Kwok-Hon Chan

Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial.

OBJECTIVE To test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery. MATERIAL AND METHODS Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group. RESULTS In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12.8 [7.0] units vs 21.5 [12.7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival. CONCLUSION Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.

Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide–Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1

Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF. Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. In addition, propofol showed less inhibitory effects in non-FPR1–induced cell responses. The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells. To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.

Perioperative plasma concentrations of tumor necrosis factor-alpha and interleukin-6 in infected patients.

OBJECTIVE To characterize the sequential plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and their relationship with the clinical outcome in patients with intra-abdominal infection who underwent surgical intervention. DESIGN A prospective, comparative study. SETTING Surgical intensive care unit of a university hospital. PATIENTS Fifteen patients with surgically proved intra-abdominal infection were included as the infected group. The comparative noninfected group consisted of ten patients who underwent major abdominal surgery without infection. INTERVENTIONS Blood samples were obtained from the indwelling arterial catheter before induction of general anesthesia, and 1, 1.5, 2, 3, 4, 6, and 24 hrs after skin incision. MEASUREMENTS AND MAIN RESULTS Plasma cytokine concentrations were measured using radioimmunoassay. The hemodynamic and physiologic parameters were recorded for comparison with cytokine concentrations. In the noninfected group, the TNF-alpha concentration was very low throughout the observation period, and the IL-6 concentration increased 4 hrs after skin incision. The infected group had significantly higher TNF-alpha and IL-6 concentrations than the noninfected group. The TNF-alpha concentration increased from 129.2 +/- 46.4 to 1196.0 +/- 445.8 pg/mL and the IL-6 concentration increased from 54.2 +/- 24.3 to 560.3 +/- 187.5 pg/mL 2 hrs after skin incision in the infected group. The postoperative APACHE II score correlated significantly with both peak IL-6 (r2=.39) and peak TNF-alpha (r2=.32) concentrations. CONCLUSIONS Both TNF-alpha and IL-6 concentrations increased significantly after surgical intervention in patients with intra-abdominal infection. The pulse increase in TNF-alpha concentration and the persistent increase in IL-6 concentration were related to the poor postoperative clinical condition in infected patients.

Effect of Oral Clonidine Premedication on Perioperative Hemodynamic Response and Postoperative Analgesic Requirement for Patients Undergoing Laparoscopic Cholecystectomy

BACKGROUND To investigate the clinical efficacy of oral clonidine premedication in anesthesia and analgesia in patients undergoing laparoscopic cholecystectomy (LC). METHODS One hundred and ten patients, scheduled for elective laparoscopic cholecystectomy, were recruited for the prospective, randomized, single-blind, comparative study. They were randomly allotted to either of the placebo or clonidine group. Patients of the placebo group (n = 65) were premedicated with oral antacid (alugel hydroxide 300 mg), while those in the clonidine group (n = 45) were premedicated with oral clonidine 150 micrograms prior to anesthesia. The premedication was given 60 to 90 min before the anticipated time of induction of anesthesia. Normocapnia was maintained throughout the perioperative period. Mass spectrometer was used to assess the inspired and expiratory concentrations of isoflurane, the anesthetic used for maintenance of anesthesia. Postoperative pain intensity, sedation scores, adverse events, time to the first dose of postoperative analgesic and cumulative analgesic requirement in 24 hours were recorded. Data were expressed as mean +/- SD. RESULTS Patients in the clonidine group displayed greater hemodynamic stability perioperatively and the isoflurane requirement was also reduced (30% less). The postoperative analgesic requirement was less (1.5 +/- 1.3 vs. 2.2 +/- 1.3 dose, P < 0.05) and the time for the first dose of analgesic was prolonged (411 +/- 565 vs. 264 +/- 441 min) in comparison with the placebo group but no statistic difference was found. CONCLUSIONS Oral clonidine premedication helped to provide perioperative hemodynamic stability, spared the use of isoflurane and reduced the requirement of postoperative analgesia so as to smoother the way to recovery in patients undergoing LC.

