Central-line-associated bloodstream infections in a surgical paediatric intensive care unit: Risk factors and prevention with chlorhexidine bathing.

AIM: The aims of the study are to evaluate the impact of a 4% chlorhexidine (CHG4%) bathing on the occurrence of central-line-associated bloodstream infection (CLABSI) and to identify risk factors (RFs) for CLABSI in our population. This is a retrospective monocentric cohort study in the paediatric surgical intensive care unit at the Necker Enfants Malades Hospital, Paris, France. METHODS: All hospitalised patients with central venous catheters (CVCs) in 2015 were included. CHG4% bathing was prescribed in CLABSI high-risk patients, defined by the presence of exposition factors (EFs): constitutive or acquired immunosuppression, presence of an invasive medical device (IMD) and the carriage of Staphylococcus aureus. The overall 2015 CLABSI incidence rate was compared with 2014 CLABSI incidence rate (before CHG4% bathing). RESULTS: In all, 775 patients were analysed. Some 182 had at least one EF, and 49 received CHG4%. The incidence rates of CLABSI in 2014 and 2015 were, respectively, 6.1 and 2.3/1000 days CVC (P < 0.01). The presence of at least one EF was associated with the CLABSI's occurrence: odds ratio = 15.13 (95% confidence interval: 4.26-53.71; P < 0.0001), particularly acquired immunosuppression, IMD and S. aureus colonisation. Other RFs were age <1 year and carrying duration >16 days. CONCLUSIONS: This study showed a significant reduction in incidence of CLABSI after introduction of a targeted CHG4% bathing protocol. Presence of IMD, S. aureus colonisation, immunosuppression, age <1 year and carrying duration >16 days were CLABSI RFs. Regarding the literature, the presence of IMD seems to be underestimated in CLABSI prevention.

Anterior fronto-orbital remodeling for trigonocephay.

INTRODUCTION: Trigonocephaly secondary to the premature fusion of the metopic synostosis is associated to a risk of cerebral compression and several craniofacial morphological alterations. Numerous surgical techniques have been proposed. They all carry a risk of secondary temporal hollowing PURPOSE: The aim of this paper is to describe the surgical technique used for trigonocephaly at the craniofacial unit of Hopital Necker Enfants Malades (French National Referral Center for Faciocraniosynostosis) focusing on its advantages and limitations. Resorbable osteosynthesis should be part of the current techniques.

A survey of blood transfusion practice in French-speaking pediatric anesthesiologists.

BACKGROUND: There are so far no existing consensus guidelines regarding red blood cell transfusion during pediatric surgery, and there is a little information regarding red blood cell transfusion policy among pediatric anesthesiologists. OBJECTIVES: To determine the transfusion threshold and the volumes of packed red blood cell (PRBC) transfusion among French-speaking pediatric anesthesiologists. MATERIALS AND METHODS: A questionnaire of case scenarios was sent to active members of the French Language Society of Pediatrics Anesthesiologists (ADARPEF). RESULTS: Of the 324 active members of the ADARPEF, 175 (54%) completed the questionnaire. The threshold for blood transfusion varied from 6 to 12 g·dl(-1) depending on the scenario. The hemoglobin threshold for blood transfusion and the volume of blood transfused vary among ADARPEF physicians, for the same class of patients. The median [95% CI] hemoglobin threshold for starting blood transfusion was 7.9 [6.9-8.9], 7.3 [6.4-8.2], and 8.1 [7.0-9.2] g·dl(-1) in the pre-, intra-, and postoperative phase, respectively. The median [95% CI] PRBC volume transfused was 11.7 [6.6-16.8] ml·kg(-1), and the median hemoglobin target was 11.3 [9.8-12.8] g·dl(-1). Physicians ranked age (79%), clinical tolerance of anemia (99%), underlying medical conditions (95%), hemodynamic instability (89%), hemostasis disorder (86%), and sepsis (79%) as the most significant factors affecting their transfusion decisions. Most pediatric anesthesiologists (89%) measure the hemoglobin level before PRBC transfusion. CONCLUSIONS: This survey identifies significant differences in transfusion practice patterns among pediatric anesthesiologists with a median transfusion threshold of 7.6 [6.6-8.6] g·dl(-1) and a median PRBC volume transfusion of 11.7 [16.8-6.6] ml·kg(-1).

Acute hyperglycemia is a reliable outcome predictor in children with severe traumatic brain injury.

