Perioperative Injection Research Articles

The effect of a split-dose intravenous dexamethasone and a single high-dose on postoperative blood glucose after total joint arthroplasty: a randomized double-blind placebo-controlled trial

BackgroundIn patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels.MethodsIn this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated.ResultsCompared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively.ConclusionPerioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl.Trial registrationChinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760.

Perioperative multimodal analgesic injection for patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion surgery.

This retrospective cohort study compared postoperative as-needed (PRN) opioid consumption pre and postimplementation of a perioperative multimodal analgesic injection composed of ropivacaine, epinephrine, ketorolac, and morphine in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Secondary outcomes include pain score measurements, time to ambulation, length of stay, blood loss, 90-day complication rate, operating room time, nonopioid medication usage, and total inpatient medication cost before and after the initiation of this practice. Consecutive patients weighing ≥ 20kg who underwent PSF for a primary diagnosis of AIS between January 2017 and December 2020 were included. Data from 2018 were excluded to account for standardization of the practice. Patients treated in 2017 only received PCA. Patients treated in 2019 and 2020 only received the injection. Excluded were patients who had any diagnoses other than AIS, allergies to any of the experimental medications, or who were nonambulatory. Data were analyzed utilizing the two-sample t-test or Chi-squared test as appropriate. Results of this study show that compared with 47 patients treated postoperatively with patient-controlled analgesia (PCA), 55 patients treated with a multimodal perioperative injection have significantly less consumption of PRN morphine equivalents (0.3mEq/kg vs. 0.5mEq/kg; p = 0.02). Furthermore, patients treated with a perioperative injection have significantly higher rates of ambulation on postoperative day 1 compared with those treated with PCA (70.9 vs. 40.4%; p = 0.0023). Administration of a perioperative injection is effective and should be considered in the perioperative protocol in patients undergoing PSF for AIS. Therapeutic Level III.

Efficacy of topical dexamethasone eye drops in preventing ocular inflammation and cystoid macular edema following uncomplicated cataract surgery with or without injection of a single dose perioperative subtenon triamcinolone acetonide

Purpose To evaluate the efficacy and safety of topical dexamethasone (DEX) eye drops in combination with a single perioperative subtenon triamcinolone acetonide (sTA) injection versus conventional topical DEX eye drops in the prevention of ocular inflammation and cystoid macular edema following cataract surgery. Materials and methods Medical records of 245 eyes of 245 patients who underwent uncomplicated cataract surgery were analyzed in this retrospective controlled clinical study. Topical DEX eye drops were administered to 128 eyes routinely postoperatively, and 117 eyes were given a single dose of sTA (40 mg/ml) together with topical DEX eye drops for postoperative care. Postoperative topical antibiotic prophylaxis was applied to all eyes. The primary outcomes were anterior chamber (AC) cells and flare, central macular thickness (CMT), best corrected visual acuity (BCVA), and intraocular pressure (IOP) measurements on day 7, day 30, day 90, and day 180 following surgery. Results Although CMT increased in the DEX group, no increment was observed in the DEX + sTA treated group for all follow-up periods (on day 7 (+1.3 ± 18.6 and −8.7 ± 21.9 μm, p = 0.038), on day 30 (+20.5 ± 58.4 and −4.1 ± 25.2 μm, p = 0.009), on day 90 (+7.2 ± 19.9 and −5.7 ± 30.6 μm, p = 0.029), and on day 180 (+8.2 ± 22.6 and −6.4 ± 32.9 μm, p = 0.032)). There was no significant difference in terms of AC cells and flare between the two groups during the entire follow-up period (p > 0.05). Significant improvement in BCVA was observed in the DEX + sTA group at day 30 (p = 0.008). IOP differences were comparable, and both groups had high ocular tolerance. There were no severe adverse effects recorded. Conclusions Topical DEX eye drops in combination with single dose perioperative injection of sTA have robust efficacy in preventing ocular inflammation and the development of cystoid macular edema following uncomplicated cataract surgery.

Management of Perioperative Anemia in Patients that Performed Abdominal Major Surgery.

