노인의학 CoreReview 섬망 2018 년 4 월 15 일 서울대병원가정의학과 손정식
COI (Conflict of Interest) Declaration 본강좌의내용에대해서본강의의발표자는직접적또는간접적인어떠한이해관계도없음을밝힙니다. 2018 년대한가정의학회춘계학술대회
요약 (1) 왜섬망이생겼을까원인을찾자. (2) 약주기보다는약끊기 (3) 환자의말을수용적으로잘들어드리자 (4) 임상시험결과섬망약물치료는큰효과가없었다. (5) 치매환자에서비정형항정신병약물은뇌졸중, 폐렴발생, 사망의증가와관련이있으므로주의하여야한다. (6) 약물을사용하게되면목표증상을정하고최소량, 단기간사용한다. (Repeat 하지마세요.)
섬망 인지기능과의식수준이 급성경과로악화되는상태
섬망 (Delirium) 의진단 Confusion Assessment Method 1. 급성변동성의정신상태변화 (Acute onset and fluctuating course) 2. 주의집중불능 (Inattention) 3. 지리멸렬한사고 (Disorganized thinking) 4. 의식수준의변화 (Altered level of consciousness) NOTE: 섬망진단은 (1) and (2) + (3) or (4) 일때
한국판간호섬망선별도구 (Nursing Delirium Screening Scale, Nu-DESC) 한국판간호섬망선별도구점수 (Score) 증상 / 징후 (Symptom/Sign) O (No) 1 (Yes) 1. 지남력장애 (Disorientation) 시간, 장소, 사람에대한잘못된인식으로지남력 (orientation) 이명확하지않거나, 헷갈려하고, 못알아본다. 2. 부적절한행동 (Inappropriate behavior) 튜브나드레싱, 의료기구를함부로빼거나제거하려하고, 침대에서막무가내로내려가려고하거나폭력적인행동 ( 물어뜯고, 때리고, 꼬집는 ) 을한다. 3. 부적절한의사소통 (Inappropriate communication) 지리멸렬함, 상황에맞지않거나엉뚱하고, 무의미하거나뜻을알수없는말을중얼거리거나횡설수설한다. 욕을하거나소리를지른다. 4. 착각 / 환각 (Illusions/Hallucinations) 현재없는무언가 ( 사람, 사물, 생명체, 귀신등 ) 가눈앞에보이거나환청이들린다고하며이러한것을만지거나잡으려고허공에손짓을하는등의행동을보인다. 누군가자신을해하려하거나, 지켜보고있다고생각한다. 5. 정신운동지연 (Psychomotor retardation) 질문에응답하는시간이느려지고, 반응하지않으려고하고, 행동이나말이없거나느려진다. 계속잠을자려고하며졸려한다. NOTE: 5 점만점에 2 점을변별점 Ref) J Korean Acad Nurs. 2012 Jun;42(3):414-23.
섬망의발생률및유병률 SETTING RATE Incidence during hospital admission After hip fracture 28% to 61% After surgery 15% to 53% During hospitalization (medical inpatients) 3% to 29% Prevalence Intensive care unit With mechanical ventilation 60% to 80% Without mechanical ventilation 20% to 50% Hospice 29% Community (persons 85 years or older) 14% At hospital admission 10% to 31% Long-term care facility and postacute care 1% to 60% Ref) Am Fam Physician. 2014 Aug 1;90(3):150-8.
