The use of vitamin K for coagulopathy in critically ill children.

OBJECTIVES: Coagulopathy is associated with increased mortality in children in the intensive care unit (ICU). Recommended management of vitamin K-deficient coagulopathy is vitamin K administration. The goal of this study was to evaluate vitamin K administration for coagulopathy in critically ill children and determine a relationship between vitamin K dose and change in prothrombin time (PT) and international normalized ratio (INR). METHODS: This retrospective cohort study reviewed electronic medical records of patients ≤17 years who received vitamin K for acute coagulopathy in the pediatric ICU from January 2013 to January 2021. Patients receiving vitamin K antagonists were excluded. Effectiveness data included change in PT/INR after vitamin K administration. Safety data included incidence of hypersensitivity or anaphylaxis. RESULTS: A total of 310 patients (median age 6.8 years, range 22 days-17.7 years) received vitamin K. A median of three doses (range 1-8) and 0.14 mg/kg per dose (range 0.09-0.22 mg/kg) were given, most frequently intravenously (892/949, 94%). Most patients (304/310, 98%) had at least one risk factor for vitamin K deficiency. Mean PT/INR was 21.5/2.1 prior to vitamin K administration, which decreased by 4.4 (SD = 9.0, 95% CI 16.011 to 18.015, p < 0.001) and 0.5 (SD = 1.0, 95% CI 1.490 to 1.705, p < 0.001) to means of 17.0 and 1.6, respectively, after the first vitamin K dose. No linear relationship was found between vitamin K dose and change in PT/INR. No hypersensitivity or anaphylaxis occurred following vitamin K administration; 27% (84/310) of patients died. CONCLUSIONS: Administration of vitamin K is effective and safe for the management of vitamin K-deficient coagulopathy in critically ill pediatric patients. Further study is needed to determine a relationship between vitamin K dose and change in PT/INR.

Pharmacist-Led Discharge Transitions of Care Interventions for Pediatric Patients: A Narrative Review.

Transitions of care (TOC) before, during, and after hospital discharge are an opportune setting to optimize medication management. The quality standards for pediatric care transitions, however, are lacking, leading to reduced health outcomes in children. This narrative review characterizes the pediatric populations that would benefit from focused, TOC interventions. Different types of medication-focused TOC interventions during hospital discharge are described, including medication reconciliation, education, access, and adherence tools. Various TOC intervention delivery models following hospital discharge are also reviewed. The goal of this narrative review is to help pediatric pharmacists and pharmacy leaders better understand TOC interventions and integrate them into the hospital discharge process for children and their caregivers.

Methylnaltrexone for Opioid-Induced Dysmotility in Critically Ill Infants and Children: A Pilot Study.

OBJECTIVE: Critically ill pediatric patients commonly experience opioid-induced dysmotility. Methylnaltrexone, a subcutaneously administered, peripherally acting mu-opioid receptor antagonist, is a compelling adjunct to enteral laxatives in patients with opioid-induced dysmotility. Data for methylnaltrexone use in critically ill pediatric patients are limited. The purpose of this study was to determine the effectiveness and safety of methylnaltrexone for opioid-induced dysmotility in critically ill infants and children. METHODS: Patients younger than 18 years who received subcutaneous methylnaltrexone from January 1, 2013, through September 15, 2020, in the pediatric intensive care units at an academic institution were included in this retrospective analysis. Outcomes included incidence of bowel movement, enteral nutrition feeding volume, and adverse drug events. RESULTS: Twenty-four patients, median age 3.5 years (IQR, 0.58-11.1), received 72 methylnaltrexone doses. The median dose was 0.15 mg/kg (IQR, 0.15-0.15). Patients were receiving a mean ± SD of 7.5 ± 4.5 mg/kg/day of oral morphine milligram equivalents (MMEs) at methylnaltrexone administration and received opioids for median 13 days (IQR, 8.8-21) prior to methylnaltrexone administration. A bowel movement occurred within 4 hours following 43 (60%) administrations and within 24 hours following 58 (81%) administrations. Enteral nutrition volume increased by 81% (p = 0.002) following administration. Three patients had emesis and 2 received anti-nausea medication. No significant changes in sedation or pain scores were observed. Withdrawal scores and daily oral MMEs decreased following administration (p = 0.008 and p = 0.002, respectively). CONCLUSIONS: Methylnaltrexone may be an effective treatment for opioid-induced dysmotility in critically ill pediatric patients with low risk of adverse effects.

