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Showing papers in "Critical Care in 2009"


Journal ArticleDOI
TL;DR: Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate.
Abstract: Introduction Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain. Methods We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time

465 citations


Journal ArticleDOI
TL;DR: Models based on SOFA scores at admission had only slightly worse performance than APACHE II/III and were competitive with SAPS II models in predicting mortality in patients in the general medical and/or surgical ICU.
Abstract: Introduction To systematically review studies evaluating the performance of Sequential Organ Failure Assessment (SOFA)-based models for predicting mortality in patients in the intensive care unit (ICU).

440 citations


Journal ArticleDOI
TL;DR: The results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.
Abstract: Introduction Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO 2 and VO 2 ), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (ΔPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. Results Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures,

382 citations


Journal ArticleDOI
TL;DR: The proportion of patients aged ≥ 80 years admitted to intensive care in Australia and New Zealand is rapidly increasing, and although these patients have more co-morbid illness, are less likely to be discharged home, and have a greater mortality than younger patients, approximately 80% survive to hospital discharge.
Abstract: Older age is associated with higher prevalence of chronic illness and functional impairment, contributing to an increased rate of hospitalization and admission to intensive care. The primary objective was to evaluate the rate, characteristics and outcomes of very old (age ≥ 80 years) patients admitted to intensive care units (ICUs). Retrospective analysis of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were obtained for 120,123 adult admissions for ≥ 24 hours across 57 ICUs from 1 January 2000 to 31 December 2005. A total of 15,640 very old patients (13.0%) were admitted during the study. These patients were more likely to be from a chronic care facility, had greater co-morbid illness, greater illness severity, and were less likely to receive mechanical ventilation. Crude ICU and hospital mortalities were higher (ICU: 12% vs. 8.2%, P < 0.001; hospital: 24.0% vs. 13%, P < 0.001). By multivariable analysis, age ≥ 80 years was associated with higher ICU and hospital death compared with younger age strata (ICU: odds ratio (OR) = 2.7, 95% confidence interval (CI) = 2.4 to 3.0; hospital: OR = 5.4, 95% CI = 4.9 to 5.9). Factors associated with lower survival included admission from a chronic care facility, co-morbid illness, nonsurgical admission, greater illness severity, mechanical ventilation, and longer stay in the ICU. Those aged ≥ 80 years were more likely to be discharged to rehabilitation/long-term care (12.3% vs. 4.9%, OR = 2.7, 95% CI = 2.6 to 2.9). The admission rates of very old patients increased by 5.6% per year. This potentially translates to a 72.4% increase in demand for ICU bed-days by 2015. The proportion of patients aged ≥ 80 years admitted to intensive care in Australia and New Zealand is rapidly increasing. Although these patients have more co-morbid illness, are less likely to be discharged home, and have a greater mortality than younger patients, approximately 80% survive to hospital discharge. These data also imply a potential major increase in demand for ICU bed-days for very old patients within a decade.

377 citations


Journal ArticleDOI
TL;DR: This multicenter study indicated risk factors for delirium in the intensive care unit related to patient characteristics, chronic pathology, acute illness, and the environment and several factors are suitable for preventive action.
Abstract: Delirium is a common complication in the intensive care unit. The attention of researchers has shifted from the treatment to the prevention of the syndrome necessitating the study of associated risk factors. In a multicenter study at one university hospital, two community hospitals and one private hospital, all consecutive newly admitted adult patients were screened and included when reaching a Glasgow Coma Scale greater than 10. Nurse researchers assessed the patients for delirium using the NEECHAM Confusion Scale. Risk factors covered four domains: patient characteristics, chronic pathology, acute illness and environmental factors. Odds ratios were calculated using univariate binary logistic regression. A total population of 523 patients was screened for delirium. The studied factors showed some variability according to the participating hospitals. The overall delirium incidence was 30%. Age was not a significant risk factor. Intensive smoking (OR 2.04), daily use of more than three units of alcohol (OR 3.23), and living alone at home (OR 1.94), however, contributed to the development of delirium. In the domain of chronic pathology a pre-existing cognitive impairment was an important risk factor (OR 2.41). In the domain of factors related to acute illness the use of drains, tubes and catheters, acute illness scores, the use of psychoactive medication, a preceding period of sedation, coma or mechanical ventilation showed significant risk with odds ratios ranging from 1.04 to 13.66. Environmental risk factors were isolation (OR 2.89), the absence of visit (OR 3.73), the absence of visible daylight (OR 2.39), a transfer from another ward (OR 1.98), and the use of physical restraints (OR 33.84). This multicenter study indicated risk factors for delirium in the intensive care unit related to patient characteristics, chronic pathology, acute illness, and the environment. Particularly among those related to the acute illness and the environment, several factors are suitable for preventive action.

