Pattern of Fluid Overload and its Impact on Mortality Among Mechanically Ventilated Children: Secondary Analysis of the ReLiSCh Trial.

OBJECTIVES: To assess the pattern of fluid overload (FO) and its impact on mortality among mechanically ventilated children. METHODS: In this secondary analysis of an open-label randomized controlled trial (ReLiSCh trial, October 2020-September 2021), hemodynamically stable mechanically ventilated children (n = 100) admitted to a tertiary level pediatric intensive care unit (PICU) in North India were enrolled. The primary outcome was pattern of FO (FO% >10% and cumulative FO% from day 1-7); and secondary outcomes were pattern of FO among survivors and non-survivors, and prescription practices of maintenance fluid. RESULTS: The median (IQR) age was 3.5 (0.85-7.5) y and 57% were males. Common diagnoses were pneumonia (27%), scrub typhus (14%), Landry-Guillain-Barré syndrome (9%), dengue (8%), central nervous system infections (7%) and staphylococcal sepsis (6%). Common organ dysfunction included acute respiratory distress syndrome (ARDS) (41%), shock (38%), and acute kidney injury (AKI) (9%). The duration PICU stay was 11 (7-17) d and mortality was 12%. The FO% >10% was noted in 19% children; and there was significant increase in cumulative FO% from day 1-7 [1.2 (0.2-2.6)% to 8.5 (1.7-14.3)%, (p = 0.000)]. Among non-survivors, higher proportion had FO% >10% (66.7% vs. 12.5%, p 0.0001); and trend towards higher cumulative FO% on first seven days. From day 1-7, the percentage of maintenance fluid received increased from 60 (50-71)% to 70 (60-77)% (p = 0.691). CONCLUSIONS: One-fifth of mechanically ventilated children had FO% >10% and there was significant increase in cumulative FO% from day 1-7. Non-survivors had significantly higher degree of FO.

Restricted versus Usual/Liberal Maintenance Fluid Strategy in Mechanically Ventilated Children: An Open-Label Randomized Trial (ReLiSCh Trial).

OBJECTIVES: To assess the impact of restricted vs. usual/liberal maintenance fluid strategy on fluid overload (FO) among mechanically ventilated children. METHODS: This open-label randomized controlled trial was conducted over a period of 1 y (October 2020-September 2021) in a Pediatric intensive care unit (PICU) in North India. Hemodynamically stable mechanically ventilated children were randomized to 40% (restricted group, n = 50) and 70-80% (usual/liberal group, n = 50) of maintenance fluids. The primary outcome was cumulative fluid overload percentage (FO%) on day 7. Secondary outcomes were FO% >10%; vasoactive inotropic score, sequential organ failure assessment score, pediatric logistic organ dysfunction score and oxygenation index from day 1-7; ventilation free days (VFDs) and PICU free days (PFDs) through day 28; and mortality. RESULTS: The restricted group had statistically non-significant trend towards lower cumulative FO% at day 7 [7.6 vs. 9.5, p = 0.40]; and proportion of children with FO% >10% (12% vs. 26%, p = 0.21) as compared to usual/liberal group. The increase in FO% from day 1-7 was significant in usual/liberal group as compared to restricted group (p <0.001 and p = 0.134, respectively). Restricted group received significantly lower amount of fluid in the first 5 d; had significantly higher VFDs (23 vs. 17 d, p = 0.008) and PFDs (19 vs. 15 d, p = 0.007); and trend towards lower mortality (8% vs. 16%, p = 0.21). CONCLUSIONS: Restricted as compared to usual/liberal maintenance fluid strategy among mechanically ventilated children was associated with a trend towards lower rate and severity of FO and mortality; and significantly lower fluid volume received, and higher VFDs and PFDs.

The First 24 Hours: Burn Shock Resuscitation and Early Complications.

