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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. 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

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sedation in the intensive care unit a general overview

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

current forces in critical care
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
slide4
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)

slide5

Death Caused by Physical Restrains

Steven H.(1992) The Gerontologist

slide6

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)
slide7
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。

slide11
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)

slide12
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。

agitation stress hormone
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
pain assessment
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
slide15

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

pain rating scale

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

behavioral physiological scale
Behavioral-physiological scale
  • Observation of pain-related behaviors
    • Movement, facial expression, posturing
  • Physiological indicators
    • HR, BP, RR
how to do pain control
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
a response from the past morphine and its side effects
A response from the past : Morphine (and its side-effects)

Active metabolites: accumulation

 Constipation

 Respiratory depression

slide27
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

fentanyl patch
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

slide29

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

delirium and critical illness brain syndrome
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

slide31

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)

risk factors prevention and treatment
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

1st prevent 2nd treat icu delirium
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

haloperidol
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
agitation
Patients factors

Environmental

People

Drugs and devices

Technology

 pain

anxiety

VO2 increase

respiratory drive

sleep disturbances

Agitation

Measures process (Ramsay scale) and communication

slide38
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
goals of analgo sedation
Goals of Analgo-Sedation

Ability to tolerate physical enviroment

 Ability to tolerate ICU procedures

 Prevention/reduction of stress

 Patient safety

sedation agitation scale i
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
sedation agitation scale ii
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
ramsay sedation scale
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

slide44

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

slide45

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

over sedation drawbacks
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

lorazepam
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
midazolam
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。

midazolam51
Midazolam

Midazolam與某些抑制肝臟酵素(特別是cytochrome P450 IIIA)之藥物間具潛在交互作用。數據顯示這些化合物會影響midazolam的藥物動力學,而改變鎮靜作用的程度及作用時間,因此使用上必須小心 titeate 劑量。

藥物種類 相關文獻

  • ketoconazole (Olkkola et al., 1994)
  • fluronazole (Ahonen et al., 1999)
  • itraconazole (Olkkola et al., 1993)
  • erythromycin (Olkkola et al., 1994)
  • diltiazem (Backman et al., 1994)
  • verapamil (Backman et al., 1994)
  • cimetidine (Sanders et al., 1993; Kanto et al., 1983),
benzodiazepine pharmacology
benzodiazepine (Pharmacology)

藥理作用 進行的試驗 效力比較

Anxiolytic effect Conflict test Valium : Dormicum = 1 : 1

Sedative effect Conflict test Valium : Dormicum = 1 : 2

Irritation threshold Anger reaction Valium : Dormicum = 1 : 2

Muscle relaxant Pole-climbing test Valium : Dormicum = 1 : 1

Anticonvulsant Standard test Valium : Dormicum = 1 : 1

Data from F. Hoffmann La Roche Ltd., Basel, Switzerland

anexate flumazenil
Anexate®(Flumazenil)
  • Flumazenil限使用於:
  • 全身麻醉病例
  • Benzodiazepin類藥物中毒之鑑別診斷與治療病例。
  • 【全民健康保險藥品使用規範】
slide56
Midazolam-Induced Sedation for Upper Gastrointestinal Endoscopy: Assessment of Endoscopist and Patient SatisfactionAnterograde amnesia
  • 352 patients upper gastrointestinal endoscopy were sedated with midazolam given
  • Ages of the patients ranged between 16 and 79 years (average: 41.6 ± 12.7 years).
  • Anterograde memory was found in 310 (88.0%)
  • 342 patients (98.0%) cooperated well
  • Side effects were rarely seen (3.6%), and included nausea, vertigo, and vomiting
  • Acceptability of further endoscopy in 338 (96.0%)
  • No significant cardiopulmonary problems

Gastroenterology Nursing: Volume 26(4) July/August 2003 pp 164-167

slide57

Lorazepam vs Midazolam

Infusion data

Prospective randomized trial

Pohlman A.S., et al. Crit Care Med 1994; 22: 1241-1247

slide58

Lorazepam vs Midazolam

Time to achieve adequate sedation

Time of neurologic recovery

p= NS

p= NS

4000

300

250

3000

200

2000

Time (mins)

