Asian Nursing Research 6 (2012) 60e66

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Asian Nursing Research

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Research Article

Sodium Bicarbonate Solution versus Chlorhexidine Mouthwash in Oral Care of

Acute Leukemia Patients Undergoing Induction Chemotherapy: A Randomized
Controlled Trial
So-Eun Choi, RN, PhD 1, Hee-Seung Kim, RN, PhD 2, *
1
Department of Nursing, Nambu University, Gwangju, South Korea
2
College of Nursing, The Catholic University, Seoul, South Korea

a r t i c l e i n f o s u m m a r y

Article history: Purpose: The objective of this study was to compare the effectiveness of sodium bicarbonate (SB) solution
Received 16 September 2011 with chlorhexidine (CHX) mouthwash in oral care of acute leukemia patients under induction
Received in revised form chemotherapy.
8 May 2012
Methods: Forty-eight patients were randomly selected and assigned to a SB solution group or a CHX-
Accepted 8 May 2012
based product group according to acute myelogenous leukemia or acute lymphoblastic leukemia.
Patients were asked to rinse their mouth four times a day from the day before chemotherapy started
until discharge. The World Health Organization mucositis grade, patient-reported Oral Mucositis Daily
Keywords:
sodium bicarbonate
Questionnaire, and clinical signs associated with infection were assessed on a daily basis. The oral
leukemia microbial count was assessed on a weekly basis from the 1st day of chemotherapy started to the 28th day
stomatitis or to the day of discharge from the hospital.
oral hygiene Results: Of all the patients in the SB group, 25.0% developed ulcerative oral mucositis, whereas 62.5% in
the CHX group did. The onset of oral mucositis was later in the SB group than the CHX group. The oral
bacterial colonization in the SB group was significantly higher than that in the CHX group, but clinical
signs associated with infection did not differ in both groups.
Conclusion: As a result of this study, it was found that oral care by SB solution for acute leukemia patients
undergoing chemotherapy was an effective intervention to improve oral health.
Copyright Ó 2012, Korean Society of Nursing Science. Published by Elsevier. All rights reserved.

Introduction
The remission rate of acute leukemia is on the rise due to strong
myelosuppression after chemotherapy. However, oral mucositis is
one of the most debilitating side effects of cancer treatment (Bellm
et al., 2002; Rose-Ped et al., 2002). Damage to the oral mucous
membranes can occur as a consequence of the direct effects of
cytostatic drugs on the rapidly dividing cells in the tissues in the
mouth (Turhal, Erdal, & Karacay, 2000).
Oral mucositis has been associated with particular high-risk
groups, such as individuals receiving conditioning regimens for
stem cell transplantation and patients getting specific induction
protocols for acute leukemia (Scully, Sonis, & Diz, 2006). Oral
mucositis has been consistently reported to occur in at least 75% of
* Correspondence to: Hee-Seung Kim, The Catholic University, 505 Banpo-dong,
Seocho-gu, Seoul 137-701, Korea.
E-mail address: hees@catholic.ac.kr (H. S. Kim).
patients under treatment in these groups (Scully et al., 2006). These
patients with hematological malignancies develop oral problems
twice or three times more than patients with solid tumors do
(Rutkauskas & Davis, 1993). Among patients receiving cancer
chemotherapy, the frequency and severity of oral mucositis is
mainly determined by the type of cancer, the agents selected, and
the dose and timing of treatment (Raber-Durlacher et al., 2000;
Sonis et al., 2004). Combined treatment with different chemo-
therapeutic drugs further intensifies the likelihood of mucositis
(Scully et al.).
The severity of oral mucositis varies from redness or edema of
oral mucous membranes to ulcerative lesions (Sonis et al., 2004).
These lesions are accompanied with considerable pain and seri-
ously hinder eating and drinking (Bellm et al., 2002; Rogers, 2001).
Therefore, opioid treatment and use of total parenteral nutrition are
required (Wardley et al., 2000). The high incidence and severe
consequences of oral mucositis among patients who undergo
chemotherapy underlie the importance of good prevention and
management.

