Wen-Jinn Liaw

Intraarticular triamcinolone acetonide for pain control after arthroscopic knee surgery

Intraarticular corticosteroids provide valuable local therapy for chronic joint pain caused by inflammatory joint diseases.In this inpatient study, we evaluated the effect of intraarticular triamcinolone acetonide on acute pain after arthroscopic knee surgery. Sixty patients who underwent arthroscopic knee surgery under spinal anesthesia were enrolled into this double-blind, randomized trial. At the end of surgery, Group 1 (n = 30) received intraarticular triamcinolone acetonide 10 mg in isotonic saline 20 mL, and Group 2 (n = 30) received intraarticular isotonic saline 20 mL. After surgery, pain was assessed by using a visual analog scale. The time to first analgesic request (IV morphine) was recorded, and the proportion of patients requiring rescue analgesia was calculated. The results demonstrated that patients in Group 1 had lower pain scores than those in Group 2 from 6 to 24 h postoperatively (P < 0.05 to P < 0.01). From 6 h to 24 h, no patient in Group 1, compared with 53% of patients in Group 2, requested rescue analgesia (P < 0.001). We conclude that intraarticular triamcinolone acetonide provides a valuable local therapy of acute joint pain after arthroscopic knee surgery. Implications: The value of intraarticular triamcinolone acetonide in the management of pain after arthroscopic knee surgery has been evaluated. Patients who received intraarticular triamcinolone acetonide 10 mg at the end of surgery had lower pain scores and used less systemic analgesia than the saline control group. These data are important to the clinical use of this new therapy. (Anesth Analg 1998;87:1113-6)

Determination of tramadol by capillary gas chromatography with flame ionization detection. Application to human and rabbit pharmacokinetic studies.

A rapid, sensitive, precise and accurate capillary gas chromatographic assay with flame ionization detection was developed for the determination of tramadol in human, rabbit, pig and dog plasma. It is comprised of only a one-step extraction procedure with dichloromethane at pH 11.15 and gas chromatography on a capillary column. The recoveries of tramadol and meperidine (internal standard) were greater than 88%. Calibration graphs were linear over the concentration range 12.5-10,000 ng/ml with a coefficient of variation, both within-day and between-day, of less than 10% at any level. The limit of detection was 8 ng/ml of plasma based on signal-to-noise ratio of 3. Six other clinically used analgesics were investigated to check for potential interferences and their analytical conditions. The specificity of this assay was checked with two major metabolites of tramadol (M1: O-demethyltramadol; M2: N-demethyltramadol). Tramadol in plasma did not decompose significantly at -20 degrees C for 56 days. Pharmacokinetic application with intravenous tramadol in humans and rabbits revealed that tramadol followed a two-compartment open model with one distribution phase and one elimination phase. The distribution and elimination half-lives in humans were 1.02 and 141.9 min. The distribution and elimination half-lives in rabbits were 7.31 and 63.2 min, respectively.

Therapeutic effects of hypertonic saline on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats.

Objective:Significant mortality in patients with sepsis results from the development of multiple organ dysfunction syndrome. Small-volume resuscitation with 7.5% NaCl hypertonic saline has been proposed to restore physiologic hemodynamics in hemorrhagic shock. Therefore, we hypothesized that hypertonic saline resuscitation could alleviate the development of multiple organ dysfunction syndrome in sepsis induced by cecal ligation and puncture. Design:Randomized, prospective animal experiment. Setting:Academic research laboratory. Subjects:Male Wistar rats. Interventions:The animals were randomly allocated to one of four groups: 1) sham operation (0.9% NaCl, 4 mL/kg intravenously, at 3 hrs after laparotomy); 2) sham operation plus hypertonic saline (7.5% NaCl, 4 mL/kg intravenously, at 3 hrs after laparotomy); 3) cecal ligation and puncture (0.9% NaCl, 4 mL/kg intravenously, at 3 hrs after cecal ligation and puncture); and 4) cecal ligation and puncture plus hypertonic saline (7.5% NaCl, 4 mL/kg intravenously, at 3 hrs after cecal ligation and puncture). Measurements and Main Results:Cecal ligation and puncture for 18 hrs was associated with circulatory failure (i.e., hypotension and vascular hyporeactivity to norepinephrine), multiple organ dysfunction syndrome (examined by biochemical variables and histologic studies), and 18-hr mortality. Hypertonic saline not only ameliorated the deterioration of hemodynamic changes but also attenuated neutrophil infiltration in the lung and the liver of septic animals. Hypertonic saline increased the survival rate at 9 and 18 hrs compared with the cecal ligation and puncture group. Moreover, hypertonic saline reduced plasma nitric oxide and interleukin-1&bgr; and organ O2−· levels in rats that underwent cecal ligation and puncture. Conclusions:Hypertonic saline prevented circulatory failure, alleviated multiple organ dysfunction syndrome, and decreased the mortality rate in animals receiving cecal ligation and puncture. These beneficial effects of hypertonic saline may be attributed to reducing the plasma concentration of nitric oxide and interleukin-1&bgr; as well as the organ O2−· level and decreasing lung neutrophil infiltration and liver necrosis. Our study suggests that hypertonic saline could be a potential and inexpensive therapeutic agent in the early sepsis of animals or patients.

