氯氮平急性中毒所致吸入性肺炎(學(xué)習(xí))

1、氯氮平所致吸入性肺炎氯氮平所致吸入性肺炎 孫玲孫玲 主任醫(yī)師主任醫(yī)師吸入性肺炎的簡(jiǎn)介 吸入性肺炎是由于上呼吸道、口咽部分泌物及食道、胃內(nèi)容物誤吸入下呼吸道引起的肺實(shí)質(zhì)感染。吸入性肺炎的常見(jiàn)原因有誤吸、嘔吐、咽反射異常、吞咽功能障礙、咳嗽反射減弱等。氯氮平常引起吸入性肺炎 氯氮平為二苯二氮雜卓類抗精神病藥，對(duì)治療急、慢性精神分裂癥，難治性精神病患者有較好的效果，且費(fèi)用低廉，但副作用多。流涎是氯氮平的主要副作用之一，也是引起吸入性肺炎的主要原因。氯氮平所致吸入性肺炎的臨床表現(xiàn) 氯氮平所致吸入性肺炎的常見(jiàn)癥狀有：發(fā)熱、咳嗽、呼吸困難、有時(shí)還會(huì)出現(xiàn)意識(shí)障礙。 氯氮平所致吸入性肺炎的典型體征是：肺部聞及

2、濕羅音。 實(shí)驗(yàn)室檢查顯示：白細(xì)胞計(jì)數(shù)及比值升高。 影像學(xué)改變有：肺內(nèi)單發(fā)或多發(fā)斑片狀模糊影。氯氮平引起吸入性肺炎的機(jī)制使用氯氮平治療的患者中有31-54%的患者存在流涎。流涎常常出現(xiàn)在氯氮平治療的早期、并且與加量過(guò)快有關(guān)。在抗精神病藥物中，氯氮平的抗膽堿能效應(yīng)最強(qiáng)，人們預(yù)期氯氮平會(huì)導(dǎo)致口干，然而事實(shí)與預(yù)期相反，氯氮平常引起流涎。氯氮平引起吸入性肺炎的機(jī)制有人認(rèn)為，氯氮平可通過(guò)激動(dòng)唾液腺腺泡上的膽堿能M4受體和2腎上腺素能受體，導(dǎo)致唾液分泌增加。然而有研究顯示，流涎的患者與正常人群相比，唾液分泌量并無(wú)增加。因此氯氮平所致流涎可能與抗多巴胺能作用導(dǎo)致的吞咽障礙有關(guān)。此外，由于睡眠時(shí)喉肌處于松馳狀態(tài)

3、,吞咽反射減弱。在睡眠姿勢(shì)不當(dāng)時(shí),尤其是仰臥時(shí)易受涎液返流經(jīng)會(huì)厭部滲入支氣管,從而引起肺炎。病例討論Mr. C, a 26 year old male with schizophrenia paranoid type and a long history of numerous psychiatric hospitalizations was admitted to our inpatient unit for treatment of difficulty sleeping, paranoia, auditory hallucinations and inability to functio

4、n following non-compliance with his medication (risperidone). His medical history was unremarkable. Complete blood count, basic metabolic panel, and thyroid stimulating hormone levels were within normal limits. On our inpatient unit, he was found to be irritable, guarded, internally preoccupied, ges

5、turing and talking to himself. His pastpsychiatric history was significant for failure to respond to multiple typical and atypical antipsychotics(chlorpromazine, fluphenazine, perphenazine, quetiapine, olanzapine, aripiprazole, ziprazidone). He had partial response to risperidone described by hisout

6、patient psychiatrist as moderate reduction of paranoia and hallucination.Mr. C was restarted on risperidone which was titrated up to 4 mg twice a day. He remained paranoid, disorganized with auditory hallucinations telling him that he was the son of a famous singer. On day 10 of admission, haloperid

7、ol was added and titrated up to 10 mg bid. Despite being on two antipsychotics for more than 3 weeks, Mr. C didnt improve and the decision was made to discontinue risperidone, haloperidol and start clozapine. C先生是一位26歲的偏執(zhí)型精神分裂癥患者，曾多次住院。曾用過(guò)多種抗精神病藥，包括奧氮平、喹硫平、阿立哌唑、奮乃靜、氯丙嗪，療效欠佳。C先生對(duì)利培酮反應(yīng)為部分有效，入院時(shí)利培酮的劑量為

8、4mg Bid，仍存在妄想、言行紊亂、幻聽(tīng)。 入院第10天聯(lián)合使用氟哌啶醇10mg Bid。聯(lián)合用藥3周后，癥狀無(wú)緩解，遂停用利培酮和氟哌啶醇，開(kāi)始使用氯氮平治療。病例討論Four days after clozapine was begun (25 mg orally in the morning, 50 mg orally at bedtime), Mr. C experienced side effects from the medication, including severe drooling, sedation, headache and tachycardia. The fol

9、lowing day, the patient spiked a fever of 103F and developed altered mental status with difficulty breathing. He was transferred to the emergency room where findings on physical examination and radiographic evidence of an infiltrate lead to a diagnosis of pneumonia. Further investigations revealed a

10、 positive sputum culture for peptostreptococcus, as the causative organism.氯氮平使用到第4天，患者出現(xiàn)藥物副反應(yīng)，表現(xiàn)為：唾液分泌增多、鎮(zhèn)靜、頭痛和心動(dòng)過(guò)速，此時(shí)氯氮平的劑量為：早25mg、晚50mg。第2天，患者出現(xiàn)發(fā)熱、呼吸困難、意識(shí)改變。體查及胸片檢查提示為肺炎。痰培養(yǎng)顯示消化道鏈球菌陽(yáng)性。診斷為吸入性肺炎。予頭孢夫辛和氟喹諾酮治療，并停用氯氮平。經(jīng)過(guò)抗生素治療，患者的肺部感染治愈。使用氟哌啶醇20mg Bid抗精神病治療，療效一般，無(wú)明顯藥物副反應(yīng)。病例討論The commonly cited risk fac

11、tors for developing aspiration pneumonia include dysphagia, esophageal dysfunction, impairment of consciousness, and increased bacterial inoculum. Sialorrhea likely contributed to aspiration pneumonia in our patient. Our patient developed hypersalivation and sedation 13 days after initiation of cloz

12、apine. This is in keeping with data that shows the most significant increase in sialorrhea during the second and third weeks of clozapine titration . One day after he was noted to have profuse salivation, Mr. C developed pyrexia. The time course is highly suggestive of aspiration pneumonia, which was confirmed by chest x-ray and sputum culture.導(dǎo)致吸入性肺炎的常見(jiàn)原因有：吞咽困難、食道功能障礙、意識(shí)障礙。在本病例中，流涎是導(dǎo)致吸入性肺炎的原因。氯氮平導(dǎo)致的唾液分泌增多往往發(fā)生在用藥的第23周。這位患者是在使用氯氮平13天后出現(xiàn)唾液分泌增多和鎮(zhèn)靜?；颊呤窃诖罅糠置谕僖褐蟪霈F(xiàn)發(fā)熱的，從時(shí)間關(guān)系說(shuō)明吸入性肺炎的可能性大，另外胸片的結(jié)果和痰培養(yǎng)發(fā)現(xiàn)致病菌為消化道鏈球菌可證實(shí)這一推論。氯氮平所致吸入性肺炎的處理（一）吸入性肺炎的處理：臨床醫(yī)生需要對(duì)氯氮平導(dǎo)致的吸入性肺炎保持高度警惕。吸入性肺炎是氯氮平治療導(dǎo)致死亡的獨(dú)立因素之一。一旦發(fā)生吸