Nairne Scott-Douglas

Overview of the Alberta Kidney Disease Network

BackgroundThe Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.DescriptionThe laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.ConclusionThe unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.

Prevention of Dialysis Catheter Malfunction with Recombinant Tissue Plasminogen Activator

BACKGROUND The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session (catheter locking solutions) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown. METHODS We randomly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin (5000 U per milliliter) three times per week or recombinant tissue plasminogen activator (rt-PA) (1 mg in each lumen) substituted for heparin at the midweek session (with heparin used in the other two sessions). The primary outcome was catheter malfunction, and the secondary outcome was catheter-related bacteremia. The treatment period was 6 months; treatment assignments were concealed from the patients, investigators, and trial personnel. RESULTS A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only (34.8%) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly (hazard ratio, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P = 0.02). Catheter-related bacteremia occurred in 15 patients (13.0%) assigned to heparin only, as compared with 5 (4.5%) assigned to rt-PA (corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups, respectively; P = 0.02). The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 (hazard ratio, 3.30; 95% CI, 1.18 to 9.22; P = 0.02). The risk of adverse events, including bleeding, was similar in the two groups. CONCLUSIONS The use of rt-PA instead of heparin once weekly, as compared with the use of heparin three times a week, as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia. (Current Controlled Trials number, ISRCTN35253449.).

Hyperhomocyst(e)inemia and the prevalence of atherosclerotic vascular disease in patients with end-stage renal disease

Hyperhomocyst(e)inemia is now recognized as an independent risk factor for atherosclerotic cardiovascular disease in patients with normal renal function. Hyperhomocyst(e)inemia is common in patients with chronic renal failure. This study is designed to look for an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients with end-stage renal disease (ESRD). Two hundred eighteen patients undergoing hemodialysis were enrolled onto the study and had predialysis bloodwork performed for total homocyst(e)ine, red blood cell folate, and vitamin B(12) levels. A history of clinically significant atherosclerotic vascular disease (ischemic heart disease, cerebrovascular disease, or peripheral vascular disease) was elicited by patient questionnaire and verified by careful inpatient and outpatient chart review. Atherosclerotic vascular disease was present in 45.9% of patients. Mean homocyst(e)ine concentration was 26.7 micromol/L (95% confidence interval [CI], 25.0 to 28.4) overall. Mean homocyst(e)ine concentration was 28.6 micromol/L (95% CI, 25.6 to 31.7) and 25.0 micromol/L (95% CI, 23.2 to 26.8) in patients with and without atherosclerotic disease, respectively (P = 0.036). The adjusted odds ratio for atherosclerotic disease was 2.12 (95% CI, 1.03 to 4.39) for those subjects with a homocyst(e)ine level in the highest quartile compared with the lowest 3 quartiles. In the 126 men, the adjusted odds ratio for atherosclerotic disease was 3.4 (95% CI, 1. 24 to 9.42) for those with homocyst(e)ine levels in the highest quartile compared with the lowest 3 quartiles. No association was found between homocyst(e)ine level and atherosclerotic disease in women. In conclusion, there is an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients undergoing dialysis. Prospective studies need to further examine the relationship between homocyst(e)ine level and atherosclerosis in women with ESRD.

Nonuniformity of pericardial surface pressure in dogs.

Previously, we have shown that pericardial constraint cannot be measured by true (hydrostatic) pressure except when an excess of pericardial fluid is present and that a device such as a balloon (which reflects radial contact stress as well as hydrostatic pressure) must be used. Since radial contact stress is the major component of the constraint exerted by the pericardium when little pericardial liquid is present, it follows that the pressure measured by the balloon might be different over different parts of the heart. In an attempt to test this hypothesis, in 11 anesthetized dogs we placed pericardial balloons over the right and left ventricular free walls, instrumented the animals to measure ventricular dimensions (sonomicrometry) and pressure, mounted pneumatic constrictors on the aortic and pulmonary artery, reapproximated the pericardium, and closed the chest under suction. We studied the transient effects of constrictions of the ascending aorta and pulmonary artery and of angiotensin infusion before and after intravenous saline infusion. Aortic constriction and, to a lesser degree, angiotensin increased pericardial pressure over the left ventricle more than over the right ventricle. Pulmonary artery occlusion increased pericardial pressure over the right ventricle but significantly decreased pericardial pressure over the left ventricle. We conclude that there are significant local differences in pericardial pressure (recorded by balloon) over the lateral ventricular surfaces during acute changes in afterload. These observations may be explained in part by decreased venous return to the contralateral ventricle, the tendency of the heart to resist lateral displacement, and the limited mobility of the pericardium.

