Continuous Renal Replacement Therapy Circuit Research Articles

The Relationship Between Acute-Phase Circuit Occlusion and Blood Calcium Concentration in an Ex Vivo Continuous Renal Replacement Therapy Model.

Background and objective Continuous renal replacement therapy (CRRT) is a blood purification therapy modalityfor the treatment of renal failure in critically ill hospitalized patients with multiorgan dysfunction, effectively preventing uremia and multiple organ failure while improving renal function. However, the perfusion of patient blood through extracorporeal circulation often results in unexpected early occlusion of the CRRT circuit or hemofilter,leading to frequent interruptions in CRRT and wastage of medical resources. Moreover, clinical research on such circuit occlusions is limited. In Japan, CRRT circuits require long-term perfusion, often lasting 24 hours or more, indicating the need for a model capable of inducing occlusion at any arbitrary time; this model can evaluate various aspects, including causes and underlying mechanisms, and contribute to the development of an occlusion prediction method. Hence, we hypothesized the need for a model for inducing occlusion at arbitrary time points. Consequently, we strove to develop an ex vivo circuit occlusion model involving the injection of calcium into circulating citrated animal blood to evaluate the relationship between the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time. Methods We developed a circuit occlusion model using a commercially available CRRT circuit, polysulfone membrane hemofilter, heating extension tube, and thermostatic water bath, along withcommercially available citrated bovine whole blood. The circuit was filled with blood over a 10-min duration using a roller pump and was occluded after a specific period by varying the flow rate of calcium injected into bovine whole blood. Additionally, continuous injection of 1 mEq/mL calcium chloride into the circuit was maintained while bovine whole blood circulated. Measurements were performed at each calcium injection flow rate (2, 3, and 4 mL/h), with each measurement performed five times. The group that did not receive calcium injection was used as the control (0 mL/h: Con), and the experiment was performed three times. Groups were defined as "0, 2, 3, and 4" for each calcium injection flow rate. The relationship among the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time was evaluated. Furthermore, blood tests and blood viscoelastic tests were performed at arbitrary times. Results The circuit occlusion time varied with each calcium injection flow rate, and a significant difference was observed between each group (p<0.05). Circuit pressure gradually changed at four minbefore occlusion when calcium was injected at 2, 3, and 4 mL/h, with a more rapid change at one minbefore occlusion. We measured circuit pressure at four and one minbefore occlusion (-4 min, and -1 min, respectively), and at the time of circuit occlusion (0 min) in the Con and 4 mL/h groups. Significant differences were observed in AP between -4 min and 0 min and -1 min and 0 min at a calcium flow rate of 4 mL/h. Additionally, significant differences were seen in prefilter and return pressures between -4 min and 0 min, -4 min and -1 min, and -1 min and 0 min at a calcium flow rate of 4 mL/h (p<0.05). Conclusions Our proposed model accurately estimated the occlusion time based on changes in circuit pressure. This model can be used to create various experimental systems depending on the desired occlusion time.

Spallation and particles infusion into the extracorporeal circuit during CRRT: a preventable phenomenon

Patients in intensive care are exposed to the risk of microparticle infusion via extracorporeal lines and the resulting complications. A possible source of microparticle release could be the extracorporeal circuit used in blood purification techniques, such as continuous renal replacement therapy (CRRT). Disposable components of CRRT circuits, such as replacement bags and circuit tubing, might release microparticles such as salt crystals produced by precipitation in replacement bags and plastic microparticles produced by spallation. In-line filtration has proven effective in retaining microparticles both in in-vitro and in-vivo studies. In our study, we performed an in-vitro model of CRRT-treatment with the aim of detecting the microparticles produced and released into the circuit by means of a qualitative and quantitative analysis, after sampling the replacement and patient lines straddling a series of in-line filters. Working pressures and flows were monitored during the experiment. This study showed that microparticles are indeed produced and released into the CRRT circuit. The inclusion of in-line filters in the replacement lines allows to reduce the burden of microparticles infused into the bloodstream during extracorporeal treatments, reducing the concentration of microparticles from 14 mg/mL pre in-line filter to 11 mg/mL post in-line filter. Particle infusion and related damage must be counted among the pathophysiological mechanisms supporting iatrogenic damage due to artificial cross-talk between organs during CRRT applied to critically ill patients. This damage can be reduced by using in-line filters in the extracorporeal circuit.

