Shigeki Sakuraba

Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats

Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs) exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10 mM), alpha4beta2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100 mM), alpha4beta2 antagonist dihydro-beta-erythroidine (0.1-100 mM), alpha7 antagonist methyllycaconitine (0.1-100 mM), and a-bungarotoxin (0.01-10 mM) all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20 mM dihydro-beta-erythroidine and 20mM methyllycaconitine on respiratory neurons. Dihydro-beta-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that alpha4beta2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas alpha7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate.

A neuronal mechanism of propofol-induced central respiratory depression in newborn rats.

The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of γ-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro withoxygenatedartificialcerebrospinalfluid.Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.

Upper airway obstruction associated with flexed cervical position after posterior occipitocervical fusion

Upper airway obstruction resulting from overflexion fixation of the cervical spine is a rare but life-threatening complication after cervical spine surgery. There are few reports of dyspnea after a posterior cervical fusion. We present the case of a 63-year-old woman with rheumatoid arthritis who developed an upper airway obstruction immediately after an O–C4 fusion. She was reintubated with a fiberoptic scope. Revision surgery allowing the angle to return to the neutral position was performed to ameliorate the overflexion of the cervical spine fixation and the consequent upper airway obstruction. After revision surgery, the upper airway obstruction disappeared. Our experience suggests that intraoperative use of fluoroscopy and extubation with a tube exchanger are recommended to avoid this complication, especially in patients at high risk of upper airway obstruction.

Application of nasal flexible laryngeal mask airway in anesthesia for oral surgery

The laryngeal mask airway has been used increasingly in clinics but is seldom applied in anesthesia for oral surgery, as the mask occupies the middle of the mouth and tends to obstruct the surgical field. Here, we report the successful placement and usage of a nasal flexible laryngeal mask airway (FLMA) in an oral surgical procedure. Fifteen patients undergoing dental procedures under general anesthesia were studied. We clinically applied a previously reported method for inserting an FLMA with some modifications. There was no significant bleeding from the intubated nostril in any of the patients. None of the patients complained of sore throat, coughing, hoarseness, or any discomfort in the nose. Although we anticipate that further refinements of the technique may be possible and that the safety of this method using a nasal FLMA needs to be assessed in a greater number of patients, in this preliminary study we provide a proof-of-principle demonstration of the efficacy of nasal LMA ventilation as a method of airway management for oral surgery.

Neural Mechanisms of Sevoflurane-induced Respiratory Depression in Newborn Rats

Background:Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of &ggr;-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression. Methods:In the isolated brainstem–spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the &ggr;-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques. Results:Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons. Conclusion:Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. &ggr;-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit.

Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimers disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C02. In the other experiment, apneic threshold PaC02 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit.

Continuous spinal anesthesia and postoperative analgesia for elective cesarean section in a parturient with Eisenmenger's syndrome

We describe the use of continuous spinal anesthesia (CSA) for an elective cesarean section in a 29-year-old parturient with Eisenmenger’s syndrome at 30 weeks of gestation. It is essential in patients with Eisenmenger’s syndrome to prevent significant increases in right-to-left shunt following the reduction in systemic vascular resistance. In this case, the patient hoped to be awake during the operation because of her fear of death. We therefore applied CSA to this patient because single-shot spinal anesthesia and epidural anesthesia might cause sudden cardiovascular depression. In fact, sudden cardiovascular changes were avoided by the titration of local anesthetics and the operation was uneventful, although prompt treatment of hypotension was essential and adjustment of the anesthetic levels was difficult. Postoperative patient-controlled spinal analgesia provided satisfactory pain relief with hemodynamic stability and no significant side effects. However, thorough experience with the requisite techniques is critical in CSA because of the technical difficulty of the procedure, and anesthesiologists must gain such experience in less-demanding cases before attempting to administer it in patients presenting extreme challenges as described in this case report.

Application of gum elastic bougie to nasal intubation.

Gum elastic bougie (GEB), a useful device for difficult airway management, has seldom been used for nasotracheal intubation. Among 632 patients undergoing dental procedures or oral surgery, GEB was used successfully in 16 patients in whom conventional nasal intubation had failed because of anatomical problems or maldirection of the tip of the tracheal tube. We recommend that GEB should be applied from the first attempt for nasal intubation in patients with difficult airways.

Effects of neuromuscular blocking agents on central respiratory control in the isolated brainstem-spinal cord of neonatal rat.

Although neuromuscular blocking agents (NMBAs) function as muscular nicotinic acetylcholine receptor (nAChR) antagonists, several studies have shown that they block neuronal nAChRs as well, which led us to hypothesize that these agents can affect neuronal nAChRs expressed in respiratory centers. To test this hypothesis, we studied the effects of two NMBAs on respiratory activity and respiratory neurons in brainstem-spinal cord preparations from neonatal rats. The application of either D-tubocurarine or vecuronium resulted in dose-dependent reductions in C4 respiratory rate. These reductions were concomitant with reductions in the depolarizing cycle rate of inspiratory (Insp) neurons; the depolarizing cycle rate of preinspiratory (Pre-I) neurons, however, was not affected. We also detected C4 burst activity during the depolarizing phase in Pre-I neurons, even during NMBA-induced respiratory depression. Both NMBAs inhibited drive potential amplitude and intraburst firing frequency in Insp and Pre-I neurons. These agents also induced a hyperpolarization and an increase in membrane resistance in Pre-I neurons, however they had no effect on these membrane properties in Insp neurons. Our findings indicate that these agents suppress central respiratory activity mainly through their inhibitory effects on Pre-I neurons and the Pre-I to Insp neuron synaptic drive, and that nAChRs are involved in central respiratory control.

Pentax-AWS-assisted insertion of a transesophageal echocardiography probe

a brief case description of ETT kinking in which tube removal could have been avoided. A post-neurosurgical patient in the Surgical Intensive Care Unit was noted to have increasing pulmonary inflation pressures, and a suction catheter could be advanced no deeper than 10 cm. The ETT used was a 7.5 Mallinckrodt Intermediate Hi-Lo (Mallinckrodt, St Louis, MO.) The diagnosis, made on visual and tactile examination, was that the tube had kinked at the level of the oropharynx. Manipulation of the ventilator tubing and of the tube fixation at the level of the lips did not improve the degree of kinking. The tube was therefore removed, and the patients trachea was reintubated without complication. On examination, the ETTwas found to be kinked at 18 cm (Fig. 1). There were no visible defects in the ETTs construction. It was evident, however, that the ETT had been inserted with the preformed curvature of the tube deviated to the right; that is, at approximately 90 degrees to the normal sagittal plane. Kinking was caused by the ETT being bent against its natural curvature. Many anesthesiologists rotate the ETT to the right so as to optimize visualization of the glottic opening during intubation. Once the tip of the ETT has passed between the vocal cords, the ETT is rotated back to the sagittal plane so that the preformed curvature follows the natural curvature of the trachea, the hypopharynx, and the mouth. In this case, the anesthesiologist who had intubated the patients trachea had not rotated the ETT back to the normal position. Most ETTs have a radio-opaque line running longitudinally along the convex curvature, which, if the ETT is inserted correctly, should be visible on the convex aspect of the ETT. If the ETT had been examined carefully, it would have been noted that the radio-opaque line was in the left lateral position. Simply rotating the tube 90° after careful suctioning of the hypopharynx and the subglottic region, and deflating the cuff, would have avoided an unnecessary extubation and reintubation.