Brain ; drug effects ; physiopathology ; Consciousness ; drug effects ; physiology ; Consciousness Disorders ; diagnosis ; drug therapy ; Humans ; Research

Treatment for disorders of consciousness (DOCs) is still a Gordian knot. Evidence-based guidelines on the treatment of DOC patients are not currently available, while neuromodulation techniques are seen as a potential treatment. Multiple neuromodulation therapies have been applied. This article reviews the most relevant studies in the literature in order to describe a clear picture of the current state of neuromodulation therapies that could be used to treat DOC patients. Both invasive and non-invasive brain stimulation is discussed. Significant behavioral improvements in prolonged DOCs under neuromodulation therapies are rare. The efficacy of various such therapies remains a matter of debate. Further clinical investigations of existing techniques in larger samples properly controlling for spontaneous recovery are needed, and new approaches are awaited.
Brain ; drug effects ; physiopathology ; surgery ; Consciousness ; physiology ; Consciousness Disorders ; therapy ; Humans ; Neurotransmitter Agents ; therapeutic use ; Transcranial Magnetic Stimulation ; methods ; Treatment Outcome

OBJECTIVETo investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring.

METHODSForty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level.

RESULTSMild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei.

CONCLUSIONMild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

Adult ; Brain ; drug effects ; Consciousness Monitors ; Deep Sedation ; Dose-Response Relationship, Drug ; Humans ; Hypnotics and Sedatives ; pharmacology ; Male ; Propofol ; pharmacology

AIMTo investigate a possible potentiation effect of apomorphine (APO) on sildenafil-induced penile erection in the conscious rabbit.

METHODSErection of male New Zealand White rabbits (3.5 - 4.0 kg, n=12) was assessed by measuring the length of the uncovered penile mucosa and the duration of erection before and after intravenous administration of agents. After injection of APO (0, 0.05, 0.1 and 0.4 mg/kg), sildenafil was administered intravenously in a dose-response manner (0.5, 1 and 5 mg/kg). In additional experiments, the effect of increasing doses of sildenafil in combination with APO on systemic blood pressure was evaluated.

RESULTSSystemic administration of sildenafil induced a dose-dependent increase in the penile length. Intravenous injection of APO alone did not produce any change in the penile length, while significantly enhanced the penile erection induced by sildenafil. The co-administration of 0.1 mg/kg of APO and 1 mg/kg of sildenafil was found to be the most effective combination in producing penile erection. Intravenous administration of sildenafil caused a concentration-dependent decrease in systemic blood pressure, but no additional decrease was observed with co-administration of APO.

CONCLUSIONAPO enhances the penile erection induced by sildenafil in the conscious rabbit without causing an additional decrease in blood pressure.

Animals ; Apomorphine ; pharmacology ; Blood Pressure ; drug effects ; Consciousness ; Drug Synergism ; Male ; Penile Erection ; drug effects ; physiology ; Piperazines ; pharmacology ; Purines ; Rabbits ; Sildenafil Citrate ; Sulfones

BACKGROUNDRecently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer's assessment of alertness/sedation (OAA/S) and the bispectral index (BIS) by response surface analysis.

METHODSTotally 65 American Society of Anesthesiologists (ASA) I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion (TCI) system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program.

RESULTSSevoflurane and remifentanil acted synergistically on OAA/S. Sevoflurane alone could produce OAA/S ≤ 1 at a minimal alveolar concentration (MAC) of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OAA/S score was ≥ 3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of (1.04 ± 0.19)% to (1.81 ± 0.21)% could maintain a BIS between 60 and 40.

CONCLUSIONSThe response surface method can analyze the pharmacodynamic interactions between remifentanil and sevoflurane qualitatively and quantitatively. Within the range of our study (remifentanil ≤ 10 ng/ml, sevoflurane ≤ 3.4%), the two drugs produced synergistic effects on OAA/S but had no interactive effect on BIS. A guideline of BIS between 40 and 60 may cause excessive anesthesia when opioids are used to maintain anesthesia.

