The effect of some ointment bases on the systemic absorption of tobramycin from various wound surfaces of burned patients

Three kinds of 0·2 per cent tobramycin ointment were prepared with tobramycin and 3 ointment bases (cream, polyethylene glycol and hydrophilic petrolatum), and applied to the various wound surfaces of 5 burned patients. The systemic absorptions of tobramycin were compared with the values of the tentative AUC (area under the curve of tobramycin blood level, μg.h/ml.g) until 12 hours after the applications, by determining tobramycin level in blood. Similar values of AUC from the cream and polyethylene glycol ointments were obtained, while that of hydrophilic petrolatum ointment was very low. The systemic absorption of tobramycin from the polyethylene glycol ointment was studied when the ointment was applied to the wound surfaces of 7 patients with partial-thickness bum, 9 patients with full-thickness burn and 6 patients with burn ulcer. The mean values of the tentative AUC of patients with partial-thickness burn, full-thickness burn and burn ulcer were found to be 0·06, 0·03 and 0·15, respectively. These results showed that cream and polyethylene glycol bases should be used carefully as a vehicle of tobramycin ointments because of the rapid systemic absorption of tobramycin from human burn wounds, especially burn ulcer.     

Bactericidal efficacy of 5 per cent povidone iodine cream in Pseudomonas aeruginosa burn wound infection

A new topical antiseptic agent, 5 per cent polyvinylpyrrolidone-iodine (PVP-I) cream, with altered physicochemical properties, incorporated in a different carrier base has proved in vivo to be more effective in controlling burn wound infections than 10 per cent PVP-I ointment. Important biodynamic properties of the new formulation have not, however, been elucidated in vivo. Hence the need for a controlled study to evaluate the bioavailability of the active component after penetration through burn eschar; the bactericidal efficacy of the cream and determination of the bactericidal time of the cream in comparison with 10 per cent PVP-I ointment. A modified Walker burn wound model was used to define the rate of trans-eschar penetration, biodynamic availability and bactericidal efficacy of 5 per cent povidone iodine cream in established Pseudomonas aeruginosa burn wound infection. In vitro penetration confirmed the effective diffusion of PVP-I cream through 1.5 mm eschar within 6 h. A single topical application of PVP-I cream resulted in a 98.8 per cent (6.088 x 10(9) c.f.u./g of tissue to 7.367 x 10(7) c.f.u./g of tissue) reduction in intra-eschar viable organisms within 18 h after application. A second topical application of PVP-I cream at 18 h resulted in a total reduction of 99.8 per cent in viable organisms (2.90 x 10(9) c.f.u./g of tissue to 7.009 x 10(6) c.f.u./g of tissue) within 48 h. Comparing the in vitro bactericidal time of povidone iodine ointment with cream against Pseudomonas aeruginosa, Staphylococcus aureus and a Klebsiella pneumoniae revealed that the PVP-I cream killed organisms ten-fold more quickly than the ointment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preliminary clinical studies of a biological skin equivalent in burned patients

The possibility of covering large areas of full thickness skin loss with 'living skin equivalent' produced by a modification of Bell's method was studied. Living skin equivalents, composed of a dermal equivalent (fibroblasts plus collagen) covered by epithelial cells were grafted, meshed or non-meshed, onto granulation tissue and, in one patient, onto fascia. Eight patients with full skin thickness burn wounds covering over 15 per cent of the body surface area were thus partially covered. The graft 'take' was evaluated every 48 h. In every patient grafted, an extensive lysis (60-90 per cent) of the skin equivalent graft was observed at the first dressing (48 h). In one patient only, a significant percentage of 'take' (40 per cent) was observed 14 days after grafting. These disappointing results were probably related to the presence of collagenases or proteases produced on the wound bed either by bacteria or by surrounding human cells. It appears that at the present time the biochemical nature of the dermal equivalent used is not yet completely appropriate to serve routinely as a substitute for human skin.     

