Studies on systemic absorption of tobramycin in polyethylene glycol ointment applied to wounds of burn patients

The penetration of tobramycin ointment (0.2 per cent) through human burn wounds was studied in two patients with superficial dermal burn (SDB) and deep dermal burn (DDB), two patients with DDB, one patient with full thickness burn (FB) and one patient with burn ulcer (BU). After application of the ointment, the absorption of tobramycin occurred promptly with a peak level at 2-6 h in the sera of patients with SDB + DDB and DDB only. In the BU patient it was found at 2 h; while in the FB, at 10-12 h. The excretion of tobramycin into the urine was also studied. The absorption rate constants (ka) of the two SDB + DDB patients were 0.31 and 0.74, of the two DDB patients, 0.079 and 0.18, and those of the DB and the BU patients, 0.053 and 0.95, respectively. The absorption ratios of tobramycin (amount excreted into the urine during 24 h/applied dose) were different, depending on the condition of the burn wound, and ranged from a low of 10.3 per cent (FB) to a high of 44.0 per cent (BU). These results show that the treatment of burn patients with tobramycin ointment to control burn wound infection should be carefully supervised, especially in the case of BU.     

The effect of age on the systemic absorption and systemic disposition of ropivacaine after epidural administration

Knowledge about the systemic absorption and disposition of ropivacaine after epidural administration is important in regard to its clinical profile and the risk of systemic toxicity. We investigated the influence of age on the pharmacokinetics of ropivacaine 1.0% after epidural administration, using a stable-isotope method. Twenty-four patients were enrolled in 1 of 3 groups according to age (group 1: 18-40 yr; group 2: 41-60 yr; group 3: > or =61 yr). Patients received 150 mg ropivacaine hydrochloride epidurally. After 25 min, patients received 50 mL 0.44 mg/mL deuterium-labeled ropivacaine (D3-ropivacaine) IV. Arterial blood samples were collected up to 24 h after epidural administration. Total plasma concentrations of ropivacaine and D3-ropivacaine were determined using liquid chromatography mass spectrometry. In the oldest patients, elimination half-life was significantly longer (ratio of the geometric means 0.60; 95% confidence interval, 0.37-0.99) and clearance was significantly decreased (mean difference, 194 mL/min; 95% confidence interval, 18-370 mL/min) compared with the youngest patients. The systemic absorption was biphasic. Absorption kinetics for ropivacaine (fractions absorbed: (F1, F2) and half-lives: (t(1/2),a1), t(1/2),a2) during the fast and slow absorption process: 0.27 +/- 0.08 and 0.77 +/- 0.12, respectively; 10.7 +/- 5.2 min and 248 +/- 64 min, respectively) were in the same range as for other long-acting local anesthetics. F1 was on average 0.11 (95% confidence interval, 0.002-0.22) higher in the youngest compared with the middle age group. Observed age-dependent pharmacokinetic differences do not likely influence the risk of systemic toxicity in the elderly after a single epidural dose of ropivacaine.     

The effect of sampling method on the elution of tobramycin from calcium sulfate

Release rate is a critical property of all drug delivery vehicles, including antibiotic-laden bioerodibles. In vitro elution studies, used to evaluate release rates, use different sampling methods, including changing the entire amount of buffer and partial exchanges each day. Two groups of 10% calcium sulfate-tobramycin pellets were eluted in 20 mL of buffer for 30 days. Group I had 5 mL of buffer withdrawn and replaced daily whereas Group II had the entire 20 mL of buffer changed daily. The results show that the complete exchange method caused a significantly faster release of antibiotic than the partial exchange method. In the complete exchange group, greater than 50% of the tobramycin was released by 24 hours, whereas in the partial exchange group, 50% of the antibiotic was not released until Day 6. The two methods of sampling used to evaluate this bioerodible material provide data that allow the user to anticipate how the material will function in relatively inert and volatile environments. The method used to sample the elution of antibiotics from bioerodible materials affects the amount of antibiotic eluted. It therefore is important to know the method of sampling when making a decision to use a bioerodible material to deliver antibiotics locally.     

