Impact of different intravenous bolus rates on fluid and electrolyte balance and mortality in critically ill patients

Abstract

The effect of intravenous bolus rates on patient outcomes is a complex and crucial aspect of critical care. Fluid challenges are commonly used in critically ill patients to manage their hemodynamic status, but there is limited information available on the specifics of when, how much, and at what rate fluids should be administered during these challenges. The aim of this review is to thoroughly examine the relationship between intravenous bolus rates, fluid-electrolyte balance, and mortality and to analyze key research findings and methodologies to understand these complex dynamics better. Fluid challenges are commonly employed in managing hemodynamic status in this population, yet there is limited information on the optimal timing, volume, and rate of fluid administration. Utilizing a narrative review approach, the analysis identified nine relevant studies that investigate these variables. The findings underscore the importance of a precise and individualized approach in clinical settings, highlighting the need to tailor intravenous bolus rates to each patient's specific needs to maximize outcomes. This review provides valuable insights that can inform and optimize clinical practices in critical care, emphasizing the necessity of meticulous and exact strategies in fluid administration.

Key Words: Fluid balance; Fluid resuscitation; Intensive care unit; Precision medicine; Mortality

Core Tip: This review aims to emphasize the importance of a meticulous and exact approach in medical settings, focusing on tailoring intravenous bolus rates to suit the specific needs of individual patients. This review seeks to provide valuable insights that can inform and optimize clinical practices in the critical care setting by maximizing desired outcomes through tailored strategies.

INTRODUCTION

Fluid management is crucial in managing critically ill patients, and involves flow and pressure variables, systemic shock responses, and various fluid types. The relationship between preload, stroke volume, and fluid administration is complex; the volume and rate of infusion have an impact on venous return. Precise fluid management is essential to prevent fluid overload in conditions such as septic shock. Crystalloids are the most common choice for fluid therapy, with balanced solutions possibly leading to an improved outcome[1]. Fluid management plays a crucial role in regulating hemodynamic parameters and tissue perfusion. It is difficult to precisely determine the critical oxygen delivery threshold to cells; however, several clinical indicators and parameters can function as surrogates, such as cardiac function's central role in therapy[1]. The daily fluid balance (FB) encompasses the cumulative intake and excretion of fluids over a 24-hour timeframe. On a daily basis, over 20% of patients in intensive care units (ICUs) require intravenous fluid resuscitation, with more than 30% receiving this type of therapy within the first day of admission to the ICU[2]. This encompasses all sources of fluid intake, including resuscitation and maintenance fluids, as well as different types of outputs like urine, ultrafiltration fluids, gastrointestinal losses, and third space losses. It is important to consider all these factors when prescribing administrative fluids. These fluids should only be administered to fulfill the patient's daily fluid needs. If the patient is currently receiving fluids and electrolytes through alternative methods, such as enteral or parenteral nutrition or medication solutions, it is recommended to discontinue the use of specific intravenous maintenance fluids. Per the definition of FB, maintenance fluids are given to patients to fulfill their daily baseline needs of electrolytes, glucose, and water[3]. These fluids are intended to cover the daily needs of the patient, including 25-30 mL/kg of body weight for water, 1 mmoL/kg of potassium, 1-1.5 mmol/kg of sodium, and, to prevent starvation ketoacidosis, the recommended intake of glucose, or dextrose (5% or 10%), is between 1.4 g/kg and 1.6 g/kg of body weight[4].

The fluid challenge is a widely used method for evaluating fluid responsiveness. It involves the administration of a fluid bolus and subsequent monitoring of the hemodynamic response. It is crucial to recognize that multiple fluid challenges have the potential to result in fluid overload. Thus, there is variation in the successful completion of fluid challenges in clinical settings. Fluid challenges are frequently utilized in patients who are critically ill, playing a crucial role in managing their hemodynamics. However, data regarding the indication, type, amount, and rate of fluid administered during a fluid challenge are scarce.

