WISP1 and TLR4 on Macrophages Contribute to Ventilator-Induced Lung Injury.

Injurious mechanical ventilation has been shown to directly affect pulmonary and systemic immune responses. How these responses propagate or attenuate remains unknown. The goal of this study was to further determine whether toll-like receptor (TLR) 4 and WNT1-inducible signaling pathway protein 1 (WISP1) could contribute to injurious mechanical ventilation, especially focusing on the role of macrophages during experimental ventilator-induced lung injury. A prospective, randomized, and controlled animal study was designed, and male, wild-type (WT) C57BL/6 mice, TLR4 knockout (TLR4-/-), and lyzTLR4 knockout (lyzTLR4-/-) mice aging 8~12 weeks were used. Animals were anesthetized and randomized to spontaneous breathing (SB) group or to high tidal volume (VT, 20 ml/kg) mechanical ventilation (HTV) group. Histological evaluation, alveolar-capillary permeability of Evan's blue albumin (EBA), WISP1 protein levels, macrophage inflammatory protein-2 (MIP-2), and interleukin-6 (IL-6) in plasma and bronchoalveolar lavage fluid (BALF) concentrations were analyzed. HTV group was associated with a significant increase of WISP1 and EBA ratio in C57BL/6 mice, a significant decrease of WISP1 protein levels, and a significant decrease of IL-6, MIP-2 in plasma, and BALF concentrations of pro-inflammatory cytokines in TLR4-/- and lyzTLR4-/- knockout mice. In TLR4-/- mice and lyzTLR4-/- mice, there were also significant differences between SB group and HTV group in terms of H&E score and EBA ratio and level of pro-inflammation cytokines. The entire TLR4-targeted mice could further improve various inflammatory changes and damages when compared with lyzTLR4-targeted mice. What is more, TLR4-/- mice and lyzTLR4-/- mice reacted differently to rWISP1 and/or BMMC treated. TLR4-/- mice had no response to rWISP1, while lyzTLR4-/- mice still showed drastic response to both treatments. TLR4 and WISP1, especially the former one, on macrophages could contribute to releasing of pro-inflammatory cytokines during ventilator-induced lung injury. Injurious mechanical ventilation may result in an immune response which is similar to that of infection.

The IL-33-ST2 Pathway Contributes to Ventilator-Induced Lung Injury in Septic Mice in a Tidal Volume-Dependent Manner.

Mechanical ventilation (MV) is frequently employed to manage respiratory failure in sepsis patients and is required for the surgical management of intra-abdominal sepsis. The impact of MV varies dramatically depending on tidal volume, with even moderate tidal volume (MTV) ventilation leading to ventilator-induced lung injury, whereas low tidal volume (LTV) ventilation protects against sepsis-induced acute respiratory distress syndrome. Interleukin (IL)-33 is known to contribute to lung injury in sepsis and its release can be induced by mechanical stress. To determine the relationship between the IL-33-suppression of tumorigenicity 2 (ST2) pathway and patterns of lung injury associated with MV in sepsis, mice were subjected to cecal ligation and puncture (CLP) followed 6 h later by either MTV (10 mL/kg) or LTV (6 mL/kg) ventilation for 4 h. MTV and LTV ventilation alone for 4 h had no impact on lung injury. MTV markedly exacerbated lung injury and inflammation, while LTV significantly suppressed these parameters in septic mice. Lung and plasma levels of IL-33 ST2 were significantly elevated by CLP alone at 10 h. MTV caused further and significant increases in IL-33 and sST2 levels, while LTV significantly suppressed levels induced by CLP. Deletion of IL-33 or ST2 prevented the increase in lung injury and inflammation induced by MTV in septic mice, while administration of recombinant IL-33 in the airway reversed the protection seen with LTV. Taken together, these findings implicate the IL-33-ST2 pathway in the pro-inflammatory changes induced by the mechanical ventilation that leads to lung injury in the setting of intra-abdominal sepsis in a tidal volume-dependent manner.

