Elisabeth De Waele

Newly designed CRRT membranes for sepsis and SIRS--a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review.

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 m2). 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.

Septic AKI in ICU patients. diagnosis, pathophysiology, and treatment type, dosing, and timing: a comprehensive review of recent and future developments.

Evidence is accumulating showing that septic acute kidney injury (AKI) is different from non-septic AKI. Specifically, a large body of research points to apoptotic processes underlying septic AKI. Unravelling the complex and intertwined apoptotic and immuno-inflammatory pathways at the cellular level will undoubtedly create new and exciting perspectives for the future development (e.g., caspase inhibition) or refinement (specific vasopressor use) of therapeutic strategies. Shock complicating sepsis may cause more AKI but also will render treatment of this condition in an hemodynamically unstable patient more difficult. Expert opinion, along with the aggregated results of two recent large randomized trials, favors continuous renal replacement therapy (CRRT) as preferential treatment for septic AKI (hemodynamically unstable). It is suggested that this approach might decrease the need for subsequent chronic dialysis. Large-scale introduction of citrate as an anticoagulant most likely will change CRRT management in intensive care units (ICU), because it not only significantly increases filter lifespan but also better preserves filter porosity. A possible role of citrate in reducing mortality and morbidity, mainly in surgical ICU patients, remains to be proven. Also, citrate administration in the predilution mode appears to be safe and exempt of relevant side effects, yet still requires rigorous monitoring. Current consensus exists about using a CRRT dose of 25 ml/kg/h in non-septic AKI. However, because patients should not be undertreated, this implies that doses as high as 30 to 35 ml/kg/h must be prescribed to account for eventual treatment interruptions. Awaiting results from large, ongoing trials, 35 ml/kg/h should remain the standard dose in septic AKI, particularly when shock is present. To date, exact timing of CRRT is not well defined. A widely accepted composite definition of timing is needed before an appropriate study challenging this major issue can be launched.

Prevention and treatment of sepsis-induced acute kidney injury: an update

Sepsis-induced acute kidney injury (SAKI) remains an important challenge in critical care medicine. We reviewed current available evidence on prevention and treatment of SAKI with focus on some recent advances and developments. Prevention of SAKI starts with early and ample fluid resuscitation preferentially with crystalloid solutions. Balanced crystalloids have no proven superior benefit. Renal function can be evaluated by measuring lactate clearance rate, renal Doppler, or central venous oxygenation monitoring. Assuring sufficiently high central venous oxygenation most optimally prevents SAKI, especially in the post-operative setting, whereas lactate clearance better assesses mortality risk when SAKI is present. Although the adverse effects of an excessive “kidney afterload” are increasingly recognized, there is actually no consensus regarding an optimal central venous pressure. Noradrenaline is the vasopressor of choice for preventing SAKI. Intra-abdominal hypertension, a potent trigger of AKI in post-operative and trauma patients, should not be neglected in sepsis. Early renal replacement therapy (RRT) is recommended in fluid-overloaded patients’ refractory to diuretics but compelling evidence about its usefulness is still lacking. Continuous RRT (CRRT) is advocated, though not sustained by convincing data, as the preferred modality in hemodynamically unstable SAKI. Diuretics should be avoided in the absence of hypervolemia. Antimicrobial dosing during CRRT needs to be thoroughly reconsidered to assure adequate infection control.

Acute respiratory muscle weakness and apnea in a critically ill patient induced by colistin neurotoxicity: key potential role of hemoadsorption elimination during continuous venovenous hemofiltration

We describe a patient with severe New Delhi metallo-β-lactamase-1 Escherichia coli infection who developed convulsions rapidly followed by acute respiratory muscle weakness and apnea while receiving intravenous colistin. Toxic levels of colistin were rapidly removed by hemofiltration and, more specifically, by hemoadsorption.

Indirect calorimetry in nutritional therapy. A position paper by the ICALIC study group

BACKGROUND & AIMS This review aims to clarify the use of indirect calorimetry (IC) in nutritional therapy for critically ill and other patient populations. It features a comprehensive overview of the technical concepts, the practical application and current developments of IC. METHODS Pubmed-referenced publications were analyzed to generate an overview about the basic knowledge of IC, to describe advantages and disadvantages of the current technology, to clarify technical issues and provide pragmatic solutions for clinical practice and metabolic research. The International Multicentric Study Group for Indirect Calorimetry (ICALIC) has generated this position paper. RESULTS IC can be performed in in- and out-patients, including those in the intensive care unit, to measure energy expenditure (EE). Optimal nutritional therapy, defined as energy prescription based on measured EE by IC has been associated with better clinical outcome. Equations based on simple anthropometric measurements to predict EE are inaccurate when applied to individual patients. An ongoing international academic initiative to develop a new indirect calorimeter aims at providing innovative and affordable technical solutions for many of the current limitations of IC. CONCLUSION Indirect calorimetry is a tool of paramount importance, necessary to optimize the nutrition therapy of patients with various pathologies and conditions. Recent technical developments allow broader use of IC for in- and out-patients.