Dexamethasone for preventing nausea and vomiting associated with epidural morphine: a dose-ranging study.

We conducted a dose-ranging study of dexamethasone for preventing nausea and vomiting within the first 24 h after the administration of epidural morphine. Two hundred twenty-five women (n = 45 in each of the five groups) undergoing simple abdominal total hysterectomy under epidural anesthesia were enrolled in this randomized, double-blind, placebo-controlled study. When the incision closure was completed, patients received IV dexamethasone, 10 mg, 5 mg, or 2.5 mg; IV droperidol 1.25 mg; or saline 2 mL. All patients received epidural morphine 3 mg for postoperative analgesia. We found that patients who received dexamethasone 5 mg or 10 mg or droperidol 1.25 mg were significantly different from those who received saline alone in the following variables: the total incidence of nausea and vomiting, the incidence of more than four vomiting episodes, the number of patients requiring rescue antiemetics, the total number of patients with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences among dexamethasone 10 mg and 5 mg and droperidol 1.25 mg were not significant. Dexamethasone 2.5 mg was ineffective. In conclusion, because dexamethasone 5 mg was as effective as 10 mg as an antiemetic, we recommend the smaller dose for preventing nausea and vomiting associated with epidural morphine.

Pain relief after arthroscopic knee surgery : Intravenous morphine, epidural morphine, and intra-articular morphine

OBJECTIVE The aim of this study was to compare the analgesic efficacy and side effects of intravenous (IV), epidural, and intra-articular (IA) morphine after arthroscopic knee surgery. DESIGN Prospective, randomized, double-blind clinical investigation. SETTING Medical center, university teaching hospital. PATIENTS Inpatients with an American Society of Anesthesiologists physical status of I or II who were scheduled for elective arthroscopic knee surgery. INTERVENTIONS AND OUTCOME MEASURES A total of 75 patients scheduled for arthroscopic knee surgery under epidural anesthesia were randomly divided into three groups (n = 25 in each group). At the end of surgery, patients in group 1 received 3 mg of IV morphine, patients in group 2 received 3 mg of epidural morphine, and patients in group 3 received 3 mg of IA morphine. Patients were then observed for 24 hours. During the observation period, the proportion of patients requiring rescue analgesia with intramuscular diclofenac in each group was calculated and the occurrence of morphine-related side effects was recorded. RESULTS We found that patients who received IV morphine requested more rescue analgesia than those who received either epidural or IA morphine. The proportions of patients requiring rescue analgesia in the IV, epidural, and IA groups were 65%, 13%, and 9%, respectively (p < 0.01 in group 1 vs. group 2 and in group 1 vs. group 3). Epidural morphine was associated with higher incidences of nausea and vomiting, pruritus, and urinary retention than IA morphine (range, p < 0.05-0.01 in group 2 vs. group 3). CONCLUSIONS Patients who received IA morphine consumed less rescue analgesia than those who received IV morphine. They also reported fewer side effects than those patients who received epidural morphine. Intra-articular morphine may be the method of choice for pain relief after arthroscopic knee surgery.

