Vous êtes sur la page 1sur 23

Author's Accepted Manuscript

A Randomized Control Trial of Preoperative Prophylactic Antibiotics Prior to


Percutaneous Nephrolithotomy in Low Infectious Risk Population: A Report from
the EDGE Consortium

Ben H. Chew , Nicole L. Miller , Joel E. Abbott , Dirk Lange , Mitchell R.


Humphreys , Vernon M. Pais , Jr., Manoj Monga , Amy E. Krambeck , Roger L. Sur

PII: S0022-5347(18)43035-2
DOI: 10.1016/j.juro.2018.04.062
Reference: JURO 15568

To appear in: The Journal of Urology


Accepted Date: 13 April 2018

Please cite this article as: Chew BH, Miller NL, Abbott JE, Lange D, Humphreys MR, Pais VM Jr, Monga
M, Krambeck AE, Sur RL, A Randomized Control Trial of Preoperative Prophylactic Antibiotics Prior to
Percutaneous Nephrolithotomy in Low Infectious Risk Population: A Report from the EDGE Consortium,
The Journal of Urology® (2018), doi: 10.1016/j.juro.2018.04.062.

DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a
service to our subscribers we are providing this early version of the article. The paper will be copy edited
and typeset, and proof will be reviewed before it is published in its final form. Please note that during the
production process errors may be discovered which could affect the content, and all legal disclaimers
that apply to The Journal pertain.

Embargo Policy

All article content is under embargo until uncorrected proof of the article becomes available
online.

We will provide journalists and editors with full-text copies of the articles in question prior to the embargo
date so that stories can be adequately researched and written. The standard embargo time is
12:01 AM ET on that date. Questions regarding embargo should be directed to jumedia@elsevier.com.
ACCEPTED MANUSCRIPT

A Randomized Control Trial of Preoperative Prophylactic Antibiotics Prior to


Percutaneous Nephrolithotomy in Low Infectious Risk Population: A Report from the
EDGE Consortium

Ben H. Chew1,2, MD; Nicole L. Miller1,3, MD; Joel E. Abbott, DO4; Dirk Lange1,2, PhD;
Mitchell R. Humphreys1,5, MD; Vernon M. Pais Jr1,6, MD; Manoj Monga1,7, MD; Amy E.
Krambeck1,8, MD; Roger L. Sur1,9, MD

PT
Institutions:
1 – Member, EDGE Research Consortium, 2-The University of British Columbia,

RI
Vancouver, British Columbia, 3 - Vanderbilt University, Nashville, Tennessee, 4 –
Chesapeake Urology Associates, Hanover, Maryland, 5 - The Mayo Clinic Arizona,
Phoenix, Arizona 6 –Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 7 –

SC
Cleveland Clinic, Cleveland, OH 8-Indiana University 9- University of California, San
Diego, California,

U
Funding sources: The Project described was partially supported by the National
AN
Institutes of Health, Grant UL1TR001442 of CTSA, as well as UL1TR002377
(REDCap). The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH.
M

Registered under ClinicalTrials.gov ID NCT02384200


D
TE

Potential conflicts of interest: None

Keywords: percutaneous nephrolithotomy, antibiotics, infection, SIRS, sepsis


EP

Running title:
Preoperative antibiotics prior to PCNL
C
AC
ACCEPTED MANUSCRIPT

Abstract

Introduction

Single institution studies suggest a benefit of a week of preoperative antibiotics prior to

PT
percutaneous nephrolithotomy (PCNL). These studies are limited by lower quality

methodology such as the inclusion of heterogeneous populations or the use of non-

RI
standard definitions of sepsis. The American Urological Association (AUA) Best Practice

SC
Statement recommends <24 hours of IV antibiotics, but no other data exist about the

duration/benefit of preoperative antibiotics. We sought to perform a rigorous (using

U
CONSORT guidelines), multi-institutional trial to assess preoperative antibiotics in PCNL
AN
patients at low risk of developing infections.
M

Methods
D

In a randomized controlled trial, “low risk” patients (negative pre-operative urine


TE

cultures and without any urinary drains) undergoing PCNL were enrolled. Subjects were

randomized to nitrofurantoin 100 mg BID for 7 days preceding surgery (n=43) and
EP

control arm with no oral antibiotics (n=43). All subjects received peri-operative doses of

ampicillin and gentamicin. Prone PCNL was performed by urologists blinded to


C

randomization. The primary outcome was development of sepsis.


