Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial.

BACKGROUND: Findings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis. METHODS: A multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit. Participants were randomly assigned (1:1) to a strategy combining thoracic epidural analgesia and usual care (intervention group) or a strategy of usual care alone (control group). The primary outcome was the number of ventilator-free days from randomization until day 30. RESULTS: Between June 2014 and January 2019, 148 patients were enrolled, and 135 patients were included in the intention-to-treat analysis, with 65 patients randomly assigned to the intervention group and 70 to the control group. The number of ventilator-free days did not differ significantly between the intervention and control groups (median [interquartile range], 30 days [15-30] and 30 days [18-30], respectively; median absolute difference of - 0.0 days, 95% CI - 3.3 to 3.3; p = 0.59). Epidural analgesia was significantly associated with longer duration of invasive ventilation (median [interquartile range], 14 days [5-28] versus 6 days [2-13], p = 0.02). CONCLUSIONS: In a population of intensive care unit adults with acute pancreatitis and low requirement for intubation, this first multicenter randomized trial did not show the hypothesized benefit of epidural analgesia in addition to usual care. Safety of epidural analgesia in this setting requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02126332 , April 30, 2014.

The central and biodynamic role of gut microbiota in critically ill patients.

Gut microbiota plays an essential role in health and disease. It is constantly evolving and in permanent communication with its host. The gut microbiota is increasingly seen as an organ, and its failure, reflected by dysbiosis, is seen as an organ failure associated with poor outcomes. Critically ill patients may have an altered gut microbiota, namely dysbiosis, with a severe reduction in "health-promoting" commensal intestinal bacteria (such as Firmicutes or Bacteroidetes) and an increase in potentially pathogenic bacteria (e.g. Proteobacteria). Many factors that occur in critically ill patients favour dysbiosis, such as medications or changes in nutrition patterns. Dysbiosis leads to several important effects, including changes in gut integrity and in the production of metabolites such as short-chain fatty acids and trimethylamine N-oxide. There is increasing evidence that gut microbiota and its alteration interact with other organs, highlighting the concept of the gut-organ axis. Thus, dysbiosis will affect other organs and could have an impact on the progression of critical diseases. Current knowledge is only a small part of what remains to be discovered. The precise role and contribution of the gut microbiota and its interactions with various organs is an intense and challenging research area that offers exciting opportunities for disease prevention, management and therapy, particularly in critical care where multi-organ failure is often the focus. This narrative review provides an overview of the normal composition of the gut microbiota, its functions, the mechanisms leading to dysbiosis, its consequences in an intensive care setting, and highlights the concept of the gut-organ axis.

Usability study of a new tool for nutritional and glycemic management in adult intensive care: Glucosafe 2.

The new decision support tool Glucosafe 2 (GS2) is based on a mathematical model of glucose and insulin dynamics, designed to assist caregivers in blood glucose control and nutrition. This study aims to assess end-user acceptance and usability of this bedside decision support tool in an adult intensive care setting. Caregivers were first trained and then invited to trial GS2 prototype on bedside computers. Data for qualitative analysis were collected through semi-structured interviews from twenty users after minimum three trial days. Most caregivers (70%) rated GS2 as convenient and believed it would help improving adherence to current guidelines (85%). Moreover, most nurses (80%) believed that GS2 would be timesaving. Nurses' risk perceptions and manual data entry emerged as central barriers to use GS2 in routine practice. Issues emerged from the caregivers were compiled into a list of 12 modifications of the GS2 prototype to increase end-user acceptance and usability. This usability study showed that GS2 was considered by ICU caregivers as helpful in daily clinical practice, allowing time-saving and better standardization of ICU patient's care. Important issues were raised by the users with implications for the development and deployment of GS2. Integrating the technology into existing IT infrastructure may facilitate caregivers' acceptance. Further clinical studies of the performance and potential health outcomes are warranted.

Can calculation of energy expenditure based on CO2 measurements replace indirect calorimetry?