Introduction: Anemia is a recognized predictor of adverse postoperative outcomes in patients during abdominal major surgery. The management of perioperative anemia involves many strategies. Pre-operative anemia has adverse outcomes in major surgery and is called the fourth factor. Anemia was then classified into mild, moderate, and severe depending on hemoglobin level. It is present almost in 40% of patients that performed elective major surgery. Patients with preoperative anemia are associated with an increased rate of blood transfusion together with a risk for high morbidity and mortality. The most usual cause of preoperative anemia is iron deficiency, which can be treated with oral/intravenous iron depending on the time scheduled for surgery. A review concluded that anemia recovery earlier with preoperative intravenous iron than with oral iron supplement. A perioperative erythropoietin injection is also a reasonable approach for patients with hemoglobin between 10 and 13 g/dL and if autologous blood donation is performed. The protocol requires a baseline complete blood count and iron studies and all patients should receive iron supplementation during erythropoietin therapy. The next strategy is stabilized macro/ microcirculation to optimize the patient´s tolerance to bleeding. Recent recommendation, in general, suggests no bridging therapy consider it only if high thrombotic risk. Finally, targeted surgery should be used to reduce intraoperative and postoperative bleeding. We recommend a restrictive transfusion strategy. Allogeneic blood transfusion is associated with an increased incidence of nosocomial infections. Postoperative anemia must be treated with the use of intravenous iron. We ought to know fresh frozen plasma used in deficit in factor V, XI, in dose 15-30ml/kg and be aware of its complications as immunomodulation, acute lung injury, and cardiac overload.
 Conclusion: Our goal is to improve patients´ clinical outcomes.

The risk factors and predictive nomogram of human albumin infusion during the perioperative period of posterior lumbar interbody fusion: a study based on 2015\u20132020 data from a local hospital

BackgroundPerioperative hypoalbuminemia of the posterior lumbar interbody fusion (PLIF) can increase the risk of infection of the incision site, and it is challenging to accurately predict perioperative hypoproteinemia. The objective of this study was to create a clinical predictive nomogram and validate its accuracy by finding the independent risk factors for perioperative hypoalbuminemia of PLIF.MethodsThe patients who underwent PLIF at the Affiliated Hospital of Qingdao University between January 2015 and December 2020 were selected in this study. Besides, variables such as age, gender, BMI, current and past medical history, indications for surgery, surgery-related information, and results of preoperative blood routine tests were also collected from each patient. These patients were divided into injection group and non-injection group according to whether they were injected with human albumin. And they were also divided into training group and validation group, with the ratio of 4:1. Univariate and multivariate logistic regression analyses were performed in the training group to find the independent risk factors. The nomogram was developed based on these independent predictors. In addition, the area under the curve (AUC), the calibration curve and the decision curve analysis (DCA) were drawn in the training and validation groups to evaluate the prediction, calibration and clinical validity of the model. Finally, the nomograms in the training and validation groups and the receiver operating characteristic (ROC) curves of each independent risk factor were drawn to analyze the performance of this model.ResultsA total of 2482 patients who met our criteria were recruited in this study and 256 (10.31%) patients were injected with human albumin perioperatively. There were 1985 people in the training group and 497 in the validation group. Multivariate logistic regression analysis revealed 5 independent risk factors, including old age, accompanying T2DM, level of preoperative albumin, amount of intraoperative blood loss and fusion stage. We drew nomograms. The AUC of the nomograms in the training group and the validation group were 0.807, 95% CI 0.774–0.840 and 0.859, 95% CI 0.797–0.920, respectively. The calibration curve shows consistency between the prediction and observation results. DCA showed a high net benefit from using nomograms to predict the risk of perioperative injection of human albumin. The AUCs of nomograms in the training and the validation groups were significantly higher than those of five independent risk factors mentioned above (P < 0.001), suggesting that the model is strongly predictive.ConclusionPreoperative low protein, operative stage ≥ 3, a relatively large amount of intraoperative blood loss, old age and history of diabetes were independent predictors of albumin infusion after PLIF. A predictive model for the risk of albumin injection during the perioperative period of PLIF was created using the above 5 predictors, and then validated. The model can be used to assess the risk of albumin injection in patients during the perioperative period of PLIF. The model is highly predictive, so it can be clinically applied to reduce the incidence of perioperative hypoalbuminemia.

