Vancomycin removal and pharmacokinetics during accelerated venovenous hemofiltration.

INTRODUCTION: Vancomycin pharmacokinetics are affected by renal replacement therapy and physiologic changes in critically ill patients. Literature regarding vancomycin removal and pharmacokinetics during accelerated venovenous hemofiltration (AVVH), a form of prolonged intermittent renal replacement therapy, is limited. OBJECTIVE: To describe the removal and pharmacokinetics of vancomycin during AVVH. METHODS: Eighteen critically ill adults receiving vancomycin and AVVH were included. Vancomycin serum concentrations were obtained within 4 h before and 2-6 h after the AVVH session. Patients' serum concentrations were plotted against time, and individual pharmacokinetic parameters were determined by a one-compartmental analysis. Continuous data are reported as a median (interquartile range [IQR]) and categorical data as a percentage. RESULTS: The median AVVH effluent rate was 39.3 mL/kg/h (IQR 35.5-48 mL/kg/h) for a duration of 9 h (IQR 8-9.75 h). AVVH decreased vancomycin concentrations by 29.8% (IQR 24.9%-35.9%), at a rate of 3.4% per hour (IQR 3.1%-4.3% per hour) of AVVH. The vancomycin elimination rate constant and half-life were 0.039 h-1 (IQR 0.036-0.053 h-1 ) and 17.6 h (IQR 13.1-18.8 h), respectively. The area under the curve during AVVH was 171.7 mg*h/L (IQR 149.1-190 mg*h/L). The volume of distribution in 10 patients was 1 L/kg (IQR 0.73-1.1 L/kg). After AVVH, vancomycin 1000 mg (IQR 750-1000 mg) was needed to maintain a serum trough concentration ≥15 mg/L. CONCLUSION: Vancomycin is significantly removed by AVVH, which requires supplemental dosing after completion of the AVVH session to maintain desired serum concentrations. Therapeutic drug monitoring of vancomycin serum concentrations is recommended for patients undergoing AVVH.

Meropenem Clearance in a Child With End-stage Renal Disease Undergoing Prolonged Intermittent Renal Replacement Therapy: A Case Report and Literature Review.

BACKGROUND: Meropenem is frequently used to treat severe infections in critically ill children. However, pharmacokinetic data on meropenem in children with end-stage renal disease (ESRD) undergoing prolonged intermittent renal replacement therapy (PIRRT) is limited. Our objectives were to evaluate meropenem clearance in a child with ESRD with and without PIRRT, compare the results to previous continuous renal replacement therapy studies in children, toddlers and neonates, and assess whether the currently used dose of meropenem is sufficient. CASE DESCRIPTION: A 5-year-old girl with an estimated glomerular filtration rate of 12.8 mL/min/1.73 m 2 was diagnosed with pulmonary infection and treated with 300 mg meropenem once a day. PIRRT was performed for 8 hours every 2 days. We used WinNonlin to evaluate meropenem clearance with and without PIRRT. RESULTS: Our case showed that PIRRT increased the clearance of meropenem from 1.39 (1.3) to 2.42 L/h (2.3 mL/kg/min) and caught up 42.6% of the total clearance. This result is in accordance with previous studies in children but slightly less than seen in toddlers and neonates under continuous renal replacement therapy. The current dose of 300 mg once a day is not sufficient to reach the therapeutic target. CONCLUSIONS: Predicting meropenem clearance in children with ESRD undergoing PIRRT is difficult as clearance will be affected by renal function, PIRRT settings and other factors. Further studies are needed to explore the individual variability of meropenem clearance and optimize the dosing regimen.

Antimicrobial pharmacokinetics and dosing in critically ill adults receiving prolonged intermittent renal replacement therapy: A systematic review.

Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: (1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, (2) evaluate the quality of evidence supporting these data, and (3) propose dosing recommendations based on the synthesis of these data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT. Quality assessment, evaluation of reporting, and relevant data extraction were conducted in duplicate. Synthesis of PK/pharmacodynamic (PD) outcomes, dosing recommendations from study authors, and physicochemical properties of included antibiotics were assessed by investigators in addition to the quality of evidence to develop dosing recommendations. Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. Nineteen studies describe both PK and PD outcomes. Vancomycin (12 studies, 171 patients), meropenem (7 studies, 84 patients), and piperacillin/tazobactam (5 studies, 56 patients) were the most frequent antimicrobials encountered. The quality of evidence was deemed strong for 7/20 antimicrobials, and strong dosing recommendations were determined for 9/20 antimicrobials. This systematic review updates and addresses issues of quality in previous systematic reviews on this topic. Despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. Knowledge gaps persist for many antimicrobials, and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.

Short-term prognostic models for severe acute kidney injury patients receiving prolonged intermittent renal replacement therapy based on machine learning.

BACKGROUND: As an effective measurement for severe acute kidney injury (AKI), the prolonged intermittent renal replacement therapy (PIRRT) received attention. Also, machine learning has advanced and been applied to medicine. This study aimed to establish short-term prognosis prediction models for severe AKI patients who received PIRRT by machine learning. METHODS: The hospitalized AKI patients who received PIRRT were assigned to this retrospective case-control study. They were grouped based on survival situation and renal recovery status. To screen the correlation, Pearson's correlation coefficient, partial ETA square, and chi-square test were applied, eight machine learning models were used for training. RESULTS: Among 493 subjects, the mortality rate was 51.93% and the kidney recovery rate was 30.43% at 30 days post-discharge, respectively. The indices related to survival were Sodium, Total protein, Lactate dehydrogenase (LDH), Phosphorus, Thrombin time, Liver cirrhosis, chronic kidney disease stage, number of vital organ injuries, and AKI stage, while Sodium, Total protein, LDH, Phosphorus, Thrombin time, Diabetes, peripherally inserted central catheter and AKI stage were selected to predict the 30-day renal recovery. Naive Bayes has a good performance in the prediction model for survival, Random Forest has a good performance in 30-day renal recovery prediction model, while for 90-day renal recovery prediction model, it's K-Nearest Neighbor. CONCLUSIONS: Machine learning can not only screen out indicators influencing prognosis of AKI patients receiving PIRRT, but also establish prediction models to optimize the risk assessment of these people. Moreover, attention should be paid to serum electrolytes to improve prognosis.

A therapeutic regimen of ceftazidime-avibactam for a critical patient receiving prolonged intermittent renal replacement therapy.

The present report firstly described a critically ill patient receiving a dosing regimen of ceftazidime-avibactam (CAZ-AVI) (1.875g q24h) to eliminate multidrug-resistant Klebsiella pneumoniae and a scheduled time for prolonged intermittent renal replacement therapy (PIRRT) every 48h (6h-session beginning 12h after the previous dosage on hemodialysis day). This dosing regimen for CAZ-AVI and a scheduled time for PIRRT allowed pharmacodynamic parameters of ceftazidime and avibactam to have little difference on hemodialysis and non-hemodialysis days so that we can maintain a relatively stable drug concentration. Our report highlighted not only the importance of dosing regimens in patients with PIRRT but also the significance of hemodialysis time points during the dosing interval. The innovative therapeutic plan proved to be suitable for patients infected with Klebsiella pneumoniae when on PIRRT according to the trough plasma concentrations of ceftazidime and avibactam which were maintained above the minimum inhibitory concentration during the dosing interval.

Long-term arteriovenous fistula prognosis for maintenance hemodialysis patients who accepted PIRRT by using arteriovenous fistula.

