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American Journal of Infection Control ■■ (2018) ■■-■■

Contents lists available at ScienceDirect

American Journal of Infection Control American Journal of


Infection Control

j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g

Major Article

Efficacy of bladder irrigation in preventing urinary tract infections


associated with short-term catheterization in comatose patients:
A randomized controlled clinical trial
Farahnaz Ramezani MSN a, Mahnaz Khatiban PhD b,*, Farshid Rahimbashar MD c,
Ali Reza Soltanian d
a
School of Nursing and Midwifery, Hamadan University of Medical Sciences, Hamadan, Iran
b Mother & Child Care Research Center, Department of Medical Surgical Nursing, School of Nursing and Midwifery, Hamadan University of Medical
Sciences, Hamadan, Iran
c
Department of Anesthesiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
d Modeling of Noncommunicable Disease Research Center, Department of Biostatistics and Epidemiology, School of Public Health, Hamadan University of

Medical Sciences, Hamadan, Iran

Key Words: Background: Bladder irrigation can be performed to prevent catheter-associated urinary tract infec-
Coma tions (CAUTI), but its efficacy has been not reported in short-term indwelling urinary catheterization. This
intensive care units clinical trial aimed to examine the efficacy of bladder irrigation with normal saline solution in prevent-
ing CAUTI in comatose patients admitted to intensive care units.
Materials and methods: Eligible patients were randomized to the experimental group or control group.
The experimental group received daily bladder irrigation with 450 cc sterile normal saline, in 3 150-mL
doses, for 3 consecutive days. Data on signs of CAUTI, including urine culture, axillary body temperature
(primary outcomes), and other urine and blood parameters (secondary outcomes) were obtained at base-
line and 5 days later.
Results: Results of group comparisons and logistic regression analysis that controlled for fluid intake showed
that the risk of CAUTI decreased by 99% in the experimental group compared with the control group (odds
ratio, 0.01; P < .001). Additional findings indicated a decrease in axillary body temperature and improve-
ments in urine appearance, urinary red cells and white cells, and erythrocyte sedimentation rates and
white-cell counts in the blood following bladder irrigation.
Conclusion: Daily bladder irrigation with normal saline during 3 days demonstrated efficacy in prevent-
ing CAUTI in comatose patients.
© 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier
Inc. All rights reserved.

* Address correspondence to Mahnaz Khatiban, PhD, Mother & Child Care Research
Center, Department of Medical Surgical Nursing, School of Nursing and Midwifery,
In intensive care units, short-term indwelling urinary catheter-
Hamadan University of Medical Sciences, Hamadan, Iran. ization is a fairly routine practice. It is done for 15%-25% of critically
E-mail address: mahnaz.khatiban@gmail.com (M. Khatiban). ill adult patients1,2 to monitor urine output and guide fluid resus-
FR and FR are currently affiliated with Besat Specialized and Super-Specialized citation, as well as to facilitate daily patient care.3 Catheterization
Hospital, Hamadan, Iran.
has been shown to increase the risk of catheter-associated urinary
MK is currently affiliated with Mother & Child Care Research Center, School of
Nursing and Midwifery, Hamadan University of Medical Sciences, Hamadan, Iran. tract infections (CAUTIs). CAUTIs are manifested by positive urine
ARS is currently affiliated with Modeling of Noncommunicable Disease Re- culture and at least 1 of these signs and symptoms: fever, supra-
search Center, School of Public Health, Hamadan University of Medical Sciences, pubic or costovertebral angle pain or tenderness, urinary urgency,
Hamadan, Iran. urinary frequency, and dysuria.4 It is estimated that 97% of UTIs re-
Supported by the research and technology vice-chancellor at Hamadan Univer-
sity of Medical Sciences. The funding source had no role in the course of study,
ported in hospitals occurred in catheterized patients.5 UTIs can
research, or assembly of the manuscript. develop in less than a week following catheterization and are related
Conflicts of interest: None to report. to several risk factors. Health care providers’ inappropriate

