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BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] +/- 1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD +/- 1.1] vs 3.5 [SD +/- 1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.

The adult human body contains about 4 g of iron. About 1–2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.

Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©

IMPORTANCE: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. OBJECTIVE: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTS: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONS: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P

IntroductionAcute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.Methods and analysisWe plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes.Ethics and disseminationThe PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial.Trial registration numberNCT03244514.

Background: Post-operative anaemia is associated with increased morbidity and mortality. Positive effects of post-operative intravenous iron (IVI) after elective orthopaedic, abdominal and genitourinary surgery have been reported. The current observational trial investigated the prevalence of post-operative anaemia, the effect of IVI on haemoglobin levels, the use of blood transfusions and diagnoses related to infections. Methods: 1,265 patients on five ICUs of Münster University Hospital were screened for post-operative anaemia. On one ICU, patients were screened for iron deficiency and, if indicated, supplemented with 500 mg of ferric carboxymaltose. Primary outcome measures were haemoglobin levels, C-reactive protein, white blood cell count, transfusion requirements, documented infection and antibiotic treatment. Results: Anaemia was prevalent in 86.2% of patients upon ICU admission. 429 patients were screened for iron deficiency anaemia. 95 patients were eligible, 35 were treated with IVI. An increase of +0.4 g/dl in Hb levels 7 days after IVI compared to -0.1 g/dl in non-treated anaemic patients was observed. The number of RBC transfusions, ICD codes related to infections and infectious parameters were similar between groups. Conclusions: IVI treatment was safe and resulted in higher median Hb levels. Randomized controlled trials are required to support the hypotheses of this study.

Trials 20(1), 213 (2019). doi:10.1186/s13063-019-3208-8

Neurophysiological mechanisms leading to chronicity of pruritus are not yet fully understood and it is not known whether these mechanisms diverge between different underlying diseases of chronic pruritus (CP). This study aimed to detect such mechanisms in CP of various origins. A total of 120 patients with CP of inflammatory origin (atopic dermatitis), neuropathic origin (brachioradial pruritus), and chronic prurigo of nodular type, the latter as a model for chronic scratching, as well as 40 matched healthy controls participated in this study. Stimulation with cowhage induced a more intensive itch sensation compared with stimulation with other substances in all patient groups but not in healthy controls, arguing for sensitization of cutaneous mechano- and heat-sensitive C-fibers in CP. All patient groups showed a decreased intraepidermal nerve fiber density compared with controls. A decreased condition pain modulation effect was observed in all patient groups compared with controls, suggesting a reduced descending inhibitory system in CP. In sum, CP of different etiologies showed a mixed peripheral and central pattern of neuronal alterations, which might contribute to the chronicity of pruritus with no differences between pruritus entities. Our findings may contribute to the development of future treatment strategies targeting these pathomechanisms.

Care bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.In this single-center trial, we examined the effect of a "KDIGO bundle" consisting of optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs, and preventing hyperglycemia in high risk patients defined as urinary [TIMP-2]·[IGFBP7] 0.3 undergoing cardiac surgery. The primary endpoint was the rate of AKI defined by KDIGO criteria within the first 72 h after surgery. Secondary endpoints included AKI severity, need for dialysis, length of stay, and major adverse kidney events (MAKE) at days 30, 60, and 90.AKI was significantly reduced with the intervention compared to controls [55.1 vs. 71.7%; ARR 16.6% (95 CI 5.5-27.9%); p = 0.004]. The implementation of the bundle resulted in significantly improved hemodynamic parameters at different time points (p 0.05), less hyperglycemia (p 0.001) and use of ACEi/ARBs (p 0.001) compared to controls. Rates of moderate to severe AKI were also significantly reduced by the intervention compared to controls. There were no significant effects on other secondary outcomes.An implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients. Adequately powered multicenter trials are warranted to examine mortality and long-term renal outcomes.