The comparison of circuit lifespan between integration and separation approach in extracorporeal membrane oxygenation (ECMO) patient requiring continuous renal replacement therapy (CRRT) support, (E-CRRT Trial)

Background: The estimated incidence of acute kidney injury requiring continuous renal replacement therapy (CRRT) in patients necessitating extracorporeal membrane oxygenation (ECMO) is approximately 50%. Currently, two well-known techniques—integration and separation—are utilized for combining CRRT and ECMO circuits. The efficacy of these two techniques is still unknown. Therefore, this study aimed to compare the circuit lifespan of CRRT between the integration and separation techniques. Methods: A multicentered randomized controlled study with an unblinded design will be conducted to determine circuit lifespan differences between integration and separation techniques. Hypothesis: We hypothesize that the integration technique will yield a longer circuit lifespan for CRRT compared to the separation technique. Trial registration: NCT05036616

Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis.

Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown. The objectives of this study were to investigate the anakinra-circuit interaction and quantify the rate of removal from plasma. The anakinra-circuit interaction was evaluated using a closed-loop ex vivo CRRT circuit. CRRT was performed in three phases based on the method of solute removal: 1) hemofiltration, 2) hemodialysis, and 3) hemodiafiltration. Standard control samples of anakinra were included to assess drug degradation. University research laboratory. None. Anakinra was administered to the CRRT circuit and serial prefilter blood samples were collected along with time-matched control and hemofiltrate samples. Each circuit was run in triplicate to assess inter-run variability. Concentrations of anakinra in each reference fluid were measured by enzyme-linked immunosorbent assay. Transmembrane filter clearance was estimated by the product of the sieving coefficient/dialysate saturation constant and circuit flow rates. Removal of anakinra from plasma occurred within minutes for each CRRT modality. Average drug remaining (%) in plasma following anakinra administration was lowest with hemodiafiltration (34.9%). The average sieving coefficient was 0.34, 0.37, and 0.41 for hemodiafiltration, hemofiltration, and hemodialysis, respectively. Transmembrane clearance was fairly consistent across each modality with the highest during hemodialysis (5.53 mL/min), followed by hemodiafiltration (4.99 mL/min), and hemofiltration (3.94 mL/min). Percent drug remaining within the control samples (93.1%) remained consistent across each experiment, indicating negligible degradation within the blood. The results of this analysis are the first to demonstrate that large molecule therapeutic proteins such as anakinra, are removed from plasma with modern CRRT technology. Current dosing recommendations for patients with severe renal impairment may result in subtherapeutic anakinra concentrations in those receiving CRRT.

Meropenem extraction by ex vivo extracorporeal life support circuits.

Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem. The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction. Standard doses of meropenem were administered to three different configurations (n=3 per configuration) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24h. Similarly, standard doses of meropenem were administered to CRRT circuits (n=4) and serial sampling was conducted over 4h. Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation. Meropenem concentrations were quantified, and percent recovery was calculated for each sample. Meropenem was cleared at a similar rate in ECMO circuits of different configurations (n=3) and controls (n=6), with mean (standard deviation) recovery at 24h of 15.6% (12.9) in Complete circuits, 37.9% (8.3) in Oxygenator circuits, 47.1% (8.2) in Pump circuits, and 20.6% (20.6) in controls. In CRRT circuits (n=4) meropenem was cleared rapidly compared with controls (n=6) with a mean recovery at 2h of 2.36% (1.44) in circuits and 93.0% (7.1) in controls. Meropenem is rapidly cleared by hemodiafiltration during CRRT. There is minimal adsorption of meropenem to ECMO circuit components; however, meropenem undergoes significant degradation and/or plasma metabolism at physiological conditions. These ex vivo findings will advise pharmacists and physicians on the appropriate dosing of meropenem.

Clinical Factors Affecting Continuous Renal Replacement Therapy Circuit Survival

Clinical Factors Affecting Continuous Renal Replacement Therapy Circuit Survival

Comparison of diluted vs concentrated regional citrate anticoagulation in continuous renal replacement therapy: A quasi-experimental study.

