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Three Part Question

In [an adult patient with burns] is [Silver sulphadiazine cream better than normal dressings] at [reducing infection and decreasing the time required for healing]?

Clinical Scenario

A 25 year old science teacher comes into the emergency department with a partial thickness burn to her hand after being careless with a bunsen burner. You wonder if silver sulphadiazine cream is better than normal dressings at reducing the risk of infection and healing time.

Search Strategy

Medline using the OVID interface 1966 to September Week 3 2006.
Cochrane Database.of Systematic Reviews Issue 2 2006
Medline:[exp Silver Sulfadiazine/ OR silver sulphadiazine.mp. OR exp Sulfadiazine/ OR flamazine OR flammazine] AND [exp Burns/ OR thermal injury.mp. OR thermal burn$.mp. OR exp BURNS, INHALATION/ or exp BURNS/ OR burn$.mp. OR thermal injur$.mp OR scald.mp. OR heat injur$.mp.] LIMIT to English language and humans
Cochrane:'silver sulphadiazine' or 'flamazine'

Search Outcome

410 papers were found in Medline of which 12 were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Subrahmanyam M, 1998, India	50 patients with superficial thermal burn treated over 16 months, <40% TBSA and treated within 6 h of the burn. Group 1 (n=25)-treated with pure honey. Group 2 (n=25)-treated with silver sulphadiazine.	Randomised Controlled Trial	Healing rates by day 21	Group 1 - 100% of wounds healed, Group 2 - 84% of wounds healed (p=0.1)	No control group where wounds were left to heal naturally or compared with normal dressings. The four patients in group 2 were stated to have converted to deep burns and required grafting. Method of randomisation not stated. Not blinded. Calculated P values on percentages rather than actual figures.
Stern. H 1989 Australia	8 patients with 15 burn areas, half burn area dressed with control dressing (tulle gras) and half dressed with silver sulphadiazine (SSD) Group 2-20 donor site patients, dressings applied as (Inman, 1989)	Controlled clinical trial	Healing time	Group 1, SSD-19.25 days Tulle-14.41 days. Statistically significant (paired t-test p<0.05). Group 2, SSD-10.85 days Tulle-10.5 days. No significant difference.	Patients with complicating factors such as inhalation injury or myoglobinuria were not excluded. 3 burns areas that required grafting excluded from analysis. Limb burns split into proximal and distal sections and distal sections selected for ssd treatment. Not blinded, subjective end-point. Cross contamination of dressings.
Wyatt et al, 1990, USA	42 patients presenting to the emergency room with second degree burns over 8 months. 20 patients treated with Silvadene (silver sulphadiazine), 22 patients treated with Duoderm (hydrocolloid dressing). Followed up until wound healed. Healing assessment by blinded investigator.	Randomised study	Pain	More severe in Silvadene group (two tailed t-test p<0.01)	Small numbers of patients were used. Patients in silvadene group instructed to wash burns with soap and reapply silvadene on 12hrly basis. Duoderm group had dressings left intact unless fell off.
			Infection	No signs of clinical infection in either treatment group
			Mean healing time	Silvadene-15.59+/-1.86 days, Duoderm-10.23+/-0.68 days. Statistically different (two tailed t-test p<0.01)
Gerding et al, 1990, USA	52 patients with 56 partial thickness burns. Group 1(n=30) treated with Biobrane Group 2(n=26) treated with silver sulphadiazine	Randomised Controlled Trial	Infection	Two groups similar. 10% in group 1 vs 7.7% in group 2.	Study used small numbers. Trial was not blinded. Group 2 patients were required to change their own dressing, removing and then replacing all of the cream every 12h. Group 1 patients had the dressing replaced or removed at clinic 24-36h following the injury. Unblinded, subjective end-point.
			Healing time	Significantly less in group 1 than group 2. (10.6+/-0.8 vs 15.0+/-1.2 days, p<0.01)
