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ORIGINAL ARTICLE
Year : 2020  |  Volume : 14  |  Issue : 4  |  Page : 578-583  

Premedication for induced hypotension in functional endoscopic sinus surgeries: Intravenous dexmedetomidine infusion vs oral metoprolol vs placebo: A comparative study


Department of Anaesthesiology and Critical Care, SGRD Medical College and Hospital, Amritsar, Punjab, India

Date of Submission10-Feb-2021
Date of Decision15-Feb-2021
Date of Acceptance01-Mar-2021
Date of Web Publication27-May-2021

Correspondence Address:
Dr. Lakshmi Mahajan
Associate Professor, Department of Anaesthesiology and Critical Care, SGRD Medical College and Hospital, Amritsar, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_19_21

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   Abstract 

Background: Controlled hypotension has been used to reduce bleeding and the need for blood transfusions and provide a satisfactory bloodless surgical field. In this double-blind, randomized controlled trial, we are comparing intravenous (i.v.) dexmedetomidine infusion and oral metoprolol as a premedication for controlled hypotension in functional endoscopic sinus surgery (FESS) for evaluating surgical field visibility. Subjects and Methods: A total of 90 patients undergoing FESS were randomly divided into three groups of 30 each. Group A received intraoperative i.v. infusion of dexmedetomidine (loading 1 μg.kg−1 over 10 min followed by the maintenance of 0.2–0.5 μg.kg−1.h−1), Group B received oral metoprolol 50 mg on night and 2 h before surgery as a premedication, and Group C was taken as a control group and patients received oral placebo tablet as premedication and intraoperative normal saline infusion. General anesthesia was given using sevoflurane. Intraoperative target mean arterial blood pressure was set 55–65 mmHg. Various parameters were recorded and statistically compared. Results: The three groups were statistically comparable in demographics. Quality of surgical field was better in Group A compared to other two groups. Total blood loss was also less in Group A. The incidence of adverse reactions was more in Group A. Conclusion: Dexmedetomidine provides a better surgical field compared to oral metoprolol in FESS along with the desired hemodynamics with lesser blood loss and better outcome.

Keywords: Controlled hypotension, functional endoscopic sinus surgery, intravenous dexmedetomidine, mean arterial blood pressure, oral metoprolol, sevoflurane, surgical field visibility


How to cite this article:
Mahajan L, Singh AP, Chawla S, Gill S. Premedication for induced hypotension in functional endoscopic sinus surgeries: Intravenous dexmedetomidine infusion vs oral metoprolol vs placebo: A comparative study. Anesth Essays Res 2020;14:578-83

How to cite this URL:
Mahajan L, Singh AP, Chawla S, Gill S. Premedication for induced hypotension in functional endoscopic sinus surgeries: Intravenous dexmedetomidine infusion vs oral metoprolol vs placebo: A comparative study. Anesth Essays Res [serial online] 2020 [cited 2021 Jun 16];14:578-83. Available from: https://www.aeronline.org/text.asp?2020/14/4/578/316971


   Highlight Top


Controlled hypotension has been used to reduce bleeding and the need for blood transfusions and provide a satisfactory bloodless surgical field. A total of 90 patients undergoing functional endoscopic sinus surgery were randomly divided into three groups of 30 each. Group A received intra-operative intravenous infusion of dexmedetomidine (loading 1 μg.kg−1 over 10 min followed by maintenance of 0.2–0.5 μg.kg−1.h−1), Group B received oral metoprolol 50 mg on night and 2 h prior to surgery as a premedication, and Group C was taken as a control group and patients received oral placebo tablet as premedication and intra-operative normal saline infusion. General anesthesia was given using sevoflurane. Intraoperative target MAP was set 55–65 mmHg. Various parameters were recorded and statistically compared. Quality of surgical field was better in Group A compared to other two groups.