AC

Results

86 subjects were enrolled. Pre-operative patient characteristics were similar between

treatment and control cohorts, (stone size 19mm and 17mm, p=0.47). Intra-operative
ACCEPTED MANUSCRIPT

characteristics also demonstrated no differences. Rate of sepsis was not statistically

different between the treatment and control groups (12% and 14%, 95% CI [-0.163,

0.122], p=1.0). Other infectious parameters and complications were similar (intensive

PT
care admission, fever, hypotension, leukocytosis).

RI
Conclusion

SC
Our study demonstrated no advantage to providing one week of preoperative oral

antibiotics in PCNL patients at “low risk” for infectious complications. Peri-operative

U
antibiotics per AUA Best Practice Statement appears sufficient.
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT

Introduction

Sepsis is one of the most devastating complications following PCNL with rates reported

between 0.3%-2.5%.1, 2 The AUA Best Practice Statement recommends peri-operative

PT
antibiotics for this procedure based on numerous studies demonstrating mitigation of

infectious complications with peri-operative antibiotics.3-5

RI
SC
Recently, investigations have concluded there may be benefit to prolonged antecedent

antimicrobial treatment prior to PCNL, specifically 7 days of preoperative oral

U
antibiotics.6, 7 These investigations reported 30% and 8% reduction in the risk of sepsis,
AN
respectively, leading to the suggestion that the use of prolonged pre-operative oral
M

antibiotics prior to PCNL may reduce infectious complications.8 Moreover, extended

perioperative antibiotic use has been shown to produce few adverse antibiotic-related
D

events.9 Interestingly, practice patterns for pre-operative antibiotics use is quite


TE

variable depending on practitioner preference; ranging from just peri-operative to

several weeks prior to PCNL.10


C EP

However, critical appraisal of current reports demonstrates several areas of concern


AC

that threaten the internal validity of these studies and therefore potentially limit their

generalizability. There was little adherence to accepted guidelines for randomized

controlled trials as reported by the Consolidated Reporting of Trials (CONSORT), which

aim to minimize risk of systematic errors.11 Furthermore, antiquated definitions of

systemic inflammatory response syndrome (SIRS) were utilized.12 Lastly, single


ACCEPTED MANUSCRIPT

institution reports are enhanced by multi-institutional investigations that support or

refute findings. Of note, SIRS is an acceptable surrogate for sepsis in that sepsis is

defined as presence (probable or documented) of infection with systemic manifestation

of infection.12 The Endourological Disease Group for Excellence (EDGE), a dedicated

PT
kidney stone consortium of tertiary care centers (www.endoedge.org), hypothesized

RI
that prolonged pre-operative antibiotics would not reduce post-operative sepsis from

SC
PCNL. We therefore sought to determine if 7 days of pre-operative oral antibiotics

decreased the sepsis rate compared to peri-operative antibiotics in patients undergoing

U
PCNL in a prospective randomized trial.
AN
Methods
M

This multicenter, prospective, randomized, single blind, superiority trial was conducted
D

between January 2015 and July 2017 at 7 locations throughout the United States and
TE

Canada (ClinicalTrials.gov identifier NCT02384200). The protocol was approved by each

institutional review board (IRB) (UC San Diego, University of British Columbia, Vanderbilt
EP

University, Mayo Clinic Arizona, Dartmouth Hitchcock, Cleveland Clinic, Mayo Clinic

Rochester, Indiana University), and participants provided written informed consent prior
C

to enrollment. It was conducted in accordance with the World Medical Association


AC

Declaration of Helsinki and all amendments and the International Conference on

Harmonisation Guideline for Good Clinical Practice. UC San Diego (UCSD) served as the

principal investigating and study data safety monitoring regulating site. No protocol

deviations or protocol modifications were noted. A concealed block randomization (1:1)


ACCEPTED MANUSCRIPT

was created using an online tool (www.sealedenvelope.com) by a UCSD non-

investigator study person who provided each institution their randomization list to a

similar non-investigator person, who then disclosed allocation when requested by each

PT
site investigator.