Ang et al, 2000, Singapore	Patients between 6 and 80y presenting with partial thickness burns to the face excluding chemical and electrical burns.	Patients were randomised to receive treatment with silver sulfadiazine cream or Moist Exposed Burn Ointment (MEBO - based on petrolatum). After exclusions 17 received MEBO and 22 Flammazine	Healing rates by day 10	14/17 in MEBO group and 17/22 in Flammazine group. NS	Small, unblinded study with subjective outcome.
			Overall healing time	No signficant difference between groups.
Bugmann et al, 1998, Switzerland	76 paediatric patients presenting with burns. Patients with facial burns and burns >24h old excluded. 5 patients withdrawn from each group due to need for skin grafting.	The patients were randomised and 35 children received Flammazine dressings while 41 received Mepitel dressings (silicon coated nylon dressing with no biological compounds).	Mean healing time in days.	Mepitel 8.11 days, Flammazine 11.67 days. P=0.0036.	Small study, not blinded.
			Infection rates	1 patient in Flammazine group, no patients in Mepitel group. NS
Barret et al, 2000, USA	20 paediatric patients with thermal flame or scald burns with the total burn surface area between 2 and 29%.	10 patients randomised to Biobrane dressing (bilaminated composite) and 10 patients to Flammazine. Flammazine dressings were changed 12hrly, Biobrane dressings were left in place.	Days till wound healed	16.1±0.6 days for F group, 9.7±0.7 for B group. P<0.001	Small groups, unblinded. Power calculation has been done but not stated which outcome this was based upon. Study underpowered to look at infection rates.
de Gracia, C 2001, Phillipines	60 patients aged >4 months with burns areas >15% who had been admitted within 24h of the injury.	Patients were randomised to receive silver sulphadiazine (SSD) dressings or silver suphadiazine with cerium nitrate (SSD-CN).	Mean days till wound healed	17.2±8.3 in SSD-CN group vs. 25.1±19.4 in SSD group. p=0.03	Relatively small study. Unblinded.
			Development of sepsis	1/30 in SSD-CN group and 4/30 in SSD group. NS
			Mortality rate	1/30 in SSD-CN group and 4/30 in SSD group. NS
Inman et al, 1984 Canada	121 patients over the age of 1y presenting to one centre, within 24h of receiving a burn which had a full-thickness component to it.	Patients were randomised to receive Silvazine (1% silver sulphadiazine plus 0.2% chlorhexidine gluconate, 54 patients) or Flamazine (1% silver sulphadiazine, 67 patients) dressings for their burns.	Wound infection rates	10 patients (19%) in Silvazine group, 12 patients (18%) in the Flamazine group.	Small group. Not blinded.
			Mortality rate	3 deaths in the Silvazine group and 4 deaths in the Flamazine group.
Afilalo et al, 1992, Canada	48 patients presenting to one centre with partial-thickness burns <15% in size and <48h old were initially randomised. 18 patients dropped out leaving 15 in each group.	Patients were randomised to receive a Duoderm dressing or silver sulphadiazine dressing.	Healing time	10.7±4.8 days for duoderm group, 11.2±4.2 days for SSD, not significant.	Small study with large drop-out rate. Wound evaluation not blinded.
Soroff and Sasvary, 1994, USA	15 adult patients with noncontiguous partial-thickness burns of similar size and severity. 2 patients dropped out, one due to infection at another site and one due to discomfort at collagenase site.	2 burns on each patients were randomised to silver sulphadiazine dressing or collagenase ointment with polymyxin B sulphate / Bacitracin spray.	Median time to clean wound bed	6 days in collagenase group vs. 12 days in SSD group (p=0.0012)	Small group. Unblinded, subjective assessment. Method of randomisation unclear.
			Median time to epithelialisation	10 days in collagenase group vs. 15 in SSD group, (p=0.0007)
Costagliola M, Agrosi M, 2005, France, Italy	111 patients with partial-thickness burns not exceeding 5% of BSA were recruited from various centres. 1 patient in the SSD lost to follow up.	Patients were randomised to receive dressings using 0.2% hyaluronic acid and 1% silver sulphadiazine or 1% silver sulphadiazine. Creams provided in unmarked tubes and appeared identical.	Median time to healing	9.5 days (95% CI 7, 14) for the HA-SSD group vs. 14 days (95% CI 13,14) in the SSD group.(p=0.0073)
			Pain evaluation	No signficant difference between groups.

