Antimicrobial Disposition During Pediatric Continuous Renal Replacement Therapy Using an Ex Vivo Model.

OBJECTIVES: Little is known on the impact of continuous renal replacement therapy on antimicrobial dose requirements in children. In this study, we evaluated the pharmacokinetics of commonly administered antimicrobials in an ex vivo continuous renal replacement therapy model. DESIGN: An ex vivo continuous renal replacement therapy circuit was used to evaluate drug-circuit interactions and determine the disposition of five commonly used antimicrobials (meropenem, piperacillin, liposomal amphotericin B, caspofungin, and voriconazole). SETTING: University research laboratory. PATIENTS: None. INTERVENTIONS: Antimicrobials were administered into a reservoir containing whole human blood. The reservoir was connected to a pediatric continuous renal replacement therapy circuit programmed for a 10 kg child. Continuous renal replacement therapy was performed in the hemodiafiltration mode and in three phases correlating with three different continuous renal replacement therapy clearance rates: 1) no clearance (0 mL/kg/hr, to measure adsorption), 2) low clearance (20 mL/kg/hr), and 3) high clearance (40 mL/kg/hr). Blood samples were drawn directly from the reservoir at baseline and at 5, 20, 60, and 180 minutes during each phase. Five independent continuous renal replacement therapy runs were performed to assess inter-run variability. Antimicrobial concentrations were measured using validated liquid chromatography-mass spectrometry assays. A closed-loop, flow-through pharmacokinetic model was developed to analyze concentration-time profiles for each drug. MEASUREMENTS AND MAIN RESULTS: Circuit adsorption of antimicrobials ranged between 13% and 27%. Meropenem, piperacillin, and voriconazole were cleared by the continuous renal replacement therapy circuit and clearance increased with increasing continuous renal replacement therapy clearance rates (7.66 mL/min, 4.97 mL/min, and 2.67 mL/min, respectively, for high continuous renal replacement therapy clearance). Amphotericin B and caspofungin had minimal circuit clearance and did not change with increasing continuous renal replacement therapy clearance rates. CONCLUSIONS: Careful consideration of drug-circuit interactions during continuous renal replacement therapy is essential for appropriate drug dosing in critically ill children. Antimicrobials have unique adsorption and clearance profiles during continuous renal replacement therapy, and this knowledge is important to optimize antimicrobial therapy.

Subglottic Stenosis Following Cardiac Surgery With Cardiopulmonary Bypass in Infants and Children.

OBJECTIVES: To determine the 1) incidence of subglottic stenosis in infants and children following cardiac surgery with cardiopulmonary bypass and 2) risk factors associated with its development. DESIGN: Retrospective cohort study. SETTING: Tertiary children's hospital in California. PATIENTS: Infants and children who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Diagnosis of subglottic stenosis by tracheoscopy. MEASUREMENTS AND MAIN RESULTS: The incidence of subglottic stenosis at our institution during the study period was 0.7%. Young age (p = 0.014), prolonged cardiopulmonary bypass (p = 0.03), and prolonged mechanical ventilation (p < 0.01) were associated with the development of subglottic stenosis. Gender, chromosomal anomaly, presence of a cuffed endotracheal tube, and lowest core temperature during cardiopulmonary bypass were not associated with the development of subglottic stenosis. CONCLUSIONS: The incidence of subglottic stenosis was less than that previously reported in this population. Although the incidence is relatively low, subglottic stenosis is a serious complication of tracheal intubation and all measures to prevent subglottic stenosis should be undertaken.

Mothball Ingestion in the Setting of G6PD Deficiency Causing Severe Hemolytic Anemia, Methemoglobinemia, and Multiple Organ Failure in a Toddler.