Effects of early hypnosis on the cardiovascular and renal physiology of burn patients

Sixteen patients with body surface area (BSA) burns of 4 per cent to 83 per cent, with whom single hypnotherapeutic interventions were attempted 5·3±3·4 h post burn, were compared to 16 matched controls. Ten physiological parameters related to fluid volume and haemodynamics were recorded on the first two post burn days. The only significant difference discovered was elevated urine output 0–48 h post burn in successfully hypnotized patients (P=0·01). This difference was inversely related (r=?0·94, P=0·009) to burn size from a 10 per cent BSA burn (3·9 litres/48 h) to a 35 per cent BSA burn (1·6 litres/48 h). A statistically suggestive (P=0·13) increase in urine output occurred in patients in whom hypnotic trance induction was unsuccessfully attempted. Patients with BSA burn sizes ≥ 50 per cent, who presented with significant physiological stress and hypovolemia, were found not to be susceptible to hypnotic trance induction, and derived no physiological benefit. Attempted hypnotherapeutic intervention per se, with its psychotherapeutic component, may act only to reduce affective or psychological stress and anxiety. This psychological stress reduction apparently facilitates the loss of retained fluid in patients with small burns by a mechanism which is overwhelmed by the physiological stress of a major burn injury.     

The effect of heparin on dermal ischaemia after burning

Heparin has been said to improve microvascular perfusion in the burn wound. Using 75°C, 10 s, 5 per cent body surface area guinea-pig scald burns, histology was studied and the amount of dermal perfusion was measured periodically after burning. Microcirculatory dermal perfusion was evaluated after indian ink injection. Untreated control animals were compared with animals treated with topical heparin, animals treated with systemic heparin and animals treated with both topical and systemic heparin.Immediately and up to 2 h post burn there was vascular filling to 85 percent thickness of the dermis in all animals. By 8 h, the dermal perfusion had fallen to 40 per cent dermal thickness and at 24 h no dermal perfusion occurred. At 24 h only the subdermal vessels contained indian ink. The animals' wounds which were allowed to heal showed no regeneration of dermal appendages, grossly or microscopically.In this model, heparin failed to prevent progressive dermal ischaemia or to allow regeneration of dermal appendages.     

Randomized clinical trial of the effect of applying ointment to surgical wounds before occlusive dressing

BACKGROUND: A blinded randomized clinical trial was undertaken to evaluate the effect of applying ointment to a wound before occlusive dressing, in comparison with no ointment or sterile paraffin. METHODS: Some 778 patients with 1801 surgical wounds following excision of skin lesions were enrolled in the trial. No ointment was placed on 510 sutured wounds of 247 patients, paraffin ointment was put on 729 wounds (269 patients) and mupirocin ointment on 562 wounds (262 patients). Wound infection, scar, haemorrhage, dehiscence and other complications were assessed at suture removal. At 6-9 months after surgery, patients were surveyed to assess the wounds, with a response rate of 74.0 per cent. RESULTS: There were no significant differences in outcome for all endpoints evaluated. The infection rate was 1.4 per cent with no ointment, 1.6 per cent for paraffin and 2.3 per cent for mupirocin (P = 0.490). Total complication rates were 3.5, 4.7 and 4.8 per cent for no ointment, paraffin and mupirocin respectively (P = 0.590). Some 10.9, 10.3 and 8.2 per cent of patients respectively had a neutral or negative perception of their wounds at 6-9 months after surgery (P = 0.650). There was no difference in postoperative pain, degree of inconvenience or overall level of satisfaction with treatment. CONCLUSION: Putting ointment on a surgical wound before occlusive dressing does not benefit the patient. In view of the risk of antibiotic resistance, mupirocin ointment is not indicated for clean surgical wounds.     