This paper explores the importance of different intravenous fluid infusion rates for critically ill patients. It emphasizes the significance of immediately providing enough fluids to resuscitate patients and adopting a cautious strategy for subsequent fluid management, which can lead to better outcomes for patients. This review aims to look at the effects of different rates of intravenous fluid infusion in critically ill patients. This study seeks to enhance our understanding of the complicated dynamics of fluid and electrolyte management in critically ill patients through an analysis of extensive research findings, methodologies, and key studies.

STUDY DESIGN

This review aimed to synthesize existing literature on the impact of different intravenous bolus rates on fluid and electrolyte balance, and mortality in critically ill patients. A narrative review approach was employed to summarize and analyze the findings from relevant studies.

Literature search

From 2014 to 2024, a comprehensive literature review was conducted in electronic databases such as PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library. The search approach used a combination of medical subject headings terms and keywords related to intravenous fluid management, bolus infusion, critically ill patients, fluid and electrolyte balance, and mortality. The study selection criteria focused on peer-reviewed scholarly articles that examined the impact of different intravenous bolus rates on fluid and electrolyte balances, and mortality outcomes in critically ill adult patients. The studies needed to present relevant facts or findings on this specific issue to be considered for inclusion. Exclusion criteria involved articles that were not original research, such as reviews, case reports, editorials, conference abstracts, and animal studies.

Data extraction and synthesis

Two reviewers separately conducted data extraction using a standardized form. The abstracts of discovered articles were reviewed based on the search strategies. Papers in English meeting the eligibility requirements were then obtained in full text. Furthermore, reference lists of selected papers were examined for further relevant studies. Multiple studies were found, but only a small number satisfied the requirements. Two reviewers were involved, with the second reviewer focusing on ensuring transparency in the study selection process and preserving the reliability of the review outcomes.

Findings from the investigations were summarized and analyzed using a narrative synthesis approach. A full review was conducted on data regarding the effects of various intravenous bolus rates on fluid and electrolyte balance as well as mortality outcomes. The review focused on major results, trends, and areas of agreement or disagreement.

Quality assessment

No formal quality evaluation or risk of bias assessment was performed due to the review's nature as a narrative synthesis of current material. The interpretation of findings considered the level of evidence and limitations of the investigations.

FINDINGS

Nine relevant papers were found during the literature review (Table 1). The studies examined the correlation between intravenous bolus rates, fluid and electrolyte balance, and mortality outcomes in critically ill patients. The results from the studies differed in various clinical contexts, such as acute kidney injury, traumatic brain injury, cancer, acute respiratory distress syndrome (ARDS), and patients needing mechanical ventilation and vasopressor support. Although there were variations in the optimal intravenous infusion rates, the majority of studies examined the relationship between FB and mortality and found it to be significantly associated despite differences in study populations and methodologies. An investigation into the significance of FB in critically ill patients, specifically those with cardiovascular disorders in the ICU, revealed that a positive FB exceeding 1000 mL within the initial 72 hours of admission is associated with elevated mortality risk[5]. A study conducted in Poland exhibited reduced daily FBs during the first 24, 48, and 72 hours, along with cumulative balances at the end of 7 days. Factors such as excessive FB, colloid solution use, stroke, and shock diagnosis were correlated with mortality.

Table 1 Literature review of intravenous bolus rates on fluid and electrolyte balance and mortality in critically ill patients.

