Clinical pharmacist Lihua FangKoo Foundation cancer center

(2015/01/08)

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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 ICUsRespiratory, cardiac, and neurosurgical ICUs

Open : managed by their primary admitting physician

Close : qualified intensive care physicians and nursesspecialist training programs : intensive care

medicine

ICU revolutionThe 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 catheterFluid , blood transfusions, oxygen, and

vasopressors

Education and Training ofClinical PharmacistsASHP established a formal accreditation process in 1962ASHP : 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 112/04/21

Critical care: the presentMechanical ventilators : smaller, more mobile, and more

user-friendlyPortable ultrasoundLess invasive, less interventional, more humane

Unrestricted visiting Improved communication with pts and families in daily

practice and decision-makingMultidisciplinary approach

nutritionists, physiotherapists, pharmacists, infectious disease consultants, other relevant specialties

Local, regional, and international surveillance systems to monitor antibiotic resistance and microbiology patterns.

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Critical Care 2013, 17(Suppl 1):S2

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Critical care: the presentIn 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 presentSepsis

Tight glucose controlModerate-dose steroids in septic shockActivated protein C 

Guidelines Sepsis management, Nutrition, red blood cell

transfusion, ICU designChecklists ( FastHug (Feeding, Analgesia, Sedation,

Thromboembolic prophylaxis, Head-of-bed elevation, stress Ulcer prevention, and Glucose control)

Bundles

Dr. Peter Pronovost is accredited with developing the 1st Care Bundle – insertion and management of CVC’s

Intensivist in a hospital in MichiganDeveloped 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

Background to Care Bundles

1. Hand decontamination pre insertion 2. Full sterile barrier precautions (operator &

patient)3. 2% chlorhexidine for skin disinfectant4. Avoiding use of femoral site5. Removing unnecessary catheters

Interventions relating to CVC’s

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

Results 

WHO Surgery Safety ChecklistUrinary Catheter Care Bundle

Insertion and ManagementClostridium difficile care bundleVentilator assisted Pneumonia care bundle Palliative care bundlePressure area care bundleSepsis care bundlePVC care Bundle

Types of Care Bundles

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Critical care: the futureIn 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 futureTo provide adequately trained medical and

paramedical staff To deal with the shortages in physician cover

Computerized,Nurse-run protocolsUse 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 pharmacistsGetting started (set the scene)

One sentence for this patientAge, gender, occupation, presentation,

duration

Major past medical historiesMajor events and treatment

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Collecting and organizing pertinent patient-specific information  Demographic

Name, age, sex, occupationMedical

Weight, high, medical problems, vital signs, allergies, past medical history, lab data, diagnosis.

Medication therapyMedications, medication used prior to admission,

Life styleTabacco, alcohol, substance use or abuse, sexual

history

What pharmacist need to prepare  ? 

Disease and reason for ICUInfection, which Organ failure

BP/ HR, I/O, FiO2Lab data interpretation

Disease/ Lab dataGot/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  03/08BUN       14                          11CRE B.    0.9                         0.9Albumin                                             3.5   2.5    2.8T. BIL           0.8    0.8                        1.3    2.3D. BIL           0.2    0.2 1.1 1.6ALP       253 478 425

AST/GOT   108                                   156 434

ALT/GPT   51                                       71 656 425GGT 337 279 Na        137                         140           134K         4.1                         4.2           4.1

AFP        7304.00

HBsAg (+), HBeAg       0.3 (Ne), Anti-HBs (-), Anti-HBe         0.86 (P

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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 catheterI & O, diets, fluids, transfusionsLines, tubes & ostomiesMedicationsVentilator setting Blood testsImage

Checklist  Pain control  (morphine, NSAIDs) Intensive Care Unit Sedation ProtocolSepsis 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 AnalgesiaCrit 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 2002The 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 : dexmedetomidineμ-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 AGENTFor 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 ventilationnot 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 trialsNot a common choice in most ICUs.

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評估工具 (sedation) 

112/04/21Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive 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 protocolMidazolam 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

Table 1. The Behavioral Pain Scale13

Copyright © 2015 International Anesthesia Research Society. Published by Lippincott Williams & Wilkins. 48

The Use of the Behavioral Pain Scale to Assess Pain in Conscious Sedated PatientsAhlers, 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

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Analgesia therapy （ Opiates ） ＊ Pharmacology of selected IV analgesics

DrugActive

metabolites

Equiv.

Dose(mg)

onsetHalf-life

(hr)Dosage

Fentanyl N 0.2 1-2min 1.5~6 0.35~1.5mcg/kg, q0.5~1h

0.1~10mcg/kg/hr

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(hydrolysis in plasma)

N 1-3 min 3~4 min 1.5mcg/kg IV loading

0.15-15mcg/kg/hr

Methadone Y 7.5~10 1-2h 15~29 Not recommended

(0.1mg/kg, q6~12h)

UnitCrit Care Med 2013; 41:263–306

Analgesia therapy （ NonOpiates ） ＊ Pharmacology of selected IV analgesics

DrugActive

metabolites

onsetHalf-life

(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 12-17 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

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Haloperidol vs olanzapine showed equivalent dexmedetomidine : a more rapid resolution of delirium versus midazolam

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PREVENTION AND TREATMENT OF DELIRIUM(DSM-IV) : Delirium

Disturbance of consciousnessChange in cognition, Development over a short periodFluctuation

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 deliriumcardinal sign, inattention. reversible

manifestation of acute illness , including recovery from a sedated or oversedated state.

The pathophysiology of deliriumUncharacterized 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 deliriumHypoactive 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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Presentation of CaseA 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 low-tidal-volume protocol with positive end-expiratory pressure (PEEP)

Norepinephrine infusion Analgesia : continuous morphine infusion

QuestionWhat sedation should be provided to this

patient? 

AnswerMajor 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 deliriumRiker Sedation–Agitation Scale (SAS) or the Richmond

Agitation–Sedation Scale (RASS)Daily interruption of sedation

Short-acting, minimum dose : be beneficialThe avoidance of benzodiazepines : reduce the risk of

delirium.

Thanks for listening 

www.sylvianickerson.ca

May start your ICU 

pharmaceutical service !