Page 1369 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

942 PART 8: Renal and Metabolic Disorders

ability to recover from their critical illness with respect to overcoming improved, nitrogen balance. Thus, existing data support the notion that
83
life-threatening infection, liberation from mechanical ventilation, and a high level of protein supplementation, above the ESPEN recommended
recovery of organ function. 73,74 1.5 g/kg/day, is necessary in patients with AKI undergoing CRRT.
Acute kidney injury is a highly catabolic state. Thus, in combination The impact of the modality of CRRT on nitrogen balance is unclear.
with critical illness, AKI creates an environment of severe protein wast- Limited data from pediatric patients undergoing CVVH or CVVHD for
ing and malnutrition. The optimal nutritional support for individuals acute kidney injury suggest that amino acid loss and net nitrogen balance
75
with acute kidney injury and critical illness is unclear. Variations in are similar between the two modalities at a fixed dose of 2000 mL/h.
84
the optimal diet exist due to concerns of electrolyte abnormalities However, this comparison has not been repeated or studied in an adult
(hyperkalemia, hyperphosphatemia, etc), metabolic parameters (protein population.
breakdown leading to worsening metabolic acidosis), as well as volume In order to optimize nutritional support, determine the validity of
overload. However, the nutritional support in the setting of critical ill- the ESPEN guidelines and better understand the effect of current CRRT
ness is especially important for those with acute kidney injury. Animal dosing on nitrogen balance in the setting of acute kidney injury and
and human data have demonstrated a potential positive impact of nutri- critical illness, studies assessing nitrogen balance in critically ill patients
tional support on recovery of renal function. 76,77 with AKI not on CRRT and those with AKI receiving CRRT are required.
Identification of optimal nutritional support is further complicated Until further data are available, we recommend prescribing nutritional
by the increased removal of small solutes via the use of RRT, especially support consistent with the current ESPEN guidelines, and monitoring
CRRT. The removal of these nutritionally valuable solutes is further of parameters of nutritional status in critically ill patients receiving RRT.
accelerated via the combination of high-flux membranes and high blood ■
flow rates (similar to intermittent hemodialysis). Further, because of MEDICATION DOSING
data demonstrating improved outcomes with higher doses of delivered Medication dosing must be adjusted in patients with AKI to prevent
dialysis outlined above (compared to doses from 20 years ago), pre- excessive medication administration and toxicity. Individuals with AKI
scribed and delivered doses of dialysis have increased. Unlike the receiving RRT, however, may be at risk for underdosing of medications,
kidney, RRT is nonselective in its removal of small and middle as administered medications are often removed by extracorporeal therapy.
molecules. Observational human data have consistently demonstrated Severe sepsis and septic shock are common comorbid conditions in the
the significant removal of essential amino acids, water-soluble vitamins, setting of AKI and critical illness. A key component of supportive care for
and trace minerals with CRRT. 78,79 Undoubtedly, the combination of patients with severe sepsis and septic shock is the timely administration
critical illness, AKI, and amino acid removal via CRRT (teamed with of adequate antimicrobial therapy. The spread of nosocomial pathogens
85
technical and/or pathologic limitations impairing their ability to receive and the variable susceptibilities of bacteria to conventional antibiotic ther-
nutritional support) leaves many patients with significant negative nitro- apy have highlighted the importance of not only selecting the appropriate
gen balance contributing to their state of malnutrition and inability to antimicrobial but also the appropriate dose of antimicrobial. Inadequate
86
recover from their critical illness. or inappropriate antimicrobial therapy has been demonstrated to be
The European Society for Clinical Nutrition and Metabolism (ESPEN) common, occurring between 17% and 45% of documented bloodstream
recommends that individuals with AKI undergoing intermittent dialysis infections in an academic intensive care unit. Further, underdosing and
87
