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Objective: Mitochondrial DNA (mtDNA) reportedly has diagnostic and predictive value in critically ill patients. This study evaluated the diagnostic and predictive value of mtDNA in patients undergoing continuous venovenous haemofiltration (CVVH). Methods: We consecutively enrolled 41 patients who were treated with CVVH from September 2018 to December 2019. Prefilter, postfilter, and ultrafiltrate samples were collected before the initiation of CVVH (T0) and 6 and 12 h after CVVH. The total mass removal rate (Mtr), total mass adsorption rate (Mad), plasma clearance (PC), and sieving coefficient (SC) were calculated based on the mass conservation principle. Results: The plasma mtDNA concentration in patients at T0 prefilter was higher than that in healthy volunteers [13.77 (12.45–15.86) vs. 1.24 (1.15–1.34) ng/mL, P < 0.001]. Prefilter, but not postfilter or ultrafiltrate, mtDNA decreased during CVVH (P = 0.02), with a total CVVH clearance of 25.9%. The postfilter and ultrafiltrate mtDNA levels were lower than the prefilter level at each time point (P < 0.05 for all). The Mtr, Mad, PC, and SC did not change over time (P > 0.05 for all). Conclusions: Plasma mtDNA in critically ill patients was significantly affected by CVVH. Trial registration: Retrospectively registered on 20 August 2019 at ClinicalTrials.gov (NCT04083482). [ABSTRACT FROM AUTHOR]

Cefiderocol is a broad‐spectrum cephalosporin antibiotic and is indicated in patients with difficult‐to‐treat Gram‐negative bacterial infections. Cefiderocol is applied as a 2–4‐times daily prolonged 3‐h infusion. The therapeutic target of cefiderocol suggests that continuous infusion (CI) may be advantageous, since it is more likely to achieve 100% of time of the unbound concentration above the minimal inhibitory concentration (MIC). However, limited information on cefiderocol as CI has been assessed. We present a case of a critically ill 37‐year‐old woman with continuous venovenous haemofiltration (CVVH) treated with a CI of cefiderocol for multidrug‐resistant Pseudomonas aeruginosa. She received 4 g per 24 h, in accordance with the recommendations for the total daily dose during CVVH with an effluent flow rate of 2.1–3 L/h. We evaluated intraperitoneal, plasma arterial pre‐ and postfilter and ultrafiltrate (urine) total cefiderocol concentrations and discussed the pharmacokinetics in respect to the CVVH settings. The predicted unbound plasma concentrations during CI resulted in 6.8–9.5‐fold higher concentrations than the adopted MIC of 2 mg/L for cefiderocol against P. aeruginosa. The optimal time of the unbound concentration >MIC target of cefiderocol was met during the sampling period, suggesting adequate exposure during the total treatment period. The obtained intraperitoneal concentration indicated adequate cefiderocol exposure at the site of infection. Continuous infusion of 4 g cefiderocol per 24 h led to sufficient plasma concentrations in our anuric critically ill patient treated with CVVH. This case is supportive to the use of cefiderocol as continuous infusion. [ABSTRACT FROM AUTHOR]

Introduction: To date, the prognosis of patients with sepsis and underlying chronic kidney disease (CKD) had been poor. However, the impact of preseptic renal function on the short-term prognosis of patients with extremely severe septic shock with acute kidney injury (AKI) that requires renal replacement therapy (RRT) is unclear. Methods: Of the septic shock cases treated at the intensive care unit for ≥48 h, 131 adults who were diagnosed as septic AKI and underwent continuous venovenous hemodiafiltration were retrospectively analyzed. The relationships of demographic, clinical, and laboratory data with mortality were evaluated, and the independent risk factors for death were identified. Results: The median age of the subjects was 73 (range, 63–80) years, and 76 (58%) were men. The rate of mortality was significantly higher among patients with CKD (n = 42) than in those without CKD (n = 89) (43% vs. 22%, p < 0.016). On univariate and multivariate logistic regression analyses, the associated factors and independent predictors of death were Sequential Organ Failure Assessment score (odds ratios [ORs] 1.151, 95% confidence intervals [CIs] 1.026–1.293, p = 0.017, and OR 1.129, 95% CI 1.003–1.271, respectively); baseline estimated glomerular filtration rate (OR 0.986, 95% CI 0.975–0.997, p = 0.016, and OR 0.983, 95% CI 0.970–0.996, respectively); and lactic acid (OR 1.094, 95% CI 1.005–1.190, p = 0.038, and OR 1.110 CI 1.015–1.215, respectively). Conclusion: Reduced baseline renal function may be a factor for poor short-term prognosis in severe septic AKI cases requiring RRT. [ABSTRACT FROM AUTHOR]

