Socioeconomic status and risk of intensive care unit admission with sepsis.

BACKGROUND: A recent study showed higher risk of bacteremia among individuals with low socioeconomic status (SES). We hypothesized that patients with a low SES have a higher risk of intensive care unit (ICU) admission with sepsis compared to patients with higher SES. METHODS: This was a case-control study on patients with sepsis admitted to the ICU at Aarhus University Hospital, Denmark (2008-2010). Three hundred eighty-three sepsis patients were matched on sex, age, and zip code with controls retrieved from the background population. SES was defined as highest accomplished educational level, yearly income, cohabitation status, and occupation. The odds ratio (OR) of being admitted with sepsis to the ICU was calculated using conditional logistic regression, adjusting for the Charlson Comorbidity Index and the remaining socioeconomic variables. RESULTS: The adjusted odds of being admitted to the ICU with sepsis were significantly higher among individuals living alone (OR 1.72, 95% confidence interval (CI) 1.33-2.24, P < 0.001) compared to individuals living with a cohabitant. Individuals outside the labor force had an adjusted OR of 3.50 (CI 2.36-5.18, P < 0.001) compared to individuals in the labor force. Individuals with a medium level of education had an increased risk of admission to the ICU with sepsis compared to a high level of education (adjusted OR 1.43, CI 1.02-2.00, P = 0.04). There was no significant association between income and risk of ICU admission with sepsis after adjustment. CONCLUSION: Individuals living alone, being outside the labor force, or having a medium level of education had significantly higher risk of ICU admission with sepsis.

Gene flow and population structure of a common agricultural wild species (Microtus agrestis) under different land management regimes.

The impact of landscape structure and land management on dispersal of populations of wild species inhabiting the agricultural landscape was investigated focusing on the field vole (Microtus agrestis) in three different areas in Denmark using molecular genetic markers. The main hypotheses were the following: (i) organic farms act as genetic sources and diversity reservoirs for species living in agricultural areas and (ii) gene flow and genetic structure in the agricultural landscape are influenced by the degree of landscape complexity and connectivity. A total of 443 individual voles were sampled within 2 consecutive years from two agricultural areas and one relatively undisturbed grassland area. As genetic markers, 15 polymorphic microsatellite loci (nuclear markers) and the central part of the cytochrome-b (mitochondrial sequence) were analysed for all samples. The results indicate that management (that is, organic or conventional management) was important for genetic population structure across the landscape, but that landscape structure was the main factor shaping gene flow and genetic diversity. More importantly, the presence of organically managed areas did not act as a genetic reservoir for conventional areas, instead the most important predictor of effective population size was the amount of unmanaged available habitat (core area). The relatively undisturbed natural area showed a lower level of genetic structuring and genetic diversity compared with the two agricultural areas. These findings altogether suggest that political decisions for supporting wildlife friendly land management should take into account both management and landscape structure factors.

Permanent genetic resources added to Molecular Ecology Resources Database 1 August 2012 - 30 September 2012.

This article documents the addition of 83 microsatellite marker loci and 96 pairs of single-nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Bembidion lampros, Inimicus japonicus, Lymnaea stagnalis, Panopea abbreviata, Pentadesma butyracea, Sycoscapter hirticola and Thanatephorus cucumeris (anamorph: Rhizoctonia solani). These loci were cross-tested on the following species: Pentadesma grandifolia and Pentadesma reyndersii. This article also documents the addition of 96 sequencing primer pairs and 88 allele-specific primers or probes for Plutella xylostella.

Lack of agreement and trending ability of the endotracheal cardiac output monitor compared with thermodilution.

