14 research outputs found
A neuroanatomical construct for the amnesic effects of propofol,ā
Background: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task. Methods: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H 2 15 O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline. Results: Nonoverlapping memory effects were evident: low (n ā«Ųā¬ 4; propofol concentration 523 Ų 138 ng/ml; 44 Ų 13% decrement from baseline memory) and high (n ā«Ųā¬ 7; 829 Ų 246 ng/ml; 87 Ų 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z ā«Ųā¬ 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases. Conclusions: As amnesia becomes maximal, rCBF reductions induced by propofol occur in brain regions identified with working memory processes. In contrast, medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation. The authors postulate that the episodic memory effect of propofol is produced by interference wit
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The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial
Introduction: Postoperative delirium is one of the most common complications of major surgery, affecting 10ā70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial. Methods: The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study is an international, multicentre, randomised controlled trial. 600 cardiac and major non-cardiac surgery patients will be randomised to receive ketamine (0.5 or 1 mg/kg) or placebo following anaesthetic induction and prior to surgical incision. For the primary outcome, blinded observers will assess delirium on the day of surgery (postoperative day 0) and twice daily from postoperative days 1ā3 using the Confusion Assessment Method or the Confusion Assessment Method for the ICU. For the secondary outcomes, blinded observers will estimate pain using the Behavioral Pain Scale or the Behavioral Pain Scale for Non-Intubated Patients and patient self-report. Ethics and dissemination The PODCAST trial has been approved by the ethics boards of five participating institutions; approval is ongoing at other sites. Recruitment began in February 2014 and will continue until the end of 2016. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement and popular media. Registration details The study is registered at clinicaltrials.gov, NCT01690988 (last updated March 2014). The PODCAST trial is being conducted under the auspices of the Neurological Outcomes Network for Surgery (NEURONS). Trial registration number NCT01690988 (last updated December 2013)
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Low-dose Propofolāinduced Amnesia Is Not due to a Failure of Encoding
BackgroundāPropofol may produce amnesia by affecting encoding. The hypothesis that propofol
weakens encoding was tested by measuring regional cerebral blood flow during verbal encoding.
Methodsā17 volunteer participants (12 M, 30.4Ā±6.5 years old) had regional cerebral blood flow
measured using H2O15 positron emission tomography during complex and simple encoding tasks
(deep vs. shallow level of processing), to identify a region of interest in the left inferior prefrontal
cortex (LIPFC). The effect of either propofol (n=6, 0.9 mcg/ml target concentration), placebo with
a divided attention task (n=5), or thiopental at sedative doses (n=6, 3 mcg/ml) on regional cerebral
blood flow activation in the LIPFC was tested. The divided attention task was expected to decrease
activation in the LIPFC.
ResultsāPropofol did not impair encoding performance or reaction times, but impaired recognition
memory of deeply encoded words 4 hours later (median recognition of 35% (17ā54 interquartile) of
words presented during propofol versus 65% (38ā91) before drug, p<0.05). Statistical parametric
mapping analysis identified a region of interest of 6.6 cu.cm. in the LIPFC (T=7.44, p=0.014).
Regional cerebral blood flow response to deep encoding was present in this region of interest in each
group before drug (T>4.41, p<0.04). During drug infusion only the propofol group continued to have
borderline significant activation in this region (T=4.00, p=0.063).
ConclusionsāIf the amnesic effect of propofol were solely due to effects on encoding, then
activation in LIPFC should be minimal. As LIPFC activation was not totally eliminated by propofol,
the amnesic action of propofol must be present in other brain regions and/or affect other memory
processes