receive 1.5 g/kg body weight protein. Individuals undergoing CRRT inappropriate dosing has significant impact on patient outcomes and is
receive 1.5 to 1.7 g/kg body weight protein intake daily (as a part of a associated with a greater than twofold risk of hospital mortality. 88
total 20 to 30 kcal/kg body weight daily diet). These recommendations Depending on the modality of RRT (ie, intermittent versus CRRT),
80
may be suboptimal as they are based on studies with RRT practices the dosing strategies for antimicrobials differ. Further, the significant
that significantly differ from current clinical practice. Specifically, the small solute clearance achieved with higher doses of CRRT increases
guideline is based on an observational study demonstrating that protein the potential risk for excessive antimicrobial clearance and resulting
supplementation of at least 1.5 g/kg body weight was associated with underdosing of antibiotics. Piperacillin and cefepime are both commonly
less negative nitrogen (and some positive nitrogen balance) in patients utilized, broad-spectrum, β-lactam antibiotics that have demonstrated
with acute kidney injury receiving CVVH. Importantly, the dose of significant increases in drug clearance with increased dose of dialysis. 89,90
CRRT in this study was far less than what is currently recommended Other antimicrobials with similar characteristics (with regard to size
and commonly practiced: ultrafiltration rate of about 12 mL/kg/h versus and volume of distribution) may carry similar dose-response effects and
current rates of 25 to 35 mL/kg/h. A more recent observational study require increased dosing in the setting of higher-dose dialysis therapy.
assessing the protein equivalent nitrogen appearance and nitrogen While pharmacokinetic data are limited, existing literature has guided the
balance in critically ill patients undergoing CVVHDF also determined a development of guidelines for antimicrobial dosing for patients under-
protein requirement of approximately 1.5 g/kg/daily, but the patients in going CRRT. Individuals caring for these patients should utilize these
91
this study were also prescribed a suboptimal dose of CRRT (blood flow guidelines, recruit the assistance of clinical pharmacists, and use therapeu-
rate of 150 mL/h, dialysate dose of 1000 mL/h with an effluent rate of tic drug levels, when available, to ensure adequate dosing of antibiotics.
300 mL/h—totaling 1300 mL/h of dialysis dosing). 81
Theoretically, both an increase in dose and the choice of modality FUTURE DIRECTIONS
will influence the degree of amino acid removal and, thus, nitrogen
balance. A study assessing nitrogen balance in critically ill patients While much progress has been made in making RRT safer and more
with anuric acute kidney injury receiving CVVHD corroborates this effective at achieving therapeutic goals (volume control, solute clearance,
theory. At protein intake of 1.5 g or 2 g/kg daily, individuals undergoing etc), further improvements are still needed. In the future, the prediction
CVVHD with blood flow rate of 100 to 175 mL/h and dialysate dose of and timing of RRT initiation and discontinuation in patients with AKI
2000 mL/h remained in progressive negative nitrogen balance. Only at will probably be guided by the use of a panel of AKI. Advancing RRT
92
a protein supplementation rate of 2.5 g/kg daily did individuals achieve beyond solute and water clearance to better reflect the intervention as
positive nitrogen balance. While differences beyond the modality and a true renal “replacement” has started with using RRT to ameliorate
82
dose of CRRT exist between the two study populations, the later study the inflammatory milieu of severe sepsis-associated AKI. Development
certainly suggests that 1.5 g/kg protein supplementation, as suggested in of more selective membranes that can function as adsorptive and fil-
the ESPEN guidelines, may not be applicable to clinical scenarios where tration devices, membranes with larger pore size allowing for more
CVVHD or CVVHDF is delivered at a higher dose. A study measuring effective cytokine removal (high-cutoff hemofiltration/hemodialysis
the effect of high-dose amino acid supplementation in patients receiving or HCO) and adding renal tubular cells in-line with a standard RRT
CVVHDF at a dose of 2500 mL/h demonstrated that even at 2.5 g/kg circuit (referred to as the renal assist device, or RAD) represent potential
amino acid supplementation patients remained in negative, albeit areas of future direction that may provide promising advances in RRT.

section08.indd 942 1/14/2015 8:28:01 AM