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Objective: To study the applicability of on table extubation (OTE) protocol following congenital cardiac surgery in a low-resource setting and its impact on the length of intensive care unit (ICU) stay, hospital stay, hospitalization cost, parental anxiety, and nurse anxiety. Materials and Methods: In this prospective, nonrandomized, observational single-center study, we included all children above 1 year of age undergoing congenital cardiac surgery. We evaluated them for the feasibility of OTE using a prespecified protocol following separation from cardiopulmonary bypass. The data were prospectively collected on 60 children more than 1 year of age, belonging to the Risk Adjustment for Congenital Heart Surgery 1, 2, 3, and 4 groups and divided into two groups: those who underwent successful OTE and those who were ventilated for any duration postoperatively (30 children in each group). Duration of hospital stay, ICU stay, and total hospital cost were collected. Anxiety levels of the primary caregiver (nurse) in the ICU and the mother were assessed immediately after the arrival of the child in the ICU using the State Trait Anxiety Inventory (STAI). Results: Children who were extubated immediately following congenital cardiac surgery had significantly shorter ICU stay (median 20 [19, 22] h vs. 22 [20, 43] h [P < 0.05]). Patients extubated on table had a significant reduction in hospital cost {median Rs. 161,000 (138,330; 211,900), approximately USD 1970 (P < 0.05)} when compared to children who were ventilated postoperatively {median Rs. 201,422 (151,211; 211,900), approximately USD 2464}. The anxiety level in mothers was significantly less when their child was extubated in the operating room (STAI 36.5 ± 5.4 vs. 47.4 ± 7.4, P < 0.001). However, for the same subset of patients, anxiety level was significantly higher in the ICU nurse (STAI 46.0 ± 5.6 vs. 37.8 ± 4.1, P < 0.05). Conclusion: OTE following congenital cardiac surgery is associated with a shorter duration of ICU stay and hospital stay. It also reduces the total hospital cost and the anxiety level in mothers of children undergoing congenital heart surgery. However, the primary bedside caregiver during the child's ICU stay had increased anxiety managing patients with OTE. [ABSTRACT FROM AUTHOR]

During agonist stimulation of airway smooth muscle (ASM), agonists such as ACh induce a transient increase in cytosolic Ca2+ concentration ([Ca2+ ]cyt), which leads to a contractile response [excitation-contraction (E-C) coupling]. Previously, the sensitivity of the contractile response of ASM to elevated [Ca2+ ]cyt (Ca2+ sensitivity) was assessed as the ratio of maximum force to maximum [Ca2+ ]cyt. However, this static assessment of Ca2+ sensitivity overlooks the dynamic nature of E-C coupling in ASM. In this study, we simultaneously measured [Ca2+ ]cyt and isometric force responses to three concentrations of ACh (1, 2.6, and 10 μM). Both maximum [Ca2+ ]cyt and maximum force responses were ACh concentration dependent, but force increased disproportionately, thereby increasing static Ca2+ sensitivity. The dynamic properties of E-C coupling were assessed in several ways. The temporal delay between the onset of ACh-induced [Ca2+ ]cyt and onset force responses was not affected by ACh concentration. The rates of rise of the ACh-induced [Ca2+ ]cyt and force responses increased with increasing ACh concentration. The integral of the phase-loop plot of [Ca2+ ]cyt and force from onset to steady state also increased with increasing ACh concentration, whereas the rate of relaxation remained unchanged. Although these results suggest an ACh concentration-dependent increase in the rate of cross-bridge recruitment and in the rate of rise of [Ca2+ ]cyt, the extent of regulatory myosin light-chain (rMLC20) phosphorylation was not dependent on ACh concentration. We conclude that the dynamic properties of [Ca2+ ]cyt and force responses in ASM are dependent on ACh concentration but reflect more than changes in the extent of rMLC20 phosphorylation. [ABSTRACT FROM AUTHOR]

