Which factors influence glycemic control in the intensive care unit?

PURPOSE OF REVIEW: Intensive insulin therapy titrated to restore and maintain blood glucose between 80 and 110 mg/dl (4.4-6.1 mmol/l) was found to improve survival of critically ill patients in one pioneering proof-of-concept study performed in a surgical intensive care unit. The external validity of these findings was investigated. RECENT FINDINGS: Six independent prospective randomized controlled trials, involving 9877 patients in total, were unable to confirm the survival benefit reported in the pioneering trial. Several hypotheses were proposed to explain this discrepancy, including the case-mix, the features of the usual care, the quality of glucose control and the risks associated with hypoglycemia. SUMMARY: Before a better understanding and delineation of the conditions associated with and improved outcome by tight glycemic control, the choice of an intermediate glycemic target appears as a safe and effective solution.

Trends in risk factors, patterns and causes in hospitalized strokes over 25 years: The Lausanne Stroke Registry.

BACKGROUND AND OBJECTIVE: The Lausanne Stroke Registry includes, from 1979, all patients admitted to the department of Neurology of the Lausanne University Hospital with the diagnosis of first clinical stroke. Using the Lausanne Stroke Registry, we aimed to determine trends in risk factors, causes, localization and inhospital mortality over 25 years in hospitalized stroke patients. METHODS: We assessed temporal trends in stroke patients characteristics through the following consecutive periods: 1979-1987, 1988-1995 and 1996-2003. Age-adjusted cardiovascular risk factors, etiologies, stroke localizations and mortality were compared between the three periods. RESULTS: Overall, 5,759 patients were included. Age was significantly different among the analyzed periods (p < 0.001), showing an increment in older patients throughout time. After adjustment for age, hypercholesterolemia increased (p < 0.001), as opposed to cigarette smoking (p < 0.001), hypertension (p < 0.001) and diabetes and hyperglycemia (p < 0.001). In patients with ischemic strokes, there were significant changes in the distribution of causes with an increase in cardioembolic strokes (p < 0.001), and in the localization of strokes with an increase in entire middle cerebral artery (MCA) and posterior circulation strokes together with a decrease in superficial middle cerebral artery stroke (p < 0.001). In patients with hemorrhagic strokes, the thalamic localizations increased, whereas the proportion of striatocapsular hemorrhage decreased (p = 0.022). Except in the older patient group, the mortality rate decreased. CONCLUSIONS: This study shows major trends in the characteristics of stroke patients admitted to a department of neurology over a 25-year time span, which may result from referral biases, development of acute stroke management and possibly from the evolution of cerebrovascular risk factors.

Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.

While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2(Akita/+) mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2(Akita/+) and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2(Akita/+) mice and sex-matched littermate controls. Our phenotypic analysis of Ins2(Akita/+) mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM.

Is diabetes a risk factor for a severe clinical presentation of dengue?--review and meta-analysis.

BACKGROUND: The mean age of acute dengue has undergone a shift towards older ages. This fact points towards the relevance of assessing the influence of age-related comorbidities, such as diabetes, on the clinical presentation of dengue episodes. Identification of factors associated with a severe presentation is of high relevance, because timely treatment is the most important intervention to avert complications and death. This review summarizes and evaluates the published evidence on the association between diabetes and the risk of a severe clinical presentation of dengue. METHODOLOGY/FINDINGS: A systematic literature review was conducted using the MEDLINE database to access any relevant association between dengue and diabetes. Five case-control studies (4 hospital-based, 1 population-based) compared the prevalence of diabetes (self-reported or abstracted from medical records) of persons with dengue (acute or past; controls) and patients with severe clinical manifestations. All except one study were conducted before 2009 and all studies collected information towards WHO 1997 classification system. The reported odds ratios were formally summarized by random-effects meta-analyses. A diagnosis of diabetes was associated with an increased risk for a severe clinical presentation of dengue (OR 1.75; 95% CI: 1.08-2.84, p = 0.022). CONCLUSIONS/SIGNIFICANCE: Large prospective studies that systematically and objectively obtain relevant signs and symptoms of dengue fever episodes as well as of hyperglycemia in the past, and at the time of dengue diagnosis, are needed to properly address the effect of diabetes on the clinical presentation of an acute dengue fever episode. The currently available epidemiological evidence is very limited and only suggestive. The increasing global prevalence of both dengue and diabetes justifies further studies. At this point, confirmation of dengue infection as early as possible in diabetes patients with fever if living in dengue endemic regions seems justified. The presence of this co-morbidity may warrant closer observation for glycemic control and adapted fluid management to diminish the risk for a severe clinical presentation of dengue.

Quantitative Analysis of Myelin and Axonal Remodeling in the Uninjured Motor Network After Stroke.

