Failed epidural: Causes and management

British Journal of Anaesthesia

Volumn 109, Issue 2, 2012, Pages 144-154

  Hermanides, J ^a   Hollmann, M W ^a   Stevens, M F ^a   Lirk, P ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

anaesthetics local; analgesic techniques; epidural; extradural

Indexed keywords

ADRENALIN; BUPIVACAINE; LEVOBUPIVACAINE; LIDOCAINE; OPIATE; ROPIVACAINE;

ANTINOCICEPTION; BACTERIAL COLONIZATION; CATHETER INFECTION; CATHETER OCCLUSION; EPIDURAL ANESTHESIA; EPIDURAL CATHETER; EPIDURAL SPACE; HUMAN; META ANALYSIS (TOPIC); MICRODIALYSIS; PATIENT CONTROLLED ANALGESIA; PATIENT POSITIONING; POSTOPERATIVE NAUSEA AND VOMITING; PRIORITY JOURNAL; PUNCTURE; REVIEW;

EID: 84863943379     PISSN: 00070912     EISSN: 14716771     Source Type: Journal    
DOI: 10.1093/bja/aes214     Document Type: Review

References (102)

1. Ready LB. Acute pain: lessons learned from 25,000 patients. Reg Anesth Pain Med 1999; 24: 499-505
2. Pan PH, Bogard TD, Owen MD. Incidence and characteristics of failures in obstetric neuraxial analgesia and anesthesia: a retrospective analysis of 19,259 deliveries. Int J Obstet Anesth 2004; 13: 227-33 (Pubitemid 39349703)
3. Motamed C, Farhat F, Remerand F, Stephanazzi J, Laplanche A, Jayr C. An analysis of postoperative epidural analgesia failure by computed tomography epidurography. Anesth Analg 2006; 103: 1026-32 (Pubitemid 44576716)
4. Collier CB. Why obstetric epidurals fail: a study of epidurograms. Int J Obstet Anesth 1996; 5: 19-31 (Pubitemid 26026774)
5. Hamilton CL, Riley ET, Cohen SE. Changes in the position of epidural catheters associated with patient movement. Anesthesiology 1997; 86: 778-84; discussion 29A (Pubitemid 27174717)
6. Eide PK, Sorteberg W. Simultaneous measurements of intracranial pressure parameters in the epidural space and in brain parenchyma in patients with hydrocephalus. J Neurosurg 2010; 113: 1317-25
7. Hogan QH. Epidural anatomy: new observations. Can J Anaesth 1998; 45: R40-8 (Pubitemid 28401629)
8. Lee RA, van Zundert AA, Botha CP, et al. The anatomy of the thoracic spinal canal in different postures: a magnetic resonance imaging investigation. Reg Anesth Pain Med 2010; 35: 364-9
9. Takiguchi T, Yamaguchi S, Tezuka M, Kitajima T. Measurement of shift of the cauda equina in the subarachnoid space by changing position. Reg Anesth Pain Med 2009; 34: 326-9
10. Nishi M, Usukaura A, Kidani Y, Tsubokawa T, Yamamoto K. Which is a better position for insertion of a high thoracic epidural catheter: sitting or lateral decubitus? J Cardiothorac Vasc Anesth 2006; 20: 656-8 (Pubitemid 44470830)
11. Rucklidge MW, Paech MJ, Yentis SM. A comparison of the lateral, Oxford and sitting positions for performing combined spinal- epidural anaesthesia for elective Caesarean section. Anaesthesia 2005; 60: 535-40 (Pubitemid 40762559)
12. Coppejans HC, Hendrickx E, Goossens J, Vercauteren MP. The sitting versus right lateral position during combined spinal- epidural anesthesia for cesarean delivery: block characteristics and severity of hypotension. Anesth Analg 2006; 102: 243-7 (Pubitemid 43038315)
13. Hamza J, Smida M, Benhamou D, Cohen SE. Parturient's posture during epidural puncture affects the distance from skin to epidural space. J Clin Anesth 1995; 7: 1-4
14. Stone PA, Kilpatrick AW, Thorburn J. Posture and epidural catheter insertion. The relationship between skill, experience and maternal posture on the outcome of epidural catheter insertion. Anaesthesia 1990; 45: 920-3
