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Martine Leblanc

Publications and source records attributed to Martine Leblanc.

31 records · Page 2Linked to original sources

Quinine pharmacokinetics in chronic haemodialysis patients.

AIMS: Quinine is often used to prevent muscle cramps in patients with chronic renal failure. A standard dose of 300 mg at bedtime is usually recommended, but little is known about the pharmacokinetics of quinine in the presence of renal failure. METHODS: We studied the pharmacokinetics of quinine in eight normal subjects and eight patients with chronic renal failure on haemodialysis after a single oral dose of quinine sulphate (300 mg). RESULTS: The concentration of alpha1-acid glycoprotein (AAG), the major binding protein for quinine, was increased in haemodialysis patients compared with control subjects (1.52 g l-1 vs 0.63 g l-1 [mean difference 1.033; 95% CI 0.735, 1.330]) whereas albumin levels were decreased (30 g l-1 vs 40 g l-1 [mean difference 9.5; 95% CI 3.048, 15.952]). Accordingly, the free fraction of quinine was decreased (0.024 vs 0.063 [mean difference 0.0380; 95% CI 0.0221, 0.0539]) and the apparent volume of distribution tended to decrease (0.95 l kg-1 vs 1.43 l kg-1 [mean difference 0.480; 95% CI 0.193, 1.154]). The quinine binding ratio correlated with the plasma concentration of AAG but not that of albumin. The clearance of free (unbound) quinine was increased in haemodialysis patients compared with controls (67.9 ml min-1 kg-1 vs 41.1 ml min-1 kg-1 [mean difference -26.8; 95% CI, -56.994, 3.469]), and the area under the curve (AUC) of the two main metabolites, 3-hydroxyquinine and 10,11-dihydroxydihydroquinine were increased. CONCLUSIONS: In patients with chronic renal failure, there is an increase in plasma protein binding and in the clearance of free drug, resulting in lower plasma concentration of free quinine.

Administration, Oral↗

Prospective evaluation of the intra-access flow of recently created native arteriovenous fistulae.

BACKGROUND: The aim of this study is to assess the evolution of intra-access flow (Q(ac)) in recently created native arteriovenous fistulae (AVFs) during the first few months of use. METHODS: All AVFs were monitored by means of ultrasound dilution using Transonic (Transonic Systems Inc, Ithaca, NY). First Q(ac) measurements were obtained between 6 to 10 weeks after creation and subsequently every 3 to 6 weeks during the following 4 months. Per routine, AVFs are cannulated 6 weeks after their creation in our unit. Fifty-seven patients with new AVFs were initially enrolled, but 12 patients were lost at follow-up. There was a 69% to 31% ratio of brachiocephalic (BC) to radiocephalic (RC) AVFs, and diabetes affected an equal proportion of patients in both subtypes. RESULTS: Mean initial and final Q(ac)s were 1,132 +/- 681 and 1,097 +/- 644 mL/min, respectively; there was no significant difference during the study period. However, the Q(ac) of BC AVFs remained approximately twice as high as the Q(ac) of RC AVFs during the observation period (initial Q(ac), 1,336 +/- 689 versus 645 +/- 332 mL/min; final Q(ac), 1,285 +/- 652 versus 647 +/- 331 mL/min, respectively). Male sex was associated with a greater Q(ac) throughout the evaluation (1,263 +/- 754 versus 852 +/- 375 mL/min for women). No significant difference was noted between different age groups, and diabetes did not significantly affect Q(ac). Finally, the initial Q(ac) of a BC AVF was influenced by the presence of a previously functioning RC AVF on the same arm. The initial Q(ac) in BC AVFs was 1,800 +/- 919 mL/min in that subgroup (and decreased to 1,302 +/- 733 mL/min by the end of the study, therefore becoming similar to the mean Q(ac) of other BC AVFs). CONCLUSION: From these results, we conclude that newly created native AVFs have an initial Q(ac) that does not vary significantly during the first 6 months and may already be maximal at 6 weeks or at the time of first needle puncture in our hands. Among demographic factors, sex influences the Q(ac) of native AVFs, whereas age and diabetes do not.

Aged↗

The Acute Dialysis Quality Initiative--part IV: membranes for CRRT.

The extracorporeal membrane used in a continuous renal replacement therapy (CRRT) for the treatment of a critically ill patient with acute renal failure (ARF) is vitally important for several reasons, including its influence on biocompatibility and filter performance. The clinical relevance of membrane-related biocompatibility markers traditionally used in chronic hemodialysis remains unclear in CRRT. Numerous approaches may be used to assess membrane and filter performance in CRRT, but no specific methodology is accepted widely at present. Although a potential benefit of certain membranes used for CRRT is adsorptive removal of inflammatory mediators, this issue has not been assessed carefully in well-designed clinical trials. These and other issues should be the subject of future clinical research efforts.