Comment(s)

Silver sulphadiazine has been shown to decrease the bacterial colonisation of burn wounds. The mechanism is not clear but each of the components has a synergistic effect on the other to provide a bacteriocidal effect in vivo. Adverse effects include local skin reaction, hypersensitivity reactions and occasionally leucopenia though this is usually self-limiting. Despite this fact there is little evidence to show that the use of this topical agent reduces bacterial wound infections or sepsis in patients with burns. There is a suggestion from the small studies listed here that it may, in fact, delay wound healing and the way forward may be to simply provide a clean, moist and undisturbed environment to allow healing. One confounding factor in these studies may be that the flamazine dressings tended to be changed 12hrly while the other dressings were left intact for longer.

Clinical Bottom Line

Despite evidence of the antibacterial properties of this compound no evidence was found showing a definitive improvement in outcome in terms of infection rates or healing time. Local advice should be followed.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Subrahmanyam M. A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine. Burns 24(2):157-61, 1998 Mar.
2. Stern. H Silver Sulphadiazine and the healing of partial thickness burns: a prospective clinical trial. British Journal of Plastic Surgery 42(5):581-5, 1989 Sep.
3. Wyatt D, McGowan D, Najarian P. Comparison of a Hydrocolloid Dressing and Silver Sulphadiazine Cream in the Outpatient Management of Second-degree burn. The Journal of Trauma 30(7):857-65, 1990 Jul.
4. Gerding RL, Emerman CL, Effron D et al. Outpatient management of partial-thickness burns: Biobrane versus 1% silver sulfadiazine. Annals of Emergency medicine 19(2):121-4, 1990 Feb.
5. Ang E, Lee S, Gan C et al. The Role of Alternative Therapy in the Management of Partial Thickness Burns of the Face- Experience with the Use of Moist Exposed Burn Ointment Compared with Silver Sulphadiazine. Annals of the Acad Med Singapore 29(1):7-10, 2000 Jan.
6. Bugmann P, Taylor S, Gyger D et al. A silicon-coated nylon dressing reduces healing time in burned paediatric patients in comparison with standard sulfadiazine treatment: a prospective randomised trial. Burns 24(7):609-12, 1998 Nov.
7. Barret J, Dziewulski P, Ramzy P, et al. Biobrane versus 1% Silver Sulfadiazine in Second-Degree Paediatric Burns. Plastic and Reconstructive Surgery 105(1):62-5, 2000 Jan.
8. de Gracia, C An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns. Burns 27(1):67-74, 2001 Feb.
9. Inman R, Snelling C, Roberts et al. Prospective comparison of silver sulfadiazine 1 per cent plus chlorhexidine digluconate 0.2 % (Silvazine) and silver sulfadiazine 1 % (Flammazine) as prophylaxis against burn wound infection. Burns 11(1):35-40, 1984 Oct.
10. Afilalo M, Dankoff J, Guttman A et al. DuoDERM hydroactive dressing versus silver sulphadiazine/Bactigras in the emergency treatment of partial skin thickness burns. Burns 18(4):313-6, 1992 Aug.
11. Soroff H, Sasvary D. Collagenase Ointment and Polymyxin B Sulfate/Bacitracin Spray Versus Silver Sulfadiazine Cream in Partial-Thickness Burns: A Pilot Study. Journal of Burn Care & Rehabilitation 15(1):13-7, 1994 Jan-Feb.
12. Costagliola M, Agrosi M. Second-degree burns: a comparative, multicenter, randomized trial of hyaluronic acid plus silver sulfadiazine vs. silver sulfadiazine alone. Current Medical Research and Opinions 21(8):1235-40, 2005 Aug.