Patient-Focused Sedation and Delirium Management in ICU

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Patient-Focused Sedation and

Delirium Management in ICU

廖文進Wen-Jinn Liaw, MD, PhD

三軍總醫院麻醉部外科加護中心Surgical Intensive Care Unit, Department of Anesthesiology,

Tri-Service General Hospital

Wen-Jinn Liaw

Patient-Focused Sedation and

Delirium Management in ICU

� Introduction

– Patient-focused sedation

� Characteristics of critically ill patients

� Medication selection for ICU sedation

� Strategies to optimize ICU sedation

� Monitoring of sedation in ICU

� Delirium management in ICU

� Conclusion

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IntroductionIntroduction::

PatientPatient--Focused SedationFocused Sedation

Wen-Jinn Liaw Sessler CN et al. Semin Respir Crit Care Med 2001; 22:211–225.

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疼痛或躁動不治療造成的危險疼痛或躁動不治療造成的危險疼痛或躁動不治療造成的危險疼痛或躁動不治療造成的危險

�� 疼痛不治療疼痛不治療疼痛不治療疼痛不治療疼痛不治療疼痛不治療疼痛不治療疼痛不治療

–– increased endogenous increased endogenous

catecholamine activitycatecholamine activity

–– myocardial ischemiamyocardial ischemia

–– hypercoagulabilityhypercoagulability

–– hypermetabolic stateshypermetabolic states

–– sleep deprivationsleep deprivation

–– anxietyanxiety

–– deliriumdelirium

�� 躁動不治療躁動不治療躁動不治療躁動不治療躁動不治療躁動不治療躁動不治療躁動不治療

––病人自我傷害病人自我傷害病人自我傷害病人自我傷害病人自我傷害病人自我傷害病人自我傷害病人自我傷害

�� 拔除為生導管或裝置拔除為生導管或裝置拔除為生導管或裝置拔除為生導管或裝置拔除為生導管或裝置拔除為生導管或裝置拔除為生導管或裝置拔除為生導管或裝置

Wen-Jinn Liaw

急性照護時止痛與鎮靜的目的急性照護時止痛與鎮靜的目的急性照護時止痛與鎮靜的目的急性照護時止痛與鎮靜的目的

1.1. Reduce anxiety Reduce anxiety 減低焦慮減低焦慮減低焦慮減低焦慮減低焦慮減低焦慮減低焦慮減低焦慮

2.2. Prevent delirium Prevent delirium 避免妄想瞻望避免妄想瞻望避免妄想瞻望避免妄想瞻望

3.3. Enhance patient comfort Enhance patient comfort 增加舒適增加舒適增加舒適增加舒適增加舒適增加舒適增加舒適增加舒適

4.4. Induce sleep when required Induce sleep when required 誘導睡眠誘導睡眠誘導睡眠誘導睡眠誘導睡眠誘導睡眠誘導睡眠誘導睡眠

5.5. Provide adequate pain control Provide adequate pain control 控制疼痛控制疼痛控制疼痛控制疼痛控制疼痛控制疼痛控制疼痛控制疼痛

6.6. Facilitate mechanical ventilation Facilitate mechanical ventilation 協助機器通氣協助機器通氣協助機器通氣協助機器通氣協助機器通氣協助機器通氣協助機器通氣協助機器通氣

7.7. Induce appropriate level of amnesia Induce appropriate level of amnesia 誘導適當失憶誘導適當失憶誘導適當失憶誘導適當失憶誘導適當失憶誘導適當失憶誘導適當失憶誘導適當失憶

8.8. Optimize safety for patients and their caregiversOptimize safety for patients and their caregivers

有效增進病人與照顧者的安全有效增進病人與照顧者的安全有效增進病人與照顧者的安全有效增進病人與照顧者的安全有效增進病人與照顧者的安全有效增進病人與照顧者的安全有效增進病人與照顧者的安全有效增進病人與照顧者的安全

9.9. Facilitate communication with caregivers and family members Facilitate communication with caregivers and family members

促進照顧者與家屬的溝通促進照顧者與家屬的溝通促進照顧者與家屬的溝通促進照顧者與家屬的溝通促進照顧者與家屬的溝通促進照顧者與家屬的溝通促進照顧者與家屬的溝通促進照顧者與家屬的溝通