15. Bahar M, Chanimov M, Cohen ML, et al. The lateral recumbent head-down position decreases the incidence of epidural venous puncture during catheter insertion in obese parturients. Can J Anaesth 2004; 51: 577-80 (Pubitemid 38867924)
16. Lirk P, Messner H, Deibl M, et al. Accuracy in estimating the correct intervertebral space level during lumbar, thoracic and cervical epidural anaesthesia. Acta Anaesthesiol Scand 2004; 48: 347-9 (Pubitemid 38295348)
17. Hehre FW, Sayig JM, Lowman RM. Etiologic aspects of failure of continuous lumbar peridural anesthesia. Anesth Analg 1960; 39: 511-7
18. Blomberg RG. Technical advantages of the paramedian approach for lumbar epidural puncture and catheter introduction. A study using epiduroscopy in autopsy subjects. Anaesthesia 1988; 43: 837-43
19. Leeda M, Stienstra R, Arbous MS, et al. Lumbar epidural catheter insertion: the midline vs. the paramedian approach. Eur J Anaesthesiol 2005; 22: 839-42 (Pubitemid 41725977)
20. Griffin RM, Scott RP. Forum. A comparison between the midline and paramedian approaches to the extradural space. Anaesthesia 1984; 39: 584-6 (Pubitemid 15092414)
21. Podder S, Kumar N, Yaddanapudi LN, Chari P. Paramedian lumbar epidural catheter insertion with patients in the sitting position is equally successful in the flexed and unflexed spine. Anesth Analg 2004; 99: 1829-32 (Pubitemid 39551930)
22. Rigg JR, Jamrozik K, Myles PS, et al. Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet 2002; 359: 1276-82 (Pubitemid 34310632)
23. Wantman A, Hancox N, Howell PR. Techniques for identifying the epidural space: a survey of practice amongst anaesthetists in the UK. Anaesthesia 2006; 61: 370-5 (Pubitemid 43740624)
24. Schier R, Guerra D, Aguilar J, et al. Epidural space identification: a meta-analysis of complications after air versus liquid as the medium for loss of resistance. Anesth Analg 2009; 109: 2012-21
25. Grondin LS, Nelson K, Ross V, Aponte O, Lee S, Pan PH. Success of spinal and epidural labor analgesia: comparison of loss of resistance technique using air versus saline in combined spinal-epidural labor analgesia technique. Anesthesiology 2009; 111: 165-72
26. Segal N, Puterman M, Rotem E, et al. A prospective randomized double-blind trial of fibrin glue for reducing pain and bleeding after tonsillectomy. Int J Pediatr Otorhinolaryngol 2008; 72: 469-73
27. Moon JY, Lee PB, Nahm FS, Kim YC, Choi JB. Cervical epidural pressure measurement: comparison in the prone and sitting positions. Anesthesiology 2010; 113: 666-71
28. Hoffmann VL, Vercauteren MP, Vreugde JP, Hans GH, Coppejans HC, Adriaensen HA. Posterior epidural space depth: safety of the loss of resistance and hanging drop techniques. Br J Anaesth 1999; 83: 807-9 (Pubitemid 29502065)
29. Lirk P, Kolbitsch C, Putz G, et al. Cervical and high thoracic ligamentum flavum frequently fails to fuse in the midline. Anesthesiology 2003; 99: 1387-90 (Pubitemid 37475186)
30. Grau T, Bartusseck E, Conradi R, Martin E, Motsch J. Ultrasound imaging improves learning curves in obstetric epidural anesthesia: a preliminary study. Can J Anaesth 2003; 50: 1047-50 (Pubitemid 38139569)
31. Balki M, Lee Y, Halpern S, Carvalho JC. Ultrasound imaging of the lumbar spine in the transverse plane: the correlation between estimated and actual depth to the epidural space in obese parturients. Anesth Analg 2009; 108: 1876-81
32. Marhofer P, Bosenberg A, Sitzwohl C, Willschke H, Wanzel O, Kapral S. Pilot study of neuraxial imaging by ultrasound in infants and children. Paediatr Anaesth 2005; 15: 671-6 (Pubitemid 41623799)