BACKGROUND: Maintenance hemodialysis (MHD) patients are often admitted to the hospital for severe morbidities. Prolonged intermittent renal replacement therapy (PIRRT) is required during the hospital staying. There are controversial opinions on the use of arteriovenous fistula (AVF) as vascular access for PIRRT in MHD patients. METHODS: Patients with AVF who accepted PIRRT in our center between January 2014 and June 2021 were retrospectively screened. AVF dysfunction and patient mortality were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of AVF dysfunction. RESULTS: About 162 patients were included in our present study. Twenty-six experienced AVF dysfunction, of whom 53.8%, 19.2%, and 27.0% had percutaneous transluminal balloon angioplasty, surgical revision, and AVF reconstruction, respectively. The accumulated AVF dysfunction rates were 11.8%, 16.2%, and 21.0% in 1, 2, and 3 years, respectively. Multivariate analysis revealed that smoking (HR 2.750, 95% CI 1.181-6.402, p = 0.019), higher platelet (PLT, HR 1.009, 95% CI 1.000-1.017, p = 0.047), higher prothrombin activity (PTA, HR 1.039, 95% CI 1.012-1.066, p = 0.004), and lower diastolic blood pressure (DBP, HR 0.963, 95% CI 0.932-0.996, p = 0.026) were independent risk factors for AVF dysfunction. During the follow-up period, 37 patients died. CONCLUSIONS: Overall, the use of AVF for PIRRT might not dramatically increase the incidence of AVF dysfunction. And, Smoking, lower DBP, higher PLT, and higher PTA were associated with increased AVF dysfunction.

How I prescribe prolonged intermittent renal replacement therapy.

Prolonged Intermittent Renal Replacement Therapy (PIRRT) is the term used to define 'hybrid' forms of renal replacement therapy. PIRRT can be provided using an intermittent hemodialysis machine or a continuous renal replacement therapy (CRRT) machine. Treatments are provided for a longer duration than typical intermittent hemodialysis treatments (6-12 h vs. 3-4 h, respectively) but not 24 h per day as is done for continuous renal replacement therapy (CRRT). Usually, PIRRT treatments are provided 4 to 7 times per week. PIRRT is a cost-effective and flexible modality with which to safely provide RRT for critically ill patients. We present a brief review on the use of PIRRT in the ICU with a focus on how we prescribe it in that setting.

Prolonged Intermittent Renal Replacement Therapy Combined with Hemoperfusion Can Improve Early Recovery of Moderate and Severe Acute Pancreatitis, Especially in Patients with Acute Kidney Injury.

INTRODUCTION: The aim of this study was to investigate the efficacy of prolonged intermittent renal replacement therapy (PIRRT) plus hemoperfusion (HP) in treating moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). METHODS: A total of 105 MSAP and SAP patients were enrolled. Sixty of them received routine internal medical therapy (control group), and 45 received PIRRT and HP in addition to routine internal medical therapy (PIRRT + HP group). The vital signs, laboratory results, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score were compared between the two groups before treatment and on the 3rd and 7th days of treatment. RESULTS: No deaths or treatment-related serious adverse reactions occurred in both groups. After 3 and 7 days of treatment, the APACHE II score decreased more significantly in the PIRRT + HP group than in the control group (3 days: 5.47 [±3.30] vs. 7.53 [±3.89], p = 0.005. 7 days: 4.82 [±3.49] vs. 6.87 [±3.54], p = 0.004). After 3 days of treatment, the inflammatory combination parameters systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) in the PIRRT + HP group decreased more significantly than those in the control group (SII: 1,239.00 [737.80-1,769.00] vs. 2,013.00 [1,260.00-3,167.00], p = 0.001. NLR: 8.78 [±4.52] vs. 11.88 [±7.30], p = 0.009). After 7 days of treatment, SII, NLR, and hypersensitive C-reactive protein decreased significantly compared with baseline, but no statistical differences between the two groups were observed. AST in both groups remained stable with treatment. There was no significant difference in baseline creatinine between the two groups of AKI patients, but after 3 and 7 days of treatment, the proportion of acute kidney injury (AKI) patients in the PIRRT + HP group whose creatinine decreased by 50% from baseline or fell to the normal range was significantly higher than that in the control group (p < 0.05). CONCLUSION: PIRRT + HP therapy could not only improve the general conditions, as measured by APACHE II score, but also reduce the inflammatory cascade of patients with acute pancreatitis. For MSAP and SAP patients complicated with AKI, this therapy may accelerate the recovery of renal function.

