Dexmedetomidine administration is associated with improved outcomes in critically ill patients with acute myocardial infarction partly through its anti-inflammatory activity
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC11375293 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background: Patients with myocardial infarction (MI) in intensive care units (ICU) are at high risk of death. Whether treatment with ondansetron (OND) at an early stage plays a protective role in critically ill patients with MI and its underlying mechanism remains unclear. Methods: A total of 4486 patients with MI were enrolled in the study cohort from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into OND-medication groups or not. Propensity score matching (PSM) and regression analysis were performed to investigate the effect of OND on patients, accompanied by sensitivity analysis to evaluate the robustness of the results. Integrated with causal mediation analysis (CMA), we investigated the potential causal pathway mediated by the palate-to-lymphocyte ratio (PLR) between early OND treatment and clinical outcomes. Results: Among patients with MI, 976 of them were treated with OND at the early stage while 3510 patients were not. The all-cause in-hospital mortality rate was significantly lower in the OND-medication group (5.6% vs 7.7%), accompanied by lower 28-day mortality (7.8% vs 11.3%) and 90-day mortality (9.2% vs 13.1%) rates. PSM analysis further confirmed the results for in-hospital mortality (5.7% vs 8.0%), 28-day mortality (7.8% vs 10.8%), and 90-day mortality (9.2% vs 12.5%). After adjusting for confounders, multivariate logistic regression analysis revealed that OND was associated with decreased in-hospital mortality (OR = 0.67, 95% CI: 0.49-0.91), and Cox regression confirmed the results for 28-day mortality and 90-day mortality with HR = 0.71 and 0.73, respectively. Most importantly, CMA demonstrated that the protective effect of OND on patients with MI was mediated by its anti-inflammatory effect through the regulation of PLR. Conclusion: Early use of OND in critically ill patients with MI may exert protective effects by reducing in-hospital mortality and 28- and 90-day mortality. The beneficial effects of OND on these patients were exerted through anti-inflammatory effects, at least in part.
| S-EPMC10198140 | biostudies-literature
Project description:BackgroundMyocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients.MethodsThe Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out.ResultsThis study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results.ConclusionThiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.
| S-EPMC10497214 | biostudies-literature
Project description:Background and objectivesAlthough the pharmacokinetics of dexmedetomidine in healthy volunteers have been studied, there are limited data about the pharmacokinetics of long-term administration of dexmedetomidine in critically ill patients.MethodsThis population pharmacokinetic analysis was performed to quantify the pharmacokinetics of dexmedetomidine in critically ill patients following infusions up to 14 days in duration. The data consisted of three phase III studies (527 patients with sparse blood sampling, for a total of 2,144 samples). Covariates were included in a full random-effects covariate model and the most important covariate relationships were tested separately. The linearity of dexmedetomidine clearance was evaluated by observing steady-state plasma concentrations acquired at various infusion rates.ResultsThe data were adequately described with a one-compartment model. The clearance of dexmedetomidine was 39 (95 % CI 37-41) L/h and volume of distribution 104 (95 % CI 93-115) L. Both clearance and volume of distribution were highly variable between patients (coefficients of variation of 62 and 57 %, respectively), which highlights the importance of dose titration by response. Covariate analysis showed a strong correlation between body weight and clearance of dexmedetomidine. The clearance of dexmedetomidine was constant in the dose range 0.2-1.4 μg/kg/h.ConclusionsThe pharmacokinetics of dexmedetomidine are dose-proportional in prolonged infusions when dosing rates of 0.2-1.4 μg/kg/h, recommended by the Dexdor(®) summary of product characteristics, are used.
| S-EPMC3717151 | biostudies-literature
Project description:ObjectiveTo evaluate the incidence of fever in critically ill pediatric patients receiving continuously infused dexmedetomidine.MethodsThis was a retrospective study of pediatric patients admitted to the pediatric or neonatal intensive care unit (PICU or NICU) between November 2017 and December 2021 who received dexmedetomidine. The primary endpoint was defined as a fever ≥38°C while receiving dexmedetomidine. Patient- and drug-specific characteristics between the fever and non-fever groups were compared to identify possible trends.ResultsA total of 151 patients were included, with a median age of 15.8 months (IQR, 2.9-48.1). Thirteen patients (8.6%) met the criteria for the primary endpoint, with a mean maximum temperature of 38.2°C ± 0.2°C. Median time of fever onset was 9.7 hours (IQR, 2.0-29.3) into their dexmedetomidine infusion with a median dose of 0.4 mcg/kg/hr (IQR, 0.2-0.6). Patients within the fever group were younger (1.7 months [IQR, 1.1-8.6] vs 17.3 months [IQR, 3.3-65.5], p = 0.0006), reached a higher maximum infusion rate (0.8 mcg/kg/hr [IQR, 0.6-0.9] vs 0.6 mcg/kg/hr [IQR, 0.4-0.8], p = 0.0343), and received dexmedetomidine for longer durations (83.2 hours [IQR, 64.2-128.3] vs 35.2 hours [IQR, 17.6-55.7], p < 0.0001) than the non-fever group.ConclusionsFever ≥38°C was observed in 8.6% of PICU and NICU patients receiving dexmedetomidine. Younger patients or those exposed to higher doses or longer durations of dexmedetomidine may be at increased risk. Prospective studies will be required to further validate these findings.