Mothballs containing naphthalene or paradichlorobenzene are known to cause hemolysis and methemoglobinemia. They can also affect the other organs, including the kidneys, liver, lungs, and skeletal muscles. The involvement of 1 or 2 organs at a time has been commonly reported. However, more than 2 organ dysfunction in mothball intoxication is rare and usually indicates severe illness. The intoxication can have more pronounced symptoms in children with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report this case of a previously healthy 13-month-old patient who presented with severe hemolysis, lactic acidosis, methemoglobinemia, acute renal failure, hepatic dysfunction, and rhabdomyolysis. He required aggressive fluid resuscitation, blood transfusions, and mechanical ventilation. The underlying etiology of his illness was initially unclear; however, upon repeated questioning, the father recalled the patient chewing on a mothball 3-4 days before admission. Hence, mothball intoxication was considered the most plausible clinical diagnosis in this patient. He was given N-acetylcysteine, instead of methylene blue, because of hepatic dysfunction and the fact that G6PD deficiency could not be ruled out in the presence of acute hemolysis. The patient made a full recovery after 2 weeks of intensive care unit management. G6PD testing after 3 months confirmed the deficiency. These mothballs are available in Hawai'i, but this is the first report of such a severe presentation to our knowledge. The presence of methemoglobinemia, severe hemolysis, and thorough history-taking helped us determine the diagnosis of mothball intoxication and enabled definitive treatment.

Acute Rhabdomyolysis in a Child with Multiple Suspicious Gene Variants.

Rhabdomyolysis is diagnosed with creatinine kinase (CK) elevation beyond 1000 U/L or ten times above the normal upper limit. Severe episodes can be fatal from electrolyte imbalance, acute renal failure, and disseminated intravascular coagulation. A 13-month-old child was admitted with a CK of 82,090 U/L in the setting of respiratory tract infection-related hyperthermia of 106.9° farenheit. His medical history was significant for prematurity, dystonia, and recurrent rhabdomyolysis. His home medications clonazepam, clonidine, and baclofen were continued upon admission. He exhibited uncontrolled dystonia despite treatment for dystonia. Therefore, sedative infusions and forced alkaline diuresis were begun to prevent heme pigment-induced renal injury. Despite these interventions, his CK peaked at 145,920 U/L, which is rarely reported in this age group. The patient also developed pulmonary edema despite diuresis and required mechanical ventilation. Sedative infusions were not enough for dystonia management, and he needed the addition of a neuromuscular blocking infusion. He finally responded to these interventions, and the CK normalized after a month. He required a month of mechanical ventilation and two and a half months of hospitalization and extensive rehabilitation. We were able to avert renal replacement therapy despite pulmonary edema and an estimated glomerular filtration rate nadir of 21 mL/min/1.73 m2 based on the bedside Schwartz formula. He made a complete recovery and was discharged home. His growth and development were satisfactory for two years after that event. His extensive diagnostic workup was negative. Unfortunately, he died from septic and cardiogenic shock with mild rhabdomyolysis two years later. Prompt recognition, early institution of appropriate therapies, identification of underlying disease, and triggering events are pivotal in rhabdomyolysis management. Evidence-based guidelines are needed in this context.

A Rare Etiology for Ascending Paralysis in an Infant.

An 11-month-old male infant with ascending paralysis had an unremarkable initial cerebrospinal fluid (CSF) analysis and imaging. Progressive neurological symptoms resulted in repeated CSF sampling, microscopy, and plasma microbial cell-free DNA next-generation sequencing analysis, that in combination with epidemiology, confirmed the diagnosis.

Junctional Tachycardia as a Diagnostic Criterion in Acute Rheumatic Fever.

Acute rheumatic fever (ARF) is an acute inflammatory process resulting in rheumatic carditis, one of the most common acquired heart diseases in youth. Among the clinical manifestations of carditis, pathologic valve regurgitation and atrioventricular block are included in the criteria for the diagnosis of ARF. Besides atrioventricular block, ARF may often present with other arrhythmias, such as junctional tachycardia (JT). However, JT is currently not recognized as a criterion for the diagnosis of ARF. Three adolescents presented in our hospital with JT, polyarthralgia, and laboratory signs of inflammation with evidence of preceding group A Streptococcus infection. None of the patients fulfilled the diagnostic criteria of ARF. On the basis of the presumed diagnosis of ARF, all 3 patients were treated with intravenous steroids. Steroid therapy was given, and JT converted to sinus rhythm within an average of 62 hours. Subsequent electrocardiograms revealed variable degree of atrioventricular block in all 3 patients, providing clinical evidence and fulfilling the diagnostic criteria of ARF. Patients were monitored for a total 2 to 8 days before discharge on standard antiinflammatory treatment. Follow-up electrocardiograms and Holter monitoring revealed resolution of the atrioventricular block and lack of JT recurrence in all patients. On the basis of these sentinel cases, we propose that JT should be included as a diagnostic criterion for the diagnosis of ARF.

