Acute Pain and Pain Control State of the Art Annals of Emergency

Acute Pain and Pain Control: State of the Art Annals of Emergency Medicine 35:6 June 2000 日期：90-09-01 報告者：吳一青醫師 指導者：林秋梅醫師 State of the Art  發展中之科技的目前進步水準  Pain is not simply a signal of tissue injury, but is primarily a signal to the organism to seek repair and recuperation. – P.D Wall 大綱 (1)        Introduction The terminology of pain Neurobiology of pain Pain assessment Pain versus suffering Approach to pain control Analgesics 大綱 (2)       Directed analgesia Other analgesia options Pediatric pain control Chronic pain, addiction, and pseudoaddiction Analgesia after discharge Further directions and summary Introduction 在急診室，對於Pain的認知和治療在過去 十年來有相當的演變。  Emergency clinicians, educators, and researchers開始強調 undertreatment of pain， 並挑戰對於疼痛治療長久以來的 教條。  Terminology of pain (1)  Hyperalgesia – A state where a painful stimulus cause more pain than normally expected  Allodynia – With increased irritation, nerve fibers normally not associated with pain sensation are recruited, with nonpainful stimuli now inducing pain  Recruitment – The stimulation of increasing number of nerve fibers as a result of spinal neurotransmitter release Terminology of pain (2)  The plasticity of the pain sensory system – Windup and recruitment may result in permanent modification  Inflammatory pain – Result from tissue damage caused by heat, hypoxia, inflammation or trauma  Nociceptor – Pain receptor of nonmyelinated C-fiber Terminology of pain (3)  Neuropathic pain – Direct activation of either sensory nerves or central ganglia by nerve injury or disease  Neuralgic pain – Produced by direct nerve stimulation w/o necessarily causing nerve damage Neurobiology of pain  Primary afferent nociceptor pathway  Central peptides  Pain perception – Induced by stimulation of one or more types of peripheral ionic channels present in nociceptive fibers – Sodium- and calcium- mediated channels Na mediated channels in C-fiber Injury local cell release “inflammatory soup” (內 含 bradykinin, histamine, PGE2, cAMP)  soup作用於Na mediated channels (C-fiber) Release glutamate in the dorsal root ganglion (DRG) Glutamate stimulates spinal cord activation of AMPA and NMDA Glutamate also provides a positive feedback loop to the DRG (via kainate receptor)    AMPA – α-amino-3-hydroxy-5-methyl-4-isoxazoleproionate NMDA – N-methyl-D-aspartate CGRP – Calcitonin gene-related peptide Ca-mediated channels in C-fiber  Ca-mediated channels present in C-fiber are stimulated more by heat or low pH  Release substance P in the DRG  Substance P and NMDA activate central spinothalamic tract leading to CNS recruitment and stimulation  Opioids and endophins decrease Ca channel conductance and supressing this stimulation (mainly by μ receptor) Ca channel in large A beta fibers  Ca channel in large A beta fibers stimulated by heat, injury and low pH CGRP and NO release  CGRP flare response  NO increase sympathetic and central activity and induces vasodilatation and endothelial permeability tissue edema Glutamate and NMDA  Activation or recruitment of more C-fiber peripherally  increasing the perceived area of pain  Windup with the activation of further μ opioid receptor and increase central activity  hyeralgesia and allodynia Target individual pathway with focused medication  Can only succeed if the select pathway is the principal cause of pain  舉例 – Nueralgic states (Na channels are often the problem)  lidocaine is effective – Injury (all channels activated)  single focused medication should not be expected to succeed Novel ways of pain control  Windup occurs a few hours after the initial painful stimulus Intervention within that time can potentially decrease the subsequent pain and analgesia requirement  Gordon et al – Bupivicaine for oral surgery. Even given after surgery can decrease pain and analgesic requirements for the subsequent 72 hours At ED  Patients with pain already present for more than 3-4 hours before a procedure that will not benefit. Their system will have already