[Value of cerebral spinal fluid measurement of hypocretin-1 in the diagnosis of Chinese patients with narcolepsy].

OBJECTIVE: To evaluate the diagnostic value of cerebral spinal fluid (CSF) measurement of hypocretin-1 (hcrt-1) in Chinese patients with narcolepsy. METHODS: A total of 139 narcoleptic patients, including 111 narcolepsy with typical cataplexy (NC) and 28 narcolepsy without cataplexy (NWC), were diagnosed at the sleep centre of Peking University People's Hospital from April 2003 to March 2012. And 64 non-narcoleptic controls were recruited. CSF hcrt-1 levels were measured in all subjects.Receiver operating characteristic curve (ROC) was applied to determine the cutoff value of hcrt-1 for Chinese narcoleptic patients. The diagnostic utility of hcrt-1 ≤ 110.0 ng/L and hcrt-1 ≤ 30% of mean normal level defined by International Classification of Sleep Disorders-II and the new Chinese cutoff value were evaluated respectively. RESULTS: The level of hcrt-1 in narcolepsy patients was significantly lower than that of normal controls and the NC group was even lower than NWC group (20 (13, 36) vs 319 (244, 379) and 36 (15, 114) ng/L) (all P < 0.01).Using the international criteria of CSF hcrt-1 ≤ 110.0 ng/L or a level of 1/3 of mean normal control values, a specificity of 100% and sensitivity of 90.6% were generated.ROC curve indicated that CSF hcrt-1 level of 138.0 ng/L was the best cutoff value for the diagnosis of narcolepsy in Chinese narcoleptic patients. There were a specificity of 100%, a sensitivity of 92.8% and the area under the ROC curve of 0.98. CONCLUSIONS: CSF hcrt-1 measurement with high specificity and sensitivity is a useful diagnostic tool for Chinese narcoleptics. And the level of 138.0 ng/L may be the optimal cutoff for the diagnosis of narcolepsy in this group of patients.

The potential role of nerve growth factor in cryoneurolysis-induced neuropathic pain in rats.

Cryoanalgesia is suggested as a risk factor of neuropathic pain. The current study investigated the pain behavior of sciatic nerve cryoneurolysis (SCN) in adult male rats. The role of nerve growth factor (NGF) was also studied. The mechanical threshold was significantly elevated in SCN group than sham-operation group within 14days after surgery. After 28days, 22 out of 39 SCN rats (56.4%) represented mechanical hyperalgesia. There were much more NGF-immunoreactive nerve cells expressed in the dorsal horn in SCN rats with hyperalgesia. The NGF protein levels of SCN rats measured by Western blot were higher than sham-operation rats, while they were significantly higher in SCN rats with hyperalgesia than those without hyperalgesia. Pain-related behavior improved after anti-NGF treatment, compared with vehicle control group. NGF is associated with SCN-induced neuropathic pain. Peripherally secreted NGF may play an important role in this mechanism.

[Effect of flurbiprofen combined different concentrations of ropivacaine local infiltration on postoperative analgesia after laparoscopic cholecystectomy].