   Introduction Top


Controlled hypotension or deliberate or reduced hypotension is a technique where the arterial blood pressure (BP) is reduced in a deliberate but controllable manner to minimize surgical blood loss and enhance operative field visibility.[1] For half a century, controlled hypotension has been used to reduce bleeding and the need for blood transfusions and provide a satisfactory bloodless surgical field.[2] It has been indicated in oromaxillofacial surgery, endoscopic (sinus or middle ear) microsurgery, spinal surgery and other neurosurgery (aneurysm), major orthopedic surgery (hip and knee replacement), prostatectomy, cardiovascular surgery, and liver transplant surgery.[3] This technique has been used for various ENT surgeries such as tympanoplasty, functional endoscopic sinus surgery (FESS), septoplasty, rhinoplasty, and angiofibroma excision. Induced/controlled hypotension is defined as the pharmacologically induced reduction in the mean arterial BP to 50–70 mm Hg either by inducing changes in the myocardial contractility (inhalation anesthetic agents and beta-blockers) or by peripheral vasodilatation (regional anesthesia, sodium nitroprusside, nitroglycerine, and trimethaphan).[4]

FESS is the primary approach used today for the surgical treatment of chronic sinusitis. Endoscopic sinus surgery is the most commonly performed surgery for inflammatory and infectious sinus diseases. FESS is a delicate and time-consuming procedure.[5] It is performed routinely under general anesthesia but can also be done under regional anesthesia. Anesthesiologists have to plan the technique to facilitate the operating team for achieving a bloodless field for better visualization of the intranasal structures and minimize intra-operative bleeding because even a little bleeding can obstruct the view of the operating endoscope. Hence, it comes the role of hypotensive anesthesia.[6]

Dexmedetomidine is an alpha2 adrenergic receptor agonist approved by the FDA in 1999 for human use for the short-term sedation and analgesia in the intensive care unit (ICU). It also improves perioperative hemodynamic stability, causes controlled hypotension by its central and peripheral sympatholytic action.[7]

Metoprolol is a cardioselective β1-adrenergic blocking agent used for acute myocardial infarction (MI), heart failure, angina pectoris, and mild-to-moderate hypertension. Therefore, metoprolol is one of the commonly used drugs to reduce cardiac output, heart rate (HR), and BP.[8]

Several volatile anesthetic agents have been found helpful in inducing hypotension for a better surgical field in FESS.[9] Sevoflurane is a dose-related cardiac depressant. Sevoflurane is a suitable agent for inducing hypotension when bloodless field is required, i.e., neurosurgical procedures involving the spine and hip replacement procedures.[10] Hence, we chose these three drugs for comparing their hypotensive actions in FESS.


   Subjects and Methods Top


The study was a prospective, randomized controlled trial on 90 patients (18–75 years) of American Society of Anesthesiologists (ASA) Grade I and II posted for FESS. After approval from hospital ethics committee, a prior informed consent was taken from all the patients.

Inclusion criteria

  • Age: 18–75 years
  • ASA physical status I and II
  • Patients undergoing FESS exclusion criteria:
  • Patients on any of the study drugs before the surgery
  • Patients with known hypersensitivity to study drugs
  • Patients having a history of drug abuse
  • Patients who are mentally retarded
  • Coagulation defects
  • Conditions contraindicated for induced hypotension
  • Patients on anti-coagulation therapy.


Patients were randomly allocated into three groups of 30 each according to the computer-generated random numbers and sealed in envelops. The group size of the study was determined by considering alpha error of 0.05 and power of study 80%, with effect size 0.4, sample size is 80. Considering dropout rate 10%, total sample size of 90 were taken with 30 in each group. The study was conducted over a period of 2 years.

Group A (n = 30) (Dexmedetomidine group): Patients received oral placebo tablets as premedicant on the night and 2 h before surgery and received intraoperative loading dose of dexmedetomidine 1 mcg.kg−1 (0.5 ml.kg−1) over 10 min intravenously followed by maintenance infusion at a rate of 0.2–0.5 mcg.kg−1.h−1 with sevoflurane anesthesia. Dexmedetomidine infusion was made with concentration of 2 mcg.ml−1 and will be started within the range of 0.1–0.25 ml.kg−1.h−1.

