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Propofol versus midazolam/ketamine for procedural sedation in pediatric oncology.

Different pharmacologic agents have been used for sedation in children undergoing invasive procedures. The authors prospectively compared the efficacy, the occurrence of adverse effects, cardiovascular parameters, oxygen saturation and induction, and recovery time in propofol with or without morphine versus midazolam/ketamine sedation for procedural sedation in children with malignancies and hematologic disorders. Fifty children received either propofol with or without morphine or ketamine/midazolam sedation for invasive procedures. Intravenous sedation consisted of 0.1 mg midazolam/kg and 1.0 mg ketamine/kg or 2 mg propofol/kg with or without 0.1 mg morphine/kg. Incremental dosages of ketamine or propofol were given, if necessary, to achieve or to maintain adequate sedation levels. Systolic and diastolic blood pressure, heart rate, oxygen saturation, time to induce sedation, recovery time, and adverse effects were recorded. All invasive procedures were successfully completed, with satisfactory sedation levels in all 25 patients in the propofol group and 23 of the 25 patients in the ketamine group. In 14 of the 25 procedures in the propofol group and 4 of the 25 procedures in the ketamine group, sedation was associated with side effects, the most common being oxygen desaturation. There was a significant increase in diastolic blood pressure after ketamine medication and a significant decrease in systolic and diastolic blood pressure and heart rate in the propofol group. Induction and recovery times in the propofol group were significantly shorter. Both regimens for procedural sedation are efficacious in achieving satisfactory sedation levels for invasive procedures. Propofol offers a quicker onset of sedation and a faster, smoother recovery but is associated with a higher rate of side effects. Considering the substantial rate of adverse effects, these procedural sedations should be performed only by physicians trained in advanced airway management and life support.

Adolescent↗

The safe and effective use of propofol sedation in children undergoing diagnostic and therapeutic procedures: experience in a pediatric ICU and a review of the literature.

OBJECTIVES: To describe our experience using propofol sedation to facilitate elective diagnostic and therapeutic procedures, and to document the safety profile of propofol in this setting. DESIGN: Retrospective consecutive case series and review of the literature. SETTING: Pediatric intensive care unit of a United States Navy tertiary care medical center. PATIENTS: Children receiving propofol for procedural sedation over an 18-month period. OUTCOME MEASURES: Descriptive features of sedation including adverse events. RESULTS: During the study period, 91 children received propofol to facilitate the performance of 110 medical procedures. The mean induction dose was 2.41 mg/kg, the mean infusion rate was 179.3 microg/kg/min, and the mean total dose of propofol administered was 4.23 mg/kg. In all cases, sedation was successfully achieved. The average length of stay in the PICU was 108.4 minutes. Three children (3.3%) had transient episodes of oxygen desaturation that improved with repositioning of the airway. No child required placement of an endotracheal tube. Three (3.3%) children experienced hypotension requiring a decrease in the infusion rate of propofol and a 10-mL/kg bolus infusion of normal saline. No cardiac arrhythmias or adverse neurologic effects secondary to propofol infusion were identified. CONCLUSIONS: Pediatric intensivists can safely and effectively administer propofol to facilitate the performance of diagnostic and therapeutic procedures outside the operating room setting.

Child↗

Propofol in total intravenous anaesthesia without nitrous oxide.

Propofol and methohexitone were evaluated as hypnotics in a total intravenous anaesthesia technique without nitrous oxide in 50 patients of ASA grade 1 or 2. Analgesia was provided by a constant alfentanil infusion and the depth of anaesthesia was controlled by varying the infusion rate of propofol or methohexitone. Induction and intubation responses were smooth and moderate in the propofol group and side effects were few. Control of depth of anaesthesia, blood pressure and pulse rate was relatively easy in this group but more difficult and sometimes inadequate in the methohexitone group, in which side effects were more frequent. The mean infusion rate for propofol was 0.12 mg/kg/minute, similar to those found in studies using nitrous oxide without an opioid. Recovery times were short in both groups but those in the propofol group tended to be shorter. Postoperatively 96% of the propofol patients were clear-headed within 20 minutes, in contrast to only 48% in the methohexitone group. We conclude that propofol together with alfentanil, both given by a bolus plus infusion technique, provide controllable and satisfactory total intravenous anaesthesia without recourse to nitrous oxide or other inhalational agents. Methohexitone was not as satisfactory as propofol.