Photoacoustic diagnosis of burns in rats

BACKGROUND: Accurate burn depth assessment is important for determining the appropriate treatment plan for severe burn patients. However, conventional methods of diagnoses, such as visual observation and pinprick test, are often inaccurate. We previously proposed a new method for burn diagnosis in which photoacoustic signals originating from the blood in healthy tissue under the injured tissue are measured. In this study, we investigated the validity of this method by an experiment using rat scald burn models. METHODS: Superficial dermal burns (SDBs), deep dermal burns (DDBs), and deep burns (DBs) were made in the dorsal skin of rats by using a Walker-Mason template. Wounds were irradiated with low-energy, 550-nm, nanosecond pulsed light, and photoacoustic signals induced were measured with a piezoelectric film as a function of postburn time. Measurement in normal skin as a control was also performed. Temporal profiles of the photoacoustic signals were converted into depth profiles using sound velocity of tissue, and for each profile, a peak showing highest signal intensity was selected. For this peak, the depth at which the signal rose (signal rise depth) and the depth that gave a peak value (signal peak depth) were recorded. Statistical analysis was performed to clarify the difference in depth information of signals between burn groups. RESULTS: Depth profiles of photoacoustic signals showed unique features depending on the degree of burn; pronounced peaks shifted to deeper tissue as the burn severity increased. This indicates that the zone of stasis formed due to injuries can be monitored. There were significant differences in both the signal rise depth and the peak depth between the control and SDB groups, SDB and DDB groups, and DDB and DB groups (p < 0.001). CONCLUSION: SDBs, DDBs, and DBs can be differentiated by photoacoustic signals, suggesting that the method proposed is useful for diagnosing burn injuries.     

Treatment of dermal depth burn wounds with an antimicrobial agent-releasing silicone gel sheet

Silicone gel sheets containing 0.02 per cent Ofloxacin were used in the treatment of 24 patients with a total of 27 dermal depth burn wounds. The gel provided a continuing drug delivery system from the dressing to the wound. Clinically the silicone gel sheets did not adhere to the wound and could be removed easily without pain. No infection developed in any of the dermal depth burn wounds treated with the gel sheets. The silicone gel sheets were found to promote prompt epithelialization in 16 burn wounds of superficial dermal depth (mean 8.4 days) compared with ointment-impregnated gauze dressings (mean 14 days, P less than 0.01). There was less pain and discharge by macroscopic observation of the absorbent materials from both dressings. In nine wounds of mixed superficial and deep dermal burn, the silicone gel also provided prompt epithelialization (mean 12 days) compared to the control wounds (mean 22 days, P less than 0.01).     

Prospective comparison of silver sulfadiazine 1 per cent plus chlorhexidine digluconate 0·2 per cent (Silvazine) and silver sulfadiazine 1 per cent (Flamazine) as prophylaxis against burn wound infection

Patients with fresh full-thickness burn wounds were randomly assigned to receive wound treatment with daily applications of either I per cent silver sulfadiazine plus 0·2 per cent chlorhexidine digluconate cream (Silvazine) or 1 per cent silver sulfadiazine (Flamazine). Fifty-four patients treated with Silvazine were comparable to 67 treated with Flamazine with respect to extent and distribution of burn, age and all aspects of wound and associated treatment. Overall incidence of wound bacterial colonization was less in the Silvazine treated patients (65 per cent versus 88 per cent; P = 0·002). With Silvazine, wound colonization by Staphylococcus aureus was less (41 per cent versus 64 per cent; P = 0·01). Clinical wound infection with Staph. aureus developed in one Silvazine treated patient and five Flamazine treated patients (P = 0·16). Colonization by and infection due to all other organisms did not differ in the two groups. The incidence of graft failure was similar with both agents. In future increasing the concentration of chlorhexidine digluconate above 0·2 per cent might produce an improved prophylactic effect against Gram negative bacteria reported by other authors using the combined agent in in vitro and clinical trials. Silvazine was effective in reducing the incidence of Staph. aureus burn wound colonization without fostering supervening opportunistic infection.     

