Tissue distribution of lidocaine in critical care patients after intubation

We investigated tissue distribution of lidocaine in 33 patients after endotracheal intubation with Xylocaine jelly that contains 2% lidocaine hydrochloride. Blood levels of monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, were also determined. Five patients (Group A) were alive on arrival and six patients (Group B) resumed heartbeats after cardiopulmonary resuscitation (CPR). The survival times for Groups A and B ranged from 3 to 72 h. The remaining 22 patients (Group C) did not survive cardiopulmonary arrest on arrival (CPAOA). Systemic distribution of lidocaine was measured in nine patients from Group C. The liver-to-kidney lidocaine ratios and cerebrum-to-cerebrospinal fluid lidocaine ratios were: Group A, 0.1-0.7 and 1.4-3.6, respectively; Group B, 0.2-0.8 and 1.2-2.3, respectively; Group C, 0.1-17 and 0.2-1.0, respectively. MEGX was detected in all blood samples from Group A and only two samples from Group B. No MEGX was detected in samples from Group C. Our results indicate that the absorption of tracheal lidocaine during natural circulation results in a cerebrum-to-cerebrospinal fluid lidocaine ratio of 1.2 or more, whereas absorption during artificial circulation by cardiac massage gives a ratio of 1.0 or less. The cerebrum-to-cerebrospinal fluid lidocaine ratio may be a more useful index to estimate circulatory dynamics of patients during CPR than the liver-to-kidney lidocaine ratio. MEGX was not a useful parameter for monitoring circulatory changes during cardiac massage.     

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.     

Cardiac laceration and pericardial tamponade due to cardiopulmonary resuscitation after myocardial infarction.

Complications of cardiopulmonary resuscitation (CPR), such as rib fractures and pneumothorax, are not uncommon. The authors report the case of a 69-year-old woman who underwent surgery for a perforated duodenal ulcer. Eighteen hours postoperatively she sustained a cardiac arrest; vigorous resuscitation efforts, using advanced cardiac life-support procedures, failed. At autopsy, she had 350 mL of fresh blood in her pericardial sac, which had caused cardiac tamponade. Three ribs were fractured at the left sternal border. Directly underneath the fractured ribs were a 0.4-cm laceration of the pericardium and an accompanying 0.7-cm laceration of the left ventricle. There was an acute thrombus in the left anterior descending artery. Microscopic examination of the heart showed acute infarction of the left ventricle in the vicinity of the laceration. This case demonstrates that vigorous CPR performed on an acutely infarcted heart can result in lethal cardiac laceration and tamponade.     

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.     

A case of homicide by lethal injection with lidocaine

This report describes a homicide by overdosage with lidocaine. The decedent, a 32-year-old male hospitalized for a lengthy period with acute intermittent porphyria and chronic pancreatitis, suffered apparent asystole and seizure. Failed resuscitation preceded death. A forensic autopsy was conducted based upon suspicions of alleged patient mistreatment by one of the attending nurses. Toxicological analyses revealed the presence of lidocaine in blood, liver, kidney, brain, and heart at 22.2 mg/L and 43.6, 28.3, 23.1, and 13.1 mg/kg, respectively. Also present were diazepam, phenytoin, and promethazine. Both diazepam and phenytoin had been administered during resuscitation, but lidocaine had not. The cause of death was determined to be ventricular arrhythmia precipitated by lidocaine overdosage. The administered dose was calculated to have been approximately 1500 mg. The manner of death was determined to be homicide. The nurse was arrested and subsequently tried for murder by administering a lethal quantity of lidocaine.     

Distribution of lidocaine and disopyramide in human blood and tissue, a case report of death caused by spinal anesthesia

An 11-year-old girl was anesthetized with hyper-baric solution of lidocaine as spinal anesthesia for an appendectomy in a surgical clinic. Respiratory arrest which occurred soon after the injection, was not discovered for a period of time. Since spontaneous respiration recovered within 2 h of intensive resuscitation, the patient was transferred to a community hospital for intensive care. Ten hours after the spinal anesthesia, she died of cardiac failure. The concentration of lidocaine in the brain was 5-10 times more than that in other tissues. The relationship between the possibility of malpractice of spinal anesthesia and tissue distribution of the drug was discussed. In addition to lidocaine, a toxic amount of disopyramide, an antiarrhythmic drug, was detected in the body. The distribution of disopyramide was also estimated, and the pharmacokinetics of disopyramide in plasma and tissues were studied experimentally in rats.     

