Effects of plasma transfusions on antithrombin levels after paediatric liver transplantation.

BACKGROUND AND OBJECTIVES: Thrombotic complications affect 3-10% of patients after liver transplantation (LT), leading to potentially life-threatening complications. In the days following LT, antithrombin (AT) is decreased longer than pro-coagulant factors, thus favouring a pro-thrombotic profile. Plasma transfusions are given empirically in some centres to correct AT levels following LT. We assessed the effect of plasma transfusion on AT levels after paediatric LT. MATERIALS AND METHODS: Prospective single-centre observational study in 20 consecutive paediatric LT recipients over a 24-month period. Plasma was administered twice daily (10 ml/kg/dose) according to an existing protocol. AT levels were measured once daily, immediately prior to and one hour after the morning plasma transfusion. Sample size was calculated based on a non-inferiority hypothesis. RESULTS: The median age and weight were 11.6 years (IQR 2.8; 14.7) and 40 kg (IQR 12.75; 44.8), respectively. We collected 85-paired blood samples. The median AT level prior to plasma transfusion was 58%. The median difference in AT levels before and after plasma transfusion was 4.2% (P = 0.001). Changes in AT levels after plasma transfusion were not correlated with baseline AT levels (R = 0.19) or patient weight (R = 0.18). CONCLUSION: Plasma transfusions only marginally increase AT levels in children after LT. Therefore, prophylactic plasma transfusions probably do not seem to confer an advantage in the routine management of paediatric LT patients. Randomized controlled trials are needed to identify the optimal anticoagulation strategy in this specific population.

Younger age and in situ duration of peripheral intravenous catheters were risk factors for extravasation in a retrospective paediatric study.

AIM: Epidemiological data on the incidence and risk factors of extravasation of peripheral intravenous catheters (PIVC) in neonates and children are scarce and that is what this study explored. METHODS: This was a one-year retrospective study of all neonates and paediatric intensive care patients with at least one recorded PIVC at the Geneva University Hospitals, Switzerland, in 2013. The extravasation rate was determined for all patients, including neonates below 28 days, and for all PIVCs. Multivariate analysis of the associated risk factors was performed. RESULTS: We analysed 1300 PIVC in 695 paediatric patients with a median age of 1.5 years. The overall extravasation incidence was 17.6% for all patients and 11.7% for PIVC. The overall incidence rate of PIVC extravasation was 4.5 per 100 catheters days, and the risk was highest in the 201 neonates, at 28.4%. The incidence rate four days after insertion of the PIVC was around three times higher than on day one. Neonates and the in situ duration of PIVCs were associated risk factors (p < 0.001). CONCLUSION: Extravasation was frequent and neonates were particularly at risk. Younger age and longer in situ PIVC duration were independent risk factors for extravasation.

Regional respiratory inflation and deflation pressure-volume curves determined by electrical impedance tomography.

Measurement of regional lung volume changes during a quasi-static pressure-volume (PV) manoeuvre using electrical impedance tomography (EIT) could be used to assess regional respiratory system mechanics and to determine optimal ventilator settings in individual patients. Using this approach, we studied regional respiratory system mechanics in healthy and lung-injured animals, before and after surfactant administration during inflation and deflation PV manoeuvres. The comparison of the EIT-derived regional PV curves in ventral, middle and dorsal regions of the right and left lungs showed not only different amounts of hysteresis in these regions but also marked differences among different landmark pressures calculated on the inflation and deflation limbs of the curves. Regional pressures at maximum compliance as well as the lower and upper pressures of maximum compliance change differed between the inflation and deflation and increased from ventral to dorsal regions in all lung conditions. All these pressure values increased in the injured and decreased in the surfactant treated lungs. Examination of regional respiratory system mechanics using EIT enables the assessment of spatial and temporal heterogeneities in the ventilation distribution. Characteristic landmarks on the inflation and especially on the deflation limb of regional PV curves may become useful measures for guiding mechanical ventilation.

Association between plasma transfusions and clinical outcome in critically ill children: a prospective observational study.

