Critical Care Nephrology: Core Curriculum 2009

Abstract

In the inpatient setting, a high proportion of nephrology consultations are requested for patients in the intensive care unit (ICU). These patients may have acute kidney injury (AKI) or may be critically ill and have end-stage renal disease (ESRD). Thus, nephrologists need to understand recent evidence-based advances in the field of critical care, as well as areas of ongoing controversy and investigation. In this article, we summarize the diagnosis and management of shock, as well as the management of sepsis, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and fulminant hepatic failure, all of which are associated with high mortality in the critical care setting. We discuss infectious complications of critical care, including ventilator-associated pneumonia and catheter-related infections. Supportive care, including nutrition, insulin therapy, and anemia management, are reviewed. Dialysis considerations in critically ill patients are discussed. Last, we review the management of several life-threatening intoxications, many of which require early recognition and consideration of dialysis. Definition: absolute hypotension (eg, systolic blood pressure < 90 mm Hg or mean arterial pressure [MAP] < 60 mm Hg) or relative hypotension (eg, decrease in systolic blood pressure > 40 mm Hg) resulting in inadequate end-organ perfusion.1Parrillo J. Approach to the patient with shock.in: Goldman L. Ausiello D. Cecil Medicine (ed 23), chap 107. Saunders Elsevier, Philadelphia, PA2007Google Scholar, 2Herget-Rosenthal S. Saner F. Chawla L.S. Approach to hemodynamic shock and vasopressors.Clin J Am Soc Nephrol. 2008; 3: 546-553Crossref PubMed Scopus (38) Google Scholar IHypovolemic: hemorrhage, volume depletion due to decreased fluid intake or excessive fluid lossesIIDistributive: low systemic vascular resistanceASepsisBAnaphylaxisCEndocrine: adrenal insufficiencyDNeurogenic: spinal shockIIICardiogenic: acute myocardial infarction, heart failure, valvular heart disease, arrhythmiasIVObstructive: extracardiac disease resulting in poor cardiac function: decreased cardiac filling (eg, tamponade, mechanical ventilation with high positive end-expiratory pressure resulting in decreased venous return) or increased cardiac afterload (massive pulmonary embolism) IEchocardiography: transthoracic or transesophagealIIInvasive hemodynamic monitoringACentral venous catheter1Central venous pressure (CVP) may be artificially high in patients on mechanical ventilation and high levels of positive end-expiratory pressure (increases intrathoracic pressure)2Superior vena cava oxygen saturation (ScVo2) as a correlate of mixed venous oxygen saturation (which can be measured only with a pulmonary artery catheter)aCorrelation with mixed venous oxygen saturation somewhat controversial4Chawla L.S. Zia H. Gutierrez G. Katz N.M. Seneff M.G. Shah M. Lack of equivalence between central and mixed venous oxygen saturation.Chest. 2004; 126: 1891-1896Crossref PubMed Scopus (149) Google ScholarBPulmonary artery catheter1Pulmonary artery occlusion pressure/pulmonary capillary wedge pressure reflects left atrial pressure in the absence of significant valvular heart disease2Cardiac output monitoring: Fick or thermodilutionaThermodilution cardiac output monitoring unreliable with triscupid valve diseasebFick cardiac output monitoring uses mixed venous oxygen saturation (obtained from the pulmonary artery) to calculate cardiac output; assumes normal oxygen consumptionCCardiac output, systemic vascular resistance, and CVP can be used to distinguish between the different types of shock (Table 1)Table 1Hemodynamics in Various Shock StatesCVPCardiac OutputSVRCardiogenicHighLowHighHypovolemicLowLowHighDistributiveLowHighLowAbbreviations: CVP, central venous pressure; SVR, systemic vascular resistance. Open table in a new tab DPulmonary artery catheterization has not been shown to be of benefit in critically ill or surgical populations.5Sandham J.D. Hull R.D. Brant R.F. et al.A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients.N Engl J Med. 2003; 348: 5-14Crossref PubMed Scopus (1182) Google Scholar, 6Wheeler A.P. Bernard G.R. Thompson B.T. et al.Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.N Engl J Med. 2006; 354: 2213-2224Crossref PubMed Scopus (769) Google Scholar, 7Richard C. Warszawski J. Anguel N. et al.Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: A randomized controlled trial.JAMA. 2003; 290: 2713-2720Crossref PubMed Scopus (514) Google Scholar In general, CVP monitoring is sufficient. Pulmonary artery catheters may be associated with complications, including infection, arrhythmias, and pulmonary artery rupture. However, in cases of mixed shock (eg, septic and cardiogenic), invasive cardiac output monitoring may be useful to tailor vasopressor therapy. Echocardiography also may be useful in the management of complex (eg, mixed cause) shock or shock in a patient with known heart failureIIIOther methods to monitor cardiac output (partial carbon dioxide rebreathing, pulse contour analysis) are less well validatedAArterial catheter1Allows for beat-to-beat blood pressure monitoring2Radial, femoral, or dorsalis pedis sites preferred3Perform Allen test before radial arterial catheter placement to confirm adequate collateral circulation4Avoid ulnar and brachial arteries because of greater risk of limb ischemiaIVSerum tryptase levels can be useful in anaphylaxis Abbreviations: CVP, central venous pressure; SVR, systemic vascular resistance. ITreat underlying cause of shock (infection, myocardial infarction)IIVolume resuscitation for hypovolemiaAData do not support the use of colloids (albumin, hydroxyethyl starch) over isotonic crystalloid solutions8Finfer S. Bellomo R. Boyce N. French J. Myburgh J. Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit.N Engl J Med. 2004; 350: 2247-2256Crossref PubMed Scopus (2104) Google Scholar, 9Perel P. Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients.Cochrane Database Syst Rev. 2007; 17: CD000567Google ScholarBIn patients with sepsis, hydroxyethyl starch administration has been associated with an increased incidence of AKI and should be avoided10Brunkhorst F.M. Engel C. Bloos F. et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med. 2008; 358: 125-139Crossref PubMed Scopus (2354) Google ScholarIIIVasoactive agents (Table 2)2Herget-Rosenthal S. Saner F. Chawla L.S. Approach to hemodynamic shock and vasopressors.Clin J Am Soc Nephrol. 2008; 3: 546-553Crossref PubMed Scopus (38) Google ScholarAVasopressors increase vascular tone, which in turn increases MAPBInotropes increase cardiac contractility and therefore cardiac outputCCommonly used medications include:1Phenylephrine (neosynephrine): pure α agonist2Dopamine: dopamine receptor, β and α agonist (dose dependent)3Dobutamine: β1 and β2 agonist, use can be associated with hypotension; often used to increase cardiac output in patients with cardiogenic shock caused by congestive heart failure4Epinephrine: β1 greater than α1, β2 receptor agonist5Norepinephrine (Levophed): α1 and β1 agonist, associated with less tachycardia than epinephrine6Vasopressin: has been used as a second-line pressor for refractory septic shock; use can be associated with significant mesenteric ischemia7Milrinone/amrinone: phosphodiesterase inhibitors with inotropic and vasodilatory effects; used along with dobutamine for the treatment of patients with cardiogenic shock in the setting of congestive heart failureTable 2Summary of Vasopressor and Inotropic Agents Open table in a new tab IVEarly goal-directed therapy for sepsis (see Sepsis IV)VCorticosteroids for adrenal insufficiency (see Sepsis VI)VIAnaphylaxis: epinephrine, H1 and H2 blockers, steroidsVIISupportive care: intubation and mechanical ventilation if needed ISystemic inflammatory response syndrome (SIRS): characterized by the presence of: (1) temperature greater than 38°C or less than 36°C, (2) heart rate greater than 90 beats/min, (3) respiratory rate greater than 20 breaths/min or need for support with mechanical ventilation, and (4) white blood cell count greater than 12,000 cells/μL or less than 