Temporal nutritional and inflammatory changes in children with severe head injury fed a regular or an immune-enhancing diet: A randomized, controlled trial.

OBJECTIVE: To analyze the effect of an immune enhancing (IE) diet on infection and metabolic indices in children with severe head injury fed either an IE or a regular formula. DESIGN: : Randomized, blinded, controlled study. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: A total of 40 mechanically ventilated children with severe head injury. INTERVENTIONS: Within 12 hrs of pediatric intensive care unit admission, patients were randomized to receive a masked formula: either IE or regular formula. Feedings were advanced to a target volume of energy intake equal to 0.50%, 100%, 125%, 150%, and 150% of the predicted basal metabolic rate on days 1-5. MEASUREMENTS AND MAIN RESULTS: Nutritional and metabolic indices; interleukins-1beta, -6, and -8; tumor necrosis factor-alpha; and outcome end points (survival, length of stay, length of mechanical ventilation) were compared between the two groups. Only interleukin-8 levels were lower in the IE group compared with the regular formula group by day 5 (23.6 +/- 1.5 vs. 35.5 +/- 4 pg/mL, p < .04). In multivariate regression analysis, interleukin-8 was also independently negatively correlated with immunonutrition (p < .04). Nitrogen balance became positive in 30.8% of patients in the regular formula group and in 69.2% of patients in the IE group by day 5 (p < .05). Less gastric cultures were positive in the IE group compared with the regular formula group (26.7% vs. 71.4%, p < .02). Nosocomial infections (15% vs. 25%), length of stay (16.7 vs. 12.2 days), length of mechanical ventilation (11 vs. 8 days), and survival (80% vs. 95%) did not differ between groups. CONCLUSIONS: Although immunonutrition might decrease interleukin-8 and gastric colonization in children with severe head injury, it might not be associated with additional advantage over the one demonstrated by regular early enteral nutrition.

Current trends of clinical and genetic characteristics influencing the resource use and the nurse-patient balance in an intensive care setting.

PURPOSE: To determine the impact of resource use on the nurse/patient ratio in a pediatric intensive care unit (PICU). To examine the longitudinal influence of chronic or genetically influenced diseases on this interrelation. MATERIALS AND METHODS: Overall, 1586 patients admitted to the PICU through various modes of admission during a 5-year period were prospectively studied. RESULTS: The mean daily number of bed use increased from 5 to 8.1, leading to a significant skew from the ideal nurse/patient ratio of 1:1, to an overloaded one of 1:3-5. An increasing longitudinal trend of patients with metabolic diseases (P < .0001) or with genetic influence (62.8% in 1997, 70.7% in 2001) was noted. More patients with a genetic influence died than those without (13.8% vs 8.5%, P < .001), and more patients supported by mechanical ventilation suffered from a genetically influenced disease (64% vs 36%, P < .03). The mortality rate showed a trend for longitudinal reduction from 12.6% to 12%. CONCLUSIONS: The increasing trend of occupation of PICU bed and ventilator days by patients with chronic diseases may be related to the increasing trend of hospitalization of patients with recognized genetic influence. Although this new trend does not influence mortality, it significantly increases resource use and has a large impact on the staffing needs.

Early enteral administration of immunonutrition in critically ill children: results of a blinded randomized controlled clinical trial.

