Project description:ObjectivesIntravenous fluids are one of the most used medical therapy for patients, especially critically ill patients. We conducted a meta-analysis comparing between balanced crystalloids and normal saline in critically ill patients and its effect on various clinical outcomes.DesignMeta-analysis and systematic review of randomized clinical trials (RCTs).Methods and data sourceElectronic search was performed using PubMed, Cochrane library, and clinical trials.gov from inception through March 1, 2018, with inclusion of prospective studies that investigated one of the primary outcomes which were acute kidney injury (AKI) and in-hospital mortality while secondary outcomes were intensive care unit (ICU) mortality and new renal replacement therapy (RRT).ResultsSix RCTs were included. Total of 19,332 patients were included in the final analysis. There was no significant difference in in-hospital mortality (11.5% vs 12.2%; OR 0.92; 95% CI 0.85-1.01; P = 0.09; I2 = 0%), incidence of AKI (12% vs 12.7%, OR 0.92; 95% CI 0.84-1.01; P = 0.1; I2 = 0), overall ICU mortality (OR 0.9, 95% CI 0.81-1.01, P = 0.08, I2 = 0%), or need for new RRT (OR 0.92, 95% CI 0.67-1.28, P = 0.65, I2 = 38%) between balanced crystalloids and isotonic saline in critically ill patients.ConclusionBalanced crystalloids and isotonic saline have no difference on various clinical outcomes including in-hospital mortality, AKI, overall ICU mortality, and new RRT. Further powerful clinical trials are required to determine the relationship between crystalloid fluid type and clinical outcomes.
Project description:BackgroundThe traditional recommendations which suggest that hypotonic intravenous (i.v.) maintenance fluids are the solutions of choice in paediatric patients have not been rigorously tested in clinical trials, and may not be appropriate for all children.AimsTo systematically review the evidence from studies evaluating the safety of administering hypotonic versus isotonic i.v. maintenance fluids in hospitalised children.MethodsData sourcesMedline (1966-2006), Embase (1980-2006), the Cochrane Library, abstract proceedings, personal files, and reference lists. Studies that compared hypotonic to isotonic maintenance solutions in children were selected. Case reports and studies in neonates or patients with a pre-existing history of hyponatraemia were excluded.ResultsSix studies met the selection criteria. A meta-analysis combining these studies showed that hypotonic solutions significantly increased the risk of developing acute hyponatraemia (OR 17.22; 95% CI 8.67 to 34.2), and resulted in greater patient morbidity.ConclusionsThe current practice of prescribing i.v. maintenance fluids in children is based on limited clinical experimental evidence from poorly and differently designed studies, where bias could possibly raise doubt about the results. They do not provide evidence for optimal fluid and electrolyte homoeostasis in hospitalised children. This systematic review indicates potential harm with hypotonic solutions in children, which can be anticipated and avoided with isotonic solutions. No single fluid rate or composition is ideal for all children. However, isotonic or near-isotonic solutions may be more physiological, and therefore a safer choice in the acute phase of illness and perioperative period.
Project description:The renal distal nephron plays an important role in the maintenance of sodium balance, extra cellular volume and blood pressure. The degree of water transport, via aquaporin2 water channels (AQP2), and sodium transport, via epithelial sodium channels (ENaC) in renal collecting duct principal cells are reflected by the level of urinary excretion of AQP2 (u-AQP2) and the ?-fraction of ENaC (u-ENaC?). The effects of an acute intravenous volume load with isotonic saline, hypertonic saline and glucose on u-AQP2, u-ENaC? and underlying mechanisms have never been studied in a randomized, placebo-controlled trial in healthy humans.We studied the effects of 0.9% saline (23 ml/kg), 3% saline (7 ml/kg) and 5% glucose (23 ml/kg) on u-AQP2 and u-ENaC?, fractional sodium excretion (FENa), free water clearance (CH2O), and plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (ANG II) and aldosterone (Aldo) in a randomized, crossover study of 23 healthy subjects, who consumed a standardized diet, regarding calories, sodium and fluid for 4 days before each examination day.After isotonic saline infusion, u-AQP2 increased (27%). CH2O and u-ENaC? were unchanged, whereas FENa increased (123%). After hypertonic saline infusion, there was an increase in u-AQP2 (25%), u-ENaC? (19%) and FENa (96%), whereas CH2O decreased (-153%). After isotonic glucose infusion, there was a decrease in u-AQP2 (-16%), ENaC? (-10%) and FENa (-44%) whereas CH2O increased (164%). AVP remained unchanged after isotonic saline and glucose, but increased after hypertonic saline (139%). PRC, AngII and p-Aldo decreased after isotonic and hypertonic saline infusion, but not after glucose infusion.Volume expansion with 3% and 0.9% saline increased u-AQP2, while isotonic glucose decreased u-AQP2. Infusion of hypertonic saline increased u-ENaC?, whereas u-ENaC? was not significantly changed after isotonic saline and tended to decrease after glucose. Thus, the transport of water and sodium is changed both via the aquaporin 2 water channels and the epithelial sodium channels during all three types of volume expansion to regulate and maintain water- and sodium homeostasis in the body.Clinical Trial no: NCT01414088.
