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The New England Journal of Medicine Feb 2023Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.
METHODS
In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed.
RESULTS
A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups.
CONCLUSIONS
Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).
Topics: Humans; Fluid Therapy; Sepsis; Hypotension; Time Factors; Treatment Outcome; Vasoconstrictor Agents
PubMed: 36688507
DOI: 10.1056/NEJMoa2212663 -
Journal of Intensive Care Medicine May 2019Among critically ill adults, sepsis remains both common and lethal. In addition to antibiotics and source control, fluid resuscitation is a fundamental sepsis therapy.... (Review)
Review
Among critically ill adults, sepsis remains both common and lethal. In addition to antibiotics and source control, fluid resuscitation is a fundamental sepsis therapy. The physiology of fluid resuscitation for sepsis, however, is complex. A landmark trial found early goal-directed sepsis resuscitation reduced mortality, but 3 recent multicenter trials did not confirm this benefit. Multiple trials in resource-limited settings have found increased mortality with early fluid bolus administration in sepsis, and the optimal approach to early sepsis resuscitation across settings remains unknown. After initial resuscitation, excessive fluid administration may contribute to edema and organ dysfunction. Using dynamic variables such as passive leg raise testing can predict a patient's hemodynamic response to fluid administration better than static variables such as central venous pressure. Whether using measures of "fluid responsiveness" to guide fluid administration improves patient outcomes, however, remains unknown. New evidence suggests improved patient outcomes with the use of balanced crystalloids compared to saline in sepsis. Albumin may be beneficial in septic shock, but other colloids such as starches, dextrans, and gelatins appear to increase the risk of death and acute kidney injury. For the clinician caring for patients with sepsis today, the initial administration of 20 mL/kg of intravenous balanced crystalloid, followed by consideration of the risks and benefits of subsequent fluid administration represents a reasonable approach. Additional research is urgently needed to define the optimal dose, rate, and composition of intravenous fluid during the management of patients with sepsis and septic shock.
Topics: Crystalloid Solutions; Fluid Therapy; Humans; Resuscitation; Risk Assessment; Sepsis
PubMed: 29986619
DOI: 10.1177/0885066618784861 -
The Veterinary Clinics of North... Mar 2017Fluid therapy is generally the most life saving and important therapeutic measure in a critical pet suffering from dehydration due to gastrointestinal losses (vomiting... (Review)
Review
Fluid therapy is generally the most life saving and important therapeutic measure in a critical pet suffering from dehydration due to gastrointestinal losses (vomiting and/or diarrhea). Fluid therapy should be personalized to the patient's history, complaint, physical examination and laboratory findings. It is directed to the patients needs and modified based of the physical and laboratory findings until fluid therapy resuscitation end points are achieved.
Topics: Acid-Base Imbalance; Animals; Cat Diseases; Cats; Dehydration; Diarrhea; Dog Diseases; Dogs; Electrolytes; Fluid Therapy; Vomiting
PubMed: 27939861
DOI: 10.1016/j.cvsm.2016.09.013 -
British Journal of Anaesthesia Nov 2014I.V. fluid therapy plays a fundamental role in the management of hospitalized patients. While the correct use of i.v. fluids can be lifesaving, recent literature... (Review)
Review
I.V. fluid therapy plays a fundamental role in the management of hospitalized patients. While the correct use of i.v. fluids can be lifesaving, recent literature demonstrates that fluid therapy is not without risks. Indeed, the use of certain types and volumes of fluid can increase the risk of harm, and even death, in some patient groups. Data from a recent audit show us that the inappropriate use of fluids may occur in up to 20% of patients receiving fluid therapy. The delegates of the 12th Acute Dialysis Quality Initiative (ADQI) Conference sought to obtain consensus on the use of i.v. fluids with the aim of producing guidance for their use. In this article, we review a recently proposed model for fluid therapy in severe sepsis and propose a framework by which it could be adopted for use in most situations where fluid management is required. Considering the dose-effect relationship and side-effects of fluids, fluid therapy should be regarded similar to other drug therapy with specific indications and tailored recommendations for the type and dose of fluid. By emphasizing the necessity to individualize fluid therapy, we hope to reduce the risk to our patients and improve their outcome.