Background: The electronic health record (EHR) is a contributor to serious patient harm occurring within a sociotechnical system. Chemotherapy ordering is a high‐risk task due to the complex nature of ordering workflows and potential detrimental effects if wrong chemotherapeutic doses are administered. Many chemotherapy ordering errors cannot be mitigated through systems‐based changes due to the limited extent to which individual institutions are able to customize proprietary EHR software. We hypothesized that simulation‐based training could improve providers' ability to identify and mitigate common chemotherapy ordering errors. Methods: Pediatric hematology/oncology providers voluntarily participated in simulations using an EHR testing ("Playground") environment. The number of safety risks identified and mitigated by each provider at baseline was recorded. Risks were reviewed one‐on‐one after initial simulations and at a group "lunch‐and‐learn" session. At three‐month follow‐up, repeat simulations assessed for improvements in error identification and mitigation, and providers were surveyed about prevention of real‐life safety events. Results: The 8 participating providers identified and mitigated an average of 5.5 out of 10 safety risks during the initial simulation, compared 7.4 safety risks at the follow up simulation (p=0.030). Two of the providers (25%) reported preventing at least one real‐world patient safety event in the clinical setting as a result of the initial training session. Conclusions: Simulation‐based training may reduce providers' susceptibility to chemotherapy ordering safety vulnerabilities within the EHR. This approach may be used when systems‐based EHR improvements are not feasible due to limited ability to customize local instances of proprietary EHR software. [ABSTRACT FROM AUTHOR]

Rewarming the intact heart after a period of hypothermia is associated with reduced myocardial contractility, decreased Ca2+ sensitivity, and increased cardiac troponin-I (cTnI) phosphorylation. We hypothesized that hypothermia/rewarming (H/R) induces left ventricular (LV) contractile dysfunction due to phosphorylation of cTnI at Ser23/24. To test this hypothesis, the response of wild-type mice (n = 7) to H/R was compared with transgenic (TG) mice expressing slow skeletal TnI (TG-ssTnI; n = 7) that lacks the Ser23/24 phosphorylation sites. Hypothermia was induced by surface cooling and maintained at 23-25°C for 3 h. Subsequently, the animals were rewarmed to 37°C. LV systolic and diastolic function was assessed using a 1.4 F pressure-volume Millar catheter introduced via the right carotid artery. At baseline conditions, there were no significant differences in LV systolic function between wild-type and TG-ssTnI mice, whereas measurements of diastolic function [isovolumic relaxation constant and end-diastolic pressure-volume relationship (EDPVR)] were significantly (P < 0.05) reduced in TGssTnI animals. Immediately after rewarming, significant differences between groups were found in cardiac output (CO; wild-type 6.6 ± 0.7 vs. TG-ssTnI 8.8 ± 0.7 mL/min), stroke work (SW; wildtype 796 ± 112 vs. TG-ssTnI 1208 ± 67 mmHg/L), and the preload recruited stroke work (PRSW; wild-type 38.3 ± 4.9 vs. TG-ssTnI 68.8 ± 8.2 mmHg). However, EDPVR and τ returned to control levels within 1 h in both groups. We conclude that H/R-induced LV systolic dysfunction results from phosphorylation of cTnI at Ser23/24. [ABSTRACT FROM AUTHOR]

Familial hypertrophic cardiomyopathy (FHC) is a disease caused by mutations in contractile proteins of the sarcomere. Our laboratory developed a mouse model of FHC with a mutation in the thin filament protein α-tropomyosin (TM) at amino acid 180 (Glu180Gly). The hearts of these mice exhibit dramatic systolic and diastolic dysfunction, and their myofilaments demonstrate increased calcium sensitivity. The mice also develop severe cardiac hypertrophy, with death ensuing by 6 mo. In an attempt to normalize calcium sensitivity in the cardiomyofilaments of the hypertrophic mice, we generated a chimeric α-/β-TM protein that decreases calcium sensitivity in transgenic mouse cardiac myofilaments. By mating mice from these two models together, we tested the hypothesis that an attenuation of myofilament calcium sensitivity would modulate the severe physiological and pathological consequences of the FHC mutation. These double-transgenic mice "rescue" the hypertrophic phenotype by exhibiting a normal morphology with no pathological abnormalities. Physiological analyses of these rescued mice show improved cardiac function and normal myofilament calcium sensitivity. These results demonstrate that alterations in calcium response by modification of contractile proteins can prevent the pathological and physiological effects of this disease. [ABSTRACT FROM AUTHOR]

Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function. [ABSTRACT FROM AUTHOR]

