Effectiveness and efficacy of nutritional therapy: A systematic review following Cochrane methodology.

BACKGROUND & AIMS: Disease-related malnutrition has deleterious consequences on patients' outcome and healthcare costs. The demonstration of improved outcome by appropriate nutritional management is on occasion difficult. The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed the Nutrition Education Study Group (ESPEN-NESG) to increase recognition of nutritional knowledge and support in health services. METHODS: To obtain the best available evidence on the potential effects of malnutrition on morbidity, mortality and hospital stay; cost of malnutrition; effect of nutritional treatment on outcome parameters and pharmaco-economics of nutritional therapy, a systematic review of the literature was performed following Cochrane methodology, to answer the following key questions: Q1) Is malnutrition an independent predictive factor for readmission within 30 days from hospital discharge? Q2) Does nutritional therapy reduce the risk of readmission within 30 days from hospital discharge? Q3) Is nutritional therapy cost-effective/does it reduce costs in hospitalized patients? and Q4) Is nutritional therapy cost effective/does it reduce costs in outpatients? RESULTS: For Q1 six of 15 identified observational studies indicated that malnutrition was predictive of re-admissions, whereas the remainder did not. For Q2 nine randomized controlled trials and two meta-analyses gave non-conclusive results whether re-admissions could be reduced by nutritional therapy. Economic benefit and cost-effectiveness of nutritional therapy was consistently reported in 16 identified studies for hospitalized patients (Q3), whereas the heterogeneous and limited corresponding data on out-patients (Q4) indicated cost-benefits in some selected sub-groups. CONCLUSIONS: This result of this review supports the use of nutritional therapy to reduce healthcare costs, most evident from large, homogeneous studies. In general, reports are too heterogeneous and overall of limited quality for conclusions on impact of malnutrition and its treatment on readmissions.

Proteins and amino acids are fundamental to optimal nutrition support in critically ill patients.

Proteins and amino acids are widely considered to be subcomponents in nutritional support. However, proteins and amino acids are fundamental to recovery and survival, not only for their ability to preserve active tissue (protein) mass but also for a variety of other functions. Understanding the optimal amount of protein intake during nutritional support is therefore fundamental to appropriate clinical care. Although the body adapts in some ways to starvation, metabolic stress in patients causes increased protein turnover and loss of lean body mass. In this review, we present the growing scientific evidence showing the importance of protein and amino acid provision in nutritional support and their impact on preservation of muscle mass and patient outcomes. Studies identifying optimal dosing for proteins and amino acids are not currently available. We discuss the challenges physicians face in administering the optimal amount of protein and amino acids. We present protein-related nutrition concepts, including adaptation to starvation and stress, anabolic resistance, and potential adverse effects of amino acid provision. We describe the methods for assessment of protein status, and outcomes related to protein nutritional support for critically ill patients. The identification of a protein target for individual critically ill patients is crucial for outcomes, particularly for specific subpopulations, such as obese and older patients. Additional research is urgently needed to address these issues.

The ratio of energy expenditure to nitrogen loss in diverse patient groups--a systematic review.

BACKGROUND & AIMS: The ratio of energy expenditure to nitrogen loss respectively of energy to nitrogen provision (E/N) is considered a valuable tool in the creation of an enteral or parenteral formulation. Specific E/N ratios for parenteral nutrition (PN) have not yet been clearly defined. To determine the range of energy expenditure, nitrogen (protein) losses, and E/N ratios for various patient groups, we performed a systematic review of the literature. METHODS: Medline 1950-2011 was searched for all studies on patients or healthy controls reporting energy expenditure and nitrogen loss at the same time. RESULTS: We identified 53 studies with 91 cohorts which comprised 1107 subjects. Mean TEE ± standard deviation (SD) was 31.2 ± 7.2 kcal/kg BW/day in patients (n = 881) and 35.6 ± 4.3 kcal/kg BW/day in healthy controls (n = 266). Mean total protein loss (TPL) was 1.50 ± 0.57 g/kg BW/day in patients and 0.94 ± 0.24 g/kg BW/day in healthy controls. A non-linear significant correlation was found between TPL and the E/N ratio. CONCLUSION: The E/N ratio is not a constant value but decreases continuously with increasing protein loss. These variations should be considered in the nutritional support of patients.

Weight gain in long-term survivors of kidney or liver transplantation--another paradigm of sarcopenic obesity?

