Effects of propofol on the inflammatory response during robot-assisted laparoscopic radical prostatectomy: a prospective randomized controlled study

Robot-assisted laparoscopic radical prostatectomy (RALRP) is a minimally invasive procedure; however, some amount of surgical trauma that can trigger systemic inflammation remains. Moreover, pneumoperitoneum during RALRP induces ischemia-reperfusion injury (IRI). Propofol, an anesthetic, is known to have anti-inflammatory and antioxidant properties. In the present study, we compared the effects of propofol with those of desflurane on inflammation and IRI during RALRP via measurements of different biomarkers and evaluation of perioperative renal function. Fifty patients were randomized to receive either desflurane (n = 25) or propofol (n = 25) with remifentanil during RALRP. Serum levels of interleukin (IL)-6 (IL-6), tumor necrosis factor alpha, C-reactive protein, and nitric oxide were measured 10 min after anesthesia induction (T1), 100 min after carbon dioxide (CO2) insufflation (T2), and 10 min after CO2 deflation (T3). Perioperative urine outputs and the serum creatinine level at 24 h after surgery were also recorded. We found that IL-6 levels at T2 and T3 were higher than those at T1 in both groups, although the increases were significant attenuated only in the propofol group. The other parameters showed no differences among the three time points in both groups. The intraoperative urine output was significantly higher in the propofol group than in the desflurane group, while the creatinine level showed no significant changes in either group. Our findings suggest that propofol can not only attenuate the inflammatory response during and after pneumoperitoneum in patients undergoing RALRP but also prevent oliguria during pneumoperitoneum.ope

Effects of positive end-expiratory pressure on intraocular pressure and optic nerve sheath diameter in robot-assisted laparoscopic radical prostatectomy: A randomized, clinical trial

BACKGROUND: There has been no study of the effect of post end-expiratory pressure (PEEP) on intraocular or intracranial pressure during pneumoperitoneum with steep Trendelenburg positioning. We investigated the effects of 5 cmH2O of PEEP on intraocular pressure and optic nerve sheath diameter as a surrogate for intracranial pressure in robot-assisted laparoscopic radical prostatectomy. METHODS: Fifty patients scheduled for robot-assisted laparoscopic radical prostatectomy were divided into a zero-PEEP (ZEEP) group and a 5 cmH2O of PEEP (PEEP) group. Intraocular pressure, optic nerve sheath diameter, and respiratory and hemodynamic parameters were measured before induction (T0), 10 minutes after induction of general anesthesia in the supine position before CO2 insufflation (T1), 5 minutes (T2), and 30 minutes (T3) after steep Trendelenburg positioning with pneumoperitoneum, after desufflation of pneumoperitoneum in the supine position (T4), and after 30 minutes in the recovery room postoperatively (T5). RESULTS: There was no significant difference in intraocular pressure or optic nerve sheath diameter between the groups during the study. The partial pressure of arterial oxygen and dynamic lung compliance at T1, T2, T3, and T4 were significantly higher in the PEEP than in the ZEEP group. There was no difference in mean arterial pressure or heart rate between groups at any time. CONCLUSION: Applying 5 cmH2O of PEEP did not increase intraocular pressure or optic nerve sheath diameter during pneumoperitoneum with steep Trendelenburg positioning in robot-assisted laparoscopic radical prostatectomy. These results suggest that low PEEP can be safely applied during surgery with pneumoperitoneum and steep Trendelenburg positioning in patients without preexisting eye disease and brain pathology.ope

Effect of erythropoietin on the incidence of acute kidney injury following complex valvular heart surgery: a double blind, randomized clinical trial of efficacy and safety

INTRODUCTION: Recombinant human erythropoietin (EPO) is known to provide organ protection against ischemia-reperfusion injury through its pleiotropic properties. The aim of this single-site, randomized, case-controlled, and double-blind study was to investigate the effect of pre-emptive EPO administration on the incidence of postoperative acute kidney injury (AKI) in patients with risk factors for AKI undergoing complex valvular heart surgery. METHODS: We studied ninety-eight patients with preoperative risk factors for AKI. The patients were randomly allocated to either the EPO group (n = 49) or the control group (n = 49). The EPO group received 300 IU/kg of EPO intravenously after anesthetic induction. The control group received an equivalent volume of normal saline. AKI was defined as an increase in serum creatinine >0.3 mg/dl or >50% from baseline. Biomarkers of renal injury were serially measured until five days postoperatively. RESULTS: Patient characteristics and operative data, including the duration of cardiopulmonary bypass, were similar between the two groups. Incidence of postoperative AKI (32.7% versus 34.7%, P = 0.831) and biomarkers of renal injury including cystatin C and neutrophil gelatinase-associated lipocalin showed no significant differences between the groups. The postoperative increase in interleukin-6 and myeloperoxidase was similar between the groups. None of the patients developed adverse complications related to EPO administration, including thromboembolic events, throughout the study period. CONCLUSIONS: Intravenous administration of 300 IU/kg of EPO did not provide renal protection in patients who are at increased risk of developing AKI after undergoing complex valvular heart surgery.ope