Adult↗

Manual versus target-controlled infusions of propofol.

Target-controlled infusion systems have been shown to result in the administration of larger doses of propofol, which may result in delayed emergence and recovery from anaesthesia. The aim of this study was to investigate if this was due to a difference in the depth of hypnosis (using the bispectral index monitoring) between the manual and target controlled systems of administration. Fifty unpremedicated patients undergoing elective surgery were randomly allocated to have their anaesthesia maintained with manual or target-controlled propofol infusion schemes. In both groups, the rate of propofol administration was adjusted according to standard clinical criteria while bispectral index scores were recorded by an observer not involved in the delivery of anaesthesia. The total dose of propofol used was higher in the target controlled group (mean 9.9 [standard deviation 1.6] compared with 8.1 [1.0] mg.kg(-1).h(-1) in the manual group [p < 0.0001]). The times to emergence and recovery end-points were comparable between the two groups. The difference in the total dosage of propofol was mainly due to higher rate of propofol administration in the first 30 min in the target controlled infusion group. The bispectral index scores were lower in the target controlled group during this time, being significantly so over the first 15 min of anaesthesia. We conclude that propofol administration by a target controlled infusion system results in the administration of higher doses of propofol and lower bispectral index values mainly in the initial period of anaesthesia.

Adolescent↗

Effect of propofol on seizure-like phenomena and electroencephalographic activity in children with epilepsy vs children with learning difficulties.

There is an ongoing debate as to whether propofol exhibits pro- or anticonvulsant effects, and whether it should be used in patients with epilepsy. We prospectively assessed the occurrence of seizure-like phenomena and the effects of intravenous propofol on the electroencephalogram (EEG) in 25 children with epilepsy (mean (SD) age: 101 (49) months) and 25 children with learning difficulties (mean (SD) age: 52 (40) months) undergoing elective sedation for MRI studies of the brain. No child demonstrated seizure-like phenomena of epileptic origin during and after propofol sedation. Immediately after stopping propofol, characteristic EEG changes in the epilepsy group consisted of increased beta wave activity (23/25 children), and suppression of pre-existing theta rhythms (11/16 children). In addition, 16 of 18 children with epilepsy and documented EEG seizure activity demonstrated suppression of spike-wave patterns after propofol sedation. In all 25 children with learning difficulties an increase in beta wave activity was seen. Suppression of theta rhythms occurred in 11 of 12 children at the end of the MRI study. In no child of either group was a primary occurrence or an increase in spike-wave patterns seen following propofol administration. The occurrence of beta wave activity (children with learning difficulties and epilepsy group) and suppression of spike-wave patterns (epilepsy group) were transient, and disappeared after 4 h. This study demonstrates characteristic, time-dependent EEG patterns induced by propofol in children with epilepsy and learning difficulties. Our data support the concept of propofol being a sedative-hypnotic agent with anticonvulsant properties as shown by depression of spike-wave patterns in children with epilepsy and by the absence of seizure-like phenomena of epileptic origin.

Adolescent↗

Propofol vs thiopentone as anaesthetic agents for short operative procedures.

In a randomized open study, 120 healthy female patients were included. For short gynaecological procedures they were anaesthetized with either propofol 2.5 mg X kg-1 (n = 60) or thiopentone 5 mg X kg-1 (n = 60) in combination with nitrous oxide/oxygen (67%/33%). Supplementary doses of propofol (10-20 mg) or thiopentone (25-50 mg) were given when necessary during the procedure. Induction characteristics for propofol and thiopentone 1 min after start of induction were similar. Propofol seemed to have a more depressant effect than thiopentone on the circulatory response to anaesthesia. Recovery times from the end of the operative procedure until the patients opened their eyes on command and were orientated were shorter in the propofol patients compared to the thiopentone patients. In the propofol group, patients recalled discomfort on injection more often than patients anaesthetized with thiopentone. Otherwise, the side-effects were similar in both groups. We conclude that propofol is similar to thiopentone in its anaesthetic qualities during induction and maintenance of short anaesthetic procedures. Propofol was associated with a more rapid emergence from anaesthesia than thiopentone.