Resuscitation is required for the management of patients with severe thermal injury. Some of the initial pathophysiologic events following burn injury include an exaggerated inflammatory state, injury to the endothelium, and increased capillary permeability, which all culminate in shock. Understanding these processes is critical to the effective management of patients with burn injuries. Formulas predicting fluid requirements during burn resuscitation have evolved over the past century in response to clinical experience and research efforts. Modern resuscitation features individualized fluid titration and monitoring along with colloid-based adjuncts. Despite these developments, complications from over-resuscitation still occur.

Implications of the Regulation of Endothelial Glycocalyx Breakdown and Reconstitution in Severe Burn Injury.

INTRODUCTION: Effective initial fluid resuscitation is the cornerstone intervention in the setting of severe burn injury. Critically, few major advances in burn resuscitation have been made since the 1970s, and since that time there has been only modest improvement in overall morbidity and mortality. Recently, investigations regarding the dynamic changes of vascular endothelium, and more specifically the vascular endothelial glycocalyx, in the setting of severe burn injury and resuscitation have offered insight into the possibility of more tightly controlling fluid shifts and understanding the consequences thereof during this critical period. METHODS: We conducted a literature search of the PubMed database using the terms "burn", and "glycocalyx" limited to studies published in the English language over the past 10 y. A total of 31 articles were initially identified. Abstracts and full text were manually reviewed to identify suitable articles. Of the identified articles, 10 were deemed relevant and included within this review, along with additional articles necessary to provide background on glycocalyx structure and function as well as principles of burn injury management. RESULTS: Glycocalyx shedding is a process known to occur early in the setting of severe burn injury and resuscitation. The degree of shedding tends to increase with age and severity of injury. Though the role and regulation of this shedding is incompletely understood, it has direct consequences on vascular unction and permeability and likely coagulation as well. CONCLUSIONS: Here in this research review, we examine what is known regarding the dynamic breakdown and reconstitution of the glycocalyx during burn injury and how it may be impacted by fluid resuscitation strategies. We further explore the need to more completely understand this mechanism and the consequences of its manipulation.

A burden of fluid, sodium, and chloride due to intravenous fluid therapy in patients with respiratory support: a post-hoc analysis of a multicenter cohort study.

BACKGROUND: Fluid creep, including fluids administered as drug diluents and for the maintenance of catheter patency, is the major source of fluid intake in critically ill patients. Although hypoxemia may lead to fluid restriction, the epidemiology of fluid creep in patients with hypoxemia is unclear. This study aimed to address the burden due to fluid creep among patients with respiratory support according to oxygenation status. METHODS: We conducted a post-hoc analysis of a prospective multicenter cohort study conducted in 23 intensive care units (ICUs) in Japan from January to March 2018. Consecutive adult patients who underwent invasive or noninvasive ventilation upon ICU admission and stayed in the ICU for more than 24 h were included. We excluded the following patients when no fluids were administered within 24 h of ICU admission and no records of the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We investigated fluid therapy until 7 days after ICU admission according to oxygenation status. Fluid creep was defined as the fluids administered as drug diluents and for the maintenance of catheter patency when administered at ≤ 20 mL/h. RESULTS: Among the 588 included patients, the median fluid creep within 24 h of ICU admission was 661 mL (25.2% of the total intravenous-fluid volume), and the proportion of fluid creep gradually increased throughout the ICU stay. Fluid creep tended to decrease throughout ICU days in patients without hypoxemia and in those with mild hypoxemia (p < 0.001 in both patients), but no significant trend was observed in those with severe hypoxemia (p = 0.159). Similar trends have been observed in the proportions of sodium and chloride caused by fluid creep. CONCLUSIONS: Fluid creep was the major source of fluid intake among patients with respiratory support, and the burden due to fluid creep was prolonged in those with severe hypoxemia. However, these findings may not be conclusive as this was an observational study. Interventional studies are, therefore, warranted to assess the feasibility of fluid creep restriction. Trial registration UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN 000028019, July 1, 2017).

