Bacteriotherapy with Lactobacillus plantarum in burns

Bacterial colonisation and infection remain the major causes of delayed healing and graft rejection following burns. Topical treatment is necessary to reduce the incidence of burn wound infection. Silver sulphadiazine (SD‐Ag) is an often used microbicidal agent. However, this treatment produces adverse reactions and side‐effects. On the basis of experimental data and clinical application of lactobacilli as probiotics, we performed this exploratory study to establish the effectiveness of bacteriotherapy with topical application of the innocuous bacteria Lactobacillus plantarum cultured in De Man, Rogosa and Sharpe medium to provide an alternative method for burn treatment using SD‐Ag as a reference. These innocuous bacteria would compete with other bacteria that are wound pathogens and would modify the wound environment and promote tissue repair. Eighty burned patients from the Plastic Surgery and Burns Unit were grouped into infected (delayed) second‐ and third‐degree and non infected (early) third‐degree burns and treated with L. plantarum or SD‐Ag. The proportion of patients with delayed second‐degree burns was 0·71 for L. plantarum and 0·73 for SD‐Ag (relative rate: ?2·72%) with respect to the decrease in bacterial load (<10⁵ bacteria/g of tissue), promotion of granulating tissue wound bed and healing. In early third‐degree burns, the values were 0·75 for L. plantarum and 0·84 for SD‐Ag (relative rate: ?1·07%) in preventing wound infection and promotion of granulation tissue, 0·90 in graft taking for both treatments (relative rate: 0%) and 0·75 for L. plantarum and 0·77 for SD‐Ag (relative rate: ?2·60%) in healing. In delayed third‐degree burns, values were 0·83 for L. plantarum and 0·71 for SD‐Ag (relative rate: +16·90%) with respect to the decrease in the bacterial load (<10⁵ bacteria/g of tissue) and providing a granulating tissue wound bed, 0·90 in graft taking for both treatments (relative rate: 0%) and 0·75 for L. plantarum and 0·64 for SD‐Ag (relative rate: + 17·19%) in healing. Although the number of patients (between 12 and 15 per group) did not enable the application of a power statistical test, these results suggest that the L. plantarum treatment should be studied in greater depth and could be used as a valid alternative for the topical treatment of burns.     

Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures

Aims: The aim of this study was to describe ketamine pharmacokinetics when administered orally to children suffering from burn injury in >10% body surface area. Methods: Children (n = 20) were given ketamine 5 or 10 mg·kg^?1 orally 20 min prior to presentation for surgical procedures. Anesthesia during procedures was maintained with a volatile anesthetic agent. Additional intravenous ketamine was given as a bolus (0.5–1 mg·kg^?1) to nine children during the procedure while a further nine children were given an infusion (0.1 mg·kg^?1·h^?1) continued for 4–19 h after the procedure. Blood was assayed for ketamine and norketamine on six occasions over the study duration of 8–24 h. Data were pooled with those from an earlier analysis (621 observations from 70 subjects). An additional time–concentration profile from an adult given oral ketamine was gleaned from the literature (17 observations). A population analysis was undertaken using nonlinear mixed‐effects models. Results: The pooled analysis comprised 852 observations from 91 subjects. There were 20 children who presented for procedures related to burns management (age 3.5 sd 2.1 years, range 1–8 years; weight 14.7 sd 4.9 kg, range 7.9–25 kg), and these children contributed 214 ketamine and norketamine observations. A two‐compartment (central, peripheral) linear disposition model fitted data better than a one‐compartment model. Bioavailability of the oral formulation was 0.45 (90% CI 0.33, 0.58). Absorption half‐time was 59 (90% CI 29.4, 109.2) min and had high between‐subject variability (BSV 148%). Population parameter estimates, standardized to a 70‐kg person, were central volume 21.1 (BSV 47.1%) l·70 kg^?1, peripheral volume of distribution 109 (27.5%) l·70 kg^?1, clearance 81.3 (46.1%) l·h^?1·70 kg^?1, and inter‐compartment clearance 259 (50.1%) l·h^?1·70 kg^?1. Under the assumption that all ketamine was converted to norketamine, the volume of the metabolite was 151.9 (BSV 39.1%) l·70 kg^?1 with an elimination clearance of 64.4 (BSV 63.4%) l·h^?1·70 kg^?1 and a rate constant for intermediate compartments of 26.2 (BSV 52.1%) h^?1·70 kg^?1. Conclusions: The ketamine pharmacokinetics in children with minor burns are similar to those without burns. The peak ratio of norketamine/ketamine at 1 h is 2.8 after oral administration allowing an analgesic contribution from the metabolite at this time. There is low relative bioavailability (<0.5) and slow variable absorption. Dose simulation in a child (3.5 years, 15 kg) suggests a dose regimen of oral ketamine 10 mg·kg^?1 followed by intravenous ketamine 1 mg·kg^?1 i.v. with the advent of short‐duration surgical dressing change at 45 min.     