Fatal cyclobenzaprine overdose with postmortem values

There are only two published cases of overdose with postmortem blood cyclobenzaprine concentrations, both with confounding factors. We report two additional cases of fatal cyclobenzaprine overdose with postmortem values. Case 1: a 56-year-old female was found in full cardiopulmonary arrest after a verbal suicide threat to a friend. Postmortem blood concentrations were cyclobenzaprine 0.96 mg/L and diazepam 0.3 mg/L. Case 2: a 37-year-old male was found in full arrest by a family member after an intentional ingestion of cyclobenzaprine. Postmortem blood concentrations were cyclobenzaprine 0.8 mg/L and ethanol 0.174 gm/dL. The concentrations of diazepam and ethanol reported in these two patients were not found in quantities usually associated with a fatal outcome, suggesting that the cyclobenzaprine was the primary cause of the fatality. Additionally, the blood was drawn from a femoral site, so that postmortem redistribution is not a likely factor. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome.     

Reporting a fatality during tumescent liposuction

Deaths of patients during elective surgery have drawn attention to the danger of anesthesia. Tumescent local anesthesia is subcutaneous infiltration of large volumes of dilute lidocaine with epinephrine to produce vasoconstriction while delivering anesthesia over large areas without lidocaine toxicity. This report documents the case of a 38-year-old woman who attended an outpatient clinic to undergo liposuction of the abdomen and bilateral hips and thighs. According to one witness, around 30 min after anesthesia administration, the victim suffered an episode of tonic–clonic convulsion. When the emergency medical services arrived the patient was in asystole. She died in spite of attempted cardiopulmonary resuscitation. The patient had no significant past medical history including no history of allergies or any known complications with anesthesia. A complete autopsy was performed and possible causes of death such as myocardial infarction, aspiration of food or foreign body, and pulmonary embolism were discarded. Anaphylactic shock was considered a possible but unlikely explanation for the fatality. Toxicological analyses revealed the presence of lidocaine and mepivacaine in heart blood, at concentrations of 4.9 and 16.2 mg/L, respectively. All drugs involved in the case were detected using gas chromatography with nitrogen–phosphorus detector and confirmed using gas chromatography–mass spectrometry full scan mode after solid-phase extraction using Chem-Elut columns. An additional high-performance liquid chromatography coupled to diode-array detection screening also obtained the same results. Based on the autopsy findings, case history, and toxicology results, the forensic pathologists ruled that the cause of death was an overdose of local anesthetic agents. The Court of Law ruled the death as an involuntary homicide due to gross negligence.     

Death following spontaneous recovery from cardiopulmonary arrest in a hospital mortuary: 'Lazarus phenomenon' in a case of alleged medical negligence

We report a possibly first forensic autopsy case of death following a spontaneous recovery from cardiopulmonary arrest (CPA) after clinical declaration of death: 'Lazarus phenomenon'. A 65-year-old male with congenital deafness and dumbness was found unconscious in his room at a public home. During pre-hospital and clinical resuscitation including defibrillation and medications for about 35 min, CPA persisted under electrocardiographic (ECG) monitoring and therefore, his death was pronounced. However, about 20 min later, a police officer who had been called for the postmortem investigation found the patient moving in the mortuary. The patient subsequently showed typical ECG signs and laboratory findings of early inferior wall myocardial infarction and died 4 days later. The forensic autopsy, due to alleged medical negligence, revealed myocardial infarction with thrombotic occlusion of the right coronary artery and secondary hypoxic brain damage. The present case and the related clinical literature suggest that, especially in cases of acute myocardial infarction in elderly patients, a careful observation to confirm death after discontinuation of resuscitation is recommended to provide appropriate medical care, irrespective of the quality or duration of advanced life supporting efforts.     

Can Neck Contusions in Unexplained Pediatric Deaths be Explained by Cardiopulmonary Resuscitation?

The distribution of cutaneous contusions in infants may raise the possibility of maltreatment. Neck contusions are particularly problematic since they seldom occur outside the setting of abuse, while cardiopulmonary resuscitation (CPR)‐related maneuvers may involve the neck. To address the role of CPR in neck findings, we examined 260 consecutive pediatric autopsies in which CPR was attempted. No neck contusions were identified in manners of death classified as natural, undetermined, or suicide. Contusions were present in two of 80 deaths classified as accident and had obvious accidental causes. About 26% of deaths classified as homicide had neck contusions with no explanation provided by the caregiver (p < 0.0001). In conclusion, neck contusions in deceased children with no apparent explanation should be regarded as suspicious for abuse and investigated accordingly. CPR is not a plausible explanation for neck contusions in children.     

