ICU registries: From tracking to fostering better outcomes.

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National ICU Registries as Enablers of Clinical Research and Quality Improvement.

OBJECTIVES: Clinical quality registries (CQRs) have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. This narrative review describes the challenges, proposed solutions, and evidence generated by National ICU registries as facilitators for research and quality improvement. DATA SOURCES: English language articles were identified in PubMed using phrases related to ICU registries, CQRs, outcomes, and case-mix. STUDY SELECTION: Original research, review articles, letters, and commentaries, were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: CQRs have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. The initial experience in European countries and in Oceania ensured that through locally generated data, ICUs could assess their performances by using risk-adjusted measures and compare their results through fair and validated benchmarking metrics with other ICUs contributing to the CQR. The accomplishment of these initiatives, coupled with the increasing adoption of information technology, resulted in a broad geographic expansion of CQRs as well as their use in quality improvement studies, clinical trials as well as international comparisons, and benchmarking for ICUs. CONCLUSIONS: ICU registries have provided increased knowledge of case-mix and outcomes of ICU patients based on real-world data and contributed to improve care delivery through quality improvement initiatives and trials. Recent increases in adoption of new technologies (i.e., cloud-based structures, artificial intelligence, machine learning) will ensure a broader and better use of data for epidemiology, healthcare policies, quality improvement, and clinical trials.

The resilient intensive care unit.

BACKGROUND: The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19. METHODS: In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement. RESULTS: We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times. CONCLUSIONS: The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.

Is There a Role for Enterohormones in the Gastroparesis of Critically Ill Patients?

OBJECTIVES: Delayed gastric emptying occurs in critically ill patients and impairs the delivery, digestion, and absorption of enteral feeding. A pathophysiologic role of the enterohormones peptide YY and ghrelin is supported by preclinical data. To compare the circulating plasma levels of peptide YY and ghrelin in control subjects and in critically ill patients, during feeding and fasting, and to search for a correlation with gastric emptying. DESIGN: A prospective observational trial. SETTINGS: Mixed ICU of an academic hospital. SUBJECTS: Healthy volunteers and patients expected to stay in ICU for at least 3 days in whom enteral nutrition was indicated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma peptide YY and ghrelin (enzyme-linked immunosorbent assay) were measured once in 10 fasting volunteers (controls) and daily from admission until day 5 of the ICU stay in 30 critically ill patients (median [interquartile range] age 63 [57-67] yr, median [interquartile range] Acute Physiology and Chronic Health Evaluation II score 21 [14-24]). Eight patients could not be fed (fasting group). In fed patients, 13 never had a gastric residual volume higher than 250 mL (low gastric residual volume group), in contrast to the high gastric residual volume group (n = 9). The plasma levels of peptide YY did not differ between patients (6.4 [0-18.1] pg/mL) and controls (4.8 [0.3-17.7] pg/mL). Ghrelin levels were lower in patients than in control (213 [54.4-522.7] vs 1,435 [1,321.9-1,869.3] pg/mL; p < 0.05). Plasma peptide YY or ghrelin did not differ between fasting and fed patients or between the high and low gastric residual volume groups. CONCLUSIONS: In critically ill patients, plasma concentration of ghrelin significantly differs from that of controls, irrespective of the feeding status. No correlation was found between the temporal profile of ghrelin or peptide YY plasma concentration with bedside functional assessment of gastric emptying.

Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response.

We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits.

Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease: stereological analysis in the albino Swiss mice model.

Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration, and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression.

Exercise and food ad libitum reduce the impact of early in life nutritional inbalances on nitrergic activity of hippocampus and striatum.

Nutritional imbalances were produced by varying litter size pups per dam: 3 (small), 6 (medium), and 12 (large). On the 21st day, 4 subjects of each litter, were sacrificed and the remaining were grouped, 2 per cage, with or without running wheels, with food and water ad libitum. Adult subjects were tested in water maze, their brains processed for NADPH-diaphorase histochemistry and quantified by densitometry. No differences were detected in water maze. At 21st day, S and L compared with M presented reduced NADPH-d in the stratum molecular of dentate gyrus (DG), stratum lacunosum of CA1 and in all CA3 layers but not in the striatum. On the 58th day, actvity remained low in S and L in CA3 and striatum and L in CA1 and DG. Voluntary exercise increased NADPH-d in DG, CA1, CA3, and striatum in S, and in the stratum lacunosum of CA1 and CA3 in L.

NADPH-diaphorase histochemical changes in the hippocampus, cerebellum and striatum are correlated with different modalities of exercise and watermaze performances.

Nitric oxide is involved in memory and motor learning. We investigated possible influences of exercise on spatial memory and NADPH-diaphorase (NADPH-d) histochemical activity in the hippocampus, striatum and cerebellum. Fifteen albino Swiss mice between the 22nd and 55th post-natal days were exercised in the following modalities: voluntary (V), acrobatic (A), acrobatic/voluntary (AV) and forced (F) and compared to inactive group (I). After the exercise period, all subjects were tested in the water maze for 3 days. Animal brains were processed for NADPH-d histochemistry. Densitometry of the neuropil of the hippocampus, striatum and cerebellum and morphometric analysis of NADPHd+ type I neurons of the striatum were done. Exercise groups presented higher levels of NADPH-d activity in the molecular and polymorphic layers of dentate gyrus and lacunosum molecular layer of CA1. The A group presented higher NADPH-d activity in the cerebellar granular layer than all other groups. Branching points and dendritic segment densities of NADPH-d type I neurons were higher in V, A and AV than in F and I groups. Exercise groups revealed best performances on water maze tests. Thus, different modalities of exercise increases in different proportions for the nitrergic activity in the hippocampus, striatum and cerebellum, and these changes seem to be beneficial to spatial memory.