Clinical evaluation of low-flow sevoflurane anaesthesia for paediatric patients

Background: Sevoflurane expenditure, inspired gas humidity, temperature, soda lime temperature, and compounds A and B were measured during high and low fresh gas flow anaesthesia in paediatric patients. Methods: Sixty ASA 1 or 2 paediatric patients were randomly allocated to two groups: low-flow circle anaesthesia (LFA) patient group (n=30) and high-flow circle anaesthesia (HFA) patient group (n=30). Initial fresh gas flow (FGF) was 4 l · min^?1 of nitrous oxide and 2 l · min^?1 of oxygen in both groups. This FGF of 6 l · min^?1 was maintained in the HFA group. After 10 min of HFA, the FGF was reduced to 600 ml · min^?1 (nitrous oxide and oxygen 300 ml · min^?1 each) in the LFA group. Results: Sevoflurane expenditure during LFA was about 1/7 of that during HFA (3.3±0.2 ml · h^?1 · vol.%^?1 compared to 22.8±0.6 ml · h^?1 · vol.%^?1, mean±SEM, respectively). Absolute humidity in the LFA patients was 4 times higher than that in the HFA patients (22.8±2.4 g · m^?3, 5.6±3.4 g · m^?3 respectively). There was no significant difference in the inspiratory gas temperature between the LFA (28.5±0.6°C) and HFA (26.9±1.3°C) groups. There was significant difference in the mean highest soda lime temperature between the LFA (35.5±1.2°C) and HFA (28.7±1.2°C) groups. The mean highest concentration of compound A was 12.2±3.8 ppm in the LFA group. The mean highest concentration of compound B was less than 1 ppm. Compounds A and B were below detectable level in the HFA group. Conclusion: In conclusion, sevoflurane used for paediatric patients in a circle system with a fresh gas flow of 0.6 l · min^?1 resulted in a significantly reduced sevoflurane expenditure, higher inspired absolute humidity, but not temperature, compared to a fresh gas flow of 6 l · min^?1. Low levels of compounds A and B were detected.     

Clonidine decreases vasoconstriction and shivering thresholds, without affecting the sweating threshold

Purpose

This study was conducted to test the hypothesis that clonidine produces a dose-dependent increase in the sweating threshold and dose-dependent decreases in vasoconstriction and shivering thresholds.

Methods

Six healthy subjects (two female) were studied on four days after taking clonidine in oral doses of either 0 (control). 3. 6 or 9 μg · kg. The order followed a balanced design in a double-blind fashion. Oesophageal temperature and mean skin temperature (from 12 sites) were measured. Subjects were seated in 37°C water which was gradually warmed until sweating occurred (sweat rate increased above 50 g · m 2 · h^?1). The water was then cooled gradually until thresholds for vasoconstnction (onset of sustained decrease in fingertip blood flow) and shivering (sustained elevation m metabolism) were determined. Thresholds were then referred to as the core temperature, adjusted to a designated mean skin temperature of 33°C.

Results

High dose clonidine similarly decreased the adjusted core temperature thresholds for vasoconstriction by 1. 16 ± 0.30°C and for shivenng by 1.63 ± 0.23°C (P< 0.01). The dose response effects were linear for both cold responses with vasoconstriction and shivenng thresholds decreasing by 0.13 ± 0.05 and 0.19 ± 0.09°C · μg^?1 respectively (P < 0.0001). The sweating threshold was unaffected by clonidine, however the interthreshold range between sweating and vasoconstnction thresholds increased from control (0.19 ± 0.48°C) to high dose donidine (1.31 ±0.54°C).