0196-6553/© 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajic.2018.05.009
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application of aseptic techniques during catheterization and poor Sample


hand hygiene facilitate the transfer of external bacteria into the
bladder. Further, less-than-optimal management of the catheter and Patients were eligible if they were aged 18 years or older, were
drainage tube, along with immobility and incomplete bladder emp- comatose, and had an indwelling urinary catheter within 48 hours
tying in comatose patients6 may lead to urinary stasis, which provides before the specimen collection resulted a positive urine culture of
a favorable medium for bacterial growth. The bacteria colonize the ≥103 CFU/mL.13 The exclusion criteria included a history of chronic
internal lumen of the catheter and form a biofilm,7 which can lead disease influencing kidney function (eg, diabetes, chronic kidney
to CAUTI and catheter blockage.8 CAUTIs increase the burden of care, disease, nephrosclerosis, acute or chronic glomerulonephritis, py-
length of intensive care and hospital stay, and the cost of care.9 elonephritis, immune deficiency disorders such as lupus
Clinical guidelines recommend a range of strategies for reduc- erythematosus, rheumatoid arthritis, urethral and/or bladder trauma,
ing the risk of CAUTI associated with long-term indwelling urinary current aminoglycoside therapy, and having an infection in other
catheterization. Bladder irrigation or washout has been advocated body systems such as respiratory or wound infection). A patient’s
as standard management of long-term catheters.10 However, a recent participation in the trial was terminated if his or her catheter was
Cochrane review11 found inconclusive evidence to support the ef- removed for any reason, or if they were transferred to another hos-
fectiveness of bladder irrigation in preventing CATUI. It is plausible pital unit.
that this finding is related to variability in the design and imple- The sample size calculation was informed by the results of a study
mentation of the irrigation protocol, including the types and volumes by Samimi et al 14 that compared the effects of 2 solutions
of the solution used, the frequency and timing at which the irri- (chlorhexidine and normal saline [NS]) used in bladder irrigations
gation procedure was done, and the specific techniques applied. on the prevention of CAUTIs. Based on these results, the probabil-
There is limited evidence of the influence of bladder irrigation on ity of a positive urine culture was estimated at 73.2% in the control
the prevention of CATUI in critically ill, comatose patients with short- group (p1) and at 50% in the experimental group (p2). Setting the
term indwelling urinary catheters. This clinical trial was designed power at 80% and a 2-sided significance level (α) at 0.05, and ap-
to address this gap in knowledge. plying the formula presented below, the number of participants
The overall purpose of this clinical trial was to examine the ef- required in each study group was 24. To account for a possible 20%
ficacy of bladder irrigation on the prevention of CAUTIs in critically dropout rate over the course of the trial, 30 participants were in-
ill, comatose patients catheterized for a short term (<30 days) and cluded in each of the experimental and the control groups, for a total
receiving care in an intensive care unit. Critically ill patients are often of 60.
sedated or comatose and unable to report on the symptoms of UTI
2
(eg, pain and dysuria).12 Therefore, the objective signs of CAUTI were ⎡ ⎤
assessed in this trial. ⎢ Z1− α p (1 − p ) + Z1− β p1 (1 − p1 ) + p2 (1 − p2 ) ⎥
n= ⎣ 2 ⎦ ≅ 24
The specific trial objectives were to determine the effects of ( p1 − p2 )2
bladder irrigation on primary outcomes, including urine colony
forming units per milliliter and patients’ axillary body tempera- Over the 7-month trial period (June-December 2017), all pa-
ture (°C). Secondary outcomes included urine parameters such as tients who were admitted to the participating intensive care unit
urine specific gravity, pH, white blood cell (WBC) and red blood cell and were catheterized (n = 139), were screened for eligibility. Of those
(WBC) deposits, epithelial cells per high power field, and nitrite, as meeting all eligibility criteria (n = 62), 60 were recruited, and their
well as blood parameters such as erythrocyte sedimentation rate family members provided written consent.
(ESR), WBCs, and RBCs.
Treatment protocol