BACKGROUND AND OBJECTIVES: Plasma transfusions are commonly used in adult and paediatric intensive care units. Recent data suggest an association between plasma transfusions and worse clinical outcome in adult trauma patients. To date, no prospective paediatric study has addressed this issue. Our objective was to prospectively analyse the association between plasma transfusions and clinical outcome of critically ill children. MATERIALS AND METHODS: Prospective, observational and single centre study that includes all consecutive admissions to a tertiary level multidisciplinary paediatric critical care unit over a 1-year period. The primary outcome measure was the incidence after transfusion of new or progressive multiple organ dysfunction syndrome. Secondary outcome measures included nosocomial infections, intensive care unit length of stay and 28-day mortality. Odds ratios were adjusted for weight, severity of illness, coagulopathy, plasma transfusions prior to admission, need for extracorporeal life support and transfusion of other labile blood products. RESULTS: A total of 831 patients were enrolled, among which 94 (11%) received at least one plasma transfusion. In the latter group of patients, the adjusted odds ratio for an increased incidence of new or progressive multiple organ dysfunction syndrome was 3.2 (P = 0.002). There was also a significant difference in the occurrence of nosocomial infections and intensive care unit length of stay, but no significant difference in the 28-day mortality. CONCLUSIONS: In critically ill children, plasma transfusions seem to be independently associated with an increased occurrence of new or progressive multiple organ dysfunction syndrome, nosocomial infections and prolonged length of stay.

Noise levels during nCPAP are flow-dependent but not device-dependent.

OBJECTIVE: Nasal continuous positive airway pressure (nCPAP) has been shown to improve the outcome of infants with respiratory distress syndrome. However, noise generation could be of concern. Therefore, our study was designed to measure the noise levels of various CPAP drivers. DESIGN: For infants admitted to our neonatal intensive care unit and paediatric critical care unit, we measured the noise level in the oral cavity, using a microphonic probe with a flexible capillary tube. Various CPAP drivers and interfaces have been tested. RESULTS: 27 measurements were made in eight infants. Mean noise level was 88.6 (SD 18.8) dB and was correlated with flow (p<0.01) but not with pressure. A noise level above 90 dB was detected in 67% of the measurements. CONCLUSIONS: nCPAP drivers are valuable devices for neonatal care that may prevent primary mechanical ventilation or re-intubation, but generate a large amount of noise, often higher than occupational limits accepted for adult workers. Therefore, new devices must be designed to minimise this possible noxious exposure of premature infants to unacceptably high noise levels.

Somato-sympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide.

AIM: Patients suffering from non-allergic chronic rhinosinusitis (NACRS) increasingly use intranasal saline sprays. They report better nasal comfort. METHODS: In order to better understand this phenomenon, we studied intranasal laser Doppler flowmetry (LDF) and nasal nitric oxide (NO) variations evoked by local administration of saline, histamine, N-acetylcysteine (NAC) and lidocaine at room temperature (22 degrees C). RESULTS: There was a significant (P < 0.05) 14 +/- 3.8% decrease in LDF signal after 30 s, which lasted for 60-90 s, for all the substances applied at 22 degrees C. This pharmaco-independent vasoconstriction was further studied in patients under general anaesthesia (GA), with saline at 37 degrees C and after intranasal adrenaline treatment. While GA did not influence the vasoconstriction, saline at 37 degrees C and adrenaline pre-treatment abolished it. Nasal NO is influenced by vasoconstriction. Therefore we investigated, whether the observed vasoconstriction also changes nasal NO. A significant (P < 0.001) 8.03 +/- 0.59% decrease in nasal NO was recorded 60 s after administration of all the substances, and under GA after 22 degrees C saline application. This NO decrease was absent after intranasal adrenaline pre-treatment. An additional experiment tested the effect of nose blowing on nasal NO concentration. We registered an NO decrease with a similar pattern than observed with the other substances. CONCLUSIONS: Intranasal fluid nebulization at 22 degrees C induces a sympathetic mediated, transient vasoconstrictor reflex response. This somato-sympathetic vasoconstriction induces a decrease in nasal NO. Both could be related to the subjective comfort experienced by NACRS patients using intranasal saline sprays.

Aerosolized iloprost induces a mild but sustained inhibition of platelet aggregation.

Pathological studies have revealed that one of the main features encountered in the pulmonary vasculature of patients with pulmonary hypertension is the presence of thrombotic lesions. Open pilot studies have indicated that aerosolized iloprost may have beneficial effects in patients with pulmonary hypertension. The effects of aerosolized iloprost on platelet function and plasma cyclic adenosine monophosphate (cAMP) were studied. Platelet aggregation and plasma cAMP were measured at baseline, 30 min, 4 and 6 h after inhalation of 15 microg iloprost in 10 healthy volunteers. Maximal platelet aggregation in response to adenosine diphosphate (ADP) (2 and 6 micromol x L(-1)), collagen (2.5 and 5 microg x mL(-1)), epinephrine (1.25 and 5 micromol x L(-1)) and arachidonic acid (0.5 mg x mL(-1)) was measured. Platelet aggregation was significantly inhibited at 30 min in response to ADP (2 and 6 micromol x L(-1), epinephrine (1.25 and 5 micromol x L(-1)) and collagen (2.5 microg x mL(-1)). It was still inhibited at 4 h in response to the same agents, but normalized at 6 h. cAMP increased at 30 min, from 27.3+/-1.2 to 31.8+/-1.2 nmol x L(-1), remained increased at 4 h (29.2+/-1.3 nmol x L(-1)) and normalized at 6 h (27.4+/-1.1 nmol x L(-1)). Aerosolized iloprost induced a mild but sustained inhibition of platelet aggregation. Platelet aggregation inhibition may be one of the mechanisms which explains the beneficial effect of repeated inhalation of iloprost in pulmonary hypertension.

