Impact of Comorbidities on Beneficial Effect of Lactated Ringers vs. Saline in Sepsis Patients.
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SUBMITTER: Tseng CH
PROVIDER: S-EPMC8710469 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Little is known regarding the optimal type of fluid resuscitation in acute pancreatitis (AP).The objective of this article was to compare the effect of lactated Ringer's solution (LR) vs normal saline (NS) in the inflammatory response in AP.We conducted a triple-blind, randomized, controlled trial. Patients???18 admitted with AP were eligible. Patients were randomized to receive LR or NS. Primary outcome variables were number of systemic inflammatory response syndrome (SIRS) criteria at 24 hours, 48 hours and 72 hours and blood C-reactive protein (CRP) levels at 48 hours and 72 hours. In vitro complementary experiments were performed to further explore the interaction between pH, lactate and inflammation.Nineteen patients receiving LR and 21 receiving NS were analyzed. The median (p25-p75) number of SIRS criteria at 48 hours were 1 (1-2) for NS vs 1 (0-1) for LR, p?=?0.060. CRP levels (mg/l) were as follows: at 48 hours NS 166 (78-281) vs LR 28 (3-124), p?=?0.037; at 72 hours NS 217 (59-323) vs LR 25 (3-169), p?=?0.043. In vitro, LR inhibited the induction of inflammatory phenotype of macrophages and NF-?B activation. This effect was not observed when using Ringer's solution without lactate, suggesting a direct anti-inflammatory effect of lactate.Lactated Ringer's is associated with an anti-inflammatory effect in patients with acute pancreatitis.
| S-EPMC5802674 | biostudies-literature
Project description:Study objectiveThe purpose of this study is to test the hypothesis that balanced crystalloids improve quality of recovery more than normal saline solution (0.9% sodium chloride) in stable emergency department (ED) patients. Secondary outcomes measured differences in health care use.MethodsA single-site, participant- and evaluator-blinded, 2-arm parallel allocation (1:1), comparative effectiveness, randomized controlled trial allocated adults receiving intravenous fluids in the ED before discharge to receive 2 L of lactated Ringer's solution or normal saline solution. The primary outcome was symptom scores measured by the validated Quality of Recovery-40 instrument (scores 40 to 200) 24 hours after enrollment. Secondary outcomes included subsequent health care use and medication compliance.ResultsParticipants (N=157) were enrolled and follow-up was analyzed for 94 (follow-up rate of 60%) with intention-to-treat methodology. There was no difference in postenrollment Quality of Recovery-40 scores between normal saline solution and lactated Ringer's solution groups (mean difference 2.4; 95% confidence interval [CI] -6.8 to 11.6). Although preenrollment scores were higher in the lactated Ringer's solution group (mean difference 10.5; 95% CI 1.9 to 19.0), adjusting for presurvey imbalances did not change the primary outcome (adjusted difference -3.9; 95% CI -12.9 to 5.2). There were no differences in return to ED (mean difference 7.5%; 95% CI -8.7% to 23.8%), prescriptions filled (mean difference 22.2%; 95% CI -3.3% to 47.6%), or seeking care from another provider (mean difference -2.0%; 95% CI -19.9% to 15.9%) at 7 days.ConclusionNormal saline solution and lactated Ringer's solution were associated with similar 24-hour recovery scores and 7-day health care use in stable ED patients. These results supplement those of recent trials by informing fluid choice for stable ED patients.
| S-EPMC6340785 | biostudies-literature
Project description:The goal of this study was to infer the effectiveness of midazolam as a comparator in preserving the blind in ketamine studies for mood disorders through patient-level analyses of efficacy trial outcomes. In this integrative data analysis (k = 9, N = 367 patients with mood disorders), clinical outcomes were compared across four groups: ketamine (midazolam-controlled), ketamine (saline-controlled), midazolam, and saline. Ketamine doses ranged from 0.5 to 0.54 mg/kg and midazolam doses ranged from 0.02 to 0.045 mg/kg. The baseline-to-Day 1 effect size was d = 0.7 (95% CI: 0.4-0.9) for ketamine (midazolam) versus midazolam and d = 1.8 (95% CI: 1.4-2.2) for ketamine (saline) versus saline. The effect of ketamine relative to control was larger in saline-controlled studies than in midazolam-controlled studies (t(276) = 2.32, p = 0.02). This was driven by a comparatively larger effect under midazolam than saline (t(111) = 5.40, p < 0.0001), whereas there was no difference between ketamine (midazolam) versus ketamine (saline) (t(177) = 0.65, p = 0.51). Model-estimated rates of response (with 95% CI) yielded similar results: ketamine (midazolam), 45% (34-56%); ketamine (saline), 46% (34-58%); midazolam, 18% (6-30%); saline, 1% (0-11%). The response rate for ketamine was higher than the control condition for both saline (t(353) = 7.41, p < 0.0001) and midazolam (t(353) = 4.59, p < 0.0001). Studies that used midazolam as a comparator yielded smaller effects of ketamine than those which used saline, which was accounted for by greater improvement following midazolam compared to saline.