Project description:PurposeWe conducted a comprehensive meta-analysis to compare the effects of balanced crystalloids (BC) and isotonic saline (IS) in pediatric sepsis.MethodsA systematic search was performed for studies comparing BC and IS in pediatric sepsis. Outcomes included mortality, acute kidney injury (AKI), need for renal replacement therapy (RRT), hospital length of stay (LOS), and pediatric intensive care unit (PICU) LOS. A random-effect models was used to calculated pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CIs).ResultsThe analysis included six studies with 8753 children. BC demonstrated significant reductions in overall mortality (OR 0.84, 95% CI 0.71 to 0.98, P = 0.03, I2 = 0%) and AKI (OR 0.74, 95% CI 0.57 to 0.96, P = 0.03, I2 = 37%) compared to IS. RRT need was similar between the BC and IS groups (OR 0.79, 95% CI 0.60 to 1.02, P = 0.07, I2 = 0%). Hospital and PICU LOS did not differ significantly. However, subgroup analysis of randomized controlled trials revealed significantly shorter hospital LOS in the BC group (mean difference -0.66 days, 95% CI -1.10 to -0.23, P = 0.003, I2 = 0%).ConclusionOur meta-analysis demonstrates that using BC in pediatric sepsis is associated with reduced mortality, AKI, and hyperchloremia rates compared to IS, while maintaining similar hospital and PICU LOS. Large-scale randomized controlled trials are needed to validate these findings.
Project description:The aim of this experiment was to test how female Japanese quail respond to being housed with sick (LPS treated) relative to control males. LPS injected females were also tested.
Project description:A quality colonoscopy examination remains as the gold standard for colorectal cancer screening, but effective large bowel cleansing prior to colonoscopy is still not achieved in all cases that undergo the procedure. Currently, the most widely used cleansing methods employ balanced electrolyte-polyethylene glycol (PEG) solutions. However, a very large volume of PEG solution is required for it to be effective, and many patients refuse to drink a sufficient amount due to non-palatability. In this study, the investigators compare a novel colon preparation method--bolus lukewarm saline with yoga exercise--with a PEG based solution (HalfLytely) for large bowel cleansing.