1976-1317/$ e see front matter Copyright Ó 2012, Korean Society of Nursing Science. Published by Elsevier. All rights reserved.
doi:10.1016/j.anr.2012.05.004
 S.-E. Choi, H.-S. Kim / Asian Nursing Research 6 (2012) 60e66
So far, various solutions and drugs such as bland rinse, antimi-
crobial rinse, anti-inflammatory agents, cryotherapy, mucosal
coating agents, growth factors, and laser therapy have been used;
several studies have been carried out (Clarkson, Worthington, &
Eden, 2007; Worthington, Clarkson, & Eden, 2007). However, the
effectiveness of such therapies has not been confirmed (Thomas,
Blume, Forman, & Appelbaum, 2004). Moreover, expensive drugs
are difficult to apply in a clinical setting because of the cost.
Antimicrobial agents are able to control oral bacterial coloni-
zation and formation of dental plaque. Antimicrobial agents most
commonly used is chlorhexidine (CHX) mouth rinse (Solomon,
Shaikh, & Arendorf, 1995; Worthington et al., 2007). Chlorhex-
idine digluconate is a bisbiguanide with a molecular structure
consisting of a hexamethylene bridge with terminal 4-chlorophenyl
groups. If lower concentrations are used, it has a bacteriostatic
effect. The positively charged molecules bind to the negatively
charged bacterial cell wall, thereby interfering with membrane
transport (Hugo & Longworth, 1966). However, effectiveness of
rinsing with CHX solution varies from reducing oral mucositis and
oral candidiasis to no effects (Dodd et al., 2000; Ferretti et al., 1990;
McGaw & Belch, 1985; Pitten, Kiefer, Buth, Doelken, & Kramer,
2003). In addition, patients complained of the side effects of CHX,
such as alteration of taste, unpleasant flavor in the mouth, and even
pain (Dodd et al.; Moon, 2006; Pitten et al.). In addition, the
mucositis guidelines of multinational association of supportive care
in cancer recommended that CHX not to be used to prevent oral
mucositis in patients with solid tumors of the head and neck who
are undergoing radiotherapy (Keefe et al., 2007). But in the actual
clinical setting, CHX is used for patients under chemotherapy from
the time of admission to discharge due to fear of the risk of infec-
tion related to oral mucositis, which is very likely to happen in
acute leukemic patients.
On the other hand, bland oral rinses such as 0.9% saline solution,
sodium bicarbonate (SB) solution, or saline-SB solution have been
used for oral hygiene care (Thomas et al., 2004). Bland rinses not
only promote patients’ comfort but help maintain moisture of the
oral epithelial barriers and thus reduce the risk of secondary infec-
tion. Among the bland rinses, 0.9% saline solution and saline-SB
solution should be used at cool temperatures, as they taste a bit
salty and fishy. In contrast, SB solution can be easily used without
any reservation, as it has almost no taste. SB is the chemical
compound with the formula NaHCO3. HCO
3 makes H2CO3 by
reacting with Hþ; H2CO3 resolves into CO2 and H2O (Hill, McCreary,
& Kolb, 2009). SB does not have any direct antimicrobial effects but
has been used as a cleansing agent because of its ability to dissolve
mucus and loosen debris. SB raises oral pH and prevents overgrowth
of aciduric bacteria (Dodd et al., 2000, 2003; Turhal et al., 2000).
In foreign and domestic studies previously conducted, the bland
rinse applied to cancer patients was salt-soda solution (Dodd et al.,
2000, 2003; Jeon, 1998; Kim, Jeon, & Choi, 1997; Madan, Sequeira,
Shenoy, & Shetty, 2008); no studies on SB solution applied to
leukemic patients have been carried out. Dodd et al. applied salt-
soda solution on various cancer patients including solid tumor
after oral mucositis occurred. These studies focused on the effec-
tiveness of salt-soda solution on the severity of established oral
mucositis and the time period required to heal. Jeon and Kim et al.
studied the effect of salt-soda solution on chemotherapy or
radiation-induced oral mucositis on leukemic patients; Madan
et al. conducted the same study on head and neck malignancies
patients. But in these studies, oral microbial counts and possibility
of systemic infection were not covered.
While several studies indicated the effectiveness of salt-soda
solution (Dodd et al., 2000, 2003; Kim et al., 1997), important
variables, such as medical diagnosis and chemotherapeutic
regimen were not considered; oral microbial counts and clinical
61
signs associated with infection were not evaluated. Thus, this study
was conducted to evaluate the effectiveness of oral care using the
SB solution and CHX mouthwash on the oral health and the risk of
infection in acute leukemic patients on the same chemotherapeutic
regimen under the same medical diagnosis.
Purpose
The objective of this study was to find out the effectiveness of
oral care by SB solution and CHX mouthwash on the severity of oral
mucositis, the limitations of daily activities caused by mouth and
throat soreness, oral bacterial colonization, and clinical signs
associated with infection in acute leukemic patients under induc-
tion chemotherapy. This study explored four hypotheses: (a) Oral
