Analgosedaton for Endoscopic Procedure Endoscopic procedures in ESAU

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Analgo-sedaton for Endoscopic Procedure 연세대학교 의과대학 유영철

Analgo-sedaton for Endoscopic Procedure 연세대학교 의과대학 유영철

Endoscopic procedures in ESAU

Endoscopic procedures in ESAU

Endoscopic Submucosal Dissection (ESD) EMR ESD

Endoscopic Submucosal Dissection (ESD) EMR ESD

Endoscopic Retrograde Cholangiopancreatography (ERCP)

Endoscopic Retrograde Cholangiopancreatography (ERCP)

Percutaneous Transhepatic Choledochoscopy (PTCS)

Percutaneous Transhepatic Choledochoscopy (PTCS)

Esophagogastroduodenoscopy (EGD) – dilation/stent

Esophagogastroduodenoscopy (EGD) – dilation/stent

Pain during procedures • C fibers from viscera transmit poorly localized dull pain. •

Pain during procedures • C fibers from viscera transmit poorly localized dull pain. • Dull, aching pain experienced in the dermatome from which the affected organ receives innervations. • Painful stimuli originating in the liver, pancreas, biliary tree, stomach, or upper bowl are felt in the epigastrium.

Variable Outcomes IMIE (1035) CPIA (450) P-value En bloc resection 983 (95. 0) 449

Variable Outcomes IMIE (1035) CPIA (450) P-value En bloc resection 983 (95. 0) 449 (99. 8) < 0. 001 R 0 resection 914 (88. 3) 424 (94. 2) < 0. 001 57. 6 ± 41. 3 48. 2 ± 32. 5 < 0. 001 < 1 hour 633 (61. 2) 330 (73. 3) 1 to 2 hours 295 (28. 5) 101 (22. 4) ≥ 2 hours 107 (10. 3) 19 (4. 2) 33 (3. 2) 17 (3. 8) 0. 563 27 (2. 6) 8 (1. 8) 0. 332 14 (1. 5) 18 (4. 4) 0. 001 Procedure time Bleeding Complications Perforation Aspiration pneumonia < 0. 001

Sedation level

Sedation level

Sedation protocol during ESD • Propofol-Remifentanil ① ② Remifentanil • Bolus: 0. 3μg/kg •

Sedation protocol during ESD • Propofol-Remifentanil ① ② Remifentanil • Bolus: 0. 3μg/kg • Infusion: 6 μg/hr/kg • Additional dose: 0. 1μg/kg bolus followed by infusion 0. 6 μg/hr/kg↑ Propofol • Bolus: 0. 5 mg/kg • Infusion: 30 μg/min/kg • Additional dose: 0. 2 mg/kg bolus • Dexmedetomidine-Remifentanil ① ② ③ Remifentanil • Bolus: 0. 5μg/kg • Infusion: 6 μg/hr/kg • Additional dose: 0. 1μg/kg bolus followed by infusion 0. 6 μg/hr/kg ↑ Dexmedetomidine • Loading: 0. 5 μg/kg for 5 minutes • Infusion: 0. 5 μg/hr/kg Propofol • Bolus of 0. 2 mg/kg for additional sedation

Total 430 patients Moderate sedation: 218 patients Propofol + Remifentanil: 155 patients Dexmedetomidine +

Total 430 patients Moderate sedation: 218 patients Propofol + Remifentanil: 155 patients Dexmedetomidine + Remifentanil: 63 patients Minimal sedation: 212 patients Propofol + Remifentanil: 138 patients Dexmedetomidine + Remifentanil: 74 patients

Patient’s baseline characteristics   Moderate Light P value Age (yr) 62. 6 ± 9.

Patient’s baseline characteristics   Moderate Light P value Age (yr) 62. 6 ± 9. 5 62. 9 ± 10. 4 0. 740 Male 144 (64. 9) 127 (71. 8) 0. 161 Height (cm) 162 ± 8. 6 163. 2 ± 10. 2 0. 164 Weight (kg) 64. 1 ± 9. 8 65. 1 ± 10. 3 0. 278 I 95 (42. 8) 77 (43. 5) 0. 688 II 96 (43. 2) 80 (45. 2) III 27 (12. 2) 19 (10. 7) IV 4 (1. 8) 1 (0. 6) 75 (33. 8) 53 (30) 0. 414 4 (1. 8) 2 (1. 1) 0. 584 45. 5 ± 27. 1 49. 5 ± 32. 4 0. 184 ASA Snoring Hx, yes URI Sx, yes Sedation time (min)

