Chlorhexidine to treat oral mucositis in patients with acute leukemia: systematic review

Macedo, Rômulo Augusto de Paiva; Morais, Everton Freitas de; Dantas, Afonso Nóbrega; Morais, Maria de Lourdes Silva de Arruda

doi:10.5935/1806-0013.20150044

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ARTIGOS DE REVISÃO • Rev. dor 16 (3) • Jul-Sep 2015 • https://doi.org/10.5935/1806-0013.20150044 linkcopy

Chlorhexidine to treat oral mucositis in patients with acute leukemia: systematic review^*

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BACKGROUND AND OBJECTIVES: Leukemias impair hematopoietic stem-cells shunting and promote a proliferation of malignant cells without functional competence. Studies point that oral manifestations such as pain, hyperplasia and gum bleeding may be one of the first signs in leukemia patients. In light of the above, this study aimed at carrying out a systematic analysis of articles published in the last 15 years, with regard to chlorhexidine to treat and prevent mucositis in acute leukemia children under chemotherapy.

CONTENTS: A systematic search of articles published between January 2000 and January 2015 was carried out in Pubmed/Medline, Science Direct and LILACS databases. After systematic search, 6 articles have fulfilled all methodological inclusion criteria. Chlorhexidine is an important means of preventing and treating oral mucositis and studies refer that 0.12% chlorhexidine gluconate effectiveness is probably related to its bactericide action. Adequate oral hygiene is important to prevent mucositis and other therapeutic modalities have shown to be effective to treat and prevent oral mucositis.

CONCLUSION: Chlorhexidine gluconate does not totally eliminate oral mucosa injuries, but is able to decrease their frequency and intensity without significant noxious effects. However, other drugs compared to chlorhexidine in this study may present better results.

Keywords:
Chemotherapy; Hematology; Oncology; Oral manifestations; Mucositis

Strategies	A	B	C
Chlorhexidine / oral mucositis	12	747	198
Chlorhexidine / oral mucositis / treatment / acute leukemia	0	727	184
Chlorhexidine / oral mucositis / (treatment OR prevention) / acute leukemia	0	733	185
Chlorhexidine / oral mucositis / (treatment OR prevention) / mucosa / acute leukemia	0	531	37
Chlorhexidine / oral mucositis / (treatment AND prevention) / oral mucosa/ acute leukemia	0	401	37

Studies	Objectives	Types of leukemia	n / age	Protocol	Oral health evaluation	Analyzed variables
Soares et al.¹⁴	Evaluate oral mucosa changes and qualitative microbiota changes in children with ALL under chemotherapy, as well as the use of 012% chlorhexidine in such patients.	ALL	17/2 to 12 years.	Chlorhexidine mouthwash for 1 minute, twice a day (30 minutes after lunch and after last meal) for 10 days.	Clinical exam of oral mucosa for detection of oral lesions and microbiological test.	Presence of mucositis; effects of 0.12% chlorhexidine on oral microbiota.
Costa et al.¹⁵	Check the effectiveness of a preventive oral protocol using 0.12% chlorhexidine mouthwashes in children with ALL submitted to anticancer treatment.	ALL	14/2 to 10 years. (7 test group /7 control group).	The experimental group received supervised oral hygiene care and chlorhexidine mouthwash twice a day. The control group received supervised hygiene care with placebo mouthwash twice a day. The experiment started 1 day after and continued for up to 10 days after chemotherapy induction phase.	Clinical oral mucosa exam.	Evaluate the effect of chlorhexidine to treat oral manifestations; compare test and control groups.
Choi & Kim¹⁶	Compare the efficacy of sodium bicarbonate and c h l o r h e x i d i n e mouthwash to prevent oral manifestations in patients with ALL during chemotherapy induction phase	ALL & AML	48/ Mean of 38 years. (chlorhexidine group=24 patients; sodium b i c a r b o n a t e group = 24 patients).	Os participantes de ambos os grupos foram orientados a realizar os bochechos 4 vezes ao dia, sendo iniciados 1 dia antes do início da quimioterapia ate o final da primeira fase do tratamento oncologico.	Questionnaire, clinical oral mucosa exam and microbiological test.	Presence of oral lesions; effect of mouthwashes on oral mucosa.
Mehdipour et al.¹⁷	Evaluate the efficacy of zinc oral antiseptic for chemotherapyinduced oral mucositis as compared to chlorhexidine mouthwash	AML	30 (15 Test/15 control) / age above 15 years.	Induction and maintenance phase patients were evaluated. Patients of chlorhexidine and zinc sulfate groups were oriented to use mouthwash twice a day during 14 days. Patients were evaluated for 8 weeks.	Clinical oral mucosa exam.	Compare patients receiving 0.2% zinc sulfate to patients receiving 0.2% chlorhexidine gluconate to prevent oral mucositis
Pereira Pinto et al.¹³	Evaluate clinical aspects of oral mucosa of children with ALL and determine the effect of 0.12% chlorhexidine to prevent oral complications in these patients.	LLA	33 Group I (23 children): Oral 0.12% chlorhexidine solution, 2X/ day, group II (10 children): not receiving solution. /2 to 15 years	The experimental group had chlorhexidine mouthwashes for 1 minute, twice a day (30 minutes after lunch and after the last meal) during 10 days. Control group was not treated.	Clinical oral cavity exam / digital palpation of oral mucosa and cytological swabs (obtained from oral mucosa in the beginning of chemotherapy intensification).	Presence of mucositis; effects of 0.12% chlorhexidine; compare results among study groups.
Setiawan, Reniarti & Oewen¹⁸	Compare the effectiveness of chlorhexidine gluconate and povidoneiodine mouthwash for oral mucositis in children receiving chemotherapy for ALL.	ALL	18/ 2 to 10 years	Children developing mucositis in the chemotherapy induction phase were evaluated. Group A received 0.12% chlorhexidine, group B povidone iodine, group C saliva solution. Mouthwashes were performed twice a day (morning and evening) being the protocol repeated every day until injury remission or for a maximum period of two weeks.	Clinical oral mucosa exam.	Evaluate the effects of chlorhexidine gluconate and povidone- iodine on oral mucosa and compare both to control group.