Congestion bleedings of the face and cardiopulmonary resuscitation--an attempt to evaluate their relationship

OBJECTIVES: Are any other factors besides the factor "cause of death" involved in the development of petechial hemorrhages (PET) of the head? The significance of the cause of death is well known, other factors have been rarely investigated in medical literature. Do they include cardiopulmonary resuscitation (CPR), as has been claimed in several forensic publications? MATERIALS AND METHODS: (a) 473 consecutive autopsy cases (without strangulation) evaluated by one examiner, which were appropriate for this investigation; (b) analysis of 181 cardiac deaths (investigated by all physicians of our institute). RESULTS: Petechiae were found in 13.3% of all cases and were clearly dependent on the cause of death, up to 20% were found in burn victims, intensive-care patients and cardiac fatalities. Petechiae were more frequently observed in the middle age groups (>20%) than in old persons (<10%). The number of PET cases increased with body mass but was lower in extremely obese persons, a greater number of cases with PET was also observed with increasing heart weight. PET were observed in 11% of the deaths without CPR compared to 19% with CPR. This difference was predominantly caused by the subgroup "acute coronary death", especially if victims younger than 60 years were considered, whereas in many other causes of death no difference in the prevalence of PET with or without CPR could be observed. CONCLUSION: Besides the cause of death, other factors (age, body mass and possibly even heart weight) influence the development of petechiae. The hypothesis that CPR alone produces PET is not confirmed by our experience.     

Postmortem atropine concentrations in resuscitation cases

The medications used during resuscitation are often in and of themselves toxic. Several reports have been published regarding toxicities of these drugs, including lidocaine, procainamide, and atropine. But how does a forensic pathologist or toxicologist differentiate a possible intoxication from therapeutic or resuscitory use especially given that the concentrations of such drugs, when used in the setting of resuscitation, have not been studied? Concentrations of a well-known resuscitation medication, atropine, were assessed in cases where it was administered before death during attempted resuscitation in an effort to address this deficiency. A review of deaths occurring in 2009 was undertaken to identify cases where drugs known to be used during resuscitation were present on toxicological analysis. Autopsy reports and medical records were examined to determine how much atropine was administered, the timing and route of administration, the time the sample was drawn (antemortem and postmortem), the source of the sample, and the ultimate cause of death. Eighty-nine cases were identified in which atropine was given before death during attempted resuscitation and was detected in the blood on postmortem toxicological screening; 11 cases were identified in which atropine was administered before death yet was not detected on the postmortem toxicological screening. Mean age was 41 years, and there were 65 males and 35 females. The overall median dose of atropine given was 3 mg, the median difference between the time of last administration of the atropine to the time of death (or draw for antemortem samples) was 15 minutes, and the median atropine concentration was 0.1 mg/L. Analysis failed to reveal significant differences in the atropine concentration based on the route of administration (intravenous or intraosseus), the cause of death, or the time since administration (within the first 2 hours). Analysis did reveal a difference between the atropine concentrations in peripheral versus central blood sources and with prolonged postmortem interval (>24 hours) suggesting postmortem redistribution.     

Rib fractures in infants due to cardiopulmonary resuscitation efforts

Although it is widely known that adults may sustain fractures of the anterior and/or lateral aspects of the ribs due to cardiopulmonary resuscitation (CPR) efforts, relatively little is written about the generation of CPR-related rib fractures in the infant age range. In a series of 70 consecutive autopsies in infants ranging in age from 2 weeks to 8 months, with no history or indications of injury, the parietal pleura of the thoracic cage was stripped and the ribs carefully examined for fracture. Subtle fractures of the anterolateral aspects of the ribs were discovered in 8 (11%) of the 70 cases. In 7 of the 8 cases, multiple ribs were fractured (ranging up to 10 rib fractures), and in 5 of these cases, the rib fractures were bilateral. All of the rib fractures were subtle, had little if any associated blood extravasation, and would have been easily missed had the parietal pleura not been stripped. These anterolateral rib fractures in infants are the likely correlate of anterolateral rib fractures that are not uncommonly seen in the adult population, resulting from resuscitation efforts. The rib fractures are subtle and may not be identified unless the parietal pleura is stripped.     