mucositis of SB group will be less severe than that of the CHX group.
(b) The limitations of daily activities caused by mouth and throat
soreness in SB group will be less severe than that of the CHX group.
(c) The oral aerobic bacterial colonization in the SB group will be
higher than that of the CHX group. (d) Clinical signs associated with
infection will not differ in both groups.
Methods
Study design
This study used a repeated measures experimental design to
examine the effects of oral care by SB solution in comparison with
CHX mouthwash on the oral health of acute leukemic patients
under induction chemotherapy. Participants were randomly
assigned to the SB group or the CHX group according to acute
myelogenous leukemia (AML) or acute lymphoblastic leukemia
(ALL). The World Health Organization (WHO) mucositis grade,
patient-reported Oral Mucositis Daily Questionnaire (OMDQ), and
clinical signs associated with infection were assessed on a daily
basis. The oral microbial count was assessed on a weekly basis.
Setting and samples
Participants were recruited from patients admitted to the
hematology clinic of a tertiary care hospital in Seoul, South Korea.
The data were collected from May to September 2008. Patients who
met the following criteria were included: (a) over 18 years of age;
(b) had never been treated with chemotherapy; (c) AML under
induction chemotherapy with Idarubicin and Enocitabine or ALL
under induction chemotherapy with cyclophosphamide, Vincris-
tine sulfate, and Daunorubicin; and (d) an oral mucositis score of
0 with no fever signs at the time of admission. Patients were
excluded from the study if they had any of the following conditions:
(a) oral mucositis or fever was present before chemotherapy, (b)
transferred to the intensive care unit due to severe complications
during hospitalization, or (c) oral care solution changed during
hospitalization.
The sample size for the study was calculated based on repeated
measures analysis of variance with an alpha value of .05, power of
80%, and an effect size of .44 (Machin, Campbell, Fayers, & Pinol,
1997). Effect size was calculated based on Kim et al. (1997).
Twenty-three individuals were required per group; however, 32
individuals per group were aimed for, taking into account a pre-
dicted 30% drop out rate. The participants who met the above
criteria and agreed to participate in the study were 31 in the SB
group, 37 in the CHX group in the beginning. However, 7 in the SB
group, 13 in the CHX group dropped out during the study Therefore,
only 48 participants (24 in the SB group and 24 in the CHX group
completed the entire study. Three participants in the SB group and
six participants in the CHX group were transferred to the intensive
62 S.-E. Choi, H.-S. Kim / Asian Nursing Research 6 (2012) 60e66
care unit while on chemotherapy. One participant in both groups
changed their chemotherapy regimen. Oral mucositis before
chemotherapy occurred in two participants in the SB group and one
in the CHX group. One participant in the SB group and five in the
CHX group wanted to change to the other solution.
Measurements
Scoring oral mucositis with WHO Oral Toxicity Scale
The severity of oral mucositis was evaluated according to the
WHO Oral Toxicity Scale (WHO, 1979) developed to describe
toxicities associated with cancer treatment. WHO Oral Toxicity
Scale contains a single question comprised of 4-point scale that
assesses overall status of the mouth. Although the widely-used
WHO Oral Toxicity Scale has never undergone validation tests, its
use is based upon the opinion of experts and almost 30 years of
accumulated experiences (Quinn et al., 2008). Historically, many
assessment scales of oral mucositis have been based on the scale
developed by the WHO for the scoring of oral mucositis of patients
receiving cancer therapy (Sonis et al., 2004). The severity of oral
mucositis is graded from 0 (no mucositis) to 4 (alimentation not
possible). The criteria for scoring severity of mucositis are as
follows: 0 ¼ no change; 1 ¼ localized erythema of oral mucosa;
2 ¼ diffuse erythema, discrete erosive lesions, can eat solid foods;
3 ¼ diffuse erythema, discrete erosive lesions, ulceration, requires
liquid diet only; and 4 ¼ multiple ulcers, necrosis of oral mucosa,
alimentation not possible. In this study, we defined more than 2
points as ulcerative oral mucositis.
Patient-reported soreness of mouth and throat and limitations on
daily activities
Patient self-reported mouth and throat soreness (MTS) and the
resulting limitations on daily functional activities were obtained
from the OMDQ.
The OMDQ was developed as a mucositis-specific questionnaire
to assess patient-reported outcomes based on one-on-one inter-
views with focus groups and cancer patients (Bellm et al., 2002). It
was administered in phase III clinical trials of palifermin in the
hematopoietic stem cell transplant setting (Fliedner et al., 2007;
Stiff et al., 2006a). Test-retest reliability and internal consistency
reliability of OMDQ was acceptable. Validity was demonstrated as
MTS-related questions were correlated with the WHO Oral Toxicity