Short-course aminoglycoside therapy in patients with spinal cord injury. Standard dose versus low dose

Twenty-nine patients with spinal cord injury and asymptomatic urinary tract infection were treated with standard or reduced doses of tobramycin and amikacin. The patients received five days of intramuscular antibiotics. Most of the patients in the tobramycin groups had Pseudomonas aeruginosa infection and most of those in the amikacin group had either Proteus rettgeri or Providencia stuartii infections. Only 1 patient had a positive urine antibody coating test. High antibiotic concentrations were demonstrated in the urine of all patients during therapy. Urine cultures were obtained two and seven days after completion of therapy. Forty-eight per cent of the patients were cured, while 31 per cent showed persistence or relapse, and 21 per cent had reinfection with other bacteria. No significant differences in results were observed between the standard-dose and low-dose regimens and between the amikacin and tobramycin groups. The low success rate of the regimens used may indicate the need to evaluate alternative therapeutic regimens to treat urinary tract infections in this special group of patients.     

Burn depth affects dermal interstitial fluid pressure, free radical production, and serum histamine levels in rats

BACKGROUND: We measured the amount of edema and the free radical production in burn-injured skin and the serum histamine levels, as well as changes in dermal interstitial fluid pressure. METHODS: Thirty-six Wistar rats with 20% total body surface area burns of different depth were resuscitated by lactated Ringer's solution intravenously. The rats were divided into a deep burn (DB) group (n = 12), a superficial dermal burn (SDB) group (n = 12), and a sham burn (Sham) group (n = 12). Dermal interstitial fluid hydrostatic pressure (Pif), total skin water and xanthine oxidase activity, and serum histamine levels were measured until 60 minutes postburn. RESULTS: In the DB group, dermal Pif significantly fell to -35.9 +/- 11.0 and -40.9 +/- 7.0 mm Hg at 10 and 15 minutes postburn, respectively (p < 0.05); it returned to preburn values at 50 minutes postburn. In the SDB group, dermal Pif was slightly negative but did not markedly change. Total skin water was significantly higher than that of the DB and the Sham groups; however, in the SDB group, serum histamine and dermal xanthine oxidase were significantly higher than in the DB group at 15, 30, and 45 minutes postburn (p < 0.05). CONCLUSION: The fluid-resuscitated DB produced a more negative dermal Pif than the SDB, but less dermal edema. In contrast, the SDB appeared to mainly generate dermal edema formation by wound free radical production and serum histamine release. The dermal Pif is one of the factors associated with edema formation immediately after deep burns. However, an increase in vascular permeability associated with oxygen radical production plays a more important role in dermal edema formation than does dermal Pif.     

Selective intestinal decontamination for prevention of wound colonization in severely burned patients: a retrospective analysis.

In this study the effect of selective intestinal decontamination of the digestive tract (SDD) on wound colonization was investigated. Ninety-one patients with at least 25 per cent total burned surface area (TBSA) were included in this study. All patients received oral polymyxin. In 63 patients oral co-trimoxazole and amphotericin B were added to the regimen. The addition of co-trimoxazole decreased the incidence of Enterobacteriaceae wound colonization from 71 per cent to 11 per cent (P less than 0.005). Colonization with Proteus was eliminated in patients treated with co-trimoxazole, compared with an incidence of 36 per cent in the group treated with polymyxin alone (P less than 0.001). The addition of amphotericin B decreased yeast colonization of the burn wound from 39 per cent to 10 per cent (P less than 0.005). A close relation was observed between burn wound colonization and colonization of the gastrointestinal tract. No resistant bacterial strains emerged during the period of study. These results suggest that SDD is an effective method for prevention of wound colonization. Further controlled studies are needed to establish the role of SDD in preventing burn wound colonization and wound sepsis.     

