Staphylococcus aureus carriage at admission predicts early-onset pneumonia after burn trauma.

Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital's computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156 S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p < 0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.

Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.

[Latin organ donation programme (LODP): an effective initiative to increase organ donation in Switzerland]. / Programme latin de don d'organes (PLDO): une initiative efficace pour augmenter les dons d'organes en Suisse.

The 1st federal transplant law was enforced in July 2007 with the obligation to promote quality and efficiency in the procedures for organ and tissue donation for transplantation. The Latin organ donation programme (LODP) created in 2008 aims to develop organ donation in 17 public hospitals in 7 Latin cantons, covering 2.2 million people; 29% of the Swiss population. The implementation of various effective measures by the LODP enabled the increase in the number of donors by 70% between 2008 and 2010, with four organs procured per donor; greatly exceeding the European average of three. The results show that LODP has successfully professionalised the system and we can only hope that similar organisations will be put into place throughout Switzerland.

Fish oil after abdominal aorta aneurysm surgery.

OBJECTIVE: Fish oil (FO) may attenuate the inflammatory response after major surgery such as abdominal aortic aneurysm (AAA) surgery. We aimed at evaluating the clinical impact and safety aspects of a FO containing parenteral nutrition (PN) after AAA surgery. METHODS: Intervention consisted in 4 days of either standard (STD: Lipofundin medium-chain triglyceride (MCT): long-chain triglyceride (LCT)50%-MCT50%) or FO containing PN (FO: Lipoplus: LCT40%-MCT50%-FO10%). Energy target were set at 1.3 times the preoperative resting energy expenditure by indirect calorimetry. Blood sampling on days 0, 2, 3 and 4. Glucose turnover by the (2)H(2)-glucose method. Muscle microdialysis. CLINICAL DATA: maximal daily T degrees, intensive care unit (ICU) and hospital stay. RESULTS: Both solutions were clinically well tolerated, without any differences in laboratory safety parameters, inflammatory, metabolic data, or in organ failures. Plasma tocopherol increased similarly; with FO, docosahexaenoic and eicosapentaenoic acid increased significantly by day 4 versus baseline or STD. To increased postoperatively, with a trend to lower values in FO group (P=0.09). After FO, a trend toward shorter ICU stay (1.6+/-0.4 versus 2.3+/-0.4), and hospital stay (9.9+/-2.4 versus 11.3+/-2.7 days: P=0.19) was observed. CONCLUSIONS: Both lipid emulsions were well tolerated. FO-PN enhanced the plasma n-3 polyunsaturated fatty acid content, and was associated with trends to lower body temperature and shorter length of stay.

[Intensive care medicine in Switzerland]. / Evolution des soins intensifs en Suisse: historique, situation actuelle et perspectives.

The authors express their views on the past, present and future of intensive care medicine in Switzerland. They point some past and present concerns in critical care medicine, but they insist on the future needs of this medical specialty: the critical patients necessitate, and have the right to obtain, a highly trained and specialized personnel, working in strong connection with the whole hospital, in a systemic way of treating patients. The authors insist on the very high complexity of the ICU-patients treated today.

[Latin program for organ donation: the intensivists are networking]. / Programme latin de don d'organes: les intensivistes se mettent en réseau.

The new Swiss federal law on organ and transplantation strengthens the responsibilities of the intensive care units. In Italian and French speaking parts of Switzerland, the Programme Latin pour le Don d'Organe (PLDO) has been launched to foster a wider collaboration between intensivists and donation coordinators. The PLDO aims at optimising knowledge and expertise in organ donation through improvements in identification, notification and management of organ donors and their next of kin. The PLDO dispenses education to all professionals involved. Such organisation should allow increasing the number of organs available, while improving healthcare professionals experience and next of kin emotion throughout the donation process.

Cerebral vascular autoregulation assessed by perfusion-CT in severe head trauma patients.