섬망의약 50% 가 저활동형섬망 (Hypoactive delirium) Ref) BMJ. 2017 May 25;357:j2047. Ref) http://www.bmj.com/content/bmj/suppl/2017/05/25/bmj.j2047.dc1/hosc038261.wi.pdf
섬망의소인인자 (predisposing factor) 와유발인자 (precipitating 소인인자 (predisposing factor) Preexisting dementia or underlying cognitive impairment Sever illness at admission Comorbidity Depression Visual and/or hearing impairment Dehydration Chronic kidney disease Structural brain injury or previous stroke Advanced age History of alcohol abuse or delirium Baseline use of psychoactive drugs Male gender Malnutrition factor) Ref) J Neurocrit Care 2015;8(2):46-52. 유발인자 (precipitating factor) Psychoactive drugs Immobilization Indwelling bladder catheters Physical restraints Dehydration Poor nutritional state Iatrogenic complications Intercurrent medical illness Major surgical procedure Metabolic derangements (eg. electrolytes, acid-base imbalance) Infections Hypoxia Alcohol or drug intoxication or withdrawal Pain Emotional stress Sleep deprivation
섬망을일으킬수있는약물 High risk Anticholinergics (e.g., antihistamines, muscle relaxants, antipsychotics) Benzodiazepines Dopamine agonists Meperidine (Demerol) Moderate to low risk Antibiotics (e.g., quinolones, antimalarials, isoniazid, linezolid [Zyvox], macrolides) Anticonvulsants Antidizziness agents Antiemetics Antihypertensives (e.g., beta blockers, clonidine [Catapres]) Antivirals (e.g., acyclovir [Zovirax], interferon) Corticosteroids Low-potency antihistamines (e.g., histamine H 2 blockers, urinary and gastrointestinal antispasmodics) Metoclopramide Narcotics other than meperidine Nonsteroidal anti-inflammatory drugs Sedatives/hypnotics Tricyclic antidepressants Ref) Am Fam Physician. 2014 Aug 1;90(3):150-8.
비약물적섬망예방알고리듬 Ref) 비약물적섬망예방알고리듬. 임상간호연구제 16 권제 3 호, 2010 년 12 월.
섬망의비약물적치료 복용하는약제수를줄인다. 통증조절, 수면환경개선, 수분및전해질보충, 영양공급, 감각이상에대해평가한다. 가능하면거동을하도록권고한다. 배변및방광기능개선 반복적으로지남력확인 장소와시간을알수있게주변환경을개선
섬망의비약물적치료 환자및가족교육 환자와분명하고간결하게의사소통을한다. 간병인이자주바뀌지않게익숙한보호자가간병한다. 날짜와시간을자주상기시키며, 지남력회복에도움이되도록시계, 달력등을환자에게제공하고, 익숙한물건들을가져다놓는다.
섬망의약물치료 할로페리돌 (haloperidol) 클로르프로마진 (chlorpromazine) 보다진정작용이적다. 근긴장이상과정좌불능증과같은추체외로증상의유무를감시 초조증상이동반 벤조디아제핀계약물병용투여고려
섬망의약물치료 (1) 심한섬망증상 Haloperidol: 0.5-2mg IM 1-4시간마다 prn으로반복한다. Lorazepam: Haloperidol 투여에도혼돈증상이지속되는과다활동섬망에서는, 0.5-2mg을 4시간마다반복투여한다. (2) 경증 증등도의섬망증상 Haloperidol: 0.5-2mg PO로하루 2-3회복용한다. Quetiapine: 12.5-25mg 취침전복용으로시작, 단계적으로증량하여 200mg까지증량가능하다. Risperidone: 0.25-1mg 취침하기전복용으로시작한다. Olanzapine: 2.5-5mg 정도로시작하고, 필요에따라증량한다.
섬망의약물치료 DRUG DOSAGE ADVERSE EFFECT COMMENT Antipsychotic Haloperidol 0.5 to 1.0 mg twice daily orall y, with additional doses every four hours as needed, or intra muscularly every 30 to 60 min utes as needed (maximum do sage of 20 mg in a 24-hour p eriod) Extrapyramidal effects, prolo nged corrected QT interval/t orsades de pointes, metaboli c syndrome with long-term use Agent of choice Avoid intravenous use because of s hort duration of action Avoid in patients with withdrawal s yndrome, hepatic insufficiency, neur olpetic malignant syndrome, or Park inson disease Associated with increased mortality rate in older patients with dementia -related psychosis Atypical antipsychotics Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal) 2.5 mg once daily orally (maxi mum dosing of 20 mg in a 24 -hour period) 25 mg twice daily orally 0.5 mg twice daily orally Extrapyramidal effects, prolo nged corrected QT interval/t orsades de pointes, increase d risk of cerebrovascular acci dent, hypotension, anticholin ergic effects, metabolic synd rome with long-term use Associated with increased mortality rate in older patients with dementia -related psychosis Benzodiazepine Lorazepam (Ativan) 0.5 to 1.0 mg every four hour s orally as needed Paradoxical excitation, respir atory depression, oversedati on May worsen delirium Antidepressant Trazodone 25 to 150 mg orally at bedtim e Oversedation Second-line agent Associated with prolonged and wor sening delirium symptoms Ref) Am Fam Physician. 2014 Aug 1;90(3):150-8.
