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."

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.

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.

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.

Optimal timing of renal replacement therapy initiation in acute kidney injury: the elephant felt by the blindmen?

Renal replacement therapy (RRT) is a key component in the management of severe acute kidney injury (AKI) in critically ill patients. Many cohort studies, meta-analyses, and two recent large randomized prospective trials which evaluated the relationship between the timing of RRT initiation and patient outcome remain inconclusive due to substantial differences in study design, patient population, AKI definition, and RRT indication. A cause-specific diagnosis of AKI based on current staging criteria plus a sensitive biomarker (panel) that allows creating a homogeneous study population is definitely needed to assess the impact of early versus late initiation of RRT on patient outcome.

Statins and the Kidney: Friend or Foe?

Statins essentially are cholesterol-lowering drugs that are extensively prescribed for primary and secondary prevention of cardiovascular disease. Compelling evidence suggests that the beneficial effects of statins may not only be due to controlling cholesterol levels but also due to a pleiotropic cholesterol-independent anti-inflammatory, antioxidant, endothelial-protective and plaque-stabilizing activity. Along this line, statins may also exert acute and long-term effects on renal function. We present a narrative literature review that summarizes arguments in favour or against the preventive and/or therapeutic use of statins in kidney-related diseases or complications. We also highlight the ongoing controversy regarding statin therapy in chronic and end-stage kidney disease.

A newly developed tracheal tube offering 'pressurised sealing' outperforms currently available tubes in preventing cuff leakage: A benchtop study.

BACKGROUND: No currently used tracheal tube offers full protection against aspiration of oropharyngeal secretions into the lower airways. OBJECTIVE: We developed a tracheal tube equipped with two polyvinylchloride (PVC) cuffs with a supplementary port opening between the cuffs through which a continuous positive pressure of 5 cmH2O is provided [double-cuffed PVC (PVCdc)]. We compared this PVCdc with four different cuff types (cylindrical PVC, conical PVC, cylindrical polyurethane and conical polyurethane). DESIGN: A comparison study using an in-vitro benchtop model of an artificial rigid trachea. INTERVENTIONS: Tracheal tubes were placed in the artificial trachea. Both cuffs were kept inflated at 25 cmH2O. Total 3 ml dyed water was placed above the cuff and leakage recorded under static and dynamic [5 cmH2O positive end-expiratory pressure (PEEP) alone or positive pressure ventilation plus 5 cmH2O PEEP] conditions. At the end of the dynamic experiments, PEEP was zeroed (PEEP alone) or the tracheal tubes were disconnected from the ventilator (positive pressure ventilation plus PEEP). RESULTS: In the static model, leakage flows [medians (range)] were 9.8 (6.2 to 20) for the cylindrical PVC, 1.3 (0.2 to 3.8) for the conical PVC, 0.03 (0.007 to 0.1) for the cylindrical polyurethane, 0.04 (0.003 to 0.2) for the conical polyurethane and 0.0 (0.0 to 0.0) ml min for the PVCdc cuff (P < 0.001, PVCdc vs. all other cuffs). In the dynamic setting, no leakage was detected for up to 60 min with any of the cuffs studied. Loss of PEEP or tracheal tube disconnection resulted in dye inflow alongside all cuffs except for the PVCdc (P < 0.001, PVCdc vs. all other cuffs). CONCLUSION: A 'pressure seal' incorporated in a double-cuffed tracheal tube prevented fluid passage into the lower airways. Clinically, this may translate into absence of inflow of bacteriologically contaminated secretions into the lungs and thus a lower incidence of ventilator-associated infection.

Renal blood flow and acute kidney injury in septic shock: an arduous conflict that smolders intrarenally?

Sepsis-induced acute kidney injury (SAKI) is traditionally viewed as a process driven by a reduced blood flow and prone to benefit from vasopressive support. In ovine hyperdynamic septic shock, Lankadeva et al. report a significant and flow-independent intrarenal perfusion and oxygenation "mismatch" jeopardizing the renal medulla that was aggravated by norepinephrine. Medullary and urinary oxygenation changed in parallel, suggesting that urinary oxygenation may act as a biomarker to predict SAKI.

New generation indirect calorimeters for measuring energy expenditure in the critically ill: a rampant or reticent revolution?

To lower the risk of incorrectly feeding critically ill patients, indirect calorimetry (IC) is proposed as the most ideal method to evaluate energy expenditure and to establish caloric goals. New IC devices are progressively introduced but validation of this new generation remains challenging and arduous.

Chloride content of solutions used for regional citrate anticoagulation might be responsible for blunting correction of metabolic acidosis during continuous veno-venous hemofiltration.