OBJECTIVE: To investigate the effects of postoperative analgesia after laparoscopic cholecystectomy using intravenous flurbiprofen combined with different concentrations of ropivacaine incision infiltration. METHODS: Eighty patients who underwent traditional laparoscopic cholecystectomy received standard general anesthesia. At the end of surgery, patients were randomly divided into four groups: group Con (control group: no analgesics was administered, n=20); group F (flurbiprofen group: 100 mg of flurbiprofen was given intravenously with no incision infiltration, n=20); group FR(0.25) (100 mg of flurbiprofen was given intravenously, combined with 0.25% ropivacaine incision infiltration, 2 mL per incision, 6 mL in total, n=20) and group FR(0.5) (100 mg of flurbiprofen was given intravenously, combined with 0.5% ropivacaine incision infiltration, 2 mL per incision, 6 mL in total, n=20). The intensity of postoperative pain was evaluated using numeric rating scale (NRS) in a double-blinded manner. Intramuscularly 50 mg of meperidin was administered as rescue medication when NRS was above 4. The NRS and the associated side effects were observed and recorded at the end of 0, 2, 6, 12, 24, and 48 hours postoperatively (T(0 h)h,T(2 h),T(6 h),T(12 h),T(24 h),and T(48 h)). RESULTS: There was no obvious difference among the four groups in respect of gender, age, body weight, baseline blood pressure, heart rate(HR), and total doses of sufentanil and remifentanil during operation and surgical time(P>0.05).There were significant differences among group FR(0.25)(2.34 ± 0.89,3.01 ± 1.27,2.79 ± 0.94), group FR(0.5)(2.42 ± 0.79, 2.69 ± 0.96, 2.03 ± 0.87)and group Con(3.42 ± 1.23, 5.98 ± 1.46, 4.53 ± 0.92)in NRS at T(2 h), T(6 h), and T(12 h)(P<0.05).Systolic blood pressures (SBP) of patients in group FR(0.25) [(114.19 ± .74) mmHg,(108.31 ± 7.62) mmHg) and group FR(0.5) [(115.26 ± 8.95) mmHg,(111.25 ± 9.12) mmHg] were significantly lower than those of patients in group Con [(137.11 ± 8.71) mmHg,(125.16 ± 8.92) mmHg] at T(2 h) and T(6 h)(P<0.05). Compared with group Con [(81.24 ± 6.64) beats/min], heart rate(HR) was also lower in patients of group FR(0.25) [(69.14 ± 5.92) beats/min] and group FR(0.5) [(70.16 ± 5.25) beats/min] at T(6 h)(P<0.05). There was no obvious adverse effect in all the four groups. CONCLUSION: Intravenous flurbiprofen combined with ropivacaine infiltration could significantly reduce postoperative pain after laparoscopic cholecystectomy, providing more stable hemodynamics. Compared with 0.25% ropivacaine, 0.5% ropivacaine infiltration combined with intravenous flurbiprofen has better and longer analgesic effects.

[Effect of cycloxygenase 2 inhibitor on levels of prostaglandin E2 in plasma and in local infiltrated fluid after functional endoscopic sinus surgery].

OBJECTIVE: To examine the time course and clinical relevance of changes in prostaglandin E2 (PGE2) to pain and outcome in surgical drainage, and circulating blood after functional endoscopic sinus surgery (FESS). METHODS: Thirty-seven patients scheduled to undergo FESS were randomized to receive celecoxib 400 mg(n=16) one hour before anesthesia induction and celecoxib 200 mg, q12 h for five consecutive days after surgery or nothing for patients in control group(n=21). Surgical site drainage and venous blood were collected up to 48 hours after surgery to test PGE2 level. Plasma levels of thromboxane A2 (TXA2) and prostacyclin (PGI2) were also tested for the same time course. RESULTS: For control patients, PGE2 level was elevated in both surgical site and circulating blood, which reached a peak concentration 6 h(177.5 ± 142.2 ng/L) and 48 h (64.5 ± 21.4 ng/L)respectively after FESS. For patients in celecoxib group, a significant reduction of surgical drainage PGE2(peak level 106.2 ± 33.4 ng/L at 6 h) and plasma PGE2 (peak level 44.7 ± 30.2 ng/L at 48 h) was observed(P<0.05). Pain scores 6 h and 48 h after surgery were positively correlated with surgical drainage PGE2 level, correlation coefficient being 0.333 (P=0.044) and 0.353(P=0.032) respectively. Celecoxib did not affect the ratio of plasma TXA2 to PGI2. CONCLUSION: Upregulation of PGE2 in surgical site after surgery was crucial in inflammatory response and postoperative pain. Cycloxygenase-2 inhibitor could significantly reduce surgical drainage and plasma PGE2 concentration.

[Effect of inhalation of aerosolized unfractioned heparin on peri alveolar coagulability and inflammatory response in endotoxin induced acute lung injury rat model].