Acute Kidney Injury↗

The Acute Dialysis Quality Initiative--part VII: fluid composition and management in CRRT.

Fluid composition and management are important parts of continuous renal replacement therapy (CRRT). Most commercially available CRRT solutions are able to reestablish electrolyte homeostasis provided some phosphate supplementation is given. Supraphysiologic glucose concentrations should be avoided. Predilution fluid replacement allows higher ultrafiltration rates and can be considered as an adjunct to the anticoagulation regimen. Lactate is an effective buffer in most CRRT patients. Bicarbonate is preferred in patients with lactic acidosis and/or liver failure. When citrate is used as anticoagulant, frequent monitoring of pH is required. The clinical consequences of CRRT-induced decreases of body temperature are not clear. Substitution fluid should be sterile, but the bacteriologic requirements for CRRT dialysate are less clear. There is no consensus on the optimal parameters to monitor fluid management. Integrated balancing systems have theoretical advantages over adaptive use of intravenous fluid pumps. Although there is evidence that volume overload is associated with adverse outcome, there is no evidence that fluid removal per se improves outcome in critically ill patients with or without acute renal failure.

Buffers↗

Acute renal failure in bone marrow transplant patients admitted to the intensive care unit.

BACKGROUND/AIMS: Review of bone marrow transplant (BMT) cases admitted to our intensive care unit (ICU) and to compare co-morbidity and outcome of BMT patients developing or not developing acute renal failure (ARF). METHODS: A case review of BMT patients admitted to the ICU (a 16-bed medico-surgical ICU in a tertiary care teaching institution) over a 4-year period. RESULTS: Between January 1994 and December 1998, 57 among 441 BMT patients (12.9%) were admitted to the ICU, mainly for respiratory distress (58%) and hypotension (32%). Forty-two patients (73.7%) presented ARF as defined as a doubling of serum creatinine. Compared to the 15 other patients, ARF patients had a higher APACHE II score (30 +/- 8 vs. 25 +/- 7, p < 0.05). For ARF vs. non-ARF patients, there was no difference in age (43.8 +/- 10.8 vs. 44.3 +/- 11.1 years), in requirement for mechanical ventilation (76 vs. 73%) and vasopressors (69 vs. 60%), and in prevalence of graft-versus-host disease (19 vs. 13%) or neutropenia (69 vs. 67%), but the prevalence of sepsis (83 vs. 60%) and liver failure (69 vs. 40%) was higher. Maximum serum bilirubin was markedly increased in ARF compared to non-ARF patients (p < 0.005). For both subgroups, no difference in the administration of potential nephrotoxic agents was identified. Usually, ARF was considered multifactorial by clinicians, with ATN being the most frequent diagnosis (55%). Maximum serum creatinine reached a mean of 330 +/- 130 micromol/l. In 74% of cases, ARF occurred concomitantly or after admission to the ICU. Oligoanuria was present in 38%, whereas polyuria was observed in 17%. Fourteen ARF patients (33%) required dialytic support. Mortality rates were significantly different in ARF vs. non-ARF patients (88 vs. 60%, p < 0.05). Predictive factors for the development of ARF were liver failure (odds ratio (OR) 5.9), low serum albumin (OR 1.2) and APACHE II score (OR 1.1), whereas variables predictive of mortality were mechanical ventilation (OR 14.8), ARF (OR 5.8), liver failure (OR 3.7), and APACHE II score (OR 1.2). CONCLUSIONS: This study confirms that ARF in BMT patients admitted to the ICU is frequent, multifactorial, related to liver failure, and that its development has a negative impact on outcome.

Acute Kidney Injury↗

Continuous versus intermittent renal replacement therapy: a meta-analysis.