Conclusion

The decreases in core temperature thresholds for cold responses and increased interthreshold range are consistent with the effects of several anaesthetic agents and opioids and is indicative of central thermoregulatory inhibition.     

Extensive deep neck burns

A total of 1402 patients were treated in the Nuffield Burns Unit between 1960 and 1970. There were 51 deaths (3·3 per cent); 40 were anticipated from mortal burns (Bull, 1954), 5 from pulmonary embolism and 1 each from airway burn, diffuse adrenal haemorrhage, septicaemia, coincidental rupture of an aortic aneurysm, toxic nephritis and hepatitis.Of the 1402, 218 (15·8 per cent) had burns involving the neck and adjacent areas; 29 of these 218 had extensive whole skin loss of the neck and adjacent skin.     

Zinc and copper replacement therapy in children with deep burns

In 22 children with burns of between 10 and 20 per cent of the body surface zinc and copper serum levels were controlled. Supplementation with zinc sulphate (20 mg kg^?1 d^?1) and copper sulphate (0·08 mg kg^?1 d^?1) was only carried out in cases of pathological findings on admission. When both zinc and copper levels were normal, no supplementation was given. In spite of this the copper level rose spontaneously to over 40 per cent. When the copper level was normal, but zinc levels were low, copper levels remained around less than 1 per cent without supplementation. When zinc and copper levels were both abnormal and supplementation was given, the zinc levels rose by 87 per cent but the copper level by only 28 per cent, and the copper levels reached only the lowest normal values. Zinc supplementation appears to antagonize the copper absorption or to influence the serum copper level. We doubt that serum zinc and copper levels are of much help in controlling the therapeutic effect of copper supplementation.     

Effects of Hypoxis hemerocallidea (Fisch. & C.A. Mey.) [Hypoxidaceae] Corm (African Potato) Aqueous Extract on Renal Electrolyte and Fluid Handling in the Rat

Current biomedical evidence suggests that Hypoxis hemerocallidea (Fisch. & C.A. Mey.) [Hypoxidaceae] (African Potato [AP]) corm extract may be useful in the management of type 2 diabetes mellitus. However, more recent reports have also indicated that certain herbal extracts attenuate the deterioration of kidney function in diabetes mellitus. Accordingly, this study investigated the effects of short- (acute) and long-term (chronic) administration of H. hemerocallidea corm aqueous extract (APE) on renal fluid and electrolyte handling in male Wistar rats. Acute effects of APE were investigated in separate groups of anesthetized rats challenged with a continuous jugular infusion of 0.077 M NaCl at 9 mL · h^{? 1}. After a 3.5-h equilibration period, consecutive 30-min urine collections were made over the subsequent 4 h of 1-h control, 1.5-h treatment, and 1.5-h recovery periods for measurements of urine flow, Na⁺, and K⁺ excretion rates. To establish the effects of acute APE, the extract was added to the infusate at doses of 90, 180, or 360 μg · h^{? 1} in separate groups of rats during the treatment period. For chronic studies, individually caged rats were administered twice with APE (30 mg · kg^{? 1} PO) every third consecutive day at 09h00 and 17h00 for 5 weeks. Control rats received distilled water (3 mL · kg^{? 1}). Urine volume and total urinary outputs of creatinine, Na⁺, and K⁺ were determined from 24-h samples. Acute infusion of APE produced a dose-dependent, significant (p < 0.01) decrease in urine flow, K⁺, and Na⁺ excretion rates. Chronic APE treatment significantly reduced urinary Na⁺ output between weeks 2 and 5, without affecting either urine flow or K⁺ excretion rates. When compared with control animals, APE significantly reduced GFR (2.54 ± 0.09 mL · min^{? 1} vs. 1.52 ± 0.02 mL · min^{? 1}) and increased plasma creatinine concentration (55 ± 3 µmol · L^{? 1} vs. 68 ± 6 µmol · L^{? 1}). The results from this study suggest that the H. hemerocallidea corm aqueous extract may impair kidney function.     

