Abstract: OBJECTIVES: To elucidate the potential role of circulating levels of transforming growth factor-beta1 (TGF-beta1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble L- and sE-Selectins (sL- and sE-Selectins) in children with sepsis, traumatic brain injury (TBI) or acute respiratory distress syndrome (ARDS). DESIGN AND METHODS: Levels of TGF-beta1, sICAM-1, L- and sE-Selectins were determined using solid-phase sandwich enzyme-linked immunosorbent assay in plasma of 10 patients with sepsis, 10 patients with TBI, 10 patients with ARDS, compared to 10 ventilated controls with chronic illness but not in acute stress, on days 1, 3, 5, 7 and 10. RESULTS: The highest values of sICAM-1 were observed in patients with TBI (p<0.001) and those of sE-Selectin in patients with sepsis (p=0.0001). Patients in the control group did not show an elevation of sE-Selectin and sICAM-1 levels longitudinally. Increased levels of measured molecules (TGF-beta1, p<0.02, sE-Selectin, p<0.02, sL-Selectin, p=0.06, sICAM-1, p<0.03) were demonstrated among survivors in the sepsis and ARDS groups of patients and were positively correlated with length of stay (p<0.04) and mechanical ventilation (p<0.001). CONCLUSIONS: A sustained increase of adhesion molecules occurs during acute stress in children which may contribute to morbidity in patients with sepsis (sE-Selectin) or traumatic brain injury (sICAM-1). Suppression of the expected response of sE-Selectins, s-ICAM-1 and TGF-beta1 is associated with poor outcome.
Abstract: We describe a 16-month-old girl who suffered from encephalopathy leading to intensive care unit hospitalization, complicated by Guillain-Barre syndrome and hydrocephalus, and who had serologic and molecular evidence of central nervous system infection by B. quintana. The possible association of B. quintana with Guillain-Barre syndrome and hydrocephalus has not been previously described and demonstrates the growing spectrum of neurologic complications of Bartonella spp. infections.
Abstract: 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.
Abstract: The case of a morbidly obese 3.5-year-old boy, with Prader-Willi syndrome (PWS), who experienced a life-threatening episode of pulmonary edema soon after induction of general anesthesia with sevoflurane and intubation for orchidopexy is presented. The patient who had history of sleep apnea and who had an uneventful laparoscopy under general anesthesia 6 months previously was supported with mechanical ventilation with positive end expiratory pressure but developed hyperthermia, pneumonia, sepsis, and Acute Respiratory Distress Syndrome in the intensive care unit. He recovered fully 11 days after surgery. The possible contributing factors for the development of pulmonary edema are discussed. Arrangements for monitoring in an intensive care setting after surgery are highly recommended for patients with PWS.
Abstract: KL-6 is a high molecular weight glycoprotein that is expressed on the apical borders of normal secretary alveolar epithelial cells. The aim of our study was to elucidate the potential role of circulating levels of KL-6, related to C-reacting protein (CRP), disease severity (PRISM, TISS), length of stay (LOS) or mechanical ventilation (LOMV), and outcome, in children with acute respiratory distress syndrome (ARDS), sepsis, or traumatic brain injury (TBI). KL-6 concentrations were monitored using solid phase sandwich enzyme-linked immunosorbent assay in plasma of nine patients with ARDS and compared to nine patients with TBI, nine with sepsis, and nine ventilated patients with cancer of matched illness severity on days 1, 3, 5, 7, and 10. Initial respiratory/ventilatory parameters (oxygenation index, plateau pressures) were recorded for ARDS patients. Patients with ARDS had higher early plasma levels of KL-6 (956 +/- 400 U/ml), as compared to patients with TBI (169 +/- 9 U/ml), sepsis (282 +/- 81 U/ml), and ventilated controls (255 +/- 40 U/ml). Significant correlations were demonstrated between plasma KL-6 concentration and oxygenation index, PaO(2): FiO(2) ratio, LOS and LOMV, but not with CRP or PRISM. Only in patients with ARDS, plasma KL-6 levels were higher in non-survivors than survivors (P < 0.03). Plasma KL-6 levels have possible prognostic significance and may provide a useful marker for ARDS in critically ill children.
Abstract: 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.