Ref.	Research findings	Methodologies employed	Clinical approaches	Fluid types and bolus rates	Gaps in current research/limitations	Practical insights for healthcare professionals
Caltabeloti et al[5], 2014	Early fluid loading worsens lung aeration without affecting oxygenation	Observational study with lung ultrasound	Early aggressive fluid loading in ARDS	Not specified	Limited by observational design, small sample size	Caution against early aggressive fluid loading in ARDS patients
Ukor et al[7], 2017	Bolus infusion causes more pronounced hemodynamic changes compared to slower infusion	Experimental study with healthy volunteers	Comparison of bolus vs slow infusion	Intravenous crystalloid at different rates	Limited to healthy volunteers, not critically ill patients	Consider slower infusion rates for better hemodynamic stability
Kattan et al[8], 2020	Identifies optimal targets for fluid resuscitation in septic shock	Review of existing studies and guidelines	Septic shock resuscitation strategies	Various fluids and administration rates	Variability in study designs and targets	Personalized resuscitation targets based on patient condition
Connor et al[9], 2021	Crystalloid composition and administration rate impact resuscitation outcomes	Analysis of ICU patient data	Different rates and compositions of crystalloids	Crystalloids at various rates	Lack of large-scale randomized trials	Importance of considering fluid composition and rate in ICU resuscitation
Trejnowska et al[11], 2019	Fluid balance is critical for outcomes in critically ill patients	Retrospective observational study	Monitoring and managing fluid balance	Not specified	Retrospective design, single-center study	Emphasizes meticulous fluid balance management
Barmparas et al[12], 2014	Positive fluid balance is associated with worse outcomes in surgical patients	Prospective observational study	Monitoring fluid balance	Crystalloids and colloids	Single-center study, observational design	Avoid positive fluid balance to improve outcomes
Zampieri et al[15], 2021	Slower bolus rates may improve mortality in critically ill patients	Randomized clinical trial	Comparison of slower and faster bolus rates	Intravenous fluids at different bolus rates	Potential variability in patient conditions	Slower bolus rates could be beneficial for critically ill patients
Shen et al[14], 2017	Negative fluid balance is linked to lower mortality in critically ill patients	Retrospective cohort study	Monitoring fluid intake and outcomes	Not specified	Retrospective design, potential confounding factors	Targeting negative fluid balance may improve survival
Chen et al[13], 2020	Early positive fluid balance was associated with higher 1-year mortality in critically ill cancer patients	Retrospective observational study	Emphasizes early fluid management in cancer patients	Not specified in the study	Retrospective design, single-center study, potential for confounding variables	Highlights the need for careful fluid management in critically ill cancer patients to improve long-term survival

ARDS: Acute respiratory distress syndrome; ICU: Intensive care unit.

The studies emphasize the importance of precise FB monitoring and management to improve patient outcomes and reduce mortality rates in critically ill patients[6,7]. Another investigation was conducted to investigate the impact of FB and fluid intake on outcomes in critically ill patients. Examined data from the Multi-parameter Intelligent Monitoring in Intensive Care III Database, specifically looked at patients who attained negative FB 48 hours after ICU admission. The study revealed a correlation between slight negative FB and decreased hospital mortality and a connection between increased fluid intake and urine output and reduced mortality. However, an increase in negative FB was not associated with reduced mortality[8]. While some studies found no significant difference between slower and faster intravenous fluid bolus rates, others suggested that slower bolus rates may be correlated with reduced mortality[9]. A study was conducted to compare the impact of different intravenous fluid bolus rates on mortality in critically ill patients. The trial involved slower (333 mL/h) and faster (999 mL/h) rates. 10520 patients in 75 ICUs across Brazil were included in the study, which concluded that there was no statistically significant difference in 90-day mortality based on the infusion rates. Findings from the trial indicated that the rate of intravenous fluid bolus administration does not significantly affect mortality outcomes in critically ill patients who need fluid challenges.

Studies indicate that positive or negative FB can affect the long-term survival of critically ill patients. Excess fluid leads to higher mortality rates, whereas inadequate fluid intake decreases short-term mortality but increases long-term mortality. Renal replacement therapy helps mitigate this risk in critically ill patients. Having a positive cumulative FB has been associated with increased mortality and decreased survival in critically ill patients[10,11].

In a randomized, double-blind trial, researchers found no significant difference in outcomes between balanced multielectrolyte solution (BMES) and saline when used in critically ill adults. A study of 5037 critically ill patients in ICUs concluded that there was no significant difference in the risk of death or acute kidney injury between those treated with BMES and saline. The main result was the absence of a significant difference between the two groups in terms of death from any cause within 90 days after randomization, as well as secondary outcomes such as receiving new renal-replacement therapy and the maximum increase in creatinine level during an ICU stay[12].

