Albert P. Bos

Long-term psychological distress in parents of child survivors of severe meningococcal disease

Objective: To study psychological distress in parents of child survivors of Severe Meningococcal Disease (SMD) after discharge of their child from the Paediatric Intensive Care Unit (PICU). Methods: This study approached parents of child survivors of SMD treated on the PICU between 1993–2001. Five cross-sectional groups were created for mothers and fathers separately. The five groups differed from each other by the period after discharge they entered the project (ranging from 3 months to 7 years after discharge). For research purposes, mothers and fathers (n = 192) individually completed the Goldberg General Health Questionnaire-30 (GHQ), measuring their level of psychological distress. Statistics: Mean group scores were examined and a one-way-analysis of variance (ANOVA) performed to study differences between groups for mothers and fathers separately. In addition, percentages of parents with GHQ scores above cut-off were calculated and it was determined whether it differed from norm data. Results: Data reveal that both mothers and fathers experience high mean levels of psychological distress after discharge, showing no significant differences in group means over time. High percentages of parents experience psychological distress after discharge, if compared with the normal population. Conclusions: Parents of child survivors of SMD experience profound and prolonged psychological distress after discharge. Future interventions should focus on follow-up care for this population to help them re-adjust after this stressful event.

Ventilator-Induced Inflammatory Response in Lipopolysaccharide-Exposed Rat Lung Is Mediated by Angiotensin-Converting Enzyme

Angiotensin-converting enzyme (ACE) mediates the ventilator-induced inflammatory response in healthy lungs via angiotensin II (Ang II). A rat model was used to examine the role of ACE and Ang II in the inflammatory response during mechanical ventilation of preinjured (ie, lipopolysaccharide [LPS]-exposed) lungs. When indicated, rats were pretreated with the ACE inhibitor captopril and/or intratracheal administration of LPS. The animals were ventilated for 4 hours with moderate pressure amplitudes. Nonventilated animals served as controls. ACE activity and levels of Ang II and inflammatory mediators (interleukin-6, Cytokine-induced Neutrophil Chemoattractant (CINC)-3, interleukin-1beta, and interleukin-10) were determined in bronchoalveolar lavage fluid (BALF). The localization of ACE and Ang II type 1 receptor in lung tissue was determined by immunohistochemistry. The role of the Ang II pathway was assessed by using its receptor antagonist Losartan. Mechanical ventilation of LPS-exposed animals increased ACE activity and levels of inflammatory mediators in BALF compared with ventilated nonexposed and LPS-exposed nonventilated animals. Blocking ACE by captopril attenuated the lung inflammatory response. Furthermore, increased ACE activity in BALF was accompanied by increased levels of Ang II and enhanced expression of its receptor on alveolar cells. Blocking the Ang II receptor attenuated the inflammatory mediator response to a larger extent than by blocking ACE. In conclusion, during mechanical ventilation ACE, via Ang II, mediates the inflammatory response of both healthy and preinjured lungs.

Total parenteral nutrition associated cholestasis: A predisposing factor for sepsis in surgical neonates?

Of 496 neonates and infants less than 1 year of age admitted to the paediatric surgical intensive care unit (PSICU) over a 5 year period (1983–1987), 94 required total parenteral nutrition (TPN) for more than 14 consecutive days, generally due to congenital anomalies of the digestive tract. Cholestasis occurred in 15 of them and 12 of these patients developed sepsis. In contrast, of the 79 patients on TPN that remained free from cholestasis, only 23 developed sepsis. The mortality rate for the TPNAC-group was substantially higher than for the group without TPNAC. It is suggested that development of TPNAC might lead to impairment of non-specific cellular immunity in neonates.

Sinusitis: hidden source of sepsis in postoperative pediatric intensive care patients.