PURPOSE: Hyperglycemia in the acute phase after trauma could adversely affect outcome in children with severe traumatic brain injury (TBI). The goal of this study was to identify the relationship between acute spontaneous hyperglycemia and outcome in children with severe TBI at hospital discharge and 6 months later. METHODS: A retrospective analysis of blood glucose levels in children with severe TBI at a Pediatric level I Trauma Center, between January 2000 and December 2005. Hyperglycemia was considered for a cut-off value of 11.1 mmol/l (200 mg/dl). Outcome was measured with Glasgow Outcome Scale (GOS) at hospital discharge and at 6 months. A multiple logistic regression analysis, the Student's t test and the chi (2) test were done. RESULTS: Hyperglycemia was noted within the first 48 h in 34% of the patients. Mortality (70% vs 14%, p < 10(-5)) was more frequent in hyperglycemic children and bad outcome upon hospital discharge in those who remained hyperglycemic during the first 48 h of hospitalization. GOS after 6 months demonstrated that those normoglycemic children had a better outcome (95%) than those who developed hyperglycemia during the first 48 h (83%, p = 0.01) after trauma. CONCLUSION: Hyperglycemia could be considered as a marker of brain injury and when present upon admission, could reflect extensive brain damage with frequently associated mortality and bad outcome. The inability to maintain normal blood glucose levels during the first 48 h could be a predictive factor of bad outcome. Avoiding hyperglycemia in the initial phase could be a major issue in children with severe TBI.

A long-term evaluation of a training program on breaking bad news in pediatric neurosurgery: a pilot study.

OBJECTIVE: Breaking bad news is a difficult task in medical practice. Several breaking-bad-news training programs have been proposed. However, long-term results of such training have rarely been investigated. The aim of this study was to compare the short- and long-term evaluations by young neurosurgeons of a training program for breaking bad news to patients and their parents. METHODS: Between 2012 and 2015, pediatric neurosurgery residents participated in a training day on breaking bad news in pediatric neurosurgery with professional actors. A personal debriefing, followed by a theoretical session, completed the training. Immediate feedback was evaluated through a survey administered at the end of the day. Long-term results were explored via an online form sent at least 3 years after the training completion. RESULTS: Seventeen participants from 9 different countries were interviewed. Their immediate feedback confirmed their interest. For 71% of them, the program was very interesting, and 77% were extremely satisfied or very satisfied. All trainees wanted more training sessions. At a mean of 4.5 years of follow-up (range 3-6 years), 71% of the trainees fully remembered the session. Most of them (86%) reported a positive impact of the training on their career. Only 21% had another training session on breaking bad news during their residency. At long-term analysis, fewer trainees considered the duration of the training to have been sufficient (p = 0.044). CONCLUSIONS: Breaking-bad-news training has a positive long-term educational impact even several years later. Such a training program should be implemented into pediatric neurosurgery residency.

Management of critically ill children with traumatic brain injury.

The management of critically ill children with traumatic brain injury (TBI) requires a precise assessment of the brain lesions but also of potentially associated extra-cranial injuries. Children with severe TBI should be treated in a pediatric trauma center, if possible. Initial assessment relies mainly upon clinical examination, trans-cranial Doppler ultrasonography and body CT scan. Neurosurgical operations are rarely necessary in these patients, except in the case of a compressive subdural or epidural hematoma. On the other hand, one of the major goals of resuscitation in these children is aimed at protecting against secondary brain insults (SBI). SBI are mainly because of systemic hypotension, hypoxia, hypercarbia, anemia and hyperglycemia. Cerebral perfusion pressure (CPP = mean arterial blood pressure - intracranial pressure: ICP) should be monitored and optimized as soon as possible, taking into account age-related differences in optimal CPP goals. Different general maneuvers must be applied in these patients early during their treatment (control of fever, avoidance of jugular venous outflow obstruction, maintenance of adequate arterial oxygenation, normocarbia, sedation-analgesia and normovolemia). In the case of increased ICP and/or decreased CPP, first-tier ICP-specific treatments may be implemented, including cerebrospinal fluid drainage, if possible, osmotic therapy and moderate hyperventilation. In the case of refractory intracranial hypertension, second-tier therapy (profound hyperventilation with P(a)CO(2) < 35 mmHg, high-dose barbiturates, moderate hypothermia, decompressive craniectomy) may be introduced, after a new cerebral CT scan.

Use of recombinant activated factor VII in intractable bleeding during pediatric neurosurgical procedures.

