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Background
Furosemide is commonly prescribed in critically ill patients with acute kidney injury (AKI). Existing data from observational studies and small clinical trials have significant limitations and have reported conflicting findings. There remains controversy on whether furosemide can impact clinical outcomes in critically ill patients with A...
Context in source publication
Context 1
... estimate of patient ideal body weight (IBW) will be used to determine the urine output target. Determina- tion of estimated IBW will be based on the formula described by Devine [45] (Table 2). From this estimated IBW, patients will be divided into 5 kg weight categories to determine urine output goals for protocol simplicity (Table 3). ...Citations
... This action mechanism can decrease the demand for oxygen in the renal tubules. Furosemide is further recognized for its significant adjunctive function in preserving fluid balance and enhancing nutritional provision in critically sick patients with acute kidney injury (AKI) [11]. There is a correlation between the presence of furosemide in plasma and the presence of albumin. ...
Medicinal plants received special attention due to their biological and medicinal activities, aspects of safety in their use, and low cost. This study aimed to prove gum Arabic (GA) extract’s preventive and therapeutic role against furosemide toxicity. Moreover, histological findings, renal functions, and the level of MDA and GSH in the serum and kidney tissues of newborn rats were assessed. Thirty pregnant rats were divided into six groups (n = 5 per group). The first group is the control group, with no treatment. The second is the GA group, administered 15% w/v GA in drinking water daily from conception day 0 until the end of pregnancy. The third group is the furosemide group; furosemide (20 mg/k, ip) was taken daily from conception day 0 until the end of pregnancy. The fourth group is the protective group (preventive group); GA was taken daily (15% w/v in drinking water) from conception day 0 to day 10, followed by furosemide (20 mg/kg, ip) daily until the end of pregnancy. The fifth group is the therapeutic group; furosemide (20 mg/kg, ip) was taken daily from conception day 0 to day 10, followed by GA (15% w/v in drinking water) daily until the end of pregnancy. The sixth group is the mixed group; GA and furosemide were administered together from conception day 0 until the end of pregnancy
... After that, every six-hourly (more frequently, if needed) fluid charting was done based on fluid balance, clinical, and laboratory parameters. The trial drug titration concept was adapted from the SPARK study [14]. The intravenous (peripheral/central) infusion of the trial drug was commenced at 0.05 mL/kg/h (= 0.05 mg/kg/h of furosemide) using a dedicated infusion pump and titrated at the rate of 0.05 mL/kg/h up to a maximum infusion of 0.4 mL/kg/h. ...
Objective To study whether furosemide infusion in early-onset acute kidney injury (AKI) in critically ill children would be
associated with a reduced proportion of patients progressing to the higher stage (Injury or Failure) as compared to placebo.
Method A double-blind, placebo-controlled, randomized pilot trial was conducted. The authors enrolled children aged 1-mo
(corrected) to 12-y, who were diagnosed with AKI (“risk” stage) using pediatric-Risk, Injury, Failure, Loss, End stage kidney
disease (p-RIFLE) criteria, and achieved immediate resuscitation goals within 24 h of admission. Participants received either
furosemide (0.05 to 0.4 mg/kg/h) or placebo (5%-dextrose) infusion. The primary outcome was the proportion of patients
progressing to a higher stage (injury or failure). Secondary outcomes were (i) need for renal replacement therapy, (ii) the effect
on neutrophil gelatinase-associated lipocalin (urine and blood), (iii) fluid balance, (iv) adverse effects, (v) time to achieve renal
recovery, (vi) duration of hospital stay and mechanical ventilation, and (vii) all-cause 28-d mortality.
Results The trial was stopped for futility, and data were analyzed on an intention-to-treat basis (furosemide-group: n = 38;
placebo-group: n = 37). No significant difference was noted in the progression of AKI to a higher stage between furosemide
and placebo groups (10.5% vs. 21.6%; relative risk = 0.49, 95% CI 0.16 to 1.48) (p = 0.22). There were no differences in the
secondary outcomes between the study groups. All-cause 28-d mortality was similar between the groups (10.5% vs. 10.8%). No
trial-related severe adverse events occurred.
Conclusions Furosemide infusion in early-onset AKI did not reduce the progression to a higher stage of AKI. A future trial with
large sample size is warranted.
... 84 Although these and other observations have provided the scientific basis for the widespread clinical use of furosemide in AKI, there remains little evidence that furosemide reduces the requirements for renal replacement therapy or reduces mortality in patients with septic AKI. 85,86 In a recent study in ovine septic AKI, a single bolus of a low dose of furosemide (20 mg) restored renal medullary PO 2 to healthy physiological levels, an effect maintained for up to 8 hours, despite no significant effects on RBF, RDO 2 , cortical perfusion, or cortical PO 2 ( Table 2). 23 In ovine septic AKI, furosemide-induced sustained improvements in renal medullary PO 2 were associated with only transient increases in fractional sodium excretion and creatinine clearance. ...
