Perioperative management of geriatric patients. Project of clinical recommendations
ISSN (print) 1726-9806     ISSN (online) 1818-474X
#2018-1
PDF_2018-1_60-74 (Russian)

Keywords

geriatrics
anesthesia
perioperative period

How to Cite

1.
Zabolotskikh I.B., Gorobets E.S., Grigoriev E.V., Kozlov I.A., Lebedinsky K.M., Musaeva T.S., Ovechkin A.M., Trembach N.V., Khoronenko V.E. Perioperative management of geriatric patients. Project of clinical recommendations. Annals of Critical Care. 2018;(1):60-74. doi:10.21320/1818-474X-2018-1-60-74

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Abstract

The need for surgical treatment in elderly patients arises four times more often than the population average. Due to the tendency to increase life expectancy, the number of elderly patients who underwent surgery increases, which requires an increase in the geriatric care, including surgical and anesthetic care. It is well known that in comparison with young patients, older subjects have a higher risk of developing adverse postoperative outcomes as a result of age-related decline in physiological functions, the presence of several comorbidities, polypharmacy, cognitive dysfunction and specific geriatric syndromes such as frailty. The presented recommendations generalize modern principles of perioperative management in patients of older age groups. Particular attention is paid to the peculiarities of preoperative examination, including the evaluation of geriatric syndromes, the choice of anesthesia method and the correct calculation of doses of drugs for anesthesia. Great importance at the present time made the role of cognitive status of older patients and post-operative cognitive dysfunction, which substantially affects the outcome of the disease. These recommendations include measures to assess cognitive status and prevent complications associated with cognitive impairment. Individualization of approach to management of geriatric patients is the basis of effective prevention of perioperative complications.
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References

  1. Tosato M., Zamboni V., Ferrini A., Cesari M. The aging process and potential interventions to extend life expectancy. Clin. Interv. Aging. 2007; 2: 401–412. PMID: 18044191.
  2. Weiser T.G., Regenbogen S.E., Thompson K.D., et al. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet. 2008; 372(9633): 139–144. doi: 10.1016/S0140–6736(08)60878–8.
  3. Monk T.G., Weldon B.C., Garvan C.W, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008; 108: 18–30. doi: 10.1097/01.anes.0000296071.19434.1e.
  4. Брискин Б.С., Ломидзе О.В. Влияние полиморбидности на диагностику и исход в абдоминальной хирургии у пожилых. Клиническая геронтология. 2008; 4: 30–33. [Briskin B.S., Lomidze O.V. Effect of polymorbidity on diagnosis and outcome in abdominal surgery in the elderly. Klinicheskaya gerontologiya. 2008; 4: 30–33. (In Russ)]
  5. Федоровский Н.М. Физиологические особенности стареющего организма в оценке специалиста по анестезиологии, реаниматологии и интенсивной терапии. Клиническая геронтология. 2003; 2: 36–40. [Fedorovsky N.M. Physiological features of the aging organism in the evaluation of a specialist in anesthesiology, resuscitation and intensive care. Klinicheskaya gerontologiya. 2003; 2: 36–40. (In Russ)]
  6. Ghaferi A.A., Birkmeyer J.D., Dimick J.B. Variation in hospital mortality associated with inpatient surgery. N. Engl. J. Med. 2009; 361(14): 1368–1375. doi: 10.1056/NEJMsa0903048.
  7. Griffiths R., Beech F., Brown A., et al. Peri-operative care of the elderly 2014: association of anesthetists of Great Britain and Ireland. Anesthesia. 2014; 69: 81–98. doi: 10.1111/anae.12524.
  8. Lakatta E.G. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003; 107: 490–497. PMID: 12551876.
  9. Corcoran T.B., Hillyard S. Cardiopulmonary aspects of anesthesia for the elderly. Best Practice and Research Clinical Anesthesiology. 2011; 25: 329–354. doi: 10.1016/j.bpa.2011.07.002.