Abstract: The authors describe a 9-year-old girl with precursor-B acute lymphoblastic leukemia (ALL) who presented with dehydration and severe hypercalcemia. She had received oral vitamin D and calcium supplementation for 4 days, the last dose 48 hours prior to admission, and required pediatric intensive care unit (PICU) hospitalization for management of the hypercalcemia and safe initiation of induction chemotherapy. Her clinical course was complicated by pancreatitis, disseminated intravascular coagulation, pleural effusion, and focal seizures. Although the exact mechanism of hypercalcemia was not elucidated, it was likely related to the underlying ALL, without dismissing the prior vitamin D and calcium supplementation as a possible contributing factor. The hypercalcemia resolved with specific antileukemic therapy along with supportive care and administration of calcitonin. Hypercalcemia is an uncommon metabolic abnormality in children with ALL, but it can be life-threatening. Children with ALL should be referred to tertiary-care institutions with PICU and subspecialty support because serious metabolic and other complications can occur before or after the administration of chemotherapy.
Abstract: BACKGROUND: The protection, which some BCG vaccines could confer against the development of tuberculosis (TB) in childhood, might be indirectly reflected by the subsequent development of BCG immune response. The objectives of the study were to examine effectiveness and possible differences of post-vaccination reaction to a lyophilized BCG at different age groups and to evaluate its protection against TB in a decade's period. METHODS: We studied the post-vaccination PPD-skin reaction and scar formation at three different school levels, corresponding to ages of 6, 12 and 15 years old, vaccinated by a lyophilized BCG vaccine (Pasteur Institute), currently used in our country. During a 10-year follow up the reported TB cases in vaccinated and non-vaccinated adolescences up to 24-years old were analyzed and compared to the number of cumulative cases observed in the adult population of two neighboring territories (vaccinated and non-vaccinated). RESULTS AND DISCUSSION: There was a significant correlation (r2 = 0.87, p < 0.0001) between tuberculin induration and scar formation. There was no statistically significant difference between the three age groups (6, 12, and 15 year-old, respectively) in regard to the diameter of tuberculin induration or scar formation. Although 34% of 10-year later indurations were unpredictably related to the initial ones (increased or decreased), they were significantly correlated (r2 = 0.45, p = 0.009). The relative percentage of TB for the 14-24 years-age group to the adult studied population was significantly lower among the immunized children compared to the non-immunized population of the same age group (17/77, 22% vs. 71/101, 70%, p < .0001). CONCLUSION: Our data suggest that the lyophilized BCG vaccine used for BCG programs at different age groups is equally effective and may confer satisfactory protection against tuberculosis in puberty.
Abstract: 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.
Abstract: 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.
Abstract: The authors describe a 4-year-old girl with acute lymphoblastic leukemia in remission who developed fulminant hepatic failure due to varicella-zoster virus (VZV). Diagnosing VZV visceral infection in immunocompromised patients is often difficult due to atypical clinical presentation with few or no skin lesions and severe abdominal or back pain. Prompt initiation of empirical treatment with acyclovir and VZV immunoglobulin pending results of the serum polymerase chain reaction for VZV is warranted in this clinical setting.
Abstract: BACKGROUND: Lower vaccination coverage among foreign-born children is of concern because they live in households and communities characterized by more intense exposure to infectious diseases. Because of their higher prevalence rates, there is an increasing occurrence of infectious diseases imported into developed countries. This case report emphasizes the emerging necessity for new clinicians and pathologists of having competence with old infectious disease pathology. CASE PRESENTATION: A three and a half year old girl, who presented with croup history of 5 days and has been in severe respiratory distress, was admitted to the Pediatric Intensive Care Unit in shock and acute respiratory failure. The patient was immediately intubated, and a grayish nonadherent membrane extending through the glottis down into the larynx was apparent during the procedure. Echocardiographic findings, which were consistent with acute myocarditis, confirmed poor left ventricular contractility despite escalating high doses of inotropes. Autopsy showed numerous strains of toxigenic corynobacterium diphtheriae, which also grew on the Loeffler cultures of membranes received during the intubation. CONCLUSION: It is critical that new generations of clinicians and bio-pathologists not only be trained in the subspecialty of infectious disease pathology, but that they also be willing participants in the diagnosis and investigation of infectious diseases.
Abstract: 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.