Contralesional brain connectivity plasticity was previously reported after stroke. This study aims at disentangling the biological mechanisms underlying connectivity plasticity in the uninjured motor network after an ischemic lesion. In particular, we measured generalized fractional anisotropy (GFA) and magnetization transfer ratio (MTR) to assess whether poststroke connectivity remodeling depends on axonal and/or myelin changes. Diffusion-spectrum imaging and magnetization transfer MRI at 3T were performed in 10 patients in acute phase, at 1 and 6 months after stroke, which was affecting motor cortical and/or subcortical areas. Ten age- and gender-matched healthy volunteers were scanned 1 month apart for longitudinal comparison. Clinical assessment was also performed in patients prior to magnetic resonance imaging (MRI). In the contralesional hemisphere, average measures and tract-based quantitative analysis of GFA and MTR were performed to assess axonal integrity and myelination along motor connections as well as their variations in time. Mean and tract-based measures of MTR and GFA showed significant changes in a number of contralesional motor connections, confirming both axonal and myelin plasticity in our cohort of patients. Moreover, density-derived features (peak height, standard deviation, and skewness) of GFA and MTR along the tracts showed additional correlation with clinical scores than mean values. These findings reveal the interplay between contralateral myelin and axonal remodeling after stroke.

How to monitor the brain in septic patients?

Brain injury is frequently observed after sepsis and may be primarily related to the direct effects of the septic insult on the brain (e.g., brain edema, ischemia, seizures) or to secondary/indirect injuries (e.g., hypotension, hypoxemia, hypocapnia, hyperglycemia). Management of brain injury in septic patients is first focused to exclude structural intracranial complications (e.g., ischemic/hemorrhagic stroke) and possible confounders (e.g., electrolyte alterations or metabolic disorders, such as dysglycemia). Sepsis-associated brain dysfunction is frequently a heterogeneous syndrome. Despite increasing understanding of main pathophysiologic determinants, therapy is essentially limited to protect the brain against further cerebral damage, by way of "simple" therapeutic manipulations of cerebral perfusion and oxygenation and by avoiding over-sedation. Non-invasive monitoring of cerebral perfusion and oxygenation with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) is feasible in septic patients. Electroencephalography (EEG) allows detection of sepsis-related seizures and holds promise also as sedation monitoring. Brain CT-scan detects intra-cerebral structural lesions, while magnetic resonance imaging (MRI) provides important insights into primary mechanisms of sepsis-related direct brain injury, (e.g., cytotoxic vs. vasogenic edema) and the development of posterior reversible encephalopathy. Together with EEG and evoked potentials (EP), MRI is also important for coma prognostication. Emerging clinical evidence suggests monitoring of the brain in septic patients can be implemented in the ICU. The objective of this review was to summarize recent clinical data about the role of brain monitoring - including TCD, NIRS, EEG, EP, CT, and MRI - in patients with sepsis and to illustrate its potential utility for the diagnosis, management and prognostication.

Moderate glycemic control safe in critically ill adult burn patients: A 15 year cohort study.

INTRODUCTION: Hyperglycemia is a metabolic alteration in major burn patients associated with complications. The study aimed at evaluating the safety of general ICU glucose control protocols applied in major burns receiving prolonged ICU treatment. METHODS: 15year retrospective analysis of consecutive, adult burn patients admitted to a single specialized centre. EXCLUSION CRITERIA: death or length of stay <10 days, age <16years. VARIABLES: demographic variables, burned surface (TBSA), severity scores, infections, ICU stay, outcome. Metabolic variables: total energy, carbohydrate and insulin delivery/24h, arterial blood glucose and CRP values. Analysis of 4 periods: 1, before protocol; 2, tight doctor driven; 3, tight nurse driven; 4, moderate nurse driven. RESULTS: 229 patients, aged 45±20 years (mean±SD), burned 32±20% TBSA were analyzed. SAPSII was 35±13. TBSA, Ryan and ABSI remained stable. Inhalation injury increased. A total of 28,690 blood glucose samples were analyzed: the median value remained unchanged with a narrower distribution over time. After the protocol initiation, the normoglycemic values increased from 34.7% to 65.9%, with a reduction of hypoglycaemic events (no extreme hypoglycemia in period 4). Severe hyperglycemia persisted throughout with a decrease in period 4 (9.25% in period 4). Energy and glucose deliveries decreased in periods 3 and 4 (p<0.0001). Infectious complications increased during the last 2 periods (p=0.01). CONCLUSION: A standardized ICU glucose control protocol improved the glycemic control in adult burn patients, reducing glucose variability. Moderate glycemic control in burns was safe specifically related to hypoglycemia, reducing the incidence of hypoglycaemic events compared to the period before. Hyperglycemia persisted at a lower level.