Renal tissue hypoxia has been implicated as a critical mediatory factor in multiple forms of acute kidney injury (AKI), including in sepsis. In sepsis, whole-kidney measures of macrocirculatory flow and oxygen delivery appear to be poor predictors of microcirculatory abnormalities. Studies in experimental hyperdynamic septic AKI have shown that the renal medulla is particularly susceptible to hypoxia early in sepsis, even in the presence of increased global renal blood flow and oxygen delivery. It has been proposed that an early onset of progressive renal medullary hypoxia, leading to oxidative stress and inflammation, can initiate a downward spiral of cellular injury culminating in AKI. Recent experimental studies have shown that clinical therapies for septic AKI, including, fluids, vasopressors, and diuretics, have distinct effects on renal macrocirculation and microcirculation. Herein, we review the clinical and experimental evidence of alterations in global and regional kidney perfusion and oxygenation during septic AKI and associated therapies. We justify the need for investigation of the effects of therapies on renal microcirculatory perfusion and oxygenation. We propose that interventions that do not worsen the underlying renal pathophysiologic and reparative processes in sepsis will reduce the development and/or progression of AKI more effectively.
... However, several studies have shown that there was an association between AKI severity (as described by RIFLE class) with higher mortality and longer hospital and ICU stay (29). The RIFLE criteria have been used in therapeutic trials for AKI, as well as in studies aiming to clarify the pathophysiology of AKI (30,31). Finally, a paediatric version (pRIFLE) proposed in 2007 (32). ...
Acute kidney injury (AKI) is a common syndrome presenting in multiple clinical settings and is frequently associated with serious short and long term adverse outcomes, which not only have impact on the patient but also on the health service increasing hospitalisation time and the costs related to the treatment. Early diagnosis and identification of the aetiology are essential for the management of the patients. During the last ten years, significant advances have been made towards the definition of this syndrome. The current consensus definitions of AKI include both changes in serum creatinine concentration and urine output. Although proposal have been made for the inclusion of novel biomarkers in the diagnostic workup of AKI as independent diagnostic markers these are not currently included in these definitions. In this review we will focus on these definitions and we will try to highlight their strengths and limitations in diagnosis and staging of AKI. Moreover, we will try to highlight the contribution of the clinical laboratory in AKI diagnosis in both the clinical and research settings.
... Conversely, meta-analyses and small trials questioned the beneficial effect of furosemide on incidence or clinical course of AKI [37,61,65]. To clarify these issues, a pilot multicenter RCT on continuous furosemide administration versus placebo in critically ill patients with AKI (the SPARK study) was planned [66]. The study aimed at enrolling 216 patients with early AKI defined according to R-RIFLE criteria [67], with worsening AKI as primary endpoint. ...
Background
Furosemide is the most common loop diuretic used worldwide. The off-label administration of furosemide bolus(es) for the prevention or to reverse acute kidney injury (AKI) is widespread but not supported by available evidence. We conducted a meta-analysis of randomized trials (RCTs) to investigate whether bolus furosemide to prevent or treat AKI is detrimental on patients’ survival.
Methods
Electronic databases were searched through October 2017 for RCTs comparing bolus furosemide administration versus any comparator in patients with or at risk for AKI. The primary endpoint was all-cause longest follow-up mortality. Secondary endpoints included new or worsening AKI, receipt of renal replacement therapy, length of hospital stay, and peak serum creatinine after randomization.
Results
A total of 28 studies randomizing 3,228 patients were included in the analysis. We found no difference in mortality between the two groups (143/892 [16%] in the furosemide group versus 141/881 [16%] in the control group; odds ratio [OR], 0.84; 95% confidence interval [CI], 0.63 to 1.13; p = 0.25). No significant differences in secondary outcomes were found. A significant improvement in survival was found in the subgroup of patients receiving furosemide bolus(es) as a preventive measure (43/613 [7.0%] versus 67/619 [10.8%], OR 0.62; 95% CI, 0.41 to 0.94; p = 0.03)
Conclusions
Intermittent furosemide administration is not associated with an increased mortality in patients with or at risk for AKI, although it may reduce mortality when used as a preventive measure. Future high-quality RCTs are needed to define the role of loop diuretics in AKI prevention and management.
Trial registration
The study protocol was registered on PROSPERO database for systematic reviews (Registration no. CRD42017078607 – http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017078607).
... 155 Two RCTs are taking place, but are probably too small to provide a defi nite answer to this question (NCT00978354). 156 The KDIGO guidelines suggest use of diuretics to treat fl uid overload in AKI. ...
... Delayed or absent nephrology referral have both been associated with a higher mortality, dialysis dependence, and length of hospital stay. [155][156][157][158][159][160] However, given the worldwide annual burden of new cases of AKI, the number of trained nephrologists available is insuffi cient to care for this number of patients. In level 3 countries, there is not only a dearth of nephrologists, but also of physicians of any specialty. ...
Background:
Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional differences in acute kidney injury recognition, management, and outcomes.
Methods:
In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person.