Abstract: BACKGROUND: Advances in paediatric critical care have resulted in increased survival of critically ill patients, many of whom require long-term ventilation as a means of life support. AIM: To determine current trends in resource utilization, and problems in the care of acute and chronic paediatric intensive care patients. DESIGN: Open observational study. METHODS: We evaluated consecutive admissions (n = 1629) to a 10-bed paediatric intensive care unit (PICU) over a 5-year period. Three previously defined criteria for resource utilization were used: mean length of stay (LOS); length of mechanical ventilation (LOMV); and LOMV/LOS ratio. RESULTS: A total of 10 310 patient bed days and 5223 ventilator days were used. Mean LOS increased from 5.3 +/- 12 days in 1998 to 8.7 +/- 27 days in 2001 (p < 0.05). Although LOMV/LOS ratio (50.7%) was significantly correlated with Paediatric Risk of Mortality score (p < 0.0001), there was no significant change in mortality rate (12.6% vs. 12%). Patients hospitalized for >2 weeks (n = 320, 20%) used 55% of LOS and 57% of LOMV, in contrast to the 1298 (80%) hospitalized for <7 days, who used only 29% of LOS and 20% of LOMV. Patients hospitalized for >3 months (11, 0.7%) consumed 17% of LOS and 23% of LOMV. Five of these (45%) were eventually discharged home, two on ventilators. CONCLUSION: The increasing trend of occupation of PICU bed and ventilator days by critically ill children may be related to the increasing trend for hospitalization of chronic care patients. Severity scoring systems were predictive of resource consumption, but not of the overall trend in mortality rate.
Abstract: The number and success rate of paediatric organ transplantation continue to improve yearly, and the number of transplanted children presenting for either elective or emergency nontransplant surgery is expected to increase accordingly. The general considerations related to any transplant recipient are the physiological and pharmacological problems of allograft denervation, the side effects of immunosuppression, the risk of infection, and the potential for rejection. Preoperative assessment of transplant recipients undergoing non-transplant surgery should focus on graft function, the risk of infection, and function of other organs. Local, regional, or general anaesthesia can be safely delivered to transplant recipients. Specific anaesthetic considerations related to the type of transplantation, have an impact directly on anaesthetic and perioperative management. Since anaesthetists and surgeons in hospitals who are not involved in transplantations, may be required to manage paediatric transplant recipients, the reviews of the existing experience in this field will be valuable tools in their hands.
Abstract: The objective was to determine stress related factors and nutritional indices affecting the nitrogen balance (NB) and the creatinine height index (CHI) in critically ill children on early enteral nutrition (EEN). Seventy-one consecutively enrolled critically ill children aged 2 to 204 months, requiring prolonged mechanical ventilation, were studied. All patients were on early intragastric nutrition (Nutrison Pediatric or Standard) from day 1 (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). Nitrogen balance and CHI changes determined efficacy. Study patients had severe depletion of somatic protein status on stress day 1 (CHI <60%) but they reached the normal range of somatic protein status at the end of the EEN, on post-stress day 5 (CHI >80%, p <.004). On day 1, none of the patients had positive NB but after 5 days of EEN, 44 (62%) had positive NB and only 27 (38%) had negative NB (p <.0001). Multivariate stepwise regression analysis showed that only the difference of daily given-recommended dietary allowances protein and the total repleted energy were positively correlated (r(2) =.47, p <.001 and r(2) = 34, p =.003, respectively) and multiple organ system failure negatively correlated with the NB (r(2) = -.24, p <.03) on the 5th day of the EEN protocol. Our data suggest that achievement of positive protein and energy balance in relation to the basic metabolic rate using an aggressive EEN protocol improves NB during the acute phase of stress in 2/3 of critically ill children.