33. Willschke H, Marhofer P, Bosenberg A, et al. Epidural catheter placement in children: comparing a novel approach using ultrasound guidance and a standard loss-of-resistance technique. Br J Anaesth 2006; 97: 200-7 (Pubitemid 44295706)
34. Lundblad M, Lonnqvist PA, Eksborg S, Marhofer P. Segmental distribution of high-volume caudal anesthesia in neonates, infants, and toddlers as assessed by ultrasonography. Paediatr Anaesth 2011; 21: 121-7
35. Konigsrainer I, Bredanger S, Drewel-Frohnmeyer R, et al. Audit of motor weakness and premature catheter dislodgement after epidural analgesia in major abdominal surgery. Anaesthesia 2009; 64: 27-31
36. Bougher RJ, Corbett AR, Ramage DT. The effect of tunnelling on epidural catheter migration. Anaesthesia 1996; 51: 191-4 (Pubitemid 26113378)
37. Burstal R, Wegener F, Hayes C, Lantry G. Subcutaneous tunnelling of epidural catheters for postoperative analgesia to prevent accidental dislodgement: a randomized controlled trial. Anaesth Intensive Care 1998; 26: 147-51 (Pubitemid 28172035)
38. Chadwick VL, Jones M, Poulton B, Fleming BG. Epidural catheter migration: a comparison of tunnelling against a new technique of catheter fixation. Anaesth Intensive Care 2003; 31: 518-22 (Pubitemid 37265246)
39. Tripathi M, Pandey M. Epidural catheter fixation: subcutaneous tunnelling with a loop to prevent displacement. Anaesthesia 2000; 55: 1113-6
40. Bubeck J, Boos K, Krause H, Thies KC. Subcutaneous tunneling of caudal catheters reduces the rate of bacterial colonization to that of lumbar epidural catheters. Anesth Analg 2004; 99: 689-93 (Pubitemid 39100354)
41. Clark MX, O'Hare K, Gorringe J, Oh T. The effect of the Lockit epidural catheter clamp on epidural migration: a controlled trial. Anaesthesia 2001; 56: 865-70 (Pubitemid 32821270)
42. Guay J. The epidural test dose: a review. Anesth Analg 2006; 102: 921-9
43. Asato F, Goto F. Radiographic findings of unilateral epidural block. Anesth Analg 1996; 83: 519-22 (Pubitemid 26296358)
44. Segal S, Eappen S, Datta S. Superiority of multi-orifice over single-orifice epidural catheters for labor analgesia and cesarean delivery. J Clin Anesth 1997; 9: 109-12 (Pubitemid 27125914)
45. Goebel A, Ovenden K, Glynn C. Incorrect distance markings on an epidural catheter. Br J Anaesth 2003; 91: 610 (Pubitemid 37258617)
46. Lin CC. Air-locked epidural filter. Anesthesiology 2003; 99: 515
47. Lim YJ, Bahk JH, Ahn WS, Lee SC. Coiling of lumbar epidural catheters. Acta Anaesthesiol Scand 2002; 46: 603-6 (Pubitemid 34547958)
48. Brichant JF, Bonhomme V, Hans P. On knots in epidural catheters: a case report and a review of the literature. Int J Obstet Anesth 2006; 15: 159-62
49. Dernedde M, Stadler M, Bardiau F, Boogaerts J. Comparison of different concentrations of levobupivacaine for post-operative epidural analgesia. Acta Anaesthesiol Scand 2003; 47: 884-90 (Pubitemid 36898037)
50. Dernedde M, Stadler M, Bardiau F, Boogaerts JG. Continuous epidural infusion of large concentration/small volume versus small concentration/large volume of levobupivacaine for postoperative analgesia. Anesth Analg 2003; 96: 796-801 (Pubitemid 36245572)
51. Kampe S, Diefenbach C, Kanis B, Auweiler M, Kiencke P, Cranfield K. Epidural combination of ropivacaine with sufentanil for postoperative analgesia after total knee replacement: a pilot study. Eur J Anaesthesiol 2002; 19: 666-71 (Pubitemid 35000838)
52. Danelli G, Venuti FS, Zasa M, et al. Continuous lumbar epidural infusion of levobupivacaine: effects of small- or large-volume regimen of infusion. Acta Anaesthesiol Scand 2009; 53: 483-8