Effets hémodynamiques comparés du midazolam et du flunitrazépam chez les traumatisés crâniens en ventilation contrôlée

The haemodynamic effects of midazolam were compared with those of flunitrazepam in 10 patients with severe head injury under controlled ventilation. Right atrial pressure, pulmonary pressure, pulmonary capillary wedge pressure and cardiac output were measured using a Swan-Ganz thermodilution catheter. Arterial pressure (P?a) was recorded by radial arterial canulation. All patients in this cross-over study received midazolam (0.15 mg · kg^?1) and flunitrazepam (0.02 mg · kg^?1) intravenously randomly, with 24 h between the two injections. The measurements were first carried out before and then 5, 10, 20, 30 and 60 min after injection. The only significant variations after midazolam and flunitrazepam were a fall in P?a (from 93±12 to 81±11 mmHg for midazolam and from 89±14 to 78±20 mmHg for flunitrazepam) and in cardiac index (from 4.80±1.03 to 4.17±1.14 l · min^?1 · m^?2 for midazolam and from 5.18±1.32 to 4.54±1.03 l · min^?1 · m^?2 for flunitrazepam). The small decrease in heart rate was not significant. The cardiovascular changes after midazolam and flunitrazepam were small and similar for both drugs. It seemed that midazolam and flunitrazepam were safe for sedating head injured patients under controlled ventilation.     

Atropine-induced heart rate changes: a comparison between midazolam-fentanyl-propofol-N2O and midazolam-fentanyl-thiopentone-enflurane-N2O anaesthesia

Atropine-induced heart rate (HR) changes were studied in 19 patients (ASA physical status I) during anaesthesia maintained predominantly with propofol-N₂O or thiopentone-enflurane-N₂O. Ten patients (Group A) received midazolam (0.07 mg · kg^?1), fentanyl (1 μg · kg^?1), propofol (2 mg · kg^?1) and succinylcholine (1 mg · kg^?1). Following tracheal intubation, anaesthesia was maintained with propofol (6 mg · kg^?1 · hr^?1), N₂O (67 per cent) and O₂ (33 per cent). In nine patients (Group B) thiopentone (4 mg · kg^?1) was substituted for propofol and anaesthesia maintained with N₂O (67 per cent) O₂ (33 per cent), and enflurane (0.5 per cent inspired concentration). The study was non-randomised because Group B patients were only included if HR before administration of atropine < 90 beats · min^?1. IPPV was performed in all patients using a Manley ventilator (minute vol. 85 ml · kg^?1; tidal vol. 7 ml · kg^?1). Ten minutes after tracheal intubation, incremental doses of atropine (equivalent cumulative doses: 1.8, 3.6, 7.2, 14.4, 28.8 μg · kg^?1) were administered at two-minute intervals and HR responses calculated during the last 45 sec of each intervening period. No differences were observed between the groups following 1.8 and 3.6 μg · kg^?1 atropine, but propofol-N₂O anaesthesia was associated with reduced responses (P < 0.01) following 7.2, 14.4 and 28.8 μg · kg^?1 atropine. These results suggest that there is a predominance of parasympathetic influences during propofol-N₂O anaesthesia compared with thiopentone-enflurane-N₂O anaesthesia.     

Characterization and evaluation of silver release from four different dressings used in burns care

For centuries silver and silver compounds have been in use to control infection and avoid septicaemia in the care of burns and chronic wounds. Renewed interest has resulted in a number of Ag based dressings that are now widely used in burns centres. Despite extensive use, a systematic study of the chemical composition, release kinetics and biochemical action of these products has yet to be published. In this work we have characterized the morphology of four commercial Ag dressings by scanning electron microscopy and the silver content was determined to range between 1.39 mg/cm² and 0.03 mg/cm². Release kinetics in three different matrices (ultra pure water, normal saline solution and a human serum substitute) were determined. The highest rates were found in serum substitute, with a maximum of 4099 μg/(h cm²) to a minimum of 0.0001 μg/(h cm²). Our results show that the mean inhibitory concentrations are exceeded for most common pathogens in serum substitute and sterile water, but the presence of high Cl^? concentrations tend to inactivate the dressings.     