  10. Monahan K.D. Effect of aging on baroreflex function in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007; 293: R3–R12. doi: 10.1152/ajpregu.00031.2007.
  11. Barodka V.M., Joshi B.L., Berkowitz D.E, et al. Review article: implications of vascular aging. Anesth. Analg. 2011; 112: 1048–1060. doi: 10.1213/ANE.0b013e3182147e3c.
  12. Sprung J., Gajic O., Warner D.O. Review article: age related alterations in respiratory function — anesthetic considerations. Can. J. Anaesth. 2006; 53: 1244–1257. doi: 10.1007/BF03021586.
  13. Presta P., Lucisano G., Fuiano L., Fuiano G. The kidney and the elderly: why does the risk increase? International Urology and Nephrology. 2012; 44: 625–632. doi: 10.1007/s11255-011-0063-2.
  14. Martin J.E., Sheaff M.T. Renal ageing. J. Pathol. 2007; 211: 198–205. doi: 10.1002/path.2111.
  15. Peters R. Ageing and the brain. Postgrad. Med. J. 2006; 82: 84–88. doi: 10.1136/pgmj.2005.036665.
  16. Farrall A.J., Wardlaw J.M. Blood-brain barrier: ageing and microvascular disease — systematic review and meta-analysis. Neurobiol. Aging. 2009; 30: 337–352. doi: 10.1016/j.neurobiolaging.2007.07.015.
  17. Strøm C., Rasmussen L.S., Sieber F.E. Should general anesthesia be avoided in the elderly? Anaesthesia. 2014; 69(Suppl. 1): 35–44. doi: 10.1111/anae.12493.
  18. Tsui B.C., Wagner A., Finucane B. Regional anesthesia in the elderly: a clinical guide. Drugs and Aging. 2004; 21: 895–910. PMID: 15554749.
  19. Merchant A.A., Roy C.N. Not so benign hematology: anemia of the elderly. British Journal of Hematology. 2012; 156: 173–185. doi: 10.1111/j.1365-2141.2011.08920.x.
  20. Panda A., Arjona A., Sapey E., et al. Human innate immunosenescence: causes and consequences for immunity in old age. Trends in Immunology. 2009; 30: 325–333. doi: 10.1016/j.it.2009.05.004.
  21. Schmucker D.L. Age-related changes in liver structure and function: Implications for disease? Exp. Gerontol. 2005; 40: 650–659. PMID: 16102930.
  22. Ward N.S. Compensatory mechanisms in the aging motor system. Ageing Res. Rev. 2006; 5(3): 239–254. doi: 10.1016/j.arr.2006.04.003.
  23. Chow W.B., Rosenthal R.A., Merkow R.P., et al. American College of Surgeons National Surgical Quality Improvement Program, American Geriatrics Society. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J. Am. Coll. Surg. 2012; 215(4): 453–466. doi: 10.1016/j.jamcollsurg.2012.06.017.
  24. Borson S., Scanlan J., Brush M., et al. The Mini-Cog: a cognitive ’vital signs’ measure for dementia screening in multi-lingual elderly. Int. J. Geriatr. Psychiatry. 2000; 15(11): 1021–1027. PMID: 11113982.
  25. Robinson T.N., Raeburn C.D., Tran Z.V., et al. Postoperative delirium in the elderly: risk factors and outcomes. Ann. Surg. 2009; 249:173–178.25.
  26. Steiner L.A. Postoperative delirium guidelines: The greater the obstacle, the more glory in overcoming it. European Journal of Anaesthesiology. 2017; 34(4): 189–191.
  27. American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement from the American Geriatrics Society. J. Am. Coll. Surg. 2015; 220(2): 136–148.e1. doi: 10.1016/j.jamcollsurg.2014.10.019.
  28. Li Y., Zhu S., Bao F., et al. The effects of age on the median effective concentration of ropivacaine for motor blockade after epidural anesthesia with ropivacaine. Anesthesia and Analgesia. 2006; 102(6): 1847–1850. doi: 10.1213/01.ane.0000215999.60513.da.
