Download PAIN AND SEDATION

Clinical pharmacist Lihua Fang
Koo Foundation cancer center
(2015/01/08)
2017/5/25
加護病房發展史
照護基本原則Basic principles
臨床服務項目(Sedation, pain control,
sepsis campaign, TDM)
How to start
Services
加護病房發展史
Critical Care 2013, 17(Suppl 1):S2
 Florence Nightingale era
 The Crimean War 1853 (mortality 40%->2%), theoretical and
technical nursing education
 Dandy era (1914-1946 in John Hopkins hospital)
 The first ICU in the world,
 In 1926 for critically ill postoperative neurosurgical patients
 Ibsen era (Copenhagen)
 In 1952 poliomyelitis outbreak in Denmark, 2722 pts/ 6-month , with 316
respiratory or airway paralysis.
 Positive pressure ventilation by intubation.
 In 1953, the world's first Medical/Surgical ICU
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加護病房發展史
 Safar era 1958
 A multidisciplinary ICU was established in Baltimore,
and, in 1962, in the University of Pittsburgh, the first
Critical Care Residency was established in the United
States.
 In 1970, the Society of Critical Care Medicine was
formed
 The first ICU in Taiwan in 1967, China in 1982
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ICU revolution
 Primary specialties
 Anesthesiology or internal medicine.
 Setting
 Surgical and Medical ICUs
Respiratory, cardiac, and neurosurgical ICUs
 Open : managed by their primary admitting physician
 Close : qualified intensive care physicians and nurses
 specialist training programs : intensive care medicine

ICU revolution
 The quantity of critical care research
 Understanding of the mechanisms of critical
illness
 More sophisticated life-support and invasive
monitoring techniques
 Interventional management
 The pulmonary artery catheter
 Fluid , blood transfusions, oxygen, and
vasopressors
Education and Training of
Clinical Pharmacists
 ASHP established a formal accreditation process in 1962
 ASHP : accreditation for 15 subspecialties of pharmacy
practice.
 Critical care pharmacy residents : 12-month program
 Multiple skill sets
 direct patient care, drug information, policy development, and practice management)
 Rounding
 providing education to various members of the healthcare team in formal and informal
settings.
 Residency applicants :11%
 Board of Pharmaceutical Specialties (BPS)
 nuclear, nutrition , pharmacotherapy, psychiatric pharmacy, and
oncology pharmacy, Ambulatory Care
 2015 : add critical care and pediatric
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Critical care: the present
 Mechanical ventilators : smaller, more mobile, and more
user-friendly
 Portable ultrasound
 Less invasive, less interventional, more humane
 Unrestricted visiting
 Improved communication with pts and families in daily
practice and decision-making
 Multidisciplinary approach
 nutritionists, physiotherapists, pharmacists, infectious
disease consultants, other relevant specialties
 Local, regional, and international surveillance systems to
monitor antibiotic resistance and microbiology patterns.
Critical Care 2013, 17(Suppl 1):S2
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ICU is a place : Complicated
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Critical care: the present
 In 1990s
 Accepted practices lack of solid, high-level evidence
 Well-designed, randomized trials




The pulmonary artery catheter, blood transfusions, the use of
albumin
Hb >10 g/dl cutoff value; high tidal volumes, low-dose
dopamine to prevent renal failure
Routine insertion of the pulmonary artery catheter :
↑complications and costs
Excess sedation : worse outcomes
Critical care: the present
 Sepsis
 Tight glucose control
 Moderate-dose steroids in septic shock
 Activated protein C
 Guidelines
 Sepsis management, Nutrition, red
blood cell transfusion, ICU
design
 Checklists ( FastHug (Feeding, Analgesia, Sedation,
Thromboembolic prophylaxis, Head-of-bed elevation, stress
Ulcer prevention, and Glucose control)
 Bundles
Background to Care Bundles
 Dr. Peter Pronovost is accredited with developing the
1st Care Bundle – insertion and management of CVC’s
 Intensivist in a hospital in Michigan
 Developed a checklist for insertion and management
of CVC’s to ensure that key interventions
recommended by the CDC 2002 guidelines were
implemented every time a CVC was inserted
Interventions relating to CVC’s
1.
2.
3.
4.
5.
Hand decontamination pre insertion
Full sterile barrier precautions (operator & patient)
2% chlorhexidine for skin disinfectant
Avoiding use of femoral site
Removing unnecessary catheters
Results
 103 ITU’s in 67 hospitals data was included in the
study results
 Medium rate of catheter-related blood stream
infections per 1000 catheter days decreased from 2.7 at
baseline to 0 at 3 months after implementation
 67% reduction in catheter related blood stream
infections over the 18 months
Types of Care Bundles
 WHO Surgery Safety Checklist
 Urinary Catheter Care Bundle
 Insertion and Management
 Clostridium difficile care bundle
 Ventilator assisted Pneumonia care bundle
 Palliative care bundle
 Pressure area care bundle
 Sepsis care bundle
 PVC care Bundle
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Critical care: the future
 In 2010 Halpern and Pastores in USA
 4% decrease hospital beds, ICU beds increased by 7%.