150

100

1000

50

0

0

Midazolam

Lorazepam

Midazolam

Lorazepam

Pohlman A.S., et al. Crit Care Med 1994; 22: 1241-1247

slide59

Propofol vs Midazolam

Effectiveness of sedation

n=97

First hour of treatment

After first hour of treatment

p= NS

p< 0.01

80

70

70

60

60

50

50

40

% Assessments

40

30

30

20

20

10

10

0

0

Effective

Acceptable

Ineffective

Effective

Acceptable

Ineffective

Chamorro C., et al. Crit Care Med 1996; 24: 932-939

midazolam

propofol

slide60

Propofol vs Midazolam

Monitoring the patient state of sedation

Prospective randomized multicenter trial

n=97

80

p< 0.05

70

60

50

% Assessments

40

30

20

10

0

Very easy

Easy

Moderate

Difficult

Chamorro C., et al. Crit Care Med 1996; 24: 932-939

propofol

midazolam

sedation in the general icu speed of recovery after sedation

Patient type

Medical, trauma,

postsurgical,

miscellaneous

Postsurgical,

medical, trauma

Postsurgical

(abdominal)

Evaluable

patients

(n)

32

18

21

18

17

17

Duration of

infusion

Mean (range) (h)

81

88

20

21

approx. 6

approx. 6

Recovery

endpoint

Maximum level of consciousness

Weaning from ventilator

Spontaneous ventilation

Recovery time

Mean (min)

0 30 60 90 120 150 180

23

p<0.05

137

5

(3-24)(4-47)

p<0.001

148

16.4

p<0.05

85.2

‘Diprivan’

Midazolam

Sedation in the general ICUSpeed of recovery after sedation

1. Chamorro C et al. 1996.

2. Aitkenhead C et al. 1989.

3. Wolfs C et al. 1991.

hemodynamic effects of midazolam and propofol
Hemodynamic Effects of Midazolam and Propofol
  • Parameter Midazolam Propofol CommentRef
  • BP, 1st hr incr 21% decr 17%1
  • SBP decr 12% decr 24% p < 0.01 2
  • MAPNC decr 17% 3
  • MAPNC decr 33% 4
  • Decr SBP31% pts 68% pts decr > 20% 5
  • Propofol (1-2.5 mg/kg bolus, then 3 mg/kg/h) decreased MAP by 43%, CI by 23%, SVRI by 30%6
  • 1.. Boeke et al. J Drug Dev 1989 2. Geller et al. Anesthesiology 1991
  • 3. Kox et al. Br J Anaesth 1990 4. Pappagallo et al. Minerva Anest 1992
  • 5. Weinbroum et al. ICM 1997 6. Martin et al. Acta Anaesth Scand ?4
slide63

Sedation of the ICU patients during mechanical ventilation: propofol or midazolam?

  •  Propofol and midazolam achieved optimal sedation when administered by specified dosing protocol
  •  Propofol had a faster awakening time
  •  Time to sedation was not significantly different
  • VO2 decreased similarly in both groups

Propofol is the preferred sedative when rapid awakening (e.g., for neurologic

assessment or extubation) is important.

(Grade of recommendation B)

Kress J., et al. AJRCCM 1996; 153: 1012-1018

slide64
propofol did not produce amnesia as often as midazolam . Like the benzodiazepines, propofol has no analgesic properties.
  • Provides 1.1 kcal/mL from fat and should be counted as a caloric source. Long-term or high-dose infusions may result in hypertriglyceridemia
  • Pancreatitis has been reported following anesthesia
  • Prolonged use (48 hours) of high doses of propofol (66 g/kg/min infusion) has been associated with lactic acidosis, bradycardia, and lipidemia in pediatric patients -***FDA against the use for the prolonged sedation
  • incidence of infectious complications---no more than 12 hours

Clinical practice guidelines for the sustained use of sedatives and

analgesics in the critically ill adultCrit Care Med 2002 Vol. 30, No. 1

continuous iv sedation and duration of mechanical ventilation
Continuous IV Sedation and Duration of Mechanical Ventilation
  • Patients receiving continuous IV sedation:
    • younger
    • lower PaO2/FIO2
    • more ARDS
  • more chemical paralysis
  • CIVS had longer LOSs after adjustment for age, SOI, mort, MV indication, paralysis, trach, # OSF

*

*

* p < 0.001, + p = 0.007

Kollef MH, et al. Chest 1998;114:541

complications of sedative medications
Complications of Sedative Medications
  • Cardiovascular alterations
  • Respiratory depression, apnea
  • Prolonged sedation

