Regional citrate anticoagulation (RCA) is now recommended over systemic heparin for continuous renal replacement therapy in patients without contraindications. Its use is likely to increase ...throughout the world. However, in the absence of citrate blood level monitoring, the diagnosis of citrate accumulation, the most feared complication of RCA, remains relatively complex. It is therefore commonly mistaken with other conditions. This review aims at providing clarifications on RCA-associated acid-base disturbances and their management at the bedside. In particular, the authors wish to propose a clear distinction between citrate accumulation and net citrate overload.
Hemoadsorption with CytoSorb Poli, Elettra C.; Rimmelé, Thomas; Schneider, Antoine G.
Intensive care medicine,
02/2019, Letnik:
45, Številka:
2
Journal Article
Recenzirano
Several extracorporeal blood purification techniques have been proposed in critically ill patients with sepsis and sepsis-like syndromes. Despite theoretical benefits, recent Surviving Sepsis ...Campaign guidelines have not formulated a recommendation in favour of or against such techniques and urged for further research 1. In this context, CytoSorb® (CytoSorbents Corporation, NJ, USA) was recently licensed for extracorporeal cytokine removal within the European Union (EU).
Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and ...organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery.
We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care (n = 15) or CytoSorb® HA (n = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors' activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII).
Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors' adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes.
CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts.
ClinicalTrials.gov NCT02775123 . Registered 17 May 2016.
Purpose
Choice of renal replacement therapy (RRT) modality may affect renal recovery after acute kidney injury (AKI). We sought to compare the rate of dialysis dependence among severe AKI survivors ...according to the choice of initial renal replacement therapy (RRT) modality applied continuous (CRRT) or intermittent (IRRT).
Methods
Systematic searches of peer-reviewed publications in MEDLINE and EMBASE were performed (last update July 2012). All studies published after 2000 reporting dialysis dependence among survivors from severe AKI requiring RRT were included. Data on follow-up duration, sex, age, chronic kidney disease, illness severity score, vasopressors, and mechanical ventilation were extracted when available. Results were pooled using a random-effects model.
Results
We identified 23 studies: seven randomized controlled trials (RCTs) and 16 observational studies involving 472 and 3,499 survivors, respectively. Pooled analyses of RCTs showed no difference in the rate of dialysis dependence among survivors (relative risk, RR 1.15 95 % confidence interval (CI) 0.78–1.68,
I
2
= 0 %). However, pooled analyses of observational studies suggested a higher rate of dialysis dependence among survivors who initially received IRRT as compared with CRRT (RR 1.99 95 % CI 1.53–2.59,
I
2
= 42 %). These findings were consistent with adjusted analyses (performed in 7/16 studies), which found a higher rate of dialysis dependence in IRRT-treated patients odds ratio (OR) 2.2–25 (5 studies) or no difference (2 studies).
Conclusions
Among AKI survivors, initial treatment with IRRT might be associated with higher rates of dialysis dependence than CRRT. However, this finding largely relies on data from observational trials, potentially subject to allocation bias, hence further high-quality studies are necessary.
Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of ...hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r
= 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.
Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain.
We ...conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days.
Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval CI, 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001).
Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).
Abstract Background Arterial carbon dioxide tension (PaCO2 ) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) ...after cardiac arrest (CA) has not been evaluated. Methods and results Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score. We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2 < 35 mmHg), 6705 (40.5%) into the normo- (35–45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 95% CI 1.00–1.24, p = 0.04), lower rate of discharge home (OR 0.81 0.70–0.94, p < 0.01) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 1.10–1.37, p < 0.001). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 0.97–1.15, p = 0.19) but higher rate of discharge home among survivors (OR 1.16 1.03–1.32, p = 0.01) and similar likelihood of fulfilling the composite outcome (OR 0.97 0.89–1.06, p = 0.52). Cox-proportional hazards modelling supported these findings. Conclusions Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.
Acute kidney injury (AKI) is common in patients undergoing cardiac surgery among whom it is associated with poor outcomes, prolonged hospital stays and increased mortality. Statin drugs can produce ...more than one effect independent of their lipid lowering effect, and may improve kidney injury through inhibition of postoperative inflammatory responses.
This review aimed to look at the evidence supporting the benefits of perioperative statins for AKI prevention in hospitalised adults after surgery who require cardiac bypass. The main objectives were to 1) determine whether use of statins was associated with preventing AKI development; 2) determine whether use of statins was associated with reductions in in-hospital mortality; 3) determine whether use of statins was associated with reduced need for RRT; and 4) determine any adverse effects associated with the use of statins.
We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
Randomised controlled trials (RCTs) that compared administration of statin therapy with placebo or standard clinical care in adult patients undergoing surgery requiring cardiopulmonary bypass and reporting AKI, serum creatinine (SCr) or need for renal replacement therapy (RRT) as an outcome were eligible for inclusion. All forms and dosages of statins in conjunction with any duration of pre-operative therapy were considered for inclusion in this review.