Patient’s lesion baseline characteristics Histology Moderate Light Adenoma 111 (48. 5) 89 (50. 6)

Patient’s lesion baseline characteristics Histology Moderate Light Adenoma 111 (48. 5) 89 (50. 6) Carcinoma 118 (51. 5) 87 (49. 4) 149 (58) 131 (65. 5) 23 (8. 9) 16 (8. 0) Mixed 85 (33. 1) 53 (26. 5) Upper third 25 (9. 5) 20 (9. 9) Middle third 16 (6. 1) 20 (9. 9) Lower third 221 (84. 4) 163 (80. 3) 34. 8 ± 11. 3 34. 2 ± 13. 0 Elevated Macroscopic Flat or appearance depressed Location Specimen size (mm) P-value 0. 676 0. 251 0. 315 0. 645

Actual administrated doses Regimen Propofol Dex   Moderate Light P value Propofol infusion rate

Actual administrated doses Regimen Propofol Dex   Moderate Light P value Propofol infusion rate (μg/min/kg) 76. 15 ± 46. 1 22. 9 ± 23. 9 <0. 001 Remifentanil infusion rate (μg/hr/kg) 4. 75 ± 3. 03 6. 75 ± 3. 10 <0. 001 Dex infusion rate (μg/hr/kg) 1. 13 ± 0. 63 0. 62 ± 0. 55 <0. 001 Remifentanil infusion rate (μg/hr/kg) 6. 78 ± 2. 84 6. 63 ± 19. 5 0. 723 Cases receiving additional propofol 63/63 (100) 24/74 (32. 4) <0. 001 Additionally administered propofol doses (μg/min/kg) 29. 2 ± 20. 1 14. 2 ± 14. 7 0. 001  

Outcomes Moderate Light P value 21 (9. 5) 3 (1. 7) 0. 001 Hi

Outcomes Moderate Light P value 21 (9. 5) 3 (1. 7) 0. 001 Hi BP 3 (1. 4) 3 (1. 7) 0. 779 Low BP 2 (0. 9) 0 (0) 0. 206 Sedation failure 1 (0. 5) 0 (0) 0. 371 25. 5 ± 14. 4 19. 5 ± 4. 7 <0. 0001   Desaturation Recovery time (min)

Outcomes Moderate Light P-value En bloc 256 (97. 7) 201 (99. 0) 0. 283

Outcomes Moderate Light P-value En bloc 256 (97. 7) 201 (99. 0) 0. 283 Complete 250 (95. 4) 193 (95. 1) 0. 862 31. 5 ± 24. 9 34. 8 ± 27. 9 0. 199 Bleeding 10 (3. 8) 7 (3. 4) 0. 834 Perforation 3 (1. 4) 4 (2. 3) 0. 591 Pneumonia 15 (6. 8) 3 (1. 7) 0. 016 Resection Procedure time (min) Complications

Comparison between sedatives Moderate   Propofol Light P value Propofol Dex P value Desaturation

Comparison between sedatives Moderate   Propofol Light P value Propofol Dex P value Desaturation 20/158 (12. 7) 1/64 (1. 6) 0. 011 2/103 (1. 9) 1/74 (1. 4) 0. 779 Pneumonia 0. 323 2/103 (1. 9) 1/74 (1. 4) 0. 779   Dex 9/158 (5. 7) 6/64 (9. 4) Desaturation and pneumonia incidence Desaturation    P value   No Yes Pneumonia 16/375 (4. 3%) 2/24 (8. 3%) 0. 352

Dexmedetomidine vs. propofol

Dexmedetomidine vs. propofol

Patient’s baseline characteristics Dex (29) Propofol (30) p-value Age 62. 1 ± 10. 3

Patient’s baseline characteristics Dex (29) Propofol (30) p-value Age 62. 1 ± 10. 3 62. 9 ± 12. 3 0. 763 Sex 19 (65. 5) 22 (73. 3) 0. 514 Height 162. 2 ± 7. 7 164. 8 ± 5. 8 0. 274 Weight 62. 8 ± 8. 5 65. 1 ± 10. 276 9 (31) 7 (23. 3) 0. 506 I 19 (65. 5) 15 (50) 0. 39 II 9 (31) 12 (40) III 1 (3. 4) 3 (10) 42. 8 ± 26. 7 37. 6 ± 18. 5   Snoring history ASA classification Sedation time 0. 477

Patient’s lesion baseline characteristics     Lesion, n Histology Location   Propofol p-value 36