Adult ; Anesthesia ; methods ; Consciousness ; drug effects ; Female ; Humans ; Male ; Methyl Ethers ; pharmacokinetics ; pharmacology ; Middle Aged ; Piperidines ; pharmacokinetics ; pharmacology ; Young Adult

BACKGROUND/AIMS: The efficacy of bispectral index (BIS) monitoring during colonoscopic sedation is debated. We aimed to determine whether BIS monitoring was useful for propofol dose titration, and to evaluate differences in sedative administration between expert and inexperienced medical personnel during colonoscopy procedures that required moderate sedation. METHODS: Between February 2012 and August 2013, 280 consecutive patients scheduled to undergo a screening colonoscopy participated in this study and were randomly allocated to the expert or inexperienced endoscopist group. Each group was further divided into either a BIS or a modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) subgroup. Trained nurses administered combined propofol sedation and monitored sedation using either the BIS or MOAA/S scale. RESULTS: The mean BIS value throughout the procedure was 74.3 +/- 6.7 for all 141 patients in the BIS group. The mean total propofol dose administered in the BIS group was higher than that in the MOAA/S group, independently of the endoscopists' experience level (36.9 +/- 29.6 and 11.3 +/- 20.7, respectively; p < 0.001). The total dose of propofol administered was not significantly different between the inexperienced endoscopist group and the expert endoscopist group, both with and without the use of BIS (p = 0.430 and p = 0.640, respectively). CONCLUSIONS: Compared with monitoring using the MOAA/S score alone, BIS monitoring was not effective for titrating the dose of propofol during colonoscopy, irrespective of colonoscopist experience.
Adult ; Aged ; Anesthetics, Intravenous/*administration & dosage/adverse effects ; *Clinical Competence ; *Colonoscopy ; Conscious Sedation/adverse effects/*nursing ; Consciousness/*drug effects ; *Consciousness Monitors ; Electroencephalography/*instrumentation/*nursing ; Female ; Humans ; Male ; Middle Aged ; *Nurse Anesthetists ; Predictive Value of Tests ; Propofol/*administration & dosage/adverse effects ; Prospective Studies ; Republic of Korea

OBJECTIVETo compare the effects of common carotid artery and femoral vein administration of propofol for electrocerebral silence (ES) on circulatory and respiratory function and the dosage of propofol required during ES in dogs.

METHODSEight dogs were anesthetized by common carotid arterial and femoral vein administration of propofol for ES for 1 h. The time of consciousness loss and recovery, dose of propofol during ES, mean arterial pressure, heart rate, respiration rate, end-tidal carbon dioxide, SpO2, cerebral state index (CSI) and anal temperature were continuously monitored. Changes in the outcome variables were analyzed at 7 time points, namely the baseline, upon loss of consciousness, at 10 s, 30 min and 1 h of CSI=0, and recovery of CSI and consciousness.

RESULTSCarotid artery propofol administration produced ES with only half of the dose for intravenous administration. Compared with the baseline values, the mean artery pressure and respiration rate remained unchanged or decreased transiently during ES with carotid artery propofol administration. In contrast, intravenous propofol administration resulted in systemic hypotension and severe respiratory depression.

CONCLUSIONCarotid artery propofol administration produces ES with a much smaller dose than intravenous propofol administration without causing systemic hypotension or respiratory depression.

Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Blood Circulation ; drug effects ; Blood Pressure ; drug effects ; Brain ; blood supply ; drug effects ; physiology ; Carotid Arteries ; Consciousness ; Dogs ; Female ; Femoral Vein ; Heart Rate ; drug effects ; Injections, Intra-Arterial ; Injections, Intravenous ; Male ; Propofol ; administration & dosage ; pharmacology ; Respiration ; drug effects

OBJECTIVETo compare the unconsciousness prediction probability (Pk) estimated by approximate entropy (ApEn) and bispectral index (BIS) during the sedation produced by target-controlled infusion (TCI) of propofol.

METHODSTwenty patients (ASA class I-II) scheduled for elective lower limb operations under epidural anesthesia were studied. TCI of propofol was initiated at target plasma concentration of 0.5 microg/ml, and increased by 0.3 to 0.5 microg/ml until loss of consciousness, and then decreased until consciousness recovery. Each target plasma concentration of propofol lasted for 12 min. ApEn and BIS were recorded simultaneously during the periods of consciousness and unconsciousness every 3 min. The Pk of unconsciousness with ApEn and BIS were calculated and compared.

RESULTSApEn was 0.84+/-0.05 in the state of consciousness and 0.71+/-0.06 upon loss of consciousness, and BIS in the corresponding stages were 80.2+/-6.2 and 67.3+/-7.9, respectively. The Pk of unconsciousness between ApEn (Pk=0.97+/-0.06) and BIS (Pk=0.91+/-0.11) did not significantly differ (P>0.05).

CONCLUSIONApEn as well as BIS is acceptable for predicting consciousness and unconsciousness produced by TCI propofol.