MATERIAL AND METHODS


A 3-way indwelling urinary catheter was needed to prevent
backflow of urine into the bladder during irrigation.15 To maintain
Design
comparability on catheter type, a 3-way catheter was used for all
patients in the control and experimental groups.
A prospective, blinded, randomized controlled trial design was
used. Eligible patients were randomly assigned to the experimen-
tal group or control group as specified by the study group code Usual care protocol
number written on a card placed in an opaque envelope. Partici- At the participating intensive care unit, usual care included
pants in the experimental group received, in addition to usual care, routine catheter care, as described in clinical practice guidelines.
bladder irrigation following the protocol described in a later section, It involved performing hand hygiene, wearing sterile gloves, main-
whereas those in the control group were exposed to usual care, taining an uncontaminated area, using an aseptic technique and
which consisted of routine catheter care. Outcome data were col- sterile insertion technique, securing catheter to the patients’ thighs
lected at the same time points in both groups: time 1, within 48 with adhesive tape and below the level of the bladder, regularly emp-
hours of catheterization (representing baseline), and time 2, 5 days tying the collecting bag, and changing indwelling catheters and the
later (representing posttest); CAUTIs can develop with the 5-day time drainage bags every 3 days or based on clinical indications such as
period. Participants’ masking was maintained because they were infection, obstruction, or leakage.
comatose. The outcome assessors and laboratory specialists were
blinded to the participants’ study group. Bladder irrigation protocol
The trial was registered the Iranian Registry of Clinical Trials In addition to usual care, participants in the experimental group
(IRCT201702134578N6). It was conducted according to the prin- received the bladder irrigation protocol, which involved these steps.
ciples of the Declaration of Helsinki. The trial protocol was approved Skilled aseptic techniques were adhered to when inserting the cath-
by the Research Ethics Committee at Hamadan University of Medical eter at the start of the study. The bladder irrigation was done once
Sciences, Iran (IR.UMSHA.REC.1395.495) and the participating hos- a day, in the evening, for 3 consecutive days. The irrigation solu-
pital. Because patients were comatose, written informed consent tion was NS (0.9%). The volume used in the irrigation was estimated
obtained from their family members. on the basis of normal bladder capacity (400-600 cc) and normal
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F. Ramezani et al. / American Journal of Infection Control ■■ (2018) ■■-■■ 3