Anesthesia, Intravenous↗

Total intravenous anaesthesia for direct laryngoscopy: propofol infusion compared to thiopentone combined with midazolam and methohexitone infusion.

Total intravenous anaesthesia for direct laryngoscopy was investigated in 40 patients, randomized into four groups of 10 patients each. First, propofol infusion was compared to thiopentone combined with midazolam. Next, a comparison of propofol infusion with methohexitone infusion was undertaken. The propofol group showed significantly lower peroperative blood pressure compared to the thiopentone/midazolam group. The second propofol group required significantly less alfentanil to stabilize the blood pressure, compared to the methohexitone group. Completeness of recovery, assessed by means of a coin counting test, was faster in the propofol group compared to the thiopentone/midazolam group, while no difference could be demonstrated between the second propofol group and the methohexitone group. It is concluded that propofol seems to be superior to both thiopentone/midazolam and methohexitone with respect to the stability of peroperative blood pressure. Concerning recovery, propofol is superior to thiopentone/midazolam, but offers no advantage over methohexitone.

Adult↗

Psychomimetic reactions after neurolept and propofol anaesthesia.

The purpose of this study was to compare the frequency of psychomimetic reactions after 24 h and 3 months following total intravenous anaesthesia with propofol and neurolept anaesthesia. Forty otherwise healthy female patients were randomly divided into two groups. All were undergoing elective gynaecological laparotomy for non-malignant disease. Nineteen patients were anaesthetized with droperidol, fentanyl, pancuronium, N2O/O2. Twenty patients received total intravenous anaesthesia with propofol, fentanyl and pancuronium. Twenty-four hours after the anaesthesia the patients were interviewed about their subjective experiences of anaesthesia and recovery. Three months after the operation the patients were sent a questionnaire concerning ability to work, sleep and memory disorders. After 24 h the anaesthesia was judged as good by 18 patients receiving propofol and 13 patients receiving NLA (n.s.). The recovery was judged as good by 16 patients in the propofol group and six patients in the NLA group (P < 0.05). Locked-in feelings were reported by one patient in the propofol group and ten patients in the NLA group (P < 0.01). Impairment of memory was reported by one patient in the propofol group and seven patients in the NLA group (P < 0.01). A questionnaire used after 3 months was answered by 18 patients in the propofol group and 17 patients in the NLA group. There were few complaints, and no differences were found between the two groups. In conclusion, total intravenous anaesthesia with propofol seems more acceptable than anaesthesia with neurolept as judged by the patients 24 h after anaesthesia. There were no differences between the two groups concerning psychomimetic reactions 3 months after anaesthesia.

Adult↗

QT interval, heart rate and arterial pressures using propofol, thiopentone or methohexitone for induction of anaesthesia in children.

The effects on corrected QT interval (QTc), heart rate and arterial pressure were studied after induction with propofol 1.5, 2 or 2.5 mg.kg-1, thiopentone 5 mg.kg-1 or methohexitone 2 mg.kg-1 in 123 ASA class I or II children undergoing outpatient otolaryngological surgery. Premedication consisted of oral midazolam and atropine. The children were randomly allocated to one of the three propofol groups or to the thiopentone or methohexitone group. After injection of the intravenous anaesthetic, the QTc interval was significantly prolonged after propofol 2.5 mg.kg-1. Thirty seconds after suxamethonium 1.5 mg.kg-1, a significant prolongation of the QTc interval occurred in the thiopentone and propofol 1.5 and 2 mg.kg-1 groups. After intubation, no further prolongation of the QTc interval occurred in any of the groups. Heart rate increased significantly after the barbiturates but not after propofol. Systolic arterial pressure decreased significantly after propofol 1.5 and 2.5 mg.kg-1. In all groups a cardiovascular intubation response occurred. Bradycardia and junctional rhythm occurred in 4% of the children in both barbiturate groups and in 19-29% in the propofol groups. It is concluded that propofol causes prolongation of the QT interval and results in a higher incidence of bradycardia and junctional rhythm than the barbiturates.

