Dialysability of sugammadex and its complex with rocuronium in intensive care patients with severe renal impairment.

BACKGROUND: Renal excretion is the primary route for the elimination of sugammadex. We evaluated the dialysability of sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment in the intensive care unit (ICU). METHODS: Six patients in the ICU with acute severe renal impairment received general anaesthesia for transoesophageal echocardiography, to replace their tracheal tubes, or for bronchoscopy. Five of the six patients were in the ICU after cardiac/vascular surgery and one for pneumonia-induced respiratory failure. They all received rocuronium 0.6 mg kg(-1), followed 15 min later by sugammadex 4.0 mg kg(-1). Two patients were studied for two dialysis episodes and four patients for four episodes. Rocuronium and sugammadex concentrations were measured in plasma and dialysate at several time points before, during, and after high-flux dialysis. Dialysis clearance in plasma and dialysate, and reduction ratio (RR) (the extent of the plasma concentration reduction at the end of a dialysis episode when compared with before dialysis) were calculated for each dialysis episode. RESULTS: Dialysis episodes lasted on average 6 h. Observed RRs indicated mean reductions of 69% and 75% in the plasma concentrations of sugammadex and rocuronium, respectively, during the first dialysis episode. Reductions were around 50% during sequential dialysis episodes. On average, dialysis clearance of sugammadex and rocuronium in blood was 78 and 89 ml min(-1), respectively. CONCLUSIONS: Haemodialysis using a high-flux dialysis method is effective in removing sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment.

Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship.

BACKGROUND: Sugammadex shows a dose-response relationship for reversal of neuromuscular block (NMB) during propofol anaesthesia. Sevoflurane, unlike propofol, can prolong the effect of neuromuscular blocking agents (NMBAs), increasing recovery time. This open-label, randomized, dose-finding trial explored sugammadex dose-response relationships, safety, and pharmacokinetics when administered for reversal of moderate rocuronium- or vecuronium-induced NMB during sevoflurane maintenance anaesthesia. METHODS: After anaesthesia induction with propofol, adult patients were randomized to receive single-dose rocuronium 0.9 mg kg⁻¹ or vecuronium 0.1 mg kg⁻¹, with maintenance doses as needed. Anaesthesia was maintained with sevoflurane. NMB was monitored using acceleromyography. After the last dose of NMBA, at reappearance of T(2), single-dose sugammadex 0.5, 1.0, 2.0, or 4.0 mg kg⁻¹ or placebo was administered. The primary efficacy variable was time from the start of sugammadex administration to recovery of T4/T1 ratio to 0.9. Safety assessments were performed throughout. RESULTS: The per-protocol population comprised 93 patients (rocuronium, n=46; vecuronium, n=47). A statistically significant dose-response relationship was demonstrated for mean recovery times of T4/T1 ratio to 0.9 with increasing sugammadex dose with both NMBAs: rocuronium, 96.3 min (placebo) to 1.5 min (sugammadex 4.0 mg kg⁻¹); vecuronium, 79.0 min (placebo) to 3.0 min (sugammadex 4.0 mg kg⁻¹). Plasma sugammadex concentrations indicated linear pharmacokinetics, independent of NMBA administered. No study drug-related serious adverse events occurred. Evidence of reoccurrence of block was reported in seven patients [sugammadex 0.5 mg kg⁻¹ (suboptimal dose), n=6; 2.0 mg kg⁻¹, n=1]. CONCLUSIONS: During sevoflurane maintenance anaesthesia, sugammadex provides well-tolerated, effective, dose-dependent reversal of moderate rocuronium- and vecuronium-induced NMB.

Monitoring of herpes simplex virus in the lower respiratory tract of critically ill patients using real-time PCR: a prospective study.

Herpes simplex virus (HSV) has increasingly been associated with pulmonary disease in critically ill patients. However, the clinical relevance of HSV is still a topic of debate. Monitoring of HSV in a quantitative way could potentially give relevant information on its role in the pathogenesis of lower respiratory tract infection. A fast and reliable quantitative real-time PCR (Q-PCR) for the quantitative detection of HSV-1 and HSV-2 DNA was developed. A prospective observational study was performed in an intensive-care unit (ICU) to monitor the HSV viral load in lower respiratory tract aspirates of long-term mechanically ventilated patients. HSV was common in the lower respiratory tract (LRT) of critically ill patients with mechanical ventilation for at least 48 h (62%, n = 65/105). Detection of HSV was significantly associated with prolonged mechanical ventilation (p <0.01), prolonged ICU stay (p <0.01), and development of ventilator-associated pneumonia (p = 0.02). Corticosteroid administration (p <0.01) in the ICU and anti-HSV IgG seropositivity (p <0.01) were risk factors for the occurrence of HSV in the LRT. The fact that no HSV-seronegative patient became positive suggests that all HSV DNA-positive patients had HSV reactivations. Monitoring the HSV viral load in the LRT of critically ill patients showed a typical homogeneous pattern of HSV kinetics. HSV emerged in tracheal and bronchial aspirates after a median of 7 days of intubation (5-11 days), and this was followed by an exponential increase (c. 1 log copies/mL/day) to reach very high HSV peaks (10(6)-10(10) copies/mL) in 78% of the HSV DNA-positive patients.