PURPOSE: To use perfusion-CT technique in order to characterize cerebral vascular autoregulation in a population of severe head trauma patients with features of cerebral edema either on the admission or on the follow-up conventional noncontrast cerebral CT. MATERIAL AND METHODS: A total of 80 perfusion-CT examinations were obtained in 42 severe head trauma patients with features of cerebral edema on conventional noncontrast cerebral CT, either on admission or during follow-up. Perfusion-CT results, i.e. the regional cerebral blood volume (rCBV) and flow (rCBF), were correlated with the mean arterial pressure (MAP) measured during each perfusion-CT examination. Ratios were defined to integrate the concept of cerebral vascular autoregulation, and cluster analysis performed, which allowed identification of different subgroups of patients. MAP values and perfusion-CT results in these groups were compared using Kruskal-Wallis and Wilcoxon (Mann-Whitney) tests. Moreover, the functional outcome of the 42 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale (GOS) score and similarly compared between groups. RESULTS: Three main groups of patients were identified: 1) 22 perfusion-CT examinations were collected in 13 patients, characterized by high rCBV and rCBF values and by significant dependence of perfusion-CT rCBV and rCBF results on MAP values (p<0.001), 2) 23 perfusion-CT examinations collected in 19 patients showing perfusion-CT results similar to control trauma subjects, and 3) 33 perfusion-CT collected in 16 patients, with low rCBV and rCBF values and near-independence of perfusion-CT results with respect to MAP values. The first group was interpreted as showing impaired cerebral vascular autoregulation, which was preserved in the third group. The second group was associated with the best functional outcome; it was linked to the first group, because eight patients went from one group to the other from admission to follow-up. CONCLUSION: Perfusion-CT in severe head trauma patients was able to provide direct and quantitative assessment of cerebral vascular autoregulation with a single measurement. It could hence be used as a guide for brain edema therapy, as well as to monitor the treatment efficiency.

[Merging of two intensive care units: preliminary observations]. / Fusion de deux services de médecine intensive: quelques observations préliminaires.

The merging of two intensive care units is a time of profound change, and constitutes a risk of mishaps. We report some aspects of such a project in our institution. The evaluation of various indicators reflecting the activity, patient's hospital pathways, mortality, as well as the use of specific techniques, has shown that no particular problem was observed during the first 9 months. Improvements in performance or productivity have not been demonstrated so far. The follow-up will permit to demonstrate long-term benefits. We believe that these observations may be of interest for other departmental or hospital reorganisations.

Ex vivo evaluation of a new extracorporeal lung assist device: NovaLung membrane oxygenator.

When lung function is compromised,alternative devices need to be deployed in order to maintain blood oxygenation. A new device, NovaLung, has been designed for acute lung failure. We went about evaluating its gas exchange capability. Three calves (79.5 +/- 7.8 kg) were connected to the NovaLung System with a priming volume of 240 mL, gas exchange surface area of 1.3 m2 and exhibiting a biologically coated surface. A standard battery of blood samples were taken before implantation and over a six hour period. Hematocrit remained stable ranging from 27 +/- 4% (baseline) to 29 +/- 5% (6 hrs). Platelets were preserved ranging from 882 +/- 27.4 U/L (baseline) to 734 +/- 147 (6 hrs). LDH remained stable at 719 +/- 85 U/L (baseline) vs 686 +/- 190 U/L (6 hrs) and the pressure drop was maintained below 20 mmHg. Minimal hemolysis was observed. Oxygen transfer peaked at two hours acute extracorporeal lung support (ECLS)with a mean value of 130 +/- 50 ml/min. In conclusion, the device is easy to use,provides adequate O2 and CO2 transfer for partial lung support in an acute setting. Shows minimal signs of hemolysis and platelets levels are maintained throughout the six hour ECLS period.

Effects of enteral carbohydrates on de novo lipogenesis in critically ill patients.

BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a possible fate of carbohydrate administered during nutritional support. It cannot be detected by conventional methods such as indirect calorimetry if it does not exceed lipid oxidation. OBJECTIVE: The objective was to evaluate the effects of carbohydrate administered as part of continuous enteral nutrition in critically ill patients. DESIGN: This was a prospective, open study including 25 patients nonconsecutively admitted to a medicosurgical intensive care unit. Glucose metabolism and hepatic DNL were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate. RESULTS: DNL increased with increasing carbohydrate intake (f1.gif" BORDER="0"> +/- SEM: 7.5 +/- 1.2% with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate, and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations. Endogenous glucose production, assessed with a dual-isotope technique, was not significantly different between the 3 groups of patients (13.7-15.3 micromol * kg(-1) * min(-1)), indicating impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with [(13)C]bicarbonate, and increased as the carbohydrate intake increased (from 2.1 +/- 0.5 micromol * kg(-1) * min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3 micromol * kg(-1) * min(-1) with 75% carbohydrate intake, P: < 0. 05). CONCLUSION: Carbohydrate feeding fails to suppress endogenous glucose production and gluconeogenesis, but stimulates DNL in critically ill patients.

Failure in measuring gas exchange in the ICU.

OBJECTIVE: This study was performed on patients after coronary artery bypass surgery, and in healthy volunteers to assess discrepant oxygen consumption (VO2) measurement between indirect calorimetry and Fick methods. Further evaluations were performed to point out the technical failure. METHODS: In this prospective study, the VO2 was assessed in the patients using a commercial indirect calorimeter and the reverse Fick method. This calorimeter does not directly measure gas flow, but it assumes a constant preset flow. Bench testing of the calorimeter was performed in spontaneous and respirator mode using a reference calorimeter in healthy volunteers. RESULTS: An important overestimation of VO2 and carbon dioxide production (VCO2) of approximately 30% was found in both groups. The actual flow was lower than the preprogrammed value. This lead to spuriously high fractions of carbon dioxide and low fraction of oxygen. VCO2 and VO2, calculated with the overestimated gas flow value were overestimated, while respiratory quotient remained unchanged. Technical check-up revealed leaks in the mixing chamber and in the sampling lines. CONCLUSION: Indirect calorimetry is a useful clinical tool, but the investigator has to be very attentive to all potentially interfering factors and hazards.

Pain location, distribution, and intensity after cardiac surgery.

STUDY OBJECTIVES: To study the location, distribution, and intensity of pain in a sample of adult cardiac surgery patients during their postoperative hospital stay. DESIGN: In a prospective study, pain location, distribution (number of pain areas per patient), and intensity (0 to 10 numerical rating scale) were documented on the first, second, third, and seventh postoperative day (POD). Patient characteristics (age, sex, size, and body mass index) were analyzed for their impact on pain intensity. SETTING: A university hospital. PATIENTS: Two hundred consecutive adult patients who underwent median sternotomy for open heart surgery. There were 121 male and 79 female patients, with a mean (+/- SD) age of 60.9 +/- 19.2 years. MEASUREMENT AND RESULTS: The maximal pain intensity was significantly higher on POD 1 and 2 (3.7 +/- 2 and 3.9 +/- 1.9, respectively) and lower on POD 3 and 7 (3.2 +/- 1.5 and 2.6 +/- 1.8, respectively). The pain distribution did not vary significantly throughout the hospital stay, but the location did, with more shoulder pain on POD 7. Only age was found to have an impact on pain intensity, with patients < 60 years having a higher pain intensity than older patients on POD 2 (4.3 +/- 2.2 vs 3.6 +/- 2.4; p = 0.02). CONCLUSIONS: In this patient population, the pain intensity diminished from POD 3 onward, although its distribution did not vary significantly during the first postoperative week. Moreover, pain location changed with time, with more osteoarticular type pain at the end of the first postoperative week. Among the patients' characteristics, only younger age had an impact on pain intensity, with a higher value on POD 2.

Impact of a bicarbonated saline solution on early resuscitation after major burns.