Purpose of Analgesia and Sedation in Acute Care Settings

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加護病房緩解焦慮的方法或策略加護病房緩解焦慮的方法或策略加護病房緩解焦慮的方法或策略加護病房緩解焦慮的方法或策略

�� Pharmacologic Pharmacologic 藥物藥物藥物藥物

– Opioids 嗎啡類嗎啡類嗎啡類嗎啡類

– Benzodiazepines

– Propofol

– Haloperidol

– Inhalational anesthetics

– Dexmedetomidine

– Barbiturates

�� Nonpharmacologic Nonpharmacologic 非藥物非藥物非藥物非藥物

– Behavior modification

– Cognitive restructuring

– Distraction 分散注意力分散注意力分散注意力分散注意力

– Hypnosis 催眠催眠催眠催眠

– Imagery 意象意象意象意象

– Music therapy 音樂治療音樂治療音樂治療音樂治療

– Patient education 病人教育病人教育病人教育病人教育

– Relaxation techniques

放鬆技巧放鬆技巧放鬆技巧放鬆技巧

Wen-Jinn Liaw

Patient-Focused Sedation

� A strategy of comprehensive structured

management that matches

– initial evaluation

– monitoring

– medication selection

– use of protocols

� with patient characteristics and needs

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� This is best accomplished through interdisciplinary management by

– physicians, nurses, and pharmacists.

� Frequent monitoring with validated tools improves communication among clinicians

– an important role in detecting and treating pain and

agitation while avoiding excessive or prolonged

sedation.

Wen-Jinn Liaw


�� May require deep sedationMay require deep sedation

– high-frequency oscillatory ventilation or prone positioning, or neuromuscular blockade (NMB)

� Patients who are receiving NMB require adequate sedation and analgesia, and periodic cessation of the NMB agent to assess adequacy of sedation and analgesia.

�� From endotracheal tube to tracheostomy tubeFrom endotracheal tube to tracheostomy tube

– less sedative and analgesic medication and

correspondingly fewer hours of deep sedation

�� Alcohol and substance abuse is associated with Alcohol and substance abuse is associated with

greater sedative drug requirements.greater sedative drug requirements.

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Characteristics of critically ill patientsCharacteristics of critically ill patients

Wen-Jinn Liaw

影響藥物分佈影響藥物分佈影響藥物分佈影響藥物分佈、、、、作用與代謝之因素作用與代謝之因素作用與代謝之因素作用與代謝之因素

� 分佈模式 (Compartment models)

� 分佈體積 (Volume of distribution)

� 蛋白質結合率 (Protein binding ratio)

� 細胞色素 (Cytochrome P450)

� 藥物交互作用(Interaction)

� 肝抽取率 (Hepatic extraction ratio)

年齡 (Age)

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Characteristics of critically ill patients

重症病人的生理特性重症病人的生理特性重症病人的生理特性重症病人的生理特性重症病人的生理特性重症病人的生理特性重症病人的生理特性重症病人的生理特性

� ↑↑↑↑ age

� ↓↓↓↓ protein binding

� ↑↑↑↑ total body water,

↓ fat body or ↓ lean body mass

� ↓↓↓↓ hepatic or ↓↓↓↓ renal function

� Hemodynamic instability

� Concurrent disease states

Wen-Jinn Liaw

Medication selection for ICU sedationMedication selection for ICU sedation

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玉山西峰山神廟

Wen-Jinn Liaw

理想的止痛與鎮靜藥物特性理想的止痛與鎮靜藥物特性理想的止痛與鎮靜藥物特性理想的止痛與鎮靜藥物特性

� Provide adequate sedation and pain control 效果好效果好效果好效果好

� Rapid onset of action 作用快作用快作用快作用快

� Rapid recovery after discontinuation 停後恢復快停後恢復快停後恢復快停後恢復快

� Minimal systemic accumulation 微量身體蓄積微量身體蓄積微量身體蓄積微量身體蓄積

� Minimal adverse effects 微量副作用微量副作用微量副作用微量副作用

� Without increasing overall health care costs 不增加成本不增加成本不增加成本不增加成本

–– ultraultra--shortshort--acting agentsacting agents such assuch as remifentanilremifentanil

–– agent other than agent other than propofolpropofol, , benzodiazepinesbenzodiazepines, and , and

opioidsopioids such as thesuch as the αααααααα22 adrenergic agonist adrenergic agonist

dexmedetomidinedexmedetomidine. .

