Implementation Strategies for Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) to Prevent Neonatal Medication-Induced Kidney Injury.

Acute kidney injury (AKI) is a common complication among patients admitted to the neonatal intensive care unit. Nephrotoxic medications (NTMs) are known to increase the incidence of AKI, but the use of these -medications is often unavoidable. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) is a -quality improvement (QI) project that may be implemented at individual institutions and aims to systematically identify AKI in neonates and infants receiving NTMs. The purpose of this review is to describe nephrotoxic AKI in the neonatal population, introduce the Baby NINJA QI project and its potential to reduce neonatal AKI, and outline strategies for effective implementation of Baby NINJA.

Neurokinin-1 receptor antagonists for the prevention of postoperative nausea and vomiting.

Despite the availability of several classes of antiemetics, postoperative nausea and vomiting (PONV) remains a substantial burden for patients following surgery, resulting in patient dissatisfaction and prolonged stays in post-anesthesia care units and ultimately increasing the cost of care. Enhanced recovery protocols and PONV management guidelines are now centered on the assessment of the individual patient's risk for developing PONV, as well as multimodal prophylaxis using antiemetics targeting different mechanisms of action. Over the last two decades, the neurokinin-1 receptor (NK1R) has emerged as a therapeutic target for the management of PONV. This review of the literature explains the role of the NK1R and its ligand-substance P-in vomiting, describes the pharmacologic and pharmacokinetic properties of NK1R antagonists (NK1RAs) and summarizes the clinical evidence supporting NK1RAs for PONV prophylaxis in patients undergoing surgery. In particular, we discuss the therapeutic application of NK1RA in PONV prophylaxis protocols owing to their advantages over other antiemetic classes in efficacy, duration of efficacy, safety, pharmacology, and ease of administration. Future studies will be aimed at further investigating the efficacy and safety of NK1RA-based multimodal combinations, particularly among vulnerable populations (e.g., children and elderly).

Treating Prehospital Pain in Children: A Retrospective Chart Review Comparing the Safety and Efficacy of Prehospital Pediatric Ketamine and Opioid Analgesia.

Prior to 2020, pain management in the Washtenaw/Livingston County Medical Control Authority (W/L MCA) Emergency Medical Service (EMS) system in Southeast Michigan was limited to morphine, fentanyl, ketorolac, and acetaminophen. Based on the increasing evidence describing its safety and efficacy, ketamine was added to local protocols for pain management. This study aimed to evaluate differences in pain management and adverse effects of ketamine and opioid administration. Data from pediatric patients who received ketamine or an opioid in the W/L MCA EMS system from October 2019 to March 2021 were analyzed. The primary outcome was the difference in pain score, and the secondary outcome was adverse effects observed after analgesic administration. The decrease in pain scores was greater among ketamine patients (mean: 5.2) compared to opioid patients (mean: 2.9), p < 0.001. The prevalence of adverse effects was higher among patients in the ketamine group (28.6%) compared to patients in the opioid group (2.4%, p < 0.001). Of 14 patients who received ketamine, one 17-year-old male experienced mild anxiety (7.1%), two teenage females experienced mild dissociation (14.3%), and one 20-year-old female experienced mild nausea (7.1%). Overall, ketamine is a safe and effective option compared to opioids for pediatric patients experiencing moderate to severe prehospital pain.

Comparative Effectiveness of Amiodarone and Lidocaine for the Treatment of In-Hospital Cardiac Arrest.

