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51.
Purpose
The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness. The critically ill population presents challenges when titrating infusions of sedatives and analgesics to maintain optimal sedation and pain levels. This systematic review examined the PK data in critically ill adult patients with prolonged infusions (>24 hours) of commonly used sedatives and analgesics to highlight possible altered PK parameters compared with noncritically ill patients.Methods
A literature search of PK studies was performed by using MEDLINE (1946–December 2017) and EMBASE (1910–December 2017); we identified further studies by citation tracking (Web of Science) and checked references of retrieved studies and review articles. All studies were included that were published in English, Chinese, or German; conducted in critically ill adult patients receiving lorazepam, midazolam, propofol, dexmedetomidine, sufentanil, alfentanil, remifentanil, morphine, or fentanyl infusion for ≥24 hours; and reported PK parameters. When appropriate, we conducted a meta-analysis on volume of distribution at steady state (Vdss) (liters), clearance (Cl) (liters per hour), and elimination t1/2 (hours) by using a DerSimonian-Laird random effects model to estimate the summary mean and 95% CIs. Results were compared with commonly reported PK ranges in 70-kg noncritically ill patients.Findings
Thirty-three randomized controlled trials and prospective cohort studies were identified involving 1803 adult critically ill patients with 35 drug treatment arms: fifteen midazolam (n?=?906) studies, three dexmedetomidine (n?=?561), nine propofol (n?=?165), four lorazepam (n?=?86), one morphine (n?=?20), two remifentanil (n?=?55), and one sufentanil (n?=?10). Each study showed large variations in Vdss, Cl, and elimination t1/2 within and between individual participants. High clinical and methodical heterogeneity between the dexmedetomidine studies prevented the direct comparison of PK parameters between critically ill and noncritically ill patients. Use of midazolam, propofol, and lorazepam in critically ill patients was associated with at least a 2- to 4-fold increase in Vdss compared with noncritically ill patients; Cl decreased ~2-fold for midazolam and 10-fold for morphine. Critically ill patients receiving prolonged infusions of midazolam, propofol, remifentanil, and sufentanil had at least 2-fold longer elimination or terminal t1/2 than noncritically ill patients.Implications
These findings show a marked difference in many PK parameters from those reported for noncritically ill patients. Initiatives to improve the delivery of prolonged sedatives and analgesic infusions should be informed by PK parameters (Vdss, context-sensitive t1/2, and elimination t1/2) and data derived from critically ill patients. 相似文献52.
Susanna K.P. Lau Alan K.L. Wu Jade L.L. Teng Herman Tse Shirly O.T. Curreem Stephen K.W. Tsui Yi Huang Jonathan H.K. Chen Rodney A. Lee Kwok-Yung Yuen Patrick C.Y. Woo 《Emerging infectious diseases》2015,21(2):232-241
Elizabethkingia anophelis, recently discovered from mosquito gut, is an emerging bacterium associated with neonatal meningitis and nosocomial outbreaks. However, its transmission route remains unknown. We use rapid genome sequencing to investigate 3 cases of E. anophelis sepsis involving 2 neonates who had meningitis and 1 neonate’s mother who had chorioamnionitis. Comparative genomics revealed evidence for perinatal vertical transmission from a mother to her neonate; the 2 isolates from these patients, HKU37 and HKU38, shared essentially identical genome sequences. In contrast, the strain from another neonate (HKU36) was genetically divergent, showing only 78.6% genome sequence identity to HKU37 and HKU38, thus excluding a clonal outbreak. Comparison to genomes from mosquito strains revealed potential metabolic adaptations in E. anophelis under different environments. Maternal infection, not mosquitoes, is most likely the source of neonatal E. anophelis infections. Our findings highlight the power of genome sequencing in gaining rapid insights on transmission and pathogenesis of emerging pathogens. 相似文献
53.
Bazoukis George Tyrovolas Konstantinos Letsas Konstantinos P. Vlachos Konstantinos Radford Danny Chung Cheuk To Liu Tong Efremidis Michael Tse Gary Baranchuk Adrian 《Heart failure reviews》2022,27(6):2067-2076
Heart Failure Reviews - Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital heart disease with autosomal dominant inheritance. This review aims to summarize the existing data... 相似文献
54.
The effects of manganese chloride (MnCl2) and verapamil on automaticity of digitlazied Purkinje fibers were studied using conventional microelectrode techniques. The stduied wer made in isolated, spontaneously beating Purkinje prearations. Quabain alone consistently increased the automatic rate, whereas no such increase was observed when the preparations were superfused with a mixture of ouabain adn MnCl2. MnCl2 was also shown to be effective is suppressing the enhanced automaticity induced by ouabain. Mncl2 alone did not have a significant effect on the spontaneous rate of Purkinje fibers. The effect of verapamil was similar to that of MnCl2 in preventing and suppressing the ouabain-induced increase in automaticity. MnCl2 and verapamil have been shown to inhibt tha slow inward calcium current of cardiac fibers. The results therefore suggest that an inward calcium ion current may play a role in the development of digitalis-induced increase in the stope of phase 4 depolarization in Purkinje fibers. 相似文献
55.
56.
Internal cardioversion is safe and effective in restoring sinus rhythm, even in patients with persistent AF of prolonged duration. Up to 40% to 50% of patients with AF lasting >1 year but <3 years could be maintained in sinus rhythm using a class III antiarrhythmic drug after successful internal cardioversion, and amiodarone appears to be more effective than sotalol in this patient population. 相似文献
57.
J. A. Kaupp M. Y. Tse S. C. Pang G. Kenworthy M. Hetzler S. D. Waldman 《Annals of biomedical engineering》2013,41(6):1106-1119
Tissue engineering is a promising approach for articular cartilage repair. However, using current technologies, the developed engineered constructs generally do not possess an organized superficial layer, which contributes to the tissue’s durability and unique mechanical properties. In this study, we investigated the efficacy of applying a moving point of contract-type stimulation (MPS) to stimulate the production of a superficial-like layer in the engineered constructs. MPS was applied to chondrocyte-agarose hydrogels at a frequency of 0.5, 1 or 2 Hz, under a constant compressive load of 10 mN for durations between 5 and 60 min over 3 consecutive days. Expression and localization of superficial zone constituents was conducted by qRT-PCR and in situ hybridization. Finite element modeling was also constructed to gain insight into the relationship between the applied stimulus and superficial zone constituent expression. Gene expression of superficial zone markers were affected in a frequency dependent manner with a physiologic frequency of 1 Hz producing maximal expression of PRG4, biglycan, decorin and collagen II. In situ hybridization revealed that localization of these markers predominantly occurred at 500–1000 μm below the construct surface which correlated to sub-surface strains between 10 and 25% as determined by finite element modeling. These results indicate that while mechanical stimuli can be used to enhance the expression of superficial zone constituents in engineered cartilage constructs, the resultant subsurface loading is a critical factor for localizing expression. Future studies will investigate altering the applied stimulus to further localize superficial zone constituent expression at the construct surface. 相似文献
58.
59.
60.
Ni Sann Khin Sze Huey Tan Michael LC Wang Tian Rui Siow Faye LWT Lim Fu Qiang Wang Matthew CH Ng Justina YC Lam Connie Yip 《The British journal of radiology》2021,94(1122)
Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC. 相似文献