Correction to: Chloride content of solutions used for regional citrate anticoagulation might be responsible for blunting correction of metabolic acidosis during continuous venovenous hemofiltration.

Following publication of the original article [1], we have been notified that the approved number by the Ethical Committee was given incorrectly. In the section "Methods" stated that: The Central Ethical Committee of the University Hospital approved the study protocol (B.U.N. 143201318818), this number is incorrect and should be expressed as follows: B.U.N. 143201318819."

Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review.

RATIONALE/METHODS: The primary aim of the present contribution is to find a literature-based agreement on dose adjustments of vitamin C in critically ill patients undergoing renal replacement therapy (RRT). AVAILABLE DATA/STUDY RESULTS: Critical illness is frequently accompanied by severe vitamin C deficiency. High-dose supplementation beneficially affects clinical outcome in small cohorts of patients with sepsis, burn injury, and trauma. There are no specific data on clinical outcomes in patients receiving renal replacement therapy (RRT). Vitamin C plasma concentrations in patients on RRT are comparable to critically ill patients not receiving RRT. Vitamin C is cleared from the circulation during RRT at a rate dependent on the plasma concentration, dose and duration of RRT. Sieving coefficient is about 1. While the dose of RRT is lower than normal renal function, tubular reabsorption is absent. Sparse evidence suggests that vitamin C dosing during continuous RRT should not exceed the dose administered to critically ill patients not receiving continuous RRT. Low plasma concentrations are expected during prolonged RRT because of persistent extracorporeal removal, absent renal reabsorption and enhanced metabolic loss due to circuit-induced oxidative stress. A dosage of twice 1 g vitamin C daily may be necessary to achieve normal plasma concentrations during RRT, but more studies are needed. There is no available evidence that high doses of vitamin C administered over a short period can induce oxalate stones or has pro-oxidant effects. CONCLUSIONS: Supplementing vitamin C 1 g twice daily to critically ill patients has a solid pathophysiological rationale and a good safety profile. Patients on RRT probably need similar doses as critically ill patients not receiving RRT. Intravenous vitamin C in a dose of 2 g/day may be necessary to achieve normal plasma concentrations during RRT. However, data on dose adjustment of vitamin C during intermittent or chronic RRT are sparse and require more thorough pharmacokinetic and dose-response studies.

How to deal with severe acute pancreatitis in the critically ill.

PURPOSE OF REVIEW: To review recent literature on the management of patients with severe acute pancreatitis (SAP) admitted to an ICU. RECENT FINDINGS: SAP is a devastating disease associated with a high morbidity and mortality. Recent evidence advocates adequate risk assessment and severity prediction (including intra-abdominal pressure monitoring), tailored fluid administration favoring balanced crystalloids, withholding prophylactic antibiotic therapy, and early detection and treatment of extra-pancreatic and fungal infections. Urgent (within 24-48 h after diagnosis) endoscopic retrograde cholangiopancreatography is indicated when persistent biliary obstruction or cholangitis are present. Corticosteroid therapy (mainly dexamethasone) can reduce the need for surgical interventions, length of hospital stay, and mortality. Peritoneal lavage may significantly lower morbidity and mortality. Hemofiltration may offer substantial benefit but more studies are needed to prove its efficacy. Enteral feeding using a polymeric formula and provided early through a nasogastric tube is recommended but has no survival benefit compared with parenteral nutrition. Probiotics could be beneficial, however no clear recommendations can be made. SUMMARY: Management of SAP is multimodal with emphasis on monitoring, adequate fluid resuscitation, avoiding prophylactic use of antibiotics, cause-directed procedures or treatment, and organ support. There is a role for early enteral nutrition including probiotics.

Pharmacokinetics and Pharmacodynamics of Anti-infective Agents during Continuous Veno-venous Hemofiltration in Critically Ill Patients: Lessons Learned from an Ancillary Study of the IVOIRE Trial.

