27 Aug 09
Posted in Sedation at 11:08 by Laci
By M Reade, K O’Sullivan, S Bates, D Goldsmith, W Ainslie and R Bellomo
Critical Care 2009, 13:R75
Agitated delirium is common in patients undergoing mechanical ventilation, and is often treated with haloperidol despite concerns about safety and efficacy. Use of conventional sedatives to control agitation can preclude extubation. Dexmedetomidine, a novel sedative and anxiolytic agent, may have particular utility in these patients. We sought to compare the efficacy of haloperidol and dexmedetomidine in facilitating extubation.
Methods
We conducted a randomised, open-label, parallel-groups pilot trial in the medical and surgical intensive care unit of a university hospital. Twenty patients undergoing mechanical ventilation in whom extubation was not possible solely because of agitated delirium were randomised to receive an infusion of either haloperidol 0.5 to 2 mg/hour or dexmedetomidine 0.2 to 0.7 μg/kg/hr, with or without loading doses of 2.5 mg haloperidol or 1 μg/kg dexmedetomidine, according to clinician preference.
Results
Dexmedetomidine significantly shortened median time to extubation from 42.5 (IQR 23.2 to 117.8) to 19.9 (IQR 7.3 to 24) hours (P = 0.016). Dexmedetomidine significantly decreased ICU length of stay, from 6.5 (IQR 4 to 9) to 1.5 (IQR 1 to 3) days (P = 0.004) after study drug commencement. Of patients who required ongoing propofol sedation, the proportion of time propofol was required was halved in those who received dexmedetomidine (79.5% (95% CI 61.8 to 97.2%) vs. 41.2% (95% CI 0 to 88.1%) of the time intubated; P = 0.05). No patients were reintubated; three receiving haloperidol could not be successfully extubated and underwent tracheostomy. One patient prematurely discontinued haloperidol due to QTc interval prolongation.
Conclusions
In this preliminary pilot study, we found dexmedetomidine a promising agent for the treatment of ICU-associated delirious agitation, and we suggest this warrants further testing in a definitive double-blind multi-centre trial.
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22 Aug 09
Posted in Nutrition, Sepsis at 11:11 by Laci
By G Oliveira, M Oliveira, R Santos, L Lima, C Dias, A AB’ Saber, W Teodoro, V Capelozzi, R Gomes, P Bozza, P Pelosi and P Rocco
Critical Care 2009, 13:R74
The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi.
Methods
Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively).
Results
CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours.
Conclusions
In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.
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12 Aug 09
Posted in COPD at 8:36 by Laci
By M Cosio, M Saetta and A Agusti
NEJM 2009;360:2445-2454
Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death throughout the world. It affects about 10% of the general population, but its prevalence among heavy smokers can reach 50%. COPD is the fourth leading cause of death in most industrialized countries, and it is projected to be the third leading cause of death worldwide by 2020. Tobacco smoking is the primary risk factor for the development of COPD, but other factors, such as burning biomass fuels for cooking and heating, are important causes of COPD in many developing countries.
A principal feature of COPD is a limitation of airflow that is not fully reversible and is associated with an abnormal inflammatory response in the small airways and alveoli. The principal abnormalities in small airways are the presence of an inflammatory cellular infiltrate and a remodeling that thickens the airway wall, thereby reducing the airway diameter and increasing resistance to flow. Additional features are prominent inflammatory infiltrates in the alveolar walls, destruction of alveoli, and enlargement of air spaces. These anatomical hallmarks of emphysema reduce the elastic pressure that generates expiratory flow. Chronic bronchitis, a condition that according to some authors has little to do with the development of airflow obstruction, develops in approximately 50% of smokers.
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09 Aug 09
Posted in Admission to ICU at 16:33 by Laci
By T Iwashyna, A Kramer, J Kahn
Critical Care Medicine 2009;37:1545-1557
Although intensive care units (ICUs) with higher overall patient volume may achieve better outcomes than lower volume ICUs, there are few data on the effects of increasing patient loads on patients within the ICU.
Objectives
To examine the association of ICU occupancy with the patient outcomes within the same ICU.
Methods
We examined 200,499 patients in 108 ICUs using the Acute Physiology and Chronic Health Evaluation IV database in 2002-2005. Daily census on the day of admission was determined for each patient and defined in relation to the mean census. We used conditional logistic regression to compare inpatient outcomes of patients admitted on high census days to those admitted in the same ICU on low census days. We controlled for severity of illness at the patient level using data on clinical, demographic, and physiologic variables on admission to the ICU.
Measurements and main results
Patients admitted on high census days had the same odds of inpatient mortality or transfer to another hospital as patients admitted on average or on low census days. These findings were robust to multiple alternative definitions of day of admission census and were confirmed in several subgroup analyses.
Conclusions
The ICUs in this data are able to function as high reliability organizations. They are able to scale up their operations to meet the needs of a wide range of operating conditions while maintaining consistent patient mortality outcomes.
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