370 citations


Journal ArticleDOI
TL;DR: In this large European study, patients with cancer were more often admitted to the ICU for sepsis and respiratory complications than other ICU patients, whereas patients with haematological cancer had a worse outcome.
Abstract: Introduction Increasing numbers of cancer patients are being admitted to the intensive care unit (ICU), either for cancer-related complications or treatment-associated side effects, yet there are relatively few data concerning the epidemiology and prognosis of cancer patients admitted to general ICUs. The aim of this study was to assess the characteristics of critically ill cancer patients, and to evaluate their prognosis.

361 citations


Journal ArticleDOI
TL;DR: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases.
Abstract: Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic

332 citations


Journal ArticleDOI
TL;DR: EMS is well tolerated and seems to preserve the muscle mass of critically ill patients, and the potential use of EMS as a preventive and rehabilitation tool in ICU patients with polyneuromyopathy needs to be further investigated.
Abstract: Introduction Critically ill patients are characterized by increased loss of muscle mass, partially attributed to sepsis and multiple organ failure, as well as immobilization. Recent studies have shown that electrical muscle stimulation (EMS) may be an alternative to active exercise in chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) patients with myopathy. The aim of our study was to investigate the EMS effects on muscle mass preservation of critically ill patients with the use of ultrasonography (US). Methods Forty-nine critically ill patients (age: 59 ± 21 years) with an APACHE II admission score ≥13 were randomly assigned after stratification upon admission to receive daily EMS sessions of both lower extremities (EMS-group) or to the control group (control group). Muscle mass was evaluated with US, by measuring the cross sectional diameter (CSD) of the vastus intermedius and the rectus femoris of the quadriceps muscle. Results Twenty-six patients were finally evaluated. Right rectus femoris and right vastus intermedius CSD decreased in both groups (EMS group: from 1.42 ± 0.48 to 1.31 ± 0.45 cm, P = 0.001 control group: from 1.59 ± 0.53 to 1.37 ± 0.5 cm, P = 0.002; EMS group: from 0.91 ± 0.39 to 0.81 ± 0.38 cm, P = 0.001 control group: from 1.40 ± 0.64 to 1.11 ± 0.56 cm, P = 0.004, respectively). However, the CSD of the right rectus femoris decreased significantly less in the EMS group (-0.11 ± 0.06 cm, -8 ± 3.9%) as compared to the control group (-0.21 ± 0.10 cm, -13.9 ± 6.4%; P < 0.05) and the CSD of the right vastus intermedius decreased significantly less in the EMS group (-0.10 ± 0.05 cm, -12.5 ± 7.4%) as compared to the control group (-0.29 ± 0.28 cm, -21.5 ± 15.3%; P < 0.05). Conclusions EMS is well tolerated and seems to preserve the muscle mass of critically ill patients. The potential use of EMS as a preventive and rehabilitation tool in ICU patients with polyneuromyopathy needs to be further investigated. Trial Registration clinicaltrials.gov: NCT00882830

312 citations


Journal ArticleDOI
TL;DR: It is concluded that it is not acceptable to present comparison studies quoting percentage error as an acceptability criteria without reporting the precision of the reference technique.
Abstract: Bland-Altman analysis is used for assessing agreement between two measurements of the same clinical variable. In the field of cardiac output monitoring, its results, in terms of bias and limits of agreement, are often difficult to interpret, leading clinicians to use a cutoff of 30% in the percentage error in order to decide whether a new technique may be considered a good alternative. This percentage error of ± 30% arises from the assumption that the commonly used reference technique, intermittent thermodilution, has a precision of ± 20% or less. The combination of two precisions of ± 20% equates to a total error of ± 28.3%, which is commonly rounded up to ± 30%. Thus, finding a percentage error of less than ± 30% should equate to the new tested technique having an error similar to the reference, which therefore should be acceptable. In a worked example in this paper, we discuss the limitations of this approach, in particular in regard to the situation in which the reference technique may be either more or less precise than would normally be expected. This can lead to inappropriate conclusions being drawn from data acquired in validation studies of new monitoring technologies. We conclude that it is not acceptable to present comparison studies quoting percentage error as an acceptability criteria without reporting the precision of the reference technique.