RI
Eligible patients were enrolled through each institution’s urology outpatient clinics.

SC
Eligible patients included any person 18 years old or older with a renal calculus of any

size for which PCNL was recommended. Exclusion criteria were eGFR < 60 mL/min/1.73

U
m2 or Glucose 6-phosphate dehydrogenase deficiency (G6PD) (both contraindications
AN
for nitrofurantoin); cirrhosis and/or hepatitis; pregnancy (urine test for pregnancy done

at pre-operative clinic); positive preoperative urine culture within 2 weeks prior to


M

randomization; history of temperature ≥ 38.3 C associated with nephrolithiasis or sepsis


D

thought to result from a urinary source within 12 months prior to randomization;


TE

current internalized ureteral stent, nephrostomy tube, or nephroureteral stent;

antibiotic use within 2 weeks before randomization; or severe hydronephrosis (defined


EP

by ≥ 2 cm renal pelvis in largest dimension) preoperatively as judged on CT scan,

abdominal X-ray, ultrasound, or fluoroscopy.


C
AC

Patients were randomly assigned to the intervention or control arm. Patients

randomized to the intervention arm were prescribed by non-investigator personnel

nitrofurantoin monohydrate/macrocrystalline 100 mg twice daily for 7 days prior to

PCNL with the final day of prophylactic course being 1 day prior to surgery.
ACCEPTED MANUSCRIPT

Nitrofurantoin monohydrate/macrocrystalline is currently indicated for the treatment of

acute uncomplicated urinary tract infections. Patients randomized to the control arm

received no preoperative antibiotic course. On the day of surgery, antibiotics were given

PT
to all patients (control and treatment arms)—a dose of ampicillin IV (2 g) and

gentamicin IV (5 mg/kg ideal body weight) within 120 minutes of surgery start time.

RI
Patients with a penicillin allergy received vancomycin IV (1 g) instead of ampicillin and

SC
patients with gentamicin/aminoglycoside allergy received ceftriaxone IV (2 g) instead of

gentamicin. Postoperative antibiotics in the absence of infection was to be <24 hours of

U
IV antibiotics. The macrobid prescription was written by a non-investigator member of
AN
the surgical team. The investigator and study team were blinded to treatment

assignment throughout the study, as the randomization list was generated by an


M

independent person. The database was unlocked after the study at which point the
D

randomization list was made available for purposes of analysis.


TE

Prone PCNL was then performed after access was obtained by either interventional
EP

radiology or the surgeon. Tracts were balloon dilated to 30Fr. Intracorporeal lithotripsy

consisted of pure ultrasound lithotripsy or combination pneumatic/ultrasound


C

lithotripsy. Flexible nephroscopy with basket extraction or laser lithotripsy was


AC

performed as necessary. At time of surgery, urine from the renal pelvis, bladder urine,

and the stone itself were sent for culture. Renal drainage devices (ureteral stents,

nephrostomy tubes, nephroureteral stents) were placed at the surgeon’s discretion.

Post-operatively, the patients were admitted to the hospital and monitored per usual
ACCEPTED MANUSCRIPT

clinical procedure. CBC and basic metabolic chemistry bloodwork was obtained on

postoperative day 1. Patients were discharged from the hospital per each institution’s

clinical protocol. After surgery, patients were followed in the clinic 1-12 weeks with

PT
imaging.

RI
Data Collection and Handling

SC
De-identified data was collected by each participating site and entered into a designated

and shared Research Electronic Data Capture (REDCap) database.