A New Technique to Assist Epidural Needle Placement Fiberoptic-guided Insertion Using Two Wavelengths

Background:Up to 10% of epidurals fail due to incorrect catheter placement. We describe a novel optical method to assist epidural catheter insertion in a porcine model. Methods:Optical emissions were tested on ex vivo tissues from porcine paravertebral tissues to identify optical reflective spectra. The wavelengths of 650 and 532 nm differentiated epidural space from the ligamentum flavum. We then used a hollow stylet that contained optical fibers to place epidural needles in anesthetized pigs. Real-time data were displayed on an oscilloscope and stored for analysis. A total of 50 punctures were done in four laboratory pigs. Data were expressed as mean ± SD. Results:Paired t test shows significant optical differences between the epidural space and the ligamentum flavum at both 650 nm (P < 0.001) and 532 nm (P = 0.014). Mean magnitudes for 650 nm, 532 nm, and their ratio were 3.565 ± 0.194, 2.542 ± 0.145, and 0.958 ± 0.172 at epidural space and 3.842 ± 0.191, 2.563 ± 0.131, and 1.228 ± 0.244 at ligamentum flavum, respectively. There were no differences in the optical characteristics of the ligamentum flavum and epidural space at different levels in the lumbar and thoracic region (two-way ANOVA P > 0.05). Conclusions:This is the first study to introduce a new optical method to localize epidural space in a porcine model. Epidural space could be identified by the changes in the reflective pattern of light emitted at 650 nm, which were specific for the ligamentum flavum and dural tissue. Real-time optical information successfully guided a modified Tuohy needle into the epidural space.

Factors Affecting Patient-controlled Analgesia Requirements

BACKGROUND/PURPOSE Intravenous patient-controlled analgesia (IVPCA) is one of the most widely used postoperative analgesic methods. Many factors could affect the total analgesic consumption of IVPCA. This retrospective study investigated the relationship between patient characteristics and total morphine consumption during a 3-day course of postoperative IVPCA. METHODS Patients receiving surgery under general anesthesia with postoperative IVPCA for 3 days during the period between January 2002 and December 2003 were included. Patient data including age, sex, weight, height, body mass index (BMI), operation type and site were collected. Total morphine consumption was recorded at the end of the 3-day IVPCA course. Stepwise regression analyses were conducted to select factors significantly associated with morphine consumption. Stratified analyses were also conducted among different surgical, BMI and age subgroups. RESULTS A total of 1308 patients (646 men, 662 women) were included in the analysis. For all operations, weight, age, procedures involving malignant disease, and surgical sites were significantly associated with total morphine consumption. The R and adjusted R2 values of the selected model were 0.509 and 0.256, respectively. Weight was the only common factor among all stratified analyses (all p < 0.001). Age was negatively correlated with morphine consumption. Gender was not a significant factor except in lower abdominal operations. Height was not associated with total morphine consumption. BMI status was not significantly associated with components of the selected factors. CONCLUSION This study demonstrated that weight and surgical sites significantly influence total IVPCA requirements. The effect of surgical sites should be considered when evaluating the influence of demographic characteristics on IVPCA demand.

P6 acupressure does not prevent emesis during spinal anesthesia for cesarean delivery.

Nausea and vomiting are major adverse effects during spinal anesthesia for cesarean delivery. Stimulation of the P6 (Neiguan) acupoint is a traditional Chinese acupuncture technique used for effective antiemetic purposes. In this study, we evaluated the antiemetic effect of P6 acupressure in parturients during spinal anesthesia for cesarean delivery. In a randomized, double-blind, controlled trial, 110 parturients scheduled for elective cesarean delivery were enrolled in the study. Thirty minutes before initiation of spinal anesthesia, parturients were randomized to acupressure bands or placebo bands bilaterally on the P6 acupoint and nausea and vomiting were observed over the study period. There were no statistically significant differences in maternal characteristics. Incidence rates for intraoperative nausea were 64% (acupressure group) and 71% (control group) (P = 0.416), with an incidence of intraoperative vomiting of 22% (acupressure group) and 27% (control group) (P = 0.506). The results suggest that prophylactic use of acupressure bands bilaterally on the P6 acupoint failed to prevent nausea and vomiting during spinal anesthesia for cesarean delivery.