OBJECTIVE: To observe the local changes in alveoli in intravenous endotoxin induced acute lung injury (ALI) rat model after inhalation of aerosolized unfractioned heparin (UFH), and to observe its effects on coagulability, fibrinolysis and inflammatory response. METHODS: Eighty seven male Wistar rats were divided into groups according to table of random number: sham, model, heparin therapy (HT) and heparin prophylaxis (HP). Endotoxin induced ALI model was reproduced by intravenous administration of lipopolysaccharide (LPS). Rats in HP and HT groups received aerosolized UFH before and after injection with LPS respectively, while rats in both sham and model groups inhaled aerosolized normal saline. Rats in each group were respectively sacrificed at 6, 12 and 24 hours after intravenous administration of LPS, and bronchoalveolar lavage fluid (BALF) was collected. Enzyme linked immunosorbent assay was used to measure the level of thrombin antithrombin (TAT), tissue type plasminogen activator (t-PA), urokinase type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) in BALF. RESULTS: At 6 hours after injury, the level of TAT (µg/L) in model group (3.346±0.585) was highest, that in HT group (2.764±0.100) was higher, and that in HP group (2.564±0.216) was lowest in BALF (all P<0.05). The t-PA (µg/L) concentration in HP group (3.037±0.524) was highest, that in HT group (2.494±0.191) was higher, and that in model group (1.716±0.125) was lowest (all P<0.05). Compared with model group, u-PA (µg/L) level in HP group dramatically enhanced (0.411±0.118 vs. 0.303±0.049, P<0.05). The concentration of PAI-1 (µg/L) in HP group was significantly lower than that of HT and model groups (2.296±0.246 vs. 2.597±0.425, 2.834±0.198, both P<0.05). In HP group, it was still lower than that in HT group at 12 hours (1.273±0.441 vs. 1.817±0.252, P<0.05). TNF-α (ng/L) levels in HT and HP groups were markedly lower compared with model group (68.154±3.915, 36.990±6.539 vs. 77.001±4.485) at 6 hours, and the level in HP group was lower than that in HT group (all P<0.05). TNF-α concentration in HP group was still the lowest at 12 hours (15.287±4.754), and there was significant difference compared with HT and model groups (26.756±5.336, 23.674±4.398, both P<0.05). The levels of IL-6 were not distinctively different among model, HT and HP groups at various time points. CONCLUSION: It was proved that inhalation of aerosolized UFH resulted in lowering local coagulability, alleviating fibrinolytic depression, improving fibrinolysis , and attenuating inflammation in endotoxin induced ALI rat model. More prominent results will be obtained when it was use as a prophylactic measure. The optimal time of usage is 6 hours after endotoxin injection.

[Selection of the early stage differentially expressed genes in rat lung tissue by cDNA microarray after total hepatic ischemia reperfusion injury].

OBJECTIVE: To examine the early changes in gene expression levels in lung tissues by cDNA microarray using a rat model of total hepatic ischemia reperfusion and to analysis function of the changes. METHODS: Twelve adult male SD rats weighting 220 - 250 g were divided randomly into two groups (6 in each group). The rats were sacrificed at end point of the operation and lung tissues were divided into several parts for either microarray analysis or RT-PCR of several genes selected from microarray data. Common change genes were selected from three chips and the final results of microarray analysis were identified by RT-PCR. At last, differentially expressed genes were classified according to their biological functions by cluster analysis. RESULTS: Analysis of the results showed those 48 genes up-regulated and 32 genes down-regulated after hepatic ischemia reperfusion lung injury. Only parts of them had we known about the function. Genes significantly up-regulated were IL-1 alpha, IL-1 beta, SLPI, MMP9, MMP14, MMP15, TIMP1, PIK3RL, MAPK, NF-kappaB, JNK and others. Genes significantly down-regulated were CYP1A1, NQO1, GSTA3, RETNLA and others. Differentially expressed genes were mainly classified into inflammatory reaction, transcription factors, cell metabolism, signals transduction, ion or receptors, cytoskeleton, etc. CONCLUSIONS: cDNA microarray technique provides a new method for detecting differentially expressed genes in rat lung tissues. Further study may reveal the molecular pathologic mechanism of hepatic ischemia reperfusion lung injury and discern new targets for therapeutic interventions.

[Total hepatic ischemia-reperfusion-induced lung injury in rats and protective effects of melatonin].