U
AN
Data Analysis

The primary outcome was rate of postoperative sepsis and was compared between the
M

intervention and control groups for the postoperative period with univariate and
D

multivariate analysis. Sepsis was defined by the 2012 International Guidelines for
TE

Management of Severe Sepsis and Septic Shock12 where an infectious source (e.g.

kidney stone) and 2 or more of the following variables are temporally associated:
EP

temperature > 38.3 Celsius or < 36 Celsius, heart rate > 90/minute (at least 12 hours

after surgery), respiratory rate > 20/minute (at least 12 hours after surgery), altered
C

mental status defined as lack of orientation to either name, place, or time/date, systolic
AC

blood pressure < 90 mmHg, mean arterial pressure < 70 mmHg, or systolic blood

pressure decrease > 40 mmHg, leucocyte count > 12000 or < 4000.
ACCEPTED MANUSCRIPT

Secondary outcomes included complication rates with attention to infectious

complications. Descriptive statistics were used to analyze the data with mean, range for

medians and variance reported for continuous variables, and proportions reported for

PT
categorical variables. Using 2-sided P values, statistical significance was set at p≤0.05.

Sample Size of 80 patients (40 per each cohort) was calculated assuming β=0.20, α=0.05,

RI
with the power to detect a 30% reduction in sepsis rate based on prior literature.6 An

SC
intent-to-treat (ITT) analysis was performed and included all randomized patients who

received at least one dose of antibiotics or were 7 days post-surgery (control).

U
AN
The null hypothesis assumed there was no difference in sepsis between one week of

pre-operative antibiotics with IV peri-operative antibiotic dose and IV peri-operative


M

antibiotic dose alone. SAS software was used for all statistical operations (SAS Institute
D

Inc, Cary, NC, USA).


TE

Results

The study failed to reject the null hypothesis—i.e. there was no difference in rates of
EP

sepsis between treatment 12% and control 14% arms (mean difference -0.020 95% CI

[-0.163, 0.122], p=1.0). There were also no differences in the rates of septic shock (0%
C

and 0%) or intensive care unit admission (treatment: 4.8% and control: 0%, p=0.24).
AC

Since univariate analysis demonstrated only one significant predictor variable—

nephrostomy tube use (p=0.017)—a multivariable analysis was performed. Controlling

for all other variables, nephrostomy tube placement following PCNL reduced the risk of

sepsis (OR=0.23, 95%CI [0.04, 0.91], p=0.049). Controlling for all variables, 1 week of
ACCEPTED MANUSCRIPT

antibiotics did not significantly reduced the risk of sepsis (OR=0.56, 95%CI [0.14, 2.2],

p=0.40)

PT
Of the 86 subjects randomized to intervention with nitrofurantoin (n=43) and control

(n=43), no subjects withdrew (Figure 1). Both baseline characteristics (Table 1) and

RI
intraoperative outcomes were essentially similar except control cohort had a larger

SC
proportion of nephrostomy tube use (Table 2).

U
Furthermore, there was no multi-organ system failure in any subject. Leukocytosis was
AN
not different, with 11 (40% and 33%, p=0.64) between treatment and control,

respectively. Intra-operatively collected bacterial pathogen cultures showed no


M

differences either. Renal pelvis cultures were concordant with intraoperative bladder
D

urine cultures in 49% and 63% of treatment and control patients, respectively (p=0.28).
TE

Stone cultures were concordant with intraoperative bladder urine cultures in 49% and

47% of treatment and control, respectively (p=1.0).


EP

The overall complication rate demonstrated no differences between cohorts (30% vs


C

42%, p=0.37) or when sub-stratified for Clavien-Dindo grades (Table 3). Treatment
AC

cohort infectious related complications included the following: serum sickness from

pre-operative antibiotics; simple urinary tract infection requiring oral antibiotics; re-

admission necessitating intravenous antibiotics; and re-admission 13 days later for

urosepsis related to infected proximal ureteral fragment. See Table 4 for all
ACCEPTED MANUSCRIPT

complications. Control cohort infectious related complication included a wound

infection necessitating oral antibiotics.