Scale, Radiation Therapy Oncology Group, and the Western
Consortium for Cancer Nursing Research scales (Stiff et al., 2006b).
The instrument is composed of 10 questions: overall health
(question 1), severity of MTS (questions 2 and 8), functional limi-
tations due to MTS (questions 3e7), and severity of diarrhea
(questions 9 and 10). Questions 2e7 and 9 are scored on a Likert-
like 5-point scale: 0 ¼ least symptom or limitation (no soreness, not
limited, or no diarrhea, respectively); and 4 ¼ worst symptom or
limitation (extreme soreness, unable to perform functional activities,
or severe diarrhea, respectively). Questions 1, 8, and 10 are scored on
a 0e10 scale. For question 1, (overall health) a higher score corre-
sponds to greater health. For question 8 (overall MTS) and question
10 (overall diarrhea), higher scores correspond to greater symptom
severities. Of the 10 questions, overall health (question 1) and
severity of diarrhea (question 9 & 10) are excluded as they have
nothing to do with oral mucositis. Questions 2 and 8 are about MTS.
Question 2 is a Likert-like 5-point scale and question 8 is on a 0e10
scale. Therefore, question 8 is excluded. In this study, severity of
MTS (question 2) and functional limitations due to MTS (questions
3e7) are used. Patients were asked to complete the questionnaire
every day from the day chemotherapy started to the 28th day or to
the day of discharge from the hospital. Two groups were compared
by mean of week.
Oral bacterial colonization
Oral microbial count was assessed on a weekly basis from the
1st day chemotherapy started to the 28th day or to the day of
discharge from the hospital. The counts of oral bacteria were
assessed by taking samples from saline-rinsed oral cavities of the
patients.
To acquire samples, patients gargled and rinsed their mouths
with 20 mL of normal saline for 30 seconds, and spit it into a sterile
cup. A sample of 0.1 mL was mixed with 9.9 mL of normal saline.
Next, 0.1 mL of the sample diluted 100 times was inoculated on
blood agar and Brucella agar plates. The same amount of diluted
sample was mixed with 0.9 mL of normal saline. A volume of 0.1 ml
of the sample diluted 1000 times was also inoculated on blood agar
and Brucella agar plates. Blood agar plates were incubated aerobi-
cally at 37 C for 24 hours. Brucella agar plates were incubated
anaerobically at 37 C for 48 hours.
Clinical signs associated with infection
Clinical signs associated with infection were evaluated by fever,
total number of days with fever, and bacteremia. It was determined
as fever when body temperature was over 38.3 C or over 38.0 C for
an hour. The number of days with fever more than once a day was
totaled. When the patient developed a fever, blood culture was
performed to identify bacteria in the blood stream according to
a doctor’s orders. It was determined as bacteremia when over two
of the same microorganism were found in the blood (Hughes et al.,
2002).
Procedure
The institutional review board of the Catholic University of
Korea, St. Mary’s Hospital approved this study. Institutional review
board number was SCMCO8MI045. Informed consent was obtained
from all patients, and the study design was approved by the
hospital ethics committee. Participants were assigned to one of the
two groups by block randomization; the blocks were divided
according to AML or ALL, and random sampling numbers were used
in each block.
SB solution was made by mixing sterile water with SB approved
by the Korea Food and Drug Administration. SB was dry-heat
sterilized in a central supply room to keep sterile status and
then individually wrapped in 2.5 g increments. Two assistant
nurses were trained in person to prepare SB solution. That was to
mix individually packed 10 g of SB in 1 L of sterile water (Thomas
et al., 2004). They provided it to patients every morning and the
left-over SB solution from the previous day was collected and
discarded.
The CHX group used Hexamedin (Bukwang Pharmacy, Seoul,
Korea; contents per 100 mL: 0.1% Chlorhexidine digluconate,
8.04 g ethanol 95%) which is now in use at the clinic of hema-
tology. The researcher explained the objective and method of the
study to participants directly in person and conducted education
on the way to do oral care. Participants were educated about the
need for oral care, oral complications related to cancer treatment,
methods of brushing and gargling, and how to clean with
a toothbrush. Patients were asked to rinse their mouth and throat
four times a day for 1 minute from the day before chemotherapy
started until the day they were discharged. The researcher visited
the participants every morning, assessed with the WHO Oral
Toxicity Scale and confirmed that the OMDQ was done by patients.
Clinical signs associated with infection were examined by refer-
ring to the nursing record and laboratory data on a daily basis. The
oral microbial count was assessed on a weekly basis from the 1st
day chemotherapy started to the 28th day or to the day of
discharge from the hospital.
 S.-E. Choi, H.-S. Kim / Asian Nursing Research 6 (2012) 60e66 63

