients with sepsis and a history of CHF
Critical Result:
The weighted OR for death was significantly higher in the <30 × 3 vs. 30 × 3
OR = 1.81, 95% CI = 1.13–2.89, p = 0.01.
Heterogeneity analysis resulted in an I2 of 0%, demonstrating a high degree of homogeneity among the results of the selected studies and pooled data.
Strengths:
Investigators addressed a practical and pertinent clinical question.
The study investigates a narrow clinical question, enhancing the study’s precision.
Authors used the PRISMA guidelines, promoting transparency and reproducibility.
Investigators conducted a thorough evaluation of the four included trials and provided a detailed assessment.
They employed two standardized tools to assess bias —selected studies were rated favorably based, increasing external validity.
The point estimates are similar and the confidence intervals overlap across all 4 trials indicating low variability in study results.
Patients across all studies exhibited sufficient similarity to enable a pooled estimation.
Limitations:
The investigators excluded studies published before 2016, non-English studies, and non-published studies, potentially missing valuable data.
Study selection was the responsibility of a single author, introducing the possibility of bias and random errors in the selection process.
The authors didn’t report the level of agreement regarding article selection, making it unclear how consistent the selection process was.
It’s not mentioned whether the authors attempted to identify additional studies by checking the references of the selected articles or by contacting the original paper authors for more information. These steps could have potentially uncovered more relevant studies.
The included studies were case-control studies, which are limited to demonstrating correlation and cannot establish causation.
The authors did not register the paper through Prospero, missing an opportunity to enhance the study’s transparency, reproducibility, and credibility.
There was no specified time-frame for the primary outcome, potentially affecting the precision of the findings.
The sample sizes of the individual papers were relatively small.
One paper contributed nearly half the weight of the meta-analysis.
Funnel plots require a large number of studies to provide an accurate assessment of publication bias, but this meta-analysis included just four trials decreasing confidence in the data.
Discussion:
The critical details from key studies are instrumental in shaping our understanding. Kuttab et al’s findings, constituting 45% of the review’s weight, suggest that administering <30cc/kg IVF is associated with increased odds of mortality, delayed hypotension, and increased ICU utilization. However, the ≥30cc/kg IVF group showed a higher prevalence of septic shock, reduced time to antibiotics by 1hr, and increased recognition of sepsis on presentation, introducing potential bias. Uchel et al’s contribution (21% weight) indicates that ≥30cc/kg IVF is linked to 2.5 times more intubations and 2.15 times more readmissions at 30 days. Interestingly, <30cc/kg IVF had a 2 times higher mortality, with over 50% of patients exhibiting diastolic HF. Taenzer et al (26% weight) suggests that <30cc/kg IVF is associated with higher mortality, albeit in a small cohort. Rai et al (8% weight) found no difference in mortality regardless of the amount of fluids given, but the sample size was very small. All four trials included in the review were retrospective, observational studies introducing significant confounders. Additionally, three of the four trials were abstracts with missing granular details, and strict inclusion/exclusion criteria severely limited the number of papers included in the systematic review and meta-analysis.
Considering these findings, specific recommendations for patients with sepsis and septic shock at risk for volume overload include checking for fluid responsiveness with passive leg raise, administering fluids based on ideal body weight rather than actual body weight, documenting reasons for not adhering to the 30mL/kg IVF guideline, and considering early vasopressor use. It is crucial for physicians to exercise clinical judgment and discretion when administering crystalloid fluids, avoiding indiscriminate fluid administration based on these nuanced considerations.
Author’s Conclusion:“Based on the published research, our meta-analysis revealed that a restricted fluid resuscitation strategy (<30 mL/kg fluid bolus within 3hrs of sepsis identification) in patients with a history of HF was associated with increased risk of in-hospital mortality, although the included primary studies didn’t achieve a statistical significance, except for the Taenzer et al. study.”
Our Conclusion:
In conclusion, this systematic review and meta-analysis provides valuable insights into the fluid resuscitation strategies for sepsis patients with a history of CHF. Although the findings suggest that a restricted fluid resuscitation approach (<30 mL/kg) may be associated with increased in-hospital mortality, it’s important to note the limitations of the current research, including small sample sizes and the retrospective nature of the studies. These limitations highlight the need for larger, more diverse, and prospective studies to establish clearer guidelines. Future research should also explore distinctions between different types of heart failure, the role of early vasopressor use, and variations in sepsis severity. Until then, this study emphasizes the importance of individualized patient care, urging clinicians to weigh guidelines against the specific circumstances and needs of each patient. As the debate continues, one thing remains clear: flexibility and clinical judgment are key to optimizing patient outcomes.
References:
Vaeli Zadeh A, Wong A, Crawford AC, Collado E, Larned JM. Guideline-based and restricted fluid resuscitation strategy in sepsis patients with heart failure: A systematic review and meta-analysis [published online ahead of print, 2023 Aug 9]. Am J Emerg Med. 2023;73:34-39. PMID: 37597449
Rai A, Dassum SR, Ahmad YR, Ansari S, Kitch BT, Filbin M, Rhee C. Association of the National Center for Medicare and Medicaid Services Sepsis Fluid Resuscitation Measure with Sepsis Outcomes in Patients with and Without Heart Failure. D25. CRITICAL CARE: HARD TIMES – RESUSCITATING MY PATIENT: FLUID, BLOOD AND OTHER STRATEGIES.May 1, 2019, A5999-A5999. [Abstract Link]
Taenzer AH, Patel SJ, Allen TL, et al. Improvement in Mortality With Early Fluid Bolus in Sepsis Patients With a History of Congestive Heart Failure. Mayo Clin Proc Innov Qual Outcomes. 2020;4(5):537-541. Published 2020 Aug 19. PMID: 33083702
Uchel, T., Hamdon, M. S., Patel, M., Gonzalez, V., & Masso, L. (2019). FLUID RESUSCITATION IN CHF PATIENTS PRESENTING WITH SEPSIS: A RETROSPECTIVE COHORT STUDY. Chest, 156(4), A1719. [Abstract Link]
Kuttab HI, Lykins JD, Hughes MD, et al. Evaluation and Predictors of Fluid Resuscitation in Patients With Severe Sepsis and Septic Shock. Crit Care Med. 2019;47(11):1582-1590. PMID: 31393324
Guest Post By:
Imogen Kane, DO
PGY-1, Emergency Medicine Resident
Vassar Brothers Hospital, Poughkeepsie, New York
E-mail: Imogen.Kane@nuvancehealth.org
Marco Propersi, DO FAAEM Vice-Chair, Emergency Medicine
Assistant Emergency Medicine Program Director
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter: @marco_propersi
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