Discussion

PT
AUA Best Practice Statement recommends < 24 hours of peri-operative antibiotics for

PCNL.4, 5 However, even with peri-operative antibiotics there is a risk of sepsis and the

RI
potential sequelae of septic shock with possible multi-organ dysfunction.2 Fortunately,

SC
the reported rates are low at 0.3-2.5%. Juxtaposed with this problem is the growing

issue of antibiotic drug resistance. Poor compliance with recommendations for

U
antibiotic stewardship is thought to contribute to increasing bacterial resistance.13 The
AN
recent patient deaths associated with carbapenam-resistant enterobacter speak to this

situation.14
M
D

There is evidence that prolonged pre-operative antibiotics reduces the risk of sepsis
TE

following stone surgery. Mariappan et al reported in a prospective comparative trial one

week of oral ciprofloxacin reduced sepsis in patients with large stones and/or
EP

hydronephrosis.7 Bag et al demonstrated in a randomized controlled trial that one week

of oral nitrofurantoin decreased sepsis in patients with large stones and/or


C

hydronephrosis.6 Yet these are the only two existing level 2b and 1b trials, respectively,
AC

that address this question. The former study is not a true prospective comparative trial

as it utilizes a historical cohort and the authors stated “a multicentre randomized

controlled trial should be done to further confirm these results.” The latter trial was a

single center RCT which could have benefited from alignment with CONSORT guidelines.
ACCEPTED MANUSCRIPT

Specific domains of concern include the following: outdated “sepsis” definition, which

did not include low body temperature < 36 Celsius, explicit hypotension definition or

change in mental status (see Appendix 1—CONSORT checklist item 6a); lack of sample

PT
size calculation but instead post hoc power calculation (not recommended by checklist

item 7a); lack of randomization list concealment (check list item 9) whereby

RI
investigators could potentially view the randomization list; it was unclear how cohorts

SC
were analyzed (intention to treat, per protocol, modified intention to treat [check list

item 12a]); and lack of flow diagram which clarifies loss of follow-up, disenrollment,

U
missing outcomes (check list item 13a).
AN
M

The goal of our study was to conduct a rigorous Level 1b multi-center trial that would

define the right balance between judicious and sufficient peri-operative antibiotic
D

prophylaxis. From this study we conclude that there was no reduced sepsis rate with
TE

prolonged pre-operative PCNL antibiotic use. Urosepsis and shock is thought to be due
EP

to intravasation of bacteria or endotoxins into bloodstream, for which there is a higher

risk with prolonged surgery, degree of hydronephrosis (surrogate for bacterial load),
C

bacterial load in the renal pelvis, and presence of large, infected stones.1, 15 From our
AC

data, the only predictors of sepsis appeared to be the lack of nephrostomy tube use

after PCNL (OR=0.23, 95% CI [0.04, 0.91], p=0.049). However, not only are the

confidence intervals wide but it should also be noted this analysis is potentially limited

by inadequate outcome variable size—i.e. for outcome events per variable values of less
ACCEPTED MANUSCRIPT

than 10-15 (in our case total sepsis events = 11), the regression coefficients can be

biased in both positive and negative directions.16

PT
How should our data be interpreted in light of two prior studies6, 7 suggesting that one

week of pre-operative antibiotics significantly reduces the risk of sepsis in patients

RI
undergoing PCNL with large stones and/or severely hydronephrotic kidneys? The

SC
nitrofurantoin study concluded that large stones necessitate prolonged antibiotics, yet

this was only seen on univariate analysis and not seen on multivariate analysis. They

U
also concluded that hydronephrotic patients benefited from treatment; however,
AN
review of their methodology does not clarify what degree of hydronephrosis benefits
M

from treatment. Was it mild, moderate or severe—or is it any hydronephrosis? They

included a category of “gross dilatation…with thinning of parenchyma as ‘severe.’” The


D

ciprofloxacin study made similar conclusions but no formal inferential statistics were
TE

performed to substantiate these statements.


