Relevance of Protein Intake for Weaning in the Mechanically Ventilated Critically Ill: Analysis of a Large International Database.

OBJECTIVES: The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients. DESIGN: Analysis of a subset of a large international point prevalence survey of nutritional practice in ICUs. SETTING: A total of 785 international ICUs. PATIENTS: A total of 12,930 patients had been in the ICU for at least 96 hours and required MV by the fourth day after ICU admission at the latest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We modeled associations between the adjusted hazard rate (aHR) of death in patients requiring MV and successful weaning (competing risks), and three categories of protein intake (low: < 0.8 g/kg/d, standard: 0.8-1.2 g/kg/d, high: > 1.2 g/kg/d). We compared five different hypothetical protein diets (an exclusively low protein intake, a standard protein intake given early (days 1-4) or late (days 5-11) after ICU admission, and an early or late high protein intake). There was no evidence that the level of protein intake was associated with time to weaning. However, compared with an exclusively low protein intake, a standard protein intake was associated with a lower hazard of death in MV: minimum aHR 0.60 (95% CI, 0.45-0.80). With an early high intake, there was a trend to a higher risk of death in patients requiring MV: maximum aHR 1.35 (95% CI, 0.99-1.85) compared with a standard diet. CONCLUSIONS: The duration of MV does not appear to depend on protein intake, whereas mortality in patients requiring MV may be improved by a standard protein intake. Adverse effects of a high protein intake cannot be excluded.

Protein intake and outcome of critically ill patients: analysis of a large international database using piece-wise exponential additive mixed models.

BACKGROUND: Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use. METHODS: Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.8 g/kg per day, standard: 0.8-1.2 g/kg per day, high: > 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet). RESULTS: Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg [IQR 0.27-0.66], standard intake 0.99 g/kg [IQR 0.89- 1.09], and high intake 1.41 g/kg [IQR 1.29-1.60]. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome. CONCLUSIONS: Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198.

Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN).

BACKGROUND: Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes. METHODS: Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10-20 kcal/kg, 0.8-1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV). RESULTS: A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (- 2.74 [- 3.28; - 2.21] and - 0.12 [- 0.15; - 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements. CONCLUSIONS: Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503 , registered on October 25, 2019.

[The New DGEM Guideline - All the Clinician Needs to Know]. / Die neue DGEM-Leitlinie ­ alles, was der Kliniker wissen muss.

The German Society for Nutritional Medicine has recently updated its guideline on clinical nutrition in critically ill patients thereby cooperating with seven other national medical societies. This article provides readers with a concise overview on selected key aspects of this guideline relevant for clinical practice. We will discuss some issues in detail such as the determination of energy expenditure and of calorie and protein intake, the choice of the route of administration (enteral or parenteral), and the handling of micronutrients.

Enteral vs. parenteral nutrition in septic shock: are they equivalent?

PURPOSE OF REVIEW: The current review focuses on recent clinical evidence and updated guideline recommendations on the effects of enteral vs. parenteral nutrition in adult critically ill patients with (septic) shock. RECENT FINDIGS: The largest multicenter randomized-controlled trial showed that the route of nutrient supply was unimportant for 28-day and 90-day mortality, infectious morbidity and length of stay in mechanically ventilated patients with shock. The enteral route, however, was associated with lower macronutrient intake and significantly higher frequency of hypoglycemia and moderate-to-severe gastrointestinal complications. Integrating these findings into recent meta-analyses confirmed that the route per se has no effect on mortality and that interactions with (infectious) morbidity are inconsistent or questionable. SUMMARY: The strong paradigm of favoring the enteral over the parenteral route in critically ill patients has been challenged. As a consequence, updated guidelines recommend withholding enteral nutrition in patients with uncontrolled shock. It is still unclear, however, whether parenteral nutrition is advantageous in patients with shock although benefits are conceivable in light of less gastrointestinal complications. Thus far, no guideline has addressed indications for parenteral nutrition in these patients. By considering recent scientific evidence, specific guideline recommendations, and expert opinions, we present a clinical algorithm that may facilitate decision-making when feeding critically ill patients with shock.

[DGEM Guideline "Clinical Nutrition in Critical Care Medicine" - short version]. / DGEM-Leitlinie: Klinische Ernährung in der Intensivmedizin ­ Kurzversion.

