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Veterinary Anaesthesia and Analgesia, 2016, 43, 571578 doi:10.1111/vaa.

12348

RESEARCH PAPER

Intraperitoneal bupivacaine with or without incisional


bupivacaine for postoperative analgesia in dogs
undergoing ovariohysterectomy

Karin S Kalchofner Guerrero*, Ivo Campagna, Rodolfo Bruhl-Day*, Cecilia Hegamin-Younger &
Tomas G Guerrero*
*Small Animal Medicine & Surgery Department, School of Veterinary Medicine, St Georges University, St.Georges, Grenada
Equine Department, Section Anaesthesiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
Department of Public Health and Preventive Medicine, School of Medicine, St. Georges University, St.Georges, Grenada

Correspondence: Karin S Kalchofner Guerrero, Small Animal Medicine & Surgery Department, School of Veterinary Medicine, St Georges
University, True Blue, Grenada, West Indies. E-mail: kguerrero@sgu.edu

Postoperative analgesia was assessed with a


Abstract
dynamic interactive visual analogue scale, the short
Objective Intraperitoneal (IP) bupivacaine pro- form of the Glasgow Composite Pain Scale, and
vides postoperative analgesia in dogs undergoing mechanical nociceptive threshold (MNT) measure-
ovariohysterectomy (OHE) alone or in combina- ment at 0.5, 1, 2, 4, 6, 8, 12 and 20 hours after
tion with incisional (INC) bupivacaine. This study surgery by one blinded observer. Parametric data
investigated whether the combination of INC and were tested using t-test; nonparametric data were
IP bupivacaine is superior to IP bupivacaine analysed using the two-sample Wilcoxon test
alone. (p < 0.05).

Study design Prospective, randomized, blinded clin- Results There was no significant difference between
ical study. groups with regard to age, weight, surgical and
anaesthetic duration, incision length, sedation and
Animals Thirty-nine privately owned dogs under- pain scores. MNT values decreased in both groups at
going OHE, aged 25  23 months and weighing all time points as compared with the baseline. No
11.8  5.7 kg. dog required rescue analgesia. No postoperative
complications were observed.
Methods Dogs were premedicated with acepro-
mazine (0.05 mg kg 1) and morphine
Conclusion and clinical relevance Bupivacaine IP
(0.5 mg kg 1) intramuscularly (IM); anaesthesia
and carprofen SC after morphine IM did provide
was induced with propofol and maintained with
satisfactory postoperative analgesia in dogs
isoflurane in oxygen. Carprofen (4 mg kg 1) was
undergoing OHE with the anaesthetic protocol
administered subcutaneously (SC) after intubation.
used. There appears to be no clinical advantage
Bupivacaine (3 mg kg 1) IP was administered
to adding bupivacaine INC. Neither protocol
before complete closure of the linea alba to all dogs.
could prevent the development of primary
Dogs were randomly assigned into two groups:
hyperalgesia.
group B received bupivacaine (n = 20; 1 mg kg 1)
and group S received saline (n = 19; 0.2 mL kg 1) Keywords canine, hyperalgesia, local anaesthesia,
INC as a subcutaneous splash before skin closure. ovariohysterectomy, pain.