BACKGROUND: Methods to calculate energy expenditure (EE) based on CO2 measurements (EEVCO2) have been proposed as a surrogate to indirect calorimetry. This study aimed at evaluating whether EEVCO2 could be considered as an alternative to EE measured by indirect calorimetry. METHODS: Indirect calorimetry measurements conducted for clinical purposes on 278 mechanically ventilated ICU patients were retrospectively analyzed. EEVCO2 was calculated by a converted Weir's equation using CO2 consumption (VCO2) measured by indirect calorimetry and assumed respiratory quotients (RQ): 0.85 (EEVCO2_0.85) and food quotient (FQ; EEVCO2_FQ). Mean calculated EEVCO2 and measured EE were compared by paired t test. Accuracy of EEVCO2 was evaluated according to the clinically relevant standard of 5% accuracy rate to the measured EE, and the more general standard of 10% accuracy rate. The effects of the timing of measurement (before or after the 7th ICU day) and energy provision rates (<90 or ≥90% of EE) on 5% accuracy rates were also analyzed (chi-square tests). RESULTS: Mean biases for EEVCO2_0.85 and EEVCO2_FQ were -21 and -48 kcal/d (p = 0.04 and 0.00, respectively), and 10% accuracy rates were 77.7 and 77.3%, respectively. However, 5% accuracy rates were 46.0 and 46.4%, respectively. Accuracy rates were not affected by the timing of the measurement, or the energy provision rates at the time of measurements. CONCLUSIONS: Calculated EE based on CO2 measurement was not sufficiently accurate to consider the results as an alternative to measured EE by indirect calorimetry. Therefore, EE measured by indirect calorimetry remains as the gold standard to guide nutrition therapy.

Thoracic epidural analgesia: a new approach for the treatment of acute pancreatitis?

This review article analyzes, through a nonsystematic approach, the pathophysiology of acute pancreatitis (AP) with a focus on the effects of thoracic epidural analgesia (TEA) on the disease. The benefit-risk balance is also discussed. AP has an overall mortality of 1 %, increasing to 30 % in its severe form. The systemic inflammation induces a strong activation of the sympathetic system, with a decrease in the blood flow supply to the gastrointestinal system that can lead to the development of pancreatic necrosis. The current treatment for severe AP is symptomatic and tries to correct the systemic inflammatory response syndrome or the multiorgan dysfunction. Besides the removal of gallstones in biliary pancreatitis, no satisfactory causal treatment exists. TEA is widely used, mainly for its analgesic effect. TEA also induces a targeted sympathectomy in the anesthetized region, which results in splanchnic vasodilatation and an improvement in local microcirculation. Increasing evidence shows benefits of TEA in animal AP: improved splanchnic and pancreatic perfusion, improved pancreatic microcirculation, reduced liver damage, and significantly reduced mortality. Until now, only few clinical studies have been performed on the use of TEA during AP with few available data regarding the effect of TEA on the splanchnic perfusion. Increasing evidence suggests that TEA is a safe procedure and could appear as a new treatment approach for human AP, based on the significant benefits observed in animal studies and safety of use for human. Further clinical studies are required to confirm the clinical benefits observed in animal studies.

Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial.