OBJECTIVE: Obesity in transplant recipients is a frequent phenomenon but data from body composition analyses in long-term survivors are limited. Body composition and energy metabolism were studied in patients after liver (LTX) and kidney (KTX) transplantation and patients with liver cirrhosis (LCI) or on chronic hemodialysis (HD) and compared to healthy controls. METHODS: In 42 patients 50.0 mo (median; range 17.1-100.6) after LTX and 30 patients 93.0 mo (31.2-180.1) after KTX as wells as in LCI (n = 39) or HD (n = 10) patients mid-arm muscle and fat area, body cell mass, and phase angle (bioimpedance analysis), and resting energy expenditure (indirect calorimetry, REE(CALO)) were measured. RESULTS: Obesity was more prevalent in LTX (17%) than LCI (3%) and in KTX (27%) than in HD (10%). In LTX and KTX, phase angle was higher than in end-stage disease (LTX 5.6° [4.1-7.2] versus LCI 4.4° [2.9-7.3], P < 0.001; KTX 5.9° [4.4-8.7] versus HD 4.3° [2.9-6.8]) but was lower in all patient groups than in controls (7.1°; 4.6-8.9; P < 0.001). In LCI and HD REE(CALO) was higher than predicted, while in LTX and KTX REE(CALO) was not different from predicted REE. CONCLUSIONS: Despite excellent graft function, many long-term LTX or KTX survivors exhibit a phenotype of sarcopenic obesity with increased fat but low muscle mass. This abnormal body composition is observed despite normalization of the hypermetabolism found in chronic disease and cannot be explained by overeating. The role of appropriate nutrition and physiotherapy after transplantation merits further investigation.

Do centrally pre-prepared solutions achieve more reliable drug concentrations than solutions prepared on the ward?

PURPOSE: To compare the concentration conformity of infusion solutions manually prepared on intensive care units (ICU) with solutions from pharmacy-based, automated production. METHODS: A prospective observational study conducted in a university hospital in Germany. Drug concentrations of 100 standardised infusion solutions manually prepared in the ICU and 100 matching solutions from automated production containing amiodarone, noradrenaline or hydrocortisone were measured by high-performance liquid chromatography analysis. Deviations from stated concentrations were calculated, and the quality of achieved concentration conformity of the two production methods was compared. RESULTS: Actual concentrations of 53% of the manually prepared and 16% of the machine-made solutions deviated by >5% above or below the stated concentration. A deviation of >10% was measured in 22% of the manually prepared samples and in 5% of samples from automated production. Of the manually prepared solutions, 15% deviated by >15% above or below the intended concentration. The mean concentration of the manually prepared solutions was 97.2% (SD 12.7%, range 45-129%) and of the machine-made solutions was 101.1% (SD 4.3%, range 90-114%) of the target concentration (p < 0.01). CONCLUSIONS: In this preliminary study, ward-based, manually prepared infusion solutions showed clinically relevant deviations in concentration conformity significantly more often than pharmacy-prepared, machine-made solutions. Centralised, automated preparation of standardised infusion solutions may be an effective means to reduce this type of medication error. Further confirmatory studies in larger settings and under conditions of routine automated production are required.

Grade of adiposity affects the impact of fat mass on resting energy expenditure in women.

Body fat mass (FM) adds to the variance in resting energy expenditure (REE). However, the nature and extent of this relationship remains unclear. Using a database of 1306 women and a linear regression model, we systematically analysed the contribution of FM to the total variance in REE at different grades of adiposity (ranges of body %FM). After adjusting for age, the relative contribution of FM on REE variance increased from low (10- 30- 40- # 50 %FM) and very high (>50 %FM) grades of adiposity according to the ratio between regression coefficients. These data suggest that the specific metabolic rate of fat tissue is reduced at high adiposity. This should be considered when REE is normalized for FM in obesity.

Development of pulmonary hypertension in adults after ventriculoatrial shunt implantation.