571
Local anaesthesia for canine ovariohysterectomy KS Kalchofner Guerrero et al.

Introduction Materials and methods


Canine ovariohysterectomy (OHE) is a very common This blinded, randomized study was approved by the
surgical procedure in veterinary practice. This pro- Animal Care and Use Committee of St Georges
cedure is performed under general anaesthesia and University (IACUC-12016-R). Written, informed
is considered to give rise to mild to moderate consent was obtained from the owner of each
abdominal pain. The pain from OHE originates from animal.
the surgical incision, from manipulation of the
abdominal viscera, and from stretching of associated
Animals
ligaments (Gaynor & Muir 2014).
Local anaesthetic techniques are part of the In all, 39 female client-owned dogs presenting for
multimodal approach to postoperative pain man- routine OHE were included in the study. Based on
agement (Slingsby 2008; Gurney 2012). The use of physical examination and haematological and bio-
wound infiltration with local anaesthesia for post- chemical profile, all dogs were considered clinically
operative pain relief may be an attractive method healthy. The age, weight and breed of the dogs were
because of its simplicity and low cost (Moiniche et al. recorded. Animals that were found to be aggressive
1998). Intraperitoneal (IP) and incisional (INC) on handling were excluded, as were pregnant or
administration of local anaesthetics have been lactating dogs. Dogs were also excluded if they were
shown to reduce postoperative pain and opioid having other procedures performed in addition to
consumption in women undergoing (ovario)hys- OHE, such as repair of an umbilical hernia. Dogs
terectomy (Hannibal et al. 1996; Zohar et al. 2001; were randomly assigned to one of two groups,
Ng et al. 2002). However, the conclusions of many bupivacaine (B) or saline (S), using a computer
clinical trials in humans have been controversial (Ng program (R 3.0.1; GNU Software Foundation,
& Smith 2002). Switzerland) before the start of the study.
There are only a few reports assessing the use of IP
and/or INC infiltration of local anaesthetics for
Anaesthesia and surgery
postoperative pain relief after OHE in dogs (Carpen-
ter et al. 2004; Fitzpatrick et al. 2010; Campagnol Dogs arrived at the surgical facilities on the morning
et al. 2012; McKune et al. 2014). The pre- and post- of the day before surgery for preoperative evaluation.
INC administration of bupivacaine  lidocaine did In the afternoon, baseline measurements were
not show analgesic benefits in two studies (Fitz- collected for heart rate (HR), respiratory rate (fR),
patrick et al. 2010; McKune et al. 2014). The rectal temperature (T), and mechanical nociceptive
combination of IP and INC bupivacaine was shown threshold (MNT) in close proximity to the planned
to provide effective analgesia in one study (Carpenter incision line. Food was withheld overnight; access to
et al. 2004), but the impact of each technique was water was given until administration of the
not clear. One study comparing IP and INC bupiva- premedication.
caine revealed lower pain scores with IP bupivacaine Premedication consisted of acepromazine
during the first hour after surgery and a trend 0.05 mg kg 1 (Acepromazine maleate injection;
towards a decreased need for rescue analgesia Vedco Inc, MO, USA) and morphine 0.5 mg kg 1
(Campagnol et al. 2012). (Martindale Pharma, UK) intramuscularly (IM).
Considering the fact that the administration of Twenty minutes later, an intravenous (IV) catheter
INC bupivacaine addresses incisional pain, whereas was placed in a cephalic vein following aseptic
the use of IP bupivacaine aims to treat the pain preparation, and anaesthesia was induced with
caused by manipulation of the viscera, we hypoth- propofol IV (PropoFlo; Abbott Laboratories, IL,
esized that the combination of both techniques USA) until conditions were adequate for orotracheal
would improve postoperative analgesia compared intubation. Anaesthesia was maintained with isoflu-
with the use of IP bupivacaine alone. To test our rane (IsoFlo; Abbott Laboratories) in 100% oxygen.
hypothesis, we conducted a study comparing post- Carprofen 4 mg kg 1 (Rimadyl, Pfizer Inc, NY, USA)
operative analgesia in two groups of dogs undergo- was administered subcutaneously (SC) after intuba-
ing OHE. One group received both INC and IP tion. Lactated Ringers solution (LRS) (Veterinary
bupivacaine and the second group received INC Lactated Ringers Injection; Abbott Animal Health,
saline and IP bupivacaine. IL, USA) was started at a constant rate of

572 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 571578
Local anaesthesia for canine ovariohysterectomy KS Kalchofner Guerrero et al.

