Critical Care - Latest Articles

Acoustic monitoring--super sonics?

John Marini — 2009-07-03T00:00:00Z

Vesicular breath sounds, wheezes, rhonchi, and crackles possess acoustic "signatures" amenable to detection, quantitation, and moment-by-moment visual display. Despite technical hurdles, new methods for sonic evaluation, once perfected, should offer innovative diagnostic and monitoring tools that add clinical value. These emerging options complement current 'static/global' monitoring of mechanics and gas exchange with dynamic regional information long missing from the optimal care of the ventilated patient with critical illness.

Reliability issues in human brain temperature measurement

Charmaine Childs — 2009-07-02T00:00:00Z

IntroductionThe influence of brain temperature on clinical outcome after severe brain trauma is currently poorly understood. When brain temperature is measured directly, different values between the inside and outside of the head can occur. It is not yet clear if these differences are 'real' or due to measurement error. Methods: The aim of this study was to assess the performance and measurement uncertainty of body and brain temperature sensors currently in use in neurocritical care. Two organic fixed-point, ultra stable temperature sources were used as the temperature references. Two different types of brain sensor (brain type 1 and brain type 2) and one body type sensor were tested under rigorous laboratory conditions and at the bedside. Measurement uncertainty was calculated using internationally recognised methods. Results: Average differences between the 26degreesC reference temperature source and the clinical temperature sensors were +0.11degreesC (brain type 1), +0.24degreesC (brain type 2) and -0.15degreesC (body type), respectively. For the 36degreesC temperature reference source, average differences between the reference source and clinical thermometers were, -0.02degreesC, +0.09degreesC and -0.03degreesC for brain type 1, brain type 2, and body type sensor, respectively. Repeat calibrations the following day confirmed that these results were within the calculated uncertainties. The results of the immersion tests revealed that the reading of the body type sensor was sensitive to position, with differences in temperature of -0.5degreesC to -1.4degreesC observed on withdrawing the thermometer from the base of the isothermal environment by 4 cm and 8 cm respectively. Taking into account all the factors tested during the calibration experiments, the measurement uncertainty of the clinical sensors against the (nominal) 26degreesC and 36degreesC temperature reference sources for the brain type 1, brain type 2 and body type sensors were +/-0.18degreesC, +/-0.10degreesC and +/-0.12degreesC, respectively Conclusions: The results show that brain temperature sensors are fundamentally accurate and the measurements are precise to within 0.1-0.2degreesC. Subtle dissociation between brain and body temperature in excess of 0.1-0.2degreesC is likely to be real. Body temperature sensors need to be secured in position to ensure that measurements are reliable.

Changes in serum adiponectin concentrations in critical illness: a preliminary investigation

Bala Venkatesh — 2009-07-02T00:00:00Z

IntroductionAdiponectin plays an important role in the regulation of tissue inflammation and insulin sensitivity. Perturbations in adiponectin concentration have been associated with obesity and the metabolic syndrome. Data on adiponectin pathophysiology in critical illness are limited. Methods: Twenty three critically ill patients (9 severe sepsis, 7 burns, 7 trauma). Adiponectin assays on Days 3 (D3) and 7 (D7). Simultaneous, cortisol, cortisone and CRP measurements. Data from 16 historical controls were used for comparison Results: The mean plasma adiponectin concentration for the ICU cohort on D3 and D7 were not significantly different (4.1 +/- 1.8 and 5.0 +/- 3.3 mcg/ml respectively, P=0.38). However, these were significantly lower than the mean plasma adiponectin in the control population (8.78 +/- 3.81 mcg/ml) at D3 (P<0.0001) and D7 (P=0.002). Plasma adiponectin showed a strong correlation with plasma cortisol in the ICU group on both D3 (R2=0.32, P<0.01) and D7 (R2=0.64, 0.001). There was an inverse correlation between plasma adiponectin and CRP on D7, R=-0.35. Conclusions: In this preliminary study, critical illness was associated with lower adiponectin concentrations as compared to controls. A significant relationship between plasma cortisol and adiponectin in critically ill patients was evident, both during the early and late phases. These data raise the possibility that adiponectin may play a part in the inflammatory response in patients with severe illness.

Incretins In The ICU: Is Insulin On Its Way Out?