| S-EPMC11809539 | biostudies-literature
Project description:Dexmedetomidine is a highly selective central α2-agonist used as a sedative in pediatric intensive care unit (PICU). However, little is known about the relationship between dexmedetomidine dose and its plasma concentration during long-term infusion. We have previously demonstrated that the sedative plasma dexmedetomidine concentration is moderately correlated with the administered dose in adults (r = 0.653, P = 0.001). We hypothesized that there would be a similar relationship between the sedative dexmedetomidine concentration and administered dose in infants.All patients admitted to the PICU at Nagoya City University Hospital, Japan, between November 2012 and March 2013 were eligible for inclusion in the study. Plasma dexmedetomidine concentration was measured by ultra-performance liquid chromatography coupled with tandem mass spectrometry.We measured the plasma dexmedetomidine concentration in 203 samples from 45 patients. Of these, 96 samples collected from 27 patients < 2 years old were included in this study. All patients received dexmedetomidine at 0.12-1.40 µg/kg/h. The median administration duration was 87.6 hours (range: 6-540 hours). Plasma dexmedetomidine concentration ranged from 0.07 to 3.17 ng/ml. Plasma dexmedetomidine concentration was not correlated with the administered dose (r = 0.273, P = 0.007). The approximate linear equation was y = 0.690x + 0.423.In infants, plasma dexmedetomidine concentration did not exhibit any correlation with administered dose, which is not a reliable means of obtaining optimal plasma concentration.
| S-EPMC5548945 | biostudies-other
Project description:BackgroundMalnutrition is common in patients with acute myocardial infarction (AMI) and is associated with a poor prognosis. The prognostic value of the prognostic nutritional index (PNI) in patients with AMI remains controversial. We aimed to explore the relationship between PNI and all-cause mortality in critically ill patients with AMI and evaluate the incremental prognostic value of PNI to commonly used prognostic assessment tools.MethodsThe Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was used to conduct a retrospective cohort analysis on 1180 critically ill patients with AMI. The primary endpoints were defined as 6-month and 1-year all-cause mortality. Cox regression analysis was used to investigate the relationship between admission PNI and all-cause mortality. The effect of adding PNI to sequential organ failure assessment (SOFA) score, or charlson comorbidity index (CCI) on its discriminative ability was assessed using C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).ResultsMultivariate cox regression analysis demonstrated that the low PNI was regarded as an independent predictor of 1-year all-cause mortality in AMI patients admitted to ICU (adjusted Hazard Ratio: 95% CI = 1.75 (1.22-2.49)). The ROC test showed that admission PNI had a moderate predictive ability to predict all-cause mortality of critically ill patients with AMI. Furthermore, the net reclassification and integrated discrimination of the CCI alone model improved significantly with PNI. [C-statistic increased from 0.669 to 0.752, p < 0.001; NRI = 0.698, p < 0.001; IDI = 0.073, p < 0.001]. When PNI was added to the SOFA score, the C-statistic significantly improved from 0.770 to 0.805 (p < 0.001), and the NRI and IDI were estimated at 0.573 (p < 0.001) and 0.041 (p < 0.001), respectively.ConclusionPNI could be a novel predictor for identifying patients at high risk of 1-year all-cause mortality in critically ill patients with AMI. The addition of PNI to the SOFA score or CCI may be useful for very early risk stratification.
| S-EPMC10318819 | biostudies-literature
Project description:OBJECTIVES: In critically ill patients with neurologic disease, pupil examination abnormalities can signify evolving intracranial pathology. Analgesic and sedative medications (analgosedatives) target pupillary pathways, but it remains unknown how analgosedatives alter pupil findings in the clinical care setting. We assessed dexmedetomidine and other analgosedative associations with pupil reactivity and size in a heterogeneous cohort of critically ill patients with acute intracranial pathology. DESIGN: Retrospective cohort study. SETTING: Two neurologic ICUs between 2016 and 2018. PATIENTS: Critically ill adult patients with pupil measurements within 60 minutes of analgosedative administration. Patients with a history of intrinsic retinal pathology, extracranial injury, inaccessible brain imaging, or no Glasgow Coma Scale (GCS) data were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used mixed-effects linear regression accounting for intrapatient correlations and adjusting for sex, age, GCS score, radiographic mass effect, medication confounders, and ambient light. We tested the association between an initiation or increased IV infusion of dexmedetomidine and pupil reactivity (Neurologic Pupil Index [NPi]) and resting pupil size (mm) obtained using NeurOptics NPi—200 (NeurOptics, Irvine, CA) pupillometer. Of our 221 patients with 9,897 pupil observations (median age, 60 [interquartile range, 50–68]; 59% male), 37 patients (166 pupil observations) were exposed to dexmedetomidine. Dexmedetomidine was associated with higher average NPi (β = 0.18 per 1 unit increase in rank-normalized NPi ± 0.04; p < 0.001) and smaller pupil size (β = –0.25 ± 0.05; p < 0.001). Exploratory analyses revealed that acetaminophen was associated with higher average NPi (β = 0.04 ± 0.02; p = 0.02) and that most IV infusion analgosedatives including propofol, fentanyl, and midazolam were associated with smaller pupil size. CONCLUSIONS: Dexmedetomidine is associated with higher pupil reactivity (high NPi) and smaller pupil size in a cohort of critically ill patients with neurologic injury. Familiarity with expected pupil changes following analgosedative administration is important for accurate interpretation of pupil examination findings, facilitating optimal management of patients with acute intracranial pathology.
