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Unintentional ingestion of 60% hydrogen peroxide by a six-year-old child. 六岁儿童误食60%过氧化氢。
Pub Date : 2004-01-01 DOI: 10.1081/clt-120030950
José Sansone, Nilda Vidal, Román Bigliardi, Ana Voitzuk, Vanina Greco, Karina Costa

Ingestion of industrial-strength hydrogen peroxide is rare. Fatal outcomes have been reported with solutions of 35%. We report a six-year-old boy who unintentionally ingested an unknown quantity of hydrogen peroxide with a concentration of 60%. Upon admission to our Pediatric Intensive Care Unit he was intubated and received ventilatory assistance for 48h. Upper gastrointestinal endoscopy was performed soon after admission and laparoscopy was performed 24h later. Recovery was satisfactory, and the patient was discharged on day 18 with no evidence of pathological sequelae.

摄取工业强度的过氧化氢是罕见的。据报道,35%的溶液会导致致命的结果。我们报告了一个六岁的男孩,他无意中摄入了未知数量的过氧化氢浓度为60%。在进入我们的儿科重症监护室后,他插管并接受了48小时的呼吸辅助。入院后不久行上消化道内镜检查,24小时后行腹腔镜检查。患者恢复良好,于第18天出院,无病理性后遗症。
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引用次数: 6
Effect of anticholinergic drugs on the efficacy of activated charcoal. 抗胆碱能药物对活性炭功效的影响。
Pub Date : 2004-01-01 DOI: 10.1081/clt-120037426
Robert Green, Daniel S Sitar, Milton Tenenbein

Background: Although it is a commonly held belief that the ingestion of drugs with an anticholinergic action would prolong the duration of time after drug ingestion for effective gastrointestinal decontamination, data are lacking to support this belief. The purpose of this study is to determine whether activated charcoal is more effective in the presence of concurrent anticholinergic activity.

Methods: A three-limbed randomized crossover study in 10 healthy volunteers was completed to determine the ability of a 50 g dose of activated charcoal to reduce the bioavailability of a simulated overdose of acetaminophen (12 x 325 mg tablets) in the presence and absence of a concurrently present anticholinergic drug, atropine (0.01 mg/kg I. M. administered 15 min prior to the acetaminophen ingestion).

Results: After the acetaminophen ingestion, median Cmax occurred at 1 h for all three exposures but was lower in the atropine-treated study arm (31+/-19 mg/L) than in the control or charcoal alone intervention arms (49+/-13 and 51+/-16 mg/L, respectively) (P<0.05). Compared to the control area under the serum concentration vs. time curve, a single dose of activated charcoal 1 h after drug ingestion reduced acetaminophen bioavailability by 20% (95% CI 4-36%) and by 47% (95% CI 35-59%) in the presence of atropine (P<0.05 atropine plus charcoal vs. charcoal alone).

Conclusions: Our data support the belief that activated charcoal is more effective in the presence of anticholinergic activity. Additional study is required to determine whether in patients with anticholinergic drug overdose, activated charcoal is effective at times beyond the recommendation for overdoses of drugs without this pharmacodynamic effect.

背景:虽然人们普遍认为,服用具有抗胆碱能作用的药物会延长药物摄入后有效胃肠净化的时间,但缺乏数据支持这一观点。本研究的目的是确定活性炭在同时存在抗胆碱能活性时是否更有效。方法:在10名健康志愿者中完成了一项三足随机交叉研究,以确定50g剂量的活性炭在同时存在和不存在抗胆碱能药物阿托品(0.01 mg/kg在摄入对乙酰氨基酚前15分钟给药)的情况下降低模拟过量对乙酰氨基酚(12 x 325 mg片)的生物利用度的能力。结果:在对乙酰氨基酚摄入后,所有三种暴露的中位Cmax均在1小时发生,但阿托品治疗组(31+/-19 mg/L)比对照或单独干预组(分别为49+/-13和51+/-16 mg/L)低(结论:我们的数据支持活性炭在抗胆碱能活性存在时更有效的观点。需要进一步的研究来确定在抗胆碱能药物过量的患者中,活性炭是否在没有这种药效学作用的过量药物的推荐时间之外有效。
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引用次数: 26
A meta-analysis of prognostic indicators to predict seizures, arrhythmias or death after tricyclic antidepressant overdose. 预测三环类抗抑郁药物过量后癫痫发作、心律失常或死亡的预后指标荟萃分析。
Pub Date : 2004-01-01 DOI: 10.1081/clt-200035286
Benoit Bailey, Nicholas A Buckley, Devendra K Amre

Objectives: To systematically review and summarize studies on the accuracy of ECG and tricyclic antidepressant (TCA) concentration as prognostic indicators of the risk of seizures, ventricular arrhythmia (VA) or death in patients with TCA overdose.