  29. Andersson C., Wissenberg M., Jørgensen M.E. Age-specific performance of the revised cardiac risk index for predicting cardiovascular risk in elective noncardiac surgery. Circ. Cardiovasc. Qual. Outcomes. 2015; 8(1): 103–108. doi: 10.1161/CIRCOUTCOMES.114.001298.
  30. Canet J., Sabaté S., Mazo V. Development and validation of a score to predict postoperative respiratory failure in a multicentre European cohort: A prospective, observational study. Eur. J. Anaesthesiol. 2015; 32(7): 458–470. doi: 10.1097/EJA.0000000000000223.
  31. Fried L.P., Ferrucci L., Darer J., et al. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J. Gerontol. A. Biol. Sci. Med. Sci. 2004; 59: 255–263. PMID: 15031310.
  32. Braga M., Ljungqvist O., Soeters P. ESPEN Guidelines on Parenteral Nutrition: Surgery Clinical Nutrition. 2009; 28: 378–386. doi:10.1016/j.clnu.2009.04.002.
  33. Robert L.M., Hanlon J.T., Hajjar E.R. Clinical Consequences of Polypharmacy in Elderly. Expert Opin. Drug. Saf. 2014; 13(1). doi: 10.1517/14740338.2013.827660.
  34. Eichhorn J.H., Cooper J.B., Cullen D.J., et al. Standards for patient monitoring during anesthesia at Harvard Medical School. JAMA. 1986; 29; 256(8): 1017–1020. PMID: 3735628.
  35. Walsh M., Devereaux P.J., Garg A.X, et al. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013; 119: 507–515. doi: 10.1097/ALN.0b013e3182a10e26.
  36. Marik P.E., Baram M., Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008; 134: 172–178. doi: 10.1378/chest.07–2331.
  37. Sieber F.E., Barnett S.R. Preventing postoperative complications in the elderly. Anesthesiology Clinics. 2011; 29: 83–97. doi: 10.1016/j.anclin.2010.11.011.
  38. Ekstein M., Gavish D., Ezri T., Weinbroum A.A. Monitored anesthesia care in the elderly: guidelines and recommendations. Drugs and Aging. 2008; 25: 477–500. PMID: 18540688.
  39. Sessler D.I., Sigl J.C., Kelley S.D, et al. Hospital stay and mortality are increased in patients having a ‘‘triple low’’ of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia. Anesthesiology. 2012; 116: 1195–1203. doi: 10.1097/ALN.0b013e31825683dc.
  40. Pietraszewski P., Gaszynski T. Residual neuromuscular block in elderly patients after surgical procedures under general anesthesia with rocuronium. Anesthesiology Intensive Therapy. 2013; 45: 77–81. doi: 10.5603/AIT.2013.0017.
  41. Reynolds L., Beckman J., Kurz A. Peri-operative complications of hypothermia. Best Practice and Research, Clinical Anesthesiology. 2008; 22: 645–657. doi 10.1016/j.bpa.2008.07.005.
  42. Schofield P. The assessment and management of perioperative pain in older people. Anesthesia. 2014; 69(Suppl. 1): 54–60. doi: 10.1111/anae.12520.
  43. Kruijt Spanjer M.R., Bakker N.A., Absalom A.R. Pharmacology in the elderly and newer anesthesia drugs. Best Practice and Research: Clinical Anesthesiology. 2011; 25: 355–365. doi: 10.1016/j.bpa.2011.06.002.
  44. Nickalls R.W., Mapleson W.W. Age-related iso-MAC charts for isoflurane, sevoflurane and desflurane in man. Br. J. Anaesth. 2003; 91: 170–174. PMID: 12878613.
  45. Schultz A., Grouven U., Zander I., et al. Age-related effects in the EEG during propofol anaesthesia. Acta Anaesthesiol. Scand. 2004; 48: 27–34. PMID: 14674970.