filling (150-300 cc), which triggers the urge to urinate.16 Accord- RESULTS
ingly, the daily bladder irrigation was done with 450 cc, given in 3
doses (150 cc each) of NS kept at room temperature; each 150 cc Table 1 presents the average values on the demographic and clin-
was injected into the bladder slowly, over a 10-minute period.17 The ical characteristics of participants in the experimental and control
catheter was clamped to keep the solution in the bladder for 10 groups. With randomization, the 2 groups did not differ on most
minutes. The clamp was reopened to allow drainage of all the in- characteristics (P > .05), as shown in Table 1. However, the volume
jected solution, determined by measuring the volume of the drained of fluid intake through intravenous or nasogastric tube was signifi-
solution and comparing it with the volume of the instilled solu- cantly larger in the control group than the experimental group
tion; the drained volume was equal to or greater than the volume (P < .05). Linear and logistic regression analyses were performed to
instilled. examine the effects of bladder irrigation, controlling for the base-
line difference in fluid intake.
Data collection
Data on participants’ demographic (eg, age and sex) and clini- Primary outcomes
cal (eg, medical diagnoses) characteristics were obtained from their
medical records at time 1. A checklist was developed to guide the Urine colonization
collection of outcome data from the medical records. The check- The urine colony forming units for patients in the control and
list included information on the specific outcome parameter and experimental groups at time 1 (baseline) and time 2 (5 days later)
instructions on what specific respective data to extract from the are shown in Figure 1. The χ2 test results indicated that the colony
records. The face and content validity of the checklist was con- forming units per milliliter was similar for both groups at time 1
firmed by a panel of 14 experts, including 8 faculty members of the (P > .05), but was significantly lower in the experimental group than
medical-surgical nursing department, 3 intensive care nurses, 2 in- that in the control group at time 2 (P < .001). The McNemar test
tensive care unit specialists, and an infection specialist. showed a significant decrease in colony forming units in the ex-
The primary outcomes were laboratory test results of the urine perimental group at time 2 (P < .001). The result of the logistic
culture, including presence and type of microorganism colony and regression analysis demonstrated that the risk of infection in the
urine colony forming units per milliliter, and axillary body tem- experimental group decreased by 99% compared with the control
perature measured by a medical thermometer after calibration. group (odds ratio, 0.01; P < .001) when controlling for fluid intake
Axillary body temperature values ranging from 35.5°C-37.0°C in- (Table 2).
dicated normal temperature and those >37.0°C indicated the presence
of fever.18 Axillary body temperature
The secondary outcomes were results of the laboratory test for The Mann-Whitney U test results showed no statistically sig-
the blood parameters of ESR, WBCs, and RBCs. Values 10-19 mm/ nificant difference in axillary body temperature between the
hour (adult men) and 15-23 mm/hour (adult women) for ESR, 5.0- experimental and control groups at time 1 (P > .05), but revealed a
10.0 (×103/μL) for WBCs, and 4.5-6.0 million/μL (adult men) and 4.2- significant difference between the 2 groups at time 2 (P < .05). The
5.0 million/μL (adult women) on RBC; results of laboratory test for experimental patients’ axillary body temperature was within normal
the urine analysis parameters of appearance (clear), specific gravity range at time 2 compared with time 1 (P < .001). The linear regres-
(normal, 1.002-1.035), pH (normal, 6-7.4), WBC (≤ 1) and RBC de- sion analysis found that, after controlling for fluid intake, bladder
posits (= 0), and epithelial cells (< 5) per high power field and nitrite irrigation contributed to a decrease in temperature (t = −0.20; B =
(negative) were considered as normal range.19 −0.193; P < .05) (Table 2).

Table 1
Comparison of differences in demographic and clinical characteristics between the 2 groups of patients

Variable Control (n = 30) Experiment (n = 30) P value


Age, y* 60.53 ± 18.70 62.97 ± 15.33 > .05
Glasgow Coma Scale/Score* 7.33 ± 3.04 7.23 ± 1.98 > .05
Length of stay in intensive care unit, d* 8.97 ± 8.93 8.53 ± 7.03 > .05
Intravenous serum, mL/24 h* 2,383.33 ± 552.16 1,983.33 ± 700.78 < .05
Nasogastric feeding, mL/24 h* 1,096.67 ± 815.57 1,318.33 ± 750.57 > .05
Gender† > .05
Female 13 (43.3) 17 (56.7)
Male 17 (56.7) 13 (43.3)
History of diseases‡ > .05
No 11 (36.7) 9 (30)
Hypertension 19 (63.3) 19 (63.3)
Colon cancer 0 (0.0) 2 (6.7)
Diuretic medications† > .05
Yes 2 (6.7) 2 (6.7)
No 28 (93.3) 28 (93.3)
Antibiotic medications† > .05
Meropenem 7 (23.3) 13 (43.3)
Cefazolin 11 (36.7) 10 (33.3)
Ceftriaxone 6 (20.0) 3 (10.0)
Metronidazole 1 (3.3) 0 (0.0)
Cefepime 1 (3.3) 1 (3.3)

NOTE. Values are presented as mean ± standard deviation or n (%).


*Based on t test.
†Based on χ2 test.

Based on Fisher exact test.
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The patients were assessed for eligibility


(n = 139).