Safety and tolerability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers.

BACKGROUND: Sugammadex rapidly reverses rocuronium- and vecuronium-induced neuromuscular block. To investigate the effect of combination of sugammadex and rocuronium or vecuronium on QT interval, it would be preferable to avoid the interference of anaesthesia. Therefore, this pilot study was performed to investigate the safety, tolerability, and plasma pharmacokinetics of single i.v. doses of sugammadex administered simultaneously with rocuronium or vecuronium to anaesthetized and non-anaesthetized healthy volunteers. METHODS: In this phase I study, 12 subjects were anaesthetized with propofol/remifentanil and received sugammadex 16, 20, or 32 mg kg(-1) combined with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1); four subjects were not anaesthetized and received sugammadex 32 mg kg(-1) with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) (n=2 per treatment). Neuromuscular function was assessed by TOF-Watch SX monitoring in anaesthetized subjects and by clinical tests in non-anaesthetized volunteers. Sugammadex, rocuronium, and vecuronium plasma concentrations were measured at several time points. RESULTS: No serious adverse events (AEs) were reported. Fourteen subjects reported 23 AEs after study drug administration. Episodes of mild headache, tiredness, cold feeling (application site), dry mouth, oral discomfort, nausea, increased aspartate aminotransferase and gamma-glutamyltransferase levels, and moderate injection site irritation were considered as possibly related to the study drug. The ECG and vital signs showed no clinically relevant changes. Rocuronium/vecuronium plasma concentrations declined faster than those of sugammadex. CONCLUSIONS: Single-dose administration of sugammadex 16, 20, or 32 mg kg(-1) in combination with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) was well tolerated with no clinical evidence of residual neuromuscular block, confirming that these combinations can safely be administered simultaneously to non-anaesthetized subjects. Rocuronium and vecuronium plasma concentrations decreased faster than those of sugammadex, reducing the theoretical risk of neuromuscular block developing over time.

Pathogens in early-onset and late-onset intensive care unit-acquired pneumonia.

OBJECTIVES: To compare the type of pathogens isolated from patients with early-onset intensive care unit (ICU)-acquired pneumonia with those isolated from patients with late-onset ICU-acquired pneumonia and to study risk factors for the isolation of pathogens that are potentially resistant to multiple drugs. DESIGN: Prospective cohort study. SETTING: Patients admitted to the ICU of a 677-bed, university-affiliated teaching hospital in Belgium during 1997-2002. METHODS: ICU-acquired pneumonia was defined as a case of pneumonia that occurred 2 days or more after admission to the ICU in combination with a positive results of radiologic analysis, clinical signs and symptoms, and a positive culture result. All cases of pneumonia were categorized as either early onset (within 7 days after admission) and late onset (7 days or more after admission), with or without previous antibiotic treatment, and the corresponding pathogens were analyzed. Risk factors for the isolation of pathogens potentially resistant to multiple drugs (ie, Pseudomonas aeruginosa, Serratia marcescens, Enterobacter species, Morganella morganii, methicillin-resistant Staphylococcus aureus, Citrobacter species, Acinetobacter species, Burkholderia species, extended-spectrum beta -lactamase-producing pathogens, and Stenotrophomonas maltophilia) were analyzed using logistic regression analysis. RESULTS: A total of 4,200 patients stayed at the ICU for 2 or more days, 298 of whom developed ICU-acquired pneumonia, for an overall incidence of 13 cases (95% confidence interval [CI], 11-14 cases) per 1,000 ICU-days. Pathogens potentially resistant to multiple drugs were isolated from 52% of patients with early-onset pneumonia. Risk factors for the isolation of these pathogens were greater age and previous receipt of antibiotic prophylaxis (adjusted odds ratio [aOR], 4.6 [95% CI, 1.6-13.0]) or antibiotic therapy (aOR, 8.2 [95% CI, 2.8-23.8]). The length of ICU admission and hospital stay were weaker risk factors for the isolation of these pathogens. CONCLUSIONS: Pathogens potentially resistant to multiple drugs were isolated in 52% of cases of early-onset ICU-acquired pneumonia. Previous antibiotic use (both prophylactic and therapeutic) is the main risk factor for the isolation of these pathogens.

Long-term sedation in the ICU: enteral versus parenteral feeding.

An open, prospective study was carried out on 45 patients with multiple injuries to compare the mortality and incidence of sepsis between those given early total enteral nutrition (TEN) when sedated with propofol and historical controls who had been given total parenteral nutrition (TPN) and sedated with midazolam. TEN was instituted immediately after surgery via gastrostomy and/or jejunostomy tube inserted during laparotomy or via an endoscope and was continued for the whole stay in the intensive care unit (ICU). Dramatic reductions in both mortality (24.4% vs 35.1% in the controls; p = 0.025) and the incidence of sepsis (8.9% vs 23.8% in the controls; p = 0.025) were found when early enteral feeding was given. The absence of pressure sores and gastro-intestinal bleeding (for example, stress ulcus), which had previously been a common occurrence in this intensive care unit, was remarkable with the introduction of TEN and propofol sedation. Tolerance problems (mainly diarrhoea) arose in only 17% of patients in the study group.