DISCUSSION

The existing literature on the impact of intravenous bolus rates on fluid and electrolyte balance in critically ill patients has a few limitations. There are several factors that contribute to the complexity of this topic. These factors include variations in study populations, differences in protocols for administering fluids, variations in the types of fluids used, differences in short-term and long-term outcomes, variations in research methods, a lack of patient-centered approaches, insufficient reporting of adverse effects, limited comparative studies, regional and institutional differences, and a tendency to focus on single-center studies. These factors pose challenges in generalizing findings across various patient groups and establishing optimal practices. In addition, it is important to consider regional and institutional differences which may influence the study results; regional and institutional variations can impact the generalizability of study results.

The limitations affect data interpretation, highlighting the necessity for additional research to overcome these constraints and offer stronger evidence. A rapid infusion of 20 mL/kg over 30 minutes had various effects on gas exchange and cardiovascular parameters. It caused a small but significant reduction in forced expiratory flow and elevated systolic blood pressure by about 9%[13]. However, there were no significant changes in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), heart rate, or lung volume. The FEV1/FVC ratio indicates how much air you can forcefully exhale. Spirometry, a test for diagnosing or monitoring lung conditions, measures this. The FEV1 measures how much air you can exhale in the first second; the FVC measures the total amount of air you can exhale forcefully in one breath[14]. On the other hand, a slow infusion over 120 minutes resulted in a greater increase in cardiac output compared to a rapid infusion[15]. A rapid infusion of 500 mL in 30 minutes increased cardiac output and decreased heart rate, which could be beneficial for patients with septic shock[16]. A study that examined crystalloid infusion rates during fluid resuscitation in patients with an acute hemorrhage found that bolus crystalloid infusion rates above 80 mL/kg/h might not make fluid resuscitation work better[17]. Additionally, the study found that colloids had a greater impact on platelet function than crystalloids[18]. Dilution with study solutions caused a platelet count drop, but hemodilution did not affect platelet function[18]. In conclusion, recommendations for the initial bolus rate of fluid administration in critically ill patients differ, but generally, intake of fluid in the first hour should be given at a rate of 30-40 mL/kg. The infusion rate for a standard adult fluid bolus can range from 20 to 30 minutes[19]. However, certain research suggests a shorter duration to minimize negative effects and enhance outcomes[20]. A summary of the findings shows the challenges associated with fluid management for critically ill patients. Additionally, it highlights the necessity for further research to determine the optimal intravenous bolus rates for preserving fluid and electrolyte balance to decrease mortality rates.

These findings highlight the significance of managing FB in critically ill patients, as both positive and negative balances can greatly impact long-term survival outcomes. It is crucial to carefully manage fluid administration to prevent excess accumulation and ensure proper resuscitation for optimal patient outcomes in critical care settings[2,21]. The randomized clinical trial conducted has limitations, including not being analyzed as an intention to treat, a discrepancy between expected and observed mortality rates, and patients receiving small amounts of fluid.

Fluid management challenges

The management of fluids in critically ill patients presents several challenges, such as optimizing FB, mitigating the risk of fluid overload, accounting for diverse patient populations, navigating complex clinical decision-making processes, and appropriately evaluating response to fluid administration[21]. Due to the dynamic nature of the patient's condition, regular reassessment and adjustment of fluid therapy are required.

Excessive administration of fluids can result in unfavorable consequences, including the development of pulmonary edema and heart failure. When making treatment options, clinicians must consider many parameters, such as hemodynamic stability, organ perfusion, electrolyte balance, and fluid categorization[22]. The evidence base for fluid management practices is incomplete and evolving, and resource constraints can limit monitoring and multidisciplinary collaboration[22]. To effectively address these challenges, adopting a comprehensive strategy that incorporates evidence-based guidelines, clinical expertise, and continuous quality improvement initiatives is necessary.