OBJECTIVE: The study aimed at assessing the impact of the introduction of a bicarbonated saline solution on total fluid load, weight gain and acid base status during acute burn resuscitation. DESIGN: Based on a retrospective patient record review. SETTING: Burn care centre of a surgical ICU in a tertiary university hospital. PATIENTS: Two groups of adult patients (20/20), with thermal burns of 25% or more body surface area were studied. INTERVENTION: Modification of the resuscitation fluid composition from lactated Ringer's solution (LR: Na 132 mmol/l, Cl 112 mmol/l, 263 mosm/l), to bicarbonated 0.9% saline (BS: Na 180 mmol/l, Cl 154 mmol/l, 340 mosm/l) METHODS: Age, weight, burn size and depth, inhalation injury, fluid intakes over 48 h post-injury, plasma sodium, chloride, creatinine, albumin levels, blood gases and ventilation support were recorded. RESULTS: The demographic characteristics of the patients (41 +/- 16 years) in the two groups were not different, with severe burns involving 44 +/- 17% body surface area. While the total fluid volumes administered did not differ, BS was associated with lower plasma pH, base excess and bicarbonate levels for 24 h and with hyperchloraemia. Clinical evolution did not differ. CONCLUSIONS: Using bicarbonated saline solution for resuscitation causes a transient hyperchloraemic dilutional acidosis compared with LR, and has no other detectable clinical impact over the first 10 days after severe burn injury.

Early metabolic and splanchnic responses to enteral nutrition in postoperative cardiac surgery patients with circulatory compromise.

OBJECTIVES: To assess the hemodynamic and metabolic adaptations to enteral nutrition (EN) in patients with hemodynamic compromise. DESIGN AND SETTING: Prospective study in a university hospital surgical ICU, comparing baseline (fasted) with continuous EN condition. PATIENTS: Nine patients requiring hemodynamic support by catecholamines (dobutamine and/or norepinephrine) 1 day after cardiac surgery under cardiopulmonary bypass. INTERVENTION: Isoenergetic EN via a postpyloric tube while catecholamine treatment remained constant. Baseline (fasted) condition was compared to continuous EN condition. MEASUREMENTS AND MAIN RESULTS: Cardiac index (CI), mean arterial pressure (MAP), pulmonary and wedge pressures, indocyanine green (ICG) clearance, gastric tonometry, plasma glucose and insulin, and glucose turnover (6,62H2-glucose infusion) were determined repetitively every 60 min during 2 h of baseline fasting condition and 3 h of EN. During EN CI increased (from 2.9 +/- 0.5 to 3.3 +/- 0.5 l min-1 m-2), MAP decreased transiently (from 78 +/- 7 to 70 +/- 11 mmHg), ICG clearance increased (from 527 +/- 396 to 690 +/- 548 ml/min), and gastric tonometry remained unchanged, while there were increases in glucose (158 +/- 23 to 216 +/- 62 mg/dl), insulin (29 +/- 23 to 181 +/- 200 mU/l), and glucose rate of appearance (2.4 +/- 0.2 to 3.3 +/- 0.2 mg min-1 kg-1). CONCLUSIONS: The introduction of EN in these postoperative patients increased CI and splanchnic blood flow, while the metabolic response indicated that nutrients were utilized. These preliminary results suggest that the hemodynamic response to early EN may be adequate after cardiac surgery even in patients requiring inotropes.

Human errors in a multidisciplinary intensive care unit: a 1-year prospective study.