OBJECTIVE: To explore total hepatic ischemia-reperfusion(I/R)-induced lung injury in rats,its related mechanism and the protective effects of melatonin on lungs. METHODS: This study was divided into 2 parts. In the first part, 72 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: I/R group(ischemia-reperfusion,n=36) and sham-operation group(n=36). Total hepatic I/R was produced by occlusion of hepatic helium for 30 minutes, and the occlusion was then released for reperfusion. The animals were killed at 5 minutes prior to ischemia and 0 h, 0.5 h, 1 h, 3 h and 6 h after reperfusion in sham-operation group and I/R group (n=6 at each time point), and the lung tissue was taken. Through comparisons of these two groups, we observed the dynamic changes of lung tissue after total hepatic I/R. In the second part, 12 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: melatonin group(n=6) and vehicle group(n=6). Melatonin (0.5%,10 mg/kg)or vehicle of the same volume was injected via femoral vein 15 min before ischemia and 10 min before reperfusion, the animals were killed at 1 h after reperfusion, and the lung tissue was taken. Through comparisons of these two groups, we observed the effects of melatonin. RESULTS: (1)Total hepatic I/R led to severe histological injury in lungs. Compared with those in sham-operation group, the MDA content and apoptotic index were increased, the SOD activity was decreased, the p-ERK/ERK ratio and PCNA-positive index were decreased respectively 0 h and 0.5 h after reperfusion, and then were increased gradually. Histological examination revealed that the alveolar architecture was destroyed with interstitial thickening and neutrophil infiltration in I/R group. Correlate analysis revealed that p-ERK/ERK ratio showed a positive correlation with PCNA-positive index(r=0.56, P<0.05) and apoptotic index (r=0.62, P<0.05) in I/R group. (2)Melatonin treatment alleviated total hepatic I/R-induced lung injury. In melatonin group, the histological change was less severe compared with that in vehicle group; the MDA content and apoptotic index were lower, the SOD activity and p-ERK/ERK ratio were higher than those in vehicle group at the same time, but PCNA-positive index showed no difference. CONCLUSION: Total hepatic I/R led to severe lung injury. The aggravation of lipid peroxidation, reduced capability of scavenging free radical and aggravation of apoptosis were important factors causing hepatic I/R induced lung injury. Melatonin had protective effect on lung injury induced by total hepatic I/R, which was mediated by anti-oxidation and anti-apoptosis, but the relationship between melatonin's protective effects and activation of ERK1/2 signal transduction pathway remained to be explored.

[Effects of isoflurane on lung surfactant protein A in rats].

OBJECTIVE: To examine the effects of different concentrations of Isoflurane on the level of surfactant protein A(SP-A) and the expression of SP-A mRNA in the lung of rats. METHODS: Thirty-two male Wistar rats were randomly divided into 4 groups: control group received 40% (volume fraction) O2 inhalation (40% O2, n=8); 0.7% isoflurane group (n=8), 1.5% isoflurane group (n=8), and 2.0% isoflurane group (n=8). They were treated with 40% O2 with 0.7%, 1.5% and 2.0% isoflurane respectively. In each group, the rats inhaled experimental gas for 8 hours, and then were put to death immediately. Morphological changes of type II pneumocytes were observed by transmission electron microscopy. Surfactant protein content in broncho-alveolar lavage fluid (BALF) was measured with Western Blotting. The level of intracellular SP-A was examined with immunohistochemistry (IHC). To assess the relative levels of SP-A mRNA in lung tissue, reverse transcriptase-polymerase chain reaction (RT-PCR) was used with the co-amplification of the "housekeeping" gene GAPDH as internal control. RESULTS: Morphological changes of type II pneumocytes were distinct in 1.5% isoflurane and 2.0% isoflurane groups. Isoflurane, after three doses, significantly reduced the SP-A content in BALF. Control group, 437,112+/-25,654; 0.7% isoflurane group, 355,789+/-28,116; 1.5% isoflurane group, 238,554+/-31,531; 2.0% isoflurane group, 223,632+/-25,710 (P<0.01); Intracellular SP-A content of 1.5% and 2.0% isoflurane groups was less than that of the control, whereas 0.7% isoflurane groups did not show any significant difference from the control. RT-PCR indicated a reduced expression of SP-A mRNA in the lung after 1.5% and 2.0% isoflurane exposure. Control group, 1.47+/-0.18; 1.5% isoflurane group, 1.19+/-0.13; 2.0% isoflurane group, 1.13+/-0.12 (P<0.01). CONCLUSION: These findings indicate that 1.5% or more than 1.5% isoflurane exposure for eight hours could decrease the expression of the SP-A mRNA and synthesis of SP-A in rats, and maybe it could also affect the secretion and reuse.

[Changes in hemodynamics and oxygen metabolism of different Child-grade patients during orthotopic liver transplantation without veno-venous bypass].

