대한내과학회지 : 제 86 권제 5 호 2014 http://dx.doi.org/10.3904/kjm.2014.86.5.546 특집 (Special Review) - 중환자의학의최신지견 중환자실환자의통증, 진정및섬망관리 성균관대학교의과대학삼성서울병원호흡기내과, 중환자의학과 전경만 Management of Pain, Agitation and Delirium in the Intensive Care Units Kyeongman Jeon Division of Pulmonary and Critical Care Medicine, Department of Medicine and Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Pain, agitation and delirium (PAD) occur frequently in mechanically ventilated patients in the intensive care unit (ICU). Consequently, analgesics and sedatives are frequently administered to critically ill patients with the aim of treating PAD, decreasing the physiological stress response, and improving synchrony with mechanical ventilation. However, many of the analgesics and sedatives in current use can lead to adverse outcomes, including longer durations of mechanical ventilation, prolonged ICU stays, delirium, and an increased risk of death, particularly when these agents are administered at excessive doses for prolonged periods. The purpose of this review is to provide an overview of the initial evaluation and monitoring of, and the medications commonly prescribed for, PAD. Moreover, we highlight the major recommendations of the recent guidelines published by the Korean Society of Critical Care Medicine and American College of Critical Care Medicine. (Korean J Med 2014;86:546-556) Keywords: Pain; Psychomotor agitation; Delirium; Intensive care units 서론중환자실에서시행되는기계환기등은환자에게불편감, 통증및불안등을유발하게되며 [1], 이로인해많은수의환자에서의식장애를동반한섬망 (delirium) 이발생하게된다 [2]. 따라서적절한진통 (analgesics) 및진정 (sedation) 이필요하며 [3,4] 이를위한많은노력들이진료지침으로개발되 어발표되고있다 [5,6]. 중환자실에서적절한진통, 진정및섬망조절을위해서는이들에대한정확한평가가필요하며이에따른적절한약물선택및용량조절이중요하다. 본종설에서는현재까지발표된진통, 진정및섬망에대한자료들을검토하고, 이를바탕으로실제진료에적용할수있는진료지침을다시정리해보고자한다. Correspondence to Kyeongman Jeon, M.D., Ph.D. Division of Pulmonary and Critical Care Medicine, Department of Medicine and Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea Tel: +82-2-3410-3429, Fax: +82-2-3410-3849, E-mail: kjeon@skku.edu Copyright c 2014 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 546 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Kyeongman Jeon. Management of pain, agitation and delirium in the intensive care units - 진통 (analgesia) 중환자실에서발생하는불편감및통증은치료적, 감시적목적으로삽입된카테터, 배액관, 기관내삽관뿐아니라기도흡인, 체위변경등의일상적인간호과정에서도발생하며 [7], 침상에오래누워있는것자체만으로도통증의원인이된다 [8]. 이러한통증이적절하게조절되지않으면빈맥, 심근의산소소모증가, 면역억제, 지속적인이화작용등의스트레스반응의원인이된다 [9,10]. 따라서통증에대한적절한조절이필요하며이를위해서는통증의평가와통증치료에대한반응이적합한방법에의해규칙적으로평가되고체계적으로기술되어야한다. 통증의평가통증의평가는환자가표현하는통증정도가표준이되어 야하므로먼저환자에게통증여부를물어보고통증정도를확인하는것이무엇보다중요하다 [6]. 이를위해 Visual Analogue Scale (VAS), Numeric Rating Scale (NRS) 등이사용되고있으며통증의정도를 무통 에서 매우심한통증또는극도로심한통증 의어구를표시하거나 0에서 10까지점수화하여이를통해환자의통증정도를표현하게한다. 등급표를읽지못하거나이해하지못하는환자에게적용하기어려운단점이있으나많은중환자실환자들에게직접적용되고있다 [11,12]. 하지만대부분의중환자실환자들은본인의의사를표현하지못하는경우가많으므로이를사용하기엔제한적이다 [13]. 이런경우환자들의통증과관련된움직임, 표정, 자세와심박수, 혈압, 호흡수같은생리적지표의변화를이용하는행동통증평가도구 (behavioral pain assessment tools) 를사용하게된다. 대표적인행동통증평가도구로 Behavioral Pain Scale (BPS) [14] 과 Critical-Care Pain Observation Tool (CPOT) [15] 이있으며자기의사를표현할수없는내과 지표 기술 (Description) 점수 얼굴표정 어떠한근육의움직임도관찰되지않음 이완 0 이마를찌푸리거나, 눈썹을찡그리거나눈꼭감음 긴장 1 이마를찌푸리거나, 눈썹을찡그림 얼굴을우거지상으로찡그림 2 안면을움직이거나눈꺼풀을단단히감음 몸의움직임 전혀움직이지않음 움직임의부재 0 느리면서조심스러운움직임, 통증부위를만지거나문지름행동에집중하는모습보임 방어적행동 1 튜브를잡아당기거나앉으려고함, 사지를움직이거나몸부림침지시에따르지않고침대에서나오려고시도함 - 547 - 가만있지못함 2 상지의근긴장도 수동적인움직임에저항없음 이완 0 수동적인움직임에저항있음 강직, 긴장 1 수동적인움직임에강한저항보임 심한강직, 긴장 2 인공호흡기와의순응도 ( 기관삽관환자 ) 혹은발성 ( 발관환자 ) 편한호흡알람울리지않음 기계호흡환자의움직임과순응도좋음 자동적으로알람멈춤 기침하나곧없어짐 1 비동시성 : 알람이자주울림 기계호흡과의충돌 2 정상적인어조로말하거나소리없음 정상어조로말하거나소리없음 0 한숨, 신음소리냄 신음, 탄식 1 소리내어울거나흐느껴움 고함을지르거나흐느껴움 2 합계 0-8 Figure 1. Translated version to Korean of critical-care pain observation tool used in Samsung Medical Center. 0
