Sedation in the Intensive Care Unit: a general overview

1. Sedation in the Intensive Care Unit: a general overview 台中榮民總醫院 內科部 加護中心 李博仁醫師

3. Current Forces in Critical Care • Institute of Medicine criteria for quality: • Patient-centered: relevant outcomes define right care • Effective: the right care • Safe: the right care all the time • Timely: the right care at the right time • Efficient: the right care and only the right care • Equitable: the right care for everyone

4. 身體約束之合併症 • 生理：約束超過4天感染率增加 皮膚撕裂傷、神經受損 肌力下降、血循減慢、便秘、失禁、 呼吸功能衰退甚至窒息或猝死 • 心理：生氣、害怕 自主性及尊嚴受威脅— 惡夢 • 社會：社交隔離 反應遲頓、社會功能變差 (David et al,2003）

5. Death Caused by Physical Restrains Steven H.(1992) The Gerontologist

6. 非計畫性拔管的盛行率8-13% • 發生自拔管患者86.7%已接受約束 (游顯妹 ,2003) • 非計畫性拔管的盛行率2-17% • 身體約束在管路自拔的預防上是失敗的 (Gerald,2003) • 美國食品藥物管理局(Food and Drug Administration)表示每年有超過100位死亡或受傷的案例是因為照護人員不當使用約束所造成 (Lusis, 2000)

7. 美國健康照護組織評鑑聯委會 約束：指限制個人在其環境中的活動自由或接近他們自己身體自由度的過程。〈醫策會〉 醫院評鑑-約束醫囑及臨床照顧指引 身體約束：使用任何器具、材料或設備，將身體固定，達到約束目的的方式。 化學性約束：使用精神用藥，限制非預期行為的產生，達到約束目的的方式。

8. 磁扣式腰腹約束衣

9. 加強型手套式〈乒乓球〉約束帶 -台中榮總創

10. 魚眼約束帶-台中榮總創

11. 約束之執行過程 1.向病患或家屬詳細解釋約束的目的。 2.選用合適的約束用物。 （1）約束用物：如手腕或腳踝約束帶、約束衣、手套 式手腕約束帶等。 （2）約束時應避免壓迫動靜脈廔管、點滴注射處及其他引流管。 3.將叫人鈴放置在病患可觸及之處。 4.躁動患者每15分鐘應觀察約束部位血液循環情形、皮膚完整性、關節活動狀況及身體擺位，評估有無合併症產生；一般患者至少每4小時評估一次並記錄。 5.每2小時應解開約束帶一次，給予肢體活動或皮膚護理，協助翻身或坐起。 6.每8小時重新評估約束的必要性 。 7.當約束的病患出現作嘔、不安等情形時，應立刻檢視病患有無其他需求或潛在危險。 (Gerald,2003)

12. 實施原則 1.持續評估病患狀況，儘可能運用身體約束替代措施。 2.當身體約束不需要時速解除約束。 3.約束用物應選用以最少的約束，提供最多的安全。 4.約束帶應以定位方式綁在床的骨架上，而不是床欄，避免拉起或放下床欄時，拉扯約束帶。 5.綁約束帶應選用可迅速鬆開的方法。例如，綁成蝴蝶結（綁在病人碰觸不到的地方 ），而不打死結。 6.作身體約束時，鬆緊應適中，保持1-2指之空隙，使肢體能稍作移動。 7.約束時以腕關節約束為優先，且不可只約束踝關節，以防病患自己鬆開約束或嘗試起來而跌倒。

13. Preexisting diseases (pancreatitis) Invasive procedures, or trauma. Monitoring and therapeutic devices (such as catheters, drains, noninvasive ventilating devices, endotracheal tubes) Routine nursing care (such as airway suctioning ,physical therapy, dressing changes, and patient mobilization) Prolonged immobility Inadequate sleep Agitation Possibly causing exhaustion and disorientation. Evokes a stress response characterized by tachycardia, increased myocardial oxygen consumption, hypercoagulability, immunosuppression, and persistent catabolism NE ,Epi ,Glucogan ,ADH , Renin, Crotsol, Aldosterone, Serotonin, bradykinin, Prostagladin Agitation & Stress hormone

