Patrick Pladys

Role of brain and peripheral angiotensin II in hypertension and altered arterial baroreflex programmed during fetal life in rat.

Intrauterine programming of hypertension is associated with evidence of increased renin-angiotensin system (RAS) activity. The current study was undertaken to investigate whether arterial baroreflex and blood pressure variability are altered in a model of in utero programming of hypertension secondary to isocaloric protein deprivation and whether activation of the RAS plays a role in this alteration. Pregnant Wistar rats were fed a normal-protein (18%) or low-protein (9%) diet during gestation, which had no effect on litter size, birth weight, or pup survival. Mean arterial blood pressure (MABP; 126 ± 3 mm Hg 9%versus 108 ± 4 mm Hg 18%; p < 0.05) and blood pressure variability were significantly greater in the adult offspring of the 9% protein–fed mothers. Arterial baroreflex control of heart rate, generated by graded i.v. infusion of phenylephrine and nitroprusside, was significantly shifted toward higher pressure; i.v. angiotensin-converting enzyme inhibitor normalized MABP and shifted the arterial baroreflex curve of the 9% offspring toward lower pressure without affecting the 18% offspring. For examining whether brain RAS is also involved in programming of hypertension, angiotensin-converting enzyme inhibitor and losartan (specific AT1 receptor antagonist) were administered intracerebroventricularly; both significantly reduced MABP of the 9% but not the 18% offspring. Autoradiographic receptor binding studies demonstrated an increase in brain AT1 expression in the subfornical organ and the vascular organ of the lamina terminalis in the 9% offspring. These data demonstrate a major tonic role of brain and peripheral RAS on hypertension associated with antenatal nutrient deprivation.

Effects of volume expansion on cardiac output in the preterm infant

Clinical and echocardiography haemodynamic evaluations of response to volume expansion are described in 12 preterm neonates aged < 7days presenting without cardiac dysfunction and with a low cardiac output. They received 10% albumin solution (20 ml kg‐1) for 3h. Measurements were made before infusion, at volumes 5, 12. 5 and 20 ml kg‐1 and 1 h later. All infants increased significantly their cardiac output (CO) (from a median of 177 to 283 ml kg‐1 min‐1). The rise of CO decreased with the volume infused. The index of systemic vascular resistance (SVR = ratio of mean arterial pressure to the CO) decreased for the six patients without PDA (from 272 to 193 mmHg 1‐1 kg‐1 min‐1, p < 0. 05) showing that the hypovolemic preterm infant is able to shut down peripherally in response to hypovolemia. The four hypotensive infants responded by increasing mean arterial blood pressure (from 29 to 44 mmHg). Cutaneous refilling time decreased during infusion (from 6. 7 to 3. 8 s, p < 0. 01). One infant had an haemodynamically significant ductus arteriosus revealed by volume expansion, another one developed myocardial dysfunction.

Therapeutic guidelines for prescribing antibiotics in neonates should be evidence-based: a French national survey

Objective This survey aims to describe and analyse the dosage regimens of antibiotics in French neonatal intensive care units (NICUs). Methods Senior doctors from 56 French NICUs were contacted by telephone and/or email to provide their local guidelines for antibiotic therapy. Results 44 (79%) NICUs agreed to participate in this survey. In total, 444 dosage regimens were identified in French NICUs for 41 antibiotics. The number of different dosage regimens varied from 1 to 32 per drug (mean 9, SD 7.8). 37% of intravenous dosage regimens used a unique mg/kg dose from preterm to full-term neonates. Doses and/or dosing intervals varied significantly for 12 antibiotics (amikacin, gentamicin, netilmicin, tobramycin, vancomycin administered as continuous infusion, ceftazidime, cloxacillin, oxacillin, penicillin G, imipenem/cilastatin, clindamycin and metronidazole). Among these antibiotics, 6 were used in more than 70% of local guidelines and had significant variations in (1) maintenance daily doses for amikacin, imipenem/cilastatin, ceftazidime and metronidazole; (2) loading doses for continuous infusion of vancomycin; and (3) dosing intervals for gentamicin and amikacin. Conclusions A considerable inter-centre variability of dosage regimens of antibiotics exists in French NICUs. Developmental pharmacokinetic–pharmacodynamic studies are essential for the evaluation of antibiotics in order to establish evidence-based dosage regimens for effective and safe administration in neonates.