53. Dernedde M, Stadler M, Taviaux N, Boogaerts JG. Postoperative patient-controlled thoracic epidural analgesia: importance of dose compared to volume or concentration. Anaesth Intensive Care 2008; 36: 814-21
54. Dernedde M, Stadler M, Bardiau F, Boogaerts JG. Comparison of 2 concentrations of levobupivacaine in postoperative patientcontrolled epidural analgesia. J Clin Anesth 2005; 17: 531-6 (Pubitemid 41627409)
55. Senard M, Joris JL, Ledoux D, Toussaint PJ, Lahaye-Goffart B, Lamy ML. A comparison of 0.1% and 0.2% ropivacaine and bupivacaine combined with morphine for postoperative patientcontrolled epidural analgesia after major abdominal surgery. Anesth Analg 2002; 95: 444-9 (Pubitemid 34793118)
56. Liu SS, Moore JM, Luo AM, Trautman WJ, Carpenter RL. Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia. Anesthesiology 1999; 90: 727-33 (Pubitemid 29113692)
57. Snijdelaar DG, Hasenbos MA, van Egmond J, Wolff AP, Liem TH. High thoracic epidural sufentanil with bupivacaine: continuous infusion of high volume versus low volume. Anesth Analg 1994; 78: 490-4 (Pubitemid 24079372)
58. Christiaens F, Verborgh C, Dierick A, Camu F. Effects of diluent volume of a single dose of epidural bupivacaine in parturients during the first stage of labor. Reg Anesth Pain Med 1998; 23: 134-41 (Pubitemid 28249325)
59. Sakura S, Sumi M, Kushizaki H, Saito Y, Kosaka Y. Concentration of lidocaine affects intensity of sensory block during lumbar epidural anesthesia. Anesth Analg 1999; 88: 123-7 (Pubitemid 29025159)
60. Salinas F. Pharmacology of drugs used for spinal and epidural anesthesia and analgesia. In: Wong CA, ed. Spinal and Epidural Anesthesia. New York: McGraw-Hill, 2007
61. Brennum J, Nielsen PT, Horn A, Arendt-Nielsen L, Secher NH. Quantitative sensory examination of epidural anaesthesia and analgesia in man; dose-response effect of bupivacaine. Pain 1994; 56: 315-26 (Pubitemid 24087982)
62. Brennum J, Petersen KL, Horn A, Arendt-Nielsen L, Secher NH, Jensen TS. Quantitative sensory examination of epidural anaesthesia and analgesia in man: combination of morphine and bupivacaine. Pain 1994; 56: 327-37 (Pubitemid 24087983)
63. COMET study group. Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet 2001; 358: 19-23
64. Olofsson C, Ekblom A, Ekman-Ordeberg G, Irestedt L. Obstetric outcome following epidural analgesia with bupivacaine- adrenaline 0.25% or bupivacaine 0.125% with sufentanil-a prospective randomized controlled study in 1000 parturients. Acta Anaesthesiol Scand 1998; 42: 284-92 (Pubitemid 28131376)
65. Meister GC, D'Angelo R, Owen M, Nelson KE, Gaver R. A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125% bupivacaine with fentanyl during labor. Anesth Analg 2000; 90: 632-7 (Pubitemid 30117524)
66. Casati A, Putzu M. Bupivacaine, levobupivacaine and ropivacaine: are they clinically different? Best Pract Res Clin Anaesthesiol 2005; 19: 247-68 (Pubitemid 40585280)
67. Guinet P, Estebe JP, Ratajczak-Enselme M, et al. Electrocardiographic and hemodynamic effects of intravenous infusion of bupivacaine, ropivacaine, levobupivacaine, and lidocaine in anesthetized ewes. Reg Anesth Pain Med 2009; 34: 17-23
68. Zausig YA, Zink W, Keil M, et al. Lipid emulsion improves recovery from bupivacaine-induced cardiac arrest, but not from ropivacaine- or mepivacaine-induced cardiac arrest. Anesth Analg 2009; 109: 1323-6
69. Wheatley RG, Schug SA, Watson D. Safety and efficacy of postoperative epidural analgesia. Br J Anaesth 2001; 87: 47-61 (Pubitemid 32631675)
