Preparation and Characterization of Celecoxib Nanosuspension Using Bead Milling.

The aim of this study is to develop nanosuspension for improved dissolution of poorly water-soluble celecoxib. We first prepared coarse suspension of celecoxib with Tween 80 and hydroxypropyl methylcellulose as stabilizers, and then fabricated nanosuspension using the bead milling technique. Depending on milling time, the physical properties of nanosuspension were evaluated by photon correlation spectroscopy (e.g., particle size and distribution) and scanning electron microscopy (SEM) (e.g., morphology). As results, the mean size of crystalline celecoxib particles was highly reduced (368.1±14.5 nm) as milling process proceeded comparing to celecoxib powder (6.5±1.0 µm). Morphology of milled celecoxib particles has changed considerably from bar-shape or plate-shape to needle-shape due to a high energy caused by milling. In the dissolution test, the celecoxib nanosuspension showed an improved dissolution profile at pH 1.2 compared to celecoxib powder (less than 1%). In contrast, 53.4% of celecoxib in nanosuspension was dissolved up to 30 minutes, demonstrating improved dissolution of celecoxib. Taken together, bead-milled nanosuspension could be an effective strategy that can improve the dissolution and bioavailability.

The effects of adjuvant intrathecal fentanyl on postoperative pain and rebound pain for anorectal surgery under saddle anesthesia.

BACKGROUND: Intrathecal opioid has been known to enhance the quality and prolong the duration of spinal anesthesia, as well as to reduce postoperative pain. The purpose of this study was to evaluate postoperative analgesic characteristics of intrathecal fentanyl for the first 48 hours after anorectal surgery under saddle anesthesia. METHODS: Eighty patients were recruited in our study. Forty patients were randomly allocated to group B that received 0.5% bupivacaine 5 mg with 0.3 ml normal saline. The other 40 patients were assigned to group BF which was given 0.5% bupivacaine 5 mg with fentanyl 15 µg. The primary outcome variable was a numeric rating scale (NRS) at six hours postoperatively. Secondary outcomes included changes in the NRS score between one and 48 hours postoperatively, consumption of rescue analgesics, and the frequency of rebound pain. RESULTS: Group BF exhibited a lower mean NRS score at postoperative six hours compared to group B (P < 0.001). However, the mean NRS score was not different after postoperative six hours between the two groups. The median consumption of rescue analgesics in group BF was less than that of group B (P = 0.028) and the frequency of rebound pain decreased in group BF when compared to group B (P = 0.021). The levels of sensory block were S1 dermatome and motor block scores were 0 for both groups. There was no significant difference in adverse effects between the groups. CONCLUSIONS: Intrathecal fentanyl 15 µg for anorectal surgery under saddle anesthesia led to an improved pain score for the first six hours after surgery and decreased postoperative analgesic use. Rebound pain diminished with intrathecal fentanyl and adverse effects did not increase.

Airway obstruction by dissection of the inner layer of a reinforced endotracheal tube in a patient with Ludwig's angina: A case report.

Intraoperative airway obstruction is perplexing to anesthesiologists because the patient may fall into danger rapidly. A 74-year-old woman underwent an emergency incision and drainage for a deep neck infection of dental origin. She was orally intubated with a 6. 0 mm internal diameter reinforced endotracheal tube by video laryngoscope using volatile induction and maintenance anesthesia (VIMA) with sevoflurane, fentanyl (100 µg), and succinylcholine (75 mg). During surgery, peak inspiratory pressure increased from 22 to 38 cmH2O and plateau pressure increased from 20 to 28 cmH2O. We maintained anesthesia because we were unable to access the airway, which was covered with surgical drapes, and tidal volume was delivered. At the end of surgery, we found a longitudinal fold inside the tube with a fiberoptic bronchoscope. The patient was reintubated with another tube and ventilation immediately improved. We recognized that the tube was obstructed due to dissection of the inner layer.

Arrhythmogenic potential develops rapidly at graft reperfusion before the start of hypotension during living-donor liver transplantation.

BACKGROUND: Detailed profiles of acute hypothermia and electrocardiographic (ECG) manifestations of arrhythmogenicity were examined to analyze acute hypothermia and ventricular arrhythmogenic potential immediately after portal vein unclamping (PVU) in living-donor liver transplantation (LT). METHODS: We retrospectively analyzed electronically archived medical records (n = 148) of beat-to-beat ECG, arterial pressure waveforms, and blood temperature (BT) from Swan-Ganz catheters in patients undergoing living-donor LT. The ECG data analyzed were selected from the start of BT drop to the initiation of systolic hypotension after PVU. RESULTS: On reperfusion, acute hypothermia of < 34℃, < 33℃ and < 32℃ developed in 75.0%, 37.2% and 11.5% of patients, respectively. BT decreased from 35.0℃ ± 0.8℃ to 33.3℃ ± 1.0℃ (range 35.8℃-30.5℃). The median time to nadir of BT was 10 s after PVU. Difference in BT (ΔBT) was weakly correlated with graft-recipient weight ratio (GRWR; r = 0.22, P = 0.008). Compared to baseline, arrhythmogenicity indices such as corrected QT (QTc), Tp-e (T wave peak to end) interval, and Tp-e/QTc ratio were prolonged (P < 0.001 each). ST height decreased and T amplitude increased (P < 0.001 each). However, no correlation was found between ΔBT and arrhythmogenic indices. CONCLUSIONS: In living-donor LT, regardless of extent of BT drop, ventricular arrhythmogenic potential developed immediately after PVU prior to occurrence of systolic hypotension.