Group B (n = 30) (Metoprolol group): Patients received tablet metoprolol 50 mg orally as premedicant on the night and 2 h before surgery and received intraoperative loading dose of normal saline 0.5 ml.kg−1 followed by infusion of normal saline within the range of 0.1–0.25 ml.kg−1.h−1 with sevoflurane anesthesia.

Group C (n = 30) (Placebo group): Patients received oral placebo tablet as premedicant on the night and 2 h before surgery and received intraoperative loading dose of normal saline 0.5 ml.kg−1 followed by infusion of normal saline within the range of 0.1–0.25 ml.kg−1.h−1 with sevoflurane anesthesia and was taken as a control group.

Complete medical history and physical examination was done for all patients, including vital signs and airway assessment. non invasive blood pressure monitoring, HR, Oxygen saturation (SpO2), and respiration rate were checked in the preoperative room.

In the operation theater, monitoring equipment were attached to the patient including 5 leads ECG, noninvasive BP and pulse oximetry. Capnography adaptor was connected to the proximal end of the circuit to measure the end-tidal CO2.

The following parameters were recorded from the induction of anesthesia till the end of the surgery:

  1. Systolic BP, diastolic BP, and mean arterial pressure
  2. Heart rate
  3. End-tidal CO2
  4. SpO2
  5. BIS monitoring.


After arrival in the operating room, baseline vitals were noted. An intravenous (i.v.) access was secured and crystalloid infusion was started at the rate of 4 ml.kg−1.h−1. All the patients were given inj. glycopyrrolate 0.01 mg.kg−1 with injection butorphanol 0.02 mg.kg−1 i.v. just before induction.

Patients were preoxygenated for 3–5 min and anesthesia were induced with 2 mg.kg−1 i.v. inj. Propofol. Succinylcholine 1–1.5 mg.kg−1 i.v. was given to facilitate tracheal intubation. Anesthesia maintenance was done with 50% O2-N2O and sevoflurane 1%–3%. Muscle relaxation was obtained by injection vecuronium 0.1 mg.kg−1 i.v. and subsequent calculated doses at required intervals. The patient was ventilated to maintain an end-tidal CO2 level of 30–35 mm of Hg and SpO2 level above 95%. Oropharynx was packed with a wet throat pack.

Immediately after intubation, a loading dose of 0.5 ml.kg−1 of the prepared infusion solution was given over 10 min followed by a maintenance infusion rate of 0.1–0.25 ml.kg−1.h−1. The target mean arterial BP (MAP) was maintained at 55–65 mm of Hg by adjusting the sevoflurane (1%–3%). The time to achieve target BP was noted. If this fails, propofol infusion was started, as a rescue, at the rate of 8–12 mg.kg−1.h−1 to achieve the target MAP of 55–65 mm of Hg.

All the vitals were noted every 1 min for 5 min, then every 5 min for 15 min and then every 15 min till the end of the surgery. Intraoperative bleeding was measured by collecting blood in a marked container of 25 ml capacity with the precision of 0.5 ml. The blood soaked by gauge pieces and nasal packs were measured by weighing the gauge pieces before and after the procedures. The volume of blood collected in suction jars was also calculated and added to the blood loss.

After completion of surgery, the patient was reversed with neostigmine 0.05 mg.kg−1 i.v. body weight and glycopyrrolate 0.01 mg.kg−1 i.v. On awakening, the patient was extubated. After tracheal extubation, the patient was shifted to the recovery room.

The visibility/dryness of surgical field was assessed on monitor used with endoscope every half-hour intervals using a predefined average category scale (ACS) from Fromme and Boezaart[11] quality scale.

  • Grade 0: No bleeding
  • Grade 1: Slight bleeding – no blood suctioning required
  • Grade 2: Slight bleeding – occasional suctioning required
  • Grade 3: Slight bleeding – frequent suctioning required. Operative field is visible for some seconds after evacuation
  • Grade 4: Moderate bleeding – frequent suctioning required. Operative field is only visible immediately after evacuation
  • Grade 5: Severe bleeding – constant suctioning required. Bleeding appears faster than can be removed by suction. Surgery is hardly possible, and sometimes impossible.


