Bioaccumulation of pharmaceuticals and personal care products in the unionid mussel Lasmigona costata in a river receiving wastewater effluent.

Freshwater mussels are frequently found in rivers receiving effluent from wastewater treatment plants (WWTP), and there is strong evidence that poor water quality is deleterious to freshwater mussel populations. WWTPs are among the main sources of pharmaceuticals and personal care products (PPCPs) in surface waters. We monitored 145 PPCPs in wild and caged mussels both upstream and downstream of the Kitchener WWTP in the Grand River, Ontario, as well as 118 PPCPs in water samples. Our objectives were to characterize the seasonal changes in PPCP concentrations in water, to calculate bioaccumulation factors (BAFs) of PPCPs in mussels, and to determine the chemical and physical properties of PPCPs driving the bioaccumulation. Seventy PPCPs were detected in water, and concentrations were highest in the summer or early fall, which corresponded to low river flow. Forty-three PPCPs from many pharmaceutical classes were detected in mussel tissues, including stimulants, a contrasting agent, anti-inflammatory drugs, anti-bacterial agents, antibiotics, antidepressants, antihistamines, progestins, and illicit drugs such as cocaine and amphetamines. The BAFs ranged from 0.66 for metformin to 32,022 for sertraline. Using partial least squares to predict BAFs based upon chemical properties, log KOC, Log KOW, and fugacity ratio (sediment) all had similar and positive loadings with BAFs (R(2)X = 0.70; caged mussels). BAFs of PPCPs in mussels were predictable from fugacity models that estimate bioconcentration factors using log KOW. Our study demonstrated that mussels readily bioaccumulate PPCPs, in a manner consistent with expectations based upon BCF models and the chemical characteristics of each compound.

Predictors and outcome impact of perioperative serum sodium changes in a high-risk population.

BACKGROUND: The perioperative period may be associated with a marked neurohumoral stress response, significant fluid losses, and varied fluid replacement regimes. Acute changes in serum sodium concentration are therefore common, but predictors and outcomes of these changes have not been investigated in a large surgical population. METHODS: We carried out a retrospective cohort analysis of 27 068 in-patient non-cardiac surgical procedures in a tertiary teaching hospital setting. Data on preoperative conditions, perioperative events, hospital length of stay, and mortality were collected, along with preoperative and postoperative serum sodium measurements up to 7 days after surgery. Logistic regression was used to investigate the association between sodium changes and mortality, and to identify clinical characteristics associated with a deviation from baseline sodium >5 mmol litre(-1). RESULTS: Changes in sodium concentration >5 mmol litre(-1) were associated with increased mortality risk (adjusted odds ratio 1.49 for a decrease, 3.02 for an increase). Factors independently associated with a perioperative decrease in serum sodium concentration >5 mmol litre(-1) included age >60, diabetes mellitus, and the use of patient-controlled opioid analgesia. Factors associated with a similar increase were preoperative oxygen dependency, mechanical ventilation, central nervous system depression, non-elective surgery, and major operative haemorrhage. CONCLUSIONS: Maximum deviation from preoperative serum sodium value is associated with increased hospital mortality in patients undergoing in-patient non-cardiac surgery. Specific preoperative and perioperative factors are associated with significant serum sodium changes.

Intraoperative fluid and pharmacologic management and the anesthesiologist's supervisory role for nontraditional technologies during liver transplantation: a survey of US academic centers.

BACKGROUND: Volume resuscitation and use of vasoactive medications during liver transplantation has not been systematically assessed. Furthermore, the anesthesiologist's role for intraoperative oversight of technologies such as renal replacement therapy and procedures such as venovenous bypass is poorly defined, and it is unclear if the center's annual transplant frequency affects these practices. METHODS: We conducted a database analysis of the Liver Transplant Anesthesia Consortium survey 202 that addresses these questions. Data from US academic liver transplant anesthesia programs meeting inclusion criteria were included. Results were categorized by their annual transplant volume. RESULTS: A representative sample of 66% of all eligible centers contributed to the results. Normal saline among crystalloids and albumin among colloids were the most frequently chosen maintenance and non-blood product volume expansion fluids, with little variation by center size. A large variety of vasoactive agents is routinely utilized across programs, with vasopressors as a cornerstone of hemodynamic support. Large programs seem to use less of these agents compared with lower volume centers. CONCLUSION: Anesthesiologists are increasingly involved in oversight and management of intraoperative renal replacement therapies, venovenous bypass and cell saver devices with rising transplant frequency. This new insight may be indicative of skill sets needed by members of liver transplantation anesthesia teams and should be considered in curriculum design for hepatobiliary transplant anesthesia fellowships.