WISP1 mediates lung injury following hepatic ischemia reperfusion dependent on TLR4 in mice.

BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) is a common pathological phenomenon, which causes hepatic injury as well as remote organ injuries such as the lung. Several mediators, such as oxidative stress, Ca2+ overload and neutrophil infiltration, have been implied in the pathogenesis of liver and remote organ injuries following reperfusion. WNT1 inducible signaling pathway protein 1 (WISP1) is an extracellular matrix protein that has been associated with the onset of several malignant diseases. Previous work in our group has demonstrated WISP1 is upregulated and contributes to proinflammatory cascades in hepatic IRI. However, the role of WISP1 in the pathogenesis of lung injury after hepatic IRI still remains unknown. METHODS: Male C57BL/6 mice were used to examine the expression and role of WISP1 in the pathogenesis of lung injuries after hepatic IRI and explore its potential mechanisms in mediating lung injuries. RESULTS: We found WISP1 was upregulated in lung tissues following hepatic IRI. Treatment with anti-WISP1 antibody ameliorated lung injuries with alteration of cytokine profiles. Administration with rWISP1 aggravated lung injuries following hepatic IRI through excessive production of proinflammatory cytokines and inhibition of anti-inflammatory cytokines. CONCLUSIONS: In this study, we concluded that WISP1 contributed to lung injuries following hepatic IRI through TLR4 pathway.

Mechanical ventilation enhances extrapulmonary sepsis-induced lung injury: role of WISP1-αvß5 integrin pathway in TLR4-mediated inflammation and injury.

BACKGROUND: High tidal volume ventilation of healthy lungs or exacerbation of existing acute lung injury (ALI) by more moderate mechanical ventilation (MTV) produces ventilator-induced lung injury. It is less clear whether extrapulmonary sepsis sensitizes the lung to MTV. METHODS: We used a two-hit model of cecal ligation and puncture (CLP) followed 12 h later by MTV (10 ml/kg; 6 h) to determine whether otherwise noninjurious MTV enhances CLP-induced ALI by contrasting wildtype and TLR4-/- mice with respect to: alveolar-capillary permeability, histopathology and intrapulmonary levels of WNT-inducible secreted protein 1 (WISP1) and integrin ß5; plasma levels of cytokines and chemokines (TNF-α, IL-6, MIP-2, MCP-1) and intrapulmonary neutrophil infiltration; and other inflammatory signaling via intrapulmonary activation of JNK, p38 and ERK. A separate cohort of mice was pretreated with intratracheal neutralizing antibodies to WISP1, integrin ß5 or IgG as control and the presented phenotyping repeated in a two-hit model; there were 10 mice per group in these first three experiments. Also, isolated peritoneal macrophages (PM) from wildtype and TLR4-/-, MyD88-/- and TRIF-/- mice were used to identify a WISP1-TLR4-integrin ß5 pathway; and the requisite role of integrin ß5 in WISP1-induced cytokine and chemokine production in LPS-primed PM was examined by siRNA treatment. RESULTS: MTV, that in itself did not cause ALI, exacerbated increases in alveolar-capillary permeability, histopathologic scoring and indices of pulmonary inflammation in mice that previously underwent CLP; the effects of this two-hit model were abrogated in TLR4-/- mice. Attendant with these findings was a significant increase in intrapulmonary WISP1 and integrin ß5 in the two-hit model. Anti-WISP1 or anti-integrin ß5 antibodies partially inhibited the two-hit phenotype. In PM, activation of TLR4 led to an increase in integrin ß5 expression that was MyD88 and NF-κB dependent. Recombinant WISP1 increased LPS-induced cytokine release in PM that was inhibited by silencing either TLR4 or integrin ß5. CONCLUSIONS: These data show for the first time that otherwise noninjurious mechanical ventilation can exacerbate ALI due to extrapulmonary sepsis underscoring a potential interactive contribution of common events (sepsis and mechanical ventilation) in critical care, and that a WISP1-TLR4-integrin ß5 pathway contributes to this phenomenon.

