A novel technique for assessment of post-extubation airway obstruction can successfully replace the conventional cuff leak test: a pilot study.

BACKGROUND: Post-extubation airway obstruction is an important complication of tracheal intubation. The cuff leak test is traditionally used to estimate the risk of this complication. However, the cuff leak test parameters are not constant and may depend on the respiratory system and ventilator settings. Furthermore, deflating the cuff also be a risk factor for patient-ventilator asynchrony and ventilator-associated pneumonia. Instead of using the cuff leak test, we measured the pressure of the leak to the upper airway through the gap between the tube and glottis with a constant low flow from the lumen above the cuff without deflating the cuff and called it "pressure above the cuff." The purpose of this study was to investigate whether pressure above the cuff can be used as an alternative to the cuff leak volume. METHODS: This prospective observational study was conducted at Kumamoto University Hospital after obtaining approval from the institutional review board. The pressure above the cuff was measured using an endotracheal tube with an evacuation lumen above the cuff and an automated cuff pressure modulation device. We pumped 0.16 L per minute of air and measured the steady-state pressure using an automated cuff pressure modulation device. Then, the cuff leak test was performed, and the cuff leak volume was recorded. The cuff leak volume was defined as the difference between the expiratory tidal volume with the cuff inflated and deflated. The relationship between the pressure above the cuff and cuff leak volume was evaluated. The patient-ventilator asynchrony during each measurement was also examined. RESULTS: The pressure above the cuff was measured, and the cuff leak volume was assessed 27 times. The pressure above the cuff was significantly correlated with the cuff leak volume (r = -0.76, p < 0.001). Patient-ventilator asynchrony was detected in 37% of measurements during the cuff leak test, but not during the pressure above the cuff test. CONCLUSIONS: This study suggests that pressure above the cuff measurement may be a less complicated alternative to the conventional cuff leak test for evaluation of the risk of post-extubation airway obstruction. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000039987; March 30, 2020). https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044604.

Donepezil improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus.

Insulin-like growth factor-I (IGF-I) exerts beneficial effects on cognitive function. The selective acetylcholinesterase inhibitor donepezil increases serum IGF-I levels in elderly subjects. Because stimulation of sensory neurons induces IGF-I production by releasing calcitonin gene-related peptide (CGRP) in the mouse brain, we hypothesized that donepezil increases IGF-I production by sensory neuron stimulation to improve the cognitive function in mice. Donepezil, but not tacrine, increased the CGRP release from dorsal root ganglion neurons isolated from wild-type (WT) mice. Pretreatment with the protein kinase A inhibitor KT5720 [(9S,10S,12R)-2,3,9,10,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg: 3',2',1'-kl]pyrrolo[3,4-i][1,6]-benzo-diazocine-10-carboxylic acid hexyl ester] reversed the effects induced by donepezil. Increase in tissue levels of CGRP, IGF-I, and IGF-I mRNA in the hippocampus was observed at 4 weeks after oral administration of donepezil in WT mice. In these animals, c-fos expression in spinal dorsal horns, parabrachial nuclei, the solitary tract nucleus, and the hippocampus was increased. Enhancement in angiogenesis and neurogenesis was observed in the dentate gyrus of the hippocampus of WT mice after donepezil administration. Improvement of spatial learning was observed in WT mice after donepezil administration. Oral administration of tacrine for 4 weeks produced none of the aforementioned effects induced by donepezil in WT mice. However, none of the effects observed in WT mice was seen after donepezil administration in CGRP-knockout mice and WT mice subjected to functional denervation. These observations suggest that donepezil may improve cognitive function in mice by increasing the hippocampal production of IGF-I through sensory neuron stimulation. These effects of donepezil may not be dependent on its acetylcholinesterase inhibitory activity.

Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans.

Sensory neurons release calcitonin gene-related peptide (CGRP) on activation. We recently reported that topical application of capsaicin increases facial skin elasticity and promotes hair growth by increasing dermal insulin-like growth factor-I (IGF-I) production through activation of sensory neurons in mice and humans. Raspberry ketone (RK), a major aromatic compound contained in red raspberries (Rubus idaeus), has a structure similar to that of capsaicin. Thus, it is possible that RK activates sensory neurons, thereby increasing skin elasticity and promoting hair growth by increasing dermal IGF-I production. In the present study, we examined this possibility in mice and humans. RK, at concentrations higher than 1 microM, significantly increased CGRP release from dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this increase was completely reversed by capsazepine, an inhibitor of vanilloid receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I levels at 30 min after application in WT mice, but not in CGRP-knockout mice. Topical application of 0.01% RK increased immunohistochemical expression of IGF-I at dermal papillae in hair follicles and promoted hair re-growth in WT mice at 4 weeks after the application. When applied topically to the scalp and facial skin, 0.01% RK promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months after application and increased cheek skin elasticity at 2 weeks after application in 5 females (p<0.04). These observations strongly suggest that RK might increase dermal IGF-I production through sensory neuron activation, thereby promoting hair growth and increasing skin elasticity.

