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  • Author: Olivier Joannes-Boyau x
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Multidisciplinarity in emergency and critical care medicine: Specific care is best care!
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New insights in prevention and treatment of sepsis-induced acute kidney injury


Sepsis-induced acute kidney injury (SAKI) remains an important challenge for intensive care unit clinicians. We reviewed current available evidence regarding prevention and treatment of SAKI thereby incorporating some major recent advances and developments. Prevention includes early and ample administration of “balanced” crystalloid solutions such as Ringer’s lactate. For monitoring of renal function during resuscitation, lactate clearance rate is preferred above ScvO2 or renal Doppler. Aiming at high central venous pressures seems to be deleterious in light of the novel “kidney afterload” concept. Noradrenaline is the vasopressor of choice for preventing SAKI. Intra-abdominal hypertension, a potent trigger of acute kidney injury in postoperative and trauma patients, should not be neglected in sepsis. Renal replacement therapy (RRT) must be started early in fluid-overloaded patients refractory to diuretics. Continuous RRT (CRRT) is the preferred modality in hemodynamically unstable SAKI but its use in more stable SAKI is increasing. In the absence of hypervolemia, diuretics should be avoided. Antimicrobial dosing during CRRT needs to be thoroughly reconsidered to assure adequate infection control.

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Biomarkers in acute kidney injury, sepsis and ARDS: Guiding clinicians…. but where to?
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Continuous renal replacement therapy allows higher colistin dosing without increasing toxicity


Polymyxins are ‘‘old’’ antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise of multi-resistant Gramnegative 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 pro-drug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used for treatment of pneumonia and bacteremia in critically ill patients. During their ICU stay, many of these subjects will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and 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 up to 4.5 million IU tid). 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 ‘‘CRRT rescue’’ therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.

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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



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.


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.


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).


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.

Open access