Invasive species related to climate change and/or globalization may be associated with novel forms of kidney disease. This is the case for wasps. Several species of Asian wasps are increasingly found in America (e.g. Asian giant hornet, Vespa mandarinia) and Europe (e.g. yellow-legged Asian hornet, V. velutina ; black shield hornet, V. bicolor ; and Oriental hornet, V. orientalis). Some of these species have been associated with human deaths and acute kidney injury. The literature on wasps and acute kidney injury is scarce and mostly originates from Asia, so nephrologists outside Asia are not familiar with this health problem. In a recent issue of ckj , Liu et al. describe a simple, four-item Wasp Sting Severity Score (WSS) developed from 1131 wasp sting patients. Vespa mandarinia and V. velutina were among those causing hospitalization, although most cases were caused by the black-bellied hornet (V. basalis). Liu et al. propose that a WSS ≥3 should guide early (<24 h after stings) plasma exchange, as plasma exchange was associated with lower mortality in severely affected patients but continuous venovenous haemofiltration and haemoperfusion were not. The WSS will require external validation. This manuscript should raise awareness about the potentially fatal consequences of stings by wasp species making their way into America and Europe. [ABSTRACT FROM AUTHOR]

Background. Lacosamide and levetiracetam are commonly used in critically ill patients, who need an antiepileptic treatment in addition to several other medications. Since both drugs are eliminated via the kidneys, dosage has to be adapted to renal function especially in renal replacement therapy (RRT). In 2016 recommendations of dosage in this condition were based on three case reports only. Aim. To elucidate the current data basis for recommendations on the dosage of Lacosamide and levetiracetam in patients on renal replacement therapy. Material and methods. A search in MEDLINE and Web of Science with several core terms was performed. Papers reporting on doses and concentrations of lacosamide or levetiracetam in patients with renal replacement therapy were analysed. Results and discussion. One phase-I study and three case reports concerning lacosamide and one case series with 22 patients and nine case reports concerning levetiracetam were identified. Whether 200 mg Lacosamide twice/day results in trough concentrations at least in the lower therapeutic range depends on the replacement rate used in continuous venovenous haemofiltration. Peritoneal dialysis seems to remove only a small portion of levetiracetam. Levetiracetam (1000 mg) every 12 hours may generate a trough concentration in the lower therapeutic range in continuous venovenous haemofiltration. Conclusion. Due to the sparse and low quality data, current recommendations on dosing lacosamide or levetiracetam in patients undergoing renal replacement therapy have to be considered with caution and therapeutic drug monitoring may be useful in guiding patient management. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: There is a lack of data regarding therapeutic drug monitoring (TDM) of antitubercular agents in the setting of continuous venovenous haemofiltration (CVVH). We describe TDM results of numerous antitubercular agents in a critically ill patient during CVVH and haemodialysis. Case summary: A 49‐year‐old man was initiated on treatment for disseminated Mycobacterium tuberculosis. During hospital admission, the patient developed critical illness and required renal replacement therapy. TDM results and pharmacokinetic calculations showed adequate serum concentrations of rifampin, ethambutol and amikacin during CVVH and of rifampin, pyrazinamide, ethambutol and levofloxacin during intermittent haemodialysis. What is new and conclusion: The presence of critical illness and renal replacement therapy can induce pharmacokinetic changes that may warrant vigilant TDM to ensure optimal therapy. To our knowledge, this is the first report to describe TDM for several antitubercular agents during CVVH in a critically patient with disseminated M. tuberculosis. [ABSTRACT FROM AUTHOR]