295 citations


Journal ArticleDOI
TL;DR: Some of the principles and possible strategies to further develop and encourage the implementation of checklists into medical practice are explored and the benefits they offer to improve care are explored.
Abstract: Checklists are common tools used in many industries. Unfortunately, their adoption in the field of medicine has been limited to equipment operations or part of specific algorithms. Yet they have tremendous potential to improve patient outcomes by democratizing knowledge and helping ensure that all patients receive evidence-based best practices and safe high-quality care. Checklist adoption has been slowed by a variety of factors, including provider resistance, delays in knowledge dissemination and integration, limited methodology to guide development and maintenance, and lack of effective technical strategies to make them available and easy to use. In this article, we explore some of the principles and possible strategies to further develop and encourage the implementation of checklists into medical practice. We describe different types of checklists using examples and explore the benefits they offer to improve care. We suggest methods to create checklists and offer suggestions for how we might apply them, using some examples from our own experience, and finally, offer some possible directions for future research.

286 citations


Journal ArticleDOI
TL;DR: Sepsis is the leading cause of death after burn injury, and multiple antibiotic resistant bacteria now account for the bulk of deaths due to sepsis.
Abstract: Severe thermal injury is characterized by profound morbidity and mortality. Advances in burn and critical care, including early excision and grafting, aggressive resuscitation and advances in antimicrobial therapy have made substantial contributions to decrease morbidity and mortality. Despite these advances, death still occurs. Our aim was to determine the predominant causes of death in burned pediatric patients in order to develop new treatment avenues and future trajectories associated with increased survival. Primary causes of death were reviewed from 144 pediatric autopsy reports. Percentages of patients that died from anoxic brain injuries, sepsis, or multi-organ failure were calculated by comparing to the total number of deaths. Data was stratified by time (from 1989 to 1999, and 1999 to 2009), and gender. Statistical analysis was done by chi-squared, Student's t-test and Kaplan-Meier for survival where applicable. Significance was accepted as P < 0.05. Five-thousand two-hundred-sixty patients were admitted after burn injury from July 1989 to June 2009, and of those, 145 patients died after burn injury. Of these patients, 144 patients had an autopsy. The leading causes of death over 20 years were sepsis (47%), respiratory failure (29%), anoxic brain injury (16%), and shock (8%). From 1989 to 1999, sepsis accounted for 35% of deaths but increased to 54% from 1999 to 2009, with a significant increase in the proportion due to antibiotic resistant organisms (P < 0.05). Sepsis is the leading cause of death after burn injury. Multiple antibiotic resistant bacteria now account for the bulk of deaths due to sepsis. Further improvement in survival may require improved strategies to deal with this problem.

Journal ArticleDOI
TL;DR: Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients and may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine.
Abstract: The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients. All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to 1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days. A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome. Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine. Results were previously published in German in Anaesthesist 2008; 57: 571–577 (PMID: 18463831). ISRCTN10288268

Journal ArticleDOI
TL;DR: Early mobility requires a significant change in ICU practice, with reductions in heavy sedation and bed rest, and further research is required to determine whether early mobility in the ICU can improve patients' short-term and long-term outcomes.
Abstract: As the mortality from critical illness has improved in recent years, there has been increasing focus on patient outcomes after hospital discharge. Neuromuscular weakness acquired in the intensive care unit (ICU) is common, persistent, and often severe. Immobility due to prolonged bed rest in the ICU may play an important role in the development of ICU-acquired weakness. Studies in other patient populations have demonstrated that moderate exercise is beneficial in altering the inflammatory milieu associated with immobility, and in improving muscle strength and physical function. Recent studies have demonstrated that early mobility in the ICU is safe and feasible, with a potential reduction in short-term physical impairment. However, early mobility requires a significant change in ICU practice, with reductions in heavy sedation and bed rest. Further research is required to determine whether early mobility in the ICU can improve patients' short-term and long-term outcomes.

Journal ArticleDOI
TL;DR: Sound-absorbing treatment is a relatively effective noise reduction strategy, whereas sound masking appears to be the most effective technique for improving sleep.
Abstract: Excessive noise is becoming a significant problem for intensive care units (ICUs). This paper first reviews the impact of noise on patients' sleep in ICUs. Five previous studies have demonstrated such impacts, whereas six other studies have shown other factors to be more important. Staff conversation and alarms are generally regarded as the most disturbing noises for patients' sleep in ICUs. Most research in this area has focused purely on noise level, but work has been very limited on the relationships between sleep quality and other acoustic parameters, including spectrum and reverberation time. Sound-absorbing treatment is a relatively effective noise reduction strategy, whereas sound masking appears to be the most effective technique for improving sleep. For future research, there should be close collaboration between medical researchers and acousticians.

