Colistin is a complex polypeptide antibiotic composed mainly of colistin A and B. It was abandoned from clinical use in the 1970s because of significant renal and, to a lesser extent, neurological toxicity. Actually, colistin is increasingly put forward as salvage or even first-line treatment for severe multidrug-resistant, Gram-negative bacterial infections, particularly in the intensive care setting. We reviewed the most recent literature on colistin treatment, focusing on efficacy and toxicity issues. The method used for literature search was based on a PubMed retrieval using very precise criteria.Despite large variations in dose and duration, colistin treatment produces relatively high clinical cure rates. Colistin is potentially nephrotoxic but currently used criteria tend to overestimate the incidence of kidney injury. Nephrotoxicity independently predicts fewer cures of infection and increased mortality. Total cumulative colistin dose is associated with kidney damage, suggesting that shortening of treatment duration could decrease the incidence of nephrotoxicity. Factors that may enhance colistin nephrotoxicity (i.e., shock, hypoalbuminemia, concomitant use of potentially nephrotoxic drugs) must be combated or controlled. Neurotoxicity does not seem to be a major issue during colistin treatment. A better knowledge of colistin pharmacokinetics in critically ill patients is imperative for obtaining colistin dosing regimens that ensure maximal antibacterial activity at minimal toxicity.
In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.
Although improving, the mortality from septic shock still remains high despite increased international awareness. As a consequence, much effort has focused on alternative treatment strategies in an effort to improve outcomes. The application of blood purification therapies to improve immune homeostasis has been suggested as one such method, but these approaches, such as high-volume continuous haemofiltration or cytokine and/or endotoxin removal, have enjoyed little success to date. More recently, the use of sorbent technologies has attracted much attention. These adsorbers are highly effective at removing inflammatory mediators, in particular, cytokines, from the bloodstream. This narrative review is the executive summary of meetings held throughout the 6th International Fluid Academy Days in Antwerp, Belgium (Nov 23–25, 2017), focusing on the current understanding regarding the use of such adsorbers in humans with septic shock. We followed a modified Delphi approach involving a combination of evidence appraisal together with expert opinion in order to achieve recommendations for practice and, importantly, future research.
In recent years, after all the attention has been focused on the dose for continuous renal replacement therapy (CRRT) in sepsis and systemic inflammation response syndrome (SIRS), the relatively negative results of all those studies did urge our expectations on new approaches regarding CRRT in sepsis and SIRS. So far, after the failure of the major randomized studies on dose, attention is now drawn to new membranes that could better eliminate massive amounts of unbound mediators in wider spectrum and also in greater magnitude Nevertheless, for septic acute kidney injury, the recommended dose will remain 35 ml/kg/h until the IVOIRE (hIgh VOlume in Intensive Care) study will be published. In this new armamentarium, we have distinguished the first tools that can still be called membranes ranging from AN69 Surface Treated (ST), SEPTEX, polymethylmetacrylate, to Oxiris that can still run with a CRRT device. Polymyxin B is still a kind of membrane although it has a larger surface, but it can run in a hemoperfusion system and is also much more selective. Adsorptive columns and sorbents are not anymore membranes but are seen as cartridges as the surface is extremely huge when compared with that of membranes (more than 500 m). They can still run in a hemoperfusion device. At the very end, we do have apheresis or selective plasma exchange (also very close to sorbents and columns) but we have very few data up to now regarding sepsis. Regarding spectrum, CytoSorb seems to be very promising although it is not able to capture endotoxin and IL-10. Oxiris is also promising as it can capture endotoxin and cytokines. AN69 ST is very powerful to capture numerous cytokines and especially high-mobility group box 1 protein (a very upstream cytokine). Polymethylmetacrylate has also the power to capture endotoxin and numerous other cytokines probably with a larger magnitude than Oxiris although this is not proven. Lastly, high-porosity membranes (Septex) may play a role especially when used in continuous venovenous hemodialysis mode. At the end, if we look for a more enlarged spectrum and a higher magnitude, CytoSorb might be seen as the most promising although not having the ability to fix endotoxin. Future studies will tell us which membrane or sorbent will be most useful in the adjunctive treatment for sepsis.
Adequate feeding of critically ill patients under continuous renal replacement therapy (CRRT) remains a challenging issue. We performed a systematic search of the literature published between 1992 and 2012 using the quorum guidelines regarding nutrition in intensive care unit patients treated with CRRT. Daily recommended energy requirements during CRRT are between 25 and 35 kcal/kg with carbohydrates and lipids accounting for 60-70% and 30-40% of calorie intake, respectively. Daily protein needs range from 1.5 to 1.8 g/kg. Indirect calorimetry corrected for CRRT-induced CO2 diversion should be used to more correctly match calorie intake to the real needs. This type of tool is not yet available but hopefully soon. Electrolyte deficit as well as overload have been described during CRRT but, in general, can be easily controlled. Although not strongly evidenced, consensus exists to supplement important micronutrients such as amino acids (glutamine), water-soluble vitamins and trace elements.
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