Propofol Sedation During Awake Craniotomy for
Seizures: Patient-Controlled Administration Versus
Ian A. Herrick, BSC, MD, FRCW, Rosemary A. Craen, MBBS, FANZCA*,
Adrian W. Gelb, MB, ChB, FRCPC*, Laurie A. Miller, PhDt, Cynthia S. Kubu, PhDt,
John P. Girvin, MD, FRCSCS, Andrew G. Parrent, MD, FRCSCS, Michael Eliasziw, PhD§, and
Joyce Kirkby, RNA*
Departments of *Anaesthesia, tPsychology, SClinical Neurological Sciences, and §Epidemiology and Biostatistics, London
Health Sciences Centre, University of Western Ontario, J. I’. Robarts Research Institute, London, Ontario, Canada
This prospective study evaluated the safety and effi- intraoperative sedation and patient satisfaction were
cacy of patient-controlled sedation (PCS) using propo- similar between groups. Memory and cognitive func-
fol during awake seizure surgery performed under bu- tion were well preserved in both groups. The incidence
pivacaine scalp blocks. Thirty-seven patients were of transient episodes of ventilatory rate depression
randomized to receive either propofol PCS combined (~8 bpm) was more frequent among the propofol pa-
with a basal infusion of propofol (n = 20) or neurolept tients (5 vs 0, P = 0.04), particularly after supplemental
analgesia using an initial bolus dose of fentanyl and doses of opioid. Intraoperative seizures were more
droperidol followed by a fentanyl infusion (n = 17). common among the neurolept patients (7 vs 0, P =
Both groups received supplemental fentanyl and di- 0.002). PCS using propofol represents an effective alter-
menhydrinate for intraoperative pain and nausea, re- native to neurolept analgesia during awake seizure sur-
spectively. Comparisons were made between groups gery performed in a monitored care environment.
for sedation, memory, and cognitive function, patient
satisfaction, and incidence of complications. Levels of (Anesth Analg 1997;84:1285-91)
ortical resection for the management of refrac- a popular technique (1,2). Recently, the use of propo-
tory seizures or cerebral lesions located in close fol sedation during these procedures has been re-
proximity to eloquent areas of the brain is often ported (3,4) and has become popular at our hospital.
performed with the patient awake. Anesthesia is usu- Patient-controlled sedation (PCS) with propofol, us-
ally provided using a combination of local anesthesia ing patient-controlled analgesia (PCA) technology,
(local infiltration and regional blockade) and intra- has been reported to be safe, to provide effective se-
venous (IV) medications to provide sedation, anxioly- dation, and to be associated with a high degree of
sis, and supplemental analgesia during these long patient satisfaction and acceptance (5-7). Most of the
procedures. available data involving PCS relate to surgical proce-
The need to minimize interference with intraopera- dures of relatively short duration.
tive electrocorticography (ECoG), when this is used, This prospective, randomized study was designed
limits the repertoire of drugs available for sedation. to evaluate the safety and efficacy of propofol PCS
Traditionally, neurolept analgesia using a combina- during awake craniotomy for seizure surgery. The
tion of opioid (often fentanyl) and droperidol has been impact of propofol sedation on intraoperative ECoG is
addressed in an accompanying article.
This study was supported by a grant from the Physicians’ Ser-
vices Incorporated (PSI) Foundation.
Accepted for publication March 6, 1997. Methods
Address correspondence to Ian A. Herrick, MD, Department of
Anaesthesia, London Health Sciences Centre, University Campus, After institutional ethics approval and acquisition of
339 Windermere Road, London, Ontario N6A 5A5, Canada. written, informed consent, adult patients (aged 18-65
01997 by the International Anesthesia Research Society
0003.2999/97/$5.00 Anesth Analg 1997;84:1285-91 1285
1286 NEUROSURGICAL ANESTHESIA HERRICK ET AL. ANESTH ANALG
PCS PROPOFOL & SEIZURE SURGERY 1997;84:1285-91
yr) scheduled for cortical resection for refractory sei- preoperatively, intraoperatively (at 1 h after the com-
zures were randomized to receive either propofol PCS mencement of sedation), postoperatively in the post-
or neurolept analgesia (fentanyl and droperidol). anesthesia care unit (PACU), and on postoperative
Sedation for the PCS group consisted of patient- day (POD) 1. Memory was also evaluated on POD 1
administered propofol using a bolus dose of 0.5 mg/ and 2 by free recall of specific intraoperative events.
