Tissue distribution of intubation-related lidocaine in brain-dead patients

Tissue distribution of lidocaine that was used for endotracheal intubation during cardiopulmonary resuscitation (CPR) was measured in 3 patients who were brain-dead or near brain death. Case 1 was a 69-year-old female whose heartbeat was restored by CPR but stopped 10 hours later. The lidocaine ratios of cerebrum to blood (2.04) and diencephalon to blood (1.01) were within ranges of those found in non-brain-dead patients. Case 2 was a 77-year-old female whose heart resumed beating after CPR but stopped 66 hours later. The lidocaine ratios of cerebrum to blood (5.69), diencephalon to blood (18.7), and cerebellum to blood (11.3) were much higher than those in non-brain-dead patients. Case 3 was a 48-year-old male who had cardiopulmonary arrest following an acute subarachnoid hemorrhage. His heart resumed beating after resuscitation but ceased beating 114 hours after admission. Lidocaine was detected only from the cerebrum, cerebellum, and blood clots in the superior sagittal sinus at levels of 0.028, 0.024, and 0.007 mug/g, respectively. Tissue distribution of intubation-related lidocaine in brain-dead patients is useful as supplementary data for reviewing hemodynamic changes in their brains during medical treatment.     

Tissue distribution of lidocaine after fatal accidental injection

The accidental death of a 64-year-old heart patient as a result of the injection of an incorrect dose of lidocaine is presented. The attending nurse inadvertently administered an intravenous bolus of 10 mL of 20% lidocaine (2g). The patient should have received 5 mL of 2% lidocaine (0.1 g). Such iatrogenic overdoses of lidocaine arise from confusion between prepackaged dosage forms. Lidocaine concentrations (mg/L or mg/kg were: blood, 30; brain, 135; heart, 106; kidney, 204; lung, 89; spleen, 115; skeletal muscle, 20; and adipose, 1.3. The results indicate that even during cardiopulmonary resuscitation as much as 38% of the administered dose of lidocaine may be found in poorly perfused tissue such as skeletal muscle and adipose.     

Tissue distribution of DDVP after fatal ingestion

Tissue distribution of dichlorvos (DDVP) was determined in a case of fatal ingestion using a rapid and simple gas chromatographic (GC) assay. Remarkable autopsy findings were congestion of the lung and kidneys and bleeding ulcer extending from the dorsum of the tongue to the upper pharynx. The serum cholinesterase activity was 2 IU/l, however, miosis was not observed. In the stomach, 250 ml of volatile fluid was found. Tissue distribution of DDVP was determined using a newly developed simple and rapid GC method. DDVP was found in the spleen and heart at higher concentrations (3340 and 815 μg/g, respectively), and also detected in the urine at the lowest level (4.5 μg/ml). The DDVP concentrations in blood, brain, lung, kidney and liver were 29, 9.7, 81, 80 and 20 μg/ml or g, respectively.     

Tissue distribution of paraquat and diquat after oral administration in rats

The differential distribution of paraquat and diquat in liver, kidney, lung, brain and heart has been studied after oral administration of the LD50 or LD50/2 to rats. Paraquat concentrations were highest in all organs at 24 hours; at this time concentrations in kidney and lung were 2 to 3 times higher than at 2 hours. In contrast, with the exception of kidney, tissue diquat concentrations were highest at 2 hours. There was severe lung damage at 24 hours after paraquat; diquat aid not produce severe lung lesions, but caused intestinal distention and diarrhea. These findings suggest that the difference in the toxicity of paraquat and diquat is related to their difference in tissue distribution and excretion.     

Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.     

Tissue distribution of cocaine in a pregnant woman

Reports of cocaine-related obstetrical problems, including abruptio placentae and spontaneous abortion, have become increasingly evident in the medical literature; however, little is known about tissue distribution of cocaine in the pregnant woman. We report the toxicologic results of distribution studies performed on a pregnant woman and her fetus. Maternal/fetal cocaine concentration ratios were high when comparing blood (9:1), brain (6:5), and kidney (10:6). Possible explanations of the mechanism for lower fetal cocaine concentrations may include uterine vasoconstriction, incomplete maternal/fetal equalibration, or rapid placental/fetal clearance.     