Dexmedetomidine attenuates subarachnoid hemorrhage-induced acute lung injury through regulating autophagy and TLR/NFκB signaling pathway

Background: Acute lung injury (ALI) is the most serious complication of subarachnoid hemorrhage (SAH). We investigated role of autophagy and inflammatory signaling pathways in lung damage and therapeutic effects of dexmedetomidine (DEX). Methods: Fifty male Wistar rats were randomly divided into five groups: sham, SAH, SAH+ DEX5, SAH+DEX25, and SAH+DEX50. SAH was induced using endovascular perforation technique. All rats received mechanical ventilation for 60 minutes. At 2 and 24 h of SAH induction, SAH+DEX groups were treated with 5, 25, and 50 µg/kg of DEX, respectively. Histological ALI score and pulmonary edema were assessed after 48 h. Lung expression of LC3B, ATG3, p62, TLR4, TLR9, and NFκB was assessed using western blotting and quantitative PCR. Blood levels of IL-6, IL-1β, IFN-γ, and TNFα were also assessed. Results: SAH induced ALI and pulmonary edema, which were attenuated in SAH+DEX5 (P < 0.001 for both) and SAH+DEX25 groups (P = 0.001 and P < 0.001 for ALI and edema, respectively). Lung expressions of LC3B and ATG3 were upregulated in SAH group, which was attenuated in SAH+DEX5 and SAH+DEX25 groups. Lung expressions of TLR4, TLR9, and NFκB were increased in SAH group, which was attenuated in SAH+DEX5 group. Blood IL-6 level was increased in SAH group and attenuated in SAH+DEX5 and SAH+DEX25 groups. Blood IFN-γ level was lower in SAH group than in sham group, and it was increased in SAH+DEX25 group. Conclusions: Low-dose DEX treatment after SAH may protect against ALI by disrupting pathological brain-lung crosstalk and alleviating autophagy flux and TLR-dependent inflammatory pathways.ope

Effect of pregabalin administration upon reperfusion in a rat model of hyperglycemic stroke: Mechanistic insights associated with high-mobility group box 1

Hyperglycemia, which reduces the efficacy of treatments and worsens clinical outcomes, is common in stroke. Ability of pregabalin to reduce neuroexcitotoxicity may provide protection against stroke, even under hyperglycemia. We investigated its protective effect against hyperglycemic stroke and its possible molecular mechanisms. Male Wistar rats administered dextrose to cause hyperglycemia, underwent middle cerebral artery occlusion for 1 h and subsequent reperfusion. Rats were treated with an intraperitoneal injection of 30 mg/kg pregabalin or an equal amount of normal saline at the onset of reperfusion (n = 16 per group). At 24 h after reperfusion, neurological deficit, infarct volume, and apoptotic cell count were assessed. Western blot analysis was performed to determine protein expression of high-mobility group box 1 (HMGB1), toll-like receptor-4 (TLR-4), phosphorylated nuclear factor-kappa B (p-NF-κB), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), phosphorylated inducible and endothelial nitric oxide synthase (p-iNOS, p-eNOS), Bcl-2, Bax, Cytochrome C, and caspase-3 in the brain. Pregabalin-treated rats showed significantly improved neurological function (31% decrease in score), reduced infarct size (by 33%), fewer apoptotic cells (by 63%), and lower expression levels of HMGB1, TLR4, p-NF-κB, IL-1β, and TNF- α, compared with control rats. Decreased p-iNOS and increased p-eNOS expressions were also observed. Expression of Bax, Cytochrome C, and cleaved caspase-3/caspase3 was significantly downregulated, while Bcl-2 expression was increased by pregabalin treatment. Pregabalin administration upon reperfusion decreased neuronal death and improved neurological function in hyperglycemic stroke rats. Cogent mechanisms would include attenuation of HMGB1/TLR-4-mediated inflammation and favorable modulation of the NOS.ope