Guidelines on the use of dialysis treatment in patients with chronic kidney disease (CKD) and TPM (Topiramate) intoxication are controversial. A 51-year-old man with epilepsy and CKD was carried to our emergency department for dysuria and sickness. He chronically assumed TPM 100 mg 3/day. Creatinine level was 2.1 mg/dL, blood urea nitrogen 70 mg/dL, and inflammation indexes were increased. We started empirical antibiotic therapy and rehydration. The day two he had diarrhea and an acute insurgence of dizziness, confusion, and bicarbonate levels reduction. Brain CT resulted negative for acute events. During the night his mental status worsened, and urinary output results were about 200 mL in 12h. EEG showed desynchronized brain bioelectric activity. Thereafter, there was an episode of seizure and then anuria, hemodynamic instability, and loss of consciousness. Creatinine value was 5.39 mg/dL with a serious metabolic acidosis non-anion gap. We decided to start 6-hours Sustained Low Efficiency Hemo-Dia-Filtration (SLE-HDF). We assisted in the recovery of consciousness and later in the improvement of kidney function after 4 hours of treatment. TPM levels before SLE-HDF resulted in 123.1 µg/mL. At the end of treatment resulted in 30 µg/mL. To our knowledge, this is the first report of TPM involuntary intoxication in a patient affected by CKD who survived such a high TPM concentration treated with renal replacement therapy. SLE-HDF resulted in moderate elimination of TPM and acidemia resolution, continuous monitoring patient's vital parameters in relation to his hemodynamic instability, since blood flow and dialysate flow are lower than conventional hemodialysis., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Background: To evaluate the efficacy and safety of continuous renal replacement therapy (CRRT) modalities with regional sodium citrate anticoagulation (RCA) in children., Methods: This retrospective study was conducted at the paediatric intensive care unit of Hunan Children's Hospital in China. Medical records of paediatric patients hospitalised for RCA-CRRT between April 2017 and March 2021 were reviewed. Patients received continuous venovenous haemodialysis, continuous venovenous haemofiltration (CVVH), or continuous venovenous haemodiafiltration (CVVHDF)., Results: Patients on continuous venovenous haemodialysis ( n  = 2) were excluded because of their small sample size. The remaining participants were divided into CVVH and CVVHDF groups; 80 patients received CRRT, with 40 and 62 sessions in the CVVH and CVVHDF groups, respectively. The filtre lifespan was longer in the CVVHDF group than in the CVVH group (median value [interquartile range]; 47 [15] hours vs. 35 [17.5] hours; p  = 0.029). Compared with the CVVHDF group, the hazard ratio for filtre lifespan in the CVVH group was 3.023 (95% confidence interval 1.820-5.023, p  < 0.001). There were no significant differences in ionised calcium levels of the circuits between the two groups at different time points ( p  < 0.05). Metabolic alkalosis, hyperlactataemia, hypocalcaemia, and hypercalcaemia occurred in both groups, with metabolic alkalosis being the most common complication. No patients in either group experienced sodium citrate accumulation or hypernatraemia. Inter-group differences in the incidence of these complications were not statistically significant ( p  > 0.05)., Conclusions: Our results suggest that CVVHDF is a better option for RCA-CRRT than CVVH.

• Data on polymyxin B pharmacokinetics (PK) in patients undergoing continuous renal replacement therapy are very limited. • Population PK models were performed with 53 patients undergoing continuous venovenous haemofiltration (CVVH). • Clearance of polymyxin B was higher among patients on CCVH compared with patients off CVVH, accounting for 65% of total polymyxin B clearance. • A loading dose of polymyxin B 200 mg plus a fixed maintenance dose of 150 mg q12h for patients on CVVH would be an optimal regimen. Antibiotic dosing in critically ill patients undergoing continuous renal replacement therapy is considered challenging. This study aimed to analyse the population pharmacokinetics of polymyxin B in patients receiving continuous venovenous haemofiltration (CVVH), and to optimize individual dosing regimens in specific clinical scenarios. Patients treated with CVVH and polymyxin B for multi-drug-resistant Gram-negative bacterial infections were enrolled from two hospitals. Blood samples were collected during and outside CVVH, and assayed using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Phoenix NLME software. In total, 53 patients were included. The area under the concentration curve across 24 hours at steady state (AUC ss,24h) of polymyxin B during CVVH was 27.94 ± 10.92 mg‧h/L, which was significantly lower than that outside CVVH (77.89 ± 35.66 mg‧h/L) (P =1.65 × 10−8). The population pharmacokinetic model revealed that CVVH significantly increased the clearance of polymyxin B. Monte Carlo simulations showed that for patients on CVVH, a loading dose of 200 mg plus a fixed maintenance dose of 150 mg every 12 h had a high probability of achieving AUC ss,24h of 50–100 mg•h/L and the pharmacokinetic/pharmacodynamic target with a minimum inhibitory concentration ≤0.5 mg/L. For patients undergoing CVVH, high doses of polymyxin B and a dose-adjustment regimen based on therapeutic drug monitoring should be considered to improve efficacy. [ABSTRACT FROM AUTHOR]