OBJECTIVE: Patients with critical illness commonly develop acute renal failure requiring mechanical support in the form of either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IRRT). As controversy exists regarding which modality should be used for most patients with critically illness, we sought to determine whether CRRT or IRRT is associated with better survival. DESIGN: We performed a meta-analysis of all prior randomized and observational studies that compared CRRT with IRRT. Studies were identified through a MEDLINE search, the authors' files, bibliographies of review articles, abstracts and proceedings of scientific meetings. Studies were assessed for baseline characteristics, intervention, outcome and overall quality through blinded review. The primary end-point was hospital mortality, assessed by cumulative relative risk (RR). MEASUREMENTS AND RESULTS: We identified 13 studies ( n=1400), only three of which were randomized. Overall there was no difference in mortality (RR 0.93 (0.79-1.09), p=0.29). However, study quality was poor and only six studies compared groups of equal severity of illness at baseline (time of enrollment). Adjusting for study quality and severity of illness, mortality was lower in patients treated with CRRT (RR 0.72 (0.60-0.87), p<0.01). In the six studies with similar baseline severity, unadjusted mortality was also lower with CRRT (RR 0.48 (0.34 -0.69), p<0.0005). CONCLUSIONS: Current evidence is insufficient to draw strong conclusions regarding the mode of replacement therapy for acute renal failure in the critically ill. However, the life-saving potential with CRRT suggested in our secondary analyses warrants further investigation by a large, randomized trial.

Critical Care↗

Hemodialysis catheter tip embolization in the right pulmonary vasculature: report of a cardiac arrest.

A 44 year old woman on hemodialysis presented a sudden cardiorespiratory arrest at the end of an otherwise uneventful dialysis session. It occurred while disconnecting the circuit from her tunneled catheter. She was reanimated and then transferred to the intensive care unit; the endotracheal intubation had been difficult, and she had been severely hypoxic. It was noted that the external venous clamp of the tunneled catheter was broken and the hypothesis of a break during the reanimation process was entertained. The routine chest x-ray postintubation showed that the tip of the catheter was ruptured and visible in one branch of the right pulmonary artery. The catheter was changed over a guide wire, and the broken catheter was sent for analysis to the manufacturer. A selective angiography of the right pulmonary artery was performed with the purpose of removing the fractured catheter tip but was unsuccessful. The patient recovered neurologic function slowly over the next 4 months. The exact etiology of the arrest remains incompletely understood; it is unknown whether it was caused by the catheter tip embolization or if an air embolism occurred.

Adult↗

Blood flow and recirculation rates in tunneled hemodialysis catheters.

Long-term catheters are widely used in some dialysis units. Because of higher dialysis dose targets, high flow catheters have been made available. We measured blood flow (Qb in ml/min) and recirculation rate (R%) in two types of tunneled dialysis catheters using ultrasound-dilution technology (Transonic). Thirty-seven catheters were evaluated (27 Opti-Flow, 10 High-Flow), as inserted in jugular or subclavian veins. Real Qb and R were measured at increasing pump blood flows (250, 300, 350, 400, and 450 ml/min) in absence of ultrafiltration. For all, real Qb was similar to pump Qb (261 vs. 250, 304 vs. 300, 349 vs. 350, 389 vs. 400, and 431 vs. 450 ml/min, respectively). Catheters with reversed lines were all recirculating (R between 18% and 24%). Sixteen nonreversed catheters had no R at all Qb, whereas four nonreversed catheters had minimal R (between 7% and 11%); R did not increase significantly with the rise in pump Qb. The two types of tunneled catheters deliver high Qb without high R if ports are not reversed. The relative decrease in treatment efficiency should be accounted for in dialysis prescription if such tunneled catheters are used as long-term access, especially if lines have to be reversed.

Arteriovenous Shunt, Surgical↗

Dialyzer fiber bundle volume during hemodialysis using large-surface dialyzers.

Our aim was to measure and compare fiber bundle volume (FBV) of three large-surface dialyzers during chronic hemodialysis; FBV was evaluated in patients without heparin (n = 6), with tight heparinization (n = 6), and with large doses of heparin (n = 6). Each patient was treated consecutively with three dialyzers: Nephral ST500, Tricea210, and Optiflux200NR. FBV was measured hourly by ultrasound dilution in 54 sessions (n = 270). For all patients (without heparin, tight heparin, and large heparin doses) FBV did not vary significantly from 0 to 4 hours for the three types of dialyzers. There was no significant difference in aspect of filters/tubings at the end of dialysis and the presence of clots in the circuit assessed hourly. In addition, 6 other patients on hemodialysis without heparin were treated with Nephral ST500 alternatively with and without saline flushes; thus, 12 more sessions were monitored hourly for FBV (n = 60). There was no change in FBV from 0 to 4 hours between the two approaches, and the appearance of dialyzers/tubings was similar. We conclude that the FBV of large-surface dialyzers is well maintained during 4-hour chronic high-flux hemodialysis and that the loss of dialyzer surface does not explain the difference between prescribed and delivered dialysis dose in such circumstances. The membrane AN69ST does not appear more thrombogenic nor require saline flushes for heparin-free hemodialysis.

Anticoagulants↗

Altered laboratory findings associated with end-stage renal disease.