kg, a lockout interval of 3 min, and a basal infusion of Cognitive functioning was assessed preoperatively,
0.5 mg * kg-’ * h-’ via a standard PCA device (Baxter, intraoperatively at 1 h, in the PACU, and on POD 1
McGaw Park, ILPCAII). Patients were shown how to using examination questions listed in Appendix 1.
use the device preoperatively and were instructed to Intraoperative sedation was assessedprior to seda-
administer sedation if they wished to be more tion (baseline) and then hourly by the attending anes-
“sleepy” or if they experienced anxiety or discomfort. thesiologist based on a 5-point scale (Appendix 2). The
Patients were encouraged to use the PCS device early technical difficulty associated with each surgical pro-
in the operative procedure (to ensure that they under- cedure was evaluated by the attending surgeon based
stood how to use it and what effect it would have on on a 5-point scale (technically easy = 1, technically
them) and were reminded that they could use the difficult = 5).
pump if they requested more sedation or became rest- Intraoperative and postoperative complications
less during the operation. They were also told that were noted. These included hemodynamic instability
supplemental analgesia was available from their an- (systolic blood pressure ~85 or >170 mm Hg, heart
esthesiologist if they were uncomfortable and that the rate ~45 or >llO bpm), decreased ventilatory fre-
anesthesiologist would take over administration of quency (~8 bpm), pulse oximetric desaturation
sedation if they were unable or unwilling to do so at (<90%), intraoperative vomiting, and inappropriate
any point in the operation. To avoid potential inter- seizures (seizures not associated with ECoG recording
ference with ECoG recordings, propofol administra- or cortical mapping). The ability to perform appropri-
tion (both the PCS boluses and the basal infusion) was ately during cortical mapping was also noted. Patient
satisfaction was evaluated using a short questionnaire
suspended 15 min prior to ECoG recording and func-
completed by each patient in the PACU and on PODS
tional cortical mapping.
1 and 5 (Appendix 3).
For the neurolept group, sedation consisted of ini-
Nonparametric data (e.g., the incidence of compli-
tial IV boluses of droperidol (0.04 mg / kg) and fenta-
cations) were analyzed using Fisher’s exact test or 2
nyl (0.7 pg/kg) followed by an anesthesiologist-
analysis. The unpaired Student’s t-test was used to
controlled continuous infusion of fentanyl at
analyze parametric data (e.g., drug dose comparisons
0.7 pg - kg-’ . h-‘. Administration of supplemental
between groups). Satisfaction questionnaire and cog-
droperidol was performed at the discretion of the
nitive function test results were reported in parametric
attending anesthesiologist. terms and analyzed using Students t-test. Identical
Both groups received supplemental anesthesiologist- results were obtained using nonparametric methods
administered fentanyl (25-pg boluses) and dimenhydri- (Mann-Whitney U-test). Sedation scores were ana-
nate (25-mg boluses) as needed for intraoperative pain lyzed parametrically using analysis of variance for
and nausea or vomiting, respectively. repeated measures and the Student-Newman-Keuls
Regional blockade of the scalp was performed by test. To confirm the acceptability of parametric analy-
the surgeon l-2 h preoperatively using bupivacaine sis methods, the sedation scores were also subjected to
0.5% with epinephrine. Supplemental local anesthetic nonparametric analysis, which yielded identical re-
solution (bupivacaine 0.33% with epinephrine) was sults. A level of P 5 0.05 was accepted as statistically
used to infiltrate along the incision lines prior to sur- significant.
gery. During craniotomy, dura mater was anesthe-
tized using a mixture of lidocaine 1% and 0.25% bu-
pivacaine without epinephrine. Our block technique
for craniotomy under local anesthesia has been previ- Results
ously described in detail (8). Thirty-seven adult patients scheduled for cortical re-
All patients received supplemental oxygen via nasal section for refractory seizures were studied; 20 re-
prongs during surgery. Intraoperative monitoring in- ceived propofol PCS, and 17 received neurolept anal-
cluded ECG, pulse oximetry, noninvasive automated gesia. Three additional patients were excluded from
blood pressure measurements, and capnography via the study because they required general anesthesia.
