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Biomedical subjects

Patrick T Murray

Publications and source records attributed to Patrick T Murray.

12 recordsLinked to original sources
PubMed2006

Heparin-induced thrombocytopenia in patients administered heparin solely for hemodialysis.

BACKGROUND: Heparin, universally used in patients on dialysis, is the cause for immune-mediated heparin-induced thrombocytopenia (HIT). METHODS: From an HIT registry, six patients were identified who received recent heparin solely for dialysis, developed HIT, and were treated with argatroban. Platelets counts, aPTTs, argatroban dosing, and outcomes were assessed. RESULTS: Before HIT was diagnosed, unfractionated heparin was used in doses of 2,000-12,000 units. The mean platelet count fell from 122 +/- 62 x 10(9)/L to 35 +/- 22 x 10(9)/L, and one patient experienced thrombosis. After HIT was diagnosed, heparin was discontinued, and argatroban therapy (mean dose, 1.7 +/- 0.9 microg/kg/min) was administered for 6.5 +/- 4.5 days (mean aPTT, 66.1 +/- 12.4 s). Patients continued on renal replacement therapy. Platelet counts increased during argatroban therapy. A 37-day composite endpoint of death, amputation, or new thrombosis occurred in four (66.7%) patients: three patients died from causes unrelated to thrombosis, and one patient developed new thrombosis after argatroban was discontinued. One patient experienced a hematocrit drop during treatment without overt bleeding or a need for transfusion. CONCLUSIONS: HIT can occur in patients administered heparin solely for hemodialysis. When HIT is suspected, heparin should be discontinued and an alternative anticoagulation initiated. Argatroban, which is not renally cleared, supports continued renal replacement therapy in HIT patients.

Adult↗
PubMed2005

Argatroban anticoagulation in patients with heparin-induced thrombocytopenia requiring renal replacement therapy.

BACKGROUND: Argatroban, a direct thrombin inhibitor, is used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT). The recommended initial dose is 2 microg/kg/min (0.5 microg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) values 1.5-3.0 times baseline. However, few argatroban-treated patients with HIT and renal failure requiring renal replacement therapy (RRT) have been described. OBJECTIVE: To evaluate the safety and efficacy of argatroban anticoagulation during RRT in patients with HIT. METHODS: We retrospectively reviewed records from 47 patients with HIT and renal failure requiring RRT who underwent 50 treatment courses with argatroban. Patients with HIT had received argatroban during prospective, multicenter studies. Outcomes, safety, and dosing information were summarized. RESULTS: In the multicenter experience, no patient died due to thrombosis and 2 (4%) patients developed new thrombosis while on argatroban. No adverse outcomes occurred during argatroban reexposure. Starting doses were typically 2 microg/kg/min in patients without hepatic impairment and <1.5 microg/kg/min in those with hepatic impairment. Median (range) infusion doses were 1.7 (0.2-2.8) and 0.7 (0.1-1.7) microg/kg/min, respectively, with associated median (range) aPTT ratios, relative to baseline, of 2.2 (1.6-3.6) and 2.0 (1.4-4.1), respectively. Major bleeding occurred in 3 (6%) of 50 treatment courses. CONCLUSIONS: Argatroban provides effective anticoagulation upon initial and repeated administration in patients with HIT and renal impairment requiring RRT, with an acceptably low bleeding risk. Current dosing recommendations are adequate for these patients.

Acute Kidney Injury↗
PubMed2005

Argatroban and renal replacement therapy in patients with heparin-induced thrombocytopenia.

BACKGROUND: Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT). OBJECTIVE: To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT. METHODS: Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5-2 microg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated. RESULTS: Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean +/- SD values of 74.3 +/- 34.2 seconds, 198 +/- 23 seconds, and 499 +/- 353 ng/mL before RRT, and 70.6 +/- 21.4 seconds, 181 +/- 12 seconds, and 453 +/- 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 +/- 12.8 L/h before hemodialysis and 17.0 +/- 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 +/- 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred. CONCLUSIONS: Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.

Adult↗
PubMed2005

Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Acute tubular necrosis (ATN) occurs commonly in critically ill patients and is associated with increased morbidity and mortality. Fenoldopam is a dopamine receptor alpha1-specific agonist that increases renal blood flow in patients with kidney failure. We hypothesized that administration of low-dose fenoldopam during early ATN would decrease the need for dialysis therapy and/or incidence of death at 21 days. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in 155 patients with early ATN. Patients were considered eligible for enrollment if serum creatinine level increased to 50% greater than admission levels within 24 hours and mean arterial pressure was greater than 70 mm Hg. Patients were randomly assigned to the administration of placebo or fenoldopam for 72 hours. RESULTS: Overall, 22 of 80 patients (27.5%) in the fenoldopam group reached the primary end point compared with 29 of 75 patients (38.7%) in the placebo group (P = 0.235). This 11% absolute reduction in the primary end point was not statistically significant (P = 0.23). Similarly, there was no difference in the incidence of dialysis therapy between patients randomly assigned to fenoldopam (13 of 80 patients; 16.25%) versus the placebo group (19 of 75 patients; 25.3%; P = 0.163). Moreover, there was no statistically significant difference in 21-day mortality rates between the 2 groups (fenoldopam, 13.8% versus placebo, 25.3%; P = 0.068). In secondary analyses, fenoldopam tended to reduce the primary end point in patients without diabetes and postoperative cardiothoracic surgery patients with early ATN (fenoldopam patients without diabetes, 14 of 54 patients [25.9%] versus placebo patients without diabetes, 23 of 52 patients [44.2%]; P = 0.048) and postoperative cardiothoracic patients (6 of 34 patients [17.6%] versus 14 of 36 patients [38.8%]; P = 0.049). Conversely, fenoldopam did not improve the primary end point in patients with diabetes or those with acute renal failure from other causes. A larger multicenter trial using separate randomizations for patients with and without diabetes will be needed to determine the efficacy of fenoldopam mesylate in specific subpopulations with ATN. CONCLUSION: Fenoldopam does not reduce the incidence of death or dialysis therapy in intensive care unit patients with early ATN.

