OBJECTIVES: We aimed to determine the frequency and variables associated with low femoral central venous catheter (fCVC) tip position. We also examined the association between tip position and symptomatic venous thromboembolism (VTE). DESIGN: Retrospective cohort from two PICUs. SETTING: Quaternary academic children's hospitals, 2016-2021. PATIENTS: Children (age <18 yr) in the PICU who underwent temporary fCVC placement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Low fCVC tip position occurs when the tip is inferior to the fifth lumbar vertebra (L5) on a postprocedural abdominal radiograph. Of 936 patients: 56.3% were 1-12 years old, and 80.0% had normal weight-for-age z score. fCVC tip position was low in 67.3% of patients. In the multivariable model, older age, earlier years of placement, and higher weight-for-age were associated with low fCVC tip position. Symptomatic fCVC-associated VTE occurred in 8.8% of patients, with a rate of 16.5 per 1000 CVC days (interquartile range, 13.1-20.5 per 1000 CVC days). The percentage of VTE in low vs. recommended fCVC tip position and VTE (8.6% vs. 9.2%) were equivalent (two one-sided z-tests; p < 0.001). Furthermore, in the multivariable model, we failed to identify an association between low fCVC tip position, relative to the recommended tip position, and greater odds of VTE (OR, 1.58 [95% CI, 0.92-2.69). However, we cannot exclude the possibility of low fCVC tip position being associated with up to 2.6-fold greater odds of symptomatic VTE. CONCLUSIONS: In our two PICUs, 2016-2021, low fCVC tip position occurred in two-thirds of placements and was associated with older age and higher weight-for-age patients. fCVC-associated VTE occurred in one-in-11-catheter placements, with the raw percentage of fCVCs and subsequent VTE in low and recommended tip position being equivalent. However, the multivariable modeling indicates that future research into the relationship between tip position and VTE requires ongoing surveillance and work.

Good, Ryan1; Ahern, Emily2; Conlon, Thomas3; DeVine, Mackenzie4; Mehta, Sanjiv5; Miller, Kristen2; Weber, Mark5; Himebauch, Adam6 Author Information

Background: Pediatric patients require pharmacological management of pain and agitation associated with mechanical ventilation. Pain and agitation may be refractory to opioids and alpha-2 agonists, prompting the use of adjunctive analgesics and sedatives with alternative mechanisms. The purpose of this study was to describe the use of phenobarbital as an adjunctive agent for refractory agitation in critically ill, mechanically ventilated pediatric patients. Subjects and Methods: This was a single-center, retrospective chart review at a pediatric intensive care unit (PICU) at a pediatric academic medical center in America between 2016 and 2021. Children aged 2 months to 18 years old were admitted to the PICU were mechanically ventilated and received phenobarbital for adjunct sedation. Sixty-three patients had phenobarbital dosing data evaluated, and the 38 patients who were not receiving continuous neuromuscular blockade were included in the primary and secondary outcome analysis of time within the goal sedation score. Descriptive statistics was used to assess baseline characteristics and the primary outcome. Wilcoxon signed-rank tests were used to evaluate secondary outcomes. Results: Patients spent significantly more time within the goal sedation score range after phenobarbital compared to before phenobarbital. The median number of rescue sedative boluses, morphine equivalents (MEs), and benzodiazepine equivalents (BZDE) significantly decreased 2 days after the first phenobarbital dose compared to the 2 days before the first phenobarbital dose. Conclusions: The use of phenobarbital as an adjunct sedative was associated with a statistically significant increase in time spent in the goal sedation score range and decrease in ME, BZDE, and concomitant sedative boluses.

BACKGROUND:Bacterial lymphadenitis is a common reason for antibiotic treatment and hospitalization in children. The literature available addressing the bacterial etiology of lymphadenitis recommends the use of narrow-spectrum agents to cover common pathogens. We suspect that patients at our institution receive unnecessarily broad-spectrum antimicrobial agents. The primary objective of this study was to characterize the microbiology and antibiotic use in lymphadenitis patients.METHODS:Retrospective review of children admitted over a 10-year period with an International Classification of Diseases Ninth or Tenth Edition code for lymphadenitis. Patients were included if they were <18 years old, admitted to the inpatient ward, and had intraoperative lymph node cultures collected.RESULTS:A total of 131 patients admitted with lymphadenitis had lymph node cultures collected and were included. Seventy-two (72/131; 55%) patients had positive lymph node culture results with pathogenic bacteria. The predominant pathogens were Staphylococcus aureus (56/72; 77.8%) and Streptococcus pyogenes (10/72; 13.9%). The most common inpatient empirical regimen was ampicillin-sulbactam. Of the 72 patients with typical pathogens identified, 80.6% were sensitive to a first-generation cephalosporin, whereas 86.1% were sensitive to a β-lactam/β-lactamase inhibitor.CONCLUSION:Patients presenting to our institution with acute bacterial lymphadenitis were predominantly found to have methicillin-susceptible S. aureus lymphadenitis that could be empirically treated with cefazolin. At our institution, there is little advantage to the most commonly used broad-spectrum agent, ampicillin-sulbactam.