High-mobility group box 1 protein is involved in the protective effect of Saquinavir on ventilation-induced lung injury in mice.

Saquinavir (SQV) is the first FDA approved HIV protease inhibitor. Previous studies showed that SQV can limit Toll-like receptor-4 (TLR4)-mediated inflammatory pathway and nuclear factor-κB (NF-κB) activation, thereby playing a protective role in many kinds of diseases. High-mobility group box 1 (HMGB1) has been identified as an inflammatory mediator and it might express its toxicity in a short period of time in ventilator-induced lung injury (VILI). In this study, C57BL/6 mice were randomly divided into four groups (n = 10): control group and control with SQV group (Con + SQV) were spontaneous breath. HTV group (HTV) received high tidal volume ventilation (HTV) for 4 h. HTV with SQV group (HTV + SQV) were pretreated with 5 mg/kg of SQV for 7 days before HTV. Mice were sacrificed after 4 h of HTV. Lung wet/dry weight (W/D) ratio, alveolar-capillary permeability to Evans blue albumin (EBA), cell counts, total proteins in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level in BALF and lung tissue, and lung histopathology were examined. Our results showed that HTV caused significant lung injury and NF-κB activation, which was correlated with the increase of TNF-α and IL-6 levels in BALF and plasma. SQV pretreatment significantly attenuated pulmonary inflammatory injury, as well as NF-κB activation. These findings indicate that the protective effect of SQV may be associated with the inhibition of NF-κB activation and HMGB1 expression in mice.

Saquinavir Ameliorates Liver Warm Ischemia-Reperfusion-Induced Lung Injury via HMGB-1- and P38/JNK-Mediated TLR-4-Dependent Signaling Pathways.

Liver ischemia and reperfusion (I/R) induce local and distant tissue injuries, contributing to morbidity and mortality in a wider range of pathologies. This is especially seen under uncontrolled aseptic inflammatory conditions, leading to injury of remote organs, such as lung injury, and even failure. Saquinavir (SQV) is a kind of HIV protease inhibitor that possesses an anti-inflammatory property. In this study, we investigated whether SQV suppresses Toll-like receptor 4- (TLR4-) dependent signaling pathways of high-mobility group box 1 (HMGB1) and P38/JNK, conferring protection against murine liver I/R-induced lung injury. To investigate our hypothesis, C57BL/6 mice and TLR4 knockout mice (TLR4-/-) were used to perform the study. SQV administration markedly attenuated remote lung tissue injury after 1-hour ischemia and 6-hour reperfusion of the liver. To our expectation, SQV attenuated I/R-induced lung edema, hyperpermeability, and pathological injury. The beneficial effects of SQV were associated with decreased levels of circulating and lung tissue inflammatory cytokines, such as IL-6, IL-1ß, TNF-α, and iNOS. The protective effect of SQV was also associated with decreased lung tissue expression of HMGB1, TLR-4, and p-P38/JNK, but not p-ERK in wild-type liver I/R mice. Overall, this study demonstrated a new role of SQV, facilitating negative regulation of HMGB1- and P38/JNK-mediated TLR-4-dependent signaling pathways, conferring protection against liver I/R-induced lung injury.

WISP1-αvß3 integrin signaling positively regulates TLR-triggered inflammation response in sepsis induced lung injury.

We recently noted that the matricellular protein WISP1 contributes to sepsis induced acute lung injury (ALI) via integrin ß6. In the current study, we pursued further aspects of WISP1 modulation of TLR signaling in lungs of mice after sepsis and TLR4 mediated release of TNF-α in macrophages. After confirming that TLR4 and CD14 are critical in transducing sepsis mediated ALI, we now demonstrate that intrapulmonary αvß3 is increased by polymicrobrial sepsis in a TLR4, CD14 dependent fashion. Comparison of cultured macrophages revealed that WISP1 increased release of TNF-α from RAW264.7 cells with baseline expression of αvß3, but primary cultures of peritoneal macrophages (PMø) required activation of TLR4 to induce de novo synthesis of αvß3 enabling WISP1 to stimulate release of TNF-α. The specific requirement for ß3 integrin was apparent when the effect of WISP1 was lost in PMø isolated from ß3(-/-) mice. WISP1 enhanced TLR4 mediated ERK signaling and U0126 (an ERK inhibitor) blocked LPS induced ß3 integrin expression and WISP1 enhanced TNF-α release. Collectively these data suggest that WISP1-αvß3 integrin signaling is involved in TLR4 pathways in macrophages and may be an important contributor to TLR4/CD14 mediated inflammation in sepsis induced lung injury.