The titration of the sedative dose to a defined endpoint is recommended with

systematic tapering of the dose or daily interruption with retitration to

minimize prolonged sedative effects. (Grade of recommendation A)

  • Tolerance and tachyphylaxis
  • Withdrawal Sx
  • Drug-specific
    • Propofol: Increased triglycerides
    • Lorazepam: precipitation
short term sedation 24 48 h
Short-term sedation (24-48 H)
  • Status asthmaticus
  • COPD with acute exacerbation, but without sepsis
  • Agitation due to mechanical ventilation without major sepsis
  • Delirium in ICU
  • Severe CAP, acute respiratory failure, unable to tolerate ET tube
what drugs for short term sedation
What drugs for short-term sedation
  • Midazolam 2-5mg iv until acute exacerbation event controlled
  • Check the indication of sedation on 2nd and 3rd day
    • Stop
    • Tappering
    • Switch to long-term sedation

Midazolam is recommended for shortterm use (Grade of recommendation A)

long term sedation 72 h
Long-term sedation (> 72 H)
  • Severe sepsis and septic shock
  • ARDS with refractory hypoxemia
  • Prone position
what drugs for long term sedation 1
What drugs for long-term sedation (1)
  • Midazolam 2-5mg iv q5~15 min until acute event controlled
  • Start continuous midazolam, titrated to the level of sedation
  • Check the sedation level everyday
  • Check the indication on 3rd and 4th day
    • Stop or tappering
    • Add lorazepam 1-2 amps q2-6 hours, tappering midazolam to the defined level of sedaiton
what drugs for long term sedation 2
What drugs for long-term sedation (2)
  • On 6-10th days
    • Tapering the lorazepam, depending on the indication of sedation
    • Restarting the midazolam or propofol to replace the role of lorazepam
    • Preparing the patient wake-up and weaning
slide73

Summary

 Individualized approach to sedation

 Propofol is useful for deeper level of sedation and more rapid awakening

 Benzodiazepines should be used to provide rapid amnesia (midazolam) or long-term sedation (lorazepam)

 Randomized studies needed to investigate safety profile/cost-efficiency of new generation-opioids, that present promising aspects

dexmedetomidine underused for anesthesia sedation
Dexmedetomidine Underused for Anesthesia, Sedation
  • The alpha-2 agonist is a sedative with analgesic and anxiolytic properties. It was granted FDA approval
  • SCCM 35th Critical Care Congress: Situational Sedation and Analgesia, presented January 9, 2006; abstract
  • Approximately 70% of the audience indicated that they never used the agent
  • used in combination with propofol, opioids, and anxiolytic agents
dexmedetomidine
Dexmedetomidine
  • respiratory stability and easy routine stability
  • slow the heart rate, the hemodynamic response is predictable
  • "there is no need to discontinue [the drug] prior to extubation."
  • No loading dose is required with the drug
  • High dosage cause significant bradycardia and hypotension
  • need to use caution when administering it to patients with hypovolemia or heart block
  • very expensive
  • more pain and discomfort and poorer sleep quality than other sedatives, such as propofol
slide76
dexmedetomidine in 39 children admitted to the pediatric intensive care unit (PICU) after heart surgery between October 2004 and June 2005
  • ranged in age from 3 months to 18 years
slide77
92% of the patients needed no supplemental medication with fentanyl, midazolam, or other sedative agents while receiving dexmedetomidine,
  • 79% received minimal or no supplemental analgesia
  • Reduction in systolic blood pressure was less than 8% and heart rate reduction was less than 12% in the first 4 hours
  • no appreciable hemodynamic changes
  • no evidence of respiratory depression
  • no cases of rebound or withdrawal after either weaning or abrupt discontinuation of the drug
  • Survival was 100%.
slide78
癱瘓敵軍 美考慮用肌肉鬆弛劑
  • 藥物能夠「有效影響中樞神經系統組織,並產生較不焦慮、較不具攻擊性,以及較為鎮定的行為」
  • 賓州州立大學科學家們推薦「立即考慮」使用的藥物,包括diazepam,也就是肌肉鬆弛劑煩寧的主要成分,以及用來鎮定加護病患的dexmedetomidine

〔自由時報編譯中華民國91年5月27日星期一〕