Background: There is ongoing controversy concerning optimum anticoagulation and buffering in continuous venovenous haemofiltration (CVVH). Regional anticoagulation with trisodium citrate also acting as a buffer in the replacement fluid has several advantages and disadvantages over prefilter citrate administration alone. We analysed a large cohort of patients with acute kidney injury (AKI) treated by the former method and hypothesized that it is safe and efficacious. Methods: Patients admitted at the intensive care unit with AKI and a high bleeding risk, without exclusion of liver disease, treated by CVVH with citrate in a custom-made replacement solution were prospectively included. Patient and CVVH characteristics, including citrate accumulation, were evaluated in outcome groups. A standardized mortality rate (SMR) was calculated using the simplified acute physiology score II. Results: Ninety-seven patients were included; metabolic control was adequate and did not differ between outcome groups, apart from lower pH/bicarbonate in non-survivors. Citrate accumulation was proven in 9% and was timely identified. These patients had about threefold higher plasma transaminases and higher CVVH dose and mortality. The hospital mortality was 60% with a SMR of 1.1 (95% confidence interval 0.90-1.40): age and hyperlactatemia, rather than CVVH-characteristics and citrate accumulation, predicted mortality in multivariable analysis. Conclusion: In critically ill, patients with AKI at high risk of bleeding, CVVH with citrate-containing replacement solution is safe and efficacious. The risk for citrate accumulation is 9% and best predicted by levels of transaminases. It carries, when citrate is discontinued, no attributable mortality. [ABSTRACT FROM AUTHOR]

Background. Reduced haemocompatibility and early filter failure during continuous venovenous haemofiltration (CVVH) can be attributed to various aspects from filter engineering to rheological problems. Still, little is known about the impact of acidaemia and hypoxaemia on th haemocompatibility of a CVVH. In a porcine model, weinvestigated blood and coagulation parameters, filter performance and blockage of filter capillaries to assess the impact of acidaemia and hypoxaemia on haemocompatibility. Methods. Pigs were assigned to three groups (n = 6). One group received mixed acidaemia (pH 7.2) by acid infusion (0.2 M of lactic acid and 0.2 M HCl diluted in normal saline) and low tidal volume ventilation (6-8 mL/kg-1), one group underwent an additional hypoxaemia (pH 7.2; PaO2 <70 mmHg) and another was treated with normal saline and normoventilation (control group; pH 7.4). Toaccelerate biocompatibility reactions, CVVH was operated with reinfusion of the filtrate to the venous line for 3 h based on standardized heparinization. Results. Acidaemia led to a contradictory pattern with respect to prothrombin time (prolongation), activated partial thrombin time and activated clotting time (acceleration). In comparison to normal pH homeostasis, acidaemia led to increasing activation markers such as terminal complement complex marker sC5b-9, thrombin-anti-thrombin complexes (TAT) and D-dimers. Additional hypoxaemia intensified activation with regard to TAT and complement complex marker sC5b-9. Platelet counts suffered from acidaemia and a tendency for higher rates of blocked hollow fibres was found.Conclusion. Acidaemia led to deteriorated haemocompatibility reactions to a CVVH circuit. The coagulation pattern developed towards complications for the coagulatory state. [ABSTRACT FROM AUTHOR]

Background: Acute renal failure (ARF) still bears a poor prognosis with mortality rates up to 70% and the ideal form of renal replacement therapy (RRT) remains controversial. The purpose of this study was to conduct a systematic review and meta-analysis of all randomized controlled trials (RCT) to examine the effect of dialysis modality (IHD: Intermittent haemodialysis; CRRT: continuous renal replacement therapy) on survival of patients with ARF and to also study the effect of each modality on dialysis dependence (DD). Methods: Using and combining two comprehensive search themes (ARF and RRT), we searched electronic databases from 1969 through September of 2007, supplemented by a manual review of abstracts from nephrology meetings and reference lists of review articles. All RCT comparing IHD with CRRT in adult patients with ARF and with explicit reporting of mortality were included. The primary outcome was the pooled estimate of the odds ratio (OR) of mortality for patients with ARF treated with CRRT versus IHD. The secondary outcome was OR of DD at time of discharge for surviving patients. Results: A total of 587 studies were identified, 554 of which were excluded on initial screening. Analysis of the nine RCT (1635 patients) showed an OR of 0.89 (0.63–1.24) for survival in patients on CRRT. Limiting the analysis to the seven RCT published after the year 2000, revealed an OR of 0.72 (0.58–0.90). The OR of all the studies before 2000 was 1.06 (95% CI 0.67–1.68), as compared with OR of 0.61 (95% CI 0.50–0.74) for studies post-2000. Four studies showed a significantly lower risk of DD among the CRRT group and none showed higher OR for DD. When analysis was limited to the RCT, the OR for DD was 1.07 (0.47–2.39), suggesting no difference in DD between the modalities. Conclusions: Similar to previously reported meta-analyses, we did not find a significant effect of CRRT on the OR of survival. The progressive reduction in the OR of survival with CRRT relative to IHD might reflect progressive improvements in IHD. The OR of DD was not affected by mode of RRT. In conclusion, compared with IHD, CRRT does not offer an advantage with regards to survival or DD in ARF. Considering its cost and potential disadvantages, it is imperative to identify the subset of patients with ARF that would potentially derive maximum benefit from CRRT. This will require large, adequately powered studies with sufficient follow-up. [ABSTRACT FROM AUTHOR]