Effects of Anti-Vascular Endothelial Growth Factor Drugs Before and After Pars Plana Vitrectomy in Patients with Polypoidal Choroidal Vasculopathy and Vitreous Hemorrhage.

Purpose: To compare the clinical effects of postoperative versus perioperative injection of anti-vascular endothelial growth factor (VEGF) drugs before and after pars plana vitrectomy (PPV) in patients with vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). Methods: This was a retrospective study of patients who underwent PPV due to vitreous hemorrhage between October 2013 and June 2019 at Ningbo Eye Hospital. The patients who underwent PPV surgery due to PCV-secondary vitreous hemorrhage were included. The primary outcome was the changes in best-corrected visual acuity. The secondary outcome was the central macular thickness. Results: Compared with the postoperative group (n = 20), the perioperative group (n = 18) showed a smaller number of postoperative anti-VEGF injections (5.1 ± 0.8 vs. 8.0 ± 1.5, P < 0.05) and lower frequencies of early hyphema (5.6% vs. 30.0%, P < 0.05), and recurrent vitreous hemorrhage (11.1% vs. 30.0%, P < 0.05). The logarithm of minimal angle resolution (LogMAR) was smaller in the perioperative group compared with the postoperative group at 1 week, 1 month, and 3 months after PPV (P < 0.05), but there were no differences thereafter. Compared with the postoperative group, the perioperative group had thinner fovea at 1 week, 1 month, and 3 months (P < 0.05), but the differences disappeared after 3 months. Conclusion: In patients with PCV and vitreous hemorrhage, compared with postoperative anti-VEGF, perioperative anti-VEGF could reduce the difficulty of surgery and reduce the occurrence of postoperative complications, but there were no differences in long-term vision and macular thickness after surgery.

Risk Analysis of Perioperative Injections in Arthroscopic Reconstruction of the Rotator Cuff of the Shoulder - A Systematic Review.

The present study used a systematic review to analyse the risk of perioperative injections during arthroscopic reconstruction of the rotator cuff of the shoulder. The questions of interest were whether perioperative local injection increases the infection risk and whether the number of postoperative revisions is increased. A systematic review of the U. S. National Library of Medicine/National Institutes of Health (PubMed) database and the Cochrane Library was performed using the PRISMA checklist. The keywords used were "shoulder" and "arthroscopy" and "injection" and "risk". In the course of the study, work that was not also primarily concerned with the reconstruction of the rotator cuff was excluded. English original articles and case series were included that contained at least some arthroscopic reconstructions of the rotator cuff. The risk of bias was determined using the Newcastle-Ottawa Scale. The content of the articles relevant to the research questions was analysed. 48 hits were primarily generated. 9 articles corresponded to the inclusion criteria and were analysed. In the 6 studies with details on the injected substances, cortisone was used in 98 - 100% of the cases. The reported infection and revision rates based on insurance data were higher with injection than without. The risk of bias in the studies analysed here was rather low based on the Newcastle-Ottawa Score. The risk of infection after a cortisone injection before, during or after surgery was increased. Injection was associated with infection in up to 8% of cases with injections within two weeks of surgery. The risk of infection was increased by up to 11 times with injections within 4 weeks after the operation. Likewise, the risk of revision surgery after injection was increased, with the time intervals between injection and surgery sometimes differing between studies. Local infections and to a lesser extent revision surgery are associated with perioperative injections (with cortisone) within 3 months preoperatively and 4 weeks postoperatively. However, there were only database studies of insurance data with several studies from a few centres. Thus, no causal relationships could be proven. Currently, however, the following can be recommended using a cautious approach: The interval between injection with cortisone before surgery should be at least 2 weeks, better 3 months. No cortisone injections should be applied intraoperatively. Postoperatively, cortisone should not be injected for at least 4 weeks. If, in exceptional cases, deviations from these time limits are required, patients should be informed about an increased risk of complications.