Data analysis Table 1 Demographic, Clinical, and Microbiologic Characteristics of Participants at

Baseline

All analyses were performed using the SAS program (SAS Characteristics SB CHX c2/t p
Institute, Cary, NC, USA). For all statistical analysis, significance n (%) or Mean  SD
levels were set as p < .05. The chi-square test, t-test and Fisher’s
Age (year) 37.4  12.5 40.5  12.1 0.88 .385
exact test were used to test the homogeneity of the demographic, Gender
clinical and microbiologic characteristics between the two groups. Male 13 (54.2) 16 (66.7) 0.78 .375
Chi-square test, t-test and Fisher’s exact test were used for Female 11 (45.8) 8 (33.3)
Disease
comparison of oral mucositis in both groups. Because the data of
Acute myelogenous leukemia 15 (62.5) 15 (62.5) 0.00 .999
patient-reported soreness of mouth and throat and limitations on Acute lymphoblastic leukemia 9 (37.5) 9 (37.5)
daily activities were not normally distributed, Friedman test and History of smoking
Wilcoxon rank sum test were used for comparison of patient- Yes 11 (45.8) 12 (50.0) 0.08 .772
reported soreness of mouth and throat and limitation of daily No 13 (54.2) 12 (50.0)
History of drinking alcohol
activities. The repeated measures analysis of variance and t-test
Yes 6 (25.0) 7 (29.2) 0.10 .745
were used for comparison of oral bacterial colonization. No 18 (75.0) 17 (70.8)
Dental caries
Results Yes 10 (41.7) 10 (41.7) 0.14 .927
No 9 (37.5) 8 (33.3)
Do not know 5 (20.8) 6 (25.0)
Demographic, clinical, and microbiologic characteristics Dental therapy within 2 years
of participants at baseline Yes 11 (45.8) 11 (45.8) 0.00 .999
No 13 (54.2) 13 (54.2)
The mean ages of the SB and CHX groups were 37.4 and 40.5 Scaling treatment within 6 months
Yes 6 (25.0) 5 (20.8) 0.11 .731
years, respectively. Men comprised 54.2% of the SB group and 66.7%
No 18 (75.0) 19 (79.2)
of the CHX group. In the SB and CHX groups, AML patients repre- ANC at admission day
sented 62.5% and 62.5% of the total, respectively. The remaining < 500 (mm3) 8 (33.3) 10 (41.7) 0.35 .551
patients in both groups had ALL (37.5% each). Aerobic bacteria of  500 (mm3) 16 (66.7) 14 (58.3)
the SB and CHX groups at admission measured 6.3 and 6.0 colony ANC at the first day of chemotherapy
< 500 (mm3) 11 (45.8) 11 (45.8) 0.00 1.000
forming units (CFU)/mL, respectively. Anaerobic bacteria of the SB  500 (mm3) 13 (54.2) 13 (54.2)
group at admission measured 6.5 CFU/mL and 6.3 CFU/mL for the Aerobic bacteria (log transformed, CFU/mL)
CHX group. No significant differences in demographic, clinical, or 6.3  0.7 6.0  0.7 1.17 .249
microbiologic characteristics between the two groups were Anaerobic bacteria (log transformed, CFU/mL)
6.5  0.4 6.3  0.6 1.31 .195
observed (Table 1).
Notes. SB ¼ sodium bicarbonate group (n ¼ 24); CHX ¼ chlorhexidine group
(n ¼ 24); ANC ¼ absolute neutrophil count; CFU ¼ colony forming units.
Distribution of the WHO grade of oral mucositis

No significant differences were noted in the incidence rates of

At the third week of chemotherapy, the eating limitation in the SB
oral mucositis between the two groups. However, the incidence
group (0.7 point) was significantly lower than that of the CHX
rate of ulcerative oral mucositis in the SB group (25.0%) was
group (1.6 points, p ¼ .015). At the third week of chemotherapy, the
significantly lower than that in the CHX group (62.5%, p ¼ .008). The
talking limitation in the SB group (0.3 point) was significantly lower
mean number of day to the onset of oral mucositis after chemo-
than that of the CHX group (0.7 points, p ¼ .043, Table 3).
therapy for both groups was 13 days. The onset of ulcerative
mucositis was significantly later in the SB group (16.1 days) than in
the CHX group (11.4 days, p ¼ .013). In this study, the mean duration Oral microbial counts
of oral mucositis for the participants in both groups was 12 days. No
significant differences were observed in the mean duration of oral After oral care, oral aerobic bacterial colonization differed
mucositis for participants between the SB group (11.8 days) and the significantly between the two groups (p ¼ .001). Significant differ-
CHX group (13.7 days, Table 2). ences were observed over time (p ¼ .001) and for an interaction