Long term inhalation of iloprost in a child with primary pulmonary hypertension: an alternative to continuous infusion.

Primary pulmonary hypertension is a rare disease in childhood associated with a poor prognosis. However, during the past 10 years, pulmonary vasodilator treatment has somewhat improved its prognosis. Long term continuous infusion of prostacyclin (epoprostenol) has been shown to improve physical capacity and to reduce mortality in primary and secondary pulmonary hypertension. It has been reported in adults that daily repetitive inhalation of iloprost, a prostacyclin analogue, seems also suitable for long term therapy of pulmonary hypertension. Repetitive inhalation of iloprost was administered to a 5 year old boy with severe primary pulmonary hypertension. He showed continuous clinical improvement without any side effects over the three years of treatment. This treatment may offer an alternative to continuous intravenous prostacyclin infusion and obviates the need for a permanent central venous catheter.

Acute symptomatic hyponatremia and cerebral salt wasting after head injury: an important clinical entity.

Hyponatremia is a well known complication of traumatic and nontraumatic cerebral injury, often related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Nonetheless, it also can be associated with a different entity, the syndrome of cerebral salt wasting (CSW). The authors report the case of a 4.5-year-old boy presenting with major head injury who at day 6 after admission had generalized tonic-clonic seizures caused by severe acute hyponatremia (serum sodium level, 119 mmol/L) and signs of dehydration. Despite initial isotonic rehydration, hyponatremia persisted because of excessive renal salt losses and concomitant enormous water losses, necessitating increasing amounts of sodium, up to 160 mmol/kg/d, and large amounts of intravenous fluids, up to 27 L/d. Highly increased levels of atrial natriuretic peptide (ANP) confirmed the diagnosis of CSW. The occurrence of a CSW has to be recognized early in the clinical course for adequate treatment and remains one of the important differential diagnosis of SIADH in hyponatremic states in patients with cerebral disorders, especially after head injury.

Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms.

BACKGROUND: Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. METHODS AND RESULTS: A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P:<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation (P:<0.05). CONCLUSIONS: In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Management of preterm infants with intracardiac thrombi: use of thrombolytic agents.

Improvement in neonatal care has led to improvements in survival and patient outcome in preterm infants; however, this improved survival has been associated with the development of secondary complications, such as catheter-associated intravascular and intracardiac thrombus formation with a non-negligible morbidity and mortality. The sick preterm infant is at high risk of catheter-related thrombus formation because of the combination of a high prothrombotic activity, low levels of natural anticoagulants, and various imbalances in the fibrinolytic systems. Based on clinical experience in adults and children, and several neonatal case reports demonstrating the efficacy and tolerability of specific thrombolytic treatment, this approach should be recommended as a first choice treatment in the premature infant with intracardiac or intravascular thrombosis. The thrombolytic agents of choice are urokinase or tissue plasminogen activator (tPA); however, none of them have proven to be superior to the other in terms of efficacy or tolerability, either in adult patients or premature infants. In the past, it has been suggested that newborn infants may require higher doses of thrombolytic agents than adults for effective systemic thrombolysis; however, based on more recent in vitro studies, it seems unlikely that this is true. Nevertheless, systemic (high dose) fibrinolysis is of concern as premature neonates present an increased risk of cerebral haemorrhage during the first weeks of life; therefore, low dose treatment has been proposed with, if possible, direct infusion of the fibrinolytic agent into, or close to, the thrombus. This approach has proven to be efficient and well tolerated in several small case series of newborn and preterm infants. Recommended doses are 1000 to 3000 U/kg/h for urokinase or 0.01 to 0.05 mg/kg/h for tPA. A systemic proteolytic state will not be induced by this low dose; however, specific monitoring of fibrinogen plasma levels has to be recommended. Fibrinogen levels should remain above 100 mg/dL during low dose treatment. Lower levels of fibrinogen will indicate the presence of an unwanted systemic fibrinolytic state. After successful thrombolysis, a follow-up treatment, preferentially with low-molecular-weight heparin for neonates at adjusted doses, should be instituted for at least 6 weeks in the absence of any persisting thrombophilic factor. A longer course (3 to 6 months) of anticoagulation therapy is recommended when thrombophilic factors (i.e. hereditary thrombophilia or central venous catheter still in place) are present. Furthermore, it is recommended that any neonate with thrombosis should be evaluated for hereditary thrombophilia later in life.

