ABSTRACT
Whether third-generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra-operative administration of a third-generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple-blind, non-inferiority, clinical trial randomly allocated patients aged 40-85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.4 vs. 5% human albumin. Our primary outcome was postoperative urinary neutrophil gelatinase-associated lipocalin concentrations, a sensitive and early marker of postoperative kidney injury. Secondarily, we evaluated urinary interleukin-18; acute kidney injury using creatinine RIFLE criteria, coagulation measures, platelet count and function. Non-inferiority (delta 15%) was assessed with correction for multiple comparisons. We enrolled 141 patients (69 starch, 72 albumin) as planned. Results of the primary analysis demonstrated that postoperative urine neutrophil gelatinase-associated lipocalin (median (IQR [range])) was slightly lower with hydroxyethyl starch (5 (1-68 [0-996]) ng.ml-1 ) vs. albumin (5 (2-74 [0-1604]) ng.ml-1 ), although not non-inferior [ratio of geometric means (95%CI) 0.91 (0.57, 1.44); p = 0.15] due to higher than expected variability. Urine interleukin-18 concentrations were reduced, but interleukin-18 and kidney injury were again not non-inferior. Of 11 individual coagulation measures, platelet count and function, nine were non-inferior to albumin. Two remaining measures, thromboelastographic R value and arachidonic acid-induced platelet aggregation, were clinically similar but with wide confidence intervals. Starch administration during cardiac surgery produced similar observed effects on postoperative kidney function, coagulation, platelet count and platelet function compared with albumin, though greater than expected variability and wide confidence intervals precluded the conclusion of non-inferiority. Long-term mortality and kidney function appeared similar between starch and albumin.
Subject(s)
Blood Coagulation/drug effects , Cardiac Surgical Procedures , Hydroxyethyl Starch Derivatives/pharmacology , Intraoperative Care/methods , Kidney/drug effects , Plasma Substitutes/pharmacology , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Hemostatics , Humans , Kidney/physiology , Male , Middle AgedABSTRACT
Occupational exposure to the waste anaesthetic gases (WAGs) is a crucial problem for healthcare personnel. Cancer is among the potential long-term adverse effects of WAGs. The present occupational molecular epidemiology study was conducted in healthcare personnel (anaesthetists, nurses and technicians; n = 46), working in operating rooms (ORs; n = 34) and recovery units (RUs; n = 12) of the same hospital, to assess the genotoxicity risk of WAGs exposure. Twenty-one healthy available hospital staff allocated to other wards, without the history of working in ORs and RUs were the control group. A micronucleus test was carried out for peripheral blood lymphocytes (PBLs) and buccal epithelial cells (BECs). Exposure to the anaesthetics was assessed with sevoflurane concentrations and inorganic fluoride levels in post-shift urine samples of the healthcare staff. As an exposure marker, sevoflurane concentrations in ORs and RUs were measured using passive samplers. The micronuclei frequencies were increased in both PBLs (approximately two times) and BECs (approximately three times) of the healthcare personnel. Urinary sevoflurane concentrations exceeded the biological equivalent level in 23 personnel. Air sevoflurane levels in the breathing zone in three ORs and one RU did not exceed the established occupational exposure limits. Both in surrogate tissue (PBLs) and in target tissue (BECs) of the personnel of RUs and ORs of the same hospital, the genotoxicity risk was evident and similar. Originality of this study, in addition to the WAGs exposure confirmation of the healthcare personnel, was the involvement of the RU personnel for the genotoxicity assessment, which was the first time in the scientific literature.
Subject(s)
Air Pollutants, Occupational/adverse effects , Anesthetics, Inhalation/adverse effects , Micronuclei, Chromosome-Defective/chemically induced , Occupational Exposure/adverse effects , Operating Rooms , Recovery Room , Sevoflurane/adverse effects , Adult , Air Pollutants, Occupational/analysis , Anesthetics, Inhalation/analysis , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Fluorides/urine , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Micronucleus Tests , Mouth Mucosa/cytology , Occupational Exposure/analysis , Personnel, Hospital , Sevoflurane/analysis , Waste Products/adverse effects , Waste Products/analysisABSTRACT
Diazepam is a benzodiazepine with anticonvulsant, anxiolytic, sedative and muscle-relaxing properties. Many aspects of its toxicity have been investigated, including genotoxic and carcinogenic effects in various model systems. However, it is still unclear whether diazepam is in fact a genotoxic agent. Propofol is a rapid-onset, short-acting intravenous anesthetic agent. It is used widely for the induction and maintenance of anesthesia as well as for long-term sedation in intensive care units. There is limited information in the literature on its genotoxic effects. Both drugs are commonly used as anesthetic in patients undergoing open-heart surgery. Therefore, we investigated the possible genotoxic effects of propofol and diazepam in those patients, using a chromosomal aberration (CA) assay. Peripheral blood samples were collected from 45 patients before induction of anesthesia and at the end of the anesthesia with diazepam or propofol. In Group I (n=24), anesthesia was induced with 0.2 mg kg(-1) diazepam and 10 microg kg(-1) fentanyl. In Group II (n=21), anesthesia was induced with 1 mg kg(-1) propofol and 10 microg kg(-1) fentanyl. Pancuronium bromide (0.1 mg kg(-1)) was administered for skeletal muscle relaxation in both groups. Anesthesia was maintained by diazepam administration at 5 mg kg(-1) in Group I or by continuous propofol administration at 2-4 mg (kg h)(-1) in Group II. All patients received 0.02 mg kg(-1) pancuronium and 5 microg kg(-1) fentanyl boluses at 30-40 min intervals for anesthesia maintenance. Body temperature was controlled during bypass in the two groups. We found that the mean frequency of CAs in both groups before and at the end of the anesthesia were not statistically significantly different. Our analysis also indicated that age, smoking habit and gender were not confounding factors. In conclusion, our results indicate that diazepam and propofol do not exert genotoxic effects in blood cells during open-heart surgery.
Subject(s)
Cardiac Surgical Procedures , Chromosome Aberrations/chemically induced , Diazepam/adverse effects , Lymphocytes/drug effects , Lymphocytes/physiology , Propofol/adverse effects , Adult , Aged , Anesthetics, Intravenous/adverse effects , Chromosomes, Human/drug effects , Diazepam/pharmacology , Female , Fentanyl , Humans , Hypnotics and Sedatives/adverse effects , Male , Middle Aged , SmokingABSTRACT
The study presents empirical evidence of accident risk during and following rain events in the cities of Calgary and Edmonton, Canada. The matched sample approach is used to examine data for 169 rain events and over 15,000 accidents that occurred during the years 1979-1983. The overall accident risk during rainfall conditions was found to be 70% higher than normal. The data suggest that accident risk returns to normal as soon as the rainfall has ended, despite the lingering effects of wet road conditions.