A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy.

INTRODUCTION: Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort. METHODS: We performed a retrospective analysis of all patients <18 years of age admitted to an academic quaternary care children's hospital from 2017-2022 who received epoprostenol, heparin, or citrate exclusively for CRRT anticoagulation. Efficacy was evaluated by comparing the hours to the first unintended filter change and the ratio of filters used to CRRT days. Safety was assessed by evaluating changes in platelet count and vasoactive-ionotropic score (VIS). RESULTS: Of 101 patients, 44 received epoprostenol (43.6%), 38 received heparin (37.6%), and 19 received citrate (18.8%). The first filter change was more commonly planned in patients receiving anticoagulation with epoprostenol (43%) as compared to citrate (11%) or heparin (29%) (p=0.034). Of those patients where the first filter change was unintended (n=33), there were greater median hours until the filter was replaced in those receiving epoprostenol (29) when compared to citrate (21) (p=0.002) or heparin (18) (p=0.003). There was a smaller median ratio of filters used to days on therapy in the patients that received epoprostenol (0.53) when compared to citrate (1) (p=0.003) or heparin (0.75) (p=0.001). For those receiving epoprostenol, there was no significant decrease in platelet count when comparing values prior to CRRT initiation through 7 days of therapy. There was no significant difference in VIS when comparing values prior to CRRT initiation through the first 2 days of CRRT. CONCLUSIONS: Epoprostenol-based anticoagulation is effective when compared to other anticoagulation strategies used in pediatric CRRT with a favorable side effect profile.

Therapeutic review: The role of tranexamic acid in management of traumatic brain injury, nontraumatic intracranial hemorrhage, and aneurysmal subarachnoid hemorrhage.

PURPOSE: To summarize current literature evaluating tranexamic acid in the management of intracranial bleeding associated with traumatic and nontraumatic brain injuries and implications for clinical practice. SUMMARY: Intracranial hemorrhage, regardless of etiology, is associated with high morbidity and mortality. Tranexamic acid is an antifibrinolytic with anti-inflammatory properties shown to reduce mortality in trauma patients with extracranial injuries. In traumatic brain injury, a large randomized trial found no difference in outcomes when tranexamic acid was compared to placebo; however, subgroup analyses suggested that it may reduce head injury-related mortality in the context of mild-to-moderate injury if treatment occurs within 1 hour of symptom onset. More recent out-of-hospital data have disputed these findings and even suggested harm in severely injured patients. In spontaneous, nontraumatic intracranial hemorrhage, treatment with tranexamic acid did not result in a difference in functional status; however, rates of hematoma expansion, even though modest, were significantly reduced. In aneurysmal subarachnoid hemorrhage, tranexamic acid may prevent rebleeding, but has not led to improved outcomes or reduced mortality, and there is concern for increased incidence of delayed cerebral ischemia. Overall, tranexamic acid has not been shown to result in increased risk of thromboembolic complications across these classes of brain injury. CONCLUSION: Despite its favorable safety profile overall, tranexamic acid does not seem to improve functional outcomes and cannot be routinely recommended. More data are needed to determine which head injury subpopulations are most likely to benefit from tranexamic acid and which patients are at increased risk for harm.

Reduction in Antibiotic Delivery Time Following Improving Pediatric Sepsis Outcomes Quality Improvement Initiative at a Major Children's Hospital.

OBJECTIVE: Sepsis causes morbidity and mortality in pediatric patients, but timely antibiotic administration can improve sepsis outcomes. The pharmacy department can affect the time from order to delivery of antibiotics. By evaluating the pharmacy process, this study aimed to decrease the time from antibiotic order to delivery to within 45 minutes. METHODS: All antibiotic orders placed following a positive sepsis screen for acute care patients at a freestanding children's hospital from April 1, 2019, to December 31, 2019, were reviewed. Lean Six Sigma methodology including process mapping was used to identify and implement improvements, including educational interventions for providers. Outcome measures included time from antibiotic order placement to delivery and to administration. Additional assessment of process measures included evaluation of order priority, PowerPlan (an internally created order set) use, and delivery method. RESULTS: Ninety-eight antibiotic orders for 85 patients were evaluated. In an individual chart of antibiotic delivery time, a trend towards faster delivery time was observed after interventions. Stat orders (40.5 minutes [IQR, 19.5-48]) were delivered more quickly than routine orders (51 minutes [IQR, 45-65]; p < 0.001). Orders using the PowerPlan (20.5 minutes [IQR, 18.5-38]) were delivered more quickly than those that did not (47 minutes [IQR, 34-64]; p < 0.01). Shorter time to administration was observed with pneumatic tube delivery (41 minutes [IQR, 20-50]) than with direct delivery to a health care provider (51 minutes [IQR, 31-83]; p < 0.05) or to the automated dispensing cabinet's refrigerator (47 minutes [IQR, 41-62]; p < 0.0001). CONCLUSIONS: Multifactorial coordinated interventions within the pharmacy department improve medication delivery time for pediatric sepsis antibiotic orders.

Medication Use as a Contributor to Fluid Overload in the PICU: A Prospective Observational Study.

