Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness.

BACKGROUND: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery. METHODS: Healthy participants received dexmedetomidine (n=23) or propofol (n=24) in stepwise increments until loss of responsiveness (LOR1). During TCI we attempted to arouse them for interview (return of responsiveness, ROR1). After the interview, if unresponsiveness ensued with the same dose (LOR2), the procedure was repeated (ROR2). Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness (LOC), infusion terminated, and the participants interviewed upon recovery (ROR3). An emotional sound stimulus was presented during LORs and LOC, and memory for stimuli was assessed with recognition task after recovery. Interview transcripts were content analysed. RESULTS: Of participants receiving dexmedetomidine, 18/23 were arousable from LOR1 and LOR2. Of participants receiving propofol, 10/24 were arousable from LOR1 and two of four were arousable from LOR2. Of 93 interviews performed, 84% included experiences from periods of unresponsiveness (dexmedetomidine 90%, propofol 74%). Internally generated experiences (dreaming) were present in 86% of reports from unresponsive periods, while externally generated experiences (awareness) were rare and linked to brief arousals. No within drug differences in the prevalence or content of experiences during infusion vs after recovery were observed, but participants receiving dexmedetomidine reported dreaming and awareness more often. Participants receiving dexmedetomidine recognised the emotional sounds better than participants receiving propofol (42% vs 15%), but none reported references to sounds spontaneously. CONCLUSION: Anaesthetic-induced unresponsiveness does not induce unconsciousness or necessarily even disconnectedness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Spoken words are processed during dexmedetomidine-induced unresponsiveness.

BACKGROUND: Studying the effects of anaesthetic drugs on the processing of semantic stimuli could yield insights into how brain functions change in the transition from wakefulness to unresponsiveness. Here, we explored the N400 event-related potential during dexmedetomidine- and propofol-induced unresponsiveness. METHODS: Forty-seven healthy subjects were randomised to receive either dexmedetomidine (n=23) or propofol (n=24) in this open-label parallel-group study. Loss of responsiveness was achieved by stepwise increments of pseudo-steady-state plasma concentrations, and presumed loss of consciousness was induced using 1.5 times the concentration required for loss of responsiveness. Pre-recorded spoken sentences ending either with an expected (congruous) or an unexpected (incongruous) word were presented during unresponsiveness. The resulting electroencephalogram data were analysed for the presence of the N400 component, and for the N400 effect defined as the difference between the N400 components elicited by congruous and incongruous stimuli, in the time window 300-600 ms post-stimulus. Recognition of the presented stimuli was tested after recovery of responsiveness. RESULTS: The N400 effect was not observed during dexmedetomidine- or propofol-induced unresponsiveness. The N400 component, however, persisted during dexmedetomidine administration. The N400 component elicited by congruous stimuli during unresponsiveness in the dexmedetomidine group resembled the large component evoked by incongruous stimuli at the awake baseline. After recovery, no recognition of the stimuli heard during unresponsiveness occurred. CONCLUSIONS: Dexmedetomidine and propofol disrupt the discrimination of congruous and incongruous spoken sentences, and recognition memory at loss of responsiveness. However, the processing of words is partially preserved during dexmedetomidine-induced unresponsiveness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Effect of 3 g of intravenous paracetamol on post-operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia.

BACKGROUND: Paracetamol is often given as an adjunctive analgesic to reduce opioid-related adverse effects but its optimal dose is unknown. We studied the analgesic effect and safety of a single 3-g intravenous (i.v.) dose of paracetamol in adults. METHODS: One hundred and seven patients undergoing tonsillectomy under local anaesthesia were randomly allocated to receive i.v. 3 g of paracetamol, 75 mg of diclofenac or placebo prior to surgery. The consumption of post-operative morphine using a patient-controlled analgesia-device was quantified for 6 h. Platelet aggregation and the concentrations of paracetamol, liver aminotransferases, glutathione transferase alpha 1-1 (GSTA1-1) and thromboxane B(2) were measured. RESULTS: During the first hours after surgery, both paracetamol and diclofenac reduced (P < 0.05) the consumption of morphine but had no effect thereafter. The values for the 6-h cumulative consumption of morphine in patients given paracetamol (18.7 +/- 13.8 mg), diclofenac (16.1 +/- 9.9 mg) and placebo (22.0 +/- 12.1 mg) did not differ. Paracetamol had no effect on platelet aggregation, which was impaired only by diclofenac in response to arachidonic acid (P < 0.005). Both paracetamol (P < 0.01) and diclofenac (P < 0.005) inhibited the release of thromboxane B(2) at 1 h but they did not affect serum aminotransferase and GSTA1-1 levels. One patient given paracetamol displayed a transient increase in GSTA1-1 and liver aminotransferases. CONCLUSION: During the initial hours after tonsillectomy, the administration of 3 g of i.v. paracetamol and 75 mg of diclofenac reduced the consumption of morphine. Both drugs also reduced the release of thromboxane B(2) from activated platelets but only diclofenac had a negative effect on platelet aggregation. In sensitive individuals, large doses of paracetamol may disturb the hepatocellular integrity. We do not recommend the use of i.v. doses of paracetamol higher than 1 g.