Tissue distribution of tetramethylthiuram disulfide in warm-blooded animals

The objective of the present work was to study the distribution of tetramethylthiuram disulfide (TMTD) in the body of warm-blooded animals as exemplified by white rats. TMTD was administered intragastrically and detected in the unaltered form in other internal organs. It was found to accumulate in the largest amounts in the gastric contents, kidneys, and urine.     

Arterial-esophageal fistulae in patients requiring nasogastric esophageal intubation

A rare and potentially fatal cause of hematemesis is fistula formation between the esophagus and the vascular system. A case report of a 39-year-old woman with congenital aortic arch anomalies hospitalized for treatment of head injuries demonstrates the potential for iatrogenic esophageal trauma to initiate fistula formation between the esophagus and an anomalous arterial system. A literature review revealed 6 other cases of vascular-esophageal fistulae caused by nasogastric esophageal intubation. It is concluded that aortic arch anomalies increase the risk of esophageal injury and subsequent fistula formation from nasogastric esophageal intubation. In addition, the clinical features and pathologic findings of vascular-esophageal fistulae are reviewed.     

Tissue distribution of tramadol and metabolites in an overdose fatality

Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it has some affinity for the opiate receptors, tramadol is believed to exert its analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin. There are several published cases of tramadol's involvement in drug-related deaths and impairment. Reports of deaths involving tramadol alone with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The following tramadol concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In each tissue or fluid except urine, the tramadol concentration was greater than either metabolite, consistent with other reports of drug-impaired drivers and postmortem cases. The O-desmethyl metabolite concentration was greater than the N-desmethyl metabolite concentration in all tissues; this is in contrast to other postmortem reports, in which the majority of cases report concentrations of O-desmethyl as less than those of N-desmethyl. This may be useful as an indicator of time lapse between ingestion and death.     

Tissue distribution of ethosuximide and clobazam in a seizure related fatality

The case of a six-year-old male who died in a hospital while receiving several anticonvulsant drugs is described. Phenytoin, desmethyldiazepam, clobazam (an experimental 1,5 benzodiazepine), and desmethylclobazam were quantitated in serum, liver, and brain tissue by high performance liquid chromatography. Ethosuximide was quantitated by gas chromatography. To our knowledge, this is one of few reports describing tissue concentrations of ethosuximide collected at autopsy and the first report of clobazam/desmethylclobazam tissue distribution in man.     

护理干预对气管切开病人呼吸道管理的应用

气管切开是较为常见的一种维持呼吸道通畅的有效措施,已成为抢救危重病人的主要治疗手段.对气管切开病人的呼吸道管理尤为重要,气管切开与肺部感染有直接关系,肺部感染严重时可导致病人死亡.对于气管切开病人护理的主要目的是控制感染,维持有效的机械通气功能.     

Tissue distribution of mirtazapine and desmethylmirtazapine in a case of mirtazapine poisoning

An ingestion of an unknown quantity of mirtazapine in a suicide attempt leading to death is described. Sertraline and amitriptyline have been co-ingested. Because mirtazapine is reported to be relatively safe in overdose, body fluids and tissues were investigated for both mirtazapine and desmethylmirtazapine by high-pressure liquid chromatography/tandem mass spectrometry following liquid-liquid extraction. The limit of detection was sufficiently low to also apply the assay in pharmacokinetic studies. The levels of amitriptyline and nortriptyline were very low (38 and 19 ng/mL femoral venous blood) and the amount of sertraline in blood taken from the femoral vein (880 ng/mL) was considerably lower than those seen in overdosage. Accumulation of mirtazapine and N-desmethylmirtazapine was evident in fluids and tissues involved in enterohepatic circulation and excretion. The concentration determined in a brain sample suggests a contribution of the metabolite to the drug's pharmacodynamic activity. Based on literature data, significant adverse or synergistic effects among the drugs detected as well as adverse reactions such as a serotonin reaction appeared less probable. Mirtazapine exhibits alpha(1)-antagonistic properties on the cardiac-vascular system and may cause hyponatraemia. In the face of the cardiac findings at autopsy and the lack of an apparent cause of death, these effects of mirtazapine may have initiated a process leading to death.     