the nasal prongs. One patient in the propofol group was converted to
On the day before surgery, patients were visited to general anesthesia 1.5 h after the commencement of
obtain demographic data and to perform baseline cog- sedation due to incomplete regional blockade that
nitive function and memory testing. Memory for ob- could not be remedied during dural opening. Two
jects was evaluated using recall and recognition tests patients in the neurolept group were converted to
ANESTH ANALG NEUROSURGICAL ANESTHESIA HERRICK ET AL. 1287
1997;84:1285-91 PCS I’ROPOFOL & SEIZURE SURGERY
Table 1. Demographic Data and Surgical Variables Table2. Intraoperative Drug Administration Profile and
PCS Fentanyl /
Characteristic propofol droperidol PCS Fentanyl /
+ 11 Characteristic propofol Droperidol
Age W 30 -c 8 34
Sex (M:F) 14:6 12:5 Total dosefentanyl (Fg / kg) N/A 6.3 ? 3
Weight (kg) 69 i 13 72 + 12 Supplemental fentanyl 2.9 ? 2 2.6 ? 2
Duration anesthesia 327 2 48 360 -c 62 (/-dk)
(min) Total dose droperidol N/A 0.04 2 0.01
Surgical site (T/F / C) 141214 14/l/2 (mgk)
Surgical difficulty (l-5) 3 -c 0.7 3 k 0.8 Total dosepropofol (mg/kg) 10.2 * 4 N/A
Local anesthetic scalp 20 t 1 20? 1 Total propofol bolus dose 7.2 + 4 N/A
blocks (bupivacaine (mgk)
0.5% with epinephrine PCS demand ratio (%) 40.3 N/A
1/ 200,000)(mL) (successful:totaldemands)
Local anesthetic scalp 45 + 22 51 ? 23 Total dose dimenhydrinate 13 t 22 22 ? 26
infiltration (bupivacaine (mg)
0.33% with epinephrine Number of patients given 6 9
1/ 200,000)(mL) intraoperative
Data are presented as mean + SD or number of patients.
PCS = patient-controlled sedation, T/F/C = temporal/frontal/central Intraoperative vomiting 2 3
Intraoperative seizures 0 7"
Transient respiratory rate 5 0%
general anesthesia due to marked anxiety and agita- depression
Intraoperative tachycardia 2 6
tion. For one patient, general anesthesia was induced
prior to sedation; for the other patient, anesthesia was Data are presented as mean 2 SD or number of patients.
PCS = patient-controlled sedation, N/A = not applicable
induced approximately 30 min after the commence- * P < 0.05 between groups.
ment of sedation. In both cases, the patients were
unwilling to continue the procedure awake and re-
quested general anesthesia. which was prompted by discomfort and fatigue dur-
Demographic data for the two groups are shown in ing the terminal stages of the cortical resection. In the
Table 1. The duration of anesthesia and surgery aver- neurolept group, the fentanyl infusion was increased
aged 5-6 h. The majority of patients underwent tem- to 0.9-1.8 pg. kg-i . h-l for five patients. In addition
poral lobectomy. to an increased fentanyl infusion, one of these patients
Preoperative anticonvulsant medications were sim- also received incremental doses of propofol (lo- to
ilar between groups. Thirty-five percent and 45% of 20-mg boluses, total dose 240 mg over a 1.5-h interval)
the patients in the PCS and neurolept groups, respec- at the discretion of the attending anesthesiologist to
tively, received the usual dose of anticonvulsant manage agitation during the terminal aspects of the
medications on the morning of surgery. The remain- resection and closure. Three patients also received a
der of the patients had anticonvulsant medications single supplemental dose of droperidol ranging from
tapered, partially or completely, during preopera- 0.5 to 1.25 mg. Dose adjustments, if needed, typically
tive evaluations and received a reduced dose or no reflected a response to restlessness or discomfort, of-
dose of anticonvulsant medication on the day of ten compounded by nausea, which may accompany
surgery. resection of the mesial temporal lobe or basal frontal
All patients received supplemental anesthesiologist- lobe. The predetermined sedation protocol, which in-
administered fentanyl for discomfort during the cor- cluded the suspension of propofol administration dur-
tical resection. The supplemental dose was similar for ing testing, was not altered in either group during the
the two groups (Table 2). The PCS patients received a preresection period (i.e., prior to or during ECoG
mean propofol dose of 690 + 287 mg, of which 494 2 recording).