Patent ductus arteriosus and cystic periventricular leucomalacia in preterm infants

Aim: To test the association between early disturbances in hemodynamics induced by left‐to‐right shunting through the duct and cystic periventricular leucomalacia. Patients: Forty‐six preterm infants (27–32 wk) admitted to the neonatal intensive care unit with risk criteria. Methods: Patent ductus arteriosus was evaluated on days 1 and 4, and was significant (sPDA) in cases of absent or reversed end diastolic flow in the subductal aorta. Resistance index was measured in the anterior cerebral artery and in the subductal aorta. Main outcome: Diagnosis of cystic periventricular leucomalacia between day 10 and day 50. Results: The 12 infants who developed cystic periventricular leucomalacia were compared with those who did not. On day 1, sPDA was more frequent (64% vs 26%; p= 0.03) in the cystic periventricular leucomalacia group, left ventricular output was higher (median = 341 vs 279mlkg‐1.min‐1; p= 0.005), and rescue surfactant was more frequently used (83% vs 47%; p= 0.03). This latter association was confirmed by multivariate analysis. Resistance index in the anterior cerebral artery was increased in cases of significant patent ductus arteriosus (p < 0.01) and was correlated with resistance index in the subductal aorta.

Capillary refilling time and hemodynamics in neonates: a Doppler echocardiographic evaluation.

OBJECTIVE To evaluate the correlation of the capillary refilling time measured in neonates with the hemodynamic parameters obtained by Doppler echocardiography. DESIGN Prospective study. SETTING Neonatal intensive care unit (ICU) in a university hospital. PATIENTS Neonates without congenital cardiac disease admitted to the neonatal ICU (n = 100). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The clinical parameters obtained were: heart rate; blood pressure; mean airway pressure; cutaneous temperature; and capillary refilling time. The echocardiographic data included the measurement of aortic diameter, left atrial diameter, and shortening fraction. Pulsed-Doppler echocardiography was used to measure flow velocity values in the ascending aorta, in the pulmonary artery trunk, and in the patent ductus arteriosus. Cardiac index was calculated secondarily from the volumetric equation, including measured flow velocity in the ascending aorta, aortic diameter, and body weight. Shunt severity at this level was measured by analysis of the descending aortic flow. Thereafter, three groups were defined for analysis: group 1 with obliterated ductus arteriosus; group 2 with patent ductus arteriosus without a retrograde flow in the subdiaphragmatic aorta; and group 3 with patent ductus arteriosus and a retrograde flow in the subdiaphragmatic aorta. There was no correlation between the capillary refilling time and the following parameters: shortening fraction; mean airway pressure; body weight; left atrial diameter/ aortic diameter ratio; blood pressure; and heart rate. In group 1, the capillary refilling time was significantly linked to cardiac index (r2 = .54, p < .001). A lower correlation coefficient between capillary refilling time and cardiac index was found in groups 2 (r2 =.31, p < .001) and 3 (r2 =.41, p < .001). CONCLUSION The capillary refilling time was significantly linked to cardiac index in neonates.

Intracranial epidural hematoma in newborn infants: clinical study of 15 cases.