Patient’s lesion baseline characteristics     Lesion, n Histology Location   Propofol p-value 36 32 Adenoma 19 (52. 8) 17 (53. 1) Carcinoma 16 (44. 4) 14 (43. 8) 1 (2. 8) 1 (3. 1) Elevated 32 (88. 9) 27 (84. 4) Flat or depressed 4 (11. 1) 5 (15. 6) Upper third 3 (8. 3) 3 (9. 4) Middle third 8 (22. 2) 8 (25) Lower third 25 (69. 4) 21 (65. 6) Others Macroscopic appearance Dex 0. 995 0. 584 0. 945  

Sedation depth MOAA'S Dex Propofol 7 6 5 4 3 2 1 0 Baseline

Sedation depth MOAA'S Dex Propofol 7 6 5 4 3 2 1 0 Baseline Post. Ind 1 min Scope Insert Marking Epi Inj Resection Bleeding Control End

PGroupⅹTime=0. 005 Vital sign PGroupⅹTime=0. 355 Sp. O 2 HR Dex Propofol Dex 110

PGroupⅹTime=0. 005 Vital sign PGroupⅹTime=0. 355 Sp. O 2 HR Dex Propofol Dex 110 Propofol 100 99 90 98 80 70 97 60 on t ng C En d l ro n tio di PGroupⅹTime=0. 955 SBP Dex ec ee Bl Bl PGroupⅹTime=0. 365 R es nj Ep i. I ki ng M ar rt In se d op e Sc e ee di Po st ng In C Ba se lin En d l on t tio ec es R Sc Po ro n nj Ep i. I ki ng M ar In se op e d In st rt 1 m in e lin se Ba 1 m in 96 50 Propofol DBP Dex 170 160 150 140 130 120 110 100 Propofol 92 87 82 77 tr on C g di n ee Bl d En ol n tio es ec i. I nj R ar M Ep ki ng t er e. I ns op Sc nd Po st I Ba se lin e 1 m in 72 67 62 Baseline Post. Ind 1 min Scope Marking Epi Inj Resection Bleeding Insert Control End

Actual administrated doses   Dex infusion rate Propofol infusion rate Remifentanil infusion rate Dex

Actual administrated doses   Dex infusion rate Propofol infusion rate Remifentanil infusion rate Dex   μg/hr/kg Propofol p-value 0. 47 ± 0. 3 23. 8 ± 16. 5 μg/min/kg μg/hr/kg 5. 74 ± 1. 44 6. 34 ± 4. 02 0. 451 Additional propofol μg/min/kg 4. 65 ± 9. 25 1. 33 ± 4. 34 0. 081 Additional propofol incidence(%) 8 (27. 6) 3 (10) 0. 083

Outcomes Dex Propofol p-value  En-bloc resection 36 (100) 32 (100) 0. 999 Complete resection

Outcomes Dex Propofol p-value  En-bloc resection 36 (100) 32 (100) 0. 999 Complete resection 34 (94. 4) 32 (100) 0. 176 desaturation event 0 (0)   Aldrete score at end of procedure 9. 5 ± 0. 6 9. 4 ± 0. 6 0. 924 Time to MOAAS 5 (min) 0. 62 ± 1. 1 0. 46 ± 0. 77 0. 547 PACU duration (min) 21. 2 ± 6. 8 20. 4 ± 5. 8 0. 636

Patient's satisfaction Very good Bearable Unbearable 35 P = 0. 650 30 3 4

Patient's satisfaction Very good Bearable Unbearable 35 P = 0. 650 30 3 4 25 20 15 20 21 10 5 7 4 0 Dex Propofol Swallowing very easy MOAA'S 35 Dex 30 Propofol 25 7 6 5 4 3 2 1 0 20 15 st In d 7 1 difficult 1 12 14 17 d En 1 m Sc in op e. I ns er t M ar ki ng Ep i. I nj R es Bl ec ee tio di n ng C on tr. . . lin e se Po Ba slight difficult P = 0. 01 10 5 easy 7 0 Dex Propofol

Motility Grading no mild 35 30 1 moderate Motility Grading vigorous 35 P =

Motility Grading no mild 35 30 1 moderate Motility Grading vigorous 35 P = 0. 101 7 25 20 1 30 7 25 6 20 15 15 21 10 16 5 0 0 Propofol very easy P = 0. 216 30 25 slight difficult 8 difficult 2 2 21 22 Propofol 17 difficult P = 0. 042 4 25 20 29 26 10 5 0 0 Propofol easy 30 5 Dex 28 35 15 15 10 8 Easy For Procedure 9 20 P =0. 013 Dex Easy For Procedure 35 1 moderate to vigorous 10 5 Dex minimal Dex Propofol

