Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation.
ABSTRACT: BACKGROUND: The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting. METHODS: Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111?mmol/l up to and including 154?mmol/l) or lower-chloride (concentration 111?mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling. RESULTS: The search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1.64, 95 per cent c.i. 1.27 to 2.13; P?
Project description:We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes.We identified patients who received large-volume fluid resuscitation, defined as greater than 60?mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads.University Medical Center.Patients admitted to ICUs from 2000 to 2008.None.Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or acute kidney injury after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age, and severity (p = 0.0015) over 1 year.Chloride load is associated with significant adverse effects on survival out to 1 year even after controlling for total fluid load, age, and baseline severity of illness. However, the relationship between chloride load and development of hyperchloremic acidosis or acute kidney injury is less clear, and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.
Project description:The aim of this study was to analyse the relationship between intra-abdominal hypertension (IAH) and severity of acute pancreatitis (AP) measured by the revised Atlanta classification (RAC) and determinant-based classification (DBC). Secondary objectives were to assess IAH as a predictor of morbidity and mortality in the ICU.This prospective international observational study included patients admitted to the ICU with AP and at least one organ failure. Information was collected on demographics, severity scores at admission using RAC and DBC, organ failure, mechanical ventilation, continuous renal replacement therapy (CRRT), surgery and mortality. Maximum intra-abdominal pressure (IAP) during ICU stay was used for analysis.Some 374 patients were included. The hospital mortality rate was 28·9 per cent. IAP was measured in 301 patients (80·5 per cent), of whom 274 (91·0 per cent) had IAH and 103 (34·2 per cent) acute compartment syndrome. A higher IAH grade was more likely in patients with severe AP (42 per cent for grade I versus 84 per cent for grade IV) and acute critical pancreatitis (9 versus 25 per cent; P = 0·001). Compared with grade I IAH, patients with grade IV had more infected necrosis (16 versus 28 per cent; P = 0·005), need for surgery (27 versus 50 per cent; P = 0·006), mechanical ventilation (53 versus 84 per cent; P = 0·007) and requirement for CRRT (22 versus 66 per cent; P < 0·001). IAH predicted shock (area under receiver operating characteristic (ROC) curve (AUC) 0·79, 95 per cent c.i. 0·73 to 0·84), respiratory failure (AUC 0·82, 0·77 to 0·87), renal failure (AUC 0·93, 0·89 to 0·96) and mortality (AUC 0·89, 0·86 to 0·93).IAH was associated with severity of AP classified according to both RAC and DBC systems. IAP grade can predict outcome of AP during ICU stay.
Project description:There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT.This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the 'early' strategy, RRT is initiated immediately. In the 'delayed' strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO2?<?35 mmHg) or in a context of mixed acidosis with a PaCO2???50 mmHg without possibility of increasing alveolar ventilation, acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO2?>?95% or FiO2?>?50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all.The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT.ClinicalTrials.gov NCT01932190.
Project description:BACKGROUND:Recent data suggest that hyperchloremia induced by fluid resuscitation is associated with acute kidney injury (AKI) and mortality, particularly in sepsis. Experimental studies showed that hyperchloremia could affect organ functions. In patients with septic shock, we examined the relationship between serum chloride concentration and both renal function and survival. METHODS:Post hoc analysis of the "HYPER2S" trial database (NCT01722422) including 434 patients with septic shock randomly assigned for resuscitation with 0.9% or 3% saline. Metabolic parameters were recorded up to 72 h. Metabolic effects of hyperchloremia (>?110 mmol/L) were studied stratified for hyperlactatemia (>?2 mmol/L). Cox models were constructed to assess the association between chloride parameters, day-28 mortality and AKI. RESULTS:413 patients were analysed. The presence of hyperlactatemia was significantly more frequent than hyperchloremia (62% versus 71% of patients, respectively, p?=?0.006). Metabolic acidosis was significantly more frequent in patients with hyperchloremia, no matter the presence of hyperlactatemia, p?<?0.001. Adjusted risk of AKI and mortality were not significantly associated with serum chloride, hyperchloremia, maximal chloremia and delta chloremia (maximal-H0 [Cl]). CONCLUSIONS:Despite more frequent metabolic acidosis, hyperchloremia was not associated with an increased risk for AKI or mortality. Trial registration ClinicalTrials.gov, identifier: NCT01722422, registered 2 November 2012.