Aim: Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score. Methods: Septic patients with an end-organ dysfunction or septic shock were randomized to receive 6 h of CVVH (ultrafiltration dose of 2 L/h equivalent to about 35 mL/kg per hour or HVHF (ultrafiltration dose of 100 mL/kg per hour or 6 L/h, whichever was higher). The sequential organ failures were scored for the 24 hours preceding recruitment; at day 1, day 7, at discharge from the intensive care unit and at hospital discharge. Results: Thirty-three patients were enrolled. Fifteen received HVHF and 18 received CVVH. The serum IL-6 levels (pg/mL) at baseline were similarly elevated in both groups ( P = 0.745). The HVHF group showed a significant reduction after 6 h of treatment with a median interquartile range (IQR) of 20.62 (49.21) pg/mL ( P = 0.025) with no similar result in the CVVH group. Non-survivors showed a higher baseline serum IL-6 compared with the survivors (median (IQR) 172.31 (261.34) vs 58.9 (104.21), P = 0.044). In the HVHF group there was a positive association between the IL-6 levels at 6 h with the SOFA scores at day 1 ( r = 0.392, P = 0.001) but not at day 7. After 6 h of treatment in the HVHF group there was a direct correlation between the IL-6 levels and number of hospital days ( r = 0.90, P = 0.040). The maximum SOFA scores were persistently recorded before treatment. The SOFA scores reduced in both groups from baseline to day 7 (HVHF P = 0.048; CVVH P = 0.006). The SOFA scores at day 1 is significantly higher in the non-survivors compared with the survivors ( P = 0.038). Conclusions: High-volume haemofiltration at 6 L/h may seem to successfully remove some inflammatory cytokines in septic patients. The improvement in the SOFA scores at day 7 promises benefit of continuous renal replacement therapy in septic patients, but after 20 days this effect may be lost. In addition, the baseline serum IL-6 and IL-1-ra were independent predictors of a poor outcome as reflected by the higher SOFA scores at day 1. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to test the feasibility of using commercial preparations of replacement and citrate anticoagulation solution in continuous venovenous haemofiltration (CVVH) in a safe, efficient and simple manner. Methods: Retrospective review of the database of a large continuous renal replacement therapy programme that uses a standardized prescription of high ultrafiltrate CVVH with commercial solutions for replacement fluid and regional citrate anticoagulation was performed. Results: Records of 28 patients who underwent 91 CVVH sessions were analysed. Median circuit survival time was 37 (59.5–15.5) h and the 48 h survival probability was 40%. Bleeding or metabolic complications were not noted, and the procedure was simple to administer. Conclusion: Continuous venovenous haemofiltration using commercial preparations of replacement fluid and citrate anticoagulation can be safe, efficient and simple. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to elucidate the most practical and effective laboratory measurement for monitoring citrate in critically ill patients undergoing citrate-anticoagulated continuous venovenous haemofiltration (CVVH). Methods: This observational study was performed at the mixed medical and surgical intensive care unit of a regional teaching hospital. The study population comprised ten consecutive critically ill patients with acute renal failure and indication for haemofiltration with the use of regional anticoagulation with citrate. Serum samples for the measurement of citrate and total and ionised calcium were taken from the pre- and post-filter compartments and from the arterial circulation of patients during citrate-anticoagulated CVVH. Results: Receiver operating characteristic (ROC) curve analysis showed that for detecting citrate overdose (defined as a citrate concentration >1.0 mmol/L) the best cut-off limits for total/ionised calcium and ionised calcium were 2.1 and 0.8 mmol/L, respectively. Sensitivity and specificity for the cut-off limit of 2.1 for total/ionised calcium were 89% and 100%, and 84% and 100%, respectively, for the cut-off limit of 0.8 mmol/L for ionised calcium. Conclusions: In patients without liver insufficiency, total/ionised calcium performed slightly better than ionised calcium in detecting elevated citrate concentrations. However, because of the simplicity of its measurement, ionised calcium is preferred. Measurement of citrate is not necessary. Clin Chem Lab Med 2006;44:962–6. [ABSTRACT FROM AUTHOR]