Distribution of tetracaine and its metabolite in rabbits after high versus normal spinal anesthesia.

High spinal anesthesia is one cause of sudden death associated with the spinal anesthesia. We did animal experiments to verify high spinal anesthesia by analyzing tetracaine and its metabolite, p-butylaminobenzoic acid in tissue samples. Tetracaine (0.25% in 10% glucose solution) 0.21-0.28 mg/kg was administered to two groups of rabbits to induce high and normal spinal anesthesia. Tetracaine and the metabolite in rabbit tissues were analyzed by gas chromatography-mass spectrometry, as a free base for tetracaine and as tert-butyldimethylsilyl derivative for the metabolite. In the group given high spinal anesthesia, levels of the metabolite in the brain stem were higher than in the cerebrum, cerebellum and whole blood. On the other hand, in the group given normal spinal anesthesia, the opposite results were obtained. Therefore, high spinal anesthesia induced by tetracaine can be diagnosed by comparing the concentrations of metabolite in whole blood, cerebrum, cerebellum and brain stem.     

Oronasal blood in sudden infant death.

Oronasal secretions are observed frequently in sudden infant death syndrome (SIDS), but overt blood is uncommonly reported. The literature on oronasal blood in sudden infant death is limited. The goal of this study was to determine the frequency of oronasal blood in sudden infant deaths and to examine possible causative factors. Oronasal blood was described in 28 (7%) of 406 cases of sudden infant death. Oronasal blood could not be attributed to cardiopulmonary resuscitation in 14 cases, including 10 (3%) of 300 cases of SIDS, 2 (14%) of 14 accidental suffocation cases, and 2 (15%) of 13 undetermined cases. Eight of the 10 infants in cases of sudden infant death were bedsharing: 5 with both parents, 2 between both parents. The infant in 1 SIDS case was from a family that had had three referrals to Child Protective Services. Oronasal blood not attributable to cardiopulmonary resuscitation occurs rarely in SIDS when the infant is sleeping supine in a safe environment. Bedsharing may place infants at risk of suffocation from overlaying. Oronasal blood observed before cardiopulmonary resuscitation is given is probably of oronasal skin or mucous membrane origin and may be a sign of accidental or inflicted suffocation. Sanguineous secretions that are mucoid or frothy are likely of remote origin, such as lung alveoli. The use of an otoscope to establish the origin of oronasal blood in cases of sudden infant death is recommended.     

Cardiopulmonary resuscitation-related injuries and homicidal blunt abdominal trauma in children

Defendants accused of inflicting fatal abdominal injuries to children occasionally raise the defense that the injuries were caused by cardiopulmonary resuscitation (CPR). The purpose of this study is to answer the question: Does closed chest CPR result in fatal blunt abdominal injuries that can be mistaken for homicidal assault? To that end, a retrospective study was conducted of all homicidal blunt abdominal injuries in children 10 years and younger from the Dade, Broward, and Palm Beach Medical Examiner's Offices from 1981 through 1997. These were compared to cases of children who died of natural causes during the same time period in Broward County who had CPR (control group 1) and to children who died of nonvehicular accidental blunt abdominal trauma (control group 2). Children with life-threatening head injuries were excluded. Medical examiner records, autopsy reports, documenting photographs, and clinical records were reviewed. The data analyzed included subject demographics, whether CPR was performed and by whom, and autopsy findings. Thirty-three child homicides with fatal abdominal injuries were reviewed. Twenty-four (73%) of the homicides received CPR. There was no difference in the nature and severity of injuries between the 24 children who received CPR and the 9 who did not. Three hundred and twenty-four cases of pediatric natural deaths were reviewed, all of which had CPR. No traumatic abdominal injuries were found in any of the children who died of natural causes. Only four children who died of natural causes had evidence of extraabdominal trauma related to CPR. No cases of nonvehicular accidental blunt abdominal trauma were identified during the 17-year period, although there were nonvehicular accidental fatalities due to extraabdominal injuries. The likelihood of CPR-related primary abdominal trauma in child homicides is very low.     

Post-mortem toxico-kinetics of trazodone.