Hypothesis for generation of the unstable Hb Bucuresti (beta 42 Phe-->Leu) mutation.

INTRODUCTION: Unstable hemoglobin disorders are characterized by a congenital, mostly familial chronic hemolytic anemia with episodes of severe hemolysis during febrile illnesses. Usually, isopropanol and heat stability tests lead to the diagnosis which is confirmed by protein and gene sequencing. Generation of the mutations is still a subject of controversy. PATIENT, MATERIALS AND METHODS: We describe a 6-year-old Swiss child with congenital hemolytic anemia and a negative family history. Hemoglobin was studied by IEF, HPLC reverse phase chromatography, heat stability and isopropranol tests. DNA was sequenced in both coding and non-coding strands. RESULTS: An unstable Hb was diagnosed on the basis of positive heat stability and isopropranol tests. The TTT-->TTG mutation at codon 42 corresponding to a Phe-->Leu substitution was found on DNA sequencing. Paternity was confirmed indicating that we are dealing with a new mutation. CONCLUSION: So far, three different mutations at codon 42 of the beta-chain, and two at the corresponding position of the alpha-chain have been described, all leading to a hemolytic anemia. These mutations can either represent random phenomena occurring at an important location in the heme pocket, or may be secondary to the two highly homologous zones present in this region. These homologous zones may indicate a hot spot for point mutations created by abnormal crossing over or formation of loops, and an imperfect DNA repair process.

Lung recruitment and lung volume maintenance: a strategy for improving oxygenation and preventing lung injury during both conventional mechanical ventilation and high-frequency oscillation.

OBJECTIVE: To determine whether using a small tidal volume (5 ml/kg) ventilation following sustained inflation with positive endexpiratory pressure (PEEP) set above the critical closing pressure (CCP) allows oxygenation equally well and induces as little lung damage as high-frequency oscillation following sustained inflation with a continuous distending pressure (CDP) slightly above the CCP of the lung. MATERIAL AND METHODS: Twelve surfactant-depleted adult New Zealand rabbits were ventilated for 4 h after being randomly assigned to one of two groups: group 1, conventional mechanical ventilation, tidal volume 5 ml/kg, sustained inflation followed by PEEP > CCP; group 2, high-frequency oscillation, sustained inflation followed by CDP > CCP. RESULTS: In both groups oxygenation improved substantially after sustained inflation (P < 0.05) and remained stable over 4 h of ventilation without any differences between the groups. Histologically, both groups showed only little airway injury to bronchioles, alveolar ducts, and alveolar airspace, with no difference between the two groups. Myeloperoxidase content in homogenized lung tissue, as a marker of leukocyte infiltration, was equivalent in the two groups. CONCLUSIONS: We conclude that a volume recruitment strategy during small tidal volume ventilation and maintaining lung volumes above lung closing is as protective as that of high-frequency oscillation at similar lung volumes in this model of lung injury

First intention high-frequency oscillation with early lung volume optimization improves pulmonary outcome in very low birth weight infants with respiratory distress syndrome.

OBJECTIVES: The lack of decline in chronic lung disease of prematurity despite the generalized use of surfactant and alternative modes of ventilation such as high-frequency oscillation (HFO) has been attributed to some misunderstanding of how HFO has to be used. We used a new ventilatory strategy in very low birth weight (VLBW) infants, by initiating HFO immediately after intubation and attempting early lung volume optimization before surfactant was administered. STUDY DESIGN: The outcome of 32 VLBW infants, managed with first intention HFO over a period of 24 months (September 1, 1996 and August 31, 1998) was compared by chart review with 39 historical controls, consecutively managed with conventional mechanical ventilation (CMV) over a period of 24 months (January 1, 1994 and December 31, 1995). SETTING: An 11-bed tertiary care pediatric and neonatal intensive care unit of a university teaching hospital. RESULTS: The 2 groups of patients were similar in demographic distribution of birth weight, gestational age, race, and gender. Patients on first intention HFO were ventilator-dependent (median [95% confidence interval]: 5 [3-6] vs 14 [6-23] days) and oxygen-dependent (12 [4-17] vs 51 [20-60] days) for a shorter time than patients on CMV. The incidence of chronic lung disease at 36 weeks of gestational age was significantly lower in the HFO group compared with the CMV group (0% vs 34%). CONCLUSIONS: First intention HFO with early lung volume optimization shortened the need for respiratory support and improved pulmonary outcome of VLBW infants with respiratory distress syndrome significantly.