Journal ArticleDOI
TL;DR: This study shows that age, emergency and high risk surgery, ischemicHeart disease, congestive heart disease, ASA physical status and RCRI score were considered risk factors for the development of AKI, in patients needing intensive care after surgery.
Abstract: Development of acute kidney injury (AKI) during the perioperative period is associated with increases in morbidity and mortality. Our aim was to evaluate the incidence and determinants of postoperative AKI after major noncardiac surgery in patients with previously normal renal function. This retrospective cohort study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. The study population consisted of 1166 patients with no previous renal insufficiency who were admitted to these intensive care unit (ICU) beds over 2 years. After admission patients were followed for the development of AKI, defined as proposed by The Acute Kidney Injury Network (increment of serum creatinine [greater than or equal to] 0.3 mg/dL or 50% from baseline within 48 hours or urine output 6 hours despite fluid resuscitation when applicable). Patient preoperative characteristics, intraoperative management and outcome were evaluated for associations with acute kidney injury using an univariate and multiple logistic regression model. A total of 1597 patients were admitted to the PACU and of these, 1166 met the inclusion criteria. Eighty-seven patients (7.5%) met AKI criteria. Univariate analysis identified age, American Society of Anesthesiologists (ASA) physical status, emergency surgery, high risk surgery, ischemic heart disease, congestive heart disease and Revised Cardiac Risk Index (RCRI) score as independent preoperative determinants for AKI in the postoperative period. Multivariate analysis identified ASA physical status, RCRI score, high risk surgery and congestive heart disease as preoperative determinants for AKI in the postoperative period. Patients that developed AKI had higher Simplified Acute Physiology Score (SAPS) II and Acute Physiology and Chronic Health Evaluation (APACHE) II, higher PACU length of stay (LOS), higher PACU mortality, higher hospital mortality and higher mortality at 6 months follow-up. AKI was an independent risk factor for hospital mortality (OR 3.12, 95% CI 1.41 to 6.93, P = 0.005). This study shows that age, emergency and high risk surgery, ischemic heart disease, congestive heart disease, ASA physical status and RCRI score were considered risk factors for the development of AKI, in patients needing intensive care after surgery. AKI has serious impact on PACU length of stay and mortality. AKI was an independent risk factor for hospital mortality.

Journal ArticleDOI
TL;DR: For the first time, plasma levels of HMGB1 are demonstrated to be released into the bloodstream early after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis.
Abstract: High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study. One hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry. Plasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma. The results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.

Journal ArticleDOI
TL;DR: In critically ill patients, both early hypoglycemia and early variability in BG are relatively common, and independently portend an increased risk for mortality.
Abstract: In critical illness, the association of hypoglycemia, blood glucose (BG) variability and outcome are not well understood. We describe the incidence, clinical factors and outcomes associated with an early hypoglycemia and BG variability in critically ill patients. Retrospective interrogation of prospectively collected data from the Australia New Zealand Intensive Care Society Adult Patient Database on 66184 adult admissions to 24 intensive care units (ICUs) from 1 January 2000 to 31 December 2005. Primary exposure was hypoglycemia (BG < 4.5 mmol/L) and BG variability (BG < 4.5 and ≥ 12.0 mmol/L) within 24 hours of admission. Primary outcome was all-cause mortality. The cumulative incidence of hypoglycemia and BG variability were 13.8% (95% confidence interval (CI) = 13.5 to 14.0; n = 9122) and 2.9% (95%CI = 2.8 to 3.0, n = 1913), respectively. Several clinical factors were associated with both hypoglycemia and BG variability including: co-morbid disease (P < 0.001), non-elective admissions (P < 0.001), higher illness severity (P < 0.001), and primary septic diagnosis (P < 0.001). Hypoglycemia was associated with greater odds of adjusted ICU (odds ratio (OR) = 1.41, 95% CI = 1.31 to 1.54) and hospital death (OR = 1.36, 95% CI = 1.27 to 1.46). Hypoglycemia severity was associated with 'dose-response' increases in mortality. BG variability was associated with greater odds of adjusted ICU (1.5, 95% CI = 1.4 to 1.6) and hospital (1.4, 95% CI = 1.3 to 1.5) mortality, when compared with either hypoglycemia only or neither. In critically ill patients, both early hypoglycemia and early variability in BG are relatively common, and independently portend an increased risk for mortality.