OBJECTIVES: In a blinded, prospective, randomized, controlled clinical trial, we compared nitrogen balance (NB), nutritional indices, antioxidant catalysts, and outcome in critically ill children given an immune-enhancing formula (I) or conventional early enteral nutrition (C). METHODS: Fifty patients, 103 +/- 7 months old, with disorders prompting admission to the pediatric intensive care unit, including sepsis, respiratory failure, and severe head injury, were enrolled in the study. Within 12 h of admission, patients were randomized to receive I (n=25) or C (n=25). Caloric intake was aimed at meeting patient's predicted basal metabolic rate by day 2 and predicted energy expenditure by day 4, irrespective of group assignment. Outcome endpoints and complications were recorded; NB, transthyretin, retinol-binding protein, transferrin, zinc, copper, and metabolic indices were measured on days 1 and 5 and compared with clinical and nutritional characteristics within and between groups. RESULTS: Both diets achieved their initial targets of covering predicted basal metabolic rate by day 2 and predicted energy expenditure by day 4. Twenty four-hour NB became positive in 40% of patients in group C and occurred in 64% of patients in group I by day 5. Only in group I did the mean NB become positive by day 5 (0.07+/-0.07 g/kg versus -0.24+/-0.03 g/kg on day 1, P<0.001) compared with group C in which the mean NB remained negative (-0.06+/-0.04 g/kg versus -0.25+/-0.06 g/kg on day 1, P<0.001). By day 5, nutritional indices and antioxidant catalysts showed a higher increasing trend in group I compared with group C and higher osmolality (P<0.02), sodium (P<0.03), and urea (P<0.04). Diarrhea for group I (P<0.02) and gastric distention for group C (P<0.04) were the most frequently recorded complications. Mortality or length of stay did not differ between groups, but there was a trend for less gastric gram plus isolates (P<0.05) or for Candida species (P<0.04) and nosocomial infections in group I compared with group C. CONCLUSIONS: Although less well tolerated, immunonutrition is a feasible method of early enteral nutrition in the pediatric intensive care unit. It has a favorable effect on nutritional indices and antioxidant catalysts, but not on outcome hard endpoints. Although it poses a higher metabolic burden to the patient, it shows a trend to improve colonization and infection rates. Appropriate modifications for specific age populations might improve its tolerability and benefits among critically ill children.

Comparative effects of early randomized immune or non-immune-enhancing enteral nutrition on cytokine production in children with septic shock.

OBJECTIVE: To compare the effect of early enteral feeding using immune-enhancing (IE) vs. non-immune-enhancing (NIE) formulas on cytokines in children with septic shock. DESIGN AND SETTING: A single-center, randomized, blinded controlled trial in a pediatric intensive care unit of a university hospital. PATIENTS: We randomized 38 patients with septic shock to either IE or NIE. Feedings were advanced to a target volume of energy intake equal to 1/2, 1, 5/4, 6/4, and 6/4 of the predicted basal metabolic rate on days 1-5, respectively. MEASUREMENTS AND RESULTS: Interleukins (IL) 1beta, 6, and 8, tumor necrosis factor alpha, C-reactive protein, Pediatric Risk of Mortality (PRISM) score, survival, secondary infections, length of stay, and mechanical ventilation were compared within and between the two groups. Actual mean energy and protein intakes did not differ between the two groups and the caloric-protein balance was not correlated to cytokine levels. On day 5 IL-6 levels were significantly lower (11.8+/-2.4 vs. 38.3+/-3.6) and IL-8 significantly higher in the IE than in the NIE group (65.4+/-17 vs. 21+/-2.5). After 5 days of nutritional support a significant decrease in IL-6 levels was recorded only in group IE (mean of paired differences 39.4+/-3 pg/ml). In multivariate regression analysis the variation in cytokines was independently correlated only to PRISM (R(2)=-0.50), but pediatric intensive care unit outcome endpoints did not differ between the two groups. CONCLUSIONS: Early IE nutrition may modulate cytokines in children with septic shock, but there is no evidence that this immunomodulation has any impact on short-term outcome.

Activity of the growth hormone/insulin-like growth factor-I axis in critically ill children.

Critical illness has an important impact on the human endocrine system. Very few studies have been performed to elucidate the alterations of the GH/IGF-I axis in acutely ill children. The aim of this study was to investigate several parameters of this axis in children with trauma (TRA) and sepsis (SEP) requiring admission to the pediatric intensive care unit (PICU). A total of 16 children, ten with TRA and six with SEP (age 1-10 years) as well as 18 healthy children (CS) of similar age and gender were included in the study. Two children, one with TRA and one with SEP, died. Serum IGF-I and -II, IGFBP-1 and -3, and GH levels were measured on days 1, 3 and 7 after admission. GH levels were higher in the patients than in CS (p = 0.04), with no difference between TRA and SEP, and were elevated during PICU stay (p = 0.05). Serum IGF-I, -II and IGFBP-3 were lower in the patients than in CS (p = 0.03, 0.02 and 0.001, respectively) with a tendency to increase up to day 7. Finally, IGFBP-1 levels were similar in the patients and CS. These findings indicate that critically ill children are characterized by low levels of IGF-I and -II as well as IGFBP-3 accompanied by elevated levels of GH, probably reflecting the development of peripheral GH resistance. No significant differences were found between the different catabolic conditions, sepsis and trauma.

Use of recombinant tissue plasminogen activator in children with meningococcal purpura fulminans: a retrospective study.

