Shinji Kurata

Mouth-opening Increases Upper-airway Collapsibility without Changing Resistance during Midazolam Sedation

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to −3.6 ± 2.9 cm H2O compared with −8.7 ± 2.8 (p = 0.002) for closed mouths and −7.2 ± 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 ± 6.6 vs. 17.7 ± 7.6 vs. 21.5 ± 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 ± 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

The compensatory responses to upper airway obstruction in normal subjects under propofol anesthesia

Upper airway obstruction during sleep can trigger compensatory neuromuscular responses and/or prolong inspiration in order to maintain adequate minute ventilation. The aim of this study was to investigate the strength of these compensatory responses during upper airway obstruction during propofol anesthesia. We assessed respiratory timing and upper airway responses to decreases in nasal pressure in nine propofol anesthetized normal subjects under condition of decreased (passive) and increased (active) neuromuscular activity. Critical closing pressure (PCRIT) and upstream resistance (RUS) were derived from pressure-flow relationships generated from each condition. The inspiratory duty cycle (IDC), maximum inspiratory flow (V1max) and respiratory rate (f) were determined at two levels of mean inspiratory airflow (VI; mild airflow limitation with VI > or = 150 ml s-1; severe airflow limitation with VI < 150 ml s-1). Compared to the passive condition, PCRIT decreased significantly (5.3 +/- 3.8 cm H2O, p < 0.05) and RUS increased (7.4 cm H2O ml-1 s, p < 0.05) in the active condition. The IDC increased progressively and comparably as decreased in both the passive and active conditions (p < 0.05). These findings imply that distinct compensatory mechanisms govern the modulation of respiratory pattern and pharyngeal patency during periods of airway obstruction under propofol anesthesia.

Effect of Mandibular Position on Upper Airway Collapsibility and Resistance

It has been proposed that advancement of the mandible is a useful method for decreasing upper airway collapsibility. We carried out this study to test the hypothesis that mandibular advancement induces changes in upper airway patency during midazolam sedation. To explore its effect, we examined upper airway pressure-flow relationships in each of 4 conditions of mouth position in normal, healthy subjects (n = 9). In the neutral position, Pcrit (i.e., critical closing pressure, an index of upper airway collapsibility) was −4.2 cm H2O, and upstream resistance (Rua) was 21.2 cm H2O/L/sec. In the centric occlusal position, Pcrit was −7.1 cm H2O, and Rua was 16.6 cm H2O/L/sec. In the incisor position, Pcrit was significantly reduced to −10.7 cm H2O, and Rua was significantly reduced to 14.0 cm H2O/L/sec. Mandibular advancement significantly decreased Pcrit to −13.3 cm H2O, but did not significantly influence Rua (22.1 cm H2O/L/sec). We conclude that the mandibular incisors’ position improved airway patency and decreased resistance during midazolam sedation.

The Effect of Gender on Compensatory Neuromuscular Response to Upper Airway Obstruction in Normal Subjects Under Midazolam General Anesthesia

BACKGROUND: Upper airway patency may be compromised during sleep and anesthesia by either anatomical alterations (mechanical properties) or disturbances in the neural control (compensatory neuromuscular responses). The pathophysiology of upper airway obstruction during anesthesia may differ between men and women. Recently, we reported that the upper airway mechanical properties were comparable with those found during natural nonrapid eye movement sleep, as evaluated by measurements of passive critical closing pressure (PCRIT) and upstream resistance (RUS) during midazolam sedation. In this study, we compared the effects of gender on compensatory neuromuscular responses to upper airway obstruction during midazolam general anesthesia. METHOD: Thirty-two subjects (14 men and 18 women) were studied. We constructed pressure-flow relationships to evaluate PCRIT and RUS during midazolam anesthesia. The midazolam anesthesia was induced with an initial dose of midazolam (0.07–0.08 mg/kg bolus) and maintained by midazolam infusion (0.3–0.4 &mgr;g · kg−1 · min−1), and the level of anesthesia was assessed by Ramsay score (Level 5) and Observer’s Assessment of Alertness/Sedation score (Level 2). Polysomnographic and hemodynamic variables were monitored while nasal pressure (via mask), inspiratory air flow (via pneumotachograph), and genioglossal electromyograph (EMGGG) were recorded. PCRIT was obtained in both the passive condition, under conditions of decreased EMGGG (passive PCRIT), and in an active condition, whereas EMGGG was increased (active PCRIT). The difference between the active PCRIT and passive PCRIT (&Dgr;PCRIT P − A) was calculated in each subject to determine the compensatory neuromuscular response. RESULTS: The difference between the active PCRIT and passive PCRIT (&Dgr;PCRIT A − P) was significantly greater in women than in men (4.6 ± 2.8 cm H2O and 2.2 ± 1.7 cm H2O, respectively; P < 0.01), suggesting greater compensatory neuromuscular response to upper airway obstruction independent of arousal. CONCLUSION: We demonstrate that the arousal-independent compensatory neuromuscular responses to upper airway obstruction during midazolam anesthesia were partially maintained in women, and that gender may be a major determinant of the strength of compensatory responses during anesthesia.