291 mg (72%) was patient-administered.
Adjustments to predetermined dose regimens (in- Sedation Scores
creases in the rate of the fentanyl infusion or increases
in the bolus dose or basal infusion of propofol) were Compared with baseline, sedation scores increased in
required for five patients in the neurolept group and a similar fashion in both groups except at the 2-h
four patients in the PCS group. Three of the patients in assessment, at which point sedation scores in the
the PCS group had the propofol bolus dose increased propofol group decreased significantly. This assess-
to 0.75-1.0 pg/kg. The fourth PCS patient was con- ment coincided with the period during which propo-
verted to a propofol infusion (2-3 mg * kg-’ * h-i) in fol administration was suspended during intraopera-
response to a request to stop using the PCS device, tive testing (Figure 1).
1288 NEUROSURGICAL ANESTHESIA HERRICK ET AL ANESTH ANALG
PCS PROPOFOL & SEIZURE SURGERY 1997;84:1285-91
/ I I PCS NEUROLEPT PCS NEUROLEPT PCS NEUROLEPT
PREOP 1 2 3 4 5 I-HOUR PACU POD1
TIME FROM PREOP (Hrs)
iIfIUUI = RECALL
Figure 1. Patient sedation scores assessed intraoperatively by the = = RECOGNITION
attending anesthesiologist. Scoring based on a 5-point scale (Appen-
dix 1). Scores for propofol PCS (0) and neurolept analgesia (a) were Figure 2. Object recall and recognition test results at 1 h intraop-
assessed at l-h intervals intraoperatively. Error bars represent SEM. eratively, in the postanesthesia care unit, and on the first postoper-
*P < 0.05 between groups. ative day (PODl). Prior to sedation, patients were shown three
objects, and memory for these objects was tested 1 h after the
commencement of sedation. Patients were then shown three addi-
Memory and Cognitive Functioning tional objects, and memory was evaluated for all six objects in the
postanesthesia care unit and on PODl. The mean number of objects
recalled directly is shown by the height of the vertically striped area
Based on recall and recognition tests, memory for of each bar. The additional contribution of recognition to the total
objects was not different between the two groups (Fig- number of objects remembered is depicted by the open area of each
ure 2). Memory encoding and retrieval were not af- bar.
fected substantially by either type of sedation. Cogni-
tive function test results were similar between the two Table 3. Patient Satisfaction Questionnaire Results
groups. Free recall of intraoperative events was not
depressed in either group. Questionnaire score (l-4)
Satisfaction index PACU POD 1 POD 5
Patient Satisfaction General level of comfort
Patient satisfaction was similar between groups with PCS 2.7 5 0.8 2.7 t 1.1 2.9 +- 1.1
respect to the general level of comfort and willingness NEUROLEPT 2.7 +- 0.8 2.5 -c 0.8 2.8 ? 0.9
Willingness to use same
to repeat the procedure using the same sedation tech- technique in future
nique (Table 3). Satisfaction with the option of self- PCS 2.9 -c 0.8 3.1 ? 0.9 3.0 ? 1.1
administering sedation (assessed only in the PCS NEUROLEPT 2.7 IL 0.9 2.7 +- 0.9 2.6 ? 1.2
group) was high. Satisfaction with PCS was main- Satisfaction with
tained through the fifth postoperative day. patient-administration
PCS only 3.3 i 0.7 3.6 -c 0.5 3.6 ? 0.6
Complications Data are presented as mean +- SD
PACU = postanesthesra care umt, POD = postoperatrve day, PCS =
Transient decreases in respiratory rate (<8 bpm) after
supplemental doses of fentanyl were more common in
the PCS group (PO.04, Fisher’s exact test) (Table 2). neurolept analgesia to manage agitation (as discussed
These episodes were short in duration (<l min) and previously).