Spinal cord infarction following epidural and general anesthesia: a case report.

BACKGROUND: Epidural anesthesia is widely used for postoperative analgesia and rarely causes permanent neurological complications. We report a case of paraplegia following abdominal surgery under combined epidural/general anesthesia. CASE PRESENTATION: A 75-year-old woman underwent a scheduled abdominal total hysterectomy and bilateral salpingo-oophorectomy for suspected endometrial cancer. In the operating room, an epidural catheter was inserted at T11/12 while the patient was conscious. The needle entered smoothly, with no observed bleeding, paresthesia, or pain, and general anesthesia was induced. During surgery, 4 mL of 0.25% levobupivacaine and 0.1 mg of fentanyl were administered via the epidural catheter, and a solution of 2.5 µg/mL fentanyl and 0.2% levobupivacaine was continuously infused at 4 mL/h for postoperative analgesia. The patient promptly regained consciousness and could move her bilateral lower extremities without difficulty upon leaving the operating room. During the first postoperative night, she complained of an absence of sensation and weakness in the lower extremities. By the morning of the second postoperative day, she had developed paralysis and sensory losses associated with touch, temperature, pinprick, and vibration below T5. The epidural infusion was stopped. Magnetic resonance imaging (MRI) revealed a hyperintense area of the thoracic cord from T8 to T11, and spinal cord infarction was suspected. Ossification of the yellow spinal ligaments between T11 and T12, resulting in thoracic canal stenosis and thoracic spinal cord compression, were observed. Notably, the epidural catheter was inserted at the same site where the thoracic canal stenosis was present. CONCLUSIONS: Permanent neurological complications of epidural anesthesia are rare. Studies of neurological complications after epidural/spinal anesthesia have noted the possibility of spinal anomalies, such as lumbar stenosis, in relation to neurological complications after epidural/spinal anesthesia. In this case, the onset of spinal cord infarction may have occurred coincidentally with catheter insertion into the site of existing spinal stenosis. Therefore, it is important to evaluate lower extremity symptoms and consider spinal disease before administering epidural anesthesia. Spinal cord infarction may be prevented by preoperatively identifying spinal lesions using computed tomography or MRI in cases of suspected spinal disease.

Stimulation of sensory neurons improves cognitive function by promoting the hippocampal production of insulin-like growth factor-I in mice.

Calcitonin gene-related peptide (CGRP) increases the production of insulin-like growth factor-I (IGF-I) in the mouse brain. IGF-I exerts beneficial effects on the cognitive function by increasing synaptic transmission and by inducing angiogenesis and neurogenesis in the hippocampus. In the current study, we examined whether stimulation of sensory neurons by capsaicin improved the cognitive function by increasing the production of IGF-I in the hippocampus using wild-type (WT) and CGRP-knockout (CGRP-/-) mice. Significant increases of the hippocampal tissue levels of CGRP, IGF-I, and IGF-I messenger RNA (mRNA) were observed after capsaicin administration in WT mice (P < 0.01) but not in CGRP-/- mice. Increase in the expression of c-fos was also observed in the spinal dorsal horn, the parabrachial nuclei, and the hippocampus after capsaicin administration in WT mice but not in CGRP-/- mice. Significant enhancement of angiogenesis and neurogenesis was observed in the dentate gyrus of the hippocampus after capsaicin administration in WT mice (P < 0.01) but not in CGRP-/- mice. Although capsaicin administration improved spatial learning in WT mice, no such effect was observed in CGRP-/- mice. Capsaicin-induced improvement of the spatial learning was reversed by administration of an anti-IGF-I antibody and by that of a CGRP receptor antagonist CGRP (8-37) in WT mice. The administration of IGF-I improved the spatial learning in both WT and CGRP-/- mice. These observations strongly suggest that the stimulation of sensory neurons by capsaicin might increase IGF-I production via increasing the hippocampal tissue CGRP levels, and it may thereby promote angiogenesis and neurogenesis to produce improvement of the cognitive function in mice.