Prophylactic Chlorhexidine

Prophylactic Chlorhexidine

PEP Topic 
Mucositis
Description 

Chlorhexidine is an antiseptic that has a broad spectrum effect against both gram-positive and -negative bacteria. Chlorhexidine gluconate oral rinse that contains glycerol, coloring, flavoring, and other compounds has been studied in patients with cancer for the prevention and treatment of mucositis. It is important to note that prophylactic use, before development of mucositis, has a different PEP category than the use of chlorhexidine in patients who already have mucositis symptoms.

Likely to Be Effective

Research Evidence Summaries

Cheng, K.K., Molassiotis, A., Chang, A.M., Wai, W.C., & Cheung, S.S. (2001). Evaluation of an oral care protocol intervention in the prevention of chemotherapy-induced oral mucositis in pediatric cancer patients. European Journal of Cancer, 37, 2056–2063.

doi: 10.1016/S0959-8049(01)00098-3
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Intervention Characteristics/Basic Study Process:

The study was conducted over an eight-month period. The first four months were with the control group, which received routine care, no oral protocol, and the center's standard use of 0.9% sodium chloride (NaCl) and benzydamine hydrochloride rinse to control oral mucositis (OM) when it developed.

The last four months involved the experimental group, which received an oral care protocol consisting of patient education, maintenance of patient diaries, and rinsing with normal saline chlorhexidine every two hours on days 1–21. The oral protocol prescribed toothbrushing; NaCl solution rinse for gums, tongue, and soft tissue; and chlorhexidine rinse every morning and evening, as well as NaCl rinse after each meal and every two hours for the second week only.

Sample Characteristics:

  • The study reported on 42 children (21 in the control group and 21 in the experimental group) with hemotological or solid malignancies.
  • Mean age was 10.3 years and a range of 6–18 years.

Study Design:

This was a prospective, comparative study.

Measurement Instruments/Methods:

  • Oral assessment was performed initially and two times per week in each group.
  • The Eilers Oral Assessment Guide was used.
  • The Faces Pain Scale was used.
  • Patients were observed for fevers and neutropenia.

Results:

  • The oral protocol group experienced a 38% reduction of OM.
  • Severity of OM (p = 0.000002) and related pain (p = 0.0001) were significantly reduced in the intervention group.
  • The mean neutrophil count varied significantly between the seven time point evaluations (p = 0.008). A moderate negative correlation was found between the presence of OM and neutrophil count of the control group (p = 0.46) and protocol group (p = 0.15). Intensity of OM pain was significantly correlated with score of OM in two groups (p = 0.007).

Limitations:

  • Assessment was performed twice per week.
  • The results may not be generalizable to adult patients.
  • The sample size was smal.
  • A variety of chemotherapy protocols were used.
  • The experimental group may have experienced a study effect.
  • Use of chlorhexidine recommendation is in conflict with Multinational Association of Supportive Care in Cancer (MASCC) recommendations.

Nursing Implications:

Although the sample is small, the evidence supports the use of normal saline found in other studies.

Cheng, K.K., Chang, A.M., & Yuen, M.P. (2004). Prevention of oral mucositis in pediatric patients treated with chemotherapy: A randomized crossover trial comparing two protocols of oral care. European Journal of Cancer, 40, 1208–1216.

doi: 10.1016/j.ejca.2003.10.023
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Study Purpose:

To compare two oral care protocols with children receiving chemotherapy using either benzydamine or chlorhexidine oral rinses

Intervention Characteristics/Basic Study Process:

Patients used each mouthwash for three weeks and then crossed over. Patients also used a standard mouthcare protocol consisting of toothbrushing using the Bass method and mouth rinsing with either of the allocated rinses in the early morning and at bedtime, normal saline rinsing within 30 minutes of meals, and normal saline rinsing every 4 hours in the first and third week and every 2 hours in the second week after chemotherapy. Patients were instructed in using a ballooning and sucking motion of the cheeks for 30 seconds without swallowing. Researchers provided reinforcement practice sessions every week and a cartoon reminder.