A systematic review of cost-effectiveness analyses of continuous versus intermittent renal replacement therapy in acute kidney injury.

INTRODUCTION: Though cost-effectiveness analyses (CEAs) have evaluated continuous renal replacement therapy (RRTs) and intermittent RRTs in acute kidney injury (AKI) patients; it is yet to establish which RRT technique is most cost-effective. We systematically reviewed the current evidence from CEAs of CRRT versus IRRT in patients with AKI. AREAS COVERED: PubMed, EMBASE, and Cochrane databases searched for CEAs comparing two RRTs. Overall, seven CEAs, two from Brazil and one from US, Canada, Colombia, Belgium, and Argentina were included. Five CEAs used Markov model, three reported following CHEERS, none accounted indirect costs. Time horizon varied from 1-year-lifetime. Marginal QALY gain with CRRT compared to IRRT was reported across CEAs. Older CEAs found CRRT to be costlier and not cost-effective than IRRT (ICER 2019 US$: 152,671$/QALY); latest CEAs (industry-sponsored) reported CRRT to be cost-saving versus IRRT (-117,614$/QALY). Risk of mortality, dialysis dependence, and incidence of renal recovery were the key drivers of cost-effectiveness. EXPERT OPINION: CEAs of RRTs for AKI show conflicting findings with secular trends. Latest CEAs suggested CRRT to be cost-effective versus IRRT with dialysis dependence rate as major driver of cost-effectiveness. Future CEAs, preferably non-industry sponsored, may account for indirect costs to improve the generalizability of CEAs.

Fosfomycin single- and multiple-dose pharmacokinetics in patients undergoing prolonged intermittent renal replacement therapy.

BACKGROUND: Fosfomycin is used increasingly in the treatment of MDR bacteria. It is eliminated by renal excretion, but data regarding dosing recommendations for patients undergoing modern means of renal replacement therapies are scarce. OBJECTIVES: Evaluation of the pharmacokinetics (PK) of fosfomycin in patients undergoing prolonged intermittent renal replacement therapy (PIRRT) to guide dosing recommendations. METHODS: Fosfomycin was given in 11 (7 female) patients with severe infections undergoing PIRRT. Plasma levels were measured at several timepoints on the first day of fosfomycin therapy, as well as 5-6 days into therapy, before and after the dialyser, to calculate its clearance. Fosfomycin was measured in the collected spent dialysate. RESULTS: The median (IQR) plasma dialyser clearance for fosfomycin was 183.4 (156.9-214.9) mL/min, eliminating a total amount of 8834 (4556-10 440) mg of fosfomycin, i.e. 73.9% (45.3%-93.5%) of the initial dose. During PIRRT, the fosfomycin half-life was 2.5 (2.2-3.4) h. Data from multiple-dose PK showed an increase in fosfomycin Cmax from 266.8 (166.3-438.1) to 926.1 (446.8-1168.0) mg/L and AUC0-14 from 2540.5 (1815.2-3644.3) to 6714 (4060.6-10612.6) mg·h/L. Dialysis intensity during the study was 1.5 L/h. T>MIC was 100% in all patients. CONCLUSIONS: Patients undergoing PIRRT experience significant fosfomycin elimination, requiring a dose of 5 g/8 h to reach adequate plasma levels. However, drug accumulation may occur, depending on dialysis frequency and intensity.

Short-term prognosis and influencing factors of patients with acute kidney injury treated with prolonged intermittent renal replacement therapy.