Comparative Effects of Dexmedetomidine and Propofol on US-Guided Radiofrequency Ablation of Hepatic Neoplasm Under Monitored Anesthesia Care: A Randomized Controlled Study.

Percutaneous radiofrequency ablation (RFA) is a useful and safe procedure for treating hepatic neoplasm. However, liver RFA causes severe pain, which thereby increases the demand for monitored anesthesia care (MAC). Here, we compared the efficacy and safety of propofol and dexmedetomidine, which are commonly administered during MAC when performing RFA to assess hepatic neoplasm.In this randomized controlled trial, 40 patients were randomly allocated to 2 groups for elective RFA. Patients received either dexmedetomidine (group D) or propofol (group P). Both groups received the continuous infusion of remifentanil for pain control. The primary outcomes were opioid consumption and differences in partial pressure of arterial carbon dioxide (PaCO2) between pre- and postprocedure RFA. In addition, hemodynamic parameters, patient satisfaction, and interventional radiologist satisfaction were determined.There were significant differences in opioid consumption (50.1 ±â€Š16.8 ng/kg/min [group D] vs 71.2 ±â€Š18.7 ng/kg/min [group P]; P = 0.001) and delta PaCO2 (10.4 ±â€Š6.4 mm Hg vs 17.2 ±â€Š9.2 mm Hg, respectively; P = 0.016). Moreover, respiratory rates were significantly different between groups during RFA (P < 0.001). However, blood pressure and heart rate did not significantly change during RFA. Neither patient nor interventional radiologist satisfaction was significantly different between groups.Dexmedetomidine provides better respiratory stability and reduces opioid consumption in comparison with propofol when administered under MAC when performing RFA for hepatic neoplasm.

Prolonged post-reperfusion syndrome during multivisceral organ transplantation in a pediatric patient: a case report.

Multivisceral organ transplantation involves the transplantation of three or more abdominal organs, including small bowel, duodenum, stomach, liver, pancreas, colon, and so on. The large amounts of cold and acidic loading into systemic circulation from the graft during multivisceral organ transplantation may result in severe post-reperfusion syndrome (PRS). We describe here a 6-year-old pediatric patient with chronic intestinal pseudo-obstruction who experienced prolonged PRS and severe metabolic acidosis during seven abdominal organ transplantation including the liver, spleen, stomach, duodenum, small bowel, colon and pancreas. The hypotensive period lasted approximately 10 minutes after graft reperfusion and was accompanied by severe metabolic acidosis and hypothermia. Since PRS can be easily associated with adverse outcomes, such as poor early graft function and primary non-function, not only meticulous surveillance for aggravating factors for PRS but also their immediate correction were necessary in managing a pediatric patient undergoing multivisceral organ transplantation.

Anesthetic considerations of percutaneous transcatheter aortic valve implantation: first attempt in Korea -A report of 2 cases-.

Conventional aortic valve replacement for severe aortic stenosis is associated with a high operative mortality in the elderly patients with significant comorbidities, including severe respiratory dysfunction, renal insufficiency, and compromised cardiac function. Human transcatheter aortic valve implantation was first reported in 2002 and has become a valid alternative in selected high-risk patients in Europe and North America. This article describes the first attempt of transfemoral transcatheter aortic valve implantation in Korea. The procedure was applied in two consecutive patients with severe aortic stenosis. Despite several intra-operative complications during procedure, the post-operative outcomes were good for both patients. At post-operative 30 days there was satisfactory prosthetic valve function and hemodynamic stability.

A novel approach to simultaneous screening and confirmation of regulated pharmaceutical compounds in dietary supplements by LC/MS/MS with an information-dependent acquisition method.

