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.

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.

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.

Deployment of a New CRRT/PIRRT Device during the COVID-19 Pandemic Emergency: Organizational Challenges and Implementation Results.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to increased demand nationwide for dialysis equipment, including supplies and machines. To meet the demand in our institution, our surge plan included rapid mobilization of a novel continuous renal replacement treatment (CRRT) machine named SAMI. The SAMI is a push-pull filtration enhanced dialysis machine that can conjugate extremely high single-pass solute removal efficiency with very precise fluid balance control. MATERIAL AND METHODS: Machine assembly was conducted on-site by local biomedical engineers with remote assistance by the vendor. One 3-h virtual training session of 3 dialysis nurses was conducted before SAMI deployment. The SAMI was deployed in prolonged intermittent replacement therapy (PIRRT) mode to maximize patients covered per machine per day. Live on-demand vendor support was provided to troubleshoot any issues for the first few cases. After 4 weeks of the SAMI implementation, data on treatments with the SAMI were collected, and a questionnaire was provided to the nurse trainees to assess device usability. RESULTS: On-site installation of the SAMI was accomplished with remote assistance. Delivery of remote training was successfully achieved. 23 PIRRT treatments were conducted in 10 patients. 7/10 of patients had CO-VID-19. The median PIRRT dose was 50 mL/kg/h (IQR [interquartile range] 44 - 62 mL/kg/h), and duration of the treatment was 8 h (IQR 6.3 - 8 h). Solute control was adequate. The user response was favorable to the set of usability questions involving user interface, on-screen instructions, machine setup, troubleshooting, and the ease of moving the machine. CONCLUSION: Assembly of the SAMI and training of nurses remotely are possible when access to vendor employees is restricted during states of emergency. The successful deployment of the SAMI in our institution during the pandemic with only 3-h virtual training supports that operating the SAMI is simple and safe.

Management of Acute Kidney Injury in Coronavirus Disease 2019.

Acute kidney injury is a common complication in hospitalized patients with coronavirus disease 2019. Similar to acute kidney injury associated with other conditions such as sepsis and cardiac surgery, morbidity and mortality are much higher in patients with coronavirus disease 2019 who develop acute kidney injury, especially in the intensive care unit. Management of coronavirus disease 2019-associated acute kidney injury with kidney replacement therapy should follow existing recommendations regarding modality, dose, and timing of initiation. However, patients with coronavirus disease 2019 are very hypercoagulable, and close vigilance to anticoagulation strategies is necessary to prevent circuit clotting. During situations of acute surge, where demand for kidney replacement therapy outweighs supplies, conservative measures have to be implemented to safely delay kidney replacement therapy. A collaborative effort and careful planning is needed to conserve dialysis supplies, to ensure that treatment can be safely delivered to every patient who will benefit for kidney replacement therapy.

Net ultrafiltration prescription survey in Europe.

BACKGROUND: Fluid overload is common in patients in the intensive care unit (ICU) and ultrafiltration (UF) is frequently required. There is lack of guidance on optimal UF practice. We aimed to explore patterns of UF practice, barriers to achieving UF targets, and concerns related to UF practice among practitioners working in Europe. METHODS: This was a sub-study of an international open survey with focus on adult intensivists and nephrologists, advanced practice providers, and ICU and dialysis nurses working in Europe. RESULTS: Four hundred eighty-five practitioners (75% intensivists) from 31 countries completed the survey. The most common criteria for UF initiation was persistent oliguria/anuria (45.6%), followed by pulmonary edema (16.7%). Continuous renal replacement therapy was the preferred initial modality (90.0%). The median initial and maximal rate of net ultrafiltration (UFNET) prescription in hemodynamically stable patients were 149 mL/hr. (IQR 100-200) and 300 mL/hr. (IQR 201-352), respectively, compared to a median UFNET rate of 98 mL/hr. (IQR 51-108) in hemodynamically unstable patients and varied significantly between countries. Two-thirds of nurses and 15.5% of physicians reported assessing fluid balance hourly. When hemodynamic instability occurred, 70.1% of practitioners reported decreasing the rate of fluid removal, followed by starting or increasing the dose of a vasopressor (51.3%). Most respondents (90.7%) believed in early fluid removal and expressed willingness to participate in a study comparing protocol-based fluid removal versus usual care. CONCLUSIONS: There was a significant variation in UF practice and perception among practitioners in Europe. Future research should focus on identifying the best strategies of prescribing and managing ultrafiltration in critically ill patients.