BACKGROUND: Studies assessing prognosis after prolonged intermittent renal replacement therapy (PIRRT) for acute kidney injury (AKI) are scarce. AIM: To assess the impact of PIRRT on AKI and factors associated with short-term prognosis. METHODS: In this retrospective nested case-control study, AKI patients administered PIRRT in Shanghai General Hospital from 01/2012 to 10/2018 were assigned to the 30-day survivor and death groups. Surviving patients were further divided into the kidney recovery and non-recovery groups at 30 and 90 days post-discharge, respectively. Propensity score matching was performed. RESULTS: Totally 576 patients were included in the non-matched study population, mortality and kidney recovery rates were 51.7% and 33.4%, respectively. After propensity score matching, there were 250 patients in each of the death and survival groups. Low PIRRT frequency (OR = 2.165, 95% CI = 1.178-3.978), infection (OR = 0.447, 95% CI = 0.251-0.795), number of damaged vital organs (OR = 0.478, 95% CI = 0.346-0.661), sodium (OR = 0.958, 95% CI = 0.928-0.988), total protein (OR = 1.047, 95% CI = 1.022-1.072), pre-dialysis thrombin time (TT; OR = 0.959, 95% CI = 0.936-0.983), pre-discharge glomerular filtration rate (GFR; OR = 1.024, 95% CI = 1.017-1.031) and admission ward [reference: renal ward; intensive care unit (OR = 0.042, 95% CI = 0.008-0.211); surgery (OR = 0.092, 95% CI = 0.018-0.465); medical (OR = 0.049, 95% C% CI = 0.009-0.259); other (OR = 0.097, 95% CI = 0.016-0.572)] independently predicted 30-day mortality. Peripherally inserted central catheter (OR = 13.970, 95% CI = 1.439-135.589), urea nitrogen (OR = 0.961, 95% CI = 0.933-0.990) and pre-discharge GFR (OR = 1.102, 95% CI = 1.067-1.137) independently predicted 30-day kidney recovery. Pre-dialysis Scr (OR = 0.997, 95% CI = 0.995-0.999), urea nitrogen (OR = 0.948, 95% CI = 0.912-0.986) and pre-discharge GFR (OR = 1.137 95% CI = 1.088-1.189) independently predicted 90-day kidney recovery. CONCLUSIONS: PIRRT improves survival and kidney function recovery in AKI patients. In patients with previous GFR ≥ 30 mL/(min-1.73 m2 ) and no prior maintenance dialysis, PIRRT at 3-5 sessions/week might be appropriate.

Provision of acute renal replacement therapy, using three separate modalities, in critically ill patients during the COVID-19 pandemic. An after action review from a UK tertiary critical care centre.

PURPOSE: The aim of this study is to describe the incidence of Acute Kidney Injury (AKI) amongst patients admitted to the Intensive Care Unit (ICU) with COVID-19. In addition we aim to detail the range of Renal Replacement Therapy (RRT) modalities offered to these patients (including peritoneal dialysis - PD - and intermittent haemodialysis - IHD) in order to meet demand during pandemic conditions. MATERIALS AND METHODS: Single-centre retrospective case note review of adult patients with confirmed COVID-19 admitted to ICU. RESULTS: Amongst 136 patients without a prior history of End Stage Kidney Disease (ESKD), 108 (79%) developed AKI and 63% of admitted patients received RRT. Due to resource limitations the range of RRT options were expanded from solely Continuous Veno-Venous HaemoDiaFiltration (CVVHDF - our usual standard of care) to include PD (in 35 patients) and IHD (in 15 patients). During the study period the proportion of RRT provided within ICU as CVVHDF fell from 100% to a nadir of 39%. There were no significant complications of either PD or IHD. CONCLUSIONS: During periods of resource limitations PD and IHD can safely be used to reduce dependence on CVVHDF in select patients with AKI secondary to COVID-19.

Prolonged Intermittent Renal Replacement Therapy for Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome.