The use of Urgotul™ in the treatment of partial thickness burns and split‐thickness skin graft donor sites: a prospective control study

The use of paraffin‐impregnated gauze for burns and skin graft donor sites is commonly associated with wound adherence with consequent pain and trauma upon removal. This prospective clinical study was performed to evaluate a new class of lipido‐colloid dressings (Urgotul^?) in promoting healing and in reducing tissue adherence. In a 6‐month period, 25 consecutive patients were recruited. Two separate burn or donor sites on each patient were dressed with tulle‐gras (TG) or Urgotul^? and covered with standard secondary dressings. Objective assessment of wounds by two reviewers, and patients' subjective assessments were recorded. Twenty‐three (92%) patients were followed up for a mean of 3 months. Mean time to complete epithelialisation was 9·6 and 11·9 days for the Urgotul^? and TG sites respectively (P < 0·05). Bleeding was seen in 52% of Urgotul^? sites compared with 100% of the TG sites at first dressing change (P < 0·05). Patients reported ‘moderate pain’ during dressing change in 22% and 57% in the Urgotul^? and TG groups respectively (P < 0·05), with 35% of TG sites being ‘very painful’ requiring extra analgesia. We found that compared with TG, Urgotul^? was associated with faster epithelialisation, less pain and trauma (bleeding) during dressing changes.     

Pulmonary gas exchange effects by nitroglycerin,dopamine and dobutamine during one-lung ventilation in man

The effects of nitroglycerin, dopamine and dobutamine on pulmonary gas exchange were determined in 21 adult patients during two-lung and one-lung ventilation. Nitroglycerin, in I μg·kg^?1·min^?1, decreased cardiac index (CI) andPaO₂ during both two-and one-lung ventilation, and increased in Qs/Qt during one-lung ventilation. There were no significant changes in the measured variables during infusion of dopamine, 5 μg·kg^?1·min^?1. Dobutamine, 5μg·kg^?1·min^?1, increased Cl and PaO₂ did not change during two-lung ventilation. During one-lung ventilation, PaO₂ increased from (mean value ±SD) 168 ± 46 to 201 ± 52 mmHg (P < 0.01) with dobutamine infusion. Qs/Qt decreased from 29.2 ± 7.0 to 26.0 ± 6.2 per cent (P < 0.05) without any change in pulmonary vascular resistance index during one-lung ventilation. We conclude that dobutamine has advantages over dopamine and nitroglycerin during one-lung ventilation.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

A prospective,randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns

Silver sulfadiazine has been used as a topical burn wound treatment for many years. Pain associated with dressing changes is a common problem in burn wounds. Aquacel Ag, a hydrofiber dressing coated with ionic silver has been reported to reduce burn wound infection and promote antimicrobial activity. The purpose of this study was to show the benefits of Aquacel Ag for the treatment of partial thickness burns. This prospective randomized study was conducted in 70 patients who had partial thickness burns less than 15% of total body surface area and were treated at Siriraj outpatient burn clinic during December 2006–February 2008. Patients were divided into two groups: Aquacel Ag‐treated group with dressing changes every 3 days (35 patients) and 1% silver sulfadiazine‐treated group, with daily dressing changes (35 patients). There was no difference in demographic data including age, gender, burn percentage between groups. Time‐to‐wound healing pain score during dressing change and cost of treatment were compared between both groups. Time‐to‐wound closure was significantly shorter in the Aquacel Ag‐treated group (10 ± 3 versus 13.7 ± 4 days, P < 0·02) as well as pain scores at days 1, 3 and 7 (4·1 ± 2·1, 2·1 ± 1·8, 0·9 ± 1·4 versus 6·1 ± 2·3, 5·2 ± 2·1, 3·3 ± 1·9, respectively, P < 0·02). Total cost of treatment was 52 ± 29 US dollars for the Aquacel Ag‐treated group versus 93 ± 36 US dollars for the silver sulfadiazine‐treated group. This study showed that Aquacel Ag increased time to healing, decreased pain symptoms and increased patient convenience because of limiting the frequency of replacement of the dressing at lower total cost. This study confirms the efficacy of Aquacel Ag for the treatment of partial thickness burns at an outpatient clinic.     