4,000 cells/μLIISepsis: suspected or documented infection in association with 2 or more SIRS criteriaIIISevere sepsis: sepsis with acute organ dysfunctionIVSeptic shock: severe sepsis with hypotension despite adequate fluid resuscitation IApproximately 750,000 cases/y in the United States, resulting in approximately 200,000 deathsIIMortality rate approximately 30% to 40%, but greater in sicker populationsIIIMajor risk factor for AKI IAppropriate broad-spectrum antibiotics and control of source of infection (eg, debridement, removal of infected catheter)IIVolume resuscitationIIIVasopressors as neededAData supporting choice of first vasopressor limitedBNorepinephrine/Levophed may be reasonable because it will increase systemic vascular resistance and increase cardiac output13Martin C. Viviand X. Leone M. Thirion X. Effect of norepinephrine on the outcome of septic shock.Crit Care Med. 2000; 28: 2758-2765Crossref PubMed Scopus (301) Google ScholarCA recent clinical trial does not support the use of vasopressin as a first-line agent in combination with norepinephrine (Vasopressin and Septic Shock Trial [VASST])14Russell J.A. Walley K.R. Singer J. et al.Vasopressin versus norepinephrine infusion in patients with septic shock.N Engl J Med. 2008; 358: 877-887Crossref PubMed Scopus (1229) Google ScholarIVEarly goal-directed therapy: refers to the combination of volume resuscitation/vasopressors and inotropes/transfusion guided by CVP (target CVP, 8 to 12 mm Hg), arterial blood pressure (MAP > 65 mm Hg), ScVo2 (ScVo2 > 70%), and evidence of end-organ perfusion (urine output > 0.5 mL/kg/h)AA single-center randomized clinical trial showed mortality benefit with early institution of these interventions (within 6 hours of diagnosis)15Rivers E. Nguyen B. Havstad S. et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7864) Google Scholar1A multicenter clinical trial (Protocolized Care for Early Septic Shock [PROCESS]) is ongoing to confirm results of the initial study and try to better correlate these interventions with benefitVActivated protein C was shown to have mortality benefit for patients with severe sepsis with Acute Physiology and Chronic Health Evaluation (APACHE) II score of 25 or higher in a large randomized multicenter clinical trial16Bernard G.R. Vincent J.L. Laterre P.F. et al.Efficacy and safety of recombinant human activated protein C for severe sepsis.N Engl J Med. 2001; 344: 699-709Crossref PubMed Scopus (5070) Google ScholarAActivated protein C has not been shown to be of benefit in children or less critically ill adults17Abraham E. Laterre P.F. Garg R. et al.Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death.N Engl J Med. 2005; 353: 1332-1341Crossref PubMed Scopus (768) Google Scholar, 18Nadel S. Goldstein B. Williams M.D. et al.Drotrecogin alfa (activated) in children with severe sepsis: A multicentre phase III randomised controlled trial.Lancet. 2007; 369: 836-843Abstract Full Text Full Text PDF PubMed Scopus (420) Google ScholarBA clinical trial of critically ill adults with refractory shock (PROWESS-SHOCK) is ongoing19Barie P.S. “All in” for a huge pot: The PROWESS-SHOCK trial for refractory septic shock.Surg Infect (Larchmt). 2007; 8: 491-494Crossref PubMed Scopus (20) Google ScholarVIRole of steroids for relative adrenal insufficiency is controversial20Marik P.E. Pastores S.M. Annane D. et al.Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine.Crit Care Med. 2008; 36: 1937-1949Crossref PubMed Scopus (686) Google ScholarADiagnosis of relative adrenal insufficiency should be considered with refractory shock after volume resuscitationBBoth basal cortisol level and response to high-dose corticotropin (ACTH) stimulation test have been used to define adrenal insufficiency in the critically ill,21Cooper M.S. Stewart P.M. Adrenal insufficiency in critical illness.J Intensive Care Med. 2007; 22: 348-362Crossref PubMed Scopus (76) Google Scholar although criteria for adrenal insufficiency are controversialCAnnane et al22Annane D. Sebille V. Charpentier C. et al.Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.JAMA. 2002; 288: 862-871Crossref PubMed Scopus (2529) Google Scholar showed a mortality benefit with hydrocortisone/fludrocortisone treatment for 7 days in patients with relative adrenal insufficiency and early septic shock in a multicenter placebo-controlled randomized clinical trialDHowever, in a subsequent multicenter placebo-controlled randomized clinical trial, low-dose hydrocortisone therapy did not improve survival in patients with septic shock23Sprung C.L. Annane D. Keh D. et al.Hydrocortisone therapy for patients with septic shock.N Engl J Med. 2008; 358: 111-124Crossref PubMed Scopus (1647) Google Scholar1Treatment with hydrocortisone was associated with a shorter time on vasopressor therapy, but also with an increase in new sepsis and new septic shock2Differing results may be attributable to differences in duration of septic shock, severity of illness, steroid administration (patients in study by Annane et al22Annane D. Sebille V. Charpentier C. et al.Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.JAMA. 2002; 288: 862-871Crossref PubMed Scopus (2529) Google Scholar randomly assigned earlier, had higher severity of illness scores, and received fludrocortisone and hydrocortisone)EIn both studies, patients were randomly assigned after the ACTH stimulation test, but before results were available; thus, patients should be treated empirically with steroids if there is a concern for relative adrenal insufficiency, rather than waiting for results of the stimulation testVIIOther supportive care as warranted by the clinical condition: intubation and mechanical ventilation, nutrition, glycemic controlVIIIData for some of the Surviving Sepsis guidelines are limited Acute onset (<7 days) of:IHypoxemia: Pao2/fraction of inspired oxygen (Fio2) less than 300 for ALI, less than 200 for ARDSIIBilateral infiltrates on chest radiographIIINo clinical evidence of left atrial hypertension IInfection: pneumonia, sepsisIIAspirationIIITraumaIVTransfusion I. Mortality rate 25% to 40% in most recent studies ILung protection with a low tidal volume ventilation strategy has mortality benefit for patients with ALI/ARDS27Brower R.G. Shanholtz C.B. Fessler H.E. et al.Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients.Crit Care Med. 1999; 27: 1492-1498Crossref PubMed Scopus (480) Google ScholarATidal volume, 6 mL/kg ideal body weight (versus 12 mL/kg ideal body weight)BIdeal body weight: 50 + 2.3 × (height in inches − 60) for men, 45.5 + 2.3 × (height in inches − 60) for womenCPlateau pressure less than 30 mm H2ODGoal Pao2, 55 to 80 mm HgETarget pH, 7.30 to 7.451For moderate acidosis (pH, 7.15 to 7.30), can increase respiratory rate (not to exceed 35) until pH 7.35 or Paco2 less than 25 mm Hg2For severe acidosis (pH < 7.15), can increase respiratory rate (not to exceed 35), increase tidal volume, or administer intravenous bicarbonateFPermissive hypercapnia/respiratory acidosis may be problematic in patients with concomitant AKI or chronic kidney disease who may have concurrent metabolic acidosis28Liu K.D. Matthay M.A. Chertow G.M. Evolving practices in critical care and potential implications for management of acute kidney injury.Clin J Am Soc Nephrol. 2006; 1: 869-873Crossref PubMed Scopus (24) Google ScholarIIA fluid conservative management strategy increases ventilator-free days in patients with ALI/ARDS29Wiedemann H.P. Wheeler A.P. Bernard G.R. et al.Comparison of two fluid-management strategies in acute lung injury.N Engl J Med. 2006; 354: 2564-2575Crossref PubMed Scopus (2636) Google ScholarAPatients with ESRD or AKI requiring dialysis at the time of study enrollment were excluded from the fluid management studyBThe fluid conservative management strategy was not associated with an increased requirement for dialysisCPatients in the fluid-conservative group received diuretics to achieve a target CVP of 4 to 8 mm Hg or pulmonary artery occlusion pressure of 8 to 12 mm Hg provided they: (1) were out of shock for 12 hours, (2) had effective circulation based on cardiac index or physical examination, and (3) were not oliguric, defined as urine output less than 0.5 mL/kg/hIIIHigher levels of positive end-expiratory pressure do not appear to have mortality benefit for patients with ALI30Brower R. Lanken P. MacIntyre N. et al.Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.N Engl J Med. 2004; 351: 327-336Crossref PubMed Scopus (1859) Google Scholar, 31Meade M.O. Cook D.J. Guyatt G.H. et al.Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: A randomized controlled trial.JAMA. 2008; 299: 637-645Crossref PubMed Scopus (1083) Google Scholar, 32Mercat A. Richard J.C. Vielle B. et al.Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: A randomized controlled trial.JAMA. 2008; 299: 646-655Crossref PubMed Scopus (1016) Google ScholarIVRescue therapies include:AExtracorporeal membrane oxygenation (ECMO)BHigh-frequency ventilationCPartial liquid ventilation with a perflurocarbonDInhaled nitric oxideEProstacyclinVAnimal studies suggest that injurious mechanical ventilation (eg, high tidal volume) and lung injury can lead to AKI,33Imai Y. Parodo J. Kajikawa O. et al.Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome.JAMA. 2003; 289: 2104-2112Crossref PubMed Scopus (565) Google Scholar, 34Choi W.I. Quinn D.A. Park K.M. et al.Systemic microvascular leak in an in vivo rat model of ventilator-induced lung injury.Am J Respir Crit Care Med. 2003; 167: 1627-1632Crossref PubMed Scopus (110) Google Scholar, 35Kuiper J.W. Groeneveld A.B. Slutsky A.S. Plotz F.B. Mechanical ventilation and acute renal failure.Crit Care Med. 2005; 33: 1408-1415Crossref PubMed Scopus (156) Google Scholar although the molecular mechanisms have not been fully elucidated. Similarly, AKI may lead to or exacerbate existing lung injury in animal models IClinical suspicion of infection: new fevers, leukocytosis or purulent respiratory secretions, worsening respiratory failure/increased ventilator supportIICulture: gold-standard methods are unclearAMany ways to obtain culture specimens, including such quantitative methods as bronchoalveolar lavage and protected specimen brush, as well as nonquantitative cultures and endotracheal aspiratesBAlthough bronchoalveolar lavage and protected brush specimens with quantitative cultures may allow for more rapid antibiotic deescalation, superiority to nonquantitative methods is not clear37Shorr A.F. Sherner J.H. Jackson W.L. Kollef M.H. Invasive approaches to the diagnosis of ventilator-associated pneumonia: A meta-analysis.Crit Care Med. 2005; 33: 46-53Crossref PubMed Scopus (156) Google Scholar, 38Kollef M.H. Diagnosis of ventilator-associated pneumonia.N Engl J Med. 2006; 355: 2691-2693Crossref PubMed Scopus (52) Google Scholar, 39The Canadian Critical Care Trials Group: A randomized trial of diagnostic techniques for ventilator-associated pneumonia.N Engl J Med. 2006; 355: 2619-2630Crossref PubMed Scopus (417) Google ScholarIIIAppropriate empiric initial antibiotic therapy is key: antibiotics should be tailored to known local antimicrobial resistance patternsIVPatients with ventilator-associated pneumonia are at high risk of sepsis and associated AKI ICatheter colonization: presence of bacteria or fungi in a quantitative or semiquantitative culture of catheter material, but without signs of local or systemic infection. Microorganisms grow in a biofilm that coats the surface of the catheterIIExit-site/insertion-site infection: erythema, tenderness, induration, or purulence at the site the catheter exits the skinIIITunnel infection: erythema, tenderness, induration, or purulence in the tract where a venous catheter is tunneled under the skinIVCatheter-related bloodstream infection: bacteremia in the presence of positive cultures from the catheter itself (see Diagnosis section) ICatheter-related bloodstream infections are more common with nontunneled than tunneled central cathetersIIMajor risk factors for infection include duration of catheter use, number of catheter lumens (multilumen catheters carry greater risk of infection), poor technique at the time of catheter insertion, use of total parenteral nutritition (TPN)41Safdar N. Kluger D.M. Maki D.G. A review of risk factors for catheter-related bloodstream infection caused by percutaneously inserted, noncuffed central venous catheters: Implications for preventive strategies.Medicine (Baltimore). 