18 Jan 09
Posted in Acid-Base disorders, Inotropic support at 0:35 by Laci
By J A Myburgh, A Higgins, A Jovanovska, J Lipman, N Ramakrishnan, J Santamaria and the CAT Study investigators
Intensive Care Med 2008:34;2226-2234
To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients.
Design
Prospective, double-blind, randomised-controlled trial.
Setting
Four Australian university-affiliated multidisciplinary ICUs.
Patients and participants
Patients who required vasopressors for any cause at randomisation. Patients with septic shock and acute circulatory failure were analysed separately.
Interventions
Blinded infusions of epinephrine or norepinephrine to achieve a MAP =70 mmHg for the duration of ICU admission.
Measurements
Primary outcome was achievement of MAP goal >24 h without vasopressors. Secondary outcomes were 28 and 90-day mortality. Two hundred and eighty patients were randomised to receive either epinephrine or norepinephrine. Median time to achieve the MAP goal was 35.1 h (interquartile range (IQR) 13.8ñ70.4 h) with epinephrine compared to 40.0 h (IQR 14.5ñ120 h) with norepinephrine (relative risk (RR) 0.88; 95% confidence interval (CI) 0.69ñ1.12; P = 0.26). There was no difference in the time to achieve MAP goals in the subgroups of patients with severe sepsis (n = 158; RR 0.81; 95% CI 0.59ñ1.12; P = 0.18) or those with acute circulatory failure (n = 192; RR 0.89; 95% CI 0.62ñ1.27; P = 0.49) between epinephrine and norepinephrine. Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study by attending clinicians. There was no difference in 28 and 90-day mortality.
Conclusions
Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients.
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14 Jan 09
Posted in ALI/ARDS, Transfusion medicine at 0:40 by Laci
By S Wright, C Snowden, S Athey, AA Leaver, J-M Clarkson et al
Crit Care Med 2008:36;1796-1802
Transfusion-related acute lung injury may contribute to the development of acute lung injury in the critically ill, due to plasma from female donors containing antileukocyte antibodies. In July 2003, the U.K. National Blood Service stopped using female donor plasma for the production of fresh frozen plasma. Patients undergoing repair of a ruptured abdominal aortic aneurysm receive large amounts of fresh frozen plasma and often develop acute lung injury. We investigated whether the change to male fresh frozen plasma was associated with a change in the frequency of acute lung injury in these patients.
Design
A retrospective, before and after, observational, single-center study.
Setting
Tertiary care center and a regional blood center.
Patients
The study included 211 patients undergoing open repair of a ruptured abdominal aortic aneurysm between 1998 and 2006.
Interventions
None.
Measurements and main results
Primary outcome was the development of acute lung injury in the first 6 hrs after surgery. Secondary outcomes were significant hypoxia (Pao2/Fio2 ratio <300), time to extubation, and survival at 30 days. Groups were well matched and received similar volumes of intravenous fluids and blood components. There was significantly less acute lung injury following the change to male fresh frozen plasma (36% before vs. 21% after, p = .04). At 6 hrs after surgery, fewer patients were hypoxic (87% before vs. 62% after, p < .01). In multivariate analysis, the change in donor policy was associated with a decreased risk of developing acute lung injury (odds ratio 0.39; 95% confidence interval, 0.16ñ0.90). Time to extubation and survival at 30 days were not statistically different between groups.
Conclusions
The policy to exclude female donors from the production of fresh frozen plasma was associated with a decrease in the frequency of acute lung injury in patients undergoing repair of a ruptured abdominal aortic aneurysm.
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12 Jan 09
Posted in IABP, Inotropic support, Sepsis at 0:05 by Laci
By SB Solomon, PC Minneci, KJ Deans, J Feng, PQ Eichacker, SM Banks, RL Danner, C Natanson and MA Solomon
Critical Care Med 2008;37:7-18
Fluid refractory septic shock can develop into a hypodynamic cardiovascular state in both children and adults. Despite management of these patients with empirical inotropic therapy (with or without a vasodilator), mortality remains high.
Objectives
The effect of cardiovascular support using intra-aortic balloon counterpulsation was investigated in a hypodynamic, mechanically ventilated canine sepsis model in which cardiovascular and pulmonary support were titrated based on treatment protocols.
Methods
Each week, three animals (n = 33, 10-12 kg) were administered intrabronchial Staphylococcus aureus challenge and then randomized to receive intra-aortic balloon counterpulsation for 68 hrs or no intra-aortic balloon counterpulsation (control). Bacterial doses were increased over the study (4-8 x 109 cfu/kg) to assess the effects of intra-aortic balloon counterpulsation during sepsis with increasing risk of death.
Main results
Compared with lower bacterial doses (4-7 x 109 colony-forming units/kg), control animals challenged with the highest dose (8 x 109 colony-forming units/kg) had a greater risk of death (mortality rate 86% vs. 17%), with worse lung injury ([A - a]o2), and renal dysfunction (creatinine). These sicker animals required higher norepinephrine infusion rates to maintain blood pressure (and higher Fio2) and positive end-expiratory pressure levels to maintain oxygenation (p <= 0.04 for all). In animals receiving the highest bacterial dose, intra-aortic balloon counterpulsation improved survival time (23.4 +/- 10 hrs longer; p = 0.003) and lowered norepinephrine requirements (0.43 +/- 0.17 [mu]g/kg/min; p = 0.002) and systemic vascular resistance index (1.44 +/- 0.57 dynes/s/cm5/kg; p = 0.0001) compared with controls. Despite these beneficial effects, intra-aortic balloon counterpulsation was associated with an increase in blood urea nitrogen (p = 0.002) and creatinine (p = 0.12). In animals receiving lower doses of bacteria, intra-aortic balloon counterpulsation had no significant effects on survival or renal function.
Conclusions
In a canine model of severe septic shock with a low cardiac index, intra-aortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements.
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05 Jan 09
Posted in General at 0:40 by Laci
By A S Kesselheim, A S Misono, J L Lee, M R Stedman, M A Brookhart, N K Choudhry and W H Shrank
JAMA 2008;300:2514-2526
Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs.
Objectives
To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue.
Data sources
Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008.
Study selection
Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution.
Data extraction
We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors’ positions on generic substitution as negative, positive, or neutral.
Results
We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of β-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of {alpha}-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was –0.03 (95% confidence interval, –0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution.
Conclusions
Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.
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