Amfetamine/methylphenidate/modafinil

Abstract

Excited delirium syndrome and abuse of amfetamine and methylphenidate: case report A 25-year-old woman developed excited delirium syndrome following abuse of amfetamine and methylphenidate. Additionally, modafinil contributed in the development of excited delirium syndrome [dosages and durations of treatments to reaction onset not stated]. The woman had traumatic stress disorder, eating disorder, attention deficit hyperactivity disorder and chronic addiction. She was known to abuse methylphenidate, amfetamine [amphetamine] and cocaine. On the day in question, the woman was consuming drugs together with friends in a private apartment. According to witnesses, she had been shooting up amfetamine and methylphenidate as well as taking alprazolam. She possibly suffered a psychosis resulting in running disoriented and half-naked out of the house into a larger street, where there was traffic. Civilian witnesses called the police. When the police arrived, she was standing in the middle of a larger street. As soon as she recognised the police, she ran away. After a distance of approximately 100 meters, she climbed/fell over a wall, which was approximately 90cm high on the rising and approximately 200cm high on the down falling side. According to the police officers, the victim fell onto soft grass, immediately stood up and continued to flee. As she tried to break into a low-level apartment through a glass window, the police managed to stop her, and put her face forward onto the soft ground. During the following struggle, as the police handcuffed her and bound her feet, she suddenly became still and her vital signs started to waver. According to the police officers, just minor force was necessary to control the woman. At no time, had they kneeled on the victim or in any other way compressed her thorax. When she was put in a prone position, empty-hand submission techniques were used to handcuff her. After that no force was used and she could move freely. As soon as they realised that the she had breathing difficulty and she went into cardiac arrest, they released the handcuffs, turned her on the back and started cardiopulmonary resuscitation. An ambulance was called and she was taken to the hospital. On arrival, she was in asystole and had no pulse. Resuscitation and adrenaline, bicarbonate, noradrenaline and phenylephrine were given. Her BP was 76/60mm Hg and pulse rate was 160 beats per minute. She exhibited a low pH level and elevated electrolyte, creatinine, lactate and muscle enzymes. Her body temperature was elevated at 38.6°C. On the same day, she was transferred to the emergency ward with Glasgow Coma Scale score of 3 and received propofol and fentanyl. A CT scan revealed severe brain oedema and there were no fractures. She was pronounced dead later that day. According to a witness, both police officers were kneeling on the woman’s back for a considerable amount of time. The witness also described having heard muffling sounds, as if the victim’s mouth was blocked. An autopsy was performed 22 hours after the woman’s death. No pathological changes to the internal organs could be identified, which would explain a sudden loss of consciousness or a clear mechanism of death. The deceased showed normal, age appropriate internal organs. Especially her heart and lungs did not reveal any pathological changes. Signs of multiple blunt traumas and blunt traumas with a tangential component to various body regions could be identified. Some of these injuries were located at typically exposed body regions and thus could have occurred during a fall to the ground. However, the majority of injuries indicated a struggle with a second party. None of the injuries affected major organs or caused internal bleedings. Multiple haematomas were identified on the deceased’s upper and forearm, which were consistent with multiple hard grips onto these regions. Double striated haematomas were visible reaching circular around the right wrist. These injuries were consistent with marks from handcuffs, which would occur when the cuffed person strongly resists. On both the lower legs, several spotty haematomas were visible of which some could indicate hard grips onto the legs. On the right lower leg’s medial side, a double-striated haematoma was visible with a central brightening, an injury, which resembled contact with a hard, long rigid instrument, for instance a police baton. On the posterior thorax, several larger areas with spotty haematomas could be identified. These injuries were the result of intense blunt trauma and could have occurred due to pressure onto these areas during a longer time period, such as kneeling onto the back of the deceased. Upon preparation of the soft tissue of the back, superficial as well as deeper reaching hematomas could be seen covering both diagonally reaching inferior fibres of the trapezius muscle, more developed on the left side, reaching into the middle fibres of the muscle. On the right side, the haemorrhages covered an area of approximately 8 × 4cm and on the left side of approximately 12 × 5cm. The hyoid bone and thyroid cartilage were intact and unremarkable. They still had some residual elasticity. The brain showed signs of oedema (weight: 1380g). The heart had a normal size and configuration (weight: 330g). The coronary arteries were normally wide, thin-walled and without any signs of arteriosclerotic changes. The liver was slightly enlarged (weight: 1915g) with spotty discolourations. According to the medical files, the deceased had hepatitis C. No fractures, especially no fractured ribs were detectable. The rib cage had a high elasticity, consistent with a younger woman. The deceased had high liver enzymes, which were most likely due to her underlying hepatitis C. No signs of jaundice or haemorrhagic diathesis were detected during autopsy. According to medical files and witnesses, the victim had shown no signs of hepatic encephalopathy. Since no ischaemic areas could be identified during histological examination of the organ and no larger areas of acute inflammation were detected, hepatotoxicity was excluded. Toxicology studies revealed elevated levels of amfetamine and gabapentin. However, the levels of methylphenidate, modafinil, alprazolam and nitrazepam were found to be in a therapeutic range. Based on the patient’s medical history, autopsy findings, contradicting witness testimonies and reliable clinical and toxicological blood parameters, the cause of her death was determined as cardiac arrest subsequent to a combination of excited delirium syndrome, physical exhaustion and respiratory impairment. The manner of death was unnatural. The authors concluded that the woman in the present case was brought to the hospital in a delirious state. Amfetamine, modafinil and methylphenidate are all CNS stimulants and it is possible that these drugs had additive effects. It was probable that the woman was under the strong stimulating effects of a mixture of amfetamine, modafinil and methylphenidate at the time of her death. She showed signs of intoxication and delirious behaviour. She was sparsely dressed and running disoriented through the streets. Her clinical blood parameters showed a low pH level and elevated electrolyte, lactate and muscle enzymes, consistent with metabolic acidosis. Such behavioural pattern, together with these distinct changes in clinical blood parameters and a rise in core body temperature (38.6°C) are characteristic symptoms of excited delirium syndrome. The elevated levels of amfetamine together with presence of modafinil and methylphenidate favoured the development of excited delirium syndrome. Her underlying psychiatric condition (traumatic stress disorder, eating disorder, attention deficit hyperactivity disorder) also contributed in the development of excited delirium syndrome.