The effect of nitroglycerin ointment on cardiovascular functions in hypertensive patients during emergence from anesthesia

The present study was designed to investigate the effect of nitroglycerin (TNG) ointment to attenuate the cardiovascular response of hypertensive patients during emergence from anesthesia compared with the effects of TNG infusion and nifedipine instillation in the nose. In addition, plasma TNG concentration was measured in the TNG ointment group and TNG infusion group. TNG 30 mg in ointment reduced the arterial pressure during extubation without producing hypotension and tachycardia. There was no significant difference in plasma TNG concentration between TNG ointment group and TNG infusion group each receiving 0.3 micrograms.kg-1.min-1. The study suggests that TNG ointment is useful for regulation of arterial pressure in hypertensive patients during emergence from anesthesia.     

The effect of age on systemic absorption and systemic disposition of bupivacaine after subarachnoid administration

In order to evaluate the role of the pharmacokinetics of the age-related changes in the clinical profile of spinal anesthesia with bupivacaine, we studied the influence of age on the systemic absorption and systemic disposition of bupivacaine after subarachnoid administration in 20 male patients (22-81 yr), ASA Physical Status 1 or 2, by a stable isotope method. After subarachnoid administration of 3 ml 0.5% bupivacaine in 8% glucose, a deuterium-labeled analog (13.4 mg) was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of unlabeled and deuterium-labeled bupivacaine were determined with a combination of gas chromatography and mass fragmentography. Biexponential functions were fitted to the plasma concentration-time data of the deuterium-labeled bupivacaine. The systemic absorption was evaluated by means of deconvolution. Mono- and biexponential functions were fitted to the data of fraction absorbed versus time. The maximal height of analgesia and the duration of analgesia at T12 increased with age (r = 0.715, P less than 0.001; r = 0.640, P less than 0.01, respectively). In 18 patients the systemic absorption of bupivacaine was best described by a biexponential equation. The half-life of the slow systemic absorption process (r = -0.478; P less than 0.05) and the mean absorption time (r = -0.551; P less than 0.02) decreased with age. The total plasma clearance decreased with age (r = -0.650, P less than 0.002), whereas the mean residence time and terminal half-life increased with age (r = 0.597, P less than 0.01; r = 0.503, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

烧伤病人早期血清和创面水肿液对中性粒细胞凋亡的影响

目的 探讨烧伤病人早期血清、水泡液和痂下组织液对中性粒细胞(PMN)凋亡的影响。方法 采用伤后3d内重度以上烧伤患血清、24h内水泡液以及1周内Ⅲ度创面痂下组织液体外培养正常PMN,以正常血清作对照,应用流式细胞分析等方法观察PMN凋亡。结果 烧伤病人早期血清、水泡液和痂下液能抑制PMN凋亡,使PMN凋亡百分率下降、DNA断裂百分率降低,DAN凝胶电泳不出现细胞凋亡特有的“梯形带”;且痂下液与烧伤病人早期血清对PMN凋亡的抑制程度几乎相同,而水泡液的抑制作用稍弱于前两。结论 烧伤病人早期血清、水泡液和痂下组织液能抑制PMN凋亡。     

综合治疗手段进步促进烧伤创面愈合--近20年大面积烧伤治疗结果回顾

目的了解近10年来改进并应用于临床的全身及局部治疗措施在提高大面积烧伤病人治愈率的同时,是否对创面愈合速度也产生了影响.方法将1970年以来我科收治的大面积烧伤病人657例,以1990年1月为界分为两组,对比分析全身创面综合治疗措施改进前后,创面侵袭性感染发生率、植皮成活率,创面愈合速度的变化.1990年开始改进并应用于临床的全身性治疗措施包括器官功能保护、合理营养支持、创面感染有效控制、生长激素应用等;创面方面包括尽早切痂植皮、胶原酶促进脱痂、促愈药物银锌霜和生长因子等积极干预手,段.结果1990年后创面侵袭性感染发生率显著降低;植皮成活率显著提高;创面愈合时间显著缩短.创面基本愈合时间和痊愈时间较前分别提前了20天和22天.结论全身和创面局部治疗手段的进步极大地促进了大面积烧伤病人创面愈合时间,减轻了病人的痛苦.     