BACKGROUND: The insertion of ventriculoatrial (VA) shunts for the treatment of hydrocephalus is thought to be associated with the development of pulmonary hypertension in adults. OBJECTIVES: It was the aim of this study to describe the frequency and the clinical spectrum of pulmonary hypertension in adults with VA shunts. METHODS: Patients with pulmonary hypertension were retrospectively evaluated from January 1999 to December 2006. RESULTS: Among the 575 patients with pulmonary hypertension, 6 (mean age 42.5 +/- 8.3 years) were identified as having received a VA shunt. Mean pulmonary artery pressure for these patients was 53.3 +/- 14.9 mm Hg. The interval between shunt placement and the diagnosis of pulmonary hypertension was 9-27 years (median 16.5). While ventilation perfusion scans showed multiple bilateral perfusion defects in all patients, chest CT or pulmonary angiography demonstrated pulmonary thromboembolism in only 2 of the 6 patients. These 2 patients subsequently underwent pulmonary endarterectomy. Another patient required heart-lung transplantation because of severe pulmonary hypertension; lung histology showed prominent eccentric medial hypertrophy and intimal proliferation without evidence of thromboembolism. Contrary to earlier reports, outcomes were generally good, with a 100% survival rate for the first 8 years following diagnosis. CONCLUSIONS: Severe pulmonary hypertension can develop in adult patients with VA shunts. Therefore, clinicians should consider pulmonary hypertension as a potential cause for respiratory symptoms in patients who have received VA shunts.

Tracheostomy in the intensive care unit: a nationwide survey.

BACKGROUND: The indication, timing and technique of tracheostomy have changed over the last several years. We performed a survey to assess the current practice of tracheostomy in German intensive care units (ICUs). METHODS: A postal questionnaire was sent to the head physicians of 513 German ICUs, excluding pediatric ICUs. RESULTS: We obtained responses from 455 of the 513 ICUs (89%). In 90% of the ICUs, tracheostomies were performed during the first 14 d of mechanical ventilation. Eighty-six percent of the ICUs routinely performed percutaneous dilatational tracheostomy; the modified Ciaglia technique was the most popular percutaneous technique (69%). The majority (98%) of the percutaneous procedures were performed under bronchoscopic control. Surgical tracheostomy is usually performed in the operating room (72%) by a surgeon (61%), whereas percutaneous dilatational tracheostomies are usually performed at the patient's bedside in the ICU (98%) by an intensivist (93%). Tracheostomized patients were followed up routinely in 26% of the ICUs, and in 45% of the ICUs there were guidelines regarding the indication, the timing and the technique of tracheostomy. CONCLUSION: Percutaneous dilatational tracheostomy is the procedure of choice for tracheostomy in critically ill patients in Germany. The modified Ciaglia technique is the preferred percutaneous technique, and nearly all physicians routinely use bronchoscopic guidance. Most tracheostomies are done during the second week of mechanical ventilation.

Safety of percutaneous dilational tracheostomy in hematopoietic stem cell transplantation recipients requiring long-term mechanical ventilation.

PURPOSE: Recent reports have shown that the outcome of mechanically ventilated patients after hematopoietic stem cell transplantation (HSCT) has improved. This study was conducted to clarify if percutaneous dilational tracheostomy is safe in this group of patients and to report the outcome of HSCT recipients requiring long-term mechanical ventilation. METHODS: A retrospective review of our 8-year experience with patients with acute respiratory insufficiency after HSCT, requiring long-term mechanical ventilation and percutaneous dilational tracheostomy and an analysis of patient outcomes were made. RESULTS: Percutaneous dilational tracheostomy was safely performed in all 51 patients. Although 1 patient (2%) developed a pneumothorax that required drainage, stoma infections or severe bleeding complications were not observed. Of the 51 patients in the study, 14 (27%) survived the intensive care unit stay, and 10 of them were ventilated for more than 20 days. The intensive care unit survival rate for the period from 1998 to 2001 was 11% compared with 38% for the period from 2002 to 2005 (P = .053). CONCLUSIONS: Percutaneous dilational tracheostomy can be safely performed on patients with acute respiratory failure after HSCT. This procedure did not result in postoperative wound infections or significant bleeding complications. Furthermore, the results of our study indicate that today even patients with prolonged mechanical ventilation (>20 days) have a chance of long-term survival.

Yield and safety of bedside open lung biopsy in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome.