Peri-operative Botulinum Neurotoxin injection to improve outcomes of surgeries on spastic limbs: A systematic review

Our objective was to systematically review literature regarding the rationale and current evidence for peri-operative Botulinum Neurotoxin (BoNT) injection to improve outcomes of surgeries on spastic limbs. We conducted a systematic search of databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled until March 2020, using the PRISMA guidelines. After assessing all titles and abstracts against inclusion criteria, full texts were reviewed for studies of potential interest. The inclusion criteria were studies on humans with any study design, published in all languages. Participants had to have underlying limb spasticity and be scheduled to undergo surgery on one or more spastic limb(s). BoNT had to be administered peri-operatively to improve surgical outcomes and not solely for the purpose of alleviating spasticity. The risk of bias was evaluated using the Physiotherapy Evidence Database (PEDro) scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Further, the level of evidence was evaluated using a five-level scale (simplified form of Sackett). Five studies met our inclusion criteria comprising a total of 90 participants, of both pediatric and adult age groups, with underlying limb spasticity, who received BoNT perioperatively to improve outcomes of the surgeries performed on spastic limbs. Interventions were intramuscular BoNT injection prior to, at the time of, or after surgery on a spastic limb for the purpose of improving surgical outcomes, and not solely for alleviating muscle spasticity. Outcome measures were surgical success/failure, post-operative pain and analgesic use, sleep quality, adverse events, spasticity control e.g. Modified Ashworth Scale. Our literature search yielded 5 articles that met the inclusion criteria. Current evidence supports peri-operative injection of BoNT to improve outcomes of surgeries performed on spastic limbs. There is level 1 evidence that BoNT administered pre-operatively is effective for reducing pain, spasticity, and analgesic use in pediatric patients with cerebral palsy (CP). This is supported by level 4 evidence from a retrospective case series. Level 5 evidence from case reports highlights the potential for the use of BONT in the peri-operative period. There is level 1 evidence that BoNT administered intra-operatively is not effective for reducing pain and analgesic use in pediatric patients with CP. This lack of benefit may reflect sub-optimal timing of injections, different methods of injection, different timing of the primary outcome measure, and/or differences in adjunctive therapies, but further research is required.

Temporary inhibition of the plasminogen activator inhibits periosteal chondrogenesis and promotes periosteal osteogenesis during appendicular bone fracture healing

Aminocaproic acid is approved as an anti-fibrinolytic for use in joint replacement and spinal fusion surgeries to limit perioperative blood loss. Previous animal studies have demonstrated a pro-osteogenic effect of aminocaproic acid in spine fusion models. Here, we tested if aminocaproic acid enhances appendicular bone healing and we sought to uncover the effect of aminocaproic acid on osteoprogenitor cells (OPCs) during bone regeneration. We employed a well-established murine femur fracture model in adult C57BL/6J mice after receiving two peri-operative injections of aminocaproic acid. Routine histological assays, biomechanical testing and micro-CT analyses were utilized to assess callus volume, and strength, progenitor cell proliferation, differentiation, and remodeling in vivo. Two disparate ectopic transplantation models were used to study the effect of the growth factor milieu within the early fracture hematoma on osteoprogenitor cell fate decisions. Aminocaproic acid treated femur fractures healed with a significantly smaller cartilaginous callus, and this effect was also observed in the ectopic transplantation assays. We hypothesized that aminocaproic acid treatment resulted in a stabilization of the early fracture hematoma, leading to a change in the growth factor milieu created by the early hematoma. Gene and protein expression analysis confirmed that aminocaproic acid treatment resulted in an increase in Wnt and BMP signaling and a decrease in TGF-β-signaling, resulting in a shift from chondrogenic to osteogenic differentiation in this model of endochondral bone formation. These experiments demonstrate for the first time that inhibition of the plasminogen activator during fracture healing using aminocaproic acid leads to a change in cell fate decision of periosteal osteoprogenitor cells, with a predominance of osteogenic differentiation, resulting in a larger and stronger bony callus. These findings may offer a promising new use of aminocaproic acid, which is already FDA-approved and offers a very safe risk profile.

A Single Perioperative Injection of Dexamethasone Decreases Nausea, Vomiting, and Pain after Laparoscopic Donor Nephrectomy.