Patient-reported soreness of mouth and throat and limitations on

daily activities Table 2 Distribution of the WHO Grade of Oral Mucositis by Group

SB CHX c2/t p
The MTS score in the SB group and CHX group significantly
n (%) or Mean  SD
increased over time respectively (p < .001, p < .001). At the second
week of chemotherapy, the MTS score in the SB group (0.2 point) Mucositis grade
0 7 (29.2) 3 (12.5) .134a
was significantly lower than that of the CHX group (0.8 point,
1 11 (45.8) 6 (25.0)
p ¼ .001). At the third week of chemotherapy, the MTS score in the 2 3 (12.5) 8 (33.3)
SB group (0.7 point) was significantly lower than that of the CHX 3 2 ( 8.3) 5 (20.9)
group (1.5 points, p ¼ .009). 4 1 ( 4.2) 2 ( 8.3)
The scores of limitations on daily activities caused by mouth and Mucositis grouping
throat soreness were significantly increased over time. At the 0e1 18 (75.0) 9 (37.5) 6.85 .008
second week of chemotherapy, the swallowing and drinking limi- 2e4 6 (25.0) 15 (62.5)
tation in the SB group were significantly lower than those of the Onset of mucositis (day) 16.1  3.0 11.4  3.7 2.73 .013
CHX group (p ¼ .042, p ¼ .024). At the second week of chemo- Duration of mucositis (day) 11.8  4.9 13.7  5.4 0.74 .467
therapy, the eating limitation in the SB group (0.2 point) was Notes. SB ¼ sodium bicarbonate group (n ¼ 24); CHX ¼ chlorhexidine group (n ¼ 24).
significantly lower than that of the CHX group (0.7 point, p ¼ .008). a
Fisher’s exact test.
64 S.-E. Choi, H.-S. Kim / Asian Nursing Research 6 (2012) 60e66

Table 3 Patient-reported Soreness of Mouth and Throat and Limitations on Daily Activities

Variables Group 1st week 2nd week 3rd week 4th week or discharge c2 p

Mean  SD
Mouth and throat soreness SB 0.0  0.1 0.2  0.4a 0.7  1.0a 0.5  0.5 28.36 < .001
CHX 0.1  0.2 0.8  0.8a 1.5  1.1a 0.8  0.9 38.61 < .001

Limitations on daily activities

Swallowing SB 0.0  0.1 0.1  0.4a 0.4  0.9 0.2  0.4 20.45 < .001
CHX 0.0  0.1 0.3  0.5a 0.8  1.1 0.4  0.7 17.03 .001

Drinking SB 0.0  0.1 0.1  0.4a 0.4  0.9 0.2  0.4 20.45 < .001
CHX 0.0  0.1 0.3  0.5a 0.8  1.0 0.5  0.7 18.03 < .001

Eating SB 0.0  0.1 0.2  0.4a 0.7  1.1a 0.5  0.6 28.33 < .001
CHX 0.0  0.1 0.7  0.7a 1.6  1.1a 0.9  1.0 37.17 < .001

Talking SB 0.0  0.1 0.1  0.3 0.3  0.8a 0.2  0.3 22.43 < .001
CHX 0.0  0.1 0.2  0.3 0.7  0.9a 0.3  0.6 21.87 < .001

Sleeping SB 0.0  0.1 0.1  0.3 0.2  0.6 0.1  0.2 21.05 < .001
CHX 0.0  0.2 0.2  0.6 0.6  0.9 0.2  0.4 14.46 .002

Notes. SB ¼ sodium bicarbonate group (n ¼ 24); CHX ¼ chlorhexidine group (n ¼ 24).

a
Wilcoxon rank sum test: Means with the same letters are significantly different between the two groups.

