Early Phase Of Critical Illness Research Articles

Achievement of adequate nutrition contributes to maintaining the skeletal muscle area in patients with sepsis undergoing early mobilization: a retrospective observational study

BackgroundThe onset of muscle loss in critically ill patients, known as intensive care unit-acquired weakness (ICU-AW), worsens their outcomes. Preventing muscle loss, which begins in the early phase of critical illness, is crucial in patient care. Adequate nutrition management may contribute to maintaining muscles; however, its evidence in patients with sepsis is insufficient. This study aimed to analyze the association between energy achievement rate in the first 7-days of critical care and muscle area changes evaluated by computed tomography (CT).MethodsThis was a retrospective observational study. Patients with sepsis admitted to the intensive care (ICU) of a tertiary care hospital in Japan were included. They were divided into three groups according to tertiles of the first 7-day energy achievement rate calculated using administered energy doses and basement energy expenditure. Skeletal muscle area (SMA) and changes in SMA were determined by CT on ICU admission and within days 7–10 of ICU admission. SMA maintenance was defined as SMA change ≥ 100%. Logistic regression analyses were performed to analyze the association of energy achievement rate with SMA changes (primary outcome) and in-hospital 28-day mortality (secondary outcome).ResultsPatients (n = 93) were classified into low, middle, and high groups according to their 7-day energy achievement rate (median rates, 16.8%, 38.8%, and 73.4%, respectively). The CT scans showed that SMA decreased between the CT scans in the low and middle groups, whereas it was maintained in the high group (median changes, -8.5%, -11.7%, and 2.8%, respectively). Univariate and multivariate logistic regression analyses showed that high energy achievement rate was significantly associated with SMA maintenance (reference, middle energy achieved group; univariate, odds ratio [95% confidence interval] 6.23 [2.04–19.10], P = 0.0013; multivariate, odds ratio [95% confidence interval] 5.92 [1.90–18.40], P = 0.0021). There was no significant difference in the association between energy achievement rate and mortality among the three groups.ConclusionsOur study found that a fulfillment of energy achievement in the first 7 days of hospitalization was associated with maintenance of muscle area. Thus, satisfying adequate energy should be considered even in patients with sepsis.

Adequacy of cefepime concentrations in the early phase of critical illness: A case for precision pharmacotherapy.

In critically ill patients, adequacy of early antibiotic exposure has been incompletely evaluated. This study characterized factors associated with inadequate cefepime exposure in the first 24 h of critical illness. Prospective cohort study. Academic Medical Center. Critically ill adults treated with cefepime. Patients with acute kidney injury or treated with kidney replacement therapy or extracorporeal membrane oxygenation were excluded. None. A nonlinear mixed-effects pharmacokinetic (PK) model was developed to estimate cefepime concentrations for each patient over time. The percentage of time the free drug concentration exceeded 8 mg/L during the first 24 h of therapy was calculated (%ƒT>8; appropriate for the susceptible breakpoint for Pseudomonas aeruginosa). Factors predictive of low %ƒT>8 were explored with multivariable regression. In the 100 included patients, a one-compartment PK model was developed with first-order elimination with covariates for weight and estimated glomerular filtration rate based on creatinine and cystatin C (eGFRSCr-CysC). The median (interquartile range) %ƒT>8 for cefepime in the first 24 h of therapy based on this model was 85% (66%, 100%). Less than 100% ƒT>8 during first 24 h of therapy occurred in 70 (70%) individuals. Lower Sequential Organ Failure Assessment score (p = 0.032) and higher eGFRSCr-CysC (p< 0.001) predicted a lower %ƒT>8. Central nervous system infection source was protective (i.e., associated with a higher %ƒT>8; p = 0.008). During early critical illness, cefepime concentrations were inadequate in a significant proportion of patients. Antimicrobial optimization is needed to improve the precision of pharmacotherapy in the critically ill patients.