Ketamine boluses with continuous low-dose fentanyl for paediatric sedation during diagnostic cardiac catheterization

During cardiac catheterization, 202 children aged 1 month to 16 yrs were sedated intravenously half an hour after oral premedication with flunitrazepam 0.1 mg·kg^?1 (maximum dose 2 mg) to maintain spontaneous breathing and stable and calm conditions for the investigation. Standard fentanyl doses for induction and maintenance were 1 μg·kg^?1 and 1 μg·kg^?1·h^?1, respectively, for all patients. Requirements for supplementary ketamine for induction and maintenance of stable sedation were studied in five age groups (≤0.5 yr, >0.5–2 yr, >2.0–5.0 yr, >5.0–10.0 yr and >10.0 yr). Ketamine doses for induction were 1.5 ± 0.1, 1.5 ± 0.1, 1.2 ± 0.1, 0.9 ± 0.1 and 0.2 ± 0.1 (mean ± SEM) mg·kg^?1 in these age groups, respectively. Ketamine requirements for maintenance of sedation were 1.9 ± 0.1, 1.7 ± 0.1, 1.4 ± 0.1, 1.1 ± 0.1 and 0.2 ± 0.1 mg·kg^?1·h^?1 in the same age groups, respectively. Age dependency of ketamine requirement was shown; the older the patient the less was the need for supplementation. Intravenous sedation with low-dose fentanyl and ketamine after flunitrazepam premedication provided favourable anaesthesia for cardiac catheterization.     

Kinetics of bupivacaine after clonidine pretreatment in mice

Previous studies have reported that clonidine pretreatment causes an increase in the local anaesthetic activity of bupivacaine. This study was designed to document possible changes in the pharmacokinetic behaviour of bupivacaine and its main metabolite, desbutylbupivacaine, PPX, in mice after a single, 0.1 mg · kg^?1, injection of clonidine. Kinetic variables of bupivacaine were determined after a single 20 mg · kg^?1 ip dose of bupivacaine in controls (Group I) and in clonidine (0.1 mg · kg^?1 ip) pretreated mice (Group 2). The maximal concentration in serum (Cmax, 2.553 ± 0.862 μg · ml^?1 versus 0.962 ± 0.141 μg · ml^?1 for. Groups 2 and 1, respectively, P = 0.01) and the area under the concentration curve (AUC, 3.530 ± 0.330 μ · ml^?1·^?1 versus 1.755 ± 0.252 Hg · ml^?1 · hr^?1 for Groups 2 and 1, respectively, P < 0.01) of bupivacaine were higher in clonidine pretreated mice while the Clearance (Cl) was decreased in clonidine pretreated animals (0.603 ± 0.054 μ · ml^?1 versus 1.264 ± 0.447 μg · ml^?1 for Groups 2 and 1, respectively, P < 0.01). The ratio of AUC PPX/AUC bupivacaine (which may partially indicate the rate of metabolism) was lower in presence of clonidine (0.220 ± 0.019 against 0.425 ± 0.033 for Groups 2 and 1, respectively, P < 0.01). Our data indicate decreased metabolism in the clonidine-treated mice which suggests altered hepatic metabolism of bupivacaine by clonidine. This may explain the previously reported enhanced anaesthetic activity of bupivacaine in the presence of clonidine.     

Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery

It has been reported that interleukin 8 (IL-8) and interleukin 6 (IL-6) are two of the chemical mediators causing myocardial injury. It is not clear whether treatment with corticosteroids in vitro in these patients can prevent the production of interleukin 8 and 6. This prospective study was conducted to investigate whether methylprednisolone (MP) pretreatment (30 mg · kg^?1 before CPB and before declamping of aorta) influenced the production of IL-8 and 6 in the peripheral circulation in 27 patients undergoing elective coronary artery bypass surgery. The IL-8 and IL-6 concentrations were measured by ELISA kit. We also studied the effect of MP pretreatment on postoperative cardiac Junction. Serum concentration of IL-8 in non-MP-treated patients (37 ± 44 pg · ml^?1 preoperatively) increased to 169 ± 86 pg · ml^?1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 22 ± 8.9 pg · ml^?1 to 52 ± 35 pg · ml^?1 in the MP-treated patients (P < 0.01). Serum IL-6 concentration in non-MP-treated patients increased from the preoperative value of 59 ± 30 pg · ml^?1 to 436 ± 143 pg · ml^?1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 36 ± 15 pg · ml^?1 to 135 ± 55 pg · ml^?1 in the MP-treated patients (P < 0.01). Furthermore, postoperative cardiac index in MP-treated patients (3.6 ± 1.1 L · min^?1· m^?2) was higher than 2.3 ± 0.8 L · min^?1 · m^?2 of non MP-treated patients (P < 0.05). The levels of IL-8 max during surgery correlated negatively with postoperative cardiac index (γ = ?0.67). These results suggest that methylprednisolone suppresses production of IL-8 and 6.     