C EP

Although we did not find large stone size or hydronephrosis to be predictors of sepsis,
AC

we do think these findings from prior studies make intuitive sense. Large stones and

hydronephrosis appear to be suitable surrogate markers for bacterial load. Our average

axial stone size of 1.6 cm indicates our study was admittedly not enriched with large

stones. The Bag et al study suggested that females on multivariate analysis (OR=3.3)

were at increased risk of sepsis, though we did not see these findings.6 Additionally, our
ACCEPTED MANUSCRIPT

cases were all performed at high volume stone centers where operative time is often

under 2 hours (mean OR time 111 min) which decreases patients’ risk of sepsis. Lastly,

this trial is one of two that the EDGE consortium has performed with an ongoing trial

PT
targeting “moderate to high risk” PCNL patients—i.e. patients who have positive pre-

operative urine cultures, existing ureteral stents or nephrostomy tubes. This “moderate

RI
to high risk” cohort has yet to be evaluated with respect to appropriate duration of pre-

SC
operative antibiotics. We acknowledge the findings of the current trial should not be

applied to moderate-high risk PCNL patients until data is available. Moreover, we also

U
caution over-generalization of this data as clinician’s judgement may justify a more
AN
liberal approach to antibiotic use.
M

Limitations notwithstanding, we report a rigorous study performed in a multi-


D

institutional setting which attempts to answer the controversy behind prolonged pre-
TE

operative antibiotics. For both the safety of PCNL patients in averting sepsis and for the
EP

ongoing attempt to balance judicious antibiotic use, we believe this study adds

significant value to the fund of knowledge to urological practice. It supports adherence


C

to the AUA Best Practice Statement for only peri-operative antibiotics at time of PCNL.3
AC

Conclusions

Our study demonstrated no advantage to providing one week of pre-operative oral

antibiotics in PCNL patients at “low risk” for infectious complications. Peri-operative


ACCEPTED MANUSCRIPT

antibiotics per AUA Best Practice Statement offer similar protection to one week of pre-

operative antibiotics against the occurrence of sepsis post PCNL . A study evaluating the

role of pre-operative antibiotics in cohorts at higher risk for infection is currently under

PT
way within this consortium.

RI
SC
Figure 1: Flow Diagram of the progress through phases of randomized control trial as per

U
CONSORT statement. AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT

References
1. O'Keeffe, N. K., Mortimer, A. J., Sambrook, P. A. et al, Severe sepsis following
percutaneous or endoscopic procedures for urinary tract stones. Br J Urol, 72:
277, 1993.
2. Segura, J. W., Endourology. J Urol, 132: 1079, 1984.
3. Wolf, J. S., Jr., Bennett, C. J., Dmochowski, R. R. et al, Urologic Surgery

PT
Antimicrobial Prophylaxis Best Practice Policy, P.: Best practice policy statement
on urologic surgery antimicrobial prophylaxis. J Urol, 179: 1379, 2008.
4. Charton, M., Vallancien, G., Veillon, B. et al, Urinary tract infection in
percutaneous surgery for renal calculi. J Urol, 135: 15, 1986.

RI
5. Darenkov, A. F., Derevianko, II, Martov, A. G. et al, [The prevention of infectious-
inflammatory complications in the postoperative period in percutaneous surgical

SC
interventions in patients with urolithiasis]. Urol Nefrol (Mosk): 24, 1994.
6. Bag, S., Kumar, S., Taneja, N. et al, One week of nitrofurantoin before
percutaneous nephrolithotomy significantly reduces upper tract infection and
urosepsis: a prospective controlled study. Urology, 77: 45, 2011.

U
7. Mariappan, P., Smith, G., Moussa, S. A. et al, One week of ciprofloxacin before
percutaneous nephrolithotomy significantly reduces upper tract infection and
AN
urosepsis: a prospective controlled study. BJU Int, 98: 1075, 2006.
8. Lai, W. S., Assimos, D., The Role of Antibiotic Prophylaxis in Percutaneous
Nephrolithotomy. Rev Urol, 18: 10, 2016.
M

9. Viers, B. R., Cockerill, P. A., Mehta, R. A. et al, Extended antimicrobial use in


patients undergoing percutaneous nephrolithotomy and associated antibiotic
related complications. J Urol, 192: 1667, 2014.
D

10. Iqbal, M. W., Youssef, R. F., Neisius, A. et al, Contemporary Management of


Struvite Stones Using Combined Endourologic and Medical Treatment: Predictors
TE

of Unfavorable Clinical Outcome. J Endourol, 30: 771, 2016.