BACKGROUND: Minimally invasive monitoring systems of central haemodynamics are gaining increasing popularity. The present study investigated the precision of the endotracheal cardiac output monitor (ECOM) system and its agreement with pulmonary artery catheter thermodilution (PAC TD) for measuring cardiac output (CO) during steady state and with induced haemodynamic changes in patients scheduled for elective cardiac surgery. METHODS: Twenty-five patients were enrolled. After induction of anaesthesia, endotracheal intubation using a dedicated ECOM tube, and insertion of the pulmonary artery catheter (PAC), the patient was placed in the following successive positions: (a) supine, (b) head-down tilt, (c) head-up tilt, (d) supine, (e) supine with phenylephrine administration. CO was measured simultaneously using the ECOM and the PAC. RESULTS: Both methods showed an equally good precision < 10%. Compared to PAC TD, the ECOM system was associated with a bias in supine position of -0.45 l/min (95% confidence interval: -0.86; -0.05), limits of agreement -2.40 l/min to 1.49 l/min and a percentage error of 41.0%. There was no agreement in trending ability between the two methods, with a concordance rate of 30%, shown in a four-quadrant plot. CONCLUSION: In a direct comparison with PAC TD, the ECOM system did not show an acceptable agreement, with wide limits of agreement, a much larger percentage error than should be expected from the precision of the two methods and a very poor trending ability. Thus, the ECOM does not replace measurements done by thermodilution using a pulmonary artery catheter in cardiac surgery patients.

Rapid decline in 51Cr-EDTA measured renal function during the first weeks following lung transplantation.

We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx. Thirty-one consecutive patients (16 females/15 males), mean age 49 (+/-13) years, with emphysema, cystic fibrosis/bronchiectasis or idiopathic pulmonary fibrosis were included in an analysis of renal function before and after LTx. The glomerular filtration rate (GFR) was measured using the (51)Cr-ethylenediaminetetra acetic acid plasma clearance single injection technique (mGFR) at baseline before transplantation and at 1, 2, 3 and 12 weeks postoperatively. Mean mGFR declined from 103 +/- 18 to 65 +/- 22, 53 +/- 16 and 57 +/- 18 mL/min/1.73m(2) at 1-, 3- and 12-weeks post-LTx (p < 0.0001), respectively. In a time-dependent repeated measures ANOVA, risk factors for a decline in mGFR posttransplant included: time (p < 0.0001), acute renal failure within 2 weeks post-LTx (p = 0.0003), use of heart and lung machine (p = 0.04), and the use of ephedrine (p = 0.048), as well as increasing age, older than 18 years at LTx (p = 0.006). These data demonstrate that renal function, measured with an isotope method, decreases dramatically during the first week after LTx.

Increased concentrations of L-lactate in the rectal lumen in patients undergoing cardiopulmonary bypass.

BACKGROUND: Gut ischaemia may contribute to morbidity in patients after cardiopulmonary bypass (CPB), but little is known about the metabolic state of the large bowel in such patients. Therefore we estimated the concentrations of L-lactate and Pco(2) in rectal mucosa in patients undergoing cardiac surgery with or without the use of CPB. METHODS: Patients undergoing coronary artery bypass grafting (CABG) (n=12) or off-pump CABG (n=10) were subjected to equilibrium dialysis of the rectal lumen during the procedure and in the first 4 h afterwards. Dialysate concentrations of L-lactate and Pco(2) were measured using an auto-analyser and compared with values obtained in healthy subjects (n=10). RESULTS: During CPB, a 2- to 3-fold increase in luminal concentrations of L-lactate was observed (CABG vs off-pump CABG, P=0.05; CABG vs healthy subjects, P<0.01). The dialysate concentrations of L-lactate were higher than the mean systemic values (luminal-arterial gradient mean (sd) 0.9 (1.0) mmol litre(-1), P<0.05), and the two values were positively correlated (P<0.05). Luminal L-lactate concentrations remained elevated 4 h after the operation. In contrast, dialysate Pco(2) was equally high in patient and control groups and substantially higher than values observed in arterial blood. CONCLUSIONS: Uncomplicated CPB is associated with moderate but sustained increases in luminal concentrations of L-lactate in the rectum, indicating metabolic dysfunction of the mucosa in the large bowel.

Enlarged clitoris in wild polar bears (Ursus maritimus) can be misdiagnosed as pseudohermaphroditism.