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Analgesics in ICUAnalgesics in ICU

�� MorphineMorphine

�� FentanylFentanyl

� Hydromorphone

�� RemifentanilRemifentanil

� Sufentanil

� Alfentanil (Rapifen)

� Meperidine

(Pethidine, Demeral)

�� KetololacKetololac (Keto)

�� MidazolamMidazolam (Dormicum)

�� PropofolPropofol (Diprivan, Anesvan,

Recofol, Fresofol, Lipuro)

�� LorazepamLorazepam (Ativan, Neuropam,

Anxicam)

�� HaloperidolHaloperidol (Haldol, Binin-U,

Pandol)

�� DexmedetomidineDexmedetomidine

(Precedex)

Sedatives in ICUSedatives in ICU

Wen-Jinn Liaw

Ongoing sedationLorazepam: 1–4 mg IVP q 10–20 min until goal,

then q 2-6 hr scheduled + prn or

Propofol: start 5 mcg/kg/min, titrate q 5 min

until at goal (if ≥≥≥≥3 days, convert to lorazepam)

Ongoing sedationLorazepam: 1–4 mg IVP q 10–20 min until goal,

then q 2-6 hr scheduled + prn or

Propofol: start 5 mcg/kg/min, titrate q 5 min

until at goal (if ≥≥≥≥3 days, convert to lorazepam)

2002 SCCM Guidelines for ICU Sedation

Nonpharmacologic treatmentNonpharmacologic treatment

Use pain scale to assess for

pain and set goal for analgesia

Use pain scale to assess for

pain and set goal for analgesia

Use sedation scale to assess anxiety/agitation and set goal for sedation

Use sedation scale to assess anxiety/agitation and set goal for sedation

Use delirium scale to assess for delirium and set goal for delirium

Use delirium scale to assess for delirium and set goal for delirium

Hemodynamically unstable

Fentanyl: 25–100 mcg IVP q 5–15 min or

Hydromorphone: 0.25–0.75 mg IVP q 5–15 min

Hemodynamically stable

Morphine: 2–5 mg IVP q 5–15 min

Repeat until pain controlled, then

scheduled doses + prn

Hemodynamically unstable

Fentanyl: 25–100 mcg IVP q 5–15 min or

Hydromorphone: 0.25–0.75 mg IVP q 5–15 min

Hemodynamically stable

Morphine: 2–5 mg IVP q 5–15 min

Repeat until pain controlled, then

scheduled doses + prn

Acute agitation

Midazolam: 2–5 mg IVP q 5–15 min until acute event controlled

Acute agitation

Midazolam: 2–5 mg IVP q 5–15 min until acute event controlled

Haloperidol: 2–10 mg IVP q 20–30 min,

then 25% of loading dose q 6 hr

Haloperidol: 2–10 mg IVP q 20–30 min,

then 25% of loading dose q 6 hr

Reassess all goals daily; titrate to maintain goal

Reassess all goals daily; titrate to maintain goal Jacobi et al. Crit Care Med 2002;30:119-141

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αααα-hydroxymidazolam

Midazolam

αααα-hydroxymidazolamconjugate

Flumazenil

Midazolam

Limit of detection

Seru

m c

on

cen

trati

on

(n

g/m

l)

Time (days)

Serum concentration time profile of midazolam and

metabolites in a patient with acute renal failure.

Bauer et al. Lancet 1995

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Morphine

� Morphine is the preferred analgesic agent

for critically ill patients.

– can induce histamine release

� Onset of action: 2-3 mins

� Duration: 4-5 hrs

� Half-life: 2-3 hrs to 4.5 hrs

� Initial dose: 0.05 mg/kg (2-10 mg)(over 5-15 mins)

� maintain: 1-4 mg/hr

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Fentanyl

� Fentanyl is the preferred analgesic agent

for critically ill patients with hemodynamic

instability.– 100-300 times potent as morphine

– high lipophilicity


� Duration: 0.5-1 hr

� Half-life: 30-60 mins (9-16 hrs after prolonged dosing)

� Initial dose: 1-2 µg/kg

� maintain: 1-2 µg/kg/hr

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Midazolam (Dormicum)