Sample Characteristics:

  • The study reported on 40 patients.
  • Patients had a median age of 10.3 years with a range of 6–17 years.
  • Patients had solid and hematologic tumors.

Setting:

The study was conducted from April 2000 to April 2001.

Study Design:

This was a prospective randomized, non-blinded, two-period crossover study with continual sequential analysis.

Measurement Instruments/Methods:

  • Patient diaries were used. Researchers checked the remainder of rinse weekly to assess compliance.
  • Parents and children were interviewed at each assessment about oral performance. The nurse or investigator assessed patients two times per week.
  • Eilers' Oral Assessment Guide (OAG) was used with minor modifications. Interrelater reliability was established.

Results:

  • A total of 34 participants completed the two protocols.
  • No significant differences were found in patients' mean area under the curve (AUC) or oral mucositis according to order of protocols (t = 1.31, p > 0.05). No carry-over effect was found from initial oral care protocol.
  • Fewer patients receiving chlorhexidin developed ulcerative lesions (27% versus 59%).
  • A statistically significant reduction in ulcerative lesions was found using AUC (p < 0.05) and severity of mucositis (p < 0.05) in children on the chlorhexidine protocol.

Conclusions:

This study did not demonstrate the superiority of the oral rinses over oral care.

Limitations:

  • The study used a crossover methodology for control.
  • The sample size was small.
  • The study was not blinded.
  • The study involved a wide age range.
  • Patients were receiving a variety of chemotherapy protocols.
  • Patients continued systematic oral care along with the protocol.
  • Results may not apply to adult populations.

Dodd, M.J., Dibble, S.L., Miaskowski, C., MacPhail, L., Greenspan, D., Paul, S.M., et al. (2000). Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy-induced mucositis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, 90(1), 39–47.

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Study Purpose:

Test the effectiveness of three mouthwashes used to treat chemo-induced OM. Compared: salt/soda, (1 t each/pint of water) chlorhexidine and magic mouthwash (lidocaine, benadryl Maalox).
 

Intervention Characteristics/Basic Study Process:

Also used the Pro-Self program for all patients. Nurses presented the Pro-Self Mouth Aware program to patients and provided them with mouthwash. This program incorporates good oral hygiene, new toothbrush, daily flossing, regular oral assessments, and instruction of oral conditions that the patient must bring attention to the nurse.

Oral assessment and oral protocol 4x/day. Swished MW for 20 sec and then discard. The MW bottles were collected after their sx subsided or after 12 days supply. Measured amount remaining in bottles.
 

Sample Characteristics:

The mean age was 59.05 years.  
Chemo- not RT to head and neck or leukemia
 

Setting:

23 outpatient/office settings, 202 patients (142 final pts)

Study Design:

Randomized, double-blind trial to 1 of 3 mouthwashes.

Measurement Instruments/Methods:

  • Oral assessment done when patient entered study. Oral assessment guide was taught to all patients by nurses.
  • Patient reports QOD via phone to nurse.
  • Use chi-square test, one-way analysis of variance
     

Results:

Forty-seven patients dropped out, 11 took > 12 days to report a cessation of s/s.
No significance in three groups of demographics, disease-related variables. No significant difference in the time to reported cessation of the signs and symptoms from chemo-induced mucositis among the three groups (p = 0.59).
The average pain scores did not differ significantly (p = 0.79).
 

Limitations:

Patient reports, no clinician assessment during mucositis

Limitation of OAG tool – this guide addresses information of oral cavity changes and not strictly mucositis

Structure of oral care program may have been the greatest effect on mucositis.
 

Nursing Implications:

Findings support use of NS/baking soda over chlorhexidine and magic mouthwash – especially with established oral care program.