- 대한내과학회지 : 제 86 권제 5 호통권제 645 호 2014 - 계, 외과계및외상환자들에서통증의정도를평가하는데가장유효하고신뢰할수있는도구들이다 [6]. 국내일부병원에서도 CPOT 를한국어로번역하여사용하고있으나이에대한유효성과신뢰에대한평가가필요하다 (Fig. 1). 통증조절을위한약물의선택통증의조절을위해서는진통제를사용하게되나먼저적절한체위유지, 기타물리적자극의제거등을통해환자의안락함을유지할수있는비약물요법이선행되어야한다 [5, 6]. 이는불필요한진통제사용을줄이고진통제의효과를최대화할수있다 [16]. 하지만대부분의환자들은약물을통한진통이필요하게되며환자의상태와약물의약리학적정보에따라적절한약물을선택하게된다. 예를들어쇼크환자의경우간혹은신장의혈류가감소하여약물의대사및청소율이감소할수있고, 지속적주입은약동학 (pharmacokinetics) 을변화시킬수있다 [17]. 또한비만의경우약물분포용적 (volume of distribution) 에영향을주고유전적소인에따라약물의반응및대사에차이가있을수있다 [18]. 이외에도약물주입이중단되었을때혈중농도가 50% 까지감소하는데소요되는시간을의미하는 'context-sensitive halflife' 개념을이해하는것이매우중요하다 [19]. 중환자실에서사용되는모든진통, 진정제는시간이지남에따라혈액, 지방및중추신경계수용체등각종구획 (compartment) 사이에존재하는약물의농도차에따라혈중농도는변하게된다. 따라서 context-sensitive half life는주입되는약물의분포와대사에따라다르며일반적으로주입되는시간이길어질수록길어지게된다 [3]. Benzodiazepines, morphine, fentanyl 같은약물은정주시간이길어질수록 context-sensitive half- time이늘어나며 propofol, remifentanil은상대적으로영향이적은편이다 [20,21]. 중환자실에서진통을위해사용할수있는약제로는마약성진통제, 비스테로이드성소염진통제, 그리고 acetaminophen 등이있으나비신경병증통증의경우 fentanyl, hydromorphone, morphine 및 remifentanil 등의마약성진통제를정주할것을추천하고있다 [20]. 이외에도 gabapentin이나 carbamazepine 같은항경련제는신경병증통증조절에마약성진통제와더불어추천된다 [20]. 또한비마약성진통제의사용은마약성진통제의사용을줄이거나마약성진통제의부작용을감소 시키기위해고려될수있다. 마약성진통제는 μ1 opioid receptor 를자극하여중추신경계통증반응을억제하며, 그외수용체들은호흡저하나진정효과도나타낸다 [22]. 특히이산화탄소반응곡선을우측편위시켜환기량은유지되나호흡수는저하되는 'slow and deep respiration' 양상을보이며이는 benzodiazepine 에의한호흡억제패턴과구분이된다. 일반적으로마약성진통제는간에서대사되고콩팥으로배설된다. 따라서 morphine은체내에서분해되어활성대사물질 (active metabolites) 이되고이는콩팥에축적될수있어신기능저하시사용에주의가필요하다. Hydromorphone은 morphine에비해 5-10배강한진통효과를내며활성대사물질을가지고있지않으나신기능저하시약물 (parent drug) 이체내에축적되어혈중농도가증가된다. Fentanyl은지용성때문에작용시간이빠르지만지용성때문에지방조직에축적되어중단후에도장기효과가있을수있으므로주의해야한다 [23]. 하지만 fentanyl은신장으로대사물질을배설하지않는다. Remifentanil 은작용시간이빠르고혈액내비특이적효소에의해불활성화되므로간및신기능저하에영향을받지않는다. 아직무작위대조연구가적은편이나중환자실에서사용되는마약성진통제중진통제의장기효과를줄이고 morphine 이나 fentanyl에비해적은용량으로진통을조절할수있다는점으로각광받고있다. 하지만 remifentanil을포함한모든마약성진통제는내성이유도되어동일한진통효과를위해서는약제를증량해야하는단점이있다. 또한통각과민 (hyperalgesia) 같은통증에대한과민성은 remifentanil 같은속효성약물에서발생할수있으며 [24], 특히 remifentanil 은빠른시간내에대사되므로약제중단시바로진통조절이되지않는상황이발생할수있다. 진정 (sedation) 중환자실환자들은자주흥분하고불안하게되며이는부정적인임상결과를초래하게된다. 따라서적절한통증조절후에도이에대한평가및조절이필요하며 [6], 적절한통증조절만으로도추가적인진정제없이환자의안정을유지할수도있다 [25]. 중환자실환자들은체위변경이나구두를통한안심시키기같은비약물적처치로도도움이될수있으나대부분의경우이들만으론적절하지않아진정제투여가필요하다. 적절한진정제는환자의스트레스를완화시키고 - 548 -
- 전경만. 중환자실환자의통증, 진정및섬망관리 - 중환자실의일반적인시술이용이하게이루어지도록도와주며환자의안전과편안함을유지하는데크게도움이되므로중환자치료에필수적이지만, 과도한사용으로인해발행하는부작용을주의하여야한다 [25]. 진정수준의평가적절한진정을위해서는진정상태에대한객관적인평가가우선되어야하며, 이상적인평가를위해서는평가하기편 리하고진정수준이명확하게분리되어있고평가된진정수준에따라진정제사용량의조절이가능하고중환자들에게사용이효과적이고신뢰성이높아야한다. 현재까지많은주관적인평가방법들이보고되고있으며이중 Ramsay Sedation Scale 이가장많이사용되고있는진정평가도구이다. Ramsay scale [26] 은세단계의각성상태와세단계의기면상태를측정하는것으로되어있으나각단계를구별하는명확한기술이되어있지않고각단계의특징적인구별법이없다 (Fig. 2). Sedation-Agitation Scale (SAS) [27] 은 Ramsay scale을 Scores Level of sedation-agitation Description Ramsay Sedation Scale [26] 1 Awake levels Anxious or restless or both 2 Cooperative, orientated and tranquil 3 Responding to commands 4 Asleep levels Brisk response to stimulus 5 Sluggish response to stimulus 6 No response to stimulus Sedation Agitation Scale [11] 7 Dangerous agitation Pulling at endotracheal tube (ETT), trying to remove catheters, climbing over bedrail, striking