Findings:
Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 [40%] patients) and dehydration (1536 [38%] patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 [46%] of 1153 vs 518 [32%] of 1605 in UMICs vs 492 [39%] of 1260 in HICs) and hypotension in HICs (564 [45%] of 1260 vs 611 [38%%] of 1605 in UMICs vs 440 [38%] of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 [12%] of 1076) than in HICs (125 [10%] of 1230) and UMICs (169 [11%] of 1549).
Interpretation:
We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs.
Funding:
International Society of Nephrology.
... 155 Two RCTs are taking place, but are probably too small to provide a defi nite answer to this question (NCT00978354). 156 The KDIGO guidelines suggest use of diuretics to treat fl uid overload in AKI. ...
... Delayed or absent nephrology referral have both been associated with a higher mortality, dialysis dependence, and length of hospital stay. [155][156][157][158][159][160] However, given the worldwide annual burden of new cases of AKI, the number of trained nephrologists available is insuffi cient to care for this number of patients. In level 3 countries, there is not only a dearth of nephrologists, but also of physicians of any specialty. ...
... In both groups, RRT was started if one of the following criteria was fulfilled [5,14]: ...
Acute kidney injury after cardiac surgery (CS-AKI) is strongly associated with in-hospital mortality and morbidity. We aimed to investigate whether 'early' or 'late' initiation of renal replacement therapy (RRT) in patients with CS-AKI is associated with a survival benefit or more favourable outcomes.
All patients who had undergone cardiac surgery at 'Ospedali Riuniti' of Ancona from July 2011 to February 2013 were prospectively enrolled and divided into two treatment groups: the 'early' approach was used during the first 10 months, and the 'late' approach during the next 10 months. 'Early' RRT was started after 6 h of urine output less than 0.5 ml/kg/h, whereas in the 'late' group, therapy started on the basis of persistent (>12 h) oliguria. A total of 1658 patients were enrolled in the trial. The primary outcome was operative mortality, and the secondary outcomes were length of intensive care unit and hospital stay.
The total number of patients treated with RRT was 59 (3.6%): 46 (5.5%) in the 'early' group and 13 (1.6%) in the 'late' group (P < 0.0001). Although RRT was significantly less utilized in the 'late' group, no significant difference in the primary and secondary outcomes was found, but a trend towards a better outcome in the 'late' group was observed. Furthermore, we found a significant difference in mortality between the two approaches in the subgroups of patients with preoperative renal dysfunction and in patients suffering from CS-AKI with a clear advantage of the late strategy.
Our results do not support the use of early RRT in CS-AKI.
This trial is registered in the clinicaltrial.gov registry: NCT01961999.
© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
... Some investigators have suggested that furosemide is protective in AKI because its administration may decrease tubular oxygen consumption, in which case its early administration in AKI would be protective [31]. Clinical trials using furosemide early in the course of AKI are underway and may help determine whether furosemide has a role in the treatment of AKI [32]. In addition, we did not specifically study patients with acute decompensated heart failure, nephrotic syndrome, or other patient populations with diuretic resistance. ...
In the setting of early acute kidney injury (AKI), no test has been shown to definitively predict the progression to more severe stages. Materials and Methods: We investigated the ability of a furosemide stress test (FST) (one-time dose of 1.0 or 1.5 mg/kg depending on prior furosemide-exposure) to predict the development of Acute Kidney Injury Network (AKIN) Stage-III in two cohorts of critically ill subjects with early AKI. Cohort 1 was a retrospective cohort who received a FST in the setting of AKI in critically ill patients part of Southern AKI Network. Cohort 2 was a prospective multicenter group of critical patients who received their FST in the setting of early AKI.
We studied 77 subjects; 23 from cohort 1 and 54 from cohort 2; 25 (32.4%) met the primary endpoint of progression to AKIN-III. Subjects with progressive AKI had significantly lower urine output following FST in each of the first 6 hours (p<0.001). The area under the receiver operator characteristic curves for the total urine output over the first 2 hours following FST to predict progression to AKIN-III was 0.87 (p = 0.001). The ideal-cutoff for predicting AKI progression during the first 2 hours following FST was a urine volume of less than 200mls(100ml/hr) with a sensitivity of 87.1% and specificity 84.1%.
The FST in subjects with early AKI serves as a novel assessment of tubular function with robust predictive capacity to identify those patients with severe and progressive AKI. Future studies to validate these findings are warranted. Clinical trial numbers: NCT00673244, NCT01275729.
... They reduce the oxygen demand and prevent hypoxic damage, and furosemide has been shown to improve renal hemodynamics, attenuate ischemic-related renal angiogenesis and reduce ischemic-induced apoptosis in animal models [39][40][41]. A pilot phase II randomized, blinded, placebo-controlled trial comparing furosemide to placebo in ICU patients with early AKI is in progress [42]; this study aims to compare the efficacy and safety of furosemide versus placebo on the progression of AKI severity and fluid balance. The results of this trial will help us to understand better the role of diuretics in AKI in the critical care setting. ...
Introduction:
In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI.
Methods:
We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression.
Results:
Of the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95%CI 0.12 to 0.52; <0.001).
Conclusions:
In this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients.