PURPOSE: Variations of clinical nutrition may affect outcome of critically ill patients. Here we present the short version of the updated consenus-based guideline (S2k classification) "Clinical nutrition in critical care medicine" of the German Society for Nutritional Medicine (DGEM) in cooperation with 7 other national societies. The target population of the guideline was defined as critically ill adult patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g. mechanical ventilation) to maintain organ function. METHODS: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. We considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of international societies. The liability of each recommendation was indicated using linguistic terms. Each recommendation was finally validated and consented by a Delphi process. RESULTS: The short version presents a summary of all 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in the target population. A specific focus is the adjustment of nutrition according to the phases of critical illness, and to the individual tolerance to exogenous substrates. Among others, recommendations include the assessment of nutritional status, the indication for clinical nutrition, the timing, route, magnitude and composition of nutrition (macro- and micronutrients) as well as distinctive aspects of nutrition therapy in obese critically ill patients and those with extracorporeal support devices. CONCLUSION: The current short version of the guideline provides a concise summary of the updated recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring pharmacological and/or mechanical support. The validity of the guideline is approximately fixed at five years (2018 - 2023).

[Laboratory and calorimetric monitoring of medical nutrition therapy in intensive and intermediate care units : Second position paper of the Section Metabolism and Nutrition of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI)]. / Laborchemisches und kalorimetrisches Monitoring der medizinischen Ernährungstherapie auf der Intensiv- und Intermediate Care Station : Zweites Positionspapier der Sektion Metabolismus und Ernährung der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

This second position paper of the Section Metabolism and Nutrition of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) provides recommendations on the laboratory monitoring of macro- and micronutrient intake as well as the use of indirect calorimetry in the context of medical nutrition therapy of critically ill adult patients. In addition, recommendations are given for disease-related or individual (level determination) substitution and (high-dose) pharmacotherapy of vitamins and trace elements.

[Assessment and technical monitoring of nutritional status of patients in intensive and intermediate care units : Position paper of the Section Metabolism and Nutrition of the German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI)]. / Erfassung und apparatives Monitoring des Ernährungsstatus von Patient*innen auf der Intensiv- und Intermediate Care Station : Positionspapier der Sektion Metabolismus und Ernährung der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

At the time of admission to an intensive or intermediate care unit, assessment of the patients' nutritional status may have both prognostic and therapeutic relevance with regard to the planning of individualized medical nutrition therapy (MNT). MNT has definitely no priority in the initial treatment of a critically ill patient, but is often also neglected during the course of the disease. Especially with prolonged length of stay, there is an increasing risk of malnutrition with considerable prognostic macro- and/or micronutrient deficit. So far, there are no structured, evidence-based recommendations for assessing nutritional status in intensive or intermediate care patients. This position paper of the Section Metabolism and Nutrition of the German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI) presents consensus-based recommendations for the assessment and technical monitoring of nutritional status of patients in intensive and intermediate care units. These recommendations supplement the current S2k guideline "Clinical Nutrition in Intensive Care Medicine" of the German Society for Nutritional Medicine (DGEM) and the DIVI.

Long-term survival after surgical critical illness: the impact of prolonged preceding organ support therapy.

OBJECTIVE: To identify the prognostic importance of preceding invasive ventilation, renal replacement therapy, and catecholamine therapy for long-term survivors after surgical critical illness. SUMMARY BACKGROUND DATA: Nothing is known about the effect of preceding intensive care unit (ICU)-related therapies on long-term outcome. METHODS: We performed a retrospective analysis of prospectively collected data of an ICU patient cohort linked to a local database. Adult patients (n = 1462) admitted to a 12-bed ICU between 1993 and 2005, who had an ICU length of stay of more than 4 days, were followed up until the end of the second year after ICU admission. Hazard function was explored by Weibull modeling and likelihood ratio tests. Cox-type structured hazard regression models were used to analyze linear, nonlinear, or time-varying associations of therapeutic variables with 2-year survival time of a patient subgroup, which had survived the period of high hazard. RESULTS: Hazard rate declined exponentially up to day 195 after ICU admission, and became constant thereafter. A total of 808 patients reached this stable stage of their disease forming the study population. Of these patients, 648 (80.2%) were still alive at the end of the second year after ICU admission. Underlying diseases were major determinants for long-term outcome. Long-term mortality was significantly associated with the acute extent of physiological derangement during ICU stay (maximum Apache II score), but was independent from the duration of preceding invasive organ support. CONCLUSION: In surgical patients with a prolonged ICU length of stay, an exorbitant mortality exists for about half a year after ICU admission. Later on, life expectancy of surviving patients is largely determined by the underlying disease and, to a minor degree, by the acute extent of homeostatic disturbance during ICU stay. The duration of preceding invasive therapies does not limit long-term survival.