Trajectories of protein intake and 28-day mortality in critically ill patients: A secondary analysis of a cluster-randomized controlled trial

The optimal protein intake approach during the early phase of critical illness remains controversial. This study aimed to evaluate the association between different trajectories of protein intake and 28-day mortality in a cohort of critically ill patients. The NEED trial is a multicenter, cluster-randomized controlled trial assessing the impact of an actively implemented evidence-based nutrition guideline on mortality in critically ill patients. This secondary analysis included the patients who stayed in ICU for at least seven days. Group-based trajectory modeling was applied to identify subgroups with similar protein intake trajectories in this cohort. Cox proportional hazards models were used to analyze the impact of different trajectories on 28-day mortality. Overall, 2191 patients were included for analysis. A distinct triple-group trajectory of protein intake was identified, with 919 patients categorized into the low-level protein intake group, 1146 the medium-level group, and 126 the high-level group. The mean daily protein intake from the low-to high-level protein intake group during the first week of enrollment were 0.38±0.14, 0.8±0.18, and 1.68±0.39g/kg/d, respectively. Compared with the medium-level protein intake group, the low-level or high-level protein intake group was associated with significantly increased 28-day mortality (hazard ratio [HR]=1.348, 95% confidence interval [CI]: 1.067-1.704; HR=2.291, 95% CI: 1.533-3.423, respectively). After controlling for potential confounders, the adjusted HRs were 1.365 (95% CI: 1.032-1.807) for the low-level group and 1.921 (95% CI: 1.274-2.896) for the high-level group. However, when taking energy intake into account, low-level protein intake was no longer related to mortality. In contrast, the detrimental effects of high-level protein intake remain tenable (Adjusted HR=2.324, 95% CI: 1.524-3.543, P<0.001). Low-level or high-level protein intake in the early phase of critical illness was associated with increased 28-day mortality than medium-level protein intake. However, when adjusted for energy intake, low-level protein intake in the early phase was no longer associated with increased 28-day mortality.

Mitochondrial dysfunction in critical illness during acute metabolic stress and convalescence: consequences for nutrition therapy.

Mitochondrial dysfunction is associated with increased morbidity and mortality during and after critical illness. The concept of adaptive mitochondrial metabolic-bio-energetic downregulation rather than bio-energetic failure during the acute phase of critical illness has gained traction. As mitochondria are not able to utilize substrate during adaptive hibernation and aggressive feeding induces further harm, this condition has consequences for nutrition therapy. Meeting resting energy expenditure in early critical illness is associated with enhanced oxidative stress and attenuation of autophagy, as is hyperglycemia. The negative effect of early high protein administration remains unclear, whereas fat appears bio-energetically inert. Although antioxidant micronutrients are essential to mitochondrial function, high-dosage studies of single vitamins (C and D) failed to show benefit. Convalescence probably requires increased micronutrient and macronutrient administration to aid anabolism and restore mitochondrial function, although robust data on requirements and actual intake are lacking. Optimal nutrition therapy in the early phase of critical illness should avoid overfeeding and preserve (adaptive) mitochondrial function. Micronutrient supplementation probably requires a strategic cocktail instead of a high dosage of a single nutrient. Focus on identification of distinct metabolic phases to adapt nutrition during and after critical illness is essential.

Liver Steatosis in Brain-Dead Donors: Progression Pattern and Affecting Factors

ObjectivesNo study has investigated the short-term effect of acute insulin resistance on liver steatosis in critically ill condition. We analyzed the effects of critically ill conditions of brain-dead donors (BDDs) on the development and progression of liver steatosis to investigate the influencing factors. MethodsThis study was conducted retrospectively between January 2003 and December 2017. BDDs were for organ procurement. BDDs with body mass indexes (BMIs) < 18.5 kg/m2 and ≥ 30 kg/m2 were excluded. Liver steatosis was defined as ≥5% of the fat vacuole. The serum glucose level (SGL) was used to reflect insulin resistance. ResultsOf the 179 BDDs, 87 (48.6%) had liver steatosis. BMI (r = 0.176, P = .019) and SGL (r = 0.267, P < .001) were correlated with steatosis. The length of the predonation period (LPDP) was negatively correlated with steatosis (r = -0.379, P < .001). BMI (odds ratio 1.266, P = .002), SGL ≥180 mg/dL (odds ratio 2.825, P = .003), and LPDP (odds ratio 0.885, P = .001) were independent risk factors for liver steatosis. ConclusionLiver steatosis is related to the SGL and BMI. Liver steatosis develops acutely in the early phase of critical illness and patients recover gradually.