A 23-year-old female polar bear (Ursus maritimus) killed in an Inuit hunt in East Greenland on July 9, 1999 had a significantly enlarged clitoris resembling, in size, form and colour, those of previously reported 'pseudohermaphroditic' polar bears from Svalbard. It has been suggested that an enzyme defect (21-hydroxylase deficiency), androgen producing tumour or high exposure to organochlorines during the foetal stage or early development could be the reason for the supposed pseudohermaphroditism observed for Svalbard bears. Except for the enlarged clitoris, all dimensions of the external and internal reproductive organs of the present were similar to a reference group of 23 normal adult female polar bears from East Greenland collected in 1999-2002. The aberrant bear was a female genotype, and macroscopic examination of her internal reproductive organs indicated that she was reproductively functional. A histological examination of the clitoral enlargement in the present East Greenland specimen allows a first-time histological evaluation of the earlier macroscopic field diagnosis from Svalbard. This examination revealed intense chronic ulcerative and perivascular clitoriditis similar to "acral lick dermatitis" frequently seen in domestic dogs (i.e., we did not find any signs of pseudohermaphroditic hyperplasia of clitoral tissue due to androgenic or antiestrogenic endocrine disruption). The levels of organohalogens and TEQ values were lower than concentration thresholds of toxicological risk. It is hence possible that the previously reported adult female polar bear pseudohermaphrodites from Svalbard are in fact misdiagnoses. Therefore, future studies examining pseudohermaphroditism in wildlife should consider that certain occurrences are natural events, e.g., enlarged clitoris in the present East Greenland polar bear. Furthermore, caution should be exercised in suggesting linkages of such inflammatory abnormalities with correlations to anthropogenic pollutant exposures.

[Heart transplantation]. / Hjertetransplantation.

In carefully selected patients with end-stage heart failure heart transplantation has developed from an experimental procedure to standard therapy during the last 30 years. It is currently accepted as a procedure for prolonging life and also for improving quality of life. According to the Registry of the International Society for Heart and Lung Transplantation the overall one-year actuarial survival is 79% and 10-year survival barely 50%. Nine years after the start of the Heart Transplant Program at Rigshospitalet the overall actuarial survival of 157 consecutive patients is 66%. Due to the limited donor access a decline of heart transplant recipients has been recorded during the late nineties. Mechanical replacement of the heart may develop from technological advances and possibly this therapy may gain a complementary status in heart failure, however the human biological replacement is currently the standard.

The effect of modified ultrafiltration on the amount of circulating endotoxins in children undergoing cardiopulmonary bypass.

OBJECTIVE: To determine whether the use of modified ultrafiltration during pediatric cardiopulmonary bypass (CPB) diminishes the load of circulating endotoxins. DESIGN: Single-arm prospective observational study. SETTING: A university hospital operating room and intensive care unit. PARTICIPANTS: Twenty children undergoing CPB for correction of various congenital heart diseases. INTERVENTIONS: The amount of endotoxins in plasma was measured during CPB and before and after modified ultrafiltration. The ultrafiltrate was assayed for the presence of endotoxins. Postoperatively, the children were followed with relevant infectious parameters and cultures. MEASUREMENTS AND MAIN RESULTS: The amount of endotoxins increased significantly during the CPB procedure (from a median of 1.3 ng [range, 0 to 13.7 ng] to 24.2 ng [range, 2.1 to 75.9 ng]). After termination of CPB, modified ultrafiltration was shown to lower the amount of circulating endotoxins in blood (from a median of 24.2 ng [range, 2.1 to 75.4 ng] to 9.0 [range, 0.1 to 40.6 ng]). The major bulk of this reduction in endotoxin load was retrieved in the ultrafiltrate (median of 11.9 ng [range, 0 to 12.1 ng]). CONCLUSION: This study strongly suggests that modified ultrafiltration decreases the amount of circulating endotoxins in children undergoing cardiac surgery.

Markers of splanchnic perfusion and intestinal translocation of endotoxins during cardiopulmonary bypass: effects of dopamine and milrinone.

