The prognostic variables predictive of mortality in patients with an exacerbation of COPD admitted to the ICU: an integrative review.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) frequently presents with an acute exacerbation (AECOPD). Debate exists as to whether these patients should be admitted to intensive care units (ICUs). An integrative review was performed to determine whether clinical variables available at the time of ICU admission are predictive of the intermediate-term mortality of patients with an AECOPD. METHODS: An integrative review was structured to incorporate a five-stage review framework to facilitate data extraction, analysis and presentation. The quality of the studies contributing to the integrative review was assessed with a novel scoring system developed from previously published data and adapted to this setting. RESULTS: The integrative review search strategy identified 28 studies assessing prognostic variables in this setting. Prognostic variables associated with intermediate-term mortality were low Glasgow Coma Scale (GCS) on admission to ICU, cardio-respiratory arrest prior to ICU admission, cardiac dysrhythmia prior to ICU admission, length of hospital stay prior to ICU admission and higher values of acute physiology scoring systems. Premorbid variables such as age, functional capacity, pulmonary function tests, prior hospital or ICU admissions, body mass index and long-term oxygen therapy were not found to be associated with intermediate-term mortality nor was the diagnosis attributed to the cause of the AECOPD. DISCUSSION: Variables associated with intermediate-term mortality after AECOPD requiring ICU admission are those variables, which reflect underlying severity of acute illness. Premorbid and diagnostic data have not been shown to be predictive of outcome. A scoring system is proposed to assess studies of prognosis in AECOPD.

Large scale mtDNA sequencing reveals sequence and functional conservation as major determinants of homoplasmic mtDNA variant distribution.

The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level. Analysis of tRNA secondary structures indicated a preference of variants for the loops and some acceptor stem positions. This comprehensive overview of mtDNA variants distinguishes between regions and positions which are likely not critical, mainly conserved regions with pathogenic mutations and essential regions containing no mutations at all.

A common UCP2 polymorphism predisposes to stress hyperglycaemia in severe sepsis.

BACKGROUND: Insulin resistance and hyperglycaemia are common in severe sepsis. Mitochondrial uncoupling protein 2 (UCP2) plays a role in insulin release and sensitivity. OBJECTIVES: To determine if a common, functional polymorphism in the UCP2 gene promoter region (the -866 G/A polymorphism) contributes to the risk of hyperglycaemia in severe sepsis. RESULTS: In the prospective group 120 non-diabetic patients who were carriers of the G allele had significantly higher maximum blood glucose recordings than non-carriers (mean (SD) AA 8.5 (2.2) mmol/l; GA 8.5 (2.4) mmol/l; GG 10.1 (3.1) mmol/l; p = 0.0042) and required significantly more insulin to maintain target blood glucose (p = 0.0007). In the retrospective study 103 non-diabetic patients showed a similar relationship between maximum glucose and UCP genotype (AA 6.8 (2.3) mmol/l; GA 7.8 (2.2) mmol/l; GG 9.2 (2.9) mmol/l; p = 0.0078). CONCLUSIONS: A common, functional polymorphism in the promoter region of the UCP2 gene is associated with hyperglycaemia and insulin resistance in severe sepsis. This has implications for our understanding of the genetic pathophysiology of sepsis and is of use in the stratification of patients for more intensive management.

Patient flow from critical care to renal services: a year-long survey in a critical care network.

BACKGROUND: The NSF for Renal Services stresses the importance of collaboration between renal services and critical care networks in managing patients with acute renal failure in the most clinically appropriate setting. Anecdotal evidence in our region suggested that some patients were remaining on critical care inappropriately because of a lack of capacity for step-down care in local renal units. AIM: To determine the number of extra days patients spend on critical care receiving single-organ renal support before transfer to a renal unit. DESIGN: Prospective, multi-centre, service evaluation. METHODS: Prospective data were collected over a one-year period by either daily telephone calls or bedside review. Follow-up data were retrieved from electronic and patient records. RESULTS: Five hundred and forty-two patients received renal replacement therapy (RRT) in critical care. With 68 (12.5%) patients already receiving RRT for end-stage renal failure, this gave an incidence of new RRT on critical care of 234 per million population per year. The median duration of RRT on critical care was 4 days (range 1-30). One hundred and twenty-seven patients (23%) were discharged from critical care still requiring RRT. A period of single-organ renal support (median 2 days, range 1-8) was provided to 74 of these patients (58%) using 113 critical care bed days. DISCUSSION: Over half of patients receiving RRT on discharge from critical care in our network received a short period of single-organ renal support before step-down. This may represent either delayed discharge from critical care or a potential opportunity for care in an alternative high-dependency facility.

