Continuous Venovenous Hemodialysis Research Articles

Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience

PurposeStandard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with β-lactams in critically ill patients, particularly in those with sepsis and septic shock. We assessed the effect of therapeutic drug monitoring-guided (TDM), continuous infusion (CI) and individual dosing of piperacillin/tazobactam (PIP) on PK-target attainment in critically ill patients.MethodsThis is a retrospective, single-center analysis of a database including 484 patients [933 serum concentrations (SC)] with severe infections, sepsis and septic shock who received TDM-guided CI of PIP in the intensive care unit (ICU) of an academic teaching hospital. The PK-target was defined as a PIP SC between 33 and 64 mg/L [fT > 2–4 times the epidemiological cutoff value (ECOFF) of Pseudomonas aeruginosa (PSA)].ResultsPK-target attainment with standard dosing (initial dose) was observed in 166 patients (34.3%), whereas only 49 patients (10.1%) demonstrated target non-attainment. The minimum PK-target of ≥ 33 mg/L was overall realized in 89.9% (n = 435/484) of patients after the first PIP dose including 146 patients (30.2%) with potentially harmful SCs ≥ 100 mg/L. Subsequent TDM-guided dose adjustments significantly enhanced PK-target attainment to 280 patients (62.4%) and significantly reduced the fraction of potentially overdosed (≥ 100 mg/L) patients to 4.5% (n = 20/449). Renal replacement therapy (RRT) resulted in a relevant reduction of PIP clearance (CLPIP): no RRT CLPIP 6.8/6.3 L/h (median/IQR) [SCs n = 752, patients n = 405], continuous veno-venous hemodialysis (CVVHD) CLPIP 4.3/2.6 L/h [SCs n = 160, n = 71 patients], intermittent hemodialysis (iHD) CLPIP 2.6/2.3 L/h [SCs n = 21, n = 8 patients]). A body mass index (BMI) of > 40 kg/m2 significantly increased CLPIP 9.6/7.7 L/h [SC n = 43, n = 18 patients] in these patients. Age was significantly associated with supratherapeutic PIP concentrations (p < 0.0005), whereas high CrCL led to non-target attainment (p < 0.0005). Patients with target attainment (33–64 mg/L) within the first 24 h exhibited the lowest hospital mortality rates (13.9% [n = 23/166], p < 0.005). Those with target non-attainment demonstrated higher mortality rates (≤ 32 mg/L; 20.8% [n = 10/49] ≥ 64 mg/L; 29.4% [n = 79/269]).ConclusionTDM-guided CI of PIP is safe in critically ill patients and improves PK-target attainment. Exposure to defined PK-targets impacts patient mortality while lower and higher than intended SCs may influence the outcome of critically ill patients. Renal function and renal replacement therapy are main determinants of PK-target attainment. These results are only valid for CI of PIP and not for prolonged or intermittent bolus administration of PIP.

Impact of Cytokine Adsorption Treatment in Liver Failure

Sepsis causes life-threatening organ dysfunction and is the leading cause of morbidity and mortality in critically ill patients worldwide. Mortality rate of sepsis is close to 30% to 50% despite better understanding of the pathophysiology of sepsis, and advances in antimicrobial therapy, resuscitation strategies, and mechanical ventilation.Liver failure is characterized by accumulation of potentially toxic substances in the systemic circulation of the patient. Toxic effects of these molecules can induce cellular injuries leading to multiorgan dysfunction. Hydrophobic unconjugated bilirubin and bile acids, hydrophilic conjugated bilirubin, and ammonium are the main toxins accumulated in liver failure.We carried out cytokine adsorbtion (CytoSorb) procedure with continuous venovenous hemodialysis in 12-hour sessions. The biochemical values of the patients before and after the use of the filter were recorded. The parameters compared were as follows: total bilirubin, direct bilirubin, C-reactive protein, leukocyte, neutrophil, alanine aminotransferase, aspartate aminotransferase, creatinine, colloid oncotic pressure, ammonia, gamma-glutamyl transferase, alkaline phosphatase, procalcitonin, hematocrit, hemoglobin, pH, albumin, international normalized ratio, fibrinogen, lactate dehydrogenase, platelet, temperature, changes in vasoactive medication requirement, temperature.According to these results, cytokine adsorption systems can be considered as an option to lower bilirubin levels in cases of liver failure. Its inability to lower ammonia level is considered a disadvantage compared with other bilirubin-lowering methods. Although further studies are needed to compare different methods, cytokine adsorption systems may be considered in treatment planning as it contributes to the treatment of sepsis and hyperbilirubinemia in liver failure patients with sepsis.