In this prospective observational study, we explored the association of daily fluid intake from medication use with fluid overload in 75 children beginning 24 hours after intubation. The mean percent daily fluid intake from medications was 29% in the overall cohort. Excess intake and inadequate output contributed significantly to fluid overload. In the 28 patients who became ≥10% fluid overloaded, the mean percent daily fluid intake from medications was 34%, but just 23% in the patients who did not. Awareness of volume contribution and maximized concentration of parenteral medications when able may lessen the burden of fluid overload.

Case Study of High-Dose Ketamine for Treatment of Complex Regional Pain Syndrome in the Pediatric Intensive Care Unit.

Complex regional pain syndrome (CRPS) is a life-altering and debilitating chronic pain condition. The authors are presenting a case study of a female who received high-dose ketamine for the management of her CRPS. The innovative treatment lies not only within the pharmacologic management of her pain, but also in the fact that she was the first patient to be admitted to our pediatric intensive care unit solely for pain control. The primary component of the pharmacotherapy treatment strategy plan was escalating-dose ketamine infusion via patient-controlled-analgesia approved by the pharmacy and therapeutics committee guided therapy for this patient. The expertise of advanced practice nurses blended exquisitely to ensure patient and family-centered care and the coordination of care across the illness trajectory. The patient experienced positive outcomes.

A Quality Assessment of a Collaborative Model of a Pediatric Antimicrobial Stewardship Program.

BACKGROUND: Infectious Diseases Society of America guidelines recommend that key antimicrobial stewardship program (ASP) personnel include an infectious disease (ID) physician leader and dedicated ID-trained clinical pharmacist. Limited resources prompted development of an alternative model by using ID physicians and service-based clinical pharmacists at a pediatric hospital. The aim of this study was to analyze the effectiveness and impact of this alternative ASP model. METHODS: The collaborative ASP model incorporated key strategies of education, antimicrobial restriction, day 3 audits, and practice guidelines. High-use and/or high-cost antimicrobial agents were chosen with audits targeting vancomycin, caspofungin, and meropenem. The electronic medical record was used to identify patients requiring day 3 audits and to communicate ASP recommendations. Segmented regression analyses were used to analyze quarterly antimicrobial agent prescription data for the institution and selected services over time. RESULTS: Initiation of ASP and day 3 auditing was associated with blunting of a preexisting increasing trend for caspofungin drug starts and use and a significant downward trend for vancomycin drug starts (relative change -12%) and use (-25%), with the largest reduction in critical care areas. Although meropenem use was already low due to preexisting requirements for preauthorization, a decline in drug use (-31%, P = .021) and a nonsignificant decline in drug starts (-21%, P = .067) were noted. A 3-month review of acceptance of ASP recommendations found rates of 90%, 93%, and 100% for vancomycin, caspofungin, and meropenem, respectively. CONCLUSIONS: This nontraditional ASP model significantly reduced targeted drug usage demonstrating acceptance of integration of service-based clinical pharmacists and ID consultants.

Implementation of a standardized process for ordering and dispensing of high-alert emergency medication infusions.

OBJECTIVES: Pharmacies encounter challenges when ensuring safe, timely medication dispensing to patients in the pediatric intensive care unit, when high-alert medications are needed in emergent situations. Removal of these medications from nursing stock presented challenges to providing timely administration to critical patients. The project's purpose was to develop a new method for reducing dispensing time while improving patient safety in pediatric intensive care units. METHODS: A committee of physicians, nurses, a clinical pharmacist, and pharmacy administration collaborated for process development. The process established a list of compounded, ready-to-use infusions stored in the pharmacy, immediately available for dispensing. The dispensing mechanism includes ordering and dispensing processes using an "Urgent Drip Request" form. Most frequently ordered infusions (dopamine, epinephrine, norepinephrine) were added to automated dispensing cabinets in critical care units in concentrations that could be safely infused centrally or peripherally. RESULTS: During the initial 4 months, 71 "Urgent Drip Request" sheets were processed. Drug utilization evaluation demonstrated a dispensing time of less than 1 minute for drip medications leaving the pharmacy after the form was received. No sheets processed exceeded the institutional 30-minute turnaround time, nor were errors or delays documented. Limited turnaround time data existed preimplementation but was not robust enough for analysis. It was not ethically feasible to perform a head-to-head comparison with the previous method, as it might have resulted in delay of therapy and negative patient outcomes. CONCLUSIONS: This program allows high-alert medication infusion availability in an expedited manner, removes potential for compounding errors at the bedside, and assures clean room preparation. This has improved pharmacy efficiency in provision of safe patient care to critically ill pediatric patients.

Linezolid and lactic acidosis: a role for lactate monitoring with long-term linezolid use in children.

Linezolid administration has been associated with lactic acidosis in adults; however, the same phenomenon has not been reported in children. Mitochondrial protein synthesis inhibition is a demonstrated mechanism for toxicity, which therefore may manifest as lactic acidosis. Three cases of linezolid-associated lactic acidosis in children are reported to reinforce the need for pediatric caregivers to be vigilant of this potential side effect.