start to wind up. Once the system is up regulated, then agents such as opioids alone or in combination with NMDA antagonists should be more effective than peripherally acting medications. Pain assessment 臨床上，急性疼痛何時可以停止止痛目 前缺乏gold standard  多數研究著重於statistically significant decrease of pain  Statistical significance ≠ clinical significance  Clinical significant change bear little relationship to patient care  Incomplete pain relief  Patient may prefer a certain degree of pain in stead of sedation to have greater daily functionality  Adverse effect  Past experience  Personal beliefs In such cases, pain measurement is of little value Complete pain relief  Migraine: less headache recurrence at 24 hours if complete pain relief in ED  Pain measurement is a important tool in obtaining the desire endpoint Pain assessment on arrival      Patient with severe pain should be triaged as priority Door-to-analgesia time Pain level versus triage level Initial pain assessment  type and route of medication Dosing: has little relation to type of pathology, severity of injury, or initial pain level Pain versus suffering  Suffering= Pain + Emotion (Anxiety)  The feeling of loss of control  Patient-controlled analgesia less analgesic dose than controlled by Dr or nurse  Reassurance or explanation, or anxiolytic  Anxiolytic or sedatives can not replace analgesic therapy Approach to pain control  Enthusiasm, rapport, and suggestion during the physician-patient relationship important roles in pain management 沒有積極的控制疼痛可能會增加以後的 痛苦。  老年人的帶狀皰疹，早期使用抗病毒藥 物和amitriptyline，可以減少治療後3個月 的神經痛。  截肢手術使用epidural analgesia，可以減 少phantom limb pain的機率。  Rapid intervention prevents windup of CNS   Local long-acting analgesia at the time of dental extraction can decrease pain and analgesia requirement in the ensuing days. The principles of pain control (1)  Analgesia should be integrated into a comprehensive patient evaluation and management  The emotional and cognitive aspects of pain must be recognized and treat  There is no reliable way to measure the pain  Pain is most often under-treated, not overtreated The principles of pain control (2) Beware of the “squeaky-wheel-gets-the-oil” phenomenon of pain control  Pain control must be individualized  Anticipate rather than react to pain  Whenever possible, let the patient control his or her own pain  The principles of pain control (3)  Pain control is often best achieved by combination therapy  Pain control requires a multidisciplinary (有關 各種學問的), team approach  Establish the cause of the pain if it is still in question  Evaluation of a painful condition should not delay treating the pain  Acute abdominal pain that providing pain relief while investigating the cause has not negatively affected the result Many causes of pain are iatrogenic 像是放置鼻胃管等等例行治療  身為醫生的責任: 當病患反應他們急性的 問題時，不應該繼續受罪。  我們必須認知，當病患繼續受罪時，這 是我們選擇讓它發生的，而非它是不可 避免的。  Analgesics Acetaminophen:  Excellent for mild to moderate pain  Low adverse event profile NASIDs  Relatively high rate of adverse effects (GI bleeding, nephropathy, worsening of heart failure, HTN)  COX-2 agents: lower rate of GI bleeding, but nephropathy and salt retention still occurred  All NSAIDs have a rapid analgesic ceiling, preventing titration to effect  Do not have ceiling effect of anti-inflammatory effect NSAIDs  As dose increase so does the adverse effects  Less effective if there is little or no PG-mediated activity (edema-induced pressure or from neuralgia)  Effective if PG activity has been stimulated: tissue injury, ischemia, increased smooth muscle tension (menstrual pain or ureteral colic)  就止痛和onset時間而言，Oral route 和其他途 徑一樣有效 Oral Opioids  Oral opoids are affective for all levels of pain  在scanol和NSAIDs劑量增加時，副作用也上升， 和oral opioids合併使用時，不適合用在中度到 嚴重疼痛  Oral opioids combined with codeine, propoxyphene, and oxycodone  Should be prescribed as fixed time interval with additional as-needed doses as required IM or SC route of opioids  No evidence support the idea that the routes are safer  Erratic absorption and not allow