BACKGROUND: Enteral nutrition (EN) is recommended for patients in the intensive-care unit (ICU), but it does not consistently achieve nutritional goals. We assessed whether delivery of 100% of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition (SPN) could optimise clinical outcome. METHODS: This randomised controlled trial was undertaken in two centres in Switzerland. We enrolled patients on day 3 of admission to the ICU who had received less than 60% of their energy target from EN, were expected to stay for longer than 5 days, and to survive for longer than 7 days. We calculated energy targets with indirect calorimetry on day 3, or if not possible, set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men, respectively. Patients were randomly assigned (1:1) by a computer-generated randomisation sequence to receive EN or SPN. The primary outcome was occurrence of nosocomial infection after cessation of intervention (day 8), measured until end of follow-up (day 28), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00802503. FINDINGS: We randomly assigned 153 patients to SPN and 152 to EN. 30 patients discontinued before the study end. Mean energy delivery between day 4 and 8 was 28 kcal/kg per day (SD 5) for the SPN group (103% [SD 18%] of energy target), compared with 20 kcal/kg per day (7) for the EN group (77% [27%]). Between days 9 and 28, 41 (27%) of 153 patients in the SPN group had a nosocomial infection compared with 58 (38%) of 152 patients in the EN group (hazard ratio 0·65, 95% CI 0·43-0·97; p=0·0338), and the SPN group had a lower mean number of nosocomial infections per patient (-0·42 [-0·79 to -0·05]; p=0·0248). INTERPRETATION: Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient. FUNDING: Foundation Nutrition 2000Plus, ICU Quality Funds, Baxter, and Fresenius Kabi.

Long-stay ICU patients with frailty: mortality and recovery outcomes at 6 months.

BACKGROUND: Prolonged intensive care unit (ICU) stay is associated with physical, cognitive, and psychological disabilities. The impact of baseline frailty on long-stay ICU patients remains uncertain. This study aims to investigate how baseline frailty influences mortality and post-ICU disability 6 months after critical illness in long-stay ICU patients. METHODS: In this retrospective cohort study, we assessed patients hospitalized for ≥ 7 days in the ICU between May 2018 and May 2021, following them for up to 6 months or until death. Based on the Clinical Frailty Scale (CFS) at ICU admissions, patients were categorized as frail (CFS ≥ 5), pre-frail (CFS 3-4) and non-frail (CFS 1-2). Kaplan-Meier curves and a multivariate Cox model were used to examine the association between frailty and mortality. At the 6 month follow-up, we assessed psychological, physical, cognitive outcomes, and health-related quality of life (QoL) using descriptive statistics and linear regressions. RESULTS: We enrolled 531 patients, of which 178 (33.6%) were frail, 200 (37.6%) pre-frail and 153 (28.8%) non-frail. Frail patients were older, had more comorbidities, and greater disease severity at ICU admission. At 6 months, frail patients presented higher mortality rates than pre-frail and non-frail patients (34.3% (61/178) vs. 21% (42/200) vs. 13.1% (20/153) respectively, p < 0.01). The rate of withdrawing or withholding of care did not differ significantly between the groups. Compared with CFS 1-2, the adjusted hazard ratios of death at 6 months were 1.7 (95% CI 0.9-2.9) for CFS 3-4 and 2.9 (95% CI 1.7-4.9) for CFS ≥ 5. At 6 months, 192 patients were seen at a follow-up consultation. In multivariate linear regressions, CFS ≥ 5 was associated with poorer physical health-related QoL, but not with poorer mental health-related QoL, compared with CFS 1-2. CONCLUSION: Frailty is associated with increased mortality and poorer physical health-related QoL in long-stay ICU patients at 6 months. The admission CFS can help inform patients and families about the complexities of survivorship during a prolonged ICU stay.

Diarrhoea in the ICU: respective contribution of feeding and antibiotics.