Objectives: The American College of Surgeons Trauma Quality Improvement Program (TQIP) and Committee on Trauma released a best practice guideline for palliative care in trauma patients in 2017. Utilization of pediatric palliative care services for pediatric trauma patients has not been studied. We sought to identify patients who received the consultation and develop criteria for patients who would benefit from these resources at our institution., Methods: The institutional pediatric trauma registry was queried to identify all admissions age 0-17 years old to the pediatric intensive care unit (PICU) or trauma ICU (TICU) from 2014 to 2021. Demographic and clinical features were obtained from the registry. Electronic medical records were reviewed to identify and review consultations to the ComPASS team. A clinical practice guideline (CPG) for palliative care consultations was developed based on the TQIP guideline and applied retrospectively to patients admitted 2014-2021. The CPG was then prospectively applied to patients admitted from March through November 2022., Results: A total of 399 patients were admitted to the PICU/TICU. There were 30 (7.5%) deaths, 20 (66.7%) within 24 hours of admission. Palliative care consultations were obtained in 21 (5.3%). Of these, 10 (47.6%) patients were infants/toddlers

Cardiovascular instability and reduced oxygenation are regular perioperative critical events associated with anesthesia requiring intervention in neonates and young infants. This review article addresses the current modalities of assessing this population's adequate end-organ perfusion in the perioperative period. Assuring adequate tissue oxygenation in critically ill infants is based on parameters that measure acceptable macrocirculatory hemodynamic parameters such as vital signs (mean arterial blood pressure, heart rate, urinary output) and chemical parameters (lactic acidosis, mixed venous oxygen saturation, base deficit). Microcirculation assessment represents a promising candidate for assessing and improving hemodynamic management strategies in perioperative and critically ill populations. Evaluation of the functional state of the microcirculation can parallel improvement in tissue perfusion, a term coined as "hemodynamic coherence". Less information is available to assess microcirculatory disturbances related to higher mortality risk in critically ill adults and pediatric patients with septic shock. Techniques for measuring microcirculation have substantially improved in the past decade and have evolved from methods that are limited in scope, such as velocity-based laser Doppler and near-infrared spectroscopy, to handheld vital microscopy (HVM), also referred to as videomicroscopy. Available technologies to assess microcirculation include sublingual incident dark field (IDF) and sublingual sidestream dark field (SDF) devices. This chapter addresses (1) the physiological basis of microcirculation and its relevance to the neonatal and pediatric populations, (2) the pathophysiology associated with altered microcirculation and endothelium, and (3) the current literature reviewing modalities to detect and quantify the presence of microcirculatory alterations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Arteaga and Crow.)

During agonist stimulation of airway smooth muscle (ASM), agonists such as ACh induce a transient increase in cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ), which leads to a contractile response [excitation-contraction (E-C) coupling]. Previously, the sensitivity of the contractile response of ASM to elevated [Ca 2+ ] cyt (Ca 2+ sensitivity) was assessed as the ratio of maximum force to maximum [Ca 2+ ] cyt . However, this static assessment of Ca 2+ sensitivity overlooks the dynamic nature of E-C coupling in ASM. In this study, we simultaneously measured [Ca 2+ ] cyt and isometric force responses to three concentrations of ACh (1, 2.6, and 10 μM). Both maximum [Ca 2+ ] cyt and maximum force responses were ACh concentration dependent, but force increased disproportionately, thereby increasing static Ca 2+ sensitivity. The dynamic properties of E-C coupling were assessed in several ways. The temporal delay between the onset of ACh-induced [Ca 2+ ] cyt and onset force responses was not affected by ACh concentration. The rates of rise of the ACh-induced [Ca 2+ ] cyt and force responses increased with increasing ACh concentration. The integral of the phase-loop plot of [Ca 2+ ] cyt and force from onset to steady state also increased with increasing ACh concentration, whereas the rate of relaxation remained unchanged. Although these results suggest an ACh concentration-dependent increase in the rate of cross-bridge recruitment and in the rate of rise of [Ca 2+ ] cyt , the extent of regulatory myosin light-chain (rMLC 20 ) phosphorylation was not dependent on ACh concentration. We conclude that the dynamic properties of [Ca 2+ ] cyt and force responses in ASM are dependent on ACh concentration but reflect more than changes in the extent of rMLC 20 phosphorylation.