Studies	More frequent oral manifestations	More frequent manifestation sites	Results
Soares et al.¹⁴	Mucositis was the most frequent oral manifestation affecting 5 children.	Not mentioned in the study.	Prophylactic use of 0.12% chlorhexidine gluconate decreases the frequency of mucositis and oral pathogens in ALL children under chemotherapy.
Costa et al.¹⁵	One experimental group (14.3%) and one control group (71.4%) child developed oral mucositis.	Most frequent in lip and jugal mucosa.	There has been significant decrease in the incidence of mucositis and oral ulcers in children with prophylactic chlorhexidine mouthwash.
Choie Kim¹⁶	Six (25%) patients of the sodium bicarbonate group have developed mucositis versus 15 (62.5%) of the chlorhexidine group.	Not mentioned in the study.	Sodium bicarbonate was more effective as compared to chlorhexidine to fight oral mucositis.
Mehdipour et al.¹⁷	Frequency of mucositis varied according to exams performed. 1^st exam (0 - zinc sulfate / 2 chlorhexidine); 2^nd exam (3 zinc sulfate / 8 chlorhexidine); 3^rdexam (5 zinc sulfate / 8 chlorhexidine); 4^th exam (3 zinc sulfate / 6 chlorhexidine)	Not mentioned in the study.	Zinc sulfate was better to control oral mucositis as compared to chlorhexidine in initial weeks, without statistically significant difference in the last exam.
Pereira Pinto et al.¹³	Mucositis was observed in six group I and eight group II children and was characterized by the presence of edema, erythema and ulcers.	Not mentioned in the study.	Chlorhexidine was beneficial in decreasing oral manifestations in children.
Setiawan, Reniartie Oewen¹⁸	All children had oral mucositis in the beginning of the study.	Not mentioned in the study.	The study showed that mucositis and related pain presented remission in 5 to 7 days for the chlorhexidine solution group, 8 to 14 days for the povidoneiodine group and 13 to 14 days for the control group.

Studies	Chemotherapic agents
Soares et al.¹⁴	Combinations for chemotherapeutic treatment were not mentioned.
Costa et al.¹⁵	Therapy consisted of 6-mercaptopurine (one 50/mg/m2/day oral dose during six weeks), methotrexate (one 2mg;m2 intravenous dose in continuous infusion during 24 h in days 1, 15, 30 and 45 of treatment, respectively), leucovorin (one 15mg/m2 oral dose four times a day in days 2, 3, 16, 17, 31, 32, 46 and 47) and spinal MADIT (combination of 12 mg methotrexate + 70mg cytosine-arabinoside + 2 mg/m2 dexamethasone) in days 1, 15, 30 and 45.
Choie Kim¹⁶	Under induction chemotherapy with idarubicin and enocitabine or LLA cyclophosphamide, vincristin and daunorubicin.
Mehdipour et al.¹⁷	Citarabine in the induction phase and novantrone in the consolidation phase.
Pereira Pinto et al.¹³	Protocol for acute leukemia treatment proposed by the Brazilian Society of Pediatric Oncology¹⁶. Methotrexate was a drug used in this therapy. 0.12% chlorhexidine gluconate was administered for 10 consecutive days, after each methotrexate infusion during intensification chemotherapy.
Setiawan, Reniartie Oewen¹⁸	Methotrexate (one spinal dose in days 1, 14 and 42), Dexamethasone (one 6mg/m2/day oral dose during 5 weeks), vincristin (one 1.5mg/m2 intravenous dose in continuous infusion in 5 minutes in days 7, 14, 21, 28, 35), and L-asparaginase (one 6000ug/m2 intravenous dose in weeks 4 and 5).

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[TFN01] A = LILACS; B = Science Direct; C = Pubmed/Medline.

Chlorhexidine to treat oral mucositis in patients with acute leukemia: systematic review*

Chlorhexidine to treat oral mucositis in patients with acute leukemia: systematic review^*