Amikacin population pharmacokinetics among paediatric burn patients

Introduction

The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.

Methods

Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10–20 mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.

Results

The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean C_max was 33.2 ± 9.4 μg/mL and the mean C_min was 3.8 ± 4.6 μg/mL. The final covariate model estimated clearance as 5.98 L/h/70 kg (4.97–6.99, 95% CI), the volume of distribution in the central compartment as 16.7 L/70 kg (14.0–19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1 L/70 kg (15.0–80.4, 95% CI), and the inter-compartmental clearance as 3.38 L/h/70 kg (2.44–4.32, 95% CI). In multivariate analyses, current weight (P < 0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.

Discussion

Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.     

Perineal burn care: French working group recommendations

Objectives

Burns to the perineum are frequently exposed to faeces. Diverting colostomy is often described to prevent faecal soiling. Because this technique is invasive with frequent complications, use of non-surgical devices including specifically designed faecal management systems has been reported in perineal burns.

Methods

In order to standardise the faecal management strategy in patients with perineal burns, a group of French experts was assembled. This group first evaluated the ongoing practice in France by analysing a questionnaire sent to every French burn centre. Based on the results of this study and on literature data, the experts proposed recommendations on the management of perineal burns in adults.

Results

Specifically designed faecal management systems are the first-line method to divert faeces in perineal burns. The working group proposed recommendations and an algorithm to assist in decisions in the management of perineal burns in four categories of patients, depending on total burn skin area, depth and extent of the perineal burn.

Conclusion

In France, non-surgical devices are the leading means of faecal diversion in perineal burns. The proposed algorithm may assist in decisions in the management of perineal burns. The expert group emphasises that large clinical studies are needed to better evaluate these devices.     

Variation in acute fluid resuscitation among pediatric burn centers

BackgroundAccurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.MethodsFive pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.ResultsDifferences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35 ml/kg/% TBSA, p < 0.001), (4.90 versus 6.35 ml/kg/TBSA, p = 0.002) and (3.38 versus 6.35 ml/kg/TBSA, p < 0.0001).ConclusionsThis variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.     

急性重度眼烧伤135例临床分析

目的了解急性重度眼烧伤的临床特点、预后及并发症发生情况。方法对笔者单位病案室保存的1977--2002年住院眼烧伤患者135例（155只眼）的病历进行回顾性统计分析。分析不同深度、原因眼烧伤的眼表修复率、修复时间、致盲情况及并发症。结果治疗后Ⅲ度眼烧伤的修复时间短于Ⅳ度眼烧伤，其修复率也明显高于Ⅳ度眼烧伤（P〈0．01）；在不能修复的Ⅳ度眼烧伤中，酸烧伤致角膜穿孔6只眼，显著高于碱烧伤（1只眼，P〈0．05）。Ⅲ度眼烧伤视力≥0．05者有38只眼，〈0．05者51只眼；Ⅳ度眼烧伤视力≥0．05者0只眼，〈0．05着66只眼。78只酸、碱烧伤眼中，52只眼致盲，致盲率为66．7％；77只热烧伤眼中，65只眼致盲，致盲率为84．4％。Ⅲ度眼烧伤的并发症发生率低于Ⅳ度眼烧伤。其中Ⅲ度眼烧伤角膜穿孔、睑球粘连的发生率（1．1％、36．O％）均显著低于Ⅳ度眼烧伤（27．3％、59．1％，P〈0．01）。在酸烧伤患者中，角膜穿孔及睑外翻的发生率（29．2％、37．5％）较高。而热烧伤患者中眼睑球粘连的发生率（53．2％）较高。结论Ⅳ度眼烧伤伤后的预后差，致盲率高。目前的治疗方法尚不能完全改善其视功能及预后，有待进一步研究。     

MEBO联合ADM治愈大面积深度烧伤并发多部位骨外露1例报告

目的观察湿润烧伤膏(Moist Exposed Burn Ointment,MEBO)联合猪脱细胞真皮基质(Acellular Dermis Matrix,ADM)治疗大面积深度烧伤并发多部位骨外露的临床疗效。方法对宁夏医科大学附属石嘴山市第一人民医院烧伤科收治的1例大面积烧伤并发多部位骨外露患者在抗感染、营养支持等全身综合治疗的同时,烧伤早期对深度烧伤创面进行常规切痂+自体微粒皮移植+ADM覆盖治疔;治疗3周后,见双侧髌骨、胫骨、内外踝骨及跖骨大部分骨质外露,行外露骨面电钻打孔,ADM覆盖与MEBO涂抹治疗,观察治疗效果。结果患者于入院治疗242 d后,外露骨面全部封闭,创面痊愈出院;出院后随访3个月,创面愈合良好,双下肢上抬可达75°,双膝关节屈曲可达45°,能够搀扶站立,恢复了部分肢体功能。结论 MEBO联合ADM治疗大面积深度烧伤并发多部位骨外露,创面愈合良好,能够避免截肢,且在最大程度上保留患者肢体功能,疗效显著,值得临床推广应用。     

内毒素增敏系统与严重烧伤脓毒症的关系及其临床意义

目的 探讨严重烧伤患者内毒素增敏系统--脂多糖结合蛋白/脂多糖受体CD14(LBP/CD14)的变化与严重脓毒症的关系及其临床意义.方法 选择35例烧伤体表总面积大于30%患者,根据烧伤脓毒症的定义和诊断标准分为脓毒症组(19例)和非脓毒症组(16例),应用酶联免疫吸附试验检测患者烧伤后1、3、5、7、14、21、28...     