Feasibility and safety of combined cytokine adsorption and continuous veno-venous hemodialysis with regional citrate anticoagulation in patients with septic shock.

Septic shock is characterized by severe metabolic and hemodynamic alterations. It is often accompanied by acute kidney injury. A new adjunct treatment is hemoadsorption using a cytokine adsorber in line with continuous veno-venous renal replacement therapy. We studied the feasibility, efficacy, and safety of cytokine adsorption with citrate-anticoagulated continuous veno-venous hemodialysis (regional citrate anticoagulation-continuous veno-venous hemodialysis). In 11 patients with septic shock and acute kidney injury stage 3, we studied 12 cycles of cytokine adsorption and regional citrate anticoagulation-continuous veno-venous hemodialysis. We monitored parameters of citrate anticoagulation, circuit lifetime, laboratory parameters, hemodynamics, and vasopressor demand. Ten out of 12 adsorber/continuous veno-venous hemodialysis circuits reached the target lifetime of 24 h for the adsorber. One system clotted and one was stopped for non-device-related reasons. Nine of the remaining continuous renal replacement therapy circuits reached 72 h lifetime. With default settings for regional citrate anticoagulation, serum ionized calcium and pH were in the normal range. Urea and creatinine were reduced significantly, and norepinephrine dose decreased from 0.47 (±0.09) to 0.16 (±0.04) µg/kg/min (p = 0.016) after 24 h. We show that combined cytokine adsorption/continuous veno-venous hemodialysis is effective to control pH, to reduce urea and creatinine, and to improve hemodynamics by reducing norepinephrine doses in patients with septic shock. It can be applied safely with standard settings of regional citrate anticoagulation rendering sufficiently long filter lifetimes for the adsorber and the continuous veno-venous hemodialysis circuit. Further studies are on the way to investigate whether these effects translate into improved outcomes in septic shock patients.

Intermittent high‐flux albumin dialysis with continuous venovenous hemodialysis for acute‐on‐chronic liver failure and acute kidney injury

Acute-on-chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high-flux single-pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28-day and 90-day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3±1.4]. The baseline MELD-Na score was 37.6±6.6 and decreased to 33.4±8.7 after SPAD/CVVHD (P<0.001). In parallel, the CLIF-C ACLF grade and OF score, estimated at 28- and 90-day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P=0.001-0.032). The 28- and 90-day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n=11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High-performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.

Pharmacokinetics of Micafungin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis With High Cutoff Membranes.