14. Pain assessment • Visual analogue scale (VAS) 視覺類比量表來評估病患之疼痛程度 • Numeric rating scale 0-10 數字等級量尺(0-10 numeric rating scale) (Geret al., 1999; Ger et al., 2004) • Behavioral-physiological scales • Family assessment • Verbal rating scale

15. 疼痛分數1-4 分為輕度痛，5-6 分為中度痛，而7-10 分為重度痛

16. 1 2 3 4 5 6 7 8 10 0 9 不痛 痛極了 痛極了 不痛 . . . . . . . . . . . . . . . . . Pain rating scale 1. Simple descriptor scale 不痛,一點點,有些痛,很痛,痛極了 2. 0-10 numeric rating scale 3. Visual analog scale (VAS) 4. Faces rating scale

17. Behavioral-physiological scale • Observation of pain-related behaviors • Movement, facial expression, posturing • Physiological indicators • HR, BP, RR

23. How to do pain control • Set the goal and plan of analgesia • Opioid: fentanyl, hydromorphine, morphine • Scheduled opioid dose/ continuous IV better than “ as needed” • Hemodynamic instability, renal insufficiency: fentanyl, hydromorphine

24. Patient-controlled analgesia vs conventional pain control

25. A response from the past : Morphine (and its side-effects) Active metabolites: accumulation  Constipation  Respiratory depression

27. 加護病房常使用的止痛劑性質及最小建議劑量 藥名 排除半衰期 尖峰時間 最小建議劑量 Morphine 2-4 h 30 min 1-4mg bolus 1-10mg/h infusion Fentanyl 2-5 h 4 min 25-100μg bolus 25-200μg/h infusion Hydromorphone 2-4 h 20 min 0.2-1mg bolus 0.2-2mg/h infusion Ketamine 2-3 h 30-60 sec 1-2μg/kg/min infusion

28. Fentanyl patch • 強力的麻醉性止痛藥 (80-100xMorphine)過量中毒可致死 • 2005/7/15 FDA Issues Public Health Advisory • 呼吸困難、呼吸深度變淺、深度睡眠、無力正常思考、無力正常說話及行走、有快昏倒的感覺、頭暈 • Fentanyl patch不應該使用於短期的疼痛、非持續的疼痛、或手術後的疼痛。 Fentanyl patch只應該用於已經使用過其他其他麻醉性止痛劑（對鴉片止痛劑opioids具耐受性）的病患，還有使用短效的止痛劑卻無法有效控制的慢性疼痛病患 FDA Public Health Advisory 2005/07/15

29. Delirium :an acutely changing or fluctuating mental status, inattention, disorganized thinking, and an altered level of consciousness

30. Delirium and Critical IllnessBrain Syndrome • Rates of delirium in non-critical care setting are around 10% to 20% • Rates of delirium in critical care settings are around 60% to 80% • Rates of acquired “dementia-like” critical illness brain syndrome following ICU care exceed 50% With an increasing proportion of inpatient critical care beds 1. Inouye et al, NEJM 1999;340:669-676 2. Ely et al, JAMA 2004;291-1753-1762

31. 1.Ely, Shintani, Speroff, JAMA 2003;289:2983-91 2.Milbrandt, Crit Care Med 2004;32:955-962 1.delirium was associated with a 3-fold higher rate of death by 6 months 2. 1.6-fold increase in ICU costs, and 10-fold higher rate of cognitive impairment at hospital discharge (p<0.001)

33. Aging Baseline dementia Underlying illness – Inflammation – Coagulation Metabolic disturbances Hypoxemia Genetic Predisposition Psychoactive Medications Sleep Deprivation Risk Factors, Prevention,and Treatment Inouye, JAMA 1996;275:852-57 Dubois, Intens Care Med 2001;27:1297-1304 Inouye, NEJM 1999;340:669-676 Jacobi, Crit Care Med 2002;30:119-141 Milbrandt, Crit Care Med. 2005;33:226-9

35. 1st prevent... 2nd treat ICU delirium • Treat underlying infection and CHF • Correct metabolic disturbances and hypoxemia • Goal-directed delivery of sedation/analgesia • Frequent reorientation of patient by nurse and family • Stop the ventilator each day to test readiness for liberation • Early mobilization and physical therapy • Attention to optimizing sleep patterns