In vitro characterization of calcium transport along the gastrointestinal tract of freshwater rainbow trout Oncorhynchus mykiss.

Using an in vitro gut-sac technique, this study examined the mechanisms of calcium (Ca) uptake along the gastrointestinal tract (GIT) of rainbow trout Oncorhynchus mykiss. Ca uptake into three different compartments (mucous-bound, mucosal epithelium and blood space) of four distinct GIT segments (stomach, anterior intestine, mid intestine and posterior intestine) was monitored after luminal exposure to 10 mM Ca saline (radiolabelled with (45) Ca). Ca transport was determined to be both time-dependent and concentration-dependent. The concentration-dependent kinetics of Ca uptake was investigated using varying luminal concentrations of Ca (1, 10, 30, 60 and 100 mM). In the blood-space compartment, Ca uptake was saturable at high Ca concentrations in the mid intestine (suggesting mediated transport), while linear uptake was found in the other gut segments. In the mucous-bound and mucosal epithelium compartments, however, saturation kinetics were found for most GIT segments, also suggesting mediated transport. Manipulation of serosal saline osmotic pressure with mannitol demonstrated that Ca uptake was not greatly affected by solvent drag. Elevated mucosal cadmium (Cd) did not appear to inhibit Ca uptake into the blood space in any of the GIT sections, and Ca uptake did not appear to be sodium dependent. Maximum transport capacities for Ca and Cd were found to be comparable between the gills and gut, but affinities were much higher at the gills (up to 3000 times).

Branchial cadmium and copper binding and intestinal cadmium uptake in wild yellow perch (Perca flavescens) from clean and metal-contaminated lakes.

Branchial binding kinetics and gastro-intestinal uptake of copper and cadmium where examined in yellow perch (Perca flavescens) from a metal-contaminated lake (Hannah Lake, Sudbury, Ontario, Canada) and an uncontaminated lake (James Lake, North Bay, Ontario, Canada). An in vivo approach was taken for gill binding comparisons while an in vitro gut binding assay was employed for gastro-intestinal tract (GIT) uptake analysis. By investigating metal uptake at the gill and the gut we cover the two main routes of metal entry into fish. Comparisons of water and sediment chemistries, metal burdens in benthic invertebrate, and metal burdens in the livers of perch from the two study lakes clearly show that yellow perch from Hannah L. are chronically exposed to a highly metal-contaminated environment compared to a reference lake. We found that metal-contaminated yellow perch showed no significant difference in gill Cd binding compared to reference fish, but they did show significant decreases in new Cd binding and absorption in their GITs. The results show that gill Cd binding may involve low-capacity, high-affinity binding sites, while gastro-intestinal Cd uptake involves binding sites that are high-capacity, low-affinity. From this we infer that Cd may be more critically controlled at the gut rather than gills. Significant differences in branchial Cu binding (increased binding) were observed in metal-contaminated yellow perch. We suggest that chronic waterborne exposure to Cu (and/or other metals) may be the dominant influence in gill Cu binding rather than chronic exposure to high Cu diets. We give supporting evidence that Cd is taken up in the GIT, at least in part, by a similar pathway as Ca(2+), principally that elevated dietary Ca(2+) reduces Cd binding and uptake. Overall our study reveals that metal pre-exposure via water and diet can alter uptake kinetics of Cu and Cd at the gill and/or the gut.