Abstract: A 6-year old girl was examined having two years previously presented a transient Cushing's syndrome, followed by recurrent hyponatremia, attributed to inappropriate ADH secretion (SIADH). The brain MRI showed no abnormalities on repeated examinations, except for a suggestion of empty sella syndrome. During the past two years she also presented recurrent episodes of a prolonged febrile illness of unknown origin. All investigations related to infectious, autoimmune neoplastic diseases, histiocytosis-X or neurosarcoidosis were negative and the fever was characterized as central. The patient also presented episodes of tonic-clonic seizures, myoclonias and behavioral problems (alternating states of irritability, sleepiness and apathy, optic and hearing illusions and phobias) with or without hyponatremia. Her cerebrospinal fluid (CSF) examination was not indicative of encephalitis and the encephalogram (EEG) showed only slowing of background activity. At the age of 4.75 years she, started to have recurrent episodes of hypopnoea/apnoea with severe desaturation and hypercapnia, occasionally requiring intubation and ventilation. She also developed unilateral miosis corneal ulceration and bilateral ptosis (oculo-sympathetic paresis). Repeat brain MRI and CT scans of the mediastinum excluded organic causes of apnoeas and of oculo-sympathetic paresis, such as neuroblastoma or lymphoma. Furthermore, on a 24 hour electrocardiogram recording, using power spectral analysis, significantly reduced heart rate variability was observed, by comparison with age-specific normal ranges. Thus the apnoeas, ptosis, miosis and temperature instability were attributed to autonomic dysfunction. During the same period, the patient presented significant growth retardation and growth hormone (GH) deficiency was confirmed during two provocative tests (peak GH levels: 3.1 and 2.9 ng/ml (normal>10). Moreover, thyrotropin (TSH) deficiency and persistent hyperprolactinemia were detected. She was started on hGH and thyroxine. She was also put on fluid restriction and increased sodium intake for her SIADH. She was advised to use O2 administration by mask in case of apnoeas. The child died at age 6 6/12 years as a result of apnoea during sleep. In conclusion: Multiple pituitary hormonal abnormalities, together with symptoms of autonomic neuropathy (apnoeas, ptosis, miosis, tachycardia, temperature instability) and encephalopathy (seizures, myoclonias and behavioral problems) developed in a 4-year old girl. The suggested diagnoses were: 1.Neurometabolic disorder, 2. Mitochondrial disorder, 3. Post infectious autoimmune process.
Abstract: (1) Respiratory distress and seizures developed in an 18-month-old boy following brief exposure to low-strength (17.6%) N,N-diethyl-m-toluamide (DEET). A review of the literature revealed 17 reports of DEET-induced encephalopathy in children. The objective of this study was to test the hypothesis that the potential toxicity of DEET is high and that available repellents containing DEET, irrespective of their strength, are not safe when applied to children's skin. (2) Although this is a case report, we used the features of published reports of DEET-induced encephalopathy in children to support the diagnosis, since the evidence that the child's illness was caused by DEET was circumstantial. In the following case analysis, clinical reports of children < 16 years old have been reviewed and analyzed in an effort to relate direct DEET toxicity to various clinical, demographic, and toxic compound exposure factors (Fisher's exacttest and logistic regression analysis). (3) DEET-induced encephalopathy in children (56% girls) followed not only ingestion or repeated and extensive application of repellents, but also a brief exposure to DEET (45%). Of those who reported a dermal exposure, 33% reported an exposure to a product containing DEET < 20%. Seizures, the most prominent symptom (72%), were significantly more frequent when DEET solutions were applied to the skin (P<0.01). Mortality (16.6%) did not correlate significantly with the concentration of the DEET liquid used, duration of skin exposure, pattern of use, age, or sex. (4) Data of this case analysis suggest that repellents containing DEET are not safe when applied to children's skin and should be avoided in children. Additionally, since the potential toxicity of DEET is high, less toxic preparations should be probably substituted for DEET-containing repellents, whenever possible.
Abstract: OBJECTIVES: To investigate the feasibility, adequacy, and efficacy of early poststress intragastric feeding (EPIGF) in critically ill children. DESIGN: A prospective clinical study. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: Seventy-one consecutively enrolled critically ill children requiring prolonged mechanical ventilation. INTERVENTIONS: Full-strength intragastric tube feedings (Nutrison Pediatric, Standard) were initiated within 12 hrs of the study-entry event. Enteral feedings were advanced to a target volume of energy intake = 1/2, 1, 5/4, 6/4, and 6/4 of the predicted basal metabolic rate (PBMR) on days 1-5, respectively. MEASUREMENTS AND MAIN RESULTS: Nutritional status by the caloric intake, recommended dietary allowances, PBMR, predicted energy expenditure (PEE), anthropometry, and clinical indices were evaluated on days 1 and 5. Safety was assessed by the clinical course of disease, laboratory findings, and occurrence of complications. Success was determined by accomplishment of the PEE target. The early success rate was 94.4% and predicted late enteral feeding success accurately (p =.0001). Caloric intake approached PBMR the second day (43 +/- 1.7 kcal/kg/day vs. 43.2 +/- 1.1 kcal/kg/day) and PEE the fifth day (66.2 +/- 2.7 kcal/kg/day vs. 67.7 +/- 6.4 kcal/kg/day). Multivariate stepwise regression analysis showed that poor outcome and a high Therapeutic Intervention Scoring System score correlated with failure of EPIGF (p <.0001). Patients who succeeded EPIGF had significantly higher myocardial ejection (65% vs. 43%; p <.0001) or shortening fractions (34% vs. 20%; p =.0001) on day 1 than those who failed. Patients tolerated EPIGF well; 9.9% developed nosocomial pneumonia, 5.6% developed diarrhea, and 8.5% needed treatment with cisapride because of a delay of gastric emptying. The mortality rate (5.6%) was different between initial and final success and failure groups (p <.0001) and was lower than predicted by the admission severity scores (12% +/- 2%). CONCLUSIONS: This study showed that increases of caloric intake during the acute phase of a critical illness are well tolerated and may approach PBMR by the second day and PEE by the fourth day in critically ill children. Caloric intake lower than PBMR is associated with higher mortality and morbidity rates.