BACKGROUND: Citrate, the currently preferred anticoagulant for continuous veno-venous hemofiltration (CVVH), may influence acid-base equilibrium. METHODS: The effect of 2 different citrate solutions on acid-base status was assessed according to the Stewart-Figge approach in two consecutive cohorts of critically ill adult patients. The first group received Prismocitrate 10/2 (PC10/2; 10 mmol citrate/L). The next group was treated with Prismocitrate 18/0 (PC18; 18 mmol citrate/L). Both groups received bicarbonate-buffered fluids in post-dilution. RESULTS: At similar citrate flow, the metabolic acidosis present at baseline in both groups was significantly attenuated in PC18 patients but persisted in PC10/2 patients after 24 h of treatment (median pH 7,42 vs 7,28; p = 0.0001). Acidosis in the PC10/2 group was associated with a decreased strong ion difference and an increased strong ion gap (respectively 43 vs. 51 mmol/L and 17 vs. 12 mmol/L, PC10/2 vs. PC18; both p = 0.001). Chloride flow was higher in PC10/2 than in PC18 subjects (25.9 vs 14.3 mmol/L blood; p < 0.05). CONCLUSION: Correction of acidosis was blunted in patients who received 10 mmol citrate/L as regional anticoagulation during CVVH. This could be explained by differences in chloride flow between the applied citrate solutions inducing hyperchloremic acidosis.

Citrate Formulation Determines Filter Lifespan during Continuous Veno-Venous Hemofiltration: A Prospective Cohort Study.

INTRODUCTION: We conducted an 8-month prospective single-center observational study in patients with acute kidney injury treated with continuous veno-venous hemofiltration (CVVH) to compare the impact of two citrate formulations on filter lifespan (FLS). METHODS: Patients received CVVH at a delivered dose of 25 ml/kg/h. Multivariable linear regression was performed to assess the influence of different variables on circuit lifespan. RESULTS: We included 59 patients, 28 received the 10/2 formulation and 31 received the 18/0 formulation. Median (interquartile range) FLS was significantly prolonged with the 18/0 solution compared with the 10/2 solution (4.10 (2.45-5.75) vs. 2.68 (0.47-4.99) days, p = 0.001). No confounding variables (difference in ionized calcium target, citrate flow or dose, platelet count, hematocrit, vascular access location) affecting filter capacity or lifespan between the 2 formulations were identified. CONCLUSIONS: Under similar conditions of CVVH and calcium targets, a Prismocitrate 18/0 formulation significantly improved FLS as compared with Prismocitrate 10/2.

What do we know about steroids metabolism and 'PK/PD approach' in AKI and CKD especially while on RRT--current status in 2014.

The knowledge on PK behavior of steroid drugs such as prednisolone or prednisone has indeed been expanding but at a rather slow pace. First, convenient, rapid, and specific determination of plasma levels of these steroids was largely indebted to the breakthrough of high performance liquid chromatography (HPLC). Second, prednisolone is non-linearly protein-bound. Since unbound prednisolone is the biologically active compound, only the measurement of this free fraction in plasma is relevant. Third, the short half-life of prednisolone precludes to reach steady-state levels and requires determination of the area under the concentration-time curve. Fourth, prednisolone and prednisone are mutually convertible. Intravenous prednisolone, however, is administered as a pro-drug ester, which renders comparison and interpretation of reported PK data of both agents unreliable. A poignant lack of awareness and knowledge regarding catabolism, clearance mechanisms, and elimination route of steroids fuels the ongoing controversy that surrounds adjunctive corticosteroid therapy in patients with chronic or acute inflammatory disease. This particular patient population is also more prone to develop early and significant kidney dysfunction, necessitating extra-renal support. A better understanding of steroid PK/PD, preferentially guided by HPLC measurement of plasma steroid concentrations, likely will have direct clinical implications, for instance by adapting steroid doses in IHD or implementing higher dose regimens during CRRT.

Continuous renal replacement therapy-related strategies to avoid colistin toxicity: a clinically orientated review.

Polymyxins are 'old' antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise in multiresistant Gram-negative bacterial infections worldwide has revived interest in these 'forgotten' agents. Colistin (polymyxin E) is one of the main antibiotics of this class. It is most often administered as the prodrug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used to treat pneumonia and bacteremia in critically ill patients. During their intensive care unit stay, many of these patients will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and our own experience, we postulate that patients undergoing CRRT may receive substantially higher doses of colistin (i.e. a high loading dose, followed by a maintenance dose of up to 4.5 million IU t.i.d.). Treatment can be continued for a prolonged time period without increasing toxicity. CRRT counteracts colistin accumulation because the drug is continuously filtered and also significantly adsorbed in the bulk of the dialysis membrane. Implementing such a 'CRRT rescue' therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.

Con: Dialy- and continuous renal replacement (CRRT) trauma during renal replacement therapy: still under-recognized but on the way to better diagnostic understanding and prevention.

Dialy- and continuous renal replacement (CRRT) trauma are still un(der)recognized conditions that may be encountered during blood purification therapy. This particular form of trauma requires timely identification, a better understanding of pathophysiology and a definition of at-risk groups to prevent or correct any associated unwarranted effects. Among others, progress in the knowledge of antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) behaviour during CRRT to obtain more efficient antimicrobial therapy with less side-effects is one key example of limiting CRRT trauma. Optimal anticipation and prevention of CRRT trauma will preserve the safe use of CRRT in haemodynamically unstable critically ill patients with acute kidney injury (AKI), especially in septic patients who are at the greatest risk.