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The use of moist exposed burn ointment (MEBO) for the treatment of burn
wounds: a systematic review
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The use of moist exposed burn ointment (MEBO) for the treatment of
burn wounds: a systematic review
Nigel Tapiwa Mabvuure, Christopher Felix Brewer, Kevin Gervin, and Siobhan Duffy
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4 N. T. MABVUURE ET AL.
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388 Figure 3. Risk of bias graph: review authors’ judgements about each risk of bias 451
389 item presented as percentages across all included studies. 452
390 453
391 concealed allocation. Across most trials, the risk of selection bias 454
392 is unclear (Figure 3). 455
393 None of the trials had a low risk of performance bias although 456
394 there was insufficient information in three of the trials [24–26] to 457
395 allow an assessment. The remaining three trials were at high risk 458
396 of performance bias due to the non-blinding of patients and 459
397 some study personnel [16,17,19,22,27]. 460
398 Three trials [16,19,22,26,27] were at low at risk of detection 461
399 bias because outcome-assessors were either blinded or non-blind- 462
400 ing was unlikely to have affected outcome measurement. Two tri- 463
401 als [24,25] had an unclear risk of bias whilst one had a high risk 464
402 of detection bias [17]. 465
403 Four trials had low risk [17,22,24,26], one was at high risk 466
404 [16,19,27] and the remaining trial had an unclear risk of attrition 467
405 bias [25]. 468
406 Only two trials had a low risk of reporting bias [16,19,22,27]. 469
407 Three trials had a high risk of reporting bias [17,24,25] and the 470
408 risk in the remaining trial was unclear [26]. 471
409 472
410 473
411 Effects of interventions 474
412 Meta-analysis was precluded by the heterogeneous reporting of 475
413 outcomes; poor definition of the study population (i.e. not sepa- 476
Figure 2. Risk of bias summary: review authors’ judgements about each risk of
414 bias item for each included study. rating SPT and DPT burns); missing data and poor reporting 477
415 (Table 1). A narrative synthesis was performed. 478
416 479
Three studies compared MEBO with 1% SSD cream
417 Measures of wound healing (primary outcome) 480
[16,17,19,25,27]. Others compared with sodium carboxymethylcel-
418 Both Ang [16,19,27], Allam [25] et al. observed faster healing in 481
lulose silver (Aquacel Ag) [24], povidene iodine plus bepanthenol
419 patients treated with MEBO compared to SSD. The mean number 482
cream [22] and Helix aspersa extract (Elicina cream) [26]. Only
420 of days to 75% wound healing recorded by Ang et al. for the 483
Hindy [24] included a negative control group (saline-soaked
421 MEBO and SSD groups were 17 and 20 respectively [16,19,27]. In 484
gauze dressing).
422 Allam et al’s study [25], patients with SPT burns healed faster 485
423 compared to when treated with MEBO compared to SSD 486
424 Characteristics of studies excluded after reading full-texts (10.5 ± 2.7 versus 4.5 ± 3.8 days) (p < 0.05). Similarly, patients with 487
425 DPT burns treated with MEBO healed faster (30.5 ± 5.1 vs. 488
Two studies were excluded after reading full-texts: an economic
426 36.6 ± 5.1 days) (p < 0.05). Hirsch et al. measured day 12 TEWL and 489
analysis that did not assess efficacy [29] and a nonrandomised
427 markers of inflammation such as CRP and leukocyte count as 490
study [18].
428 491
markers of wound healing [17] comparing MEBO with SSD. The
429 492
Risk of bias in included studies finding that patients treated with MEBO had greater loss of water
430 493
Figures 2 and 3 summarise and illustrate the authors’ risk of bias transepidermally (11 vs. 7) suggests that these wounds healed
431 494
assessment. The trials by Hirsch [17], Hindy [24], Allam [25] and slower than those treated with SSD. However, the levels of other
432 495
their respective colleagues had the highest or unknown risk of markers were not reported.
433 496
bias across all domains (Figure 2). The studies by Ang [16,19,27] Patients treated with Helix aspersa cream by Tsoutsos et al.
434 497
and Tsoutsos’ [26] teams had a lower risk of bias whilst Carayanni healed significantly faster compared to MEBO, as assessed on
435 498
et al. [22] was judged least likely to be biased. photographs by blinded assessors (11 ± 2 vs. 15.3 days) [26]. This
436 499
Three trials had a low risk of selection bias owing to detailed planimetric finding was corroborated by another that the eschar
437 500
random sequence generation [16,19,22,26,27]. Although the detachment was faster in patients treated with Helix aspersa
438 501
remaining three trials all randomised patients into study arms, cream [26].