OBJECTIVES: To determine the incidence and identify risk factors of critical incidents in an ICU. DESIGN: Prospective observational study of consecutive patients admitted over 1 year to an ICU. Critical incidents were recorded using predefined criteria. Their causes and consequences were analysed. The causes were classified as technical failure, patient's underlying disease, or human errors (subclassified as planning, execution, or surveillance). The consequences were classified as lethal, leading to sequelae, prolonging the ICU stay, minor, or without consequences. The correlation between critical incidents and specific factors including patient's diagnosis and severity score, use of monitoring and therapeutic modalities was analysed by uni- and multivariate analysis. SETTING: An 11-bed multidisciplinary ICU in a non-university teaching hospital. PATIENTS: 1,024 consecutive patients admitted to the ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The median length of ICU stay by the 1,024 patients was 1.9 days. Of the 777 critical incidents reported 2% were due to technical failure and 67 % to secondary to underlying disease. There were 241 human errors (31%) in 161 patients, evenly distributed among planning (n = 75), execution (n = 88), and surveillance (n = 78). One error was lethal, two led to sequelae, 26 % prolonged ICU stay, and 57 % were minor and 16 % without consequence. Errors with significant consequences were related mainly to planning. Human errors prolonged ICU stay by 425 patient-days, amounting to 15 % of ICU time. Readmitted patients had more frequent and more severe critical incidents than primarily admitted patients. CONCLUSIONS: Critical incidents add morbidity, workload, and financial burden. A substantial proportion of them are related to human factors with dire consequences. Efforts must focus on timely, appropriate care to avoid planning and execution mishaps at the beginning of the ICU stay; surveillance intensity must be maintained, specially after the fourth day.

Effects of endotoxin on isolated porcine liver: pressure-flow analysis.

The peripheral vascular response to sepsis is characterized by a vasodilatation of the systemic arterial vessels. Pulmonary hypertension with an increase in resistance and back pressure to flow defined by pressure-flow (P-Q) relationships has been reported in experimental sepsis. We hypothesized that endotoxin can induce differential alterations in resistance and back pressure to flow in the liver venous and arterial beds. Ninety minutes after endotoxin administration in intact anesthetized pigs (n = 8), the liver was vascularly isolated and perfused. Steady-state P-Q relationships in both the portal vein (PV) and hepatic artery (HA) were generated at multiple outflow pressures (Pout; 0, 5, 10, and 15 mmHg) and compared with those obtained in control livers (n = 6). Extrapolated zero-flow pressure intercepts (Pback) and slopes of the P-Q relationships were obtained by least squares linear regression analysis. Endotoxemia increased PV Pback (P < 0.05), and Pback always exceeded Pout (P < 0.05) when the latter was raised. In contrast, in controls, no difference was observed between Pback and Pout when the latter was raised. Endotoxemia also increased the PV slope compared with control. Raising Pout from 0 to 15 mmHg decreased PV slope in the endotoxin group to a greater degree than in controls (P < 0.05). In the HA, endotoxin caused a decrease in slope but did not alter Pback. The simultaneous increase in the PV Pback and slope that occurs with endotoxemia decreases splanchnic venous return, pooling blood in the splanchnic compartment for a given total blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide in porcine liver circulation under normal and endotoxemic conditions.

The role of nitric oxide (NO) in the liver vasculature during baseline and endotoxic shock states was evaluated in 17 anesthetized pigs. Mean systemic arterial pressure, pulmonary arterial pressure, and portal venous pressure and flow, hepatic arterial pressure and flow, and cardiac output were measured. Pressure-flow (P-Q) relationships defined resistances as a back pressure and a slope. Inhibition of nitric oxide synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) at baseline increased mean arterial pressure, pulmonary arterial pressure, hepatic arterial pressure, and the slopes of their P-Q relationships (P < 0.05) but had no effect on portal venous pressure or its P-Q relationship. After endotoxin (10 micrograms/kg iv), NO induced arterial dilation and attenuated increases in portal venous and pulmonary arterial resistances (P < 0.05) that were reversed by L-NAME. NOS inhibition was stereospecifically reversed by L-arginine. Local control of liver blood flow at baseline via the hepatic arterial buffer response and hepatic arterial autoregulation were increased in gain after L-NAME. Endotoxic shock ablated the hepatic arterial buffer response and autoregulation independent of either NO or an alpha-adrenergic-receptor agonist (P < 0.05). Under baseline conditions, NO modulates pulmonary, systemic, and hepatic arterial but not portal venous resistances. NO production during endotoxic shock induces arterial hypotension and hepatic arterial vasodilation and attenuates increases in both portal and pulmonary resistances. NOS inhibition in endotoxic shock could increase morbidity due to a loss of local control of liver blood flow and marked increases in resistance to venous return across both the liver and lungs.

