Interprofessional team management in pediatric critical care: some challenges and possible solutions.

BACKGROUND: Aiming for and ensuring effective patient safety is a major priority in the management and culture of every health care organization. The pediatric intensive care unit (PICU) has become a workplace with a high diversity of multidisciplinary physicians and professionals. Therefore, delivery of high-quality care with optimal patient safety in a PICU is dependent on effective interprofessional team management. Nevertheless, ineffective interprofessional teamwork remains ubiquitous. METHODS: We based our review on the framework for interprofessional teamwork recently published in association with the UK Centre for Advancement of Interprofessional Education. Articles were selected to achieve better understanding and to include and translate new ideas and concepts. FINDINGS: The barrier between autonomous nurses and doctors in the PICU within their silos of specialization, the failure of shared mental models, a culture of disrespect, and the lack of empowering parents as team members preclude interprofessional team management and patient safety. A mindset of individual responsibility and accountability embedded in a network of equivalent partners, including the patient and their family members, is required to achieve optimal interprofessional care. Second, working competently as an interprofessional team is a learning process. Working declared as a learning process, psychological safety, and speaking up are pivotal factors to learning in daily practice. Finally, changes in small steps at the level of the microlevel unit are the bases to improve interprofessional team management and patient safety. Once small things with potential impact can be changed in one's own unit, engagement of health care professionals occurs and projects become accepted. CONCLUSION: Bottom-up patient safety initiatives encouraging participation of every single care provider by learning effective interprofessional team management within daily practice may be an effective way of fostering patient safety.

Genetic polymorphisms in the endotoxin receptor may influence platelet count as part of the acute phase response in critically ill children.

PURPOSE: To determine if common polymorphisms in the endotoxin recognition complex influence the acute phase response as determined by the development of the systemic inflammatory response syndrome (SIRS) and platelet count on admission. METHODS: This was a prospective observational cohort study. Paediatric intensive care patients (n = 913) were genotyped for common functional polymorphisms in the endotoxin recognition complex, including Toll-like receptor 4 (TLR4). We also selected potentially confounding polymorphisms in other genes of the innate immune system. SIRS was defined by age-specific consensus criteria. Platelet counts were recorded on admission. RESULTS: The development of SIRS was primarily determined by the nature of the insult, but carriers of TLR4 variant alleles had lower platelet counts than children with wild-type genotype [mean +/- standard error of the mean (SEM) 143 +/- 7 vs. 175 +/- 4; p = 0.0001)--independent of other innate immune system polymorphisms. These findings were validated using a patient cohort of 1,170 adults with coronary artery disease. Carriers of TLR4 polymorphisms with a history of myocardial infarction (n = 573) had lower platelet counts than those with the wild-type genotype (217 +/- 7 vs. 237 +/- 2.8; p = 0.021). CONCLUSIONS: Our results show that TLR4 variant alleles are associated with lower platelet counts across a range of ages and precipitating insults but that they do not influence the incidence of SIRS. This result may reflect redundancy and 'robustness' in the pathways leading to SIRS or the lack of specificity of this endpoint. Platelet count may vary with TLR4 genotype because it may be sufficiently sensitive and more linearly related to inflammation than other markers or, alternatively, there may be a direct TLR4-mediated platelet effect.

Genetic variability in complement activation modulates the systemic inflammatory response syndrome in children.

OBJECTIVE: To determine the impact of genetic variability in complement activation on early development of the systemic inflammatory response syndrome (SIRS) in general pediatric critical care. DESIGN: Prospective, observational, cohort study. SETTING: A tertiary pediatric intensive care unit in the United Kingdom. PATIENTS: Children with at least one organ failure expected to stay in the intensive care unit >12 hrs, or an expected death within 12 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 299 children were genotyped for functional polymorphisms in the complement activation cascade. We identified complement factor H as an important independent genetic modifier of SIRS/sepsis. Homozygosity for the complement factor H Y402H polymorphism, which is thought to reduce complement inhibition, was associated with less frequent SIRS/sepsis (the adjusted odds ratio for the homozygous variant complement factor H Y402H [CC] carriers was 0.3, 95% confidence interval, 0.1-0.7, p = .005). We also confirmed that structural and promoter variant mannose-binding lectin genotypes are a risk factor for SIRS/sepsis in pediatric critical care (adjusted odds ratio, 2.5; 95% confidence interval, 1.3-5.0, p = .008). Both findings were independent of clinical characteristics and other potentially confounding genetic polymorphisms in the innate immune system. CONCLUSIONS: Functional polymorphisms in the complement activation cascade modify the risk for early SIRS/sepsis in general pediatric critical care. The complement factor H Y402H variant allele is protective, whereas the mannose-binding lectin variant polymorphisms increase risk. A genotype that permits vigorous complement activation to an infectious or inflammatory insult may offer protection from development of systemic inflammation.

Interleukin-10 and its role in clinical immunoparalysis following pediatric cardiac surgery.