[Extracorporeal renal replacement therapies in lithium intoxication].

Drug poisoning is a significant source of morbidity, mortality and health care expenditure worldwide. Lithium, methanol, ethylene glycol and salicylates are the most important ones, included in the list of poisons, that may require extracorporeal depuration. Lithium is the cornerstone of treatment for bipolar disorders, but it has a narrow therapeutic window. The therapeutic range is 0.6-1.2 mEq/L and toxicity manifestations begin to appear as soon as serum levels exceed 1.5 mEq/L. Severe toxicity can be observed when plasma levels are more than 3.5 mEq/L. Lithium poisoning can be life threatening and extracorporeal renal replacement therapies can reverse toxic symptoms. Currently, conventional intermittent hemodialysis (IHD) is the preferred extracorporeal treatment modality. Preliminary data with prolonged intermittent renal replacement (PIRRT) therapies - hybrid forms of renal replacement therapy (RRT) such as sustained low efficiency dialysis (SLED) - seem to justify their role as potential alternative to conventional IHD. Indeed, SLED allows rapid and effective lithium removal with resolution of symptoms, also minimizing rebound phenomenon.

Pediatric Continuous Renal Replacement Therapy (PCRRT) expert committee recommendation on prescribing prolonged intermittent renal replacement therapy (PIRRT) in critically ill children.

INTRODUCTION: Recently, prolonged intermittent renal replacement therapies (PIRRT) have emerged as cost-effective alternatives to conventional CRRT and their use in the pediatric population has started to become more prominent. However, there is a lack of consensus guidelines on the use of PIRRT in pediatric patients in an intensive care setting. METHODS: A literature search was performed on PubMed/Medline, Embase, and Google Scholar in conjunction with medical librarians from both India and the Cleveland Clinic hospital system to find relevant articles. The Pediatric Continuous Renal Replacement Therapy workgroup analyzed all articles for relevancy, proposed recommendations, and graded each recommendation for their strength of evidence. RESULTS: Of the 60 studies eligible for review, the workgroup considered data from 37 studies to formulate guidelines for the use of PIRRT in children. The guidelines focused on the definition, indications, machines, and prescription of PIRRT. CONCLUSION: Although the literature on the use of PIRRT in children is limited, the current studies give credence to their benefits and these expert recommendations are a valuable first step in the continued study of PIRRT in the pediatric population.

Elimination of Contrast Agent Gadobutrol with Sustained Low Efficiency Daily Dialysis Compared to Intermittent Hemodialysis.

BACKGROUND: In patients with renal failure, gadolinium-based contrast agents (GBCA) can be removed by intermittent hemodialysis (iHD) to prevent possible toxic effects. There is no data on the efficacy of GBCA removal via sustained low efficiency daily dialysis (SLEDD) which is mainly used in intensive care unit (ICU) patients. METHODS: We compared the elimination of the GBCA gadobutrol in 6 ICU patients treated with SLEDD (6-12 h, 90 L dialysate) with 7 normal ward inpatients treated with iHD (4 h, dialysate flow 500 mL/min). Both groups received 3 dialysis sessions on 3 consecutive days starting after the application of gadobutrol. Blood samples were drawn before and after each session and total dialysate, as well as urine was collected. Gadolinium (Gd) concentrations were measured using mass spectrometry and eliminated Gd was calculated from dialysate and urine. RESULTS: The initial mean plasma Gd concentration was 385 ± 183 µM for the iHD and 270 ± 97 µM for the SLEDD group, respectively (p > 0.05). The Gd-reduction rate after the first dialysis session was 83 ± 9 and 67 ± 9% for the iHD and the SLEDD groups, respectively (p = 0.0083). The Gd-reduction rate after the second and third dialysis was 94-98 and 89-96% for the iHD and the SLEDD groups (p > 0.05). The total eliminated Gd was 89 ± 14 and 91 ± 4% of the dose in the iHD and the SLEDD groups, respectively (p > 0.05). Gd dialyzer clearance was 95 ± 22 mL/min and 79 ± 19 mL/min for iHD and SLEDD, respectively (p > 0.05). CONCLUSIONS: Gd-elimination with SLEDD is equally effective as iHD and can be safely used to remove GBCA in ICU patients.