Methods: Articles were identified with MedLine and Cochrane register of controlled clinical trials searches and review of medical toxicology textbooks. Quality of the included studies was assessed. Pooled estimates of sensitivity, specificity, likelihood ratios and Summary Receiver Operating Characteristics (SROC) curves were generated.

Results: A total of 18 studies were included in the analysis. The pooled sensitivity (Se) and specificity (Sp) of the QRS for predicting seizures were 0.69 [95% CI 0.57-0.78] and 0.69 [95% CI 0.58-0.78] as compared to 0.75 [95% CI 0.61-0.85] and 0.72 [95% CI 0.61-0.81] for the TCA concentration. The Se and Sp of the QRS to predict VA were 0.79 [95% CI 0.58-0.91] and 0.46 [95% CI 0.35-0.59] compared to 0.78 [95% CI 0.56-0.90] and 0.57 [95% CI 0.46-0.67] for the TCA concentration. The Se and Sp of the QRS to predict death were 0.81 [95% CI 0.54-0.94] and 0.62 [95% CI 0.55-0.68] compared to 0.76 [95% CI 0.49-0.91] and 0.60 [95% CI 0.47-0.72] for the TCA concentration. Very few studies evaluated the accuracy of QTc, T 40 ms axis and the R/S ratio.

Conclusions: Overall, the studies suggested that the ECG and TCA concentration have similar but relatively poor performance for predicting complications, such as seizures, VA or death, associated with TCA overdose.

目的:系统回顾和总结三环抗抑郁药(TCA)浓度作为TCA过量患者癫痫发作、室性心律失常(VA)或死亡风险预后指标的准确性研究。方法:文章通过MedLine和Cochrane对照临床试验注册检索和医学毒理学教科书进行鉴定。评估纳入研究的质量。产生敏感性、特异性、似然比和总受试者工作特征(SROC)曲线的汇总估计。结果:共纳入18项研究。QRS预测癫痫发作的总敏感性(Se)和特异性(Sp)分别为0.69 [95% CI 0.57-0.78]和0.69 [95% CI 0.58-0.78],而TCA浓度的总敏感性(Se)和特异性(Sp)分别为0.75 [95% CI 0.61-0.85]和0.72 [95% CI 0.61-0.81]。QRS预测VA的Se和Sp分别为0.79 [95% CI 0.58-0.91]和0.46 [95% CI 0.35-0.59],而TCA浓度的Se和Sp分别为0.78 [95% CI 0.56-0.90]和0.57 [95% CI 0.46-0.67]。QRS预测死亡的Se和Sp分别为0.81 [95% CI 0.54-0.94]和0.62 [95% CI 0.55-0.68],而TCA浓度的Se和Sp分别为0.76 [95% CI 0.49-0.91]和0.60 [95% CI 0.47-0.72]。很少有研究评估QTc、t40ms轴和R/S比的准确性。结论:总体而言,研究表明,ECG和TCA浓度在预测TCA过量相关的并发症(如癫痫发作、VA或死亡)方面具有相似但相对较差的性能。
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引用次数: 57
Single-dose activated charcoal-backup and reassess. 单剂量活性炭备用并重新评估。
Pub Date : 2004-01-01 DOI: 10.1081/clt-120028754
Donna Seger

Single-dose activated charcoal (SDAC) is frequently administered to poisoned patients. The assumption is that toxin absorption is prevented and that toxicity (as defined by morbidity and mortality) of the poisoning is decreased. Yet there is no evidence that SDAC improves outcome. Risks of this procedure have not been determined. The reported adverse events following SDAC administration are reviewed and risk:benefit ratio for this procedure is discussed.