WISP1 mediates hepatic warm ischemia reperfusion injury via TLR4 signaling in mice.

Wnt-induced secreted protein-1 (WISP1) is an extracellular matrix protein that has been reported in cancer researches. Our previous studies on WISP1 implied it could be a harmful mediator in septic mice. However, its role in liver ischemia reperfusion (I/R) injury is unknown. This study investigated the effects of WISP1 on liver I/R damage. Male C57BL/6 wild-type mice were used to undergo 60 min segmental (70%) ischemia. WISP1 expression was measured after indicated time points of reperfusion. Anti-WISP1 antibody was injected intraperitoneally to mice. Toll-like receptor 4 (TLR4) knockout mice and TIR-domain-containing adaptor inducing interferon-ß (TRIF) knockout mice were adopted in this study. WISP1 was significantly enhanced after 6 h of reperfusion when compared with sham treated mice and significantly decreased either by TLR4 knockout mice or TRIF knockout mice. Anti-WISP1 antibody significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological changes and pro-inflammatory cytokine levels in the mice following I/R. Furthermore, significantly increased serum transaminase levels were found in C57 wild-type mice treated with recombinant WISP1 protein, but not found in TLR4 knockout or TRIF knockout mice subjected to liver I/R. Taken together, WISP1 might contribute to hepatic ischemia reperfusion injury in mice and possibly depends on TLR4/TRIF signaling.

Analgesia for total knee arthroplasty: a meta-analysis comparing local infiltration and femoral nerve block

Patients frequently experience postoperative pain after a total knee arthroplasty; such pain is always challenging to treat and may delay the patient’s recovery. It is unclear whether local infiltration or a femoral nerve block offers a better analgesic effect after total knee arthroplasty.We performed a systematic review and meta-analysis of randomized controlled trials to compare local infiltration with a femoral nerve block in patients who underwent a primary unilateral total knee arthroplasty. We searched Pubmed, EMBASE, and the Cochrane Library through December 2014. Two reviewers scanned abstracts and extracted data. The data collected included numeric rating scale values for pain at rest and pain upon movement and opioid consumption in the first 24 hours. Mean differences with 95% confidence intervals were calculated for each end point. A sensitivity analysis was conducted to evaluate potential sources of heterogeneity.While the numeric rating scale values for pain upon movement (MD-0.62; 95%CI: -1.13 to -0.12; p=0.02) in the first 24 hours differed significantly between the patients who received local infiltration and those who received a femoral nerve block, there were no differences in the numeric rating scale results for pain at rest (MD-0.42; 95%CI:-1.32 to 0.47; p=0.35) or opioid consumption (MD 2.92; 95%CI:-1.32 to 7.16; p=0.18) in the first 24 hours.Local infiltration and femoral nerve block showed no significant differences in pain intensity at rest or opioid consumption after total knee arthroplasty, but the femoral nerve block was associated with reduced pain upon movement.

Effect of saphenous nerve block for postoperative pain on knee surgery: a meta-analysis.