OBJECTIVES: To investigate markers of splanchnic perfusion and the extent of endotoxemia during cardiopulmonary bypass (CPB) and to compare the effects of dopamine and milrinone on both splanchnic perfusion and endotoxemia. DESIGN: Prospective, randomized, blinded study. SETTING: University teaching hospital. PARTICIPANTS: Twenty-four patients scheduled for elective coronary artery bypass graft surgery (CABG). INTERVENTIONS: Patients were allocated to receive placebo (eight patients), dopamine (eight patients), or milrinone (eight patients) during CPB, and at seven times intraoperatively assays were performed of arterial and hepatic venous endotoxin levels, as well as measurements and/or calculations of intramucosal gastric pH (pHi), arterial and hepatic venous lactate-pyruvate ratio (lac/pyr), and hepatic venous oxygen saturation (S(HV)O2). MEASUREMENTS AND MAIN RESULTS: Both splanchnic and systemic endotoxin levels increased significantly, and this was unaffected by either dopamine or milrinone. Gastric pHi did not change, and there were only modest increases in lac/pyr, which remained within the normal range of less than 10 in both splanchnic and systemic blood. In the placebo group, S(HV)O2 decreased at the onset of CPB and also significantly decreased during rewarming and at the end of CPB and surgery. In the dopamine-treated patients, S(HV)O2 was greater compared with placebo and milrinone during both hypothermic and rewarming phases. CONCLUSION: Endotoxemia occurs during routine CPB. Neither pHi nor lac/pyr values showed adverse change, but hepatic venous oximetry may be a more sensitive indicator of splanchnic dysoxia in that S(HV)O2 was reduced during rewarming. Whether dopamine or milrinone confer protection against splanchnic ischemia remains uncertain.

Population structure and gene flow of the Atlantic walrus (Odobenus rosmarus rosmarus) in the eastern Atlantic Arctic based on mitochondrial DNA and microsatellite variation.

The population structure of the Atlantic walrus, Odobenus rosmarus rosmarus, was studied using 11 polymorphic microsatellites and restriction fragment length polymorphism detected in the NADH-dehydrogenase ND1, ND2 and ND3/4 segments in mtDNA. A total of 105 walrus samples were analysed from northwest (NW) Greenland, east (E) Greenland, Svalbard and Franz Joseph Land. Two of the 10 haplotypes detected in the four samples were diagnostic for the NW Greenland sample, which implied that the group of walruses in this area is evolutionary distinct from walruses in the other three areas. One individual sampled in E Greenland exhibited a Pacific haplotype, which proved a connection between the Pacific walrus and walruses in eastern Greenland. The Franz Joseph Land, Svalbard and E Greenland samples shared the most common haplotype, indicating very little differentiation at the mtDNA level. Gene flow (Nm) estimates among the four areas indicated a very restricted exchange of female genes between NW Greenland and the more eastern Atlantic Arctic samples, and a closer relationship between the three samples composing the eastern Atlantic Arctic. The genetic variation at 11 polymorphic microsatellite loci grouped individuals into three populations, NW Greenland, E Greenland and a common Franz Joseph Land-Svalbard population, which were connected by moderate gene flow.

A combined DNA-microsatellite and isozyme analysis of the population structure of the harbour porpoise in Danish waters and west Greenland.

One hundred and twenty-four specimens of the harbour porpoise, Phocoena phocoena, occurring in inner Danish waters (IDW), the North Sea and West Greenland were analysed to study subdivision into genetically differentiated subpopulations using PCR-amplified DNA-microsatellites and isozyme markers. Three polymorphic microsatellites, 415/416, 417/418 and Igf-I (insulin-like growth factor I) were detected with nine, eight and 15 alleles, respectively, and from a former study two polymorphic isozymes, Mpi-1 and Pgm, with three and two alleles, respectively, were used in the analysis. Overall deviations from the expected Hardy-Weinberg distribution were only observed in the total sample and at a single locus in the North Sea-summer sample and at two loci in the West Greenland sample. Whenever this occurred a surplus of homozygotes was observed, suggesting a Wahlund effect, a null allele or nonrandom mating. The analysis of the genetical population structure showed that harbour porpoises from West Greenland, the North Sea and IDW were three geographically, genetically differentiated populations even though connected through some degree of gene flow. A tendency for females to be more stationary than males was suggested. Furthermore, the population structure suggested a closer relationship between IDW and the North Sea.