2002; 81: 466-479Crossref PubMed Scopus (211) Google ScholarIIIAlthough subclavian catheters generally are associated with lower risk of infections compared with internal jugular and femoral catheters, these should be avoided in patients with AKI or ESRD because of the risk of subclavian stenosisIVAlthough the internal jugular site generally is believed to be associated with less risk of infection than the femoral site, a recent randomized clinical trial suggests that the risk of infection is similar with nontunnelled femoral and internal jugular dialysis catheters in critically ill immobilized patients.42Parienti J.J. Thirion M. Megarbane B. et al.Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: A randomized controlled trial.JAMA. 2008; 299: 2413-2422Crossref PubMed Scopus (276) Google Scholar However, in patients in the highest tertile of body mass index (>28.4 kg/m2), femoral catheters were associated with increased risk of infection compared with internal jugular catheters. Furthermore, these results cannot be generalized to mobile non–critically ill individuals IDifferential time to positivity: if a blood sample drawn from the catheter is positive more than 2 hours before the peripheral-blood culture, this is highly suggestive of catheter-related bloodstream infectionIIQuantitative blood cultures: if a blood sample drawn through the catheter has a greater concentration (≥5:1 ratio) of microorganisms than the peripheral-blood culture, this is highly suggestive of catheter-related bloodstream infectionIIIQuantitative culture of catheter segment or catheter tip: requires removal of central venous catheter IEmpiric broad-spectrum antibiotics; staphylococci are common pathogensIIRemoval of central venous catheter; however, this decision will depend on: (1) ongoing need for central venous access, (2) ability to replace the catheter at another site, (3) clinical status of the patient, and (4) type of infection/pathogenIIIIndications for catheter removal include: septic shock, presence of a tunnel infection, polymicrobial bacteremia, gram-negative rod bacteremia, fungemia, evidence of distant infection (abscesses, endocarditis), and failure to respond to antibiotic therapy IPatients who are critically ill frequently are hypermetabolic/hypercatabolic and therefore at increased risk of nutritional complications45Stralovich-Romani A. Mahutte C. Luce J. Nutritional and ethical principles in critical illness and injury.in: George R. Light R. Matthay M. Matthay R. Chest Medicine. (ed 5). Lippincott Williams & Wilkins, Philadelphia, PA2005: 497-516Google ScholarIICalorie requirements can be estimated by using predictive equations (Harris-Benedict or Mifflin-St Jeor for obesity) or measured by using indirect calorimetry (in which oxygen consumption and carbon dioxide generation are measured in expired gas and used to calculate resting energy expenditure and the respiratory quotient [RQ])AIndirect calorimetry is less accurate as oxygen requirements increase and generally is not useful when the patient requires an Fio2 greater than 0.60BIndirect calorimetry also allows for calculation of the RQ; a high RQ (≥1.0) suggests overfeeding (of either total calories or carbohydrates) or a hypermetabolic stateIIINitrogen balance can be used to determine whether provision of nutrition therapy (particularly protein) is adequateAProtein requirements of patients with AKI vary based on the underlying cause of AKI and type of renal support provided (both intermittent hemodialysis and continuous renal replacement therapy [CRRT] associated with ongoing protein losses)46Liu K.D. Stralovich-Romani A. Chertow G.M. Nutrition support for adult patients with acute renal failure.in: Merritt R. American Society for Parenteral and Enteral Nutrition (ASPEN) Nutrition Support Guidelines. American Society for Parenteral and Enteral Nutrition, Silver Spring, MD2006: 281-286Google