Effect of head elevation on passive upper airway collapsibility in normal subjects during propofol anesthesia.

Background:Head elevation can restore airway patency during anesthesia, although its effect may be offset by concomitant bite opening or accidental neck flexion. The aim of this study is to examine the effect of head elevation on the passive upper airway collapsibility during propofol anesthesia. Method:Twenty male subjects were studied, randomized to one of two experimental groups: fixed-jaw or free-jaw. Propofol infusion was used for induction and to maintain blood at a constant target concentration between 1.5 and 2.0 &mgr;g/ml. Nasal mask pressure (PN) was intermittently reduced to evaluate the upper airway collapsibility (passive PCRIT) and upstream resistance (RUS) at each level of head elevation (0, 3, 6, and 9 cm). The authors measured the Frankfort plane (head flexion) and the mandible plane (jaw opening) angles at each level of head elevation. Analysis of variance was used to determine the effect of head elevation on PCRIT, head flexion, and jaw opening within each group. Results:In both groups the Frankfort plane and mandible plane angles increased with head elevation (P < 0.05), although the mandible plane angle was smaller in the free-jaw group (i.e., increased jaw opening). In the fixed-jaw group, head elevation decreased upper airway collapsibility (PCRIT ∼ −7 cm H2O at greater than 6 cm elevation) compared with the baseline position (PCRIT ∼ −3 cm H2O at 0 cm elevation; P < 0.05). Conclusion:Elevating the head position by 6 cm while ensuring mouth closure (centric occlusion) produces substantial decreases in upper airway collapsibility and maintains upper airway patency during anesthesia.

GABAB receptors do not internalize after baclofen treatment, possibly due to a lack of β-arrestin association: Study with a real-time visualizing assay

The mechanism of agonist‐induced GABAB receptor (GABABR) internalization is not well understood. To investigate this process, we focused on the interaction of GABABR with β‐arrestins, which are key proteins in the internalization of most of the G protein‐coupled receptors, and the agonist‐induced GABABR internalization and the interaction of GABABR with β‐arrestin1 and β‐arrestin2 were investigated in real time using GABABR and β‐arrestins both of which were fluorescent protein‐tagged. We then compared these profiles with those of μ‐opioid receptors (μOR), well‐studied receptors that associate and cointernalize with β‐arrestins. When stimulated by the specific GABABR agonist baclofen, GABABR composed of GABAB1aR (GB1aR) and fluorescent protein‐tagged GABAB2R‐Venus (GB2R‐V) formed functional GABABR; they elicited G protein‐activated inwardly rectifying potassium channels as well as nontagged GABABR. In cells coexpressing GB1aR, GB2R‐V, and β‐arrestin1‐Cerulean (βarr1‐C) or β‐arrestin2‐Cerulean (βarr2‐C), real‐time imaging studies showed that baclofen treatment neither internalized GB2R‐V nor mobilized βarr1‐C or βarr2‐C to the cell surface. This happened regardless of the presence of G protein‐coupled receptor kinase 4 (GRK4), which forms a complex with GABABR and causes GABABR desensitization. On the other hand, in cells coexpressing μOR‐Venus, GRK2, and βarr1‐C or βarr2‐C, the μOR molecule formed μOR/βarr1 or μOR/βarr2 complexes on the cell surface, which were then internalized into the cytoplasm in a time‐dependent manner. Fluorescence resonance energy transfer assay also indicated scarce association of GB2R‐V and β‐arrestins‐C with or without the stimulation of baclofen, while robust association of μOR‐V with β‐arrestins‐C was detected after μOR activation. These findings suggest that GABABRs failure to undergo agonist‐induced internalization results in part from its failure to interact with β‐arrestins. Synapse 66:759–769, 2012.© 2012 Wiley Periodicals, Inc.

Protective Effect of Nitric Oxide on Liver Circulation from Ischemia Reperfusion Injury.