Background. A single dose of perioperative dexamethasone (8–10 mg) reportedly decreases postoperative nausea, vomiting, and pain but has not been widely used in laparoscopic donor nephrectomy (LDN). Methods. We performed a retrospective cohort study of living donors who underwent LDN between 2013 and 2015. Donors who received a lower dose (4–6 mg) (n = 70) or a higher dose (8–14 mg) of dexamethasone (n = 100) were compared with 111 donors who did not receive dexamethasone (control). Outcomes and incidence of postoperative nausea, vomiting, and pain within 24 h after LDN were compared before and after propensity-score matching. Results. The higher dose of dexamethasone reduced postoperative nausea and vomiting incidences by 28% (P = 0.010) compared to control, but the lower dose did not. Total opioid use was 29% lower in donors who received the higher dose than in control (P = 0.004). The higher dose was identified as an independent factor for preventing postoperative nausea and vomiting. Postoperative complication rates and hospital stays did not differ between the groups. After propensity-score matching, the results were the same as for the unmatched analysis. Conclusion. A single perioperative injection of 8–14 mg dexamethasone decreases antiemetic and narcotic requirements in the first 24 h, with no increase in surgical complications.

AN APPROACH FOR MEDIASTINITIS PREVENTIONIN PATIENTS FOLLOWING CARDIAC SURGERY

The aim of this study was to reduce incidence of sternal deep wound infection (DWI) in patients following cardiac surgery. An experience of cardiac surgery by sternotomy access in 429 consecutive patients was presented. Perioperative intravenous injections of cefazolin were used in 225 patients (control group). Combination of perioperative intravenous injections with local retrosternal irrigation of cefazolin before sternum closure was used in 204 patients (study group). In control group sternal DWI occurred in 10 patients (4.4%), and in 4 patients a resternotomy sanation required. There were no deaths in this group due to infection or sepsis. In follow-up period (3 years), instability of sternum occurred in 3 patients (1.3%), and in 1 (0.4%) sternum reosteosynthesis required. In studied group the sternal DWI did not occur (p&lt;0.01). Sternum instability and/or indications for sternum reosteosynthesis were not determined in follow-up period (2 years). It was concluded, that combination of intravenous and local usage of cefazolin in cardiac surgery patients is a simple and effective approach to prevent sternal DWI. Application of this method significantly (p&lt;0.01) reduces the incidence rate of mediastinitis.

Protocol for a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus single-agent femoral nerve blockade as analgesia for total knee arthroplasty: Perioperative Analgesia for Knee Arthroplasty (PAKA)

IntroductionTotal knee arthroplasty (TKA) surgery causes postoperative pain. The use of perioperative injections around the knee containing local anaesthetic, opiates and non-steroidal anti-inflammatory drugs has increased in popularity to manage...

Sequential Therapy with Saratin, Bevacizumab and Ilomastat to Prolong Bleb Function following Glaucoma Filtration Surgery in a Rabbit Model.

To determine if sequential treatment with Bevacizumab (Avastin), a monoclonal, VEGF antibody that blocks angiogenesis; Saratin, a 12 kD polypeptide with anti-inflammatory and anti-thrombotic properties; and Ilomastat, a matrix metalloproteinase (MMP) inhibitor, prolongs bleb life following glaucoma filtration surgery (GFS) in a rabbit model. Thirty-two New Zealand White rabbits (eight rabbits per group) underwent GFS in the left eye. Group 1 received a perioperative injection of both Saratin and Bevacizumab, and later, subconjuctival injections of Ilomastat on days 8 and 15. Group 2 received only Saratin perioperatively, and also received Ilomastat injections on days 8 and 15. Group 3, the negative control, received a single perioperative injection of Balanced Saline Solution (BSS) along with post-operative BSS injections on days 8 and 15. Group 4, the positive control, received topical treatment with Mitomycin-C (MMC) at the time of surgery with no further treatment. Blebs were evaluated by an observer masked to treatment every third day. Histology was obtained on two eyes in each group on post-op day twelve as well as all eyes following bleb failure. Eyes in group 1 had a mean bleb survival time of 29 ± 2.7 days, whereas those in group 2 that received the experimental treatment without Bevacizumab had a mean survival time of 25.5 ± 2.7 days. An ANOVA test showed that the Saratin/Ilomastat/Bevacizumab group demonstrated a significant prolongation of bleb survival compared to the BSS control—mean survival time of 19.7 ±2.7 days—(p = 0.0252) and was not significantly different from the MMC positive control group (p = 0.4238)—mean survival time of 32.5 ± 3.3. From tissue histology at day 12, the four different groups showed marked differences in the cellularity and capsule fibrosis. The MMC eyes showed minimal cellularity, were avascular and had minimal fibrous tissue. BSS group showed high cellularity, moderate to high fibrosis, and thicker and more defined capsules than either of the treatment groups and the positive control. Both the Saratin/Ilomastat/Bevacizumab and Saratin/Ilomastat only eyes showed moderate cellularity with minimal fibrosis, with less cellularity and fibrosis present in the triple treatment group. Sequential therapy with multiple agents, including Bevacizumab, prolonged bleb function following GFS in the rabbit model and were significantly better than the negative BSS control. The experimental group did not show the same surface tissue histological thinning and side effects associated with MMC treatment.