BACKGROUND: American Heart Association Advanced Cardiac Life Support (ACLS) guidelines support the use of either amiodarone or lidocaine for cardiac arrest caused by ventricular tachycardia or ventricular fibrillation (VT/VF) based on studies of out-of-hospital cardiac arrest. Studies comparing amiodarone and lidocaine in adult populations with in-hospital VT/VF arrest are lacking. RESEARCH QUESTION: Does treatment with amiodarone vs lidocaine therapy have differential associations with outcomes among adult patients with in-hospital cardiac arrest from VT/VF? STUDY DESIGN AND METHODS: This retrospective cohort study of adult patients receiving amiodarone or lidocaine for VT/VF in-hospital cardiac arrest refractory to CPR and defibrillation between January 1, 2000, and December 31, 2014, was conducted within American Heart Association Get With the Guidelines-Resuscitation (GWTG-R) participating hospitals. The primary outcome was return of spontaneous circulation (ROSC). Secondary outcomes were 24 h survival, survival to hospital discharge, and favorable neurologic outcome. RESULTS: Among 14,630 patients with in-hospital VT/VF arrest, 68.7% (n = 10,058) were treated with amiodarone and 31.3% (n = 4,572) with lidocaine. When all covariates were statistically controlled, compared with amiodarone, lidocaine was associated with statistically significantly higher odds of the following: (1) ROSC (adjusted OR [AOR], 1.15, P = .01; average marginal effect [AME], 2.3; 95% CI, 0.5 to 4.2); (2) 24 h survival (AOR, 1.16; P = 004; AME, 3.0; 95% CI, 0.9 to 5.1); (3) survival to discharge (AOR, 1.19; P < .001; AME, 3.3; 95% CI, 1.5 to 5.2); and (4) favorable neurologic outcome at hospital discharge (AOR, 1.18; P < .001; AME, 3.1; 95% CI, 1.3 to 4.9). Results using propensity score methods were similar to those from multivariable logistic regression analyses. INTERPRETATION: Compared with amiodarone, lidocaine therapy among adult patients with in-hospital cardiac arrest from VT/VF was associated with statistically significantly higher rates of ROSC, 24 h survival, survival to hospital discharge, and favorable neurologic outcome.

Safety, Efficacy, and Cost of 0.4-mg Versus 2-mg Intranasal Naloxone for Treatment of Prehospital Opioid Overdose.

BACKGROUND: Intranasal naloxone is commonly used to treat prehospital opioid overdose. However, the optimal dose is unclear, and currently, no study exists comparing the clinical effect of intranasal naloxone at different doses. OBJECTIVE: The goal of this investigation was to compare the safety, efficacy, and cost of 0.4- versus 2-mg intranasal naloxone for treatment of prehospital opioid overdose. METHODS: A retrospective, cross-sectional study was performed of 218 consecutive adult patients receiving intranasal naloxone in 2 neighboring counties in Southeast Michigan: one that used a 0.4-mg protocol and one that used a 2-mg protocol. Primary outcomes were response to initial dose, requirement of additional dosing, and incidence of adverse effects. Unpooled, 2-tailed, 2-sample t-tests and χ2 tests for homogeneity were performed with statistical significance defined as P <0.05. RESULTS: There was no statistically significant difference between the 2 populations in age, mass, gender, proportion of exposures suspected as heroin, response to initial dose, required redosing, or total number of doses by any route. The overall rate of adverse effects was 2.1% under the lower-dose protocol and 29% under the higher-dose protocol (P < 0.001). The lower-dose protocol was 79% less costly. CONCLUSION AND RELEVANCE: Treatment of prehospital opioid overdose using intranasal naloxone at an initial dose of 0.4 mg was equally effective during the prehospital period as treatment at an initial dose of 2 mg, was associated with a lower rate of adverse effects, and represented a 79% reduction in cost.

Optimization of Antibiotic Prophylaxis Delivery for Pediatric Surgical Procedures.

OBJECTIVES: To optimize prophylactic antibiotic timing and delivery across all surgeries performed at a single large pediatric tertiary care center. METHODS: A multidisciplinary surgical quality team conducted a quality improvement initiative from July 2015 to December 2019 by using the A3 problem-solving method to identify and evaluate interventions for appropriate antibiotic administration. The primary outcome measure was the percentage of surgical encounters for pediatric patients with appropriate timing of antibiotic administration before surgical incision. Surgical site infection rates was the secondary outcome. Intervention effectiveness was assessed by using statistical process control. RESULTS: A total of 32 192 eligible surgical cases for pediatric patients were completed during the study period. Identified barriers to timely perioperative antibiotic administration included failure to order antibiotics before the surgical date and lack of antibiotic availability in the operating room at the time of administration. Resulting sequential interventions included updating institutional guidelines to reflect procedure-specific antibiotic choices and clarifying timing of administration to optimize pharmacokinetics, creating a hard-stop antibiotic order within electronic health record case requests, optimizing pharmacy and nursing workflow, and implementing an automatic antibiotic prophylaxis timer in the operating room. Administration of prophylactic antibiotics during the recommended preincision time window significantly improved; the correct timing was recorded in 38.6% of preintervention cases versus 94.0% at the conclusion of rollout of the sequential interventions (P < .001). Surgical site infection rates remained stable. CONCLUSIONS: Here we demonstrate utility of the A3 problem-solving schematic to successfully optimize prophylactic antibiotic timing and delivery in the surgical setting for pediatric patients by implementing systems-based interventions.