10 mL kg 1 hour 1. Intraoperative monitoring the os pubis and the xyphoid, and the ratio was
included an electrocardiogram, noninvasive (oscil- calculated.
lometric and Doppler) blood pressure measurement, Postoperative measurements and assessments
oesophageal temperature, and haemoglobin satura- were performed 0.5, 1, 2, 4, 6, 8, 12 and
tion with oxygen (SpO2) (UT6000A; Goldway, NY, 20 hours after extubation by one observer (I.C.)
USA). Respiratory rate was assessed via oesophageal who was unaware of the treatment given. Vital
stethoscope. The isoflurane vaporizer dial was parameters (HR, fR, body temperature, capillary
adjusted to deliver adequate concentration for refill time and colour of mucous membranes) were
surgery based on clinical signs, including absence assessed at the same time points. Sedation was
of palpebral reflex, absence of jaw tone and mean assessed using a scale from 0 to 3 points as
arterial pressure (MAP) between 60 and 90 mmHg. follows; 0, dog is completely awake, can walk; 1,
Body temperature was maintained using forced-air dog is slightly sedated, can lift head; 2, dog is
warming system (Bair Hugger 505; Augustine heavily sedated, reacts upon vocal interaction; 3,
Medical, MN, USA). Hypotension, defined as dog sleeps, does not react upon vocal stimulation.
MAP < 60 mmHg, was treated by lowering the Pain scoring was performed using three different
isoflurane percentage, if indicated, and administer- methods: 1) a dynamic interactive visual analogue
ing one 10 mL kg 1 bolus of LRS. When hypoten- scale (DIVAS; Lascelles et al. 1998) of 100 mm
sion persisted for >10 minutes, dogs received was used with the ends anchored at 0 (no pain
hydroxethyl starch (510 mL kg 1; Vetstarch, after OHE) and 100 (worst possible pain after
Abbott Animal Health). OHE); 2) the short form of the Glasgow Composite
Ovariohysterectomy via midline coeliotomy was Pain Scale (GCPS; Reid et al. 2007), with a
performed by third-year veterinary students under possible maximum of 24 points, or 20 if mobility
close supervision of an experienced clinical faculty or is impossible to assess (additionally, the ratio of the
board-certified surgeon. Anaesthesia was performed actual score versus the maximum possible score
by third-year veterinary students under close super- was calculated); and 3) an MNT measurement
vision of a board-certified anaesthesiologist. using a force algometer (probe tip, 4 mm; Prod;
Prior to complete closure of the linea alba, Topcat Metrology Ltd, UK). To measure MNT,
bupivacaine 3 mg kg 1 (Carbostesin 0.5%; Astra- steadily increasing pressure was applied in close
Zeneca AG, Switzerland) was administered IP at the proximity (10 mm) around the incision line until
cranial portion of the incision using a 20 gauge IV the animal showed a response. Any sudden move-
catheter to all dogs; the surgeon gently lifted the ment of the dog away from the device, turning of
cranial edge of the incision with a spay hook during the head towards the device, vocalization, a sudden
IP instillation. Prior to skin closure, dogs in group B tense abdomen or attempts to bite were considered
received bupivacaine (n = 20; 1 mg kg 1) and dogs a response. Pressure was then instantly released
in group S received saline (n = 19; 0.2 mL kg 1) as and the applied force [in newtons (N)] was read
a SC splash (INC). The entire volume was dripped from the display. Three measurements were taken
slowly over 1 minute on the SC tissue; no attempt at three different sides along the wound at each
was made to prevent it from running off during time point, one next to the middle of the wound
closure of the skin. Administration of IP and INC and two at the edges of the wound (force range,
drugs was performed by one single anaesthesiologist 0.525 N, accuracy, 0.5 N, according to the
(K.K.). General anaesthesia was discontinued when manufacturer). The highest preoperative measure-
suturing of the skin was complete. Dogs were placed ment (baseline) was taken as the individual limit
in the sternal position and transported to the kennel not to be exceeded when performing the postoper-
after extubation. ative measurements. The average of the three
Surgery and anaesthesia duration were recorded, measurements was recorded as the MNT value for
as well as any complications that occurred during statistical analysis. The interactions with the dogs
the perioperative period. were standardized and measurements were always
performed in exactly the same sequence, with
increasing order of invasiveness. Rescue morphine
Postoperative measurements
0.3 mg kg 1 IM was administered if > 6/24 or 5/
The length of the surgical incision was measured at 20 points were reached in the GCPS or > 30 mm
the end of anaesthesia, as well as the length between in the DIVAS.

2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 571578 573
Local anaesthesia for canine ovariohysterectomy KS Kalchofner Guerrero et al.

