The incidence of unpleasant dreams after sub-anaesthetic ketamine

Blagrove, Mark; Morgan, Philip G.; Curran, H. Valerie; Bromley, Lesley; Brandner, Brigitta

doi:10.1007/s00213-008-1377-3

Cited by 35 publications

(19 citation statements)

References 95 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior generations of competitive and noncompetitive NMDAR antagonists cause a variety of off-target and on-target adverse effects that prevented clinical development, including motor dysfunction, cognitive impairment, and psychotomimetic effects including hallucinations, paranoia, disorganized thought, and blunted affect (Lees et al, 2000; Sacco et al, 2001; Diener et al, 2002; Rowland 2005; Wood 2005; Muir 2006; Blagrove et al, 2009). Although the GluN2B-selective class of antagonists are better tolerated than competitive antagonists or channel blockers, they are not necessarily free from on-target side effects (Chaperon et al, 2003; DeVry and Jentzsch 2003; Yurkewicz et al, 2005; Nicholson et al, 2007; Preskorn et al, 2008; Nutt et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Context-Dependent GluN2B-Selective Inhibitors of NMDA Receptor Function Are Neuroprotective with Minimal Side Effects

Yuan

Myers

Wells

et al. 2015

Neuron

View full text Add to dashboard Cite

SUMMARY Stroke remains a significant problem despite decades of work on neuroprotective strategies. NMDA receptor (NMDAR) antagonists are neuroprotective in preclinical models, but have been clinically unsuccessful, in part due to side effects. Here we describe a prototypical GluN2B-selective antagonist with an IC50 value that is 10-fold more potent at acidic pH 6.9 associated with ischemic tissue compared to pH 7.6, a value close to the pH in healthy brain tissue. This should maximize neuroprotection in ischemic tissue while minimizing on-target side-effects associated with NMDAR blockade in non-injured brain regions. We have determined the mechanism underlying pH-dependent inhibition and demonstrate the utility of this approach in vivo. We also identify dicarboxylate dimers as a novel proton sensor in proteins. These results provide insight into the molecular basis of pH-dependent neuroprotective NMDAR block, which could be beneficial in a wide range of neurological insults associated with tissue acidification.

show abstract

Section: Resultsmentioning

confidence: 99%

Context-Dependent GluN2B-Selective Inhibitors of NMDA Receptor Function Are Neuroprotective with Minimal Side Effects

Yuan

Myers

Wells

et al. 2015

Neuron

View full text Add to dashboard Cite

show abstract

“…The possible reason for our frequent incidence of not achieving loss of consciousness was our relatively low dose of ketamine (0.6 mg/kg) in comparison with other studies, which used 1 to 2 mg/kg. Blagrove et al 3 found that individual differences in the incidence of unpleasant dreams after ketamine administration were significantly associated with retrospective home nightmare frequency, which was an important predictor of the incidence of unpleasant dreams. 9,10 In our study, the STAI, which can affect dream content, was not different between the 2 groups.…”

Section: Discussionmentioning

confidence: 98%

The Effect of Suggestion on Unpleasant Dreams Induced by Ketamine Administration

Cheong

Lee²,

Lim³

et al. 2011

Anesthesia &Amp; Analgesia

View full text Add to dashboard Cite

The use of ketamine may be associated with the recall of unpleasant dreams after sedation. We hypothesized that a positive suggestion before sedation could reduce the incidence of ketamine-induced unpleasant dreams. To test this hypothesis, we randomized 100 patients receiving sedation with ketamine for their procedure into 2 groups with 1 group having an anesthesiologist provide a mood-elevating suggestion to the patient before ketamine administration (suggestion group), whereas in the control group no suggestion was provided. Patients were provided with a pleasantness/unpleasantness scale to rate "the overall mood of the dream" as very unpleasant (grade 1), quite unpleasant (grade 2), neither or mixed (grade 3), quite pleasant (grade 4), and very pleasant (grade 5). In those patients who lost consciousness, the frequencies of grades 1, 2, 3, 4, and 5 were 0%, 0%, 46%, 24%, and 30% in the suggestion group and were 6%, 2%, 70%, 12%, and 10%, respectively, in the control group (P=0.01). In the intent-to-treat population the overall frequency between groups was very similar. This study implies that when administering ketamine as part of a sedation regimen, positive suggestion may help reduce the recall of unpleasant dreaming.

show abstract

“…We specifically chose ketamine because it shares some traits with rapid eye movement sleep, including cortical activation, increased cholinergic tone, and dream states. 38,16,23,17,24 …”

Section: Discussionmentioning

confidence: 99%

Paradoxical Emergence

Hambrecht-Wiedbusch

Mashour

2017

Anesthesiology

View full text Add to dashboard Cite

Background Promoting arousal by manipulating certain brain regions and/or neurotransmitters has been a recent research focus, with the goal of trying to improve recovery from general anesthesia. The current study tested the hypothesis that a single subanesthetic dose of ketamine during isoflurane anesthesia would increase cholinergic tone in the prefrontal cortex and accelerate recovery. Methods Adult male rats were implanted with electroencephalography electrodes (frontal, parietal, and occipital cortex) and a microdialysis guide cannula targeted for the prefrontal cortex. After establishing general anesthesia with isoflurane, animals were randomly assigned to receive a saline control or ketamine injection. When isoflurane was discontinued nearly 90 min after drug or saline administration, recovery from anesthesia was measured by experimenters and blinded observers. During the entire experiment, electrophysiologic signals were recorded and acetylcholine was quantified by high-performance liquid chromatography with electrochemical detection. Results A single dose of subanesthetic ketamine caused an initial 125% increase in burst suppression ratio (last isoflurane sample: 37.48 ± 24.11% vs. isoflurane after ketamine injection: 84.36 ± 8.95%; P < 0.0001), but also a significant 44% reduction in emergence time (saline: 877 ± 335 s vs. ketamine: 494 ± 108 s; P = 0.0005; n = 10 per treatment). Furthermore, ketamine caused a significant 317% increase in cortical acetylcholine release (mean after ketamine injection: 0.18 ± 0.16 pmol vs. ketamine recovery: 0.75 ± 0.41 pmol; P = 0.0002) after isoflurane anesthesia was discontinued. Conclusions Administration of subanesthetic doses of ketamine during isoflurane anesthesia increases anesthetic depth but—paradoxically—accelerates the recovery of consciousness, possibly through cholinergic mechanisms.

show abstract

The incidence of unpleasant dreams after sub-anaesthetic ketamine

Abstract: Ketamine causes unpleasant dreams over the three post-administration nights. This may be evidence of a residual psychotogenic effect that is not found on standard self-report symptomatology measures or a result of disturbed sleep electrophysiology.

Cited by 35 publications

References 95 publications

Context-Dependent GluN2B-Selective Inhibitors of NMDA Receptor Function Are Neuroprotective with Minimal Side Effects

Context-Dependent GluN2B-Selective Inhibitors of NMDA Receptor Function Are Neuroprotective with Minimal Side Effects

The Effect of Suggestion on Unpleasant Dreams Induced by Ketamine Administration

Paradoxical Emergence

Contact Info

Product

Resources

About