Pain pattern and left internal mammary artery grafting.

BACKGROUND: This study was designed to determine whether the pain pattern in patients with an internal mammary artery (IMA) harvest differs from that in other cardiac operations and whether these patients present specific characteristics with clinical implications. METHODS: One hundred patients with left IMA grafting (IMA group) were compared prospectively with 100 patients who had a heart operation without IMA harvest (non-IMA group). Pain assessment was performed on postoperative days (POD) 1, 2, 3, and 7, and included pain intensity (10-point scale) and pain localization. RESULTS: In the IMA group, pain intensity was higher on POD 2 (4.2 +/- 2.4 versus 3.2 +/- 2.3, p < 0.01), and there were more patients without pain on POD 7 (32 versus 19, p = 0.03). In the IMA group, more patients had left basal thoracic pain throughout the entire study period and had sternal pain on POD 7, whereas more patients in the non-IMA group complained about back pain during the early postoperative period. CONCLUSIONS: The impact of IMA harvest on pain intensity is moderate, but the pain localization pattern of each group exhibits specific features that could help to better target pain management.

Fractional hepatic de novo lipogenesis in healthy subjects during near-continuous oral nutrition and bed rest: a comparison with published data in artificially fed, critically ill patients.

BACKGROUND AND AIMS: In critically ill patients, fractional hepatic de novo lipogenesis increases in proportion to carbohydrate administration during isoenergetic nutrition. In this study, we sought to determine whether this increase may be the consequence of continuous enteral nutrition and bed rest. We, therefore, measured fractional hepatic de novo lipogenesis in a group of 12 healthy subjects during near-continuous oral feeding (hourly isoenergetic meals with a liquid formula containing 55% carbohydrate). In eight subjects, near-continuous enteral nutrition and bed rest were applied over a 10 h period. In the other four subjects, it was extended to 34 h. Fractional hepatic de novo lipogenesis was measured by infusing(13) C-labeled acetate and monitoring VLDL-(13)C palmitate enrichment with mass isotopomer distribution analysis. Fractional hepatic de novo lipogenesis was 3.2% (range 1.5-7.5%) in the eight subjects after 10 h of near continuous nutrition and 1.6% (range 1.3-2.0%) in the four subjects after 34 h of near-continuous nutrition and bed rest. This indicates that continuous nutrition and physical inactivity do not increase hepatic de novo lipogenesis. Fractional hepatic de novo lipogenesis previously reported in critically ill patients under similar nutritional conditions (9.3%) (range 5.3-15.8%) was markedly higher than in healthy subjects (P<0.001). These data from healthy subjects indicate that fractional hepatic de novo lipogenesis is increased in critically ill patients.

Energy metabolism in sepsis and injury.

The development of malnutrition is often rapid in critically ill patients with sepsis and severe trauma. In such patients, a wide array of hormonal and nonhormonal mediators are released, inducing complex metabolic changes. Hypermetabolism, associated with protein and fat catabolism, negative nitrogen balance, hyperglycemia, and resistance to insulin, constitute the hallmark of this response. Critically ill patients demonstrate a marked alteration in the adaptation to prolonged starvation: resting metabolic rate and tissue catabolism stay elevated, while ketogenesis remains suppressed. The response to nutrition support is impaired. Substrate use is modified in septic and traumatized patients. Glucose administration during severe aggression does not suppress the enhanced hepatic glucose production and the lipolysis. This phenomenon, related to tissue insulin resistance, ensures a high flow of glucose to the predominantly glucose-consuming cells, such as the wound, the inflammatory, and immune cells, all insulin-independent cells. In addition, the elevated protein catabolism is difficult to abolish, even during aggressive nutrition support. Thus, in patients with prolonged aggression, these alterations produce a progressive loss of body cell mass and foster the development of malnutrition and it dire complications. In this review, the relevant physiologic data and the nutritional implications related to energy metabolism in septic and injured patients are discussed, while potential therapeutic strategies are proposed.