单剂量活性炭(SDAC)常用于中毒患者。假设毒素的吸收被阻止,中毒的毒性(根据发病率和死亡率的定义)被降低。然而,没有证据表明SDAC可以改善结果。该手术的风险尚未确定。回顾了SDAC治疗后报告的不良事件,并讨论了该方法的风险:收益比。
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引用次数: 33
Compliance with poisons center referral advice and implications for toxicovigilance. 依从毒物中心转诊建议和对毒物警戒的影响。
Pub Date : 2004-01-01 DOI: 10.1081/clt-200026972
Martin Watts, John S Fountain, David Reith, Leo Schep

Background: When Poisons Information, or Poisons Control Centers (PCC) give directive advice in response to general public calls it is usually assumed that the advice will be followed, but it is difficult to measure the actual compliance of callers to a PCC. Epidemiological data regarding the incidence of poisoning incidents (Toxicovigilance) often utilizes reports of calls to a PCC.

Methods: Retrospective review of advice given to all callers to the New Zealand National Poisons Centre (NZNPC) from a defined area for the calendar year 2001. Callers to the NZNPC telephone hotlines who were advised to attend or not to attend the hospital Emergency Department (ED) were subsequently matched with actual ED visits.

Results: The compliance rate for those advised to attend the ED was 76.1%, whereas those advised not to attend had a compliance rate of 98.7%. The overall compliance rate was 94.1%. Of the patients presenting to the ED with a potential poisoning, only 10.2% were referred by the PCC. The callers referred by PCC and direct ED visitors appeared to differ in some respects.

Conclusions: Compliance with PCC telephone advice is similar to the compliance rates in many other health interventions. Comparisons between populations calling a PCC and those self-presenting to an ED show that PCC data may not reflect the true burden of poisoning to health care systems.

背景:当毒物信息中心或毒物控制中心(PCC)对公众电话给出指示建议时,通常假设这些建议会被遵循,但很难衡量呼叫者对PCC的实际依从性。关于中毒事件发生率的流行病学数据(毒物警戒)通常利用呼叫PCC的报告。方法:回顾性审查2001年历年从指定地区向新西兰国家毒物中心(NZNPC)的所有来电者提供的建议。拨打新西兰全国人大热线电话的人被建议去或不去医院急诊科(ED),随后与实际的急诊科就诊相匹配。结果:建议去急诊的依从率为76.1%,建议不去急诊的依从率为98.7%。总体合规率为94.1%。在向急诊科提出潜在中毒的患者中,只有10.2%是由PCC转诊的。投诉投诉委员会和急诊科直接访客转介的来电者在某些方面似乎有所不同。结论:PCC电话咨询的依从率与许多其他健康干预措施的依从率相似。对呼叫PCC的人群和那些自行到急诊室就诊的人群的比较表明,PCC的数据可能不能反映中毒给卫生保健系统带来的真正负担。
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引用次数: 17
Survival pattern in patients with acute organophosphate poisoning receiving intensive care. 急性有机磷中毒重症监护患者的生存模式。
Pub Date : 2004-01-01 DOI: 10.1081/clt-120039539
U A D D Munidasa, I B Gawarammana, S A M Kularatne, P V R Kumarasiri, C D A Goonasekera

Background: Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high.

Objective: To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months.

Methods: Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001.

Results: During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1-27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO2 of >40% to maintain a SpO2 of >92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients.

Conclusion: Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One-third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO2>40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU.