Data analysis Postoperative assessments


Initial power calculations were performed before No difference in sedation could be detected postop-
starting the study. An alpha error was set at 5%. eratively [0.5 hours after extubation: B, 1 (11); S, 1
Standard deviation (SD) was set at 1.8 GCPS units (02) (p = 0.44); 1 hour after extubation: B, 1 (0
(Morton et al. 2005). A beta error level was set at 1); S, 0.5 (02) (p = 0.4); 2 hours after extubation:
20%. According to these calculations, 19 dogs were B, 0 (01); S, 0 (01) (p = 0.73)]. Sedation was
needed in each group, considering a difference of 2.6 scored as 0 for all dogs from time point 4 hours until
on the GCPS as significant (Morton et al. 2005). the end of the study (p = 1).
Data were analysed using the statistical software No significant difference between groups could be
SPSS v21 (IBM Corporation, NY, US). Data were found with any of the pain scores used at any time
assessed with the ShapiroWilk normality test. For point (Figs 13). Similarly, the ratio of GCPS to the
analysis of parametric data, two-tailed t-tests were maximum possible score did not differ. Values for
used; nonparametric data were analysed using the MNT decreased significantly in both groups at all
two-sample Wilcoxon test. Results of normally time points when compared with the baseline
distributed data are presented as means  SD. (p 0.002), with no difference between groups.
Nonparametric results (sedation, GCPS, DIVAS) are Heart rate was higher at baseline in group B; there
presented as median [interquartile range (IQR)]. was no other difference with respect to HR or fR at
Significance was identified at p < 0.05. any of the time points measured postoperatively. HR
and fR decreased significantly in both groups when
compared with baseline at every time point, with the
Results
exception of 0.5 and 20 hours after extubation
(Table 2). No dog required rescue analgesia. No peri-
Demographical data
or postoperative complications were observed. Dogs
A total of 36 dogs completed the study (B, n = 18; S, were discharged from the hospital on the day after
n = 18). Three dogs were excluded: one dog needed surgery and the owners reported no problems when
additional sedation after premedication to allow IV contacted 7 days after surgery.
catheter placement; one dog had already been
spayed; and in one dog deciduous canine teeth were
Discussion
removed during the same anaesthesia. Mixed-breed
dogs (n = 35) and one German Shepherd dog were The combination of INC and IP bupivacaine did not
included. Groups did not differ with regard to age, show any additional analgesic benefits in the post-
body weight, duration of surgery and anaesthesia, operative phase in dogs undergoing OHE as com-
ratio of the length of incision to the length from the pared with IP bupivacaine alone.
os pubis to the xyphoid, and time to extubation In the scope of multimodal pain treatment, all
(Table 1). dogs received morphine and carprofen before

Table 1 Demographic data, duration of anaesthesia and surgery, ratio of length of incision (IL) to length from os pubis to
xyphoid, and time to extubation for 36 dogs undergoing ovariohysterectomy treated with intraperitoneal bupivacaine plus
either incisional bupivacaine (group B) or saline (group S). Results are expressed as means  SD (range)

Group

Variable Group B Group S p-Value

Age (months) 23  15 (660) 27  28 (5120) 0.27


Weight (kg) 11.5  6.5 (3.722.8) 12.1  5 (5.121.7) 0.38
Duration of anaesthesia (minutes) 190  24 (130235) 196  26 (150240) 0.26
Duration of surgery (minutes) 141  25 (87190) 145  22 (115190) 0.28
Ratio of IL:length from os pubis to xyphoid (mm) 0.47  0.15 (0.30.81) 0.43  0.06 (0.320.56) 0.18
Time to extubation (minutes) 7  3 (314) 9  6 (120) 0.13

574 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 571578
Local anaesthesia for canine ovariohysterectomy KS Kalchofner Guerrero et al.