Effect of age and repeated hyperbaric oxygen treatments on vagal tone.

OBJECTIVES: To evaluate the influence of repeated hyperbaric oxygen (HBO2) exposures and age on vagal response to hyperbaric oxygenation, and to evaluate the timing of changes in vagal activity during the treatments. STUDY DESIGN: Open, controlled, non-randomized study. METHODS: Heart rate variability of 23 patients with chronic osteomyelitis or radionecrosis of the jaw or reconstructive surgery of the facial region was studied during repeated treatments. During each treatment, the patients were exposed to HBO2 at 2.5 ATA and heart rate variability was measured using power spectral analysis before compression, three times at 2.5 ATA and during and after decompression. The patients were grouped according to age (Cut-off point 50 years). Statistical analysis was carried out using analysis of variance for repeated measurements. RESULTS: Repeated exposures did not change vagal response to hyperbaric oxygenation. Vagal activity measured by HF power increased significantly in both age groups during the HBO2 exposures but there were no significant difference between the groups in the response. However, the level of HF power was significantly higher in the subjects under 50 years old. Significant differences between consecutive measurements were related to pressure changes. CONCLUSIONS: Repeated therapeutic HBO2exposures are not causing permanent changes in vagal control of the heart. Vagal responsiveness to hyperbaric hyperoxia is preserved in advanced age.

Instantaneous beat-to-beat variability reflects vagal tone during hyperbaric hyperoxia.

Hyperbaric hyperoxia affects heart rate variability (HRV) by increasing parasympathetic activity. The purpose of this study was to evaluate the applicability of instantaneous beat-to-beat variability (SD1 of Poincaré plot analysis) in detecting changes in vagal tone and to evaluate possible changes in the fractality of heart rate dynamics (alpha1 of detrended fluctuation analysis) during hyperbaric hyperoxia. Continuous three-lead ECG recordings were taken in ten divers who were treated at 2.5 ATA with air (PO2 47 kPa) and oxygen (PO2 235 kPa) for 60 min. Power spectral analysis, Poincaré plot analysis and alpha1 were analyzed before compression, after 30 min and after 55 min at 2.5 ATA. Correlations between the variables were calculated after 55 min exposure. SD1 and high frequency (HF) power increased significantly but alpha1 decreased during hyperbaric hyperoxia (PO2 235 kPa). HF power and SD1 also correlated significantly. However, HF power and SD1 correlated inversely with alpha1. During hyperbaric hyperoxia, SD1 reflects vagal activity and can be used instead of HF power, if stationary conditions cannot be achieved. The decreasing alpha1 indicates more random heart rate dynamics during hyperbaric hyperoxia.

Hyperbaric oxygen increases parasympathetic activity in professional divers.

The role of autonomic nervous system in hyperoxic bradycardia was evaluated by using the power-spectral analysis of heart-rate variability (HRV). Ten professional divers went through two hyperbaric hyperoxic experiments: (1) hyperbaric oxygen (HBO), 100% oxygen at 2.5 ATA, (2) hyperbaric air (HBAIR), O(2) 21% at 2.5 ATA. Four-minute traces of ECG were registered and subjected to power-spectral analysis. Cardiac conduction parameters were evaluated by a diagnostic 12-lead ECG and arrhythmias by a continuous 3-lead ECG. Statistical analysis was made using analysis of variance for repeated measurements. Heart rate decreased (P < 0. 001), but the response was similar during both treatments (P=0.14). Total power increased significantly more during HBO than HBAIR (P=0.003). High-frequency (HF) power (P < 0.001), Hayano's index (P=0.001) and normalized units of HF power (P=0.002) increased and LF/HF index (P < 0.001) decreased more during HBO than HBAIR. There were no changes in cardiac conduction or incidence of arrhythmias. In conclusion, 100% oxygen at 2.5 ATA caused marked increase in parasympathetic tone compared with 21% oxygen at 2.5 ATA.