Early post-operative mobilization is important both to reduce immobility-related complications and to get the best functional result following surgery on knee. We hypothesized that saphenous nerve block would reduce pain in this patient category compared with placebo injection. In this study, two reviewers independently searched the databases of PubMed, EMBASE, and Cochrane Library (last performed on 12 October, 2014) to retrieve eligible randomized controlled clinical trials. The primary outcomes were visual analog scale (VAS) pain scores within 24 hours after operation when at rest and at an active flexion of knee. Mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) was calculated for each end point. Subgroup analysis was calculated to evaluate potential sources of heterogeneity. Nine randomized controlled trials were retrieved and analyzed. We found that VAS pain scores at rest within postoperative 24 hours were significantly decreased in saphenous nerve block group than that in placebo group (MD = -0.79; 95% CI -1.35 to -0.22; P = 0.007), as well as VAS pain scores at an active flexion of knee within postoperative 24 hours (MD = -0.92; 95% CI -1.61 to -0.22; P = 0.010). In addition, compared to placebo injection group, saphenous nerve block resulted in significantly less morphine consumption during the first postoperative 24 hours (MD = -6.56; 95% CI -11.26 to -1.86; P = 0.006). To conclude, this meta-analysis suggests that saphenous nerve block has an advantage in pain relief both at an active flexion of knee and at rest after knee surgery. Further studies are still wanted to validate these conclusions.

RGD peptides protects against acute lung injury in septic mice through Wisp1-integrin ß6 pathway inhibition.

Acute lung injury is a common consequence of sepsis, a life-threatening inflammatory response caused by severe infection. In this study, we elucidate the attenuating effects of synthetic Arg-Gly-Asp-Ser peptides (RGDs) on acute lung injury in a sepsis mouse model. We further reveal that the beneficial effects of RGDs stem from their negative regulation of the Wisp1 (WNT1-inducible signaling pathway)-integrin ß6 pathway. After inducing sepsis using cecal ligation and puncture (CLP), mice were randomized into experimental and control groups, and survival rates were recorded over 7 days, whereas only 20% of mice subjected to CLP survived when compared with untreated controls; the addition of RGDs to this treatment regimen dramatically increased the survival rate to 80%. Histological analysis revealed acute lung injury in CLP-treated mice, whereas those subjected to the combined treatment of CLP and RGDs showed a considerable decrease in lung injury severity. The addition of RGDs also dramatically attenuated other common sepsis-associated effects, such as increased white blood cell number in bronchoalveolar lavage fluid and decreased pulmonary capillary barrier function. Furthermore, treatment with RGDs decreased the serum and bronchoalveolar lavage fluid levels of inflammatory cytokines such as tumor necrosis factor α and interleukin 6, contrary to the CLP treatment alone that increased the levels of these proteins. Interestingly, however, RGDs had no detectable effect on bacterial invasion following sepsis induction. In addition, mice treated with RGDs showed decreased levels of wisp1 and integrin ß6 when compared with CLP-treated mice. In the present study, a linkage between Wisp1 and integrin ß6 was evaluated in vivo. Most strikingly, RGDs resulted in a decreased association of Wisp1 with integrin ß6 based on coimmunoprecipitation analyses. These data suggest that RGDs ameliorate acute lung injury in a sepsis mouse model by inhibiting the Wisp1-integrin ß6 pathway.

Transversus abdominis plane block for postoperative analgesia after laparoscopic surgery: a systematic review and meta-analysis.

BACKGROUND: The increasing use of the transversus abdominis plane (TAP) block, as a form of pain relief after laparoscopic surgery, warrants evaluation of its effectiveness, when compared with other analgesic techniques. METHODS: We searched online databases of MEDLINE, EMBASE, Google scholar and The Cochrane Database of Systematic Review. Mean differences (MD) were formulated for continuous data; odds ratios (OR) were calculated for dichotomous data. Results were produced with a random effects model with 95% confidence intervals (CI). RESULTS: 14 trials with a total of 905 patients were included for the analysis, TAP block resulted in significantly less postoperative analgesic consumption at 24 h (MD = -25.46, 95% CI [-32.22, -18.69], P < 0.00001), and less number of patients requiring analgesic postoperatively (OR = 0.16, 95% CI 0.03-0.87, P = 0.03). Meanwhile, pain sores were significantly different at 2 h (MD = -1.55, 95% CI [-2.50, -0.59], P < 0.00001), a borderline difference between the groups seen at 6 hours ( MD = -1.13, 95% CI [-1.69, -0.56], P = 0.05), and there was not affect pain at 24 h (MD = -0.33, 95% CI [-0.08, 0.15], P = 0.14) with TAP block groups compared with the groups without TAP block. There was a significant difference in postoperative nausea and vomiting (random effects model: OR = 2.04, 95% CI [1.19-3.48], P = 0.34). CONCLUSION: TAP block would result in less analgesic consumption, less requirement of analgesic, and less pain at 2 h and slightly at 6 h but at 24 h after laparoscopic surgery in comparison with usual care alone or placebo block. In addition TAP block can increase the incidence of postoperative nausea and vomiting.