439 502
their procedures were unclear [17,24,25]. Only Ang et al. Hindy found no difference in the healing times of MEBO and
440 503
441 [16,19,27] detailed allocation concealment making it unclear Aquacel Ag (10.35 ± 2.8 vs. 10.05 ± 2.3 days) [24]. Compared to 504
whether the remaining five trials [17,22,24–26] adequately povidone-iodine þ bepanthenol cream, patients treated with
JOURNAL OF PLASTIC SURGERY AND HAND SURGERY 5
505 MEBO healed faster as shown by faster 50% TEWL reduction (8.7 [16,19,27]. Similarly, no statistically significant difference was seen 568
506 vs. 10.75 days) [22]. in the incidence of Staphylococcus and Pseudomonas infections 569
507 In summary, more trials comparing wound healing between in groups receiving either MEBO or povidone-iodi- 570
508 MEBO and SSD favoured MEBO. There may be improved healing ne þ bepanthenol creams (5.8 vs. 7.5%, respectively) [22]. 571
509 in MEBO-treated wounds vs. those treated with povidone-iodi- In summary, the incidences of adverse reactions and wound 572
510 ne þ bepanthenol cream. There was no difference between MEBO infections were low and no statistically significant differences 573
511 and Acquacel Ag, but Helix Aspersa had faster healing rates were noted between MEBO and any of the comparators. 574
512 than MEBO. 575
513 576
Discussion
514 577
Pain and itch
515 There has been a suggestion that there are “double standards” in 578
516 Two studies found no difference in the analgesic effects of MEBO assessing complementary and alternative therapies in medicine 579
517 and SSD. Hirsch et al. found no statistically significant difference [30]. It is therefore crucial that these treatments are subjected to 580
518 in mean VAS scores between the MEBO and SSD groups on both the same scientifically rigorous analysis as used for ‘traditional’ 581
519 days 1 and 12 (both mean 5 on day 1 then 3.8 and 3.5, respect- treatments. As such, this systematic review was performed with 582
520 ively on day 12) [17]. Similarly, Allam et al. found no statistically the aim of pooling data relating to the efficacy of MEBO for the 583
521 significant difference in pain scores between MEBO and SSD [25]. treatment of burn wounds. Such a synthesis for the first time 584
522 One study found a statistically significant difference in pain pro- allows both surgeons and patients to appraise collated and syn- 585
523 files between MEBO and SSD [16,19,27]. MEBO patients rated their thesised evidence of MEBO and several comparators and is there- 586
524 pain as less than that of the SSD group after one week (2.9 vs 3.5 fore crucial to cost-effectiveness calculations by these groups. 587
525 mean post-dressing verbal numerical pain rating (VNPR) score). Data from six RCTs, all level 3 evidence, mostly poorly reported, 588
526 However, the MEBO group had a higher mean VNPR on admission 589
were eligible for inclusion. The heterogeneity of study methods,
527 (5.09 vs. 4.72) (p-value unreported) which may partially explain the 590
comparators and outcome measures precluded meta-analysis.
528 pain score differences. Furthermore, by the third week, there were 591
Even the three studies comparing MEBO to 1% SSD were suffi-
529 no longer any differences in analgesic effect. 592
ciently heterogeneous to preclude meta-analysis of only
530 In Hindy’s study, the MEBO group rated their pain as signifi- 593
these studies.
531 cantly less than that of the Aquacel Ag and saline control groups 594
The results of this review should be interpreted with the fol-
532 during the first 48 h [24]. However, although the mean VAS score 595
533 lowing caveats in mind. There were varying anatomical locations 596
for the MEBO group was 3.1 ± 1.9, those of the Aquacel Ag and
534 and not all papers specified. The appropriateness of 1% SSD as a 597
saline control groups were not reported. MEBO also had a greater
535 comparator or standard treatment is debatable since SSD has 598
ichthyotic effect than Acquacel Ag as shown greater proportions
536 been shown to be consistently associated with poorer healing 599
itch-free patients in the MEBO group compared to the Aquacel
537 outcomes compared to treatments such as skin substitutes, silver- 600
Ag and saline control groups (65 vs. 25% and 10%, respect-
538 containing dressings and silicon-coated dressings [1]. Other fac- 601
ively) [24]
539 There was no difference in the analgesic properties of MEBO
tors precluding meta-analysis included variability in outcome 602
540 and povidone-iodine þ bepanthenol cream (mean morning VAS
measurement. Surrogates included time to complete wound heal- 603
541 scores: 3.0 vs. 4.2, respectively, mean evening VAS scores: 3.8 vs. ing [24–26], TEWL [17], time to 75% healing [16,19,27] and 50% 604
542 4.7 respectively) [22]. reduction in TEWL [26]. 605
543 Tsoutsos et al. found that pain scores were significantly 606
544 improved with Helix Aspersa compared to MEBO (4.50 ± 0.52 vs. 607
MEBO effect on wound healing
545 3.52 ± 0.80) [26]. In this trial, mean VAS scores were similar 608
546 between the MEBO and Helix aspersa groups before dressings
The results do not consistently favour MEBO or any of its compa- 609
547 were applied (6.50 ± 0.89 vs. 6.22 ± 1.25). rators. Of the three studies comparing the wound healing proper- 610
548 In summary, the majority of trials comparing wound healing ties of SSD with MEBO, two favoured MEBO [16,25] whilst one 611
549 between MEBO and SSD favoured MEBO. There may be improved favoured SSD [17]. One of the favourable studies was poorly 612
550 healing in MEBO-treated wounds vs. those treated with povidone- reported, exposing it to significant biases [25]. The small improve- 613
551 ment in the other favourable study was not statistically significant 614
iodine þ bepanthenol cream. There was no difference between
552 [16,19,27]. This small and statistically insignificant benefit should 615
MEBO and Acquacel Ag, but Helix Aspersa had faster healing rates
553 be interpreted in the context of moderate risk of bias due to 616
than MEBO.