Sedation protocol during ERCP, PTCS, and EGD dilation/stent 1. Fentanyl – Bolus: 1μg/kg –

Sedation protocol during ERCP, PTCS, and EGD dilation/stent 1. Fentanyl – Bolus: 1μg/kg – Additional dose: 0. 5μg/kg 2. Propofol – Bolus: 0. 5 mg/kg – Infusion: 60μg/min/kg – Additional dose: 10 mg bolus

Patient’s baseline characteristics   Age (yr) P (499) PF (311) P value 61. 4

Patient’s baseline characteristics   Age (yr) P (499) PF (311) P value 61. 4 ± 14. 7 61 ± 14. 5 0. 682 315 (63. 1) 203 (65. 3) 0. 536 163. 2 ± 8. 5 163. 5 ± 8. 4 0. 627 59 ± 10. 6 59. 8 ± 12. 5 0. 330 I 154 (30. 9) 78 (25. 1) II 192 (38. 5) 119 (38. 3) III 137 (27. 5) 101 (32. 5) IV 16 (3. 2) 13 (4. 2) 73 (14. 6) 61 (19. 6) 0. 063 1 (0. 2) 3 (1) 0. 131 PB-Dx 79 (15. 8) 57 (18. 3) PB-Stone 140 (28. 1) 80 (25. 7) PB-D/S 193 (38. 7) 105 (33. 8) HV -D/S 87 (17. 4) 61 (22. 2)   Male Height (cm) Weight (kg) ASA Snoring Hx URI Sx Procedure 0. 222 0. 204

Actual administrated doses     Propofol infusion PF PB-stone PB-D/S HV-D/S P value 102.

Actual administrated doses     Propofol infusion PF PB-stone PB-D/S HV-D/S P value 102. 5 ± 52. 6 107. 7 ± 62. 8 102. 1 ± 69. 7 123. 1 ± 60. 2 0. 135 3. 7 ± 1. 5 4. 3 ± 2. 5 4. 2 ± 2. 2 5. 5 ± 3. 7 < 0. 001 181. 3 ± 73. 8 195. 5 ± 93. 8 186. 3 ± 13. 2 195. 3 ± 66. 4 0. 428 (μg/min/kg) Fentanyl (μg/hr/kg) P PB-Dx Propofol infusion (μg/min/kg)

Outcomes P (499) PF (311) P value 188. 8 ± 82. 3 107. 9±

Outcomes P (499) PF (311) P value 188. 8 ± 82. 3 107. 9± 62. 6 <0. 001 28. 7 ± 17 27. 5 ± 14. 5 0. 302 Procedure failure 37 (7. 4) 17 (5. 5) 0. 280 Respiratory events 30 (6) 4 (1. 3) 0. 001 Pneumonia 1 (0. 2) 0 (0) 0. 430 Hi BP 17 (3. 2) 4 (1. 3) 0. 065 Low BP 6 (1. 1) 0 (0) 0. 052 Procedure interruption 10 (2) 1 (0. 3) 0. 044 19. 4 ± 5 20. 1 ± 5. 4 0. 055   Propofol infusion rate (μg/min/kg) Procedure time (min) Recovery time (min)

Risk factors for desaturation OR 95% CI P value Male 1. 570 0. 606

Risk factors for desaturation OR 95% CI P value Male 1. 570 0. 606 -4. 066 0. 353 Age (yr) 1. 010 0. 975 -1. 041 0. 542 Height (cm) 0. 991 0. 972 -1. 011 0. 385 Weight (kg) 0. 978 0. 933 -1. 026 0. 370 ASA class 1. 133 0. 654 -1. 962 0. 656 Snoring, yes 36. 912 14. 012 -97. 236 < 0. 001 Regimen (PF) 0. 224 0. 069 -0. 724 0. 012 Emergency, yes 1. 606 0. 397 -6. 493 0. 506 Propofol infusion rate (μg) 1. 007 1. 003 -1. 011 0. 001 PB-Stone 2. 904 0. 727 -11. 599 0. 131 PB-D/S 1. 867 0. 469 -7. 431 0. 376 HV-D/S 1. 337 0. 222 -8. 042 0. 751   1. 019 0. 995 -1. 044 0. 117   Procedure time (min)  

Take home messages • Therapeutic GI endoscopic procedures are associated with significant pain and

Take home messages • Therapeutic GI endoscopic procedures are associated with significant pain and discomfort. • Unnecessary over-sedation and its side-effects can be avoided by administrating a sufficient amount of analgesics.