Is slower advancement of enteral feeding superior to aggressive full feeding regimens in the early phase of critical illness.

An excessive caloric intake during the acute phase of critical illness is associated with adverse effects, presumably related to overfeeding, inhibition of autophagy and refeeding syndrome. The purpose of this review is to summarize recently published clinical evidence in this area. Several observational studies, a few interventional trials, and systematic reviews/metaanalyses were published in 2017-2019. Most observational studies reported an association between caloric intakes below 70% of energy expenditure and a better vital outcome. In interventional trials, or systematic reviews, neither a benefit nor a harm was related to increases or decreases in caloric intake. Gastrointestinal dysfunction can be worsened by forced enteral feeding, whereas the absorption of nutrients can be impaired. Owing to the risks of the delivery of an excessive caloric intake, a strategy of permissive underfeeding implying a caloric intake matching a maximum of 70% of energy expenditure provides the best risk-to-benefit ratio during the acute phase of critical illness.

Influence of Early versus Late supplemental ParenteraL Nutrition on long-term quality of life in ICU patients after gastrointestinal oncological surgery (hELPLiNe): study protocol for a randomized controlled trial

BackgroundNutrition plays a major role in intensive care unit (ICU) treatment, influencing ICU length of stay and patient’s survival. If preferable enteral nutrition administration is not feasible, ESPEN and ASPEN guidelines recommend initiation of a supplemental parenteral route between the first and seventh day, but exact timing remains elusive. While rapid development in critical care enabled significant reduction in the mortality rate of ICU patients, this improvement also tripled the number of patients going to rehabilitation. Thus, it is quality of life after ICU that has become the subject of interest of clinicians and healthcare policy-makers. A growing body of evidence indicates that protein turnover in the early phase of critical illness may play a crucial role in the preservation of lean body mass. A negative protein balance may lead to muscle wasting that persists weeks and months after ICU stay, resulting in deterioration of physical functioning. Folliwing oncological gastrointestinal tract surgery, patients are threatened with negative protein turnover due to cancer and extensive surgical insult.MethodsThis is a multi-centre, single-blinded, randomised controlled trial. The study population includes patients admitted to ICU units after major oncological gastrointestinal surgery that require supplemental parenteral nutrition. After initiation of enteral nutrition, the intervention group receives remaining daily requirement via supplemental parenteral nutrition on the first day of ICU stay while the control group is not supplemented parenterally until the seventh day of ICU stay while enteral nutrition is gradually increased.Primary endpoint: long-term quality of life measured in the physical component score (PCS) of SF-36 questionnaire at 3 and 6 months after ICU admission.DiscussionTo our knowledge, this is the first trial to investigate the influence of early supplemental parenteral nutrition on long-term quality of life after major oncological gastrointestinal surgery. We assume that, particularly in this population of patients, early supplemental parenteral nutrition may increase the long-term quality of life. The study construction also allows establishment of patients’ PCS SF-36 score prior to surgery and mean change in PCS SF-36 score during the recovery period, which is rarely seen in studies on critically ill patients.Trial registrationClinicalTrials.gov: NCT03699371 registered on 12 October 2018.

2457-PUB: Microcirculatory Alterations Are Associated with Increased Risk of Total Death in Patients with Type 2 Diabetes

Rationale and Objective: It has been well known that patients with diabetes had shorter life expectancy, compared to patients without diabetes. Although several studies have been reported the significance of microciculatory dysfunction particularly in the early phase of critical illness, it has been not reported the association between microcirculatory dysfunction and long-term prognosis. Therefore, we evaluated the relationship between microcirculatory dysfunction and the risk of total death in patients with type 2 diabetes. Methods: A total of 1017 patients with diabetes (657 men and 360 women), who were admitted to the department of internal medicine from September 2015 to December 2017, were included in this study. We measured perfusion index (PI), which could reflect microcirculation, using a pulse oximeter (Masimo Radical 7; Masimo Corp., Irvine, CA, U.S.) on the day of admission. Cox proportional hazards models was used in multivariate analysis. Results: The median duration of follow-up was 670.0 days and a total of 117 patients died during follow-up duration. The average age, HbA1c and PI value was 71.0 ± 11.6 years, 7.7 ± 1.9% and 3.2 ± 2.4%. PI value was negatively correlated with age (β = -0.18, P &amp;lt; 0.0001), pulse rate (β = -0.06, P = 0.04) and serum creatinine (β = -0.16, P &amp;lt; 0.0001). PI value was positively correlated with body mass index (β = 0.11, P = 0.0007) and hemoglobin level (β = 0.19, P &amp;lt; 0.0001). Adjusted Cox regression analyses demonstrated that PI value was associated with an increased hazard of total death; hazard ratios were 1.11 (95% confidence interval, 1.01 - 1.23). Conclusion: The present study indicates the importance of microciculatory dysfunction and monitoring as a potential independent prognostic factor of mortality in patients with type 2 diabetes. Disclosure H. Okada: None. Y. Okada: None. M. Fukui: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Johnson &amp; Johnson, Kyowa Hakko Kirin Co., Ltd., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; AstraZeneca, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.