at staff, thrashing side-to-side 6 Very agitated Does not calm despite frequent verbal reminding of limits, requires physical restraints, biting ETT 5 Agitated Anxious or mildly agitated, attempting to sit up, calms down to verbal instructions 4 Calm and cooperative Calm, awakens easily, follow commands 3 Sedated Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands 2 Very agitated 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 Richmond Agitation Sedation Scale [13] +4 Combative Overtly combative, violent, immediate danger to staff +3 Very agitated Pulls or removes tube(s) or catheter(s); aggressive +2 Agitated Frequent non-purposeful movement, fights ventilator +1 Restless Anxious but movements not aggressive vigorous 0 Alert and calm -1 Drowsy -2 Light sedation Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice (> 10 sec) Briefly awakens with eye contact to voice (< 10 sec) -3 Moderate sedation Movement or eye opening to voice (but no eye contact) -4 Deep sedation No response to voice, but movement or eye opening to physical stimulation -5 Unarousable No response to voice or physical stimulation Figure 2. Subjective sedation scales used in the intensive care units. - 549 -
- The Korean Journal of Medicine: Vol. 86, No. 5, 2014 - 바탕으로흥분정도를좀더세분화한것이며 (Fig. 2), Richmond Agitation-Sedation Scale (RASS) [28] 은각성상태, 인지기능및응답에대한지속가능성을바탕으로평가하는도구 (Fig. 2) 로 SAS와함께진정의정도와깊이를측정하기위한가장유효하고안정적인진정평가도구로권고되고있다 [24]. 주관적인평가도구외에 bispectral index (BIS) 같은진정수준의객관적인평가는매우깊은진정상태또는치료적근이완제사용으로환자행동이관찰되지않을때유용하게사용하게된다. 하지만이러한객관적인평가도구를비혼수, 비마비상태의환자들의진정정도를평가하는주관적인평가도구대신에사용하는것은권고되지않는다 [5,6]. 진정제의선택과거부터많이사용되는진정제로 benzodiazepines, propofol 및 α2-agonist 등이있다. Benzodiazepine 계열의약물은 GABA 수용체길항작용을통해불안완화, 진정및최면효과를나타내며대표적으로 midazolam과 lorazepam이많이사용된다 [17]. 두약물모두지용성을보이며 midazolam은혈관- 뇌장벽을보다빨리통과하여 lorazepam보다빠른진정효과를보인다. 하지만지용성때문에쉽게대사되지않는체내지방조직에축적되게된다 [29]. 또한간내 CYP450 효소에의해대사되어간기능이상시혈중약물농도가높아지므로주의가필요하다. Midazolam은활성대사물질로분해되어신기능이떨어진경우체내에축적될수있어신기능이상시사용하지않는것이좋다 [30]. 하지만 lorazepam의경우 midazolam에비해지용성이낮으므로진정효과가늦게나타나나대사물질이활성화되지않아신기능저하시선호되는 benzodiazepine 계열약물이다 [17]. Benzodiazepine 계열의약물또한마약성진통제와같이호흡을억제하며이경우호흡수및환기량모두억제되게된다. Benzodiazepine 은드물게역설반응이나타나흥분상태를악화시키는데고령의환자에서더자주발생한다. 또한 benzodiazepine 을사용하는환자에서섬망발생의빈도가높으며 [31] 고용량으로장기간사용시금단증상이발생할수있다 [32]. 드물지만 lorazepam 용매내의 propylene glycol 성분으로인한독성반응이나타날수있으며고삼투압성대사성산증, lactic acidosis, 저혈압및부정맥등의증상을보인다 [33]. 전통적으로 benzodiazepine 은일차약제로사용되고있으나새로운약제인 propofol이나 dexmedetomidine과직접비교한여러무작위연구에서섬망, 과도한진정, 기관발관지연및퇴원의지연등부정적인임상결과와관련이있다고보고되고있다 [34-39]. 따라서 American College of Critical Care Medicine에서는진정제선택시 benzodiazepine 계열의약물을지양할것을권고하고있다 [6]. Propofol 또한서구에서많이사용되는진정제로아직기전에대해명확히알려져있지않으나 GABA를포함한신경전달물질의분비를조절하여뇌에직접영향을주는것으로알려져있다 [40]. Propofol 역시지용성으로혈관- 뇌장벽을빨리통과하여작용시간이짧고약물분포용적 (volume of distribution) 이커말초조직으로의분포가빠르다. 이러한약물동택학적특성때문에장기간투여하는경우에도약물중단시회복이빨라장기간진정이필요한경우이상적인약물이며, 실제 benzodiazepine 과비교한여러연구에서 propofol 이의식의회복이나기계환기이탈시간이빠르다고보고하고있다 [34,41-45]. 하지만혈관의긴장도및심박출량을떨어뜨려저혈압이흔하게발생하며, 장기간사용시고중성지방혈증 (hypertriglyceridemia) 을유발하므로주의하여야한다. 또한고용량으로사용시대사성산증, 횡문근융해증및고칼륨혈증을특징으로하는 propofol infusion syndrome (PRIS) 이발생할수있으며서맥및심부전으로인해심정지까지진행할수있다. 따라서 4-5 mg/kg/hr 미만의용량이추천되며고용량사용시혈중 ph, lactate 및 creatine kinase 등의모니터가필요하다. 최근개발된 α2-agonist의하나인 dexmedetomidine은중추신경계에서 norepinephrine의분비를억제하여진정및진통효과를동시에가지므로중환자실에서사용되는이상적인진정제로생각되고있다. 또한다른진정제와달리호흡억제효과도없다 [46]. 앞서기술한대로 benzodiazepine 과비교시각성정도가좋고섬망의발생이적다 [36,38]. 최근보고된메타분석에서도타약제에비해기계환기기간및재원일수를줄인다고보고하고있다 [47]. 하지만약물작용기전에의해저혈압및서맥등의부작용이발생할수있다. 또한장기간의사용경험이적어미국 Food and Drug Administration (FDA) 에서는 24시간이내의단기간사용만을권고하고있다 [48]. 하지만최근보고된다기관비교임상연구에서 5-14일까지사용되어 24시간이상사용도가능할것으로기대된다 [36,42,49]. - 550 -