Adrenal vein sampling may not be a gold-standard diagnostic test in primary aldosteronism: final diagnosis depends upon which interpretation rule is used

BackgroundAdrenal vein sampling (AVS) is considered the gold-standard test to demonstrate unilateral aldosterone excess in primary aldosteronism, yet no single approach to interpretation of AVS has been externally validated.HypothesisThere may be significant inter-observer variability in the final diagnosis of unilateral vs. bilateral aldosterone excess depending on which AVS interpretation rule is used.MethodsRetrospective chart review of 63 subjects with primary aldosteronism undergoing AVS and 40 subsequent adrenalectomies for presumed unilateral aldosteronism. The data from the AVS were retrospectively re-analyzed according to a variety of interpretation criteria published in the literature. Using 40 subjects undergoing surgery, pathology and clinical outcomes defined the final diagnosis of aldosteronism subtype, and these subjects’ AVS results were used to estimate the true sensitivity and specificity of the various approaches to AVS interpretation.ResultsDiagnostic discrepancies exist between the different AVS interpretation rules. Successful adrenal vein catheterization was confirmed in between 13% and 77% of AVS attempts. Sensitivity of AVS ranged from 47% to 100% and specificity 55–100%. Only 17% of all cases would be categorized uniformly by all interpretation criteria. Use of biochemical catheter placement criteria and ACTH infusion improved the proportions of AVS results defined as successful and showing lateralization.ConclusionsWe found substantial variabilty in final diagnosis by using different systems of interpreting AVS results as suggested in the literature This suggests AVS may not always be considered a gold-standard diagnostic test.

Splanchnic Venous Pressure–Volume Relation During Experimental Acute Ischemic Heart Failure Differential Effects of Hydralazine, Enalaprilat, and Nitroglycerin

BACKGROUND Vasodilator drugs have variable effects on veins and arteries. However, direct measurements of their effects on the splanchnic veins, perhaps the most important volume reservoir, have not been reported. We assessed the effect of acute heart failure and the subsequent administration of hydralazine, enalaprilat, and nitroglycerin on the splanchnic venous pressure-volume relation in intact dogs. METHODS AND RESULTS Experimental acute ischemic heart failure was induced in 19 splenectomized dogs by microsphere embolization of the left main coronary artery. Embolization was repeated until left ventricular end-diastolic pressure (LVEDP) reached 20 mm Hg and cardiac output decreased by 50%. The splanchnic vascular pressure-volume relation was determined by radionuclide plethysmography during the control stage, after acute heart failure had been established, and after administration of a vasodilator (hydralazine, enalaprilat, or nitroglycerin) at a dose sufficient to reduce mean aortic pressure by approximately 20%. Induction of acute heart failure was associated with a decrease in the splanchnic vascular volume from 100% to 86 +/- 2% and an increase in LVEDP from 6 +/- 1 to 21 +/- 1 mm Hg (P < .001). There was a parallel leftward shift of the splanchnic vascular pressure-volume curve. After the administration of hydralazine, enalaprilat, and nitroglycerin, the splanchnic vascular volumes increased from 86% to 88 +/- 3%, 96 +/- 3%, and 113 +/- 3%, respectively (P = NS, P < .01, and P < .001, respectively, versus heart failure). After drug administration, the LVEDPs were 18 +/- 2, 16 +/- 1, and 13 +/- 1 mm Hg (P = NS, P < .05, and P < .001, respectively, versus heart failure). CONCLUSIONS Acute heart failure was associated with a parallel leftward shift of the splanchnic venous pressure-volume relation (venoconstriction). Splanchnic (systemic) venoconstriction may in part explain the increased LVEDP during acute heart failure by displacement of blood to the central compartment. Subsequently administered enalaprilat and, to a greater degree, nitroglycerin produced splanchnic venodilation, thereby lowering LVEDP. Hydralazine had no significant effect on the splanchnic veins and only a modest effect on LVEDP. In this model, splanchnic capacitance changes appear to modulate change in left ventricular preload.

Modulation of vascular capacitance by angiotensin and nitroprusside: a mechanism of changes in pericardial pressure.