Anesthesia, Intravenous↗

Effective concentration 50 for propofol with and without 67% nitrous oxide.

The Effective Blood Concentration (EC) of propofol required to prevent response to surgical incision was determined in 65 ASA I or II female patients breathing either 100% oxygen or 67% N2O in oxygen. Propofol was administered via a microcomputer-controlled infusion system programmed to maintain the blood propofol concentration at predetermined target values. The blood propofol concentrations predicted by the micro-computer were validated by measurement of whole blood propofol concentration. Predicted and measured concentrations differed during infusion of propofol, but became similar after discontinuing the infusion for at least 90 s, suggesting that equilibration within the central compartment was incomplete during infusion. The response to the initial incision was observed and probit analysis used to determine the predicted blood concentration at which 50% of patients responded. The predicted EC50 for propofol/N2O/O2 and propofol/O2 was 4.5 micrograms ml-1 and 6.0 micrograms ml-1 respectively, and the measured EC50 propofol/N2O/O2 and propofol/O2 was 5.36 micrograms ml-1 and 8.1 micrograms ml-1, 67% nitrous oxide in oxygen reducing the predicted EC50 by 25% and the measured EC50 of propofol by 33%. The predicted EC may be more representative of the equilibrated concentration in the central compartment and thus reflective of tissue propofol concentrations.

Adolescent↗

Disturbance of hepatocellular integrity associated with propofol anaesthesia in surgical patients.

Propofol anaesthesia has not been associated with any hepatic consequences. We used glutathione transferase Alpha (GSTA), a very sensitive indicator of hepatocellular integrity, to evaluate the effect of propofol on the liver. Total intravenous anaesthesia was induced and maintained with propofol without any supplements in 30 female patients undergoing breast surgery. Ten healthy female volunteers given the lipid vehicle of propofol served as controls. Serum GSTA concentration was measured with a sensitive time-resolved immunofluorometric assay. Total intravenous propofol anaesthesia was stable and postoperative nausea negligible. A significant increase in GSTA from 3.1 micrograms.l-1 (mean baseline) to 10.0 micrograms.l-1 (mean peak) was noted after propofol infusion, indicating subclinical disturbance in hepatocellular integrity. No change in aminotransferases and no clinical signs of hepatotoxicity were observed. A small increase in GSTA from 2.4 micrograms.l-1 (mean baseline) to 4.1 micrograms.l-1 (mean peak) was observed during lipid infusion. We detected a subclinical disturbance in hepatocellular integrity after propofol anaesthesia for breast surgery. The mechanisms of hepatocellular impairment are not clear but the lipid vehicle of propofol alone does not explain it.

Adult↗

Influence of body compartments on propofol induction dose in female patients.

BACKGROUND: For induction of anaesthesia, drugs such as propofol are commonly administered according to a per weight basis. However, drugs are primarily distributed to the fat-free mass. This study was undertaken to determine the relationship between propofol requirement for induction and body mass determined by bioimpedance analysis (BIA) or by body mass index (BMI). METHODS: Twenty-one ASA 1 female patients scheduled for gynaecologic surgery received propofol for induction at 133 mg.min-1. Stepwise regression analysis was used to describe the relationships between propofol requirement for loss of consciousness and age, body weight, and lean body mass measured by BIA and BMI (independent variables). RESULTS: Loss of consciousness was obtained with a propofol dose (Mean (SEM)) of 2.17 +/- 0.10 mg.kg-1. Stepwise analysis showed that propofol requirement (total dose) was not proportional to weight or age but related to lean body mass as determined by BIA and to body mass index (r2 = 0.447; global P- value < 0.007). BMI was the only regressor variable when the propofol dose was expressed in mg.kg-1 (r2 = 0.661; P < 0.001). CONCLUSIONS: Our results indicate that propofol requirements for induction are proportional to the lean body mass rather than total body weight.