Localized Enzyme-Assisted Self-Assembly in the Presence of Hyaluronic Acid for Hybrid Supramolecular Hydrogel Coating.

Hydrogel coating is highly suitable in biomaterial design. It provides biocompatibility and avoids protein adsorption leading to inflammation and rejection of implants. Moreover, hydrogels can be loaded with biologically active compounds. In this field, hyaluronic acid has been largely studied as an additional component since this polysaccharide is naturally present in extracellular matrix. Strategies to direct hydrogelation processes exclusively from the surface using a fully biocompatible approach are rare. Herein we have applied the concept of localized enzyme-assisted self-assembly to direct supramolecular hydrogels in the presence of HA. Based on electronic and fluorescent confocal microscopy, rheological measurements and cell culture investigations, this work highlights the following aspects: (i) the possibility to control the thickness of peptide-based hydrogels at the micrometer scale (18-41 µm) through the proportion of HA (2, 5 or 10 mg/mL); (ii) the structure of the self-assembled peptide nanofibrous network is affected by the growing amount of HA which induces the collapse of nanofibers leading to large assembled microstructures underpinning the supramolecular hydrogel matrix; (iii) this changing internal architecture induces a decrease of the elastic modulus from 2 to 0.2 kPa when concentration of HA is increasing; (iv) concomitantly, the presence of HA in supramolecular hydrogel coatings is suitable for cell viability and adhesion of NIH 3T3 fibroblasts.

Transportation of a commercial premixed intravenous insulin product through a pneumatic tube system.

PURPOSE: Delivery of insulin products via pneumatic tubes is often avoided in health systems, as agitation may cause insulin proteins to destabilize, resulting in loss of function through denaturation, aggregation, or other processes. The actual loss of potency due to delivery via pneumatic tubes has not been reported for new, ready-to-use insulin products. METHODS: Samples were drawn from 7 commercial intravenous (IV) bags containing a 100 units/100 mL premixed solution of regular insulin in sodium chloride injection (Myxredlin, Baxter). The bags were then exposed to 7 unique long-distance pneumatic tube routes. The posttransportation bags were visually inspected for evidence of foaming. Samples were drawn from the posttransportation bags and insulin concentrations were analyzed via an enzyme immunoassay and compared to pretransportation concentrations. RESULTS: All seven posttransportation insulin samples were within 10% of their respective pretransportation sample. No foaming was observed in any of the Myxredlin bags after transportation through the pneumatic tube system. CONCLUSION: Transporting 100 unit/100 mL Myxredlin i.v. bags through a pneumatic tube system does not result in a clinically significant loss of potency. Therefore, delivery of this drug product via a pneumatic tube system to patient care areas can be considered in daily practice.

Low-Dose Ketamine Infusion as Adjuvant Therapy during an Acute Pain Crisis in Pediatric Patients.

Recent studies in pediatric patients have suggested that ketamine, an N-methyl-D-aspartate receptor (NMDA) antagonist, given at sub-anesthetic doses can effectively decrease pain scores, provide analgesic effects, and in some cases, reduce opioid requirements. Our study aims to assess impact of low-dose ketamine on reducing pain scores and total opioid requirements during an acute pain crisis in pediatric patients. From November 2016 to December 2018, eight patients between the ages of 2 and 17 years admitted to the pediatric intensive care unit (PICU) were treated with LDK infusions to manage severe, opioid-refractory, acute pain crises. Subjective pain scores and total morphine milligram equivalent (MME) intake before, during, and after ketamine infusion were collected through a structured chart review. Overall, the addition of ketamine appeared to reduce subjective pain scores and opioid requirements. Two patients were in palliative care and expired shortly after ketamine was started and two patients were discharged within 48 hours of LDK infusion cessation. Ketamine seemed to reduce heart rate and had no appreciable effect on respiratory rate, blood pressure, or oxygen saturation. Hallucination was reported in one patient which resolved upon dose reduction. LDK infusion could be considered as an adjuvant therapy to optimize pain control in pediatric patients experiencing acute pain crises. Further investigation with a larger patient population is warranted to establish the effects of LDK on pain improvement and reducing total opioid requirements.

