Philippe Hubert

Epidemiology and treatment of painful procedures in neonates in intensive care units.

CONTEXT Effective strategies to improve pain management in neonates require a clear understanding of the epidemiology and management of procedural pain. OBJECTIVE To report epidemiological data on neonatal pain collected from a geographically defined region, based on direct bedside observation of neonates. DESIGN, SETTING, AND PATIENTS Between September 2005 and January 2006, data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospectively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France (11.3 millions inhabitants) for the Epidemiology of Procedural Pain in Neonates (EPIPPAIN) study. MAIN OUTCOME MEASURE Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy. RESULTS The mean (SD) gestational age and intensive care unit stay were 33.0 (4.6) weeks and 8.4 (4.6) calendar days, respectively. Neonates experienced 60,969 first-attempt procedures, with 42,413 (69.6%) painful and 18,556 (30.4%) stressful procedures; 11,546 supplemental attempts were performed during procedures including 10,366 (89.8%) for painful and 1180 (10.2%) for stressful procedures. Each neonate experienced a median of 115 (range, 4-613) procedures during the study period and 16 (range, 0-62) procedures per day of hospitalization. Of these, each neonate experienced a median of 75 (range, 3-364) painful procedures during the study period and 10 (range, 0-51) painful procedures per day of hospitalization. Of the 42,413 painful procedures, 2.1% were performed with pharmacological-only therapy; 18.2% with nonpharmacological-only interventions, 20.8% with pharmacological, nonpharmacological, or both types of therapy; and 79.2% without specific analgesia, and 34.2% were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons. Prematurity, category of procedure, parental presence, surgery, daytime, and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia, whereas mechanical ventilation, noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia. CONCLUSION During neonatal intensive care in the Paris region, large numbers of painful and stressful procedures were performed, the majority of which were not accompanied by analgesia.

Symptoms of anxiety and depression in family members of intensive care unit patients: Ethical hypothesis regarding decision-making capacity

ObjectiveAnxiety and depression may have a major impact on a person’s ability to make decisions. Characterization of symptoms that reflect anxiety and depression in family members visiting intensive care patients should be of major relevance to the ethics of involving family members in decision-making, particularly about end-of-life issues. DesignProspective multicenter study. SettingForty-three French intensive care units (37 adult and six pediatric); each unit included 15 patients admitted for longer than 2 days. PatientsSix hundred thirty-seven patients and 920 family members. InterventionsIntensive care unit characteristics and data on the patient and family members were collected. Family members completed the Hospital Anxiety and Depression Scale to allow evaluation of the prevalence and potential factors associated with symptoms of anxiety and depression. Measurements and Main ResultsOf 920 Hospital Anxiety and Depression Scale questionnaires that were completed by family members, all items were completed in 836 questionnaires, which formed the basis for this study. The prevalence of symptoms of anxiety and depression in family members was 69.1% and 35.4%, respectively. Symptoms of anxiety or depression were present in 72.7% of family members and 84% of spouses. Factors associated with symptoms of anxiety in a multivariate model included patient-related factors (absence of chronic disease), family-related factors (spouse, female gender, desire for professional psychological help, help being received by general practitioner), and caregiver-related factors (absence of regular physician and nurse meetings, absence of a room used only for meetings with family members). The multivariate model also identified three groups of factors associated with symptoms of depression: patient-related (age), family-related (spouse, female gender, not of French descent), and caregiver-related (no waiting room, perceived contradictions in the information provided by caregivers). ConclusionsMore than two-thirds of family members visiting patients in the intensive care unit suffer from symptoms of anxiety or depression. Involvement of anxious or depressed family members in end-of-life decisions should be carefully discussed.

Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study

BACKGROUND Multiple organ dysfunction syndrome is more frequent than death in paediatric intensive care units. Estimation of the severity of this syndrome could be a useful additional outcome measure in clinical trials in such units. We aimed to validate the paediatric logistic organ dysfunction (PELOD) score and estimate its validity when recorded daily (dPELOD). METHODS We did a prospective, observational, multicentre cohort study in seven multidisciplinary, tertiary-care paediatric intensive care units of university-affiliated hospitals (two French, three Canadian, and two Swiss). We included 1806 consecutive patients (median age 24 months; IQR 5-90). PELOD score includes six organ dysfunctions and 12 variables and was recorded daily. For each variable, the most abnormal value each day and during the whole stay were used in calculating the dPELOD and PELOD scores, respectively. Outcome was vital status at discharge. We used Hosmer-Lemeshow goodness-of-fit tests to evaluate calibration and areas under receiver operating characteristic curve (AUC) to estimate discrimination. FINDINGS 370 (21%) patients had no organ dysfunction, 471 (26%) had one, 457 (25%) had two, and 508 (28%) had three or more. Case fatality rate was 6.4% (115 deaths). PELOD score was significantly higher in non-survivors (mean 31.0 [SE 1.2]) than survivors (9.4 [0.2]; p<0.0001). Calibration (p=0.54) and discrimination (AUC=0.91, SE=0.01) of PELOD and dPELOD (p> or =0.39; AUC> or =0.79) scores were good. INTERPRETATION PELOD and dPELOD scores are valid outcome measures of the severity of multiple organ dysfunction syndrome in paediatric intensive care units; their use should significantly reduce the sample size required to complete clinical trials in critically ill children.

CHARGE syndrome: Report of 47 cases and review

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.

Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: Report of five cases

OBJECTIVES To evaluate the efficacy of cyclosporine A in the treatment of macrophage activation syndrome (MAS) occurring in children with juvenile arthritis. STUDY DESIGN MAS developed in two boys and three girls with systemic juvenile arthritis (four) and polyarticular juvenile arthritis (one). In three children whose condition was life-threatening, increased parenteral administration of corticosteroids failed to improve their condition; therefore cyclosporine A (2 to 5 mg/kg per day) was added. In two other patients with less severe clinical manifestations, cyclosporine A alone (2 to 8 mg/kg per day) was given. RESULTS After the introduction of cyclosporine A, rapid improvement was obtained in all patients and apyrexia occurred within 24 to 48 hours. The biologic abnormalities disappeared more slowly (up to 5 weeks for liver enzymes). CONCLUSIONS These observations underline the usefulness of cyclosporine A in this complication. The use of this drug may circumvent the need for increased doses of corticosteroids in some patients. The mechanism of action of cyclosporine A remains speculative, but these results indicate indirectly that T-helper lymphocytes may play a role in the pathogenesis of MAS.

Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES)

Purpose:  Fever induced refractory epileptic encephalopathy in school age children (FIRES) is a devastating condition initiated by prolonged perisylvian refractory status epilepticus (SE) triggered by fever of unknown cause. SE may last more than 1 month, and this condition may evolve into pharmacoresistant epilepsy associated with severe cognitive impairment. We aimed to report the effect of ketogenic diet (KD) in this condition.

Parental involvement in treatment decisions regarding their critically ill child: a comparative study of France and Quebec.

Objective: To examine whether physicians or parents assume responsibility for treatment decisions for critically ill children and how this relates to subsequent parental experience. A significant controversy has emerged regarding the role of parents, relative to physicians, in relation to treatment decisions for critically ill children. Anglo-American settings have adopted decision-making models where parents are regarded as responsible for such life-support decisions, while in France physicians are commonly considered the decision makers. Design: Grounded theory qualitative methodology. Setting: Four pediatric intensive care units (two in France and two in Quebec, Canada). Patients: Thirty-one parents of critically ill children; nine physicians and 13 nurses who cared for their children. Interventions: None. Measurements and Main Results: Semistructured interviews were conducted. In France, physicians were predominantly the decision makers for treatment decisions. In Quebec, decisional authority practices were more varied; parents were the most common decision maker, but sometimes it was physicians, while for some decisional responsibility depended on the type of decision to be made. French parents appeared more satisfied with their communication and relationship experiences than Quebec parents. French parents referred primarily to the importance of the quality of communication rather than decisional authority. There was no relationship between parents’ actual responsibility for decisions and their subsequent guilt experience. Conclusions: It was remarkable that a certain degree of medical paternalism was unavoidable, regardless of the legal and ethical norms that were in place. This may not necessarily harm parents’ moral experiences. Further research is required to examine parental decisional experience in other pediatric settings.

Blind protected specimen brush and bronchoalveolar lavage in ventilated children.

