Application of intranasal dexmedetomidine in magnetic resonance imaging of preterm infants: The ED50, efficacy and safety analysis.

BACKGROUND: Infants undergoing magnetic resonance imaging (MRI) often require pharmacological sedation. Dexmedetomidine serves as a novel sedative agent that induces a unique unconsciousness similar to natural sleep, and therefore has currently been used as the first choice for sedation in infants and young children. OBJECTIVE: To determine the 50% effective dose (ED50) and 95% confidence interval (95%CI) of intranasal dexmedetomidine for MRI in preterm and term infants, and to observe the incidence of adverse events. To explore whether there were differences in ED50 and 95%CI, heart rate (HR) and blood oxygen saturation (SpO2), the induction time and wake-up time and the incidence of adverse events between the 2 groups, so as to provide guidance for clinical safe medication for the meanwhile. METHODS: A total of 68 infants were prospectively recruited for MRI examination under drug sedation (1 week ≤ age ≤ 23 weeks or weight ≤ 5kg). The children were divided into 2 groups according to whether they had preterm birth experience (Preterm group, Atterm group). The Dixon up-and-down method was used to explore ED50. The basic vital signs of the 2 groups were recorded, and the heart rate and SpO2 were recorded every 5 minutes until the infants were discharged from the hospital. The induction time, wake-up time and adverse events were recorded. RESULTS: The ED50 (95%CI) of intranasal dexmedetomidine in the Preterm group and the Atterm group were 2.23 (2.03-2.66) µg/kg and 2.64 (2.49-2.83) µg/kg, respectively (P < .05). the wake-up time was longer in Preterm group (98.00min) than in Atterm group (81.00 min) (P < .05), the incidence of bradycardia in Preterm group was 3/33, which was higher than that in Atterm group (1/35). There was no difference in the induction time between the 2 groups (P > .05), and there was no significant difference in other adverse events. CONCLUSIONS: Intranasal dexmedetomidine can be safely used for sedation in preterm infants undergoing MRI. Compared with term infants, preterm infants have a lower dose of dexmedetomidine, a higher incidence of bradycardia, and a longer weak-up time.

Effect of Dexmedetomidine Combined with Ropivacaine on Cognitive Dysfunction and Inflammatory Response in Patients Undergoing Craniocerebral Surgery.

OBJECTIVE: To study the effects of dexmedetomidine in combination with ropivacaine in patients undergoing craniocerebral surgery and their efficiency on cognitive function and inflammatory response of patients. METHODS: 100 patients undergoing craniocerebral surgery in our hospital from November 2018 to September 2020 were randomly selected and divided into a control group and an experimental group by drawing lots, with 50 cases in each group. Patients in the control group received routine anesthesia, while those in the experimental group received 1 µg/kg of dexmedetomidine combined with 0.5% of ropivacaine for anesthesia to compare the anesthesia onset time, analgesic time, postoperative awake time, Social Disability Screening Schedule (SDSS) cognitive function score after waking, visual analogue scale (VAS) pain score, Ramsay sedation score, incidence of adverse reactions, postoperative inflammatory factor expression levels, and changes in heart rate, oxygen saturation, and blood pressure at T0, T1, T2, T3, and T4 between the two groups. RESULTS: The anesthesia onset time, SDSS cognitive function score after waking, VAS pain score, Ramsay sedation score, incidence of adverse reactions, and postoperative inflammatory factor expression levels in the experimental group were significantly lower than those in the control group (P < 0.05). The analgesic time and postoperative awake time in the experimental group were significantly longer than those in the control group, with statistical significance (P < 0.05). There were no statistically significant differences in the changes of heart rate, oxygen saturation, and blood pressure at T0, T1, T2, T3, and T4 between the two groups (P > 0.05). CONCLUSION: Dexmedetomidine combined with ropivacaine has high application value in craniocerebral surgery.

Magnetic Resonance Imaging Features under Deep Learning Algorithms in Evaluated Cerebral Protection of Craniotomy Evacuation of Hematoma under Propofol Anesthesia.

