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 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.

Effect of patient- and team-related factors on stabilization time during pediatric intensive care transport.

OBJECTIVES: To examine the effects of patient- and transport-related factors on the time spent at the referring hospital by an intensive care retrieval team to stabilize critically ill children and to study the relationship between stabilization time and patient outcome. DESIGN: : Analysis of prospectively collected data during pediatric intensive care transport. SETTING: A dedicated regional pediatric intensive care retrieval service performing interhospital transports in England. PATIENTS: Critically ill children transported to intensive care units over a 2-yr period between April 1, 2006 and March 31, 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Factors related to the patient (age group, diagnostic category, and severity of illness) and transport (time of referral, team response time, and number of major and minor interventions performed) were analyzed for their effect on stabilization time in univariate and multivariate analyses. The relationship between stabilization time and patient outcome in the first 24 hrs post intensive care unit admission was also studied. Patient acuity was high in the transported population (84% invasively ventilated; 28% on vasoactive agents). Predicted mortality risk (Pediatric Index of Mortality 2 score), diagnostic category, team response time, and number of major interventions performed had an independent effect on stabilization time, whereas the length of stabilization itself did not influence early mortality on the intensive care unit. Each minor intervention prolonged the stabilization time by an average of 10 mins. CONCLUSIONS: Stabilization time during intensive care transport is influenced by a number of patient- and transport-related factors, and cannot be used in isolation as an indicator of team efficiency. Time spent undertaking intensive care interventions early in the course of patient illness at the referring hospital does not worsen patient outcome, suggesting that the "scoop and run" model can be safely abandoned in interhospital transport.

A pilot study of neonatal and pediatric esophageal pulse oximetry.

BACKGROUND: In this pilot study we explored the suitability of the esophagus as a new measuring site for blood oxygen saturation (Spo(2)) in neonates. METHODS: A new miniaturized esophageal pulse oximeter has been developed. Five patients (one child and four neonates) were studied. RESULTS: Spo(2) values were obtained in the esophagus of all patients. A Bland and Altman plot of the difference between Spo(2) values from the esophageal pulse oximeter and a commercial toe pulse oximeter against their mean showed that the bias and the limits of agreement between the two pulse oximeters were +0.3% and +1.7% to -1.0%, respectively. CONCLUSIONS: This study suggests that the esophagus can be used as an alternative site for monitoring blood oxygen saturation in children and neonates.

Effects of blood sample volume on hematocrit in critically ill children and neonates.

BACKGROUND: There are no studies correlating the volume of blood taken from children and hematocrit (Hct) stability, relating those changes to duration of stay, severity of illness or weight. Earlier studies in neonates suggest that repeated sampling results in a drop in Hct. AIM: To characterize the changes in Hct in children of all ages admitted to intensive care over a 5-day period following routine blood volume sampling. METHODS: We undertook an open prospective observational study. Eligible children were recruited sequentially and data recorded for 5 days following admission. The bedside nurse recorded the daily volume of blood samples taken and transfusions given. Daily Hct was noted from the routine full blood count. The relationship between changes in Hct and blood sample volume and transfusion requirement was studied. RESULTS: There were no differences in mean Hct on admission at end of the study (P = 0.69, n = 30) nor in the median blood volume sampled between transfused and nontransfused groups (7.5 ml.kg(-1) vs 7.9 ml.kg(-1), P = 0.88). The largest blood sample volumes were taken on admission and from the smallest patients. CONCLUSION: We have quantitated the change in Hct and size of blood volume taken for routine laboratory studies. We suggest that children can tolerate 0.25 ml.kg(-1).day(-1) blood sampling without a fall in Hct and sampling can be tailored to the individual child according to the admission Hct.

Asymmetric dimethyl arginine and symmetric dimethyl arginine levels in infants with persistent pulmonary hypertension of the newborn.

OBJECTIVE: We investigated whether infants with persistent pulmonary hypertension had elevated levels of asymmetric dimethyl arginine, an endogenous inhibitor of nitric oxide synthase, and symmetric dimethyl arginine, a regioisomer. DESIGN: Prospective observational cohort study. SETTING: A 10-bed neonatal intensive care unit in a tertiary referral center. PATIENTS: Forty five infants >34 wks gestation and <2 wks old admitted to our intensive care unit. INTERVENTIONS: Samples of urine on days 1, 3, and 5 were analyzed by high-performance liquid chromatography to determine asymmetric dimethyl arginine and symmetric dimethyl arginine levels. The clinical progression and treatment of the infants were noted. MEASUREMENTS AND MAIN RESULTS: Twenty-nine infants had a clinical diagnosis of persistent pulmonary hypertension confirmed on echocardiography, and there were 16 control infants. Median asymmetric dimethyl arginine levels on day 1 were significantly higher in the persistent pulmonary hypertension group (n = 29), 14.8 (10.3-21.7) mmol.mmol creatinine(-1).L(-1), compared with controls (n = 16), 3.6 (1.4-5.2) mmol.mmol creatinine(-1).L(-1) (p < .001). Asymmetric dimethyl arginine levels decreased to control levels by day 5 (p = .33). Symmetric dimethyl arginine levels were significantly higher than controls on day 1, 31.0 (21.7-65.9) vs. 14.7 (4.1-20.2) mmol.mmol creatinine(-1).L(-1) (p = .001) and day 3, 34.7(20.3-42.5) mmol.mmol creatinine(-1).L(-1) (p = .0001) and by day 5 had decreased significantly (p = .007) back to 16.7 (12.3-23.8) mmol.mmol creatinine(-1).L(-1), which was not significantly different than the control group values. CONCLUSIONS: These results support the hypothesis that asymmetric dimethyl arginine and symmetric dimethyl arginine levels are elevated in patients with persistent pulmonary hypertension. Thus, endogenous inhibition of nitric oxide synthase by asymmetric dimethyl arginine may be responsible for the development of persistent pulmonary hypertension, suggesting novel therapeutic options in persistent pulmonary hypertension.