� Midazolam is one of the preferred agents

only for the short-term (< 24hrs) treatment of

anxiety in the critically ill adult.– 96-98% protein bound

– high lipophilicity & short-acting

– compatibility with IV solutions

– stability in aqueous solutions

– absence of pain at the injection site

– less incidence of thrombophlebitis

– dose not suppress the adrenal gland

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Midazolam (continued)


� Duration: 30-120 mins

� Elimination half-life: 1.2-12.3 hrs

� Initial dose: 0.03 mg/kg/hr (1-2 mg)

� maintain: 0.03-0.25 mg/kg/hr titrated to effect

� Active metabolite: α-hydroxymidazolam

� Antagonist: flumazenil

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Propofol

� Propofol is another preferred agents only

for the short-term (<24 hrs) treatment of

anxiety in the critically ill adult.

– ultra-short-acting general anesthetic

– 2,6-diisopropylphenol (alkyl phenol derivatives)

– oil-in-water emulsion [0.1 g fat (1.1 Kcal) /ml]

� 1.0 % propofol, 10% soybean oil, 2.25% glycerol,

1.2% egg phosphatide

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� anticonvulsant activity

� very little analgesic properties

� high lipophilicity & 98% plasma-protein bound

� ↓↓↓↓ cerebral blood flow (50%)( ↓↓↓↓ ICP) & ↓↓↓↓ cerebral metabolic oxygen requirements (18-36%)

�� Administration Guidelines: Administration Guidelines:

–– 1. Through a central vein1. Through a central vein

–– 2. Aseptic technique2. Aseptic technique

� disinfection of the rubber stopper

� avoiding excessive manipulation of the line

� discarding the vial and tubing within 12 h

� opened, unused propofol is discarded immediately.

Propofol (continued)

Wen-Jinn Liaw


� Duration: 10-15 mins

� Elimination Half-life: 1.8-4.1 mins

� Terminal half-life: ~3 days

� Initial dose: 0.5-1 mg/kg/hr, titrated in

increments of 0.5 mg/kg every 5 to 10 mins

� maintain: 0.5-3 mg/kg/hr

Propofol (continued)

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Lorazepam

� Lorazepam is the preferred agent for the prolonged

treatment of anxiety in the critically ill adult.

– intermediate-acting benzodiazepine

– 90-96% protein bound & less lipophilic than diazepam

– causes less hypotension, lower in cost than midazolam


� Duration: 6-8 hrs

� Elimination Half-life: 12-18 hrs

� Initial dose: 0.01-0.1 mg/kg (1-2 mg)

� maintain: intermittent IV bolus or continuous infusion

Wen-Jinn Liaw

Haloperidol

� Haloperidol is the preferred agent for the treatment

of delirium in the critically ill adult.

– A butyrophenone neuroleptic drug

– Indication for continuous infusion

� ≥ 8 boluses of 10-mg within 24 hrs or > 10 mg/hr for 5

consecutive hrs

� Onset: 30-60 mins (duration of 4-8 hrs)

� Elimination Half-life: 33 hrs

� Initial dose: 2-10 mg IV

� maintain: the dosage is repeated every 2-4 hrs

or infusion with 10 mg/hr

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Dexmedetomidine

� A highly selective αααα2-adrenergic agonist

– αααα2:αααα1 ratio of about 1600:1. By comparison, clonidine has a αααα2:αααα1

ratio of about 220:1.

– The most frequently reported adverse effects were hypotension,

bradycardia, and dry mouth.

– No significant respiratory depression in conventional clinical doses

– 94% protein bound


� Elimination Half-life:

– t1/2β: 2-3 hr with hepatic glucuronidation and conjugation

� Infusion dose: loading 1 µg/kg, then 0.2-0.7 µg/kg/hr

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Pharmacokinetic of Precedex

� Target Plasma Concentration 0.6 µg/L

LiverMetabolism

95% renalRoute of elimination

2 hrElimination T1/2

6 minDistribution T1/2

0.495 L/h*kgClearance

1.33 L/kgVolume of distribution at

steady-state

5.1 µµµµg/L.hArea under the plasma

concentration-time curve

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Less Morphine Need

Arain SR, et al. Anesth Analg. 2004;98:153-158.

