Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial

Background Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D. Methods Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325–0.4 mmol/L vs. 0.2–0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D). Results 35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs − 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was − 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th–75th percentile 140–384) to 162 (111–265) pg/ml (p = 0.002); oxPTH from 192 (124–353) to 154 pg/ml (87–231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups. Conclusions A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group. Trial registration ClinicalTrials.gov: NCT02194569. Registered 18 July 2014.

Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy

(1) Purpose of this study: determination of adsorption and transmembrane clearances (CLTM) of imipenem and relebactam in ex vivo continuous hemofiltration (CH) and continuous hemodialysis (CHD) models. These clearances were incorporated into a Monte Carlo Simulation (MCS), to develop drug dosing recommendations for critically ill patients requiring continuous renal replacement therapy (CRRT); (2) Methods: A validated ex vivo bovine blood CH and CHD model using two hemodiafilters. Imipenem/relebactam and urea CLTM at different ultrafiltrate/dialysate flow rates were evaluated in both CH and CHD. MCS was performed to determine dose recommendations for patients receiving CRRT; (3) Results: Neither imipenem nor relebactam adsorbed to the CRRT apparatus. The CLTM of imipenem, relebactam, and urea approximated the effluent rates (ultrafiltrate/dialysate flow rates). The types of hemodiafilter and effluent rates did not influence CLTM except in a dialysis flow rate of 1 L/h and 6 L/h in the CHD with relebactam (p < 0.05). Imipenem and relebactam 200 mg/100 mg every 6 h were sufficient to meet the standard time above the MIC pharmacodynamic targets in the modeled CRRT regimen of 25 kg/mL/h. (4) Conclusions: Imipenem and relebactam are not removed by adsorption to the CRRT apparatus, but readily cross the hemodiafilter membrane in CH and CHD. Dosage adjustment of imipenem/relebactam is likely required for critically ill patients receiving CRRT.

Sequential Blood Purification for Pediatric Fatal Toxic Epidermal Necrolysis: A Case Series

<b><i>Background:</i></b> Extracorporeal therapy that included therapeutic plasma exchange (TPE) or continuous hemofiltration (CHF) for toxic epidermal necrolysis (TEN) syndrome was used in small number of patients. We aimed to describe the sequential mode of combined application of CHF and TPE in 3 TEN patients with multiple organ dysfunction (MODS) in pediatric intensive care unit. <b><i>Methods:</i></b> Three patients with fatal TEN received sequential CHF and TPE due to unsatisfactorily conventional treatments. CHF was initiated and performed on a daily basis with 35–50 mL/kg.h replacement fluid at the rate of 3–5 mL/kg.min blood flow. CHF was temporarily interrupted for TPE, which was performed with exchange 1–1.5-fold of one body calculated plasma volume in each section. <b><i>Results:</i></b> All 3 fatal TEN (with &#x3e;30% involvement of body surface and MODS) following unsuccessful treatment with corticosteroids and intravenous immunoglobulin. Antibiotics were suspected in the TEN-triggered drugs. The range number of TPE sessions was 3–5 and the duration of CHF was from 120 h to 202 h. After initiation of TPE and CHF, blistering with extensive epidermal necrosis halted and the skin re-epithelialized within 2 weeks. Serum C-reactive protein, procalcitonin, tumor necrosis factor-α , and interlukin-6 decreased and percentage of natural killer cells increased in surviving children. Two patients survived to discharge and one case died due to nosocomial infection with multidrug-resistant <i>Acinetobacter baumannii.</i> <b><i>Conclusion:</i></b> After sequential TPE and CHF, skin lesions and inflammatory response improved in TEN. Our result indicates extracorporeal therapy could be used as an alternative modality for fatal pediatric TEN.

PMMA-Based Continuous Hemofiltration Modulated Complement Activation and Renal Dysfunction in LPS-Induced Acute Kidney Injury

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy of polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) in modulating systemic and tissue immune activation in a swine model of LPS-induced AKI. After 3 h from LPS infusion, animals underwent to PMMA-CVVH or polysulfone (PS)-CVVH. Renal deposition of terminal complement mediator C5b-9 and of Pentraxin-3 (PTX3) deposits were evaluated on biopsies whereas systemic Complement activation was assessed by ELISA assay. Gene expression profile was performed from isolated peripheral blood mononuclear cells (PBMC) by microarrays and the results validated by Real-time PCR. Endotoxemic pigs presented oliguric AKI with increased tubulo-interstitial infiltrate, extensive collagen deposition, and glomerular thrombi; local PTX-3 and C5b-9 renal deposits and increased serum activation of classical and alternative Complement pathways were found in endotoxemic animals. PMMA-CVVH treatment significantly reduced tissue and systemic Complement activation limiting renal damage and fibrosis. By microarray analysis, we identified 711 and 913 differentially expressed genes with a fold change &gt;2 and a false discovery rate &lt;0.05 in endotoxemic pigs and PMMA-CVVH treated-animals, respectively. The most modulated genes were Granzyme B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, and SERPINB-1 that were closely related to sepsis-induced immunological process. Our data suggest that PMMA-based CVVH can efficiently modulate immunological dysfunction in LPS-induced AKI.

