Taku Oshima

TNF-α contributes to axonal sprouting and functional recovery following traumatic brain injury

In response to a central nervous system (CNS) injury, microglia and astrocytes release tumor necrosis factor-alpha (TNF-alpha). This proinflammatory cytokine has been implicated in both neuronal cell death and survival. Here, we show that TNF-alpha is involved in the recovery of neuromotor function following traumatic brain injury. Composite neuroscore and accel rotarod were employed to measure neuromotor function. TNF-alpha-deficient (TNF-alpha(-/-)) mice showed no improvement in their locomotor function up to 28 days following controlled cortical impact brain injury. Although collateral sprouting of the unlesioned corticospinal tract, as assessed by retrograde biotin dextran amine labeling, at the cervical spinal cord was observed following injury in the wild-type mice, such changes were not induced in the TNF-alpha(-/-) mice at 4 weeks after injury. These results provide evidence that TNF-alpha is involved in neuroanatomical plasticity and functional recovery following CNS injury.

The effects of body temperature control on cytokine production in a rat model of ventilator-induced lung injury

BACKGROUND AND PURPOSE Injurious ventilation with high peak inspiratory pressure (PIP) is known to cause systemic inflammatory response through cytokine production. This study was performed to examine whether body temperature could regulate cytokine production in ventilator-induced lung injury (VILI) model. METHODS After performing anesthesia, tracheostomy, and catheter insertion, rats were ventilated with 17cmH(2)O of PIP in the low-pressure (LP) group or 35cmH(2)O in the high-pressure (HP) group. Then, each group was divided into three subgroups; hyperthermia (39 degrees C), normothermia (37 degrees C), and hypothermia (34 degrees C) group. Six groups were observed for 6h. RESULTS Plasma levels of pro-inflammatory cytokines, TNF-a and IL-6 at 1h after the start of observation were highest in 39 degrees C-HP group and were lowest in 34 degrees C-HP group. Furthermore, sustained high plasma levels of IL-6 were observed only in 39 degrees C-HP group. In contrast, plasma levels of anti-inflammatory cytokine, IL-10 at 1h were highest in 34 degrees C-HP group, and lowest in 39 degrees C-HP group. CONCLUSION The body temperature significantly affects cytokine production in a model of VILI. Body temperature control may be a potentially effective therapeutic modality to regulate cytokine production in VILI.

Indirect calorimetry in nutritional therapy. A position paper by the ICALIC study group

BACKGROUND & AIMS This review aims to clarify the use of indirect calorimetry (IC) in nutritional therapy for critically ill and other patient populations. It features a comprehensive overview of the technical concepts, the practical application and current developments of IC. METHODS Pubmed-referenced publications were analyzed to generate an overview about the basic knowledge of IC, to describe advantages and disadvantages of the current technology, to clarify technical issues and provide pragmatic solutions for clinical practice and metabolic research. The International Multicentric Study Group for Indirect Calorimetry (ICALIC) has generated this position paper. RESULTS IC can be performed in in- and out-patients, including those in the intensive care unit, to measure energy expenditure (EE). Optimal nutritional therapy, defined as energy prescription based on measured EE by IC has been associated with better clinical outcome. Equations based on simple anthropometric measurements to predict EE are inaccurate when applied to individual patients. An ongoing international academic initiative to develop a new indirect calorimeter aims at providing innovative and affordable technical solutions for many of the current limitations of IC. CONCLUSION Indirect calorimetry is a tool of paramount importance, necessary to optimize the nutrition therapy of patients with various pathologies and conditions. Recent technical developments allow broader use of IC for in- and out-patients.

Protein-energy nutrition in the ICU is the power couple: A hypothesis forming analysis

BACKGROUND & AIMS We hypothesize that an optimal and simultaneous provision of energy and protein is favorable to clinical outcome of the critically ill patients. METHODS We conducted a review of the literature, obtained via electronic databases and focused on the metabolic alterations during critical illness, the estimation of energy and protein requirements, as well as the impact of their administration. RESULTS Critically ill patients undergo severe metabolic stress during which time a great amount of energy and protein is utilized in a variety of reactions essential for survival. Energy provision for critically ill patients has drawn attention given its association with morbidity, survival and long-term recovery, but protein provision is not sufficiently taken into account as a critical component of nutrition support that influences clinical outcome. Measurement of energy expenditure is done by indirect calorimetry, but protein status cannot be measured with a bedside technology at present. CONCLUSIONS Recent studies suggest the importance of optimal and combined provision of energy and protein to optimize clinical outcome. Clinical randomized controlled studies measuring energy and protein targets should confirm this hypothesis and therefore establish energy and protein as a power couple.

