Continuous veno-venous hemofiltration using a phosphate-containing replacement fluid in the setting of regional citrate anticoagulation

Purpose: The need for prolonged anticoagulation and the occurrence of hypophosphatemia are well known drawbacks of continuous renal replacement therapies (CRRT). The aim was to evaluate the effects on acid-base status and serum phosphate of a regional citrate anticoagulation (RCA) protocol for continuous veno-venous hemofiltration (CVVH) combining the use of citrate with a phosphate-containing replacement fluid. Methods: In a small cohort of heart surgery patients undergoing CRRT for acute kidney injury, we adopted an RCA-CVVH protocol based on a commercially available citrate solution (18 mmol/l) combined with a recently introduced phosphate-containing replacement fluid (HCO3- 30 mmol/l, phosphate 1.2), aimed at preventing phosphate depletion. Results: In 10 high bleeding-risk patients, the RCA-CVVH protocol provided an adequate circuit lifetime (46.8 ± 30.3 h) despite the adoption of a low citrate dose and a higher than usual target circuit Ca2+ (≤0.5 mmol/l). Acid-base status was adequately maintained without the need for additional interventions on RCA-CVVH parameters and without indirect sign of citrate accumulation [(pH 7.43 (7.41-7.47), bicarbonate 24.4 mmol/l (23.2-25.6), BE 0 (-1.5 to 1.1), calcium ratio 1.97 (1.82-2.01); median (IQR)]. Serum phosphate was steadily maintained in a narrow range throughout RCA-CVVH days [1.1 mmol/l (0.9-1.4)]. A low amount of phosphorus supplementation (0.9 ± 2 g/day) was required in only 30% of patients. Conclusions: Although needing further evaluation, the proposed RCA-CVVH protocol ensured a safe and effective RCA without electrolyte and/or acid-base derangements. CRRT-induced hypophospha-temia was prevented in most of the patients by the adoption of a phosphate-containing replacement solution, minimizing phosphate supplementation needs. © 2013 Wichtig Editore

Preventing Continuous Renal Replacement Therapy-Induced Hypophosphatemia: An Extended Clinical Experience with a Phosphate-Containing Solution in the Setting of Regional Citrate Anticoagulation

Aims: To evaluate the efficacy and safety of a commercially available phosphate-containing solution for continuous renal replacement therapy (CRRT) in preventing CRRT-related hypophosphatemia. Methods: In heart surgery patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), we combined an 18 mmol/l citrate solution with a phosphate-containing (1.2 mmol/l) dialysate/replacement fluid evaluating the incidence of hypophosphatemia and the need for parenteral phosphorus supplementation. Results: In 75 patients on RCA-CVVHDF, the mean filter life was 53.9 ± 33.6 h. Regardless of baseline levels, phosphoremia was progressively corrected and maintained in a narrow normality range throughout RCA-CRRT days (after 72 h: 1.14 ± 0.25 mmol/l). Considering the whole CRRT period, 45 out of 975 (4.6%) serum phosphorus determinations met the criteria for mild (<0.81 mmol/l) or moderate (<0.61 mmol/l) hypophosphatemia; severe hypophosphatemia (<0.32 mmol/l) never occurred. After 72 h 88% of the patients were normophosphatemic, 9% hyperphosphatemic and 3% hypophosphatemic. Conclusions: RCA-CVVHDF with a phosphate-containing solution enabled the maintenance of phosphorus levels within normophosphatemic range in most of the patients, minimizing the occurrence of CRRT-related hypophosphatemia

Humoral and T-cell mediated response after administration of mRNA vaccine BNT162b2 in frail populations

Patients with frailty are considered to be at greater risk to get severe infection from SARS-CoV-2. One of the most effective strategies is vaccination. In our study we evaluated both the humoral immune response elicited by the vaccination at different time points, and the T-cell response in terms of interferon (IFN)-γ production in frail patients and healthy donors. Fifty-seven patients (31 patients undergoing hemodialysis and 26 HIV positive subjects) and 39 healthcare workers were enrolled. All participants received two doses of the mRNA vaccine BNT162b2. Healthcare workers showed a significantly higher antibody titer than patients twenty-one days after the first dose (p&nbsp;&lt;&nbsp;0.001). From the same time point we observed for both groups a decay of the antibody levels with a steeper slope of decline in the patients group. Regarding T-cell response the only significant difference between non-reactive and reactive subjects was found in median antibody levels, higher in the responders group than in non-responders. The healthcare workers seem to better respond to the vaccination in terms of antibodies production; the lack of T-cell response in about 50% of the participants seems to suggest that in our study population both humoral and cell-mediated response decline over time remarking the importance of the booster doses, particularly for frail patients