ScholarBPatients on CRRT likely will require at least 1.6 to 1.8 g/kg/d of amino acids and, in some studies, have received up to 2.5 g/kg/d without complicationsIVSerum markers for nutritional adequacy in the critically ill are controversial45Stralovich-Romani A. Mahutte C. Luce J. Nutritional and ethical principles in critical illness and injury.in: George R. Light R. Matthay M. Matthay R. Chest Medicine. (ed 5). Lippincott Williams & Wilkins, Philadelphia, PA2005: 497-516Google ScholarAAlthough serum albumin level is a valuable prognostic indicator of morbidity and mortality, serum albumin levels decrease with metabolic stress and with specific disease states that are common in the ICU, such as liver failureBTransferrin, prealbumin, and retinol-binding protein levels may be superior markers of nutritional status; however, in patients with critical illness, synthesis of these proteins may decrease because of preferential production of acute-phase reactants (ie, C-reactive protein)CPrealbumin level may be falsely increased in patients with kidney failure because of reduced clearance and in patients on high-dose steroid therapyDTrends of prealbumin and C-reactive protein levels may be more useful than absolute values to follow up response to nutrition therapyVIn an observational cohort study, critically ill patients with AKI did not have significantly more major gastrointestinal complications (vomiting, diarrhea, abdominal distention) or more infectious complications (aspiration pneumonia)47Fiaccadori E. Maggiore U. Giacosa R. et al.Enteral nutrition in patients with acute renal failure.Kidney Int. 2004; 64: 999-1004Crossref Scopus (77) Google ScholarVITPN is associated with increased risk of infection and should be used only if efforts to provide enteral nutrition have failed or the patient has a strict contraindication to enteral feeding IA large randomized clinical trial of surgical patients showed mortality benefit and decreased length of ICU stay in patients who received intensive insulin therapy (target blood glucose, 80 to 110 mg/dL [4.4 to 6.1 mmol/L])48Van den Berghe G. Wouters P. Weekers F. et al.Intensive insulin therapy in the critically ill patient.N Engl J Med. 2001; 345: 1359-1367Crossref PubMed Scopus (8192) Google ScholarIIA subsequent randomized clinical trial of medical patients did not show the same mortality benefit49Van den Berghe G. Wilmer A. Hermans G. et al.Intensive insulin therapy in the medical ICU.N Engl J Med. 2006; 354: 449-461Crossref PubMed Scopus (2955) Google ScholarAHowever, patients who had longer ICU stays (defined as ≥3 days) had decreased in-hospital and ICU mortality with intensive insulin therapyIIIIntensive insulin therapy is associated with an increased incidence of severe hypoglycemia50Schetz M.R.C. Classical and alternative indications for continuous renal replacement therapy.Kidney Int Suppl. 1999; 66: S129-S132Google ScholarIVIt is unclear whether the benefit is from glycemic control or a direct effect of the insulin itselfVA pooled analysis of the large medical and surgical clinical trials suggest that patients with better glycemic control had lower mortality rates; however, it is unclear whether this was a result of the improved glycemic control or differences in severity of illness51Van den Berghe G. Wilmer A. Milants I. et al.Intensive insulin therapy in mixed medical/surgical intensive care units: Benefit versus harm.Diabetes. 2006; 55: 3151-3159Crossref PubMed Scopus (480) Google ScholarVISimilarly, a pooled analysis of the 2 large clinical trials and a meta-analysis suggest that intensive insulin therapy has a renoprotective effect52Thomas G. Rojas M.C. Epstein S.K. Balk E.M. Liangos O. Jaber B.L. Insulin therapy and acute kidney injury in critically ill patients: A systematic review.Nephrol Dial Transplant. 2007; 22: 2849-2855Crossref PubMed Scopus (45) Google Scholar, 53Schetz M. Vanhorebeek I. Wouters P.J. Wilmer A. Van den Berghe G. Tight blood glucose control is renoprotective in critically ill patients.J Am Soc Nephrol. 2008; 19: 571-578Crossref PubMed Scopus (112)