OBJECTIVE:: To report the use of recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) in children undergoing major neurosurgical procedures and experiencing massive uncontrolled hemorrhagic shock. DESIGN:: Retrospective review of patients and analysis of clinical and biological effects of an intravenous administration of recombinant activated factor VII. SETTING:: Neurosurgical anesthesia and critical care unit of a pediatric university hospital. PATIENTS/SUBJECTS:: Four children, <12-kg body weight, experiencing life-threatening perioperative hemorrhage required conventional treatment (massive red blood cells, fresh frozen plasma, platelet transfusion, and surgical hemostatic maneuvers) that failed to obtain definite hemostasis. INTERVENTIONS:: Intravenous administration of recombinant activated factor VII (100 mug/kg). RESULTS:: Intravenous administration resulted in a significant decrease in blood loss within minutes (preventing further need of transfusion), normalization of biological hemostasis markers, and improved surgical hemostasis. No side effects of recombinant activated factor VII were noted, and all patients, except one, had a good recovery. CONCLUSIONS:: These four patients support the use of recombinant activated factor VII as a useful adjunct to control massive life-threatening bleeding during pediatric neurosurgical procedures when other means failed. However, the data are still limited in children, and more extensive research is needed to define the indications of recombinant activated factor VII in massive surgical hemorrhage in low-weight children.

Use of recombinant activated factor VII in intractable bleeding during pediatric neurosurgical procedures.

OBJECTIVE: To report the use of recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) in children undergoing major neurosurgical procedures and experiencing massive uncontrolled hemorrhagic shock. DESIGN: Retrospective review of patients and analysis of clinical and biological effects of an intravenous administration of recombinant activated factor VII. SETTING: Neurosurgical anesthesia and critical care unit of a pediatric university hospital. PATIENTS/SUBJECTS: Four children, <12-kg body weight, experiencing life-threatening perioperative hemorrhage required conventional treatment (massive red blood cells, fresh frozen plasma, platelet transfusion, and surgical hemostatic maneuvers) that failed to obtain definite hemostasis. INTERVENTIONS: Intravenous administration of recombinant activated factor VII (100 microg/kg). RESULTS: Intravenous administration resulted in a significant decrease in blood loss within minutes (preventing further need of transfusion), normalization of biological hemostasis markers, and improved surgical hemostasis. No side effects of recombinant activated factor VII were noted, and all patients, except one, had a good recovery. CONCLUSIONS: These four patients support the use of recombinant activated factor VII as a useful adjunct to control massive life-threatening bleeding during pediatric neurosurgical procedures when other means failed. However, the data are still limited in children, and more extensive research is needed to define the indications of recombinant activated factor VII in massive surgical hemorrhage in low-weight children.

Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial.

BACKGROUND: Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2-4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy. METHODS: Local regulatory authorities in France allowed inclusion of up to four children in this phase 1/2 study. Treatment was 16 intraparenchymal deposits (four in the cerebellum) of a recombinant adenoassociated viral vector serotype 2/5 (rAAV2/5) encoding human α-N-acetylglucosaminidase (NAGLU) plus immunosuppressive therapy. We assessed tolerance, neurocognitive progression, brain growth, NAGLU enzymatic activity in CSF, and specific anti-NAGLU immune response for 30 months after surgery. This trial is registered with EudraCT, number 2012-000856-33, and the International Standard Clinical Trial Registry, number ISRCTN19853672. FINDINGS: Of seven eligible children, the four youngest, from France (n=2), Italy (n=1), and Greece (n=1), aged 20, 26, 30, and 53 months, were included between February, 2012, and February, 2014. 125 adverse events were recorded, of which 117 were treatment emergent and included six classified as severe, but no suspected unexpected serious adverse drug reactions were seen. Vector genomes were detected in blood for 2 days after surgery. Compared with the natural history of mucopolysaccharidosis type III syndromes, neurocognitive progression was improved in all patients, with the youngest patient having function close to that in healthy children. Decrease in developmental quotient was -11·0 points in patient one, -23·0 in patient two, -29·0 in patient three, and -17·0 in patient four, compared with -37·7 in the natural history of the disease. NAGLU activity was detected in lumbar CSF and was 15-20% of that in unaffected children. Circulating T lymphocytes that proliferated and produced tumour necrosis factor α upon ex-vivo exposure to NAGLU antigens were detectable at 1-12 months and 3-12 months, respectively, but not at 30 months in three of four patients. INTERPRETATION: Intracerebral rAVV2/5 was well tolerated and induced sustained enzyme production in the brain. The initial specific anti-NAGLU immune response that later subsided suggested acquired immunological tolerance. The best results being obtained in the youngest patient implies a potential window of opportunity. Longer follow-up is needed to further assess safety outcomes and persistence of improved cognitive development. FUNDING: Association Française Contre les Myopathies, Vaincre les Maladies Lysosomales, Institut Pasteur, and UniQure.

Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation.

The postresuscitation phase after out-of-hospital circulatory arrest shares similarities with severe sepsis. Corticosteroid replacement is beneficial in patients with septic shock and adrenal dysfunction. The goal of this study was to assess baseline cortisol and adrenal reserve of out-of-hospital circulatory arrest patients after recovery of spontaneous circulation. Thirty-three consecutive patients successfully resuscitated after cardiac arrest were prospectively included between March 2002 and June 2003. A serum cortisol assay and a corticotropin test (250 microg i.v.) were done 6 to 36 h after circulatory arrest. A cortisol increase smaller than 9 microg/dL after corticotropin (nonresponders) defined adrenal reserve insufficiency. Response status was compared in the three outcome groups: survival with full neurologic recovery (n = 4), early death from refractory shock (n = 10), or later death from neurologic dysfunction (n = 19). Patients who died of early refractory shock had lower baseline cortisol levels than patients who died of neurologic dysfunction (27 microg/dL [15-47] vs. 52 microg/dL [28-73], respectively; P < 0.01), suggesting an inadequate adrenal response to severe systemic inflammation. Corticotropin response status was not associated with standard severity markers and seemed uninfluenced by therapeutic hypothermia. In conclusion, patients who die of early refractory shock after cardiopulmonary resuscitation may have an inadequate adrenal response to the stress associated with this condition. Thresholds for cortisol levels at baseline and after corticotropin need to be determined in this clinical setting.

Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial.

Mucopolysaccharidosis type IIIA is a severe degenerative disease caused by an autosomal recessive defect of a gene encoding a lysosomal heparan-N-sulfamidase, the N-sulfoglycosamine sulfohydrolase (SGSH), the catalytic site of which is activated by a sulfatase-modifying factor (SUMF1). Four children (Patients 1-3, aged between 5.5 and 6 years; Patient 4 aged 2 years 8 months) received intracerebral injections of an adeno-associated viral vector serotype rh.10-SGSH-IRES-SUMF1 vector in a phase I/II clinical trial. All children were able to walk, but their cognitive abilities were abnormal and had declined (Patients 1-3). Patients 1-3 presented with brain atrophy. The therapeutic vector was delivered in a frameless stereotaxic device, at a dose of 7.2×10(11) viral genomes/patient simultaneously via 12 needles as deposits of 60 µl over a period of 2 hr. The vector was delivered bilaterally to the white matter anterior, medial, and posterior to the basal ganglia. Immunosuppressive treatment (mycophenolate mofetil and tacrolimus) was initiated 15 days before surgery and maintained for 8 weeks (mycophenolate mofetil) or throughout follow-up (tacrolimus, with progressive dose reduction) to prevent elimination of transduced cells. Safety data collected from inclusion, during the neurosurgery period and over the year of follow-up, showed good tolerance, absence of adverse events related to the injected product, no increase in the number of infectious events, and no biological sign of toxicity related to immunosuppressive drugs. Efficacy analysis was necessarily preliminary in this phase I/II trial on four children, in the absence of validated surrogate markers. Brain atrophy evaluated by magnetic resonance imaging seemed to be stable in Patients 1 and 3 but tended to increase in Patients 2 and 4. Neuropsychological evaluations suggested a possible although moderate improvement in behavior, attention, and sleep in Patients 1-3. The youngest patient was the most likely to display neurocognitive benefit.

Hemorrhagic shock and encephalopathy syndrome in a quadriplegic child: an argument for the triggering role of impaired thermoregulatory response.