Terlipressin bolus induces systemic vasoconstriction in septic shock.

OBJECTIVE: To report the use of a synthetic, long-acting, vasopressin analog, terlipressin, as an effective vasoconstrictor in septic shock. DESIGN: Case report. SETTING: A 22-bed pediatric intensive care unit in a tertiary referral center. PATIENT: An 11-yr-old male with multiple-organism Gram-negative septic shock with high normal cardiac output as assessed by pulse contour analysis and low systemic vascular resistance despite norepinephrine infusion. INTERVENTION: Two peripherally administered doses of terlipressin (0.5 mg). MEASUREMENTS AND MAIN RESULTS: Each dose of terlipressin was associated with a rapid increase in systemic vascular resistance, despite weaning and discontinuation of norepinephrine infusion from 0.15 microg.kg(-1).min(-1) lasting approximately 6 hrs. CONCLUSION: Terlipressin may be useful for sepsis-induced vasodilation.

Comparison of the bispectral index monitor with the Comfort score in assessing level of sedation of critically ill children.

OBJECTIVE: To compare the value of bispectral index as a monitor of sedation in critically ill children with a validated sedation scoring system. DESIGN: Prospective convenience sample. SETTING: Paediatric intensive care unit in a tertiary paediatric centre. PATIENTS AND PARTICIPANTS: Forty-three critically ill children receiving sedation and mechanical ventilation. MEASUREMENTS AND RESULTS: Simultaneous recording of bispectral index (BIS) and assessment of depth of sedation using the Comfort score were performed at regular intervals. To determine if BIS could detect episodes of arousal, times of endotracheal suctioning and the corresponding BIS score were recorded. There was an overall moderate correlation between BIS scores and Comfort scores ( r=0.50, r(2)=0.25, p<0.0001). Children who had a neurological reason for their current admission ( n=25) showed a weaker correlation ( r=0.26, r(2)=0.06, p<0.007) than those ( n=15) with normal neurology ( r=0.51, r(2)=0.26, p<0.0001). There were no significant differences in the rise in BIS following endotracheal suctioning among any of the predefined depths of sedation. There was a correlation of r=0.84 ( r(2)=0.71) (SE of slope 0.49, CI(95) 1.79-3.88) for mean BIS values for each individual Comfort score from 8-23. Using Spearman's rank correlation of Comfort versus mean BIS, the correlation coefficient was r=0.92. CONCLUSIONS: Bispectral index scores correlate with Comfort scores to a moderate degree. BIS is able to discriminate between light and deep levels of sedation, but not between deep and very deep levels of sedation. The BIS monitor may provide a useful method for assessing sedation in critically ill children, especially those receiving neuromuscular blockers.

All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth.

OBJECTIVE: The objective was to compare evidence of the effectiveness, costs and safety of the traditional parenteral antibiotic-only approach against that gathered from 53 randomised trials involving more than 8,500 patients and six meta-analyses on selective decontamination of the digestive tract (SDD) to control infection on the intensive care unit (ICU). PHILOSOPHY: Traditionalists believe that all infections are due to breaches of hygiene except those established in the first 2 days, and that all micro-organisms can cause death. In contrast, newer insights show that transmission via the hands of carers are responsible only for infections occurring after one week, and that only a limited range of 15 potential pathogens contribute to mortality. INTERVENTIONS TO PREVENT ICU INFECTION: The traditional approach is based on hand disinfection aiming at the prevention of transmission of all micro-organisms, to control all infections that occur after 2 days on the ICU. The second feature is the restrictive use of systemic antibiotics, only in cases of microbiologically proven infection. In contrast, SDD aims to control the three types of infection: primary, secondary endogenous and exogenous due to 15 potential pathogens. The classical SDD tetralogy comprises four components: (i) a parenteral antibiotic, cefotaxime, administered for three days to prevent primary endogenous infections typically occurring "early"; (ii) the oropharyngeal and enteral antimicrobials, polymyxin E, tobramycin and amphotericin B administered in throat and gut throughout the treatment on the ICU to prevent secondary endogenous infections tending to develop "late"; (iii) a high standard of hygiene to control transmission of potential pathogens; and (iv) surveillance samples of throat and rectum to monitor the efficacy of the treatment. ENDPOINTS: (i) Infectious morbidity; (ii) mortality; (iii) antimicrobial resistance; and (iv) costs. RESULTS: Properly designed trials on hand disinfection have never demonstrated a reduction in either pneumonia and septicaemia, or mortality. Two randomised trials using restrictive antibiotic policies failed to show a survival benefit at 28 days. In both trials the proportion of resistant isolates obtained from the lower ways was >60% despite significantly less use of antibiotics in the test group. A formal cost effectiveness analysis of the traditional antibiotic policies has not been performed. On the other hand, two meta-analyses have shown that SDD reduces the odds ratio for lower airway infections to 0.35 (0.29-0.41) and mortality to 0.80 (0.69-0.93), with a 6% overall mortality reduction from 30% to 24%. No increase in the rate of super infections due to resistant bacteria could be demonstrated over a period of 20 years of clinical research. Four randomised trials found the cost per survivor to be substantially lower in patients receiving SDD than for those traditionally managed. CONCLUSIONS: The traditionalists still rely on level 5 evidence, i.e. expert opinion, with a grade E recommendation, whilst the proponents of SDD are able to cite level 1 evidence allowing a grade A recommendation in their attempts to control infection on the ICU. The main reason for SDD not being widely used is the primacy of opinion over evidence.