titration  Onset of action approximately the same as with oral opioids IV route of opioids  If patient can not tolerate oral medication  If the pain is severe Iontophoretic transdermal medication  Fentanyl  A more constant level of analgesia for chronic pain Opioid-induced emesis  20% of patients  Related to short-lived histamine release or direct gastroparetic effect  Can treat with antihistamine or ondansetron  Persistent emesis is caused by gastroparesis and should be controlled by gastric motility agent (metoclopramide) – Phenothiazines: 其他藥物都無效才考慮 Ketamine  NMDA antagonist  For polytrauma patients, continuous low dose infusion is effective Dextromethorphan  NMDA antagonist  Being studied in combination with opioids Directed analgesia  Target the specific mechanisms of particular pathologic conditions to prevent or treat the painful condition  Five examples are presented 1. Neuralgia  Blocking Na channel can usually control it  Anesthetic agents (Lidocaine iv or topical) can block action potential of such channels  Anticonvulsants (Gabapentin, Carbamazepine) can be effective for neuralgia (by Na channel blockade or by GABA effect) 2. Migraine  Triptan-type medication – CGRP activity believed to cause migraine headache – Serotonin 5-HT1A and 5-HT1D receptors present on trigeminal nerve can be stimulated to decrease CGRP activity  Dopamine antagonist (prochloperazine): not understand 3. Ureteral colic  increases in intraluminal pressure (directly mediated by PG) increases ureteral smooth muscle tension  Pain arise  Can prevented and aborted by NSAIDs 4. Osteoarthritis  Degeneration of synovium and decreases in synovial lubrication  increased friction  Stimulation of intra-articular pain receptors  Pain  Intra-articular injection of hylan (viscous lubrication) decrease friction and decrease the pain 5. Vertebral compression fracture  Often as a result of micro-trauma  會使病患失能數週  Calcitonin – accelerating osteoblastic activity and decrease the pain more repidly – Increase central beta-endorphin level  Salmon Calcitonin (nasal aerosol) Other analgesia options  Music  Distract patient from the anxiety  Hypnosis  Listen to patients and encourage them to continue methods they have found helpful in decreasing pain  Immobilization of injured extremities Other analgesia options  Immobilization itself may be very ainful – Use of NO in a 7/3 mixture with oxygen for casting and splinting – Use of short-acting opioids (fentanyl, sulfentanyl, remifentanyl)  應該提供病患可選擇的止痛，而不是告 訴他，只是痛一下下 Other analgesia options  Immobilization – 相較於簡單地將肢體擺到比較舒服的姿勢， 有一些固定方式沒有止痛的好處: figure-8 dressing for clavicle fracture; cutaneous traction for hip fracture – Ankle sprain: 會造成delay healing和lessen range of motion Other analgesia options  Regional anesthesia for fracture in elderly patient  elderly patient – – – – may had mild cognitive dysfunction Opioid may further confuse and agitate them Parenteral ketorolac GI or renal complicaiton Femoral nerve block effective for hip fracture Femoral nerve block for hip fr. Eliminate the pain without altering patient’s mental status  Not masking the pain of other injuries  Providing long relief if bupivicaine used  Allow painless displacement of the affected joints  Decreasing subsequent analgesic requirement  Other analgesia options  Regional anesthesia in other settings – Epidural anesthesia : permit better pulmonary function in patient with chest trauma (相較於 iv opioids)  Microsphere – Drager et al: bupivicaine and dextramethasone in microshere for intercostal nerve blocks in sheep provides anesthesia lasting as long as 12 days Pediatric pain control  Children and neonates – They do feel pain – May suffer adverse events if pain is not properly controlled  Lack of sedation and pain control during intubation or other invasive procedure increased rate of ICH and worsened neurological outcome  Lumbar puncture without local anesthesia cause infant to struggle more – 是因為要抓著小孩讓他不舒服還是procedure 本身的痛？  