Dose Of Renal Replacement Therapy Research Articles

Acute Kidney Injury in Sepsis.

Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological factors contribute to its presentation and perpetuation, including macrocirculatory and microcirculatory changes, mitochondrial dysfunction, and metabolic reprogramming. Recovery from acute kidney injury (AKI) relies on the evolution towards adaptive mechanisms such as endothelial repair and tubular cell regeneration, while maladaptive repair increases the risk of progression to chronic kidney disease. Fundamental management strategies include early sepsis recognition and prompt treatment, through the administration of adequate antimicrobial agents, fluid resuscitation, and vasoactive agents as needed. In septic patients, organ-specific support is often required, particularly renal replacement therapy (RRT) in the setting of severe AKI, although ongoing debates persist regarding the ideal timing of initiation and dosing of RRT. A comprehensive approach integrating early recognition, targeted interventions, and close monitoring is essential to mitigate the burden of SA-AKI and improve patient outcomes in critical care settings.

A New Dosing Frontier: Retrospective Assessment of Effluent Flow Rates and Residual Renal Function Among Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

In 2020, cefiderocol became the first Food and Drug Administration-approved medication with continuous renal replacement therapy (CRRT) dosing recommendations based on effluent flow rates (QE). We aimed to evaluate the magnitude and frequency of factors that may influence these recommendations, that is, QE intrapatient variability and residual renal function. Retrospective observational cohort study. ICUs within Hartford Hospital (890-bed, acute-care hospital) in Connecticut from 2017 to 2023. Adult ICU patients receiving CRRT for greater than 72 hours. CRRT settings including QE and urine output (UOP) were extracted from the time of CRRT initiation (0 hr) and trends were assessed. To assess the impact on antibiotic dosing, cefiderocol doses were assigned to 0 hour, 24 hours, 48 hours, and 72 hours QE values per product label, and the proportion of antibiotic dose changes required as a result of changes in inpatient's QE was evaluated. Among the 380 ICU patients receiving CRRT for greater than 72 hours, the median (interquartile range) 0 hour QE was 2.96 (2.35-3.29) L/hr. Approximately 9 QE values were documented per patient per 24-hour window. QE changes of greater than 0.75 L/hr were observed in 21.6% of patients over the first 24 hours and in 7.9% (24-48 hr) and 5.8% (48-72 hr) of patients. Approximately 40% of patients had UOP greater than 500 mL at 24 hours post-CRRT initiation. Due to QE changes within 24 hours of CRRT initiation, a potential cefiderocol dose adjustment would have been warranted in 38% of patients (increase of 21.3%; decrease of 16.6%). QE changes were less common after 24 hours, warranting cefiderocol dose adjustments in less than 15% of patients. Results highlight the temporal and variable dynamics of QE and prevalence of residual renal function. Data also demonstrate a risk of antibiotic under-dosing in the first 24 hours of CRRT initiation due to increases in QE. For antibiotics with QE-based dosing recommendations, empiric dose escalation may be warranted in the first 24 hours of CRRT initiation.

Influence of utilizing hemodialysis membranes outside-in on solute clearance and filtration efficiency – One step towards a novel combined lung and kidney support device

Many membrane oxygenator patients suffer from renal disfunction. For these patients, a novel device integrating artificial lung and kidney support is being developed. Although outside-in blood flow is standard for membrane oxygenators, this is not typical for hemodialysis systems. The effect of outside-in blood flow on the efficiency of hemodialysis fibers for continuous hemodialysis and hemofiltration is yet unclear.This study evaluates the efficiency of commercial hemodialyzer membranes utilized outside-in compared to traditional inside-out mode regarding clearance of urea and creatinine, and ultrafiltration coefficient during in-vitro tests with porcine blood. Our results showed that dialyzers (1.2 m2, asymmetric hollow fibers) utilized outside-in had similar clearances of urea and creatinine compared to dialyzers used in the traditional mode (p > 0.7). However, outside-in dialyzers had an ultrafiltration coefficient four times lower than dialyzers applied in a conventional way, but adequate fluid removal could be achieved by controlling pressures in the system. This in-vitro study indicates that outside-in fibers could be sufficiently effective to maintain typical continuous renal replacement therapy doses. We regard this as one step towards a novel device with a mixed membrane fiber bundle utilizing blood flow outside both hemodialysis fibers and gas exchange fibers to provide simultaneous lung and kidney support.