 Non-ICU inpatient days increased by 5%, but ICU
inpatient days increased by 10%.
 Annual critical care medicine costs : increased 44%,
 the proportion of hospital costs and national health
expenditures allocated to critical care medicine
decreased by 1.6% and 1.8%
Crit Care Med 2010, 38:65-71
Critical care: the future
 To provide adequately trained medical and paramedical
staff
 To deal with the shortages in physician cover
 Computerized,
 Nurse-run protocols
 Use of telemedicine
 Effective admission and discharge criteria to limit use
of ICU beds for those who will really benefit from
them
 Financial, academic, and job satisfaction incentives to
encourage staffs to move into critical care
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Clinical pharmacists
Getting started (set the scene)
 One sentence for this patient
 Age, gender, occupation, presentation, duration
 Major past medical histories
 Major events and treatment
Collecting and organizing pertinent
patient-specific information
 Demographic
 Name, age, sex, occupation
 Medical
 Weight, high, medical problems, vital signs,
allergies, past medical history, lab data, diagnosis.
 Medication therapy
 Medications, medication used prior to admission,
 Life style
 Tabacco, alcohol, substance use or abuse, sexual
history
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What pharmacist need to prepare ?
 Disease and reason for ICU
 Infection, which Organ failure
 BP/ HR, I/O, FiO2
 Lab data interpretation
 Disease/ Lab data
 Got/Gpt, total bilirubin, Na, K, Mg, P, INR, Hb, WBC,
Plt, BUN/Cr.
 Blood gas
 EKG : sinus rhythm, Af, QT interval prolongation,
VT
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48歲男性 B 肝帶原，經過部份肝切除，但有局部復發且 IVC栓塞
。最後一次 經動脈化學栓塞TACE (2/18)後。病人開始有腹脹,懷
疑肝癌惡化。
02/10 02/11 02/11 02/14 02/14 02/14 02/26 03/01 03/04 03/08
BUN
14
11
CRE B. 0.9
0.9
Albumin
3.5
2.5
2.8
T. BIL
0.8 0.8
1.3
2.3
D. BIL
0.2 0.2
1.1
1.6
ALP
253
478
425
AST/GOT 108
156
434
ALT/GPT 51
GGT
Na
137
K
4.1
71
656
337
AFP
HBsAg (+), HBeAg
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140
4.2
425
279
134
4.1
ation
7304.00
0.3 (Ne), Anti-HBs (-), Anti-HBe
Lab data
interpret
0.86 (P
Hyperkalemia
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Sinus slowing and atrioventricular block
with one junctional escape beat
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Atrial fibrillation
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Active problems ?
 Forming a hypothesis
 Looking for supportive evidence
 Management and intervention
 A dynamic feedback loop !
Apply parameters !
 Vitals (TPR)
 Sp02, EKG monitor, Swan-Ganz catheter
 I & O, diets, fluids, transfusions
 Lines, tubes & ostomies
 Medications
 Ventilator setting
 Blood tests
 Image
Checklist
 Pain control (morphine, NSAIDs)
 Intensive Care Unit Sedation Protocol
 Sepsis campaign
 Pressors (dopamine, norepinephrine), fluid
(albumin, N/S), steroid (hydrocortisone dose,
when to give), antibiotics (how to choose)
 Stress ulcer prophylaxis ( who is candidate? )
 Sugar control ( <150mg/dl,<200mg/dl)
 Drug adjustment
 Renal , liver impairment
 ADR
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Sedation and Analgesia
Crit Care Med 2013; 41:263–306
 The Society of Critical Care Medicine（SCCM）and
the American College of critical care medicine
（ACCM）in 1995
 published clinical practice guideline for sedation and
analgesia for the critically ill patients.
 ACCM and SCCM have joined with ASHP to develop
new clinical practice guidelines in 2002
 The recommendations were graded according to the
strength and quality of the scientific evidence.
 “pain, agitation, and delirium” (PAD) guidelines
N Engl J Med 2014; 370:444-454
Recommendation
 The quality of evidence
 High (level A), moderate (level B), or low/very low (level
C), based on both study design
 The strength of recommendations was defined
 Strong (1)
 Weak (2),
 Either for (+) or against (–) an intervention
 A no recommendation (0)
 A strong recommendation either in favor of (+1) or
against (–1)
ICU 病房的止痛與鎮靜
 目的:
 不痛
 使病人在半睡半醒中，保持安靜與放鬆狀態.
