Cause Of Critical Illness Research Articles

Impact of Rapid Leukodepletion on the Outcome of Severe Clinical Pertussis in Young Infants

Bordetella pertussis is a common, underrecognized, and vaccine-preventable cause of critical illness with a high mortality in infants worldwide. Patients with severe cases present with extreme leukocytosis and develop refractory hypoxemia and pulmonary hypertension that is unresponsive to maximal intensive care. This may reflect a hyperviscosity syndrome from the raised white blood cell (WBC) count. Case reports suggest improved outcomes with exchange transfusion to reduce the WBC count. Our objective was to quantify possible benefits of aggressive leukodepletion. We, as a regional PICU and extracorporeal membrane oxygenation referral center, adopted a strategy of aggressive leukodepletion in January 2005. The impact of this strategy on crude and case mix-adjusted survival of all infants who were critically ill with B pertussis were compared with control subjects from January 2001 to December 2004 and Extracorporeal Life Support Organisation registry data. Nineteen infants (7 [37%] boys) received intensive care for B pertussis from 2001 to 2009. Admission WBC counts were equivalent in 2 time periods: 2001-2004 (mean: 52,000/μL) and 2005-2009 (mean: 75,000/μL). In 2001-2004, 5 (55%) of 9 patients survived the ICU. Between 2005 and 2009, 9 (90%) of 10 patients survived. When case-mix adjustment for age, WBC count, and extracorporeal membrane oxygenation referral were considered, the 2001-2004 predicted survival (4.4 [49%] of 9.0) was equivalent to the observed mortality (4.0 [44%] of 9.0). Between 2005 and 2009, observed mortality (1.0 [10%] of 10.0) was significantly better than predicted (4.7 [47%] of 10.0). Leukodepletion should be considered in critically ill infants with B pertussis and leukocytosis.

Impact of pneumococcal vaccination on the incidence of invasive pneumococcal disease in UK PICUs

Aims To determine the impact of pneumococcal vaccination (introduced in 2006) on the incidence of invasive pneumococcal disease (IPD) seen in UK paediatric intensive care units (PICUs). Methods Retrospective review of cases of IPD seen in UK PICUs from 2005 to 2009, identified by primary diagnosis reported to PICANET (the national PICU Audit Network). Results Total numbers of cases of IPD have not changed significantly since vaccination was introduced, with 64 cases in a total of 14 056 PICU admissions in 2005, 72/14 328 in 2006, 54/15 579 in 2007 and 64/16 089 in 2008 (χ2 p=0.18). The presentation has also remained unchanged over this period, with around 60% of cases presenting as meningitis±sepsis, 20% cases presenting as sepsis±pneumonia and 20% presenting as isolated pneumonia. Conclusions The seven valent pneumococcal vaccine (PCV7), which covers serotypes 4, 6B, 9V, 14, 18C, 19F and 23F, was introduced in September 2006. The authors9 findings suggest that despite good uptake of this vaccine, there has been no decrease in the number of cases of IPD admitted to UK PICUs. These findings are consistent with data from the Health Protection Agency,1 which demonstrate that although vaccine serotypes have been almost eradicated since vaccination, there has been no change in the total number of cases of IPD. This is due to serotype replacement with non-vaccine serotypes. IPD is still an important cause of critical illness in children despite the pneumococcal vaccination programme.

β2-Adrenergic Receptor Polymorphisms Affect Response to Treatment in Children With Severe Asthma Exacerbations

beta(2)-adrenergic receptor (AR) agonists are the mainstay of treatment for severe asthma exacerbations, one of the most common causes of critical illness in children. Genotypic differences in the beta(2)-AR gene, particularly at amino acid positions 16 and 27, have been shown to affect the response to beta(2)-AR agonist therapy. Our hypothesis is that genotypic differences contribute to patient response to beta(2)-AR agonist treatment during severe asthma exacerbations in children. Children admitted to the hospital ICU for a severe asthma exacerbation between 2002 and 2005 were located, and genetic samples were obtained from saliva. Children hospitalized during this period were treated with a protocol that titrated beta(2)-AR therapy (first nebulized, then IV) according to a validated clinical asthma score. Thirty-seven children hospitalized during the study period were enrolled into the study. At amino acid position 16 in the beta(2)-AR gene, 13 children were homozygous for the glycine (Gly) allele (Gly/Gly), 8 were homozygous for the arginine (Arg) allele (Arg/Arg), and 16 were heterozygous (Arg/Gly). Despite similar clinical asthma scores on hospital admission, the children with the Gly/Gly genotype had significantly shorter hospital ICU length of stay and duration of continuously nebulized albuterol therapy and were significantly less likely to require IV beta(2)-AR therapy than those with Arg/Arg or Arg/Gly genotypes. No association existed among polymorphisms at amino acid position 27 and response to beta(2)-AR therapy. In this cohort of children with severe asthma exacerbations, children whose genotypes were homozygous for Gly at amino acid position 16 of the beta(2)-AR gene had a more rapid response to beta(2)-AR agonist treatment. The beta(2)-AR genotype appears to influence the response to therapy in this population.