背景:在斯里兰卡等发展中国家,大约35%的急性有机磷中毒患者需要重症监护和机械通气。然而,死亡率仍然很高。目的:研究斯里兰卡某区域中心为期40个月需要强化治疗的急性OP中毒患者的结局和死亡率预测因素。方法:回顾性分析1998年3月至2001年7月ICU收治的急性OP中毒患者的重症监护记录。结果:研究期间共有126例急性OP中毒患者入住ICU。10例患者的记录丢失,37例患者的记录不完整,因此排除。其余71例患者(59例男性)均需要气管插管和机械通气4天(中位数)(范围1-27天),此外还需要洗胃、阿托品和肟类药物的标准治疗以及适当的水合作用。71例患者中,36例(男性28例)死亡。生命表分析显示,前三天的累积存活率急剧下降至67%。收缩压< 100mmhg, 24 h内FiO2 >40%以维持SpO2 >92%为机械通气患者预后不良指标。结论:尽管有足够的呼吸支持、重症监护和阿托品和肟类药物的特异性治疗,OP中毒的死亡率仍然很高。三分之一需要机械通气并到达重症监护病房的受试者在中毒后72小时内死亡。收缩压低于100 mmHg和FiO2>40%维持足够氧合的必要性是ICU机械通气患者预后不良的预测因素。
{"title":"Survival pattern in patients with acute organophosphate poisoning receiving intensive care.","authors":"U A D D Munidasa,&nbsp;I B Gawarammana,&nbsp;S A M Kularatne,&nbsp;P V R Kumarasiri,&nbsp;C D A Goonasekera","doi":"10.1081/clt-120039539","DOIUrl":"https://doi.org/10.1081/clt-120039539","url":null,"abstract":"<p><strong>Background: </strong>Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high.</p><p><strong>Objective: </strong>To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months.</p><p><strong>Methods: </strong>Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001.</p><p><strong>Results: </strong>During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1-27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO2 of >40% to maintain a SpO2 of >92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients.</p><p><strong>Conclusion: </strong>Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One-third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO2>40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU.</p>","PeriodicalId":17447,"journal":{"name":"Journal of toxicology. Clinical toxicology","volume":"42 4","pages":"343-7"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1081/clt-120039539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40899268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 72
The oral toxicity of resorcinol during pregnancy: a case report. 间苯二酚妊娠期口服毒性1例报告。
Pub Date : 2004-01-01 DOI: 10.1081/clt-200026966
Bulent Duran, Sinan Gursoy, Meral Cetin, Nihal Demirkoprulu, Yeltekin Demirel, Bilge Gurelik

Resorcinol (1,3 benzenediol; m-dihydroxybenzene: resorcin) is a pharmaceutical agent used topically in dermatological treatments such as acne and related skin conditions. It could also be used in combination with the other acne treatment agents such as sulphur. It could be very hazardous if taken orally and there are limited reports on its toxic effects in human. The present work aimed to report a resorcinol poisoning case in which resorcinol was taken accidentally by a woman at 30 weeks of pregnancy. The major clinical findings were unconsciousness, drowsiness, and respiratory failure that required mechanical ventilation along with tonic-clonic seizures and hypothermia. In addition, the laboratory findings were leucocytosis, high bilirubin levels, severe metabolic acidosis, and green-colored urine. The fetus was considered dead 24 h after delivery; however, mother's prognosis was well with supportive management. It could be concluded that the basic approach to the patient with resorcinol poisoning should include the initial stabilization of immediate life-threatening problems and elimination of the toxin. This is the first report on resorcinol poisoning in pregnant women, indicating its major clinical and laboratory findings.

间苯二酚(1,3苯二醇;间二羟基苯:间苯二酚)是一种药物制剂,局部用于皮肤病学治疗,如痤疮和相关的皮肤状况。它也可以与其他痤疮治疗剂(如硫磺)联合使用。口服可能非常危险,关于其对人体毒性作用的报道有限。目前的工作旨在报告一个间苯二酚中毒的情况下,其中间苯二酚意外服用的妇女在怀孕30周。主要临床表现为意识不清、嗜睡和呼吸衰竭,需要机械通气,同时伴有强直阵挛性发作和体温过低。此外,实验室检查结果为白细胞增多,胆红素水平高,严重代谢性酸中毒,尿液呈绿色。胎儿在分娩后24小时视为死亡;然而,在支持性治疗下,母亲的预后良好。由此可见,间苯二酚中毒患者的基本治疗方法应包括立即危及生命的问题的初步稳定和毒素的消除。这是关于孕妇间苯二酚中毒的第一份报告,指出了其主要的临床和实验室发现。
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引用次数: 24
Iron bezoar retained in colon despite 3 days of whole bowel irrigation. 全肠灌洗3天后,铁牛黄仍留在结肠内。
Pub Date : 2004-01-01 DOI: 10.1081/clt-200026974
Larissa I Velez, Rebeca Gracia, Lisa D Mills, Greene Shepherd, Sing-Yi Feng