between the groups and time (p ¼ .001). The oral aerobic bacterial Discussion
colonization in the SB group was significantly higher than that of
the CHX group at the 1st, 7th, 14th, 21st, and 28th day of chemo- Diverse oral care solutions have been applied to decrease the
therapy (p ¼ .001 for each day measured). incidence of oral mucositis and risk of infection due to oral muco-
The oral anaerobic bacterial colonization differed significantly sitis in acute leukemic patients under chemotherapy. However,
between the two groups (p ¼ .001). Significant differences were conflicting effects on these solutions were reported (McGuire,
observed over time (p ¼ .001) and for an interaction between the Correa, Johnson, & Wienandts, 2006).
groups and time (p ¼ .001). The oral anaerobic bacterial coloniza- In this study, the severity of oral mucositis was evaluated by the
tion in the SB group was significantly higher than that of the CHX WHO Oral Toxicity Scale (1979) generally used in the clinical
group at the 1st, 7th, 14th, 21st, and 28th day of chemotherapy setting, in addition to a patient-reported OMDQ.
(p ¼ .001 for each day measured, Table 4). No significant differences were seen in the incidence rates of
oral mucositis between the SB group (70.8%) and the CHX group
Clinical signs associated with infection (87.5%). This result was similar to that of studies conducted on
patients with head and neck malignances and acute leukemia with
The number of patients with fever and the number of days with saline-SB solution and CHX (Dodd et al., 2000; Jeon, 1998; Madan
fever did not differ significantly between the groups. The causal et al., 2008).
microorganisms of bacteremia in the SB group were identified as The incidence rate of ulcerative oral mucositis in the SB group
Escherichia coli (62.5%), Klebsiella pneumonia (25.0%) and Strepto- (25.0%) was significantly lower than that in the CHX group (62.5%).
coccus species (12.5%), and in the CHX group, they were Klebsiella Our results support the data by Pitten et al. (2003) who compared
pneumonia (42.8%), Escherichia coli (28.6%) and Streptococcus species the effects of CHX mouthwash with amine-stannous fluoride
(28.6%). However, no significant difference was found in bacteremia mouthwash in cancer patients. According to their study, more
between the groups in terms of better controlling the oral mucositis patients in the CHX group developed ulcerative mucositis. Potting,
caused by the types of bacteria. Uitterhoeve, Op Reimer, and Van Achterberg (2006) conducted
a meta-analysis to evaluate the effectiveness of prophylactic agents
Table 4 Oral Bacterial Colonization (CFU/mL, Log Transformed) for chemotherapy-induced oral mucositis. Studies done before
1992 reported a positive effect of rinsing with CHX, whereas those
SB CHX Source F p conducted between 1992 and 2004 reported either no effect or
Mean  SD a negative effect. In addition, evidence-based clinical practice
Aerobic bacteria guidelines for care of patients with oral mucositis recommended
At admission 6.3  0.7 6.0  0.7 Group 62.49 .001 that CHX not to be used to treat established oral mucositis for
1st day of chemotherapy 5.7  0.6a 4.7  0.9a Time 21.13 .001 patients under standard-dose chemotherapy (Keefe et al., 2007).
7th day 5.9  0.5a 4.6  0.7a GT 4.97 .001 The onset of ulcerative mucositis was significantly later in the SB
14th day 5.7  0.7a 4.4  1.0a
21th day 5.8  0.7a 4.4  1.0a
group (16.1 days) than in the CHX group (11.4 days). Scully et al.
28th day or discharge 5.5  0.7a 4.4  0.9a (2006) reported that early clinical signs of mucositis, such as
erythema, presented about 4e7days following chemotherapy
Anaerobic bacteria
At admission 6.5  0.4 6.3  0.6 Group 80.21 .001 infusion, and ulcers developed about 7e10 days after
1st day of chemotherapy 6.0  0.6a 4.9  0.9a Time 20.67 .001 chemotherapy.
7th day 6.3  0.3a 5.1  0.7a GT 5.81 .001 At the second and third week of chemotherapy, patient-
14th day 6.0  0.6a 4.8  0.9a reported MTS score in the SB group was significantly lower than
21th day 6.0  0.7a 4.5  1.0a
that of the CHX group. Djuric, Hillier-Kolarov, Belic, and Jankovic’s
28th day or discharge 5.9  0.8a 4.5  0.9a
study (2006) on acute leukemic patients reported that from day 14
Notes. SB ¼ sodium bicarbonate group (n ¼ 24); CHX ¼ chlorhexidine group
to day 21, the majority of patients had mucositis with high severity.
(n ¼ 24); G  T ¼ Group  Time.
a
t-test: Means with the same letters are significantly different between the two Ulcer developed after about 10 days of chemotherapy resulted in
groups. severe discomfort as to require opioid intervention (Scully et al.,
 S.-E. Choi, H.-S. Kim / Asian Nursing Research 6 (2012) 60e66
2006). It was interpreted that tingling sensation of CHX increased
MTS score in patients with ulcer. Among the limitations of daily
activities caused by mouth and throat soreness, the item, “eating”
was significantly limited. This result was similar to that of the
Fliedner et al. study (2007) on hematopoietic stem cell transplant
patients. Eating, swallowing, drinking, talking, and sleeping were
the activities affected or limited by MTS, in order from most severe
to least. It can be interpreted as that if oral mucositis becomes