OBJECTIVE: To investigate the changes in hemodynamics and oxygen metabolism of different Child-grade patients during orthotopic liver transplantation (OLT) without veno-venous bypass. METHODS: Forty patients with end-stage liver disease undergoing non veno-venous OLT under general anesthesia were enrolled in this research. Swan-Ganz catheter was placed in the pulmonary artery via right internal jugular vein and right radial artery was cannulated to monitor mean pulmonary artery pressure (mPAP) and artery blood pressure (ABP) continuously. Pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) were also recorded. Cardiac output (CO) was recorded at several time points, such as, 30 min after induction (T1), when inferior vena cava and portal vein were clamped (T2), 30 min after portal vein was clamped (T3), 10 min after unclamping of portal vein (T4), 60 min after graft reperfusion (T5) and at the end of the operation (T6). Blood samples were taken from radial and pulmonary artery for blood gas analysis and hemodynamic parameters, such as, cardiac index (CI), stroke volume index (SVI), pulmonary vascular resistance index (PVRI), and system vascular resistance index (SVRI); oxygen delivery (DO2) and oxygen consumption (VO2) were also calculated at these time points. RESULTS: (1) The mPAP values were much higher in group C than in group A or B at all time points. CVP was significantly increased at T1 or T2 in group C as compared with those points of Child's B or C. PCWP was increased significantly after unclamping of portal vein in all three groups and was much higher at several points in Child's C than in Child's A or B. The SVRI value of T1 and the PVRI value of T3 were much lower in group C than those points in group A and the value of SVRI/PVRI was less than normal except at T3 point. And blood gas analysis elucidated that PaO2 was higher than 400 mm Hg at any points. (2) Oxygen consumption was significantly decreased during the operation due to less blood supply and was reverted to normal at the end point of the operation in all patients. Oxygen delivery was all at least 1,000 mL/min during OLT and there was no significant difference between different groups or different points. CONCLUSION: The hemodynamic state of high cardiac output with low peripheral resistance deteriorated when patients' Child-grade shifted from A to C. VO2 was less than normal value during OLT until the end point.

Effect of nicardipine combined with esmolol on systemic and tissue oxygenation during off-pump coronary artery bypass grafting surgery.

BACKGROUND: The hemodynamics and oxygenation severely fluctuated during the off-pump coronary artery bypass grafting (OPCABG). This study aimed at investigating whether or not nicardipine combined with esmolol (1:10) can maintain systemic and tissue oxygenation during OPCABG. METHODS: Twenty patients scheduled for OPCABG were divided ramdomly into Group nicardipine (N) and Group nitroglycerine (X) respectively combined with esmolol (E) (Dosage ratio: 1 to 10) (Group N + E and Group X + E) with 10 patients in each group. The mixed solution of N + E or X + E were titrated to maintain mean arterial blood pressure between 70 and 80 mmHg following anesthesia induction. The variables of hemodynamics, arterial blood lactate content (Lac) and gastric intramucosal partial pressure of carbon dioxide were measured at the following time points: after induction of anesthesia (T1), pre-revascularization (T2), grafting of left anterior descending (T3), right coronary descending (T4) and left coronary circumflexus branches (T5), post-revascularization (T6), the end of operation (T7). The delivery of oxygen (DO2), consumption of oxygen (VO2) and gastric intramucosal pH (pHi) were calculated. RESULTS: The cardiac index (CI) in Group N + E was significantly increased (P < 0.05) as compared with T1 during OPCABG, while it was mildly decreased in Group X + E. The stroke volumes at T4, T5 in Group N + E and at T3-T6 in Group X + E were significantly decreased (P < 0.05). The systemic vascular resistance indices in Group N + E were significantly decreased as compared with T1 (P < 0.05). The heart rates in these two Groups were significantly elevated intraoperatively (P < 0.05). The DO2 after the infusion of N + E was significantly increased (P < 0.05) or leveled to T1, and the Lac were within the normal range. But the DO2 in Group X + E was decreased throughout the procedure, reaching significant level at T5 (P < 0.05), and the Lac was significantly increased beyond normal range (P < 0.05). The pHi in Group N + E was maintained above 7.35 during OPCABG, while it was less than 7.35 from T4 to T7 in Group X + E. CONCLUSION: Nicardipine combined with esmolol (1:10) regimen may maintain systemic and tissue oxygenation during OPCABG.