Pharmacokinetics of flucloxacillin during prolonged intermittent renal replacement therapy in a 76-year-old man.

Prolonged intermittent renal replacement therapy (PIRRT) use has been increasing in critically ill patients with kidney dysfunction. PIRRT can affect the pharmacokinetics of many drugs, although no data is available to guide flucloxacillin dosing in this clinical scenario. Herein, we describe the pharmacokinetics of flucloxacillin, given at 1 g every 4 h during PIRRT, in a 76-year-old, critically ill patient with a methicillin-susceptible Staphylococcus aureus (MSSA) prosthetic joint infection complicated by bacteraemia. Blood samples were taken over 2 days including during a 9-h PIRRT session. A two-compartment model was developed to describe differences in clearance of flucloxacillin during PIRRT and off-PIRRT (9.45 vs. 6.89 L/h). A flucloxacillin dose of 1 g every 4 h during PIRRT therapy appeared to attain adequate exposures for MSSA sepsis in this patient, however higher doses may be required for infection sites with poor drug penetration.

Single- and multiple-dose pharmacokinetics and total removal of colistin in critically ill patients with acute kidney injury undergoing prolonged intermittent renal replacement therapy.

BACKGROUND: Owing to the emerging problem of MDR bacteria, interest in 'old' antibiotics such as colistin has re-emerged. However, research on the dosing of colistin in patients undergoing renal replacement therapy (RRT), such as prolonged intermittent renal replacement therapy (PIRRT), is scarce. OBJECTIVES: The aim of this study was to evaluate single- and multiple-dose pharmacokinetics of colistin and its prodrug colistin methanesulfonate in ICU patients with acute kidney injury (AKI) undergoing PIRRT. METHODS: We performed a prospective clinical pharmacokinetic single- and multiple-dose study. Eight ICU patients with AKI undergoing treatment with PIRRT and receiving intravenous colistin were studied on day 1 and days 5-9 of treatment, depending on the timing of dialysis. Six million IU (MIU) of colistin methanesulfonate was administered 8 h prior to the PIRRT session followed by 3 MIU every 8 h. The study was registered under clinicaltrails.gov (NCT02556190). RESULTS: PIRRT removed a considerable amount of colistin and colistin methanesulfonate with a median dialyser plasma CL of 70.1 mL/min (IQR 36.6-96.2) for colistin and 69.3 mL/min (IQR 56.3-318.7) for colistin methanesulfonate. The median amount of colistin in the total collected dialysate was 154 mg (IQR 105-175), corresponding to about 50% of the daily dose. Median colistin peak concentrations accumulated from 5.79 mg/L (IQR 4.14-8.79) on day 1 to 9.49 mg/L (IQR 8.39-10.41) on days 5-9. Cmax was significantly and inversely correlated with body weight. CONCLUSIONS: PIRRT eliminates about half of the daily administered colistin dose. Even a 6 MIU loading dose of colistin methanesulfonate may not ensure immediate sufficient colistin plasma levels in all critically ill patients. However, we measured significant colistin accumulation, suggesting that the dose of colistin methanesulfonate should be adjusted according to body weight and RRT intensity.