Dynamic dosing for continuous renal replacement therapy: Service evaluation of the safety and effectiveness of titrating dose to biochemistry

Introduction: Continuous renal replacement therapy (CRRT) dose is usually fixed and primarily weight-based. Whilst this is safe, theoretically, underdosing or overdosing may occur in those requiring acute versus maintenance CRRT respectively. We have developed a dynamic dosing protocol for CRRT which individualises and updates dosing according to biochemistry. Here we describe the protocol and compare it to a fixed dose protocol to evaluate its safety and effectiveness. Methods: We conducted a service evaluation of this novel protocol using data from consecutive non-COVID-19 admissions receiving CRRT within Barts Health NHS trust, United Kingdom (UK). Fifty admissions using the dynamic protocol were compared to historically collected data from 108 admissions who used the fixed protocol. Acute and maintenance CRRT subgroups were analysed. Results: For the dynamic protocol 49 patients were treated with 135 CRRT circuits. One patient had two admissions. Protocol compliance (compared in one ICU) was 76% (dynamic) vs 61% (fixed) ( p < 0.05). For the dynamic versus fixed protocol, median CRRT lifespan censored for reasons other than clotting was: 56 h vs 58 h RCA (ns), 27 h versus 20 h heparin (ns) and 79 h versus 22 h no anticoagulation ( p < 0.05). The dynamic vs fixed protocol average CRRT dose was: 30 ml/kg/h (14–57) vs 26 ml/kg/h (20–62) ( p < 0.05). The dynamic protocol generated a similar rate of increase of bicarbonate in an acute phase (RCA: 0.2 mmol/l/h vs 0.21 mmol/l/h, ns) and maintained a more stable level in a maintenance phase (RCA: −0.01 mmol/l/h vs 0.07 mmol/l/h, p < 0.05). Discussion: Dynamic dosing for CRRT in this institution was safe and may lead to more tailored maintenance of biochemical homoeostasis.

Yoğun Bakım Hastalarında Antimikrobiyal İlaç Dozajlarının Uygunluğunun Değerlendirilmesi

The purpose of this study was to investigate the factors that required dose adjustments of antimicrobial drugs in intensive care unit (ICU) patients and to identify the drugs that required the most dose adjustments.
 The 26-bed reanimation ICU of a university-affiliated hospital hosted this study from September to December 2022. Two clinical pharmacists on duty examined patients' antimicrobial drug dosages daily. The acceptance status of the recommendations and the patients' demographic information were recorded.
 The study involved 133 ICU patients, and antimicrobial drug recommendations were made for 48 patients, 31 (64.6%) of whom were male. The median (IQR) age of the 48 patients was 67 (54–77). The number of recommendations was 94, and all of them were accepted by the physician. The recommendation rates according to the causes were: inappropriate dosages based on renal functions (71.3%), presence of continuous renal replacement therapy (11.7%), indication (10.6%), body weight (4.3%), and loading dose (2.1%).
 The top 3 drugs for which recommendations were made the most were colistin (21.3%), meropenem (18.1%), and piperacillin-tazobactam (12.8%). The most troublesome drug was colistin, which is frequently used to treat Acinetobacter pneumonia. Clinical pharmacist and physician collaboration may help rationalize ICU antimicrobial drug use.

Results of the 2018 Japan Society for Blood Purification in Critical Care survey: current status and outcomes

BackgroundThe Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data from the nationwide JSBPCC registry in 2018.MethodsWe analyzed data of 2371 patients who underwent BPT in the intensive care units of 43 facilities to investigate patient characteristics, disease severity, modes of BPTs, including the dose of continuous renal replacement therapy (CRRT) and hemofilters, treated diseases, and the survival rate for each disease. Disease severity was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores.ResultsBPT was performed 2867 times in the 2371 patients. Mean APACHE II and SOFA scores were 23.5 ± 9.4 and 10.0 ± 4.4, respectively. The most frequently used mode of BPT was CRRT (67.4%), followed by intermittent renal replacement therapy (19.1%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (7.3%). The most commonly used anticoagulant was nafamostat mesilate (78.6%). Among all patients, the 28-day survival rate was 61.7%. CRRT was the most commonly used mode for many diseases, including acute kidney injury (AKI), multiple organ failure (MOF), and sepsis. The survival rate decreased according to the severity of AKI (P = 0.001). The survival rate was significantly lower in patients with multiple organ failure (MOF) (34.6%) compared with acute lung injury (ALI) (48.0%) and sepsis (58.0%). Multivariate logistic regression analysis revealed that sepsis, ALI, acute liver failure, cardiovascular hypotension, central nervous system disorders, and higher APACHE II scores were significant predictors of higher 28-day mortality.ConclusionThis large-scale cohort study revealed the current status of BPT in Japan. It was found that CRRT was the most frequently used mode for critically ill patients in Japan and that 28-day survival was lower in those with MOF or sepsis. Further investigations are required to clarify the efficacy of BPT for critically ill patients.Trial Registration: UMIN000027678.

ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy.

Mishra RC, Sodhi K, Prakash KC, Tyagi N, Chanchalani G, Annigeri RA, et al. ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy. Indian J Crit Care Med 2022;26(S2):S13-S42.

Sepsis-associated acute kidney injury

Acute kidney injury (AKI) is a condition that develops as a result of a rapid decrease in the glomerular filtration rate, which leads to the accumulation of nitrogenous, including urea and creatinine, and non-nitrogenous metabolic products with electrolytic disorders, impairment of the acid-base balance, and the volume of fluid excreted by the kidneys. Objective: to provide a review of the literature concerning sepsis-associated acute kidney injury. We presented the problems of diagnosis, risk factors, the pathogenesis of sepsis-associated acute kidney injury, as well as to outline terminologically the clinical form of sepsis-associated acute kidney injury: the paradigm shifts from ischemia and vasoconstriction to hyperemia and vasodilation, from acute tubular necrosis to acute tubular apoptosis. Sepsis contributes significantly to the development of AKI: in sepsis, it occurs in 19 % of patients; nevertheless, it is much more frequent in septic shock (45 % of cases), the mortality of individuals with AKI is especially high in non-septic and septic conditions (45 and 73 %, respectively). To effectively diagnose the functional state of the kidneys and conduct nephroprotective therapy, stratification scales for assessing the severity of acute kidney damage are applied, which are based on the determination of plasma creatinine level and urine output: RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure), AKIN (Acute Kidney Injury Network), KDIGO (Kidney Disease Improving Global Outcomes); the experts considered KDIGO scale more modern and perfect. It has been found that plasma creatinine is not an early biomarker of AKI that indicates the advisability of using other integral indicators. AKI biomarkers are substances that either participate in the pathological process or witness it allowing diagnose AKI even before an increase in plasma creatinine level. The characteristics of the structure, role of functions of such biomarkers as neutrophil gelatinase-associated lipocalin, cystatin C, interleukin-18, kidney injury molecule-1 and others are given. Intensive care for sepsis-associated acute kidney injury includes the standard therapy corresponding to 2016 Surviving Sepsis Campaign and KDIGO guidelines. Also, the paper focuses on renal replacement therapy (RRT): renal and extrarenal indications for the initiation, factors affecting the initiation of RRT, the timing of initiation, ways of optimization, the timing of RRT discontinuation, recommendations for the dose of RRT, the dose of renal replacement therapy in sepsis-associated AKI, choice of method, advantages and disadvantages of continuous RRT and intermittent hemodialysis, medication support for continuous therapy, the role of hemodialysis machine in the intensive care unit.

Regional citrate anti-coagulation dose titration: impact on dose of continuous renal replacement therapy

Regional citrate anti-coagulation (RCA) is the recommended anti-coagulation for continuous renal replacement therapy (CRRT). Citrated replacement fluids provide convenience but may compromise effluent delivery when adjusted to maintain circuit ionised calcium levels (circuit-iCa). This study aims to evaluate the effect of RCA titration on the delivered CRRT effluent dose. This prospective observational study evaluated patients on RCA-CRRT in continuous veno-venous hemodiafiltration mode. Citrated replacement fluid was titrated to target circuit-iCa 0.26-0.40mmol/L. Patients were then stratified into 'reduced-dose' who required citrate down-titration and 'stable-dose' who did not. Data from 200 RCA-CRRT sessions were collected. The reduced-dose RCA group (n = 114) had higher median initial citrate dose (3.00 vs 2.50; P < 0.001) but lower time-averaged dose (2.49 vs 2.60; P < 0.001). In addition, median prescribed effluent dose was 33.3mL/kg/h (28.6-39.2) but median delivered effluent dose was significantly lower at 29.9mL/kg/h (25.4-36.9; P < 0.001). Mortality was higher in the reduced-dose RCA group (39.5% vs 25.6%; P = 0.022) and in patients with delivered-to-prescribed effluent dose ratio of < 0.9 vs ≥ 0.9 (51.3% vs 29.2%; P = 0.014). RCA titration can significantly impact delivered CRRT effluent dose. Measures should be taken to address the CRRT dose deficit and prevent poor outcomes due to inadequate dialysis.