Adoption of rescue colloid during burn resuscitation decreases fluid administered and restores end-organ perfusion.

INTRODUCTION: Traditionally, lactated Ringer's solution (LR) has been utilized for the resuscitation of thermally injured patients via the Parkland or Brooke formulas. Both of these formulas include colloid supplementation after 24 h of resuscitation. Recently, the addition of albumin within the initial resuscitation has been reported to decrease fluid creep and hourly fluids given. Our institution has previously advocated for a crystalloid-driven resuscitation. Given reports of improved outcomes with albumin, we pragmatically adjusted these practices and present our findings for doing so. METHODS: Our burn registry, consisting of prospectively collected patient data, was queried for those at least 18 years of age who, between July 2017 and December 2018, sustained a thermal injury and completed a formal resuscitation (24 h). At the attending physician's discretion, rescue colloid was administered using 25% albumin for those failing to respond to traditional resuscitation (patients with sustained urine output of <0.5 mL/kg over 2-3 h, or unstable vital signs and ongoing fluid administration). We compared the total volume of the crystalloid-only and rescue colloid resuscitation fluids given to patients. We also examined the in/out fluid balances during resuscitation. Statistical analysis was performed using Stata software. RESULTS: A total of 91 patients with thermal injuries were included: the median age was 40 (IQR 31-57), 73% were male, and 30 patients received rescue albumin. The percentage of total body surface area burned (%TBSA) was greater in those who received rescue albumin (40.3% vs. 34%; p = 0.047). Despite a higher %TBSA in the albumin group, the total LR given during resuscitation was not significantly different between groups (15,914.43 mL vs. 11,828.71 mL; p = 0.129) even when normalized for TBSA and weight (ml LR/kg/%TBSA: 4.31 vs. 3.66; p = 0.129. The average in/out fluid ratio for the rescue group was higher than for the crystalloid group (0.83 ± 0.05 vs. 0.59 ± 0.11; p = 0.06) and returned to normal after colloid administration. CONCLUSION: Rescue albumin administration decreases the amount of fluid administered per %TBSA during resuscitation, and also increases end organ function as evidenced by increased urinary output. These effects occurred in patients who sustained larger burns and failed to respond to traditional crystalloid resuscitation. Our findings led us to modify our current protocol and a related prospective study of clinical outcomes.

Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population.

PURPOSE: Research on intravenous fluid therapy and its side effects, volume, sodium, and chloride overload, has focused almost exclusively on the resuscitation setting. We aimed to quantify all fluid sources in the ICU and assess fluid creep, the hidden and unintentional volume administered as a vehicle for medication or electrolytes. METHODS: We precisely recorded the volume, sodium, and chloride burdens imposed by every fluid source administered to 14,654 patients during the cumulative 103,098 days they resided in our 45-bed tertiary ICU and simulated the impact of important strategic fluid choices on patients' chloride burdens. In septic patients, we assessed the impact of the different fluid sources on cumulative fluid balance, an established marker of morbidity. RESULTS: Maintenance and replacement fluids accounted for 24.7% of the mean daily total fluid volume, thereby far exceeding resuscitation fluids (6.5%) and were the most important sources of sodium and chloride. Fluid creep represented a striking 32.6% of the mean daily total fluid volume [median 645 mL (IQR 308-1039 mL)]. Chloride levels can be more effectively reduced by adopting a hypotonic maintenance strategy [a daily difference in chloride burden of 30.8 mmol (95% CI 30.5-31.1)] than a balanced resuscitation strategy [daily difference 3.0 mmol (95% CI 2.9-3.1)]. In septic patients, non-resuscitation fluids had a larger absolute impact on cumulative fluid balance than did resuscitation fluids. CONCLUSIONS: Inadvertent daily volume, sodium, and chloride loading should be avoided when prescribing maintenance fluids in view of the vast amounts of fluid creep. This is especially important when adopting an isotonic maintenance strategy.