Epidural anesthesia can protect fibrinolytic function after surgery.

OBJECTIVE: To study the influences of different anesthesia techniques on stress response, coagulation and fibrinolytic function. METHODS: Thirty patients undergoing hysterectomy were randomized into three groups: Group E (continuous epidural anesthesia, n=10), Group G+E (epidural anesthesia combined general anesthesia, n=10) and Group G (general anesthesia, n=10). The blocking level with epidural anesthesia was maintained between T(6)-L(3) with 0.75% bupivacaine followed by Patient Controlled Epidural Analgesia (PCEA). General anesthesia was finished with convention followed by Patient-Controlled Analgesia (PCA). Blood samples were taken at pre-anesthesia (T(0)), the end of operation (T(1)) and postoperative 24 h (T(2)), 72 h (T(3)) to determine catecholamine concentration, coagulation and fibrinolysis variables. RESULTS: The nonepinephrine (NE) levels in Group E and Group G+E were not changed throughout the procedure, but obviously elevated in Group G (P<0.01) as compared with the baseline and those in the other Groups (P<0.05). The epinephrine (E) levels at T(1) in all groups were markedly increased as compared with those at T(0) and peaked (P<0.01), and then returned to the baseline at T(3). Fibrinogen (FIB) levels in all groups were obviously decreased at T(1), postoperatively elevated rapidly and peaked at T(3) (P<0.01). FIB levels at T(3) in groups G+E and G were much higher than that in Group E (P<0.05). The thrombin-anti-thrombin III complex (TAT) levels at T(1) in Group G+E and G were significantly increased as compared with those at Group E (P<0.01), and subsequently recovered to pre-anesthesia following surgery. TAT level in Group E was more decreased postoperatively than the baseline and those in the other groups (P<0.05). The D-dimer level in Group E over time was remarkably increased as compared with the baseline (P<0.05), and the D-dimer levels peaked at T(2) in all groups (P<0.01). The tissue-type plasminogen activator (t-PA) was more elevated than T(0) at T(1) (P<0.01) in all groups, and then returned to normal in Group E. But the marked decrease of t-PA in Groups G+E and G was revealed 72 h after surgery and became much lower than that in Group E (P<0.01). The plasminogen activating inhibitor-1(PAI-1) in Group G and Group G+E was more elevated perioperatively and became higher than that in Group E (P<0.01). CONCLUSION: Epidural anesthesia can preserve fibrinolytic function after lower-abdomen surgery by the inhibitory effects on surgical stress, PAI-1 and other mechanisms. The thromboprophylactic effects are revealed only following epidural anesthesia.

[Postoperative analgesic and anti-inflammatory effects of rofecoxib after total knee replacement].

OBJECTIVE: To evaluate the analgesic efficacy and systemic anti-inflammation of preoperative cyclooxygenase-2 nonsteroidal antiinflammatory drug, rofecoxib, after total knee replacement (TKR). METHODS: Thirty patients underwent elective knee replacement were randomly given oral rofecoxib 25 mg (group RE, n = 15) or placebo (group E, n = 15) 1 hour prior to surgery. All patients received epidural combined isoflurane anesthesia during surgery and patient-controlled epidural analgesia after surgery for 72 hrs (0.1 mg/ml morphine + 1.2 mg/ml bupivacaine + 0.02 mg/ml droperidol). Modified verbal rate scale was used to evaluate postoperative pain intensity. The outcomes included pain scores during rest and movement of knee joints and analgesia satisfaction. Daily morphine consumption was recorded. Circulation leucocyte and serum cytokine concentrations (including interleukin 6, interleukin 8, interleukin 10, Tumor necrosis factor-alpha) were determined before surgery, at the end of surgery, 2 h, 6 h, 12 h, 24 h and 48 h after surgery in two groups using RIA. The amount of intraoperative blood loss and postoperative drainage from the knees were measured. RESULTS: The pain scores were significantly less in the group RE than in group E during rest and knee joints movement on the first and second postoperative day, with an improvement in total analgesia satisfaction (P < 0.05). The mean dose of morphine for first 24 h was (8.1 +/- 1.5) mg in the E group and (6.8 +/- 0.7) mg in the RE group (t = -2.71, P < 0.01). Leucocyte and neutrophil counts were much higher in group E than in group RE at 12 h, 24 h post-operatively (P < 0.05). Serum TNF-alpha concentration was significantly lower in group RE than group E at the end of surgery, 6 h, 12 h postoperatively, as well as IL6 at 48 h, IL8 at 24h after surgery (P < 0.05). There were no significant differences in respect to the amount of intraoperative and postoperative blood loss between two groups (P > 0.05). CONCLUSION: Preoperative cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug rofecoxib increases analgesia satisfaction, reduces opioid requirement and demonstrates a systemic anti-inflammatory effect after TKR.

Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats.

BACKGROUND: Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant inhibition, fibrinolytic supression and fibrin deposition. We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces, it could block the procoagulant tendency, lessen depletion of coagulation factors, and even influence the inflammatory response. We also assessed the effects of different administration regimens of heparin. METHODS: Male Wistar rats were given inhaled heparin starting 30 minutes before (prophylactic heparin) or 2 hours after (therapeutic heparin) intravenous lipopolysaccharide (LPS) was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS. Thrombin-antithrombin complexes, activated protein C, tissue type and urokinase type plasminogen activators (t-PA/u-PA), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α, interleukin-6 in bronchoalveolar lavage, and lung tissue myeloperoxidase activity, and histology score were measured at three time-points. PAI-1/(t-PA + u-PA) was calculated based on the before-mentioned parameters. Statistical analysis was made using one-way analysis of variance (ANOVA) with post hoc test or Student's t test in the case of heterogeneity of variance. RESULTS: An alveolar procoagulant reaction, depressed fibrinolysis, and inflammatory response occurred in endotoxemia-induced lung injury. Local prophylactic application of heparin attenuated coagulation and early inflammation, promoted fibrinolysis, and reduced the histology score. Therapeutic application of heparin had similar, but weaker effects. CONCLUSIONS: Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response, promote fibrinolysis, and alleviate pulmonary pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.

Population pharmacokinetics of rocuronium delivered by target-controlled infusion in adult patients.

BACKGROUND: Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model (NONMEM), and to investigate the influence of relevant factors in adult patients. METHODS: Fourteen ASA I-II patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration (Cpt) was 2.0 µg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90% - 95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The population pharmacokinetics analysis was performed using NONMEM program. RESULTS: The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-compartment model. Pharmacokinetic parameters were clearance (CL)1 = 0.205 L/min, CL2 = 0.324 L/min, CL3 = 0.0292 L/min, volumes of distribution (V)1 = 4.00 L, V2 = 2.28 L, V3 = 4.26 L, Vdss = 10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight. CONCLUSIONS: No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.

Comparison of epidural analgesia and intercostal nerve cryoanalgesia for post-thoracotomy pain control.

Epidural analgesia is regarded as the gold method for controlling post-thoracotomy pain. Intercostal nerve cryoanalgesia can also produce satisfactory analgesic effects, but is suspected to increase the incidence of chronic pain. However, randomized controlled trials comparing these two methods for post-thoracotomy acute pain analgesic effects and chronic pain incidents have not been conducted previously. We studied 107 adult patients, allocated randomly to thoracic epidural bupivacaine and morphine or intercostal nerve cryoanalgesia. Acute pain scores and opioid-related side effects were evaluated for three postoperative days. Chronic pain information, including the incidence, severity, and allodynia-like pain, was acquired on the first, third, sixth and twelfth months postoperatively. There was no significant difference on numeral rating scales (NRS) at rest or on motion between the two groups during the three postoperative days. The patient satisfaction results were also similar between the groups. The side effects, especially mild pruritus, were reported more often in the epidural group. Both groups showed high incidence of chronic pain (42.1-72.1%), and no significance between the groups. The incidence of allodynia-like pain reported in cryo group was higher than that in Epidural group on any postoperative month, with significance on the sixth and the twelfth months postoperatively (P<0.05). More patients rated their chronic pain intensity on moderate and severe in cryo group and interfered with daily life (P<0.05). Both thoracic epidural analgesia and intercostal nerve cryoanalgesia showed satisfactory analgesia for post-thoracotomy acute pain. The incidence of post-thoracotomy chronic pain is high. Cryoanalgesia may be a factor that increases the incidence of neuropathic pain.