항정신병약물의부작용특징 Drug Sedation Hypotension/ dizziness Extrapyramidal side effects Anticholinergic effects Haloperidol + + +++ + Levomepromazine (methotrimeprazine) +++ +++ ++ +++ Chlorpromazine +++ +++ ++ +++ Olanzapine +++ + + ++ Quetiapine +++ ++ + +++ Risperidone ++ ++ ++ + Aripiprazole ++ + + + Ref) Drugs. 2017 Oct;77(15):1623-1643.
비정형항정신병약물의위험성 노인, 치매환자에서비정형항정신병약물은 뇌졸중, 폐렴발생, 사망의증가와관련이있 었다.
비정형항정신병약물의위험성 사망률증가 미국 65세이상의노인치매환자대규모코호트연구 치매환자에서비정형항정신병약물사용은사망률을증가 각약물비사용군의사망률은 7.2-9.8% Haloperidol 20.7%, Risperidone 13.9%, Olanzapine 13.9%, Valproic acid 12.2%, Quetiapine 11.8% 로높은사망률 Antidepressants 복용군의사망률은 8.3% Ref) JAMA Psychiatry. 2015 May;72(5):438-45.
비정형항정신병약물의위험성사망률, 뇌졸중증가 문헌검토결과 항정신병약물복용군의사망률이비복용군에비해 1.2~1.6배였고, 뇌졸중발생률도 1.3~2배였다. Ref) Am J Alzheimers Dis Other Demen. 2011 Feb;26(1):10-28.
비정형항정신병약물의위험성폐렴증가 관찰연구의메타분석결과 비정형항정신병약물복용군의폐렴발생률이비복용군에비해 1.98배 Ref) Pharmacoepidemiol Drug Saf. 2015 Aug;24(8):812-20.
약물치료의객관적효과 호주호스피스의말기환자들대상 RCT 경구 Risperidone, Haloperidol, Placebo의섬망치료효과와안전성을비교 모두에게 supportive care, individualized treatment of delirium precipitants가제공 severe distress가있거나 safety 문제가있으면필요시 subcutaneous midazolam 투여 Ref) JAMA Intern Med. 2017 Jan 1;177(1):34-42.
약물치료의객관적효과 Risperidone, Haloperidol 복용군이 Placebo 보다섬망을호전시키지못함 extrapyramidal effect 부작용큼 overall survival 도좋지못함 Ref) JAMA Intern Med. 2017 Jan 1;177(1):34-42.
섬망예방과치료에대한 RCT 와관찰연구들을메타분석한결과 수술후섬망예방을위한항정신병약물의효과는없었다. 항정신병약물사용은섬망의기간, 심각도, 입원기간에차이가없었고사망률도차이가없었다. Ref) J Am Geriatr Soc. 2016 Apr;64(4):705-14.