Validation of pulse pressure variation and corrected flow time as predictors of fluid responsiveness in patients in the prone position

BACKGROUND: The aim of this prospective trial was to investigate the ability of pulse pressure variation (PPV) and corrected flow time (FTc) to predict fluid responsiveness in the prone position. METHODS: Forty-four patients undergoing lumbar spine surgery in the prone position on a Wilson frame were prospectively studied. PPV and FTc were measured before and after a colloid bolus (6 ml kg(-1)) both in the supine and in the prone positions. Fluid responsiveness was defined as an increase in the stroke volume index of ≥ 10% as measured by oesophageal Doppler. RESULTS: In the supine position, 26 patients were responders and the areas under the curve (AUC) of the receiver-operator characteristic (ROC) curves of PPV and FTc were 0.935 [95% confidence interval (CI): 0.870-0.999, P<0.001] and 0.822 (95% CI: 0.682-0.961, P<0.001), respectively. The optimal cut-off PPV and FTc values were 15% (sensitivity 73%, specificity 94%) and 358 ms (sensitivity 88%, specificity 78%), respectively. In the prone position, 34 patients were responders and the AUCs of PPV and FTc were 0.969 (95% CI: 0.912-1.000, P<0.001) and 0.846 (95% CI: 0.706-0.985, P=0.001), respectively. The optimal cut-off PPV and FTc values were 14% (sensitivity 97%, specificity 90%) and 331 ms (sensitivity 77%, specificity 90%), respectively. CONCLUSIONS: While the predictability of PPV was significantly higher than that of FTc in the prone position, both variables showed high predictability and remained as useful indices for guiding fluid therapy in prone patients with minimal alterations in their optimal cut-off values to predict fluid responsiveness. Clinical trial registration URL: http://www.clinicaltrials.gov/ct2/show/NCT01646359?term=NCT01646359&rank=1 and unique identification number NCT01646359.ope

Pulmonary effects of dexmedetomidine infusion in thoracic aortic surgery under hypothermic circulatory arrest: a randomized placebo-controlled trial

Dexmedetomidine has emerged as a promising organ protective agent. We performed prospective randomized placebo-controlled trial investigating effects of perioperative dexmedetomidine infusion on pulmonary function following thoracic aortic surgery with cardiopulmonary bypass and moderate hypothermic circulatory arrest. Fifty-two patients were randomized to two groups: the dexmedetomidine group received 1 µg/kg of dexmedetomidine over 20 min after induction of anesthesia, followed by 0.5 µg/kg/h infusion until 12 h after aortic cross clamp (ACC)-off, while the control group received the same volume of normal saline. The primary endpoints were oxygenation indices including arterial O2 partial pressure (PaO2) to alveolar O2 partial pressure ratio (a/A ratio), (A-a) O2 gradient, PaO2/FiO2 and lung mechanics including peak inspiratory and plateau pressures and compliances, which were assessed after anesthesia induction, 1 h, 6 h, 12 h, and 24 h after ACC-off. The secondary endpoints were serum biomarkers including interleukin-6, tumor necrosis factor-α, superoxide dismutase, and malondialdehyde (MDA). As a result, dexmedetomidine did not confer protective effects on the lungs, but inhibited elevation of serum MDA level, indicative of anti-oxidative stress property, and improved urine output and lower requirements of vasopressors.ope

Optimal Anticoagulation during Off Pump Coronary Artery Bypass in Patients Recently Exposed to Clopidogrel

PURPOSE: The aim of this study was to find an optimal range of activated clotting time (ACT) during off-pump coronary artery bypass surgery (OPCAB) yielding ischemic protection without the risk of hemorrhagic complications in patients with recent exposure to dual antiplatelet therapy. MATERIALS AND METHODS: Three hundred and five patients who received aspirin and clopidogrel within 7 days of isolated multi-vessel OPCAB were retrospectively studied. Combined hemorrhagic and ischemic outcome was defined as the occurrence of 1 of the following: significant perioperative bleeding (>30% of estimated blood volume), transfusion of packed red blood cell (pRBC) ≥ 2 U, or myocardial infarction (MI). This was compared in relation to the tertile distribution of the time-weighted average ACT-212-291 sec (first tertile), 292-334 sec (second tertile), 335-485 sec (third tertile). RESULTS: The amount of perioperative blood loss was 937 ± 313 mL, 1014 ± 340 mL, and 1076 ± 383 mL, respectively (p=0.022). Significantly more patients in the third tertile developed MI (4%, 4%, and 12%, respectively, p=0.034). The incidence of significant perioperative blood loss and transfusion of pRBC ≥ 2 U were lower in the first tertile than those of other tertiles without statistical significance. In the multivariate analysis, the first tertile was associated with a 52% risk reduction of combined hemorrhagic and ischemic outcomes (95% confidence interval: 0.25-0.92, p= 0.027). CONCLUSION: A lower degree of anticoagulation with a reduced initial heparin loading dose should be carefully considered for patients undergoing OPCAB who have recently been exposed to clopidogrel.ope