莫匹罗星对烧伤创面金黄色葡萄球菌感染的治疗

应用2%莫匹罗星软膏(实验组)及磺胺嘧啶银(对照组)治疗41例平均面积2.1%±1.12%的金黄色葡萄球菌感染创面,结果表明:试验组总有效率为88.9%,创面细菌清除率为96.3%,金葡菌清除率高达88.8%;而 SD-Ag 对照组依次分别为45%、70%及40%。从烧伤创面分离的金葡菌对多种抗生药物的敏感试验表明,对莫匹罗星敏感率为92.68%,仅低于万古霉素而高于头孢噻吩、亚胺硫霉素、环丙氟哌酸等,差异有显著意义。莫匹罗星对金葡菌的 MIC_(50)≤0.25 mg/L、MIC_(90)≤4 mg/L,(MIC范围0.25～256mg/L)。提示莫匹罗星软膏可作为烧伤创面金葡菌感染的首选药物。     

莫匹罗星对烧伤创面金黄色葡萄球菌感染的治疗

应用２％莫匹罗星软膏（实验组）及磺胺嘧啶银（对照组）治疗４１例平均面积２．１％±１．１２％的金黄色葡萄球菌感染创面，结果表明：试验组总有效率为８８．９％，创面细菌清除率为９６．３％，金葡菌清除率高达８８．８％；而ＳＤ－Ａｇ对照组依次分别为４５％、７０％及４０％。从烧伤创面分离的金葡菌对多种抗生药物的敏感试验表明，对莫匹罗星敏感率为９２．６８％，仅低于万古霉素而高于头孢噻吩、亚胺硫霉素、环丙氟哌酸等，差异有显著意义。莫匹罗星对金葡菌的ＭＩＣ５０≤０．２５ｍｇ／Ｌ、ＭＩＣ９０≤４ｍｇ／Ｌ，（ＭＩＣ范围０．２５～２５６ｍｇ／Ｌ）。提示莫匹罗星软膏可作为烧伤创面金葡菌感染的首选药物。     

The effect of henna and linseed herbal ointment blend on wound healing in rats with second-degree burns

The treatment of skin burns is one of the most important challenge in medical science. The aim of this study is evaluation of the efficacy of Artaderm herbal ointment containing the Henna (Lawsonia inermis) extract, Linseed (Linum usitatissimum) oil, and Honey Wax on wound healing in the rat with second-degree burn wounds. The Artaderm ointment had an effective role in controlling burn wound infections due to its antimicrobial and anti-inflammatory properties. In this study, 64 male Wistar rats were randomly divided into 8 groups (n = 8). Four groups received Artaderm, 1% Silver Sulfadiazine (SSD 1%), Cod Liver Oil and Fundermol (Alpha) ointments which used in common practices for burn injuries. Another three groups received Henna, Linseed, and Honey Wax alone and a control group that just underwent a second-degree burn injury without any treatments. A second-degree burn was formed on the back of each rat and dressed daily with one of the agents. Burn wounds were macroscopically and microscopically evaluated on the 7th, 14th, and 21st day after burn induction. Rats treated with the Artaderm ointment had significantly faster wound contraction as well as shorter healing time than the rest groups. No scar was observed in rats treated with the Artaderm ointment on the 21st day, while this level of improvement was not observed in other groups at the same time. More than 90% of wounds were healed after on the 14th day in rats treated with Artaderm (94.10 ± 0.18) and Alpha (92.05 ± 0.23) ointments. According to these findings, it can be concluded that Artaderm herbal ointment can be used as a proper alternative for healing of wounds in second-degree burns.     