Topics: Consensus; Endpoint Determination; Fluid Therapy; Humans; Monitoring, Physiologic; Sepsis; Shock, Septic; Terminology as Topic
PubMed: 25204700
DOI: 10.1093/bja/aeu300 -
American Journal of Respiratory and... Apr 2019Intravenous fluid therapy is the most common intervention received by acutely ill patients. Historically, saline (0.9% sodium chloride) has been the most frequently... (Review)
Review
Intravenous fluid therapy is the most common intervention received by acutely ill patients. Historically, saline (0.9% sodium chloride) has been the most frequently administered intravenous fluid, especially in North America. Balanced crystalloid solutions (e.g., lactated Ringer's, Plasma-Lyte) are an increasingly used alternative to saline. Balanced crystalloids have a sodium, potassium, and chloride content closer to that of extracellular fluid and, when given intravenously, have fewer adverse effects on acid-base balance. Preclinical research has demonstrated that saline may cause hyperchloremic metabolic acidosis, inflammation, hypotension, acute kidney injury, and death. Studies of patients and healthy human volunteers suggest that even relatively small volumes of saline may exert physiological effects. Randomized trials in the operating room have demonstrated that using balanced crystalloids rather than saline prevents the development of hyperchloremic metabolic acidosis and may reduce the need for vasopressors. Observational studies among critically ill adults have associated receipt of balanced crystalloids with lower rates of complications, including acute kidney injury and death. Most recently, large randomized trials among critically ill adults have examined whether balanced crystalloids result in less death or severe renal dysfunction than saline. Although some of these trials are still ongoing, a growing body of evidence raises fundamental concerns regarding saline as the primary intravenous crystalloid for critically ill adults and highlights fundamental unanswered questions for future research about fluid therapy in critical illness.
Topics: Critical Illness; Crystalloid Solutions; Fluid Therapy; Humans
PubMed: 30407838
DOI: 10.1164/rccm.201809-1677CI -
Clinical Nutrition (Edinburgh, Scotland) Nov 2020Malnutrition has been recognized as a major risk factor for adverse postoperative outcomes. The ESPEN Symposium on perioperative nutrition was held in Nottingham, UK, on... (Review)
Review
BACKGROUND & AIMS
Malnutrition has been recognized as a major risk factor for adverse postoperative outcomes. The ESPEN Symposium on perioperative nutrition was held in Nottingham, UK, on 14-15 October 2018 and the aims of this document were to highlight the scientific basis for the nutritional and metabolic management of surgical patients.
METHODS
This paper represents the opinion of experts in this multidisciplinary field and those of a patient and caregiver, based on current evidence. It highlights the current state of the art.
RESULTS
Surgical patients may present with varying degrees of malnutrition, sarcopenia, cachexia, obesity and myosteatosis. Preoperative optimization can help improve outcomes. Perioperative fluid therapy should aim at keeping the patient in as near zero fluid and electrolyte balance as possible. Similarly, glycemic control is especially important in those patients with poorly controlled diabetes, with a stepwise increase in the risk of infectious complications and mortality per increasing HbA1c. Immobilization can induce a decline in basal energy expenditure, reduced insulin sensitivity, anabolic resistance to protein nutrition and muscle strength, all of which impair clinical outcomes. There is a role for pharmaconutrition, pre-, pro- and syn-biotics, with the evidence being stronger in those undergoing surgery for gastrointestinal cancer.
CONCLUSIONS
Nutritional assessment of the surgical patient together with the appropriate interventions to restore the energy deficit, avoid weight loss, preserve the gut microbiome and improve functional performance are all necessary components of the nutritional, metabolic and functional conditioning of the surgical patient.
Topics: Congresses as Topic; Europe; Fluid Therapy; Humans; Malnutrition; Nutrition Therapy; Perioperative Care; Practice Guidelines as Topic; Societies, Medical; Surgical Procedures, Operative; Water-Electrolyte Imbalance
PubMed: 32362485
DOI: 10.1016/j.clnu.2020.03.038 -
British Journal of Anaesthesia Sep 2016Since 1968, when Baxter and Shires developed the Parkland formula, little progress has been made in the field of fluid therapy for burn resuscitation, despite advances... (Review)
Review
Since 1968, when Baxter and Shires developed the Parkland formula, little progress has been made in the field of fluid therapy for burn resuscitation, despite advances in haemodynamic monitoring, establishment of the 'goal-directed therapy' concept, and the development of new colloid and crystalloid solutions. Burn patients receive a larger amount of fluids in the first hours than any other trauma patients. Initial resuscitation is based on crystalloids because of the increased capillary permeability occurring during the first 24 h. After that time, some colloids, but not all, are accepted. Since the emergence of the Pharmacovigilance Risk Assessment Committee alert from the European Medicines Agency concerning hydroxyethyl starches, solutions containing this component are not recommended for burns. But the question is: what do we really know about fluid resuscitation in burns? To provide an answer, we carried out a non-systematic review to clarify how to quantify the amount of fluids needed, what the current evidence says about the available solutions, and which solution is the most appropriate for burn patients based on the available knowledge.