Michelle Kovalaske — 2009-07-02T00:00:00Z

Incretin such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that stimulate insulin secretion and suppress glucagon secretion, thus playing a key role in glucose homeostasis. While incretin mimetics and enhancers are approved for treatment of outpatients with diabetes, evidence is only starting to accumulate regarding the therapeutic potential of incretins in hospitalized patients. Small exploratory studies suggest that GLP-1 safely reduces hyperglycemia without causing hypoglycemia, a key advantage over insulin if efficacy is established in lager studies. Potential limitations include the need for a continuous infusion for delivery, attenuation but not normalization of glucose levels, increased deceleration of gastric emptying and nausea. The exact mechanism of action, dosing, adverse effects, patient subgroups that would be most suitable and safety of combination treatment with insulin remain to be studied. While promising, additional research is required studying effects on hard clinical endpoints.

Serum Interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study

Kathleen Liu — 2009-07-01T00:00:00Z

IntroductionAcute kidney injury (AKI) is associated with high mortality rates. New biomarkers that can identify subjects with early AKI (before the rise 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. Methods: This was a case-control study of children undergoing cardiac surgery. AKI was defined as a 50% rise in serum creatinine from baseline within 3 days. Levels of serum interleukin (IL)-1beta, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN)-gamma, tumor necrosis factor-alpha (TNF-alpha), 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 by single analyte ELISA; IL-18 was also measured by single analyte ELISA. Results: 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 by 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 post-operatively) 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. Conclusions: Serum IL-6 and IL-8 identifies AKI early in patients undergoing cardiopulmonary bypass surgery. Furthermore, amongst 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.

Broadening our perspectives on ICU delirium risk factors

Yoanna Skrobik — 2009-07-01T00:00:00Z

ICU delirium is associated with poor patient outcome. Risk factor stratification is essential to the understanding, prevention and treatment of this disorder. Alcohol consumption, smoking and prior cognitive impairment appear strongly correlated with delirium risk. Several potentially modifiable associations deserve prospective study: these include administration of sedatives and opiates; multiple catheters; as well as minimizing physical restraints and enabling visitors.

The international PROGRESS registry of patients with severe sepsis: drotrecogin alfa (activated) use and patient outcomes

Greg Martin — 2009-06-30T00:00:00Z

IntroductionSince the launch of drotrecogin alfa activated (DrotAA), institutions and individual countries have published data on its use in clinical practice, based on audit or registry data. These studies were limited in size and geographic locale and included patients with greater disease severity and higher mortality than those in clinical trials. The purpose of this study was to compare baseline characteristics and clinical outcomes (using appropriate statistical adjustments) of patients treated or not treated with DrotAA from the international PROGRESS (Promoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis. Methods: PROGRESS was a global, non-interventional, multi-center, prospective, observational study of patients having a diagnosis of severe sepsis treated in intensive care units at a participating institution. All treatment modalities were as per standard of care at the participating institutions. Baseline characteristics and hospital mortality were analyzed and regression techniques used to develop propensity and outcome models adjusted for baseline imbalances between groups. Results: Overall, 14,543 patients from 37 countries were enrolled and 12,492 had complete data for analysis. Germany was the highest enrolling country (1,810; 14.5%) and the United States had the most DrotAA patients (206, 23.3%); 882 (7%) overall received DrotAA therapy. DrotAA-treated patients were younger (median age 58 vs. 61 years), had greater organ dysfunction (cardiovascular: 90% vs. 74%; respiratory: 90% vs. 81%; renal: 60% vs. 45%; metabolic: 63% versus 42%; 3 or more organ dysfunctions: 84% vs. 67%) and had a higher median APACHE II score (26 vs. 23, all with p<0.001). Although in-hospital mortality was similar for DrotAA and non-DrotAA-treated patients (49.6% vs. 49.7%, respectively), after adjusting for imbalances, patients receiving DrotAA had a 28% (0.60 - 0.86, 95% Confidence Intervals) reduction in the odds of death and a relative risk reduction of 17% (p=0.0003). Conclusions: In the PROGRESS registry, DrotAA-treated patients were younger, more severely ill, and had fewer co-morbidities than patients not treated with DrotAA. After adjustment for group differences, a significant reduction in the odds of death was observed for patients that received DrotAA compared to those that did not.