All authors extracted data independently and assessments were cross-checked by a second author. Likewise, assessment of study risk of bias was initially conducted by one author and then by a second author to ensure accuracy. Disagreements were arbitrated among authors until consensus was reached. Authors from two of the included studies provided additional data surrounding post-operative SCr as well as need for RRT. Meta-analyses were used to assess the outcomes of AKI, SCr and mortality rate. Data for the outcomes of RRT and adverse effects were not pooled. Adverse effects taken into account were those reported by the authors of included studies.
We included seven studies (662 participants) in this review. All except one study was assessed as being at high risk of bias. Three studies assessed atorvastatin, three assessed simvastatin and one investigated rosuvastatin. All studies collected data during the immediate perioperative period only; data collection to hospital discharge and postoperative biochemical data collection ranged from 24 hours to 7 days. Overall, pre-operative statin treatment was not associated with a reduction in postoperative AKI, need for RRT, or mortality. Only two studies (195 participants) reported postoperative SCr level. In those studies, patients allocated to receive statins had lower postoperative SCr concentrations compared with those allocated to no drug treatment/placebo (MD 21.2 µmol/L, 95% CI -31.1 to -11.1). Adverse effects were adequately reported in only one study; no difference was found between the statin group compared to placebo.
Analysis of currently available data did not suggest that preoperative statin use is associated with decreased incidence of AKI in adults after surgery who required cardiac bypass. Although a significant reduction in SCr was seen postoperatively in people treated with statins, this result was driven by results from a single study, where SCr was considered as a secondary outcome. The results of the meta-analysis should be interpreted with caution; few studies were included in subgroup analyses, and significant differences in methodology exist among the included studies. Large high quality RCTs are required to establish the safety and efficacy of statins to prevent AKI after cardiac surgery.
Hypophosphatemia in critically ill patients Suzuki, Satoshi, MD, PhD; Egi, Moritoki, MD, PhD; Schneider, Antoine G., MD ...
Journal of critical care,
08/2013, Letnik:
28, Številka:
4
Journal Article
Recenzirano
Abstract Purpose The aim of this study was to assess the association of phosphate concentration with key clinical outcomes in a heterogeneous cohort of critically ill patients. Materials and Methods ...This was a retrospective observational study at a general intensive care unit (ICU) of an Australian university teaching hospital enrolling 2730 adult critically ill patients. Results We studied 10 504 phosphate measurements with a mean value of 1.17 mmol/L (measurements every 28.8 hours on average). Hyperphosphatemia (inorganic phosphate iP concentration > 1.4 mmol/L) occurred in 45% and hypophosphatemia (iP ≤ 0.6 mmol/L) in 20%. Among patients without any episodes of hyperphosphatemia, patients with at least 1 episode of hypophosphatemia had a higher ICU mortality than those without hypophosphatemia ( P = .004). In addition, ICU nonsurvivors had lower minimum phosphate concentrations than did survivors ( P = .009). Similar results were seen for hospital mortality. However, on multivariable logistic regression analysis, hypophosphatemia was not independently associated with ICU mortality (adjusted odds ratio, 0.86 95% confidence interval, 0.66-1.10; P = .24) and hospital mortality (odds ratio, 0.89 0.73-1.07; P = .21). Even when different cutoff points were used for hypophosphatemia (iP ≤ 0.5, 0.4, 0.3, or 0.2 mmol/L), hypophosphatemia was not an independent risk factor for ICU and hospital morality. In addition, timing of onset and duration of hypophosphatemia were not independent risk factor for ICU and hospital mortality. Conclusions Hypophosphatemia behaves like a general marker of illness severity and not as an independent predictor of ICU or in-hospital mortality in critically ill patients.
We used contrast-enhanced ultrasound (CEUS) to estimate the effect of an increase in mean arterial pressure (MAP) induced by noradrenaline infusion on renal microvascular cortical perfusion in ...critically ill patients.
Twelve patients requiring a noradrenaline infusion to maintain a MAP more than 60 mmHg within 48 hours of intensive care unit admission were included in the study. Renal CEUS scans with destruction-replenishment sequences and Sonovue® (Bracco, Milano Italy) as a contrast agent, were performed at baseline (MAP 60 to 65 mmHg) and after a noradrenaline-induced increase in MAP to 80 to 85 mmHg.
There was no adverse effect associated with ultrasound contrast agent administration or increase in noradrenaline infusion rate. Adequate images were obtained in all patients at all study times. To reach the higher MAP target, median noradrenaline infusion rate was increased from 10 to 14 μg/min. Noradrenaline-induced increases in MAP were not associated with a significant change in overall CEUS derived mean perfusion indices (median perfusion index 3056 (interquartile range: 2438 to 6771) arbitrary units (a.u.) at baseline versus 4101 (3067 to 5981) a.u. after MAP increase, P = 0.38). At individual level, however, we observed important heterogeneity in responses (range -51% to +97% changes from baseline).
A noradrenaline-induced increase in MAP was not associated with an overall increase in renal cortical perfusion as estimated by CEUS. However, at individual level, such response was heterogeneous and unpredictable suggesting great variability in pressure responsiveness within a cohort with a similar clinical phenotype.
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