Creatinine↗
PubMed2004

Prevention of perioperative acute renal failure: what works?

Perioperative acute renal failure (ARF) is associated with increased morbidity and mortality. Patients undergoing cardiac, vascular and major abdominal surgery and those with pre-operative renal insufficiency are at increased risk for developing post-operative ARF. The aetiologies of perioperative ARF are multi-factorial. However, pre-renal azotaemia and ischaemic acute tubular necrosis (ATN) are the predominant causes. Preventive strategies involve identifying patients at risk, optimizing intravascular volume as well as renal function with perioperative haemodynamic monitoring, and avoiding nephrotoxins. Various pharmacological agents have been used to optimize renal perfusion and tubular function. Unfortunately, none has been shown to be effective in randomized placebo-controlled trials. In this chapter, we discuss the prophylactic use of fluids, vasoactive drugs, diuretics and other agents, as well as modification of surgical techniques to reduce the incidence of perioperative ARF.

Acute Kidney Injury↗
PubMed2004

A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease.

BACKGROUND: We prospectively evaluated 3 treatment regimens of argatroban, a direct thrombin inhibitor, for providing adequate, safe anticoagulation in patients with end-stage renal disease (ESRD) during hemodialysis. METHODS: In this randomized, 3-way crossover study, ESRD patients underwent hemodialysis sessions of 3- or 4-hour duration using high-flux membranes and each of 3 argatroban treatment regimens (A: 250-microg/kg bolus, with an additional 250-microg/kg bolus allowed; B: 250-microg/kg bolus followed by 2-microg/kg/min infusion; C: steady-state, 2-microg/kg/min infusion initiated 4 hours before dialysis). Pharmacodynamic effects including activated clotting times (ACTs); hemodialysis efficacy including single-pool Kt/V, urea reduction ratio (URR), and circuit flow; and safety through a 3-day follow-up were monitored. Argatroban pharmacokinetic parameters including dialytic clearance were evaluated during regimen C. RESULTS: Thirteen patients completed 38 hemodialysis sessions (1 patient withdrew consent after 2 sessions). Mean +/- SD ACTs increased from 131 +/- 14 seconds at baseline to 153 +/- 24, 200 +/- 30, and 197 +/- 33 seconds, respectively, after 60 minutes of hemodialysis using regimens A, B, and C. Across regimens, mean Kt/Vs (1.5-1.6) and URRs (70%-73%) were comparable. No dialyzer was changed; 1 session was shortened 15 minutes because of circuit clot formation. Systemic argatroban clearance increased approximately 20% during hemodialysis, without clinically significantly affecting ACTs. Upon argatroban discontinuation, ACTs and plasma argatroban decreased concurrently (elimination half-life, 35 +/- 6 min). No thrombosis, bleeding, serious adverse events, or clinically significant changes in vital signs or routine laboratory measures occurred. CONCLUSION: Argatroban, administered by each treatment regimen, provides safe, adequate anticoagulation to enable successful hemodialysis in ESRD patients. Argatroban dialytic clearance by high-flux membranes is clinically insignificant.

Adult↗
PubMed2003

Approach to intradialytic hypotension in intensive care unit patients with acute renal failure.

The increasing prevalence of acute renal failure (ARF) patients with hemodynamic intolerance of intermittent hemodialysis (HD), generally because of septic vasoparesis or severe cardiac dysfunction, has led to the development of several strategies to improve the delivery of renal replacement therapy (RRT) in ARF patients. Intradialytic hypotension (IDH) is caused by the interaction of dialysis-dependent and dialysis-independent factors. Dialysis-dependent factors include the prescriptions for fluid removal, solute removal, and dialysate components such as sodium, buffer, and calcium. Dialysis-independent factors include hemodynamic compromise caused by hypovolemic, cardiogenic, vasodilatory, and mixed mechanisms. We propose an approach to the prevention and management of IDH in critically ill ARF patients, which minimizes hypovolemic, cardiogenic, and vasodilatory insults by optimizing fluid removal, cardiac function, and vascular contractility.

Acute Kidney Injury↗
PubMed2002

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↗
PubMed2002

Physiologic endpoints (efficacy) for acute renal failure studies.

Acute renal failure research has been hampered by the lack of useful physiologic surrogate endpoints. Acute renal failure prevention and therapy studies using variables such as urine output and serum and urine chemistries have not yielded interventions proven to decrease the morbidity and mortality associated with acute renal dysfunction. Of those interventions that have been successful in smaller, phase II-level efficacy studies, none subsequently decreased the incidence of clinical (effectiveness) endpoints such as dialysis requirement or mortality in larger phase III trials. Suitable physiologic endpoints are needed to test the efficacy of new proposed therapies for the prevention and management of acute renal failure. Candidate endpoints for efficacy studies in acute renal failure prevention and management include glomerular filtration rate markers, renal blood flow, urine markers, and urine output. Possible endpoints for efficacy studies of renal replacement therapy in acute renal failure include serum markers of renal function and a variety of nonrenal markers. In this article, we present an approach to the choice of physiologic endpoints to determine the efficacy of interventions in acute renal failure.

Acute Kidney Injury↗