- Kyeongman Jeon. Management of pain, agitation and delirium in the intensive care units - 섬망 (delirium) 섬망의진단 섬망은주의력결핍을동반한의식저하, 인지기능장애등을특징으로하는급성및아급성의식장애증후군으로보고에따라다르지만적게는 20% 에서많게는 80% 의중환자실입실환자에서발생한다 [2]. 중환자실에서섬망이발생할경우우발적삽관, 카테터제거등의합병증이증가하고기계환기이탈이길어지며결국이로인해중환자실재원기간이길어지게된다. 또한이로인해단기및장기생존율의저하로이어지게된다 [50]. 미국에서시행된 1년간의관찰연구에따르면섬망이발생한환자에서병원재원기간이 10일더길어지게되고 (adjusted HR, 2.0; 95% CI, 1.4-3.0), 6개월째사망률이약 2배 (34% vs 15%; adjusted HR, 3.2; 95% CI, 1.4-7.7) 증가하게된다고하며 [50], 이러한결과는후속연구에서도관찰되고있다 [51,52]. 국립국어원의표준국어대사전에따르면섬망은 ' 외계에대한의식이흐리고착각과망상을일으키며헛소리나잠꼬대또는알아들을수없는말을하며, 몹시흥분했다가불안해하기도하고비애나고민에빠지기도하면서마침내마비를일으키는의식장애 ' 라고정의된다. 미국정신의학협회 (American Psychiatric Association) 의정신질환진단및통계편람 (Diagnostic and Statistical Manual of Mental Disorders, DSM-IV- TR. 4 th ed.) 에따르면다음의항목으로설명하고있고 (Table 1), 국제보건기구 (WHO) 의질병및관련건강문제의국제적통계분류 (International Statistical Classification of Diseases and Related Health Problems, ICD) 에서도비슷한섬망의특징들을나열하여섬망을정의하고있다. 하지만전공에따라섬망의표현도다양하며정신의학에경험이적은중환자실의 Table 1. Diagnostic criteria of delirium by DSM-IV-TR. 4th ed. Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain or shift attention. A change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established or evolving dementia. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. There is evidence from the history, physical examination or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition. Table 2. Intensive Care Delirium Screening Checklist (ICDSC) [58] Altered level of consciousness * A No response (score 0) B Response to intense and repeated stimulation (score 0) C Response to mild or moderate stimulation (score 1) D Normal wakefulness (score 0) E Exaggerated response to normal stimulation (score 1) Inattentiveness Difficulty following instructions or easily distracted Disorientation To time, place, or person Hallucination-delusion-psychosis Clinical manifestation or suggestive behavior Psychomotor agitation or retardation Agitation requiring use of drugs or restraints, or slowing Inappropriate speech or mood Related to events or situation, or incoherent speech Sleep/wake cycle disturbance Sleeping < 4 hr/day, waking at night, sleeping all day Symptom fluctuation Symptoms above occurring intermittently Total score (0-8) * If A or B, then no other items are assessed that day. - 551 -
- 대한내과학회지 : 제 86 권제 5 호통권제 645 호 2014 - 료진들이위의정의만으로중환자실환자들의섬망을진단하기는쉽지않으며많은수에서우울증등의다른정신질환으로오진되어부적절한약물이투여되고있다 [53,54]. 또한적지않은수의섬망이중환자실의료진들에의해진단되지않고있다 [55-57]. 실제중환자실에서섬망의진단에 DSM-IV나 ICD-10을적용하기는쉽지않다. 따라서기계환기등의중환자실환자들의상태와이를관찰하는중환자실의료진의특성을고려하여중환자실에서쉽게이용할수있는여러가지진단도구들이개발되고있다. 대표적인도구로 Intensive Care Delirium Screening Checklist (ICDSC) 와 Confusion Assessment Method for the ICU (CAM-ICU) 가있다. ICDSC 는의식수준의변화 (altered level of consciousness), 주의력결핍 (inattention), 인지장애 (disorientation), 정신증상 (hallucination-delusion-psychosis), 흥분 (psychomotor agitation or retardation), 부적절한언어또는기분 (inappropriate speech or mood), 수면상태 (sleep/wake cycle disturbance) 및동요정도 (symptom fluctuation) 등여덟 가지항목을조사하여각항목의점수를합하여 4점이상일경우섬망으로진단하게된다 (Table 2) [58]. 이보다더많이사용되는도구로 CAM-ICU가있다 [59,60]. 