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Benzodiazepines Propofol Opioids Dexmedetomidine Haloperidol

Sedation √√√√ √√√√ √√√√ √√√√ √√√√

Alleviate anxiety1,2 √√√√ √√√√

Analgesic Properties1-4 √√√√ √√√√

Promote arousability

during sedation2-4 √√√√

Facilitate ventilation during weaning2-4 √√√√

No respiratory depression1-4 √√√√ √√√√

Control delirium1-4 √√√√ √√√√

Comparison of Clinical Effects

1Blanchard AR. Postgrad Med. 2002;111:59-74. 2Kamibayashi T, et al Anesthesiology. 2000;95:1345-1349.

3Maze M. et al. Anesthetic Pharmacology: Physiologic Principals and Clinical Practice. Churchill Livingstone; 2004. 4Maze M, et al. Crit Care Clin. 2001;4:881.

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Prolonged weaning1 √√√√ √√√√ √√√√ *

Respiratory

depression1 √√√√ √√√√ √√√√

Hypotension1-3 √√√√ √√√√ √√√√ √√√√ √√√√

Constipation1 X

Deliriogenic √√√√ √√√√ √√√√

Tachycardia1 Morphine

Bradycardia1 Fentanyl √√√√ √√√√

Comparison of Adverse Effects

*Excluding remifentanil1Harvey MA. Am J Crit Care. 1996;5:7-16.

2Aantaa R, et al. Drugs of the Future. 1993;18:49-56.3Maze M. Crit Care Clin. 2001;4:881;

Benzodiazepines Propofol Opioids Dexmedetomidine Haloperidol

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Ranges Reported in Healthy Patients* and ICU Patients

Systemic Clearance

(mL/kg/min)EliminationHalf-life (hr)Agent

Potential for Accumulation

Comparison of Pharmacokinetics

1Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426-453;2Khan ZP, et al. Anaesthesia. 1999;54:146-165;

3Bhana N, et al. Drugs. 2000;59:263

8.6-15.06.9-36.0Fentanyl1 Hepatic impairment

0.32-0.64 mL/hr/kg2Dexmedetomidine3

1.9-4.36-23Clonidine217-316.3-32Propofol1

1.2-4.110-15 Lorazepam1

4.3-6.63.4-11Midazolam1

0.4-0.921-120Diazepam1

10-1328-38Haloperidol1

Hepatic/renal insufficiency

Hepatic/renal insufficiency

Hepatic insufficiency



Renal insufficiency

–

*Healthy patients: no renal or hepatic disease.

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Strategies to Optimize ICU SedationStrategies to Optimize ICU Sedation

Wen-Jinn Liaw

玉山北峰氣象站玉山北峰氣象站玉山北峰氣象站玉山北峰氣象站

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Protocols to Optimize Sedation

� The use of protocols is a key component of

management:

– reductions in the duration of sedation, mechanical

ventilation, and ICU length of stay (LOS)

� a shorter half-life titrating medications to end-points

identified by sedation scales

� daily interruption of sedation

� intermittent rather than continuous therapy

� analgesia based therapy

– algorithms that proactively identify pain, agitation, and/or

patient/ventilator asynchrony.

� De-escalation

– Protocol-guided withdrawal

� avoid analgesic or sedative withdrawal

Wen-Jinn Liaw Kress et al. N Engl J Med 2000;342:1471-7

A Wake-Up Call in the Intensive Care Unit

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Daily interruption of sedative-drugs infusions decrease the duration of mechanical ventilation

Kress et al. N Engl J Med 2000;342:1471-7

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Daily interruption of sedative-drugs infusions decrease the length of stay

Kress et al. N Engl J Med 2000;342:1471-7

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☆ IV bolus of 2 mg, then

continuous IV infusion of

5 mg/hr ×××× 12 hr, then

4 mg/hr ×××× 12 hr, then

3 mg/hr thereafter for a

total of 3 days.