36. Commonly given via intermittent i.v. injection The optimal dose and regimen of haloperidol have not been well defined. Haloperidol has a long half-life (10–24 hours) and loading regimens are used to achieve a rapid response in acutely delirious patients IM、IV 2-5 mg loading, M= 5 mg /h Eric MilbrandtESICM 17th Annual Congress: Abstract 251. Presented Oct. 11, 2004 Haloperidol Improves Survival in Mechanically Ventilated, Critically Ill Patients Haloperidol has anti-inflammatory effects on cytokinesby mean dose of 11.5 (± 11.6) mg/day for a mean period of 3.5 (± 4.6) days record 1,095 ICU patients during the past year that were mechanically ventilated for a period of longer than 48 hours Haloperidol

37. Patients factors Environmental People Drugs and devices Technology  pain anxiety VO2 increase respiratory drive sleep disturbances Agitation Measures process (Ramsay scale) and communication

38. 理想的鎮靜劑 • (l)對血液動力學或肺功能沒有不良影響 • (2)重覆給藥時無毒性代謝物之產生或積聚 • (3)不影響其它藥物之代謝 • (4)藥物代謝途徑不依靠腎、肝、肺等器官 • (5)短效並具高療效、便宜、不需複雜或昂貴的配備 • (6)給藥途徑可經由靜注(持續性或間歇性)並 可依病人病情之需要隨時調整劑量

39. Goals of Analgo-Sedation Ability to tolerate physical enviroment  Ability to tolerate ICU procedures  Prevention/reduction of stress  Patient safety

41. Sedation-agitation scale-I • 7. Dangerous agitation • Pulling ET tube, cath, climbing over bed rail, striking at staffs, thrashing side to side • 6. Very agitated • Not calm, depite frequent verbal reminding of limits, requires physical restraints, bites ET tube • 5. Agitated • Anxious ormildly agitated, attempting to sit up, calms down to verbal instructions

42. Sedation-agitation scale-II • 4. Calm and cooperative • Calm, awakens easily, follows commands • 3. Sedated • Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands • 2. Very sedated • Arouses to physical stimuli but does not communicate or follow commands, may move spontaneously • 1. Unarousable • Minimal or no response to noxious stimuli, does not communicate or follow commands

43. Ramsay Sedation Scale Level of sedation: 1. Patient is anxious and agitated • Patient is cooperative, oriented and tranquil 3. Patient responds to command only 4. Patient exhibits brisk response to light glabellar tap or loud auditory stimulus 5. Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus 6. No response to stimuli

44. Why should we adopt sedation scoring? Objective assessment and close, prospective control of the level of sedation DeJonghe B et al: Using and understanding sedation scoring systems: A systematic review. Intensive Care Med 2000; 26: 275–285 Brook AD et al: Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med 1999; 27:2609–2615

45. Advantages of Sedation scales No risk of over-sedation and under- sedation  Optimal end-point for titration of sedation  Prospective management of care  Comparability of drugs effects

46. Over-sedation:drawbacks Respiratory depression  Hypotension  Bradycardia  Venous stasis  Increased lenght of ventilation  Increased ICU lenght of stay  Increased costs  Failure to evaluate CNS alterations

47. benzodiazepine

49. lorazepam 2 mg bolus iv 2mg /h for 7 days Residual lorazepam effect > 3 days after discontinuation of the infusion • Lorazepam solvent: polyethtlene glycol (PEG), propylene glycol (PG) • Lactic acidosis • Acute tubular necrosis

50. Midazolam Anterograde amnesia:會造成前進性記憶喪失,通常在手術及診斷療程前或進行中時，非常有用 代謝(Metabolism) Midazolam在體內可完全且迅速被代謝。主要代謝物為-hydroxy-midazolam。約有40-50%的劑量乃經肝臟代謝。 排泄(Elimination) 健康志願者之排除半衰期為1.5-2.5小時，血中廓清率為300-400公撮/分鐘。當靜脈輸注midazolam，其排除動力學與bolus注射時並無不同。主要代謝物-hydroxy-midazolam之排除半衰期較原成份短。該代謝物會與glucuronic acid結合(無活性)並由腎臟排出體外 60歲以上成人之排除半衰期可能延長達三倍，而有些需以靜脈輸注midazolam以達長效鎮靜之ICU患者，可能高達六倍。這些病患在不改變輸注速率下，於穩定狀態時可得較高的血中濃度。 充血性心衰竭及肝功能降低(reduced hepatic function)的患者可能有較長之排除半衰期。