BACKGROUND: The utility of open lung biopsy (OLB) in mechanically ventilated patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) of unknown origin has been questioned because of its potentially low diagnostic yield and possibly related morbidity. To quantify possible benefits and risks, and especially so for bedside lung biopsy, we reviewed retrospectively our 8-year, single unit experience with this procedure. METHODS: Mechanically ventilated, critically ill patients with acute respiratory failure of unknown origin who underwent OLB were analyzed in a retrospective, single-center, cohort study in a medical intensive care unit in a university medical center. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients were analyzed (15 female, 12 male, of mean 48 years [standard deviation, 14]), 67% of whom were immunocompromised. All patients underwent bronchoscopy and bronchoalveolar lavage before OLB. PaO2/Fraction of inspired oxygen at the time of biopsy was 188 +/- 109 mm Hg. Biopsies were performed in the operating room on 9 patients and at bedside on 18. A specific diagnosis was obtained in 70% of biopsies. Biopsy results led to alteration in treatment in 81% of patients. Minor complications occurred in 52% of patients and major complications in 7%. The rate of complications did not appear to differ with the location of the procedure (bedside vs operating room). No deaths were attributed to the procedure. CONCLUSIONS: Bedside OLB can be performed safely in selected, mechanically ventilated, critically ill patients with ALI or ARDS. Our results support the concept that lung biopsy often leads to management alterations in patients where a standardized diagnostic workup failed to yield a definitive diagnosis.

Prediction of short-term and long-term outcomes after cardiac arrest: a prospective multivariate approach combining biochemical, clinical, electrophysiological, and neuropsychological investigations.

OBJECTIVE: To determine the prognostic accuracy of biochemical, clinical, electrophysiological, and neuropsychological investigations in predicting outcomes after cardiac arrest. DESIGN: Prospective study. SETTING: Intensive care unit of the Hamburg-Eppendorf University Medical Center, Hamburg, Germany. PATIENTS: A total of 80 patients (mean age, 63.79 +/- 15.85 yrs) after cardiopulmonary resuscitation. INTERVENTIONS: Serial blood samples (days 2-4), clinical examinations (days 2 and 4), sensory-evoked potentials (day 4), and neuropsychological assessments (

[Mild hypothermia for neuroprotection after cardiac arrest]. / Milde Hypothermie zur Neuroprotektion nach Herz-Kreislauf-Stillstand.

The favorable effect of hypothermia on brain damage resulting from cardiac arrest was first demonstrated in animal studies. Subsequent small-scale human studies have also shown positive effects. In 2002, two large randomized studies investigating the use of controlled mild hypothermia after resuscitation were published in the New England Journal of Medicine. The results convincingly showed a positive effect on survival and neurologic outcome. Based on the currently available data, the International Liaison Committee on Resuscitation (ILCOR) strongly recommends that unconscious adult patients who are resuscitated after ventricular fibrillation be cooled to temperatures between 32 and 34 degrees C for 12-24 h.

World Health Organization equations have shortcomings for predicting resting energy expenditure in persons from a modern, affluent population: generation of a new reference standard from a retrospective analysis of a German database of resting energy expenditure.

BACKGROUND: Reference standards for resting energy expenditure (REE) are widely used. Current standards are based on measurements made in the first part of the past century in various races and locations. OBJECTIVE: The aim of the present study was to investigate the application of the World Health Organization (WHO) equations from 1985 in healthy subjects living in a modern, affluent society in Germany and to generate a new formula for predicting REE. DESIGN: The study was a cross-sectional and retrospective analysis of data on REE and body composition obtained from 2528 subjects aged 5-91 y in 7 different centers between 1985 and 2002. RESULTS: Mean REE varied between 5.63 and 8.07 MJ/d in males and between 5.35 and 6.46 MJ/d in females. WHO prediction equations systematically overestimated REE at low REE values but underestimated REE at high REE values. There were significant and independent effects of sex, age, body mass or fat-free mass, and fat mass on REE. Multivariate regression analysis explained up to 75% of the variance in REE. Two prediction formulas including weight, sex, and age or fat-free mass, fat mass, sex, and age, respectively, were generated in a subpopulation and cross-validated in another subpopulation. Significant deviations were still observed for underweight and normal-weight subjects. REE prediction formulas for specific body mass index groups reduced the deviations. The normative data for REE from the Institute of Medicine underestimated our data by 0.3 MJ/d. CONCLUSIONS: REE prediction by WHO formulas systematically over- and underestimates REE. REE prediction from a weight group-specific formula is recommended in underweight subjects.

Percutaneous tracheostomy is safe in patients with severe thrombocytopenia.