Heart rate variability in healthy volunteers during normobaric and hyperbaric hyperoxia.

Inhaled supranormal partial pressure of oxygen induces bradycardia and peripheral vasoconstriction. The exact mechanism of the decreasing heart rate is not clear, but the autonomic nervous system is partly involved. In the present study the role of the autonomic nervous system in hyperoxic bradycardia was evaluated by using the power spectral analysis of heart rate variability. Ten healthy volunteers participated in four experiments: (i) hyperbaric oxygen treatment (100% oxygen at 2.5 ATA), (ii) hyperbaric air treatment (O2 21% at 2.5 ATA), (iii) oxygen treatment at normal pressure (100% O2, 1 ATA) and (iv) air breathing at normal pressure (21% O2, 1 ATA). During the experiments, ECG was registered and subjected to power spectral analysis. The volunteers rated their perception of temperature, ear discomfort, sweating and excitement on a visual analogue scale. Statistical comparison of the results of the four trials was conducted with a two-way ANOVA for repeated measurements. Heart rate decreased during all interventions, but there were no statistically significant differences between the sessions. High frequency variability of heart rate variability and Hayano's index of HF power increased and LF/HF ratio decreased with increasing partial pressure of oxygen. Our results suggest, that normobaric and hyperbaric hyperoxia increase parasympathetic influence in the regulation of the heart.

Effect of hyperbaric conditions on plasma stress hormone levels and endothelin-1.

To study a generalized stress reaction as well as endothelin-1 concentrations during moderate hyperbaria and hyperbaric oxygen (HBO2), eight professional divers were exposed to air (O2 21%, AIR) and oxygen (O2 100%, HBO2) at 2.5 atm abs for 60 min in separate sessions. Plasma concentrations of epinephrine, norepinephrine, dihydroxyphenylglycol (metabolite of norepinephrine), cortisol, ADH, renin, aldosterone, pro-ANP, and endothelin-1 were analyzed before, during, and 20 min after the treatments. Endothelin-1 increased significantly (6% during HBO2 and 18% during AIR, and 30 and 34% after the treatments, respectively, P = 0.032). There was no statistically significant difference in the changes of mean norepinephrine and dihydroxyphenylglycol levels between the treatments, although both seemed to change slightly during the treatments, but not over the baseline (time effect P = 0.031 and P = 0.011, respectively). Cortisol levels decreased significantly (P = 0.001) during the treatments. No significant changes were found in other analyzed hormones. The authors concluded that a) HBO2, and hyperbaric air at 2.5 atm abs do not induce a generalized hormonal stress reaction, and b) endothelin-1 increases during HBO2 and hyperbaric air at 2.5 atm abs.

Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation.

Ninety-six women undergoing laparoscopic tubal ligation were randomized to receive intravenously either 0.2 or 0.4 microgram/kg of dexmedetomidine, 60 micrograms/kg of oxycodone, or 250 micrograms/kg of diclofenac for postoperative pain in a double-blind study design. The study drugs were administered in the recovery room for moderate or severe pain and were repeated until pain subsided or disappeared. In the group receiving diclofenac, 83% of the patients required analgesic supplementation with morphine. This contrasted (P less than 0.01) with 33% of the patients receiving either oxycodone or the higher dose of dexmedetomidine. After the first dose of oxycodone was injected, the visual analogue scale for pain (0%-100%) was reduced from 58% to 33%, whereas corresponding pain relief was only achieved after the third injection of 0.4 microgram/kg of dexmedetomidine. Repeated doses of 0.2 microgram/kg of diclofenac or dexmedetomidine did not reduce the visual analogue scale value by more than 17%. More sedation was seen with the higher dose of dexmedetomidine than with either diclofenac or oxycodone (P less than 0.001). Both doses of dexmedetomidine decreased heart rate when compared with diclofenac (P less than 0.001). In the group given 0.4 microgram/kg of dexmedetomidine, 33% of the patients required atropine for bradycardia. The authors conclude that after laparoscopic tubal ligation, intravenously administered dexmedetomidine relieves pain and reduces opioid drug requirement but is attended by sedation and a high incidence of bradycardia.