High protein intake during the early phase of critical illness: yes or no?

The rationale for the provision of nitrogen from proteins given via the enteral route or from intravenous amino acids is to boost the synthesis of muscle proteins, and thereby to limit the severity of intensive care unit-acquired weakness by the prevention of muscle loss. However, the optimal timing for supplemental nitrogen provision is a matter of debate and controversy. Indeed, consistent data from retrospective studies support an association between high early protein intakes and better outcomes, while recent post-hoc findings from prospective studies raise safety concerns. This pro–con paper details the arguments of both sides and highlights the need for large-scale prospective studies assessing the safety and efficacy of different levels of protein intake in combination with physical activity and summarizes the currently recruiting clinical trials.

Protein requirement in critical illness

How much protein do critically ill patients require? For the many decades that nutritional support has been used there was a broad consensus that critically ill patients need much more protein than required for normal health. Now, however, some clinical investigators recommend limiting all macronutrient provision during the early phase of critical illness. How did these conflicting recommendations emerge? Which of them is correct? This review explains the longstanding recommendation for generous protein provision in critical illness, analyzes the clinical trials now being claimed to refute it, and concludes with suggestions for clinical investigation and practice.

Gastric residual volume in critically ill patients: a dead marker or still alive?

Early enteral nutrition (EN) is consistently recommended as first-line nutrition therapy in critically ill patients since it favorably alters outcome, providing both nutrition and nonnutrition benefits. However, critically ill patients receiving mechanical ventilation are at risk for regurgitation, pulmonary aspiration, and eventually ventilator-associated pneumonia (VAP). EN may increase these risks when gastrointestinal (GI) dysfunction is present. Gastric residual volume (GRV) is considered a surrogate parameter of GI dysfunction during the progression of enteral feeding in the early phase of critical illness and beyond. By monitoring GRV, clinicians may detect patients with delayed gastric emptying earlier and intervene with strategies that minimize or prevent VAP as one of the major risks of EN. The value of periodic GRV measurements with regard to risk reduction of VAP incidence has frequently been questioned in the past years. Increasing the GRV threshold before interrupting gastric feeding results in marginal increases in EN delivery. More recently, a large randomized clinical trial revealed that abandoning GRV monitoring did not negatively affect clinical outcomes (including VAP) in mechanically ventilated patients. The results have revived the discussion on the role of GRV monitoring in critically ill, mechanically ventilated patients receiving early EN. This review summarizes the most recent clinical evidence on the use of GRV monitoring in critically ill patients. Based on the clinical evidence, it discusses the pros and cons and further addresses whether GRV is a dead marker or still alive for the nutrition management of critically ill patients.