Paranasal sinusitis is reported as a complication of prolonged nasal intubation and the source of sepsis in adult intensive care patients. In surgical neonates with congenital malformations, prolonged intubation with a nasotracheal (NT) or NG tube is often necessary, but sinusitis with complicating sepsis is seldom reported. Sinus x-rays may confirm the diagnosis; in infancy, prolonged nasal intubation delays the pneumatization of the sinuses and the mastoids, resulting in additional diagnostic problems. In a 1-yr period, we saw three patients with multiple septic episodes in which the source of sepsis was undetectable. Despite the absence of clinical symptoms and radiologic evidence of sinusitis or mastoiditis, surgical drainage revealed pus and led to the disappearance of septic episodes and ear, nose, and throat problems. There is an association between prolonged NT and NG intubation, and sinusitis or mastoiditis as an unrecognized source of sepsis in young infants. Absence of radiologic evidence of sinusitis or mastoiditis causes pitfalls in diagnosis and is related to delayed pneumatization of the sinuses and the mastoid in prolonged nasal intubation in young infants.

GRANZYME A AND B-CLUSTER DEFICIENCY DELAYS ACUTE LUNG INJURY IN PNEUMOVIRUS-INFECTED MICE

Lower respiratory tract infection by the human pneumovirus respiratory syncytial virus is a frequent cause of acute lung injury in children. Severe pneumovirus disease in humans is associated with activation of the granzyme pathway by effector lymphocytes, which may promote pathology by exaggerating proapoptotic caspase activity and proinflammatory activity. The main goal of this study was to determine whether granzymes contribute to the development of acute lung injury in pneumovirus-infected mice. Granzyme-expressing mice and granzyme A- and B-cluster single- and double-knockout mice were inoculated with the rodent pneumovirus pneumonia virus of mice strain J3666, and were studied for markers of lung inflammation and injury. Expression of granzyme A and B is detected in effector lymphocytes in mouse lungs in response to pneumovirus infection. Mice deficient for granzyme A and the granzyme B cluster have unchanged virus titers in the lungs but show a significantly delayed clinical response to fatal pneumovirus infection, a feature that is associated with delayed neutrophil recruitment, diminished activation of caspase-3, and reduced lung permeability. We conclude that granzyme A- and B-cluster deficiency delays the acute progression of pneumovirus disease by reducing alveolar injury.

Carnitine deficiency in surgical neonates receiving total parenteral nutrition

Carnitine plays a key role in the oxidation of fatty acids. Most solutions for parenteral nutrition do not contain carnitine. Because endogenous carnitine synthesis is insufficient in newborns, they are prone to developing a carnitine deficiency when they are dependent on total parenteral nutrition (TPN). Stimulated by the clinical observation of manifest clinical symptoms of carnitine deficiency in one patient, a study of 13 consecutive neonates who received TPN for over 2 weeks was begun. Their plasma carnitine levels before and during carnitine supplementation were determined. All patients had a carnitine intake far below the recommended minimal need of 11 mumol/kg per day. Although only three of them clearly showed clinical symptoms described as carnitine deficiency, carnitine supplementation for all neonates receiving TPN for over 2 weeks is recommended.

Experiences with Guillain-Barré syndrome in a pediatric intensive care unit

During a 10-year period 16 children with acute Guillain-Barré syndrome were seen. Eleven were admitted to the Pediatric Intensive Care Unit, either because of difficulty of breathing and swallowing or because of symptoms of autonomic disturbance. Six patients were mechanically ventilated for a mean period of 17 days. Symptoms of autonomic disturbance were frequently seen especially in the mechanically ventilated patients. Two patients died because of cardiac arrhythmia. Methods of detecting patients at risk for cardiac dysrhythmia are suggested.

