Validation of a model-based virtual trials method for tight glycemic control in intensive care

Background  

In-silico virtual patients and trials offer significant advantages in cost, time and safety for designing effective tight glycemic control (TGC) protocols. However, no such method has fully validated the independence of virtual patients (or resulting clinical trial predictions) from the data used to create them. This study uses matched cohorts from a TGC clinical trial to validate virtual patients and in-silico virtual trial models and methods.     

Human albumin administration in critically ill patients: systematic review of randomised controlled trials

Objective: To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients. Design: Systematic review of randomised controlled trials comparing administration of albumin or plasma protein fraction with no administration or with administration of crystalloid solution in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia. Subjects: 30 randomised controlled trials including 1419 randomised patients. Main outcome measure: Mortality from all causes at end of follow up for each trial. Results: For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death after albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia it was 1.69 (1.07 to 2.67). Pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Pooled difference in the risk of death with albumin was 6% (95% confidence interval 3% to 9%) with a fixed effects model. These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. Conclusions: There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia and a strong suggestion that it may increase mortality. These data suggest that use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of rigorously conducted, randomised controlled trials.

Key messages

• Human albumin solution has been used in the treatment of critically ill patients for over 50 years
• Currently, the licensed indications for use of albumin are emergency treatment of shock, acute management of burns, and clinical situations associated with hypoproteinaemia
• Our systematic review of randomised controlled trials showed that, for each of these patient categories, the risk of death in the albumin treated group was higher than in the comparison group
• The pooled relative risk of death with albumin was 1.68 (95% confidence interval 1.26 to 2.23) and the pooled difference in the risk of death was 6% (3% to 9%) or six additional deaths for every 100 patients treated
• We consider that use of human albumin solution in critically ill patients should be urgently reviewed

     

Study of multiparameter respiratory pattern complexity in surgical critically ill patients during weaning trials

Background  

Separation from mechanical ventilation is a difficult task, whereas conventional predictive indices have not been proven accurate enough, so far. A few studies have explored changes of breathing pattern variability for weaning outcome prediction, with conflicting results. In this study, we tried to assess respiratory complexity during weaning trials, using different non-linear methods derived from theory of complex systems, in a cohort of surgical critically ill patients.     

Choice of fluids in critically ill patients

Background

Fluids are by far the most commonly administered intravenous treatment in patient care. During critical illness, fluids are widely administered to maintain or increase cardiac output, thereby relieving overt tissue hypoperfusion and hypoxia.

Main text

Until recently, because of their excellent safety profile, fluids were not considered “medications”. However, it is now understood that intravenous fluid should be viewed as drugs. They affect the cardiovascular, renal, gastrointestinal and immune systems. Fluid administration should therefore always be accompanied by careful consideration of the risk/benefit ratio, not only of the additional volume being administered but also of the effect of its composition on the physiology of the patient. Apart from the need to constantly assess fluid responsiveness, it is also important to periodically reconsider the type of fluid being administered and the evidence regarding the relationship between specific disease states and different fluid solutions.

Conclusions

The current review presents the state of the art regarding fluid solutions and presents the existing evidence on routine fluid management of critically ill patients in specific clinical settings (sepsis, Adult Respiratory Distress Syndrome, major abdominal surgery, acute kidney injury and trauma).

     

Risk factors for vancomycin-resistant enterococci colonisation in critically ill patients

Vancomycin-resistant enterococci (VRE) are important hospital pathogens and have become increasingly common in patients admitted to the intensive care unit (ICU). To determine the incidence and the risk factors associated with VRE colonisation among ICU patients, active surveillance cultures for VRE faecal carriages were carried out in patients admitted to the ICU of the University Hospital of Uberlandia, Minas Gerais, Brazil. Risk factors were assessed using a case-control study. Seventy-seven patients (23.1%) were found to be colonised with vanC VRE and only one patient (0.3%) was colonised with vanA VRE. Independent risk factors for VRE colonisation included nephropathy [odds ratio (OR) = 13.6, p < 0.001], prior antibiotic use (OR = 5.5, p < 0.03) and carbapenem use (OR = 17.3, p < 0.001). Our results showed a higher frequency (23.1%) of Enterococcus gallinarum and Enterococcus casseliflavus, species that are intrinsically resistant to low levels of vancomycin (vanC), without an associated infection, associated with prior antibiotic use, carbapenem use and nephropathy as comorbidity. This study is the first to demonstrate the risk factors associated with vanC VRE colonisation in ICU hospitalised patients. Although vanA and vanB enterococci are of great importance, the epidemiology of vanC VRE needs to be better understood. Even though the clinical relevance of vanC VRE is uncertain, these species are opportunistic pathogens and vanC VRE-colonised patients are a potential epidemiologic reservoir of resistance genes.     