Pitten, F.A., Kiefer, T., Buth, C., Doelken, G., & Kramer, A. (2003). Do cancer patients with chemotherapy-induced leukopenia benefit from an antiseptic chlorhexidine-based oral rinse? A double-blind, block-randomized, controlled study. Journal of Hospital Infection, 53(4), 283–291.

doi: 10.1053/jhin.2002.1391
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Study Purpose:

To assess the benefit of antiseptic mouthwash in patients with leukopenia because of a decrease in micro-organisms

Intervention Characteristics/Basic Study Process:

  • Patients were randomized to chlorhexidine or fluoride rinse (control group).
  • Patients rinsed three times per day for 30 seconds from the start of chemotherapy to the end of leukopenia.
  • Pre-rinsing during and after leukopenia, aerobic and anaerobic bacteria in oral cavity were counted.
  • Patients were assessed for oral mucositis.
  • Patients did not brush teeth when leukopenic.

Sample Characteristics:

  • The sample consisted of 47 patients.
  • Patients had solid tumor and hematologic diagnoses.

Measurement Instruments/Methods:

  • Bacterial swabs were taken pre-, during and post-treatment.
  • Clinician assessment and mucositis scores were taken.
  • C-reactive protein was measured.

Results:

  • In the chlorhexidine group, a significant decrease in aerobic (p = 0.042) and anaerobic (p = 0.008) bacterial flora were identified.
  • In the control group, the numbers of bacteria were unchanged (p > 0.05).
  • More patients in the chlorhexidine group had severe mucositis and inflammation, but this was not significant.

Conclusions:

Chlorhexidine did not provide a clinical benefit against mucositis.

Limitations:

  • The study had a small sample.
  • The oral assessment was unclear.

Sorensen, J.B., Skovsgaard, T., Bork, E., Damstrup, L., & Ingeberg, S. (2008). Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil–based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies. Cancer, 112(7), 1600–1606.

doi: 10.1002/cncr.23328
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Study Purpose:

To evaluate chlorhexadine prophylaxis for flouruoracil- (5-FU-) based chemotherapy versus normal saline or cryotherapy

Intervention Characteristics/Basic Study Process:

The study involved three arms. Arm A received chlorhexidine mouth rinse three times per day for three weeks (n = 70), Arm B received normal saline placebo (n = 64), and Arm C received cryotherapy with crushed ice for 45 minutes during chemotherapy (n = 63).

Sample Characteristics:

  • The study reported on 225 randomized patients, 206 of which were evaluable.
  • All patients had gastrointestinal cancers.

Setting:

The study was conducted from 2001–2005.

Study Design:

This was a double-blind, placebo-controlled, randomized study, powered for 225 patients (75 in each arm).

Measurement Instruments/Methods:

The National Cancer Institute (NCI) Common Toxicity Criteria (CTC)  for oral mucositis was used.

Results:

Mucositis grade 3–4 occurred more frequently in arm B (33%) than in arm A (13%) (p < 0.01) and arm C (11%) p > 0.005). Duration was significantly longer in arm B than arm A (p = 0.035) and arm C (p = 0.003).

Systematic Review/Meta-Analysis

Donnelly, J.P., Bellm, L.A., Epstien, J.B., Sonis, S.T., & Symonds, R.P. (2003). Antimicrobial therapy to prevent or treat oral mucositis. Lancet Infectious Diseases, 3, 405–412.

doi: 10.1016/S1473-3099(03)00668-6
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Search Strategy:

Database searched was Medline (1964–June 2002).

Keywords searched were anti-infective agents and mucositis or stomatitis

Articles were included in the review if they were written in English language and described human clinical trials.

Studies were excluded if they involved meta-analyses.

Study quality was scored on 0–5 scale (with 5 being the highest) depending on previously established criteria. Five studies scored 4, and eight scored 0. The mean score was 2.1, indicating overall lack of quality in published material.