Fulfilling caloric demands according to indirect calorimetry may be beneficial for post cardiac arrest patients under therapeutic hypothermia

INTRODUCTION We sought to investigate the energy requirements for patients under therapeutic hypothermia, and the relationship of energy fulfillment to patient outcome. PATIENTS AND METHODS Adult patients admitted to our ICU after successful resuscitation from cardiac arrest for post resuscitation therapeutic hypothermia from April, 2012 to March, 2014 were enrolled. Body temperature was managed using the surface cooling device (Arctic Sun(®), IMI). Calorimeter module on the ventilator (Engström carestation(®), GE) was used for indirect calorimetry. Energy expenditure (EE) and respiratory quotient (RQ) were recorded continuously, as the average of the recent 2h. Measurements were started at the hypothermic phase and continued until the rewarming was completed. Cumulative energy deficit was calculated as the sum of difference between EE and daily energy provision for the 4 days during hypothermia therapy. RESULTS Seven patients were eligible for analysis. Median EE for the hypothermic phase (day 1) was 1557.0kcald(-1). EE was elevated according with the rise in body temperature, reaching 2375kcald(-1) at normothermic phase. There was significant association between cumulative energy deficit and the length of ICU stay, among patients with good neurologic recovery (cerebral performance category (CPC): 1-3). CONCLUSION The EE for patients under therapeutic hypothermia was higher than expected. Meeting the energy demand may improve patient outcome, as observed in the length of ICU stay for the present study. A larger, prospective study is awaited to validate the results of our study.

Parenteral nutrition in the ICU setting: need for a shift in utilization

Purpose of reviewThe difficulties to feed the patients adequately with enteral nutrition alone have drawn the attention of the clinicians toward the use of parenteral nutrition, although recommendations by the recent guidelines are conflicting. This review focuses on the intrinsic role of parenteral nutrition, its new indication, and modalities of use for the critically ill patients. Recent findingsA recent trial demonstrated that selecting either parenteral nutrition or enteral nutrition for early nutrition has no impact on clinical outcomes. However, it must be acknowledged that the risk of relative overfeeding is greater when using parenteral nutrition and the risk of underfeeding is greater when using enteral nutrition because of gastrointestinal intolerance. Both overfeeding and underfeeding in the critically ill patients are associated with deleterious outcomes. Thus, early and adequate feeding according to the specific energy needs can be recommended as the optimal feeding strategy. SummaryParenteral nutrition can be used to substitute or supplement enteral nutrition, if adequately prescribed. Testing for enteral nutrition tolerance during 2–3 days after ICU admission provides the perfect timing to start parenteral nutrition, if needed. In case of absolute contraindication for enteral nutrition, consider starting parenteral nutrition carefully to avoid overfeeding.

Serum Procalcitonin Level and SOFA Score at Discharge from the Intensive Care Unit Predict Post-Intensive Care Unit Mortality: A Prospective Study

Purpose The final decision for discharge from the intensive care unit (ICU) is uncertain because it is made according to various patient parameters; however, it should be made on an objective evaluation. Previous reports have been inconsistent and unreliable in predicting post-ICU mortality. To identify predictive factors associated with post-ICU mortality, we analyzed physiological and laboratory data at ICU discharge. Methods Patients admitted to our ICU between September 2012 and August 2013 and staying for critical care>2 days were included. Sequential Organ Failure Assessment (SOFA) score; systemic inflammatory response syndrome score; white blood cell count; and serum C reactive protein, procalcitonin (PCT), interleukin-6 (IL-6), lactate, albumin, and hemoglobin levels were recorded. The primary end point was 90-day mortality after ICU discharge. Two hundred eighteen patients were enrolled (195 survivors, 23 non-survivors). Results Non-survivors presented a higher SOFA score and serum PCT, and IL-6 levels, as well as lower serum albumin and hemoglobin levels. Serum PCT, albumin, and SOFA score were associated with 90-day mortality in multiple logistic regression analysis. Hosmer-Lemeshow test showed chi-square value of 6.96, and P value of 0.54. The area under the curve (95% confidence interval) was 0.830 (0.771–0.890) for PCT, 0.688 (0.566–0.810) for albumin, 0.861 (0.796–0.927) for SOFA score, and increased to 0.913 (0.858–0.969) when these were combined. Serum PCT level at 0.57 ng/mL, serum albumin at 2.5 g/dL and SOFA score at 5.5 predict 90-day mortality, and high PCT, low albumin and high SOFA groups had significantly higher mortality. Serum PCT and SOFA score were significantly associated with survival days after ICU discharge in Cox regression analysis. Conclusions Serum PCT level and SOFA score at ICU discharge predict post-ICU mortality and survival days after ICU discharge. The combination of these two and albumin level might enable accurate prediction.