Multiple low doses of erythropoietin delay the proliferation of hepatocytes but promote liver function in a rat model of subtotal hepatectomy

The impact of various doses of erythropoietin (EPO) on liver regeneration after partial hepatectomy (PH) in different animal models is still under debate. We investigated the impact of low doses of EPO on liver regeneration in a rat model of subtotal hepatectomy. We established a 90 % PH rat model with perioperative injections of low-dose EPO (1,000 IU/kg). We analyzed survival and hepatocyte proliferation in animals treated with or without EPO and assessed liver function by blood ammonia measurement and the indocyanine green 15-min retention test. Low doses of EPO treatment improved the survival of rats after 90 % PH. Unexpectedly, during the first 24 h after the operation, liver regeneration in the EPO-treated rats was inhibited. DNA synthesis, cell proliferation, and the expression of cyclins and p-STAT3 peaked 48 h after PH, which was delayed by about 24 h vs. the control rats. Furthermore, EPO treatment increased the serum level of IL-6 and protected the hepatocytes from apoptosis. Low doses of EPO do not stimulate early hepatocyte proliferation in the regenerating liver, but contribute to liver protection by inducing IL-6 and inhibiting apoptosis.

Hypoxia preconditioned bone marrow mesenchymal stem cells promote liver regeneration in a rat massive hepatectomy model

IntroductionBone marrow mesenchymal stem cells (BMMSCs) have been reported to facilitate liver regeneration after toxic injuries. However, the effect of BMMSCs on liver regeneration after massive hepatectomy is barely studied. Here we explored whether infusion of BMMSCs promotes liver regeneration in a rat massive hepatectomy model.MethodsHypoxia preconditioning was achieved by culturing BMMSCs under a hypoxia environment. Then 85% hepatectomy was performed and hypoxia or normoxia preconditioned BMMSCs were infused into the portal vein. A group of rats received vascular endothelial growth factor (VEGF) neutralizing antibody perioperatively, and underwent 85% hepatectomy and a subsequent infusion of hypoxia preconditioned BMMSCs to verify the role of VEGF in the effects of BMMSCs on liver regeneration. Liver samples were collected and liver regeneration was evaluated postoperatively.ResultsHypoxia preconditioning enhanced the expression of VEGF in BMMSCs in vitro. Infusion of BMMSCs promoted proliferation of hepatocytes, reflected by elevated cyclin D1 expression and proliferating cell nuclear antigen-positive hepatocytes. However, BMMSC infusion did not improve the serum albumin level, liver weight/body weight ratio, and survival after operation. Infusion of hypoxia preconditioned BMMSCs significantly elevated cyclin D1, proliferating cell nuclear antigen-positive hepatocytes, liver weight/body weight ratio, and survival compared with normoxia preconditioned BMMSCs, accompanied by an increased serum albumin level. The level of VEGF in liver homogenate was much higher in hypoxia preconditioned BMMSC-treated animals than in other groups. In addition, the perioperative injection of VEGF neutralizing antibody significantly blocked the therapeutic effects of hypoxia preconditioned BMMSCs on liver injury and regeneration in this model.ConclusionHypoxia preconditioned BMMSCs enhanced liver regeneration after massive hepatectomy in rats, possibly by upregulating the level of VEGF.

