Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric Intensive Care Unit in Israel.

OBJECTIVES: We studied profile of the bloodstream infections (BSI) in the pediatric intensive care unit (PICU) and identified predictors of mortality. METHODS: The study collected data from hospital records for children younger than 18-years who developed BSI during their PICU stay between 2014 and 2019. RESULTS: In 114 patients, 136 PICU-acquired BSIs with 152 pathogens were documented. The incidence of BSI was 47.12/1,000 PICU admissions and 7.95/1000 PICU hospital days. Gram-negative rods accounted for 75% of isolates, Gram-positive cocci accounted for 21.7% of isolates, and fungi accounted for 3.3% of isolated pathogens. ICU mortality was observed in 25 (21.9%) patients with a BSI compared to 94 (3.1%) patients without a BSI (P<0.001). Hemodynamic instability (P=0.014, OR 4.10, CI 1.33-12.66), higher blood urea nitrogen (BUN) (P=0.044), and lower albumin levels (P=0.029) were associated with increased risk of ICU mortality. CONCLUSION: BSI in the PICU is associated with increased mortality. Early identification and management of risk factors independently associated with poor clinical outcomes in these patients should be aimed to ensure improved survival.

Acute hemodialysis therapy in neonates with inborn errors of metabolism.

BACKGROUND: Inborn errors of metabolism (IEM), including organic acidemias and urea cycle defects, are characterized by systemic accumulation of toxic metabolites with deleterious effect on the developing brain. While hemodialysis (HD) is most efficient in clearing IEM-induced metabolic toxins, data regarding its use during the neonatal period is scarce. METHODS: We retrospectively summarize our experience with HD in 20 neonates with IEM-induced metabolic intoxication (seven with maple syrup urine disease, 13 with primary hyperammonia), over a 16-year period, between 2004 and 2020. All patients presented with IEM-induced neurologic deterioration at 48 h to 14 days post-delivery, and were managed with HD in a pediatric intensive care setting. HD was performed through an internal jugular acute double-lumen catheter (6.5-7.0 French), using an AK-200S (Gambro, Sweden) dialysis machine and tubing, with F3 or FXpaed (Fresenius, Germany) dialyzers. RESULTS: Median (interquartile range) age and weight at presentation were 5 (3-8) days and 2830 (2725-3115) g, respectively. Two consecutive HD sessions decreased the mean leucine levels from 2281 ± 631 to 179 ± 91 µmol/L (92.1% reduction) in MSUD patients, and the mean ammonia levels from 955 ± 444 to 129 ± 55 µmol/L (86.5% reduction), in patients with hyperammonemia. HD was uneventful in all patients, and led to marked clinical improvement in 17 patients (85%). Three patients (15%) died during the neonatal period, and four died during long-term follow-up. CONCLUSIONS: Taken together, our results indicate that HD is safe, effective, and life-saving for most neonates with severe IEM-induced metabolic intoxication, when promptly performed by an experienced and multidisciplinary team. A higher resolution version of the Graphical abstract is available as Supplementary information.

Individual Meropenem Clearance in Infants on ECMO and CVVHDF is Difficult to Predict: A Case Report and Review of the Literature.

OBJECTIVES: Meropenem is a broad-spectrum carbapenem antibiotic with mostly renal excretion. Conflicting data are available regarding meropenem pharmacokinetics in critically ill neonates on concomitant continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Our objectives were to assess meropenem clearance in a neonate on CRRT and ECMO, compare it to previously published data and assess whether dose recommendations can be generalized in this population. CASE DESCRIPTION: A 2.5 kg male infant with a large diaphragmatic hernia was delivered by cesarean section at week 35 and immediately mechanically ventilated due to shock and respiratory insufficiency. He underwent surgical correction of the hernia, but developed recurrent sepsis, multiorgan failure and pulmonary hypertension. He remained mechanically ventilated and required ECMO and continuous venovenous hemodiafiltration. He was started on meropenem 40 mg/kg/dose, every 8 hs for Enterobacter cloacae bacteremia and sepsis, but due to lack of clinical and microbiologic response despite in vitro susceptibility, he was started on a continuous meropenem infusion of 240 mg/kg/d, based on dose recommendations in a similar case. We measured steady state meropenem plasma concentrations on 2 occasions, during ECMO and continuous venovenous hemodiafiltration (CVVHDF) and then on CVVHDF only. RESULTS: Meropenem serum concentrations were 90 and 64 mg/L on the first and second occasion (therapeutic target concentration, 10 mg/L) corresponding to a clearance of 1.9 and 2.6 mL/kg/min. This clearance estimate was substantially lower than that reported in toddlers on CRRT and ECMO in some studies. CONCLUSION: In neonates and infants, meropenem clearance is difficult to predict because of dynamic ontogenetic changes in renal function. This problem is further aggravated in acutely ill infants with decreased renal function, renal replacement therapy and/or ECMO. Therefore, Target Concentration Intervention based on meropenem plasma concentrations is indispensable to ensure therapeutic exposure in this population.