  46. Kazama T., Ikeda K., Morita K., et al. Comparison of the effect-site k(eO)s of propofol for blood pressure and EEG bispectral index in elderly and younger patients. Anesthesiology. 1999; 90: 1517–1527. PMID: 10360846.
  47. Jacobs J.R., Reves J.G., Marty J., et al. Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam. Anesth. Analg. 1995; 80:143–148. PMID: 7802272.
  48. Barr J., Fraser G.L., Puntillo K., et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit. Care Med. 2013; 41: 263–306. doi: 10.1097/CCM.0b013e3182783b72.
  49. Cepeda M.S., Farrar J.T., Baumgarten M., et al. Side effects of opioids during short-term administration: effect of age, gender, and race. Clin. Pharmacol. Ther. 2003; 74: 102–112. doi: 10.1016/S0009–9236(03)00152–8.
  50. Vuyk J., Lichtenbelt B.J., Olofsen E., et al. Mixed-effects modeling of the influence of midazolam on propofol pharmacokinetics. Anesth. Analg. 2009; 108: 1522–1530. doi: 10.1213/ane.0b013e31819e4058.
  51. Smith C., McEwan A.I., Jhaveri R., et al. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology. 1994; 81: 820–828. PMID: 7943832.
  52. Cressey D.M., Claydon P., Bhaskaran N.C, et al. Effect of midazolam pretreatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults. Anaesthesia. 2001; 56: 108–113. doi: 10.1046/j.1365-2044.2001.01789.x.
  53. Rooke G.A. Cardiovascular aging and anesthetic implications. J. Cardiothorac. Vasc. Anesth. 2003; 17: 512–523. doi: http://dx.doi.org/10.1016/S1053–0770(03)00161–7.
  54. Reich D.L., Hossain S., Krol M., et al. Predictors of hypotension after induction of general anesthesia. Anesth. Analg. 2005; 101: 622–628. doi: 10.1213/01.ANE.0000175214.38450.91.
  55. Cedborg A.I., Sundman E., Boden K., et al. Pharyngeal function and breathing pattern during partial neuromuscular block in the elderly: effects on airway protection. Anesthesiology. 2014; 120: 312–325. doi: 10.1097/ALN.0000000000000043.
  56. Ornstein E., Lien C.A., Matteo R.S., et al. Pharmacodynamics and pharmacokinetics of cisatracurium in geriatric surgical patients. Anesthesiology. 1996; 84: 520–525. PMID: 8659778.
  57. McDonagh D.L., Benedict P.E., Kovac A.L, et al. Efficacy, safety, and pharmacokinetics of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in elderly patients. Anesthesiology. 2011; 114(2): 318–329. doi: 10.1097/ALN.0b013e3182065c36.
  58. Soreide E., Eriksson L.I., Hirlekar G., et al. Preoperative fasting guidelines: an update(review). Acta Anaesthesiol. Scand. 2005; 49: 1041–1047. doi: 10.1111/j.1399-6576.2005.00781.x.
  59. Kristensen S.D., Knuuti J., Saraste A., et al. ESC/ESA Non-Cardiac Surgery Guidelines. Eur. Heart J. 2014; 35: 2383–2431. doi: 10.1093/eurheartj/ehu282.
  60. Gelman S. Is norepinephrine infusion during intraoperative period justified? Anesthesiology. 2014; 121(2): 433–434. doi: 10.1097/ALN.0000000000000322.
  61. Keats A.S. Anesthesia mortality-a new mechanism. Anesthesiology. 1988; 68(1): 2–4.
  62. Keats A.S. Anesthesia mortality in perspective. Anesth. Analg. 1990; 71(2): 113–119.
  63. Wu W.C., Smith T.S., Henderson W.G, et al. Operative blood loss, blood transfusion, and 30-day mortality in older patients after major noncardiac surgery. Annals of Surgery. 2010; 252: 11–7. doi: 10.1097/SLA.0b013e3181e3e43f.
