Bupivacaine infiltration in children for postoperative analgesia after tonsillectomy: A randomised controlled trial.

BACKGROUND: Adenotonsillectomy is a frequently performed procedure in paediatric day-case surgery. Postoperative pain can be significant and standard analgesia protocols are often insufficient. OBJECTIVE: Our primary objective was to investigate if infiltration of the peritonsillar space with bupivacaine would reduce the need for postoperative opioids compared with pre-emptive intravenous tramadol. DESIGN: A double-blind, randomised controlled trial. SETTING: Ambulatory surgical day care centre, University Hospitals of Leuven, Belgium, from January 2012 to September 2016. PATIENTS: Two hundred children, between 4 and 10 years old, undergoing elective adenotonsillectomy were included in the study. INTERVENTION: Children were randomly allocated to receive either a bolus of 3 mg kg intravenous tramadol or infiltration of the tonsillar lodge with 5-ml bupivacaine 0.25%. Reasons for exclusion were American Society of Anesthesiologists classification greater than 2, allergies to the investigated products, psychomotor retardation, bleeding disorders and lack of proficiency in Flemish. MAIN OUTCOME MEASURES: The primary endpoint was the number of children in need of piritramide postoperatively. Secondary outcomes included the cumulative dose of postoperative piritramide, pain scores and the incidence of postoperative nausea and vomiting during the first 24 postoperative hours, time to discharge and adverse effects. RESULTS: The proportion of children in need of postoperative piritramide was significantly lower in the tramadol group than in children with peritonsillar infiltration (57 vs. 81%, P < 0.001). When in need of postoperative piritramide, the tramadol-group required a significantly lower dose (median [IQR] 0.7 [0.6 to 1] vs. 1 [0.6 to 1.5] mg, P < 0.007) and had lower pain scores during the first 60 min after surgery. There were no statistically significant differences in postoperative nausea and vomiting incidence, need for antiemetics or complications. CONCLUSION: Compared with peritonsillar infiltration, preemptive intravenous tramadol decreases the need for postoperative opioids after tonsillectomy in children without increasing the incidence of side effects. TRIAL REGISTRATION: EudraCT 2011-005467-25.

Dorsal penile nerve block for circumcision in pediatric patients: A prospective, observer-blinded, randomized controlled clinical trial for the comparison of ultrasound-guided vs landmark technique.

BACKGROUND AND AIMS: Circumcision is a frequently performed procedure in day case pediatric surgery. Dorsal penile nerve block has proven its effectiveness for the management of acute postoperative pain after circumcision. We investigated if the ultrasound-guided placement of a dorsal penile nerve block could reduce opioid requirement as compared to a landmark-based technique. METHODS: Three hundred and ten prepubertal children, aged between 52 weeks postconception and 11 years, were included in this prospective, observer-blinded, randomized controlled trial and received either a landmark- or an ultrasound-guided dorsal penile nerve block, using a caudal needle and injecting 0.1 mL/kg levobupivacaine 0.5% bilaterally. A single, experienced investigator performed all blocks. The primary endpoint was the number of patients in need of piritramide postoperatively as triggered by the Objective Pain Scale. Secondary outcome parameters included the cumulative dose of postoperatively administered opioids, the requirement to administer fentanyl intraoperatively, the need for paracetamol and ibuprofen during the first 24 postoperative hours, postoperative pain scores, the incidence of postoperative nausea and vomiting, the anesthesia induction time, and the time to discharge. RESULTS: The proportion of patients requiring postoperative piritramide did not differ significantly between both groups (Landmark: 38% vs Ultrasound: 47%, with a difference in proportion between both conditions (95% CI): 0.09 (0.2 to 0.02); P = .135). In addition, the cumulative doses of postoperative piritramide and intraoperative fentanyl, the postoperative need for paracetamol or ibuprofen, pain scores, the incidence of postoperative nausea and vomiting, and the time to discharge were not different either. However, the anesthesia induction time was significantly longer in the ultrasound-guided dorsal penile nerve block (median time [IQR]: Landmark: 11[9; 13] min vs Ultrasound: 13[11; 15] min, P < .001). CONCLUSION: Compared with the landmark-guided, the ultrasound-guided dorsal penile nerve block did not reduce the need for postoperative analgesia after circumcision in children, but was associated with an increase in the procedural time.

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

INTRODUCTION: Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. METHODS: In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. RESULTS: At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. CONCLUSIONS: OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01409057.

SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX-trial): study design of an international multicenter randomized double-blinded controlled trial of high dose sodium-selenite administration in high-risk cardiac surgical patients.