70. Curatolo M, Petersen-Felix S, Scaramozzino P, Zbinden AM. Epidural fentanyl, adrenaline and clonidine as adjuvants to local anaesthetics for surgical analgesia: meta-analyses of analgesia and side-effects. Acta Anaesthesiol Scand 1998; 42: 910-20 (Pubitemid 28416860)
71. Boulier V, Gomis P, Lautner C, Visseaux H, Palot M, Malinovsky JM. Minimum local analgesic concentrations of ropivacaine and levobupivacaine with sufentanil for epidural analgesia in labour. Int J Obstet Anesth 2009; 18: 226-30
72. Whiteside R, Jones D, Bignell S, Lang C, Lo SK. Epidural ropivacaine with fentanyl following major gynaecological surgery: the effect of volume and concentration on pain relief and motor impairment. Br J Anaesth 2000; 84: 720-4 (Pubitemid 30312039)
73. Hong JY, Yang SC, Yi J, Kil HK. Epidural ropivacaine and sufentanil and the perioperative stress response after a radical retropubic prostatectomy. Acta Anaesthesiol Scand 2011; 55: 282-9
74. Bernards CM, Shen DD, Sterling ES, et al. Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids. Anesthesiology 2003; 99: 455-65 (Pubitemid 36909573)
75. Negre I, Gueneron JP, Jamali SJ, Monin S, Ecoffey C. Preoperative analgesia with epidural morphine. Anesth Analg 1994; 79: 298-302 (Pubitemid 24240868)
76. Ginosar Y, Columb MO, Cohen SE, et al. The site of action of epidural fentanyl infusions in the presence of local anesthetics: a minimum local analgesic concentration infusion study in nulliparous labor. Anesth Analg 2003; 97: 1439-45 (Pubitemid 37310144)
77. Guinard JP, Mavrocordatos P, Chiolero R, Carpenter RL. A randomized comparison of intravenous versus lumbar and thoracic epidural fentanyl for analgesia after thoracotomy. Anesthesiology 1992; 77: 1108-15 (Pubitemid 23001121)
78. George MJ. The site of action of epidurally administered opioids and its relevance to postoperative pain management. Anaesthesia 2006; 61: 659-64 (Pubitemid 43871474)
79. Beilin Y, Bodian CA, Weiser J, et al. Effect of labor epidural analgesia with and without fentanyl on infant breast-feeding: a prospective, randomized, double-blind study. Anesthesiology 2005; 103: 1211-7 (Pubitemid 41692505)
80. Wilson MJ, MacArthur C, Cooper GM, Bick D, Moore PA, Shennan A. Epidural analgesia and breastfeeding: a randomised controlled trial of epidural techniques with and without fentanyl and a non-epidural comparison group. Anaesthesia 2010; 65: 145-53
81. Carvalho B. Respiratory depression after neuraxial opioids in the obstetric setting. Anesth Analg 2008; 107: 956-61
82. Polley LS, Columb MO, Naughton NN, Wagner DS, van de Ven CJ. Effect of epidural epinephrine on the minimum local analgesic concentration of epidural bupivacaine in labor. Anesthesiology 2002; 96: 1123-8 (Pubitemid 34462573)
83. Niemi G, Breivik H. Epinephrine markedly improves thoracic epidural analgesia produced by a small-dose infusion of ropivacaine, fentanyl, and epinephrine after major thoracic or abdominal surgery: a randomized, double-blinded crossover study with and without epinephrine. Anesth Analg 2002; 94: 1598-605 (Pubitemid 34556653)
84. Thomas JM, Schug SA. Recent advances in the pharmacokinetics of local anaesthetics. Long-acting amide enantiomers and continuous infusions. Clin Pharmacokinet 1999; 36: 67-83 (Pubitemid 29056001)
85. Lee BB, Ngan Kee WD, Plummer JL, Karmakar MK, Wong AS. The effect of the addition of epinephrine on early systemic absorption of epidural ropivacaine in humans. Anesth Analg 2002; 95: 1402-7 (Pubitemid 35239147)
