| Una encuesta del uso indebido del propofol en los programas de la anestesia académica. |
A survey of propofol abuse in academic anesthesia programs.
Wischmeyer PE, Johnson BR, Wilson JE, Dingmann C, Bachman HM, Roller E, Tran ZV, Henthorn TK.
Department of Anesthesiology, University of Colorado, Denver, Colorado, USA. Paul.Wischmeyer@UCHSC.edu
Anesth Analg. 2007 Oct;105(4):1066-71
Abstract
BACKGROUND: Although propofol has not traditionally been considered a drug of abuse, subanesthetic doses may have an abuse potential. We used this survey to assess prevalence and outcome of propofol abuse in academic anesthesiology programs. METHODS: E-mail surveys were sent to the 126 academic anesthesiology training programs in the United States. RESULTS: The survey response rate was 100%. One or more incidents of propofol abuse or diversion in the past 10 yr were reported by 18% of departments. The observed incidence of propofol abuse was 10 per 10,000 anesthesia providers per decade, a fivefold increase from previous surveys of propofol abuse (P = 0.005). Of the 25 reported individuals abusing propofol, 7 died as a result of the propofol abuse (28%), 6 of whom were residents. There was no established system to control or monitor propofol as is done with opioids at 71% of programs. There was an association between lack of control of propofol (e.g., pharmacy accounting) at the time of abuse and incidence of abuse at the program (P = 0.048). CONCLUSIONS: Propofol abuse in academic anesthesiology likely has increased over the last 10 yr. Much of the mortality is in residents. Most programs have no pharmacy accounting or control of propofol stocks. This may be of concern, given that all programs reporting deaths from propofol abuse were centers in which there was no pharmacy accounting for the drug
http://www.anesthesia-analgesia.org/content/105/4/1066.full.pdf+html
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| Muerte por propofol: ¿Accidente, suicidio, o asesinato? |
Death from propofol: accident, suicide, or murder?
Kirby RR, Colaw JM, Douglas MM.
Department of Anesthesiology, University of Florida College of Medicine, Box 100254 JHMHSC, Gainesville, FL 32610-0254, USA.RKirby@anest.ufl.edu
Anesth Analg. 2009 Apr;108(4):1182-4.
Abstract
A 24-yr-old woman was found dead in her home from apparent propofol "toxicity." Her blood level of propofol was 4.3 microg/mL. She had no history of drug abuse and no evidence of such behavior at autopsy. The medical examiner and police investigators felt that she died from probable homicide. Attention was focused on a male registered nurse acquaintance, who had acquired propofol and other drugs in the course of his regular duties in a surgical intensive care unit. This is the first reported case of murder with propofol
http://www.anesthesia-analgesia.org/content/108/4/1182.full.pdf+html
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| Propofol nanomolar estimula la trasmisión de glutamato a las neuronas dopamina: ¿Un posible mecanismo del potencial de abuso? |
Nanomolar propofol stimulates glutamate transmission to dopamine neurons: a possible mechanism of abuse potential?
Li KY, Xiao C, Xiong M, Delphin E, Ye JH.
Department of Anesthesiology, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103-2714, USA.
J Pharmacol Exp Ther. 2008 Apr;325(1):165-74. Epub 2008 Jan 23.
Abstract
Anesthesiologists among physicians are on the top of the drug abuse list, and the mechanism is unclear. Recent studies suggest occupation-related second-hand exposure to i.v. drugs, including propofol, may play a role. Growing evidence indicates that propofol is one of the choices of drugs being abused. In this study, we show that propofol at minute concentrations increases glutamatergic excitatory synaptic transmission and discharges of dopamine neurons in the ventral tegmental area (VTA). We found that acute application of propofol (0.1-10 nM) to the VTA in midbrain slices of rats increased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. We observed that propofol increased the amplitude but decreased the paired-pulse ratio of EPSCs evoked by stimulation in the absence and the presence of gabazine (SR 95531), a GABA(A) receptor antagonist. Moreover, the propofol-induced facilitation of EPSCs was mimicked by 6-phenyl-4-azabicyclo[5.4.0]undeca-7,9,11-triene-9,10-diol (SKF38393), an agonist of dopamine D(1) receptor, and by 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12935), a dopamine reuptake inhibitor, but blocked by (+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrochloride (SKF83566), a D(1) antagonist, or by depleting dopamine stores with reserpine. Finally, 1 nM propofol increased the spontaneous discharge rate of dopamine neurons. These findings suggest that propofol at minute concentrations enhances presynaptic D(1) receptor-mediated facilitation of glutamatergic synaptic transmission and the excitability of VTA dopamine neurons, probably by increasing extracellular dopamine levels. These changes in synaptic plasticity in the VTA, an addiction-related brain area might contribute to the development of propofol abuse and the increased susceptibility to addiction of other drugs.
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| Tolerancia al efecto sedante del propofol en Conejos con ventilación mecánica. |
Tolerance to propofol's sedative effect in mechanically ventilated Rabbits.
Ypsilantis P, Mikroulis D, Politou M, Tsoukali H, Pitiakoudis M, Didilis V, Theodoridis G, Bougioukas G, Simopoulos C.
Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.pipsil@med.duth.gr
Anesth Analg. 2006 Aug;103(2):359-65
Abstract
Propofol is commonly used for the sedation of critically ill patients undergoing mechanical ventilation. These patients may develop tolerance during long-term administration. Here, we describe the development of tolerance to propofol's sedative effect in rabbits during prolonged mechanical ventilation. Six healthy male New Zealand White rabbits were endotracheally intubated and received propofol by continuous IV infusion to maintain sedation for 48 h. The propofol infusion rate (IR) was adjusted to maintain the desired level of sedation. Assessments of the sedation level were made every 30 min or earlier if there were signs of awakening. Propofol concentrations were measured in arterial plasma after every other IR adjustment, provided there was an adequate level of sedation, using high performance liquid chromatography, and calculations of systemic clearance rates were made. The mortality rate was 100% with a survival period of 30.8 +/- 6.0 h (mean +/- sd). The course of IR adjustments followed a 5-phase pattern: 1) steady IR (mean +/- sd duration; 1.2 +/- 0.6 h), 2) increasing IR (9.4 +/- 5.5 h), 3) steady high-IR (2.3 +/- 1.2 h), 4) decreasing IR (13.7 +/- 1.9 h), and 5) steady low-IR (5.0 +/- 2.7 h). The course of propofol concentrations during the experiment in relation to propofol IR followed a 3-phase pattern: 1) steady concentration with increasing IRs (6.0 +/- 2.7 h), 2) increasing concentrations with increasing IR (5.8 +/- 2.5 h), and 3) increasing concentrations with decreasing IR (18.8 +/- 3.3 h). Propofol systemic clearance rates were progressively increased for 6.0 +/- 2.7 h and then gradually decreased for 24.6 +/- 4.7 h. In conclusion, all rabbits developed tolerance to propofol's sedative effect within the first hours of administration related to changes to the drug's metabolic clearance
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