Residual effects: ≈≈≈≈ 10 hrs

☆ IV bolus of 2 mg, then

continuous IV infusion of

5 mg/hr for 3 days

Residual effects: ≥≥≥≥ 24 hrs

Barr and Donner, Crit Care Clin 1995

Optimal IV dosing strategiesOptimal IV dosing strategies

Mid

azo

lam

pla

sm

a c

on

ce

ntr

ati

on

(n

g/m

l)

Therapeutic

range

Time (min)

從北峰回眸望玉山主峰站從北峰回眸望玉山主峰站從北峰回眸望玉山主峰站從北峰回眸望玉山主峰站

Monitoring of sedation in ICUMonitoring of sedation in ICU

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Assessment of pain in ICU

� Behavior Rating Scales (1 & 2)

� Picture Scales (facial expressions)

� Hemodynamic parameters

� Behavioral Pain Scale (BPS)

� Critical Care Pain Observation Tool (CPOT)

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The facial expressions of

the Picture Scales:

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Behavioral Pain Scale

Scores from each of the three domains are summed, with a total score of 3 to 12.

Payen et al. Crit Care Med 2001, 29:2258-2263.

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Scores for each of the four domains are summed, with a total score of 0 to 8.

Critical Care Pain Observational Tool

Gelinas et al. Am J Crit Care 2006, 15:420-427.

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�� Ramsay Sedation Scale (RSS)Ramsay Sedation Scale (RSS) 19741974

�� Sedation Agitation Scale (SAS)Sedation Agitation Scale (SAS) 19941994

� Motor Activity Assessment Scale (MAAS) 19991999

� Vancouver Interactive and Calmness Scale 20002000

�� Richmond AgitationRichmond Agitation--Sedation Scale (RASS)Sedation Scale (RASS) 20022002

� Adaptation to Intensive Care Environment (ATICE) 20032003

� Minnesota Sedation Assessment Tool (MSAT) 20042004

� EEG, Bis, AEP

Assessment of sedation in ICU

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Ramsay Sedation ScaleRamsay Sedation Scale

Level Response

1 Anxious and agitated or restless or both

2 Cooperative, oriented, and tranquil

3 Responds only to verbal commands

4 Asleep with brisk response to light stimulus

5 Asleep with sluggish response to stimulus

6 Asleep with no response to stimulus

白天

晚上

Ramsay et al. Br Med J 2:656-659, 1974

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Level Response

7 Dangerous agitation: trying to remove tubes & catheters

6 Very agitated: biting endotracheal tube & needs restraints

5 Agitated: attempting to sit up & calm to verbal instruction

4 Calm and cooperative: awakens easily & follow commands

3 Sedated: awakens to verbal stimuli or gentle shaking

2 Very sedated: arouses to physical stimuli but does not communicate

1 Unarousable: no response to noxious stimuli

SedationSedation--Agitation Scale (SAS)Agitation Scale (SAS)

Riker et al. Crit Care Med 27:1325-1329, 1999

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Richmond agitationRichmond agitation--sedation scale (RASS) sedation scale (RASS)

躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表

Sessler et al. Am J Respir Care Med 166:1338-1344, 2002

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記分歸類用詞敘述

--------------------------------------------------------------------------------------------

+4 戰鬥性明顯戰鬥性，暴力相向，對工作人員具有立即危險性

+3 非常躁動拉扯或拔除導管或內管，具攻擊性

+2 躁動經常無目的性動作，與人工呼吸器對抗

+1 煩躁焦慮但其動作無攻擊性或不劇烈

0 警覺又安靜

-1 嗜睡沒有完全警覺，但對言語反應保持清醒

(眼睛張開/眼神接觸) (超過10秒鐘)

-2 輕度鎮靜短暫對言語反應時間(眼神接觸少於10秒鐘)

-3 中度鎮靜對言語反應只有張眼或動一下(無眼神接觸)

-4 深度鎮靜對言語無反應，但對身體刺激能張眼或動一下

-5 無法叫醒對言語或身體刺激都沒有反應

Richmond agitationRichmond agitation--sedation scale (RASS) sedation scale (RASS)

躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表躁動鎮靜評分表

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Delirium Management in ICUDelirium Management in ICU

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玉山北峰氣象站玉山北峰氣象站玉山北峰氣象站玉山北峰氣象站

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� Delirium

– may be a marker for worse outcomes,

� increased incidence of posttraumatic stress disorder

(PTSD) and increased long-term mortality

– classical hyperactive delirium

� intermittent agitation, hallucinations, and disruptive

behavior

– hypoactive form appears to be more common in the ICU

– Precipitated factors

� CNS disorders, infections, hypoxia, pain, withdrawal

syndromes, electrolyte and metabolic disorders, and

various organ dysfunctions as well as a long list of

medications

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� Delirium

– Many cases of hypoactive or mixed delirium in the

ICU are related to the sedative effects of anxiolytic

and analgesic drugs,

� particularly lorazepam

� Strategies that emphasize using the lowest effective

sedative drug dose may help avoid delirium.