Figure 1 Box-and-whisker plots of the dynamic interactive


visual analogue scale (DIVAS) in 36 dogs undergoing Figure 3 Box-and-whisker plots of mechanical nociceptive
ovariohysterectomy with intraperitoneal bupivacaine, threshold (MNT) measurement in 36 dogs undergoing
combined with either incisional bupivacaine (group B) or ovariohysterectomy with intraperitoneal bupivacaine,
saline (group S). Each box represents the interquartile combined with either incisional bupivacaine (group B) or
range, and the median value is the horizontal line within saline (group S). For an explanation of the plots, see Fig. 1
each box. The upper and lower whiskers represent the caption.
upper and lower range of values, respectively.

evaluate local anaesthesia as part of multimodal


analgesia, not as a sole analgesic technique. Fur-
thermore, it has been shown that inexperienced
surgeons affect their patients differently from expe-
rienced surgeons through the degree of tissue
trauma and anaesthesia duration (Michelsen et al.
2012); with third-year students performing the
surgeries it was deemed ethical to provide the dogs
with a well-established analgesic protocol before
surgery.
Three different pain measurements were used in
this study to optimize pain scoring. None of the pain
measurements was able to show a difference
between treatments. The DIVAS scoring system
Figure 2 Box-and-whisker plots of the Glasgow Composite
and the GCPS both involve interaction with the
Pain Scale (GCPS) in 36 dogs undergoing ovariohysterec-
animal (Lascelles et al. 1998; Reid et al. 2007),
tomy with intraperitoneal bupivacaine, combined with
which is important for sensitive detections of pain in
either incisional bupivacaine (group B) or saline (group S).
For an explanation of the plots, see Fig. 1 caption. animals (Anil et al. 2002). MNT measurement using
a calibrated tool capable of recording an applied
force is regarded as an objective method for grading
nociceptive thresholds by some authors (Conzemius
surgery. It cannot be excluded completely that et al. 1997); however, we could not detect any
premedication with morphine had an impact on significant difference between groups by MNT
early postoperative pain scores, but considering the testing.
mean duration of anaesthesia plus the time from The fact that no dog required rescue analgesia
premedication until induction of anaesthesia, and raises the question of whether the cut-off points for
the pharmacokinetics of morphine in dogs (Barnhart providing additional analgesia were adequate. The
et al. 2000; Kukanich et al. 2005), we believe that cut-off for GCPS was chosen as > 6/24 or 5/20; if the
the effect of morphine was negligent during the cut-off had been set as > 5/24 or > 4/20, eight dogs
postoperative phase. A potential difference between in group B and nine in group S would have received
groups may have been masked by the analgesic rescue analgesia within the first 2 hours after
protocol used; however, the aim of this study was to surgery. In contrast, DIVAS scores never reached

2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 571578 575
Local anaesthesia for canine ovariohysterectomy KS Kalchofner Guerrero et al.

Table 2 Heart rate (HR) and respiratory rate (fR) at baseline and during the first 20 hours postoperatively in 36 dogs undergoing ovariohysterectomy treated with intraperitoneal
more than 30 mm throughout the entire study. In

17
26

14
13
104 
104 

24 
26 
one study comparing different analgesic treatments

0.93

0.61
20
in dogs undergoing OHE, rescue analgesia was
administered if a dog was deemed to be unaccept-
ably uncomfortable by one of two experienced pain

16*
25*

5*
4*
assessors (Shih et al. 2008); rescued animals, on

98 
92 

17 
16 
0.35

0.48
average, had a GCPS of 8.7  3.2, and a DIVAS of
12

53  18.2. The decision on the ideal cut-off point


for provision of rescue analgesia is a delicate matter,
18*
20*

3*
4*
as discussed by Brondani et al. (2013), who deter-
92 
88 

17 
15  mined a cut-off point for visual analogue scale in cats
0.56

0.18 of >28 mm.


8

The MNT was measured to investigate the devel-


17*
25*

11*

opment of primary hyperalgesia, which is mainly


5*

related to incisional pain (Lascelles et al. 1998).