OBJECTIVE To determine whether nonbronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) are contributive for diagnosing ventilator-associated pneumonia in mechanically ventilated children. DESIGN Prospective study. SETTING Fifteen-bed pediatric intensive care unit in a university hospital. PATIENTS A total of 103 mechanically ventilated children, ranging in age from 7 days to 8.8 yrs, most with a high clinical suspicion for bacterial pneumonia. INTERVENTIONS All the children underwent nonbronchoscopic PSB and BAL. Nonbronchoscopic PSB was performed with a plugged double-sheathed brush and BAL with a double-lumen plugged catheter. Endotracheal secretions and blood cultures were also collected. Open-lung biopsy was performed for any child who died within 7 days after the inclusion in the study, according to the parental consent. MEASUREMENTS AND MAIN RESULTS The PSB specimens were submitted for bacteriologic quantitative culture (positive threshold, 10(3) colony-forming units [cfu]/mL). The BAL samples were processed for microscopic quantification of the polymorphonuclear cells containing intracellular bacteria (positive threshold, 1%) and quantitative culture (positive threshold, 10(4) cfu/mL). According to diagnostic categories based on clinical, biological, radiologic, and pathologic criteria, 29 children had bacterial pneumonia and 64 did not Ten children were classified as having an uncertain status. Of the 29 children with bacterial pneumonia, 26 (90%) met one of the following three criteria: a) PSB specimen culture, > or =10(3) cfu/mL; b) intracellular bacteria in cells retrieved by BAL, > or =1%; and c) BAL fluid culture, > or =10(4) cfu/mL. In contrast, 56 (88%) of the 64 patients without pneumonia did not. CONCLUSION The results of this study indicate the following: a) nonbronchoscopic PSB and BAL were feasible in a large population of mechanically ventilated children; b) nonbronchoscopic techniques were contributive for diagnosing ventilator-associated pneumonia in children; and c) a combined diagnostic approach, using nonbronchoscopic PSB and BAL, was superior to using either test alone.

The moral experience of parents regarding life-support decisions for their critically-ill children: a preliminary study in France

The common paediatric critical care practice in France is for physicians (rather than parents) to maintain the ultimate responsibility for lifesupport decisions in children. Some French literature asserts that it is inappropriate for parents to bear such responsibilities because they do not have the required knowledge and should be protected from feeling culpable for such decisions. The aim of this grounded theory preliminary study was to examine the moral experience of parents of critically-ill children that required life-support decisions in France. A convenience purposive sample of seven parents was recruited in Paris. Five principal themes emerged as significant from these interviews: (1) a need for more information; (2) physicians should be responsible for life-support decisions; (3) the childs concerns and wishes need to be better heard; (4) maternal guilt; and (5) physicians require better training in parent communication. These findings raise important issues for clinical practice and further research in France.

Weaning children from mechanical ventilation with a computer-driven system (closed-loop protocol): a pilot study.

Objective: To evaluate the applicability, tolerance, and efficacy of a closed-loop protocol to wean children from mechanical ventilation. Design: Prospective single-center pilot study. Setting: Tertiary care university hospital. Patients: Twenty mechanically ventilated children aged between 1 and 17 yrs, with a body weight ≥10 kg, no inotropes, and no heavy sedation. Interventions: Patients were weaned in pressure support mode by a closed-loop computerized protocol (closed-loop protocol) that interprets clinical data in real time and controls pressure support levels. Measurements and Main Results: The closed-loop protocol applicability and tolerance were evaluated. The efficacy of this protocol was evaluated by comparing the duration of mechanical ventilation with a historical group of 20 patients weaned with a clinician-decision protocol. The closed-loop protocol successfully decreased pressure support ventilation in 16 children, recommended separation from the ventilator in 14 children, and did not cause any serious adverse events. Mechanical ventilation duration was 5.1 ± 4.2 days in the closed-loop group and 6.7 ± 11.5 days (mean ± sd) in the clinician-decision group (p = .33) with no difference in the need for reintubation or noninvasive mechanical ventilation (one of 20 and four of 20, respectively; p = .20). Conclusions: A closed-loop protocol was successfully used to wean children from mechanical ventilation. Further studies are required to assess the impact of this novel therapeutic strategy on the length of mechanical ventilation.