Project description:Background.:Daily and globally, millions of adult hospitalized patients are exposed to maintenance i.v. fluid solutions supported by limited scientific evidence. In particular, it remains unclear whether fluid tonicity contributes to the recently established detrimental effects of fluid, sodium, and chloride overload. Methods.:This crossover study consisted of two 48?h study periods, during which 12 fasting healthy adults were treated with a frequently prescribed solution (NaCl 0.9% in glucose 5% supplemented by 40?mmol litre -1 of potassium chloride) and a premixed hypotonic fluid (NaCl 0.32% in glucose 5% containing 26?mmol litre -1 of potassium) at a daily rate of 25?ml kg -1 of body weight. The primary end point was cumulative urine volume; fluid balance was thus calculated. We also explored the physiological mechanisms behind our findings and assessed electrolyte concentrations. Results.:After 48?h, 595?ml (95% CI: 454-735) less urine was voided with isotonic fluids than hypotonic fluids ( P <0.001), or 803?ml (95% CI: 692-915) after excluding an outlier with 'exaggerated natriuresis of hypertension'. The isotonic treatment was characterized by a significant decrease in aldosterone ( P <0.001). Sodium concentrations were higher in the isotonic arm ( P <0.001), but all measurements remained within the normal range. Potassium concentrations did not differ between the two solutions ( P =0.45). Chloride concentrations were higher with the isotonic treatment ( P <0.001), even causing hyperchloraemia. Conclusions.:Even at maintenance rate, isotonic solutions caused lower urine output, characterized by decreased aldosterone concentrations indicating (unintentional) volume expansion, than hypotonic solutions and were associated with hyperchloraemia. Despite their lower sodium and potassium content, hypotonic fluids were not associated with hyponatraemia or hypokalaemia. Clinical trial registration.:ClinicalTrials.gov (NCT02822898) and EudraCT (2016-001846-24).
Project description:Background:Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany. Methods:Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identified from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume. Results:Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5·8 per cent, ranging from 6·9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4·8 per cent (1239 of 25 825) in very high-volume centres (P < 0·001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0·75 (95 per cent c.i. 0·66 to 0·84) in very high-volume hospitals performing a mean of 85·0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12·7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion. Conclusion:In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals.
Project description:Sleep quality and quantity are severely reduced in critically ill patients receiving mechanical ventilation with a potential for adverse consequences. Our objective was to synthesize the randomized controlled trials (RCTs) that measured the efficacy of sleep-promoting interventions on sleep quality and quantity in critically ill patients.We included RCTs that objectively measured sleep with electroencephalography or its derivatives and excluded observational studies and those that measured sleep by subjective reports. The research was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Of 6022 studies identified, 13 met eligibility criteria involving 296 critically ill patients. Eight trials looked at different modes of mechanical ventilation as sleep interventions, and the remaining 5 involved pharmacologic, nonpharmacologic, or environmental interventions. Meta-analysis of the studies revealed that sleep-promoting interventions improved sleep quantity (pooled standardized mean difference [SMD], 0.37; 95% confidence interval [CI], 0.05-0.69; P = .02) and sleep quality through reduction in sleep fragmentation (SMD, -0.31; 95% CI, -0.60 to -0.01; P = .04). Subgroup analysis revealed that timed modes of ventilation improved sleep quantity when compared with spontaneous modes of ventilation (SMD, 0.45; 95% CI, 0.10-0.81; P = .01). Nonmechanical ventilation interventions tended to improve sleep quantity (SMD, 0.65; 95% CI, -0.03 to 1.33; P = .06) and to reduce sleep fragmentation (SMD, -0.29; 95% CI, -0.61 to 0.03; P = .07).The synthesized evidence suggests that both mechanical ventilation- and nonmechanical ventilation-based therapies improve sleep quantity and quality in critically ill patients, but the clinical significance is unclear. In the future, adequately powered multicenter RCTs involving pharmacologic interventions to promote sleep in critically ill patients are warranted.