Analgesic effect and adverse events of dexmedetomidine as additive for pediatric caudal anesthesia: a meta-analysis.

BACKGROUND: Dexmedetomidine has become a popular additive for regional anesthesia. Aim of this meta-analysis was to assess the effect of this additive on the duration of postoperative analgesia and possible adverse events in pediatrics undergoing orchidopexy or lower abdominal surgery. METHODS: The literature databases of PubMed, Google Scholar, and Cochrane Library were searched for randomized, controlled trials (RCTs). Odds ratio (OR), weighted mean difference (WMD), and the corresponding 95% confidence intervals (CIs) were calculated using the RevMan software, version 5.2, for data synthesis and statistical analysis, which in accordance with the PRISMA statement. RESULTS: Six RCTs were selected for this meta-analysis, involving a total of 328 pediatric patients. There was a significant longer duration of caudal analgesia (time to first analgesic requirements) in patients receiving dexmedetomidine with CA compared with CA alone (WMD: -8.21 h; 95% CI: -11.40 to -5.02; P < 0.00001). Side effects in these two groups were comparable (OR: 1.02; 95% CI: 0.51-2.04; P = 0.95). Subgroup analysis indicated there was no significant difference in hemodynamic changes during operation (WMD: 1.78; 95% CI: -3.20 to 6.77; P = 0.48) and the emergence time (time from the end of surgery to opening the eyes on calling) after surgery (WMD: 0.47 min; 95% CI: -5.27 to 6.22; P = 0.87). CONCLUSIONS: Dexmedetomidine as an additive to local anesthetic provides a significantly longer postoperative analgesia with comparable adverse effects and hemodynamic changes, when compared to local anesthetics alone. There were insufficient data of the effects of different concentrations of dexmedetomidine; further studies are required to explore this issue.

Ketamine peritonsillar infiltration during tonsillectomy in pediatric patients: An updated meta-analysis.

OBJECTIVES: Peri-operative ketamine peritonsillar infiltration in children can reduce the incidence of postoperative nausea and vomiting (PONV), but its postoperative analgesic time is short. A previous meta-analysis in 2011 was inconclusive due to insufficient data. Consequently, we updated the meta-analysis to verify the role of ketamine peritonsillar infiltration for tonsillectomy in pediatric patients. METHODS: Ten randomized controlled trials with a total of 522 cases were included. Pain intensity was measured by standard modified CHEOPS score. RESULTS: The pain scores of ketamine group at 30 min and 60 min were significantly lower than placebo group after surgery [weighted mean difference (WMD) -1.20, 95% CI -2.20 to -0.19, P=0.02; WMD -1.71, 95% CI -2.12 to -0.22, P=0.02]. Analgesic requirement in ketamine group were less than placebo group [risk ratio (RR) 0.51, 95% CI 0.26-0.97; P=0.04]. Moreover, the incidence of PONV was lower in ketamine group. (RR 0.73, 95% CI 0.54-0.97; P=0.03). However, there were no differences between these two groups in operation time, anesthesia time, first analgesic time and pain score at 120 min. CONCLUSIONS: Compared to placebo, ketamine peritonsillar infiltration can relieve postoperative pain within one hour but not at 120 min and reduces analgesic requirement and incidence of PONV. Moreover, there was no difference in the first analgesic time.

Abdominal wall-lifting versus CO2 pneumoperitoneum in laparoscopy: a review and meta-analysis.