INTRODUCTION: Diarrhoea is frequently reported in the ICU. Little is known about diarrhoea incidence and the role of the different risk factors alone or in combination. This prospective observational study aims at determining diarrhoea incidence and risk factors in the first 2 weeks of ICU stay, focusing on the respective contribution of feeding, antibiotics, and antifungal drugs. METHODS: Out of 422 patients consecutively admitted into a mixed medical-surgical ICU during a 2-month period, 278 patients were included according to the following criteria: ICU stay >24 hours, no admission diagnosis of gastrointestinal bleeding, and absence of enterostomy or colostomy. Diarrhoea was defined as at least three liquid stools per day. Diarrhoea episodes occurring during the first day in the ICU, related to the use of laxative drugs or Clostridium difficile infection, were not analysed. Multivariate and stratified analyses were performed to determine diarrhoea risk factors, and the impact of the combination of enteral nutrition (EN) with antibiotics or antifungal drugs. RESULTS: A total of 1,595 patient-days were analysed. Diarrhoea was observed in 38 patients (14%) and on 83 patient-days (incidence rate: 5.2 per 100 patient-days). The median day of diarrhoea onset was the sixth day, and 89% of patients had ≤4 diarrhoea days. The incidence of C. difficile infection was 0.7%. Diarrhoea risk factors were EN covering >60% of energy target (relative risk = 1.75 (1.02 to 3.01)), antibiotics (relative risk = 3.64 (1.26 to 10.51)) and antifungal drugs (relative risk = 2.79 (1.16 to 6.70)). EN delivery per se was not a diarrhoea risk factor. In patients receiving >60% of energy target by EN, diarrhoea risk was increased by the presence of antibiotics (relative risk = 4.8 (2.1 to 13.7)) or antifungal drugs (relative risk = 5.0 (2.8 to 8.7)). CONCLUSION: Diarrhoea incidence during the first 2 weeks in a mixed population of patients in a tertiary ICU is 14%. Diarrhoea risk factors are EN covering >60% of energy target, use of antibiotics, and use of antifungal drugs. The combination of EN covering >60% of energy target with antibiotics or antifungal drugs increases the incidence of diarrhoea.

Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients.

The primary objective of this study was to compare the plasma levels of copper, selenium, and zinc between critically ill COVID-19 patients and less severe COVID-19 patients. The secondary objective was to investigate the association of these trace element levels with adverse outcomes, including the duration of mechanical ventilation, occurrence of septic shock, and mortality in critically ill COVID-19 patients. All COVID-19 patients admitted to the ICU of the Geneva University Hospitals between 9 March 2020 and 19 May 2020 were included in the study. Plasma levels of copper, selenium and zinc were measured on admission to the ICU and compared with levels measured in COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. To analyze the association of trace elements with clinical outcomes, multivariate linear and logistic regressions were performed. Patients in the ICU had significantly lower levels of selenium and zinc and higher levels of copper compared to COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. In ICU patients, lower zinc levels tended to be associated with more septic shock and increased mortality compared to those with higher zinc levels (p = 0.07 for both). Having lower copper or selenium levels was associated with a longer time under mechanical ventilation (p = 0.01 and 0.04, respectively). These associations remained significant in multivariate analyses (p = 0.03 for copper and p = 0.04 for selenium). These data support the need for interventional studies to assess the potential benefit of zinc, copper and selenium supplementation in severe COVID-19 patients.

Impact of nutritional therapy during the first wave of the COVID-19 pandemic in intensive care patients: A retrospective observational study.

BACKGROUND & AIMS: The COVID-19 pandemic has caused major organizational challenges to healthcare systems concerning staff, material and bed availability. Nutrition was not a priority in the intensive care unit (ICU) at the beginning of the pandemic with the need for simplified protocols. We aimed to assess the impact of a simplified nutritional protocol for critically ill COVID-19 patients during the pandemic first wave. METHODS: We included all patients with SARS-CoV-2 infections, admitted to the ICU of the Geneva University Hospitals for at least 4 days from March 9 to May 19, 2020. Data on the route and solution of nutritional therapy, prescribed and received volume, calorie and protein intake, amount of insulin, propofol and glucose administered were collected daily during the entire ICU stay. We compared nutritional outcomes between patients admitted to the ICU before and after implementing the simplified nutritional protocol using unpaired t-test. RESULTS: Out of 119 patients, 48 were hospitalized in the ICU before, 47 across and 24 after the implementation of the nutritional protocol. The mean age was 63.2 (±12.7) years and 76% were men without significant difference between before and after group. The nutritional protocol implementation led to an increase in caloric intake (1070 vs. 1357 kcal/day, p = 0.018) and in the percentage of days within 80-100% of the energy target (11 vs. 20%, p = 0.021). The protein debt decreased significantly from 48 g/day to 37 g/day (p = 0.015). No significant difference in the percentage of days within the protein target (80-100%) was observed. CONCLUSIONS: Calorie and protein coverage improved after the implementation of the simplified nutritional protocol in critically ill COVID-19 patients. Further studies are needed to assess the impact of such an approach on patients' clinical outcomes.

