Ciszowski Krzysztof, Sein Anand Jacek, Wilimowska Jolanta, Jawień Wojciech
Klinika Toksykologii i Chorób Srodowiskowych, Uniwersytet Jagielloński, Collegium Medicum w Krakowie.
Przegl Lek. 2011;68(8):426-33.
Olanzapine is a second generation antipsychotic of thienobenzodiazepin group, which is used in the treatment of schizophrenia, bipolar disorder, and others, mainly psychiatric. Its multireceptor action (antagonism to dopaminergic D1, D2, D4, serotoninergic 5-HT2A, 5-HT2C, histaminergic H1, cholinergic M1-5, and a1--adrenergic receptors) results in multiple clinical symptoms in the course of acute poisoning.
Evaluation of incidence and intensity of clinical symptoms in patients with of acute olanzapine intoxication. The pathophysiological mechanisms of particular symptoms are also described.
26 patients (mean age 37.7 +/- 15.3 years) hospitalized in 2005-2008 in toxicological centers in Krakow and Gdansk because of acute olanzapine poisoning (all patients had the toxic serum level of olanzapine above 100 ng/mL). The study group consisted of 11 men (29.3 +/- 8.5 years) and 13 women (44.9 +/- 16.4 years); 1 man and 1 woman were poisoned twice.
Prospective analysis (using descriptive statistics) of data taken from medical anamnesis and results of physical examination, considering the following ones: consciousness disturbances (Glasgow Coma Scale, Matthew's scale, qualitative disturbances), vital signs (arterial blood pressure, heart rate, breathing rate, temperature), neurological findings (muscular tension, tendon reflexes, extrapyramidal symptoms, pupils) and others (oral and bronchial secretion, Poisoning Severity Score).
The mean dose of ingested olanzapine in the study group was 352.5 +/- 220.0 mg, while the mean time since ingestion to hospital admission was 4.4 +/- 3.5 h. The half of the patients took other medicines together with olanzapine, and 23% consumed alcohol, as well. The following intensity of quantitative consciousness disturbances according to Matthew's scale were observed: grade 0 - 8%, I - 15%, II - 23%, III - 50%, and IV - 4%. The minimal and maximal values of blood pressure were: 102/63 +/- 16/14 and 163/ 97 +/- 27/18 mmHg, respectively; heart rate: 77 +/- 15 and 138 +/- 22 beats/min; temperature: 36.3 +/- 0.5 and 37.9 +/- 0.8 degrees C; breathing rate in non-intubated patients: 14 +/- 2 and 22 +/- 7 breaths/min. The mean duration of consciousness disturbances, endotracheal intubation and mechanical ventilation were: 44.9 +/- 31.3; 22.0 +/- 33.3 and 7.0 +/- 25.9 h, respectively. The study revealed tachycardia (85%), psychomotor agitation (81%), hypertension (73%), miosis (65%), and coma (54%) as the most common symptoms of poisoning. The hospitalization of poisoned patients lasted on average 5.7 +/- 3.6 days and the half of them were poisoned severely (PSS 3).
In the course of acute olanzapine poisoning: (1) the prevailing symptoms come from circulatory and central nervous systems; (2) some symptoms are mutually opposed, eg.: coma - psychomotor agitation, hypertension - hypotension, tachycardia - bradycardia, hyperthermia - hypothermia, miosis - mydriasis; (3) rarely consciousness disturbances may persist for up to 6 days after olanzapine overdose; (4) the course of poisoning can be severe, sometimes complicated, but fatal outcomes are rare.
奥氮平是噻吩并苯二氮䓬类第二代抗精神病药物,主要用于治疗精神分裂症、双相情感障碍等精神疾病。其多受体作用(对多巴胺能D1、D2、D4、5-羟色胺能5-HT2A、5-HT2C、组胺能H1、胆碱能M1-5及α1-肾上腺素能受体的拮抗作用)导致急性中毒过程中出现多种临床症状。
评估急性奥氮平中毒患者临床症状的发生率及严重程度,并描述特定症状的病理生理机制。
2005年至2008年期间,因急性奥氮平中毒入住克拉科夫和格但斯克毒理学中心的26例患者(平均年龄37.7±15.3岁)(所有患者奥氮平血清中毒水平均高于100 ng/mL)。研究组包括11名男性(29.3±8.5岁)和13名女性(44.9±16.4岁);1名男性和1名女性曾两次中毒。
对取自医学病史和体格检查结果的数据进行前瞻性分析(采用描述性统计),考虑以下方面:意识障碍(格拉斯哥昏迷量表、马修斯量表、定性障碍)、生命体征(动脉血压、心率、呼吸频率、体温)、神经学表现(肌张力、腱反射、锥体外系症状、瞳孔)及其他(口腔和支气管分泌物、中毒严重程度评分)。
研究组摄入奥氮平的平均剂量为352.5±220.0 mg,摄入至入院的平均时间为4.4±3.5小时。半数患者同时服用了其他药物,23%的患者还饮酒。根据马修斯量表观察到以下定量意识障碍程度:0级-8%,I级-15%,II级-23%,III级-50%,IV级-4%。血压的最小值和最大值分别为:102/63±16/14和163/97±27/18 mmHg;心率:77±15和138±22次/分钟;体温:36.3±0.5和37.9±0.8℃;未插管患者的呼吸频率:14±2和22±7次/分钟。意识障碍、气管插管和机械通气的平均持续时间分别为:44.9±31.3;22.0±33.3和7.0±25.9小时。研究显示心动过速(85%)、精神运动性激越(81%)、高血压(73%)、瞳孔缩小(65%)和昏迷(54%)是最常见的中毒症状。中毒患者的住院时间平均为5.7±3.6天,其中半数患者中毒严重(中毒严重程度评分3分)。
在急性奥氮平中毒过程中:(1)主要症状来自循环系统和中枢神经系统;(2)某些症状相互对立,如:昏迷-精神运动性激越、高血压-低血压、心动过速-心动过缓、体温过高-体温过低、瞳孔缩小-瞳孔散大;(3)奥氮平过量后意识障碍很少持续长达6天;(4)中毒过程可能严重,有时会出现并发症,但致命后果罕见。