554 issues with blinding and failure to analyse on an intention to treat 617
555 basis. 618
Incidence of adverse effects
556 Wound healing was also reportedly improved in MEBO com- 619
The incidence of adverse effects was very low in all studies and
557 pared to Acquacel Ag [24] and povidone-iodine þ bepanthenol 620
for all interventions. One MEBO vs. SSD RCT reported no adverse
558 cream groups [22]. The results in the Acquacel Ag trial were at 621
outcomes for either intervention but the other two RCTs did not
559 risk of bias due to poor reporting [24]. The highest quality study 622
report their incidence of adverse effects [16,19,25,27]. There was
560 used an indirect surrogate measure, that is, reduction in TEWL to 623
no difference in allergy rates between MEBO and either Helix
561 624
aspersa [26] or povidone-iodine þ bepanthenol creams [22]. The suggest faster healing in SPT but not DPT burns [22]. This trial by
562 625
respective rates of adverse effects of MEBO and Aquacel Ag were Carayanni et al. was at risk of intrinsic bias as it was funded by a
563 626
not reported in the sole trial comparing the two [24] manufacturer of MEBO [31].
564 627
Only two trials reported the incidence of wound infections Patients receiving Helix aspersa cream healed faster than those
565 628
[16,19,22,27]. There was no difference in the incidence of methicil- receiving MEBO [26]. This study by Tsoutsos et al. [26] was at
566 629
lin-resistant Staphylococcus aureus infections between the MEBO moderate risk of bias and also compared MEBO to a treatment
567 630
and SSD groups in one trial (37.4 vs. 38.5%, respectively) that is not standard of care. Due to these quality issues, these
6 N. T. MABVUURE ET AL.
631 results should, therefore, be interpreted with caution. At present, [2] Hoogewerf CJ, Van Baar ME, Hop MJ, et al. Topical treat- 694
632 poor evidence shows no difference in wound healing properties. ment for facial burns. Cochrane Database Syst Rev. 2013. Q5 695
633 [3] Nirmal SA, Pal Subodh C, Subhash CM, et al. Analgesic and 696
634 anti-inflammatory activity of b-sitosterol isolated from 697
MEBO effect on secondary outcomes
635 Nyctanthes arbortristis leaves. Inflammopharmacology. 2012; 698
636 Similar caution should be exercised in interpreting the effects of 20(4):219–224. 699
637 the interventions on secondary outcomes. In summary, there was [4] Loizou S, Lekakis I, Chrousos GP, et al. Beta-sitosterol exhib- 700
638 no difference in pain profiles in two [17,25] of three trials compar- its anti-inflammatory activity in human aortic endothelial 701
639 ing MEBO with SSD and in one trial comparing MEBO with povi- cells. Mol Nutr Food Res. 2010;54(4):551–558. 702
640 done-iodine þ bepanthenol cream [22]. One 3-week trial found [5] Gupta MB, Nath R, Srivastava N, et al. Anti-inflammatory 703
641 that MEBO had better analgesis than SSD but only in the first and antipyretic activities of beta-sitosterol. Planta Med. 704
642 week [16,19,27]. Helix aspersa cream had a greater analgesic effect 1980;39(2):157–163. 705
643 than MEBO [26]. [6] Dyson M, Young S, Pendle CL, et al. Comparison of the 706
644 The claim that MEBO was more analgesic than Acquacel Ag effects of moist and dry conditions on dermal repair. J 707
645 could not be verified since pre-treatment VAS scores were not Invest Dermatol. 1988;91(5):434–439. 708
646 reported [24]. Furthermore, the Acquacel Ag trial was either inad- [7] Eriksson E, Perez N, Slama J, et al. Treatment of chronic, 709
647 equately randomised, poorly reported or both. The identity of nonhealing abdominal wound in a liquid environment. Ann 710
648 outcome assessors and blinding protocols were also not specified. Plast Surg. 1996;36(1):80–83. 711
649 Wound infection and adverse effects rates were similarly low [8] Breuing K, Eriksson E, Liu P, et al. Healing of partial thick- 712
650 in both MEBO and comparator groups in all studies. However, ness porcine skin wounds in a liquid environment. J Surg 713
651 none of the studies reported adverse events according to item 19 714
Res. 1992;52(1):50–58.