Measurement of liver tissue oxygenation after orthotopic liver transplantation using a multiparameter sensor. A pilot study.

The currently used methods of monitoring liver perfusion and oxygenation after liver transplantation have major limitations in clinical use. We describe the use of a multiparameter sensor to enable continuous monitoring of liver tissue oxygen tension, carbon dioxide tension and hydrogen ion concentration in the early postoperative period in 12 patients after liver transplantation. The sensor was inserted under direct vision via the falciform ligament into the liver before skin closure. Tissue oxygen tension values decreased in the first 24 h and subsequently increased to a mean (SD) = 7.3 (2.8) kPa at 48 h after surgery. This was associated with a decrease in the degree of acidosis. There were no complications attributable to the sensor. This study demonstrates that continuous measurement of liver oxygen tension, carbon dioxide tension and pH is possible. This technique may be useful as a continuous monitor to help identify grafts at risk of ischaemia.

Reducing the demand for admission to intensive care after major abdominal surgery by a change in anaesthetic practice and the use of remifentanil.

We have used a remifentanil-based anaesthetic for patients undergoing major abdominal surgery who would normally have gone to the intensive care unit in this hospital. Avoiding intensive care unit admission was considered an advantage as a shortage of intensive care unit beds was leading to the cancellation of operations. We first used remifentanil as part of a safety and efficacy study. The aim was to see if the rapid and complete awakening obtained when using this drug would allow us to avoid the need for admission to an intensive care unit and use a high dependency unit instead. This was shown to be practicable. In comparison with a group of patients matched retrospectively for the type of operation before remifentanil was used there was a reduction in the length of time (mean+/- SD) patients' lungs were ventilated (612+/-417 vs. 9.9+/-28.9 min P< 0.0001). There was no saving in cost ( pound808.71+/- pound187.06 vs. pound795.27+/- pound253.49). When remifentanil was used routinely (after the safety and efficacy study), there were significant reductions in the time to tracheal extubation (612+/-417 vs. 4+/-10 min P < 0.0001) and costs (808.71I vs. 392.10 I P < 0.0001) compared with other patients in whom it was not used. Patients waiting for a liver transplant were also being cancelled when a donor organ became available because of the shortage of intensive care unit beds. Based on our other experience with remifentanil, we used a similar anaesthetic technique for these patients. It proved possible to extubate the trachea in 12 of 15 patients at the end of the operation. No patient needed re-intubation. The need for intensive care and therefore cancellation of surgery was reduced. In contrast, only one patient's trachea was extubated immediately after surgery in the group of patients anaesthetized before the introduction of remifentanil. A remifentanil-based technique in combination with a change in organization has therefore enabled us to avoid admission to the intensive care unit for these patients.

A randomized trial of solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver transplantation.

BACKGROUND: Virus inactivation of pooled fresh-frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation. STUDY DESIGN AND METHODS: Forty-nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD-treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment. RESULTS: In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups. CONCLUSION: SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected.

Purification, characterization and immunochemical properties of a novel 60-kDa protein of Vibrio anguillarum strains.

Vibrio anguillarum strains expressed increased amounts of a novel 60-kDa protein when cells were grown at physiologically elevated temperatures. The relative amounts of the 60-kDa protein were unaltered by changes in osmolarity or ionic concentration of the growth medium in cells grown at optimal growth temperatures. The N-terminal amino acid sequence analysis of the V. anguillarum 60-kDa protein showed extensive (94-89%) sequence identity with the 60-kDa heat shock protein of Yersinia enterocolitica and with Serratia rubidaea GroEL protein. Monoclonal antibodies against the Y. enterocolitica chaperonin reacted with the 60-kDa protein from V. anguillarum strains, and with a temperature-induced protein of similar molecular mass in other Gram-negative pathogens of fish.

Epidural bupivacaine-morphine analgesia versus patient-controlled analgesia following abdominal aortic surgery: analgesic, respiratory, and myocardial effects.