Hypophosphatemia on ICU Admission Is Associated with an Increased Length of Stay in the ICU and Time under Mechanical Ventilation.

Hypophosphatemia is frequently observed in the ICU and is associated with several impairments such as respiratory failure or infections. We hypothesized that hypophosphatemia on ICU admission is associated with a prolonged duration of mechanical ventilation and ICU length of stay (LOS), particularly in COVID-19 patients. This cross-sectional study analyzed data from 1226 patients hospitalized in the ICU of the Geneva University Hospitals from August 2020 to April 2021. Patients were categorized as having hypophosphatemia (phosphatemia ≤ 0.8 mmol/L) or non-hypophosphatemia (phosphatemia > 0.8 mmol/L) on ICU admission. Linear regressions were performed to investigate the association between hypophosphatemia on ICU admission and ICU LOS and duration of mechanical ventilation. Overall, 250 (20%) patients presented hypophosphatemia on ICU admission. In the univariable analysis, hypophosphatemic patients had longer ICU LOS than non-hypophosphatemic patients, 7.4 days (±10.4) versus 5.6 days (±8.3), (p < 0.01). Hypophosphatemia on ICU admission was associated with a prolonged duration of mechanical ventilation, 7.4 days (±11.2) versus 5.6 days (±8.9), (p < 0.01). These associations were confirmed in the multivariable analysis (p < 0.01). In the subgroup of COVID-19 patients, a significant association between hypophosphatemia and ICU LOS and duration of mechanical ventilation was also observed. In conclusion, hypophosphatemia on ICU admission is associated with a longer ICU LOS and time under mechanical ventilation, both in the general ICU population and in COVID-19 patients.

Easy-to-prescribe nutrition support in the intensive care in the era of COVID-19.

BACKGROUND & AIMS: COVID-19 pandemic had resulted in a massive increase in the number of patients admitted to intensive care units (ICUs). This created significant organizational challenges including numerous non-specialist ICU caregivers who came to work in the ICU. In this context, pragmatic protocols were essential to simplify nutritional care. We aimed at providing a simple and easy-to-prescribe nutritional protocol and evaluated its usefulness with questionnaires sent to physicians involved in the care of ICU COVID-19 patients. METHODS: A simplified nutrition protocol was distributed to all physicians (n = 122) of the ICU medical team during COVID-19 pandemic. Clinical dieticians estimated energy targets for acute and post-acute phases at patient's admission and suggested adaptations of nutrition therapy. More complex situations were discussed with clinical nutrition doctors and, if required, a clinical evaluation was performed. To further facilitate the procedure, a chart with prescription aids was also distributed to the whole medical ICU team. At the end of the current pandemic wave, a 13-item questionnaire was emailed to the ICU medical team to obtain their opinion on the suggested nutritional therapy. RESULTS: Answers were received from 81/122 medical doctors (MDs) (66% response rate), from intensive care physicians (41%), anaesthesiologists (53%) and MDs from other specialties (6%). Thirty-two percent of MDs felt that their knowledge of nutrition management was insufficient and 45% of the physicians surveyed did not face nutrition management in their daily practice prior to the pandemic. The initially proposed nutritional protocol, the chart with prescription aids and the suggested nutritional proposals were considered as useful to very useful by the majority of physicians surveyed (89.9, 90.7 and 92.1% respectively). The protocol was followed by 92% of MDs, and almost all participants (95%) were convinced that adaptations of nutritional therapy had beneficial effects on patients' outcomes. CONCLUSIONS: Nutritional therapy in critically ill COVID-19 patients is a challenge and the implementation of this specific pandemic simplified nutritional protocol was assessed as useful by a great majority of physicians. Pragmatic and simplified protocols are useful for ensuring the quality of nutritional therapy and could be used in future studies to assess its actual impact on the clinical outcomes of COVID-19 patients.