Activated partial thromboplastin time waveform analysis as specific sepsis marker in cardiopulmonary bypass surgery.

Throughout the last years, several new diagnostic biomarkers have been introduced into clinical routine to identify a systemic inflammatory response syndrome (SIRS) or a septic state and to discriminate between these two entities. According to studies in selected patients, measurement of these biomarkers may be advantageous under certain clinical conditions. On an individual basis, however, these sepsis markers usually lack an adequate negative or positive predictive power. Therefore, physicians in charge still have to rely on a combination of personal experience and results from clinical or laboratory tests when deciding on a patient's therapy. For surgical patients, a key problem consists of the time delay which is associated with the diagnosis of serious postoperative infections and which may negatively affect outcome. It is in this context where the activated partial thromboplastin time waveform analysis may represent a promising new method to discriminate between SIRS and sepsis, thereby shortening the time to therapy. Nevertheless, studies involving large patient populations will be necessary to prove the efficacy of this new diagnostic concept either as a single tool or in combination with the measurement of other biomarkers.

Perioperative fluid retention and clinical outcome in elective, high-risk colorectal surgery.

BACKGROUNDS AND AIMS: There is some controversy regarding concepts currently propagated for an optimal perioperative fluid management in colorectal surgery. We wanted to analyze the association of net intraoperative and postoperative fluid balances with postoperative morbidity and length of stay. MATERIALS AND METHODS: We performed a retrospective analysis of data collected prospectively from March 1993 through February 2005. A subgroup from 4,658 patients was studied who had undergone major elective colorectal surgery during that time. This subgroup included 198 patients with a particularly high preoperative risk profile requiring immediate postoperative intensive care unit (ICU) admission. Fluid therapy was guided by established clinical end points. Results were adjusted for various confounding variables (extent of the operative trauma, individual response to the injury, type of analgesia, underlying disease, treatment era). RESULTS/FINDINGS: After adjustment for relevant covariates, the magnitude of fluid balance was unimportant for morbidity and postoperative hospital length of stay. A high Apache II score after ICU admission, an increased perioperative blood loss, and palliative surgical procedures were associated with a significantly higher complication rate, whereas use of epidural analgesia improved morbidity and shortened hospital stay. INTERPRETATION/CONCLUSION: If guided by established standards, even large perioperative fluid retentions do not appear to be associated with a worse outcome after extended colorectal surgery. Epidural analgesia may provide a significant benefit in those high-risk patients.

Calorie intake and short-term survival of critically ill patients.

BACKGROUND & AIMS: The association between calorie supply and outcome of critically ill patients is unclear. Results from observational studies contradict findings of randomized studies, and have been questioned because of unrecognized confounding by indication. The present study wanted to re-examine the associations between the daily amount of calorie intake and short-term survival of critically ill patients using several novel statistical approaches. METHODS: 9661 critically ill patients from 451 ICUs were extracted from an international database. We examined associations between survival time and three pragmatic nutritional categories (I: <30% of target, II: 30-70%, III: >70%) reflecting different amounts of total daily calorie intake. We compared hazard ratios for the 30-day risk of dying estimated for different hypothetical nutrition support plans (different categories of daily calorie intake during the first 11 days after ICU admission). To minimize indication bias, we used a lag time between nutrition and outcome, we particularly considered daily amounts of calorie intake, and we adjusted results to the route of calorie supply (enteral, parenteral, oral). RESULTS: 1974 patients (20.4%) died in hospital before day 30. Median of daily artificial calorie intake was 1.0 kcal/kg [IQR 0.0-4.1] in category I, 12.3 kcal/kg [9.4-15.4] in category II, and 23.5 kcal/kg [19.5-27.8] in category III. When compared to a plan providing daily minimal amounts of calories (category I), the adjusted minimal hazard ratios for a delayed (from day 5-11) or an early (from day 1-11) mildly hypocaloric nutrition (category II) were 0.71 (95% confidence interval [CI], 0.54 to 0.94) and 0.56 (95% CI, 0.38 to 0.82), respectively. No substantial hazard change could be detected, when a delayed or an early, near target calorie intake (category III) was compared to an early, mildly hypocaloric nutrition. CONCLUSIONS: Compared to a severely hypocaloric nutrition, a mildly hypocaloric nutrition is associated with a decreased risk of death. In unselected critically ill patients, this risk cannot be reduced further by providing amounts of calories close to the calculated target. STUDY REGISTRATION: ID number ISRCTN17829198, website http://www.isrctn.org.