Prevalence of endotoxemia after surgery and its association with ICU length of stay

Franco Valenza — 2009-06-29T00:00:00Z

IntroductionThe aim of this observational study was to investigate the prevalence of endotoxemia after surgery and its association with ICU length of stay. Methods: 102 patients admitted to a university ICU after surgery were recruited. Within four hours from admission functional data were collected and APACHE II severity score calculated. Arterial blood samples were taken and endotoxemia was measured by chemiluminescence (Endotoxin Activity [EA]). Patients were stratified according to their endotoxin levels (low, intermediate and high) and according to their surgical procedures. Differences between endotoxin levels were assessed by ANOVA, accepting P<0.05 as significant. Data are expressed as mean +/- SD. Results: EA levels were low in 68 (66%) patients, intermediate in 17 (17%) and high in 17 (17%). Age (61+/-17 years) and APACHE II score 8.3+/-3.7 (P=0.542) were not significantly different in the three EA groups. Functional parameters on admission were similar between EA groups: white blood cells 11093+/-4605 cells/mm3 (P=0.385), heart rate 76+/-16 bpm (P=0.898), mean arterial pressure 88.8+/-13.6 mmHg (P=0.576), lactate 1.18+/-0.77 mmol/L (P=0.370), PaO2/FiO2 383+/-109 mmHg (P=0.474). Patients with high levels of EA were characterized by longer length of stay in the ICU: 1.9+/-3.0 days in the low EA group, 1.8+/-1.4 days in intermediate and 5.2+/-7.8 days in high group (P=0.038). Conclusions: 17% of our patients were characterized by high levels of endotoxemia as assessed by EA assay, despite their low level of complexity on admission. High levels of endotoxin were associated with a longer ICU length of stay.

Burn-induced cerebral inflammation - a neglected entity?

Michael Flierl — 2009-06-29T00:00:00Z

Severe burn injury remains a major burden on patients and health care systems. Following severe burns, the injured tissues mount a local inflammatory response aiming to restore homeostasis. With excessive burn load, the immune response becomes disproportionate and patients may develop an overshooting systemic inflammatory response, compromising multiple physiological barriers in the lung, kidney, liver and brain. If the blood-brain barrier (BBB) is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system (CNS). Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema. Despite the correlation between cerebral complications in severe burn victims with mortality, burn-induced neuroinflammation continues to "fly under the radar" as an underestimated entity in the critically ill burn patient. In this paper, we illustrate the molecular events leading to BBB breakdown, with a focus on the subsequent neuroinflammatory changes leading to cerebral edema in patients with severe burns.

Macrophage migration inhibitory factor in cerebrospinal fluid from patients with central nervous system infection

Christian Ostergaard — 2009-06-26T00:00:00Z

IntroductionMacrophage Migration Inhibitory Factor (MIF) plays an essential pathophysiological role in septic shock; however, its role in central nervous system infection (CNS) remains to be defined. Methods: The aim of the present study was to investigate cerebrospinal fluid (CSF) levels of MIF in 171 patients clinically suspected of having meningitis on admission. Of these, 31 were found to have purulent meningitis with a known aetiology, 20 to have purulent meningitis with an unknown aetiology, 59 to have lymphocytic meningitis, and 11 to have encephalitis, whereas 50 were suspected of but had no evidence of CNS infection. Results: CSF MIF levels were significantly higher in patients with purulent meningitis of known aetiology (8639 ng/L (3344-20600)) as compared to patients with purulent meningitis of unknown aetiology (2209 ng/L (1516-6550), Mann Whitney test, P=0.003), to patients with lymphocytic meningitis (1912 ng/L (1302-4105), P< 0.001), and to patients suspected but without evidence of CNS infection (1472 ng/L (672-3447), P< 0.001), respectively. Also, patients with encephalitis (6937 ng/L (3961-8353) had higher CSF MIF levels than patients without CNS infection (P<0.01). Among patients with purulent meningitis, CSF MIF levels were significantly higher in patients infected with pneumococci as compared to infection due to meningococci (11569 ng/L (8615-21935) vs. 5006 ng/L (1717-10905) respectively, P=0.02), in patients requiring assisted ventilation (10493 ng/L (5961-22725) vs. 3240ng/L (1563-9302), respectively, P=0.003), and in patients with impaired consciousness (8614 ng/L (3344-20935) vs. 2625 ng/L (1561-7530), respectively, P=0.02). CSF MIF levels correlated significantly to the meningeal inflammation (P<0.05), but not to the systemic inflammatory response (P>0.05) in patients with purulent meningitis of known aetiology, in patients with lymphocytic meningitis, and in patients with encephalitis. Conclusions: MIF was significantly increased in the CSF of patients with purulent meningitis and encephalitis and was to some degree associated with disease severity of the infection. Our results indicate that MIF may play an important role in CNS infection.