An optimal antifungal therapy for invasive candidiasis in critically ill patients is essential to reduce the high mortality rates. Acute kidney injury is common, and continuous renal replacement therapies are frequently used. Previous studies have demonstrated a lack of effect from different continuous renal replacement techniques on micafungin clearance. However, the use of high cutoff pore size membranes could potentially allow for the loss of albumin and alter micafungin pharmacokinetics. The objective was to explore the pharmacokinetics of micafungin in critically ill patients undergoing continuous venovenous high cutoff membrane hemodialysis (CVVHD-HCO). Prospective observational study performed in critically ill patients treated with 100 mg/d of micafungin and undergoing CVVHD-HCO. CVVHD-HCO sessions were performed using Prisma-Flex monitors and dialyzers with a membrane of polyarylethersulfone of 1.1-m surface area and 45-kDa pore size. Blood samples were collected from arterial prefilter, venous postfilter, and the drainage line ports at 0 (predose), 1, 4, 12, 24 hours after dose, and micafungin concentrations were determined using HPLC-UV. Nine patients (55.6% male; age: 28-80 years) were included. Median (range) of micafungin concentrations in the effluent were <0.2 (<0.2-0.4) mg/L at low (predose) and 0.4 (<0.2-0.7) mg/L at high (1 h) concentrations. The extraction ratio was <12% at each time point. A 2-compartment model best described the time course of plasma concentrations, and body weight was the only covariate that improved the model. This is the first study demonstrating that CVVHD-HCO does not alter the pharmacokinetics of micafungin, and that standard doses of this antifungal can be used.

Continuous renal replacement therapy in Iran; current practice, indications and outcomes in hemodynamically unstable patients

Introduction: Continuous renal replacement therapy (CRRT) is the gold standard renal replacement therapy (RRT) for hemodynamically unstable patients. Objectives: To study the characteristics and survival of patients undergoing CRRT in Iran. Patients and Methods: This is a retrospective study conducted on 58 patients indicated for CRRT at the Shahid-Modarres hospital of Tehran during 2016-2017. Gender, age, underlying diseases, comorbidities, history of surgery, dialysis indication, and survival were gathered by reviewing patients’ medical records. The data was analyzed in SPSS version 21. Results: Sepsis constituted the most common underlying condition at admission. Overall, continuous venovenous hemodialysis (CVVHD) was performed in 72.4% of the patients. Diabetes and hypertension were the most common causes leading to RRT. The most common indication for CRRT was unstable hemodynamic condition. The patients were most frequently referred from ICU (34.5%), emergency department (20.7%), and CCU (15.5%). Conclusion: We here reviewed the characteristics of hemodynamically unstable patients undergoing CRRT. Our findings can help to understand the most important indications for CRRT and to standardize CRRT practice in Iran.

The Role of Supportive Treatment in the Management of Hyperammonemia in Neonates and Infants

Background: The objective of this study is to investigate the efficacy of continuous renal replacement therapy (CRRT), mainly continuous venovenous hemodiafiltration (CVVHDF), and evaluate vasoactive requirements in hyperammonemic neonates and infants. Methods: Patients who underwent CRRT for hyperammonemia were retrospectively analyzed. Measurements and Main Results: Patients in 7 of the encounters were treated solely by CVVHDF. During 3 encounters, patients who received continuous venovenous hemodialysis (CVVHD) were transitioned to CVVHDF. CVVHD was used in 3 encounters. The median 50% reduction time for ammonia was 8 h (range 3–15 h). The median duration of CRRT treatment was 40 h (range 24–89 h). Survival to hospital discharge occurred in 12 encounters (92.3%). Eleven encounters (84.6%) were treated with different vasoactive agents. In those encounters, the median vasoactive medications’ start time was the 6th hours (range 2–60 h) of CRRT. There was no association between the vasoactive index score and pre-dialysis ammonia concentration. Conclusions: CRRT achieves timely control of hypeammonemic states. Hemodynamic instability necessitating intervention with vasoactive medications is a common finding in patients with hyperammonemia.

Hemodynamic efficiency of hemodialysis treatment with high cut-off membrane during the early period of post-resuscitation shock: The HYPERDIA trial