负压封闭引流治疗深度烧伤创面及对炎性因子、致痛因子的影响

目的研究负压封闭引流(VSD)治疗深度烧伤创面(DBW)及对血清炎性因子、致痛因子的影响。方法 2015年1月—2017年12月内江市第一人民医院治疗DBW患者106例,其中男性69例,女性37例;年龄25～59岁,平均44. 5岁;受伤至入院时间0. 5～13d,平均5. 65d。致伤原因:火烧伤75例,热液烧伤31例。按照治疗方法分为VSD组(n=53)和对照组(n=53),VSD组行VSD+游离植皮治疗,对照组行常规清创换药+游离植皮治疗。治疗7d后观察两组创面愈合率及视觉模拟疼痛评分(VAS)、创面完全愈合时间、住院时间、住院费用,治疗前及治疗后7d血清超敏C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-8(IL-8)、补体C3a等炎性因子及血清5-羟色胺(5-HT)、脑内神经肽(NPY)、前列腺素E2(PGE2)等致痛因子水平。结果治疗后7d VSD组创面愈合率大于对照组[(80. 86±9. 12)%vs.(69. 58±7. 30)%],疼痛评分、创面完全愈合时间、住院时间及住院费用均少于对照组[(2. 78±0. 29)分vs.(5. 79±0. 62)分,(19. 26±2. 04) d vs.(25. 74±2. 65) d,(23. 63±2. 44) d vs.(30. 51±3. 19) d,(3. 29±0. 35)万元vs.(3. 92±0. 41)万元](P <0. 05)]。治疗后7d,VSD组血清CRP、TNF-α、IL-8、补体C3a及5-HT、NPY、PGE2水平均低于对照组[(8. 92±9. 93) mg/L vs.(18. 87±1. 96) mg/L,(35. 74±3. 61)μg/L vs.(67. 94±6. 88)μg/L,(32. 92±4. 37)μg/L vs.(60. 76±6. 19)μg/L,(13. 52±1. 50)μg/L vs.(16. 77±1. 72)μg/L,(109. 92±10. 16) ng/L vs.(143. 97±15. 22) ng/L,(112. 86±11. 41)μg/L vs.(154. 37±16. 03)μg/L,(121. 33±12. 42) pg/m L vs.(186. 93±18. 72) pg/m L,P <0. 05)]。结论 VSD可促进DBW愈合,降低炎性因子及致痛因子水平,患者康复快。     

早期肠道营养对烧伤后肠源性高代谢的影响

从８０年代末起，通过对６００只大（豚）鼠、６０只兔和６０头小香猪所建立的４种烧伤后早期营养的动物模型，以及２１例严重烧伤病人对比分析，发现烧伤后早期肠道喂养可改善胃肠道血流供应，减轻肠道缺血再灌流损伤；可维护肠粘膜结构以及吸收、分泌、运动功能，降低门脉、中心静脉血内毒素水平，减少肠道内毒素易位；可降低伤后枯否细胞获得数、吞噬墨汁枯否细胞数和面积，以及其培养上清中肿瘤坏死因子（ＴＮＦ）量，对伤后枯否细胞的活化有刺激作用；可降低血胰高糖素、皮质醇、儿茶酚胺、ＴＮＦ、ＩＬ－８前列腺素Ｅ２（ＰＧＥ２）等递质的水平，降低高代谢，使烧伤４５％成人静息能量消耗（ＲＥＥ）在烧伤后４、８、１４ｄ的均值降低２８．６％。通过相关分析发现ＲＥＥ与血丙二醛（ＭＤＡ）、内毒素、分解激素、ＴＮＦ均呈显著正相关（ｒ＝０．７３８６～０．９９２２，Ｐ＜０．０５～０．０１）。     

大鼠烧伤后急性期蛋白mRNA的表达

分析了不同烧伤程度大鼠肝、脾、肾和骨骼骨内４种急性期蛋白，即ａ１－酸性糖蛋白、ａ１－抗胰蛋白酶、白蛋白和转铁蛋白（Ｔｒｆ）ｍＲＮＡ水平的动态变化特征，结果表明：（１）肝脏是合成各种ＡＰＲ的主要场所；（２）即使是小面积的烧伤也可以诱发急性期反应。（３）烧伤后血清Ａｌｂ水平下降是急性期反应的特征，但在ｍＲＮＡ水平上并不下降而是增加。     

MEBO治疗食道化学烧伤5例临床观察

目的：探讨ＭＥＢＯ口服治疗食道化学烧伤的疗效。方法：５例食道化学烧伤采用口服ＭＥＢＯ治疗,局部治疗先用清水漱口后口服ＭＥＢＯ,每次１５克,每２小时一次,据情予以全身防治感染及营养支持治疗。结果：５例均治愈,平均愈合时间２０天,半年随访,未发生食道狭窄。结论：ＭＥＢＯ口服治疗食道化学烧伤效果良好,病人无痛苦,亦无并发症发生。