Seong-Heon Lee

Neuroprotective effects of remifentanil against transient focal cerebral ischemia in rats.

Background: Opioid agonists have been implicated in neuroprotection from hypoxic injury through regulating mitogen-activated protein kinases and cytokines. We determined the effects of remifentanil in focal brain ischemia and reperfusion (I/R) injury. Mechanisms linked to mitogen-activated protein kinases, including extracellular signaling-regulated kinase (ERK) 1/2, p38 kinases, and c-Jun N-terminal kinase (JNK), and various cytokines were also examined. Methods: Male Sprague-Dawley rats were subjected to an I/R insult consisting of 90 minutes’ middle cerebral artery occlusion (MCAO) followed by reperfusion under general anesthesia. Neurological deficit scores and infarct volume were determined after 24 hours of reperfusion. Remifentanil (5 &mgr;g/kg/min) was given alone or combined with naltrindole (&dgr;-opioid receptor antagonist; 1 mg/kg), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (&mgr;-opioid receptor antagonist; 1 mg/kg), or 5′-guanidinonaltrindole (&kgr;-opioid receptor antagonist; 1 mg/kg). Opioid antagonists were administered 20 minutes before MCAO. Remifentanil infusion was started 10 minutes before MCAO and continued throughout. The control group was without drugs. The expression levels of ERK1/2, p38, and JNK, and also those of tumor necrosis factor-&agr; (TNF-&agr;) and interleukin-6, were determined after 1, 3, and 24 hours of reperfusion. Results: Remifentanil significantly improved the functional outcome and reduced the infarct volumes (69.0±24.3 mm3 vs. 108.9±24.8 mm3), which were not affected by D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 or 5′-guanidinonaltrindole, but were abolished by naltrindole. The I/R insult enhanced the phosphorylation of ERK 1/2 and the expression of TNF-&agr;, which were significantly reduced by remifentanil. Neither the phosphorylation of p38 and JNK nor the production of interleukin-6 was altered throughout the experiment. Conclusions: Remifentanil may be neuroprotective against focal I/R injury, possibly through the activation of &dgr;-opioid receptors and attenuation of ERK 1/2 activity and TNF-&agr; production, in the rat brain.

Current Status of Intensive Care Units Registered as Critical Care Subspecialty Training Hospitals in Korea

There is a lack of information on critical care in Korea. The aim of this study was to determine the current status of Korean intensive care units (ICUs), focusing on the organization, characteristics of admitted patients, and nurse and physician staffing. Critical care specialists in charge of all 105 critical care specialty training hospitals nationwide completed a questionnaire survey. Among the ICUs, 56.4% were located in or near the capital city. Only 38 ICUs (17.3%) had intensive care specialists with a 5-day work week. The average daytime nurse-to-patient ratio was 1:2.7. Elderly people ≥ 65 yr of age comprised 53% of the adult patients. The most common reasons for admission to adult ICUs were respiratory insufficiency and postoperative management. Nurse and physician staffing was insufficient for the appropriate critical care in many ICUs. Staffing was worse in areas outside the capital city. Much effort, including enhanced reimbursement of critical care costs, must be made to improve the quality of critical care at the national level. Graphical Abstract

Dexmedetomidine for sedation of patients undergoing elective surgery under regional anesthesia

Background Dexmedetomidine may be useful as a sedative agent. However, it has been reported that dexmedetomidine decreases systemic blood pressure, heart rate, and cardiac output in a dose-dependent manner. The purpose of this study was to determine the appropriate dose of intravenously administered dexmedetomidine for sedation. Methods Forty-five American Society of Anesthesiologists physical status I-II patients under spinal anesthesia received dexmedetomidine 1 µg/kg intravenously as a loading dose. The patients were randomly allocated to one of three groups for maintenance dose: Group A (0.25 µg/kg/hr), Group B (0.50 µg/kg/hr), and Group C (0.75 µg/kg/hr). The hemodynamic variables and the Ramsay Sedation Scale (RSS) score were recorded for all patients. The numbers of patients who developed hypotension, bradycardia, or inadequate sedation necessitating further drug treatment were also recorded. Results Systolic blood pressure, heart rate, and SpO2 were decreased, and RSS score was increased significantly at both 20 min and 40 min after injection of dexmedetomidine in the three study groups compared to baseline, without significant differences between the groups. The prevalence of hypotension, but not that of bradycardia or adjunctive midazolam administration, exhibited a positive correlation with the dose of dexmedetomidine. Conclusions Intravenous injection of dexmedetomidine 1 µg/kg followed by continuous administration at infusion rates of 0.25, 0.50, or 0.75 µg/kg/hr produced adequate levels of sedation. However, there was a tendency for the incidence of hypotension to increase as the dose increased. To minimize the risk of hemodynamic instability, a dose of 0.25 µg/kg/hr may be the most appropriate for continuous administration of dexmedetomidine.