血液滤过治疗严重烧伤脓毒症伴发的高钠血症

目的探讨血液滤过对严重烧伤脓毒症合并高钠血症病人的疗效.方法应用持续静脉-静脉血液滤过方法治疗8例严重烧伤脓毒症合并高钠血症的病人.观察病情、外周血电解质、血流动力学、氧摄取率变化;检测血滤开始时、血滤结束时血浆内炎性介质(IL-1β、IL-6、IL-8和TNF-α)浓度变化以及滤液中上述炎性介质的含量,计算跨膜清除率.结果病人经血液滤过治疗后,临床症状好转,血流动力学趋于稳定,血钠浓度恢复至生理水平.动脉血氧饱和度、氧分压以及氧摄取率均明显升高,差异有显著意义(P＜0.01).血滤结束时血浆内IL-1β、IL 6、IL-8和TNF-α的浓度较血滤前明显下降,差异有显著意义(P＜0.01).超滤液中也检测到上述4种细胞因子.随血滤时间延长,IL-1β、IL-6跨膜清除率明显下降,差异有显著意义(P＜0.01),IL-8和TNF-α跨膜清除率无明显变化,差异无显著意义(P＞0.05).结论血液滤过能在较短的时间内平稳而有效降低病人外周血钠离子浓度,并能部分清除体内IL-1β、IL-6、IL-8和TNF-α等炎性介质,平衡机体炎性反应,稳定血流动力学、改善病情,对治疗烧伤脓毒症伴发的高钠血症,降低其高病死率有积极作用.     

烧伤创面羟脯氨酸含量动态变化的实验研究

为探讨浅Ⅱ度烧伤创面胶原含量的变化及其与创面上皮化的关系，我们对浅Ⅱ度烧伤创面的羟脯氨酸（ＯＨＰ）水平及创面的形态学变化作了动态检测。结果发现烧伤后早期创面表皮缺损，ＯＨＰ含量增高，伤后第３天达峰值，继之随着上皮化的完善，ＯＨＰ水平逐渐下降至正常。我们认为，浅Ⅱ度烧伤创面胶原的含量与上皮化程度有关，良好的上皮化过程有利于控制胶原的过度增生。表皮细胞源因子（ＥＤＦ）可能是表皮细胞调控抑制胶原合成的主要因素。     

银锌霜在大面积烧伤中的应用

目的总结1991年1月至1995年11月银锌霜在48例TBSA大于30％的烧伤病人创面的应用。方法将同期应用碘络醚的35例病人作为对照,两组病人的平均年龄、烧伤面积、Ⅲ度面积无显著差别,用药方式均以半暴露为主。结果银锌霜组能显著增加细菌转阴率,减少抗生素应用时间及植皮手术次数,缩短愈合时间。结论银锌霜具有较强的抗感染能力,是大面积烧伤病人的良好外用药。     

Peroxidation of the small intestine and its effect on absorption of amino acids in burned rats

The purpose of this study was to investigate the dynamic changes of the level of lipid peroxidation products (malonaldehyde, MDA) of intestine, intestinal water, Na-K ATPase activity of intestinal mucosa and the intestinal leucine absorption rate of rats subjected to 30% III degrees burns. The results showed that the value of the intestinal MDA was higher, the Na-K ATPase activity of the intestinal mucosa reduced markedly, the wet/dry ratio of intestinal weight was increased significantly and the intestinal leucine absorption rate in vivo was distinctly reduced postburn. However, the content of intestinal MDA and the wet/dry ratio of intestine weight was significantly reduced, and the Na-K ATPase activity and leucine absorption rate was increased in burn rats treated with SOD and CAT than in untreated burn rats. These results strongly suggested that lipid peroxide may play an important role in the impairment of leucine absorption rate of intestine after burns, and the edema and reduced Na-K ATPase activity of intestinal mucosa resulted from the increased lipid peroxide might take active parts impairing the intestinal absorption.