OBJECTIVE: A systemic insult is associated with subsequent hyporesponsiveness to endotoxin (as measured by ex vivo tumor necrosis factor [TNF]-alpha production) and an increased risk of late nosocomial infection in some patients. When combined with low monocyte surface major histocompatibility complex class II expression, this state of altered host defense is now commonly referred to as immunoparalysis. This study was undertaken to delineate the relationship between observed levels of the anti-inflammatory cytokine interleukin-10, common genetic polymorphisms that influence these levels, and the occurrence and severity of endotoxin hyporesponsiveness in children following elective cardiac surgery requiring cardiopulmonary bypass. DESIGN: A prospective observational clinical study. SETTING: A tertiary pediatric cardiac center. PATIENTS: Thirty-six infants and children <2 yrs of age undergoing elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We investigated the production of TNF-alpha, interleukin-6, interleukin-8, interleukin-1 receptor antagonist, and interleukin-10 in whole blood in response to lipopolysaccharide (Neisseria meningitides 10 ng/mL) in samples drawn before, during, and up to 48 hrs after surgery. Patients were genotyped for the -1082, -819, and -592 interleukin-10 promoter polymorphisms. Whole blood cytokine response to lipopolysaccharide was reduced postoperatively to 100 pg/mL) over the first 48 hrs were more likely to have an uncomplicated short stay (odds ratio 4.7, 95% confidence interval 1-22). CONCLUSIONS: Immediately following cardiac surgery, many children become relatively refractory to lipopolysaccharide stimulation. This immunoparalysis appears to be related in part to high circulating levels of interleukin-10 and places these patients at increased risk of postoperative complications. Interleukin-10 genotype may be a risk factor for immunoparalysis.

An analysis of oxygen consumption and oxygen delivery in euthermic infants after cardiopulmonary bypass with modified ultrafiltration.

BACKGROUND: The balance between systemic oxygen consumption (VO2) and delivery (DO2) is impaired after cardiopulmonary bypass (CPB) and is related to systemic inflammatory response syndrome. We sought to assess VO2 and DO2 and their relationship with proinflammatory cytokines after CPB with the use of modified ultrafiltration (MUF) in infants. METHODS: Sixteen infants, aged 1-11.5 months (median, 6.3 months), undergoing hypothermic CPB with MUF were studied during the first 12 hours after arrival in the intensive care unit (ICU). The central temperature was maintained at 36.8-37.1 degrees C using external cooling or warming. VO2 was continuously measured using respiratory mass spectrometry. Arterial blood samples for the tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) were taken and DO2 was calculated using the Fick principle on arrival at the ICU, and 2, 4, 8, and 12 hours postoperatively. Cytokines were additionally measured after induction of anesthesia and at the end of MUF. RESULTS: VO2 significantly decreased by 18.8% during the study period. DO2 was depressed throughout this period and reached a nadir at 8 hours (357.1 +/- 136.2 ml x min(-1) x m(-2)). The decrease in cytokines was accompanied with the decrease in VO2 despite varied relationships between the levels of each of the cytokines and VO2 measurements. CONCLUSIONS: Our data indicate an unusual continuous decrease in VO2 during the first 12 hours after CPB in infants. Control of body temperature to maintain euthermia in addition to the use of MUF may be beneficial to the balance between VO2 and DO2 in the early postoperative period.

CSF and serum immune parameters in Sydenham's chorea: evidence of an autoimmune syndrome?

Previous investigations have suggested that Sydenham's chorea (SC) may be an autoantibody mediated disorder. We examined this autoimmune hypothesis by measuring Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-10) cytokines, oligoclonal bands (OCB) and anti-basal ganglia antibodies (ABGA). CSF IL-4 was elevated in 31% of acute SC and 50% of persistent SC. CSF IL-10 was also elevated in 31% of acute SC but 0% of persistent SC. CSF IFN-gamma was undetectable in all patients. Serums IL-4, IL-10 and IL-12 were elevated in acute compared to persistent SC. OCB were found in 46% of acute SC, ABGA were in 93% of acute SC and 50% of persistent SC was of IgG(1) and IgG(3) subclass. These findings support an autoantibody pathogenesis.

Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care.

OBJECTIVE: Sepsis and systemic inflammatory response syndrome (SIRS) are major causes of morbidity and mortality after cardiopulmonary bypass. Attempts to suppress proinflammatory mediators have failed to improve outcomes in sepsis or in patients undergoing cardiopulmonary bypass. Recent work in adult patients has suggested that the balance between pro- and anti-inflammatory mediators is more important than the level of proinflammatory response alone. This balance may be reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with low concentrations indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the relationship between monocyte HLA-DR expression and the subsequent development of sepsis/SIRS in children undergoing cardiopulmonary bypass. DESIGN: A prospective, observational, clinical study. SETTING: A tertiary pediatric cardiac center. PATIENTS: Eighty-two infants and children undergoing elective cardiac surgery between March and December 1999. MEASUREMENTS AND MAIN RESULTS: Monocyte HLA-DR expression was assessed before and after surgery and was found to be related to the length of hospital stay and the development of complications including sepsis/SIRS. The inflammatory insult of cardiopulmonary bypass decreased monocyte HLA-DR expression in all children. Lowest concentrations were seen within 72 hrs of surgery and were significantly lower in cases that subsequently required prolonged intensive care support (p <.0001, Mann-Whitney). HLA-DR expression on <60% of circulating monocytes was associated with a greatly increased risk of later (minimum 4 days) development of sepsis/SIRS (odds ratio, 12.9; 95% confidence interval, 3.4-47.5). Low HLA-DR was an independent predictor for the development of sepsis/SIRS after correction for age, bypass time, complexity of surgery, Paediatric Index of Mortality, and surgeon on multiple logistic regression analysis. CONCLUSIONS: Patients with decreased HLA-DR in the early postoperative period represent a subpopulation at greatly increased risk of later sepsis/SIRS. Such patients may benefit from strategies aimed to reduce this risk.