GC-MS analysis of the designer drug α-pyrrolidinovalerophenone and its metabolites in urine and blood in an acute poisoning case.

α-Pyrrolidinovalerophenone (α-PVP) is a synthetic cathinone belonging to the group of "second generation" pyrrolidinophenones that becomes more and more popular as a designer psychostimulant. Here we provide toxicological analytical support for a severe poisoning with α-PVP. Serum and urine samples that were sent to our laboratory were subjected to a general unknown screening procedure. The procedure includes immunoassay-based screening of drugs of abuse in serum and systematic toxicological analysis of urine and serum after neutral and basic liquid-liquid extraction followed by gas chromatography-mass spectrometry (GC-MS). Whereas the immunoassay delivered negative results, analyzing the urine sample by GC-MS in full scan mode disclosed the presence of α-PVP and its metabolites α-(2″-oxo-pyrrolidino)valerophenone (2″-oxo-α-PVP) and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-ol (OH-α-PVP). In the acetylated urine sample we found additionally N,N-bis-dealkyl-PVP. In serum, α-PVP could be detected after solid phase extraction and a concentration of 29ng/mL was determined. Other forensic relevant substances were not detected. The presented data can explain the psychotic symptoms and behavioural pattern of the subject after abuse of α-PVP, leading to a clinical condition similar to excited delirium syndrome.

Impact of multicomponent, nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients.

OBJECTIVE: To investigate the impact of multicomponent, nonpharmacologic interventions (MNI) on perioperative cortisol and melatonin levels, as well as postoperative delirium (PD), in elderly oral cancer patients. METHODS: A total of 160 elderly oral cancer patients who underwent tumor resection surgery and completed our investigation were included in this study. The cancer patients were randomly divided into 2 groups: Group U or Group I. During the perioperative period, Group U received usual care, while Group I received MNI, which is based on usual care and aims to decrease the risk of PD. MNI focused on general geriatric approaches and supportive nursing care. On the day before surgery and the first three postoperative days, nocturnal (20:00-8:00) urine samples were collected. The melatonin sulfate and cortisol levels in the urine samples were determined. Moreover, the RASS (Richmond Agitation Sedation Scale), CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) and QoR40 (40-item quality of recovery score) scores were dynamically monitored. RESULTS: There were no significant differences in the general characteristics between the 2 groups. After surgery, the melatonin sulfate levels in the nocturnal urine of Group I were higher than those in Group U. The cortisol concentrations were lower in Group I compared to those in Group U. Group I achieved better postoperative RASS and QoR40 scores than Group U. Compared to Group U, Group I also experienced less PD (incidence and duration). CONCLUSIONS: MNI ameliorated some postoperative disturbances regarding sleep and stress, decreased the incidence of PD and improved recovery quality.

Delirium and Circadian Rhythm of Melatonin During Weaning From Mechanical Ventilation: An Ancillary Study of a Weaning Trial.

BACKGROUND: Delirium is frequent in patients in the ICU, but its association with the outcome of weaning from mechanical ventilation has not been assessed. Circadian rhythm alteration may favor delirium. In the current study, we assessed the impact of delirium during weaning and associated alterations in the circadian rhythm of melatonin excretion. METHODS: This was a substudy of 70 participants of the B-type Natriuretic Peptide for the Fluid Management of Weaning trial, comparing two fluid management strategies during weaning. Patients with or without delirium (as assessed using the Confusion Assessment Method for the ICU) were compared in terms of baseline characteristics and outcomes and the circadian rhythm of melatonin excretion using the 24-h excretion of its urinary metabolite 6-sulfatoxymelatonin (aMT6s). RESULTS: Among the 70 patients included, 43 (61.4%) experienced delirium at the initiation of weaning. Delirium at the initiation of weaning was associated with more alcohol consumption, a greater severity of illness, and medication use before weaning (including neuromuscular blockade, antibiotics, sedatives, and narcotics). Delirium at the initiation of weaning was associated with more respiratory and neurologic complications and a reduced probability of successful extubation (Cox multivariate model hazard ratio of successful extubation = 0.54; 95% CI, 0.30-0.95; P = .03). Delirium was also associated with a significant reduction in peak, mean, amplitude, and total values of aMT6s urinary excretion during the first 24 h of weaning (general linear model F statistic = 5.81, P = .019). CONCLUSIONS: Delirium is frequent at the initiation of ventilator weaning. It is associated with a prolongation of weaning and an alteration in the circadian rhythm of melatonin excretion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov.

The relation between the clinical subtypes of delirium and the urinary level of 6-SMT.

Delirium is a common syndrome among hospitalized elderly patients. In humans, sleep and circadian rhythms are disturbed during delirium, and both are influenced by the hormone melatonin. This prompted us to investigate the relationship of the clinical subtypes of delirium: 1). hyperactive, 2). hypoactive, and 3). mixed, with melatonin, as reflected by a patient's urinary metabolite 6-SMT. Results support our hypothesis that urinary 6-SMT during delirium was higher in hypoactive and lower in hyperactive patients. Because this is the first time a biochemical parameter related to the clinical subtypes of delirium has been reported, further research on the link between melatonin and delirium is necessary.

The effectiveness of lumbar puncture in the evaluation of delirium and fever in the hospitalized elderly.

OBJECTIVE: To determine the value of the cerebrospinal fluid examination in the evaluation of hospitalized; elderly patients with delirium and fever. DESIGN: A retrospective case series of consecutive events during a 15-month period. SETTING: Tertiary care center. PARTICIPANTS: Elderly patients admitted to the University of Cincinnati (Ohio) Hospital between July 1, 1988, and October 1, 1989, who had a lumbar puncture and cerebrospinal fluid evaluation to evaluate fever and mental status changes. MAIN OUTCOME MEASURES: Primary intracranial causes and the clinical characteristics of delirium and fever. RESULTS: Eighty-one hospital admissions were reviewed. Fifty-seven (70%) of the lumbar punctures were performed as part of the admitting workup, and the remaining 24 (30%) were performed during the hospitalization. Eighty of the 81 cerebrospinal fluid cultures were negative for bacterial growth. The primary origins for fever and delirium included urinary tract infections (25%), pneumonia (22%), viral causes (17%), and metabolic causes/dehydration (14%). One case of bacterial meningitis was diagnosed in an alcoholic, 73-year-old man who was unresponsive in the emergency department. One case of presumed aseptic meningitis was diagnosed in a 65-year-old man who presented with fever and headaches and a blood pressure of 230/100 mm Hg. CONCLUSIONS: Most hospitalized, older patients with fever and delirium have primary causes of the confusion outside the central nervous system and may not require a routine evaluation of their cerebrospinal fluid.

Urinary amine metabolite excretion in a patient with adrenergic hyperactivity state: reaction to phenelzine withdrawal and combined treatment.

Urinary MHPG (3-methoxy-4-hydroxyphenylglycol) amounts increased threefold during a toxic delirious state in a 57-year-old bipolar patient 3 days after phenelzine treatment was stopped. This norepinephrine metabolite was not expected to rise as monoamine oxidase (MAO) was completely blocked. In addition, the delirious state appeared as a rebound phenomenon and not an acute toxic state during drug administration. It seems that phenelzine acts more through catecholamine release phenomenon than by inhibition of MAO.