Feasibility of neuromuscular electrical stimulation in critically ill patients

ObjectiveCritically ill patients often develop intensive care unit–acquired weakness. Reduction in muscle mass and muscle strength occurs early after admission to the intensive care unit (ICU). Although early active muscle training could attenuate this intensive care unit–acquired weakness, in the early phase of critical illness, a large proportion of patients are unable to participate in any active mobilization. Neuromuscular electrical stimulation (NMES) could be an alternative strategy for muscle training. The aim of this study was to investigate the safety and feasibility of NMES in critically ill patients. DesignThis is an observational study. SettingThe setting is in the medical and surgical ICUs of a tertiary referral university hospital. PatientsFifty patients with a prognosticated prolonged stay of at least 6 days were included on day 3 to 5 of their ICU stay. Patients with preexisting neuromuscular disorders and patients with musculoskeletal conditions limiting quadriceps contraction were excluded. InterventionTwenty-five minutes of simultaneous bilateral NMES of the quadriceps femoris muscle. This intervention was performed 5 days per week (Monday-Friday). Effective muscle stimulation was defined as a palpable and visible contraction (partial or full muscle bulk). MeasurementsThe following parameters, potentially affecting contraction upon NMES, were assessed: functional status before admission to the ICU (Barthel index), type and severity of illness (Acute Physiology And Chronic Health Evaluation II score and sepsis), treatments possibly influencing the muscle contraction (corticosteroids, vasopressors, inotropes, aminoglycosides, and neuromuscular blocking agents), level of consciousness (Glasgow Coma Scale, score on 5 standardized questions evaluating awakening, and sedation agitation scale), characteristics of stimulation (intensity of the NMES, number of sessions per patient, and edema), and neuromuscular electrophysiologic characteristics. Changes in heart rate, blood pressure, oxygen saturation, respiratory rate, and skin reactions were registered to assess the safety of the technique. ResultsIn 50% of the patients, an adequate quadriceps contraction was obtained in at least 75% of the NMES sessions. Univariate analysis showed that lower limb edema (P < .001), sepsis (P = .008), admission to the medical ICU (P = .041), and treatment with vasopressors (P = .011) were associated with impaired quadriceps contraction. A backward multivariate analysis identified presence of sepsis, lower limb edema, and use of vasopressors as independent predictors of impaired quadriceps contraction (R2 = 59.5%). Patients responded better to NMES in the beginning of their ICU stay in comparison with after 1 week of ICU stay. There was no change in any of the safety end points with NMES. ConclusionsCritically ill patients having sepsis, edema, or receiving vasopressors were less likely to respond to NMES with an adequate quadriceps contraction. Neuromuscular electrical stimulation is a safe intervention to be administered in the ICU.

Gender-specific differences in energy metabolism during the initial phase of critical illness

Women and men differ in substrate and energy metabolism. Such differences may affect energy requirements during the acute phase of critical illness. Data of 155 critically ill medical patients were reviewed for this study. Indirect calorimetry in each patient was performed within the first 72 h following admission to the medical intensive care unit after an overnight fast. In overweight (body mass index (BMI) ≥25 kg/m(2)) but not in normal-weight patients, resting energy expenditure (REE) adjusted for body weight (REEaBW) differed significantly between women and men (17.2 (interquartile range (IQR) 15.2-20.7) vs 20.9 (IQR 17.9-23.4) kcal/kg/day, P<0.01). Similarly, REE adjusted for ideal body weight (REEaIBW) was significantly lower in women compared with men (25.5 (IQR 22.6-28.1) vs 28.0 (IQR 25.2-30.0) kcal/kg/day, P<0.05). In overweight patients, gender was identified as an independent predictor of REEaBW in the multivariate regression model (r=-2.57 (95% CI -4.57 to -0.57); P<0.05), even after adjustment for age, simplified acute physiology score (SAPS II), body temperature, body weight and height. REEaBW decreases with increasing body mass in both sexes. This relationship differs between women and men. Overweight critically ill women show significantly lower REEaBW and REEaIBW, respectively, compared with men. These findings could affect the current practice of nutritional support during the early phase of critical illness.

