External validation of the modified Marsh and Schnider models for medium-chain triglyceride propofol in target-controlled infusion anesthesia.

BACKGROUND: Propofol formulated with medium- and long-chain triglycerides (MCT/LCT propofol) has rapidly replaced propofol formulated with long-chain triglycerides (LCT propofol). Despite this shift, the modified Marsh and Schnider pharmacokinetic models developed using LCT propofol are still widely used for target-controlled infusion (TCI) of propofol. This study aimed to validate the external applicability of these models by evaluating their predictive performance during TCI of MCT/LCT propofol in general anesthesia. METHODS: Adult patients (n = 48) undergoing elective surgery received MCT/LCT propofol via a TCI system using either the modified Marsh or Schnider models. Blood samples were collected at various target propofol concentrations and at specific time points, including the loss of consciousness and the recovery of consciousness (13 samples per patient). The actual plasma concentration of propofol was determined using high-performance liquid chromatography. The predictive performance of each pharmacokinetic model was assessed by calculating four parameters: inaccuracy, bias, divergence, and wobble. RESULTS: Both the modified Marsh and Schnider models demonstrated predictive performances within clinically acceptable ranges for MCT/LCT propofol. The inaccuracy values were 24.4% for the modified Marsh model and 26.9% for the Schnider model. Both models showed an overall positive bias, 16.4% for the modified Marsh model and 16.6% for the Schnider model. The predictive performance of MCT/LCT propofol was comparable to that of LCT propofol, suggesting formulation changes might exert only a minor impact on the reliability of the TCI system during general anesthesia. Additionally, both models exhibited higher bias and inaccuracy at target concentrations ranging from 3.5 ~ 5 ug/ml than at concentrations between 2 ~ 3 ug/ml. CONCLUSIONS: The modified Marsh and Schnider models, initially developed for LCT propofol, remain clinically acceptable for TCI with MCT/LCT propofol. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service of the Korean National Institute of Health ( https://cris.nih.go.kr ; registration number: KCT0002191; 06/01/2017).

Ramped versus sniffing position in the videolaryngoscopy-guided tracheal intubation of morbidly obese patients: a prospective randomized study.

BACKGROUND: Ramped positioning is recommended for intubating obese patients undergoing direct laryngoscopy. However, whether the use of the ramped position can provide any benefit in videolaryngoscopy-guided intubation remains unclear. This study assessed intubation time using videolaryngoscopy in morbidly obese patients in the ramped versus sniffing positions. METHODS: This is a prospective randomized study in patients with morbid obesity (n = 82; body mass index [BMI] ≥ 35 kg/m2). Patients were randomly allocated to either the ramped or the standard sniffing position groups. During the induction of general anesthesia, difficulty in mask ventilation was assessed using the Warters scale. Tracheal intubation was performed using a C-MAC® D-Blade videolaryngoscope, and intubation difficulty was assessed using the intubation difficulty scale (IDS). The primary endpoint was the total intubation time calculated as the sum of the laryngoscopy and tube insertion times. RESULTS: The percentage of difficult mask ventilation (Warters scale ≥ 4) was significantly lower in the ramped (n = 40) than in the sniffing group (n = 41) (2.5% vs. 34.1%, P < 0.001). The percentage of easy intubation (IDS = 0) was significantly higher in the ramped than in the sniffing group (70.0% vs. 7.3%, P < 0.001). The total intubation time was significantly shorter in the ramped than in the sniffing group (22.5 ± 6.2 vs. 40.9 ± 9.0, P < 0.001). CONCLUSIONS: Compared with the sniffing position, the ramped position reduced intubation time in morbidly obese patients and effectively facilitated both mask ventilation and tracheal intubation using videolaryngoscopy.

Different intraoperative decisions for undiagnosed paraganglioma: Two case reports.