Nutritional and Metabolic Alterations during Continuous Renal Replacement Therapy

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.

Nutrition therapy in cachectic cancer patients. The Tight Caloric Control (TiCaCo) pilot trial.

BACKGROUND Cancer is a common disease and many patients are diagnosed with advanced stages. Due to cancer generalization, patients may become ill-nourished and even cachectic. Malignancy-related cachexia is associated with worsening physical function, reduced tolerance to anticancer therapy and increased mortality. We assessed the effect of a patient-tailored nutritional approach in newly discovered, treatment-naive cancer patients with cachexia. METHODS In a randomized, single-blinded, controlled pilot study, patients were treated with either intensive, biometric parameter-oriented dietary counseling (nutrition therapy) compared to regular dietary counseling (control), before and during conventional cancer treatment. Twenty patients were enrolled over a one-year period, 10 receiving nutrition therapy and 10 controls. The primary endpoint was recovery of body composition after nutrition therapy. Secondary endpoints declined in morbidity and mortality with nutrition therapy. RESULTS Average weight evolution in the control group after 3, 6 and 12 months was 0.19 ± 7.87 kg, -9.78 ± 7.00 kg and -5.8 kg, and in the nutrition therapy group 0.69 ± 2.4 kg, 0.77 ± 2.58 kg and 1.29 ± 3.76 kg. Control patients had a significantly longer average hospital stay than subjects from the nutrition therapy group (37.6 vs. 3.4 days). Eight nutrition therapy patients and 1 control patient were still alive after 2 years. CONCLUSIONS Nutrition therapy based on patient-specific biophysical parameters helps to maintain body weight and induces a more optimal nutritional balance in cachectic cancer patients. Moreover, survival in cancer patients improved when their nutritional status, even partially, ameliorated.

Bedside Calculation of Energy Expenditure Does Not Guarantee Adequate Caloric Prescription in Long-Term Mechanically Ventilated Critically Ill Patients: A Quality Control Study

Nutrition is essential in critically ill patients, but translating caloric prescriptions into adequate caloric intake remains challenging. Caloric prescriptions (P), effective intake (I), and caloric needs (N), calculated with modified Harris-Benedict formulas, were recorded during seven consecutive days in ventilated patients. Adequacy of prescription was estimated by P/N ratio. I/P ratio assessed accuracy of translating a prescription into administered feeding. I/N ratio compared delivered calories with theoretical caloric needs. Fifty patients were prospectively studied in a mixed medicosurgical ICU in a teaching hospital. Basal and total energy expenditure were, respectively, 1361 ± 171 kcal/d and 1649 ± 233 kcal/d. P and I attained 1536 ± 602 kcal/d and 1424 ± 572 kcal/d, respectively. 24.6% prescriptions were accurate, and 24.3% calories were correctly administered. Excessive calories were prescribed in 35.4% of patients, 27.4% being overfed. Caloric needs were underestimated in 40% prescriptions, with 48.3% patients underfed. Calculating caloric requirements by a modified standard formula covered energy needs in only 25% of long-term mechanically ventilated patients, leaving many over- or underfed. Nutritional imbalance mainly resulted from incorrect prescription. Failure of “simple” calculations to direct caloric prescription in these patients suggests systematic use of more reliable methods, for example, indirect calorimetry.

Biomarkers for early diagnosis of AKI in the ICU: ready for prime time use at the bedside?

Because of its still rising incidence and high mortality rate in intensive care unit (ICU) patients, early recognition of acute kidney injury (AKI) remains a critical issue. Surprisingly, effective biomarkers for early detection and hence appropriate and timely therapy of AKI have not yet entered the clinical arena. We performed a systematic search of the literature published between 1999 and 2011 on potential early biomarkers for acute renal failure/kidney injury in an at-risk adult and pediatric population following the Quorum Guidelines. Based on this review, recommendations for the clinical use of these biomarkers were proposed. In general, kidney biomarkers may aid to direct early aggressive treatment strategies for AKI thereby decreasing the associated high mortality. To date, however, sensitivity and specificity of individual biomarker assays are low and do not sustain their routine clinical use. “Kits” containing a combination of established biomarkers, in conjunction with measured glomerular filtration rate, may enhance diagnostic and prognostic accuracy in the future.

Continuous renal replacement therapy allows higher colistin dosing without increasing toxicity

Abstract 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.