Literature Evaluated:

Thirty-one eligible studies were identified. Twenty-eight of the studies used some kind of control, usually a placebo mouthwash or sterile water. Seventeen studies assessed chlorehexidine, and five studies investigated preparations containing polymyxin, tobramycin, and amphotericin; others included povidone-iodine; fluconazole; clindamycin; bacitracin, clotrimazole, and gentamicin; tetrachlorodecaoxide, ciprofloxacin, or ampicillin with clortrimazole; sucralfate versus sucralfate; ofloxacin, miconazole, tetracain, and guaiazulene; triacetin versus topical anesthetics or system icanalgesics; tetracycline, nystatin; hydrocortisone; and diphenhydramine versus placebo. The chlorexidine studies also included the following agents: benzydamine, nystatin, povidone-iodine, salt and soda, magic mouthwash, and clotrimazole.

The scale used was reported in 22 studies. Scales were World Health Organization (n = 4), Oral Assessment Guide (n = 7), 0–5 scale (n = 1), and 0–4 scale (n = 10).

Sample Characteristics:

The number of patients across studies ranged from 12–275.

Results:

  • Of the 30 studies reporting a measurable outcome, 14 reported a benefit, 15 reported no benefit, and 1 reported an unfavorable outcome.
  • Of the 17 studies involving chlorhexidine, one had an unfavorable outcome (i.e., increased oral mucositis and discomfort), 11 showed no benefit, and 7 groups showed some benefit.
  • Four of the studies using other agents reported a benefit, four reported no benefit, and one reported only microbiologic data.

Conclusions:

No clear pattern emerged regarding the benefit of antimicrobial use to manage oral mucositis.

Nursing Implications:

Results draw attention to the multifaceted pathophysiology of oral mucositis, which presents a challenge for effective measures for prevention and treatment of mucositis.

McGuire, D.B., Fulton, J.S., Park, J., Brown, C.G., Correa, M.E.P., Eilers, J., . . . Lalla, R.V. (2013). Systematic review of basic oral care for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21, 3165–3177.

doi: 10.1007/s00520-013-1942-0
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Purpose:

STUDY PURPOSE: To systematically review oral care interventions for the prevention and treatment of oral mucositis (OM) in patients undergoing cancer treatment

TYPE OF STUDY: Systematic review

Search Strategy:

DATABASES USED: Ovid MEDLINE

KEYWORDS: mucositis, stomatitis, cancer, oral care, oral care protocol, dental care, dental cleaning, oral decontamination, oral hygiene, saline, sodium bicarbonate, baking soda, chlorhexidine, magic/miracle mouthwash, calcium phosphate

INCLUSION CRITERIA: Primary research article, reflects a variety of research designs, rested the effects of intervention on severity of OM or mucositis-related symptoms

EXCLUSION CRITERIA: Review articles, clinical case reports, literature reviews, non-research articles

Literature Evaluated:

TOTAL REFERENCES RETRIEVED = 129

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Hadorn et al. criteria was used to assess the flaws in the selected publications, and levels of evidence were rated using the Somerfield schema.

Sample Characteristics:

FINAL NUMBER STUDIES INCLUDED = 52

SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not stated

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Results:

The guidelines are as follows.

  • Oral care protocols: Oral care was suggested for the prevention of OM in adult and pediatric populations for all types of cancer therapies. No population-specific guidelines were recommended.
  • Dental care (by a professional): No guidelines were recommended for dental care in the prevention of OM.
  • Normal saline: No guidelines were recommended for normal saline for the prevention or treatment of OM.
  • Sodium bicarbonate rinse: No guidelines were recommended for sodium bicarbonate for the prevention or treatment of OM.
  • Chlorhexidine: No guidelines were recommended for chlorhexidine for the prevention or treatment of OM in patients receiving standard chemotherapy or hematopoietic stem cell transplantation. Guidelines suggest that chlorhexidine not be used to prevent OM in patients with head and neck cancer treated with radiotherapy.
  • Mixed medication mouthwash: No guidelines were recommended for mixed medication mouthwash for the prevention or treatment of OM.
  • Calcium phosphate: No guidelines were recommended for calcium phosphate for the prevention or treatment of OM.