A comparison of CFU-GM, BFU-E and endothelial progenitor cells using ex vivo expansion of selected cord blood CD133(+) and CD34(+) cells.

BACKGROUND: CD133 is a newly developed hematopoietic stem cell marker but little is known about its function. Whether CD133(+) cell selection provides any advantage over CD34(+) selection for hematopoietic stem cell isolation and transplantation is unclear. The present study compared colony formation and endothelial cell differentiation of these two cell types from umbilical cord blood (UCB). METHODS: Mononuclear cells from the same UCB samples were used for both CD133(+) and CD34(+) cell selection. Cells with 97.1% purity were incubated in semi-solid culture medium containing stem cell growth factor (SCGF) and G-CSF or erythropoietin (EPO). Purified cells were also cultured in M199 containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1). RESULTS: CD34(+) and CD133(+) cells produced similar numbers of CFU-GM colonies (median 43.25 and 30.5, respectively; P>0.2). However, a greater than four-fold difference in BFU-E colony formation was observed from CD34(+) cells compared with CD133(+) cells (median 35 and 8, respectively; P<0.04). CD34(+) cells gave rise to endothelial-like cells when stimulated with VEGF, bFGF and IGF-1. CD133(+) cells were unable produce this cell type under the same conditions. DISCUSSION: CD133(+) cells produced smaller BFU-E colonies and were unable to differentiate into mature endothelial cells. CD34(+) cells contained endothelial progenitors that could differentiate into mature cells of this lineage. Based on these data, it appears that CD133 offers no distinct advantage over CD34 as a selective marker for immunoaffinity-based isolation of hematopoietic stem cells and endothelial progenitor cells.

Weaning units: lessons from North America?

In the United Kingdom over 5% of critical care beds are occupied by stable patients weaning from mechanical ventilation. In North America, diagnosis related groups (DRGs) were introduced over a decade ago. These provided an economic impetus to develop more cost effective regional weaning centres. The imminent introduction of Payment By Results may encourage similar developments in the UK. The evidence for weaning centres is reviewed and detailed organisational and outcome data from two North American centres presented. These units differ from UK critical care units in terms of nurse : patient ratios and types and numbers of ancillary staff. Limited data, mostly from North America, suggest that weaning centres may be better at improving outcome in ventilator-dependent patients compared with standard critical care. The existing evidence is not conclusive and highlights the need for UK-based studies on organisational approaches to the provision of weaning and longer term critical care.

Alveolar and plasma concentrations of interleukin-8 and vascular endothelial growth factor following oesophagectomy.

The acute respiratory distress syndrome occurs in approximately 10% of all patients undergoing elective oesophagectomy. Local increases in lung pro-inflammatory cytokines have been previously detected in high-risk patients before the development of the acute respiratory distress syndrome. We hypothesised that similar changes would occur following oesophagectomy. Two groups of patients were studied. In the collapsed lung group (n = 11), interelukin-8 and vascular endothelial growth factor were measured in bronchoalveolar lavage samples obtained from the intra-operative collapsed lung after operation. In the ventilated lung group (n = 10), bronchoalveolar lavage was performed after operation from the ventilated lung and cytokines measured. Cytokines were also measured in peripheral blood samples before and after operation. Bronchoalveolar lavage cytokine levels in both lungs were of an order of magnitude greater than in peripheral blood. Pulmonary pro-inflammatory cytokine release occurs following oesophageal surgery and may indicate subclinical lung injury.

The need for a regional weaning centre, a one-year survey of intensive care weaning delay in the Northern Region of England.

Over a period of one year, a weekly telephone survey identified 161 stable patients with weaning delay (defined as patients ventilated for at least 6 h per day for more than 2 weeks) in intensive care units in the Northern Region of England. Their median age was 69 years (range 21-88 years). Sixty patients (37%) were admitted with medical conditions, 89 (55%) were postoperative patients, whereas 12 (8%) were surgical but required non-operative admission. One hundred and thirty (89%) were weaned and discharged from the intensive care unit during the year. Twenty-two (14%) died and two were transferred to the home ventilation service. Seven patients remained ventilated in intensive care at the end of the study period. Twenty patients (12%) required more than 28 days of respiratory support. These patients occupied on average 6.0% of available intensive care unit beds in the region. This study suggests that in the Northern Region of England there are a significant number of stable but ventilator-dependent patients occupying intensive care beds.

The pulmonary physician in critical care . 3: critical care management of community acquired pneumonia.

Severe community acquired pneumonia carries a high mortality. Early recognition of the severity of the illness, rapid and appropriate resuscitation, targeted antibiotic treatment, and the critical care support of multiple failing organ systems are all important in this group of patients. Only by improving all these aspects of care is it likely that survival will increase.

Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass.

OBJECTIVE: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the beta2 integrin CD11b. METHODS: Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay. RESULTS: After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated. CONCLUSIONS: CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptors.

Peri-operative risk factors for acute lung injury after elective oesophagectomy.

Acute lung injury after oesophagectomy is well recognized but the risk factors associated with its development are poorly defined. We analysed retrospectively the effect of a number of pre-, peri- and post-operative risk factors on the development of lung injury in 168 patients after elective oesophagectomy performed at a single centre. The acute respiratory distress syndrome (ARDS) developed in 14.5% of patients and acute lung injury in 23.8%. Mortality in patients developing ARDS was 50% compared with 3.5% in the remainder. Features associated with the development of ARDS included a low pre-operative body mass index, a history of cigarette smoking, the experience of the surgeon, the duration of both the operation and of one-lung ventilation, and the occurrence of a post-operative anastomotic leak. Peri-operative cardiorespiratory instability (measured by peri-operative hypoxaemia, hypotension, fluid and blood requirements and the need for inotropic support) was also associated with ARDS. Acute lung injury after elective oesophagectomy is associated with intraoperative cardiorespiratory instability.

Circulating endothelial cells in patients with septic shock.

The vascular endothelium has a central role in the control of microvascular tone, and it has been proposed that vascular endothelial damage occurs in septic shock, producing multiorgan failure. We have developed a method of detecting circulating endothelial cells (EC) that provides direct evidence of EC shedding in human sepsis. Human umbilical vein endothelial cells (HUVEC) were seeded in whole blood and recovered by isopycnic centrifugation to validate the technique. Blood samples were subsequently taken from 11 healthy volunteers, nine ventilated intensive care unit (ICU) control patients without sepsis, eight patients with sepsis but without shock, and 15 patients with septic shock. EC were identified by indirect immunofluorescence, using antibodies to von Willebrand factor (vWf) and the vascular endothelial growth factor receptor KDR. Mean HUVEC recovery was 86% for 20 to 100 seeded cells/ml of blood. vWf-positive EC counts per milliliter were significantly higher (analysis of variance [ANOVA], p < 0.0001) in patients with sepsis (16.1 +/- 2.7 [mean +/- SEM]) and septic shock (30.1 +/- 3.3) than in healthy (1.9 +/- 0.5) or ICU controls (2.6 +/- 0.6). KDR-positive EC counts per milliliter were also significantly higher (ANOVA, p < 0.0001) in patients with sepsis (4.2 +/- 1.1/ml) and septic shock (10.4 +/- 1.2/ml) than in healthy (0.7 +/- 0.3/ml) or ICU controls (0.5 +/- 0.2/ml). Cell counts made with anti-vWf antibody were consistently higher than those made with anti KDR antibody, but correlation between the two counts was high (r(2) = 0.93). The number of circulating KDR-positive EC was significantly higher in patients who died of septic shock than in survivors (12.0 +/- 1.6/ml versus 7.1 +/- 1.2/ml, p = 0.026). An increase in circulating EC can be identified during sepsis and septic shock. This supports the hypothesis that endothelial damage occurs in human sepsis.

Sleep-related breathing disorders following discharge from intensive care.

OBJECTIVES: To determine the incidence of sleep-related breathing disorders and nocturnal hypoxaemia in patients discharged from ICU following prolonged mechanical ventilation. DESIGN: Prospective, consecutive patient observational study. SETTING: The medical and surgical wards of a University Hospital. PATIENTS AND PARTICIPANTS: Fifteen consecutive, adult patients discharged from the ICU who had received more than 48 h of mechanical ventilation were studied. Ten healthy volunteers acted as controls. MEASUREMENTS AND RESULTS: Overnight, multi-channel pneumographic studies were performed on all patients and controls. Chest and abdominal wall movement, air flow, oxygen saturation and snoring were continuously recorded. Data was analysed by both visual inspection of the traces and by computer-based algorithms. An apnoea/hypopnoea index was calculated for each patient and volunteer. Volunteers had an apnoea/hypopnoea index of less than 5 and had no episodes of nocturnal oxygen desaturation (SaO2 < 90%). Despite oxygen therapy 13/15 patients had episodes of desaturation and 9/15 spent more than 2 h with an SaO2 < 90%. Eleven patients had an abnormal apnoea/hypopnoea index (range 5-34 events/h). Four patients had predominantly obstructive events while 7 primarily had hypopnoeas. CONCLUSIONS: Significant overnight oxygen desaturation is common in patients discharged from ICU who have received prolonged mechanical ventilation. This group also has a significant incidence of sleep-related breathing disorders and this mechanism is likely to be important in the pathogenesis of the hypoxaemia.