The aim of the present study was to test the hypothesis that vasoactive drugs may modify left ventricular diastolic function by shifting blood between the systemic vascular bed and the heart, thereby changing pericardial and left ventricular pressure. The experiments were done in 10 open-chest, anesthetized, previously splenectomized dogs in which changes in pericardial surface pressure in response to intravenous sodium nitroprusside and angiotensin were related to changes in blood volume in the abdominal region. Blood volume was determined by blood pool scintigraphy (99mTc) and regions of interest were drawn in the liver and in the mesenteric area. Angiotensin was infused at rates that were adjusted to increase mean aortic pressure by 20 and 30 mm Hg, and nitroprusside was infused at rates to decrease mean aortic pressure by 30 and 50 mm Hg. Angiotensin increased pericardial pressure by 3 and 5 mm Hg at the respective doses and there were increments in left ventricular end-diastolic pressure (LVEDP) and left ventricular diameter (sonomicrometry). Angiotensin decreased blood volume in the mesenteric region by 14% and 17%, but did not significantly change blood volume in the liver region. Angiotensin increased portal venous pressure and decreased mesenteric blood volume, suggesting decreased mesenteric venous compliance. Nitroprusside had opposite effects: pericardial pressure was decreased by 5.5 and 6.5 mm Hg by the respective doses. The doses of nitroprusside increased blood volume in the mesenteric region by 14% and 20%, but did not significantly change blood volume in the liver region.(ABSTRACT TRUNCATED AT 250 WORDS)

Concentration of heparin-locking solution and risk of central venous hemodialysis catheter malfunction.

Heparin is used as an interdialytic locking solution for hemodialysis (HD) central venous catheters (CVCs). The purpose of this study was to compare effectiveness of two heparin concentrations (10,000 and 1,000 U/mL) in preventing catheter malfunction. We compared two time periods: a 6-month period with heparin 10,000 U/mL and a 3-month period with heparin 1,000 U/mL. Adults on HD using a CVC (tunneled or untunneled) in Calgary, Alberta, were included. The primary outcome was catheter malfunction. A total of 139 and 134 patients in the heparin 10,000 and 1,000 U/mL periods, respectively, were included. The crude rate of catheter malfunction, per 1,000 HD sessions, was similar for heparin 10,000 (7.6; 95% CI, 5.3 to 10.8) and 1,000 (6.7; 95% CI, 4.3 to 10.3) U/mL periods, respectively (p = 0.76). After adjusting for CVC characteristics and use of recombinant tissue plasminogen activator (rt-PA), there was no association between heparin concentration and CVC malfunction (hazard ratio, 0.77; 95% CI, 0.37 to 1.61). In conclusion, the use of a lower concentration of heparin was not associated with an increased risk of catheter malfunction but may be associated with greater rt-PA use. The association between heparin concentration and rt-PA use requires further study.

The right and left ventricular intracavitary and transmural pressure-strain relationships

The magnitude of pericardial pressure and therefore the shape of the right ventricular end-diastolic transmural pressure-volume relationship remains controversial. To investigate ventricular compliance, eight dogs anesthetized with fentanyl were instrumented as follows. Right and left ventricular intracavitary pressures were measured with micromanometer-tipped catheters. Right and left ventricular free wall segment lengths were measured by sonomicrometry. Pericardial pressure was measured over the right and left ventricles by means of flat liquid-containing balloon transducers, and transmural pressures were calculated as the difference between intracavitary and pericardial pressures. After defining the pressure-segment length relationship by vena caval constriction followed by release and blood transfusion, the pericardium and chest were opened widely and the cardiac volume manipulation was repeated; this allowed direct measurement of transmural right ventricular end-diastolic pressure for each level of strain recorded with the chest and pericardium closed. When intracavitary right or left ventricular end-diastolic pressure was raised from zero to 20 mm Hg, the respective transmural pressures increased from 0.2 +/- 0.6 (SD) mm Hg to 2.5 +/- 1.8 mm Hg and from 0.3 +/- 0.7 mm Hg to 6.0 +/- 2.5 mm Hg. Ventricular segmental strain increased by 7.0 +/- 0.8% and 6.0 +/- 0.2%, respectively. No statistically significant differences were found between right ventricular calculated (intracavitary minus pericardial pressure) and measured (open pericardium, open chest) transmural pressures at a given strain, thereby confirming the accuracy of our pericardial pressure measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

An Economic Evaluation of rt-PA Locking Solution in Dialysis Catheters

In a recent randomized trial, weekly recombinant tissue plasminogen activator (rt-PA), 1 mg per lumen, once per week, and twice-weekly heparin as a locking solution (rt-PA/heparin) resulted in lower risks of hemodialysis catheter malfunction and catheter-related bacteremia compared with thrice-weekly heparin (heparin alone). We collected detailed costs within this trial to determine how choice of locking solution would affect overall health care costs, including the cost of locking solutions and all other relevant medical costs over the course of the 6-month trial. Nonparametric bootstrap estimates were used to derive 95% confidence intervals (CIs) and mean cost differences between the treatment groups. The cost of the locking solution was higher in patients receiving rt-PA/heparin, but this was partially offset by lower costs for managing complications. Overall, the difference in unadjusted mean cost for managing patients with rt-PA/heparin versus heparin alone was Can