Concretion formation is a documented complication of large iron ingestions. The generally accepted treatment is supportive care, whole bowel irrigation, and intravenous deferoxamine for systemic toxicity. Laparotomy and gastrotomy have also been used in patients with a high iron burden and bezoar formation. Though experiments suggest that iron is poorly absorbed in the colon, there are no case reports of iron overdose without systemic toxicity, despite a retained colonic bezoar. We report the case of a 16-month-old who presented to an Emergency Department 19 h after an iron ingestion. Initial laboratory studies revealed an anion gap of 14 mEq/L, and a 20 h serum iron concentration of 429 mcg/dL. An abdominal radiograph revealed multiple pills throughout the stomach and small bowel; whole bowel irrigation was initiated. Deferoxamine was administered at 10 mg/kg/h and then stopped when the serum iron level reached 27 mcg/dL, 36 h later. At this time, the abdominal radiograph showed an iron bezoar remaining in the ascending colon despite a clear rectal effluent from whole bowel irrigation. Despite whole bowel irrigation over the next 36 h, the iron bezoar was not removed and actually migrated proximally in the colon. Treatment was stopped on the third day and a normal diet was instituted with prompt passage of the bezoar.

结块的形成是大量铁摄入的并发症。一般接受的治疗是支持治疗,全肠冲洗,静脉注射去铁胺治疗全身毒性。对于高铁负荷和牛黄形成的患者,也可采用剖腹和胃切除术。虽然实验表明铁在结肠中吸收不良,但没有铁过量而不引起全身毒性的病例报告,尽管保留了结肠牛黄。我们报告一个16个月大的病例谁提出了一个急诊科19小时后铁摄入。最初的实验室研究显示阴离子间隙为14 mEq/L, 20 h血清铁浓度为429 mcg/dL。腹部x光片显示胃和小肠内有多个药片;开始全肠冲洗。去铁胺按10 mg/kg/h给药,36 h后血清铁水平达到27 mcg/dL时停用。此时,腹部x线片显示升结肠中残留铁牛黄,尽管全肠冲洗后直肠流出物清晰。尽管在接下来的36小时内对整个肠道进行了冲洗,但铁牛黄并没有被移除,实际上是在结肠的近端迁移。第三天停止治疗,开始正常饮食,并迅速排出牛黄。
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引用次数: 11
Position paper: whole bowel irrigation. 立场纸:全肠灌洗。
Pub Date : 2004-01-01 DOI: 10.1081/clt-200035932

Whole bowel irrigation (WBI) should not be used routinely in the management of the poisoned patient. Although some volunteer studies have shown substantial decreases in the bioavailability of ingested drugs, no controlled clinical trials have been performed and there is no conclusive evidence that WBI improves the outcome of the poisoned patient. Based on volunteer studies, WBI should be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting greater than two hours after drug ingestion. WBI should be considered for patients who have ingested substantial amounts of iron as the morbidity is high and there is a lack of other options for gastrointestinal decontamination. The use of WBI for the removal of ingested packets of illicit drugs is also a potential indication. WBI is contraindicated in patients with bowel obstruction, perforation, ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients or in patients with medical conditions that may be further compromised by its use. The concurrent administration of activated charcoal and WBI may decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. A review of the literature since the preparation of the 1997 Whole Bowel Irrigation Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.

全肠灌洗(WBI)不应常规应用于中毒患者的治疗。尽管一些志愿者研究表明,摄入药物的生物利用度大幅降低,但尚未进行对照临床试验,也没有确凿证据表明WBI改善了中毒患者的预后。根据志愿者研究,对于缓释或肠溶药物的潜在毒性摄入,特别是那些在药物摄入后超过2小时出现症状的患者,应考虑WBI。对于摄入大量铁的患者,应考虑WBI,因为发病率高,而且缺乏其他的胃肠道净化选择。使用WBI清除摄入的非法药物包也是一种潜在的指征。WBI禁忌用于肠梗阻、穿孔、肠梗阻、血流动力学不稳定或未保护气道受损的患者。对于身体虚弱的患者或有可能因使用WBI而进一步恶化的医疗状况的患者,应谨慎使用WBI。同时施用活性炭和WBI可能会降低活性炭的有效性。这种相互作用的临床意义尚不确定。回顾1997年《全肠灌洗位置声明》编制以来的文献,没有发现需要修订该声明结论的新证据。
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引用次数: 126
Do adenosine receptors play a role in amitriptyline-induced cardiovascular toxicity in rats? 腺苷受体在阿米替林诱导的大鼠心血管毒性中起作用吗?
Pub Date : 2004-01-01 DOI: 10.1081/clt-200041845
Sule Kalkan, Oguz Aygoren, Aylin Akgun, Sedef Gidener, Hulya Guven, Yesim Tuncok

Objective: The aim of the our study was to investigate the role of adenosine receptors on cardiovascular toxicity induced by amitriptyline, a tricyclic antidepressant agent. Therefore, the hypothesis of this study was that adenosine receptor antagonists would improve and/or prevent amitriptyline-induced hypotension and conduction abnormalities in an anesthetized rat model of amitriptyline intoxication.