Supramolecular tripeptide self-assembly initiated at the surface of coacervates by polyelectrolyte exchange.

Spatial control of supramolecular self-assembly can yield compartmentalized structures, a key feature for the design of artificial cells. Inducing self-assembly from and on compartments is still a challenge. Polyelectrolyte complex coacervates are simple model droplet systems able to reproduce the basic features of membrane-less organelles, appearing in cells. Here, we demonstrate the supramolecular self-assembly of a phosphorylated tripeptide, Fmoc-FFpY (Fmoc: fluorenyl-methoxycarbonyl; F: phenyl alanine, pY: phosphorylated tyrosine), on the surface of poly(l-glutamic acid)/poly(allylamine hydrochloride) (PGA/PAH) complex coacervate microdroplets. The phosphorylated peptides self-assemble, without dephosphorylation, through ion pairing between the phosphate groups of Fmoc-FFpY and the amine groups of PAH. This process provides spontaneous capsules formed by an amorphous polyelectrolyte complex core surrounded by a structured peptide/PAH shell. Similar fibrillar Fmoc-FFpY self-assembled structures are obtained at the interface between the peptide solution and a PGA/PAH polyelectrolyte multilayer, a complex coacervate in the thin film or "multilayer" format. In contact with the peptide solution, PAH chains diffuse out of the coacervate or multilayer film and complex with Fmoc-FFpY at the solution interface, exchanging any PGA with which they were associated. Self-assembly of Fmoc-FFpY, now concentrated by complexation with PAH, follows quickly.

Enzyme-assisted self-assembly within a hydrogel induced by peptide diffusion.

The diffusion of adequate peptide through an enzyme-embedded host hydrogel leads to the in situ start-up and growth of an interpenetrated fibrous network. Based on the enzyme-assisted self-assembly concept, both chemistry and mechanical features of the hybrid hydrogel can be tuned.

Piloting Medication Histories in a Pediatric Postanesthesia Care Unit.

PURPOSE: Develop a medication history process for pediatric postanesthesia care unit (PACU) patients to identify discrepancies between home and inpatient medications and prevent medication errors. DESIGN: Pilot an evidence-based practice change to perform PACU medication histories. METHODS: Inpatients or surgical admissions to general care units at a pediatric tertiary care 348-bed hospital ages 2-18 years were included. Parents/guardians were asked about their child's prescription and over-the-counter medications, allergies, and adherence. Data included patient age, surgery, medication categories, and error classifications. Information was compared to the patient's medical record. FINDINGS: From June to July 2016, 75 medication histories were performed, covering 44.6% of eligible cases within the period. Seventy-four discrepancies were found, the most frequent being omission. The medication category with the most errors was vitamins/herbals/supplements. CONCLUSION: The workflow designed assessed discrepancy frequency and type in surgical patients' medication lists when transitioning from the PACU to general care units.

Propofol Drug Shortage Associated With Worse Postoperative Nausea and Vomiting Outcomes Despite a Mitigation Strategy.

Drug shortages negatively affect patient care and outcomes. Postoperative nausea and vomiting (PONV) can be mitigated using risk assessment and prophylaxis. A 2012 propofol shortage provided an opportunity to study the impact of using prophylactic antiemetics and changing the technique from a propofol infusion to inhaled agents in an ambulatory surgery setting. We retrospectively collected data for 2,090 patients regarding PONV risk factors, anesthetic management, and PONV outcomes for periods before, during, and after the shortage. Patients during the propofol shortage experienced a higher incidence of PONV (11% vs 5% before the shortage), greater need for rescue antiemetics (3% vs 1%), and longer duration of stay (mean [SD] = 124 [115] minutes vs 118 [108] minutes). More patients in this group reported PONV at home (14% vs 7%), and 2 required unplanned admission or return to the hospital. During the shortage, patients had a 2-fold increase in the odds of PONV when adjusted for all risk factors. Antiemetics moderated the association between gender and PONV but did not change the effect of the shortage. Findings suggest that despite mitigation efforts, the inability to use propofol infusion was associated with worse PONV outcomes.

Acetaminophen clearance during ex vivo continuous renal replacement therapies.