did not require intervention. One patient in the neu- Intraoperative inappropriate seizures were mark-
rolept group experienced a brief episode of pulse oxi- edly more common in the neurolept group (P = 0.002,
metric desaturation (Spo,89%) associated with the ad- Fisher’s exact test). Five patients experienced general-
ministration of small doses of propofol during ized convulsions, and two experienced focal motor
ANESTH ANALG NEUROSURGICAL ANESTHESIA HERRICK ET AL. 1289
1997;84:1285-91 PCS PROPOFOL & SEIZURE SURGERY
seizures. Four of the patients who experienced gener- Based on our experience, the inclusion of a basal
alized convulsions received IV thiopental (50- to infusion is advantageous during propofol PCS for
75-mg boluses) to terminate the seizures (mean dose long procedures during which patients often become
125 mg, range 50-200 mg). Each patient recovered restless or fatigued as the procedure progresses (15). A
satisfactorily to complete the procedure under neuro- basal infusion provides a baseline level of sedation
lept analgesia. ECoG recordings were satisfactory in that patients may augment using PCS demands in
both groups, although a low frequency of ECoG spike response to clinical circumstances. The PCS demand
activity noted in one of the patients in the neurolept ratio in this study was 40%. This is consistent with the
group was attributed to the administration of thiopen- results of other investigators (7,16). Although the tech-
tal to terminate a seizure that occurred during the nique is associated with a relatively high number of
period preceding ECoG recording. The frequency of ineffective demands, patients achieved effective levels
ECoG spike activity did not correlate with the type of of sedation and expressed a high degree of satisfaction
sedation administered, as discussed in detail in the with PCS. These findings probably reflect a favorable
accompanying article. All patients performed satisfac- response to the sense of control or participation pro-
torily during functional cortical mapping. vided by PCS.
Two patients in the PCS group and six patients in Propofol may exert a positive or euphoric effect on
the neurolept group developed tachycardia in excess mood (17-19), which has been postulated to contribute
of 110 bpm in response to intraoperative discomfort to the high levels of patient satisfaction reported with
(P = 0.07, Fisher’s exact test) (Table 2). In all cases,this PCS, particularly when assessmentsare conducted in-
response was satisfactorily attenuated with supple- traoperatively or during the early postoperative pe-
mental fentanyl. The incidence of intraoperative vom- riod (6,14). Our results suggest that patient satisfaction
iting and the administration of antiemetic medication with propofol PCS is independent of these effects, if
were similar between the two groups. they exist, since satisfaction is maintained well into the
postoperative period, up to POD 5.
Complications associated with the two sedation
Discussion techniques were similar. A higher incidence of tran-
Sedation during awake craniotomy has traditionally sient respiratory rate depression was found in the
been provided using a combination of fentanyl and propofol group after doses of supplemental fentanyl.
droperidol. Propofol offers several potential advan- However, the fact that these events were not associ-
tages over traditional techniques: its short duration of ated with pulse oximetric desaturation emphasizes the
action facilitates titration of sedation, it has a wide advantage associated with providing supplemental
spectrum of applications (including conversion to oxygen during these procedures. Patients receiving
general anesthesia if clinical circumstances warrant), propofol sedation appear to be prone to respiratory
and it has been reported to have both antiemetic and depression associated with the administration of opi-
amnestic properties at sedative doses (9-12). oids. This observation has also been reported by oth-
Several studies (5,6,13,14) have endorsed the use of ers (20).
propofol for sedation during procedures of short du- Patients receiving neurolept analgesia experienced a
ration, both by continuous infusion and via PCA de- higher incidence of inappropriate intraoperative sei-
livery systems. Although the use of propofol sedation zures compared with the patients who received
has been reported during epilepsy surgery (3,4), there propofol. Since the management of anticonvulsant
is no information available regarding the safety or medications in the preoperative period was similar
efficacy of patient-administered propofol sedation between the two groups, these findings suggest that
during these procedures. PCS offers the opportunity propofol may suppress seizure activity or that neuro-
to combine bolus doses of sedative medication admin- lept analgesia may either facilitate seizures or at least
istered by the patient with a continuous basal infusion permit normal convulsions. Although its proconvul-
controlled by the anesthesiologist. This strategy offers sant and anticonvulsant profile remains controversial,
the patient a sense of control and provides the capac- propofol has anticonvulsant activity at sedative doses
ity to administer sedation in response to the individ- (21). In contrast, many neuroleptic drugs, including
ual needs of the patient while enabling the anesthesi- butyrophenones such as droperidol, have been re-
ologist to determine the background level of sedation. ported to lower the seizure threshold, and caution has
Our results demonstrate that patient-administered been advised when administering these drugs to pa-
propofol is just as effective as anesthesiologist- tients with untreated epilepsy (22,23). The facilitation
administered neurolept analgesia during these proce- of seizure activity has not been reported in association
dures. Patients achieved similar levels of sedation and with the administration of droperidol during anesthe-
were similarly satisfied with both techniques. Patients sia for intractable epilepsy (21). However, compara-
using PCS were satisfied with the option of controlling tive studies involving the use of distinctly different
the administration of sedation. sedation techniques during epilepsy surgery have not
1290 NEUROSURGICAL ANESTHESIA HERRICK ET AL ANESTH ANALG
PCS PROPOFOL & SEIZURE SURGERY 1997;84:1285-91
been reported previously. Further investigations are sedation doses, our findings, consistent with the re-
needed to define the basis for the observed difference sults of other investigators, show that at lower doses,
in the incidence of seizures. the amnestic effects of propofol are negligible
ECoG recordings were satisfactory to proceed with (10,12,19).