BackgroundAfter resuscitation of cardiac arrest (CA), an acute circulatory failure occurs in about 50% of cases, which shares many characteristics with septic shock. Most frequently, supportive treatments are poorly efficient to prevent multiple organ failure and death. We evaluated whether an early plasma removal of inflammatory mediators using high cut-off continuous veno-venous hemodialysis (HCO-CVVHD) could improve hemodynamic status and outcome of these patients. Patients and methodsWe performed a randomized open-label trial. Patients with post-cardiac arrest shock (defined as requirement of norepinephrine or epinephrine infusion > 1 mg/h) were included. The experimental group received 2 distinct sessions of HCO-CVVHD during the first 48 h following ICU admission. The control group received continuous veno-venous hemofiltration (CVVH) with standard membranes if needed. The primary endpoint was the delay to shock resolution asssessed by the length of catecholamine infusion. Number of vasopressors-free days at day 28, arterial blood pressure measures every 6-hours, daily fluid balance and mortality (ICU and day-28) were evaluated as secondary endpoints. Results35 patients were included: 17 (median age 68.4, 59% male) in the HCO-CVVHD group and 18 (median age 66.3, 83% male) in the control group. Baseline characteristics did not differ between the two groups. Day-28 mortality rate was 64.7% and 72.2% in the HCO-CVVHD and control group, respectively (p = 0.72). Probability of vasopressors discontinuation over time was similar in the two groups (p for logrank test = 0.67). Number of day-28 catecholamine-free days was 25.1 [0, 26.5] and 24.5 [0, 26.2] in the HCO-CVVHD and control group, respectively (p = 0.65). No difference was observed regarding the daily-dose of vasopressors, arterial pressure profile and fluid balance. ConclusionIn cardiac arrest patients, HCO-CVVHD did not decrease the lenght of post-resuscitation shock and had no significant effect on hemodynamic profile. RegistrationNCT00780299.

The efficacy of renal replacement therapy strategies for septic-acute kidney injury: A PRISMA-compliant network meta-analysis.

Background:Renal replacement therapy (RRT) is the main treatment for patients with sepsis-induced acute kidney injury (SAKI). However, the choice of RRT strategy remains controversial.Objective:This study assessed the effectiveness of RRT variants in SAKI patients by a network meta-analysis.Methods:This study searched the literature in the PubMed, EmBase, and Cochrane Library databases up to August 18, 2018. The outcomes of the analysis were the survival rate, renal recovery rate, intensive care unit (ICU) duration, and hospital duration.Results:Twenty-two articles were included in the analysis. The results showed that only the negative control was inferior to the regimens of RRT with polymyxin B-immobilized fiber (PMXF), PMXF alone, continuous venovenous hemofiltration (CVVH), CVVH plus alkaline phosphatase (AP), continuous venovenous hemodialysis (CVVHD), high-volume CVVH, and extra high-volume CVVH in terms of the survival rate. According to the surface under the cumulative ranking , RRT with PMXF (84.4%) and PMXF (84.3%) were the treatments most likely to improve the survival rate among SAKI patients, followed by CVVH plus AP (69%). Continuous venovenous hemodiafiltration (CVVHDF), extra high-volume CVVHDF, intermittent venovenous hemodiafiltration (IVVHDF), and low-volume CVVHDF resulted in very similar survival rates. CVVH plus AP conferred relative advantages in the renal recovery rate and ICU duration.Conclusion:CVVH, CVVHD, and their derived RRT strategies can improve survival rates in SAKI patients, but there is no significant difference among the RRT strategies. There was also no significant difference in the survival rate among CVVHDF, IVVHDF, and their derived strategies. More high-quality randomized controlled trials with large sample sizes are needed for further research.

THU-048-Intermittent high-flux albumin dialysis with continuous venovenous hemodialysis for acute-on-chronic liver failure and acute kidney injury

THU-048-Intermittent high-flux albumin dialysis with continuous venovenous hemodialysis for acute-on-chronic liver failure and acute kidney injury

Continuous veno-venous hemodialysis and suspected pacemaker malfunction on telemetry monitoring

Continuous veno-venous hemodialysis and suspected pacemaker malfunction on telemetry monitoring

Effect of continuous venovenous haemodialysis on outcome and pharmacokinetics of arsenic species in a patient with acute promyelocytic leukaemia and acute kidney injury.