AICAR Enhances the Phagocytic Ability of Macrophages towards Apoptotic Cells through P38 Mitogen Activated Protein Kinase Activation Independent of AMP-Activated Protein Kinase

Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by macrophages, known as efferocytosis, which is essential in maintaining tissue homeostasis and resolving inflammation. AICAR increased p38 MAPK activation and the phagocytosis of apoptotic cells by macrophages, which were inhibited by the p38 MAPK inhibitor, SB203580, the TGF-beta-activated kinase 1 (TAK1) inhibitor, (5Z)-7-oxozeaenol, and siRNA-mediated knock-down of p38α. AICAR increased phosphorylation of Akt, but the inhibition of PI3K/Akt activity using LY294002 did not affect the AICAR-induced changes in efferocytosis in macrophages. CGS15943, a non-selective adenosine receptor antagonist, did not affect AICAR-induced changes in efferocytosis, but dipyridamole, an adenosine transporter inhibitor, diminished the AICAR-mediated increases in efferocytosis. AICAR-induced p38 MAPK phosphorylation was not inhibited by the AMPK inhibitor, compound C, or siRNA-mediated knock-down of AMPKα1. Inhibition of AMPK using compound C or 5’-iodotubercidin did not completely block AICAR-mediated increases in efferocytosis. Furthermore, AICAR also increased the removal of apoptotic neutrophils or thymocytes in mouse lungs. These results reveal a novel mechanism by which AICAR increases macrophage-mediated phagocytosis of apoptotic cells and suggest that AICAR may be used to treat efferocytosis-related inflammatory conditions.

Effect of sauchinone, a lignan from Saururus chinensis, on bacterial phagocytosis by macrophages.

AMP-activated protein kinase (AMPK) plays an important role in inflammation in various cells and increases the phagocytic ability of macrophages. In this study, we found that sauchinone increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in mouse peritoneal macrophages. Sauchinone increased macrophage phagocytosis of fluorescent Escherichia coli, which was blocked by compound C, an AMPK inhibitor. Sauchinone also increased the phosphorylation of p38 mitogen activated protein kinase (MAPK) in cultured macrophages in a concentration-dependent fashion, which was not blocked by compound C. However, the increase of sauchinone-induced phagocytosis was prevented by SB203580. An inhibitor of the upstream kinase TGF-beta-activated kinase (TAK1), (5z)-7-oxozeaenol, abolished the phosphorylation of ACC and p38 MAPK. Systemic administration of sauchinone to mice led to increased phosphorylation of AMPK and p38 MAPK in the lung, and enhanced phagocytosis of fluorescent E. coli in bronchoalveolar lavage fluid as compared with control mice. These results suggest sauchinone to be a useful adjunctive treatment for bacterial infection.

Use of triazolam and alprazolam as premedication for general anesthesia.

Background Triazolam has similar pharmacological properties as other benzodiazepines and is generally used as a sedative to treat insomnia. Alprazolam represents a possible alternative to midazolam for the premedication of surgical patients. The purpose of this study was to evaluate the anxiolytic, sedative, and amnestic properties of triazolam and alprazolam as pre-anesthetic medications. Methods Sixty adult patients were randomly allocated to receive oral triazolam 0.25 mg or alprazolam 0.5 mg one hour prior to surgery. A structured assessment interview was performed in the operating room (OR), the recovery room, and the ward. The levels of anxiety and sedation were assessed on a 7-point scale (0 = relaxation to 6 = very severe anxiety) and a 5-point scale (0 = alert to 4 = lack of responsiveness), respectively. The psychomotor performance was estimated using a digit symbol substitution test. As a memory test, we asked the patients the day after the surgery if they remembered being moved from the ward to the OR, and what object we had shown them in the OR. Results There were no significant differences between the groups with respect to anxiety and sedation. The postoperative interviews showed that 22.2% of the triazolam-treated patients experienced a loss of memory in the OR, against a 0% memory loss in the alprazolam-treated patients. In comparison with alprazolam 0.5 mg, triazolam 0.25 mg produced a higher incidence of amnesia without causing respiratory depression. Conclusions Oral triazolam 0.25 mg can be an effective preanesthetic medication for psychomotor performance.

Urinary trypsin inhibitor attenuates liver enzyme elevation after liver resection.

