Hydrogen Sulfide in Exhaled Gases From Ventilated Septic Neonates and Children: A Preliminary Report.

OBJECTIVES: There is increasing interest in hydrogen sulfide as a marker of pathologic conditions or predictors of outcome. We speculate that as hydrogen sulfide is a diffusible molecule, if there is an increase in plasma hydrogen sulfide in sepsis, it may accumulate in the alveolar space and be detected in exhaled gas. We wished to determine whether we could detect hydrogen sulfide in exhaled gases of ventilated children and neonates and if the levels changed in sepsis. DESIGN: Prospective, observational study. SETTING: The study was conducted across three intensive care units, pediatric, neonatal and cardiac in a large tertiary children's hospital. PATIENTS: We studied ventilated children and neonates with sepsis, defined by having two or more systemic inflammatory response syndrome criteria and one organ failure or suspected infection. A control group of ventilated non-septic patients was also included. INTERVENTION: A portable gas chromatograph (OralChroma; Envin Scientific, Chester, United Kingdom) was used to measure H2S in parts per billion. MEASUREMENTS AND MAIN RESULTS: A 1-2 mL sample of expired gas was taken from the endotracheal tube and analyzed. A repeat sample was taken after 30 minutes and a further single daily sample up to a maximum of 5 days or until the patient was extubated. WBC and C-reactive protein were measured around the time of gas sampling. Each group contained 20 subjects. Levels of H2S were significantly higher in septic patients (Mann Whitney U-test; p < 0.0001) and trended to control levels over five days. C- reactive protein levels were also significantly raised (p < 0.001) and mirrored the decrease in H2S levels. CONCLUSION: Hydrogen sulfide can be detected in expired pulmonary gases in very low concentrations of parts per billion. Significantly higher levels are seen in septic patients compared with controls. The pattern of response was similar to that of C-reactive protein.

Selective decontamination of the digestive tract in critically ill children: systematic review and meta-analysis.

OBJECTIVE: We examined the impact of selective decontamination of the digestive tract on morbidity and mortality in critically ill children. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and previous meta-analyses. STUDY SELECTION: We included all randomized controlled trials comparing administration of enteral antimicrobials in selective decontamination of the digestive tract with or without a parenteral component with placebo or standard therapy used in the controls. DATA EXTRACTION: The primary end point was the number of acquired pneumonias. Secondary end points were number of infections and overall mortality. Odds ratios were pooled with the random effect model. DATA SYNTHESIS: Four randomized controlled trials including 335 patients were identified. Pneumonia was diagnosed in five of 170 patients (2.9%) for selective decontamination of the digestive tract and 16 of 165 patients (9.7%) for controls (odds ratio 0.31; 95% confidence interval 0.11-0.87; p = .027). Overall mortality for selective decontamination of the digestive tract was 13 of 170 (7.6%) vs. control, 11 of 165 (6.7%) (odds ratio 1.18; 95% confidence interval 0.50-2.76; p = .70). In three studies (n = 109), infection occurred in ten of 54 (18.5%) patients on selective decontamination of the digestive tract and 24 of 55 (43.6%) in the controls (odds ratio 0.34; 95% confidence interval 0.05-2.18; p = .25). CONCLUSIONS: In the four available pediatric randomized controlled trials, selective decontamination of the digestive tract significantly reduced the number of children who developed pneumonia.

Should religious beliefs be allowed to stonewall a secular approach to withdrawing and withholding treatment in children?

Religion is an important element of end-of-life care on the paediatric intensive care unit with religious belief providing support for many families and for some staff. However, religious claims used by families to challenge cessation of aggressive therapies considered futile and burdensome by a wide range of medical and lay people can cause considerable problems and be very difficult to resolve. While it is vital to support families in such difficult times, we are increasingly concerned that deeply held belief in religion can lead to children being potentially subjected to burdensome care in expectation of 'miraculous' intervention. We reviewed cases involving end-of-life decisions over a 3-year period. In 186 of 203 cases in which withdrawal or limitation of invasive therapy was recommended, agreement was achieved. However, in the 17 remaining cases extended discussions with medical teams and local support mechanisms did not lead to resolution. Of these cases, 11 (65%) involved explicit religious claims that intensive care should not be stopped due to expectation of divine intervention and complete cure together with conviction that overly pessimistic medical predictions were wrong. The distribution of the religions included Protestant, Muslim, Jewish and Roman Catholic groups. Five of the 11 cases were resolved after meeting religious community leaders; one child had intensive care withdrawn following a High Court order, and in the remaining five, all Christian, no resolution was possible due to expressed expectations that a 'miracle' would happen.

Selective digestive tract decontamination in critically ill patients.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) has been proposed to prevent endogenous and exogenous infections and to reduce mortality in critically ill patients. Although the efficacy of SDD has been confirmed by randomized controlled trials (RCTs) and systematic reviews, SDD has been the subject of intense controversy, based mainly on an insufficient evidence of efficacy and on concerns about resistance. AREAS COVERED: This article reviews the philosophy, the current evidence on the efficacy of SDD and the issue of emergence of resistance. All SDD RCTs were searched using Embase and Medline, with no restriction of language, gender or age. Personal archives were also explored, including abstracts from major scientific meetings; references in papers and published meta-analyses on SDD were crosschecked. Up-to-date evidence of the impact of SDD on carriage, infections and mortality is presented, and the efficacy of SDD in selected patient groups was investigated, along with the problem of the emergence of resistance. EXPERT OPINION: SDD significantly reduces the number of infections of the lower respiratory tract and bloodstream, multiple organ failure and mortality. It also controls resistance, particularly when the full protocol of parenteral and enteral antimicrobials is used.

Germline gain-of-function mutations of ALK disrupt central nervous system development.

Neuroblastoma (NB) is a frequent embryonal tumor of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harboring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes.

Does triage to critical care during a pandemic necessarily result in more survivors?

OBJECTIVE: The 2009 H1N1 pandemic reinforced the need for a planned response to increased demand for critical care. Triage protocols have been proposed incorporating the exclusion of specified subgroups of patients from critical care. There have been no studies that explore the theoretical underpinning of triage at referral, and it is not clear under what circumstances triage would confer the intended benefits. We sought to explore the mechanisms whereby triage could lead to fewer deaths across a critical care population in the context of a pandemic. DESIGN: We constructed a mathematical model based on queuing theory to compare the estimated short-term survival achieved by using a critical care service with and without triage at referral. Illustrative scenarios concerning a hypothetical critical care population were constructed to explore the roles of length of stay and critical care survival in determining the impact of triage and to identify "tipping points" of demand at which triage would result in more survivors. SETTING: Not applicable as this was a data-free mathematical modeling exercise. MAIN RESULTS: We identified circumstances in which triage would be expected to result in more survivors and circumstances in which it would not. In some scenarios, excluding patient groups solely on the basis of anticipated length of stay could be effective due to a more efficient use of critical care bed days. CONCLUSIONS: The impact of triage is dependent on the level of demand and on the scale of achievable differences between included and excluded groups in terms of anticipated length of stay and critical care survival. It cannot be assumed that triage can or will result in fewer deaths. It should be remembered that there are considerations other than population-level short-term survival when determining the objectives of triage and its ethical implementation.