This study aimed to explore the value of magnetic resonance imaging (MRI) features based on deep learning super-resolution algorithms in evaluating the value of propofol anesthesia for brain protection of patients undergoing craniotomy evacuation of the hematoma. An optimized super-resolution algorithm was obtained through the multiscale network reconstruction model based on the traditional algorithm. A total of 100 patients undergoing craniotomy evacuation of hematoma were recruited and rolled into sevoflurane control group and propofol experimental group. Both were evaluated using diffusion tensor imaging (DTI) images based on deep learning super-resolution algorithms. The results showed that the fractional anisotropic image (FA) value of the hind limb corticospinal tract of the affected side of the internal capsule of the experimental group after the operation was 0.67 ± 0.28. The National Institute of Health Stroke Scale (NIHSS) score was 6.14 ± 3.29. The oxygen saturation in jugular venous (SjvO2) at T4 and T5 was 61.93 ± 6.58% and 59.38 ± 6.2%, respectively, and cerebral oxygen uptake rate (CO2ER) was 31.12 ± 6.07% and 35.83 ± 7.91%, respectively. The difference in jugular venous oxygen (Da-jvO2) at T3, T4, and T5 was 63.28 ± 10.15 mL/dL, 64.89 ± 13.11 mL/dL, and 66.03 ± 11.78 mL/dL, respectively. The neuron-specific enolase (NSE) and central-nerve-specific protein (S100ß) levels at T5 were 53.85 ± 12.31 ng/mL and 7.49 ± 3.16 ng/mL, respectively. In terms of the number of postoperative complications, the patients in the experimental group were better than the control group under sevoflurane anesthesia, and the differences were substantial (P < 0.05). In conclusion, MRI images based on deep learning super-resolution algorithm have great clinical value in evaluating the degree of brain injury in patients anesthetized with propofol and the protective effect of propofol on brain nerves.

Effect of difelikefalin, a selective kappa opioid receptor agonist, on respiratory depression: A randomized, double-blind, placebo-controlled trial.

Difelikefalin, a selective kappa opioid receptor agonist designed to limit central nervous system (CNS) penetration, is under development for the treatment of pruritus. Its hydrophilic, small-peptidic structure limits CNS entry, minimizing potential CNS-mediated adverse events (AEs). This study assessed the effect of difelikefalin on key relevant measures of respiratory depression in healthy volunteers. This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers. Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period. The primary end points included incidence of increased end-tidal carbon dioxide (ETCO2 ) greater than or equal to 10 mm Hg versus baseline or a level greater than 50 mm Hg sustained greater than or equal to 30 seconds, and incidence of reduction in saturation of peripheral oxygen (SpO2 ) to less than 92% sustained greater than or equal to 30 seconds. Secondary end points included incidence of reduced respiratory rate and other safety assessments. Fifteen subjects were randomized and completed the study. No subject on placebo or difelikefalin met the increased ETCO2 or reduced SpO2 primary end point criteria for respiratory depression. All respiratory measures in each group remained near baseline values during 4-h postdose observations. No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO2 , SpO2 , or respiratory rate. The most commonly reported treatment-emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms. All TEAEs were mild and resolved without intervention. Difelikefalin 1.0 and 5.0 mcg/kg i.v. did not produce respiratory depression.

The Effect of Antenatal Neuroprotective Magnesium Sulfate Treatment on Cerebral Oxygenation in Preterm Infants.

OBJECTIVE: Antenatal magnesium sulfate (MgSO4) treatment is associated with reduced risk of cerebral palsy in preterm infants. We aimed to investigate whether this treatment leads to any alterations on cerebral hemodynamics which could be detected by near-infrared spectroscopy (NIRS) readings in early postnatal life. STUDY DESIGN: Infants with gestational ages (GAs) ≤ 32 weeks were divided into two groups regarding their exposure to antenatal neuroprotective MgSO4 treatment or not. NIRS monitoring was performed to all infants, and readings were recorded for 2 hours each day during the first 3 days of life. The primary aim was to compare regional cerebral oxygen saturation (rcSO2) and cerebral fractional tissue oxygen extraction (cFTOE) between the groups. RESULTS: Sixty-six infants were exposed to antenatal MgSO4, while 64 of them did not. GA and birth weight were significantly lower in the treatment group (p < 0.01). No difference was observed in rcSO2 and cFTOE levels in the first, second, and the third days of life (p > 0.05). An insignificant reduction in severe intraventricular hemorrhage rates was observed (8 vs. 15%, p = 0.24). CONCLUSION: We could not demonstrate any effect on cerebral oxygenation of preterm infants in early postnatal life that could be attributed to antenatal neuroprotective MgSO4 treatment. Future studies are warranted to clarify the exact underlying mechanisms of neuroprotection.

Effects of Single Loading Dose of Intravenous Caffeine on Cerebral Oxygenation in Preterm Infants.