 止痛劑(analgesia)
 Morphine 是最好的選擇。
 Meperidine (no more than 48 hrs or
dose>600mg/24hrs): metabolize to
normeperidine.
 Contraindication 1. renal impairment 2. MAOI.
 Duration of the morphine and meperidine : 3-4
hrs.
CHOICE OF SEDATIVE AGENT
 No sedative drug is clearly superior to all others.
 Midazolam, lorazepam , propofol, dexmedetomidine.
 Remifentanil, an opioid, is also used as a sole agent because




of its sedative effects.
Benzodiazepines : γ-aminobutyric acid type A (GABAA)
receptors, as in part does propofol
An α2-adrenoceptor agonist : dexmedetomidine
μ-opioid receptor agonist : remifentanil is a Sedatives and
Analgesics in Common Use in the ICU.).
The choice of agent
 by tradition and familiarity
CHOICE OF SEDATIVE AGENT
 For rapidly adjusted : propofol or remifentanil
 Propofol vs BZD : reduction in the length of stay in the ICU.
 Dexmedetomidine has advantages over benzodiazepines
analgesia, less respiratory depression, more interactive to
communicate their needs.
 Less delirium and a shorter duration of mechanical ventilation
 not reduced stays in the ICU or hospital.
 Remifentanil : T1/2 3 to 4 minutes that is independent of the
infusion duration or organ function.
 Surgical patients in ICU
 Small trials
 Not a common choice in most ICUs.

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評估工具 (sedation)
Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive
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Care UnitCrit Care Med 2013; 41:263–306
ICU 病房的鎮靜藥物使用
 Propofol
 用於BZA (lorazepam)無法成功鎮靜的病人。as a last
resort for patients not successfully sedated with high
dose lorazepam (>20mg/h or >240mg/day, morphine,
and haloperidol.
 限住加護病房使用人工呼吸器治療且需要每日進行
神智評估之病例使用。
 每日劑量10-25amps，每次使用以不超過72小時為
原則。
 不得作為例如性使用。
Propofol
 Propofol 主要用於鎮靜安眠，但也有抗癲癇與輕微失
憶作用。
 高脂溶性，開始作用速度快 (< 1 minute)與停藥快速恢
復。經肝臟 conjugation 成為不活性代謝物， 再經腎臟
排除。 肝腎功能不全並不影響藥物排除。
 抗嘔吐作用 : short duration of action.
 副作用 : 低血壓 ( especially a bolus dose)
 重要問題
 propofol is prepared in a solution of soybean oil, glycerol,
and purified egg phosphatide.( sepsis and death)
 呼吸與心臟. (Apnea and hypotension )
Propofol
 輸注時間超過 24到 48 hrs
 hypertriglyceridemia, pancreatitis, increased
carbon dioxide production, and an excessive
caloric load (the emulsion contains approximately
1.1 kcal/mL).
 藥廠建議每12小時丟棄針筒(Tube )
 5個案報告 “ propofol 增加兒童死亡率.
 漸進式代謝性酸中毒, bradyarrhythmia, 心臟衰竭，
急救反應無效. propofol 不建議用於兒童
ICU 病房的鎮靜藥物使用
 Lorazepam
 用於所有 ICU 病人，使用鎮靜時間超過24小時 (starting
dose=2-4 mg iv q1-4 hrs)
 如果插管超過24 小時，可考慮將 midazolam 轉換成
lorazepam。.
 Intermittent iv bolus administration is preferred. (no
maximum dose)
 Midazolam
 限於會在24小時內拔管病人 (starting dose =1-2 mg iv every
1-2 hrs)
 用於短期的鎮靜。
建議as 和信醫院protocol
 Midazolam 或 diazepam 可用於急性躁動的快速鎮靜。
(Grade of recommendation = C)
 Propofol 用於需要快速醒來的鎮靜劑 (用於神經學評估
或拔管)。(Grade of recommendation = B)
 Midazolam 只建議用於短期使用,如果使用超過48至72小
時，從清醒至拔管時間，因為有活性代謝產物，而使得
清醒時間無法預估。(Grade of recommendation = A)
 Lorazepam 建議用於大部份病人的鎮靜，可用靜脈注射
或持續輸注。 (Grade of recommendation = B)
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Table 1
The Use of the Behavioral Pain Scale
to Assess Pain in Conscious Sedated
Patients
Ahlers, Sabine J. G. M.; van der Veen,
Aletta M.; van Dijk, Monique; Tibboel,
Dick; Knibbe, Catherijne A. J.
Anesthesia & Analgesia. 110(1):127-133,
January 2010.
doi: 10.1213/ANE.0b013e3181c3119e
Table 1. The Behavioral Pain Scale13
Copyright © 2015 International Anesthesia Research Society. Published by Lippincott Williams & Wilkins.