Pediatric Code Blue: How Prepared Are We? A Self-Efficacy Assessment Project.

Pediatric advanced life support (PALS) recertification every two years is inadequate to maintain proficiency. The authors hypothesized that a standardized, recurring curriculum may enhance retention of cardiopulmonary resuscitation (CPR) skills. Monthly in situ mock code training and an annual online self-directed learning module were implemented for pediatric intensive care unit nurses, pediatric residents, and respiratory therapists at a women and children's hospital. The in situ mock codes were linked to PALS training self-efficacy (pre- and post-mock code) and feedback related surveys. CPR knowledge was assessed using an online module with pre- and post-tests. A total of 82 in situ mock code surveys and 137 online modules were completed over a 20-month period. Medical knowledge (P < .05 for 7/10 questions) and self-confidence improved (P < .001. Several staff reported a negative impact on their patient care assignments in order to participate in the mock code. However, a significant number of participants (65%) concurred with the benefits of monthly mock codes. The curriculum improved CPR efficacy by improving knowledge-based retention as well as self-confidence in their skills.

Central Pontine Myelinolysis in Pediatric Diabetic Ketoacidosis.

Central pontine myelinolysis (CPM) is rarely reported in pediatric patients with diabetic ketoacidosis (DKA). We report this case of a 16-year-old female with new onset diabetes presenting with DKA, who received aggressive fluid resuscitation and sodium bicarbonate in the emergency department. Later she developed altered mental status concerning for cerebral edema and received hyperosmolar therapy with only transient improvement. Soon she became apneic requiring emergent endotracheal intubation. MRI brain showed cerebral edema, CPM, and subdural hemorrhage. She was extubated on day seven and exhibited mild dysmetria, ataxia, unilateral weakness, and neglect. Upon discharge she was able to ambulate with a walker and speak and eat without difficulty. Although less common than cerebral edema, CPM should be considered in DKA patients with acute neurologic deterioration. Fluid and bicarbonate therapy should be individualized, but larger studies would help guide the management. Although poor outcomes are reported in CPM, favorable outcomes are possible.

Coronary artery dilation in acute Kawasaki disease and acute illnesses associated with Fever.

BACKGROUND: In the absence of a specific test, the diagnosis of clinically incomplete Kawasaki disease (KD) can be challenging. The 2004 American Heart Association guidelines state that the diagnosis of KD is supported by the presence of coronary artery dilation documented by echocardiography. However, the specificity of coronary artery dilation and its prevalence in children with other acute illnesses associated with fever has not been studied. METHODS: A 2-center, prospective study compared the internal diameters and Z-scores (standard deviation [SD] units from the mean internal diameter normalized for body surface area) of the proximal left anterior descending and right coronary arteries measured by echocardiography in febrile children (FC) and children with KD. RESULTS: The median Z-score (interquartile range) of the left anterior descending coronary artery was -0.05 (-0.86, 0.62) and 1.06 (0.36, 2.06) SD units for the 45 FC and the 145 KD patients, respectively (P < 0.0001). For the right coronary artery, the median Z-score was 0.21 (-0.20, 0.87) and 1.04 (0.31, 1.85) SD units for the FC and KD patients, respectively (P < 0.0001). There was no correlation between body temperature at the time of echocardiography and coronary artery Z-score. No febrile child had a coronary artery Z-score ≥ 2.5 SD units. CONCLUSIONS: Z-scores ≥ 2.5 SD units were not observed in our cohort of FC. Therefore, echocardiographic evidence of coronary artery dilation can be used to support the diagnosis of KD.