Methylene Blue Administration for Distributive Shock States in Critically Ill Children.

BACKGROUND: Methylene blue (MB), an inhibitor of nitric oxide synthesis and its effects is a potentially effective treatment against distributive shock states such as septic shock and vasoplegic syndrome. MB has been shown to alleviate vasoplegia and promote an increase in blood pressure. It may reduce mortality. However, in the pediatric population, there are few case reports and only one controlled study on administration of MB use for vasoplegia, sepsis, or shock in general. OBJECTIVES: To summarize the experience of administering MB for vasoplegic shock in a tertiary care pediatric intensive care unit. METHODS: A retrospective chart review of seven pediatric cases treated with MB for vasoplegic shock was conducted. MB was administered as a bolus followed by continuous infusion. The authors measured blood pressure, vasopressor, and inotropic support. Patient outcome was monitored. RESULTS: The authors observed a favorable hemodynamic response with an increase in blood pressure and a reduction in vasopressor and inotropic support needed following MB administration in six patients. No side effects were observed. Three patients eventually died one to two days later, secondary to their underlying disease. CONCLUSIONS: This case series adds to the small body of evidence in the pediatric population supporting the use of MB for distributive shock states and emphasizes the need for larger, randomized trials evaluating its role in vasoplegic shock treatment.

Adenovirus Respiratory Infection among Immunocompetent Patients in a Pediatric Intensive Care Unit During 10-year period: Co-morbidity is common.

BACKGROUND: Adenovirus is responsible for 2-7% of childhood viral respiratory infections, 5-11% of viral pneumonia and bronchiolitis. Most are self-limited but may cause severe respiratory infection. OBJECTIVES: To describe adenovirus respiratory infection in immunocompetent children in a pediatric intensive care unit (PICU). METHODS: Children with adenovirus respiratory infection in our PICU from 2007 to 2016 were included. Data were retrospectively retrieved, including background, clinical manifestation, and treatment. Adenovirus was diagnosed by polymerase chain reaction, immune fluorescence, or both. RESULTS: Of 9397 samples, 956 were positive for adenovirus in children hospitalized during the study period. In total, 49 patients (aged 2 months-11.5 years) were admitted to our PICU, five were immunocompromised and excluded from the study, 19/44 (43%) were referred from other hospitals. Twenty-eight (64%) had underlying conditions, 66% had fever and cough, 11% had conjunctivitis, and 34% received antibiotics before admission. White blood cell counts ranged from 790 to 34,300 (mean 14,600) and 36% had counts above 15,000. Chest X-ray was consistent with viral infection in 77% of patients and normal in three (13.6%). Viral co-infection was found in 9 patients, 7 had presumed bacterial super-infection, and 27 (61.4%) needed mechanical ventilation. Two patients received cidofovir, 33 (75%) steroids, and 37 (84 %) antibiotics. Four patients died. CONCLUSIONS: Adenovirus respiratory infection may cause severe disease necessitating PICU admission and mechanical ventilation, mostly in patients with underlying conditions. Many patients received steroids and antibiotics, which may be unnecessary. Mortality was 9%, mainly among young infants and those with underlying conditions.

Methylene blue treatment for resistant shock following renal transplantation.

We report a case of a 19-year-old female with a history of hyperoxaluria type 1 and renal failure. The patient presented for a second renal transplantation 17 years after her first combined liver and kidney transplantation. Postoperative shock was highly resistant to fluids and required massive pharmacologic hemodynamic support. Vasoplegic shock was the presumed diagnosis, and methylene blue was utilized as a rescue therapy, with a rapid hemodynamic response and no apparent side effects.