| S-EPMC6785710 | biostudies-literature
Project description:Perioperative hemorrhage may depend on coagulation competence and this study evaluated the influence of coagulation competence on blood loss during cystectomy due to bladder cancer.Forty patients undergoing radical cystectomy were included in a randomized controlled trial to receive either lactated Ringer's solution or Dextran 70 (Macrodex ®) that affects coagulation competence.By thrombelastography evaluated coagulation competence, Dextran 70 reduced "maximal amplitude" (MA) by 25 % versus a 1 % reduction with the administration of lactated Ringer's solution (P <0.001). Blinded evaluation of the blood loss was similar in the two groups of patients - 2339 ml with the use of Dextran 70 and 1822 ml in the lactated Ringer's group (P?=?0.27). Yet, the blood loss was related to the reduction in MA (r?=?-0.427, P?=?0.008) and by multiple regression analysis independently associated with MA (P?=?0.01). Thus, 11 patients in the dextran group (58 %) developed a clinical significant blood loss (>1500 ml) compared to only four patients (22 %) in the lactated Ringer's group (P?=?0.04).With the use of Dextran 70 vs. lactated Ringer's solution during cystectomy, a relation between hemorrhage and coagulation competence is demonstrated. Significant bleeding develops based on an about 25 % reduction in thrombelastography determined maximal amplitude. A multivariable model including maximal amplitude discriminates patients with severe perioperative bleeding during cystectomy.The study was accepted on January 7(th), 2013 at www.clinicaltrialsregister.eu EudraCT 2012-005040-20.
| S-EPMC4672483 | biostudies-literature
Project description:BACKGROUND: Despite best supportive intensive care, the development of severe sepsis and septic shock after trauma is still associated with a high mortality rate in intensive care units (ICU). Incomplete knowledge of the pathophysiological and biochemical mechanisms that lead to perturbations of the host system is a major cause for this clinical entity. This lack of knowledge is mirrored in a delay in both diagnosis of sepsis and stratification of patients at risk. The current diagnostic and classification methods do not provide an early and reliable evidence for the development of sepsis and consequently lead to uncertainty in the classification and a delay in the initiation of an adequate therapy. Here, we present a prospective study performed with a well-defined patient cohort suffering from severe multiple trauma (n=85), in which we aimed to uncover the biological reasons why patients with multiple trauma can have dramatically different outcomes after suffering similar traumatic insults. METHODS: We used peripheral whole blood obtained with the PaxGene system at the time of admission to the ICU, i.e., 12 hours after trauma, for transcriptome analysis and monitored clinically the sequence of events from the admission to the ICU, to the very onset of sepsis and finally to the full development of multiple organ dysfunction syndrome (MODS). Study protocols and standard operating procedures (SOPs) regarding ethics, patient recruitment, logistics in sample acquisition and storage, microarray experiments, data analysis and data management have been developed and provided for a high feasibility and reproducibility of the investigations. FINDINGS: The transcriptome analysis from peripheral blood revealed a strong host response upon severe injury and demonstrated the suitability of whole blood in the PaxGene system as a surrogate marker in clinical gene expression studies. It was evident that patients who developed sepsis in the course of the disease (3-5 days after admission) showed an imbalance in the TH1/TH2 response towards a pronounced TH2 response, soon after trauma. The imbalanced TH1/TH2 shift along with inactivation of T cells, neutrophils, monocytes and macrophages might be critical factors for the initiation of a septic program seen in these patients 12 hours after trauma. INTERPRETATION: First, in this study, we provide protocols for logistics and infrastructure that can be applied generally to successfully integrate gene expression analysis studies in a clinical routine and demonstrate that by following these protocols, dedicated and reproducible results can be obtained. Second, we showed that peripheral whole blood is a suitable surrogate marker for the host response as it contains lots of “information” and is easily accessible. Third, we identified mechanisms involved in the perturbations of the immune system that lead to sepsis. Keywords: Prospective study
2010-12-22 | GSE12624 | GEO
Project description:Background/aimsDespite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock.MethodsThe Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under "exception from informed consent" in the USA or "deferred consent" in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed.DiscussionPRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings.Trial registrationPRoMPT BOLUS was first registered at ClinicalTrials.gov ( NCT04102371 ) on September 25, 2019. Enrollment started on August 25, 2020.
