Intravenous ephedrine abolished suspected bronchoconstriction during general anesthesia in a patient undergoing beta-adrenergic blocker therapy for hypertension

We report a case of intravenous ephedrine administration that abolished suspected bronchoconstriction during general anesthesia in a patient undergoing beta-adrenergic blocker therapy for hypertension and who was subsequently diagnosed postoperatively as having bronchial asthma. A 54-year-old man who had childhood asthma was scheduled for laparoscopic cholecystectomy at our institution. The preanesthetic interview suggested full resolution of his childhood asthma. His capnogram showed an airway obstructive pattern immediately after the initiation of mechanical ventilation. However, after administration of ephedrine due to low blood pressure during surgery, his obstructive capnogram reverted to normal. On postoperative day 3, he was diagnosed as having bronchial asthma. Furthermore, we found that small airway obstruction as indicated in his preoperative pulmonary function test (PFT) had been overlooked. Two important points arise from this case. First, the use of beta-blockers for the treatment of hypertension in patients potentially having obstructive lung disease should be avoided. Second, clinicians should carefully check the preoperative PFT results in detail to ensure that nothing has been overlooked

Effects of lubrication on air-sealing performance of a pediatric cuffed tracheal tube

Abstract Background Lubrication of cuffed tracheal tubes (CTTs) reduces liquid leakage. However, it is not clear how cuff lubrication influences air leakage. We aimed to test the hypothesis that pretreatment with K-Y jelly, a water-soluble lubricant, would improve the air-sealing performance of pediatric CTTs in a model study. Methods We placed Parker Flex-Tip™ CTT with 4.0- and 5.0-mm internal diameter (ID) into a tracheal model with 9- and 12-mm ID. The tracheal model was connected to a test lung ventilated in pressure control mode. We compared three cuff lubrication conditions: none (N), water (W), and K-Y jelly (KY). We measured the leak airway pressure (LAWP), defined as the lowest peak airway pressure (PAWP) at which leakage was detected, with the fixed cuff pressure (CP) at 20 cmH2O and varied PAWP. We also measured the leak CP (LCP), defined as the highest CP at which leakage was detected, with fixed PAWP at 25 cmH2O and varied CP. We confirmed air leakage when an apparent elevation of oxygen concentration was detected above the cuff after changing the inspiratory gas from air to oxygen. Results For both 4.0-mm ID and 5.0-mm ID endotracheal tubes, the KY group showed significantly higher LAWP and lower LCP than the other two groups. For the 4.0-mm ID, median values and ranges of LAWP and LCP were K-Y group: 25 (25) and 15 (15); N group: 5 (5) and 35 (35): and W group: 5 (5) and 35 (15–35) cmH2O. For the 5.0-mm ID, median values and ranges of LAWP and LCP were K-Y group: 25 (15–25) and 15 (15–35); N group: 5 (5) and 35 (35); and W group: 5 (5) and 35 (15–35) cmH2O. Water application did not change these outcomes compared with the N group. Conclusion Pre-treatment of the cuff with K-Y jelly significantly improved the air-sealing performance of a pediatric CTT in our model study

Lung-protective properties of expiratory flow-initiated pressure-controlled inverse ratio ventilation: A randomised controlled trial.

BackgroundExpiratory flow-initiated pressure-controlled inverse ratio ventilation (EF-initiated PC-IRV) reduces physiological dead space. We hypothesised that EF-initiated PC-IRV would be lung protective compared with volume-controlled ventilation (VCV).MethodsTwenty-eight men undergoing robot-assisted laparoscopic radical prostatectomy were enrolled in this randomised controlled trial. The EF-initiated PC-IRV group (n = 14) used pressure-controlled ventilation with the volume guaranteed mode. The inspiratory to expiratory (I:E) ratio was individually adjusted by observing the expiratory flow-time wave. The VCV group (n = 14) used the volume control mode with a 1:2 I:E ratio. The Mann-Whitney U test was used to compare differences in the serum cytokine levels.ResultsThere were no significant differences in serum IL-6 between the EF-initiated PC-IRV (median 34 pg ml-1 (IQR 20.5 to 63.5)) and VCV (31 pg ml-1 (24.5 to 59)) groups (P = 0.84). The physiological dead space rate (physiological dead space/expired tidal volume) was significantly reduced in the EF-initiated PC-IRV group as compared with that in the VCV group (0.31 ± 0.06 vs 0.4 ± 0.07; PConclusionsThere were no differences in the lung-protective properties between the two ventilatory strategies. However, EF-initiated PC-IRV reduced physiological dead space rate; thus, it may be useful for reducing the ventilatory volume that is necessary to maintain normocapnia in patients with low forced vital capacity (% predicted) during robot-assisted laparoscopic radical prostatectomy

CLP290 promotes the sedative effects of midazolam in neonatal rats in a KCC2-dependent manner: A laboratory study in rats.