Background Dysregulations of blood glucose (BG) are associated with adverse outcome in critical illness; controlling BG to target appears to improve outcome. Since BG-control is challenging in daily intensive care practice BG-control remains poor especially in patients with rapidly fluctuating BG. To improve BG-control and to avoid deleterious hypoglycemia, automated online-measurement tools are advocated. We thus evaluated the point-accuracy of the subcutaneous Sentrino® Continuous Glucose Monitoring System (CGM, Medtronic Diabetes, Northridge, California) in patients undergoing extracorporeal cardiac life support (ECLS) for cardiogenic shock. Methods Management of BG was performed according to institute’s standard aiming at BG-levels between 100–145 mg/dl. CGM-values were recorded without taking measures into therapeutic account. Point-accuracy in comparison to intermittent BG-measurement by the ABL-blood-gas analyzer was determined. Results CGM (n = 25 patients) correlated significantly with ABL-values (r = 0.733, p

OBJECTIVE Tight glycemic control (TGC) in critically ill patients is associated with an increased risk of hypoglycemia. Whether those short episodes of hypoglycemia are associated with adverse morbidity and mortality is a matter of discussion. Using a case-control study design, we investigated whether hypoglycemia under TGC causes permanent neurocognitive dysfunction in patients surviving critical illness. RESEARCH DESIGN AND METHODS From our patient data management system, we identified adult survivors treated for >72 h in our surgical intensive care unit (ICU) between 2004 and 2007 (n = 4,635) without a history of neurocognitive dysfunction or structural brain abnormalities who experienced at least one episode of hypoglycemia during treatment (hypo group) (n = 37). For each hypo group patient, one patient stringently matched for demographic- and disease-related data were identified as a control subject. We performed a battery of neuropsychological tests investigating five areas of cognitive functioning in both groups at least 1 year after ICU discharge. Test results were compared with data from healthy control subjects and between groups. RESULTS Critical illness caused neurocognitive dysfunction in all tested domains in both groups. The dysfunction was aggravated in hypo group patients in one domain, namely that of visuospatial skills (P < 0.01). Besides hypoglycemia, both hyperglycemia (r = −0.322; P = 0.005) and fluctuations of blood glucose (r = −0.309; P = 0.008) were associated with worse test results in this domain. CONCLUSIONS Hypoglycemia was found to aggravate critical illness–induced neurocognitive dysfunction to a limited, but significant, extent; however, an impact of hyperglycemia and fluctuations of blood glucose on neurocognitive function cannot be excluded.

Optimal timing of initiation of renal replacement therapy (RRT) for severe acute kidney injury (AKI) but without life-threatening indications is still unknown.To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality.Single-center randomized clinical trial of 231 critically ill patients with AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 (≥2 times baseline or urinary output0.5 mL/kg/h for ≥12 hours) and plasma neutrophil gelatinase-associated lipocalin level higher than 150 ng/mL enrolled between August 2013 and June 2015 from a university hospital in Germany.Early (within 8 hours of diagnosis of KDIGO stage 2; n = 112) or delayed (within 12 hours of stage 3 AKI or no initiation; n = 119) initiation of RRT.The primary end point was mortality at 90 days after randomization. Secondary end points included 28- and 60-day mortality, clinical evidence of organ dysfunction, recovery of renal function, requirement of RRT after day 90, duration of renal support, and intensive care unit (ICU) and hospital length of stay.Among 231 patients (mean age, 67 years; men, 146 [63.2%]), all patients in the early group (n = 112) and 108 of 119 patients (90.8%) in the delayed group received RRT. All patients completed follow-up at 90 days. Median time (Q1, Q3) from meeting full eligibility criteria to RRT initiation was significantly shorter in the early group (6.0 hours [Q1, Q3: 4.0, 7.0]) than in the delayed group (25.5 h [Q1, Q3: 18.8, 40.3]; difference, -21.0 [95% CI, -24.0 to -18.0]; P .001). Early initiation of RRT significantly reduced 90-day mortality (44 of 112 patients [39.3%]) compared with delayed initiation of RRT (65 of 119 patients [54.7%]; hazard ratio [HR], 0.66 [95% CI, 0.45 to 0.97]; difference, -15.4% [95% CI, -28.1% to -2.6%]; P = .03). More patients in the early group recovered renal function by day 90 (60 of 112 patients [53.6%] in the early group vs 46 of 119 patients [38.7%] in the delayed group; odds ratio [OR], 0.55 [95% CI, 0.32 to 0. 93]; difference, 14.9% [95% CI, 2.2% to 27.6%]; P = .02). Duration of RRT and length of hospital stay were significantly shorter in the early group than in the delayed group (RRT: 9 days [Q1, Q3: 4, 44] in the early group vs 25 days [Q1, Q3: 7,90] in the delayed group; P = .04; HR, 0.69 [95% CI, 0.48 to 1.00]; difference, -18 days [95% CI, -41 to 4]; hospital stay: 51 days [Q1, Q3: 31, 74] in the early group vs 82 days [Q1, Q3: 67,90] in the delayed group; P .001; HR, 0.34 [95% CI, 0.22 to 0.52]; difference, -37 days [95% CI, -∞ to -19.5]), but there was no significant effect on requirement of RRT after day 90, organ dysfunction, and length of ICU stay.Among critically ill patients with AKI, early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days. Further multicenter trials of this intervention are warranted.German Clinical Trial Registry Identifier: DRKS00004367.