| S-EPMC8572061 | biostudies-literature
Project description:Background: With new randomised pieces of evidence and the latest clinical practice guideline from the BMJ emerging in 2018, an updated analysis of best available evidence on the controversial effects of corticosteroids in sepsis is warranted. Objectives: To comprehensively evaluate whether corticosteroids are beneficial in reducing mortality and what cumulative dosage, daily dosage, and duration of corticosteroid treatment would enable adult patients with sepsis to reach the critical point of benefits. Methods: Ovid MEDLINE, Ovid EMbase, Cochrane Library, and LILACS database were searched until March 22, 2019. Results: Thirty RCTs with 8,836 participants were identified. Long course low-dose corticosteroid therapy could improve 28-day mortality (RR = 0.90, 95% CI = 0.84-0.97; high quality), intensive care unit mortality (RR = 0.87; 95% CI = 0.79-0.95; moderate quality), and in-hospital mortality (RR = 0.88, 95% CI = 0.79-0.997; high quality). However, we found no benefits for 90-day, 180-day, and 1-year mortality. Subgroup results of long course corticosteroid treatment in a population with septic shock and vasopressor-dependent septic shock, corticosteroid regimen with hydrocortisone plus fludrocortisone, corticosteroid dosing strategies including bolus dosing and infusion dosing, the strategies of abrupt discontinuation, timing of randomisation ?24 h, impact factor of ?10, and sample size ?500 were associated with a marginally reduction in 28-day mortality. Conclusions: This meta-analysis found that the long course low-dose and not short course high-dose corticosteroid treatment could marginally improve short-term 28-day mortality with high quality, especially septic shock and vasopressor-dependent septic shock, and it is recommended that long course (about 7 days) low-dose (about 200-300mg per day) hydrocortisone (or equivalent) with cumulative dose (at least about 1,000mg) may be a viable management option for overall patients with sepsis, and it can be also adapted to patient with septic shock alone. Early hydrocortisone plus fludrocortisone administration, via continuous infusion or bolus dosing, is also particularly important for the prognosis. Abrupt discontinuation of corticosteroids, as opposed to the conventional tapered discontinuation, may be considered as a desirable option in 28-day mortality. The safety profile of long course low-dose corticosteroid treatment, including adverse hyperglycaemia and hypernatraemia events, remains a concern, although these events could be easily treated. Clinical Trial Registration: PROSPERO, identifier CRD 42018092849.
| S-EPMC6771229 | biostudies-literature
Project description:BACKGROUND: Despite best supportive intensive care, the development of severe sepsis and septic shock after trauma is still associated with a high mortality rate in intensive care units (ICU). Incomplete knowledge of the pathophysiological and biochemical mechanisms that lead to perturbations of the host system is a major cause for this clinical entity. This lack of knowledge is mirrored in a delay in both diagnosis of sepsis and stratification of patients at risk. The current diagnostic and classification methods do not provide an early and reliable evidence for the development of sepsis and consequently lead to uncertainty in the classification and a delay in the initiation of an adequate therapy. Here, we present a prospective study performed with a well-defined patient cohort suffering from severe multiple trauma (n=85), in which we aimed to uncover the biological reasons why patients with multiple trauma can have dramatically different outcomes after suffering similar traumatic insults. METHODS: We used peripheral whole blood obtained with the PaxGene system at the time of admission to the ICU, i.e., 12 hours after trauma, for transcriptome analysis and monitored clinically the sequence of events from the admission to the ICU, to the very onset of sepsis and finally to the full development of multiple organ dysfunction syndrome (MODS). Study protocols and standard operating procedures (SOPs) regarding ethics, patient recruitment, logistics in sample acquisition and storage, microarray experiments, data analysis and data management have been developed and provided for a high feasibility and reproducibility of the investigations. FINDINGS: The transcriptome analysis from peripheral blood revealed a strong host response upon severe injury and demonstrated the suitability of whole blood in the PaxGene system as a surrogate marker in clinical gene expression studies. It was evident that patients who developed sepsis in the course of the disease (3-5 days after admission) showed an imbalance in the TH1/TH2 response towards a pronounced TH2 response, soon after trauma. The imbalanced TH1/TH2 shift along with inactivation of T cells, neutrophils, monocytes and macrophages might be critical factors for the initiation of a septic program seen in these patients 12 hours after trauma. INTERPRETATION: First, in this study, we provide protocols for logistics and infrastructure that can be applied generally to successfully integrate gene expression analysis studies in a clinical routine and demonstrate that by following these protocols, dedicated and