Breastfeeding may improve nocturnal sleep and reduce infantile colic: potential role of breast milk melatonin.

UNLABELLED: Melatonin is secreted during the night in adults but not in infants. It has a hypnotic effect as well as a relaxing effect on the smooth muscle of the gastrointestinal tract. It is plausible that breast milk, which consists of melatonin, may have an effect on improving infants' sleep and reducing infantile colic. Our first goal was to assess the differences in the prevalence and severity of infantile colic and nocturnal sleep between breast-fed infants and supplement-fed infants. The second was to characterize the profile of melatonin secretion in human breast milk compared to artificial formulas. Ninety-four mothers of healthy 2 to 4-month-old infants filled a questionnaire regarding irritability/potential infantile colic and sleep characteristics. For the second part, we measured melatonin levels in breast milk of five women every 2 h during 24 h and in three samples of commonly used artificial formulas. Exclusively breast-fed infants had a significantly lower incidence of colic attacks (p = 0.04), lower severity of irritability attacks (p = 0.03), and a trend for longer nocturnal sleep duration (p = 0.06). Melatonin in human milk showed a clear circadian curve and was unmeasurable in all artificial milks. CONCLUSIONS: Exclusive breastfeeding is associated with reduced irritability/colic and a tendency toward longer nocturnal sleep. Breast milk (nocturnal) consists of substantial melatonin levels, whereas artificial formulas do not. We speculate that melatonin which is supplied to the infant via breast milk plays a role in improving sleep and reducing colic in breast-fed infants compared to formula-fed ones.

The renin-angiotensin system, blood pressure, and heart structure in patients with hereditary vitamin D-resistance rickets (HVDRR).

Vitamin D deficiency has been linked to hypertension and an increased prevalence of cardiovascular risk factors and disease. Studies in vitamin D receptor knockout (VDR KO) mice revealed an overstimulated renin-angiotensin system (RAS) and consequent high blood pressure and cardiac hypertrophy. VDR KO mice correspond phenotypically and metabolically to humans with hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR). There are no data on the cardiovascular system in human HVDRR. To better understand the effects of vitamin D on the human cardiovascular system, the RAS, blood pressure levels, and cardiac structures were examined in HVDRR patients. Seventeen patients (9 males, 8 females, aged 6 to 36 years) with hereditary HVDRR were enrolled. The control group included age- and gender-matched healthy subjects. Serum calcium, phosphorous, creatinine, 25-hydroxyvitamin D [25(OH)D],1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ], parathyroid hormone (PTH), plasma rennin activity (PRA), aldosterone, angiotensin II (AT-II), and angiotensin-converting enzyme (ACE) levels were determined. Ambulatory 24-hour blood pressure measurements and echocardiographic examinations were performed. Serum calcium, phosphorus, and alkaline phosphatase values were normal. Serum 1,25(OH)(2) D(3) and PTH but not PRA and ACE levels were elevated in the HVDRR patients. AT-II levels were higher than normal in the HVDRR patients but not significantly different from those of the controls. Aldosterone levels were normal in all HVDRR patients. No HVDRR patient had hypertension or echocardiographic pathology. These findings reveal that 6- to 36-year-old humans with HVDRR have normal renin and ACE activity, mild but nonsignificant elevation of AT-II, normal aldosterone levels, and no hypertension or gross heart abnormalities.

Lidocaine-based topical anesthetic with disinfectant (LidoDin) versus EMLA for venipuncture: a randomized controlled trial.

OBJECTIVE: To examine the efficacy and safety of a new topical anesthetic containing a disinfection ingredient (LidoDin cream) in reducing the pain associated with venipuncture by comparing it with the proven eutectic mixture of lidocaine 2.5% and prilocaine 2.5% (EMLA cream). METHODS: A single-blind, randomized, controlled trial was conducted on a study population consisting of a convenience sample of patients aged 12 to 16 years who presented at our Emergency Department between November 2007 and April 2008. The Visual Analog Scale (VAS) was used for pain assessment. Before the study, the bactericidal effect of the LidoDin cream on skin flora was tested. RESULTS: Twenty patients were enrolled to each arm of the study. Mean patient age was 13.6 years for the LidoDin group and 14.12 years for the EMLA group (P=0.347). Male patients accounted for 55% of the patients in the LidoDin group, compared with 40% in the EMLA group (P=0.527). Skin reaction scores of the LidoDin group for erythema and edema were not statistically different than those of the EMLA group (P=0.73 and P=0.75, respectively). Patient VAS scores and nurse VAS scores of the LidoDin group were not statistically different than those of the EMLA group (P=0.57 and P=0.93, respectively). DISCUSSION: This pilot study demonstrated that LidoDin and EMLA seem to be equally safe and effective topical anesthetics for venipuncture. Future studies are planned to determine, if LidoDin reduces the rate of local skin infection in patients treated with multiple daily subcutaneous injections of medications.