Pseudomonas aeruginosa infections in burns

Observations were carried out on 32 patients with burns. In 20 cases of extensive and severe burns Pseudomonas aeruginosa infections were found.Twenty-eight strains of Ps. aeruginosa were isolated from burn wounds and blood of the burn patients.These strains were typed by pyocine method. Among investigated strains of Ps. aeruginosa, the pyocine type A (39·2 per cent) dominated. When Ps. aeruginosa type A was present in burn wounds, the level of antibodies in blood sera of patients was distinctly increased.In 3 cases of septicaemia, low level of antibodies in blood sera of patients was found. Two patients died.All isolated strains of Ps. aeruginosa were sensitive to gentamycin and colimycin.     

Clonidine does not affect lidocaine seizure threshold in rats

We investigated the effect of clonidine on intravenous (iv) lidocaine-induced haemodynamic changes and convulsions in awake rats. Wistar rats (200–250 g) were divided into three groups of eight and were pretreated with iv clonidine or normal saline 15 min before lidocaine infusion. Group 1 received normal saline; Group 2, 1 μg · kg^?1 clonidine; and Group 3, 10 μg · kg^?1 clonidine. After surgical preparation and recovery from anaesthesia, all groups received a continuous iv infusion of lidocaine (15 mg · ml^?1) at a rate of 4 mg · kg^?1 · min^?1 until generalized convulsions occurred. Oxygenation was well maintained in all groups. Pretreatment with clonidine changed neither cumulative convulsant doses (Group 1: 41.8 ± 2.2, Group 2: 43.8 ± 2.6, Group 3: 42.3 ± 2.0 mg · kg^?1, respectively) nor plasma concentrations of lidocaine at the onset of convulsions (Group 1: 10.5 ± 0.3, Group 2: 10.8 ± 0.3, Group 3: 10.6 ± 0.3 μg · ml^?1, respectively). The mean arterial blood pressures in Groups 2 and 3 were decreased after clonidine pretreatment (Group 2: 93 ± 1, P < 0.01, Group 3: 90 ± 1%, P < 0.01, respectively) and they gradually increased during lidocaine infusion. The heart rates decreased after clonidine pretreatment (Group 2: 94 ± 2, P < 0.05, Group 3: 86 ± 2%, P < 0.01, respectively) and the combination of clonidine and lidocaine potentiated the bradycardic effect of lidocaine at a subconvulsant dose. Our results indicate that clonidine has neither anticonvulsant nor proconvulsant effects on lidocaineinduced convulsions. However, the interactions of clonidine and lidocaine on blood pressure and heart rate should be investigated further.     

Comparison of fentanyl,sufentanil and alfentanil during awake craniotomy for epilepsy

Neurolept anaesthesia is used during awake craniotomy for epilepsy surgery. This study compares analgesia, sedation and the side effects of the newer opioids sufentanil and alfentanil, with those of fentanyl in patients undergoing awake craniotomy. Thirty patients were randomized into three groups, each received droperidol, dimenhydrinate and the chosen opioid as a bolus followed by an infusion. The opioid doses used were fentanyl 0.75 μg · kg^?1 plus 0.01 μg · kg^?1 · min^?1; sufentanil 0.075 μg · kg^?1 plus 0.0015 μg · kg^?1 · min^?1, and alfentanil 7.5 μg · kg^?1 plus 0.5 μg · kg^?1 · min^?1. There were no differences in the requirements for droperidol, dimenhydrinate or in the incidence of complications among the three groups. The total doses of the opioids required were fentanyl 4.9 ±1.3 μg · kg^?1, sufentanil 0.6 ±0.2 μg · kg^?1 and alfentanil 149 ±36 μg · kg^?1. Two patients became uncooperative requiring general anaesthesia. The conditions for surgery, electrocorticography and for stimulation testing were satisfactory in all other patients. We conclude that the newer opioids did not offer any benefit over fentanyl.