Journal ArticleDOI
TL;DR: In this paper, Dexmedetomidine, a novel sedative and anxiolytic agent, may have particular utility in ICUassociated delirious agitation, and they suggest this warrants further testing in a definitive double-blind multi-centre trial.
Abstract: Introduction 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, parallelgroups 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 ICUassociated delirious agitation, and we suggest this warrants further testing in a definitive double-blind multi-centre trial. Trial registration Clinicaltrials.gov NCT00505804

Journal ArticleDOI
TL;DR: Sleep deprivation may prove to be a modifiable risk factor for the development of delirium with important implications for the acute and long-term outcome of critically ill patients.
Abstract: Delirium occurs frequently in critically ill patients and has been associated with both short-term and long-term consequences. Efforts to decrease delirium prevalence have been directed at identifying and modifying its risk factors. One potentially modifiable risk factor is sleep deprivation. Critically ill patients are known to experience poor sleep quality with severe sleep fragmentation and disruption of sleep architecture. Poor sleep while in the intensive care unit is one of the most common complaints of patients who survive critical illness. The relationship between delirium and sleep deprivation remains controversial. However, studies have demonstrated many similarities between the clinical and physiologic profiles of patients with delirium and sleep deprivation. This article aims to review the literature, the clinical and neurobiologic consequences of sleep deprivation, and the potential relationship between sleep deprivation and delirium in intensive care unit patients. Sleep deprivation may prove to be a modifiable risk factor for the development of delirium with important implications for the acute and long-term outcome of critically ill patients.

Journal ArticleDOI
TL;DR: MV induces VILI, in the absence of a priming pulmonary insult and even with use of relevant (least injurious) ventilator settings, even if the animals are ventilated for a relative short period of time and only after a 'priming' pulmonary insult.
Abstract: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI). Present models of VILI use exceptionally large tidal volumes, causing gross lung injury and haemodynamic shock. In addition, animals are ventilated for a relative short period of time and only after a 'priming' pulmonary insult. Finally, it is uncertain whether metabolic acidosis, which frequently develops in models of VILI, should be prevented. To study VILI in healthy mice, the authors used a MV model with clinically relevant ventilator settings, avoiding massive damage of lung structures and shock, and preventing metabolic acidosis. Healthy C57Bl/6 mice (n = 66) or BALB/c mice (n = 66) were ventilated (tidal volume = 7.5 ml/kg or 15 ml/kg; positive end-expiratory pressure = 2 cmH2O; fraction of inspired oxygen = 0.5) for five hours. Normal saline or sodium bicarbonate were used to correct for hypovolaemia. Lung histopathology, lung wet-to-dry ratio, bronchoalveolar lavage fluid protein content, neutrophil influx and levels of proinflammatory cytokines and coagulation factors were measured. Animals remained haemodynamically stable throughout the whole experiment. Lung histopathological changes were minor, although significantly more histopathological changes were found after five hours of MV with a larger tidal volume. Lung histopathological changes were no different between the strains. In both strains and with both ventilator settings, MV caused higher wet-to-dry ratios, higher bronchoalveolar lavage fluid protein levels and more influx of neutrophils, and higher levels of proinflammatory cytokines and coagulation factors. Also, with MV higher systemic levels of cytokines were measured. All parameters were higher with larger tidal volumes. Correcting for metabolic acidosis did not alter endpoints. MV induces VILI, in the absence of a priming pulmonary insult and even with use of relevant (least injurious) ventilator settings. This model offers opportunities to study the pathophysiological mechanisms behind VILI and the contribution of MV to lung injury in the absence of pre-existing lung injury.

Journal ArticleDOI
TL;DR: In trauma patients transfused ≥5 units of R BCs, transfusion of RBCs ≥ 28 days of storage may be associated with deep vein thrombosis and death from multi-organ failure.
Abstract: In critically ill patients the relationship between the storage age of red blood cells (RBCs) transfused and outcomes are controversial. To determine if duration of RBC storage is associated with adverse outcomes we studied critically ill trauma patients requiring transfusion. This retrospective cohort study included patients with traumatic injuries transfused ≥5 RBC units. Patients transfused ≥ 1 unit of RBCs with a maximum storage age of up to 27 days were compared with those transfused 1 or more RBC units with a maximum storage age of ≥ 28 days. These study groups were also matched by RBC amount (+/- 1 unit) transfused. Primary outcomes were deep vein thrombosis and in-hospital mortality. Two hundred and two patients were studied with 101 in both decreased and increased RBC age groups. No differences in admission vital signs, laboratory values, use of DVT prophylaxis, blood products or Injury Severity Scores were measured between study groups. In the decreased compared with increased RBC storage age groups, deep vein thrombosis occurred in 16.7% vs 34.5%, (P = 0.006), and mortality was 13.9% vs 26.7%, (P = 0.02), respectively. Patients transfused RBCs of increased storage age had an independent association with mortality, OR (95% CI), 4.0 (1.34 - 11.61), (P = 0.01), and had an increased incidence of death from multi-organ failure compared with the decreased RBC age group, 16% vs 7%, respectively, (P = 0.037). In trauma patients transfused ≥5 units of RBCs, transfusion of RBCs ≥ 28 days of storage may be associated with deep vein thrombosis and death from multi-organ failure.