Trace element requirements in critically ill burned patients

Critically ill burned patients are characterized by a strong oxidative stress, an intense inflammatory response, and months-long hypermetabolism, all of which are proportional to the severity of injury. Trace element (TE) deficiencies have repeatedly been described. The clinical course is complicated by organ failures, infections, and delayed wound healing, which can be partly attributed to TE deficiencies.Among critically ill patients, TE deficiencies are the most severe in major burns, who suffer a specific copper deficiency. Plasma TE concentrations are low during any critical illness, as a result of TE losses in biological fluids, low intakes, dilution by fluid resuscitation, and redistribution from plasma to tissues mediated by the inflammatory response. The large exudative losses cause negative TE balances. Intravenous supplementation trials show that early substitution improves recovery, reduces infectious complications (particularly nosocomial pneumonia), normalize thyroid function, normalize skin tissue levels, improve wound healing and shorten hospital stay.Nevertheless, prolonged high dose delivery may be deleterious, as TE have potential for toxicity. In major burns, supplements up to 4 mg of Cu/day, 500 mg Se/day and 40 mg Zn/day for 3 weeks have been found to be safe and effective. The intravenous route appears the only way to deliver the doses required to achieve antioxidant and clinical effects. Further research is required to determine the optimal combination and doses for different severities of injury.     

Effects of ambulance transport in critically ill patients.

Two groups of critically ill patients were transferred by ambulance from other hospitals to a central intensive therapy unit. The effect of transport was reviewed retrospectively in 46 patients and prospectively in 20 patients. Of the 46 patients reviewed retrospectively six became hypotensive, six became hypertensive, and seven developed delayed hypotension. One patient developed fits and six out of 13 patients had a rise in arterial PCO-2 of 1-6-4-1 kPa (12-31 mm Hg). Of the 20 patients reviewed prospectively, one patient became hypertensive due to overtransfusion, one had a fit, but none became hypotensive. Three out of four cases of delayed hypotension were related to starting intermittent positive pressure ventilation. Arterial PCO-2 fell in one patient and arterial PCO-2 rose in two, each change being related to changed oxygen therapy or narcotics. There were no changes in other cardiovascular or respiratory indices, body temperature, or urine production. Earlier transfer, resuscitation before transfer, continuing medical care during the journey, and hence a slower smoother journey seemed to be important factors in the management of these patients. Our findings, may have important implications in the future regional organization of the care of critically ill patients.     

Targeted metabolomics for discrimination of systemic inflammatory disorders in critically ill patients

The occurrence of systemic inflammatory response syndrome (SIRS) remains a major problem in intensive care units with high morbidity and mortality. The differentiation between noninfectious and infectious etiologies of this disorder is challenging in routine clinical practice. Many biomarkers have been suggested for this purpose; however, sensitivity and specificity even of high-ranking biomarkers remain insufficient. Recently, metabolic profiling has attracted interest for biomarker discovery. The objective of this study was to identify metabolic biomarkers for differentiation of SIRS/sepsis. A total of 186 meta-bolites comprising six analyte classes were determined in 143 patients (74 SIRS, 69 sepsis) by LC-MS/MS. Two markers (C10:1 and PCaaC32:0) revealed significantly higher concentrations in sepsis. A classification model comprising these markers resulted in 80% and 70% correct classifications in a training set and a test set, respectively.This study demonstrates that acylcarnitines and glycerophosphatidylcholines may be helpful for differentiation of infectious from noninfectious systemic inflammation due to their significantly higher concentration in sepsis patients. Considering the well known pathophysiological relevance of lipid induction by bacterial components, metabolites as identified in this study are promising biomarker candidates in the differential diagnosis of SIRS and sepsis.     

Cardiopulmonary interactions during mechanical ventilation in critically ill patients

Cardiopulmonary interactions induced by mechanical ventilation are complex and only partly understood. Applied tidal volumes and/or airway pressures largely mediate changes in right ventricular preload and afterload. Effects on left ventricular function are mostly secondary to changes in right ventricular loading conditions. It is imperative to dissect the several causes of haemodynamic compromise during mechanical ventilation as undiagnosed ventricular dysfunction may contribute to morbidity and mortality.     

Increased carbon monoxide in exhaled air of critically ill patients

Heme oxygenase produces carbon monoxide (CO) during breakdown of heme molecules primarily in liver and spleen. Recent data suggest that CO is also produced in the lungs. CO is excreted by exhalation via the lungs. A number of inflammatory agents induce the expression of heme oxygenase, possibly leading to increased CO production. To investigate whether critical illness results in increased CO production we measured the CO concentration in exhaled air in 30 critically ill patients and in healthy controls (n = 6). Critically ill patients showed a significantly higher CO concentration in exhaled air (median 2.4 ppm, 95% CI 1.0-7.0 ppm vs median 1.55 ppm, 95% CI 1.2-1.7 ppm, P = 0.01) as well as total CO production (median 20 ml/min, 95% CI 8 to 90 ml/min vs median 13.5 ml/min, 95% CI 11 to 19 ml/min, P = 0.026) compared to healthy controls. No correlation was found between CO concentration in exhaled air and carboxyhemoglobin concentration in arterial and central venous blood (P > 0.05). The increase of CO concentration in exhaled air in critical illness suggests an induction of inducible heme oxygenase (HO-1) and might reflect the severity of illness.