Adult ; Aged ; Anesthesia, Epidural ; methods ; Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Conscious Sedation ; methods ; Consciousness ; drug effects ; Electroencephalography ; drug effects ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Propofol ; administration & dosage ; pharmacology

OBJECTIVETo compare the accuracies of cerebral state index (CSI) and bispectral index (BIS) in sedation monitoring during target control infusion of midazolam.

METHODSTwenty informed adult male volunteers were intravenously administered with midazolam through plasma target control infusion from 30ng/ml (in increments of 10ng/ml every time) until they became unresponsive to tactile stimulation (i. e., mild prodding or shaking). The BIS and CSI were continuously recorded simultaneously. Sedation was assessed using the Observers' Assessment of Alertness/Sedation (OAA/S) scale at each time when Ct equaled to Ce. The electroencephalogram (EEG) parameters were correlated with the OAA/S scores using nonparametric Spearman's correlation analysis. The prediction probabilities were calculated at the points of lost of verbal contact (LVC) and lost of responses to stimulus (LOR). BIS05, BIS50, BIS95, and CSI05, CSI50, CSI95 were also calculated for LVC and LOR.

RESULTSBIS and CSI were well correlation with OAA/S scales during both the onset and recovery phases. When the sedation level increased, BIS and CSI progressively decreased. The prediction probabilities of BIS and CSI were 84%, 74% for LVC and 79%, 68% for LOR, while the BIS05, BIS50, and BIS95 as well as CSI05, CSI50, and CSI95 were 85.5, 60.6, and 35.7 (for BISs) and 82.2, 65.2, and 30.3 (for CSIs) at the point of LVC and 79.7, 47.6, and 15.6 (for BISs) and 75.9, 43.4, and 11 (for CSIs) at the point of LOR.

CONCLUSIONSBoth CSI and BIS seem to be useful parameters for assessing midazolam-induced sedation. BIS is superior in the prediction of LVC and LOR.

Adult ; Anesthetics, Intravenous ; administration & dosage ; therapeutic use ; Brain ; drug effects ; physiology ; Conscious Sedation ; methods ; Consciousness ; drug effects ; Electroencephalography ; Humans ; Infusions, Intravenous ; Male ; Midazolam ; administration & dosage ; therapeutic use ; Young Adult

BACKGROUNDWavelet index (WLI) is a new parameter for monitoring depth of anesthesia based on Wavelet analysis. We observed the change of WLI and bispectral index (BIS) in patients regain of consciousness (ROC) in the absence of frontalis electromyographic (EMG) interference. The aim of this study was to compare the ability of WLI and BIS for reflecting ROC in patients undergone surgery.

METHODSTwelve patients who were scheduled for maxillofacial surgeries were enrolled in the study. BIS and WLI values were monitored continually. After being given midazolam and remifentanil, patients were asked to squeeze the investigator's hand ever 30 seconds. Patients were continuously given propofol until loss of consciousness (LOC1). Tunstall's isolated forearm technique was used to test the surgical consciousness in patients. After total muscle relaxation, endotracheal intubations were performed, and the patients were connected to a ventilator. Then, propofol was withdrawn until the patients showed regain of consciousness (ROC1) and an awareness reaction. After the command test, patients were readministered with propofol until loss of consciousness (LOC2). After surgery, all of the sedatives were withdrawn, and the patients were let to regain consciousness (ROC2).

RESULTSThe BIS values of twelve patients at ROC1 after using muscle relaxant were much lower than those at LOC1 and ROC2 without using muscle relaxant, showing statistical significance (P < 0.05). Meanwhile, the WLI values of twelve patients at ROC1 after using muscle relaxant were much higher than those at LOC1 and equal to ROC2 without using muscle relaxant, showing statistical significances (P < 0.05) between ROC1 and LOC1.

CONCLUSIONSThis study showed that under muscle relaxation or facial paralysis, when there is no EMG signal, BIS can not accurately reflect regain of consciousness in surgical patients, but WLI can reflect it accurately. So WLI may have advantages for reflecting state of consciousness in surgical patients.

Adolescent ; Adult ; Anesthesia, Intravenous ; methods ; Anesthetics, Intravenous ; therapeutic use ; Consciousness ; drug effects ; Female ; Humans ; Male ; Midazolam ; therapeutic use ; Middle Aged ; Monitoring, Intraoperative ; Piperidines ; therapeutic use ; Propofol ; therapeutic use ; Surgery, Oral ; Young Adult