reproducible results can be obtained. Second, we showed that peripheral whole blood is a suitable surrogate marker for the host response as it contains lots of “information” and is easily accessible. Third, we identified mechanisms involved in the perturbations of the immune system that lead to sepsis. Keywords: Prospective study 159 consecutive traumatized patients were included in the study upon admission to the intensive care unit (ICU), fulfilling all of the following inclusion criteria: severe injuries to at least two body regions or three major fractures, between 18 and 65 years of age, an estimated Injury Severity Score (ISS) of ?15 points after thorough assessment of injuries, <12 hours between the occurrence of the accident and the time of admission to the ICU, and at least greater than 3 days of survival. None of the patients underwent neuro- or cardiac surgery. We excluded patients with severe intracranial head injuries, coagulation abnormalities known at the day of admission to the ICU, acute renal failure, liver failure, malignant disease, or hemofiltration in the patient`s history. The Patients were divided into two groups depending on their posttraumatic course: Patients not complicatd by sepsis (Group: N) and Patients complicated by sepsis (Group: S). Using the CodeLink UniSet Human 10 K Bioarrays (GE Healthcare, Freiburg, Germany), we searched for early differences in the transcriptome of these two groups. Only whole blood samples drawn upon admission to the ICU were used for this investigation. Microarray results were validated by quantification of mRNA by TaqMan® technology. Each patient sample was hybridized in duplicate or triplicate on microarrays (label-extract technical replicate). A total of 72 arrays (36 group N, 36 group S) were subjected to microarray quality analysis. Of these, 2 arrays (0 group N, 2 group S) were excluded from the data set due to quality reasons and a final set of 70 arrays (36 group N and 34 group S) were subjected to microarray analysis. Since the eliminated 2 arrays belonged to patients with three replicates, they were treated as two replicates in the further analysis. The arrays were designated N_xx_yy_z or S_xx_yy_z, with x for the patient-ID (1,2,3,4..) and z for the technical replicate number (1,2 or 3).
2010-12-22 | E-GEOD-12624 | biostudies-arrayexpress
Project description:Background and study aims Post-ERCP pancreatitis (PEP) is a common adverse event in high-risk patients. Current intervention known to reduce the incidence and severity of PEP include pancreatic duct stent placement, nonsteroidal anti-inflammatory drugs per rectum, and intravenous (IV) fluids. We compared aggressive normal saline (NS) vs aggressive lactated Ringer's (LR) infusion for the prevention of PEP in high-risk patients undergoing ERCP. Patients and methods Patients were randomized to receive either an aggressive infusion of NS or LR. The infusion was started at a rate of 3 mL/kg/hr and continued throughout the ERCP procedure. A 20 mL/kg bolus was given at the end of the procedure, then continued at a rate of 3 mL/kg/hr. Results A total of 136 patients were included in our analysis. The incidence of PEP was 4 % (3/72 patients) in the LR group versus 11 % (7/64 patients) in the NS group resulting in a relative risk (RR) of 0.38 (95 % confidence interval [CI] 0.10 to 1.42; P = 0.19). The relative risk reduction (RRR) was 0.62 (95 % CI -0.41 to 0.90) along with an absolute risk reduction (ARR) of 0.07 (95 % CI -0.025 to 0.17) and an number needed to treat of 15 (95 % CI -41 to 6). Conclusions To our knowledge, this is the first study comparing aggressive IV NS to aggressive IV LR in high-risk patients. The incidence of PEP was lower in the group receiving an aggressive LR infusion (4 %) compared to NS infusion (11 %). However, the difference was not statistically significant likely due to poor accrual thereby impacting the power of the study.
| S-EPMC9286764 | biostudies-literature
Project description:ObjectiveThe aim of the study was to evaluate lactated ringers (LR) versus normal saline (NS) in pediatric acute pancreatitis (AP).MethodsThis retrospective study used Pediatric Health Information System database of primary AP patients, 2013 to 2017.ResultsThe study included 1581 first time AP patients with exclusive use of a single fluid (111 LR, 1470 NS) for the first 48 hours. The LR cohort had a significantly shorter length of stay (P < 0.001) compared with NS. A multivariable logistic regression analysis suggests use of NS in the first 48 hours (after controlling for total parenteral nutrition, operation, and infection during the admission) had a significantly increased likelihood of requiring a hospitalization for 4 days or more compared with the LR group (odds ratio, 3.31; 95% confidence interval, 1.95-5.62). The overall cost was significantly less in the LR group. There was no statistical difference observed in risk factors for AP, intensive care transfer, organ dysfunction, or mortality.ConclusionsThis represents the first large data set analysis of LR versus NS in pediatric AP. The use of LR was associated with a shorter length of stay and reduced cost compared with NS. Future randomized trials will help determine the ideal fluid choice for pediatric AP.
| S-EPMC7100996 | biostudies-literature