Fluid management and precision medicine

Precision medicine and genomics can improve fluid management for critically ill patients. By customizing treatments according to individual genetic profiles and characteristics, we can effectively address the challenges in this area[23]. Advancements in genomics have opened possibilities for a personalized approach to critical care, which could significantly impact the administration of fluid therapy in the ICU[24].

One approach to addressing the difficulties associated with fluid management in critically ill patients is by implementing personalized care and precision medicine. By examining genetic factors that impact responses to fluid therapy, clinicians can customize treatment plans according to an individual patient's genetic characteristics and medical history. Genomic insights, working together with other omics technologies, offer valuable information regarding the genetic basis of significant medical conditions such as sepsis and ARDS[25]. This insight contributes to the prediction of patient responses to fluid management strategies. Biomarkers are essential for predicting prognosis and advising treatment decisions in the ICU. A personalized approach to therapy is necessary, given the complexity of critical illness syndromes. Genomic analysis can assist in distinguishing genetically defined patient subgroups, allowing for customized treatment strategies. With the advancement of precision medicine, the integration of genomic data into fluid management strategies holds promise for enhancing patient outcomes[26]. Intravenous fluid resuscitation in the ICU can be done more accurately and more effectively with the help of genetic information and biomarkers. Incorporating precision medicine and genomics into critical care practices has the potential to improve fluid management strategies and provide personalized care for critically ill patients[27] (Figure 1). The relationship between fluid type, bolus fluid rate, and mortality is complicated and influenced by various patient-specific factors and the clinical context. The goal of patient-specific fluid therapy should be to maintain hemodynamic stability while minimizing adverse effects; both crystalloid and colloid solutions have advantages as well as disadvantages (Figure 2).

Figure 1 Contributing factors considered in fluid management strategies. FEV1: Forced expiratory volume in the first second; FVC: Forced vital capacity.

Figure 2 Contributing factors considered in precision fluid bolus rate decision.

Challenges in implementing precision medicine for fluid management in critically ill patients

Implementing precision medicine for fluid management in critically ill patients presents several challenges that need to be addressed to optimize patient care. The implementation of precision medicine in the ICU is complex due to the requirement of customizing treatments for each patient, taking into account their specific genetic profiles and medical backgrounds, potentially leading to longer recruitment times, increased complexity, and higher costs for clinical trials[28]. The heterogeneity and comorbidities commonly seen in critical care patients further complicate the application of precision medicine; considering the interaction of combination treatments, dynamic physiological changes, and the presence of comorbid conditions, disease complexity can be significantly heightened[28]. Additionally, the effective implementation of precision medicine strategies for fluid management in critically ill patients is impeded by terminology and patient stratification challenges. There is also ambiguity regarding how to categorize patients into distinct groups for precise treatment approaches, which poses an important challenge[26]. Furthermore, integrating and interpreting large amounts of data, including genomic information, biomarkers, and clinical data, poses a significant challenge in implementing precision medicine for fluid management, requiring advanced data analytics and interpretation capabilities that may not always be readily available in clinical settings[26]. Overcoming these challenges is essential to harnessing the full potential of precision medicine and improving outcomes for critically ill individuals.

CONCLUSION

This paper discusses how various bolus rates affect FB in critically ill patients, highlighting the necessity for additional research given the complexity and variations among individual patients. Various factors, including patient characteristics, the clinical context, and the timing and volume of fluid administration, can influence the impact of IV fluid bolus intervention on mortality. Research should be conducted on precision medicine and genomics to optimize fluid bolus rate administration in critically ill patients by considering individual patient characteristics and genetic factors. Additional large-scale randomized controlled trials with stratified analyses are necessary to establish the optimal fluid infusion rates and their impact on mortality, organ dysfunction, and other clinical outcomes in critically ill patients. Managing fluid levels in critically ill patients is a complex task that calls for personalized treatment in parallel to prescribing medication tailored to the patient's unique requirements and tolerances.