The incidence of coagulation of continuous renal replacement therapy circuits remains high. To the best of our knowledge, no scholar has published a protocol to avoid management errors when different types of citrates coexist in the same Intensive Care Unit. To assess the safety and efficacy of the unification of two protocols with different concentrations of citrate solution. A prospective, quasi-experimental study was carried out in the intensive care unit of a tertiary referral hospital (in Barcelona, Spain), over 3 years. Consecutive adult patients requiring continuous renal replacement therapy with citrate were included. The sample was divided into two groups, a control group (concentrated citrate) and an intervention group (diluted citrate). The decision to initiate anticoagulation with diluted (18 mmol/L) or concentrated (136 mmol/L) citrate was made based on the machine available and the decision of the doctor responsible for the patient. It was not possible to randomize the sample. Both protocols were matched with a starting citrate dose of 3.5 mmol/L, and a dialysis solution was used. Post-filter replacement was not used, and the citrate solution was the only fluid administered pre-filter. The analysis included 59 circuits in the concentrated citrate group and 40 circuits in the diluted citrate group. An increased need for electrolyte replacement was observed in the diluted group (p < .001). The concentrated citrate group had a longer filter life (p < .05), and there was a slight trend toward alkalosis. The diluted citrate group had a higher incidence of electrolyte replacement. The concentrated citrate group had longer circuit lifespan and a trend toward metabolic alkalosis, although this was not statistically significant. If these conclusions are considered, the protocol can be unified. The present work aims to provide information on the differences in the use of regional anticoagulation with diluted or concentrated citrate. The objective is to pay special attention to aspects that can lead to complications. The unified protocol proposed in this paper could be extrapolated to any machine on the market that uses either of these two types of citrate concentration.

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 &lt; 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 &lt; 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 &lt; 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 &lt; 0.05). Discussion: Dynamic dosing for CRRT in this institution was safe and may lead to more tailored maintenance of biochemical homoeostasis.

Propofol infusion syndrome as a cause for CRRT circuit malfunction: a case report with literature review

BackgroundPropofol is commonly used for sedation in the Intensive Care Unit (ICU). When administered in high doses and for a prolonged time, it can cause a rare but hazardous complication: Propofol Infusion Syndrome (PRIS). Along with other findings, PRIS can cause lipemia and clotting of the Continuous Renal Replacement Therapy (CRRT) circuit.Case presentationA 62-year-old woman admitted to the ICU after an acute ischemic stroke was sedated with Propofol for neuroprotection. On the sixteenth day of infusion (mean daily dose: 4 mg/kg/h), she presented with hyperlactatemia (7.7 mg/dL), acute kidney injury, metabolic acidosis (pH: 7.23 / HCO3–: 12.2 mEq/L), hyperkalemia (6.9 mEq/L), and hypotension requiring high doses of norepinephrine. CRRT and corticosteroids were initiated. After 15 min of CRRT, the blood in the circuit had a milky color, and the therapy was interrupted because of high transmembrane pressure, despite adequate anticoagulation with heparin. Laboratory tests showed hypertriglyceridemia (782 mg/dL), increased transaminases, and creatine phosphokinase (5008 U/L), suggesting the rare and fatal PRIS.ConclusionThere is no established guideline for treating PRIS other than early discontinuation of Propofol and supportive care. Although CRRT is an important tool in managing PRIS, hypertriglyceridemia can cause circuit malfunction. Clinical hypervigilance and serial monitoring in at-risk patients are advised to minimize potentially lethal complications.

Continuous Renal Replacement Therapy during Extracorporeal Membrane Oxygenation: Circuit Haemodynamics and Circuit Failure