Journal ArticleDOI
TL;DR: The use of the consensus definitions of acute kidney injury (RIFLE and AKIN) in the literature has increased substantially as discussed by the authors, indicating a highly encouraging acceptance by the medical community of a unifying definition for acute kidney injuries.
Abstract: In recent years, the use of the consensus definitions of acute kidney injury (RIFLE and AKIN) in the literature has increased substantially. This indicates a highly encouraging acceptance by the medical community of a unifying definition for acute kidney injury. This is a very important and positive step in the right direction. There remains some variation in how the criteria are interpreted and used in the literature, including use/nonuse of urine output criteria, use of change in estimated glomerular filtration rate rather than change in creatinine, and choice of baseline creatinine. The present review is intended to aid the reader in critically appraising studies using these consensus definitions. Since no single definition will be perfect, a logical next step would be to reconcile existing definitions, moving the medical community towards using a single consensus definition as has been done with sepsis and acute lung injury/acute respiratory distress syndrome. As new data emerge, integration of novel biomarkers into the consensus definition will be a welcome refinement.

Journal ArticleDOI
TL;DR: The rapid rise in sepsis mortality seen in previous decades has slowed, but population ageing continues to drive the growth of sepsi-associated mortality in the United States.
Abstract: Sepsis is the 10th leading cause of death in the United States. The National Center for Health Statistics' multiple-cause-of-death (MCOD) dataset is a large, publicly available, population-based source of information on disease burden in the United States. We have analysed MCOD data from 1999 to 2005 to investigate trends, assess disparities and provide population-based estimates of sepsis-associated mortality during this period. Sepsis-associated deaths occurring in the United States from 1999 to 2005 were identified in MCOD data using International Classification of Disease, 10th Revision (ICD-10) codes. Population-based mortality rates were calculated using bridged-race population estimates from the National Center for Health Statistics. Comparisons across age, sex and racial/ethnic groups were achieved by calculating mortality rate ratios. From 1999 to 2005 there were 16,948,482 deaths in the United States. Of these, 1,017,616 were associated with sepsis (6.0% of all deaths). The age-adjusted rate of sepsis-associated mortality was 50.37 deaths per 100,000 (95% confidence interval (CI) = 50.28 to 50.47). There were significant disparities in sepsis-associated mortality in race/ethnicity and sex groups (P < 0.0001). After controlling for age, Asians were less likely than whites to experience sepsis-related death (rate ratio (RR) = 0.78, 95% CI = 0.77 to 0.78), while Blacks (RR = 2.24, 95% CI = 2.23 to 2.24), American Indians/Alaska Natives (RR = 1.24, 95% CI = 1.24 to 1.25) and Hispanics (RR = 1.14, 95% CI = 1.13 to 1.14) were more likely than whites to experience sepsis-related death. Men were at increased risk for sepsis-associated death in all race/ethnicity categories (RR = 1.27, 95% CI = 1.27 to 1.28), but the degree of increased susceptibility associated with being male differed among racial/ethnic groups (P < 0.0001). Although crude sepsis-associated mortality increased by 0.67% per year during the study period (P < 0.0001), the age-adjusted mortality rate decreased by 0.18% per year (P < 0.01). The rapid rise in sepsis mortality seen in previous decades has slowed, but population ageing continues to drive the growth of sepsis-associated mortality in the United States. Disparities in sepsis-associated mortality mirror those previously reported for sepsis incidence. Sepsis in Asians, Hispanics and American Indian/Alaska Natives should be studied separately because aggregate measures may obscure important differences among these groups.

Journal ArticleDOI
TL;DR: Implementing an intraoperative PLV protocol in patients undergoing lung cancer resection was associated with improved postoperative respiratory outcomes as evidence by significantly reduced incidences of acute lung injury and atelectasis along with reduced utilization of intensive care unit resources.
Abstract: Introduction In lung cancer surgery, large tidal volume and elevated inspiratory pressure are known risk factors of acute lung (ALI). Mechanical ventilation with low tidal volume has been shown to attenuate lung injuries in critically ill patients. In the current study, we assessed the impact of a protective lung ventilation (PLV) protocol in patients undergoing lung cancer resection.