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Introduction: Fluid overload (FO) is a common problem in critically ill children and has been associated with adverse outcomes. However, the impact of fluid accumulation occurring during early phase of critical illness is not known. Methods: We performed a retrospective chart review of children admitted to a tertiary level pediatric ICU over a 7 month period to identify a cohort of patients with sepsis and/or shock requiring an ICU stay > 2 days. 'Early FO' was defined as cumulative fluid accumulation ≥ 10% of admission body weight during the initial 3 days of ICU stay. Children with 'early FO' in the cohort were designated as 'cases'. Matched 'controls' without 'early FO' were selected from the same cohort by matching for age, severity of illness, respiratory failure, shock and extra-corporeal life support (ECLS), using a 'nearest neighbor' matching algorithm. Cases and controls were compared with respect to ICU mortality. Results: A total of 114 children were in the cohort. Of these, 35 children had 'early FO' (mortality 31%) and 79 did not have 'early FO' (mortality 5%). 34 'cases' and 34 matched 'controls' nested in this cohort were selected. 'Cases' differed significantly from 'controls' with respect mortality (32% vs. 3%, p < 0.0001). They did not differ significantly with respect to other covariates including age, gender, primary diagnoses, reason for ICU admission, presence of oncologic diagnosis and presence of respiratory failure and shock. However, 10 of the 34 'cases' required ECLS as compared to only 1 of the 34 'controls'. Hence a sub-group analysis of non-ECLS children was performed to compare 24 'cases' with 24 matched 'controls'. The difference in mortality between 'cases' and 'controls' continued to be significant in the non-ECLS children (17% vs. 0%, p 0.03). Conclusions: In our cohort of critically ill children, 'early FO' was associated with higher ICU mortality. Future studies prospectively evaluating the association between fluid accumulation patterns and outcomes are required to understand the impact of fluid kinetics.

Energy Estimation and Measurement in Critically Ill Patients

The estimation of caloric needs of critically ill patients is usually based on energy expenditure (EE), while current recommendations for caloric intake most often rely on a fixed amount of calories. In fact, during the early phase of critical illness, caloric needs are probably lower than EE, as a substantial proportion of EE is covered by the non-inhibitable endogenous glucose production. Hence, the risk of overfeeding is higher during the early phase than the late phase, while the risk of underfeeding is higher during the late phase of critical illness. Therefore, an accurate measurement of EE can be helpful to prevent early overfeeding and late underfeeding. Available techniques to assess EE include predictive equations, calorimetry, and doubly labeled water, the reference method. The available predictive equations are often inaccurate, while indirect calorimetry is difficult to perform for several reasons, including a shortage of reliable devices and technical limitations. In this review, the authors intend to discuss the different techniques and the influence of the method used on the interpretation of the results of clinical studies.

Gastrointestinal tract access for enteral nutrition in critically ill and trauma patients: indications, techniques, and complications.

Enteral nutrition (EN) is a widely used, standard-of-care technique for nutrition support in critically ill and trauma patients. To review the current techniques of gastrointestinal tract access for EN. For this traditional narrative review, we accessed English-language articles and abstracts published from January 1988 through October 2012, using three research engines (MEDLINE, Scopus, and EMBASE) and the following key terms: "enteral nutrition," "critically ill," and "gut access." We excluded outdated abstracts. For our nearly 25-year search period, 44 articles matched all three terms. The most common gut access techniques included nasoenteric tube placement (nasogastric, nasoduodenal, or nasojejunal), as well as a percutaneous endoscopic gastrostomy (PEG). Other open or laparoscopic techniques, such as a jejunostomy or a gastrojejunostomy, were also used. Early EN continues to be preferred whenever feasible. In addition, evidence is mounting that EN during the early phase of critical illness or trauma trophic feeding has an outcome comparable to that of full-strength formulas. Most patients tolerate EN through the stomach, so postpyloric tube feeding is not needed initially. In critically ill and trauma patients, early EN through the stomach should be instituted whenever feasible. Other approaches can be used according to patient needs, available expertise, and institutional guidelines. More research is needed in order to ensure the safe use of surgical tubes in the open abdomen.

Bench-to-bedside review: The gut as an endocrine organ in the critically ill

In health, hormones secreted from the gastrointestinal tract have an important role in regulating gastrointestinal motility, glucose metabolism and immune function. Recent studies in the critically ill have established that the secretion of a number of these hormones is abnormal, which probably contributes to disordered gastrointestinal and metabolic function. Furthermore, manipulation of endogenous secretion, physiological replacement and supra-physiological treatment (pharmacological dosing) of these hormones are likely to be novel therapeutic targets in this group. Fasting ghrelin concentrations are reduced in the early phase of critical illness, and exogenous ghrelin is a potential therapy that could be used to accelerate gastric emptying and/or stimulate appetite. Motilin agonists, such as erythromycin, are effective gastrokinetic drugs in the critically ill. Cholecystokinin and peptide YY concentrations are elevated in both the fasting and postprandial states, and are likely to contribute to slow gastric emptying. Accordingly, there is a rationale for the therapeutic use of their antagonists. So-called incretin therapies (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) warrant evaluation in the management of hyperglycaemia in the critically ill. Exogenous glucagon-like peptide-2 (or its analogues) may be a potential therapy because of its intestinotropic properties.