Concentrations of lidocaine and monoethylglycylxylidide (MEGX) in lidocaine associated deaths

Concentrations of lidocaine and MEGX were determined in a variety of tissues and other samples collected at autopsy. In 13 of the cases examined in which lidocaine was associated with death, tissue concentrations were greater than 15 mg/kg. Tissue concentrations in other patients treated with lidocaine were significantly lower.     

Tissue distribution of nitrazepam and 7-aminonitrazepam in a case of nitrazepam intoxication

We report a case of nitrazepam poisoning in which the distribution of nitrazepam and 7-aminonitrazepam was determined in body fluids and tissues. A 52-year-old woman was found dead in a shallow ditch (approximately 5 cm in depth), in the winter. Ambient temperature was 2-8 degrees C. The postmortem interval was estimated to be approximately 1 day and no putrefaction was observed. The cause of death was thought to be drowning due to nitrazepam overdose and cold exposure. Blood concentrations of nitrazepam and 7-aminonitrazepam were very site dependent (0.400-0.973 microg/ml and 0.418-1.82 microg/ml). In addition, the concentration of the same analytes in the bile were 4.08 and 1.67 microg/ml, respectively, and in the urine: 0.580 and 1.09 microg/ml, respectively. A high accumulation of both substances was observed in various types of brain tissue (2.17-6.22 microg/g and 2.49-5.11 microg/g). Only small amounts of nitrazepam and 7-aminonitrazepam were detected in the liver (0.059 and 0.113 microg/g, respectively). Large differences in the observed concentrations of nitrazepam and 7-aminonitrazepam among arterial and venous blood samples were thought to be mainly due to dilution of arterial blood by water entering the circulation through lungs at the time of death. Bacterial metabolism of nitrazepam may also have contributed to the observed differences.     

Tissue distribution of trichloroethylene in a case of accidental acute intoxication by inhalation

This article describes the toxicological findings in a fatality due to an accidental inhalation of trichloroethylene which took place during wall coating of a poorly ventilated well using trichloroethylene. The man was wearing protective clothing and a mouthmask with adsorbent. He was found dead on the floor of the well 5h after descending. Trichloroethylene was added to the mortar to enhance drying. Identification and quantitation of trichloroethylene in the postmortem samples (blood, lung, liver, kidney, stomach content and bile) and identification of its metabolite trichloroacetic acid in urine was performed using static headspace gas chromatography with mass spectrometric detector. The compounds were separated on a CP-SIL 5CB Low Bleed/MS column using n-butanol as internal standard. The method was linear over the specific range investigated, and showed an accuracy of 104% and an intra-day precision of 11%. Trichloroethylene concentrations of 84mg/l in subclavian blood, 40mg/l in femoral blood, 72mg/kg in liver, 12mg/kg in kidney, 78mg/kg in stomach content, 104mg/l in bile and 21mg/kg in lung were found. Trichloroacetic acid was identified in the urine.     

Determining the state of the deceased during cardiopulmonary resuscitation from tissue distribution patterns of intubation-related lidocaine

The objective of this study was to determine whether the concentrations of lidocaine, used for endotracheal intubation, in body fluids and tissues reflect the state of the circulation of the deceased during cardiopulmonary resuscitation. The tissue distribution of lidocaine was investigated in seven individuals (Cases 1-7) who underwent medical treatment with endotracheal intubation using Xylocaine jelly (a 2% lidocaine hydrochloride preparation), before being pronounced dead. Six patients (Cases 1-6) had cardiopulmonary arrest on arrival at hospital. In Cases 1-4, there was no restoration of heartbeat during cardiopulmonary resuscitation. However, systemic distribution of intubation-related lidocaine was observed and the kidney-to-liver ratios of lidocaine were less than 1. In Cases 5 and 6, the heartbeat resumed temporarily with cardiac massage, and a kidney-to-liver lidocaine ratio greater than 1 was observed. In Case 7, where the patient was comatose upon admission to hospital, the kidney-to-liver ratio of lidocaine was also greater than 1. These phenomena were substantiated in animal experiments. Our results indicate that the absorption of tracheal lidocaine during the artificial circulation resulting from cardiopulmonary resuscitation results in a kidney to liver ratio of less than 1, whereas absorption during natural circulation gives a ratio greater than 1. The kidney-to-liver ratio of intubation-related lidocaine may give useful information on the state of a patient during cardiopulmonary resuscitation.     