  64. Partridge J., Harari D., Martin F., Dhesi J. The impact of preoperative comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery: a systematic review. Anesthesia. 2014; 69(Suppl. 1): 8–16. doi: 10.1111/anae.12494.
  65. Rosenfeld B.A., Beattie C., Christopherson R., et al. The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology. 1993; 79: 435–443. PMID: 8363067.
  66. Shir Y., Raja S.N., Frank S.M., Brendler C.B. Intraoperative blood loss during radical retropubic prostatectomy: Epidural versus general anesthesia. Urology. 1995; 45: 993–999. doi: http://dx.doi.org/10.1016/S0090–4295(99)80120–4.
  67. Memtsoudis S.G., Sun X., Chiu Y.L, et al. Perioperative comparative effectiveness of anesthetic technique in orthopedic patients. Anesthesiology. 2013; 118: 1046–1058. doi: 10.1097/ALN.0b013e318286061d.
  68. Hersh E., Moore P. Drug interactions in dentistry. J. Am. Dent. Assoc. 2004; 136: 298–311. doi: http://dx.doi.org/10.14219/jada.archive.2004.0178.
  69. Veering B.T., Burm A.G., Spierdijk J. Spinal anesthesia with hyperbaric bupivacaine: Effects of age on neural blockade and pharmacokinetics. Br. J. Anaesth. 1988; 60: 187–194. PMID: 3345280.
  70. Li C., Friedman B., Conwell Y., Fiscella K. Validity of the Patient Health Questionnaire 2 (PHQ-2) in identifying major depression in older people. J. Am. Geriatr. Soc. 2007; 55: 596–602. doi: 10.1111/j.1532-5415.2007.01103.x.
  71. Cheema S., Richardson J., McGurgan P. Factors affecting the spread of bupivacaine in the adult thoracic paravertebral space. Anaesthesia. 2003; 58(7): 684–687. PMID: 12886912.
  72. Hanks R.K., Pietrobon R., Nielsen K.C., et al. The effect of age on sciatic nerve block duration. Anesth. Analg. 2006; 2(2): 588–592.
  73. Paqueron X., Boccara G., Bendahou M., et al. Brachial plexus nerve block exhibits prolonged duration in the elderly. Anesthesiology. 2002; 97(5): 1245–1249. PMID: 12411811.
  74. Vaurio L.E., Sands L.P., Wang Y., et al. Postoperative delirium: the importance of pain and pain management. Anesthesia and Analgesia. 2006; 102: 1267–1273. doi: 10.1213/01.ane.0000199156.59226.af.
  75. Aubrun F. Management of postoperative analgesia in elderly patients. Regional Anesthesia and Pain Medicine. 2005; 30: 369–379. PMID: 16032589.
  76. Falzone E., Hoffmann C., Keita H. Postoperative analgesia in elderly patients. Drugs and Aging. 2013; 30: 81–90. doi: 10.1007/s40266-012-0047-7.
  77. Abdulla A., Adams N., Bone M., et al. Guidance on the management of pain in older people. Age and Ageing. 2013; 42(Suppl. 1): i1–57. doi: 10.1093/ageing/afs200.
  78. Cohen-Mansfield J., Lipson S. Pain in cognitively impaired nursing home residents: How well are physicians diagnosing it? J. Am. Geriatr. Soc. 2002; 50: 1039–1044. doi: 10.1046/j.1532-5415.2002.50258.x.
  79. Sauaia A., Min S.J., Leber C., et al. Postoperative pain management in elderly patients: correlation between adherence to treatment guidelines and patient satisfaction. Journal of the American Geriatrics Society. 2005; 53: 274–282. doi: 10.1111/j.1532-5415.2005.53114.x.
  80. Inouye S.K., van Dyck C.H., Alessi C.A., et al. Clarifying confusion: the Confusion Assessment Method. A new method for detection of delirium. Ann. Intern. Med. 1990; 113(12): 941–948. PMID: 2240918.