Beta2-Adrenergic Receptor Polymorphisms Influence Response To Treatment In African-American Children With Near Fatal Asthma

RATIONALE: Near fatal asthma exacerbations are a common cause of critical illness in children and β2-adrenergic receptor (β2-AR) agonists are the foundation of treatment for these exacerbations. Genotypic differences in the β2-AR, particularly at amino acid positions 16 and 27, have been linked to response to β2-AR agonist therapy. African-American children with asthma are a population particularly susceptible to near fatal exacerbations. Our hypothesis was that genotypic differences in the β2-AR are associated with treatment response in African-American children with near fatal asthma exacerbations.

Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children

Asthma exacerbations are a common cause of critical illness in children. To determine factors associated with exacerbations in children with persistent asthma. Regression modeling was used to identify historical, phenotypic, treatment, and time-dependent factors associated with the occurrence of exacerbations, defined by need for oral corticosteroids or emergency or hospital care in the 48-week Pediatric Asthma Controller Trial study. Children age 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive either fluticasone propionate 100 microg twice daily (FP monotherapy), combination fluticasone 100 microg AM and salmeterol twice daily, or montelukast 5 mg once daily. Of the 285 participants randomized, 48% had 231 exacerbations. Using a multivariate analysis, which included numerous demographic, pulmonary, and inflammatory parameters, only a history of an asthma exacerbation requiring a systemic corticosteroid in the past year (odds ratio [OR], 2.10; P < .001) was associated with a subsequent exacerbation during the trial. During the trial, treatment with montelukast versus FP monotherapy (OR, 2.00; P = .005), season (spring, fall, or winter vs summer; P < or = .001), and average seasonal 5% reduction in AM peak expiratory flow (OR, 1.21; P = .01) were each associated with exacerbations. Changes in worsening of symptoms, beta-agonist use, and low peak expiratory flow track together before an exacerbation, but have poor positive predictive value of exacerbation. Children with mild-to-moderate persistent asthma with previous exacerbations are more likely to have a repeat exacerbation despite controller treatment. Inhaled corticosteroids are superior to montelukast at modifying the exacerbation risk. Available physiologic measures and biomarkers and diary card tracking are not reliable predictors of asthma exacerbations.

Endocrine Problems in Critically Ill Children

The endocrine system maintains a delicate balance of physiologic processes including growth and sexual maturation, energy production and utilization, fluid and electrolyte balance, and circulatory function. Although endocrine regulation of growth and sexual maturation is a significant issue in general pediatrics, disorders of energy production and utilization, fluid and electrolyte balance, and circulatory function are the endocrine causes of critical illness in children. Care of the child with critical endocrine disease requires an understanding of endocrine pathophysiology, keen history taking and assessment skills, and knowledge of the pharmacology of synthetic hormone treatment. This article will provide an overview of common endocrine problems encountered in critically ill children with attention to endocrine problems that are unique to pediatrics and that may pose diagnostic and treatment dilemmas for healthcare providers without experience or education in pediatric critical care.

Future directions in the management of tertiary peritonitis.

Tertiary peritonitis represents the current limit of the surgical approach to severe intra-abdominal infection. Specific pathogens are cultured from the peritoneal cavity, although these appear to be more a symptom than the cause of critical illness. Therefore, the role of antimicrobial agents is debatable and currently reserved for infection with systemic toxicity and secondary sepsis. Short, narrow-spectrum courses are recommended with attention being paid to the individual pharmacokinetic profile of the drugs used. Lack of peritoneal inflammation with systemic anergy suggests immune paralysis. This anti-inflammatory state can have endogenous (primary massive insult, gut-associated sepsis, immune deficiency) or exogenous (repeated surgery, blood transfusions, immune suppressive drugs, malnutrition) origins. By development of immune monitoring assays, selective use of immune-modulating therapies could be beneficial. Pilot trials with immune stimulation show promising results. Finally, the endocrine stress response is essential for metabolic, cardiovascular and immunological homeostasis. Derangement of this response is likely in patients with prolonged stress such as tertiary peritonitis. Monitoring of endocrine function with substitution of cortisol when necessary could be beneficial in patients with tertiary peritonitis. The role of anabolic steroids like growth hormone is yet unclear.

Acquired subglottic stenosis caused by methicillin resistantStaphylococcus aureus that produce epidermal cell differentiation inhibitor

Local infection of the trachea in intubated neonates is one of the main risk factors for development of acquired subglottic stenosis, although its role in the pathogenesis is unclear. Methicillin...