Minocycline and fluorocitrate suppress spinal nociceptive signaling in intrathecal IL‐1β–induced thermal hyperalgesic rats

We previously demonstrated that intrathecal IL‐1β caused thermal hyperalgesia in rats. This study was conducted to examine the effects and cellular mechanisms of glial inhibitors on IL‐1β–induced nociception in rats. The effects of minocycline (20 μg), fluorocitrate (1 nmol), and SB203580 (5 μg) on IL‐1β (100 ng) treatment in rats were measured by nociceptive behaviors, western blotting of p38 mitogen‐activated protein kinase (MAPK) and inducible nitric oxide synthase (iNOS) expression, cerebrospinal fluid nitric oxide (NO) levels, and immunohistochemical analyses. The results demonstrated that intrathecal IL‐1β activated microglia and astrocytes, but not neurons, in the dorsal horn of the lumbar spinal cord, as evidenced by morphological changes and increased immunoreactivity, phosphorylated p38 (P‐p38) MAPK, and iNOS expression; the activation of microglia and astrocytes peaked at 30 min and lasted for 6 h. The immunoreactivities of microglia and astrocytes were significantly increased at 30 min (6.6‐ and 2.7‐fold, respectively) and 6 h (3.3‐ and 4.0‐fold, respectively) following IL‐1β injection, as compared with saline controls at 30 min (all P < 0.01). IL‐1β induced P‐p38 MAPK and iNOS expression predominantly in microglia and less in astrocytes. Minocycline, fluorocitrate, or SB203580 pretreatment suppressed this IL‐1β–upregulated P‐p38 MAPK mainly in microglia and iNOS mainly in astrocytes; minocycline exhibited the most potent effect. Minocycline and fluorocitrate pretreatment abrogated IL‐1β–induced NO release and thermal hyperalgesia in rats. In conclusion, minocycline, fluorocitrate, and SB203580 effectively suppressed the IL‐1β–induced central sensitization and hyperalgesia in rats.

Intraoperative administration of tramadol for postoperative nurse-controlled analgesia resulted in earlier awakening and less sedation than morphine in children after cardiac surgery

In adults, intraoperative administration of tramadol could result in earlier recovery and less sedation than morphine. In this controlled, randomized, double-blind study, we investigated whether an intraoperative initial dose of tramadol could cause more rapid awakening from general anesthesia, less sedation, and earlier tracheal extubation than morphine in children during the immediate postoperative period. Forty children aged 1–6 yr, scheduled for atrial or ventricular septal defect repair and tracheal extubation in the pediatric intensive care unit, were randomly allocated to receive morphine, initial dose 0.2 mg/kg, or tramadol 2 mg/kg given at the end of sternal closure, followed by nurse-controlled analgesia (bolus 0.02 mg/kg of morphine and 0.2 mg/kg of tramadol) with background infusions (0.015 mg · kg−1 · h−1 for morphine and 0.15 mg · kg−1 · h−1 for tramadol). Postoperatively, children receiving tramadol had earlier awakening from general anesthesia (P = 0.02) and were less sedated at 1 and 2 h postoperatively (P = 0.03 and P = 0.01, respectively). Tracheal extubation was earlier in the tramadol group (P = 0.01). Lengths of pediatric intensive care unit stay did not differ between groups. Times to first trigger of nurse-controlled analgesia bolus and objective pain scores during the 48 h observation period were comparable between groups. The incidence of desaturation and emesis were similar between groups. The patients ate well and did not differ on Day 1 or Day 2.

Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery

Plasma‐containing products are given during the pre‐anhepatic stage of liver transplant surgery to correct abnormal thromboelastogram (TEG) values and prevent blood loss due to coagulation defects. However, evidence suggests that abnormal TEG results do not always predict bleeding. We questioned what effect using higher TEG values to initiate treatment would have on blood loss. A single transfusion protocol was used for all patients who underwent liver transplantation between 2007 and 2010. Thirty‐eight patients received coagulation products when standard TEG cutoff values were exceeded, whereas another 39 patients received coagulation products when the TEG values were 35% greater than normal. The results of postoperative coagulation tests for total blood loss and the use of blood products were compared for the 2 groups. When the critical TEG values for transfusion were higher, significantly fewer units of fresh frozen plasma (5.58 ± 6.49 versus 11.53 ± 6.66 U) and pheresis platelets (1.84 ± 1.33 versus 3.55 ± 1.43 U) were used. There were no differences in blood loss or postoperative blood product use. In conclusion, the use of higher critical TEG values to initiate the transfusion of plasma‐containing products is not associated with increased blood loss. Further testing is necessary to identify what TEG value predicts bleeding due to a deficit in coagulation factors. Liver Transpl 18:1254–1258, 2012.