Trazodone is a structurally unique bicyclic anti-depressant, said to be significantly less toxic than other anti-depressants following an acute overdose. We studied the tissue distribution and post-mortem redistribution of trazodone in two fatalities, one of which allowed comparison with trimipramine, a typical tricyclic anti-depressant. Case 1, a 53-year-old female weighing 72 kg, had femoral vein concentrations of trimipramine 5.5 micrograms/ml, trazodone 14.4 micrograms/ml and alcohol 107 mg%. Case 2, a 48-year-old female of 70 kg, had a femoral vein trazodone of 15.5 micrograms/ml and alcohol 34 mg%, with no other drugs detected. For case 1 and case 2 respectively, trazodone tissue concentrations were: skeletal muscle 7.3 and 9.0 micrograms/g; left and right lungs 13.3, 12.9 and 35.3, 40.1; myocardium, 30.9 and 28.9; kidneys 34.7 and 39.6; liver 73.7 and 82.4; fat 18.5 and 16.5; brain 48.6 and 20.9. For case 1 and 2, respectively, blood trazodone concentrations in 10 initial autopsy samples ranged from 13.7-17.3 and 14.4-16.9 micrograms/ml. Twenty-four and forty-eight hours later the respective ranges were 12.8-18.0 and 12.4-19.9 for case 1, 12.5-20.1 and 12.7-27.0 for case 2. By contrast, for trimipramine, blood concentrations at 0 time, 24 h and 48 hours ranged from 5.5-11.4, 5.2-14.3, and 4.2-18.2, respectively. We conclude that trazodone shows little preferential concentration in solid organs and consequently has relatively stable post-mortem blood concentrations with little drug redistribution artefact. Both the clinical pharmacokinetics and post-mortem toxicokinetics of trazodone differ significantly from the tricyclic anti-depressants.     

The deadly broomstick: an unusual missile injury to the neck

A 51-year-old man was struck by the tip of a broomstick weighing 1000 g at the left side of the neck, upon which he collapsed. Intense but delayed cardiopulmonary resuscitation restored the circulation roughly 30 minutes after the incident. Upon admittance to a nearby hospital, an extensive hypoxic cerebral damage was diagnosed. Death due to the severe cerebral damage occurred 5 hours after the incident. An autopsy demonstrated a severe subcutaneous traumatization of the left side of the neck, with a hemorrhage compressing the carotid bifurcation. A prolonged excitation due to this ongoing compression of the baroreceptors in the carotid sinus was assumed to have led to a cardiac arrest. In this case report, the authors discuss the underlying pathophysiology of this potentially lethal and rare reflexogenic incident also known as the Hering reflex and discuss possible therapeutic measures.     

The effect of time of death on extravascular tissue/blood secobarbital concentration ratios in the rat

Extravascular liver/blood and brain/blood ratios were found to be an average of 6% and 1% higher, respectively, in all experiments than total liver/blood and brain/blood ratios. This difference may be informative in establishing true tissue levels. There was a significant time effect (P less than 0.05) with the extravascular liver/blood ratios but not with the extravscular brain/blood ratios. Extravascular liver/blood ratios were slightly higher in phenobarbital-pretreated animals than in non-pretreated animals. Tissue secobarbital levels in pretreated and non-pretreated animals are not different at 1/4 or 1 h, even though pretreated animals received higher doses than non-pretreated animals. Tissue levels are significantly higher (P less than 0.01) in pretreated animals than in non-pretreated animals at 4 h. It is possible that, at this time period, the barbiturate-metabolizing enzymes have become saturated or exhausted.     

An unusual case of accidental poisoning: fatal methadone inhalation

In this report, the authors present a case of unusual, accidental methadone intoxication in a 40-year-old man, who had inhaled methadone powder. The drug dealer was a pharmacy technician; methadone had been stolen from a pharmacy and sold as cocaine. After having inhaled methadone powder, he suffered cardiopulmonary arrest. He was admitted to hospital where he died after 24 h of intensive care. The autopsy revealed congestion of internal organs and cerebral and pulmonary edema. Microscopically, the heart showed no changes. The toxicological analyses performed on blood and urine taken at the hospital revealed methadone, cannabinoids, and ethanol. The blood methadone concentration was 290 μg/L. The urine methadone concentration was 160 μg/L. Midazolam and lidocaine, which were administered to the patient at the hospital, were also detected in the blood. The cause of death was determined to be methadone intoxication. The literature has been reviewed and discussed. To date, and to our knowledge, only very few cases of accidental death resulting from methadone inhalation have been described up to the case presented herein.