Eligible patients (n = 62)

Excluded patients (n = 2, no consent)

Random
Allocation

Control group (n = 30 patients) Experimental group (n = 30 patients)


Baseline
Routine care Assessment Routine care + Bladder irrigation

Analysis (n = 30) Final Analysis (n = 30)


Assessment

Fig 1. Trial profile.

Table 2
Comparing differences in catheter-associated urinary tract infection variables between the 2 groups of patients before and after intervention

Variable Control (n = 30) Experiment (n = 30) P value P value


Urine, CFU/mL < .001 (Odds ratio, 0.01)
Baseline
< 100,000 12 (40.0) 4 (13.3) .05*
≥ 100,000 18 (60.0) 26 (86.7)
Day 5
< 100,000 7 (23.3) 28 (93.3) < .001*
≥ 100,000 23 (76.7) 2 (6.7)
P value .05† < .001†
Axillary temperature, °C .032 (t = −0.20;
Baseline 37.76 ± 0.43 37.77 ± 0.28 > .05‡ B = −0.193)
Day 5 37.67 ± 0.39 37.46 ± 0.25 < .05‡
P value > .05§ < .001§

NOTE. Values are presented as n (%) or mean ± standard deviation.


*Based on χ2 test.
†Based on McNemar test.
‡Based on Mann-Whitney U test.
§
Based on Wilcoxon test.

Secondary outcomes RBC. This difference was maintained after controlling for fluid intake
in the regression analysis (Table 4).
Urine parameters
No statistically significant between-group differences in all urine DISCUSSION
parameters were found at time 1. However, significant differences
were reported for urine appearance, WBC and RBC deposits, and pH, Overall, the trial’s findings suggest that bladder irrigation was
by the Fisher exact test. Although the appearance of urine in most successful in preventing CAUTI in short-term catheterization of crit-
patients was turbid at time 1, the number of patients who had turbid ically ill, comatose patients. Significant improvements were observed
urine decreased only in the experimental group at time 1 (P < .05) in the primary outcomes, urine colony forming units, and axillary
(Table 3). Similarly, the RBC and WBC deposits in the urine and urine body temperature, in patients who received bladder irrigation, using
pH decreased significantly in the experimental group, as found by 450 cc NS, once a day, over a 3-day period. Significant improve-
Fisher exact test and regression analysis. Bladder irrigation had no ments were also found for 3 secondary outcomes; specifically urine
effect on the other urine parameters, including epithelial cell appearance, urinary RBC and WBC deposits, and erythrocyte sed-
numbers, specific gravity, and urine nitrite level (P > .05) (Table 3). imentation rates.
The results of the trial are comparable with those of 2 previous
Blood parameters studies17,20 despite differences in duration of catheterization, target
Although comparable at time 1, the experimental and control population, and bladder irrigation protocol. van den Heijkant et al20
groups differed at time 2 in the blood parameters of ESR, WBC, and conducted a small-scale study involving children catheterized
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Table 3
Comparing differences in categorical variables between the 2 groups of patients before and after intervention