BACKGROUND: The efficacy and effects of epidural analgesia compared with patient-controlled analgesia (PCA) have not been reported in patients undergoing major vascular surgery. We compared the effects of epidural bupivacaine-morphine with those of intravenous PCA morphine after elective infrarenal aortic surgery. METHODS: Forty patients classified as American Society of Anesthesiologists physical status 2 or 3 received general anesthesia plus postoperative PCA using morphine sulfate (group PCA; n = 21) or general anesthesia plus perioperative epidural morphine-bupivacaine (group EPI; n = 19) during a period of 48 h. During operation, EPI patients received 0.05 mg/kg epidural morphine and 5 ml 0.25% bupivacaine followed by an infusion of 0.125% bupivacaine with 0.1% morphine (0.1 mg/ ml); group PCA received 0.1 mg/kg intravenous morphine sulfate. Continuous electrocardiographic monitoring (V4 and V5 leads) was performed from the night before surgery until 48 h afterward. Respiratory inductive plethysmographic data were recorded after tracheal extubation. Visual analog pain scores at rest and after movement were performed every 4 h after extubation. RESULTS: Nurse-administered intravenous morphine and time to tracheal extubation were less in group EPI, as were visual analog pain scores at rest and after movement from 20 to 48 h. Complications and the duration of intensive care unit and hospital stay were comparable. There was a similar, low incidence of postoperative apneas, slow respiratory rates, desaturation, and S-T segment depression. CONCLUSIONS: Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements, more rapid tracheal extubation, and superior analgesia after abdominal aortic surgery, with comparable respiratory effects.

Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation.

BACKGROUND: Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis. METHODS: Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay. RESULTS: Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation. CONCLUSIONS: High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.

Infective endocarditis of the pulmonary valve following pulmonary artery catheterisation.

The risk of infective endocarditis following pulmonary artery catheterisation in patients with sepsis remains unquantified. Although catheter-induced endocardial and valvular injury are well recognised, valve infection is rare. A case of mixed pulmonary valve endocarditis associated with the use of a pulmonary artery catheter (PAC) in a patient with multisystem failure following liver trauma is described. This illustrates that diagnosis of infective endocarditis in critically ill patients can be difficult because concurrent illness and therapy may mimic or mask the usual presenting signs. The value of transoesophageal echocardiography in this context is emphasised.

Elderly patients' preferences concerning life-support treatment.

The preferences of 118 elderly patients, aged from 70 to 97 years, concerning the institution of artificial ventilation in the event of an overwhelming illness, were investigated using a questionnaire. Most patients wanted treatment if the outcome was likely to be good, but in approximately half, the desire for treatment declined as anticipated quality of life or chances of recovery fell. Forty percent wanted to make the decision about institution of artificial ventilation themselves if mentally competent and 24% wanted to use some form of advance directive if mentally incompetent.

Mortality during intensive care after orthotopic liver transplantation.

The postoperative course of 335 adult patients who underwent orthotopic liver transplantation from 1968-1987 was reviewed retrospectively to identify patients who died in the intensive care unit and the causes of death. Forty-four percent of all deaths occurred in the intensive care unit. The mortality rate in the intensive care unit peaked in 1984 (48%), but decreased to 11% in 1987. The main causes for death in the intensive care unit were infection (55%) and haemorrhage (19%). The patients who died spent more time in the intensive care unit, had a longer period of tracheal intubation and received a larger intra-operative blood transfusion than patients who died in other locations.

Epidural morphine in the elderly. A controlled trial after upper abdominal surgery.

The effectiveness of epidurally administered morphine in the relief of pain after upper abdominal surgery was assessed in a controlled study involving 20 patients aged 61 to 78 years. Analgesia provided by epidural morphine was comparable to that obtained in matched patients given an intramuscular regime. The total dose required by the epidural route was less than one-fifth that required intramuscularly, and sedation was correspondingly reduced. Postoperative respiratory mechanics, however, were not significantly improved and delayed respiratory depression was observed in one patient. It is concluded that in elderly patients undergoing upper abdominal surgery the risks related to the use of morphine by the epidural route outweigh the marginal advantages it may offer over conventional analgesic techniques.