48
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Analgesia therapy（Opiates）
＊Pharmacology of selected IV analgesics
Drug
Active
Equiv.
metabol Dose(m
ites
g)
onset
Halflife
(hr)
1.5~6
Dosage
Fentanyl
N
0.2
1-2min
Hydromorphone
N
1.5
5-15 min 2~3
10~30mcg/kg, q1~2h
7~15mcg/kg/hr
Morphine
Y
10
5-10 min 3~7
0.01~0.15mg/kg, q1~2h
0.07~0.5mg/kg/hr
Ramifentanil
N
1-3 min
3~4 min
1.5mcg/kg IV loading
0.15-15mcg/kg/hr
1-2h
15~29
Not recommended
(0.1mg/kg, q6~12h)
(hydrolysis in plasma)
Methadone
Y
UnitCrit Care Med 2013; 41:263–306
7.5~10
0.35~1.5mcg/kg, q0.5~1h
0.1~10mcg/kg/hr
Analgesia therapy（NonOpiates）
＊Pharmacology of selected IV analgesics
Drug
Active
metaboli
tes
onset
Halflife
(hr)
Dosage
Ketamine
Y
30-40
sec
2~3 hr
0.1~0.5 mg/kg followed by
0.05~0.4mcg/kg/hr
Ketorolac
N
10 min
2-8 hr
30mg IV/IM q6h up to 5 days max
dose=120mg х5 days
ACT
N
30-60
min
2-4 hr
325mg-1gm q4-6 hrs
MAX<4gm/daily
Ibuprofen
N
25 min
2-2.5hr
400mg q4h
Max dose: 2.4g/day
Carbamazepine
N
4-5 hr
Initial
25-65,
then 1217 hr
50-100mg bid, titrate 100-200mg
q4-6hr (max 1200 mg/day)
Gabapentin
N
N/A
5-7 hr
100mg tid maintain: 900-3600mg
UnitCrit Care Med 2013; 41:263–306
Haloperidol vs olanzapine showed equivalent
 dexmedetomidine : a more rapid resolution of delirium versus
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midazolam
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PREVENTION AND TREATMENT OF DELIRIUM
 (DSM-IV) : Delirium
Disturbance of consciousness
Change in cognition,
Development over a short period
Fluctuation
 Delirium defined by NIH
 “sudden severe confusion and rapid changes in brain
function that occur with physical or mental illness.”
 The most common feature of delirium
 cardinal sign, inattention. reversible manifestation of
acute illness , including recovery from a sedated or
oversedated state.




The pathophysiology of delirium
 Uncharacterized and may vary depending on the cause.
 Increased risk : GABAA agonists and anticholinergic drugs
 Central cholinergic deficiency
 Excess dopaminergic activity
 Pharmacologic management : empirical.
 A clinical diagnosis (incidence in the ICU 16% to 89%)
 Risk factors
 Advanced age, more than one condition associated with
coma, followed by treatment with sedative medications, a
neurologic diagnosis, and increased severity of illness.
 Increased mortality
 10% increase in the relative risk of death for each day of
delirium, and decreased long-term cognitive function.
Two distinct forms of delirium
 Hypoactive and agitated (or hyperactive).mixed delirium.
 Hypoactive form
 inattention, disordered thinking, and a decreased level
of consciousness without agitation. Pure agitated
delirium < 2% in the ICU.
 least likely to survive, better long-term function than
those with agitated or mixed delirium.
Algorithm for the Coordinated Management of Pain, Agitation, and Delirium.
Reade MC, Finfer S. N Engl J Med 2014;370:444-454.
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multidisciplinary medical
rounds
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Presentation of Case
 A 77-y/d man
 Hypertension and hypercholesterolemia, previous
heavy alcohol intake, and mild cognitive impairment is
admitted to the ICU after a Hartmann’s procedure for
fecal peritonitis due to a perforated sigmoid colon.
 In septic shock, on mechanical ventilation with a lowtidal-volume protocol with positive end-expiratory
pressure (PEEP)
 Norepinephrine infusion
 Analgesia : continuous morphine infusion
 Question
 What sedation should be provided to this patient?
Answer
 Major surgery : a laparotomy,
 Pain assessment and control
 Sedation to ensure ventilator synchrony and to prevent
self-harm through the accidental removal of vascular
access lines or the endotracheal tube.
 Benzodiazepines : most commonly
 Short-acting anesthetic agent : propofol
 α2-adrenoceptor agonist : dexmedetomidine, popular
 Previous heavy alcohol intake and mild cognitive
impairment
 At high risk for delirium
 Riker Sedation–Agitation Scale (SAS) or the Richmond
Agitation–Sedation Scale (RASS)
 Daily interruption of sedation
 Short-acting, minimum dose : be beneficial
 The avoidance of benzodiazepines : reduce the risk of
delirium.
Thanks for
listening
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your ICU
pharmaceuti
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