BACKGROUND: Paragangliomas may be preoperatively misdiagnosed as non-functioning retroperitoneal tumors and are sometimes suspected only at the time of intraoperative manipulation. Without preoperative alpha blockade preparation, a hypertensive crisis during tumor manipulation and hypotension after tumor removal may result in critical consequences. Therefore, primary consideration should be given to the continuation or discontinuation of surgery on the basis of the possibility of gentle surgical manipulation and hemodynamic stabilization. We report two cases of paragangliomas detected intraoperatively. CASE SUMMARY: A 65-year-woman underwent laparoscopic small-bowel wedge resection. A hypertensive crisis occurred during manipulation of the mass, and an unrecognized catecholamine-producing paraganglioma was suspected. The surgeon and anesthesiologists believed that tumor excision could be performed with minimal manipulation of the tumor because the tumor was in a favorable location. Serious hemodynamic instability did not occur with aggressive use of vasoactive drugs. A week later, a 54-year-man underwent open resection of a 3-cm-sized retroperitoneal mass and showed the same findings during mass manipulation. For this patient, continuous manipulation of the mass seemed inevitable due to adhesion between the right adrenal gland and the mass in a narrow surgical field. The surgeon and anesthesiologists decided to cancel the surgical procedure and planned to perform a reoperation after alpha blockade therapy. Two weeks later, the tumor was uneventfully removed with small doses of vasoactive drugs. CONCLUSION: When an undiagnosed paraganglioma is suspected intraoperatively, reoperation after adequate preparation should be considered as an option to avoid fatal outcomes.

Head-neck movement may predispose to the development of arytenoid dislocation in the intubated patient: a 5-year retrospective single-center study.

BACKGROUND: Arytenoid dislocation is a rare laryngeal injury that may follow endotracheal intubation. We aimed to determine the incidence and risk factors for arytenoid dislocation after surgery under general anaesthesia. METHODS: We reviewed the medical records of patients who underwent operation under general anaesthesia with endotracheal intubation from January 2014 to December 2018. Patients were divided into the non-dislocation and dislocation groups depending on the presence or absence of arytenoid dislocation. Patient, anaesthetic, and surgical factors associated with arytenoid dislocation were determined using Poisson regression analysis. RESULTS: Among the 25,538 patients enrolled, 33 (0.13%) had arytenoid dislocation, with higher incidence after anterior neck and brain surgery. Patients in the dislocation group were younger (52.6 ± 14.4 vs 58.2 ± 14.2 yrs, P = 0.025), more likely to be female (78.8 vs 56.5%, P = 0.014), and more likely to be intubated by a first-year anaesthesia resident (33.3 vs 18.5%, P = 0.048) compared to those in the non-dislocation group. Patient positions during surgery were significantly different between the groups (P = 0.000). Multivariable Poisson regression identified head-neck positioning (incidence rate ratio [IRR], 3.10; 95% confidence interval [CI], 1.50-6.25, P = 0.002), endotracheal intubation by a first-year anaesthesia resident (IRR, 2.30; 95% CI, 1.07-4.64, P = 0.024), and female (IRR, 3.05; 95% CI, 1.38-7.73, P = 0.010) as risk factors for arytenoid dislocation. CONCLUSION: This study showed that the incidence of arytenoid dislocation was 0.13%, and that head-neck positioning during surgery, less anaesthetist experience, and female were significantly associated with arytenoid dislocation in patients who underwent surgeries under general anaesthesia with endotracheal intubation.

Comparisons of surgical conditions of deep and moderate neuromuscular blockade through multiple assessments and the quality of postoperative recovery in upper abdominal laparoscopic surgery.