Surgical field was graded as good, fair, and poor as under:

  • GOOD-ACS scale 0 or 1
  • FAIR-ACS scale 2 or 3
  • POOR-ACS scale 4 or 5.


Overall, surgeon's opinion was also taken on the same grading.

The Chi-square test for nonparametric data and Student's t-test for parametric data were applied to find the level of significance. P < 0.05 and P < 0.01 were considered significant, P < 0.001 as highly significant and P > 0.05 was considered as insignificant.


   Results Top


Demographic data, including patient age, sex, height, weight, body mass index, and ASA grade distribution and duration of surgery, were comparable in the two groups with P > 0.05 [Table 1].
Table 1: Demographic data

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Hemodynamic parameters (systolic BP, diastolic BP, mean arterial BP, and HR) were significantly lower in Group A receiving I/V dexmedetomidine compared to other two groups [Figure 1]. Time to reach target MAP of 55–65 mmhg was significantly less in Group A compared to other two groups [Figure 2]. Other parameters such as EtCO2 and SpO2 were comparable among the groups. BIS scores were significantly lower in Group A compared to other two groups [Figure 3].
Figure 1: Mean arterial blood pressure in various study groups at different time intervals intraoperatively

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Figure 2: Mean time to reach target mean arterial blood pressure in various study groups

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Figure 3: Mean BIS level variations in various study groups at different time intervals intra-operatively

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The use of rescue drug propofol for achieving desired MAP was significantly high in Groups B and C as compared to Group A [Figure 4].
Figure 4: Number of patients that needed rescue drug propofol in various study groups

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Total blood loss during the surgery was significantly less in Group A compared to other two groups [Figure 5].
Figure 5: Total blood loss in various study groups

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Quality of surgical field was statistically better in Group A compared to other two groups along with a better surgeons satisfaction [Figure 6].
Figure 6: Assessment of quality of surgical field on the basis of average category scale in various study groups (intergroup comparison)

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   Discussion Top


Number of patients distribution according to surgeons satisfaction in group A were higher as compared to group B and C [Figure 7]. The present study has been designed to compare the hypotensive effects of i.v. dexmedetomidine intraoperatively with oral metoprolol as a premedicant and a control group where only sevoflurane is used for FESS under general anesthesia. The three groups were compared in terms of hemodynamics, surgical field visibility, surgeon's satisfaction, and total blood loss.
Figure 7: Number of patients distribution according to surgeons satisfaction in various study groups

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Over the past two decades, the number of patients undergoing nasal surgeries for pathological or cosmetic reasons has increased.[12] The most common pathological defect being sinusitis, functional endoscopic sinus surgeries is being performed routinely as a primary approach for the surgical treatment of chronic sinusitis. FESS can be performed under local or general anesthesia but both have their own advantages and disadvantages.[13]

Under local anesthesia while nasal bleeding is less due to vasoconstriction, but patients ease and comfort is compromised. Under general anesthesia, there are many apparent advantages: An immobile surgical field for performing a surgical operation, effective protection of the respiratory tract, adequate analgesia and ventilation. As local anesthesia has been associated with discomfort and incomplete block, general anesthesia is preferred.[14]

Most common limiting factor in FESS is blood loss because the nasal and paranasal sinus mucosa is extremely well supplied with blood. It is difficult to stop bleeding from the capillaries and particularly challenging to manage bleeding during FESS.[13] Inhalational anesthetics, nitroprusside, nitroglycerine, and trimethaphan are the main drugs used for hypotensive anesthesia and β-Adrenoreceptor antagonists (atenolol, labetalol, and esmolol), calcium channel blockers (verapamil, diltiazem, and nicardipine) may also be used as monomedicines or as a supplementary drugs for sustaining the effect of the main substance. Third substances (ACE inhibitors [captopril], α2-adrenoreceptor agonists [clonidine, dexmedetomidine], opioids, and i.v. anesthetics may be used to potentiate the hypotensive effect of the main substances.[15]