Renal replacement therapy in intensive care units in KwaZulu-Natal Province, South Africa.

Background Renal replacement therapy (RRT) is a scarce resource in southern Africa. Critically ill patients are at risk of developing acute kidney injury (AKI), which may require RRT. There are few data on the utilisation of RRT in southern African intensive care units (ICUs). Objectives To determine the indications for initiating RRT in critically ill patients in ICUs in KwaZulu-Natal, South Africa (SA) and to describe the methods and dosing of RRT. Methods A prospective observational study was performed to investigate the indications for initiating, methods and dosing of RRT among patients admitted to four ICUs in KwaZulu-Natal Province, SA. All adult patients were eligible for inclusion. Results A total of 108 patients who received RRT were included in the study. The most common reasons for initiation of RRT were a high/rising creatinine, high/rising urea, acidosis and fluid balance. The majority of the patients (79.6%; n=86) had three or more indications for RRT. A total of 353 intermittent haemodialysis/slow low-efficiency dialysis (IHD/SLED) sessions and 84 continuous renal replacement therapy (CRRT) sessions were recorded. The median (interquartile range (IQR)) CRRT dose was 25.8 (19.1 - 28.8) mL/kg/h. The median (IQR) urea reduction ratio for IHD/SLED was 32.4% (15.0 - 49.8). Conclusion Patients in this study had multiple indications for initiating RRT. The dosing of RRT was not optimal, with a wide range shown in CRRT, and the majority of patients did not achieve a urea reduction ratio (URR) >65%. Contributions of the study Renal replacement therapy is a scarce resource in Africa. Little is known about the current types and dosing of RRT in critical care units in South Africa. We showed that critically ill patients had multiple indications for RRT and the dosing was not optimal.

Poor Correlation between Meropenem and Piperacillin Plasma Concentrations and Delivered Dose of Continuous Renal Replacement Therapy.

There is insufficient data on the relationship between antibiotic dosing and plasma concentrations in patients treated with continuous renal replacement therapy (CRRT). In this prospective observational study, we explored the variability in plasma concentrations of meropenem and piperacillin in critically ill patients treated with CRRT and the correlation between concentrations and CRRT intensity. Antibiotic concentrations were measured at the middle and end of the dosing interval and repeated after 2 to 3 days when feasible. Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/liter for piperacillin and meropenem, respectively. CRRT intensity was estimated by delivered, time-averaged, total effluent flow (Qeff), corrected for predilution. Concentrations were also compared between patients with different residual diuresis. We included 140 meropenem concentrations from 98 patients and 47 piperacillin concentrations from 37 patients. Concentrations at the middle of the dosing interval were above target at all occasions for both antibiotics. For meropenem, 6.5% of trough concentrations were below target, and for piperacillin, 22%. Correlations between Qeff and antibiotic concentrations or the concentration half-life (t1/2) were either statistically not significant or weak. Meropenem concentrations and t1/2 values differed between patients with different residual diuresis. Thus, when treating intensive care patients with CRRT and recommended doses of meropenem or piperacillin, both low, suboptimal plasma concentrations and unnecessarily high, potentially toxic, plasma concentrations are common. Plasma concentrations cannot be predicted from CRRT intensity. Residual diuresis is associated with lower meropenem concentrations, but the correlation is weak. Concentration measurement is probably the most useful approach to avoid suboptimal treatment.