Introduction: Treatment with continuous renal replacement therapy (CRRT) is common during extracorporeal membrane oxygenation (ECMO). Such ECMO-CRRT has specific technical characteristics, which may affect circuit life. Accordingly, we studied CRRT haemodynamics and circuit life during ECMO. Methods: ECMO and non-ECMO-CRRT treatments in two adult intensive care units were compared using data collected over a 3-year period. A potential predictor of circuit survival identified in a 60% training data subset as a time-varying covariate within a Cox proportional hazard model was subsequently assessed in the complementary remaining data (40%). Results: Median [interquartile range] CRRT circuit life was greater when associated with ECMO (28.8 [14.0–65.2] vs. 20.2 [9.8–40.2] h, p < 0.0001). Access, return, prefilter, and effluent pressures were also greater during ECMO. Higher ECMO flows were associated with higher access and return pressures. Classification and regression tree analysis identified an association between high access pressures and accelerated circuit failure, while both first access pressures ≥190 mm Hg (HR 1.58 [1.09–2.30]) and patient weight (HR 1.85 [1.15–2.97] third tertile vs. first tertile) were independently associated with circuit failure in a multivariable Cox model. Access dysfunction was associated with a stepwise increase in transfilter pressure, suggesting a potential mechanism of membrane injury. Conclusion: CRRT circuits used in conjunction with ECMO have a longer circuit life than usual CRRT despite exposure to higher circuit pressures. Markedly elevated access pressures, however, may predict early CRRT circuit failure during ECMO, possibly via progressive membrane thrombosis as evidenced by increased transfilter pressure gradients.

Hypertriglyceridemia as a Cause of Continuous Renal Replacement Therapy Circuit Clotting: A Case Series

Introduction: Hypertriglyceridemia is a rarely reported cause of early continuous renal replacement therapy (CRRT) circuit clotting. Methods: We have identified and will present 11 published cases in the literature where hypertriglyceridemia has led to CRRT circuit clotting or dysfunction. Results: The majority of cases (8/11) are related to propofol use leading to hypertriglyceridemia. The other cases (3/11) are due to total parenteral nutrition administration. Conclusion: Due to the propensity of propofol use for critically ill patients in intensive care units, and the rather common occurrence of CRRT circuit clotting, hypertriglyceridemia may be underappreciated and undiagnosed. The exact pathophysiology behind hypertriglyceridemia-induced CRRT clotting has not been fully elucidated, although there are some hypotheses which include fibrin and fat droplet deposition (identified after electron microscopic examination of the hemofilter), increased blood viscosity, and development of a procoagulant state. Premature clotting poses a multitude of problems including inadequate treatment time, increased costs, increasing nursing workload, and patient blood loss. With earlier identification, discontinuation of the inciting agent, and possible therapeutic management, we could expect improvement in CRRT hemofilter patency and decreased costs.

The effect of the AN69 ST100 versus oXiris® membrane on filter life during CRRT for non-anticoagulated liver failure patients.

In patients with liver failure, continuous renal replacement therapy (CRRT) without anticoagulation may be necessary. A new heparin coated membrane (oXiris®) may prolong circuit life in this setting. In liver failure patients not receiving anticoagulation, to compare CRRT circuit life with the oXiris® versus the AN69 ST100 (usual care) membrane. Randomized single cross-over trial. We studied 20 patients and 39 circuits. Twenty-five treatments used femoral and 14 internal jugular access catheters. Median circuit life was 21 h (IQR: 8.25-35.5) with the AN69 versus 16.0 h (14-25) with the oXiris® membrane (p = 0.36). Median first circuit duration was 14 (11.25-23) h for the AN69 ST100 versus 16 (8 -26) for the oXiris® membrane. There was also no difference between the AN69 ST100 or oXiris® membrane circuits using femoral access at 13 (8 -22.5) versus 15.5 (12.5-21.5) h (p = 0.57) or internal jugular access at 28 (13-47) versus 23 (21-29) h (p = 0.79), respectively. The oXiris® heparin-grafted membrane does not appear to prolong circuit life in liver failure patients receiving CRRT without anticoagulation.

UHPLC-MS/MS method for simultaneous quantification of doripenem, meropenem, ciprofloxacin, levofloxacin, pazufloxacin, linezolid, and tedizolid in filtrate during continuous renal replacement therapy.

Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC-MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti-MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples. Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate. The method showed good linearity over wide ranges. Within-batch and batch-to-batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations. This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.

