Addition of terlipressin to initial volume resuscitation in a pediatric model of hemorrhagic shock improves hemodynamics and cerebral perfusion.

Hemorrhagic shock is one of the leading causes of mortality and morbidity in pediatric trauma. Current treatment based on volume resuscitation is associated to adverse effects, and it has been proposed that vasopressors may be used in the pharmacological management of trauma. Terlipressin has demonstrated its usefulness in other pediatric critical care scenarios and its long half-life allows its use as a bolus in an outpatient critical settings. The aim of this study was to analyze whether the addition of a dose of terlipressin to the initial volume expansion produces an improvement in hemodynamic and cerebral perfusion at early stages of hemorrhagic shock in an infant animal model. We conducted an experimental randomized animal study with 1-month old pigs. After 30 minutes of hypotension (mean arterial blood pressure [MAP]<45 mmHg) induced by the withdrawal of blood over 30 min, animals were randomized to receive either normal saline (NS) 30 mL/kg (n = 8) or a bolus of 20 mcg/kg of terlipressin plus 30 mL/kg of normal saline (TP) (n = 8). Global hemodynamic and cerebral monitoring parameters, brain damage markers and histology samples were compared. After controlled bleeding, significant decreases were observed in MAP, cardiac index (CI), central venous pressure, global end-diastolic volume index (GEDI), left cardiac output index, SvO2, intracranial pressure, carotid blood flow, bispectral index (BIS), cerebral perfusion pressure (CPP) and increases in systemic vascular resistance index, heart rate and lactate. After treatment, MAP, GEDI, CI, CPP and BIS remained significantly higher in the TP group. The addition of a dose of terlipressin to initial fluid resuscitation was associated with hemodynamic improvement, intracranial pressure maintenance and better cerebral perfusion, which would mean protection from ischemic injury. Brain monitoring through BIS was able to detect changes caused by hemorrhagic shock and treatment.

Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10-8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10-9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10-8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

Cardiac index monitoring by femoral arterial thermodilution after cardiac surgery in children.

PURPOSE: The aim of this study is to determine whether the maintenance of cardiac index (CI) measured by femoral arterial thermodilution during the postoperative period after heart surgery in children is related to short-term outcome. MATERIALS AND METHODS: A prospective observational study in a pediatric intensive care unit at a referral hospital for congenital heart disease was conducted. Thirty-five children after open heart surgery were monitored in 5 planned times with PiCCO (Pulsion Medical System AG, Munich, Germany) during the first 24 hours after admission. Normal CI was defined as 3 L min(-1) m(-2) or greater. RESULTS: Eighteen patients hold CI at every measurement point. In this group, the median stay in the pediatric intensive care unit was 3 days (range, 2-7 days) compared with the median of 6 days (range, 2-34 days) obtained by the rest (P<.005). Duration of mechanical ventilation was 12 hours (range, 3-48 hours), and overall stay in the hospital was 6 days (range, 2-15 days) compared with 25 hours (range 6-432 hours) and 16 days (range, 4-50 days) obtained by the second group (P<.05). No complications were attributed to the use of the device. CONCLUSIONS: Monitoring by femoral arterial thermodilution has been feasible in our experience. Maintenance of a CI of 3 L min(-1) m(-2) or greater is related to a better patient's early outcome.

Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants.

A 28-day-old male newborn weighing 3.6 kg was given a diagnosis of atypical hemolytic-uremic syndrome, new-onset thrombotic microangiopathy (TMA; hemoglobin, 7.7 g/dL; schistocytes, 9%), thrombocytopenia (platelets, 49 × 10(3)/µL [49 × 10(9)/L]), and acute kidney failure (serum creatinine, 1.13 mg/dL [99.8 µmol/L], corresponding to estimated glomerular filtration rate [eGFR] of 15 mL/min/1.73 m(2) [0.25 mL/s/1.73 m(2)]). Repeated high-volume plasma infusions were ineffective. Plasma exchange was attempted, but not tolerated. The patient required mechanical ventilation and continuous renal replacement therapy. He developed multiple intestinal perforations and leg skin necrosis due to systemic TMA. A low C3 level (36 mg/dL) suggested complement activation. Eculizumab, 300 mg, was administered, and within 48 hours the patient recovered from acute kidney failure, with complete hematologic remission 2 weeks later. The infant, 14 months old at the time of writing, continues to receive eculizumab, 300 mg, every 3 weeks; he is free of disease activity and has a normal creatinine level of 0.2 mg/dL (17.68 µmol/L; corresponding to eGFR of 110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)]), but mild proteinuria (urinary protein-creatine ratio, 1 mg/g). Results of additional studies, including probing for cobalamin anomalies and measuring levels of ADAMTS13, complement factor H (CFH), factor I (CFI), and membrane cofactor protein (MCP), were unremarkable. Antibodies to CFH were undetectable, and mutation testing of the genes for CFH, CFI, and MCP gave negative results. Treatment with eculizumab was life saving, and with continued treatment, the patient showed sustained freedom from clinical TMA complications.

Pediatric cardiac arrest refractory to advanced life support: is there a role for terlipressin?

OBJECTIVE: Pediatric cardiac arrest unresponsive to advanced life support and several adrenaline doses has a very poor prognosis. Alternative vasopressors could improve the results of resuscitation in such cases. We report our experience with the compassionate administration of terlipressin in children who suffered in-pediatric intensive care unit cardiac arrest and did not respond to immediate advanced life support and at least three epinephrine doses. DESIGN: Prospective multicenter registry. SETTING: Three pediatric intensive care units at university-affiliated tertiary care children's hospitals. PATIENTS: Five pediatric patients, aged 5 mos to 12 yrs, with in-pediatric intensive care unit cardiac arrest unresponsive to advanced life support that included at least three epinephrine doses. INTERVENTIONS: Addition of terlipressin (10-20 microg/kg intravenous, up to two doses) to standard cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Sustained return of spontaneous circulation was achieved in four cases, two of them were declared dead 6 and 12 hrs later, and the remaining two survived without cardiopulmonary procedures-related sequelae and with good neurologic condition. CONCLUSIONS: Terlipressin might contribute to obtain sustained return of spontaneous circulation in children with refractory in-hospital cardiac arrest. A randomized controlled clinical trial should be conducted to investigate the optimal drug treatment in pediatric cardiac arrest.

Osteomielitis vertebral asociada a enfermedad por arañazo de gato / Vertebral osteomyelitis associated with car scratch disease

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