11. Gamble, C., Krishan, A., Stocken, D. et al, Guidelines for the Content of Statistical
Analysis Plans in Clinical Trials. JAMA, 318: 2337, 2017.
12. Dellinger, R. P., Levy, M. M., Rhodes, A. et al, Surviving sepsis campaign:
EP

international guidelines for management of severe sepsis and septic shock: 2012.
Crit Care Med, 41: 580, 2013.
13. Ventola, C. L., The antibiotic resistance crisis: part 1: causes and threats. P T, 40:
C

277, 2015.
14. Garcia-Castillo, M., Garcia-Fernandez, S., Gomez-Gil, R. et al, Activity of
AC

ceftazidime-avibactam against carbapenemase-producing Enterobacteriaceae


from urine specimens obtained during the infection-carbapenem resistance
evaluation surveillance trial (iCREST) in Spain. Int J Antimicrob Agents, 2018.
15. Rao, P. N., Dube, D. A., Weightman, N. C. et al, Prediction of septicemia following
endourological manipulation for stones in the upper urinary tract. J Urol, 146:
955, 1991.
16. Peduzzi, P., Concato, J., Kemper, E. et al, A simulation study of the number of
events per variable in logistic regression analysis. J Clin Epidemiol, 49: 1373,
1996.
ACCEPTED MANUSCRIPT

Table 1. Patient demographics and stone characteristics (mean ± SD unless specified otherwise)
Group 1
(Control) Group 2 (NFT x p
Variable (n = 43) 1 week) (n = 43) value
Male (%) 26 (39.5%) 27 (37.2%) 1.0

PT
Age 62 56 0.23
Body mass index 31 ± 9.9 30 ± 7.0 0.59
ASA Score 2.5 2.3 0.11

RI
Max axial stone diameter (mm) (range) 18 (1.6-55) 16 (5.1-65) 0.70
Max longitudinal stone diameter (mm) (range) 17 (1.6-63) 19 (3.5-56) 0.81
Hounsfield units 892 910 0.82

SC
Skin-to-stone distance (cm) 9.6 9.9 0.78
Left (%) 22 (51%) 24(56%) 0.67
Hydronephrosis 31(72%) 37(88%) 0.10

U
Stone surface area on axis (mm2) (range) 175 (0.45-2640) 202 (2.50-1973) 0.89
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT

Table 2. Operative variables (mean ± SD unless specified otherwise)


Group 1 Group 2 (NFT x
Variable (Control) (n = 43) 1 week) (n = 43) p value
Access by urologist, n (%) 33 (76.7%) 30 (71.4%) 0.62
Access:

PT
--Upper pole supracostal, n (%) 7 (16.30%) 9 (20.90%) 0.78
--Upper pole subcostal, n (%) 5 (11.60%) 9 (20.90%) 0.38
--Middle kidney, n (%) 6 (14.00%) 6 (14.00%) 1.00

RI
--Lower pole, n (%) 28 (65.10%) 25 (58.10%) 0.66
Multiple acces tracts 3 (7.00%) 6 (14.30%) 0.31
Operative time (min) 108 ± 44 115 ± 47 0.50

SC
Estimated blood loss (mL) 133 ± 115 151 ± 177 0.58
Preop creatinine (mg/dL) 0.94 0.9 0.39
Postop creatinine (mg/dL) 1.03 0.95 0.22
Preop hemoglobin (g/dL) 14 15 0.28

U
Postop hemoglobin (g/dL) 12 12 0.50
AN
Preop leukocyte count (109/L) 7.6 7.0 0.28
9
Postop leukocyte count (10 /L) 11 11 0.82
Ureteral stent placed, n (%) 16 (37%) 20 (46%) 0.51
Nephrostomy tube placed, n (%) 29 (67%) 17 (40%) 0.02*
M

Nephroureteral stent placed, n (%) 6 (14%) 9 (21%) 0.57


Days until nephrostomy removed 1.0 ± 3 2.0 ± 7 0.45
D

Days until stent removed 13 ± 7 14 ± 15 0.77


TE
C EP
AC
ACCEPTED MANUSCRIPT

Table 3. Postoperative outcomes (values are number of patients and %)