89 
89 

20 
16 
0.95

0.23

Each group showed reduced values in MNT in


6

comparison to preoperative values at all time points


postoperatively. Thus we found that hyperalgesia
14*
16*

6*
3*

occurred in both groups after surgery, suggesting


84 
86 

17 
15 
0.68

0.19

that neither analgesic protocol (morphine, carpro-


4

fen, bupivacaine IP  INC) was effective in prevent-


ing primary hyperalgesia. The fact that hyperalgesia
14*
11*

6*
3*

was present postoperatively despite satisfactory pain


87 
85 

17 
15 

scores may indicate that the pain assessment meth-


0.60

0.39
2

ods used were not sensitive enough to detect


incisional pain.
14*
21*

It is possible that the postoperative decrease of HR


3*
6*

and fR at most time points as compared with baseline


91 
94 

18 
18 
0.56

0.90

is because the dogs were comfortable and not in


1
Time after extubation (hours)

pain; the results of the different pain scores support


this theory. Furthermore, HR and fR were increasing
bupivacaine plus either incisional bupivacaine (group B) or saline (group S)

25
23

11
5

again at 20 hours after extubation, a possible sign


115 
113 

23 
23 
0.78

0.78

that carprofen was no longer effective. Another


0.5

explanation may be that dogs were nervous or


excited upon arrival, resulting in a comparatively
25
21

11
Baseline

higher baseline HR and fR.


133 
117 

37 
39 
0.04

0.79

The dose of IP bupivacaine in the present study


was lower than that in the other two canine studies
using IP bupivacaine (4.45.0 mg kg 1) (Carpenter
Number

et al. 2004; Campagnol et al. 2012). As IP doses of


*Significantly different compared with baseline.

bupivacaine in human anaesthesia range between


18
18

18
18

2.0 and 3.5 mg kg 1 (Moiniche et al. 1998; Ng


et al. 2002), we were expecting to reach analgesic
Group

effects using 3.0 mg kg 1. The difference in out-


B
S

B
S

come of studies on IP instillation of local anaesthetics


could be a result of the location, dose, type and
timing of instillation (Ng & Smith 2002). The failure
)
HR (beats minute 1)

1
fR (breaths minute

in some studies to show an analgesic effect could


result from rapid dilution of local anaesthetics in the
peritoneal cavity (Schulte-Steinberg et al. 1995). It
Variable

p-Value

p-Value

is not possible, however, to increase the dose of local


anaesthetics without increasing the risk of systemic

576 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 571578
Local anaesthesia for canine ovariohysterectomy KS Kalchofner Guerrero et al.

toxicity. Bupivacaine is known for its cardiotoxicity analgesia with carprofen and IP bupivacaine
(Marx 1984; Feldman et al. 1989), characterized by resulted in satisfactory postoperative analgesia in
depression of the myocardial conductance and dogs undergoing OHE. The addition of bupivacaine
contraction (Fujita et al. 1998). Recommended SC at the incisional site had no impact on postop-
doses for bupivacaine in veterinary and human erative pain scores and could not prevent the
anaesthesia are in the range 0.53.0 mg kg 1, occurrence of primary hyperalgesia.
dependent on the route of administration and
procedure, whereas toxic doses are reported as being
Acknowledgements
in the range 3.54.5 mg kg 1 (Berde & Strichartz
2014; Borer-Weir 2014). There were no obvious The project was supported by the Small Research
signs of cardiotoxicity in this study. Grant Initiative of St Georges University; Topcat
No complications were observed during the course Metrology Ltd sponsored the MNT measurement
of this study. This supports the technique of simple device. The authors would also like to thank Dr M.
instillation of local anaesthetics versus more targeted Lanza-Perea and the staff of SGU Junior Surgery and
administration. In one study, lidocaine was infil- Anaesthesia laboratory for their assistance with the
trated into the mesovarium before OHE in dogs dogs, and Dr K. Clarke for reviewing the manuscript.
(Bubalo et al. 2008); first, this technique did not
reduce the isoflurane requirement during surgery;
Authors contributions
and secondly, it caused a high incidence of formation
of haematomas. The infiltration of local anaesthetic KK worked on the study design, data collection and
IM and SC over the planned incision site in another preparation of the manuscript; IC performed data
study resulted in a higher complication rate, includ- collection and management, and revised the manu-
ing excessive inflammation, splenic laceration and script; RB-D worked on the study design, logistical
herniation (Fitzpatrick et al. 2010). support and revision of the manuscript; CH-Y
There are several limitations to this study. First, a analysed and interpreted the data and revised the
control group was not included because it has been manuscript; TG carried out data collection and
previously shown that the combination of bupiv- revised the manuscript.
caine IP and INC is superior to saline in providing
postoperative analgesia in dogs undergoing OHE
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