Project description:Induction methods for therapeutic cooling are under investigated. We compared the effectiveness and safety of cold infusions (CI) and nasopharyngeal cooling (NPC) for cooling induction in stroke patients.A prospective, open-label, randomised (1:1), single-centre pilot trial with partially blinded safety endpoint assessment was conducted at the neurointensive care unit of Heidelberg University. Intubated stroke patients with an indication for therapeutic cooling and an intracranial pressure (ICP)/temperature brain probe were randomly assigned to CI (4°C, 2L at 4L/h) or NPC (60L/min for 1 h). Previous data suggested a maximum decrease of tympanic temperature for CI (2.1L within 35 min) after 52 min. Therefore the study period was 1 hour (15 min subperiods I-IV). The brain temperature course was the primary endpoint. Secondary measures included continuous monitoring of neurovital parameters and extracerebral temperatures. Statistical analysis based on repeated-measures analysis of variance.Of 221 patients screened, 20 were randomized within 5 months. Infusion time of 2L CI was 33?±?4 min in 10 patients and 10 patients received NPC for 60 min. During active treatment (first 30 min), brain temperature decreased faster with CI than during NPC (I: -0.31 ± 0.2 versus -0.12 ± 0.1°C, P = 0.008; II: -1.0 ± 0.3 versus -0.49 ± 0.3°C, P = 0.001). In the CI-group, after the infusion was finished, the intervention no longer decreased brain temperature, which increased after 3.5?±?3.3 min. Oesophageal temperature correlated best with brain temperature during CI and NPC. Tympanic temperature reacted similarly to relative changes of brain temperature during CI, but absolute values slightly differed. CI provoked three severe adverse events during subperiods II-IV (two systolic arterial pressure (SAP), one shivering) compared with four in the NPC-group, all during subperiod I (three SAP, one ICP). Classified as possibly intervention-related, two cases of ventilator failure occurred during NPC.In intubated stroke patients, brain cooling is faster during CI than during NPC. Importantly, contrary to previous expectations, brain cooling stopped soon after CI cessation. Oesophageal but neither bladder nor rectal temperature is suited as surrogate for brain temperature during CI and NPC. Several severe adverse events in CI and in NPC demand further studying of safety.ClinicalTrials.gov NCT01573117. Registered 31 March 2012.
Project description:In observational studies, potential confounders may distort the causal relationship between an exposure and an outcome. However, under some conditions, a causal dose-response curve can be recovered using the G-computation formula. Most classical methods for estimating such curves when the exposure is continuous rely on restrictive parametric assumptions, which carry significant risk of model misspecification. Nonparametric estimation in this context is challenging because in a nonparametric model these curves cannot be estimated at regular rates. Many available nonparametric estimators are sensitive to the selection of certain tuning parameters, and performing valid inference with such estimators can be difficult. In this work, we propose a nonparametric estimator of a causal dose-response curve known to be monotone. We show that our proposed estimation procedure generalizes the classical least-squares isotonic regression estimator of a monotone regression function. Specifically, it does not involve tuning parameters, and is invariant to strictly monotone transformations of the exposure variable. We describe theoretical properties of our proposed estimator, including its irregular limit distribution and the potential for doubly-robust inference. Furthermore, we illustrate its performance via numerical studies, and use it to assess the relationship between BMI and immune response in HIV vaccine trials.
Project description:BackgroundChildren with chronic rheumatic disease often require intravenous (IV) therapy. Our center has instituted standardized protocols for use of IV medications in rheumatology patients. Herein, we introduce the therapeutic protocols and report on their short-term safety.MethodsThis was an institutional review board (IRB) approved retrospective chart review of all patients who had received IV infusions between the years 2012 and 2015 at a single center, prescribed by a pediatric rheumatologist. Infusion medications included abatacept, belimumab, cyclophosphamide, immune globulin, infliximab, methylprednisolone, N-acetylcysteine, pamidronate disodium, rituximab, and tocilizumab. For calendar year 2015, all adverse infusions reactions were recorded along with treatment strategies used to manage them, and outcomes. Rates of adverse events were calculated per infusion medication.ResultsDuring calendar years 2012-2015, 7585 IV infusions were administered to 398 unique patients. In the year 2015, 2187 infusions were administered to 224 patients, with 34 patients experiencing 41 infusion reactions (1.9% of all infusions). Rituximab had the highest rate of adverse drug reactions with 10 patients experiencing reactions during 106 infusions (9.4%). None of the reactions were life-threatening, and only 6 resulted in discontinuation of therapy.ConclusionsIn a recent 4-year span, the UAB Pediatric Rheumatology Infusion Center has given thousands of IV infusions with minimal adverse reactions over a one-year reporting period. The combination of standard infusion protocols, experience of and communication between physicians and nurses who staff the center, and safety of the medications themselves, allows for safe IV administration of a variety of therapies for pediatric rheumatology patients.Trial registrationNot applicable; this was a retrospective study.
Project description:Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original.Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion.The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p < .001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days.Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.