OBJECTIVE: The aim of this study was to evaluate the effects of caffeine on cerebral oxygenation in preterm infants. STUDY DESIGN: This was a prospective study of infants with a gestational age (GA) of < 34 weeks who were treated intravenously with a loading dose of 20 mg/kg caffeine citrate within the first 48 hours of life. Regional cerebral oxygen saturation (rSO2C) and cerebral fractional tissue oxygen extraction (cFTOE) were measured using near-infrared spectroscopy before administering caffeine (baseline), immediately after administering caffeine, and 1, 2, 3, 4, 6, and 12 hours after dose completion; postdose values were compared with the baseline values. RESULTS: A total of 48 infants with a mean GA of 29.0 ± 1.9 weeks, birth weight of 1,286 ± 301 g, and postnatal age of 32.4 ± 11.3 hours were included in the study. rSO2C significantly decreased from 81.3 to 76.7% soon after administering caffeine, to 77.1% at 1 hour, and to 77.8% at 2 hours with recovery at 3 hours postdose. rSO2C was 80.2% at 12 hours postdose. cFTOE increased correspondingly. Although rSO2C values were lower and cFTOE values were higher compared with the baseline values at 3, 4, 6, and 12 hours after caffeine administration, this was not statistically significant. CONCLUSION: A loading dose of caffeine temporarily reduces cerebral oxygenation and increases cerebral tissue oxygen extraction in preterm infants. Most probably these changes reflect a physiological phenomenon without any clinical importance to the cerebral hemodynamics, as the reduction in cerebral oxygenation and increase in cerebral tissue oxygen extraction remain well within acceptable range.

Combined methazolamide and theophylline improves oxygen saturation but not exercise performance or altitude illness in acute hypobaric hypoxia.

NEW FINDINGS: What is the central question of this study? Does the combination of methazolamide and theophylline reduce symptoms of acute mountain sickness (AMS) and improve aerobic performance in acute hypobaric hypoxia? What is the main finding and its importance? The oral combination of methazolamide (100 BID) and theophylline (300 BID) improved arterial oxygen saturation but did not reduce symptoms of AMS and impaired aerobic performance. We do not recommend this combination of drugs for prophylaxis against the acute negative effects of hypobaric hypoxia. ABSTRACT: A limited number of small studies have suggested that methazolamide and theophylline can independently reduce symptoms of acute mountain sickness (AMS) and, if taken together, can improve aerobic exercise performance in normobaric hypoxia. We performed a randomized, double-blind, placebo-controlled, cross-over study to determine if the combination of oral methazolamide and theophylline could provide prophylaxis against AMS and improve aerobic performance in hypobaric hypoxia (∼4875 m). Volunteers with histories of AMS were screened at low altitude (1650 m) and started combined methazolamide (100 mg BID) and theophylline (300 mg BID) treatment, or placebo, 72 h prior to decompression. Baseline AMS (Lake Louise Questionnaire), blood (haemoglobin, haematocrit), cognitive function, ventilatory and pulse oximetry ( SpO2 ) measures were assessed at low altitude and repeated between 4 and 10 h of exposure to hypobaric hypoxia (PB  = 425 mmHg). Aerobic exercise performance was assessed during a 12.5 km cycling time trial (TT) after 4 h of hypobaric hypoxia. Subjects repeated all experimental procedures after a 3-week washout period. Differences between drug and placebo trials were evaluated using repeated measures ANOVA (α = 0.05). The drugs improved resting SpO2 by ∼4% (P < 0.01), but did not affect the incidence or severity of AMS or cognitive function scores relative to placebo. Subjects' performance on the 12.5 km TT was ∼3% worse when taking the drugs (P < 0.01). The combination of methazolamide and theophylline in the prescribed dosages is not recommended for use at high altitude as it appears to have no measurable effect on AMS and can impair aerobic performance.

Effects of Caffeine on Splanchnic Oxygenation in Preterm Infants.

OBJECTIVE: The aim of this study is to assess the effects of administering 20 mg/kg loading dose of caffeine citrate intravenously on splanchnic oxygenation in preterm infants. STUDY DESIGN: The infants with a gestational age (GA) of <34 weeks who were administered with a 20 mg/kg intravenous loading dose of caffeine citrate within 48 hours after birth were investigated prospectively. Regional splanchnic oxygen saturation (rsSO2) and splanchnic fractional tissue oxygen extraction rate (sFTOE) were measured using near-infrared spectroscopy before caffeine infusion, immediately after caffeine infusion and 1, 2, 3, 4, and 6 hours (h) after dose completion; postdose values were compared with predose values. RESULTS: A total of 41 infants with a mean GA of 29.2 ± 1.6 weeks and birth weight of 1,315 ± 257 g as well as postnatal age of 32.2 ± 10.8 hours were included in the study. rsSO2 significantly reduced from 63.1 to 57.5% immediately after caffeine infusion, 55.1% after 1 hour, and 55.2% after 2 hours with partial recovery at 3-hour postdose. sFTOE increased correspondingly. CONCLUSION: Caffeine reduces splanchnic oxygenation and increases splanchnic oxygen extraction for at least 2 hours with partial recovery to predose levels at 3-hour postdose.

Protective Effects of Meldonium in Experimental Models of Cardiovascular Complications with a Potential Application in COVID-19.

Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.