Abstract: We measured the incidences of protein and fat depletions and the frequencies of acute and chronic protein-energy malnutrition during stress states in children and investigated the influence of early enteral feeding on nutrition indices and acute-phase proteins. Seventy-one, consecutively enrolled, critically ill children received early enteral feeding (energy intakes equal to 0.50, 1, 1.25, 1.5, and 1.5 of the predicted basal metabolic rates on days 1 through 5, respectively) through nasogastric tubes. On the first day of the study, 16.7% of the patients already were depleted of protein and 31% of fat stores. Overall, 16.9% were at risk for chronic protein-energy malnutrition and 21.1% for acute protein-energy malnutrition, whereas 4.2% and 5.6% already had chronic and acute, respectively protein-energy malnutrition. Only 22.7% of patients without protein deficiencies versus 37% of those at risk or already deficient developed multiple-organ system failure. Transferrin and prealbumin levels improved at the end of the period of early enteral feeding (187 +/- 6.6 versus 233 +/- 7 mg/dL, P < 0.0001; 15.1 +/- 2 versus 21.9 +/- 2.9 mg/dL, P < 0.0001; respectively); survivors had higher prealbumin levels than non-survivors (22.3 versus 15.5 mg/dL). With logistic regression analysis, only repleted energy, not anthropometric or nutrition indices, was independently associated with survival (P = 0.05). These results reinforce the observation that critically ill children are at risk for fat or protein depletion and development of malnutrition, which is associated with increased morbidity and mortality. We conclude that early enteral nutrition improves nutrition indices and outcomes.
Abstract: OBJECTIVES: To assess the incidence of myocardial ischemia in meningococcus-induced purpura fulminans in pediatric patients, to compare troponin I (cTnI) levels with changes in electrocardiogram (ECG) and to evaluate whether cTnI is related to myocardial function and contractility, to severe acquired anticoagulant deficiency and to the severity of disease. METHODS: Twenty-two patients with acute meningococcemia, supported with inotropes or vasoactive agents, were studied, Blood samples for the determination of serum cTnI and conventional myocardial ischemia and coagulopathy markers were drawn daily. Measurements of cardiac index (CI), ejection (EF) and shortening fractions (SF) and ECGs were performed daily. RESULTS: The Leclerc score, the Neisseria sepsis index (NESI) and the pediatric risk of mortality (PRISM) score predicted a mean mortality rate of 34%, 27% and 23%, respectively. Four patients died (18%). Five patients (23 %) presented with myocardial ischemia. Their ECG ischemic changes were associated with pathologically high cTnI levels (1.93 +/- 0.13 vs 0.18 +/- 0.08 ng/ml, p < 0.001 for patients with or without ischemic changes) and depressed myocardial contractility (mean difference +/- SE -14 +/- 5%, p = 0.01, for the EF and -7.4 +/- 3, p < 0.02, for the SF). High cTnI values were significantly correlated to low protein C (PC) (p < 0.0001), factor VIII (p < 0.04) and antithrombin III (AIII, p = 0.01) levels, but not to the PRISM, Leclerc or the NESI scores. Means of AIII, VII, and especially of VIII, and PC, were significantly lower in ischemic than in non-ischemic patients, although severity scoring systems and inotropic support did not differ between the two groups. Survivors tended to significantly higher PC (p < 0.01) and factor VIII levels (p = 0.001) than non-survivors and, also, to lower levels of cTnI (p = 0.05) and CPK-MB (p < 0.05), while in meningococcal shock. CONCLUSIONS: The incidence of myocardial ischemia is increased in acute meningococcemia in pediatric patients and correlates with myocardial dysfunction. High cTnI is associated with severe coagulopathy, but not with clinical prognostic scores or inotropic support. Early recognition of myocardial injury, myocardial support and early replacement therapy with PC, AIII, factor VIII or fibrinogen might improve outcome in acute meningococcemia in children.