STUDY OBJECTIVES: Severe thrombocytopenia has been described as a contraindication for percutaneous tracheostomy (PT). The objective of this study was to assess the safety of PT in mechanically ventilated patients with severe thrombocytopenia (defined by a platelet count of < 50 x 10(9) cells/L). DESIGN: Retrospective, single-center cohort study. SETTING: Medical ICU of the University Hospital Hamburg-Eppendorf, Germany. PATIENTS: Forty-two medical patients with acute respiratory failure and severe thrombocytopenia. INTERVENTIONS: Bedside PT under bronchoscopic guidance using the Griggs guidewire forceps technique. MEASUREMENTS AND MAIN RESULTS: The mean (+/- SD) intubation time prior to undergoing PT was 6.7 +/- 3.9 days (range, 1 to 20 days). The mean platelet count was 26.4 +/- 11.6 x 10(9) cells/L (range, 1 x 10(9) to 47 x 10(9) cells/L). The median transfusion of platelets before the procedure in 40 of the 42 patients was 6 +/- 2.5 U (range, 3 to 12 U). Twenty-two patients (52%) had an additional coagulopathy (activated partial thromboplastin time [APTT], > 40 s; international normalized ratio, > 1.5). PT was safely performed in all 42 patients. Only two (5%) patients developed major postprocedural bleeding complications that required suturing. Both of these patients had an elevated APTT due to heparin therapy. CONCLUSIONS: When performed by experienced personnel, PT with bronchoscopic guidance has a low complication rate in patients with severe thrombocytopenia, provided that platelets are administered beforehand. However, in order to minimize bleeding complications heparin infusions should be temporarily interrupted during the procedure.

Weight gain after transjugular intrahepatic portosystemic shunt is associated with improvement in body composition in malnourished patients with cirrhosis and hypermetabolism.

BACKGROUND/AIMS: To search for changes in body composition and energy metabolism associated with the repeatedly observed weight gain of cirrhotic patients after portosystemic shunting. METHODS: Twenty-one patients were studied prospectively before and 6 and 12 months after transjugular intrahepatic portosystemic shunt (TIPS) to assess body cell mass by two independent methods (total body potassium counting: body cell mass determined by TBP, BCMTBP, bioelectric impedance analysis: body cell mass determined by BIA, BCMBIA), muscle mass (anthropometry), resting energy expenditure (REECALO) by indirect calorimetry, and nutritional intake by dietary recall analysis. RESULTS: Prior to TIPS patients were hypermetabolic in terms of measured vs. predicted REE (REECALO median 1423 (range 1164-1838) vs. REEPRED 1279 (1067-1687) kcal; P<0.05) and their body cell mass was lower (19.1 (10.9-33.4) vs. 31.7 (16.8-47.1) kg; P=0.001). After TIPS body cell mass (BCMBIA) increased to 23.5 (12.7-44.3) (P<0.025) and 25.7 (14.2-39.7) kg (P=0.05) at 6 and 12 months after TIPS and this was confirmed by total potassium counting (BCMTBP before TIPS: 18.8 (10.6-26.7) vs. 22.4 (12.9-28.5) kg at 6 months; P<0.01). Hypermetabolism persisted throughout the study period. Energy and protein intake increased significantly by 26 and 33%. CONCLUSIONS: An increase of prognostically relevant variables body cell and muscle mass contributes to the weight gain after TIPS in malnourished patients with cirrhosis and hypermetabolism.

A young woman with persistent hypoglycemia, rhabdomyolysis, and coma: recognizing fatty acid oxidation defects in adults.

OBJECTIVE: To describe an acutely decompensated adult patient with very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency. DESIGN: Case report. SETTING: Medical intensive care unit of the University Hospital Hamburg-Eppendorf, Germany. PATIENT: A 32-yr-old female comatose patient with persistent hypoglycemia, rhabdomyolysis, and acute cardiomyopathy after a prolonged history of recurrent muscular weakness. INTERVENTIONS AND MEASUREMENTS: Treatment in the intensive care unit for 20 days. The combination of symptoms led to the detection of increased dicarboxylic acids in her urine and an abnormal profile of acylcarnitines in her blood. In cultured fibroblasts, the oxidation of palmitate, measured as the production of acetylcarnitine, was reduced. Direct measurement of VLCAD activity proved to be 30% of normal. DNA analysis showed two different mutations in the VLCAD gene of the patient. RESULTS: The patient fully recovered. CONCLUSIONS: Genetic defects of fatty acid oxidation should be suspected, even in previously healthy adults, when typical symptoms such as nonketotic hypoglycemia, rhabdomyolysis, cardiomyopathy, or unexplained organ steatosis point to such a disorder of energy metabolism.