Analgesia and sedation are integral to the care of critically ill children. However, the choice and dose of the analgesic or sedative drug is often empiric, and models predicting favorable responses ...are lacking. We aimed to compute models to predict a patient's response to intravenous morphine.
We retrospectively analyzed data from consecutive patients admitted to the Cardiac Intensive Care Unit (January 2011-January 2020) who received at least one intravenous bolus of morphine. The primary outcome was a decrease in the State Behavioral Scale (SBS) ≥1 point; the secondary outcome was a decrease in the heart rate Z-score (zHR) at 30 min. Effective doses were modeled using logistic regression, Lasso regression, and random forest modeling.
A total of 117,495 administrations of intravenous morphine among 8140 patients (median age 0.6 years interquartile range IQR 0.19, 3.3) were included. The median morphine dose was 0.051 mg/kg (IQR 0.048, 0.099) and the median 30-day cumulative dose was 2.2 mg/kg (IQR 0.4, 15.3). SBS decreased following 30% of doses, did not change following 45%, and increased following 25%. The zHR significantly decreased after morphine administration (median delta-zHR -0.34 IQR-1.03, 0.00, p < 0.001). The following factors were associated with favorable response to morphine: A concomitant infusion of propofol, higher prior 30-day cumulative dose, being invasively ventilated and/or on vasopressors. Higher morphine dose, higher zHR pre-morphine, an additional analgosedation bolus ±30 min around the index bolus, a concomitant ketamine or dexmedetomidine infusion, and showing signs of withdrawal syndrome were associated with unfavorable response. Logistic regression (area under the receiver operating characteristic ROC curve AUC 0.900) and machine learning models (AUC 0.906) performed comparably, with a sensitivity of 95%, specificity of 71%, and negative predictive value of 97%.
Statistical models identify 95% of effective intravenous morphine doses in pediatric critically ill cardiac patients, while incorrectly suggesting an effective dose in 29% of cases. This work represents an important step toward computer-aided, personalized clinical decision support tool for sedation and analgesia in ICU patients.
Oxygen delivery using engineered microparticles Seekell, Raymond P.; Lock, Andrew T.; Peng, Yifeng ...
Proceedings of the National Academy of Sciences - PNAS,
11/2016, Letnik:
113, Številka:
44
Journal Article
Recenzirano
Odprti dostop
A continuous supply of oxygen to tissues is vital to life and interruptions in its delivery are poorly tolerated. The treatment of low-blood oxygen tensions requires restoration of functional airways ...and lungs. Unfortunately, severe oxygen deprivation carries a high mortality rate and can make otherwise-survivable illnesses unsurvivable. Thus, an effective and rapid treatment for hypoxemia would be revolutionary. The i.v. injection of oxygen bubbles has recently emerged as a potential strategy to rapidly raise arterial oxygen tensions. In this report, we describe the fabrication of a polymer-based intravascular oxygen delivery agent. Polymer hollow microparticles (PHMs) are thin-walled, hollow polymer microcapsules with tunable nanoporous shells. We show that PHMs are easily charged with oxygen gas and that they release their oxygen payload only when exposed to desaturated blood. We demonstrate that oxygen release from PHMs is diffusion-controlled, that they deliver approximately five times more oxygen gas than human red blood cells (per gram), and that they are safe and effective when injected in vivo. Finally, we show that PHMs can be stored at room temperature under dry ambient conditions for at least 2 mo without any effect on particle size distribution or gas carrying capacity.
The aim of this work was to determine whether intratumoral injections of a liquid oxygen solution are effective at boosting radiation-induced abscopal effects.
A liquid oxygen solution, comprising ...slow-release polymer-shelled oxygen microparticles, was fabricated and injected intratumorally to locally elevate tumor oxygen levels before and after treatment with radiation therapy. Changes in tumor volume were monitored. In a subset of studies, CD8-positive cells were depleted and the experiments were repeated. Histologic analyses of the tumor tissues were performed to quantify the concentration of infiltrating immune cells.