INTRODUCTION: Patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 frequently develop severe acute kidney injury (AKI). Although continuous renal replacement therapy is the standard of care for critically ill patients, prolonged intermittent renal replacement therapy (PIRRT) may be a feasible option. We aimed to describe the tolerability and security of PIRRT treatments in COVID-19 patients with ARDS who required mechanical ventilation and developed severe AKI. METHODS: We prospectively analyzed patients who underwent PIRRT treatments at a COVID-19 reference hospital in Mexico City. Intradialytic hypotension was defined as a systolic blood pressure decrease of ≥20 mm Hg or an increase of 100% in vasopressor dose. RESULTS: We identified 136 AKI cases (60.7%) in 224 patients admitted to the intensive care unit. Among them, 21 (15%) underwent PIRRT (130 sessions) due to stage 3 AKI. The median age of the cohort was 49 (range 36-73) years, 17 (81%) were male, 7 (33%) had diabetes, and the median time between symptoms onset and PIRRT initiation was 12 (interquartile range [IQR] 7-14) days. The median of PIRRT procedures for each patient was 5 (IQR 4-9) sessions. In 108 (83%) PIRRT sessions, the total ultrafiltration goal was achieved. In 84 (65%) PIRRT procedures, there was a median increase in norepinephrine dose of +0.031 mcg/kg/min during PIRRT (IQR 0.00 to +0.07). Intradialytic hypotensive events occurred in 56 (43%) procedures. Fifteen (12%) PIRRT treatments were discontinued due to severe hypotension. Vasopressor treatment at PIRRT session onset (OR 6.2, 95% CI 1.4-28.0, p: 0.02) and a pre-PIRRT lactate ≥3.0 mmol/L (OR 4.63, 95% CI 1.3-12.8, p: 0.003) were independently and significantly associated with the risk of hypotension during PIRRT. During follow-up, 11 patients (52%) recovered from AKI and respiratory failure and 9 (43%) died. Several adaptations to our PIRRT protocol during the COVID-19 outbreak are presented. CONCLUSIONS: PIRRT was feasible in the majority of COVID-19 patients with ARDS and severe AKI, despite frequent transitory intradialytic hypotensive episodes. PIRRT may represent an acceptable alternative of renal replacement therapy during the COVID-19 outbreak.

Bivalirudin dosing during prolonged intermittent renal replacement therapy: a case report.

As patients transition between dialysis modalities, and from the intra- to the inter-dialytic period, medications with a narrow therapeutic index that are cleared in dialysis may require dose adjustments and close monitoring. Three cases of patients receiving bivalirudin while converting from continuous to prolonged intermittent renal replacement therapy are reported. Details provided include flow rates and ultrafiltrate volume. In these cases, it appears pre-emptive dose adjustments may be unwarranted, and clinicians should be aware of potential rebound after cessation of dialysis.

Intermittent hemodiafiltration as a down-step transition therapy in patients with acute kidney injury admitted to intensive care unit who initially underwent continuous venovenous hemodiafiltration.

BACKGROUND/AIMS: Continuous renal replacement therapies (CRRT) are initially employed in patients with acute kidney injury (AKI) in ICU setting. After the period of serious illness, hemodialysis is usually used as a mode of transition from CRRT. Intermittent hemodiafiltration (HDF) is not commonly applied in this scenario. OBJECTIVES: To evaluate the feasibility of using HDF as transition therapy after CVVHDF in critically patients with AKI. METHODS: An observational and prospective pilot study was conducted in ICU patients with dialysis-requiring AKI. Patients were initially treated with CVVHDF and, after medical improvement, those who still needed renal replacement therapy were switched to HDF treatment. RESULTS: Ten Patients underwent 53 HDF sessions (mean of 5.3 sessions/patient). The main cause of renal dysfunction was sepsis (N = 7; 70%). The APACHE II mean score was 27.6 ± 6.9. During HDF treatment, the urea reduction ratio was 64.5 ± 7.5%, for ß-2 microglobulin serum levels the percentage of decrease was 42.0 ± 7.8%, and for Cystatin C was 36.2 ± 6.9%. Five episodes of arterial hypotension occurred (9.4% of sessions). There were 20 episodes of electrolytic disturbance (37.7% of sessions), mainly hypophosphatemia. No pyrogenic or suggestive episode of bacteremia was observed. CONCLUSION: Hemodiafiltration was safe and efficient to treat critically ill patients with acute kidney injury during the transition phase from continuous to intermittent dialysis modality. Special attention should be paid regarding the occurrence of electrolytic disturbance, mainly hypophosphatemia.