Project description:INTRODUCTION:Observational evidence suggests physiological benefits and lower mortality with lower chloride solutions; however, 0.9% saline remains the most widely used fluid worldwide. Given uncertainty regarding the association of lower chloride on mortality, it is unlikely that practice will change without direct randomised clinical trial (RCT) evidence. This pilot RCT will investigate the feasibility of a large-scale trial directly comparing low chloride with high chloride fluids in patients with septic shock. METHODS AND ANALYSIS:This is a randomised, concealed, blinded parallel-group multicentre pilot trial. We will include adult critically ill patients with septic shock, defined as ongoing hypotension despite 1 L of fluid, or a serum lactate >4 mmol/L, who are within 6 hours of hospital presentation or rapid response team activation. We will exclude patients if they have an aetiology of shock other than sepsis, if they have acute burn injury, elevated intracranial pressure, intent to withdraw life support or previous enrolment in this or a competing trial. Following informed consent, patients will be randomised to a low chloride fluid strategy or a high chloride fluid strategy for the duration of their ICU stay or until 30 days postrandomisation. Clinicians, patients, families and research staff will be blinded. The primary outcome for this trial will be feasibility, assessed by consent rate, recruitment success and protocol adherence. Patient-important clinical outcomes include mortality, receipt of renal replacement therapy, intensive care unit and hospital lengths of stay and surrogate outcomes of incidence of acidosis, hyperkalaemia and acute kidney injury. ETHICS AND DISSEMINATION:This pilot trial will test the feasibility of conducting the main trial, which will examine the effect of high versus low chloride fluids in patients with septic shock on patient-important outcomes. TRIAL REGISTRATION NUMBER:NCT02748382, registered 8 April 2016. PROTOCOL DATE:1 July 2016.
Project description:OBJECTIVES:Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. DESIGN:Retrospective, multicenter, observational cohort study. SETTING:Four New York City hospitals that are part of the same health network. PATIENTS:Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ? 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). CONCLUSIONS:Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.
Project description:The Space Glucose Control (SGC) system is a computer-assisted device combining infusion pumps with the enhanced Model Predictive Control algorithm to achieve the target blood glucose (BG) level safely. The objective of this study was to evaluate the efficacy and safety of glycemic control by SGC with customized BG target range of 5.8-8.9 mmol/L in the critically ill patients.It is a randomized controlled trial of seventy critically ill patients with mechanical ventilation and hyperglycemia (BG ? 9.0 mmol/L). Thirty-six patients in the SGC group and 34 in the routine glucose management group were observed for three consecutive days. Target BG for both groups was 5.8-8.9 mmol/L. The primary outcome was the percentage time in the target range.The percentage time within BG target range in the SGC group (69 ± 15%) was significantly higher than in the routine management group (52 ± 24%; P< 0.01). No measurement was ?2.2 mmol/L, and there was only one episode of hypoglycemia (2.3-3.3 mmol/L) in each group. The average BG was significantly lower in the SGC group (7.8 ± 0.7 mmol/L) than in the routine management group (9.1 ± 1.6 mmol/L, P< 0.001). Target BG level was reached earlier in the SGC group than routine management group (2.5 ± 2.9 vs. 12.1 ± 15.3 h, P= 0.001). However, the SGC group performed worse for daily insulin requirement (59.8 ± 39.3 vs. 28.4 ± 36.7 U, P= 0.001) and sampling interval (2.0 ± 0.5 vs. 3.7 ± 0.5 h, P< 0.001) than the routine management group did. Multiple linear regression showed that the intervention group remained a significant individual predictor (P < 0.001) of the percentage time in target range.The SGC system, with a BG target of 5.8-8.9 mmol/L, resulted in effective and reliable glycemic control with few hypoglycemic episodes in critically ill patients with mechanical ventilation and hyperglycemia. However, the workload was increased.http://www.clinicaltrials.gov, NCT 02491346; https://www.clinicaltrials.gov/ct2/show/NCT02491346?term=NCT02491346&cond=Hyperglycemia&cntry1=ES%3ACN&rank=1.