Kinetics of SuPAR hemoadsorption in critical COVID-19 patients on renal replacement therapy

BackgroundSARS-CoV-2 viral infection is associated with a rapid and vigorous systemic inflammatory response syndrome. Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker, both indicative of inflammation and propagating it. Hemoadsorption has been proposed as a potential therapy in COVID-19 patients, therefore the aim of this study is to determine suPAR kinetics during hemoadsoprtion.MethodsThis was a prospective observational study of critical COVID-19 patients, enrolled when hemoperfusion therapy was initiated. Hemoadsorber was integrated into the continuous renal replacement therapy circuit. The first series of suPAR measurements was performed 10 minutes after the start of the session, sampling both incoming and outgoing lines of the adsorber. A second series of the measurements was performed beforefinishing the session with the same adsorber. Statistical significance level was set < 0.05.ResultsThis study included 18 patients. In the beginning of the session the fraction of suPAR cleared across the adsorber was 29.5% [16-41], and in the end of the session it decreased to 7.2% [4-22], 4 times lower, p = 0.003. The median length of session was 21 hours, with minimal duration of 16 hours and maximal duration of 24 hours. The median suPAR before the procedure was 8.71 [7.18-10.78] and after the session was 7.35 [6.53-11.28] ng/ml. There was no statistically significant difference in suPAR concentrations before and after the session (p = 0.831).ConclusionsThis study concluded that in the beginning of the hemoadsorption procedure significant amount of suPAR is removed from the circulation. However, in the end of the procedure there is a substantial drop in adsorbed capacity. Furthermore, despite a substantial amount of suPAR cleared there is no significant difference in systemic suPAR concentrations before and after the hemoadsorption procedure.

Safety and Effectiveness of Veno-Venous Extracorporeal Membrane Oxygenation Combined With Continuous Renal Replacement Therapy.

Patients receiving extracorporeal membrane oxygenation (ECMO) often suffer from acute kidney injury (AKI), requiring continuous renal replacement therapy (CRRT). In our clinical practice, we connected the inlet line of a CRRT machine to the postoxygenator Luer port and the outlet line to the inlet Luer port of the oxygenator. In this case series, we analyzed the interaction between the two machines. Between December 31, 2017, and December 31, 2019, we enrolled 15 patients from the ICU of the San Matteo Hospital, Pavia, Italy. All of them suffered from severe acute respiratory distress syndrome and AKI stage 3. We analyzed 570 hours of CRRT combined with venovenous ECMO and collected 261,751 CRRT data. No discontinuation of CRRT occurred before 48 hours. Most of the alarms occurred within 24 hours of the connection: 22/10,831 (0.2%) showed an outranged inlet pressure, 11/10831 (0.11%) showed an outranged transmembrane pressure, 14/10,831 (0.13%) showed an outranged inlet pressure, and 138/10,831 (1.27%) an outranged effluent pressure. The rate per minute set for the ECMO circuit was correlated with the inlet (β = 5.38; CI, 95% 1.42-9.35; p = 0.008), transmembrane (β = 4.6; CI, 95% 1.97-7.24; p = 0.001), effluent (β = 3.02; CI, 95% 1.15-4.90; p = 0.002), and outlet pressures (β = 597; CI, 95% 2.31-9.63; p = 0.001) of the CRRT circuit. We reported that our configuration could be safe and effective, however well-designed studies would be beneficial for determining the potential risks and benefits.

Cefepime Extraction by Extracorporeal Life Support Circuits

Extracorporeal life support (ECLS) devices are lifesaving for critically ill patients with multi-organ dysfunction. Despite this, patients supported with ECLS are at high risk for ECLS-related complications, including nosocomial infections, and mortality rates are high in this patient population. The high mortality rates are suspected to be, in part, a result of significantly altered drug disposition by the ECLS circuit, resulting in suboptimal antimicrobial dosing. Cefepime is commonly used in critically ill patients with serious infections. Cefepime dosing is not routinely guided by therapeutic drug monitoring and treatment success is dependent upon the percentage of time of the dosing interval that the drug concentration remains above the minimum inhibitory concentration of the organism. Thisex vivostudy measured the extraction of cefepime by continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) circuits. Cefepime was studied in four closed-loop CRRT circuit configurations and a single closed-loop ECMO circuit configuration. Circuits were primed with a physiologic human blood–plasma mixture and the drug was dosed to achieve therapeutic concentrations. Serial blood samples were collected over time and concentrations were quantified using validated assays. Inex vivoCRRT experiments, cefepime was rapidly cleared by dialysis, hemofiltration, and hemodiafiltration, with greater than 96% cefepime eliminated from the circuit by 2 hours. In the ECMO circuits, the mean recovery of cefepime was similar in both circuit and standard control. Mean (standard deviation) recovery of cefepime in the ECMO circuits (n = 6) was 39.2% (8.0) at 24 hours. Mean recovery in the standard control (n = 3) at 24 hours was 52.2% (1.5). Cefepime is rapidly cleared by dialysis, hemofiltration, and hemodiafiltration in the CRRT circuit but minimally adsorbed by either the CRRT or ECMO circuits. Dosing adjustments are needed for patients supported with CRRT.