OBJECTIVE: Meningococcal disease causes septic shock with associated disseminated intravascular coagulation and hemorrhagic skin necrosis. In severe cases, widespread vascular thrombosis leads to gangrene of limbs and digits and contributes to morbidity and mortality. Uncontrolled case reports have suggested that thrombolytic therapy may prevent some complications, and the use of tissue plasminogen activator (t-PA) has been widespread. Our aim was to summarize the clinical outcome and adverse effects where systemic t-PA has been used to treat children with fulminant meningococcemia. DESIGN: International, multiple-center, retrospective, observational case note study between January 1992 and June 2000. SETTING: Twenty-four different hospitals in seven European countries and Australia. PATIENTS: A total of 62 consecutive infants and children with severe meningococcal sepsis in whom t-PA was used for the treatment of predicted amputations and/or refractory shock (40 to treat severe ischemia, 12 to treat shock, and ten to treat both). INTERVENTIONS: t-PA was administered with a median dose of 0.3 mg.kg(-1).hr(-1) (range, 0.008-1.13) and a median duration of 9 hrs (range, 1.2-83). MAIN RESULTS: Twenty-nine of 62 patients died (47%; 95% confidence interval, 28-65). Seventeen of 33 survivors had amputations (11 below knee/elbow or greater loss; six less severe). In 12 of 50 patients to whom t-PA was given for imminent amputation, no amputations were observed. Five developed intracerebral hemorrhages (five of 62, 8%; 95% confidence interval, 0.5-16). Of these five, three died, one developed a persistent hemiparesis, and one recovered completely. CONCLUSIONS: The high incidence of intracerebral hemorrhage in our study raises concerns about the safety of t-PA in children with fulminant meningococcemia. However, due to the absence of a control group in such a severe subset of patients, whether t-PA is beneficial or harmful cannot be answered from the unrestricted use of the drug that is described in this report. Our experience highlights the need to avoid strategies that use experimental drugs in an uncontrolled fashion and to participate in multiple-center trials, which are inevitably required to study rare diseases.

Prior antimicrobial therapy in the hospital and other predisposing factors influencing the usage of antibiotics in a pediatric critical care unit.

BACKGROUND: The aim of this study was to determine whether prior antimicrobial therapy is an important risk factor for extended antimicrobial therapy among critically ill children. To evaluate other predisposing factors influencing the usage of antibiotics in a pediatric intensive care unit (PICU) setting. To examine the relationship between the extent of antimicrobial treatment and the incidence of nosocomial infections and outcome. METHODS: This prospective observational cohort study was conducted at a university-affiliated teaching hospital (760 beds) in Athens. Clinical data were collected upon admission and on each consecutive PICU day. The primary reason for PICU admission was recorded using a modified classification for mutually exclusive disease categories. All administered antibiotics to the PICU patients were recorded during a six-month period. Microbiological and pharmacological data were also collected over this period. The cumulative per patient and the maximum per day numbers of administered antibiotics, as well as the duration of administration were related to the following factors: Number of antibiotics which the patients were already receiving the day before admission, age groups, place of origin, the severity of illness, the primary disease and its complications during the course of hospitalization, the development of nosocomial infections with positive cultures, the presence of chronic disease or immunodeficiency, various interventional techniques (mechanical ventilation, central catheters), and PICU outcome. RESULTS: During a six-month period 174 patients were admitted to the PICU and received antibiotics for a total of 950 days (62.3% of the length of stay days). While in PICU, 34 patients did not receive antimicrobial treatment (19.5%), 69 received one antibiotic (39.7%), 42 two (24.1%), 17 three (9.8%), and 12 more than three (6.9%). The number of antibiotics prescribed in PICU or at discharge did not differ from that at admission. Indications for receiving antibiotics the day before admission and throughout during hospitalization into PICU were significantly correlated. Although the cumulative number of administered antibiotics did not correlate with mortality (9.8%), it was significantly related to the severity scoring systems PRISM (p <.001), TISS (p <.002) and was significantly related to the number of isolated microorganisms (p <.0001). Multiple regression analysis demonstrated that independent determinants of the cumulative number of antibiotics were: prior administration of antibiotics, presence of a bloodstream infection, positive bronchial cultures, immunodeficiency, and severity of illness. CONCLUSION: Prior antimicrobial therapy should be recognized as an important risk factor for extended antimicrobial therapy among critically ill children. Severity of illness, immunodeficiency, and prolonged length of stay are additional risk factors.