Abstract: INTRODUCTION: Children with acute meningococcemia may have impaired myocardial function resulting in low cardiac output despite normal intravascular volume. Severe meningococcal infection has been associated with acute interstitial myocarditis, endocarditis, and pericarditis, but not with myocardial infarction. CASE: We present the case of a 10-year-old girl with positive family history for premature myocardial infarction who sustained an acute myocardial infarction temporally related to meningococcemia. DISCUSSION: This is the first pediatric case of non-Q wave acute myocardial infarction associated with purpura fulminans in meningococcemia. Similarly, the association of high troponin I levels and meningococcemia has not been described previously. Although, the patient's genetic predisposition for myocardial infarction might have been a potential contributing factor, there was no angiographic evidence of coronary artery disease in this patient. Thereby, other factors related to shock, endotoxin, microthrombi of meningococcemia, and their treatment might have been also contributing. We propose possible mechanisms for this rare but serious complication of meningococcemia and review the literature.
Abstract: Our objectives were to evaluate the frequency of air leaks (AL) from the respiratory tract (pneumothorax, pneumomediastinum, pneumoperitoneum, subcutaneous emphysema) in critically ill children on mechanical ventilation (MV) for severe respiratory diseases, and to examine whether AL could be correlated with specific clinical events or ventilator settings. The study constitutes a retrospective cohort of 80 consecutive critically ill children receiving MV for severe respiratory diseases between 1986 and 1993. Patients (mean age 2.9 +/- 0.6 years, 49 males and 31 females), were admitted to the Pediatric Intensive Care Unit (PICU) with acute respiratory syndrome (ARDS) (27%), asthma (15%), bronchiolitis (10%), pneumonia (21%), pulmonary congenital diseases (9%), or foreign body aspiration (18%). Patients were divided into two groups; those with AL (n=22) and those without air-leaks (non-AL) (n = 58). Air leaks developed in 22 of 80 patients or in 27.5%. Survival was significantly lower in the AL group, compared to the non-AL group (41% vs. 76%, P < 0.01). The odds ratio that a patient with multiple organ system failure (MOSF) or infection would develop AL was 2.96 and 2.19, respectively. Candida and Pseudomonas species were recovered with significantly higher frequency in the AL group compared with the non-AL group (P < 0.025). There was a strong positive correlation between the incidence of AL and high ventilatory pressures (PIP 36 vs. 29.7 cm H(2)O, P < 0.001), or large tidal volumes (V(T) 12 vs. 9 mL/kg, P < 0.05), suggesting that large volumes might elicit injury to the pulmonary epithelium. Multiple logistic regression analysis showed that only V(T) was independently associated with the development of AL in children with primary severe respiratory disease (r(2) = -0.38, P = 0.01). In conclusion, MV will produce AL, particularly when high peak airway pressures (barotrauma) or large tidal volumes (volotrauma) are delivered by the ventilator. Sepsis, MOSF, and lung superinfection with Pseudomonas or Candida species may be also important factors in the development of AL in critically ill children.
Abstract: A 10-year-old boy with myasthenia gravis had severe post-thymectomy myasthenic crisis necessitating reintroduction of mechanical ventilation on the 5th day after thymectomy. He did not respond to therapy with oral pyridostigmine, corticosteroids, or high-dose intravenous immunoglobulin. Finally, in addition to the usual supportive care, he was treated successfully with continuous intravenous infusion of neostigmine. Continuous infusion of neostigmine was used for the first time in post-thymectomy myasthenic crisis in a child to the best of our knowledge.