Daily intratumoral injections of oxygen-filled microparticles significantly retarded primary and secondary tumor growth, boosted infiltration of cytotoxic T cells, and improved overall survival when used as an adjuvant to radiation therapy. The findings also demonstrated that efficacy requires both radiation and oxygen, suggesting that they act synergistically to enhance in situ vaccination and systemic antitumor immune responses.
This study demonstrated the potential advantages of intratumoral injections of a liquid oxygen solution as a strategy to boost radiation-induced abscopal effects, and the findings warrant future efforts toward clinical translation of the injectable liquid oxygen solution.
SignificanceThe treatment of hypoxemia that is refractory to the current standard of care is time-sensitive and requires skilled caregivers and use of specialized equipment (e.g., extracorporeal ...membrane oxygenation). Most patients experiencing refractory hypoxemia will suffer organ dysfunction, and death is common in this cohort. Here, we describe a new strategy to stabilize and support patients using a microfluidic device that administers oxygen gas directly to the bloodstream in real time and on demand using a process that we call sequential shear-induced bubble breakup. If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.
Intravascular oxygen delivery holds great potential to treat numerous hypoxic conditions and emergencies, including pulmonary disorders, hypoxic tumors, hemorrhagic shock, stroke, cardiac arrest and ...so on. Tremendous effort has been made in the past to find material solutions for the development of intravenous oxygen carriers and have ranged from blood substitutes to microbubbles with limited success. This paper highlights previous and recent progress in perfluorocarbon‐emulsions and microbubbles as intravenous gas carriers, including concerns over their long‐term stability, in vivo safety profiles, and oxygen transport efficacy. Their use as potential resuscitative therapeutics for treating various types of cardiac arrest is also discussed.
Injectable oxygen: In this concept article, different biomaterials strategies to incorporate oxygen gas as injectable resuscitative therapeutics are discussed and compared, including perfluorocarbon emulsions and microbubbles stabilized by lipids and degradable polymers.
Over the past decade, there have been many attempts to engineer systems capable of delivering oxygen to overcome the effects of both systemic and local hypoxia that occurs as a result of traumatic ...injury, cell transplantation, or tumor growth, among many others. Despite progress in this field, which has led to a new class of oxygen-generating biomaterials, most reported techniques lack the tunability necessary for independent control over the oxygen flux (volume per unit time) and the duration of delivery, both of which are key parameters for overcoming tissue hypoxia of varying etiologies. Here, we show that these critical parameters can be effectively manipulated using hyperbarically-loaded polymeric microcapsules (PMC). PMCs are micron-sized particles with hollow cores and polymeric shells. We show that oxygen delivery through PMCs is dependent on its permeability through the polymeric shell, the shell thickness, and the pressure gradient across the shell. We also demonstrate that incorporating an intermediate oil layer between the polymeric shell and the gas core prevents rapid outgassing by effectively lowering the resultant pressure gradient across the polymeric membrane following depressurization.
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•Oxygen delivery from hyperbarically-loaded polymer microcapsules is feasible.•Oxygen loading and release kinetics from hyperbaric PMCs are highly tunable•PMCs incorporating an intermediate oil layer can be loaded at significantly higher pressures and exhibit greater control over oxygen release compared to their gas-filled counterparts.
To characterize the socioeconomic and racial and/or ethnic disparities impacting the diagnosis and outcomes of multisystem inflammatory syndrome in children (MIS-C).
This multicenter retrospective ...case-control study was conducted at 3 academic centers from January 1 to September 1, 2020. Children with MIS-C were compared with 5 control groups: children with coronavirus disease 2019, children evaluated for MIS-C who did not meet case patient criteria, children hospitalized with febrile illness, children with Kawasaki disease, and children in Massachusetts based on US census data. Neighborhood socioeconomic status (SES) and social vulnerability index (SVI) were measured via a census-based scoring system. Multivariable logistic regression was used to examine associations between SES, SVI, race and ethnicity, and MIS-C diagnosis and clinical severity as outcomes.