Background Urinary trypsin inhibitors (UTI) have been widely used for the treatment of diseases including disseminated intravascular coagulation, shock, and pancreatitis. Since UTI synthesis is likely to be reduced in patients who have undergone liver resection, the incidence of inflammatory reactions may be increasing accordingly. For such patients, the liver enzyme increases after the operation can reflect liver damage. The purpose of this study was to examine if ulinastatin can inhibit liver enzyme increases after liver resection. Methods After receiving Institutional Review Board approval, a retrospective chart review was performed on 201 patients who underwent hepatic resection from 2006 to 2010. We divided the records into the control (n = 69) and ulinastatin (n = 132) groups according to the use of intraoperative ulinastatin and compared the preoperative and postoperative laboratory test results. The number of patients who had > 400 U/L elevation of aspartate transaminase (AST) level after surgery was compared between the 2 groups. Results The mean AST, alanine transaminase (ALT), and total bilirubin levels after liver resection were significantly lower in the ulinastatin group than in the control group. The number of patients who showed an AST > 400 U/L after liver resection was significantly higher in the control group (odds ratio = 3.02). Conclusions Ulinastatin attenuates the elevation of hepatic enzymes and bilirubin after liver resection.

Effective Dose of Ramosetron for Prophylaxis of Postoperative Nausea and Vomiting in High-Risk Patients

Background. Postoperative nausea and vomiting (PONV) are common adverse events with an incidence of up to 80% in high-risk patients. Ramosetron, a selective 5-HT3 receptor antagonist, is widely used to prevent PONV. The purpose of this study was to evaluate the effective dose of ramosetron for the prevention of PONV in high-risk patients. Methods. Fifty-one patients were randomly allocated to 3 groups and were administered ramosetron 0.3 mg (group A), 0.45 mg (group B), or 0.6 mg (group C), at the end of their surgery. The episodes of PONV were assessed 1, 6, 24, and 48 hours after the injection and all the adverse events were observed. Results. The complete response rate in the postoperative period 6–24 hours after the anesthesia was higher in group C than in group A: 93% versus 44%. Group Cs experience score of Rhodes index was lower than group As: 0.81 ± 2.56 versus 3.94 ± 5.25. No adverse drug reaction could be observed in all groups. Conclusions. The effective dose of ramosetron to be injected for the near-complete prophylaxis of PONV 6 to 24 hours after surgery in high-risk patients is a 0.6 mg bolus injection at the end of the surgery.

Anesthesiologist's satisfaction using between cisatracurium and rocuronium for the intubation in the anesthesia induced by remifentanil and propofol.

Background Although cisatracurium has many advantages in anesthetic practices, the best choice of a nondepolarizing neuromuscular blocking agent that can replace succinylcholine is rocuronium. However, it is reported that remifentanil with propofol might provide reliable intubating condition, even without a neuromuscular blocking agent; therefore, it might improve the intubating condition with cisatracurium. This study examined intubating conditions after administering rocuronium or cisatracurium in a rapid sequence induction with remifentanil-propofol. Methods Fifty two ASA physical status 1 or 2 adult patients scheduled for an elective surgery were enrolled in a randomized double-blinded trial. Anesthesia was induced in all patients with propofol 2.0 mg/kg and remifentanil 0.5 µg/kg, administered over 60 seconds. Rocuronium 0.9 mg/kg (3 × ED95, R group, n = 23) or cisatracurium 0.15 mg/kg (3 × ED95, C group, n = 29) was administered after the induction sequence. Laryngoscopy was attempted when the anesthesiologist thought it was 90 seconds after drug administration and appropriate time for intubation. The examiner, another anesthesiologist, recorded the exact time to intubation and suppression of maximal T1 on TOF. The intubating condition was assessed by the first anesthesiologist, as excellent, good, poor or not possible. Results The best time to laryngoscopy was predicted by measuring TOF and was found to be significantly longer in the C group (197 ± 53 s) than in the R group (102 ± 49 s) (P value < 0.05). However, time to larygoscopy, intubating condition during the laryngoscopy, and hemodynamic changes after intubation was similar in both groups. Conclusions Despite fundamentally slower onset time, cisatracurium can provide quite good intubating conditions, which were comparable to those achieved with equipotent doses of rocuronium, which is more expensive in anesthesia inducted with remifentanil and propofol.

Propofol Attenuates Pulmonary Injury Induced by Collapse and Reventilation of Lung in Rabbits

Propofol is an anesthetic drug with antioxidant and anti-inflammatory properties. We previously found that propofol attenuated lipopolysaccharide-induced acute lung injury in rabbits. This study was performed to evaluate the effects of propofol on lung injury caused by collapse and reventilation in rabbits. The wet/dry weight ratio of the lung, lung injury scores, percentage of polymorphonuclear leukocytes, albumin concentration, malondialdehyde, and interleukin-8 levels in bronchoalveolar lavage fluid were significantly increased in both lungs of the reventilation group. The degree of increase in these parameters was more significant in the right (reventilated) than in the left (non-reventilated) lung. Propofol attenuated these changes. These findings suggest that reventilation of a collapsed lung can cause injury in the contralateral non-reventilated lung as well as the reventilated lung. Propofol may provide a beneficial effect on lung injury induced by collapse and reventilation of the lung.