652 of the CONSORT scale which advises recording adverse events 715
[9] Alexander G, Rajacic N, Ebrahim MK, et al. MEBO and hot
653 with reference to standardised criteria. 716
bitumen burns. Burns. 2003;29(8):863–865.
654 717
[10] Atiyeh BS, Dham R, Yassin MF, et al. Treatment of toxic epi-
655 718
dermal necrolysis with moisture-retentive ointment: a case
656 Limitations 719
report and review of the literature. Dermatol Surg. 2003;
657 This systematic review was conducted following PRISMA guide- 720
29(2):185–188.
658 721
lines. However, some limitations remain. The methodological flaws [11] Jewo PI, Fadeyibi IO, Babalola OS, et al. A comparative
659 722
of the eligible studies and their effect on this review’s conclusions study of the wound healing properties of moist exposed
660 723
have been extensively described above. This abundance of pre- burn ointment (MEBO) and silver sulphadiazine. Ann Burns
661 724
clinical evidence of efficacy would suggest a likely positive clinical Fire Disasters. 2009;22(2):79–82.
662 725
efficacy. However, the evidence was not high quality enough to [12] Zhang HQ, Yip TP, Hui I, et al. Efficacy of moist exposed
663 726
664 definitively answer this question. Furthermore, there was a selec- burn ointment on burns. J Burn Care Rehabil. 2005;26(3): 727
665 tion bias towards trials indexed on MEDLINE and EMBASE, argu- 247–251. 728
666 ably the two preeminent general healthcare databases. Several [13] Ioannovich JD, Magliacani G, Costagliola M, et al. Moist 729
667 case reports written in unscientific formats and listed on the man- exposed therapy of partial-thickness burn wounds. A multi- 730
668 ufacturer’s website were excluded as they were largely anecdotal center study. Eur J Plast Surg. 2003;26(7):338–345. 731
669 [15]. Papers were limited to English-language publications. [14] Atiyeh BS, Dham R, Costagliola M, et al. Moist exposed 732
670 Attempts were made to contact all authors for clarification of therapy: an effective and valid alternative to occlusive 733
671 missing data required but only one author responded. dressings for postlaser resurfacing wound care. Dermatol 734
672 Surg. 2004;30(1):18–25. 735
673 Conclusions [15] MEBO GROUP n.d. http://en.mebo.com/DaShiJi/index/id/ 736
674 290.html. (accessed November 23, 2019). Q6 737
675 The evidence for MEBO in English-language literature was poor [16] Ang ES, Lee ST, Gan CS, et al. Evaluating the role of alter- 738
676 and inconsistent with respect to wound healing rate and analge- native therapy in burn wound management: randomized 739
677 sis compared to 1% SSD, Acquacel Ag, Helix aspersa cream and trial comparing moist exposed burn ointment with conven- 740
678 povidone-iodine þ bepanthenol cream. Blinded RCTs comparing tional methods in the management of patients with 741
679 MEBO to both placebo and other common topical treatments second-degree burns. MedGenMed. 2001;3(2):3. 742
680 such as paraffin wax, which may also provide a moist and [17] Hirsch T, Ashkar W, Schumacher O, et al. Moist exposed 743
681 exposed environment, may further improve the confidence in burn ointment (MEBO) in partial thickness burns - a 744
682 concluding their analysis. There is good evidence that MEBO is as randomized, comparative open mono-center study on the 745
683 safe as its comparators as shown by the low complication rate. efficacy of dermaheal (MEBO) ointment on thermal 2nd 746
684 degree burns compared to conventional therapy. Eur J 747
685 Med Res. 2008;13:505–510. 748
686 Disclosure statement 749
[18] Mabrouk A, Boughdadi NS, Helal HA, et al. Moist occlusive
687 No potential conflict of interest was reported by the author(s). R V 750
dressing (Aquacel Ag) versus moist open dressing
688 R V 751
(MEBO ) in the management of partial-thickness facial
689 752
burns: a comparative study in Ain Shams University. Burns.
690 References 753
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