섬망의진단에서 CAM-ICU 이용은 2단계의평가가필요하며, 첫번째는 RASS (Richmond Agitation Sedation Scale) 등을이용한진정수준의평가이고, 두번째는급성정신상태또는정신상태변동이심함 (acute onset or fluctuating course), 주의력결핍 (inattention), 비체계적사고 (disorganized thinking) 및의식수준의변화 (altered level of consciousness) 등의네가지특성을이용한섬망여부의평가이다 (Fig. 3) [59]. CAM-ICU는많은연구에서쉽게이용할수있음이확인되었으며, 민감도와특이도가높은도구이다. CAM-ICU는많은나라에서번역되어사용되고있고이를교육하는웹사이트 (www.icudelirium.org) 에는여러가지교육자료와서울대학교이상민교수팀에의해번역된한국어판도구할수있다. 최근한국어판을이용한연구에서도높은민감도와특이도가확인이되었다 [61]. 하지만만족스러운평가자간의일치도를위해서는많은훈련이 Features and Descriptions Positive Negative I. Acute onset or fluctuating course A. Is there evidence of an acute change in mental status from the baseline? B. Or, did the (abnormal) behavior fluctuate during the past 24 hours, that is, tend to come and go or increase and decrease in severity as evidenced by fluctuations on RASS or GCS? II. Inattention Did the patient have difficulty focusing attention as evidenced by a score of less than 8 correct answers on either the visual or auditory components of the Attention Screening Examination (ASE)? III. Disorganized thinking Is there evidence of disorganized or incoherent thinking as evidenced by incorrect answers to 3 or more of the 4 questions and inability to follow the commands? Questions 1. Will a stone float on water? 2. Are there fish in the sea? 3. Does 1 pound weigh more than 2 pounds? 4. Can you use a hammer to pound a nail? Commands 1. Are you having unclear thinking? 2. Hold up this many fingers (Examiner holds 2 fingers in front of the patient). 3. Now do the same thing with the other hand (without holding the 2 fingers in front of the patient). IV. Altered level of consciousness Positive if the actual RASS score is anything other than 0 Overall CAM-ICU: Features 1 and 2 and either Feature 3 or 4 Figure 3. Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) [59,60]. - 552 -
- 전경만. 중환자실환자의통증, 진정및섬망관리 - 필요하여 CAM-ICU을실제임상에적용하는데는많은시간과노력이필요하다. 최근에보고된전향적관찰연구에따르면 CAM-ICU를실제임상에서적용하였을때이전연구들과다르게민감도가크게떨어진다 [57]. 즉약반수의섬망환자에서 CAM-ICU를통해평가하였을때섬망이진단되지않았다. 따라서섬망의진단에는평가도구만을이용한진단보다는종합적인관찰과평가도구를이용한진단적접근이필요하다. 섬망의치료섬망의치료는크게 1) 섬망발생과관련된위험인자를조절하여섬망의발생을예방하는것과 2) 섬망의의한증상및섬망과관련된기저상태를치료하는것으로나뉜다 [2,62,63]. 섬망의예방섬망의예방은먼저위험인자를조절하는것이무엇보다중요하다. 여러후향적관찰연구를통해여러가지위험인자들이보고되고있으며 (Table 3) 이중환자의기저질환및상태는쉽게조절할수없으나중환자실에서진료와관련된처치, 약물등은관심을가지고조절하여야하는부분이다. 특히진정및통증조절을위해투여되는 benzodiazepine이나마약성진통제는가장잘알려진위험인자이다 [31,39]. 이는전향적관찰연구에서도섬망발생과관련이있다고확인되고있어가능하면적게사용하는것이좋겠다 [28,64]. 그외기계환기나중심정맥관등으로침상에환자를고정시키거나중환자실환경적문제또는여러가지처치를통한수면장애도중요한위험인자이므로이를최소화하는것이중요하다. 섬망의치료 : 비약물적치료섬망의치료에서가장중요한것은악화인자를조절하는것이다 [2,62,63]. 기저질환과관련된대사장애를해결하고환자의움직임을저해하는불필요한카테터와억제대는빠르게제거하고안경, 보청기등으로환자의감각결손을교정하여주고, 가능하면환자의생리리듬 (circadian rhythm) 을회복시키고조기에적절한지적, 환경적자극을주는것이중요하다 [2]. 특히억제대는낙상, 우발적발관, 카테터제거등의환자의위험한행동을막는데중요하나이자체가환자를흥분시키게되며섬망발생과관련된상황들을악화시키게된다. 최근보고된전향적관찰연구에서도오랜시간의억제대적용은지속적인섬망과관련이있다고보고하고있다 [65]. 섬망의치료 : 약물적치료중환자실에서사용되는수많은약물들이섬망의악화와관련이있어섬망의약물적치료에서도중요한것은섬망을악화시키는이런약물을중단하는것이다 [2,62,63]. 또한적절한진통및진정의평가와조절도중요한약물적치료이다 [62,63]. 이럼에도급성섬망을조절하기위해항정신병약물이많이상용되고있으며, 대표적인약물이 haloperidol이다. 이는미국정신의학협회 (American Psychiatric Association, 1999) 나미국중환자의학회 (Society of Critical Care Medicine, 2002) 의진료지침에서권고하고있으며여러나라에서 60-90% 의의료진들이급성섬망을조절하는데사용하고있다. 하지만최근까지효과에대해위약대조연구를통해확인된적이없다. 최근 MIND 연구를통해중환자실에서발생하는섬망의치료에서항정신병약물 (haloperidol, ziprasidone) 의 Table 3. Risk factors for the development of delirium in the intensive care unit Host factors Factors of critical illness Iatrogenic factors Old age Acidosis Immobilization Alcoholism Anemia Medications Cognitive impairment Fever (infection) Sleep disturbances Depression Hypotension Hypertension Metabolic disturbances Smoking Respiratory distress Vision/hearing impairment Severity of illness - 553 -