Enteral antipseudomonal fluoroquinolones for ventilator-associated tracheobronchitis in children with pre-existing tracheostomy.

INTRODUCTION: Pseudomonas aeruginosa is the most commonly isolated organism in tracheostomy-dependent children with ventilator-associated tracheobronchitis (VAT). Enteral treatment with an antipseudomonal fluoroquinolone such as ciprofloxacin or levofloxacin is sometimes employed, but supportive data are limited. The purpose of this study was to evaluate the effectiveness and safety of enteral antipseudomonal fluoroquinolones for VAT in children with pre-existing tracheostomy. METHODS: This was a retrospective review of electronic medical records for tracheostomy-dependent children <18 years of age who received an enteral antipseduomonal fluoroquinolone for the treatment of presumed VAT from January 2013 through January 2020 at an academic children's hospital. RESULTS: Seventy-six treatment courses representing 60 children (median age: 9.5, interquartile range [IQR]: 3.6-13.1 years) received an antipseudomonal fluoroquinolone for VAT treatment during the study period. Median treatment duration was 8 (range: 7-10) days. Most tracheostomy cultures (n = 70/82, 85%) were polymicrobial, with P. aeruginosa most commonly isolated (n = 67/224 organisms, 30%). Sixty-five courses (86%) were successfully treated with an enteral fluoroquinolone. Antibiotics were changed or extended for two (3%) children. Antibiotics were prescribed for 10 (13%) courses and eight (11%) required hospitalization for a respiratory infection within 30 days of fluoroquinolone completion. Six (8%) courses received a seizure rescue medication, seven (9%) experienced emesis, and one (1%) had elevated transaminases. Tendonitis and tendon rupture were not observed. CONCLUSIONS: The results of this study suggest enteral antipseudomonal fluoroquinolones may be effective for the treatment of VAT in children with tracheostomy. Further study is warranted to clarify the role of these agents in pediatric VAT.

Serotonin syndrome following methylene blue administration during cardiothoracic surgery.

INTRODUCTION: Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient. CASE REPORT: A 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient's symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home. DISCUSSION: Only 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome.

Human salivary MUC7 mucin peptides: effect of size, charge and cysteine residues on antifungal activity.

We have previously shown that MUC7 (human salivary low-molecular-mass mucin) 20-mer: LAHQKPFIRKSYKCLHKRCR (residues 32-51 of the parent MUC7, with a net positive charge of 7) possesses a broad-spectrum antimicrobial activity [Bobek and Situ (2003) Antimicrob. Agents Chemother. 47, 645-652]. The aims of the present study were to determine the minimum peptide chain length and its location within the 20-mer region that retains potent antifungal activity against Candida albicans and Cryptococcus neoformans and to examine the effect of net charge of the peptide as well as the role of cysteine residues on the fungicidal activity. First, several C-terminal truncated MUC7 20-mer fragments (16-mer, 12-mer, 11-mer, 10-mer and 8-mer) and one N-terminal fragment (8-mer-N) were synthesized and tested. The results showed that MUC7 12-mer, located at the C-terminal region of MUC7 20-mer, having a net charge of +6 and exhibiting an amphipathic helical conformation, not only retained but exceeded the antifungal activity of that of 20-mer. Secondly, several variants of the 12-mer peptide containing a lower or no net positive charge, or no cysteine residues were synthesized and tested. A clear correlation between the net positive charge of the 12-mer, its potency and initial interaction of peptide with fungal cells was found by killing assays, fluorescence microscopy and fungal cell-membrane potential measurements. Furthermore, cysteine residues, which play a critical role in bacterial binding, were found to be not important for the fungicidal activity of these peptides. These results identified MUC7 12-mer as a potential candidate for development into a novel antifungal therapeutic agent.