Group 1 (control) (n Group 2 (NFT x 1
Variable = 43) week) (n = 43) p value
Met sepsis criteria 6 (14%) 5 (12%) 1.0
ICU admission postop 0 (0.0%) 2 (4.8%) 0.24
Fever (T > 38.3 C) 1 (2.3%) 0 (0.0%) 1.0

PT
Hypotension 5 (11%) 6 (14%) 0.76
Tachycardia (HR > 90 bpm) 13 (30%) 11 (26%) 0.81
Tachypnea (RR > 20 rpm) 11 (26%) 7 (17%) 0.43

RI
Elevated lactate 3 (12%) 0 (0.0%) 0.11
Elevated leukocyte count (> 12,000 WBC) 16 (40%) 13 (33%) 0.64
Received ABx for > 24 hours postop 7 (16%) 9 (21%) 0.59

SC
Positive intraop bladder urine culture 1 (2.3%) 1 (2.3%) 1.0
Positive intraop renal pelvis urine culture 1 (2.3%) 1 (2.3%) 1.0
Positive stone culture 4 (9.3%) 4 (9.3%) 1.0

U
Positive postop bladder urine culture 0 (0.0%) 2 (4.7%) 0.49
Positive postop blood culture 0 (0.0%) 0 (0.0%) -
AN
Complications: none 30 (70%) 25 (58%) 0.37
--Clavien I 4 (9.3%) 8 (19%) 0.351
--Clavien II 5 (11%) 3 (7.0%) 0.71
--Clavien IIIA 1 (2.3%) 0 (0.0%) 1.00
M

--Clavien IIIB 4 (9.3%) 3 (7.0%) 1.0


--Clavien IV 0 (0.0%) 0 (0.0%) -
D

--Clavien V 0 (0.0%) 0 (0.0%) -


Length of stay 1.0 (0.0-6.0) 1.00 (0.0-2.0) 0.17
TE

Stone-free 25 (68%) 22 (61.1%) 0.63


C EP
AC
ACCEPTED MANUSCRIPT

Table 4. PCNL complications

Treatment Group (Pre-op Antibiotics)


Clavien-Dindo Description
Class
1 Additional antibiotics for possible UTI
1 Readmission (retroperitoneal hematoma. No intervention)

PT
1 ER for SOB. CXR with atelectasis.
1 Nephrostomy tube in place for longer than usual
1 Surgical site hematoma. Resolved spontaneously

RI
1 SOB post-op. CXR with atelectasis
1 Post-op hypotension requiring bolus x2
1 Post-op apical pneumothorax. Resolved spontaneously

SC
2 Admitted for hydronephrosis after stent removed
2 Admitted for infection requiring IV antibiotics
2 Serum sickness 2/2 pre-op microbic
3B JJ stent malpositioned. Return to OR for stent change

U
3B Urinary sepsis, obstructing UPJ stone requiring ureteroscopy
3B Residual obstructing stone with ureteroscopy POD #1
AN
Control Group (No Pre-op Antibiotics)
Clavien-Dindo Description
M

Class
1 Return to ER with flank pain
1 Post-op flare in Parkinson’s disease
D

1 SOB post-op. CXR atelectasis


1 Small apical pneumothorax, resolved
TE

2 ER for diarrhea, nausea, vomiting. Improved with ABx


2 Wound infection requiring ABx
2 Thrush requiring Diflucan
EP

2 Urinary sepsis
3A Re-admitted for hematuria. CT angiogram negative
3B Intra-operative bleeding -> early termination of case.
3B Hemothorax requiring chest tube, VATS, Decortication
C

3B Hydrothorax requiring chest tube


AC
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT

Abbreviations

EDGE: Endourological Disease Group for Excellence

PCNL: percutaneous nephrolithotomy

REDCap: Research Electronic Data Capture (database)

PT
SIRS: systemic inflammatory response syndrome

RI
U SC
AN
M
D
TE
C EP
AC

Vous aimerez peut-être aussi