DISCREPANZA TRA DOSE DIALITICA PRESCRITTA E DOSE DIALITICA SOMMINISTRATA NELLE TERAPIE SOSTITUTIVE RENALI CONTINUE (CRRT)

I periodi di interruzione del trattamento (down time) e la discrepanza tra dose dialitica prescritta e dose somministrata sono spesso riportati come un limite delle CRRT. Tutta- via, a nostra conoscenza, non sono disponibili studi che abbiano quantificato, oltre al down time, la “perdita” di dose determinata dalle numerose interruzioni dei flussi che si verificano durante CRRT per le cause più svariate (allarmi, sostituzione sacche, accesso vascolare). Scopo. Valutare, durante CRRT e senza considerare i periodi di down time, l’entità della discrepanza tra dose dialitica prescritta e dose somministrata cercando di identificare, inoltre, le reali cause di interruzione del trattamento. Metodi. In pazienti (pz) “critici” con IRA sottoposti a CRRT sono stati utilizzati monitor Pri- smaflex Hospal in grado di trasferire su “PC Card” le seguenti informazioni rilevate ogni minuto o al verificarsi di eventi: modifiche flussi, allarmi, pressioni (arteriosa, pre-filtro, venosa, TMP), soluzioni (quantità effettiva dialisato e/o reinfusione, rimozione liquidi, effluente). L’analisi dei dati era finalizzata a determinare: durata CRRT, dose dialitica somministrata, cause di conclusione CRRT. Quest’ultime erano messe a confronto con quelle segnalate sulla scheda infermieristica. Era prescritta una dose dialitica iniziale di 35 ml/kg/h (flusso effluente), modificabile secondo esigenze cliniche. Membrane: AN69 o PAES. Protocollo anticoagulazione: eparina standard o metodiche alternative (senza eparina, citrato). Risultati. In 36 pz (22 M, 14 F, età 64.6±10.8) sono stati esaminati 153 circuiti (104 CV- VHDF, 31 CVVHD, 18 CVVH) per un totale di 185 gg di CRRT. Durata circuiti: 29.1±20.6 h (mediana 22.9) senza differenze significative tra le metodiche (CVVHDF 29.6±19.6; CVVHD 27.4±19.7; CVVH 29.1±22.5). Cause conclusione: coagulazione (32%), malfun- zionamento CVC (24%), malfunzionamento o errore bilance (18%), allarme trasduttori- sensori (11%), programmata (7%), procedure diagnostico-terapeutiche (4%), aria circuito (4%). La coagulazione del circuito riportata sulla scheda infermieristica (51.6%) era netta- mente sovrastimata rispetto a quanto emerso dall’analisi dei dati (32%). La differenza tra dose dialitica somministrata e dose prescritta era significativa (28.6±7.5 vs 30.6±7.8 ml/ Kg/h, p10%. Conclusioni. La nostra esperienza evidenzia che le interruzioni temporanee della CRRT, le- gate alla gestione del circuito, rappresentano una causa spesso trascurata di discrepanza tra dose dialitica prescritta e dose somministrata. L’entità della “perdita” di dose potrebbe apparire modesta ma, sommandosi al down time, merita di essere rilevata potendo assu- mere significato nel singolo pz e variare notevolmente in relazione a cause tecniche e/o esperienza dell’operatore. La possibilità di individuare con maggiore precisione le cause di sospensione della CRRT potrebbe ridurre il rischio di modificazioni non necessarie del protocollo di anticoagulazione

PROTOCOLLO DI ANTICOAGULAZIONE REGIONALE CON CITRATO IN CVVH: RISULTATI PRELIMINARI.