A novel simultaneous measurement method to assess the influence of intracerebroventricular obestatin on colonic motility and secretion in conscious rats

Obestatin, a novel putative 23-amino acid peptide, is derived from mammalian preproghrelin gene via a bioinformatics approach. Although obestatin regulates thirst, sleep, memory, anxiety, activates cortical neurons in the brain and stimulate proliferation of retinal pigment epithelial cells, there is no study to explore its central impacts on the lower gut motility and secretion. We investigated the influence of intracerebroventricular (ICV) injection of obestatin on rat colonic motor and secretory functions. Colonic transit time, fecal pellet output and fecal content were assessed in freely fed, conscious rats, which were implanted with ICV and colonic catheters chronically. Human/rat corticotropin-releasing factor (h/rCRF) was applied as a stimulatory inducer of colonic motility and secretion. ICV injection of obestatin (0.1, 0.3, 1.0 nmol/rat) did not modify the colonic transit time, whereas ICV injection of h/rCRF (0.3 nmol/rat) significantly shortened colonic transit time. ICV obestatin in any dose we tested did not affect the fecal pellet output, frequency of watery diarrhea, total fecal weight, fecal dried solid weight, or fecal fluid weight in the first hour post-injection, either. In contrast, ICV injection of h/rCRF effectively stimulated fecal pellet output, as well as increased total fecal weight, fecal dried solid weight and fecal fluid weight during the first hour post-injection, compared to ICV saline controls. In conclusion, using our novel simultaneous measurement method, acutely central administration of obestatin exhibits no influence on colonic motility and secretion in conscious rats.

Composite auditory evoked potential index versus bispectral index to estimate the level of sedation in paralyzed critically ill patients: a prospective observational study.

BACKGROUND: Electromyographic activity (EMG) has been reported to elevate the Bispectral Index (BIS) in patients not receiving neuromuscular blockade while under sedation in the intensive care unit (ICU). We investigated the change of the composite A-line autoregressive index (AAI) and BIS after administration of muscle relaxants in sedated surgical ICU patients. METHODS: We prospectively investigated 38 patients who required administration of a muscle relaxant while continuously sedated with midazolam hydrochloride and fentanyl citrate to achieve a Ramsay Sedation Scale value equal to 5. BIS, EMG activity of BIS (EMG-BIS), signal quality index of BIS, AAI, EMG activity of AAI (EMG-AAI), and acceleromyography at the adductor pollicis muscle were recorded simultaneously every 5 min for 30 min before and after neuromuscular blockade. Students t-test, the Wilcoxon′s signed ranks test, and the Spearman test were calculated using the standard statistics software SPSS 10.0 (SPSS Inc., Chicago, IL). RESULTS: After administration of a muscle relaxant, BIS (58.61 ± 7.45 vs 44.68 ± 6.65, P < 0.001), EMG-BIS (37.33 ± 7.15 vs 27.24 ± 1.51, P < 0.001), AAI (34.11 ± 10.96 vs 15.97 ± 6.69, P < 0.001), and EMG-AAI (59.58 ± 9.57 vs 1.00 ± 0.00, P < 0.001) decreased significantly. Significant correlations between BIS and EMG-BIS (rs = 0.75, P < 0.001) and AAI and EMG-AAI (rs = 0.87, P < 0.001) were also found during the baseline period. CONCLUSIONS: This study demonstrated that, in sedated ICU patients, BIS and AAI markedly decreased after administration of myorelaxant, and the decreased BIS and AAI values after neuromuscular blockade were correlated to those usually seen in the state of surgical anesthesia, respectively.

The magnitude of acute tolerance to morphine analgesia: concentration-dependent or time-dependent?