Cefepime Extraction by Extracorporeal Life Support Circuits.

Extracorporeal life support (ECLS) devices are lifesaving for critically ill patients with multi-organ dysfunction. Despite this, patients supported with ECLS are at high risk for ECLS-related complications, including nosocomial infections, and mortality rates are high in this patient population. The high mortality rates are suspected to be, in part, a result of significantly altered drug disposition by the ECLS circuit, resulting in suboptimal antimicrobial dosing. Cefepime is commonly used in critically ill patients with serious infections. Cefepime dosing is not routinely guided by therapeutic drug monitoring and treatment success is dependent upon the percentage of time of the dosing interval that the drug concentration remains above the minimum inhibitory concentration of the organism. This ex vivo study measured the extraction of cefepime by continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) circuits. Cefepime was studied in four closed-loop CRRT circuit configurations and a single closed-loop ECMO circuit configuration. Circuits were primed with a physiologic human blood-plasma mixture and the drug was dosed to achieve therapeutic concentrations. Serial blood samples were collected over time and concentrations were quantified using validated assays. In ex vivo CRRT experiments, cefepime was rapidly cleared by dialysis, hemofiltration, and hemodiafiltration, with greater than 96% cefepime eliminated from the circuit by 2 hours. In the ECMO circuits, the mean recovery of cefepime was similar in both circuit and standard control. Mean (standard deviation) recovery of cefepime in the ECMO circuits (n = 6) was 39.2% (8.0) at 24 hours. Mean recovery in the standard control (n = 3) at 24 hours was 52.2% (1.5). Cefepime is rapidly cleared by dialysis, hemofiltration, and hemodiafiltration in the CRRT circuit but minimally adsorbed by either the CRRT or ECMO circuits. Dosing adjustments are needed for patients supported with CRRT.

Pharmacological Interventions to Prevent Clotting in Extracorporeal Circuits During Continuous Renal Replacement Therapy

What are the risks and benefits of pharmacological interventions to prevent clotting in extracorporeal circuits during continuous renal replacement therapy (CRRT)?Patients who are critically ill in an intensive care unit often develop kidney complications related to multiple factors such as infection, hypotension, and necessary medications. Acute kidney injury occurs in approximately 11% to 18% of hospitalized patients and contributes to an estimated 1.7 million deaths every year.1 Because these patients are hemodynamically unstable, they cannot tolerate standard dialysis, which is typically a 3- to 4-hour procedure. Instead, continuous dialysis is the treatment of choice, and critically ill patients often tolerate it better. This continuous treatment, known as CRRT, provides opportunities for the health care team to introduce treatment modalities that would otherwise cause waste products and fluid to accumulate within the injured kidneys.2Standard practice is to run CRRT continuously for 24 hours; however, the therapy is often inadvertently stopped for periods of time because of clotting in the circuits. When such clotting occurs, the circuits must be changed immediately. The need to change the circuits not only delays treatment but also takes staff time and adds costs. To maintain the full therapeutic effect of CRRT, reducing any interruptions to therapy is essential.2During CRRT, blood contacts the circuit system, which can activate the coagulation pathway. Pharmacological approaches to avoid clotting in CRRT circuits involve several medications including intravenous anticoagulants (eg, unfractionated heparin [UFH], low-molecular-weight heparin, argatroban, citrate), oral anticoagulants (warfarin), and antiplatelet agents.3 The purpose of this systematic review was to assess the benefits and harms of pharmacological interventions for preventing clotting in extracorporeal circuits during CRRT.This systematic review, conducted by Tsujimoto et al,4 included 34 randomized controlled trials (and some quasi-experimental trials) comprising 1960 adult participants. The main primary outcomes investigated included major bleeding, successful prevention of clotting (defined as not needing a circuit change during the first 24 hours), and death from any cause at day 28. The included studies evaluated many different pharmacological comparisons; the most common were heparin derivatives and citrate. Because citrate and UFH are the most commonly used medications to prevent clotting during CRRT,2 this summary describes only the comparison of these 2 interventions.Tsujimoto et al4 independently assessed the risk of bias for each study, including selection, performance, detection, attrition, reporting, and publication biases. They resolved any disagreements by reviewing the data together and through discussion. For dichotomous outcomes, risk ratios (RRs) with 95% CIs were used as measures of treatment effect between various comparisons and outcomes. The authors also used the internationally approved Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence—high, moderate, low, or very low—for each outcome5: This review showed that, when comparing citrate with UFH to prevent clotting during CRRT, moderate-certainty evidence supports citrate resulting in less major bleeding and having slightly more success at the prevention of clotting.4 The findings from this systematic review align with those of other studies showing that citrate, when compared with UFH, more effectively prolongs the duration of CRRT circuits and reduces the risk of bleeding.6 Currently, several ongoing studies could, once completed or published, be included in similar assessments in future systematic reviews.4The evidence from this systematic review can affect clinical care teams’ decisions when they are creating treatment plans for patients in this population. As nurses caring for critically ill patients, advocating for the best evidence-based treatment remains an important piece of our role. We must always consider the best available evidence and understand the feasibility, appropriateness, meaningfulness, and effectiveness of any intervention to determine whether it is most appropriate to implement in our individual context.