Parents who wish no further treatment for their child

Background In the ethical and clinical literature, cases of parents who want treatment for their child to be withdrawn against the views of the medical team have not received much attention. Yet resolution of such conflicts demands much effort of both the medical team and parents. Objective To discuss who can best protect a childs interests, which often becomes a central issue, putting considerable pressure on mutual trust and partnership. Methods We describe the case of a 3-year-old boy with acquired brain damage due to autoimmune-mediated encephalitis whose parents wanted to stop treatment. By comparing this case with relevant literature, we systematically explored the pros and cons of sharing end-of-life decisions with parents in cases where treatment is considered futile by parents and not (yet) by physicians. Conclusions Sharing end-of-life decisions with parents is a more important duty for physicians than protecting parents from guilt or doubt. Moreover, a request from parents on behalf of their child to discontinue treatment is, and should be, hard to over-rule in cases with significant prognostic uncertainty and/or in cases with divergent opinions within the medical team.

Single nucleotide polymorphisms in genes of circulatory homeostasis in surviving pediatric intensive care patients with meningococcal infection

Objective: In the course of a meningococcal infection, invasive and severe disease occurs in a restricted number of individuals. The predominant mechanism of death in case of meningococcal septic shock is circulatory failure. Inotropic requirements between patients vary widely. We investigated whether polymorphisms in genes regulating the hemodynamic response influence the amount of inotropics required or the susceptibility to severe meningococcal disease. Design: Retrospective case control study. Setting: Single-center pediatric intensive care unit (PICU). Patients: Fifty-six cases (all consecutive patients admitted to the PICU between 1993 and 2001 with a proven meningococcal infection) and 136 controls. Patients were divided into two groups according to their inotropic requirements. Intervention: DNA analysis was performed to determine the polymorphisms of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, alpha-adducin, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 genes. Results: For the alpha-adducin gene a significant difference of the genotype distribution was found between the cases and controls. The odds ratio for admission to the PICU with meningococcal sepsis with or without meningitis, for carriers of the variant allele (Gly460Trp or Trp460Trp) was 2.1 (95% confidence interval 1.11–4.04; p < 0.02). Cases, homozygote for the wild-type allele of the beta-1 adrenergic receptor at locus 389, were more likely to have a low pediatric risk of mortality score on admission (odds ratio 3.6, 95% confidence interval 1.11–11.76). No difference was found in the distribution of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 polymorphisms between the two groups of patients or between cases and controls. Conclusions: Among patients admitted to the PICU with a meningococcal infection, the variant allele of the alpha-adducin gene was more prevalent compared with controls. Patients with the variant allele of the beta-adrenergic receptor gene-1 at locus 389 were more likely to have a high pediatric risk of mortality score on admission. The mechanism and clinical relevance of these findings is unclear.

Incidence, risk factors, and outcome of transfusion-related acute lung injury in critically ill children: a retrospective study.

PURPOSE Acute lung injury (ALI) that develops within 6 hours after transfusion (TRALI) is the leading cause of transfusion-related morbidity and mortality. Both incidence and patient and transfusion-related risk factors are well studied in the adult critically ill patient population. Clinical data on TRALI in the pediatric population are sparse and are mainly limited to case reports and hemovigilance reporting systems. The objective of this study was to determine incidence, risk factors, and outcome of TRALI in critically ill children. MATERIALS AND METHODS In a retrospective cohort study, all first-time admissions to the pediatric intensive care unit from January 1, 2009, until December 31, 2012, were screened for onset of TRALI using the consensus criteria. RESULTS Of 2294 admitted patients, 304 were transfused, of whom 21 (6.9%) developed TRALI. Compared with transfused control subjects, risk factors for TRALI were mechanical ventilation (odds ratio, 18.94 [2.38-2452.56]), sepsis (odds ratio, 7.20 [2.69-19.69]), and high Pediatric Risk of Mortality III score (odds ratio, 1.05 [1.01-1.10]). Patients with TRALI had a higher mortality and a longer duration of mechanical ventilation when compared with transfused control subjects. CONCLUSIONS Transfusion-related ALI is relatively common in critically ill children. The incidence in the pediatric intensive care unit population is similar to that in adult intensive care unit patients. High PRISM score on admission, mechanical ventilation and sepsis were identified as independent risk factors, which may help to assess the risks and benefits of transfusion in critically ill patients.