OBJECTIVE:Epidural hematoma (EDH) in newborn infants is rare. We have described the history of 15 newborns with EDH to provide a better understanding of this pathology. METHODS:This is a descriptive case series study using a retrospective review of the medical records of newborns who were admitted to the Pediatric Intensive Care Unit and Neurosurgery Department with the diagnosis of birth EDH over a 24-year period (1979–2002). RESULTS:There was no sex predominance, and most of the mothers were young, nulliparous women. The time latency from birth to the first signs varied from 0 to 24 hours. Clinical presentation was nonspecific: seizures and hypotonia were the main symptoms. The parietal area was the most frequent location. Surgical drainage was required in nine patients, and no deaths were reported. CONCLUSION:This report highlights the clinicoradiological characteristics of newborn EDH, which occurs more frequently in newborns that experienced difficult delivery from a nulliparous mother. Surgery is not a rule; some patients can be managed with conservative treatment. The outcome is generally good.

The relationship between expired concentration of sevoflurane and sympathovagal tone in children.

In children, sevoflurane depresses parasympathetic tone during induction more than halothane. The effects of sevoflurane on parasympathetic activity could explain the difference in heart rate (HR) changes described between infants and children. In this study, we sought to determine the relationship between the end-tidal concentration of sevoflurane and sympathetic and parasympathetic tone in children by spectral analysis of RR intervals. Thirty-three children, ASA physical status I, who required elective surgery were studied. In 10 children (Group A), recordings were performed while gradually decreasing the inspired sevoflurane concentration from 8% to the beginning of clinical awakening. In 23 other children (Group B), recordings were performed while children were awake and at a steady-state of 1 and 2 minimum alveolar anesthetic concentration of sevoflurane. A time-varying autoregressive modeling of the interpolated RR sequences was performed, and spectral density in low-frequency (LF; 0.04–0.15 Hz) and high-frequency (HF; 0.15–0.55 Hz) bands was calculated. In Group A, HR slowing paralleled the decrease in expired sevoflurane concentration. Conversely, the decrease in expired concentration of sevoflurane led to an increase in systolic blood pressure (SBP), HF, LF, and LF/HF. The increase in LF/HF preceded the increase in HF. In Group B, the baseline HF power spectrum and normalized values HFnu (HFnu = HF/LF + HF) were significantly increased in children older than 3 yr. Changes in HR induced by sevoflurane were negatively correlated with baseline HF and HFnu (R2 = 0.6; P < 0.001). These results demonstrate that withdrawal of parasympathetic tone is the main determinant for the change in HR induced by sevoflurane.

Uncorrelated Randomness of the Heart Rate Is Associated with Sepsis in Sick Premature Infants

Background: Late-onset sepsis in the premature infant is frequently revealed by severe, unusual and recurrent bradycardias. In view of the high morbidity and mortality associated with infection, reliable markers are needed. Objectives: It was the aim of this study to determine if heart rate (HR) behavior may help the diagnosis of infection in premature infants with such cardiac decelerations. Methods: Electrocardiogram recordings were collected in 51 premature infants with a postmenstrual age <33 weeks with frequent bradycardias. Newborns in the sepsis group (C-reactive protein increase and positive blood culture) were compared with a no-sepsis group (C-reactive protein <5 mg/l before and 24 h after recording and negative blood cultures) for their HR characteristics, i.e. RR series distribution (mean, median, skewness, kurtosis, sample asymmetry), magnitude of variability in time and frequency domain, fractal exponents (α1, α2) and complexity measurements (approximate and sample entropy). Results are presented as the median (25%, 75%). Results: Gestational, chronological and postmenstrual age and gender were similar in the sepsis (n = 10) and no-sepsis group (n = 38). Three infants had an increase in C-reactive protein but negative cultures. Low entropy measurements [approximate entropy 0.4 (0.3, 0.5) vs. 0.8 (0.6, 1); p < 0.001] and long-range fractal exponent [α2 0.78 (0.71, 0.83) vs. 0.92 (0.8, 1.1); p < 0.05] were significantly associated with sepsis. No other HR characteristic was associated with sepsis. The decrease in 0.1 units of approximate entropy was associated with an over 2-fold increase in the odds of sepsis. Conclusion: Late-onset sepsis is associated with uncorrelated randomness of the HR. This abnormal HR behavior may help to monitor premature infants presenting with frequent and severe bradycardias.