Background: Although electronic health records (EHRs) are designed to improve patient safety, they have been associated with serious patient harm. An agreed-upon and standard taxonomy for classifying health information technology (HIT) related patient safety events does not exist., Objectives: We aimed to develop and evaluate a taxonomy for medication-related patient safety events associated with HIT and validate it using a set of events involving pediatric patients., Methods: We performed a literature search to identify existing classifications for HIT-related safety events, which were assessed using real-world pediatric medication-related patient safety events extracted from two sources: patient safety event reporting system (ERS) reports and information technology help desk (HD) tickets. A team of clinical and patient safety experts used iterative tests of change and consensus building to converge on a single taxonomy. The final devised taxonomy was applied to pediatric medication-related events assess its characteristics, including interrater reliability and agreement., Results: Literature review identified four existing classifications for HIT-related patient safety events, and one was iteratively adapted to converge on a singular taxonomy. Safety events relating to usability accounted for a greater proportion of ERS reports, compared with HD tickets (37 vs. 20%, p  = 0.022). Conversely, events pertaining to incorrect configuration accounted for a greater proportion of HD tickets, compared with ERS reports (63 vs. 8%, p  < 0.01). Interrater agreement (%) and reliability (kappa) were 87.8% and 0.688 for ERS reports and 73.6% and 0.556 for HD tickets, respectively., Discussion: A standardized taxonomy for medication-related patient safety events related to HIT is presented. The taxonomy was validated using pediatric events. Further evaluation can assess whether the taxonomy is suitable for nonmedication-related events and those occurring in other patient populations., Conclusion: Wider application of standardized taxonomies will allow for peer benchmarking and facilitate collaborative interinstitutional patient safety improvement efforts., Competing Interests: None declared., (Thieme. All rights reserved.)

Pediatric Fundamental Critical Care Support (PFCCS) is an educational tool for training non-intensivists, nurses, and critical care practitioners in diverse health-care settings to deal with the acute deterioration of pediatric patients. Our objective was to evaluate the PFCCS course as a tool for developing a uniform, reproducible, and sustainable model for educating local health-care workers in the optimal management of critically ill children in the Republic of Georgia. Over a period of 18 months and four visits to the country, we worked with Georgian pediatric critical care leadership to complete the following tasks: (1) survey health-care needs within the Republic of Georgia, (2) present representative PFCCS lectures and simulation scenarios to evaluate interest and obtain "buy-in" from key stakeholders throughout the Georgian educational infrastructure, and (3) identify PFCCS instructor candidates. Georgian PFCCS instructor training included the following steps: (1) US PFCCS consultant and content experts presented PFCCS course to Georgian instructor candidates. (2) Simulation learning principles were taught and basic equipment was acquired. (3) Instructor candidates presented PFCCS to Georgian learners, mentored by PFCCS course consultants. Objective evaluation and debriefing with instructor candidates concluded each visit. Between training visits Georgian instructors translated PFCCS slides to the Georgian language. Six candidates were identified and completed PFCCS instructor training. These Georgian instructors independently presented the PFCCS course to 15 Georgian medical students. Student test scores improved significantly from pretest results ( n  = 14) (pretest: 38.7 ± 7 vs. posttest 62.7 ± 6, p  < 0.05). A Likert-type scale of 1 to 5 (1 = not useful or effective, 5 = extremely useful or effective) was used to evaluate each student's perception regarding (1) relevance of course content to clinical work students rated as median (IQR): (a) relevance of PFCCS content to clinical work, 5 (4-5); (b) effectiveness of lecture delivery, 4 (3-4); and (c) value of skill stations for clinical practice, 5 (4-5). Additionally, the mean (±SD) responses were 4.6 (±0.5), 3.7 (±0.6), and 4.5 (±0.6), respectively. Training local PFCCS instructors within an international environment is an effective method for establishing a uniform, reproducible, and sustainable approach to educating health-care providers in the fundamentals of pediatric critical care. Future collaborations will evaluate the clinical impact of PFCCS throughout the Georgian health-care system.