ulcerative, it becomes difficult to chew because of the pain. Thus,
eating becomes severely limited.
Changes in subjective symptoms of oral mucositis such as pain
can precede changes in objective examinations (Dodd, Facione,
Dibble, & MacPhail, 1996). Stiff et al. (2006b) reported that
patients using the OMDQ detected changes in oral mucositis 1e3
days earlier than the clinical personnel who used the WHO scale
did. Early detection helps healthcare teams implement prevention
or palliative interventions at an early stage (Quinn et al., 2008).
Therefore, to accurately evaluate oral health of patients, oral
mucositis should be assessed both by doctors or nurses and by the
use of a patient-reported assessment tool.
This study showed that the number of microorganisms in the
oral cavity in the SB group was significantly higher than that in the
CHX group. This result was similar to that of the studies carried out
on patients with cancer and hematopoietic stem cell transplant
using CHX (Ferretti et al., 1990; Pitten et al., 2003). In spite of the
increase in the number of microorganisms in the oral cavity in the
SB group, no differences were observed between the two groups in
terms of fever, the number of days with fever, and bacteremia
associated with infection. Pitten et al. reported that body temper-
ature or application of antibiotics did not differ between CHX
mouthwash and amine-stannous fluoride mouthwash. It has been
thought that development of effective systemic antibiotics and
treatment of prophylactic antibiotics since 1990 affected oral
health and infection (Potting et al., 2006). Participants in this study
took prophylactic antibiotics from the first day of chemotherapy
according to the chemotherapy protocol, and antibiotics were
intravenously administered when patients had fever. Napeñas,
Brennan, Bahrani-Mougeot, Fox, and Lockhart (2007) reviewed 13
prospective clinical trials conducted from 1988 to 1998 to examine
the relation between oral bacterial microflora changes and oral
mucositis during chemotherapy. They found no association
between oral mucositis and oral microflora changes in these
studies. The mere colonization of oral flora does not necessarily
translate into local or systemic infection.
The oral aerobic and anaerobic bacterial colonization in the SB
group and anaerobic bacterial colonization in the CHX group at the
seventh day of chemotherapy increased more than at the first day
of chemotherapy. It was thought that reduction of salivary secretion
due to chemotherapy caused oral mucosal dryness and made
mucous more viscid. In this study, the frequency of oral care in both
groups was four times a day. However, Jansma et al. (1992) reported
that patients should rinse their mouth at least 8e10 times a day for
1 minute with a salt-soda solution. Löe and Schiott (1970) claimed
that it was proper to rinse with CHX twice per day, as antimicrobial
activity of CHX continued for 12 hours. Thomas et al. (2004) sug-
gested that oral care with CHX should be given from 2 to 4 times
a day depending on the severity of periodontal disease. Symonds
(1998) reported frequent mechanical cleansing is effective to
reduce oral bacterial colonization. Therefore, if nonirritable SB
solution is used every 2e3 hours, it will be effective to relieve oral
dryness and reduce oral bacterial colonization.
For effective oral care, oral care solutions should not only
prevent oral mucositis but be feasible to implement and easy to
adhere to for patients (Rubenstein et al., 2004). The fragrance and
flavor of mouthwash is a very important factor that affects the
65
compliance of oral care. SB solution can be easily applied as it has
almost no taste. Five in the CHX group wanted to change to the
other solution because of nausea caused by the unpleasant flavor
and tingling sensation of CHX. However, patients in the SB group
wanted to use SB after the study was over. In a study by Dodd et al.
(2000), oral care compliance of patients assigned to rinsing with
salt and soda solution was very high (92%). In a study by Epstein,
Vickars, Spinelli, and Reece (1992), patients assigned to rinsing
with CHX showed relatively poor compliance (78%), but patients
assigned to rinsing with saline solution demonstrated good
compliance (89%). Furthermore, SB solution is inexpensive and
readily available daily not only in a clinical setting but also at home.
Conclusion
This study found that oral care by SB solution for acute leukemia
patients undergoing chemotherapy was an effective intervention
to improve oral health. In the actual clinical setting, our findings
will encourage nursing practitioners to apply SB solution instead of
CHX mouth rinse for the oral care of leukemia patients under
chemotherapy.
The limitation of the study is that the survey was conducted for
patients without oral disease and oral mucositis before chemo-
therapy. Therefore, further studies are recommended for effective
oral care on patients with gingivitis, periodontal disease, and oral
mucositis prior to chemotherapy.
Conflict of interest
The authors declare no conflict of interest.
Acknowledgments
This article is based on a part of the first author’s doctoral thesis
from the Catholic University.
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