To the Editor.—I read with interest the article by DeVine et al1 on 3 pediatric patients with suprarefractory status epileptics (SRSE): patient 1, age 29 days, with traumatic brain injury; patient 2, age 52 days, with ischemic stroke due to venous malformation; and patient 3, age 60 days, with hypoxic brain injury, who benefited from ketamine continuously administered during 5 days in addition to a number of other antiseizure drugs. It was concluded that continuous ketamine infusion should be considered in SRSE.1 The study is compelling but has limitations that should be discussed.The main limitation of the study is the design. It is not possible to draw general conclusions from 3 patients. To assess the effect of a medication a multicenter, prospective, randomized, controlled trial would be desirable. It is also mandatory that the size of the verum group be large enough to allow comparison with healthy controls or a control population with the disease.Because the effect of ketamine may strongly depend on the underlying cause of epilepsy, on comorbidities, and on the current medication, it is mandatory to know the underlying cause of epilepsy and the comorbidities of the 3 included patients. Patient 1 had severe hypoglycemia throughout hospitalization.1 How was hypoglycemia ruled out as the driver of the SRSE? Regarding the cause of epilepsy, we should know how genetic causes of epilepsy were ruled out.We disagree with the notion that the index study is the first in which continuous ketamine infusions have been used to treat SRSE.1 Continuous ketamine has been previously used to treat SRSE.3Not sufficiently discussed in the study are the side effects of ketamine. Although it is generally well tolerated, ketamine can exhibit severe side effects in single patients, such as delirium, headache, hallucinations, nausea, vomiting, arterial hypertension, and abdominal compartment syndrome.2,3There is no mention that ketamine is not effective in each patient with status epilepticus. In a study of 69 pediatric patients with RSE, seizure termination could be achieved in only 46%, seizure reduction in 28%, and no change was observed in 26%.3 In a study of 11 adult patients with status epilepticus, permanent status epilepticus control could be achieved in only 27% of patients.4 In a study of 68 adult patients with SRSE, complete cessation of SRSE could be achieved in 63% of cases.5Regarding the patient with ischemic stroke, we should know the initial treatment of ischemic stroke, particularly whether or not the patient underwent thrombolysis or thrombectomy and to what degree the National Institute of Health Stroke Scale score changed before and after acute therapy.A treatment of status epilepticus, including RSE and SRSE, that has not been applied and discussed is the ketogenic diet. From ketone bodies it is known that they have an antiseizure effect and it would be interesting to know if ketamine plus ketogenic diet potentiates the antiseizure effect of ketamine. Although the ketogenic diet is usually well tolerated, it may have side effects in single patients.Overall, the interesting study has limitations that put the results and their interpretation into perspective. Addressing these issues would strengthen the conclusions and could improve the status of the study. Assessing the effect of ketamine on SRSE requires appropriately designed cohort studies.Author’s Response: We thank Dr Finsterer for his comments in the Letter to the Editor in response to our article summarizing our center’s experience with the use of ketamine for the treatment of refractory status epilepticus (RSE) and superrefractory status epilepticus (SRSE) in young infants. We agree that broad conclusions about the efficacy and safety of ketamine for status epilepticus will require further investigation. However, multicenter randomized studies for the treatment of status epilepticus in very young patients are unlikely to occur in the near future. Currently, there are no ongoing clinical trials evaluating the use of ketamine for RSE in children on Clinicaltrials.gov (searched August 6, 2023). The publication of case series and larger cohorts provides critical knowledge from real-world experiences treating status epilepticus in specific populations. This includes the larger cohort of patients published after this manuscript was accepted.We agree with Dr Finsterer’s point that understanding the underlying etiology is critical to interpreting response to any therapy. In the cases presented, given the rarity of the clinical scenarios we were describing, we limited details intentionally to avoid providing details that would risk identifying patients. Hypoglycemia was managed for the first patient with dextrose infusions; the time course of the seizures and presence outside of the hypoglycemia were more consistent with acute symptomatic seizures secondary to inflicted trauma. All cases had a proximate injury to provoke the episode of status epilepticus, and genetic evaluations were not necessary at the time. Regarding the specifics of the patient with ischemic stroke, this was related to a vascular malformation and not due to an acute end vessel occlusion. Use of thrombolytics or mechanical thrombectomy was not indicated. The Pediatric National Institutes of Health Stroke Scale is validated in children ages 2 to 18 years, but it is not intended for use in infants.We did not include a thorough discussion of potential adverse reactions to ketamine in our discussion and appreciate the attention Dr Finsterer brought to this. We discussed adverse events that were noted and described the presence or absence of some common adverse reactions reported with ketamine. Further, we agree that the efficacy of ketamine for RSE and SRSE in different clinical scenarios needs further study ­because not all patients in our series had a complete or sustained response.Research to understand the role of bolus and infusions of ketamine in the treatment of SE in children is essential given the expanding use of ketamine for the treatment of seizures in children.