Topics: Burns; Colloids; Crystalloid Solutions; Fluid Therapy; Humans; Isotonic Solutions
PubMed: 27543523
DOI: 10.1093/bja/aew266 -
Anaesthesiology Intensive Therapy 2014Sepsis is associated with generalised endothelial injury and capillary leak and has traditionally been treated with large volume fluid resuscitation. Some patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sepsis is associated with generalised endothelial injury and capillary leak and has traditionally been treated with large volume fluid resuscitation. Some patients with sepsis will accumulate bodily fluids. The aim of this study was to systematically review the association between a positive fluid balance/fluid overload and outcomes in critically ill adults, and to determine whether interventions aimed at reducing fluid balance may be linked with improved outcomes.
METHODS
We searched MEDLINE, PubMed, EMBASE, Web of Science, The Cochrane Database, clinical trials registries, and bibliographies of included articles. Two authors independently reviewed citations and selected studies examining the association between fluid balance and outcomes or where the intervention was any strategy or protocol that attempted to obtain a negative or neutral cumulative fluid balance after the third day of intensive care compared to usual care. The primary outcomes of interest were the incidence of IAH and mortality.
RESULTS
Among all identified citations, one individual patient meta-analysis, 11 randomised controlled clinical trials, seven interventional studies, 24 observational studies, and four case series met the inclusion criteria. Altogether, 19,902 critically ill patients were studied. The cumulative fluid balance after one week of ICU stay was 4.4 L more positive in non-survivors compared to survivors. A restrictive fluid management strategy resulted in a less positive cumulative fluid balance of 5.6 L compared to controls after one week of ICU stay. A restrictive fluid management was associated with a lower mortality compared to patients treated with a more liberal fluid management strategy (24.7% vs 33.2%; OR, 0.42; 95% CI 0.32-0.55; P < 0.0001). Patients with intra-abdominal hypertension (IAH) had a more positive cumulative fluid balance of 3.4 L after one week of ICU stay. Interventions to decrease fluid balance resulted in a decrease in intra-abdominal pressure (IAP): an average total body fluid removal of 4.9 L resulted in a drop in IAP from 19.3 ± 9.1 mm Hg to 11.5 ± 3.9 mm Hg.
CONCLUSIONS
A positive cumulative fluid balance is associated with IAH and worse outcomes. Interventions to limit the development of a positive cumulative fluid balance are associated with improved outcomes. In patients not transgressing spontaneously from the Ebb to Flow phases of shock, late conservative fluid management and late goal directed fluid removal (de-resuscitation) should be considered.
Topics: Critical Illness; Fluid Therapy; Humans; Resuscitation; Treatment Outcome; Wounds and Injuries
PubMed: 25432556
DOI: 10.5603/AIT.2014.0060 -
Critical Care Medicine Dec 2020Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies.
DATA SOURCES
A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases.
STUDY SELECTION AND DATA EXTRACTION
All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews.
DATA SYNTHESIS
A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03-19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51-3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55-5.00) and 1.39 (95% CI, 1.15-1.69) for cumulative fluid balance. Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75-2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81-7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39-1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30-5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03-1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11-1.28) per liter increase in positive fluid balance.
CONCLUSIONS
This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.
Topics: Adult; Critical Illness; Fluid Therapy; Humans; Observational Studies as Topic; Water-Electrolyte Imbalance
PubMed: 33009098
DOI: 10.1097/CCM.0000000000004617 -
Critical Care (London, England) Dec 2020Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients' conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients.
METHODS
Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence.
RESULTS
Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74-0.95) and L-HES (OR 0.81; 95% CI 0.69-0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65-0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35-0.87).
CONCLUSIONS
Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients.
TRIAL REGISTRATION
PROSPERO website, registration number: CRD42018115641).
Topics: Colloids; Crystalloid Solutions; Fluid Therapy; Humans; Network Meta-Analysis; Postoperative Complications; Randomized Controlled Trials as Topic; Resuscitation; Sepsis; Wounds and Injuries
PubMed: 33317590
DOI: 10.1186/s13054-020-03419-y