This study presents outcome and pharmacokinetics of arsenic trioxide (ATO) metabolites in patients on continuous venovenous haemodialysis (CVVHD). Of 3 acute promyelocytic leukaemia patients receiving CVVHD in management of acute kidney injury, only 1 patient was included. The patient presented disseminated intravascular coagulation and acute kidney injury before induction therapy was conducted. CVVHD was performed and ATO was initiated. Species of ATO metabolites in plasma and effluent were analysed using high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry. Plasma concentrations of AsIII , monomethylarsonic acid and dimethylarsinic acid with CVVHD were lower than those without CVVHD. Area under the concentration-time curve from 0 to the last sample with quantifiable concentration of AsIII without CVVHD was significantly higher than that with CVVHD (292.10ngh/mL vs 195.86ngh/mL, P=.037), which were not observed for monomethylarsonic acid and dimethylarsinic acid. Dialysate saturation of arsenic species was remarkable, especially for AsIII . Complete remission was achieved and renal function recovered. In this study, ATO can be used safely and effectively to treat acute promyelocytic leukaemia patients undergoing CVVHD without dose adjustment.

ACUsmart Continuous Renal Replacement Therapy Platform: Multicenter Pilot Study for Technical and Clinical Assessment (A.M.P. Study)

Background: ACUsmart (Medica S.P.A., Italy) is a new-generation, continuous renal replacement therapy (CRRT) machine for critically ill patients with acute kidney injury. We designed a multicenter international pilot study to provide a description of outlines of the ACUsmart system, evaluation aspects of functionality, usability, and feasibility, discriminating reasons of possible treatment’s withdrawals or discontinuations and highlighting strong and weak points of the machine. Methods: Data of 23 CRRT (and 11 plasma exchange) treatments were collected from 4 intensive care units. Parameters such as treatment duration, downtime, delivered dose, and number and type of alarms were recorded. The general perception of the machine was quantified through the administration of a survey to each component of the evaluating staff. Results: A total treatment time of 447 h was carried with ACUsmart. Eleven continuous veno-venous hemofiltration, 4 continuous veno-venous hemodialysis , and 8 continuous veno-venous hemodiafiltration were performed. The average percentage of net treatment duration with respect to total treatment duration was 92.37%. The mean prescribed dose and delivered dose were 26.33 and 24.10 mL/kg/h, respectively. In general, the machine was rated by users involved as practical and easy to use, although few components need to be slightly improved. Conclusion: ACUsmart is a new multifunctional machine that meets most of the features required in a fourth-generation CRRT equipment.

Volatile Organic Compounds in Patients With Acute Kidney Injury and Changes During Dialysis.

To characterize volatile organic compounds in breath exhaled by ventilated care patients with acute kidney injury and changes over time during dialysis. Prospective observational feasibility study. Critically ill patients on an ICU in a University Hospital, Germany. Twenty sedated, intubated, and mechanically ventilated patients with acute kidney injury and indication for dialysis. Patients exhalome was evaluated from at least 30 minutes before to 7 hours after beginning of continuous venovenous hemodialysis. Expired air samples were aspirated from the breathing circuit at 20-minute intervals and analyzed using multicapillary column ion-mobility spectrometry. Volatile organic compound intensities were compared with a ventilated control group with normal renal function. A total of 60 different signals were detected by multicapillary column ion-mobility spectrometry, of which 44 could be identified. Thirty-four volatiles decreased during hemodialysis, whereas 26 remained unaffected. Forty-five signals showed significant higher intensities in patients with acute kidney injury compared with control patients with normal renal function. Among these, 30 decreased significantly during hemodialysis. Volatile cyclohexanol (23 mV; 2575th, 19-38), 3-hydroxy-2-butanone (16 mV, 9-26), 3-methylbutanal (20 mV; 14-26), and dimer of isoprene (26 mV; 18-32) showed significant higher intensities in acute kidney impairment compared with control group (12 mV; 10-16 and 8 mV; 7-14 and not detectable and 4 mV; 0-6; p < 0.05) and a significant decline after 7 hours of continuous venovenous hemodialysis (16 mV; 13-21 and 7 mV; 6-13 and 9 mV; 8-13 and 14 mV; 10-19). Exhaled concentrations of 45 volatile organic compounds were greater in critically ill patients with acute kidney injury than in patients with normal renal function. Concentrations of two-thirds progressively decreased during dialysis. Exhalome analysis may help quantify the severity of acute kidney injury and to gauge the efficacy of dialysis.

