Atsuhiro Sakamoto

Predicting Difficult Intubation in Apparently Normal Patients A Meta-analysis of Bedside Screening Test Performance

The objective of this study was to systematically determine the diagnostic accuracy of bedside tests for predicting difficult intubation in patients with no airway pathology. Thirty-five studies (50,760 patients) were selected from electronic databases. The overall incidence of difficult intubation was 5.8% (95% confidence interval, 4.5–7.5%). Screening tests included the Mallampati oropharyngeal classification, thyromental distance, sternomental distance, mouth opening, and Wilson risk score. Each test yielded poor to moderate sensitivity (20–62%) and moderate to fair specificity (82–97%). The most useful bedside test for prediction was found to be a combination of the Mallampati classification and thyromental distance (positive likelihood ratio, 9.9; 95% confidence interval, 3.1–31.9). Currently available screening tests for difficult intubation have only poor to moderate discriminative power when used alone. Combinations of tests add some incremental diagnostic value in comparison to the value of each test alone. The clinical value of bedside screening tests for predicting difficult intubation remains limited.

Relationship between free radical production and lipid peroxidation during ischemia-reperfusion injury in the rat brain

Forebrain ischemia was produced in the rat by bilateral occlusion of the common carotid arteries combined with hemorrhagic hypotension (30 mmHg). The whole cerebral cortex was homogenized in the presence of the spin trap agent N-tert-butyl-alpha-phenyl-nitrone, followed by a Folch extract. Spin-adducts were detected using electron spin resonance spectroscopy. The lipid peroxidation was estimated from both the amount of thiobarbituric acid reactive substance and the formation of conjugated diene. After 10 or 20 min of ischemia, reperfusion was initiated which induced an abrupt burst of free radical formation. The formation peaked at 5 min, and the peak value increased with the ischemia time. The degree of lipid peroxidation, which was measured after 20 min of reperfusion, also increased with the ischemia time. The results suggest that the lipid peroxidation may be the direct consequence of the action of free radicals formed during ischemia and reperfusion periods.

Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy.

Background:Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain. Methods:Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg · kg−1 · h−1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery. Results:The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 ± 11 vs. 25 ± 20 and 9 ± 11 vs. 18 ± 13; pain on coughing, 26 ± 16 vs. 50 ± 17 and 30 ± 18 vs. 43 ± 18, mean ± SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0–4] vs. 2 [0–5] and 0 [0–5] vs. 1.5 [0–6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03). Conclusions:Very-low-dose ketamine (0.05 mg · kg−1 · h−1) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain.

The efficacy of dexmedetomidine in patients with noninvasive ventilation: a preliminary study.

BACKGROUND: Agitation is associated with failure of noninvasive ventilation (NIV). We investigated the effect of dexmedetomidine in patients with NIV. METHODS: This was a prospective clinical investigation in an intensive care unit. Dexmedetomidine was infused in 10 patients in whom NIV was difficult because of agitation. RESULTS: Ramsay and Richmond Agitation-Sedation Scale scores were maintained at 2.94 ± 0.94 and −1.23 ± 1.30, respectively. All patients were successfully weaned from NIV, and the respiratory state was not worsened. CONCLUSION: This study shows that dexmedetomidine is an effective sedative drug for patients with NIV.

The prolonged analgesic effect of epidural ropivacaine in a rat model of neuropathic pain.

BACKGROUND:In clinical practice, the analgesic effects of epidurally administered local anesthetics on chronic pain sometimes outlast the duration of drug action expected from their pharmacokinetics. To investigate the underlying mechanisms of this prolonged effect, we examined the effects of ropivacaine, a local anesthetic, on pain-related behavior in a rat model of neuropathic pain. We also analyzed changes in the expression of nerve growth factor (NGF), which is involved in plasticity of the nociceptive circuit after nerve injury. METHODS:In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from Day 3 after surgery. Ropivacaine or saline was administered through an epidural catheter once a day, every day, and from Days 7–13 after the CCI operation. NGF content was measured in the L4 dorsal root ganglion, the hindpaw skin, the L4/5 dorsal spinal cord, and the sciatic nerve, using enzyme immunoassay. RESULTS:The latency to withdrawal from thermal stimuli on the ipsilateral paw pads of CCI rats was significantly increased 4 days after the beginning of ropivacaine treatment, and thermal hyperalgesia was almost fully relieved. Similarly, mechanical allodynia was partially reduced after ropivacaine treatment. NGF content was increased in the L4 dorsal root ganglion on the ipsilateral, but not the contralateral, side, in CCI rats treated with ropivacaine. CONCLUSION:Repetitive administration of ropivacaine into the epidural space in CCI rats exerts an analgesic effect, possibly by inducing a plastic change in the nociceptive circuit.

A prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) reduces hyperalgesia, allodynia, and c-fos gene expression in rats with chronic nerve constriction.

Chronic constriction injury (CCI) of the sciatic nerve in rats induces persistent mechanical hyperalgesia and allodynia. CCI is widely known as a model of neuropathic pain, and many studies using this model have been reported. Recently, c-fos has been used as a neural marker of pain, and various studies have assessed the relationship between hyperalgesia and c-fos expression in the lumbar spinal cord. In this study, we examined the role of a prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) in a rat CCI model. EP1 receptor antagonist (EP1-ra) oral administration from day 8 to day 14 significantly reduced hyperalgesia and allodynia in the three pain tests on day 15. EP1-ra treatment from day 8 to 14 also reduced c-fos-positive cells in laminae I-II, III-IV, and V-X compared with saline treatment. A single dose of EP1-ra treatment on day 8 significantly reduced hyperalgesia and allodynia at 1 h and 2 h after administration, but the efficacy was not observed at 24 h. We conclude that EP1-ra treatment may be useful for hyperalgesia and allodynia and that EP1 receptor mechanisms are involved in the maintenance of c-fos gene expression induced by nerve injury.

Roles of Matrix Metalloproteinases in Flow-Induced Outward Vascular Remodeling:

Sustained hemodynamic stresses, especially high blood flow, result in flow-induced outward vascular remodeling. Our previous study showed that macrophage depletion reduced flow-induced outward remodeling of the rat common carotid artery, indicating that macrophages are critical in flow-induced outward vascular remodeling. Macrophage is known to release proteinases, including matrix metalloproteinases (MMPs). Degradation and loosening of extracellular matrix by MMPs may facilitate vascular remodeling. Therefore, we assessed the functions of MMPs in flow-induced outward vascular remodeling by using the flow-augmented common carotid artery model in mice. We validated that ligation of the left common carotid artery increased blood flow and luminal diameter of the right common carotid artery without significant change in blood pressure of mice. To assess the functions of MMPs in flow-induced outward vascular remodeling, we used doxycycline (broad-spectrum MMP inhibitor), SB-3CT (selective MMP inhibitor), MMP-9 knockout mice, and MMP-12 knockout mice. Although there was only a trend for doxycycline treatment to reduce flow-induced outward vascular remodeling, SB-3CT treatment significantly reduced flow-induced outward vascular remodeling. In addition, flow-induced outward vascular remodeling was significantly reduced in MMP-9 knockout mice, but not in MMP-12 knockout mice. These data revealed that MMPs, especially MMP-9, are critical in flow-induced outward vascular remodeling.

Efficacy of an ultrashort-acting beta-adrenoceptor blocker (ONO-1101) in attenuating cardiovascular responses to endotracheal intubation

AbstractObjective: To investigate the clinical effectiveness and safety of ONO-1101, a new ultrashort-acting (half-life 3–4 min), cardioselective β-adrenoceptor blocker in attenuating the cardiovascular responses to endotracheal intubation in a dose-finding open study. Methods: Laryngoscopy and tracheal intubation were performed after induction of anaesthesia with thiamylal, followed by administration of succinylcholine, and saline or ONO-1101 0.1, 0.25 or 0.5 mg · kg−1, in 53 patients. Heart rate and blood pressure were continuously recorded beginning prior to administration until 5 min after administration of the drug, and the rate-pressure product was calculated. Results: ONO-1101 was found to significantly blunt the increase in heart rate throughout the study. Administration of ONO-1101 0.25 or 0.5 mg · kg−1 decreased the incidence of tachycardia. However, these doses were not sufficient to suppress the increase in systolic blood pressure, although the maximal value in the ONO-1101 0.5 mg · kg−1 group was reduced. Rate-pressure product increased significantly after intubation in all groups, but the increase was suppressed in the ONO-1101 0.25 and 0.5 mg · kg−1 groups as compared with the saline group. Bradycardia was not observed in any patient, although hypotension might be caused by administration of ONO-1101 0.5 mg · kg−1. Conclusion: ONO-1101, especially at a dose of 0.25␣mg · kg−1, due to its β-adrenoceptor blockade and ultrashort action, was shown to be effective and well tolerated by patients in this study, when used to attenuate the cardiovascular responses to laryngoscopy and endotracheal intubation.

Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction.

Objective:To examine the association between decreased release of proinflammatory cytokines in response to urinary trypsin inhibitor pretreatment and decreased myocardial and lung injury after cardiopulmonary bypass. Design:A prospective, randomized, double-blind study. Setting:University hospital. Subjects:Thirty patients on cardiopulmonary bypass undergoing coronary artery bypass grafting. Interventions:Patients received 5000 units/kg intravenous urinary trypsin inhibitor (n = 15) or 0.9% saline (control, n = 15) immediately before aortic cannulation for cardiopulmonary bypass. Measurement and Main Results:Neutrophil elastase, tumor necrosis factor-&agr;, interleukin-6, and interleukin-8 were measured after intubation (T1), immediately before aortic cannulation (T2), after separation from cardiopulmonary bypass (T3), at the end of surgery (T4), and on postoperative days 1 (T5), 3 (T6), and 5 (T7). Simultaneous hematocrit values were obtained at all sample times. Isoenzyme of creatine kinase with muscle and brain subunits, troponin-T, and myosin light chain I were also measured. Various hemodynamic and pulmonary data were obtained perioperatively. Levels of neutrophil elastase and cytokines were corrected for hemodilution. Interleukin-6 and interleukin-8 levels were lower at T3 and T4 in the urinary trypsin inhibitor group than in the control group. Stroke volume index was significantly decreased in the control group at T3, and statistical difference was found between groups at T3 (p < .01). Respiratory index and intrapulmonary shunt were significantly higher in the control group than in the urinary trypsin inhibitor group at T3. Changes in respiratory index and intrapulmonary shunt correlated with interleukin-8 levels at T3 (r2 = .52, p < 00001; r2 = .37, p < 0001, respectively) and T4 (r2 = .44, p < .001; r2 = .24, p < .05, respectively). Neutrophil elastase levels and cardiac marker responses to coronary artery bypass grafting surgery were similar in both groups. Conclusions:Prepump administration of urinary trypsin inhibitor attenuates the elevation of interleukin-6 and interleukin-8 release immediately after cardiopulmonary bypass.

Protective effect of a new anti-oxidant on the rat brain exposed to ischemia-reperfusion injury: Inhibition of free radical formation and lipid peroxidation

A new oligomeric derivative was synthesized from prostaglandin B2 and ascorbic acid, and its effect on rat brain ischemia-reperfusion injury was studied. Brain ischemia was produced in the rat by the combination of bilateral common carotid artery occlusion and hemorrhagic hypotension (30 mmHg, 20 min). The cerebral cortex was homogenized in the presence of the spin trap agent, N-tert-butyl-alpha-phenyl-nitrone (PBN). Spin-adducts were detected using an electron spin resonance spectrometer (EPR). Lipid peroxidation was estimated from the amounts of both thiobarbituric acid reactive substances (TBAR) and conjugated diene. In control experiments, reperfusion induced a burst of free radical formation which peaked at 5 min reperfusion time (238 +/- 41%). Lipid peroxidation increased significantly after 20 min of reperfusion (TBAR, 161 +/- 50%; conjugated diene, 160 +/- 29%). When the oligomeric derivative was administered (9 mg/kg i.p. 30 min before ischemic insult), it significantly reduced both spin adduct formation (103 +/- 13%) and lipid peroxidation (TBAR, 109 +/- 14%; conjugated diene, 97 +/- 33%).