Intravenous acetaminophen is an adjuvant to opioid use in critically ill and surgical patients requiring continuous renal replacement therapy (CRRT). The objective of this study was to determine the ex vivo transmembrane clearance of intravenous acetaminophen during continuous hemofiltration and hemodialysis. Transmembrane clearance was assessed using a validated ex vivo bovine blood model for CRRT using an F8 or HF1400 hemodiafilter. Ultrafiltrate and dialysate flow rates were 1, 2, and 3 L/h. Urea and acetaminophen clearances were calculated and compared. Acetaminophen was readily cleared by continuous hemofiltration with both hemodiafilters. Acetaminophen clearance rates were 92-98% of ultrafiltrate production rates. Similarly, dialytic acetaminophen clearances approximated dialysate flow rates for both hemodiafilters. Acetaminophen is readily cleared by CRRT. Patients receiving CRRT and acetaminophen may require increased doses for adequate pain control.

Localized Supramolecular Peptide Self-Assembly Directed by Enzyme-Induced Proton Gradients.

Electrodes are ideal substrates for surface localized self-assembly processes. Spatiotemporal control over such processes is generally directed through the release of ions generated by redox reactions occurring specifically at the electrode. The so-used gradients of ions proved their effectiveness over the last decade but are in essence limited to material-based electrodes, considerably reducing the scope of applications. Herein is described a strategy to enzymatically generate proton gradients from non-conductive surfaces. In the presence of oxygen, immobilization of glucose oxidase (GOx) on a multilayer film provides a flow of protons through enzymatic oxidation of glucose by GOx. The confined acidic environment located at the solid-liquid interface allows the self-assembly of Fmoc-AA-OH (Fmoc=fluorenylmethyloxycarbonyl and A=alanine) dipeptides into ß-sheet nanofibers exclusively from and near the surface. In the absence of oxygen, a multilayer nanoreactor containing GOx and horseradish peroxidase (HRP) similarly induces Fmoc-AA-OH self-assembly.

Control of Surface-Localized, Enzyme-Assisted Self-Assembly of Peptides through Catalyzed Oligomerization.

Localized self-assembly allowing both spatial and temporal control over the assembly process is essential in many biological systems. This can be achieved through localized enzyme-assisted self-assembly (LEASA), also called enzyme-instructed self-assembly, where enzymes present on a substrate catalyze a reaction that transforms noninteracting species into self-assembling ones. Very few LEASA systems have been reported so far, and the control of the self-assembly process through the surface properties represents one essential step toward their use, for example, in artificial cell mimicry. Here, we describe a new type of LEASA system based on α-chymotrypsin adsorbed on a surface, which catalyzes the production of (KL)nOEt oligopeptides from a KLOEt (K: lysine; L: leucine; OEt ethyl ester) solution. When a critical concentration of the formed oligopeptides is reached near the surface, they self-assemble into ß-sheets resulting in a fibrillar network localized at the interface that can extend over several micrometers. One significant feature of this process is the existence of a lag time before the self-assembly process starts. We investigate, in particular, the effect of the α-chymotrypsin surface density and KLOEt concentration on the self-assembly kinetics. We find that the lag time can be finely tuned through the surface density in α-chymotrypsin and KLOEt concentration. For a given surface enzyme concentration, a critical KLOEt concentration exists below which no self-assembly takes place. This concentration increases when the surface density in enzyme decreases.

Variability in Threshold for Medication Error Reporting Between Physicians, Nurses, Pharmacists, and Families.

BACKGROUND: Voluntary medication error reporting is an imperfect resource used to improve the quality of medication administration. It requires judgment by front-line staff to determine how to report enough to identify opportunities to improve patients' safety but not jeopardize that safety by creating a culture of "report fatigue." OBJECTIVE: This study aims to provide information on interpretability of medication error and the variability between the subgroups of caregivers in the hospital setting. METHODS: Survey participants included nursing, physician (trainee and graduated), patient/families, pharmacist across a large academic health system, including an attached free-standing pediatric hospital. Demographics and survey questions were collected and analyzed using Fischer's exact testing with SAS v9.3. RESULTS: Statistically significant variability existed between the four groups for a majority of the questions. This included all cases designated as administration errors and many, but not all, cases of prescribing events. Commentary provided in the free-text portion of the survey was sub-analyzed and found to be associated with medication allergy reporting and lack of education surrounding report characteristics. CONCLUSION: There is significant variability in the threshold to report specific medication errors in the hospital setting. More work needs to be done to further improve the education surrounding error reporting in hospitals for all noted subgroups.