Laboratory studies of the effect of Pall extracorporeal leucocyte filters LG6 and AV6 on patients undergoing coronary bypass grafts.

A total of 14 patients with ischaemic heart disease undergoing coronary artery bypass grafts were studied for the effect of AV6 control filter and LG6 neutrophil filter, used in the extracorporeal circulation, on different laboratory parameters. There was no statistical difference between the effects of AV6 and LG6 filters on total white cells, neutrophils, monocytes, lymphocytes, platelets or haemoglobin. The expression of neutrophil activation antigens identified with a panel of monoclonal antibodies demonstrated that for the LG6 filter the leucocyte tyrosine phosphate CD45Ro fell during the procedure, whilst there were no significant changes in any of the other neutrophil antigens. The AV6 filter did not significantly diminish the expression of any of the neutrophil antigens. An indirect measure of superoxide production using Dihydrorhodamine 123 identified that the more activated cells appeared to be depleted across the LG6 filter which was not evident with the AV6 filter. These studies indicate that the LG6 is not capable of significantly depleting the neutrophil load generated during extracorporeal circulation but may be capable of selectively removing the more activated forms.

Studies of the effect of Pall leucocyte filters LG6 and AV6 in an in vitro simulated extracorporeal circulatory system.

Neutrophil activation is thought to play a major role in the inflammatory response seen in reperfusion injury and similar clinical situations, i.e. extracorporeal circulation. Impairment of neutrophil function or reduction of total numbers of neutrophils using a leucocyte filter may be beneficial in reducing the adverse clinical effects. In this study we have investigated the effect of the Pall LG6 and control AV6 filters during simulated in vitro cardiopulmonary bypass (CPB). Various parameters were evaluated including neutrophils, total leucocytes, monocytes, lymphocytes and platelets, expression of antigens on neutrophils using a panel of leucocyte-associated monoclonal antibodies CD13, 14, 15, 45Ro, 67, 11a, 11b and L selectin. The effects of leucocyte stimulation with phorbol myristate acetate (PMA) and a leucocyte bolus from a patient with chronic myeloid leukaemia (CML) were also investigated. We have demonstrated that the LG6 significantly reduces leucocytes, in particular neutrophils, with a modest reduction of lymphocytes, platelets and haematocrit, whereas the AV6 had no effect on leukocytes or neutrophils in the test system. In addition the LG6 was associated with a reduction in expression of all leucocyte antigens by approximately 20%; however there was no appreciable alteration of any of the antigens with AV6. Leucocyte stimulation with PMA resulted in a dramatic decrease of all cellular elements and an extra leucocyte load (using CML leucocytes) was not effectively filtered by the LG6 filter. These studies identify the capacity of the LG6 as compared with the AV6 to deplete activated neutrophils in an in vitro simulated cardiopulmonary bypass circuit.

The role of N-acetylcystein administration on the oxidative response of neutrophils during cardiopulmonary bypass.

The role of N-acetylcystein (NAC) administration on the oxidative response of neutrophils during cardiopulmonary bypass (CPB) was evaluated in a double-blind study. Twenty-four adult patients undergoing coronary artery bypass were included in the study. Twelve patients received NAC as a bolus of 100 mg/kg followed by a continuous infusion of 20 mg/kg/h in the bypass circuit from the beginning to the end of bypass. A further 12 patients received placebo. Citrated blood samples for measurement of oxidative burst response of neutrophils were obtained at different time points during bypass. The oxidative burst response of neutrophils in the patients receiving NAC was significantly low at all times during bypass. Based on these findings NAC appears to act as an oxygen free radical scavenger during open-heart surgery.