- The Korean Journal of Medicine: Vol. 86, No. 5, 2014 - 유효성과안정성을알아보고자하였으나여러가지임상적결과 (outcome) 에영향이없었으며 [66], 소수의환자를대상으로한예비조사연구이기에급성섬망의치료에서 haloperidol 사용은쉽게결론짓기는어렵다. Haloperidol 외에비특이적항정신병약물 (atypical antipsychotics) 들이급성섬망의치료에사용되고있으며경구용 risperidone, olanzapine, quetiapine 등은경구용 haloperidol과비교시동등한효과를보이면서 EPS (extrapyramidal symptoms) 가적게나타난다고보고되고있다 [67]. 하지만중환자실에서급성섬망이발생하였을때빠르게조절하기위해서는정주용약물이필요하며위약물들의정주용약물의효과에서대해서는비교되지않았다. 최근정주용 haloperidol 치료에경구용 quetiapine을추가했을때섬망에서빨리회복되고흥분정도가덜하며퇴원을빨리하는경향을보였다는연구결과가보고되어 [68] 급성섬망의치료에정주용 haloperidol과경구용 quetiapine 병합을적용해보는것이좋겠다 [69]. 결 중환자실에적절한진통, 진정및섬망을관리하기위해서는진통과진정에대한폭넓은지식과평가도구를이용한적극적인사정에의해서만적절한약물을선택할수있다. 이를통한진통, 진정및섬망의관리는중환자실환자들의합병증을감소시키고재원일수를줄일수있다. 따라서각중환자실에서는진통, 진정및섬망에대한공식적인평가도구를이용하여약제를조절해나가야할것이다. 론 중심단어 : 통증 ; 진정 ; 섬망 ; 중환자실 REFERENCES 1. Desbiens NA, Wu AW, Broste SK, et al. Pain and satisfaction with pain control in seriously ill hospitalized adults: findings from the SUPPORT research investigations: for the SUPPORT investigators: study to understand prognoses and preferences for outcomes and risks of treatments. Crit Care Med 1996;24:1953-1961. 2. Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Crit Care Clin 2008;24: 657-722. 3. Patel SB, Kress JP. Sedation and analgesia in the mechanically ventilated patient. Am J Respir Crit Care Med 2012; 185:486-497. 4. Reade MC, Finfer S. Sedation and delirium in the intensive care unit. N Engl J Med 2014;370:444-454. 5. Korean Society of Critical Care Medicine. Guideline for sedation and analgesia in adult intensive care units [Internet]. Seoul: Korean Society of Critical Care Medicine, 2014c [cited April 23, 2014]. Available from: http://ksccm.inforang. com/file/notice/kjccm_file03.pdf. 6. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:263-306. 7. Novaes MA, Aronovich A, Ferraz MB, Knobel E. Stressors in ICU: patients' evaluation. Intensive Care Med 1997;23: 1282-1285. 8. Chanques G, Sebbane M, Barbotte E, Viel E, Eledjam JJ, Jaber S. A prospective study of pain at rest: incidence and characteristics of an unrecognized symptom in surgical and trauma versus medical intensive care unit patients. Anesthesiology 2007;107:858-860. 9. Epstein J, Breslow MJ. The stress response of critical illness. Crit Care Clin 1999;15:17-33. 10. Akça O, Melischek M, Scheck T, et al. Postoperative pain and subcutaneous oxygen tension. Lancet 1999;354:41-42. 11. Ahlers SJ, van Gulik L, van der Veen AM, et al. Comparison of different pain scoring systems in critically ill patients in a general ICU. Crit Care 2008;12:R15. 12. Chanques G, Viel E, Constantin JM, et al. The measurement of pain in intensive care unit: comparison of 5 self-report intensity scales. Pain 2010;151:711-721. 13. Puntillo K, Pasero C, Li D, et al. Evaluation of pain in ICU patients. Chest 2009;135:1069-1074. 14. Payen JF, Bru O, Bosson JL, et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 2001;29:2258-2263. 15. Gélinas C, Fillion L, Puntillo KA, Viens C, Fortier M. Validation of the critical-care pain observation tool in adult patients. Am J Crit Care 2006;15:420-427. 16. Erstad BL, Puntillo K, Gilbert HC, et al. Pain management principles in the critically ill. Chest 2009;135:1075-1086. 17. Devlin JW, Roberts RJ. Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiazepines, propofol, and opioids. Crit Care Clin 2009;25:431-449. 18. Weinshilboum R. Inheritance and drug response. N Engl J Med 2003;348:529-537. 19. Hughes MA, Glass PS, Jacobs JR. Context-sensitive halftime in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992;76:334-341. 20. Malacrida R, Fritz ME, Suter PM, Crevoisier C. Phar- - 554 -