Immature neurons dominantly express the Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) rather than the K+-Cl- cotransporter isoform 2 (KCC2). The intracellular chloride ion concentration ([Cl-]i) is higher in immature neurons than in mature neurons; therefore, γ-aminobutyric acid type A (GABAA) receptor activation in immature neurons does not cause chloride ion influx and subsequent hyperpolarization. In our previous work, we found that midazolam, benzodiazepine receptor agonist, causes less sedation in neonatal rats compared to adult rats and that NKCC1 blockade by bumetanide enhances the midazolam-induced sedation in neonatal, but not in adult, rats. These results suggest that GABA receptor activation requires the predominance of KCC2 over NKCC1 to exert sedative effects. In this study, we focused on CLP290, a novel KCC2-selective activator, and found that midazolam administration at 20 mg/kg after oral CLP290 intake significantly prolonged the righting reflex latency even in neonatal rats at postnatal day 7. By contrast, CLP290 alone did not exert sedative effects. Immunohistochemistry showed that midazolam combined with CLP290 decreased the number of phosphorylated cAMP response element-binding protein-positive cells in the cerebral cortex, suggesting that CLP290 reverted the inhibitory effect of midazolam. Moreover, the sedative effect of combined CLP290 and midazolam treatment was inhibited by the administration of the KCC2-selective inhibitor VU0463271, suggesting indirectly that the sedation-promoting effect of CLP290 was mediated by KCC2 activation. To our knowledge, this study is the first report showing the sedation-promoting effect of CLP290 in neonates and providing behavioral and histological evidence that CLP290 reverted the sedative effect of GABAergic drugs through the activation of KCC2. Our data suggest that the clinical application of CLP290 may provide a breakthrough in terms of midazolam-resistant sedation

K-Y™ jelly inhibits increase in endotracheal tube cuff pressure during nitrous oxide exposure in vitro

Abstract Background The increase in endotracheal tube cuff pressure due to nitrous oxide diffusion is a well-known risk during general anesthesia using nitrous oxide. We hypothesized that lubricating endotracheal tube cuffs with K-Y™ Jelly might inhibit the increase in cuff pressure that occurs during exposure to nitrous oxide. Methods We used two types of endotracheal tube cuffs: one made from ultrathin polyurethane (PU) and another made from conventional polyvinyl chloride (PVC). Using a pediatric trachea model, which consisted of an acrylic cylinder with an internal diameter of 12 mm, we measured changes in the cuff pressure during nitrous oxide exposure in size 5.0-mm internal diameter endotracheal tubes with each type of cuff, with and without lubrication with K-Y™ Jelly. Results During nitrous oxide exposure, the increase in cuff pressure was significantly lower in the lubricated cuffs than in the non-lubricated cuffs in both types of cuffs (PVC, P < 0.0001; PU, P < 0.0001). However, the cuff compliance in the trachea model was unaffected by lubrication in both types of cuffs. Conclusions Lubrication of endotracheal tube cuffs with K-Y™ Jelly may effectively delay the increase in cuff pressure that occurs during general anesthesia using nitrous oxide

Bumetanide, an Inhibitor of NKCC1 (Na-K-2Cl Cotransporter Isoform 1), Enhances Propofol-Induced Loss of Righting Reflex but Not Its Immobilizing Actions in Neonatal Rats

<div><p>Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to increased expression of Na+-K+-2Cl- co-transporter isoform 1 (NKCC1), and the transition of GABAergic signaling from excitatory to inhibitory occurs before birth in the rat spinal cord and spreads rostrally according to the developmental changes in cation-chloride co-transporter expression. We previously showed that midazolam activates the hippocampal CA3 area and induces less sedation in neonatal rats compared with adolescent rats in an NKCC1-dependent manner. In the present study, we tested the hypothesis that propofol-induced loss of righting reflex (LORR) but not immobilizing actions are modulated by NKCC1-dependent mechanisms and reduced in neonatal rats compared with adolescent rats. We estimated neuronal activity in the cortex, hippocampus and thalamus after propofol administration with or without bumetanide, an NKCC1 inhibitor, by immunostaining of phosphorylated cyclic adenosine monophosphate-response element binding protein (pCREB). We studied effects of bumetanide on propofol-induced LORR and immobilizing actions in postnatal day 7 and 28 (P7 and P28) rats. The pCREB expression in the cortex (P = 0.001) and hippocampus (P = 0.01) was significantly greater in the rats receiving propofol only than in the rats receiving propofol plus bumetanide at P 7. Propofol-induced LORR or immobilizing effects did not differ significantly between P7 and P28. Bumetanide significantly enhanced propofol-induced LORR (P = 0.031) but not immobilization in P7 rats. These results are partially consistent with our hypothesis. They suggest that propofol may activate the rostral but not caudal central nervous system dependently on NKCC1, and these differential actions may underlie the different properties of sedative and immobilizing actions observed in neonatal rats.</p></div

Changes in the expression of phosphorylated cyclic adenosine monophosphate-response element-binding protein (pCREB) after intraperitoneal administration of propofol in postnatal day 28 rats.

<p>A, B and C (upper panels: ×4 magnification; lower panels: ×8 magnification) are photomicrographs of pCREB immunostaining in the cortex (retrosplenial granular cortex and retrosplenial granular b cortex) of rats. D, E and F (upper panels: ×4 magnification; lower panels: ×8 magnification) are those of pCREB immunostaining in the hippocampal CA3 area. G, H and I (upper panels: ×4 magnification; lower panels: ×8 magnification) are those of pCREB immunostaining in the thalamus. Graphs in J, K and L show the number of pCREB-positive cells in the cortex, hippocampus and thalamus, respectively. Data are given as mean and SD. **P<0.01 and ***P = 0.001, respectively. Data are derived from 4 slices in each group.</p