Journal ArticleDOI
TL;DR: More-intensive RRT was associated with a favourable effect on ICU stay and duration of mechanical ventilation among survivors, but there was no evidence for a survival benefit afforded by higher dose RRT.
Abstract: The optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. We sought to evaluate the relationship between renal replacement therapy (RRT) dose and outcome. We performed a prospective multicentre observational study in 30 intensive care units (ICUs) in eight countries from June 2005 to December 2007. Delivered RRT dose was calculated in patients treated exclusively with either continuous RRT (CRRT) or intermittent RRT (IRRT) during their ICU stay. Dose was categorised into more-intensive (CRRT ≥ 35 ml/kg/hour, IRRT ≥ 6 sessions/week) or less-intensive (CRRT < 35 ml/kg/hour, IRRT < 6 sessions/week). The main outcome measures were ICU mortality, ICU length of stay and duration of mechanical ventilation. Of 15,200 critically ill patients admitted during the study period, 553 AKI patients were treated with RRT, including 338 who received CRRT only and 87 who received IRRT only. For CRRT, the median delivered dose was 27.1 ml/kg/hour (interquartile range (IQR) = 22.1 to 33.9). For IRRT, the median dose was 7 sessions/week (IQR = 5 to 7). Only 22% of CRRT patients and 64% of IRRT patients received a more-intensive dose. Crude ICU mortality among CRRT patients were 60.8% vs. 52.5% (more-intensive vs. less-intensive groups, respectively). In IRRT, this was 23.6 vs. 19.4%, respectively. On multivariable analysis, there was no significant association between RRT dose and ICU mortality (Odds ratio (OR) more-intensive vs. less-intensive: CRRT OR = 1.21, 95% confidence interval (CI) = 0.66 to 2.21; IRRT OR = 1.50, 95% CI = 0.48 to 4.67). Among survivors, shorter ICU stay and duration of mechanical ventilation were observed in the more-intensive RRT groups (more-intensive vs. less-intensive for all: CRRT (median): 15 (IQR = 8 to 26) vs. 19.5 (IQR = 12 to 33.5) ICU days, P = 0.063; 7 (IQR = 4 to 17) vs. 14 (IQR = 5 to 24) ventilation days, P = 0.031; IRRT: 8 (IQR = 5.5 to 14) vs. 18 (IQR = 13 to 35) ICU days, P = 0.008; 2.5 (IQR = 0 to 10) vs. 12 (IQR = 3 to 24) ventilation days, P = 0.026). After adjustment for multiple variables, these data provide no evidence for a survival benefit afforded by higher dose RRT. However, more-intensive RRT was associated with a favourable effect on ICU stay and duration of mechanical ventilation among survivors. This result warrants further exploration. Cochrane Renal Group (CRG110600093).

Journal ArticleDOI
TL;DR: The initial validation of the Bedside PEWS score can quantify severity of illness in hospitalized children and identify critically ill children with at least one hours notice and Prospective validation in other populations is required.
Abstract: Introduction Adverse outcomes following clinical deterioration in children admitted to hospital wards is frequently preventable. Identification of children for referral to critical care experts remains problematic. Our objective was to develop and validate a simple bedside score to quantify severity of illness in hospitalized children. Methods A case-control design was used to evaluate 11 candidate items and identify a pragmatic score for routine bedside use. Case-patients were urgently admitted to the intensive care unit (ICU). Control-patients had no 'code blue', ICU admission or care restrictions. Validation was performed using two prospectively collected datasets. Results Data from 60 case and 120 control-patients was obtained. Four out of eleven candidate-items were removed. The seven-item Bedside Paediatric Early Warning System (PEWS) score ranges from 0–26. The mean maximum scores were 10.1 in case-patients and 3.4 in control-patients. The area under the receiver operating characteristics curve was 0.91, compared with 0.84 for the retrospective nurse-rating of patient risk for near or actual cardiopulmonary arrest. At a score of 8 the sensitivity and specificity were 82% and 93%, respectively. The score increased over 24 hours preceding urgent paediatric intensive care unit (PICU) admission (P < 0.0001). In 436 urgent consultations, the Bedside PEWS score was higher in patients admitted to the ICU than patients who were not admitted (P < 0.0001).