86. Cohen S, Amar D, Pantuck CB, et al. Epidural patient-controlled analgesia after cesarean section: buprenorphine-0.015% bupivacaine with epinephrine versus fentanyl-0.015% bupivacaine with and without epinephrine. Anesth Analg 1992; 74: 226-30
87. Niemi G. Advantages and disadvantages of adrenaline in regional anaesthesia. Best Pract Res Clin Anaesthesiol 2005; 19: 229-45 (Pubitemid 40585279)
88. Niemi G, Breivik H. The minimally effective concentration of adrenaline in a low-concentration thoracic epidural analgesic infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomized, double-blind, dose-finding study. Acta Anaesthesiol Scand 2003; 47: 439-50 (Pubitemid 36438861)
89. Soetens FM, Soetens MA, Vercauteren MP. Levobupivacaine- sufentanil with or without epinephrine during epidural labor analgesia. Anesth Analg 2006; 103: 182-6 (Pubitemid 44036056)
90. Neal JM. Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: neurotoxicity and neural blood flow. Reg Anesth Pain Med 2003; 28: 124-34 (Pubitemid 36397788)
91. van der Vyver M, Halpern S, Joseph G. Patient-controlled epidural analgesia versus continuous infusion for labour analgesia: a meta-analysis. Br J Anaesth 2002; 89: 459-65 (Pubitemid 34993977)
92. Chang KY, Dai CY, Ger LP, et al. Determinants of patientcontrolled epidural analgesia requirements: a prospective analysis of 1753 patients. Clin J Pain 2006; 22: 751-6
93. Missant C, Teunkenst A, Vandermeersch E, Van de Velde M. Patient-controlled epidural analgesia following combined spinal-epidural analgesia in labour: the effects of adding a continuous epidural infusion. Anaesth Intensive Care 2005; 33: 452-6 (Pubitemid 41131581)
94. Vallejo MC, Ramesh V, Phelps AL, Sah N. Epidural labor analgesia: continuous infusion versus patient-controlled epidural analgesia with background infusion versus without a background infusion. J Pain 2007; 8: 970-5 (Pubitemid 350161440)
95. Lim Y, Ocampo CE, Supandji M, Teoh WH, Sia AT. A randomized controlled trial of three patient-controlled epidural analgesia regimens for labor. Anesth Analg 2008; 107: 1968-72
96. Wong CA, Ratliff JT, Sullivan JT, Scavone BM, Toledo P, McCarthy RJ. A randomized comparison of programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg 2006; 102: 904-9
97. Eappen S, Blinn A, Segal S. Incidence of epidural catheter replacement in parturients: a retrospective chart review. Int J Obstet Anesth 1998; 7: 220-5 (Pubitemid 28502255)
98. McLeod G, Davies H, Munnoch N, Bannister J, MacRae W. Postoperative pain relief using thoracic epidural analgesia: outstanding success and disappointing failures. Anaesthesia 2001; 56: 75-81 (Pubitemid 32111878)
99. Pratt WB, Steinbrook RA, Maithel SK, Vanounou T, Callery MP, Vollmer CM Jr. Epidural analgesia for pancreatoduodenectomy: a critical appraisal. J Gastrointest Surg 2008; 12: 1207-20
100. Kinsella SM. A prospective audit of regional anaesthesia failure in 5080 Caesarean sections. Anaesthesia 2008; 63: 822-32 (Pubitemid 351951794)
101. Laveaux MM, Hasenbos MA, Harbers JB, Liem T. Thoracic epidural bupivacaine plus sufentanil: high concentration/low volume versus low concentration/high volume. Reg Anesth 1993; 18: 39-43 (Pubitemid 23088667)
102. Sitsen E, van Poorten F, van Alphen W, Rose L, Dahan A, Stienstra R. Postoperative epidural analgesia after total knee arthroplasty with sufentanil 1 mg/ml combined with ropivacaine 0.2%, ropivacaine 0.125%, or levobupivacaine 0.125%: a randomized, double-blind comparison. Reg Anesth Pain Med 2007; 32: 475-80 (Pubitemid 350116651)