BACKGROUND: Hemofiltration rate, changes in blood and ultrafiltration flow, and discrepancies between the prescribed and administered doses strongly influence pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents during continuous veno-venous hemofiltration (CVVH) in critically ill patients. METHODS: Ancillary data were from the prospective multicenter IVOIRE (hIgh VOlume in Intensive caRE) study. High volume (HV, 70 mL/kg/h) was at random compared with standard volume (SV, 35 mL/kg/h) CVVH in septic shock patients with acute kidney injury (AKI). PK/PD parameters for all antimicrobial agents used in each patient were studied during five days. RESULTS: Antimicrobial treatment met efficacy targets for both percentage of time above the minimal inhibitory concentration and inhibitory quotient. A significant correlation was observed between the ultrafiltration flow and total systemic clearance (Spearman test: P < 0.005) and between CVVH clearance and drug elimination half-life (Spearman test: P < 0.005). All agents were easily filtered. Mean sieving coefficient ranged from 38.7% to 96.7%. Mean elimination half-life of all agents was significantly shorter during HV-CVVH (from 1.29 to 28.54 h) than during SV-CVVH (from 1.51 to 33.85 h) (P < 0.05). CONCLUSIONS: This study confirms that CVVH influences the PK/PD behavior of most antimicrobial agents. Antimicrobial elimination was directly correlated with convection rate. Current antimicrobial dose recommendations will expose patients to underdosing and increase the risk for treatment failure and development of resistance. Dose recommendations are proposed for some major antibiotic and antifungal treatments in patients receiving at least 25 mL/kg/h CVVH.

Energy expenditure of patients on ECMO: A prospective pilot study.

BACKGROUND: An optimal nutritional approach sustained by convenient monitoring of metabolic status and reliable assessment of energy expenditure (EE) may improve the outcome of critically ill patients on extracorporeal membrane oxygenation (ECMO). We previously demonstrated the feasibility of indirect calorimetry (IC)-the standard of care technique to determine caloric targets-in patients undergoing ECMO. This study aims to compare measured with calculated EE during ECMO treatment. We additionally provide median EE values for use in settings where IC is not available. METHODS: IC was performed in seven stable ECMO patients. Gas exchange was analyzed at the ventilator, and ECMO side and values were introduced in a modified Weir formula to calculate resting EE. Results were compared with EE calculated with the Harris-Benedict equation and with the 25 kcal/kg/day ESPEN recommendation. RESULTS: Total median oxygen consumption rate was 196 (Q1-Q3 158-331) mL/min, and total median carbon dioxide production was 150 (Q1-Q3 104-203) mL/min. Clinically relevant differences between calculated and measured EE were observed in all patients. The median EE was 1334 (Q1-Q3 1134-2119) kcal/24 hours or 18 (Q1-Q3 15-27) kcal/kg/day. CONCLUSION: Compared with measured EE, calculation of EE both over- and underestimated caloric needs during ECMO treatment. Despite a median EE of 21 kcal/kg/day, large variability in metabolic rate was found and demands further investigation.

Citrate: How to Get Started and What, When, and How to Monitor?

In most of the case, regional citrate anticoagulation is using diluted citrate around 1% depending on the types used in clinical practice. Diluted citrate is much more safer when compared to highly concentrated citrate around 4% or even more. In clinical practice, trisodium citrate is used in high concentration (around 30%) as a bactericidal agent with anticoagulant properties for locking deep venous catheters used in hemodialysis (HD; close to 25-30% of citrate). In this review article, buffer and anticoagulant potential of citrate are discussed during renal replacement therapy in critically ill patients with particular focus on the practical approach at the bedside.

An update on membranes and cartridges for extracorporeal blood purification in sepsis and septic shock.

PURPOSE OF REVIEW: This review aims to summarize the most recent advances on different membranes and cartridges used for extracorporeal blood purification in critically ill patients with sepsis or septic shock. RECENT FINDINGS: Despite positive signals from experimental, cases and small clinical studies, blood purification showed no distinct morbidity and mortality benefit in large clinical trials. SUMMARY: None of the discussed specific membranes or cartridges can currently be recommended as sole adjunctive treatment in sepsis and septic shock. Any available technique should be timely initiated and adapted to the patient's status. Sickest patients seem to benefit more from blood purification. Patient selection is thus of crucial importance and may be optimized by focusing on disease severity and degree of organ failure. Measurement of endotoxin activity and plasma procalcitonin levels can support the selection process but ideal cutoff values need to be defined. Well-designed prospective randomized clinical trials assessing or comparing the various available membranes and cartridges are eagerly awaited.