resection in all patients. A comparison of the ECoG The results of this study demonstrate that propofol
effects of each of the sedation protocols is addressed in PCS provides an effective alternative to neurolept an-
the accompanying article. algesia during craniotomy performed under regional
Propofol reportedly has significant antiemetic prop- anesthesia. Our experience regarding the effect of
erties (9), but the incidence of intraoperative vomiting propofol sedation on the quality of intraoperative
and the administration of dimenhydrinate were simi- ECoG recordings is described in the accompanying
lar between our two groups. This may be because article.
droperidol also possesses antiemetic properties, or be-
cause intraoperative vomiting was preempted by the
The authors gratefully acknowledge the assistance of Ms. C. Hawke,
administration of dimenhydrinate in response to com- Ms. L. Szabo (secretarial assistance), and Mr. P. Lok (data analysis)
plaints of nausea. An additional possibility may relate in the preparation of this manuscript.
to the fact that many episodes of vomiting during
these operations appear to result from discomfort as-
sociated with traction on blood vessels or dura at the
base of the cortical resection. Although propofol and
droperidol are effective antiemetics for drug-induced Appendix 1
nausea and vomiting mediated by the area posterema, lntraoperative Sedation Scale
the mechanisms for intraoperative vomiting during
these procedures may be less responsive to therapy. Score Criteria
Cognitive function was well preserved in both 1 Fully awake and oriented
groups, as was memory. Patients in both groups per- 2 Drowsy, eyes open
formed well on formal memory testing involving ob- 3 Drowsy, eyes closed, but rousable to command
ject recall and recognition and demonstrated little am- 4 Drowsy, eyes closed, rousable to mild physical
nesia for intraoperative events. Although propofol has stimulation
5 Unrousable to mild physical stimulation
been reported to possess amnestic properties at higher
Mental Status Questionnaire
1. What is your name? (3)
2. What is the date today? (3)
Month Day Year
3. What is the name of this place? (3)
Hospital City Province
4. What is your address? (3)
5. What is your telephone number? (1)
6. What is your mother’s first name? (1)
7. Name the next 3 months in a calendar year after the month of August. (3)
8. Subtract serial 3’s: I I I I 41)
9. McGill Picture Anomalies Test: Two pictures will be shown. Patient is asked to demonstrate what is funny,
peculiar, or out of place in each picture. (2)
Total score = 120
ANESTH ANALG NEUROSURGICAL ANESTHESIA HERRICK ET AL. 1291
1997;84:1285-91 PCS PROI’OFOL & SEIZURE SURGERY
Patient Satisfaction Questionnaire
Please help us evaluate your anesthetic by completing the following questions. We are interested in your honest
opinion, positive or negative. We also welcome your comments and suggestions.
Circle your answer:
1. How satisfied were you with your pain management and overall level of comfort?
4 3 2 1
very satisfied mostly satisfied mildly satisfied quite dissatisfied
2. If you were to have surgery again, would you opt for the same method of management?
1 2 3 4
no, definitely not no, I don’t think so yes, I think so yes, definitely
3. Did you like the method of self-administration of sedative medication?
4 3 2 1
yes, definitely yes, I think so no, I don’t think so no, definitely not
13. Mackenzie N, Grant IS. Propofol for intravenous sedation. An-
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