Lung ultrasound score assessing the pulmonary edema in pediatric acute respiratory distress syndrome received continuous hemofiltration therapy: a prospective observational study

Background Lung ultrasound score is a potential method for determining pulmonary edema in acute respiratory distress syndrome (ARDS). Continuous renal replacement therapy (CRRT) has become the preferred modality to manage fluid overload during ARDS. The aim of this study was to evaluate the value of lung ultrasound (LUS) score on assessing the effects of CRRT on pulmonary edema and pulmonary function in pediatric ARDS. Methods We conducted a prospective cohort study in 70 children with moderate to severe ARDS in a tertiary university pediatric intensive care unit from January 2016 to December 2019. 37 patients received CRRT (CRRT group) and 33 patients treated by conventional therapy (Non-CRRT group). LUS score was measured within 2 h identified ARDS as the value of 1st, and the following three days as the 2nd, 3rd, and 4th. We used Spearman correlation analysis to develop the relationship between LUS score and parameters related to respiratory dynamics, clinical outcomes as well as daily fluid balance during the first four days after ARDS diagnosed. Results The 1st LUS score in CRRT group were significantly higher than Non-CRRT group (P < 0.001), but the LUS score decreased gradually following CRRT (P < 0.001). LUS score was significantly correlated with Cdyn (dynamic lung compliance) (1st: r = − 0.757, 2nd: r = − 0.906, 3rd: r = − 0.885, 4th: r = − 0.834), OI (oxygenation index) (1st: r = 0.678, 2nd: r = 0.689, 3rd: r = 0.486, 4th: r = 0.324) based on 1st to 4th values (all P < 0.05). Only values of the 3rd and 4th LUS score after ARDS diagnosed were correlated with duration of mechanical ventilation [1st: r = 0.167, P = 0.325; 2nd: r = 0.299, P = 0.072; 3rd: r = 0.579, P < 0.001; 4th: r = 0.483, P = 0.002]. LUS score decreased from 22 (18–25) to 15 (13–18) and OI decreased from 15.92 (14.07–17.73) to 9.49 (8.70–10.58) after CRRT for four days (both P < 0.001). Conclusions LUS score is significantly correlated with lung function parameters in pediatric ARDS. The improvement of pulmonary edema in patient with ARDS received CRRT can be assessed by the LUS score. Trial registration CCTR, ChiCTR-ONC-16009698. Registered 1 November 2016, prospectively registered, http://www.chictr.org.cn/edit.aspx?pid=16535&htm=4. This study adheres to CONSORT guidelines.

Lung ultrasound score assessing the pulmonary edema in pediatric acute respiratory distress syndrome received continuous hemofiltration therapy: A prospective observational study

Background: Lung ultrasound score is a potential method for determining pulmonary edema in acute respiratory distress syndrome (ARDS). Continuous renal replacement therapy (CRRT) has become the preferred modality to manage fluid overload during ARDS. The aim of this study was to evaluate the value of lung ultrasound (LUS) score on assessing the effects of CRRT on pulmonary edema and pulmonary function in pediatric ARDS. Methods: We conducted a prospective cohort study in 70 children with moderate to severe ARDS in a tertiary university pediatric intensive care unit from January 2016 to December 2019. 37 patients received CRRT (CRRT group) and 33 patients treated by conventional therapy (Non-CRRT group). LUS score was measured within 2 hours identified ARDS as the value of 1st，and the following three days as the 2nd, 3rd, and 4th. We used Spearman correlation analysis to develop the relationship between LUS score and parameters related to respiratory dynamics, clinical outcomes as well as daily fluid balance during the first four days after ARDS diagnosed.Results: The 1st LUS score in CRRT group were significantly higher than Non-CRRT group (P < 0.001), but the LUS score decreased gradually following CRRT (P < 0.001). LUS score was significantly correlated with Cdyn (1st: r =-0.757, 2nd: r =-0.906, 3rd: r =-0.885, 4th: r =-0.834), OI (1st: r =0.678, 2nd: r =0.689, 3rd: r =0.486, 4th: r =0.324) based on 1st to 4th values (all P <0.05). Only values of the 3rd and 4th LUS score after ARDS diagnosed were correlated with duration of mechanical ventilation [1st: r = 0.167, P = 0.325; 2nd: r = 0.299, P = 0.072; 3rd: r = 0.579, P < 0.001; 4th: r = 0.483, P = 0.002]. LUS score decreased from 22 (18 - 25) to 15 (13 - 18) and OI decreased from 15.92 (14.07 -17.73) to 9.49 (8.70 -10.58) after CRRT for four days (both P < 0.001).Conclusions: LUS score is significantly correlated with lung function parameters in pediatric ARDS. The improvement of pulmonary edema in patient with ARDS received CRRT can be assessed by the LUS score.Trial registration: CCTR, ChiCTR-ONC-16009698. Registered 1 November 2016, prospectively registered, http://www.chictr.org.cn/edit.aspx?pid=16535&htm=4. This study adheres to CONSORT guidelines.