STUDY OBJECTIVE: To determine the effect of deep neuromuscular blockade (NMB) on surgical field conditions through multiple assessments during pneumoperitoneum and evaluate the effect of the depth of intraoperative NMB on the quality of postoperative recovery over multiple time periods. DESIGN: Prospective randomized study. SETTING: Operating room of a university hospital. PATIENTS: Eighty non-morbidly obese patients (ASA physical status 1-2) who were scheduled to undergo laparoscopic gastrectomy in the reverse Trendelenburg position. INTERVENTIONS: Patients were allocated to either the deep or moderate NMB group. The depth of NMB was maintained at a post-tetanic count of 1 for deep NMB with a continuous infusion of rocuronium and at a train-of-four count of 1 for moderate NMB with a small intermittent bolus of cisatracurium. MEASUREMENTS: Single-blinded scoring of the quality of the surgical field condition was performed by a surgeon using a five-point scale in a 15-min interval during pneumoperitoneum. The quality of postoperative recovery was assessed using the Postoperative Quality of Recovery Scale (PostopQRS) on the day before surgery (baseline) and 1 h, 1 day, and 6 days after surgery. MAIN RESULTS: Optimal surgical field condition was rated in 87.0% (449/516) and 72.3% (370/512) of all measurements during deep and moderate NMB, respectively (P < 0.001). The percentage of patients maintaining a good-to-optimal condition throughout pneumoperitoneum was higher in the deep NMB group than in the moderate NMB group. There were no significant differences in the percentage of recovered patients between the two groups for all domains and all timepoints. CONCLUSIONS: Multiple assessments of the surgical field condition demonstrated that deep NMB provided a more satisfactory surgical field condition than moderate NMB during laparoscopic gastrectomy. However, the quality of postoperative recovery, assessed using the PostopQRS, was not different between the two groups according to the depth of NMB.

Donepezil-related inadequate neuromuscular blockade during laparoscopic surgery: A case report.

BACKGROUND: Donepezil is an acetylcholinesterase inhibitor used to improve cognition and delay disease progression in dementia patients by increasing acetylcholine levels. This drug may potentially interact with neuromuscular blocking agents (NMBAs) that act on muscular acetylcholine receptors during general anesthesia. Herein, we present a case of inadequate neuromuscular blockade with rocuronium, a nondepolarizing NMBA, in a dementia patient who had taken donepezil. CASE SUMMARY: A 71-year-old man was scheduled for laparoscopic gastrectomy. He had been taking donepezil 5 mg for dementia. General anesthesia was induced with propofol and remifentanil. The depth of neuromuscular blockade was monitored by train-of-four (TOF) stimulation. After the administration of rocuronium, the TOF ratio decreased at an unusually slow rate, and a TOF count of 0 was detected 7 min later. After intubation, a TOF count of 1 was detected within 1 min, and a TOF ratio of 12% was detected within 2 min. The TOF count remained at 4 even with an additional bolus and continuous infusion of rocuronium, suggesting resistance to this NMBA. Instead of propofol, an inhalation anesthetic was administered alongside another NMBA (cisatracurium). Then, the quality of neuromuscular blockade improved, and the TOF count remained at 0-1 for the next 70 min. No further problems were encountered with respect to surgery or anesthesia. CONCLUSION: Donepezil may be responsible for inadequate neuromuscular blockade during anesthesia, especially when total intravenous anesthesia is used.

Effect of transportation method on preoperative anxiety in children: a randomized controlled trial.

BACKGROUND: This study was performed to evaluate the effect of a wagon as a transport vehicle instead of the standard stretcher car to reduce children's anxiety of separation from parents. The secondary goal was to evaluate whether this anxiolytic effect was related to age. METHODS: We divided 80 children (age 2-7 years) into two groups. The stretcher group was transferred to the operating room on a conventional stretcher car, whereas the wagon group was transferred using a wagon. The level of anxiety was evaluated three times using the Modified Yale Preoperative Anxiety Scale (mYPAS): in the waiting area (T0), in the hallway to the operating room (T1), and before induction of anesthesia (T2). RESULTS: The mYPAS score was significantly lower in the wagon group (36.7 [31.7, 51.7]) than in the stretcher group (51.7 [36.7, 83.3]) at T1 (P = 0.007). However, there was no difference in the mYPAS score between the two groups at T2 (46.7 [32.5, 54.2] vs. 51.7 [36.7, 75.0], respectively, P = 0.057). The baseline anxiety tended to be lower with increasing age (r = -0.248, P = 0.031). During transportation to the operating room, the increase in the mYPAS score (T1-T0) was greater as the age of children decreased in the stretcher group (r = -0.340, P = 0.034). However, no correlation was observed in the wagon group (r = -0.053, P = 0.756). CONCLUSION: The wagon method decreased preoperative anxiety, suggesting that it may be a good alternative for reducing preoperative anxiety in children.

