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Schepens T.,University of Antwerp | Cammu G.,Onze Lieve Vrouw Ziekenhuis
Acta Anaesthesiologica Belgica | Year: 2014

Non-depolarizing neuromuscular blocking agents (NMBAs) produce neuromuscular blockade by competing with acetylcholine at the neuromuscular junction, whereas depolarizing NMBAs open receptor channels in a manner similar to that of acetylcholine. Problems with NMBAs include malignant hyperthermia caused by succinylcholine, anaphylaxis with the highest incidence for succinylcholine and rocuronium, and residual neuromuscular blockade. To reverse these blocks, anticholinesterases can act indirectly by increasing the amount of acetylcholine in the neuromuscular junction; sugammadex is the only selective relaxant binding agent (SRBA) in clinical use. At all levels of blockade, recovery after sugammadex is faster than after neostigmine. Sugammadex potentially also has some other advantages over neostigmine that are related to neostigmine's increase in the amount of acetylcholine and the necessity of co-administering anticholinergics. However, hypersensitivity reactions, including anaphylaxis, have occurred in some patients and healthy volunteers after sugammadex and remain an issue for the FDA. In the near future, we may see the emergence of new SRBAs and of easier-to-use technologies that can routinely monitor neuromuscular transmissions in daily practice. The nature of the effect of sugammadex on freeing nicotinic acetylcholine receptors located outside the neuromuscular junction from NMBAs is unknown. Moreover, it is uncertain whether the full removal of the competing antagonists (by SRBAs) at the neuromuscular junction impacts the efficiency of acetylcholine transmission. In a recent pilot study in healthy volunteers, we demonstrated increased electromyographic diaphragm activity after sugammadex, compared to neostigmine. Further research is needed to elucidate the role of NMBAs and their reversal agents in the central control of breathing, respiratory muscle activity, and respiratory outcomes. © 2014 Acta Anæsthesiologica Belgica.

Jimenez-Perez J.,Endoscopy Unit | Casellas J.,Hospital General Universitario Of Alicante | Garcia-Cano J.,Hospital Virgen de la Luz | Vandervoort J.,Onze Lieve Vrouw Ziekenhuis | And 7 more authors.
American Journal of Gastroenterology | Year: 2011

Objectives: To date, this is the largest prospective series in patients with malignant colorectal obstruction to evaluate the effectiveness and safety of colonic self-expanding metal stents (SEMSs) as an alternative to emergency surgery. SEMSs allow restoration of bowel transit and careful tumor staging in preparation for elective surgery, hence avoiding the high morbidity and mortality associated with emergency surgery and stoma creation. Methods: This report is on the SEMS bridge-to-surgery subset enrolled in two multicenter international registries. Patients were treated per standard of practice, with documentation of clinical and procedural success, safety, and surgical outcomes. Results: A total of 182 patients were enrolled with obstructive tumor in the left colon (85%), rectum (11%), or splenic flexure (4%). Of these patients, 86% had localized colorectal cancer without metastasis. Procedural success was 98% (177/181). Clinical success was 94% (141/150). Elective surgery was performed in 150 patients (9 stomas) and emergency surgery in 7 patients for treatment of a complication (3 stomas). The overall complication rate was 7.8% (13/167), including perforation in 3% (5/167), stent migration in 1.2% (2/167), bleeding in 0.6% (1/167), persistent colonic obstruction in 1.8% (3/167), and stent occlusion due to fecal impaction in 1.2% (2/167). One patient died from complications related to surgical management of a perforation. Conclusions: SEMSs provide an effective bridge to surgery treatment with an acceptable complication rate in patients with acute malignant colonic obstruction, restoring luminal patency and allowing elective surgery with primary anastomosis in most patients. © 2011 by the American College of Gastroenterology.

Fox K.A.A.,University of Edinburgh | Carruthers K.F.,University of Edinburgh | Dunbar D.R.,University of Edinburgh | Graham C.,University of Edinburgh | And 5 more authors.
European Heart Journal | Year: 2010