Clinical Nutrition in Critical Care Medicine - Guideline of the German Society for Nutritional Medicine (DGEM).

PURPOSE: Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. METHODS: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. RESULTS: In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. CONCLUSION: The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).

Independent determinants of early death in critically ill surgical patients.

Abnormalities in cardiocirculatory, respiratory, or coagulatory parameters are frequent after major surgery, but so far, no study has investigated their predictive value for early intensive care unit (ICU) mortality. We aimed to describe and quantify the relation between these parameters that are routinely determined on ICU admission and early death after complex surgery. Individual patient data were available from a local ICU database. We performed a retrospective observational cohort study using prospectively collected data from March 1, 1993, through February 28, 2005. A cohort of 4,214 cases who were admitted to the ICU immediately after operation was analyzed. We studied age, sex, number of red blood cell units transfused on admission day, and admission values for heart rate, systolic blood pressure, hemoglobin concentration, partial thromboplastin time, prothrombin time, respiratory function (Pao2/Fio2 ratio), and body temperature for their association with 4-day mortality. Effects were adjusted for the underlying disease and for disease severity during the first 24 h after admission. We used generalized additive models to fit continuous variables individually before combining them into the final generalized model. We found an independent linear association between the number of transfused red blood cell units, partial thromboplastin time, and body temperature with acute outcome. A smoothed model described the independent interaction between admission blood pressure and early death. Only values of less than 80 mmHg were associated with an increased risk of 4-day mortality. According to these results, bleeding complications after ICU admission should be treated aggressively to prevent early death of the patient. However, normotensive conditions do not seem to be required to prevent early mortality. Whether rapid rewarming may improve outcome needs further rigorous study.

Prognostic factors in critically ill surgical patients requiring continuous renal replacement therapy.

BACKGROUND: Acute mortality of unselected critically ill patients has improved during the last 15 years. Whether these benefits also affect long-term survival of critically ill surgical patients with severe acute renal failure is unclear, as are the prognostic factors relevant for survival time or mortality. METHODS: We performed a retrospective analysis of data collected prospectively from March 1993, through February 2005. Data from a cohort of 170 consecutive postoperative patients without preceding kidney diseases but requiring continuous renal replacement therapy (CRRT) during intensive care unit (ICU) stay were analyzed. RESULTS: Six-month survival rate after ICU admission was 20.6%. In patients surviving more than 6 months, 5-year survival was 71.6%. After adjustment for relevant covariates, older age, disease severity at ICU admission, peritonitis and a large number of red cell units transfused during ICU stay were associated with worse 6-month prognosis. Duration of CRRT, and the origin and type of kidney failure were unimportant for prognosis, as was ICU admission date. CONCLUSION: Six-month prognosis of critically ill surgical patients with severe acute renal failure is poor and mostly determined by the disease severity at ICU admission and by the frequency of surgical complications. Outcome had not improved over the study period, but after successful surgical and intensive care therapy, long-term survival appears to be reasonably good.

Long-term changes of patient-reported quality of life after major trauma: The importance of the time elapsed after injury.