Perinatal morbidity and mortality in twin pregnancies with dichorionic placentas following assisted reproductive techniques or ovarian induction alone: a comparative study

OBJECTIVE To compare maternal and perinatal outcome in non-spontaneously and spontaneously conceived dichorionic twin pregnancies. STUDY DESIGN We report a retrospective study of all 350 twin pregnancies delivered ≥22 weeks of gestation between January 1, 2001 and December 31, 2005 in a tertiary maternity unit. We compared maternal outcome, perinatal morbidity and neonatal mortality between spontaneous and non-spontaneous dichorionic twin pregnancies, with a subgroup analysis separating pregnancies following assisted reproduction technology (ART group) from those following ovarian induction alone (OI group). Generalized linear model and multivariate analysis were performed. RESULTS The proportion of primiparous women and the mean maternal age were higher in the non-spontaneously conceived dichorionic twin pregnancy group as expected (70.2% vs. 38.2%, p<0.001 and 32.1 ± 3.8 vs. 30.7 ± 4.6 years, p<0.01). Multivariate analysis, adjusted for maternal age and parity, revealed that non-spontaneously conceived dichorionic twin pregnancies were associated with a higher risk of very preterm birth (OR 2.20, 95% confidence interval 1.02-4.77, p<0.05), low birth weight (1.77, 1.21-2.61, p<0.01), very low birth weight (1.99, 1.13-3.49, p<0.05), NICU admission (1.66, 1.14-2.43, p<0.01), and fetal or neonatal death (3.21, 1.30-7.95, p<0.05). Multivariate analysis confirmed that the mean gestational age (p<0.01) and mean birth weight of the first (p<0.05) and second twins (p<0.01) were lower in the non-spontaneously conceived dichorionic twin pregnancy group. These associations were confirmed in the OI group analysis (n=39) but not in the ART group (n=65). Ovarian induction was associated with an increase in the risk of preterm and very preterm births (2.25, 1.06-4.75, p<0.05 and 3.47, 1.42-8.49, p<0.01, respectively), low and very low birth weights (2.87, 1.63-5.05, p<0.001 and 2.59, 1.33-5.07, p<0.01, respectively), NICU admission (2.92, 1.67-5.11, p<0.001) and fetal or neonatal death (4.20, 1.40-12.56, p<0.05). The mean gestational age (p<0.001) and mean birth weight of the first (p<0.01) and second twins (p<0.001) were also lower in the OI group. CONCLUSIONS Twin pregnancies with dichorionic placentation following non-spontaneously conceived pregnancy are associated with a higher risk of adverse perinatal outcome compared with dichorionic spontaneously conceived twin pregnancies especially in case of ovarian induction alone.

Doppler ultrasound assessment of the effects of ketamine on neonatal cerebral circulation.

The effects of a single dose of 5 mg.kg-1 of ketamine administered intravenously to 10 critically ill preterm infants prior to epicutaneo-caval catheterization were analyzed using pulsed-wave Doppler ultrasound. The infants weighed between 670 and 1,885 g and their gestational ages ranged from 26 to 33 weeks. Arterial pressure (MAP), cardiac output (CO), transcutaneous oxygen pressure (TcPO2), transcutaneous carbon dioxide pressure (TcPCO2), end-diastolic velocity (EDV), peak systolic velocity (PSV), mean arterial velocity (MAV) of the cerebral anterior artery as well as Pourcelots resistance index (PRI) were measured before and after injection of the drug. We observed a significant decrease in arterial pressure at 2 min after injection while heart rate and CO did not vary significantly. TcPO2 and TcPCO2, also remained unchanged throughout the period of measurement. EDV, PSV, and MAV did not vary significantly nor did PRI. As this drug provides major comfort to the baby during painful procedures and considerably facilitates difficult thin vessel catheterization, we believe that it may be used in such conditions.