Effect of BMS-470539 on lipopolysaccharide-induced neutrophil activation.

BACKGROUND: BMS-470539, a recently introduced selective agonist of the melanocortin 1 receptor, is known to have anti-inflammatory properties. In this study, we investigated the effects of BMS-470539 on lipopolysaccharide (LPS)-induced inflammatory responses and delayed apoptosis with its signaling pathways in human neutrophils. METHODS: Isolated human neutrophils were incubated with various concentrations of BMS-470539 (1, 10, and 100 µM) in the presence or absence of LPS (100 ng/ml), and the expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6, and IL-1ß, were assessed. The effects of BMS-470539 on the expression of mitogen-activated protein kinases (MAPKs), such as p38, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase, and the expression of nuclear factor kappa B (NF-κB) in LPS-stimulated human neutrophils, were evaluated by enzyme-linked immunosorbent assay. Neutrophil apoptosis was also measured by fluorescence-activated cell sorting (annexin V/propidium iodide) in LPS-stimulated neutrophils under treatment with BMS-470539. RESULTS: BMS-470539 attenuated LPS-induced expression of pro-inflammatory cytokines, and phosphorylation of MAPKs and NF-κB. LPS stimulation reduced neutrophil apoptosis compared to the controls; however, BMS-470539 significantly inhibited the reduction of neutrophil apoptosis. CONCLUSIONS: BMS-470539 can suppress the inflammatory responses of LPS-stimulated neutrophils by inhibition of MAPK pathways or NF-κB pathway, and it can also inhibit LPS-delayed neutrophil apoptosis.

The effects of BMS-470539 on lipopolysaccharide-induced acute lung injury.

BACKGROUND: Overactivation of inflammatory cells, including macrophages and neutrophils, is associated with acute lung injury. BMS-470539 is a selective agonist of melanocortin 1 receptor, which triggers the inhibition of proinflammatory responses, suppressing neutrophil infiltration and protecting tissue. This study evaluated the effects of BMS-470539 on lipopolysaccharide-induced acute lung injury in a mouse model. METHODS: Mice received a subcutaneous injection of saline or BMS-470539 (18.47 mg/kg) 1 hour before an intratracheal injection of saline or lipopolysaccharide (20 µg). Mice were sacrificed to analyze the severity of pulmonary edema (lung wet-to-dry weight [W/D] ratio) and inflammatory responses (level of leukocytes, polymorphonuclear neutrophils [PMNs] and tumor necrosis factor alpha [TNF-α] in bronchoalveolar lavage fluid [BALF]), and neutrophil infiltration (myeloperoxidase activity). TNF-α activation was also measured in neutrophils from bone marrow. Survival was investigated in a second-hit sepsis mouse model. RESULTS: BMS-470539 improved sepsis-induced pulmonary edema, as demonstrated by a decreased W/D ratio (5.76%±0.83% to 3.81%±0.86%, P<0.05). The inflammatory response also improved, as shown by decreased levels of leukocytes (551±116 to 357±86×10²/mm³, P<0.05), PMNs (51.52%±16.23% to 18.41%±7.25%, P<0.01), and TNF-α (550±338 to 128±52 pg/ml, P<0.01) in the BALF. BMS-470539 also improved the inflammatory response, as shown by TNF-α levels (850±158 to 423±59 pg/ml, P<0.01) in neutrophils. BMS-470539 downregulated neutrophil infiltration in the lung (myeloperoxidase: 654±98 to 218±89 U/g, P<0.001). Lastly, BMS improved the survival rate (0% to 70%, P<0.01) in a mice multiple organ failure model. CONCLUSIONS: BMS-470539 improved lipopolysaccharide-induced acute lung injury and mortality in mice by affecting the inflammatory response.