Dexmedetomidine is an alpha2 adrenergic receptor agonist approved by the FDA in 1999 for human use for short-term sedation and analgesia in ICU. It also improves perioperative hemodynamic stability, causes controlled hypotension by its central and peripheral sympatholytic action. These actions are mediated by α2 adrenergic receptors and have manifested by a dose-dependent decrease in arterial BP, heart rate, cardiac output, and norepinephrine release. It also has the properties of analgesia, sympatholysis, and titrating sedation without major respiratory depression.[7] Hence, reducing opioid requirements and stress response to surgery, ensuring a stable hemodynamic state. However, its role in induced hypotension and bloodless surgical field during surgeries has yet to be thoroughly evaluated.

Metoprolol is a cardioselective β1-adrenergic blocking agent used for acute MI, heart failure, angina pectoris, and mild-to-moderate hypertension. Therefore, metoprolol is one of the commonly used drugs to reduce cardiac output, heart rate, and BP. Its effect is neither quick nor long-lasting. Employing intermediate-acting beta-blockers, such as metoprolol, can reduce the stress response induced by surgery, thus providing hemodynamic stability. The mechanism of hemodynamic control in beta-blockers is a reduction and attenuation of the excitatory effect caused by a sudden increase of catecholamines during surgery.[8] In endoscopic sinus surgery, there is a stimulation of the branches of the trigeminal nerve which in turn stimulates the sympathetic nerve centers in the medulla resulting in tachycardia and increase in BP. Β blockers attenuate this response.

Several volatile anesthetic agents have been found helpful in inducing hypotension for a better surgical field in FESS.[9] Literature is full of examples of such anesthetics such as isoflurane, sevoflurane, and halothane, etc.[16] Volatile anesthetic agents can cause smooth muscle relaxation and decrease systemic vascular resistance. However, their role in recent studies is controversial as they cause increased tissue perfusion due to vasodilation and may further contribute to surgical field bleeding. When used alone, inhalational anesthetics require such a high concentration to achieve a significant reduction in bleeding that hepatic or renal injury might occur. Sevoflurane is an inhalational anesthetic with the desirable properties of a low blood-gas partition coefficient and nonpungent character. It causes the least arrhythmia in the presence of exogenous adrenaline, which is routinely infiltrated into the operative field for creating a bloodless field.[10]

Propofol can be administered to reduce the BP intraoperatively. The major cardiovascular effect of propofol is a decrease in arterial BP owing to a drop in systemic vascular resistance, cardiac contractility, and preload.[17] Hence, we took propofol as a rescue drug to achieve desired hemodynamics if our study drug fails.

In our study, hemodynamic parameters were significantly low in dexmedetomidine group compared to other two groups. Metoprolol solely was unable to achieve desired hemodynamics for hypotensive anesthesia and required rescue drug propofol in maximum of patients, but was better than control group. Quality of surgical field was better in dexmedetomidine group compared to other two groups. Surgeon's satisfaction was also better in dexmedetomidine group.

Total blood loss was significantly less in dexmedetomidine group compared to metoprolol and control group. Similar results were reported by Das et al. in 2016 where I/V dexmedetomidine was compared with oral clonidine and dexmedetomidine group was found to be better in surgical field visibility, less blood loss, and better surgeons satisfaction.[18]

Thus, we conclude that dexmedetomidine was effective and safe in inducing hypotensive anesthesia for functional endoscopic sinus surgeries to achieve desired MAP and better surgical field visibility and less blood loss with a smaller need of additional propofol as a rescue drug. It had also provided excellent surgical field with a higher surgeon satisfaction score. Metoprolol solely as a premedication is not able to achieve the target hemodynamic parameters as required for hypotensive anesthesia, needed higher additional propofol as a rescue hypotensive agent to achieve desired hemodynamics but was better when compared to placebo group.