BACKGROUND: Cardiac surgery has been shown to result in a significant decrease of the antioxidant selenium, which is associated with the development of multiorgan dysfunction and increased mortality. Thus, a large-scale study is needed to investigate the effect of perioperative selenium supplementation on the occurrence of postoperative organ dysfunction. METHODS/DESIGN: We plan a prospective, randomized double-blind, multicenter controlled trial, which will be conducted in North and South America and in Europe. In this trial we will include 1,400 high-risk patients, who are most likely to benefit from selenium supplementation. This includes patients scheduled for non-emergent combined and/or complex procedures, or with a predicted operative mortality of ≥ 5% according to the EuroSCORE II. Eligible patients will be randomly assigned to either the treatment group (bolus infusion of 2,000 µg sodium selenite immediately prior to surgery, followed by an additional dosage of 2,000 µg at ICU admission, and a further daily supplementation of 1,000 µg up to 10 days or ICU discharge) or to the control group (placebo administration at the same time points).The primary endpoint of this study is a composite of 'persistent organ dysfunction' (POD) and/or death within 30 days from surgery (POD + death). POD is defined as any need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or new intermittent hemodialysis) at any time within 30 days from surgery. DISCUSSION: The SUSTAIN-CSX™ study is a multicenter trial to investigate the effect of a perioperative high dosage sodium selenite supplementation in high-risk cardiac surgical patients. TRIAL REGISTRATION: This trial was registered at Clinicaltrials.gov (identifier: NCT02002247) on 28 November 2013.

Selenium blood concentrations in patients undergoing elective cardiac surgery and receiving perioperative sodium selenite.

OBJECTIVES: We recently reported that cardiac surgical patients in our institution exhibited low selenium blood levels preoperatively, which were further aggravated during surgery and independently associated with the development of postoperative multiorgan failure. Low circulating selenium levels result in a decreased antioxidant capacity. Both can be treated effectively by sodium-selenite administration. Little is known about the kinetics of exogenously administered sodium-selenite during acute perioperative oxidative stress. The aim of this study was to assess the effects of perioperative high-dose sodium-selenite administration on selenium blood concentrations in cardiac surgical patients. METHODS: One hundred four cardiac surgical patients were enrolled in this prospective observational trial. Patients received an intravenous bolus of 2000 µg selenium after an induction of anesthesia and 1000 µg selenium every day further during their intensive care unit (ICU) stay. Selenium blood levels were measured at regular intervals. RESULTS: Preoperative sodium-selenite administration increased selenium blood concentrations to normal values on ICU admission, but failed to prevent a significant decrease of circulating selenium on the first postoperative day. During the further ICU stay, selenium blood levels were normalized by the administration strategy and did not exceed the German reference range. No acute selenium-specific side effects occurred. When matching the participating patients to a historical control group without sodium-selenite administration, the chosen strategy was associated with a decrease in SAPS II (23 ± 7 versus 29 ± 8, P = 0.005) and SOFA scores (4 ± 3 versus 7 ± 2, P = 0.007) on the first postoperative day, but was unable to improve the postoperative outcome in patients staying >1 d in ICU. CONCLUSIONS: Despite preemptive high-dose sodium-selenite administration, cardiac surgical patients experienced a significant decrease in circulating selenium levels on the first postoperative day.

The intraoperative decrease of selenium is associated with the postoperative development of multiorgan dysfunction in cardiac surgical patients.

OBJECTIVE: The trace elements selenium, copper, and zinc are essential for maintaining the oxidative balance. A depletion of antioxidative trace elements has been observed in critically ill patients and is associated with the development of multiorgan dysfunction and an increased mortality. Cardiac surgery using cardiopulmonary bypass provokes ischemia-reperfusion-mediated oxidative stress. We hypothesized that an intraoperative decrease of circulating trace elements may be involved in this response. DESIGN: Prospective observational clinical study. SETTING: University hospital cardiothoracic operation theater and intensive care unit. PATIENTS: Sixty patients (age 65 ± 14 yrs) undergoing cardiac surgery with the use of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Whole blood concentrations of selenium, copper, and zinc were measured after induction of anesthesia and 1 hr after admission to the intensive care unit. All patients were separated in a priori defined subgroups according to the development of no organ failure, single organ failure, and ≥ 2 organ failures in the postoperative period. RESULTS: Fifty patients exhibited a significant selenium deficiency already before surgery, whereas copper and zinc concentrations were within the reference range. In all patients, blood levels of selenium, copper, and zinc were significantly reduced after end of surgery when compared to preoperative values (selenium: 89.05 ± 12.65 to 70.84 ± 10.46 µg/L; zinc: 5.15 ± 0.68 to 4.19 ± 0.73 mg/L; copper: 0.86 ± 0.15 to 0.65 ± 0.14 mg/L; p < .001). During their intensive care unit stay, 17 patients were free from any organ failure, while 31 patients developed single-organ failure and 12 patients multiple organ failure. Multilogistic regression analysis showed that selenium concentrations at end of surgery were independently associated with the postoperative occurrence of multiorgan failure (p = .0026, odds ratio 0.8479, 95% confidence interval 0.7617 to 0.9440). CONCLUSIONS: Cardiac surgery using cardiopulmonary bypass resulted in a profound intraoperative decrease of whole blood levels of antioxidant trace elements. Low selenium concentrations at end of surgery were an independent predictor for the postoperative development of multiorgan failure.