Dexmedetomidine: present and future directions.

Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist, with sedative, analgesic, anxiolytic, sympatholytic, and opioid-sparing properties. Dexmedetomidine induces a unique sedative response, which shows an easy transition from sleep to wakefulness, thus allowing a patient to be cooperative and communicative when stimulated. Dexmedetomidine may produce less delirium than other sedatives or even prevent delirium. The analgesic effect of dexmedetomidine is not strong; however, it can be administered as a useful analgesic adjuvant. As an anesthetic adjuvant, dexmedetomidine decreases the need for opioids, inhalational anesthetics, and intravenous anesthetics. The sympatholytic effect of dexmedetomidine may provide stable hemodynamics during the perioperative period. Dexmedetomidine-induced cooperative sedation with minimal respiratory depression provides safe and acceptable conditions during neurosurgical procedures in awake patients and awake fiberoptic intubation. Despite the lack of pediatric labelling, dexmedetomidine has been widely studied for pediatric use in various applications. Most adverse events associated with dexmedetomidine occur during or shortly after a loading infusion. There are some case reports of dexmedetomidine-related cardiac arrest following severe bradycardia. Some extended applications of dexmedetomidine discussed in this review are promising, but still limited, and further research is required. The pharmacological properties and possible adverse effects of dexmedetomidine should be well understood by the anesthesiologist prior to use. Moreover, it is necessary to select patients carefully and to determine the appropriate dosage of dexmedetomidine to ensure patient safety.

Population pharmacokinetics of palonosetron and model-based assessment of dosing strategies.

PURPOSE: Palonosetron is the most recent 5-hydroxytryptamine-3 receptor antagonist, and its fixed dose of 0.075 mg is indicated for the prevention of postoperative nausea and vomiting. This study aimed to examine whether fixed dosing is more appropriate than body size-based dosing through the development of a population pharmacokinetic model and model-based simulations. METHODS: Fifty-one adult patients undergoing general anesthesia received single intravenous palonosetron administrations 30 min before the end of surgery. Palonosetron concentrations were measured in blood samples collected at various timepoints within 48 h. A population pharmacokinetic analysis was performed by non-linear mixed-effects modeling, and the area under the curves (AUCs) for fixed dosing and body size-based dosing were simulated. RESULTS: The pharmacokinetics of palonosetron were best described by the three-compartment model, and lean body weight (LBW) was the most significant covariate for all pharmacokinetic parameters. In a patient with LBW of 40 kg, typical clearance and central volume of distribution were 0.102 L/min and 6.98 L, respectively. In simulations, the overall interindividual variability in AUC (0, 48 h) of fixed dosing was not much higher than that of body size-based dosing. In subgroup analysis, the AUCs (0, 48 h) of fixed dosing were considerably lower in the high-weight subgroup and higher in the low-weight subgroup than the median-weight subgroup. In contrast, LBW-based dosing showed similar AUC distributions among the three subgroups. CONCLUSION: LBW-based dosing might be suitable for high-weight patients to avoid possible underdosing. Nevertheless, the current fixed dosing of palonosetron is acceptable for adult patients with normal weight.

Comparison of vocal cord view between neutral and sniffing position during orotracheal intubation using fiberoptic bronchoscope: a prospective, randomized cross over study.

BACKGROUND: In intubation using fiberoptic bronchoscope (FOB), partial or complete obstruction of upper airway makes the FOB insertion difficult. Thus, maneuvers to relieve such obstructions are recommended. There have been no studies to determine whether the sniffing or neutral position is superior for this purpose. Therefore, this study was performed to examine the effects of these two positions including vocal cord view. METHODS: Fifty-four patients scheduled to receive general anesthesia by orotracheal intubation were eligible for inclusion in the study with informed consent. After confirmation of proper head positioning depending on the group, the view of the vocal cord was acquired in each position. Images were reviewed using the percentage of glottic opening (POGO) score. RESULTS: A total of 106 images of vocal cords from 53 patients were obtained. The mean of difference of POGO score was 11.09, higher for the neutral position and standard deviation was 23.73 (p = 0.002). Neutral position increased POGO score in 31 patients and decreased POGO score in 13 patients compare to sniffing position (p = 0.017). There were no significant differences between the two head positions with regard to intubation time or degree of convenience during intubation. CONCLUSIONS: Neutral position improved the view of glottic opening than sniffing position during oral fiberoptic intubation. However, there was no difference in the difficulty of tube insertion between the two positions. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02931019 , registered on October 12, 2016.