Indications for Dialysis in Acute Kidney Injury

Renal replacement therapy (RRT) can be used to support patient’s kidney function in cases of acute kidney injury (AKI). However, timing, modality, and dosing of RRT continue to remain in question. Recent studies have begun to provide data to help guide clinicians on when to initiate RRT, what form of RRT to use ranging from continuous venovenous hemofiltration (VVH) to intermittent hemodialysis, and the impact of high versus low-intensity dosing. Additionally, the risks associated with temporary vascular access with regard to thrombosis and infection, the impact of high efficiency and flux versus low efficiency and flux membranes, and options for anticoagulation in RRT for AKI are also discussed. This review contains 75 references. Key words: acute kidney injury, chronic kidney disease, continuous venovenous hemofiltration, continuous venovenous hemodialysis, renal replacement therapy, venovenous hemofiltration,

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Intensity of renal replacement therapy and outcomes in critically ill patients with acute kidney injury: Critical appraisal of the dosing recommendations.

The current care of critically ill patients with severe acute kidney injury requiring dialysis (AKI-D) is limited to supportive management in which renal replacement therapy (RRT) plays a central role. Renal replacement techniques are invasive bioincompatible procedures and are therefore associated with complications that may prove harmful to fragile patients. Inexperience with the standards and lacking or misinterpreted recommendations for the delivery of the RRT dose increases the risk of serious complications. Neither the optimal doses of intermittent or continuous RRTs nor the minimal or maximal effective doses are known. The Kidney Disease Improving Global outcomes (KDIGO) AKI guidelines for RRT dosing recommendations are inflexible, based on limited research, and may be at least partially outdated. High-intensity therapy may be associated with clinically relevant alterations in systemic and renal hemodynamics, profound electrolyte imbalances, the loss of nutrients or thermal energy, and underdosing of antimicrobial agents. However, higher doses of continuous renal replacement therapy (CRRT) may confer a survival benefit for certain subgroups of intensive care patients with severe AKI. Lower CRRT doses than the recommended adequate dosage may not lead to negative health outcomes, at least in Asian patients. Future research should evaluate the demand-capacity concept, recognizing that the delivery of the RRT dose is dynamic and should be modified in response to patient-related factors. There is a need for large-scale studies evaluating whether precision RRT dose modifications may improve patient-centered outcomes in subgroups of critically ill patients.

The optimal dose of renal replacement therapy in acute kidney injury

The optimal dose of renal replacement therapy in acute kidney injury

Continuous Renal Replacement Therapy Dosing in Critically Ill Patients: A Quality Improvement Initiative

Clinical practice guidelines recommend delivering a continuous renal replacement therapy (CRRT) dose of 20 to 25mL/kg/h. However, practice patterns nationwide are highly variable; this inconsistent prescribing may lead to errors in medication dosing and increase rates of electrolyte and acid-base abnormalities. We describe an initiative to standardize CRRT practice patterns and reduce dosing variability. Quality improvement study. Adult patients treated with CRRT at the University of Colorado Hospital between January 2016 and October2017. An assessment of the magnitude of the variability in CRRT dosing and the following specific interventions were implemented during the course of 1 year: (1) modification of the electronic medical record (EMR) to include calculated average 24-hour dose in real time, (2) modification of the CRRT procedure note to include comments on dosing, (3) modification of the CRRT order set to display calculations, and (4) yearly educational sessions for renal fellows outlining CRRT-specific dosing targets. The primary outcome was weekly percentage of CRRT treatments with an average delivered daily dose of 20 to 25mL/kg/h. Process and balancing outcomes included CRRT flowsheet accuracy, documentation of rates of delivered dose, and nursing satisfaction. Rates of weekly CRRT dosing in compliance with national guidelines were determined and used to create run charts showing compliance rates before and after the quality improvement interventions. Among 837 treatments before the intervention, 279 (33%) daily CRRT sessions achieved an average dose of 20 to 25mL/kg/h. Following implementation of interventions, 631 of 952 (66%) treatments achieved this goal. Week-to-week variation in dosing was significantly reduced. A single-center study generating data that may not be generalizable to institutions with different CRRT nursing models or different EMR systems. Changes to the EMR and documentation templates and education of CRRT providers about dosing were associated with doubling of the rate of appropriate CRRT dosing and reduction in dosing variability.

Renal replacement therapy: a practical update.