UNLABELLED We evaluated the relationship of either the infusion time or the plasma morphine concentrations on the magnitude of acute tolerance to morphine analgesia. Male New Zealand White rabbits were randomly allocated to one of four groups. Group 1 received an IV bolus of morphine 40 mg followed by an infusion at 20 mg/h for 8 h. Group 2 received a 20-mg morphine bolus followed by an infusion at 10 mg/h. Group 3 received a 10-mg morphine bolus followed by an infusion at 5 mg/h. Group 4 received a saline bolus and infusion. Analgesia was determined by the paw-pressure test, and the plasma concentrations of morphine were measured by high-performance liquid chromatography. We found that the plasma concentrations of morphine were maintained at a steady-state between 2 and 8 h after the morphine administration. However, from 2 to 8 h after the morphine infusion, the longer the infusion time was, the less the analgesic effect remained. Furthermore, the magnitude of acute tolerance was significantly correlated to the duration of morphine infusion (r = 0.93; P < 0.01) but not the different steady-state plasma morphine concentrations. We conclude that the magnitude of morphine tolerance is significantly correlated to the duration of infusion but not the different steady-state plasma morphine concentrations. IMPLICATIONS We evaluated the relationship of either the infusion time or the plasma morphine concentrations on the magnitude of acute tolerance to morphine analgesia in rabbits. We found that the magnitude of morphine tolerance is significantly correlated to the duration of infusion but not to the different steady-state plasma morphine concentrations.

Application of thrombelastography in liver injury induced by endotoxin in rat.

Liver injury developing in patients with sepsis may lead to an increased risk of mortality. Thrombelastography (TEG) is generally applied to evaluate hemostatic disturbance in patients undergoing liver transplantation or cardiopulmonary bypass. The aim of this study was to investigate the development of liver injury and coagulopathy in a lipopolysaccharide (LPS)-induced animal model and to assess the relationship between TEG variables and liver injury. Male Wistar rats received LPS (30 mg/kg over a 4-h intravenous infusion) to induce experimental liver injury or isotonic saline as a control. Variables of hemodynamics and liver biochemistry were measured during the subsequent 6 h after the start of infusion. TEG variables (R-time, K-time, &agr;-angle and maximal amplitude), thrombin–antithrombin complex and plasminogen activator inhibitor-1 were also measured. After LPS infusion, liver injury [examined by biochemical variables (e.g. alanine aminotransferase, ALT) and histological studies] was developed and inflammatory cytokines (tumor necrosis factor-&agr; and interleukin-6) were raised. At the initial period of LPS infusion, R-time was shortened and &agr;-angle was increased. Thereafter, &agr;-angle and maximal amplitude were decreased progressively, demonstrating that endotoxin induced coagulation disturbances. Furthermore, there were strong positive correlation between K-time and natural log (Ln)(ALT) (r = 0.823, P = 0.001); also, there were strong negative correlations between &agr;-angle and Ln(ALT) (r = −0.762, P = 0.002) as well as maximal amplitude and Ln(ALT) (r = −0.732, P = 0.004) at 6 h after LPS infusion. These results demonstrated that TEG could be a potential tool to evaluate the development of liver injury in endotoxemia.

Intracerebroventricular O-n-octanoylated ghrelin and its splice variant-induced feeding is blocked by insulin, independent of obestatin or CRF receptor, in satiated rats.

OBJECTIVE The purpose of this study was to investigate the impact of intracerebroventricular (ICV) injection of the two endogenous forms of acyl ghrelin, O-n-octanoylated ghrelin and des-Gln¹⁴-ghrelin, on feeding behavior, as well as their interactions with insulin, obestatin, and corticotropin-releasing factor receptor (CRF-R) antagonist in the forebrain to influence food intake. METHODS We examined the food intake in conscious, freely fed rats, which were chronically implanted with ICV catheters. RESULTS O-n-octanoylated ghrelin and des-Gln¹⁴-ghrelin (0.1 nmol/rat) were equally potent in stimulating food intake in freely fed rats, up to 8 h after ICV injection (P < 0.05). In contrast, ICV administration of insulin (8 mU/rat), obestatin (2 nmol/rat), and astressin (2 nmol/rat), a specific CRF-R antagonist, did not modify feeding in freely fed rats. Furthermore, pretreatment with ICV insulin (P < 0.01), but not obestatin or astressin, at the abovementioned dose, blocked central acyl-ghrelin-induced hyperphagic effects. CONCLUSION ICV O-n-octanoylated ghrelin and its splice variant, des-Gln¹⁴-ghrelin, are equally potent to elicit food intake in freely fed rats, while these feeding-stimulating effects are opposed by insulin, but independent of obestatin and endogenous CRF-R in the forebrain.