Introduzione. L’anticoagulazione (AC) rappresenta uno dei problemi più controversi nelle CRRT. In pazienti ad alto rischio emorragico è possibile effettuare la CRRT senza eparina o con protocolli di AC alternativi. Tra questi l’AC regionale con citrato sembra essere il più efficace. Scopo. Valutare, in pazienti “critici” con IRA sottoposti a CVVH, efficacia e tollerabilità dell’AC regionale con una soluzione di citrato a bassa concentrazione. Pazienti e Metodi. In pazienti post-cardiochirurgici ad elevato rischio emorragico, ab- biamo adottato l’AC regionale con citrato come protocollo di prima scelta. La CVVH è stata effettuata utilizzando, in pre-diluizione, la soluzione Prismocitrate 10/2 (Hospal) (citrato trisodico 10 mmol/l-acido citrico 2 mmol/l). La velocità iniziale di reinfusione era impostata in relazione al flusso ematico (Qb) al fine di mantenere una concentrazione di citrato nel circuito di 2-3 mmol/l e modificata in base ai controlli di Ca++ circuito (c-Ca++) eseguiti ogni 6h (target < 0.4 mmol/l). La dose dialitica prescritta era ottenuta aggiun- gendo, in post-diluizione, una soluzione con tampone bicarbonato (30 mEq/l) e Ca++ (2 mmol/l). I valori di Ca++ sistemico (s-Ca++) erano mantenuti al target di 1.1-1.25 mmol/l tramite infusione di CaCl2 (10%) in linea venosa centrale. Risultati. Sono stati sottoposti a CVVH con citrato 7 pazienti (età 69.4±9.5) con IRA post-cardiochirurgica (SOFA score 15.2±2.8, SOFA cardiovascolare 2.5±1.5). Parame- tri CVVH: dose dialitica 35.3±2.2 ml/Kg/h; Qb 138.6±28.3 mL/min; Q Prismocitrate 10/2: 2100±200 ml/h; carico metabolico di citrato 15.4±1.6 mmol/h; infusione CaCl2 6±0.8 mL/h. Sono state effettuate 1795 h di CVVH (n=39 circuiti). La durata dei circuiti è stata 46±33.5 h (mediana 38 h). In nessun caso la CVVH è stata interrotta per coagu- lazione dell’emofiltro. Cause di interruzione: 23% malfunzionamento CVC, 28% errore o problema tecnico, 15% procedure diagnostiche/terapeutiche, 13% interruzione pro- grammata, 21% altre cause. Nessun paziente ha presentato complicanze emorragiche. I valori di c-Ca++ e di s-Ca++ sono stati agevolmente mantenuti entro il target (0.37±0.07 e 1.21±0.14 mmol/l, rispettivamente). Il controllo metabolico è stato soddisfacente (Cr 1.71±0.9 e BUN 36.1±14.3 mg/dl). Nella maggior parte dei pazienti la persistenza di acidosi metabolica ha richiesto la somministrazione di NaHCO3 (110.7±109.5 mEq/die) nonostante in nessun caso siano stati evidenziati segni indiretti di accumulo di citrato (Calcemia totale /s-Ca++ ratio costantemente < 2.5). La velocità di infusione di CaCl2 è stata 4.2±1.2 ml/h (Ca elemento 2.86±0.8 mmol/h). Conclusioni. Nella nostra esperienza, la CVVH con citrato ha consentito di ottenere, in assenza di complicanze emorragiche ed elettrolitiche, una durata dei circuiti compatibile con un controllo metabolico ottimale limitando i periodi di down-time legati a problemi di coagulazione. Emerge, tuttavia, la necessità di una modulazione del bilancio dei tamponi attraverso l’impiego di soluzioni di citrato e/o bicarbonato a concentrazioni più elevate

Migration and risk: net migration in marginal ecosystems and hazardous areas

The potential for altered ecosystems and extreme weather events in the context of climate change has raised questions concerning the role that migration plays in either increasing or reducing risks to society. Using modeled data on net migration over three decades from 1970 to 2000, we identify sensitive ecosystems and regions at high risk of climate hazards that have seen high levels of net in-migration and out-migration over the time period. This paper provides a literature review on migration related to ecosystems, briefly describes the methodology used to develop the estimates of net migration, then uses those data to describe the patterns of net migration for various ecosystems and high risk regions. The study finds that negative net migration generally occurs over large areas, reflecting its largely rural character, whereas areas of positive net migration are typically smaller, reflecting its largely urban character. The countries with largest population such as China and India tend to drive global results for all the ecosystems found in those countries. Results suggest that from 1970 to 2000, migrants in developing countries have tended to move out of marginal dryland and mountain ecosystems and out of drought-prone areas, and have moved towards coastal ecosystems and areas that are prone to floods and cyclones. For North America results are reversed for dryland and mountain ecosystems, which saw large net influxes of population in the period of record. Uncertainties and potential sources of error in these estimates are addressed

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid–base status and phosphate supplementation needs

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid--base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5--3 mmol/l) and a higher than usual target circuit-Ca2+ (<=0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca2+ in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 +/- 36.5 vs 53 +/- 32.6 hours). Protocol A required additional bicarbonate supplementation (6 +/- 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid--base balance without additional interventions: pH 7.43 (7.40--7.46), Bicarbonate 25.3 (23.8--26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 +/- 2.4 g/day) and in only 30% of group B patients (0.5 +/- 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97--1.45 mmol/l, IQR)

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come