23 Jul 08

Post hoc insights from PAC-Man – The U.K. pulmonary artery catheter trial

Posted in PA catheter at 13:45 by Laci

By SE Harvey, CA Welch, DA Harrison, KM Rowan, M Singer

Crit Care Med. 2008;36:1714-1721

To provide descriptive information on patients considered for management with a pulmonary artery catheter (PAC) in U.K. intensive care units and to generate hypotheses to guide future research by examining subsets of patients included in the PAC-Man Study.

Design
Randomized controlled trial.

Setting
U.K. general intensive care units.

Patients
Adult critically ill patients deemed to require management with a PAC by the treating clinician.

Interventions
Management with a PAC.

Measurements and Main Results
A Cox proportional hazards model was used to estimate interactions between treatment effect and time to randomization, age, surgical status, Sequential Organ Failure Score (SOFA) at randomization, organs supported at randomization, and use of flow measurement devices. Type of hospital and size of unit were tested for an interaction with the treatment effect using multilevel logistic regression modeling. There was no effect (or trend) on hospital survival related to the timing of randomization in relation to intensive care unit admission, type of organ support or SOFA score at randomization, age, type of hospital, or size of intensive care unit. No overall difference in acute hospital outcome was seen between use of a PAC and no flow measurement (p = .748) or between use of an alternative flow measurement device and no flow measurement (p = .395).

Conclusions
Post hoc analyses of the PAC-Man Study data set revealed no benefit associated with being managed with a PAC in critically ill patients. However, such analyses are limited, and adequately powered clinical trials are needed of specific population subsets receiving targeted therapies delivered early in the patient’s critical illness to optimize the likelihood of reversing or preventing further organ dysfunction. Furthermore, the utility of other flow measurement devices must be investigated as these have already become integrated into critical care management without adequate evaluation.

21 Jul 08

(Ab)normal saline and physiological Hartmann’s solution: a randomized double-blind crossover study

Posted in Acid-Base disorders, Fluid management at 14:17 by Laci

By F Reid, D N Lobo, R N Williams, B J Rowlands and S P Allison

Clin Sci 2003;104:17-24

In this double-blind crossover study, the effects of bolus infusions of 0.9% saline (NaCl) and Hartmann’s solution on serum albumin, haematocrit and serum and urinary biochemistry were compared in healthy subjects. Nine young adult male volunteers received 2-litre intravenous infusions of 0.9% saline and Hartmann’s solution on separate occasions, in random order, each over 1h. Body weight, haematocrit and serum biochemistry were measured pre-infusion and at 1h intervals for 6h. Biochemical analysis was performed on pooled post-infusion urine. Blood and plasma volume expansion, estimated by dilutional effects on haematocrit and serum albumin, were greater and more sustained after saline than after Hartmann’s solution (P<0.01). At 6h, body weight measurements suggested that 56% of the infused saline was retained, in contrast with only 30% of the Hartmann’s solution. Subjects voided more urine (median: 1000 compared with 450ml) of higher sodium content (median: 122 compared with 73mmol) after Hartmann’s than after saline (both P = 0.049), despite the greater sodium content of the latter. The time to first micturition was less after Hartmann’s than after saline (median: 70 compared with 185min; P = 0.008). There were no significant differences between the effects of the two solutions on serum sodium, potassium, urea or osmolality. After saline, all subjects developed hyperchloraemia (>105mmol/l), which was sustained for >6h, while serum chloride concentrations remained normal after Hartmann’s (P<0.001 for difference between infusions). Serum bicarbonate concentration was significantly lower after saline than after Hartmann’s (P = 0.008). Thus excretion of both water and sodium is slower after a 2-litre intravenous bolus of 0.9% saline than after Hartmann’s solution, due possibly to the more physiological [Na+]/[Cl-] ratio in Hartmann’s solution (1.18:1) than in saline (1:1) and to the hyperchloraemia caused by saline.

20 Jul 08

Prevention of venous thromboembolism

Posted in Venous thromboembolism at 16:50 by Laci

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
By W H Geerts, D Bergqvist, G F Pineo, J A Heit, C M Samama et al

Chest 2008:133:381S-453S

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the “Grades of Recommendation” chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A).

For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC).

For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis > 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).

19 Jul 08

A retrospective observational study of drotrecogin alfa (activated) in adults with severe sepsis: Comparison with a controlled clinical trial

Posted in rhAPC, Sepsis at 19:34 by Laci

By A Wheeler, J Steingrub, G A Schmidt, P Sanchez, J Jacobi, W Linde-Zwirble, B Bates, R L Qualy, B  Woodward, M Zeckel

Crit Care Med 2008;36:14-23

To compare characteristics and outcomes of patients treated with drotrecogin alfa (activated) (DrotAA) in clinical practice to those treated in a phase III randomized controlled trial (PROWESS).

Design
Observational data were collected retrospectively from patients who received DrotAA as part of physician-directed treatment.

Setting
Intensive care units of five teaching institutions.

Patients
Patients were =18 yrs old, had severe sepsis (confirmed/suspected infection with one or more sepsis-induced organ dysfunctions), and received DrotAA.

Interventions
None.

Measurements and Main Results
Baseline demographics, severity of illness, time from organ dysfunction onset to DrotAA treatment, daily assessment of organ dysfunction, serious bleeding events, and in-hospital mortality were reported. Timing from severe sepsis documentation to start of DrotAA infusion was categorized: day 0 (same calendar day); day 1 (next calendar day); and day =2 (second calendar day or later). Clinical practice patients (n = 274) were younger, had more comorbidities, had higher severity of illness (as measured by organ dysfunction or greater vasopressor/ventilator use), and received DrotAA later than PROWESS patients (all p < .05). Overall hospital mortality for clinical practice patients was 42%, compared with 37% for DrotAA-treated PROWESS patients with Acute Physiology and Chronic Health Evaluation II score =25. Mortality for day 0, day 1, and day =2 groups was 33%, 40%, and 52%, respectively. In PROWESS, the vast majority were treated on day 0 or day 1. Serious bleeding events during infusion were noted in 4.0% of clinical practice patients compared with 2.2% of PROWESS DrotAA-treated patients with Acute Physiology and Chronic Health Evaluation II score =25.

Conclusions
Patients treated in clinical practice differed from those in PROWESS. Patients were younger, had more comorbidities, had greater severity of illness, and had longer mean time from severe sepsis onset to the start of DrotAA. Hospital mortality for patients treated within 1 day of severe sepsis onset was similar to DrotAA-treated PROWESS patients. While the low number of serious bleeding events precludes a definitive assessment, the observed incidence of serious bleeding events in clinical practice patients was numerically higher than in DrotAA-treated PROWESS patients.

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