The clinical evaluation of the new indirect calorimeter developed by the ICALIC project.

BACKGROUND & AIMS: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU). METHODS: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD. RESULTS: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR®: -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165). CONCLUSION: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use.

Randomized trial of light versus deep sedation on mental health after critical illness.

OBJECTIVES: : To investigate if light sedation favorably affects subsequent patient mental health compared with deep sedation. Symptoms of posttraumatic stress disorder are common in patients after they have undergone prolonged mechanical ventilation and are associated with sedation depth. DESIGN: : Randomized, open-label, controlled trial. SETTING: : Single tertiary care center. PATIENTS: : Adult patients requiring mechanical ventilation. INTERVENTIONS: : Patients were randomized to receive either light (patient awake and cooperative) or deep sedation (patient asleep, awakening upon physical stimulation). MEASUREMENTS AND MAIN RESULTS: : Self-reported measures of posttraumatic stress disorder, anxiety, and depression were collected at intensive care unit discharge and 4 wks later. The primary outcomes were symptoms of posttraumatic stress disorder, anxiety, and depression 4 wks after intensive care unit discharge.A total of 137 patients were assigned to either the light (n = 69) or the deep sedation (n = 68) group. Seven patients withdrew consent and one patient was randomized in error, leaving 129 patients (n = 65 in light sedation and n = 64 in deep sedation) available for analysis. At the 4-wk follow-up, patients in the deep sedation group tended to have more posttraumatic stress disorder symptoms (p = .07); the deep sedation group had more trouble remembering the event (37% vs. 14%; p = .02) and more disturbing memories of the intensive care unit (18% vs. 4%; p = .05). Patients in the light sedation group had an average one day less being ventilated and 1.5 fewer days in the intensive care unit. There were no differences between the two groups in the occurrence of anxiety and depression, and also no difference in mortality or in the incidence of adverse events. CONCLUSIONS: : These data suggest that a strategy of light sedation affords benefits with regard to reduction of intensive care unit stay and duration of ventilation without negatively affecting subsequent patient mental health or patient safety.

[Supplemental parenteral nutrition for intensive care patients: a logical combination with enteral nutrition]. / Nutrition parentérale compé- mentaire de la nutrition entérale aux soins intensifs: une association logique.

Undernutrition is a widespread problem in the intensive care and is associated with a worse clinical outcome. Enteral nutrition is the recommended nutritional support in ICU patients. However, enteral nutrition is frequently insufficient to cover protein-energy needs. The initiation of supplemental parenteral nutrition, when enteral nutrition is insufficient, could optimize the nutritional therapy. Such a combination could allow reducing morbidity, length of stay and recovery, as well as improving quality of life and health care costs. Prospective studies are currently underway to test this hypothesis.

In vitro validation of indirect calorimetry device developed for the ICALIC project against mass spectrometry.