The effect of triazolam premedication on anxiety, sedation, and amnesia in general anesthesia.

BACKGROUND: Benzodiazepines have been used preoperatively as part of an anesthesia regimen to attenuate the anxiety of patients. In this study, we aimed to examine the effect of oral triazolam, a short-acting benzodiazepine, on anxiety, sedation, and amnesia. METHODS: Ninety patients, aged 20-55 years, were randomly assigned to receive no premedication, or to receive triazolam 0.25 mg or 0.375 mg 1 h before anesthesia. Anxiety score, sedation score, blood pressure, heart rate and psychomotor performance were measured on the evening before surgery and on the day of surgery. Additional tests of psychomotor performance were performed in the postanesthesia care unit and on the next day of surgery. The occurrence of amnesia, bispectral index (BIS), recovery profiles and patient satisfaction with overall anesthesia care were also evaluated. RESULTS: Changes in the anxiety and sedation scores on the day of surgery were not significantly different among groups, whereas the increases in systolic blood pressure and heart rate were significantly less in both triazolam groups. The triazolam groups both showed a higher incidence of high satisfaction scores (≥ 2). The two triazolam groups also showed similar outcomes, except for a dose-dependent increase in the number of patients with amnesia and BIS values < 90. Delayed recovery from general anesthesia and psychomotor impairment were not observed in the triazolam groups. CONCLUSIONS: Triazolam 0.25 mg or 0.375 mg reduced the hemodynamic changes associated with anxiety, produced potent amnesia, and improved patient satisfaction. We suggest that triazolam can be used effectively as anesthetic premedication in adults.

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.

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 C's experience score of Rhodes index was lower than group A's: 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.

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-ß-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.

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.

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.

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.

Additive interaction of intrathecal ginsenosides and neostigmine in the rat formalin test.

BACKGROUND: The authors evaluated the effect of intrathecal mixture of ginsenosides with neostigmine on formalin-induced nociception and made further clear the role of the spinal muscarinic (M) receptors on the activity of ginsenosides. METHODS: A catheter was located in the intrathecal space of male Sprague-Dawley rats. Pain was evoked by injection of formalin solution (5%, 50 µl) to the hindpaw. Isobolographic analysis was done to characterize drug interaction between ginsenosides and neostigmine. The antagonism of ginsenosides-mediated antinociception was determined with M1 receptor antagonist (pirenzepine), M2 receptor antagonist (methoctramine), M3 receptor antagonist (4-DAMP), M4 receptor antagonist (tropicamide). The expression of muscarinic receptor subtypes was examined with RT-PCR. RESULTS: Intrathecal ginsenosides and neostigmine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed an additive interaction between ginsenosides and neostigmine in both phases. Intrathecal pirenzepine, methoctramine, 4-DAMP, and tropicamide reversed the antinociception of ginsenosides in both phases. M1-M4 receptors mRNA detected in spinal cord of naïve rats and the injection of formalin decreased the expression of M1 receptor mRNA, but it had no effect on the expression of other three muscarinic receptors mRNA. Intrathecal ginsenosides little affected the expression of all of muscarinic receptors mRNA in formalin-injected rats. CONCLUSIONS: Intrathecal ginsenosides additively interacted with neostigmine in the formalin test. Furthermore, M1-M4 receptors exist in the spinal cord, all of which contribute to the antinocieption of intrathecal ginsenosides.