AimTo define the long-term outcome of patients presenting with acute coronary syndrome [ST-segment elevation myocardial infarction (STEMI), and non-STEMI and unstable angina acute coronary syndrome (ACS) without biomarker elevation] and to test the hypothesis that the GRACE (Global Registry of Acute Coronary Events) risk score predicts mortality and death/MI at 5 years.Methods and resultsIn the GRACE long-term study, UK and Belgian centres prospectively recruited and followed ACS patients for a median of 5 years (1797 days). Primary outcome events: deaths, cardiovascular deaths (CVDs) and MIs. Secondary events: stroke and re-hospitalization for ACS. There were 736 deaths, 19.8 (482 CVDs, 13) and 347 (9.3) MIs (>24 h), 261 strokes (7.7), and 452 (17) subsequent revascularizations. Rehospitalization was common: average 1.6 per patient; 31.2 had >1 admission, 9.2 had 5+ admissions. These events were despite high rates of guideline indicated therapies. The GRACE score was highly predictive of all-cause death, CVD, and CVD/MI at 5 years (death: χ 2 likelihood ratio 632; Wald 709.9, P< 0.0001, C-statistic 0.77; for CVD C-statistic 0.75, P< 0.0001; CVD/MI C-statistic 0.70, P< 0.0001). Compared with the low-risk GRACE stratum (ESC Guideline criteria), those with intermediate [hazard ratio (HR) 2.14, 95 CI 1.63, 2.81] and those with high-risk (HR 6.36, 95 CI 4.95, 8.16) had two- and six-fold higher risk of later death (Cox proportional hazard). A landmark analysis after 6 months confirmed that the GRACE score predicted long-term death (χ 2 likelihood ratio 265.4; Wald 289.5, P< 0.0001). Although in-hospital rates of death and MI are higher following STEMI, the cumulative rates of death (and CVD) were not different, by class of ACS, over the duration of follow-up (Wilcoxon = 1.5597, df = 1, P= 0.21). At 5 years after STEMI 269/1403 (19) died; after non-STEMI 262/1170 (22) after unstable angina (UA) 149/850 (17). Two-thirds (68) of STEMI deaths occurred after initial hospital discharge, but this was 86 for non-STEMI and 97 for UA.ConclusionThe GRACE risk score predicts early and 5 year death and CVD/MI. Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI. Their morbidity burden is high (MI, stroke, readmissions) and the substantial late mortality in non-STE ACS is under-recognized. The findings highlight the importance of pursuing novel approaches to diminish long-term risk. © 2010 The Author.

Van Gestel L.,Catholic University of Leuven | Cammu G.,Onze Lieve Vrouw Ziekenhuis
Acta Anaesthesiologica Belgica | Year: 2013

The aim of this literature review was to compare the duration of the recovery effects of sugammadex. We therefore systematically searched Medline for relevant reports that investigated the recovery time to a train-of-four (TOF) ratio of 0.9 after sugammadex administration. Thirty-three reports were retrieved. For the recommended dose of 2 mg/kg of sugammadex, some studies noted maximum reversal times to a TOF ratio of 0.9 of up to 12 minutes. One study recorded a maximum delay of 22.3 minutes after the recommended dose of 4 mg/kg of sugammadex. Regarding the reversal of rocuronium immediately after its administration, a maximum delay of 16.6 minutes was noted after 16 mg/kg of sugammadex. Whereas reversal with sugammadex is likely within 2-3 minutes, unexpectedly long sugammadex recovery times were occasionally recognized in elderly patients, patients with slower hemodynamic circulation, patients with pulmonary disease, some obese patients, and some cases of renal failure. Additionally, variability in the onset of sugammadex effect was observed in healthier patients (up to 22.3 minutes). This review confirms the known rapid reversal by the recommended doses of sugammadex. However, due to possibility of an increased recovery time, any patient who receives sugammadex to reverse neuromuscular block should have his or her TOF checked prior to extubation. © Acta Anæsthesiologica Belgica, 2013.

Serruys P.W.,Erasmus Medical Center | Onuma Y.,Erasmus Medical Center | Garg S.,Erasmus Medical Center | Vranckx P.,Hartcentrum | And 11 more authors.
Journal of the American College of Cardiology | Year: 2010

Objectives: The purpose of this study is to compare the 5-year clinical outcomes, safety, and efficacy of sirolimus-eluting stents (SES) in the ARTS II (Arterial Revascularization Therapies Study II) with the outcomes of coronary artery bypass graft (CABG) and bare-metal stenting (BMS) from the ARTS I. Background: The long-term outcomes after SES implantation in patients with multivessel disease remains to be established. Methods: The ARTS I was a randomized trial of 1,205 patients with multivessel disease comparing CABG and BMS. The ARTS II study was a nonrandomized trial with the Cypher sirolimus-eluting stent (Cordis, a Johnson & Johnson Company, Warren, New Jersey), applying the same inclusion and exclusion criteria, end points, and protocol definitions. The ARTS II trial enrolled 607 patients, with an attempt to enroll at least one-third of patients with 3-vessel disease. Results: At 5-year, the death/stroke/myocardial infarction event-free survival rate was 87.1% in ARTS II SES, versus 86.0% (p = 0.1) and 81.9% (p = 0.007) in ARTS I CABG and BMS cohorts, respectively. The 5-year major adverse cardiac and cerebrovascular event (MACCE) rate in ARTS II (27.5%) was significantly higher than ARTS I CABG (21.1%, p = 0.02), and lower than in ARTS I BMS (41.5%, p < 0.001). The cumulative incidence of definite stent thrombosis was 3.8%. Thirty-two percent (56 of 176) of major adverse cardiac events (MACE) at 5 years were related to possible, probable, or definite stent thrombosis. Conclusions: At 5 years, SES had a safety record comparable to CABG and superior to BMS, and a MACCE rate that was higher than in patients treated with CABG, and lower than in those treated with BMS. Approximately one-third of the events seen with SES could be prevented through the elimination of early, late, and very late stent thrombosis. © 2010 American College of Cardiology Foundation.

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