Role of mitochondrial DNA level in epidural-related maternal fever: a single-centre, observational, pilot study.

INTRODUCTION: Epidural analgesia has been associated with intrapartum maternal fever development. Epidural-related maternal fever (ERMF) is believed to be based on a non-infectious inflammatory reaction. Circulating cell-free mitochondrial deoxyribonucleic acid (mtDNA) is one of the possible triggers of sterile inflammatory processes; however, a connection has not been investigated so far. Therefore, this study aimed to investigate cell-free mtDNA alterations in women in labour with ERMF in comparison with non-febrile women. MATERIAL AND METHODS: A total of 60 women in labour were assessed for maternal temperature every 4 h and blood samples were obtained at the beginning and after delivery. Depending on the analgesia and the development of fever (axillary temperature ≥ 37.5 °C), the women were allocated either to the group of no epidural analgesia (n = 17), to epidural analgesia no fever (n = 34) or to ERMF (n = 9). Circulating cell-free mtDNA was analysed in the maternal plasma for the primary outcome whereas secondary outcomes include the evaluation of inflammatory cytokine release, as well as placental inflammatory signs. RESULTS: Of the women with epidural analgesia, 20% (n = 9) developed ERMF and demonstrated a decrease of circulating mtDNA levels during labour (p = 0.04), but a trend towards higher free nuclear DNA. Furthermore, women with maternal pyrexia showed a 1.5 fold increased level of Interleukin-6 during labour. A correlation was found between premature rupture of membranes and ERMF. CONCLUSIONS: The pilot trial revealed an evident obstetric anaesthesia phenomenon of maternal fever due to epidural analgesia in 20% of women in labour, demonstrating counterregulated free mtDNA and nDNA. Further work is urgently required to understand the connections between the ERMF occurrence and circulating cell-free mtDNA as a potential source of sterile inflammation. TRIAL REGISTRATION: NCT0405223 on clinicaltrials.gov (registered on 25/07/2019).

Correlation between the Neuropathic PainDETECT Screening Questionnaire and Pain Intensity in Chronic Pain Patients.

Background and Objectives: Pain is a multidimensional phenomenon with a wide range regarding the location, intensity and quality. Patients with chronic pain, in particular those suffering from mixed pain, often present a special challenge. The PainDETECT questionnaire (PD-Q) is a screening instrument designed to classify whether a patient has neuropathic pain (NP), often rated as more distressing compared to nociceptive pain. The objective of this study was to investigate whether the PD-Q score correlates with pain intensity, measured with the numeric rating scale (NRS), in chronic pain patients in an outpatient setting. Materials and Methods: A questionnaire-based study was conducted to identify the associations between the unidimensional NRS scale for pain intensity and the PD-Q score for screening of an NP component in an outpatient setting. Participants were asked to fill in the questionnaire themselves. Results: One hundred seventy-six participants completed the PD-Q questionnaire and rated pain on the NRS scale at the baseline visit. The PD-Q and NRS scores significantly correlated at the baseline visit and the 1-month follow-up visit in chronic pain patients. The identification of a neuropathic component in chronic pain may permit more targeted and effective pain management. Conclusions: The findings of our questionnaire suggest that a significant proportion of chronic pain patients had manifested features of NP at the first visit to the outpatient clinic. The PD-Q is a useful screening tool to alert clinicians of NP that may need further diagnostic evaluation or therapeutic intervention and may also help to predict treatment response. Further research is needed to investigate if a correlation is predictive of treatment response when pain therapy targets NP.

Effect of Ketamine on Limbic GABA and Glutamate: A Human In Vivo Multivoxel Magnetic Resonance Spectroscopy Study.

INTRODUCTION: Converging evidence suggests that ketamine elicits antidepressant effects via enhanced neuroplasticity precipitated by a surge of glutamate and modulation of GABA. Magnetic resonance spectroscopic imaging (MRSI) illustrates changes to cerebral glutamate and GABA immediately following ketamine administration during dissociation. However, few studies assess subacute changes in the first hours following application, when ketamine's antidepressant effects emerge. Moreover, ketamine metabolites implicated in its antidepressant effects develop during this timeframe. Thus, this study aimed to investigate subacute changes in cerebral Glx (glutamate + glutamine), GABA and their ratio in seven brain regions central to depressive pathophysiology and treatment. METHODS: Twenty-five healthy subjects underwent two multivoxel MRS scans using a spiral encoded, MEGA-edited LASER-localized 3D-MRSI sequence, at baseline and 2 h following intravenous administration of racemic ketamine (0.8 mg/kg bodyweight over 50 min). Ketamine, norketamine and dehydronorketamine plasma levels were determined at routine intervals during and after infusion. Automated region-of-interest (ROI)-based quantification of mean metabolite concentration was used to assess changes in GABA+/total creatine (tCr), Glx/tCr, and GABA+/Glx ratios in the thalamus, hippocampus, insula, putamen, rostral anterior cingulate cortex (ACC), caudal ACC, and posterior cingulate cortex. Effects of ketamine on neurotransmitter levels and association with ketamine- and metabolite plasma levels were tested with repeated measures analyses of variance (rmANOVA) and correlation analyses, respectively. RESULTS: For GABA+/tCr rmANOVA revealed a measurement by region interaction effect (puncorr < 0.001) and post hoc pairwise comparisons showed a reduction in hippocampal GABA+/tCr after ketamine (pcorr = 0.02). For Glx/tCr and GABA+/Glx neither main effects of measurement nor measurement by region interactions were observed (all puncorr > 0.05). Furthermore, no statistically significant associations between changes in any of the neurotransmitter ratios and plasma levels of ketamine, norketamine, or dehydronorketamine were observed (pcorr > 0.05). CONCLUSION: This study provides evidence for decreased hippocampal GABA+/tCr ratio 2 h following ketamine administration. As MRS methodology measures total levels of intra- and extracellular GABA, results might indicate drug induced alterations in GABA turnover. Our study in healthy humans suggests that changes in GABA levels, particularly in the hippocampus, should be further assessed for their relevance to ketamine´s antidepressant effects.