Fluid Creep and Over-resuscitation.

Fluid creep is the term applied to a burn resuscitation, which requires more fluid than predicted by standard formulas. Fluid creep is common today and is linked to several serious edema-related complications. Increased fluid requirements may accompany the appropriate resuscitation of massive injuries but dangerous fluid creep is also caused by overly permissive fluid infusion and the lack of colloid supplementation. Several strategies for recognizing and treating fluid creep are presented.

Future Therapies in Burn Resuscitation.

Since the 1940s, the resuscitation of burn patients has evolved with dramatic improvements in mortality. The most significant achievement remains the creation and adoption of formulae to calculate estimated fluid requirements to guide resuscitation. Modalities to attenuate the hypermetabolic phase of injury include pharmacologic agents, early enteral nutrition, and the aggressive approach of early excision of large injuries. Recent investigations into the genomic response to severe burns and the application of computer-based decision support tools will likely guide future resuscitation, with the goal of further reducing mortality and morbidity, and improving functional and quality of life outcomes.

Albumin resuscitation in burns: a hybrid regime to mitigate fluid creep.

INTRODUCTION: Globally, many burns units moved away from colloid resuscitation in response to the Cochrane review (1998). Recent literature has introduced the concept of fluid creep: patients receiving volumes far in excess of the upper limit of the Parkland formula. The Cochrane review has been widely criticised, however, and we continued to use 4.5% human albumin solution after 8 h of crystalloid as a hybrid of Parkland and Muir & Barclay's regime. METHODS: Adult patients ⩾15% TBSA were identified from data prospectively entered into our database over a 5-year period (2003-2008). Medical notes and intensive care charts were reviewed comparing volumes of fluids received with requirement estimates. Adverse events were also documented. RESULTS: A total of 72 cases with 34 sets of intensive care charts were analysed. Mean TBSA was 35.2% (range, 15-95%). A total of 75% survived; 3% were haemofiltered. Forty-one percent of patients were resuscitated using the Parkland formula alone, while 59% switched at 8 h post burn to the Muir and Barclay formula (Hybrid group). There was a significantly greater TBSA in the Hybrid group, but they received significantly less fluid volumes than the Parkland group (P = 0.0363; the Hybrid group received 1.36 times calculated need vs. 1.62 in the Parkland group). CONCLUSION: Our patients still demonstrate fluid creep, but to a lesser extent than previously reported. Fluid creep has been mitigated but not eliminated through this strategy.

Acute burn resuscitation and fluid creep: it is time for colloid rehabilitation.

Fluid overloading has become a global phenomenon in acute burn care. The consensus Parkland formula that has excluded colloid use, the impact of goal-directed resuscitation, and the overzealous on the scene crystalloid resuscitation combined with subsequent inefficient titration of fluid administration and lack of timely reduction of infusion rates, have all contributed to this phenomenon of fluid overloading, known as fluid creep and recognized only recently, constituting a landmine in modern burn care. Solid evidence is supportive to the fact that excessive administration of crystalloid and the abandonment of colloid replenishment at some point of resuscitation are the major contributors to fluid creep. With available evidence from the literature, the present is a comprehensive review of literature about fluid creep, trying to determine the etiology behind it as well as to propose strategies to control its magnitude and complications, namely through colloid administration amongst other options.

Burn resuscitation: is it straightforward or a challenge?

Burn shock resuscitation has been extensively studied over the past four decades. Many formulas exist and many parameters have been suggested to assess the adequacy of resuscitation. The most commonly used formula is the Parkland formula, the most commonly used fluids are crystalloids, and the most commonly used parameter is urine output. However, until now, no conclusive evidence has suggested that one formula is superior to another or that one parameter is a better predictor than another. In this article we will review the updated information about the subject and we will look into new advancements in this field. We will pose some questions at the end that will help researchers concentrate their future efforts to solve this important challenge in burn care.