치매의행동 - 정신증상 (Behavioral and Psychological Symptoms of Dementia; BPSD) 관리 BPSD 를유발, 악화시킬수있는요로감염등의내 과적질환이나통증은없는지확인하고이를우선 치료 행동치료, 회상치료 (reminiscence therapy), 인정치 료 (validation therapy), 환경치료, 놀이치료등의 비약물적치료가우선
BPSD 증상별약물치료 Key symptom Depression Apathy Psychosis, Aggression Moderate Agitation/ Anxiety Severe Agitation/ Anxiety Poor sleep Drug Escitalopram, Mirtazapine Escitalopram Donepezil, Rivastigmine Galantamine Atypical Antipsychotics, Memantine Escitalopram, Trazodone, Mirtazapine, Memantine Atypical Antipsychotics, Memantine ± short term Lorazepam Mirtazapine, Trazodone Lorazepam
BPSD 약물치료용량 Drug Starting Dose Usual dose Risperidone 0.125mg-0.25mg bid 0.125mg-1mg bid Atypical Antipsyc hotics Olanzapine 1.25mg-2.5mg qd 1.25mg-5mg qd Aripiprazole 2mg qd 2mg-10mg qd Quetiapine 12.5mg-25mg qd 25mg-150mg daily Escitalopram 5mg-10mg qd 5mg-20mg qd Mirtazapine 7.5mg hs 7.5mg-30mg hs Trazodone 25mg hs 25mg-150mg/day in divided doses Lorazepam 0.5mg qd 0.5mg-1mg bid
저의 BPSD 관리 (1) 가역적인원인찾기 섬망을일으킬수있는원인들 : 내 / 외과적질환 약물 보호자, 간병인과의문제 병실, 환경의변화 통증, 변비, 급성요폐 (Acute Urinary Retention: AUR) (2) Non-Pharmacologic Treatment 가생각보다더효과적임 가역적인원인에대한처치 : 보호자, 간병인, 병실조정 Show a warm, kind, matter-of-fact manner
저의 BPSD 관리 (3) 약물치료 1) Anxiety: Lorazepam, Clonazepam 2) Depression: Escitalopram, Sertraline Neuropathic Pain 동반시 : Duloxetine, 불면증동반시 : Trazodone 3) Psychosis, Agitation & Aggression: Quetiapine, Risperidone (4) 약물치료시주의점 Quetiapine, Risperidone 같은 Antipsychotic 약물사용이 Extrapyramidal effects (EPS) 뿐만아니라사망률을증가시킴 Non-Pharmacologic Treatment 를우선고려하고 약물사용을최소량, 단기간으로제한 Target symptom 을정하고 ( 폭력, 피해망상등 ) START LOW, GO SLOW: quetiapine 12.5 mg, risperidone 0.25 mg Target symptom 호전되면약감량 / 중단
치매와섬망의구별 Ref) http://health.cdc.go.kr/
섬망 vs. 치매 섬망 치매 시간
저의임상경험 (1) 치매의가역적인원인찾기 (Reversible dementia) 약물부작용 (Anticholinergic Medication) Depression, Normal Pressure Hydrocephalus, Brain mass, Vitamin B12 Deficiency, Hypothyroidism, Alcohol-related Dementia, Wernicke's Encephalopathy 등 (2) 인지기능의호전을보인상당수의환자는치매가아니라섬망 이나섬망후인지기능저하였습니다.
섬망후인지기능저하는 오래지속될수있습니다. 심장수술후섬망여부와섬망지속시간에따른 MMSE 점수 Ref) N Engl J Med. 2012 Jul 5;367(1):30-9.
저활동형섬망 (Hypoactive delirium) 치매와비슷합니다. 섬망의약 50% 가저활동형섬망 Ref) BMJ. 2017 May 25;357:j2047. Ref) http://www.bmj.com/content/bmj/suppl/2017/05/25/bmj.j2047.dc1/hosc038261.wi.pdf
요약 (1) 왜섬망이생겼을까원인을찾자. (2) 약주기보다는약끊기 (3) 환자의말을수용적으로잘들어드리자 (4) 임상시험결과섬망약물치료는큰효과가없었다. (5) 치매환자에서비정형항정신병약물은뇌졸중, 폐렴발생, 사망의증가와관련이있으므로주의하여야한다. (6) 약물을사용하게되면목표증상을정하고최소량, 단기간사용한다. (Repeat 하지마세요.)
왜? 약끊기 약 Repeat 하지않기
감사합니다.