RATIONALE: Accurate evaluation of the energy needs is required to optimize nutrition support of critically ill patients. Recent evaluations of indirect calorimeters revealed significant differences among the devices available on the market. A new indirect calorimeter (Q-NRG®, Cosmed, Roma, Italy) has been developed by a group of investigators supporting the international calorimetry study initiative (ICALIC) to achieve ultimate accuracy for measuring energy expenditure while being easy to use, and affordable. This study aims to validate the precision and the accuracy of the Q-NRG® in the in-vitro setting, within the clinically relevant range for adults on mechanical ventilation in the ICU. Mass spectrometry is the reference method for the gas composition analysis to evaluate the analytic performances of the Q-NRG®. METHODS: The accuracy and precision of the O2 and CO2 measurements by the Q-NRG were evaluated by comparing the measurements of known O2 and CO2 gas mixtures with the measurements by the mass spectrometer (Extrel, USA). The accuracy and precision of the Q-NRG® for measurements of VO2 (oxygen consumption) and VCO2 (CO2 production) at clinically relevant ranges (150, 250 and 400 ml/min STPD) were evaluated by measuring simulated gas exchange under mechanically ventilated setting at different FiO2 settings (21-80%), in comparison to the reference measurements by the mass spectrometer-based mixing chamber system. RESULTS: The measurements of gas mixtures of predefined O2 and CO2 concentrations by the Q-NRG® were within 2% accuracy versus the mass spectrometer measurements in Passing Bablok regression analysis. In a mechanically ventilated setting of FiO2 from 21 up to 70%, the Q-NRG® measurements of simulated VO2 and VCO2 were within 5% difference of the reference mass spectrometer measurements. CONCLUSION: In vitro evaluation confirms that the accuracy of the Q-NRG® indirect calorimeter is within 5% at oxygen enrichment to 70%; i.e. maximum expected for clinical use. Further recommendations for the clinical use of the Q-NRG® by will be released once the ongoing multi-center study is completed.

Enteral vs. parenteral nutrition for the critically ill patient: a combined support should be preferred.

PURPOSE OF REVIEW: Current recommendations suggest starting enteral feeding as soon as possible whenever the gastrointestinal tract is functioning. The disadvantage of enteral support is that insufficient energy and protein coverage can occur. This review focuses on some recent findings regarding the nutritional support of critically ill patients and evaluates the data presented. RECENT FINDINGS: An increasing nutritional deficit during a long ICU stay is associated with increased morbidity (infection rate, wound healing, mechanical ventilation, length of stay, duration of recovery), and costs. Evidence shows that enteral nutrition can result in underfeeding and that nutritional goals are frequently reached only after 1 week. Contrary to former beliefs, recent meta-analyses of ICU studies showed that parenteral nutrition is not related to a surplus mortality and may even be associated with improved survival. SUMMARY: Early enteral nutrition is recommended for critically ill patients. Supplemental parenteral nutrition combined with enteral nutrition can be considered to cover the energy and protein targets when enteral nutrition alone fails to achieve the caloric goal. Whether such a combined nutritional support provides additional benefit on the overall outcome has to be proven in further studies on clinical outcome, including physical and cognitive functioning, quality of life, cost-effectiveness, and cost-utility.

Is it now time to promote mixed enteral and parenteral nutrition for the critically ill patient?

BACKGROUND: Intensive care outcome measured by morbidity and mortality is altered in the severely malnourished ICU patient, and nutritional support of the critically ill is accepted as a standard of care. Current recommendations suggest starting enteral feeding as soon as possible whenever the gastrointestinal tract is functioning. The disadvantage of enteral support is that inadequate energy and protein intake can occur. The present commentary focuses on some recent findings regarding the nutritional support of critically ill patients and proposes to promote mixed nutrition support by enteral nutrition (EN), and by parenteral nutrition (PN) whenever EN is insufficient. RECENT FINDINGS: An increasing nutrition deficit during a long ICU stay is associated with increased morbidity (increased infection rate or impaired wound healing). Evidence shows that EN can result in underfeeding and that nutrition goals are reached only after 5-7 days. Contrary to former beliefs, recent meta-analyses of studies in the ICU showed that PN is not related to excess mortality but may even be associated with improved survival. CONCLUSIONS: Optimising the increased substrate requirement for the critically ill by initiating timely nutrition support and ensuring tight glycaemic control with insulin is now considered central for improved intensive care outcomes. Supplemental PN combined with EN could be an effective alternative to achieve 100% of energy and protein targets at day 4, when EN alone fails to achieve goals greater than 60% by day 3. Whether such combined nutrition support provides additional benefit on overall outcome has to be ascertained in further studies.