Use of topically applied silver sulphadiazine plus cerium nitrate in major burns

All patients hospitalized between May 1987 and June 1988 suffering from burns covering over 50 per cent of the body surface area were treated by topical application of a cream containing cerium nitrate (0.05 M) and silver sulphadiazine (0.03 M) (CN + SSD). Eleven patients were included in this series, with a mean age of 35 years (range 22-65), a mean total burn size of 78 per cent (range 50-96 per cent) and full skin thickness covering a mean of 48 per cent (range 10-91 per cent). Eight patients survived (73 per cent) (mean age 36 years; mean total burn surface 73 per cent; mean full skin thickness burn surface, 38 per cent). These results are far better than those obtained in our Unit where a survival rate of 34 per cent was obtained in a comparable series of patients treated before 1987. Sixty positive blood cultures were obtained, which included a large variety of organisms with a slight predominance of Staph. aureus, Candida albicans and Ps. aeruginosa. Wound cultures were positive in 72 per cent of swabs and showed a predominance of Ps. aeruginosa (59 per cent of all the strains isolated). Even if CN + SSD appears in this series not to be very efficient in preventing wound colonization and septic complications, it permitted a very high survival rate in the treated patients, taking into account the extreme severity of the injuries. This beneficial effect is probably the consequence of the protective action of the yellow-green eschar formed by CN + SSD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Randomized clinical trial of 0.2 per cent glyceryl trinitrate ointment for wound healing and pain reduction after open diathermy haemorrhoidectomy

BACKGROUND: Open haemorrhoidectomy is associated with considerable postoperative pain and discomfort. This study assessed whether glyceryl trinitrate (GTN) ointment promotes wound healing and reduces pain after open haemorrhoidectomy. METHODS: A randomized prospective double-blind placebo-controlled trial was conducted. Patients were randomized to either 0.2 per cent GTN ointment or placebo ointment (petroleum jelly). Patients were asked to fill in a pain diary. Complete healing was defined as complete epithelialization. RESULTS: There were 40 patients in the GTN group and 42 in the placebo group. There were no statistically significant differences in sex, weight, type of haemorrhoid, type of surgery (emergency or elective), number of haemorrhoids excised, duration of surgery, hospital stay and complication rate between the groups. Pain scores and analgesic use were not significantly different. By week 3, however, 17 patients in the GTN group had completely epithelialized wounds compared with eight patients in the placebo group (P = 0.021). Only one patient who received GTN experienced headache requiring discontinuation of the ointment. CONCLUSION: TGN 0.2 per cent ointment improved wound healing rates, but did not reduce pain in this study.     

The study of inhibiting systematic inflammatory response syndrome by applying xenogenic (porcine) acellular dermal matrix on second-degree burns

OBJECTIVE: To investigate the influence of xenogenic (porcine) acellular dermal matrix on the systematic inflammatory reaction syndrome (SIRS), and the reaction of burn patients to tissue damage upon application to second-degree burn wounds. METHOD: Seventy-two cases of patients with acute second-degree burns were enrolled in the study. According to the total burn surface area (TBSA) and the treatment methods, we randomly divided the patients into four groups. Group A (treatment group): patients with less than 30% TBSA covered with xenogenic acellular dermal matrix. Group B (control group): patients with less than 30% TBSA covered with betadine ointment gauzes. Group C (treatment group): patients with more than 30% TBSA covered with porcine acellular dermal matrix. Group D (control group): patients with more than 30% TBSA covered with betadine ointment gauzes. Serum level of C-reactive protein (CRP) was measured by single radial immunodiffusion method on 1, 4, 7 and 14 days postburn. RESULTS: The serum level of CRP in group A was significantly less than that of in group B (P<0.05) on days 4, 7 and 14. The serum level of CRP in group C increased slowly, descended quickly and was significantly less than that of in group D on days 4, 7 and 14. CONCLUSION: The application of xenogenic (porcine) acellular dermal matrix on second-degree burn wound can decrease serum level of CRP of the patients, which may play an important role in reducing SIRS and sepsis incidence.     

Cultured epithelium as a skin substitute

Twenty-five burn patients with full or partial thickness skin loss received cultured epithelium (CE), allografts or autografts as part of their treatment. Overall, a 30 per cent graft 'take' was achieved irrespective of whether the CE was autograft or allograft, fresh or frozen. In the case of deep dermal burns this figure improved to 50 per cent. The surviving grafts merged with split thickness skin grafts (SSG) and advancing wound edges. When full thickness skin loss was grafted, only a patchy take could be achieved and the surviving islands of CE tended not to spread across the wound. No rejection of CE allograft was recorded either clinically or histologically up to 6 months. The technical problems and clinical implications are discussed.     