  81. Gaudreau J.D., Gagnon P., Harel F., et al. Fast, systematic, and continuous delirium assessment in hospitalized patients: the Nursing Delirium Screening Scale. J. Pain. Symptom Manage. 2005; 29: 368–375. doi: 10.1016/j.jpainsymman.2004.07.009.
  82. Dodds C., Foo I., Jones K., et al. Perioperative care of elderly patients — an urgent need for change: a consensus statement to provide guidance for specialist and non-specialist anaesthetists. Perioperative Medicine. 2013; 2: 6–11.doi: 10.1186/2047-0525-2-6.
  83. Clegg A., Young J.B. Which medications to avoid in people at risk of delirium: a systematic review. Age and Ageing. 2011; 40: 23–29. doi: 10.1093/ageing/afq140.
  84. Chew M.L., Mulsant B.H., Pollock B.G, et al. Anticholinergic activity of 107 medications commonly used by older adults. Journal of the American Geriatrics Society. 2008; 56:1333–1341. doi: 10.1111/j.1532-5415.2008.01737.x.
  85. Mohanty S., Rosenthal R.A., Russell M.M, Neuman M.D. Optimal Perioperative Management of the Geriatric Patient: A Best Practices Guideline from the American College of Surgeons NSQIP and the American Geriatrics Society. J. Am. Coll. Surg. 2016; 222(5): 930–947. doi: 10.1016/j.jamcollsurg.2015.12.026.
  86. Bekker A.Y., Weeks E.J. Cognitive function after anaesthesia in the elderly. Best Pract. Res. Clin. Anaesthesiol. 2003; 17: 259–272. PMID: 12817919.
  87. Silbert B., Evered L., Scott D.A. Cognitive decline in the elderly: is anaesthesia implicated? Best Pract. Res. Clin. Anaesthesiol. 2011; 25(3): 379–393. doi: 10.1016/j.bpa.2011.05.001.
  88. Mathew J.P., Mackensen G.B., Phillips-Bute B., et al. Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery. Stroke. 2009; 40: 880–887. doi: 10.1161/STROKEAHA.108.531236.
  89. Mathew J.P., White W.D., Schinderle D.B., et al. Neurologic Outcome Research Group of The Duke Heart C. Intraoperative magnesium administration does not improve neurocognitive function after cardiac surgery. Stroke. 2013; 44: 3407–3413. doi: 10.1161/STROKEAHA.113.002703.
  90. Hudetz J.A., Iqbal Z., Gandhi S.D., et al. Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery. Acta Anaesthesiol. Scand. 2009; 53: 864–872. doi: 10.1111/j.1399-6576.2009.01978.x.
  91. Ottens T.H., Dieleman J.M., Sauer A.M., et al. Group DEfCSS. Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial. Anesthesiology. 2014; 121:492–500. doi: 10.1097/ALN.0000000000000336.
  92. Hudetz J.A., Patterson K.M., Iqbal Z., et al. Remote Ischemic Preconditioning Prevents Deterioration of Short-Term Postoperative Cognitive Function After Cardiac Surgery Using Cardiopulmonary Bypass: Results of a Pilot Investigation. J. Cardiothorac. Vasc. Anesth. 2015; 29(2): 382–388. doi: 10.1053/j.jvca.2014.07.012.
  93. Ballard C., Jones E., Gauge N., et al. Optimised anaesthesia to reduce post operative cognitive decline (POCD) in older patients undergoing elective surgery, a randomised controlled trial. PLoS One. 2012; 7(6): e37410. doi: 10.1371/journal.pone.003741.
  94. Wheble G.A., Knight W.R., Khan O.A. Enteral vs total parenteral nutrition following major upper gastrointestinal surgery. International Journal of Surgery. 2012; 10: 194–197. doi:10.1016/j.ijsu.2012.02.015.
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