Myocardial dysfunction in meningococcal septic shock.

PURPOSE OF REVIEW: The underlying pathophysiology of sepsis has long been disputed. Systemic vasodilatation is important in the development of shock and, in septic critically ill adults who have been volume resuscitated, the systemic pressure is often low and the cardiac output high. In septic children however, and especially in those with meningococcal septic shock, poor cardiac output as a consequence of depressed myocardial function seems to be important, often being the cause of death in these patients. There is much evidence for disturbance of myocardial performance, yet despite the literature, there is still no consensus on how best to manage this complication of meningococcal disease. RECENT FINDINGS: Many mediators have been proposed as the cause of the reduced myocardial performance, most recently interleukin-6 has emerged as a possible candidate involved in the pathophysiology of the myocardial dysfunction. Cardiac troponin I has been shown to be a marker of myocardial injury and may be used to monitor left ventricular function. Newer treatments emerging to manage the dysfunction include reports of success with phosphodiesterase inhibitors. SUMMARY: Accepting that myocardial dysfunction may be an important cause of the shock state in overwhelming meningococcal disease, the approach to management may need to be tailored appropriately. Although presently there is no targeted treatment, it may be that therapy focused on inhibiting or antagonising interleukin-6 will be helpful in the future. Regardless of the importance of myocardial depression, fluid resuscitation remains a cornerstone in the management of severe meningococcal disease.

Infection in prolonged pediatric critical illness: A prospective four-year study based on knowledge of the carrier state.

OBJECTIVE: This study was performed to determine the rate, timing, and incidence density of infections occurring in a subgroup of patients requiring a prolonged stay in a regional pediatric intensive care unit. DESIGN: Prospective, observational cohort study over 4 yrs. SETTING: This epidemiologic descriptive study was performed in a university hospital 20-bed pediatric intensive care unit. PATIENTS: Critically ill children requiring > or = 4 days of intensive care. INTERVENTIONS: The microbial carrier state of the children was monitored by surveillance cultures of throat and rectum, obtained on admission and twice weekly afterward. MEASUREMENTS AND MAIN RESULTS: Data are presented on a total of 1,241 children, accounting for 1,443 admissions to the unit, corresponding to 18,203 patient days. The median pediatric index of mortality was 0.063 (interquartile range, 0.025-0.131), and the mortality rate in this subset of children was 9.6%. Five hundred twenty children had infections, an overall infection rate of 41.9% (520 of 1,241); 14.5% (180 of 1,241) of the children developed viral and 33.0% (410 of 1,241) developed bacterial/yeast infections. The incidence of bloodstream infection was 20.1 and lower airway infection 9.1 episodes per 1,000 patient days. We found that 13.3% of the children were infected with a bacterial/yeast microorganism acquired on the pediatric intensive care unit; 4.0% (50 of 1,241) of children developed infections due to resistant microorganisms. There were a total of 803 bacterial/yeast infectious episodes, of which 59.8% (480) were due to microorganisms imported in the patients' admission flora. These primary endogenous infections predominantly occurred within the first week of pediatric intensive care unit stay. The other 38.9% (312) were caused by microorganisms acquired on the pediatric intensive care unit. A total of 38 viral infections (24.5%) were acquired during pediatric intensive care unit stay. CONCLUSIONS: Two thirds of all infections diagnosed in children with prolonged illness on pediatric intensive care unit were due to microorganisms present in the patients' admission flora.

Severe meningococcal disease in childhood.

Meningococcal disease remains an important cause of illness in the UK (Commun Dis Rep CDR Suppl 1999; 9: S5), and is the commonest infective cause of death in children outwith the neonatal period. Although most common in children, adults are also affected. Meningococcal vaccines offer long-term protection only against Group C disease, which causes less than half of invasive meningococcal disease (Commun Dis Rep CDR Wkly 1998; 8: 2) in the UK.

Oropharyngeal carriage and lower airway colonisation/infection in 45 tracheotomised children.