The commercial success of synthetic phosphodiesterase-5 (PDE-5) inhibitors (viz. sildenafil, vardenafil and tadalafil) for erectile dysfunction (ED) has led to their widespread use as adulterants in dietary supplements (DSs). Reports on adulteration by ED drugs or their analogues in DSs suggest they may cause a serious threat to human health. The problem is becoming more complex as hidden and structurally modified analogues are continuously being reported. To analyse known drugs and their analogues, three commonly used PDE-5 inhibitors, naturally existing icariin and yohimbin, and their 19 analogues were analyzed in this study. They were identified using ion-spray liquid chromatography/tandem mass spectrometry (LC/MS/MS) using multiple reaction monitoring (MRM). This MRM procedure gave a limit of detection of less than 0.02 ng ml(-1) for the 24 compounds, selectivity of fragmentation using MRM for 2.5 - 8.5 min in a single run and peak height repeatability of coefficient of variation of 3.9 - 31.8%. An IDA method using the MRM scans to detect the presence of known analytes was set up and added to a built-in library for screening for PDE-5 inhibitors. These MRM experiments were used to trigger product ion scans using a hybrid quadrupole-linear ion trap instrument. The product ion scan was compared and confirmed by a library search of MS/MS spectra acquired from a reference standard. To search for new analogues of PDE-5 inhibitors, a precursor ion scan of an expected ion m/z 283, which was one of the mass fragments from the analogues of sildenafil or vardenafil, was performed and fragmentation of the precursor ion, by combining a precursor ion scan with automatic confirmation using EPI spectra, was acquired. Of the 37 DSs tested, two were eventually found to be adulterated with yohimbin and vardenafil, respectively. The approach proposed in this study would be valuable in characterizing chemical constituents of drug residues and their analogues with identical chemical substructures from complex natural and synthetic sources in DSs using an information-dependent acquisition-enhanced product ion (IDA-EPI) scan.

Separation and structural elucidation of a novel analogue of vardenafil included as an adulterant in a dietary supplement by liquid chromatography-electrospray ionization mass spectrometry, infrared spectroscopy and nuclear magnetic resonance spectroscopy.

MEGATON, a dietary supplement, was analyzed in order to detect PDE-5 inhibitors and their analogues. A new analogue of vardenafil could be detected by high-performance liquid chromatography (HPLC) analysis with a photodiode array detector (PDA). This compound was compared with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues such as hongdenafil and homosildenafil. The structure of this compound was elucidated by mass spectrometry (MS), infrared (IR) spectroscopy and one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. When compared with vardenafil to verify the structural difference, this compound had an acetyl group instead of a sulfonyl group in the pyrazolopyrimidine portion without any substitution in the piperazine ring of the molecule. This compound was identified as 2-(2-ethoxy-5-(2-(4-ethylpiperazin-1-yl)acetyl)phenyl)-5-methyl-7-propyl-imidazo(5,1-f)-(1,2,4)triazin-4(3H)-one, which is also called acetylvardenafil.

A survey on informed consent process for epidural analgesia in labor pain in Korea.

BACKGROUND: There is a legal obligation to explain the procedure and use of epidural analgesia in labor primarily due to the possibility of potential risks and associated complications. The present study details on the survey carried out to ascertain the current status of obtaining informed consent (IC) for explaining the epidural analgesia in labor. METHODS: The present study is based on a survey through a telephone questionnaire that covered all the hospitals in Korea where the anesthesiologists' belonged to and are registered with Korean Society of Anesthesiologists. The questionnaire included questions pertaining to administration of epidural analgesia to a parturient, information on different steps of obtaining an IC, whether patient status was evaluated, when the consent was obtained, and the reasons behind, if the consent had not being given. RESULTS: A total of 1,434 respondents took part in the survey, with a response rate of 97% (1,434/1,467). One hundred seventy-four hospitals had conducted epidural analgesia on the parturient. The overall rate of obtaining IC for epidural analgesia during labor was 85%, of which only 13% was conducted by anesthesiologists. The rate of evaluating preoperative patient status was 74%, of which 45% was conducted by anesthesiologists. Almost all of the consent was obtained prior to the procedure. CONCLUSIONS: The rate of obtaining IC for epidural analgesia in labor is relatively high (85%) in Korea. However, it is necessary to discuss the content of the consent and the procedure followed for obtaining IC during the rapid progress of labor.

Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion.

To improve the bioavailability and photostability of poorly water-soluble and photosensitive amlodipine, dry emulsion (DE) was prepared by spray-drying the oil-in-water emulsion of amlodipine. Labrafil M 1944 CS and dextrin were employed as oil phase and matrix material, respectively. Dispersing DE in distilled water formed an emulsion with a mean droplet size 1.4-fold larger than that of the homogenized amlodipine emulsion before spray-drying (0.24 +/- 0.30 microm versus 0.17 +/- 0.02 microm). The mean droplet size of DE remained unchanged during 6-month storage at room temperature. 94.4% versus 33.1% of amlodipine remained intact after 24-h UV irradiation of amlodipine as DE formulation or as powder. These data suggest that DE formulation greatly improved the photostability of amlodipine, as well as increasing the physical stability of emulsion systems. In vitro release of DE was higher than that of amlodipine powder (66% versus 48% release at 60 min). Consequently, DE formulation resulted in 2.6- and 2.9-fold higher Cmax and AUC0-24 h of amlodipine compared after oral administration of amlodipine powder in rats. Our data suggest that the DE may be a potential oral dosage form for amlodipine to improve its bioavailability.