Methods: Two separate experimental protocols were performed. Amitriptyline intoxication was induced by the infusion of amitriptyline 0.94 mg/kg/min until 40-45% reduction of mean arterial pressure (MAP). Sodium cromoglycate (10 mg/kg) was injected i.v. to inhibit the A3 receptor-mediated activation of mast cells. In protocol 1, after amitriptyline infusion, while control animals (n=8) were given dextrose solution, treatment groups received a selective adenosine A1 antagonist DPCPX (8-cyclopentyl-1,3-Dipropylxanthine, 20 microg/kg/min, n=8) or a selective A2a antagonist CSC (8-(3-chlorostyryl) caffeine, 24 microg/kg/min, n=8) for 60 minutes. In protocol 2, after the sodium cromoglycate, while control group of rats (n=8) recevied a dextrose solution, treatment groups of rats were administered DPCPX (20 microg/kg/min, n=8) or CSC (24 microg/kg/min, n=8) infusion to block adenosine A1 and A2a receptors for 20 minutes before amitriptyline infusion. After pretreatment with adenosine antagonists, all rats were given a dose of 0.94 mg/kg/min of amitriptyline infusion during 60 minutes. Outcome measures were mean arterial pressure (MAP), heart rate (HR), QRS duration and survival rate.

Results: In protocol 1, amitriptyline infusion significantly reduced MAP and prolonged QRS within 15 minutes. HR was not changed significantly during the experiments. While dextrose did not improve MAP and QRS prolongation, DPCPX or CSC administration developed a significant improvement in MAP compared to the dextrose group within 10 min (88.5 +/- 2.8%, 75.6 +/- 4.7% and 50.1 +/- 14.7%, p<0.01, p<0.05, respectively). Both DPCPX and CSC decreased QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.00001). In protocol 2, pretreatment with DPCPX or CSC prevented the reduction in MAP due to amitriptyline toxicity compared to rats administered dextrose infusion (99.5 +/- 2.6%, 102.4 +/- 2.6%, 81.8 +/- 5.4, p<0.01 at 30 min; 98.0 +/- 2.9%, 93.5 +/- 6.0%, 64.9 +/- 4.7, p<0.001, p<0.01 at 40 min, respectively). Pretreatment with DPCPX or CSC also prevented the QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.0001).

Conclusion: Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline-induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results s