ABSTRACT Introduction: The reduction of endogenous nitric oxide (NO) production during hepatic ischemia-reperfusion injury, generally via a reduction in endothelial NO synthase activity, leads to liver injury. We hypothesized that administration of an exogenous NO donor into the portal vein may ameliorate hepatic blood flow reduction after a period of ischemia. Material and Methods: A total of 90 min of ischemia (portal vein and hepatic artery) was applied in 15 anesthetized pigs, using the Pringle method under sevoflurane anesthesia. All animals were administered either saline (control group, n = 8) or sodium nitroprusside (SNP, n = 7) as exogenous NO donor drugs into the portal vein, 30 min before and after ischemia. The portal venous blood flow and hepatic artery blood flow were measured continuously using transonic flow probes attached to each vessel. Endogenous NO (NOx = NO2− + NO3−) production was measured every 10 min using a microdialysis probe placed in the left lobe of the liver. Results: In the SNP group, portal venous flow remained unchanged and hepatic artery flow significantly increased compared to baseline. Although the production of liver tissue NOx transiently decreased to 60% after ischemia, its level in the SNP group remained higher than the control saline group. Conclusion: Regional administration of SNP into the portal vein increases hepatic arterial flow during ischemia reperfusion periods without altering mean systemic arterial pressure. We speculate that administration of an exogenous NO donor may be effective in preventing liver injury via preservation of total hepatic blood flow.

Anaphylactoid-like Reaction to Midazolam During Oral and Maxillofacial Surgery

We experienced a case of life-threatening hypotension and bronchoconstriction associated with edema in a patient undergoing resection of a tumor of the right mandible following intravenous midazolam for induction of general anesthesia. We decided to postpone surgery for further examination of a possible drug-induced allergic reaction, and we rescheduled surgery for 1 week later. After administering H1 and H2 histamine antagonists, we administered a slow induction with sevoflurane in nitrous oxide and oxygen plus intravenous atropine sulfate after performing a test dose injection. We safely induced and maintained anesthesia with nitrous oxide, oxygen, and sevoflurane.

Perioperative Management of Tooth Extractions for a Patient With Hereditary Angioedema

Hereditary angioedema (HAE) is a rare genetic disorder that causes a deficiency in or dysfunction of C1 esterase inhibitor (C1-INH) and is clinically characterized by sudden and recurrent attacks of angioedema. Although almost any part of the body can be affected, HAE is of greatest concern and can be life-threatening when the upper airway is involved, particularly the larynx (laryngeal attack). HAE attacks can be triggered by physical or psychological stress or can arise spontaneously without any apparent trigger. Dental treatments and routine oral surgical procedures, such as tooth extraction, abound with factors that can trigger an attack of HAE. Indeed, several cases of death resulting from HAE attacks have been reported after such procedures. Therefore, patients with HAE are of special concern in dentistry and require precautionary preparations before treatment. This report describes the successful management of tooth extractions in a patient with HAE who was at high risk of an HAE-induced laryngeal attack.

The effects of hormonal status on upper airway patency in normal female subjects during propofol anesthesia

STUDY OBJECTIVE To determine the mechanical upper airway properties and compensatory neuromuscular responses to obstruction during propofol anesthesia in the follicular and luteal phases of the menstrual cycle. DESIGN Prospective, randomized study. SETTING University-affiliated hospital. SUBJECTS 12 premenopausal female volunteers for studies of upper airway collapse throughout their menstrual cycle during the follicular phase (6 -10 days) and mid-late luteal phase (20 - 24 days). MEASUREMENTS The level of propofol anesthesia (1.5 - 2.0 μg/mL) required to suppress arousal responses was determined by Observers Assessment of Alertness/Sedation scoring (level 2) and confirmed by bispectral index monitoring. Pressure-flow relationships were constructed to evaluate collapsibility (P(CRIT)) and up-stream resistance (R(US)) during acute [Passive; hypotonic electromyography (EMG)] and sustained (Active; elevated EMG) changes in nasal mask pressure. The difference between passive P(CRIT) and active P(CRIT) (ΔP(CRIT A-P)) represented the magnitude of the compensatory response to obstruction. MAIN RESULTS Passive P(CRIT) was significantly higher in the mid-late luteal phase (-4.7 cm H(2)O) than in the follicular phase (-6.2 cmH(2)O; P < 0.05). Active P(CRIT) significantly decreased compared with passive P(CRIT) in the follicular phase (-10.1 cm H(2)O) and in the mid-late luteal phase (-7.7 cm H(2)O) and (P < 0.05). No significant difference was noted in ΔP(CRIT) between the follicular (3.9 ± 2.9 cm H(2)O) and mid-late luteal phases (3.0 ± 2.6 cm H(2)O). No differences were seen in R(US) between the menstrual phases for either the passive (P = 0.8) or active (P = 0.75) states. CONCLUSIONS Menstrual phase has an effect on anatomical alterations (mechanical properties) in the hypotonic upper airway during propofol anesthesia.