Adult↗

Propofol sedation and gastric emptying in volunteers.

BACKGROUND: The purpose of this study was to evaluate the effects of light propofol sedation on gastric emptying and orocecal transit time (OCT). METHODS: Ten healthy male volunteers were studied on 2 occasions separated by at least 1 week and were randomly allocated to receive either propofol sedation or i.v. saline as a control. During propofol sedation the volunteers were sedated to grade 2-3 on a 5-grade scale. This was achieved by a propofol infusion of 5 mg kg(-1) h(-1) initially, which was then titrated down to a dose of 2.4+/-0.7 mg kg(-1) h(-1). Paracetamol absorption was used as an indirect measure of the rate of gastric emptying and OCT was determined by use of the hydrogen breath test after ingestion of raffinose. Student's t-test for paired samples was used and the results are presented as means+/-SD. RESULTS: During propofol sedation the maximum concentration of paracetamol (Cmax) was 115+/-26.8 micromol/L, time to peak concentration (Tmax) 50+/-38.8 min, and the area under the curve during the first 60 min (AUC60) 4793+/-1538 micromol x min/L, versus Cmax 99+/-20.8, Tmax 69+/-41.9 and AUC60 3897+/-1310 during saline infusion. These differences were not statistically significant. OCT was significantly shorter during the control study, 180+/-32.4 min, than during propofol sedation, 217+/-64.9 min (P<0.05). CONCLUSION: This study in volunteers has shown that gastric emptying of liquids seems uninfluenced by light propofol sedation. OCT was slightly prolonged during light propofol sedation.

Absorption↗

Effects of propofol on ipecacuanha-induced nausea and vomiting.

BACKGROUND: The purpose of this study was to evaluate if propofol has 5-HT3 antagonistic effects. Ipecacuanha is known to release serotonin (5-HT) in the gastrointestinal tract and therefore ipecacuanha syrup was used to induce nausea and vomiting. The 5-HT3 antagonist ondansetron was used as a control substance. METHOD: Ten healthy male volunteers (20-37 years) were studied on three occasions and were randomly allocated to receive a concomitant infusion of propofol (initial bolus 0.1 mg kg(-1) then 1 mg kg(-1)h(-1)), ondansetron (initial bolus 0.11 mg kg(-1) then 14 microg kg(-1)h(-1)) and placebo on either occasion. The infusions started 30 min before oral ingestion of 30 ml of ipecacuanha and continued until 150 min after the intake. The number of retchings was recorded and the intensity of nausea was estimated by the subjects on a visual analog scale. RESULTS: During the first 150 min after ingestion of ipecacuanha there were no retchings during the ondansetron infusion (P=0.01 vs placebo, P=0.02 vs propofol) and significantly fewer retchings during propofol infusion compared to placebo (P<0.02). There was no nausea during the ondansetron infusion (P<0.01 vs placebo and propofol) but the volunteers experienced nausea both during the placebo and propofol infusion (NS). CONCLUSION: This study in volunteers has shown that propofol reduces the intensity of retching after oral intake of ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamine, it can be concluded that propofol may have a weak 5-HT3 antagonistic effect.

Adult↗

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits.

BACKGROUND: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e.g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. METHODS: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. on the effects of propofol and fentanyl respectively on PNA were studied. RESULTS: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg.kg-1 i.v. and 32 micrograms.kg-1 i.v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg.kg-1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg.kg-1. The mean ED50s, calculated from dose-response curves, were 5.4 mg.kg-1, 3.9 micrograms.kg-1 and 0.4 mg.kg-1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg.kg-1 and 8 micrograms.kg-1, respectively. CONCLUSION: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.

Action Potentials↗

Less local pain on intravenous infusion of a new propofol emulsion.