Splanchnic ischaemia and its role in multiple organ failure.

Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor alpha, and other biologic mediators by endotoxin-stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure. Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identified and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.

Association between gastric intramucosal pH and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor-alpha concentrations in patients undergoing cardiopulmonary bypass.

OBJECTIVES: To determine the association between gastric intramucosal pH, a minimally invasive marker reflecting the adequacy of oxygen delivery to the gastrointestinal tract, and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor (TNF)-alpha concentrations in patients undergoing cardiopulmonary bypass. DESIGN: Single-arm, prospective study. SETTING: University hospital. PATIENTS: Adults (n = 10) free of hepatic, pulmonary, and renal disease undergoing nonemergent coronary artery bypass surgery. INTERVENTIONS: After induction of general anesthesia and endotracheal intubation, a tonometer nasogastric tube was positioned in the stomach, and triple-lumen fiberoptic catheters were inserted into the hepatic vein and pulmonary artery. Hepatic venous and mixed venous blood samples were analyzed for endotoxin, antibody to endotoxin, and TNF-alpha at six times: 30 mins after induction of anesthesia (time 1); during vena caval cannulation (time 2); after 15 mins of hypothermic cardiopulmonary bypass (time 3); during spontaneous left ventricular ejection after release of the aortic cross-clamp, but before termination of cardiopulmonary bypass (time 4); 15 mins after termination of cardiopulmonary bypass (time 5); and 1 hr after termination of cardiopulmonary bypass (time 6). Gastric intramucosal pH, systemic oxygen delivery (DO2), mixed venous oxygen saturation, hepatic venous oxygen saturation, and hepatic venous lactate concentrations were recorded at these same times. Data for each variable were compared with baseline values (time 1) for statistical significance. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary bypass was associated with an increase (p < .05) in systemic endotoxin concentrations from ventricular ejection until the end of the study. Virtually identical changes in the splanchnic circulation at this time approached, but did not reach, statistical significance, because hepatic venous endotoxin concentrations were higher than the mixed venous endotoxin concentrations at baseline (41.6 +/- 11.2 vs. 16.9 +/- 4.9 pg/mL). Gastric intramucosal pH was abnormal (< 7.35) at 15 mins (p > .05) and at 1 hr after termination of cardiopulmonary bypass (p > .05). The relationship between endotoxin and gastric intramucosal pH was not statistically significant (p = .15). The decrease in endotoxin antibody was small and statistically insignificant. TNF-alpha was not detected in any patient. Systemic DO2 decreased (p < .05) after 15 mins of hypothermic cardiopulmonary bypass, but returned to baseline values thereafter. There were no significant changes in mixed venous and hepatic venous oxygen saturation values. Splanchnic lactate concentrations increased at cannulation (p < .05), after 15 mins of hypothermic cardiopulmonary bypass (p < .05), and 15 mins after termination of cardiopulmonary bypass (p < .05). CONCLUSIONS: These observations are consistent with the hypothesis that impaired gut-barrier function is responsible for endotoxemia occurring during cardiopulmonary bypass. It is unclear whether increased mucosal permeability and mucosal acidosis are causally related phenomena or simply independent markers of damage to gut epithelium.

[Anesthesiologic aspects of multiorgan donation]. / Anaestesiologiske aspekter ved multiorgandonation.

As of July 1990 brain death was legally recognized in Denmark thereby rendering transplantation of heart, liver and lung possible. Brain death donors are usually treated in neurosurgical or anaesthetic intensive care units. The staff of these units influence the number of donors and also the quality of organs donated. Physiological factors pertinent to brain death donors and pre- and peroperative donor therapy in relation to multiorgan procurement are discussed from the viewpoint of the anaesthetist. Symptomatic therapy aimed at optimizing and maintaining organ function is employed; thus continuing intensive care. Sympathetic and somatic reflex responses to surgical stimulation are to be anticipated, often necessitating analgesics to blunt haemodynamic responses and neuromuscular blocking agents to inhibit movements and/or rigidity.