Postoperative pain and patient-controlled epidural analgesia-related adverse effects in young and elderly patients: a retrospective analysis of 2,435 patients

In this retrospective study, data of 2,435 patients who received fentanyl and ropivacaine-based patient-controlled epidural analgesia (PCEA) for pain relief after elective surgery under general or spinal anesthesia were reviewed. Differences in postoperative pain, incidence of patient-controlled analgesia (PCA)-related adverse effects, and risk factors for the need for rescue analgesics for 48 hours postsurgery in young (age 20-39 years) and elderly (age ≥70 years) patients were evaluated. Although there were no significant differences in postoperative pain intensity between the two groups until 6 hours postsurgery, younger patients experienced greater postoperative pain intensity compared with older patients 6-48 hours postsurgery. While younger patients exhibited greater incidence of numbness, motor weakness, and discontinuation of PCA postsurgery, elderly patients exhibited greater incidence of hypotension, nausea/vomiting, rescue analgesia, and antiemetic administration. Upon multivariate analysis, low fentanyl dosage and history of smoking were found to be associated with an increased need for rescue analgesia among younger patients, while physical status classification III/IV and thoracic surgery were associated with a decreased need for rescue analgesia among the elderly. Discontinuation of PCA was more frequent among younger patients than the elderly (18.5% vs 13.5%, P=0.001). Reasons for discontinuation of PCA among young and elderly patients, respectively, were nausea and vomiting (6.8% vs 26.6%), numbness or motor weakness (67.8% vs 11.5%), urinary retention (7.4% vs 8.7%), dizziness (2.2% vs 5.2%), and hypotension (3.1% vs 20.3%). In conclusion, PCEA was more frequently associated with numbness, motor weakness, and discontinuation of PCA in younger patients and with hypotension, nausea/vomiting, and a greater need for rescue analgesics/antiemetics among elderly patients. Therefore, in order to minimize the adverse effects of PCEA and enhance pain relief, different PCEA regimens and administration/prevention strategies should be considered for young and elderly patients.ope

Prognostic value of preoperative serum alkaline phosphatase for predicting 3-year mortality in patients undergoing kidney transplantation: A retrospective study

Serum alkaline phosphatase (ALP) levels are related to high-turnover bone disease and reflect vascular calcification and inflammation. ALP has been reported to have a prognostic impact in various cohorts including chronic kidney disease. This study investigated whether preoperative serum ALP level could be used for predicting mortality in patients undergoing kidney transplantation. We retrospectively reviewed 1,718 patients who underwent kidney transplantation between November 2005 and June 2017. Finally, 1,533 patients who met the inclusion criteria were classified into tertiles based on preoperative serum ALP level ( 72 IU/L). The incidence of mortality was compared among the three tertiles, and a stepwise logistic regression analysis was performed to evaluate the predictors for mortality. The incidence of 3-year mortality was the highest in the third tertile (1.0% vs. 2.5% vs. 4.4% in the first, second, and third tertile, respectively, p = 0.003). The third tertile of ALP level (odds ratio [OR] 1.855, 95% CI 1.192-2.886, p = 0.006), age (OR 1.052, 95% CI 1.022-1.082, p = 0.011), and history of hypertension (OR 0.401, 95% CI 0.210-0.765, p = 0.006) remained as independent predictors of mortality. Preoperative serum ALP level was significantly higher in the non-survivor group than in the survivor group (58.00 [44.00-76.00] vs. 75.00 [56.25-113.00], p = 0.003). The optimal cut-off value of serum ALP to predict 3-year mortality was 71 IU/L (area under the curve 0.636, 95% CI 0.554-0.719, p = 0.003). Therefore, preoperative serum ALP level was an independent predictor of 3-year mortality in patients undergoing kidney transplantation.ope