Trends, Advantages and Disadvantages in Combined Extracorporeal Lung and Kidney Support From a Technical Point of View.

Extracorporeal membrane oxygenation (ECMO) provides pulmonary and/or cardiac support for critically ill patients. Due to their diseases, they are at high risk of developing acute kidney injury. In that case, continuous renal replacement therapy (CRRT) is applied to provide renal support and fluid management. The ECMO and CRRT circuits can be combined by an integrated or parallel approach. So far, all methods used for combined extracorporeal lung and kidney support present serious drawbacks. This includes not only high risks of circuit related complications such as bleeding, thrombus formation, and hemolysis, but also increase in technical workload and health care costs. In this sense, the development of a novel optimized artificial lung device with integrated renal support could offer important treatment benefits. Therefore, we conducted a review to provide technical background on existing techniques for extracorporeal lung and kidney support and give insight on important aspects to be addressed in the development of this novel highly integrated artificial lung device.

Validation of a Protocol for Continuous Hemodiafiltration with Regional Citrate Anticoagulation with Omni®

Introduction: Omni® (B Braun, Melsungen, Germany) is able to run continuous renal replacement therapy (CRRT) in continuous veno-venous hemofiltration (CVVH), hemodialysis (CVVHD), and hemodiafiltration (CVVHDF) modes. However, to date, there is no validated protocol to guide the use of Omni® in CVVHDF mode with regional citrate anticoagulation (RCA). Methods: We designed a protocol for CVVHDF-RCA tailored for Omni®. This protocol was tested in patients included in an observational study conducted in our center between January and March 2021. For all study patients, we collected baseline characteristics, laboratory results, CRRT circuit lifespan as well as plasma and effluent samples at 12, 24, 48, and 72 h of CRRT circuit initiation. At each study time point, we computed urea, creatinine, and β2-microglobulin clearance as well as effluent/blood ratios. Data from circuits in CVVHDF-RCA mode are compared with those in standard therapy (CVVHD-RCA) with the same device. Results: We analyzed ten circuits (5 patients) in CVVHDF-RCA mode and 32 (13 patients) in CVVHD-RCA mode. No adverse events related to the therapy were observed. In CVVHDF-RCA mode, median circuit running time was 68 (IQR 8.1) hours versus 46 (IQR 9.0) in CVVHD mode, p = 0.053. Therapy adaptations (dialysate rate and/or blood flow) were required in one (10%) circuit (15.6% in CVVHD mode, p = 0.56). Compared to CVVHD, CVVHDF was able to achieve similar clearance and effluent/blood ratio for urea, creatinine, and β2-microglobulin across the entire duration of circuit lifetime. Conclusion: The proposed protocol for CVVHDF-RCA for Omni® was associated with similar circuit lifetime, number of required adaptations and clearances to standard CVVHD-RCA. It appears to be safe and feasible.