BACKGROUND: Local pain at the site of intravenous (iv) injection of propofol remains a considerable problem in clinical anaesthesiology, and particularly so in infants. The aim of the present study was to compare the influence of two different emulsions of propofol on local pain following iv administration. METHODS: Eighty adult patients (ASA I-II) scheduled for ear-nose-throat or plastic surgery were randomly allocated into two study groups: A and B. A 1.0-mm teflon cannula (BD, Helsingborg, Sweden) was inserted into a dorsal vein on each hand. Each patient was given two 3.0-ml iv bolus injections of two different propofol emulsions of 10 mg ml(-1) over 2 s, one in each cannula, at 5-min intervals. The first study drug administered was Diprivan (AstraZeneca, Södertälie, Sweden) in group A (n = 34) and Propofol-Lipuro (Braun, Melsungen, Germany) in group B (n = 39). Each patient was then asked by a blinded investigator to score maximal pain intensity on a visual analogue scale (VAS). RESULTS: The maximal intensity of propofol-induced local pain was significantly (P < 0.0001) lower after Propofol-Lipuro than after Diprivan--median 1 (25th percentile: 0; 75th percentile: 2) range 0-6 vs. 3 (0; 5) 0-9 VAS units. CONCLUSION: The considerably lower intensity of local pain found to be associated with iv administration of the new drug formula Propofol-Lipuro indicates that emulsions of propofol based on medium- and long-chain triglycerides have a clinical advantage over traditional ones for induction of anaesthesia.

Anesthetics, Intravenous↗

Requirements of propofol at different end-points without adjuvant and during two different steady infusions of remifentanil.

BACKGROUND: Some reports show no interaction between propofol and opioids, whereas others state such interactions. We evaluated the influence of remifentanil on propofol requirements at certain anesthesia end-points. METHODS: Elective surgical patients were randomly assigned to three groups of 15 patients each. Premedication was with oral diazepam 0.1 mg kg(-1). Patients were blindly given equal volumes of saline or remifentanil (7.5 or 30 microg kg(-1). h(-1)) 1 min before induction of anesthesia with infusion of propofol, 30 mg kg(-1). h(-1). We recorded times to, propofol requirements, and bispectral index at loss of counting (LC), loss of verbal command (LVC), loss of reaction to tetanic stimulation (LRT), and onset of burst suppression pattern (BSP) of electroencephalography. RESULTS: In the remifentanil groups end-points were attained significantly faster and with lower doses of propofol than in the saline group. BIS-values were significantly different at LRT and BSP end-points. CONCLUSIONS: We conclude that remifentanil infusion started before induction of propofol anesthesia significantly reduces propofol requirements at all end-points. The results suggest that remifentanil accelerates the hypnotic onset of propofol.

Adolescent↗

Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: a FMRI study.

BACKGROUND: Functional magnetic resonance imaging (fMRI) using blood-oxygen-level-dependent (BOLD) contrasts is a common method for studying sensory or cognitive brain functions. The aim of the present study was to assess the effect of the intravenous anaesthetic propofol on auditory-induced brain activation using BOLD contrast fMRI. METHODS: In eight neurosurgical patients, musical stimuli were presented binaurally in a block design. Imaging was performed under five conditions: no propofol (or wakefulness) and propofol plasma target concentrations of 0.5, 1.0, 1.5, and 2.0 microg ml(-1). RESULTS: During wakefulness we found activations in the superior temporal gyrus (STG) corresponding to the primary and secondary auditory cortex as well as in regions of higher functions of auditory information processing. The BOLD response decreased with increasing concentrations of propofol but remained partially preserved in areas of basic auditory processing in the STG during propofol 2.0 microg ml(-1). CONCLUSIONS: Our results suggest a dose-dependent impairment of central processing of auditory information after propofol administration. These results are consistent with electrophysiological findings measuring neuronal activity directly, thus suggesting a dose-dependent impairment of central processing of auditory information after propofol administration. However, propofol did not totally blunt primary cortical responses to acoustic stimulation, indicating that patients may process auditory information under general anaesthesia.

Acoustic Stimulation↗