Several laboratory parameters can be altered in advanced renal failure. Results may be difficult to interpret and may become misleading and unreliable in such a context. On the other hand, some of the alterations may reflect real abnormalities. Thus sufficient knowledge and careful judgment are required by the clinician. We reviewed different publications related to biochemical anomalies in renal failure and report some of the main findings. The sections are divided as follows: cardiovascular risk factors and markers, inflammation markers, pancreatic and liver function tests, hormones, bone turnover indices and parathyroid hormone assays, tumor markers, carbohydrate metabolism indicators, and others. The information provided should be useful to clinicians involved in the care of renal failure patients.

Biomarkers↗

Comparison between tinzaparin and standard heparin for chronic hemodialysis in a Canadian center.

BACKGROUND: Low-molecular-weight heparins offer several advantages over standard heparins, but their use for maintenance hemodialysis has been limited in North America because of their higher cost. Our objective was to compare tinzaparin to standard heparin during maintenance hemodialysis over an 8-week period, in regard to the visual aspect of the extracorporeal circuit, filter reuse, bleeding and time for compression of vascular access at the end of hemodialysis session, nursing time devoted to anticoagulation administration, level of satisfaction of patients and nurses, and relative cost. METHODS: Thirty-two chronic hemodialysis adult patients with peripheral accesses were randomly divided into two groups in a cross-over design: tinzaparin for 4 weeks followed by standard heparin for 4 weeks, or vice versa. Hemodialysis was performed thrice weekly over 3.5-4 h using large surface reused filters. Standard heparin was administered as an initial bolus of 50-75 units per kilogram followed by an infusion to maintain an activated clotting time (ACTESTER) between 150 and 200 s and discontinued 30-45 min before the end of the session. The initial dose of tinzaparin was 3,500 IU anti-Xa for patients usually receiving 7,500 units or less of standard heparin, or 4,500 IU anti-Xa for patients receiving more than 7,500 units of standard heparin, and it was injected as a bolus in the arterial line at the beginning of hemodialysis. Dosage adjustments were made by increments or decrements of 500 IU. RESULTS: A total of 6 patients did not require any adjustment in their dose of tinzaparin and remained at the initial dose, while the remaining 26 necessitated adjustments of the initial dose of tinzaparin: 20 patients required increments from the initial dose whereas 6 required reductions. For most patients, 27 of them, the standard heparin dose was kept at the same level throughout the study period (since it was their usual regimen and they were in stable medical conditions). According to the monitoring scale, the visual aspects of the tubing of the extracorporeal circuit and of the dialyzers at the end of the session were similar for both tinzaparin and standard heparin. The time of compression of the vascular access at the end of the hemodialysis sessions was not significantly different with tinzaparin than with standard heparin. However, as indicated below, most patients noted less bleeding (or oozing) from their access (during compression and thereafter, in the few hours after hemodialysis) with tinzaparin than with standard heparin. Clotting was observed more frequently in the arterial and venous bubble traps with tinzaparin than with standard heparin. The presence of clot(s) was observed in the arterial and venous bubble traps in, respectively, 18 +/- 12 and 10 +/- 6% of the sessions with tinzaparin, while in, respectively, 3 +/- 4 and 2 +/- 4% of the sessions with standard heparin (p < 0.005). Despite a tendency for a reduced reuse number of the dialyzers, the difference did not reach statistical significance. Among the 30 patients who completed the study, 2 reported excessive bleeding from their vascular access with tinzaparin whereas 8 reported such an excessive bleeding with standard heparin. The level of satisfaction of patients and nurses for tinzaparin was extremely good. The main reasons stated by the patients was reduced bleeding from their access after dialysis. The nurses preferred tinzaparin because of the simplicity and the rapidity of its administration, the lack of monitoring required, and the decreased bleeding/oozing tendency from the vascular access sites. The time spent for anticoagulation during a hemodialysis session was reported as 5 min with standard heparin (if no ACTESTER monitoring), 25-30 min with standard heparin (if ACTESTER monitoring required), and 1 min with tinzaparin. The cost analysis revealed that although tinzaparin is more than six times more expensive than standard heparin, the use of tinzaparin becomes similar to the use of standard heparin (USD 7.33 vs. USD 7.62 Canadian dollars for one hemodialysis session) if ACTESTER monitoring is performed (assuming that 22% of the sessions are routinely monitored and that one ACTESTER device is necessary for 8-10 dialysis stations, as applied in our unit). CONCLUSION: Our experience with tinzaparin was positive: it represents a simple and easy way to offer anticoagulation during maintenance hemodialysis, it seems associated with less postdialysis bleeding, it saves precious nursing time and is widely appreciated by patients and staff.

Aged↗