Background and Objectives: Venous thromboembolic events (VTE) complicate acute hematogenous musculoskeletal infections (MSKIs) among hospitalized children. However, there is limited guidance for which specific MSKI patients are at the greatest VTE risk. This study aimed to identify VTE risk factors for children hospitalized with MSKIs. Methods: A retrospective chart review was performed of children hospitalized with MSKIs at a single quaternary care pediatric hospital during a 9-year period. Patients with chronic MSKIs, non-hematogenous infections, or significant contributing comorbidities were excluded. Demographic and clinical characteristics were compared between patients with and without VTE using forward stepwise conditional multivariable logistic regression to identify VTE risk factors. Results: Among 335 included patients, 7 (2.1%) developed a VTE. There was no difference in age, sex, or obesity rates for those with or without VTE. Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and/or critical illness were more likely to develop a VTE with summative adjusted odds ratios of 31.7 and 26.4, respectively. In addition, patients with VTEs had longer hospitalizations (median 4.7 vs. 12.8 d, P<0.001), longer courses of intravenous antimicrobials (median 3.7 vs. 13.5 d, P=0.001), and longer time to fever resolution (median 25.7 vs. 162 h, P=0.004). Conclusions: VTE prevalence among children with acute MSKIs is low. MRSA infection and critical illness significantly increase the risk for VTE development in these patients. Future prospective studies are needed to determine if VTEs in high-risk MSKI patients can be prevented.

Continuous ketamine infusions have been studied as an adjunctive agent for refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) in older children and adults. However, minimal information exists on the efficacy, safety, and dosing for continuous ketamine in young infants. We present the clinical course of 3 young infants with RSE and SRSE who received continuous ketamine in conjunction with other antiseizure medications. The condition of these patients was refractory to an average of 6 antiseizure medications before initiation of continuous ketamine infusion. For each patient, a continuous ketamine infusion was initiated at a rate of 1 mg/kg/hr with 1 patient requiring titration to a maximum of 6 mg/kg/hr. In 1 case, the concomitant use of continuous ketamine allowed for a reduction in the benzodiazepine continuous infusion rate. In all cases, ketamine was well tolerated especially in the setting of hemodynamic instability. Ketamine may provide a safe adjunct in the acute setting in severe RSE and SRSE. This is the first case series to document the use of continuous ketamine as a treatment modality in young infants with RSE or SRSE secondary to various underlying etiologies, without adverse events. Further studies are needed to evaluate the long-term safety and efficacy of continuous ketamine in this patient population.

Relapse of infection due to SARS-CoV-2 has been rarely described and there is little guidance regarding the management of such cases in immunocompromised hosts. We present a case of an adolescent female with B-cell acute lymphoblastic leukemia hospitalized multiple times for symptomatic SARS-CoV-2 infection who was safely treated with 2 courses of remdesivir (RDV) and has had no additional readmissions to date. Though additional studies are needed to confirm the safety and efficacy of an additional course of RDV in the setting of relapsed or prolonged severe COVID-19, our observations suggest that a second course of RDV may be considered.