Wen-Jinn LiawCopyright restricions may apply. Ely et al. JAMA 2001;286:2703-2710.

CConfusion onfusion AAssessment ssessment MMethod for the ethod for the ICUICU ((CAMCAM--ICUICU))

The diagnosis of delirium requires the presence of acute

onset of changes or fluctuations in the course of mental

status, and inattention, and either disorganized thinking

or an altered level of consciousness.

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Haloperidol

� Haloperidol is the preferred agent for the treatment

of delirium in the critically ill adult.

– A butyrophenone neuroleptic drug

– Indication for continuous infusion

� ≥ 8 boluses of 10-mg within 24 hrs or > 10 mg/hr for 5

consecutive hrs


� Elimination Half-life: 33 hrs

� Initial dose: 2-10 mg IV

� maintain: the dosage is repeated every 2-4 hrs

or infusion with 10 mg/hr

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Incidence of ICU Delirium

Maldonado JR, et al. Anesthesiology. 2003; 99: A465.

De

liriu

m,

%

0

10

20

30

40

50

60

Dexmedetomidine Propofol Midazolam

• Evaluation of 90 patients

undergoing cardiac surgery

to determine the probability

of development of

postoperative delirium.

• Post-operative sedation with

dexmedetomidine may be

associated with a lower

incidence of delirium

compared with more

conventional forms of

sedation.

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Mechanism of action

Dexmedetomidine

負回饋負回饋負回饋負回饋

Precedex (Dexmedetomidine)

200Clonidine

1200Medetomidine

1600Dexmedetomidine

αααα2 /αααα1

selectivity

Drug

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Dexmedetomidine作用部位作用部位作用部位作用部位

�作用部位作用部位作用部位作用部位

– Brain (locus ceruleus)

第第第第4腦室底上角之色素隆凸腦室底上角之色素隆凸腦室底上角之色素隆凸腦室底上角之色素隆凸

– Spinal cord脊髓

– 交感神經

�中樞神經之作用中樞神經之作用中樞神經之作用中樞神經之作用

– Sedation鎮靜

– Anxiolysis抗焦慮

– Analgesia止痛

�交感神經之作用交感神經之作用交感神經之作用交感神經之作用�� Sympathetic activity

– � BP, � HR

Dexmedetomidine

Spinal Cord

LOCUSCERULEUS

FOURTHVENTRICLE

PONS

CEREBRUM

CEREBELLUM

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Anxiolysis

αααα2B

X

Physiology of Dexmedetomidine

Kamibayashi T, et al. Anesthesiology. 2000;93:1346.

α2A, α2c Locus Ceruleus

α2B CNS-based thermoregulatory inhibition

αααα2B Cerebral vessels and peripheral vasculature

α2A Peripheral smooth-muscle cells

α2A Dorsal horn of the spinal cord

α2A Brainstem vasomotor center

Blocks cardioaccelerator nerve

Vagomimetic action

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Riker et al. JAMA. 2009; 301: 489-499.

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Riker et al. JAMA. 2009; 301: 489-499.

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ConclusionConclusion

**Denotes components with evidence supporting their benefit.

Schweickert and Kress, Crit Care 2008

苦惱苦惱苦惱苦惱、、、、痛苦痛苦痛苦痛苦

清醒清醒清醒清醒疼痛疼痛疼痛疼痛

給藥給藥給藥給藥

(察覺愁眉苦臉徵候察覺愁眉苦臉徵候察覺愁眉苦臉徵候察覺愁眉苦臉徵候)

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� Patient-focused care

– assessment of predisposing and precipitating factors,

– frequent monitoring,

– careful medication selection,

– and use of strategies to precisely target therapy to

defined end points and avoid sedation that is excessive

or prolonged.

� Identify delirium

– consider regular assessment of delirium, using a

validated delirium assessment instrument.

ConclusionConclusion

Patient-Focused Sedation and Delirium Management in ICU

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