A policy of early excision and grafting in elderly burn patients shortens the hospital stay and improves survival

Early excision and grafting of the burn wound appears to shorten the hospital stay and decrease mortality in children and adults. However, whether an early surgical approach is safe in elderly burn patients has not been resolved. To answer this question we carried out a prospective study of early surgery in 114 consecutive patients over the age of 50 years. Patients were generally operated on between post-burn days 2 and 5. The mean age of the patients was 68 years, with a burn size of 22 per cent, of which 13 per cent was full thickness skin loss. The mean hospital stay of the surviving patients was reduced by 40 per cent compared to national averages (P less than 0.001). The mortality rate for the entire group of patients was 17 per cent, with 2 deaths in the 65 patients with burns less than 20 per cent total body surface area (TBSA). Although the mortality rate for patients with burns greater than 20 per cent TBSA was 35 per cent, this was less than predicted (P less than 0.05). The improvement in survival appeared to be due to a decrease in the incidence of lethal burn wound infections.     

Assessment of burn wound sepsis by swab, full thickness biopsy culture and blood culture--a comparative study

Fifty patients with burns ranging from 30 to 50 per cent of their body surface area were monitored for sepsis throughout their hospital stay using swab, blood and full thickness biopsy culture techniques. The relative merits of these techniques in the diagnosis of burn wound sepsis were evaluated. Only 62.5 per cent of the patients with a positive surface culture showed signs of clinical sepsis, while 87.5 per cent of the patients with significant bacterial count on biopsy culture showed signs of clinical sepsis. A decrease in bacterial count on follow up correlated with clinical improvement while a count of 10(8) orgs/gm indicated a bad prognosis. Wound surface cultures, though the simplest method gave poor indication of the organisms invading into the burn wound. Blood cultures were of only prognostic value. Full thickness biopsy culture and quantification of the number of bacteria in the burn wound was felt to be the best method for rapid diagnosis and for assessing the progress of burn wound infection.     

Correlation of quantitative burn wound biopsy culture and surface swab culture to burn wound sepsis

The present study includes seventeen patients with second and third degree fresh burns involving 15–50 per cent total body surface area (TBSA). Surface swabs and quantitative burn wound biopsy cultures were obtained during postburn weeks 1,2 and 3 and correlation was studied. To obtain bacterial counts the technique described by Loebel et al. (1974) was used. The patients were divided in two groups depending upon burn body surface area involved. The first group includes five patients with burns between 15–29 per cent body surface area and the second group includes the rest of the twelve patients with burns between 30–50 per cent body surface area. No patient from group I showed any sign or symptom of sepsis whereas seven patients from group II developed sepsis and three died. These three patients showed positive blood culture at the time of death. Of the 48 cultures obtained in all the patients over 3 weeks, 7 cultures showed differences between swab and biopsy cultures. Genticyn was the most effective drug against Gram-negative organisms.     

Peripheral neuropathy in burn patients

Neuropathy in burn patients is frequently overlooked. This study aimed at looking for neuropathies among burn patients. It included 55 burn patients, whether symptomatic or asymptomatic, with variable depths of burn at different stages. Their ages ranged from 8 to 55 years with a mean age of 23.6 ± 11.1 years. All patients were submitted to clinical examination, electromyographic and motor conduction velocities of burned and unburned limbs. Serum electrolyte, blood urea and creatinine were measured for all patients. Sixteen patients (29 per cent) had peripheral neuropathy. Only six had symptoms and signs of peripheral neuropathy. The most frequently diagnosed neuropathy in this study was mononeuritis multiplex in nine patients (56 per cent), then generalized distal axonal neuropathy in five patients (31 per cent) and entrapment neuropathy in two patients (13 per cent). In patients with mononcuritis, 29 nerves were affected, 24 nerves related to the site of the burn and five nerves were away from the site of the burn. All the entrapment neuropathy developed after wound healing. Age above 20 years, electric burns, burns involving full thickness of the skin and a surface area of more than 20 per cent were associated with a significantly higher prevalence of neuropathy. Other parameters were not found to be significant in the development of neuropathy.