Conclusions:

Oral care protocols are recommended to patients for the prevention and treatment of OM. Chlorhexidine is not recommended for patients with head and neck cancer who receive radiotherapy treatment.

Limitations:

Evidence for interventions to prevent and treat OM are limited, making guideline recommendations difficult.

Nursing Implications:

Nurses should teach patients appropriate oral care to help prevent OM.

Qutob, A.F., Gue, S., Revesz, T., Logan, R.M., & Keefe, D. (2013). Prevention of oral mucositis in children receiving cancer therapy: A systematic review and evidence-based analysis. Oral Oncology, 49, 102–107.

doi: 10.1016/j.oraloncology.2012.08.008
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Purpose:

To investigate, critically appraise, and rate the evidence regarding agents used for the prevention of mucositis in children

Search Strategy:

Databases searched included CINAHL, Cochrane library, Ovid MEDLINE, PubMed, BioMed Central, and other internet-based sources. A total of 19 databases were searched.

Search keywords were mucositis, stomatitis, oral inflammation, mouth mucosal inflammation, prophylaxis, management, and prevent; in addition to keywords to identify children and all types of cancer therapy.

Studies were included in the search if they

  • Involved English-speaking children.
  • Were clinical trials conducted on the prevention of oral mucositis during cancer therapy.

Studies were excluded if they

  • Were not in English
  • Did not involve children
  • Involved only gastrointestinal mucositis.
  • Involved treatment of mucositis rather than prevention.
  • Were case studies or pilot studies.
  • Were commentaries or letters to the editor.
  • Involved sample sizes of less than 20 patients.

Literature Evaluated:

  • The total number of references retrieved was 16,471.
  • The authors evaluated the references using the Canadian Task Force on Preventive Health Care evidence-based guidelines.

Sample Characteristics:

  • The final number of studies was 27. The sample range across studies was not reported.
  • Other than inclusion of pediatric cases, no other characteristics were described.

Phase of Care and Clinical Applications:

  • Patients were undergoing the active antitumor treatment phase of care.
  • The study has clinical applicability for pediatrics.

Results:

  • The studies involved the following interventions.
    • Oral care protocols (n = 5)
    • Chlorhexidine mouthwash (n = 7) 
    • Benzydamine mouthwash (n = 1)
    • Iseganan mouthwash (n = 1),
    • Granulocyte macrophage-colony stimulating factor (GM-CSF) mouthwash (n = 2)
    • Oral glutamine (n = 2)
    • Enteral glutamine (n = 1)
    • Oral propantheline and cryotherapy (n = 1)
    • Oral cryotherapy (n = 1)
    • Oral sucralfate suspension (n = 1)
    • Prostaglandin E2 tablets (n = 1)
    • Chewing gum (n = 1)
    • Laser therapy (n = 3). 
  • Good evidential support was found for the use of oral care protocols. Fair support was found for the use of chlorhexidine with some mixed results.
  • Only one article was found that studied benzydamine, CSF, and iseganan. The evidence was deemed insufficient to make a recommendation. 
  • Good evidential support was found against the use of sucralfate and prostaglandin E2 tablets.
  • Evidence regarding laser use and oral and enteral glutamine were mixed.

Conclusions:

The authors concluded that oral care protocols should be used; oral sucralfate suspension, prostaglandin E2, and GM-CSF mouthwash should not be considered based on current evidence; and chlorhexidine (without use as part of an oral care protocol), laser therapy, and glutamine should not be considered because of conflicting evidence.

Limitations:

  • No disease or treatment factors were reported or considered in the analysis. 
  • Some interventions were evaluated in only one study.
  • The quality of the evidence in general was highly variable.
  • No information was provided on how the outcome for mucositis was measured in the included studies.
  • The authors recommendations suggest no use of a specific intervention if findings were conflicting, which assumes that insufficient evidence of effectiveness is equivalent to ineffectiveness.

Nursing Implications:

Findings provide further support for use of oral care protocols. Results provided no other useful recommendations for preventive therapies but identified the need for further research in this area.


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