Antiepileptic Overdose

ABSTRACTAntiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Common signs of toxicity of these drugs are central nervous system manifestations such as altered sensorium, lethargy, ataxia, and nystagmus. Some ingestions can paradoxically precipitate seizures and even status epilepticus. Sodium valproate can cause hyperammonemic encephalopathy and cerebral edema. Carbamazepine is implicated in cardiac arrhythmias and hyponatremia. Phenobarbital causes sedation, respiratory depression, and hypotension. In suspected overdose, apart from the routine laboratory tests, serum levels of the drug should be sent. Serial levels should be measured, as drug toxicity can be prolonged. Treatment of all these overdoses begins with stabilization of airway, breathing, and circulation, and endotracheal intubation being performed to protect the airway in patients with altered mental status. For decontamination, a single dose of activated charcoal should be given. Multidose of activated charcoal may be useful in phenytoin, carbamazepine, and phenobarbital overdose. Naloxone and carnitine are indicated in valproate overdose. Carbamazepine overdose can cause a widened QRS complex and arrhythmias, which can be treated with sodium bicarbonate. Forced alkaline diuresis is no longer advocated for phenobarbital poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup have formulated guidelines for extracorporeal removal of all these drugs. In most cases, hemodialysis is preferred. Other modalities include charcoal hemoperfusion (especially for carbamazepine) or continuous venovenous hemodialysis. Patients who ingest long-acting preparations should be monitored for longer periods.How to cite this articleMurty S. Antiepileptic Overdose. Indian J Crit Care Med 2019;23(Suppl 4):S290–S295.

Metformin Toxicity in Acute Kidney Injury. A Rare Cause of Severe Lactic Acidosis

Metformin a biguanide derivative is the preferred initial pharmacologic agent for the treatment of type 2 diabetes mellitus per current guidelines of the American Diabetes Association. It is prescribed to an estimated 120 million people worldwide. Type B lactic acidosis is a reported but rare side effect of Metformin use. Serum Metformin level is not routinely monitored or available in most hospitals, but it can be a useful test to confirm the diagnosis and guide future use of Metformin in at risk patients. We present a case of a 78-year old African American diabetic female on prescribed dose of Metformin with no history of kidney disease who presented with acute encephalopathy and hemodynamic instability. Her laboratory data showed acute kidney injury (AKI) with severe lactic acidosis (LA). She required large amount of intravenous bicarbonate infusions and urgent initiation of Continuous Veno-Venous Hemodialysis (CVVHD) due to severe refractory metabolic acidosis. Her serum Metformin level sent 12 hours after initiation of CVVHD was still critically elevated at 19 mcg/ml. Her acidosis and AKI started to resolve after 48 hours of CVVHD with resolution of encephalopathy as well. Her renal function returned to baseline and she was eventually discharged home, but Metformin was not resumed back.

Tigecycline in critically ill patients on continuous renal replacement therapy: a population pharmacokinetic study

BackgroundTigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking.MethodsEleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n = 8) or hemodiafiltration (CVVHDF, n = 3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT.ResultsA two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45–94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69 L/h, CLCVVHDF: 2.71 L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3 L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ≥ 0.88 for minimal inhibitory concentration (MIC) values ≤ 0.5 mg/L and similar to patients without AKI.ConclusionsDespite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT.Trial registrationEudraCT, 2012–005617-39. Registered on 7 August 2013.

