Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study.

BACKGROUND: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. METHODS: Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio <0.9, using TOF-Watch® SX. Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness; analysed with analysis of covariance. RESULTS: Of 154 patients randomized, 150 had a TOF value measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P<0.0001). Of these 33 usual care patients, 2 also had clinical evidence of partial paralysis. Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care (14.7 vs. 18.6 min respectively; P=0.02). CONCLUSIONS: After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov:NCT01479764.

Repeat dosing of rocuronium 1.2 mg kg-1 after reversal of neuromuscular block by sugammadex 4.0 mg kg-1 in anaesthetized healthy volunteers: a modelling-based pilot study.

BACKGROUND: Re-intubation and re-operation may occasionally be required after neuromuscular block (NMB) reversal. This study evaluated block onset times of a second dose of rocuronium (1.2 mg kg(-1)) after sugammadex reversal of rocuronium 0.6 mg kg(-1). METHODS: In this open-label study of healthy anaesthetized volunteers, subjects received rocuronium 0.6 mg kg(-1), were antagonized at 1-2 post-tetanic counts with sugammadex 4.0 mg kg(-1), and received rocuronium 1.2 mg kg(-1) at 5, 7.5, 10, 15, 20, 22.5, 25, 27.5, 30, 45, or 60 min after sugammadex. Spontaneous recovery occurred after repeat rocuronium dose. Primary endpoints were the onset time of maximal block (time to lowest T(1) value reached) and the clinical duration of block (until T(1)=25%) after repeat rocuronium dose. RESULTS: Sixteen subjects were included. For subjects receiving rocuronium 1.2 mg kg(-1) 5 min after sugammadex (n=6), mean (sd) onset time (to T(1)=0) was 3.06 (0.97) min; range, 1.92-4.72 min. For repeat dose time points ≥25 min (n=5), mean onset was faster (1.73 min) than for repeat doses <25 min (3.09 min) after sugammadex. The duration of block ranged from 17.7 min (rocuronium 5 min after sugammadex) to 46 min (repeat dose at 45 min). Mean duration was 24.8 min for repeat dosing <25 min vs 38.2 min for repeat doses ≥25 min. CONCLUSIONS: Rapid re-onset of NMB occurred after repeat dose of rocuronium 1.2 mg kg(-1) as early as 5 min after sugammadex in healthy volunteers. Re-onset of block took longer if second rocuronium dose was <25 min after sugammadex. The duration of action of second rocuronium dose increased with later repeat dose time points.

The incidence and prognostic significance of elevated cardiac troponins in patients with submassive pulmonary embolism.

Although the incidence and prognostic significance of elevated cardiac troponins are known in patients with massive pulmonary embolism (PE), few studies have addressed this issue in patients with hemodynamically stable, submassive PE, who comprise the majority of patients presenting with PE. This prospective cohort study was, therefore, designed to determine the incidence and prognostic significance of elevated cardiac troponins in patients with submassive PE. Consecutive patients with acute, symptomatic, submassive PE that was confirmed by objective diagnostic testing were studied. All patients received treatment with either unfractionated heparin or fondaparinux followed by a coumarin derivative and underwent clinical follow-up for 3 months. Cardiac troponin I (cTnI) levels were measured within 24 h of clinical presentation. An elevated cTnI was defined as > 0.5 microg L(-1) and indicated myocardial injury. Major myocardial injury, that is associated with myocardial infarction, was defined by a cTnI > 2.3 microg L(-1). The clinical outcomes were recurrent venous thromboembolism and all-cause death. In 458 patients with submassive PE, the incidence of cTnI > 0.5 microg L(-1) was 13.5%[95% confidence interval (CI): 10.4-16.7], and the incidence of cTnI > 2.3 microg L(-1) was 3.5% (95% CI: 2.0-5.6). An elevated cTnI > 0.5 microg L(-1) was associated with an increased risk of all-cause death [odds ratio (OR) = 3.5; 95% CI: 1.0-11.9], but did not appear to confer an increased risk of recurrent venous thromboembolism (OR = 1.1; 95% CI: 0.2-4.9). In patients who present with submassive PE, an elevated cTnI occurs in about one in seven patients and is associated with a 3.5-fold increased risk of all-cause death.

[Prevention of traveler's diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study]. / Prophylaxe der Reisediarrhöe mit Saccharomyces boulardii. Ergebnisse einer plazebokontrollierten Doppelblindstudie.

BASIC REMARKS: Among travellers to distant countries with a low socioeconomic status and poor hygiene, traveller's diarrhea is a major problem. Once this epidemiological fact had been recognized, intensive efforts were made to reduce the incidence of this illness by prophylactic medication. Among non-antibiotic substances investigated, Saccharomyces boulardii (SB) appeared to show promising results in earlier studies. METHOD: In a placebo-controlled, double-blind study, various dosages (250 mg and 1,000 mg SB) were administered prophylactically to 3,000 Austrian travellers to distant regions. RESULTS: A significant reduction in the incidence of diarrhea was observed, with success depending directly on the rigorous use of the preparation. A tendency was noted for SB to have a varying regional effect, which was particularly marked in North Africa and in the Near-east (Turkey!); in addition, the effect also proved to be dose-dependent. The medication can be classified as low on side effects.

Investigation of the possible influence of the absorption of vinpocetine with concomitant application of magnesium-aluminium-hydroxide gel.

The concomitant application of magnesium-aluminium-hydroxide gel does not influence the absorption of vinpocetine (CAS 42971-09-5). The pharmacokinetics of vinpocetine under the influence of a concomitant application of magnesium-aluminium-hydroxide gel was investigated. 18 healthy male volunteers were included in the study. Vinpocetine was administered in the galenic form of a film-coated tablet in a dosage of 20 mg t.i.d. over 10 days. On days 5 and 6 of the study, blood samples were taken at 16 different moments over 24 h and analyzed as to their vinpocetine content. Starting with the 6th day of the study, the patients were administered in addition 1 sachet of an magnesium-aluminium-hydroxide gel 4 times a day. On day 9 of the trial, blood samples were taken again over 24 h. The parameters examined were AUC, Cmin, Cmax, tmax and Mean Residence Time. The results as to these parameters of day 5 were compared with those of day 9. As a further parameter, apovincaminic acid plasma levels were determined. There was no difference as to the vinpocetine amount absorbed with or without concomitant application of magnesium-aluminium-hydroxide gel. Apovincaminic acid plasma levels were lowered by approx. 11% when associated with the antacid.