Acute kidney injury (AKI) is defined as an abrupt decrease in kidney function, with the most severe form requiring some method of renal replacement therapy (RRT). The use of RRT is required in 5-10% of critically ill patients who develop severe AKI. Renal replacement therapy can be provided as either intermittent hemodialysis or one of the various modes of continuous renal replacement therapy (CRRT), with CRRT potentially conferring an advantage with respect to renal recovery and dialysis independence. There is no difference in mortality when comparing low (< 25 mL·kg-1·hr-1) vs high (> 40 mL·kg-1·hr-1) RRT dosing. Continuous renal replacement therapy may be run in different modes of increasing complexity depending on a given patient's clinical needs. Regional citrate anticoagulation is recommended as the therapy of choice for the majority of critically ill patients requiring CRRT.

Serum lactate level and mortality in metformin-associated lactic acidosis requiring renal replacement therapy: a systematic review of case reports and case series

BackgroundThe current practice concerning timing, mode, and dose of renal replacement therapy (RRT) in patients with metformin-associated lactic acidosis (MALA) with renal failure remains unknown. To investigate whether serum lactate level and prescription pattern of RRT are associated with mortality in patients with MALA requiring RRT.MethodsWe searched PubMed/Medline and EMBASE from inception to Sep 2014 and applied predetermined exclusion criteria. Case-level data including case’s demographics and clinical information related to MALA were abstracted. Multiple logistic regression modeling was used to examine the predictors of mortality.ResultsA total of 253 unique cases were identified with cumulative mortality of 17.2%. Eighty-seven percent of patients had acute kidney injury. Serum lactate level was significantly higher in non-survivors (median 22.5 mmol/L) than in survivors (17.0 mmol/L, p-value <0.01) and so did the median blood metformin concentrations (58.5 vs. 43.9 mg/L, p-value = 0.05). The survival advantage was not significantly different between the modalities of RRT. The adjusted odds ratio of mortality for every one mmol/L increase in serum lactate level was 1.09 (95% CI 1.02–1.17, p-value = 0.01). The dose-response curve indicated a lactate threshold greater than 20 mmol/L was significantly associated with mortality.ConclusionsOur study suggests that predialysis level of serum lactate level is an important marker of mortality in MALA patients requiring RRT with a linear dose-response relationship. To better evaluate the optimal prescription of RRT in MALA, we recommend fostering an international consortium to support prospective research and large-scale standardized case collection.

Effectiveness of heart rate control on hemodynamics in critically ill patients with atrial tachyarrhythmias managed by amiodarone

Atrial tachyarrhythmias (AT) are common in intensive care unit (ICU) patients and might contribute to hemodynamic instability if heart rate (HR) is persistently too rapid. We aimed to assess if HR control below 115 or 130bpm with amiodarone improves hemodynamics in ICU patients with AT.This observational study included 73 ICU patients with disabling AT receiving amiodarone for HR control. A total of 525 changes (mainly within 4–8h) in mean arterial pressure (MAP) and 167 changes in plasma lactate in response to HR variations above 115 or 130bpm were analyzed. Epinephrine, sedative drugs, fluid loading, use of diuretics, continuous renal replacement therapy and amiodarone dosing were among covariables assessed.Univariable analysis showed that HR variations above 115bpm were poorly correlated to change in MAP (r=0.11, p<0.01). Multivariable analysis showed that changes in MAP were still positively associated to HR variation (p<0.05) and to initiation or termination of epinephrine (p<0.05) or sedatives infusions (p<0.05). Changes in plasma lactate did not correlate to HR variations above 115bpm. When considering 130 bpm as a threshold, HR variations were not associated to changes in MAP or to changes in plasma lactate. Amiodarone dose was associated to HR decrease but not to MAP or plasma lactate increase.In ICU patients with AT, strict HR control below 115bpm or 130bpm with amiodarone does not improve hemodynamics. A prospective randomized trial assessing strict versus lenient HR control in this setting is needed.

Acute kidney injury in sepsis

Sepsis is life-threatening organ dysfunction resulting from a dysregulated host response to infection. It is one of the commonest causes of acute kidney injury (AKI) and is associated with an increase in both morbidity and mortality. Both haemodynamic and non-haemodynamic factors are involved in the pathogenesis of AKI in sepsis. Newer tests are available for the early diagnosis of AKI in septic patients and may provide an opportunity for prevention. The current mainstay of prevention is adequate fluid resuscitation and maintenance of systemic blood pressure, noradrenaline being the vasopressor of choice. Renal replacement therapy may improve outcomes. Continuous renal replacement modalities are preferred in those who are haemodynamically unstable. There is no consensus on the optimal timing or dose of renal replacement therapy.