To determine an adequate dosage of ciprofloxacin in critically ill medical patients on continuous venovenous haemofiltration, we studied the pharmacokinetics of ciprofloxacin in eight critically ill medical patients with renal failure treated with continuous venovenous heamofiltration using polysulfone membranes. Three of those patients also presented with severe liver dysfunction. For comparison, three patients with approximately normal renal function and two patients with impaired renal function were included. During haemofiltration, plasma concentrations of ciprofloxacin were variable. In all critically ill patients ciprofloxacin elimination was significantly slowed; the mean half-life was similarly prolonged to about 14 h in patients on haemofiltration and those with approximately normal renal function. in critically ill patients with impaired renal function not on haemofiltration, the mean half-life was longest. Ciprofloxacin clearance by haemofiltration was a quarter of the total clearance. Although a unique dose recommendation can hardly be made because of the high variability of pharmacokinetics during haemofiltration, a daily dose of 800 mg (400 mg b.i.d.)in average can be regarded as appropriated for reaching a target plasma concentration of 2 to 3 μg/mL (mean concentration). Because the half-life of ciprofloxacin was further prolonged by the presence of liver cirrhosis, the dose should be reduced to 600 mg in patients on haemofiltration with concomitant severe liver dysfunction. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the early haemodynamic effects of continuous arteriovenous haemofiltration (CAVH) with those of continuous venovenous haemofiltration(CVVH) in normal and endotoxic piglets, within the framework of a two-period cross-over trial. Sixteen domestic piglets (weight 6-18 kg) underwent 1 h of CAVH followed by 1 h of CVVH or 1 h of CVVH followed by 1 h of CAVH. Six were pre-treated with a graded endotoxin infusion to simulate clinical sepsis. The main measurements included: heart rate; mean arterial (MAP), pulmonary artery, central venous and pulmonary artery occlusion pressures; thermodilution cardiac output; and calculated systemic (SVRI) and pulmonary vascular resistance indexes. Each measurement was performed immediately before and 30 min after commencement of each technique of filtration. Commencement of haemofiltration in normal piglets caused minimal haemodynamic effects. In endotoxic piglets, commencement of filtration, whether CAVH or CVVH, caused a haemodynamic change which was significantly more pronounced in the first filter (SVRI −39%, MAP −32%) than the second filter (SVRI +22%, MAP +0.9%) (SVRI, P=0.01, first filter vs. second) (MAP, P=0.009 first filter vs. second). In conclusion, there were no significant differences between the early haemodynamic effects of CAVH and CVVH in normal or endotoxic piglets. The haemodynamic effects of either technique may become more significant in the presence of sepsis. [ABSTRACT FROM AUTHOR]

Background. The optimal drug dosing in anuric patients undergoing continuous haemofiltration is a difficult task. More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments. Methods. Drug elimination of various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute renal failure treated by pump-assisted continuous venovenous haemofiltration (CVVH). Concentrations of serial blood and ultrafiltrate samples were determined by HPLC or by fluorescence polarization immunoassay. Total body clearance (CL) and haemofilter clearance (CLf) rates were determined by standard model-independent equations. Data from published literature on fractions not bound to proteins (fu), non-renal drug clearance fractions (Qo) and normal clearance values (CLn) were used to derive a pharmacokinetic model, taking into account drug removal by ultrafiltration and by non-renal clearance. Results. A total of 37 treatment periods was studied. Blood flow through the haemofilters was 100 ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2±4.6 (range 3.2–22.1) ml/min. Acceptable correlations of calculated and measured haemofilter clearances and total body clearances were obtained. Conclusions. Total body clearance in anuric patients during CVVH is predictable from drug properties, which are generally known. The individual dosage requirements may be calculated by multiplying Qo+fu UFR/CLn with the dose considered appropriate in the absence of renal impairment. [ABSTRACT FROM PUBLISHER]