Among 43 patients with MIS-C, 19 (44%) were Hispanic, 11 (26%) were Black, and 12 (28%) were white; 22 (51%) were in the lowest quartile SES, and 23 (53%) were in the highest quartile SVI. SES and SVI were similar between patients with MIS-C and coronavirus disease 2019. In multivariable analysis, lowest SES quartile (odds ratio 2.2 95% confidence interval 1.1-4.4), highest SVI quartile (odds ratio 2.8 95% confidence interval 1.5-5.1), and racial and/or ethnic minority background were associated with MIS-C diagnosis. Neither SES, SVI, race, nor ethnicity were associated with disease severity.
Lower SES or higher SVI, Hispanic ethnicity, and Black race independently increased risk for MIS-C. Additional studies are required to target interventions to improve health equity for children.
Abstract Background Measurement of cerebral venous oxyhemoglobin saturation (ScvO2 ) is considered a gold standard in assessing the adequacy of tissue oxygen delivery (DO2 ) after the stage 1 ...palliation (S1P), with SvO2 <30% often representing severely compromised DO2 . Regional oxygenation index (rSO2 ) based on near-infrared resonance spectroscopy (NIRS) frequently is used to screen for compromised DO2 , although its sensitivity to detect severe abnormalities in SvO2 is uncertain. Methods ScvO2 was measured by co-oximetry from the internal jugular vein as clinically indicated in 73 neonates after S1P. These values were compared with cerebral rSO2 (FORE-SIGHT; CASMED) via mixed effects model linear regression, Bland-Altman analysis, and sensitivity analysis. Because NIRS devices measure a composite of arterial and venous blood, we calculated an rSO2 -based ScvO2 designed to remove arterial contamination from the rSO2 signal: rSO2 -based ScvO2 = (rSO2 − arterial oxygen saturation × 0.3)/0.7. Results Among 520 time-matched pairs of ScvO2 and cerebral rSO2 , the slope of the relationship between rSO2 and ScvO2 (after we adjusted for effects of hemoglobin) was 0.37 ± 0.04 with only modest correlation (r2 = 0.39), and mean bias of +8.26. When ScvO2 was <30%, cerebral rSO2 was <30 in less than 1%, <40 less than 1%, and <50 in 45.7% of data points; specificity of rSO2 in the same range is >99%. Correction of rSO2 for arterial contamination significantly decreased mean bias (+3.03) and improved the sensitivity of rSO2 to detect ScvO2 <30 to 6.5% for rSO2 <30, 29% for rSO2 <40, and 77.4% for rSO2 <50. Conclusions Cerebral rSO2 in isolation should not be used to detect low ScvO2 , because its sensitivity is low, although correction of rSO2 for arterial contamination may improve sensitivity. Cerebral rSO2 of 50 or greater should not be considered reassuring, though values below 30 are specific for low ScvO2.
Background Troponin levels are frequently obtained in pediatric patients, but the benefit remains unclear. Methods and Results This retrospective study included 1993 patients aged 0 to 21 years ...without history of cardiac disease in whom troponin levels were obtained during clinical evaluation of cardiac and noncardiac presentations. Troponin was elevated (≥0.1 ng/mL) in 182 patients (9%). A cardiac diagnosis was made in 109 (60%) of those with elevated troponin and in 208 (12%) of those without (
<0.001). The positive predictive value of elevated troponin for a cardiac diagnosis was 60% for the entire cohort and 85% for patients with a cardiac presentation. The negative predictive value of nonelevated troponin was 89% for the entire cohort and 96% in patients without a cardiac presentation. Serial testing did not improve these predictive values. However, among 404 patients with initially nonelevated levels who had serial measurements, subsequent elevation was found in 80 (20%), of whom 15 (19%) had a cardiac diagnosis. The optimal troponin cutoff value to differentiate cardiac from noncardiac diagnosis was higher in children aged <3 months (0.045 ng/mL) compared with those aged ≥3 months (0.005 ng/mL). Conclusions Troponin can be a useful adjunctive test in the evaluation of children when the differential diagnosis includes cardiac etiologies. Serial measurement was not helpful when troponin was elevated at presentation but may merit consideration when the initial level is not elevated and there is ongoing concern about cardiac involvement. Lower reference values may be appropriate when evaluating children in contrast to adults.
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