Limiting factor

The main limitation of the study was that different surgeons had different opinions regarding the surgical field.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Vinella C, Ganapathi P, Shankara Narayan P. Effect of controlled hypotension with dexmedetomidine versus Nitroglycerin on intraoperative blood loss during FESS. IOSR J Dent Med Sci 2015;14:42-5.  Back to cited text no. 1
    
2.
Andel D, Andel H, Hörauf K, Felfernig D, Millesi W, Zimpfer M. The influence of deliberate hypotension on splanchnic perfusion balance with use of either isoflurane or esmolol and nitroglycerin. Anesth Analg 2001;93:1116-20.  Back to cited text no. 2
    
3.
Maroof M, Khan RM, Bhatti TH. Clonidine premedication for induced hypotension with total intravenous anaesthesia for middle ear microsurgery. Can J Anaesth 1994;41:164-5.  Back to cited text no. 3
    
4.
Habler O. Controlled hypotension. Anaesthesist 2000;49:687-9.  Back to cited text no. 4
    
5.
Stammberger H, Posawetz W. Functional endoscopic sinus surgery. Concept, indications and results of the Messerklinger technique. Eur Arch Otorhinolaryngol 1990;247:63-76.  Back to cited text no. 5
    
6.
Stankiewicz JA. Complications of endoscopic intranasal ethmoidectomy. Laryngoscope 1987;97:1270-3.  Back to cited text no. 6
    
7.
Yazbek-Karam VG, Aouad MM. Perioperative uses of dexmedetomidine. Middle East J Anaesthesiol 2006;18:1043-56.  Back to cited text no. 7
    
8.
Nair S, Collins M, Hung P, Rees G, Close D, Wormald PJ. The effect of beta-blocker premedication on the surgical field during endoscopic sinus surgery. Laryngoscope 2004;114:1042-6.  Back to cited text no. 8
    
9.
Drozdowski A, Sieśkiewicz A, Siemiatkowski A. Reduction of intraoperative bleeding during functional endoscopic sinus surgery. Anestezjol Intens Ter 2011;43:45-50.  Back to cited text no. 9
    
10.
Cinčikas D, Ivaškevičius J, Martinkėnas JL, Balseris S. A role of anesthesiologist in reducing surgical bleeding in endoscopic sinus surgery. Medicina (Kaunas) 2010;46:730-4.  Back to cited text no. 10
    
11.
Boezaart AP, Van der Merwe J, Coetzee A. Comparison of sodium nitroprusside- and- esmolol- induced controlled hypotension for functional endoscopic sinus surgery. Can J Anaesth 1995;42:373-76.  Back to cited text no. 11
    
12.
Rice DH. Endoscopic sinus surgery. In: Donald PJ, Gluckman Jl, editors. The Sinuses. New York: Raven Press; 1995. p. 255.  Back to cited text no. 12
    
13.
Sun S. Intraoperative complications of endoscopic sinus surgery. Zhonghua Er Bi Yan Hou Ke Za Zhi 2001;36:335-7.  Back to cited text no. 13
    
14.
Gittelman PD, Jacobs JB, Skorina J. Comparison of functional endoscopic sinus surgery under local and general anesthesia. Ann Otol Rhinol Laryngol 1993;102:289-93.  Back to cited text no. 14
    
15.
Larsen R, Kleinschmidt S. Die kontrollierte Hypotension (Induced hypotension). Anaesthetist 1995;44:291-308.  Back to cited text no. 15
    
16.
Lam AM, Gelb AW. Cardiovascular effects of isoflurane-induced hypotension for cerebral aneurysm surgery. Anesth Analg 1983;62:742-8.  Back to cited text no. 16
    
17.
Blackwell KE, Ross DA, Kapur P, Calcaterra TC. Propofol for maintenance of general anesthesia: A technique to limit blood loss during endoscopic sinus surgery. Am J Otolaryngol 1993;14:262-6.  Back to cited text no. 17
    
18.
Das A, Mukherje A, Chhaule S, Chattopadhyay S, Halder PS, Mitra T, et al. Induced hypotension in ambulatory functional endoscopic sinus surgery: A comparison between dexmedetomidine and clonidine as premedication. A prospective, double-blind, and randomized study. Saudi J Anaesth 2016;10:74-80.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
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