Abstract: A 6-year-old boy presented for surgery for phimosis. The anaesthetic technique included intravenous induction with thiopentone and neuromuscular blockade with cisatracurium. Severe persistent bronchospasm and central cyanosis followed the administration of these drugs. A continuous i.v. infusion of epinephrine at 0.2 microg. kg(-1) x min(-1) was necessary to break the severe refractory bronchial hyperresponsiveness. There was no previous exposure to anaesthetic drugs and no definite family history of allergy. Through increased serum eosinophil cationic protein, tryptase and histamine levels and IgE levels specific to cisatracurium, we demonstrated an IgE-mediated anaphylactic reaction to cisatracurium in the child's first exposure to this new neuromuscular blocking agent. Anaphylactic reactions to new anaesthetic drugs may be challenging to recognize and treat during general anaesthesia in children. The pathogenesis, diagnosis and management of life threatening persistent allergic reactions to intravenous anaesthetics are discussed.
Abstract: We report a successful outcome on an acute adenovirus myocarditis treated with a 24-hour high-dose intravenous immunoglobulin (24-HDIVIG) in a 4.5-year-old girl. A postviral etiology of acute myocarditis was assessed on the basis of the polymerase chain reaction technique. Among other early markers of cardiac injury, cardiac isoform of troponin-I (cTnI) was significantly correlated to the left ventricular ejection fraction (r = -0.86, p < 0.0001). Follow-up of cTnI, which might also be correlated to the short-term outcome, allows fast, easy, and noninvasive estimation of response to the aggressive treatment with 24-HDIVIG in acute adenovirus myocarditis in children.
Abstract: OBJECTIVES: To measure energy expenditure in critically ill children and compare it with the energy expenditure predicted by recommended formulas, and relate the measured energy expenditure to nutritional and clinical indices. DESIGN: A prospective, clinical study. SETTING: Tertiary care pediatric intensive care unit in a university children's hospital. PATIENTS: A total of 37 patients with critical illness who were mechanically ventilated for > or =24 hrs were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Chronic protein-energy malnutrition (CPEM) and acute protein-energy malnutrition were defined by the Waterlow's stages and fat and protein stores were classified as defined by Frisancho, Ryan, and Martinez. Severity of illness was assessed by the Pediatric Risk of Mortality Score, the Therapeutic Intervention Scoring System, and indices of organ failure. Oxygen consumption, carbon dioxide production, and the respiratory quotient were measured by indirect calorimetry, and energy expenditure (MEE) was calculated using the modified Weir formula. Resting energy expenditure (PBMR), predicted energy expenditure, and caloric intake were calculated using recommended formulas. A total of 77 measurements were made in 37 children. MEE was significantly lower than PBMR as estimated by all equations except the Talbot equations. MEE was significantly lower than predicted energy expenditure and the recommended daily allowances. On the first day, the MEE/PBMR ratio was <0.9 in 56.8%, 0.9-1.1 in 21.6%, and >1.1 in 21.6% of patients. MEE did not differ significantly among disease groups or between medical and surgical patients. There was no difference in MEE with or without neuromuscular blockade. MEE was lower in the presence of multiple organ system failure (MOSF) (1019 + 166 kcal/m2 without MOSF vs. 862 + 241 with MOSF; p = .025). A total of 21% had CPEM and 8.1% had acute protein-energy malnutrition. Multivariate stepwise regression analysis showed that the protein intake, midarm muscle area, midarm fat area, the use of vasoactive agents, and sedation correlated with MEE (p < .05). With CPEM, MEE was correlated to the severity of illness (p < .05). Patients at risk for protein stores depletion (midarm muscle areas 1 and 2) had a higher incidence of MOSF compared with nutritionally normal children (p < .05), whereas patients with fat stores depletion (midarm fat area 2) had a higher probability of death (50% vs. 6%, respectively). CONCLUSIONS: Recommended daily allowances and energy expenditure predicted by using a stress-related correction to the resting energy expenditure grossly overestimate MEE. MEE is close to PBMR and in many patients, it is lower than PBMR. MEE that is lower than PBMR is associated with a higher morbidity. Nutritional repletion should thus be based on MEE to avoid the problems of over- or underfeeding.
Abstract: A case of acute spontaneous pneumomediastinum in a 13-year-old boy suffering from Hodgkin's disease and pulmonary fibrosis is reported. He was initially treated for Pneumocystis carinii but his respiratory function progressively deteriorated, and fibrosis secondary to bleomycin was suspected. The day before the admission to the Pediatric Intensive Care Unit the patient complained of anterior thoracic pain, and a chest x-ray revealed a left-sided small spontaneous pneumothorax and pneumomediastinum. Although air leak responded initially to conservative treatment, acute tension pneumomediastinum with cardiopulmonary decompensation recurred 6 days later, while the patient was on mechanical ventilation. Treatment with urgent evacuation of the accumulated air via subxiphoid drainage, using an old but ill-defined technique, resulted in complete resolution of pneumomediastinum and significant improvement of the hemodynamic condition.