Opioid use after propofol or sevoflurane anesthesia: a randomized trial.

BACKGROUND: The intravenous anesthetic propofol is a gamma-aminobutyric acid A receptor agonist. Propofol promotes analgesia by depressing nociceptive transmission in peripheral neurons, antagonizing N-methyl-D-aspartate receptors, and activating gamma-aminobutyric acid A receptors in dorsal root ganglion receptor cells. Nevertheless, it remains unclear whether intraoperative propofol causes clinically meaningful postoperative analgesia. We therefore tested the hypothesis that patients anesthetized with sevoflurane require a greater quantity of postoperative opioids (from the end of surgery until the next postoperative morning) than those anesthetized with propofol. METHODS: With Institutional Review Board and EudraCT Number approval (2009-011038-82) and patients' informed consent, ninety patients scheduled for open vein stripping were randomized to either sevoflurane or propofol anesthesia at the Medical University of Vienna General Hospital and the Danube Hospital, the largest regional hospital in Vienna. Pain was treated with bolus piritramide and patient-controlled morphine hydrochloride. The primary outcome was total opioid use from the end of surgery until the first postoperative morning. For the initial four postoperative hours and on the first postoperative morning, a blinded investigator recorded pain scores on an 11-point Likert verbal response scale. RESULTS: The median [interquartile range] morphine sulfate equivalents were 9.8 [4-19] mg in the sevoflurane group and 10 [6-20] mg in the propofol group. Sevoflurane was not superior to propofol on postoperative opioid consumption, giving a ratio of means of 0.91 (95% interim-adjusted confidence interval [CI], 0.33 to 2.45; P = 0.74). Additionally, no difference in pain scores was found over time between the two groups, with a mean difference on an 11-point scale of 0.20 (95% interim-adjusted CI, -0.36 to 0.73; P = 0.31). CONCLUSION: Intraoperative sevoflurane did not reduce postoperative analgesia. This finding is consistent with the results in most previous reports. This trial was registered at ClinicalTrials.gov: NCT00712517.

Pharyngeal Oxygen Insufflation During AirTraq Laryngoscopy Slows Arterial Desaturation in Infants and Small Children.

BACKGROUND: The extent to which insufflation of oxygen into the posterior pharynx during laryngoscopy prolongs adequate saturation in infants and small children remains unknown. Therefore, we compared oxygen saturation over time in preoxygenated small children with and without posterior pharynx oxygen insufflation. METHODS: After induction of anesthesia with sevoflurane and propofol, infants and small children were preoxygenated with 100% oxygen for 3 minutes. An AirTraq laryngoscope size 0 or 1 with an appropriately sized cuffed endotracheal tube positioned in the side channel was prepared. Oxygen tubing was connected to the endotracheal U-shaped tube. However, oxygen at a flow of 4 L/min was provided only to half of the randomly selected participating patients. The trachea was intubated, the tube cuff was inflated, and the laryngoscope was removed from the mouth. The oxygen tubing was disconnected from the endotracheal tube and left exposed to ambient air until oxygen saturation decreased to 95%. Thereafter, patients' lungs were manually ventilated with 100% oxygen until SpO2 returned to 100%. Subsequent anesthetic management was at the discretion of the attending anesthesiologist. RESULTS: Laryngoscopy took a median of 60 (Q1-Q3, 40-90) seconds. The mean time to 95% oxygen saturation was (mean ± SD) 166 ± 47 seconds in the oxygen insufflation group and 131 ± 39 seconds in small children without insufflation. Oxygen insufflation prolonged the mean time for saturation to decrease from 100% to 95% by an estimated 35 (95% confidence interval, 10-60) seconds, P = 0.01. CONCLUSIONS: Adding posterior pharyngeal oxygen insufflation to conventional preoxygenation prolonged the period of adequate oxygen saturation in infants and small children by an amount that is potentially clinically important.