Baseline Day 5

Variable Control Experiment Control Experiment


Urine appearance
Clear 1 (3.3) 0 (0.0) 2 (6.7) 5 (16.7)
Subturbid 2 (6.7) 2 (6.7) 2 (6.7) 9 (30.0)
Turbid 27 (90.0) 28 (93.3) 26 (86.7) 16 (53.3)
P value > .05* < .05*
Urine epithelial cell count (normal, 0-5/high power field)
≤5 29 (97.7) 25 (83.3) 28 (93.3) 30 (100)
>5 1 (3.3) 5 (16.7) 2 (6.7) 0 (0.0)
P value > .05* > .05*
Urine-specific gravity (normal, 1.002-1.035)
1,000-1,010 2 (6.7) 2 (6.7) 1 (3.3) 1 (3.3)
1,010-1,020 7 (23.3) 3 (10.0) 6 (20.0) 2 (6.7)
1,020-1,030 21 (70.0) 25 (83.3) 23 (76.7) 27 (90.0)
P value > .05* > .05*
Urine nitrite
Negative 28 (93.3) 28 (93.3) 28 (93.3) 30 (100)
Positive 2 (6.7) 2 (6.7) 2 (6.7) 0 (0.0)
P value > .05* > .05*
Colony type (urine culture)
Proteus mirabilis 2 (6.7) 3 (10.0) 1 (3.3) 1 (3.3)
Staphylococcus aureus 7 (23.3) 2 (6.7) 4 (13.3) 0 (0.0)
Providencia sp 6 (20.0) 9 (30.0) 7 (23.3) 4 (13.3)
Escherichia coli 9 (30.0) 5 (16.7) 9 (30.0) 3 (10.0)
Enterococcus 3 (10.0) 4 (13.3) 5 (16.7) 0 (0.0)
Streptococcus 1 (3.3) 1 (3.3) 1 (3.3) 0 (0.0)
Acinetobacter sp 1 (3.3) 1 (3.3) 1 (3.3) 2 (6.7)
Klebsiella 1 (3.3) 5 (16.7) 0 (0.0) 5 (16.7)
No growth 0 (0.0) 0 (0.0) 2 (6.7) 15 (50.0)

NOTE. Values are presented as n (%).


*Based on Fisher exact test.

Table 4
Comparing differences in numerical variables between the 2 groups of patients before and after intervention

Variable Control (n = 30) Experiment (n = 30) P value Linear regression model


Urine pH (normal, 6.0-7.4)
Baseline 5.9 ± 1.06 5.5 ± 0.82 ‖ > .05 t = −2.11
Day 5 5.4 ± 0.93 5.03 ± 0.13 B = –0.751
P value < .05* < .01* P = .04
Urine count of WBCs (leukocytes) (normal, < 2) t = 3.30
B = −7.877
P = .002
Baseline 16.07 ± 10.74 15.17 ± 9.81 > .05†
Day 5 13.8 ± 8.38 5.73 ± 5.21
P value > .05* < .001*
Urine count of red blood cells † (normal, 0) t = −4.52,
Baseline 19.8 ± 8.96 20.87 ± 9.74 > .05† B = −7.967
Day 5 16.77 ± 7.81 9.47 ± 6.96 P < .001
P value > .05* < .001*
Blood erythrocyte sedimentation rate, mm/h† t = −2.04
Baseline 46.9 ± 28.28 68.43 ± 30.37 < .01‡ B = −0.36
Day 5 42.91 ± 23.49 51.17 ± 26.92 P = .046
P value > .05§ < .001§
Blood WBCs, cells/μL t = 0.22
B = 205.1
P = .835
Baseline 1,3034.7 ± 1,6867.6 11,360.0 ± 3,888.3 > .05†
Day 5 9,793.33 ± 2,944.1 9,680.0 ± 4,083.1
P value > .05* < .001*

NOTE. Linear regression model after moderation effects of volume (in milliliters) of intravenous serum and nasogastric tube intake. Values are presented as mean ± stan-
dard deviation.
WBC, white blood cell.
*Based on Wilcoxon signed-rank test.

Based on t test.
†Based on Mann-Whitney U test.
§Based on paired t test.
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following bladder surgery, and a bladder irrigation protocol using ically ill, comatose patients with short-term catheterization. Bladder
50 cc NS or NS with acetylcysteine. The irrigation was performed irrigation could also decrease urine turbidity, urinary WBC and RBC
to prevent calculi formation and catheter obstruction. The find- deposits, and erythrocyte sedimentation rates that could be indi-
ings supported the benefits of bladder irrigation in preventing rectly associated with CAUTI. Bladder irrigation with NS, done once
recurrent UTIs and in reducing the incidence of calculi formation.20 a day, could be considered a promising, easy to implement, and cost-
Richter et al17 compared the effects of bladder irrigation done pre- effective intervention for preventing CAUTI in critical care settings.
operatively to those of no irrigation in patients undergoing
prostatectomy. The irrigation protocol consisted of holding 50- References
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