Journal ArticleDOI
TL;DR: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock and future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.
Abstract: Introduction It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. Methods This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP ≥ 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles ≥ 70 mmHg and mortality or the frequency and occurrence of disease-related events. Results There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or preexistent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.282.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.382.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01).

Journal ArticleDOI
TL;DR: Serum IL-6 and IL-8 values identify AKI early in patients undergoing CPB surgery, suggesting that circulating cytokines in patients with AKI may have deleterious effects on other organs, including the lungs.
Abstract: Acute kidney injury (AKI) is associated with high mortality rates. New biomarkers that can identify subjects with early AKI (before the increase in serum creatinine) are needed to facilitate appropriate treatment. The purpose of this study was to test the role of serum cytokines as biomarkers for AKI and prolonged mechanical ventilation. This was a case-control study of children undergoing cardiac surgery. AKI was defined as a 50% increase in serum creatinine from baseline within 3 days. Levels of serum interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, tumor necrosis factor-α (TNF-α), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using a bead-based multiplex cytokine kit in conjunction with flow-based protein detection and the Luminex LabMAP multiplex system in 18 cases and 21 controls. Levels of IL-6 and IL-8 were confirmed with single-analyte ELISA; IL-18 was also measured with single-analyte ELISA. IL-6 levels at 2 and 12 hours after cardiopulmonary bypass (CPB) and IL-8 levels at 2, 12 and 24 hours were associated with the development of AKI using the Wilcoxon rank-sum test and after adjustment for age, gender, race, and prior cardiac surgery in multivariate logistic regression analysis. In patients with AKI, IL-6 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation (defined as mechanical ventilation for more than 24 hours postoperatively) by receiver operator curve (ROC) analysis, with an area under the ROC curve of 0.95. IL-8 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation in all patients. Serum IL-18 levels were not different between those with and without AKI. Serum IL-6 and IL-8 values identify AKI early in patients undergoing CPB surgery. Furthermore, among patients with AKI, high IL-6 levels are associated with prolonged mechanical ventilation, suggesting that circulating cytokines in patients with AKI may have deleterious effects on other organs, including the lungs.

Journal ArticleDOI
TL;DR: Decontamination of the oral cavity with chlorhexidine did not reduce the total number of potential respiratory pathogens, but it did reduce the number of S. aureus in dental plaque of trauma intensive care patients.
Abstract: Dental plaque biofilms are colonized by respiratory pathogens in mechanically-ventilated intensive care unit patients. Thus, improvements in oral hygiene in these patients may prevent ventilator-associated pneumonia. The goal of this study was to determine the minimum frequency (once or twice a day) for 0.12% chlorhexidine gluconate application necessary to reduce oral colonization by pathogens in 175 intubated patients in a trauma intensive care unit. A randomized, double-blind, placebo-controlled clinical trial tested oral topical 0.12% chlorhexidine gluconate or placebo (vehicle alone), applied once or twice a day by staff nurses. Quantitation of colonization of the oral cavity by respiratory pathogens (teeth/denture/buccal mucosa) was measured. Subjects were recruited from 1 March, 2004 until 30 November, 2007. While 175 subjects were randomized, microbiologic baseline data was available for 146 subjects, with 115 subjects having full outcome assessment after at least 48 hours. Chlorhexidine reduced the number of Staphylococcus aureus, but not the total number of enterics, Pseudomonas or Acinetobacter in the dental plaque of test subjects. A non-significant reduction in pneumonia rate was noted in groups treated with chlorhexidine compared with the placebo group (OR = 0.54, 95% CI: 0.23 to 1.25, P = 0.15). No evidence for resistance to chlorhexidine was noted, and no adverse events were observed. No differences were noted in microbiologic or clinical outcomes between treatment arms. While decontamination of the oral cavity with chlorhexidine did not reduce the total number of potential respiratory pathogens, it did reduce the number of S. aureus in dental plaque of trauma intensive care patients. clinicaltrials.gov NCT00123123.

Journal ArticleDOI
TL;DR: Evidence is provided that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.
Abstract: Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements. We enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 μg·kg-1·h-1), vasopressin (.03 U·min-1) or norepinephrine (15 μg·min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA. There were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 μg·min-1 of norepinephrine, 1.3 μg·kg-1·h-1 of terlipressin allowed a marked reduction in catecholamine requirements (0.8 ± 1.3 and 1.2 ± 1.4 vs. 0.2 ± 0.4 μg·kg-1·min-1 at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 ± 2.8 and 2.8 ± 2.5 vs. 0.9 ± 0.3 mg·dL-1; each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL). The present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements. ClinicalTrial.gov NCT00481572.