Lung ultrasound score assessing the pulmonary edema in pediatric acute respiratory distress syndrome received continuous hemofiltration therapy: A prospective observational study

Background: Lung ultrasound score is a potential method for determining pulmonary edema in acute respiratory distress syndrome (ARDS). Continuous renal replacement therapy (CRRT) has become the preferred modality to manage fluid overload during ARDS. The aim of this study was to evaluate the value of lung ultrasound (LUS) score on assessing the effects of CRRT on pulmonary edema and pulmonary function in pediatric ARDS. Methods: We conducted a prospective cohort study in 70 children with moderate to severe ARDS in a tertiary university pediatric intensive care unit from January 2016 to December 2019. 37 patients received CRRT (CRRT group) and 33 patients treated by conventional therapy (Non-CRRT group). LUS score was measured within 2 hours identified ARDS as the value of 1st，and the following three days as the 2nd, 3rd, and 4th. We used Spearman correlation analysis to develop the relationship between LUS score and parameters related to respiratory dynamics, clinical outcomes as well as daily fluid balance during the first four days after ARDS diagnosed.Results: The 1st LUS score in CRRT group were significantly higher than Non-CRRT group (P < 0.001), but the LUS score decreased gradually following CRRT (P < 0.001). LUS score was significantly correlated with Cdyn (1st: r =-0.757, 2nd: r =-0.906, 3rd: r =-0.885, 4th: r =-0.834), OI (1st: r =0.678, 2nd: r =0.689, 3rd: r =0.486, 4th: r =0.324) based on 1st to 4th values (all P <0.05). Only values of the 3rd and 4th LUS score after ARDS diagnosed were correlated with duration of mechanical ventilation [1st: r = 0.167, P = 0.325; 2nd: r = 0.299, P = 0.072; 3rd: r = 0.579, P < 0.001; 4th: r = 0.483, P = 0.002]. LUS score decreased from 22 (18 - 25) to 15 (13 - 18) and OI decreased from 15.92 (14.07 -17.73) to 9.49 (8.70-10.58) after CRRT for four days (both P < 0.001).Conclusions: LUS score is significantly correlated with lung function parameters in pediatric ARDS. The improvement of pulmonary edema in patient with ARDS received CRRT can be assessed by the LUS score.Trial registration: CCTR, ChiCTR-ONC-16009698. Registered 1 November 2016, prospectively registered, http://www.chictr.org.cn/edit.aspx?pid=16535&htm=4. This study adheres to CONSORT guidelines.

Lung ultrasound score assessing the pulmonary edema in pediatric acute respiratory distress syndrome received continuous hemofiltration therapy: A prospective observational study

Background: Lung ultrasound score is a potential method for determining pulmonary edema in acute respiratory distress syndrome (ARDS). Continuous renal replacement therapy (CRRT) has become the preferred modality to manage fluid overload during ARDS. The aim of this study was to evaluate the value of lung ultrasound (LUS) score on assessing the effects of CRRT on pulmonary edema and pulmonary function in pediatric ARDS. Methods: We conducted a prospective cohort study in 70 children with moderate to severe ARDS in a tertiary university pediatric intensive care unit from January 2016 to December 2018. 37 patients received CRRT (CRRT group) and 33 patients treated by conventional therapy (Non-CRRT group). LUS score was measured within 2 hours identified ARDS as the value of 1st，and the following three days as the 2nd, 3rd, and 4th. We used Spearman correlation analysis to develop the relationship between LUS score and PaO2/FiO2, dynamic lung compliance (Cdyn), PaCO2, oxygen index (OI), as well as between the change in daily fluid balance volume and the change in LUS score during CRRT.Results: The 1st lung ultrasound score in CRRT group were significantly higher than Non-CRRT group (P < 0.001), but the lung ultrasound score decreased gradually following CRRT (P < 0.001). LUS score was significantly correlated with PaO2/FiO2 (1st: r =-0.800, 2nd: r =-0.807, 3rd: r =-0.703, 4th: r =-0.584), Cdyn (1st: r =-0.757, 2nd: r =-0.906, 3rd: r =-0.885, 4th: r =-0.834), and OI (1st: r =0.678, 2nd: r =0.689, 3rd: r =0.486, 4th: r =0.324) based on 1st to 4th values (all P<0.05). LUS score decreased from 22 (18 - 25) to 15 (13 - 18) and PaO2/FiO2 promoted from 106.00 (96.00 - 121.50) mmHg to 160.00 (142.50 - 173.00) mmHg after CRRT for four days (both P < 0.001).Conclusions: LUS score is significantly correlated with lung function parameters in pediatric ARDS. The improvement of pulmonary edema in patient with ARDS received CRRT can be assessed by the LUS score.