BACKGROUND: A study was undertaken to determine the oropharyngeal carrier state of potentially pathogenic microorganisms (PPM) and the magnitude of colonisation and infection rates of the lower airways with these PPM in children requiring long term ventilation first transtracheally and afterwards via a tracheotomy. METHODS: A 5 year, prospective, observational cohort study was undertaken in 45 children (33 boys) of median age 6.4 months (range 0-180) over a 5 year period at the Royal Liverpool Children's NHS Trust of Alder Hey, a university affiliated tertiary referral centre. The children were first admitted to the 20-bed paediatric intensive care unit (PICU) and, following placement of a tracheotomy, they were transferred to a four bedded respiratory ward. The two main indications were neurological disorders and airway obstruction. All children were ventilated transtracheally for a median period of 12 days (range 0-103) and, after placement of the tracheotomy, for a similar period of 12 days (range 1-281). Surveillance cultures of the oropharynx were taken on admission to the PICU and on the day of placement of the tracheotomy. Throat swabs were taken twice weekly during ventilation, both transtracheal and via the tracheotomy. Tracheal aspirates were taken once weekly and when clinically indicated (in cases where the lower airway secretions were turbid). RESULTS: Twenty five patients (55%) had abnormal flora, mainly aerobic Gram negative bacilli (AGNB), particularly Pseudomonas aeruginosa, while the community PPM Staphylococcus aureus was present in the oropharynx of 37% (17/45) of the study population. The lower airways were sterile in six children; the other 39 patients (87%) had a total of 82 episodes of colonisation. "Community" PPM significantly increased once the patients received a tracheotomy, independent of the number of patients enrolled, episodes of colonisation/infection, and the number of colonised/infected patients. "Hospital" PPM significantly decreased after tracheotomy only when episodes were compared. CONCLUSIONS: While P aeruginosa present in the admission flora caused primary endogenous colonisation/infection during mechanical ventilation on the PICU, S aureus not carried in the throat was responsible for the exogenous colonisation/infection once the patients had a tracheotomy. This is in sharp contrast to adult studies where exogenous infections are invariably caused by AGNB. This discrepancy may be explained by chronic underlying conditions such as diabetes, alcoholism, and chronic obstructive pulmonary disease which promote AGNB, whereas the children were recovering following tracheotomy.

Hypocalcaemia in severe meningococcal infections.

AIM: To determine the incidence of hypocalcaemia in critically ill children with meningococcal disease. METHODS: In a prospective cohort study, 70 of 80 patients admitted consecutively with a clinical diagnosis of meningococcal disease to intensive care had measurements of total and ionised calcium on admission. Parathormone and calcitonin were measured in a proportion of the children. RESULTS: Total and ionised calcium concentrations were low in 70% of the children. There was a weak relation of calcium concentration to the volume of blood derived colloid which had been given, but a good relation to disease severity, where sicker children had lower calcium concentrations. Although the parathormone concentration was higher in children with lower calcium concentrations, some children had low ionised calcium concentrations, without an increase of parathormone concentration. Serum calcitonin concentration was not related to calcium concentrations. CONCLUSION: Hypocalcaemia is common in meningococcal disease.

Nitric oxide production in meningococcal disease is directly related to disease severity.

OBJECTIVES: Meningococcal disease is a homogeneous and well-characterized form of sepsis. Cardiovascular collapse is prominent in severe meningococcal disease. Nitric oxide overproduction may be a mediator of cardiovascular collapse. We relate the level of nitric oxide metabolites, nitrates and nitrites, to disease severity in meningococcal disease. DESIGN: Prospective, nonrandomized study. SETTING: Tertiary referral pediatric intensive care unit. PATIENTS: Children admitted with a clinical diagnosis of meningococcal disease. INTERVENTIONS: Blood was sampled from children with meningococcal disease. Disease severity was scored using the Glasgow meningococcal septicemia prognostic score and pediatric risk of mortality score. Plasma nitrates and nitrites were measured in stored plasma using the Greiss reaction after conversion of all the nitrate to nitrite. MEASUREMENTS AND MAIN RESULTS: Twenty-two children were studied. In 19, the final diagnosis was meningococcal disease. Of the 19 children with meningococcal disease, 7 had a Glasgow meningococcal septicemia prognostic score of <8 (mild) and 12 had a Glasgow meningococcal septicemia prognostic score > or = 8 (severe). Three children died, all of these being in the severely affected group. Higher levels of nitrates and nitrites were seen in the more severely affected children (median admission nitrates and nitrites, 27.5 vs. 59.7 nmol/mL; p = 0.063; median peak nitrates and nitrites, 49.9 vs. 114 nmol/mL; p = .01) or those with an increased predicted mortality using pediatric risk of mortality (Spearman's p 0.742; p = .0003). CONCLUSIONS: Higher levels of nitrates and nitrites are seen in sicker children with meningococcal disease.

Endothelial cell adhesion molecules in meningococcal disease.

BACKGROUND: Endothelial damage is important in meningococcal disease. Cell adhesion molecules, including P selectin, E selectin, and intercellular cell adhesion molecule 1 (ICAM-1), are expressed by activated endothelium and then subsequently shed. METHODS: ICAM-1, P selectin, and E selectin were measured on admission to hospital in children with meningococcal infections. RESULTS: Concentrations of shed cell adhesion molecules are reported for 78 children. Eleven did not have meningococcal disease. Of the 67 with meningococcal disease, 40 had mild disease (Glasgow meningococcal septicaemia prognostic score (GMSPS) < 8) and 27 had severe disease (GMSPS > or = 8). E selectin and ICAM-1 values were higher in those with meningococcal disease. The E selectin values in those with severe disease were higher than in those with mild disease. P selectin concentrations were not altered in meningococcal disease, but those who died had lower concentrations. CONCLUSIONS: Endothelial activation in meningococcal disease is reflected by shed ICAM-1 and E selectin concentrations.