Comparison of adverse events during procedural sedation between specially trained pediatric residents and pediatric emergency physicians in Israel.

OBJECTIVES: The aim was to compare the rate of procedural sedation-related adverse events of pediatric residents with specific training in "patient safety during sedation" and pediatric emergency physicians (PEPs) who completed the same course or were teaching faculty for it. METHODS: This prospective single-blinded, nonrandomized study was conducted in two university-affiliated pediatric emergency departments (PEDs) in Israel. Pediatric residents who were authorized to perform unsupervised sedations had previously completed a course in patient safety during sedation. Unsupervised sedations by residents were defined as sedations where the entire procedure was performed independently. Study subjects had autonomy in choosing medications for sedation. Adverse events were defined as transient hypoxia (oxygen saturation < or = 90%) or apnea. Adverse outcomes were situations where intubation or hospitalization directly related to sedation complications would occur. Sedations over 12 consecutive months were recorded, and rates of adverse events in each group were compared. RESULTS: A total of 984 eligible sedations were recorded, 635 by unsupervised residents and 349 by PEPs. A total of 512 (80.6%) sedations were performed by residents when attending physicians were not in the ED. The total adverse event rate was 24/984 (2.44%). When the two groups used a similar type drugs, residents had 8/635 (1.26%) events, compared to 11/328 (3.35%) by PEPs. There was no statistically significant difference in the rates of hypoxia or apnea between the two groups (p = 0.29 and p = 0.18, respectively). Adverse outcomes did not occur. CONCLUSIONS: Unsupervised pediatric residents with training in patient safety during sedation performed procedural sedations with a rate of adverse events similar to that of PEPs.

Insulin pump therapy for 1-6 year old children with type 1 diabetes.

BACKGROUND: The management of diabetes in preschool children poses unique difficulties for both the families and the medical team. OBJECTIVE: To test the feasibility and safety of insulin pump therapy in the 1-6 year age group in order to improve quality of life and metabolic control. METHODS: The study group comprised 15 type 1 diabetic children aged 1-6 years old (mean +/- SD, 3.8 +/- 1.2 years) from three diabetes centers. Insulin pump therapy was applied for 12 months. Data, including insulin dose, hemoglobin A1c, hypoglycemic events, as well as scores on the Diabetes Quality of Life Measure Questionnaire and the Diabetes Treatment Satisfaction Questionnaire, were collected and compared with the multiple daily injection treatment prior to entry into the study, RESULTS: HbA1c was measured at the beginning of the study and at 2, 4, 8 and 12 months later; the respective levels (mean +/- SD) were 8.82 +/- 0.98, 8.45 +/- 1.05, 8.37 +/- 0.85, 8.32 +/- 0.71, 8.18 +/- 0.90%. HbA1c measurements after 12 months were significantly lower than at the beginning of the study (P < 0.05). There were no significant differences in insulin dose and the total number of hypoglycemic events. In both the DQOL and DTSQ scales there were significant differences in scores in favor of the insulin pump period (43.7 +/- 8.0 versus 33.7 +/- 7.9, P < 0.001; and 10.9 +/- 2.3 versus 14.5 +/- 2.3, P < 0.001), respectively. CONCLUSIONS: For very young diabetic children, insulin pump therapy improves quality of life and is feasible and safe. It should be considered as an optional mode of therapy for this age group.

Spontaneous echoes due to hypoalbuminemia.

We found spontaneous echoes in two teenagers with nephrotic syndrome and profound hypoalbuminemia, both having normal cardiac structure, function and output. The phenomenon disappeared after the level of albumin normalized. In one patient, all spontaneous echoes disappeared following convalescence, the level of albumin in the serum then being documented at normal levels. The second patient, who presented with profound hypoalbuminemia, was infused with human albumin because of oliguria, following which the spontaneous echoes disappeared.