Background: Identifying the causative pathogen for acute hematogenous musculoskeletal infections (MSKIs) allows for directed antimicrobial therapy and diagnostic confidence. However, 20% to 50% of children with acute MSKIs remain culture negative. The objective of this study was to compare characteristics of culture negative MSKI patients to those where a pathogen is identified. Methods: Electronic medical records of children admitted between July 2014 to September 2018 to a single quaternary care pediatric hospital with acute MSKIs were retrospectively reviewed. Clinical and demographic characteristics were compared between culture positive and culture negative MSKIs. Results: A total of 170 patients were included of whom 43 (25%) were culture negative. All culture negative patients had at least 1 culture type obtained, and the majority (84%) had both blood and source cultures performed. When compared with patients with a causative pathogen identified, culture negative patients were younger (2.3 vs. 9.8 y), smaller (13.5 vs. 31.6 kg), less likely to be febrile on arrival (56% vs. 77%), less likely to have an abscess on imaging (23% vs. 48%), and were more likely to have uncomplicated septic arthritis (35% vs. 8%). No critically ill patient was culture negative. Seven culture negative patients had additional Kingella kingae testing performed, none of which were positive. Conclusions: Despite targeted and standardized efforts to identify causative bacteria, 25% of children with acute MSKIs never have a pathogen identified. Culture negative patients are younger, less febrile, are less likely to have an abscess, and more likely to have isolated septic arthritis. Level of Evidence: This is a retrospective cohort study interested in identifying patient characteristics that predict rate of culture positivity for acute MSKIs. This study meets criteria for Level II evidence.

Clostridioides difficile infection (CDI) is a major public health concern for pediatric and adult patients. The management of pediatric CDI poses a challenge to healthcare providers due to lack of strong randomized controlled trials to guide pharmacological management. Additionally, recent updates to CDI guidelines recommend oral vancomycin over metronidazole for the management of CDI in adults, leaving questions regarding how to best manage pediatric patients. This continuing education pharmacotherapy review describes available evidence for the safety and efficacy of medications used in the treatment and management of pediatric CDI and aims to clarify discrepancies between pediatric and adult recommendations.

Abstract Objectives Identifying the causative bacterial pathogen for children with acute hematogenous musculoskeletal infections (MSKIs) allows for improved care. The purpose of our study was to determine if clinical markers could predict which patients will have a causative pathogen found on source culture alone, thus being highest yield to undergo operative diagnostic procedures. Methods A single-center, retrospective cohort study was performed. Medical records for patients between 6 months and 18 years of age admitted between July 2014 and September 2018 with a discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis were reviewed. Patients were stratified based on results of blood and source cultures. Predictors of interest were screened on a univariable basis with significant predictors retained in a multivariate analysis. Results There were 170 patients included. No predictors were significantly associated with increased odds of having a causative pathogen found on source culture alone. Degree of C-reactive protein elevation and history of fever were associated with decreased odds of being source culture positive, OR (95% CI); 0.92 (0.87, 0.98) and 0.39 (0.19, 0.81), respectively. Conclusions Predictive modeling failed to identify children with MSKIs whose causative pathogen was found by source culture alone. It is difficult to predict which MSKI patients will be highest yield for operative diagnostic procedures.

BACKGROUND Acute hematogenous musculoskeletal infections are a common cause of hospitalization in children. A locally developed clinical care guideline (CCG) for acute musculoskeletal infections was implemented at our quaternary care pediatric hospital in July 2012. The purpose of this study was to evaluate the long-term sustainability of previously described improvements after CCG implementation. METHODS Clinical outcomes for children hospitalized with musculoskeletal infections at Children's Hospital Colorado from June 2009 through September 2018 were retrospectively reviewed. Patients were included if they had an International Classification of Diseases, Ninth Revision or International Classification of Diseases, 10th Revision discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis and were between 6 months and 18 years of age at admission. Patients with underlying medical complexity or nonhematogenous musculoskeletal infections were excluded. Patients were categorized by date of admission as either "pre-CCG" (June 2009 to June 2011) or "sustain-CCG" (July 2014 to September 2018). Primary outcomes were hospital length of stay and intravenous antimicrobial length of therapy. RESULTS From pre-CCG to sustain-CCG, median length of stay decreased by 1.29 days (5.56 vs 4.27; P < .004) and median length of therapy decreased by 5.04 days (8.33 vs 3.29; P < .0001). Statistical process control charts support that these were sustained improvements many years after CCG implementation. Additional secondary clinical improvements were observed in the sustain-CCG group including faster fever resolution, more consistent blood and source culture acquisition, and decreased central line placement. There was no increase in related readmissions or therapeutic failures in the sustain-CCG group. CONCLUSIONS Implementation of a CCG to standardize care for musculoskeletal infections can be sustained many years after implementation.

Reiter, Pamela1; Wright, Garth2; Lieb, Ann1; DeVine, Mackenzie1; Payan, Marisa1; Good, Ryan1; Kaufman, Jon1 Author Information