STUDY DESIGN: A case presentation of hemorrhagic shock and encephalopathy syndrome (HSES). OBJECTIVE: To describe an unusual complication of uncontrolled fever in a tetraplegic child and to discuss possible pathophysiological mechanisms in these circumstances. SUMMARY OF BACKGROUND DATA: HSES is a rare and dramatic disorder of unknown origin occurring mainly in infants and young children. Clinical features of HSES associate hyperpyrexia, acute diarrhea, circulatory collapse, coma, convulsions, and multiple organ failure (MOF). Altered physiologic thermoregulatory response in infants exposed to abruptly increased core temperature or altered thermal environment, and links with heat stroke, have been mentioned in previous publications. METHODS: We report a case of HSES occurring in a 6-year-old girl with post-traumatic C4 quadriplegia. She eventually experienced hyperpyrexia, deep shock, watery diarrhea, and severe MOF developed rapidly. Despite rapidly resolving MOF, severe brain lesions consistent with HSES were observed and resulted in permanent neurologic impairment. RESULTS: Negative bacterial and viral screening eliminated a septic origin. In this child, impaired thermoregulatory response to acute hyperpyrexia resulting from complete quadriplegia could be the necessary condition for the development of HSES in the presence of acute hyperpyrexia of unknown origin. CONCLUSION: Quadriplegic patients, especially young children, could be considered at increased risk of developing severe MOF and acute central nervous system impairment consistent with HSES, when exposed to heat stress and should be treated promptly.

French experience of 2009 A/H1N1v influenza in pregnant women.

BACKGROUND: The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. METHODOLOGY/PRINCIPAL FINDINGS: A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. CONCLUSIONS: This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population.

Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis.

OBJECTIVE: To evaluate incidence and risk factors of postoperative meningitis, with special emphasis on antibiotic prophylaxis, in a series of 6243 consecutive craniotomies. METHODS: Meningitis was individualized from a prospective surveillance database of surgical site infections after craniotomy. Ventriculitis related to external ventricular drainage or cerebrospinal fluid shunt were excluded. From May 1997 until March 1999, no antibiotic prophylaxis was prescribed for scheduled, clean, lasting less than 4 hours craniotomies, whereas emergency, clean-contaminated, or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. From April 1999 until December 2003, prophylaxis was given to every craniotomy. Independent risk factors for meningitis were studied by a multivariate analysis. Efficacy of antibiotic prophylaxis in preventing meningitis was studied as well as consequences on bacterial flora. RESULTS: The overall meningitis rate was 1.52%. Independent risk factors were cerebrospinal fluid leakage, concomitant incision infection, male sex, and surgical duration. Antibiotic prophylaxis reduced incision infections from 8.8% down to 4.6% (P < 0.0001) but did not prevent meningitis: 1.63% in patients without antibiotic prophylaxis and 1.50% in those who received prophylaxis. Bacteria responsible for meningitis were mainly noncutaneous in patients receiving antibiotics and cutaneous in patients without prophylaxis. In the former, microorganisms tended to be less susceptible to the prophylactic antibiotics administered. Mortality rate was higher in meningitis caused by noncutaneous bacteria as compared with those caused by cutaneous microorganisms. CONCLUSION: Perioperative antibiotic prophylaxis, although clearly effective for the prevention of incision infections, does not prevent meningitis and tends to select prophylaxis resistant microorganisms.

Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis.

OBJECTIVE: To evaluate incidence and risk factors of postoperative meningitis, with special emphasis on antibiotic prophylaxis, in a series of 6243 consecutive craniotomies. METHODS: Meningitis was individualized from a prospective surveillance database of surgical site infections after craniotomy. Ventriculitis related to external ventricular drainage or cerebrospinal fluid shunt were excluded. From May 1997 until March 1999, no antibiotic prophylaxis was prescribed for scheduled, clean, lasting less than 4 hours craniotomies, whereas emergency, clean-contaminated, or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. From April 1999 until December 2003, prophylaxis was given to every craniotomy. Independent risk factors for meningitis were studied by a multivariate analysis. Efficacy of antibiotic prophylaxis in preventing meningitis was studied as well as consequences on bacterial flora. RESULTS: The overall meningitis rate was 1.52%. Independent risk factors were cerebrospinal fluid leakage, concomitant incision infection, male sex, and surgical duration. Antibiotic prophylaxis reduced incision infections from 8.8% down to 4.6% (P < 0.0001) but did not prevent meningitis: 1.63% in patients without antibiotic prophylaxis and 1.50% in those who received prophylaxis. Bacteria responsible for meningitis were mainly noncutaneous in patients receiving antibiotics and cutaneous in patients without prophylaxis. In the former, microorganisms tended to be less susceptible to the prophylactic antibiotics administered. Mortality rate was higher in meningitis caused by noncutaneous bacteria as compared with those caused by cutaneous microorganisms. CONCLUSION: Perioperative antibiotic prophylaxis, although clearly effective for the prevention of incision infections, does not prevent meningitis and tends to select prophylaxis resistant microorganisms.