BACKGROUND: Numerous studies have identified various risk factors for a poor health-related quality of life (HRQOL) after severe trauma. The relative importance of the time elapsed after injury, however, is unknown and results of clinical studies have been conflicting. METHODS: A cross-sectional study was performed in two trauma centres using data from the German TraumaRegister DGU®, which contained prospectively collected information on the type and severity of the injury, on critical care, and on outcome. To evaluate HRQOL in patients surviving more than 500days after the injury, we used a self-rating instrument, the EQ-5D which contains a visual analogue scale (EQ-VAS), and which allows the calculation of a global outcome indicator, the EQ-D5 index value. Complex statistical models were used to evaluate independent associations between the time elapsed after injury and a poor HRQOL. RESULTS: Of 380 contacted patients, follow-up assessments could be obtained in 168 patients (44.2%) 3.6±1.6 (SD) years after the injury. There was a linear association between the time elapsed after the injury and the% of contacted patients not participating in the study (p=0.013). In participating subjects, average EQ-5D index value was 0.599±0.299, and average EQ-VAS rating 67.8±22.0. A very poor quality of life (EQ-5D index value<0.6, EQ-VAS rating≤50) could be found in 43.5% and 28.0% of the patients, respectively. After adjusting for multiple confounders, the number of days elapsed after injury showed a complex non-linear and independent association with a poor HRQOL (low EQ-5D index value: p=0.027; low EQ-VAS rating: p=0.008). Frequencies of a poor HRQOL reached their minimum about four to five years after the injury and increased thereafter. CONCLUSIONS: There is an independent, U-shaped association between the frequency of extreme values of HRQOL and the time elapsed after injury. Time patterns of HRQOL may be sensitive to increasing rates of attrition since patients with a good outcome are less likely to respond to questionnaires. Time from injury should be incorporated into all future cross sectional studies trying to identify predictors of HRQOL.

Red cell transfusion: an essential factor for patient prognosis in surgical critical illness?

In contrast to randomized studies, previous cohort studies identified red cell transfusion as an independent predictor of mortality in critically ill patients. However, these cohort studies did not adjust for disease severity during intensive care unit (ICU) stay. We performed a retrospective, observational cohort study using prospectively collected data from March 1, 1993, through February 28, 2005. A cohort of 3037 consecutive surgical cases requiring intensive care therapy for more than one day was analyzed. We used two different sets of potentially confounding covariables (admission variables only or in combination with variables reflecting number and extent of organ dysfunction during ICU stay). We found that the total number of red cell units which a case had received during ICU stay, and the maximum number of units given on a single day, were independently associated with an increase in ICU mortality when only admission variables were considered for the analysis. After controlling for the additional effect of variables reflecting organ dysfunction during ICU stay, we found that red cell transfusion was no longer an independent risk factor for death. However, there was a significant effect of red cell transfusion on ICU LOS in survivors irrespective of the covariable sets used. We conclude that red cell transfusion during ICU stay may be only a surrogate marker for disease severity and is not causally related to ICU mortality. Relevant side effects of red cell transfusion are presumably small and may be only recognizable in surviving cases.

Dynamics of albumin synthesis after major rectal operation.

BACKGROUND: Major abdominal operations were found to be associated with long-lasting metabolic changes, such as accelerated release of stress hormones and carbohydrate turnover. It is unknown currently whether acute changes of hepatic protein metabolism persist in a similar way. We wanted to determine the long-term dynamics of albumin synthesis and its relationship to whole body protein breakdown and albumin concentration after major rectal operations. METHODS: We used stable isotope tracer techniques to determine albumin synthesis and whole body protein breakdown (rate of appearance of leucine, Ra) in postoperative patients about 1 week after low anterior rectal resection and also during convalescence (about 4 months after operation), and in healthy controls. Consecutive blood sampling was carried out during continuous isotope infusion (1-[(13)C]-leucine, 0.16 micromol/kg min). RESULTS: Serum albumin concentrations were close to the lower normal limit in patients early after operation but were comparable to controls in convalescent patients. Simultaneously, albumin synthesis was increased in the early postoperative phase (0.53 +/- 0.0.5%/h) compared with convalescent patients (0.32 +/- 0.04) and controls (0.28 +/- 0.04) (P < .01 each). A significant inverse correlation could be found between plasma albumin concentration and corresponding rates of albumin synthesis. Early after operation patients showed an increased leucine Ra (3.25 +/- 0.23 micromol/kg min) that was greater than that of convalescent patients (2.37 +/- 0.06 micromol/kg min, P < .05). Leucine Ra in both patient groups were greater than the rates in controls (2.01 +/- 0.07 micromol/kg min, P < .01) Albumin synthesis correlated weakly with whole body protein breakdown rate. CONCLUSIONS: Albumin synthesis and total body protein breakdown are increased after major abdominal operation, but albumin synthesis returns to control values only during convalescence. Hypoalbuminemia after rectal operations may be associated with high rates of albumin synthesis and is, therefore, not necessarily an indicator of insufficient hepatic function or poor nutritional status in that particular situation.