一些傳統的procedure也許不是最好的選 擇 – Heel stick is more painful than iv sampling  Pain management in child is as important as adult  In a recent study no child with an extremity fracture was discharged with an analgesic prescription  Children should receive the same type of analgesia as adult for similar degree of pain Chronic pain, addiction, and pseudoaddiction “Drug seeker”  Patients with chronic pain present to the ED for some reasons – Acute flare of chronic pain – Inadequate chronic pain management – Desperation 走投無路 Patients are labeled as “drug seeker”  懷疑oligo-analgesia  醫生必須對過度開立opioids負法律責任，加上 不想被病患愚弄，所以不願意開藥  Aberrant drug-related behaviors  Frequent use of ED  Moving from one provider to another without coordinate care  Poor f/u and compliance  Subjective complaints (often difficult to objectively verify) Differential Diagnosis  Psychiatric illness  Social problems  Illegal diversion  Addiction  Pseudoaddiction Addiction  A chronic, disabling, relapsing disease  Compulsive drug seeking and use, even in the face of negative health and social consequence  A chronic disease of the brain  Addiction 成因 – 因為藥物長期使用，影響大腦結構和功能，但是， 當然也和病患潛藏的行為和社交背景有關  在ED，一旦確認或懷疑有addiction，病患應導 入 coordinated and long term treatment Pseudoaddiction  A behavior syndrome that can be mistaken for addiction in patient receiving inadequate pain management – Drug hoarding 貯藏 – Request specific drugs – Concerns about drug availability – Clock watching – Unsanctioned dose escalation （自己加藥量）  重要特徵：當給予適當的止痛，此行為會消失 Pseudoaddiction  May require aggressive therapy including opioids  Patient with cancer, the first-line intervention is often a higher dose of opiods  Non-malignant chronic pain treat with chronic opioid therapy 使用越來越被接受，雖然還是有 爭議性 Chronic pain 也會有變化  Tolerance to the analgesic effect of opioids rarely occurs  Patients complain of more pain usually have new or worsened condition  Patient with chronic pain may have an acute deterioration or exacerbation of their condition  若無臨床上惡化的證據，注意病患是否沮喪而 尋求其他治療或是因為慢性疼痛而造成的憂鬱 Worsening of pain  Depression may present rather than typical symptoms  Treatment of depression caused by chronic pain is essential if the patient hope to maintain control of the pain  Frustrated patient若懷著不合理的期望來到急診， 應該跟他解釋我們能做什麼，不能做什麼 – 請他到門診看，幫助他提供接下來的support，可以 避免病患一直來ED並提升照護 Analgesia after discharge   Most clinical analgesic trials are single-dose comparisons, especially for acute pain 因為疼痛的程度不會一直持續，所以multidose studies 很難做  例如，目前沒有任何關於骨折打 cast 之後，疼 痛的duration, severity的資料。 適當的出院用藥  The trade-off between analgesia and adverse effects (影響到工作、注意力、情緒、睡眠等等)  舉例 Migraine: 24 hr headache recurrence after ED treatment can be as higher as 50% using more medication to ensure no-headache-atdischarge decrease the risk of headache at 24 hours (但是，為了減少頭痛再發，使病患變的 昏昏欲睡、煩躁不安，不能做正常活動是否有 價值，仍有待觀察)  Chan et al and Chan and Verdile have studied pain control after discharge in the general pediatric ED Overall pain control is good for both parents and children 要證實病患會有何種程度疼痛，我們仍需要更 多關於出院後一些特定狀況的研究，這樣我們 才能決定需要做何種處置。  我們已知，在zoster發作時及早處置，對於減 少及避免治療後的神經痛很重要，當我們開始 研究其他狀況，也許也會是這樣。  Future direction and summary  Pain mechanism  Genetics of pain – Gene expressed in nociceptor pathway – How the genotype influences the known variability in human pain sensitivity  Clinical evidence of pain genetics – De-stigmatization of pain-sensitive persons – Choice of analgesia base on individual’s genetic analysis – Discover of novel pain-related proteins – Genetic therapy of pain Petrick Wall  寫下這一段話 一個標準的原因引起標準的疼痛，這當是個神話，然 而，這個神話卻同樣地影響了病患、醫療人員和朋友， 當你手腕折斷走到急診室，你感受到了你期望中，手 腕骨折應該有的疼痛，不，它和想像中不一樣，如果 它不是很痛，你也許會很驚愕，如果你的疼痛讓你變 成無助、哭泣的可憐人，你會格外的悽慘，護士和醫 師很快的意識到你的手腕角度不正常，做出診斷，把 你分好類別，對他們而言，手腕骨折會造成該有的疼 痛，有一定的處理流程，對你而言，你也許是很緊張、 害怕、或爛醉如泥、或悲傷，但是對他們而言，你只 是第六床手腕骨折的病患 我們應該將疼痛視為 a complex constellation of symptoms and emotions unique and ineffable 難 以形容 to that individual  我們要認知到，我們永遠無法度量（也許可以 猜想）第六床骨折的病患正遭受到多少 pain and suffering  結語  Pain control is optimized by increasing our understanding of the neurobiology of pain with the interaction of patient: science and knowledge combined with empathy and humanity