| S-EPMC9243241 | biostudies-literature
Project description:CCN3 administration after surgically induced myocardial infarction
2023-02-27 | GSE217925 | GEO
Project description:BackgroundInflammation plays a critical role in acute myocardial infarction (AMI). Recent studies have shown the value of hematologic indicators in MI risk stratification and prognostic assessment. However, the association between lymphocyte-to-monocyte ratio (LMR) and the long-term mortality of critically ill MI patients remains unclear.MethodsClinical data were extracted from the Medical Information Mart for Intensive Care III database. Patients diagnosed with AMI on admission in the intensive care units were include. The optimal cutoff value of LMR was determined by X-tile software. The Cox proportional hazard model was applied for the identification of independent prognostic factors of 1-year mortality and survival curves were estimated using the Kaplan-Meier method. In order to reduce selection bias, a 1:1 propensity score matching (PSM) method was performed.ResultsA total of 1517 AMI patients were included in this study. The cutoff value for 1-year mortality of LMR determined by X-Tile software was 3.00. A total of 534 pairs of patients were matched after PSM. Multivariate analysis (HR = 1.369, 95%CI 1.110-1.687, P = 0.003) and PSM subgroups (HR = 1.299, 95%CI 1.032-1.634, P = 0.026) showed that 1-year mortality was significantly higher in patients with LMR < 3.00 than patients with LMR ≥ 3.00 in Cox proportional hazard models. The survival curves showed that patients with LMR < 3.00 had a significantly lower 1-year survival rate before (63.83 vs. 81.03%, Log rank P < 0.001) and after PSM (68.13 vs. 74.22%, Log rank P = 0.041).ConclusionIn this retrospective cohort analysis, we demonstrated that a low admission LMR (< 3.00) was associated with a higher risk of 1-year mortality in critically ill patients with AMI.
| S-EPMC9264617 | biostudies-literature
Project description:IntroductionOnly limited information exists on the pharmacokinetics of prolonged (> 24 hours) and high-dose dexmedetomidine infusions in critically ill patients. The aim of this study was to characterize the pharmacokinetics of long dexmedetomidine infusions and to assess the dose linearity of high doses. Additionally, we wanted to quantify for the first time in humans the concentrations of H-3, a practically inactive metabolite of dexmedetomidine.MethodsThirteen intensive care patients with mean age of 57 years and Simplified Acute Physiology Score (SAPS) II score of 45 were included in the study. Dexmedetomidine infusion was commenced by using a constant infusion rate for the first 12 hours. After the first 12 hours, the infusion rate of dexmedetomidine was titrated between 0.1 and 2.5 μg/kg/h by using predefined dose levels to maintain sedation in the range of 0 to -3 on the Richmond Agitation-Sedation Scale. Dexmedetomidine was continued as long as required to a maximum of 14 days. Plasma dexmedetomidine and H-3 metabolite concentrations were measured, and pharmacokinetic variables were calculated with standard noncompartmental methods. Safety and tolerability were assessed by adverse events, cardiovascular signs, and laboratory tests.ResultsThe following geometric mean values (coefficient of variation) were calculated: length of infusion, 92 hours (117%); dexmedetomidine clearance, 39.7 L/h (41%); elimination half-life, 3.7 hours (38%); and volume of distribution during the elimination phase, 223 L (35%). Altogether, 116 steady-state concentrations were found in 12 subjects. The geometric mean value for clearance at steady state was 53.1 L/h (55%). A statistically significant linear relation (r2 = 0.95; P < 0.001) was found between the areas under the dexmedetomidine plasma concentration-time curves and cumulative doses of dexmedetomidine. The elimination half-life of H-3 was 9.1 hours (37%). The ratio of AUC0-∞ of H-3 metabolite to that of dexmedetomidine was 1.47 (105%), ranging from 0.29 to 4.4. The ratio was not statistically significantly related to the total dose of dexmedetomidine or the duration of the infusion.ConclusionsThe results suggest linear pharmacokinetics of dexmedetomidine up to the dose of 2.5 μg/kg/h. Despite the high dose and prolonged infusions, safety findings were as expected for dexmedetomidine and the patient population.Trial registrationClinicalTrials.gov: NCT00747721.
| S-EPMC3334808 | biostudies-literature