Abstract: Early hepatic artery thrombosis (HAT) after pediatric orthotopic liver transplantation (OLT) can cause significant morbidity and mortality, leading to liver failure or septic complications requiring urgent retransplantation. Experimental evidence that hyperbaric oxygen (HBO) may ameliorate hepatic ischemic-reperfusion injury led to this study of HBO in pediatric liver transplant recipients who developed HAT. Children undergoing OLT under primary tacrolimus immunosuppression and University of Wisconsin organ preservation between August 1, 1989, and December 31, 1998, who developed HAT were the basis for this study. Patients who developed HAT between March 1, 1994, and December 31, 1998, were treated with HBO therapy until signs of ischemia resolved (absence of fever, normalizing liver injury test results) or for 2 weeks. The pediatric OLTs performed from August 1, 1989, to February 28, 1994, who developed HAT served as a control group. Primary outcome measures were survival, retransplantation rate, time to retransplantation, incidence of hepatic gangrene, and days to collateral formation. Three hundred seventy-five consecutive pediatric patients underwent 416 OLTs between August 1, 1989, and December 31, 1998. Thirty-one patients (7.5%) developed HAT at a mean time of 8.2 days (range, 1 to 52 days) post-OLT. In 17 patients, HBO treatment was begun within 24 hours of HAT or immediately after the revascularization attempt and performed twice daily for 90 minutes at 2.4 atmospheres pressure. Fourteen patients were treated without HBO. None of the HBO-treated patients developed hepatic gangrene. Eight HBO patients (47%) were bridged to retransplantation at a mean time of 157 days (range, 3 to 952 days) after initial OLT and all survived. Mean time to retransplant in the control group was 12.7 days (range, 1 to 64 days). HBO was well tolerated without significant complications. Although there was no significant difference in survival or retransplantation rates, HBO significantly delayed retransplantation, potentially by hastening the development of hepatic artery collaterals.
Abstract: A 2-year-old male developed generalized tonic-clonic seizure activity, tremor of limbs, muscle weakness, ataxia, and hypertonia after he swallowed 16 50-mg tablets of lamotrigine. His vital signs were normal, as were electroencephalography and laboratory investigation tests. The urine toxicologic screen revealed no other drugs. Treatment included midazolam and gastric lavage followed by activated charcoal and fluid loads. Symptoms resolved within 24 hours, and the child was discharged without any further complications. Serial blood samples revealed plasma lamotrigine levels at the high adult therapeutic range (3.8 mg/L) but a slow elimination rate. This is the first report of seizure activity reported in a patient receiving an overdose of lamotrigine. However, no evident concentration-effect-side-effect relationship has been established in children. Interestingly in this child, lamotrigine overdose presented exclusively with treatment-emergent neurologic abnormalities, sparing all other systems.
Abstract: We compared automatic oscillometric measurements of systolic, diastolic, and mean arterial pressures with simultaneous pressures measured from arterial catheters in six preterm infants. Oscillometric arterial pressure measurements were performed with the Omega automatic instrument, using the recommended cuff and the size-larger cuff. Despite highly significant overall correlation coefficients for oscillometric and catheter measurements, 29% to 42% of oscillometric measurements with both cuff sizes were outside the 5-mm Hg error limits, and 4.0% to 9.3% were more than 10 mm Hg different from catheter measurements. Changing the cuff size did not reduce inherent errors in the oscillometric method.
Abstract: Hearing thresholds were established in preterm and term newborn infants by auditory brainstem responses in the first week of life. The presence of wave V was the criterion for threshold sensitivity in infants considered neurologically optimal on the basis of stringent clinical criteria and sequential ultrasound examination. The hearing threshold was found to be at 40 dB in preterm infants between 28 and 34 weeks gestational age, at 30 dB in infants between 35 and 38 weeks, and below 20 dB in term infants. This study confirms that the thresholds of newborn infants diminish with increasing age, and there is no apparent difference whether maturation occurs inside or outside the uterus. The data should provide a baseline for objective and quantitative assessment of hearing loss early in the neonatal period.