Intracoronary Treatment with VEGF-C/D Inhibitor Enhances Cardiac Allograft Survival and Prevents Chronic Rejection by Regulating Lymphatic Endothelial Cell Activation

Purpose VEGF-C/D/VEGFR-3 signaling may regulate lymphatic vessel activation and the initiation of alloimmunity after transplantation. We investigated the effect of perioperative intracoronary injection of synthetic VEGF-C/D inhibitor on lymphatic activation, antigen-presenting cell trafficking and subsequent development of alloimmune responses in rat cardiac allografts. Methods and Materials We perfused the coronaries of DA donor rat hearts ex vivo with VEGF-C/D inhibitor or PBS and preserved the grafts in +4°C PBS for 4h and then transplanted the grafts to fully MHC-mismatched WF recipient rats. We analyzed ischemia-reperfusion injury, and acute and chronic rejection responses. In acute and chronic rejection models, the recipients received CyA as immunosuppression. Results At 6h after the reperfusion, VEGF-C/D inhibitor did not affect the myocardial injury but reduced the number of LYVE-1+ lymphatic vessels expressing VEGFR-3, ICAM-1 and VCAM-1 in the allograft and reduced the number of dendritic cells migrating out of the allograft. VEGF-C/D inhibition enhanced allograft survival in acute rejection model. In chronic rejection model, VEGF-C/D inhibitor reduced allograft inflammation and prevented the development of cardiac fibrosis and vasculopathy. Conclusions Intracoronary treatment with VEGF-C/D inhibitor prevented early activation of lymphatic endothelial cells and trapped dendritic cells into the allograft. This interfered with allorecognition resulting in reduced acute and chronic rejection responses. Our results suggest donor single-dose intracoronary treatment with VEGF-C/D inhibitor as a novel clinically feasible lymphatic vessel targeted immunomodulatory approach. [ figure 1 ]

SAFETY OF MEDIUM-CHAIN TRIGLYCERIDES USED AS AN INTRAOCULAR TAMPONADING AGENT IN AN EXPERIMENTAL VITRECTOMY MODEL RABBIT

To evaluate safety of medium-chain triglycerides used as a possible intraocular tamponading agent. A 20-gauge pars plana vitrectomy was performed in the right eye of 28 rabbits. An ophthalmologic examination was performed every week until rabbits were killed. At days 7, 30, 60, and 90, rabbits were killed and the treated eyes were examined macroscopically and prepared for histologic examination. Principal outcome was retinal toxicity evaluated by light and electron microscopy, and secondary outcomes were the presence of medium-chain triglyceride emulsification, inflammatory reactions, and the development of cataract. Histologic examination did not reveal any retinal toxicity. Two cases of moderate emulsification were observed, but in these cases, emulsification was caused by the perioperative injection of the agent and did not increase during the postoperative period. We noted 13 cases of inflammatory reaction in vitreous cavity and no case of inflammatory reaction in anterior chamber. Two eyes developed cataract as a result of perioperative trauma to the lens with the vitreous cutter and not secondary to the presence of medium-chain triglycerides in the vitreous cavity. Medium-chain triglycerides did not induce morphologic evidence of retinal toxicity. The results suggest that medium-chain triglycerides could be a promising alternative intraocular tamponading agent for the treatment of retinal detachments.

Clinical effect of perioperative injection of analgecine on patient-controlled intravenous analgesia of fentanyl in lumbotomy patients