利多卡因及MEGX在蛛网膜下腔麻醉致死犬体内死后再分布

目的研究利多卡因及其代谢产物单乙基甘氨酰二甲苯胺(MEGX)在蛛网膜下腔麻醉致死犬体内的死后再分布规律。方法犬6只随机分为A、B两组,分别经蛛网膜下腔注射0.5倍(6.34mg/kg)和5倍(63.35mg/kg)硬膜外麻醉极量的盐酸利多卡因,于死后0h、12h、24h、36h、72h取心血、外周血、肝、脑等,采用高效液相色谱法(HPLC)检测其中利多卡因及MEGX的含量。结果 A组犬死后72h,心血、外周血和脑中利多卡因含量与死亡当时的比值(Ct/C0)分别为4.74,14.87,7.67,均呈上升趋势(P0.05),MEGX含量与死亡当时含量差异无统计学意义(P0.05);B组犬死后72h,心血中利多卡因含量Ct/C0值为0.36,呈下降趋势(P0.05),脑中为3.48(P0.05)呈升高的趋势,肝中MEGX含量与死亡当时相比差异无统计学意义(P0.05)。结论蛛网膜下腔不同剂量麻醉致死犬体内利多卡因均会发生死后再分布,MEGX未发生死后再分布。     

急性心功能障碍大鼠心肌中BNP的表达

目的研究大鼠急性心功能障碍时心肌组织中脑钠肽(brain natriuretic peptide,BNP)的表达变化,探讨BNP在急性心功能障碍的法医学诊断中的应用价值。方法建立大鼠急性心功能障碍模型,运用免疫组织化学、Western印迹法、实时RT-PCR等技术检测心功能障碍过程中心肌组织BNP蛋白和BNP mRNA的表达变化。结果随心功能障碍持续时间增加,免疫阳性着色不断增强。1～2h主要表现为弱阳性,4～6h心肌细胞主要表现为阳性,10～12h大鼠心肌细胞表现为强阳性。Western印迹法和实时RT-PCR结果均显示,随心功能障碍持续时间增加,BNP明显升高,而且心功能障碍1h即能观察到BNP mRNA显著升高。结论检测心肌组织中BNP蛋白及BNP mRNA的表达能为法医病理学工作者客观评价心功能状态提供一种新的途径。     

利多卡因在蛛网膜下腔和静脉注射致死犬体内的死后分布

目的比较利多卡因在蛛网膜下腔和静脉注射致死犬体内的死后分布特点。方法犬12只,其中6只经蛛网膜下腔,另6只经股静脉匀速注入利多卡因(5×15mg/kg)致死,迅速解剖动物,取大脑、侧脑室脑脊液、腰段脊髓腔脑脊液、不同脊髓节段(颈髓、胸髓、腰髓、骶髓),心、肺、肝、脾、肾、胆汁、尿、心血、周围血、注射部位肌肉和注射部位20 cm以外肌肉等脏器组织和体液,用气质联用法定性,气相色谱法定量检测其中利多卡因含量。结果蛛网膜下腔注射致死犬体内利多卡因的含量由高到低顺序依次为腰段脊髓腔脑脊液、骶段脊髓、胸段脊髓、侧脑室脑脊液、腰段脊髓、颈段脊髓、肺、肾、注射部位肌肉、心、大脑、脾、心血、肝、周围血、胆汁、注射部位20 cm以外的肌肉、尿;静脉注射致死犬体内利多卡因的含量由高到低顺序依次为肾、心、肺、脾、大脑、肝、周围血、胆汁、心血、颈段脊髓、胸段脑脊液、注射部位肌肉、腰段脊髓、注射部位20 cm以外的肌肉、侧脑室脑脊液、尿、腰段脊髓腔脑脊液、骶段脊髓。结论蛛网膜下腔注射致死犬背侧脊髓液中利多卡因含量最高,静脉注射致死犬肾脏利多卡因含量最高,此分布特征可为利多卡因麻醉意外法医学鉴定中入体途径的判定提供参考。