Energy deficit is clinically relevant for critically ill patients: yes.

Survival mechanisms have evolved for thousand of years to optimize vital energy-dependent functions at the expense of substrates stored in lean and fat tissues. A phylogenic analysis of mammalian biology supports the concept that human beings challenged by lifethreatening conditions have been programed for energy autonomy for a few days only, as the absence of hydration for 4–5 days defines the survival limit. Beyond this limit, both water and some energy are needed for further survival and functional recovery. In addition, only the strongest and youngest individuals were likely to survive, as the ultimate goal was the reproduction of the species. Energy deficit promotes proteolysis and lipolysis to fuel the mandatory gluconeogenesis, which rapidly deteriorates most of the vital body functions (e.g., muscle strength, physical mobility, thermic control, immune response, etc.). This deficit induces auto-cannibalism, a short-term, lifesaving, genetically driven mechanism, but also a condition compromising recovery and increasing morbidity and ultimately mortality [1, 2]. In 2015, the mean age of ICU patients and the number of those with one or more chronic diseases and/or sarcopenic obesity have significantly increased. Life support techniques have increased survival up to a point where the nutritional condition becomes a limiting factor for the clinical outcome. A ‘‘simple’’ nutritional support adapted to the body’s needs and enabling a positive response to the sophisticated treatments would be highly desirable.

Parenteral nutrition: never say never

This review emphasizes the benefits of parenteral nutrition (PN) in critically ill patients, when prescribed for relevant indications, in adequate quantities, and in due time.Critically ill patients are at risk of energy deficit during their ICU stay, a condition which leads to unfavorable outcomes, due to hypercatabolism secondary to the stress response and the difficulty to optimize feeding. Indirect calorimetry is recommended to define the energy target, since no single predictive equation accurately estimates energy expenditure. Energy metabolism is intimately associated with protein metabolism. Recent evidence calls for adequate protein provision, but there is no accurate method to estimate the protein requirements, and recommendations are probably suboptimal. Enteral nutrition (EN) is the preferred route of feeding, but gastrointestinal intolerance limits its efficacy and PN allows for full coverage of energy needs.Seven recent articles concerning PN for critically ill patients were identified and carefully reviewed for the clinical and scientific relevance of their conclusions. One article addressed the unfavorable effects of early PN, although this result should be more correctly regarded as a consequence of glucose load and hypercaloric feeding. The six other articles were either in favor of PN or concluded that there was no difference in the outcome compared with EN. Hypercaloric feeding was not observed in these studies. Hypocaloric feeding led to unfavorable outcomes. This further demonstrates the beneficial effects of an early and adequate feeding with full EN, or in case of failure of EN with exclusive or supplemental PN.EN is the first choice for critically ill patients, but difficulties providing optimal nutrition through exclusive EN are frequently encountered. In cases of insufficient EN, individualized supplemental PN should be administered to reduce the infection rate and the duration of mechanical ventilation. PN is a safe therapeutic option as long as sufficient attention is given to avoid hypercaloric feeding.

Treatment of septic shock with continuous HDF using 2 PMMA hemofilters for enhanced intensity

Purpose Cytokines play pivotal roles in the pathophysiology of severe sepsis/septic shock, and continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously, mainly through adsorption to a hemofilter membrane. The aim of this study was to investigate the clinical efficacy of enhanced intensity PMMA-CHDF in treating refractory septic shock. Methods Seventy-two septic shock patients admitted to the intensive care unit (ICU) underwent critical care including PMMA-CHDF. We employed enhanced intensity PMMA-CHDF to improve the cytokine removal rate by increasing the hemofilter membrane area in 10 refractory septic shock patients (enhanced intensity group, EI group; 2 extracorporeal CHDF circuits using the hemofilter with a larger membrane area of 2.1 m2). Other patients undergoing conventional PMMA-CHDF and matched for severity with the EI group, comprised a matched conventional group (MC group; using a PMMA membrane hemofilter with a membrane area of 1.0 m2; n=15). The case-control comparison was performed between the 2 groups. Results Enhanced intensity PMMA-CHDF significantly increased mean arterial pressure by 23.8% in 1 hour (p=0.037), decreased the blood lactate level by 28.6% in 12 hours (p=0.006), and reduced blood IL-6 level in 24 hours (p=0.005). The ICU survival rate in the EI group was significantly better than that in the MC group (60% vs. 13.3%, p=0.028). Conclusion Enhanced intensity PMMA-CHDF may improve hemodynamics and survival rate in patients with refractory septic shock.