Objective To compare the effect of perioperative intravenous injection of Analgecine on the analgesic efficacy and complications of patient-controlled intravenous analgesia ( PCIA ) of different doses of fentsnyl in postoperative lumhotomy patients.Methods 200 patients underweat hmbotomy in general anesthesia were randomly divided into four groups with fifty cases each.Fentanyl 1.0mg in group A,fentanyl 0.5mg in group B,fentanyl 1.0mg in group C,fentanyl 0.5mg in group D.The drugs in each group were diluted to 100ml and infused by pumps.Besides,the patients in group C and D were injected with analgecine 3.6u and 7.2u at the night before the operation,preoperation and postoperation respectively.The visual analog scale(VAS),times of PCA and incidence of side effects were recorded during the period of postoperative 24 hours.Results The VAS of group B at 2h after operation was (5.2 ± 1.9 ) points,which was significandy higher than that of group A,C and D( P ＜ 0.05 ),VAS became similar 4h later( P ＞0.05).The demanding times for supplemental bolus in group B were also significantly higher than that of A,C and D( P ＜ 0.05 ).The incidence of nausea,vomiting,itching,somnolence in group B and D were significantly less than those in group A and C( P ＜0.05 ).No respiratory depression or abnormal bleeding occurred in the four groups.Conclusion Perioperative intravenous injection of analgecine had a better effect on PCIA of fentanyl and could reduce fentanyl requirement and its side effects in lumbotomy patients. Key words: Analgesia, patient-controlled; Orthopedic proccdures; Analgecine; Fentanyl

The history and pharmacology of fentanyl: relevance to a novel, long‐acting transdermal fentanyl solution newly approved for use in dogs

Fentanyl is a potent mu opioid receptor agonist that was discovered to identify an improved human health analgesic over morphine, an opioid frequently associated with histamine-release, bradycardia, hyper- or hypotension, and prolonged postoperative respiratory depression. Historically, the pharmacological features of fentanyl have been described primarily through the study of the human approved fentanyl citrate formulation. In conscious dogs, fentanyl has a wide margin of safety, possesses minimum effects on the cardiovascular and respiratory systems, and is readily reversible. Other pharmacological features include sedation, mild reductions in body temperature, and dose-dependent reduction in food intake. The short duration of effect of available fentanyl citrate solutions has limited its clinical use to perioperative injections or constant rate infusions (CRIs). To extend the analgesic effect, additional fentanyl delivery technologies have been developed for human health including the fentanyl patch that has been used in an extra-label manner in dogs. Beyond the slow onset and variability in fentanyl delivery, several additional disadvantages have precluded common use of patches in dogs. The recent approval of long-acting transdermal fentanyl solution for dogs provides a new approach for sustained delivery of fentanyl for the control of postoperative pain in dogs. It has a rapid onset of action, prolonged duration, and mitigates the disadvantages of oral, parenteral, and patch-delivered opioids. The availability of a safe and effective approved opioid in dogs may allow further optimization of postoperative analgesia in this species. The objective of this review is to summarize the history and pharmacology of fentanyl and to integrate information about the newly approved long-acting transdermal fentanyl solution.

23‐gauge versus 20‐gauge vitrectomy for diabetic vitreous hemorrhage

Abstract Purpose To compare 23‐gauge and 20‐gauge vitrectomy for diabetic vitreous hemorrhage (VH) regarding postoperative VH (PVH), re‐operation rates, visual acuity (VA) and safety profiles. Methods This was a retrospective chart review of diabetic patients who underwent 20‐gauge or 23‐gauge vitrectomy for persistent VH at our unit between January 2004 and June 2009. Exclusion criteria were silicone oil or gas tamponade, prior vitrectomies, perioperative injection of anti‐vascular endothelial growth factor and a follow up less than 12 months. PVH was classified as early and late PVH occurring within and &gt;2 months after surgery. Samples were compared with independent t test and Mann‐Whitney‐U test depending on distribution. Categorical data were compared with Fisher exact test. Results Hundred and six eyes met our inclusion criteria. Sixty one eyes underwent 20‐gauge and forty six 23‐gauge vitrectomy. Early PVH was observed in 27.8% and 20% in the 20‐gauge and 23‐gauge group, respectively (p=0.44). Late PVH was noted in 24.6% and 22.2% using 20‐gauge and 23‐gauge system (0.83). Re‐operation rates due to early and late PVH were similar among the groups. Final VA averaged 0.71 and 0.68 logMAR in the 20‐gauge and 23‐gauge group (p=0.81). Postoperative hypotony was observed in 8.9% of cases in the 23‐gauge group. Rhegmatogeneous retinal detachment occurred in one eye in each group. Conclusion 23‐gauge vitrectomy is a viable method for diabetic VH providing similar anatomical and functional outcome like after conventional 20‐gauge vitrectomy. The safety profile is acceptable since postoperative hypotony resolved in all cases without intervention.