- Kyeongman Jeon. Management of pain, agitation and delirium in the intensive care units - macokinetics of midazolam administered by continuous intravenous infusion to intensive care patients. Crit Care Med 1992;20:1123-1126. 21. Kapila A, Glass PS, Jacobs JR, et al. Measured contextsensitive half-times of remifentanil and alfentanil. Anesthesiology 1995;83:968-975. 22. Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician 2008;11(2 Suppl):S133-153. 23. Sessler CN, Varney K. Patient-focused sedation and analgesia in the ICU. Chest 2008;133:552-565. 24. Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg 1998;86:1307-1311. 25. Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010;375:475-480. 26. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974;2:656-659. 27. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999;27:1325-1329. 28. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002;166:1338-1344. 29. Spina SP, Ensom MH. Clinical pharmacokinetic monitoring of midazolam in critically ill patients. Pharmacotherapy 2007;27:389-398. 30. Bauer TM, Ritz R, Haberthür C, et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet 1995;346:145-147. 31. Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21-26. 32. Cammarano WB, Pittet JF, Weitz S, Schlobohm RM, Marks JD. Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients. Crit Care Med 1998;26:676-684. 33. Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines: a case series and prospective, observational pilot study. Chest 2005;128: 1674-1681. 34. Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med 2006;34:1326-1332. 35. Fong JJ, Kanji S, Dasta JF, Garpestad E, Devlin JW. Propofol associated with a shorter duration of mechanical ventilation than scheduled intermittent lorazepam: a database analysis using Project IMPACT. Ann Pharmacother 2007;41:1986-1991. 36. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007;298:2644-2653. 37. Arroliga AC, Thompson BT, Ancukiewicz M, et al. Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome. Crit Care Med 2008;36:1083-1088. 38. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009;301:489-499. 39. Esmaoglu A, Ulgey A, Akin A, Boyaci A. Comparison between dexmedetomidine and midazolam for sedation of eclampsia patients in the intensive care unit. J Crit Care 2009;24:551-555. 40. Zhang H, Wang W, Gao W, et al. Effect of propofol on the levels of neurotransmitters in normal human brain: a magnetic resonance spectroscopy study. Neurosci Lett 2009; 467:247-251. 41. Aitkenhead AR, Pepperman ML, Willatts SM, et al. Comparison of propofol and midazolam for sedation in critically ill patients. Lancet 1989;2:704-709. 42. Kress JP, O'Connor MF, Pohlman AS, et al. Sedation of critically ill patients during mechanical ventilation: a comparison of propofol and midazolam. Am J Respir Crit Care Med 1996;153:1012-1018. 43. Chamorro C, de Latorre FJ, Montero A, et al. Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial. Crit Care Med 1996;24:932-939. 44. Barrientos-Vega R, Mar Sánchez-Soria M, Morales-García C, Robas-Gómez A, Cuena-Boy R, Ayensa-Rincon A. Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. Crit Care Med 1997;25:33-40. 45. Hall RI, Sandham D, Cardinal P, et al. Propofol vs midazolam for ICU sedation: a Canadian multicenter randomized trial. Chest 2001;119:1151-1159. 46. Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care 2000;4:302-308. 47. Pasin L, Greco T, Feltracco P, et al. Dexmedetomidine as a sedative agent in critically ill patients: a meta-analysis of randomized controlled trials. PLoS One 2013;8:e82913. 48. U.S. Food and Drug Administration. Highlights of prescribing information, Precedex (dexmedetomidine hydrochloride) injection [Internet]. Silver spring: U.S. Food and - 555 -
- 대한내과학회지 : 제 86 권제 5 호통권제 645 호 2014 - Drug Administration, 2014c [cited April 22, 2014]. Available from: http://www.accessdata.fda.gov/ drugsatfda_docs/ label/2013/021038s022lbl.pdf. 49. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012;307:1151-1160. 50. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-1762. 51. Lin SM, Liu CY, Wang CH, et al. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med 2004;32:2254-2259. 52. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007;33:66-73. 53. Farrell KR, Ganzini L. Misdiagnosing delirium as depression in medically ill elderly patients. Arch Intern Med 1995;155:2459-2464. 54. Kishi Y, Kato M, Okuyama T, et al. Delirium: patient characteristics that predict a missed diagnosis at psychiatric consultation. Gen Hosp Psychiatry 2007;29:442-445. 55. Devlin JW, Fong JJ, Schumaker G, O'Connor H, Ruthazer R, Garpestad E. Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients. Crit Care Med 2007;35: 2721-2724. 56. Spronk PE, Riekerk B, Hofhuis J, Rommes JH. Occurrence of delirium is severely underestimated in the ICU during daily care. Intensive Care Med 2009;35:1276-1280. 57. Van Eijk MM, van den Boogaard M, van Marum RJ, et al. Routine use of the confusion assessment method for the intensive care unit: a multicenter study. Am J Respir Crit Care Med 2011;184:340-344. 58. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med 2001;27:859-864. 59. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001;29:1370-1379. 60. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:2703-2710. 61. Heo EY, Lee BJ, Hahm BJ, et al. Translation and validation of the Korean Confusion Assessment Method for the Intensive Care Unit. BMC Psychiatry 2011;11:94. 62. Skrobik Y. Delirium prevention and treatment. Crit Care Clin 2009;25:585-591. 63. Schiemann A, Hadzidiakos D, Spies C. Managing ICU delirium. Curr Opin Crit Care 2011;17:131-140. 64. Van Rompaey B, Elseviers MM, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care 2009;13:R77. 65. Inouye SK, Zhang Y, Jones RN, Kiely DK, Yang F, Marcantonio ER. Risk factors for delirium at discharge: development and validation of a predictive model. Arch Intern Med 2007;167:1406-1413. 66. Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 2010;38:428-437. 67. Rea RS, Battistone S, Fong JJ, Devlin JW. Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients. Pharmacotherapy 2007;27:588-594. 68. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebocontrolled pilot study. Crit Care Med 2010;38:419-427. 69. Devlin JW, Skrobik Y. Antipsychotics for the prevention and treatment of delirium in the intensive care unit: what is their role? Harv Rev Psychiatry 2011;19:59-67. - 556 -