Optimized Calcium Supplementation Approach for Regional Citrate Anticoagulation

Background: It has been confirmed that regional citrate anticoagulation (RCA) plays an effective role in extracorporeal anticoagulation. The current trial-and-error calcium supplementation approach, with intensive monitoring of calcium levels, restricts the widespread use of RCA. Therefore, this study aimed to optimize the calcium supplementation approach for RCA. Methods: Patients requiring RCA treatment for various reasons were included. Citrate was infused into the arterial port, and the ionized calcium levels in the extracorporeal circulation tubes and body were monitored to maintain them within the target range. Linear regression equations between the clearance of non-protein bound calcium (n-Ca) and prescribed effluent rate were determined; the ratio of the n-Ca concentration to total calcium concentration (fa) after the infusion of citrate was also calculated. Then, we estimated a simplified calcium supplementation approach. Results: Positive correlations were found between the clearance of n-Ca and effluent rate both during continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemofiltration (CVVH; R²: 0.66 and 0.65, respectively, p < 0.01). The fa values at the pre-filter point and after infusion of citrate were constants, but the values differed from CVVHD to CVVH. For CVVHD, fa was 0.93, and for CVVH, fa was 0.80. Using the extracorporeal removal characteristics of n-Ca, the amount of extracorporeally removed calcium per mmol per hour can be quantified with a simplified equation. Conclusion: The optimized calcium supplementation approach could provide a more precise and practical method to estimate the amount of extracorporeal calcium removal with regard to different modalities and dosages of RCA.

Continuous Veno-Venous Hemodialysis Using the Cardio-Renal Pediatric Dialysis Emergency MachineTM: First Clinical Experiences

We report the first worldwide experience with continuous veno-venous hemodialysis (CVVHD) in children using the last generation Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM)^TM device. Thirteen children received 1,008 h of CVVHD during 95 sessions, using a 0.15 (n = 7) or a 0.25 m² (n = 6) hemofilter. The median weight was 3 kg (interquartile range [IQR] 2.5–6.2). In 10 patients, CVVHD was conducted using a 5 Fr double-lumen central vascular access, whereas in 3 children, bigger sizes were used (6.5 and 8 Ch). The median prescribed Qb was 17 mL/min (IQR 10–29.5), with a median Qd of 10 mL/min. Circuits were primed with 5% albumin in 12 out of 13 patients, using anticoagulation with heparin in all 13 cases. The median delivered/prescribed time ratio yielded a 100% result (95–100%). The most common cause for “downtime” was clotting that however occurred in only 3% of all treatments. Survivals at continuous renal replacement therapy discontinuation and ICU discharge were 100 and 69% respectively. The CARPEDIEM^TM machine allowed successful delivery of diffusive blood purification modality to very small patients, using small catheters, no blood primes, and excellent concordance between delivered and prescribed treatment duration.

Cytokine Clearances in Critically Ill Patients on Continuous Renal Replacement Therapy

Background/Aims: We sought to quantify any differences in cytokine clearance between continuous venovenous hemofiltration (CVVH-convective) compared to continuous venovenous hemodialysis (CVVHD-diffusive). Methods: We conducted a 20 patient, multicenter, prospective, open-label randomized trial (CVVH or CVVHD) at continuous renal ­replacement therapy (CRRT) initiation. Blood, urine, and effluent were collected at 0, 4, 24, and 48 h after initiation of CRRT. Serum electrolytes, cytokines levels, and clearances were measured. Cytokines studies included IL-1β, IL-1RA, IL-6, IL-10, and TNFα. Results: We randomized 20 patients to receive CRRT. After 4 h of CRRT there was no difference in total cytokine levels or change in cytokine concentrations across the 2 groups. With the exception of IL-1 RA, all cytokines levels decreased across patient groups regardless of modality. There was no significant difference in cytokine concentration across CRRT modality for any time point. Conclusion: Within the first 4 h of CRRT initiation, there is no significant difference between cytokine or solute clearance between CVVH and CVVHD.