目的:探讨腺苷受体在三环抗抑郁药阿米替林诱导的心血管毒性中的作用。因此,本研究的假设是腺苷受体拮抗剂可以改善和/或预防阿米替林中毒麻醉大鼠模型中阿米替林诱导的低血压和传导异常。方法:采用两种不同的实验方案。以阿米替林0.94 mg/kg/min静脉滴注阿米替林致阿米替林中毒,至平均动脉压(MAP)下降40-45%。以10 mg/kg滴注铬甘酸钠抑制A3受体介导的肥大细胞活化。在方案1中,阿米替林输注后,对照动物(n=8)给予葡萄糖溶液,治疗组给予选择性腺苷A1拮抗剂DPCPX(8-环戊基-1,3-二丙基黄嘌呤,20微克/千克/分钟,n=8)或选择性A2a拮抗剂CSC(8-(3-氯苯乙烯)咖啡因,24微克/千克/分钟,n=8),持续60分钟。方案2:在给药后,对照组大鼠(n=8)给予葡萄糖溶液,治疗组大鼠分别给予DPCPX(20微克/千克/分钟,n=8)或CSC(24微克/千克/分钟,n=8)输注阻断腺苷A1和A2a受体20分钟后再输注阿米替林。腺苷拮抗剂预处理后,给予阿米替林0.94 mg/kg/min灌注60分钟。结果测量为平均动脉压(MAP)、心率(HR)、QRS持续时间和生存率。结果:在方案1中,阿米替林在15分钟内显著降低MAP并延长QRS。HR在实验期间无显著变化。虽然葡萄糖没有改善MAP和QRS延长,但与葡萄糖组相比,dcpx或CSC组在10分钟内显著改善MAP(88.5 +/- 2.8%, 75.6 +/- 4.7%和50.1 +/- 14.7%)。结论:腺苷拮抗剂在阿米替林毒性大鼠模型中有效改善低血压、QRS延长和生存时间。此外,腺苷受体拮抗剂预处理可消除阿米替林诱导的心脏毒性。这些结果表明腺苷受体可能在阿米替林诱导的心血管毒性的病理生理中起作用。腺苷A1和A2a受体拮抗剂可能是逆转阿米替林诱导的心血管毒性的有希望的药物。
{"title":"Do adenosine receptors play a role in amitriptyline-induced cardiovascular toxicity in rats?","authors":"Sule Kalkan,&nbsp;Oguz Aygoren,&nbsp;Aylin Akgun,&nbsp;Sedef Gidener,&nbsp;Hulya Guven,&nbsp;Yesim Tuncok","doi":"10.1081/clt-200041845","DOIUrl":"https://doi.org/10.1081/clt-200041845","url":null,"abstract":"<p><strong>Objective: </strong>The aim of the our study was to investigate the role of adenosine receptors on cardiovascular toxicity induced by amitriptyline, a tricyclic antidepressant agent. Therefore, the hypothesis of this study was that adenosine receptor antagonists would improve and/or prevent amitriptyline-induced hypotension and conduction abnormalities in an anesthetized rat model of amitriptyline intoxication.</p><p><strong>Methods: </strong>Two separate experimental protocols were performed. Amitriptyline intoxication was induced by the infusion of amitriptyline 0.94 mg/kg/min until 40-45% reduction of mean arterial pressure (MAP). Sodium cromoglycate (10 mg/kg) was injected i.v. to inhibit the A3 receptor-mediated activation of mast cells. In protocol 1, after amitriptyline infusion, while control animals (n=8) were given dextrose solution, treatment groups received a selective adenosine A1 antagonist DPCPX (8-cyclopentyl-1,3-Dipropylxanthine, 20 microg/kg/min, n=8) or a selective A2a antagonist CSC (8-(3-chlorostyryl) caffeine, 24 microg/kg/min, n=8) for 60 minutes. In protocol 2, after the sodium cromoglycate, while control group of rats (n=8) recevied a dextrose solution, treatment groups of rats were administered DPCPX (20 microg/kg/min, n=8) or CSC (24 microg/kg/min, n=8) infusion to block adenosine A1 and A2a receptors for 20 minutes before amitriptyline infusion. After pretreatment with adenosine antagonists, all rats were given a dose of 0.94 mg/kg/min of amitriptyline infusion during 60 minutes. Outcome measures were mean arterial pressure (MAP), heart rate (HR), QRS duration and survival rate.</p><p><strong>Results: </strong>In protocol 1, amitriptyline infusion significantly reduced MAP and prolonged QRS within 15 minutes. HR was not changed significantly during the experiments. While dextrose did not improve MAP and QRS prolongation, DPCPX or CSC administration developed a significant improvement in MAP compared to the dextrose group within 10 min (88.5 +/- 2.8%, 75.6 +/- 4.7% and 50.1 +/- 14.7%, p<0.01, p<0.05, respectively). Both DPCPX and CSC decreased QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.00001). In protocol 2, pretreatment with DPCPX or CSC prevented the reduction in MAP due to amitriptyline toxicity compared to rats administered dextrose infusion (99.5 +/- 2.6%, 102.4 +/- 2.6%, 81.8 +/- 5.4, p<0.01 at 30 min; 98.0 +/- 2.9%, 93.5 +/- 6.0%, 64.9 +/- 4.7, p<0.001, p<0.01 at 40 min, respectively). Pretreatment with DPCPX or CSC also prevented the QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.0001).</p><p><strong>Conclusion: </strong>Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline-induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results s","PeriodicalId":17447,"journal":{"name":"Journal of toxicology. Clinical toxicology","volume":"42 7","pages":"945-54"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1081/clt-200041845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24897185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 25
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Journal of toxicology. Clinical toxicology
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