Resident participation in international health electives (IHEs) has been shown to be beneficial, yet not all residents have the opportunity to participate. We sought to determine whether participating in simulated global health cases, via the standardized Simulation Use for Global Away Rotations (SUGAR) curriculum, was useful for all pediatric residents, not merely those planning to go on an IHE. Pediatric residents in our program took part in 2 SUGAR cases and provided feedback via an online survey. Thirty-six of 40 residents participated (90%); 72% responded to the survey. Three of 10 residents not previously planning to work in resource-limited settings indicated participation in SUGAR made them more likely to do so. Nearly all residents (88%) felt SUGAR should be part of the residency curriculum. All felt better prepared for working cross-culturally. While designed to prepare trainees for work in resource-limited settings, SUGAR may be beneficial for all residents., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: With increasing complexity of critical care medicine comes an increasing need for multidisciplinary involvement in care. In many institutions, pharmacists are an integral part of this team, but long-term data on the interventions performed by pharmacists and their effects on patient care and outcomes are limited. We aimed to describe the role of pediatric clinical pharmacists in pediatric intensive care unit (PICU) practice., Methods: We retrospectively reviewed the records of pharmacy interventions in the PICU at the Mayo Clinic in Rochester, Minnesota, from 2003-2013, with a distinct period of increased pharmacist presence in the PICU from 2008 onward. We compared demographic and outcome data on patients who did and who did not have pharmacy interventions during 2 periods (2003-2007 and 2008-2013)., Results: We identified 27,773 total interventions by pharmacists during the 11-year period, of which 79.8% were accepted by the clinical team. These interventions were made on 10,963 unique PICU admissions and prevented 5867 order entry errors. Pharmacists' interventions increased year over year, including a significant change in 2008. Patients who required pharmacy involvement were younger, sicker, and had longer intensive care unit, hospital, and ventilator duration. Average central line infections and central line entry rates decreased significantly over the study period., Conclusions: Increased pharmacist presence in the PICU is associated with increased interventions and prevention of adverse drug events. Pharmacist participation during rounds and order entry substantially improved the care of critically sick children and should be encouraged.

Tropomyosin (TM) is involved in Ca(2+)-mediated muscle contraction and relaxation in the heart. Striated muscle alpha-TM is the major isoform expressed in the heart. The expression of striated muscle beta-TM in the murine myocardium results in a decreased rate of relaxation and increased myofilament Ca(2+) sensitivity. Replacing the carboxyl terminus (amino acids 258-284) of alpha-TM with beta-TM (a troponin T-binding region) results in decreased rates of contraction and relaxation in the heart and decreased myofilament Ca(2+) sensitivity. We hypothesized that the putative internal troponin T-binding domain (amino acids 175-190) of beta-TM may be responsible for the increased myofilament Ca(2+) sensitivity observed when the entire beta-TM is expressed in the heart. To test this hypothesis, we generated transgenic mice that expressed chimeric TM containing beta-TM amino acids 175-190 in the backbone of alpha-TM (amino acids 1-174 and 191-284). These mice expressed 16-57% chimeric TM and did not develop cardiac hypertrophy or any other morphological changes. Physiological analysis showed that these hearts exhibited decreased rates of contraction and relaxation and a positive response to isoproterenol. Skinned fiber bundle analyses showed a significant increase in myofilament Ca(2+) sensitivity. Biophysical experiments demonstrated that the exchanged amino acids did not influence the flexibility of the TM. This is the first study to demonstrate that a specific domain within TM can increase the Ca(2+) sensitivity of the thin filament and affect sarcomeric performance. Furthermore, these results enhance the understanding of why TM mutations associated with familial hypertrophic cardiomyopathy demonstrate increased myofilament sensitivity to Ca(2+).

Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.

Beta-adrenergic stimulation of the heart results in an enhanced relaxation rate in association with phosphorylation of both cardiac troponin I (cTnI) and phospholamban (PLB). We studied new lines of mice generated by crossbreeding mice that express slow skeletal troponin I (ssTnI) with PLB knockout (PLBKO) mice. This crossbreeding resulted in the generation of PLB/cTnI, PLB/ssTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. Perfusion with isoproterenol (ISO) significantly increased the peak amplitude of fura-2 ratio in PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI groups of mice. However, in the presence of ISO, there were no differences in the peak amplitude of fura-2 ratio among cells isolated from hearts of PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. In cells from PLB/cTnI mice, the extent of shortening was increased and the time of relaxation was significantly decreased during beta-adrenergic stimulation. In PLBKO/cTnI cells, stimulation with ISO resulted in an increased extent of shortening and no change in time of relaxation. However, stimulation with ISO in cells isolated from PLBKO/ssTnI mice not only significantly increased the extent of cell shortening but also increased the time of relaxation. We also determined the kinetics of relaxation of papillary muscles isolated from all four groups of animals in the presence and absence of ISO. Perfusion with ISO increased the rate of relaxation only in PLB/cTnI, PLB/ssTnI, and PLBKO/cTnI muscles. During ISO stimulation, the time of relaxation was unchanged in PLBKO/ssTnI muscles. Our data directly demonstrate that phosphorylation of both PLB and cTnI contributes to increased rate of relaxation during beta-adrenergic stimulation.