The early phase of critical illness is a progressive acidic state due to unmeasured anions

Stewart's and Fencl's methods have recently been proposed to interpret acid-base disorders where traditional theory has proven inadequate. Our objectives were to evaluate: (1) the occurrence of acid-base disturbances in critically ill patients and their trend over the first 3 intensive care unit days, (2) whether Stewart's theory offers advantages over the traditional theory in the diagnosis of acid-base metabolic disturbances and (3) whether variables derived from Stewart's and Fencl's methods offer advantages over the traditional method to predict patient mortality. A prospective cohort study in a general intensive care unit. Blood samples were analysed for arterial blood gases, electrolytes and proteins. PaCO2, pH, bicarbonate, base excess, standard base-excess, sodium, potassium, chloride, phosphorous, calcium, magnesium and lactate were measured. Anion gap, Stewart's and Fencl's variables were calculated. When using Stewart's method, metabolic acidosis and metabolic alkalosis were found in 92.9% and 93.4% of samples, respectively. Corresponding figures obtained with the traditional method were 15% and 18.7%. In 245 (64.5%) samples, Stewart's method revealed that metabolic acidosis and alkalosis were simultaneously present, whereas the traditional method revealed a normal acid-base status. Strong ion gap increased significantly over the first 3 intensive care unit days. Strong ion gap and lactate were independent predictors of 28-day mortality. Metabolic acidosis by unmeasured anions is a clinically relevant phenomenon, which is correlated with mortality. Progressive metabolic acidosis may be ongoing in the early phase of critical illness despite the absence of acidaemia.

Nutritional goals, prescription and delivery in a pediatric intensive care unit

The aim of this study was to compare prescription and delivery of nutrition to predefined nutritional targets, and identify risk factors associated with inadequate nutritional intake. In 84 mechanically ventilated critically ill children with length of stay on the PICU of at least 3 days, we observed prescribed and delivered percentages of predefined targets for intake of calories and macronutrients during a 10-months study period. Factors associated with inadequate intake were identified. On the third day of admission 92.9% of the patients received nutritional therapy. The caloric goal was reached on day 5, mainly supplied by fat and carbohydrates. Mean actual daily protein delivery was about 75% of the target during the entire study period. Use of catecholamines or neuromuscular blocking agents was a risk factor for caloric undernutrition, whereas there were no specific risk factors for overnutrition. Nutritional therapy should be started in the early phase of critical illness, including adequate supply of protein. In order to prevent deficits to accumulate, parenteral nutrition should be added in an early phase, if nutritional needs cannot be met by enteral nutrition.

Feeding critically ill patients: What is the optimal amount of energy?

Hypermetabolism and malnourishment are common in the intensive care unit. Malnutrition is associated with increased morbidity and mortality, and most intensive care unit patients receive specialized nutrition therapy to attenuate the effects of malnourishment. However, the optimal amount of energy to deliver is unknown, with some studies suggesting that full calorie feeding improves clinical outcomes but other studies concluding that caloric intake may not be important in determining outcome. In this narrative review, we discuss the studies of critically ill patients that examine the relationship between dose of nutrition and clinically important outcomes. Observational studies suggest that achieving targeted caloric intake might not be necessary since provision of approximately 25% to 66% of goal calories may be sufficient. Randomized controlled trials comparing early aggressive use of enteral nutrition compared with delayed, less aggressive use of enteral nutrition suggest that providing increased calories with early, aggressive enteral nutrition is associated with improved clinical outcomes. However, energy provision with parenteral nutrition, either instead of or supplemental to enteral nutrition, does not offer additional benefits. In summary, the optimal amount of calories to provide critically ill patients is unclear given the limitations of the existing data. However, evidence suggests that improving adequacy of enteral nutrition by moving intake closer to goal calories might be associated with a clinical benefit. There is no role for supplemental parenteral nutrition to increase caloric delivery in the early phase of critical illness. Further high-quality evidence from randomized trials investigating the optimal amount of energy intake in intensive care unit patients is needed.