The aim of this study is to compare the operative parameters and outcomes of conventional CO2-pneumoperitoneum (PP) versus gasless abdominal wall-lifting (AWL) for laparoscopic surgery. The literature databases of PubMed, Google Scholar and Cochrane Library were searched for randomized controlled trials (RCTs) that had compared the CO2-PP approach with that of gasless AWL for laparoscopic surgery and which had been published between 1995 and 2012. Data for the operative parameters (i.e. surgery duration, intraoperative heart rate (HR), perioperative complications, and postoperative duration of hospital stay and time to activity) and outcomes (postoperative shoulder pain, nausea/vomiting (PONV), partial pressure of CO2 in the blood (PaCO2), blood pH, and serum levels of the inflammatory cytokine interleukin (IL)-6) were extracted from the identified RCTs. RevMan software, version 5.2, was used for data synthesis and statistical analysis. Nineteen RCTs were selected for the meta-analysis, involving a total of 791 patients who had undergone laparoscopic operations with CO2-PP (n = 399) or gasless AWL (n = 392). Sub-group analysis indicated that the patients who underwent gasless AWL had significantly shorter postoperative time to activity (weighted mean difference (WMD) = -0.23 d, 95% confidence interval (CI): -0.37 to -0.09; P = 0.001), lower incidence of PONV (odds ratio (OR) = 0.24, 95% CI: 0.10 to 0.57; P = 0.001) and lower postoperative PaCO2 level (WMD = -3.09 mmHg, 95% CI: -4.66 to -1.53; P = 0.0001), compared to the patients who underwent CO2-PP. However, the CO2-PP method was associated with a significantly shorter surgery duration than the gasless AWL method (WMD = 8.61, 95% CI: 3.19 to 14.03; P = 0.002). There were no significant advantages detected for either approach with respect to the intraoperative HR, the perioperative complication rate, or the postoperative parameters of duration of hospital stay, shoulder pain, blood pH, or serum IL-6 level. We concluded form present study that the gasless AWL method has the features of shorter time, lower postoperative PaCO2, and lower PONV incidence while the CO2-PP method for laparoscopy requires shorter surgical time.

A comparison of the analgesia efficacy and side effects of paravertebral compared with epidural blockade for thoracotomy: an updated meta-analysis.

OBJECTIVE: The most recent systematic review and meta-analysis comparing the analgesic efficacy and side effects of paravertebral and epidural blockade for thoracotomy was published in 2006. Nine well-designed randomized trials with controversial results have been published since then. The present report constitutes an updated meta-analysis of this issue. SUMMARY OF BACKGROUND: Thoracotomy is a major surgical procedure and is associated with severe postoperative pain. Epidural analgesia is the gold standard for post-thoracotomy pain management, but has its limitations and contraindications, and paravertebral blockade is increasingly popular. However, it has not been decided whether the analgesic effect of the two methods is comparable, or whether paravertebral blockade leads to a lower incidence of adverse side effects after thoracotomy. METHODS: Two reviewers independently searched the databases PubMed, EMBASE, and the Cochrane Library (last performed on 1 February, 2013) for reports of studies comparing post-thoracotomy epidural analgesia and paravertebral blockade. The same individuals independently extracted data from the appropriate studies. RESULT: Eighteen trials involving 777 patients were included in the current analysis. There was no significant difference in pain scores between paravertebral blockade and epidural analgesia at 4-8, 24, 48 hours, and the rates of pulmonary complications and morphine usage during the first 24 hours were also similar. However, paravertebral blockade was better than epidural analgesia in reducing the incidence of urinary retention (p<0.0001), nausea and vomiting (p = 0.01), hypotension (p<0.00001), and rates of failed block were lower in the paravertebral blockade group (p = 0.01). CONCLUSIONS: This meta-analysis showed that PVB can provide comparable pain relief to traditional EPI, and may have a better side-effect profile for pain relief after thoracic surgery. Further high-powered randomized trials are to need to determine whether PVB truly offers any advantages over EPI.