BACKGROUND: The most effective ropivacaine concentration for femoral infusion after total knee arthroplasty is currently ill defined. We designed the present study to compare ropivacaine in three different concentrations (0.1, 0.2, and 0.3%) to evaluate analgesic quality, when administered as a continuous infusion with frequent infusion adjustments in patients receiving a combined femoral and sciatic nerve block. Secondary aims were to evaluate side effects such as motor blockade, rehabilitation indices, and ropivacaine plasma concentrations. METHODS: One hundred twenty-two patients undergoing total knee arthroplasty under combined general and regional anesthesia received femoral infusions of ropivacaine 0.1, 0.2, or 0.3%. Infusions were started after initial loading doses of 30 mL ropivacaine 0.5% into the femoral catheter and a sciatic catheter and were targeted to dynamic pain scores of 40 mm. Pain and side effects were assessed 1 h after tracheal extubation and on the first, second, third, fourth, and fifth postoperative days. Ropivacaine plasma concentrations were measured 24, 48, and 72 h after the start and 24 h after termination of femoral infusions in patients receiving ropivacaine 0.2% or 0.3%. RESULTS: Ropivacaine 0.1% provided ineffective analgesia. Ropivacaine 0.2% and 0.3% provided equivalent analgesia. Maximum infusion rates were 15.39 and 13.77 mL/h for ropivacaine 0.2% and 0.3%, respectively. There were no significant differences in motor blockade, mobilization, or ropivacaine plasma concentrations, which remained below toxic levels throughout the study period. CONCLUSION: Ropivacaine 0.2% and 0.3% were similar in terms of analgesic quality. Initial infusion rates should be adjusted to 15 mL/h to obtain effective analgesia.

Importance No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. Objective To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. Design, Setting, and Participants In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle. Interventions Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation. Main Outcomes and Measures The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers. Results Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) ( P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor–binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL 2 /1000; difference, 0.61; 95% CI, 0.27-0.86; P Conclusions and Relevance Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation. Trial Registration German Clinical Trials Register Identifier:DRKS00005333

Many ICU patients are glutamine depleted and have low glutamine plasma concentrations. Beneficial effects by glutamine supply could be proven in these patients. In some medical conditions, especially those with acute right heart failure, elevated glutamine plasma concentrations are present and glutamine supply may be disastrous and a toxic burden. It will be prudent to reassess the use of glutamine in ICU especially in conditions with unresolved shock or right heart failure.

Glutamine is recognized as a conditionally indispensable amino acid. The purpose of the current study was to investigate whether supplemental l-alanyl-l-glutamine to parenteral nutrition can alter clinical outcome in intensive care unit patients.Prospective, open, randomized trial.Postoperative intensive care unit of a university hospital.Male and female critically ill patients with indications for parenteral nutrition and an expected stay on intensive care unit foror=5 days.Patients were randomized to receive either standard parenteral nutrition or supplemented parenteral nutrition with l-alanyl-l-glutamine (0.3 g.kg.body weight [bw] per day). Total amount of amino acids comprised 1.5 g.kg.bw per day. Caloric support was managed by metabolic variables (glucose and triglyceride plasma values). Target values for energy supply were 3 g.kg.bw carbohydrates and 1 g.kg.bw fat per day.Medical treatment, nutritional therapy, vital variables, and biochemical data were recorded. Clinical outcome was measured by average length of stay in the intensive care unit and hospital and the mortality in the intensive care unit and within 30 days and 6 months. A total of 144 patients were randomized; 95 patients were treated foror=5 days and 68 patients foror=9 days under standardized conditions. In the treatment group, plasma glutamine concentrations significantly increased within 6-9 days. Six-month survival was significantly improved for patients treated foror=9 days (66.7% [glutamine supplemented] vs. 40% [control]).Study results support the hypothesis that replacement of glutamine deficiency may correct the excess mortality in intensive care unit patients caused by inadequate parenteral nutrition.