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Nick Evans

Publications and source records attributed to Nick Evans.

17 recordsLinked to original sources
PubMed2006

Assessment and support of the preterm circulation.

There are no clinical outcome data on which to base recommendations on how to assess and support the preterm circulation. Current standards are derived from an assumed proportionality between systemic and organ blood flow and mean blood pressure. Our study of central measures of systemic blood flow suggests preterm haemodynamics are more complex than this. Low systemic blood flow is common in the first 24 h after birth in very preterm babies and is not necessarily reflected by low blood pressure. The causes of this low systemic blood flow are complex but may relate to maladaptation to high extrauterine systemic (and sometimes pulmonary) vascular resistance. After day 1, hypotensive babies are more likely to have normal or high SBF reflecting vasodilatation. Empirically, inotropes that reduce afterload (such as dobutamine) may be more appropriate in the transitional period, while those with more vasoconstrictor actions (such as dopamine) may be more appropriate later on. Defining the haemodynamic in an individual baby needs both blood pressure and echocardiographic measures of systemic blood flow. Research in this area needs to move beyond just demonstrating changes in physiological variables to showing improvements in important clinical outcomes.

Blood Circulation↗
PubMed2006

Population pharmacokinetics and dosing regimen design of milrinone in preterm infants.

AIMS: To define the pharmacokinetics of milrinone in very preterm infants and determine an optimal dose regimen to prevent low systemic blood flow in the first 12 h after birth. METHODS: A prospective open-labelled, dose-escalation pharmacokinetic study was undertaken in two stages. In stage one, infants received milrinone at 0.25 microg/kg/min (n = 8) and 0.5 microg/kg/min (n = 11) infused from 3 to 24 h of age. Infants contributed 4-5 blood samples for concentration-time data which were analysed using a population modelling approach. A simulation study was used to explore the optimal dosing regimen to achieve target milrinone concentrations (180-300 ng/ml). This milrinone regimen was evaluated in stage two (n = 10). RESULTS: Infants (n = 29) born before 29 weeks gestation were enrolled. Milrinone pharmacokinetics were described using a one-compartment model with first-order elimination rate, with a population mean clearance (CV%) of 35 ml/h (24%) and volume of distribution of 512 ml (21%) and estimated half-life of 10 h. The 0.25 and 0.5 microg/kg/min dosage regimens did not achieve optimal milrinone concentration-time profiles to prevent early low systemic blood flow. Simulation studies predicted a loading infusion (0.75 microg/kg/min for 3 h) followed by maintenance infusion (0.2 microg/kg/min until 18 h of age) would provide an optimal milrinone concentration profile. This was confirmed in stage two of the study. CONCLUSION: Population pharmacokinetic modelling in the preterm infant has established an optimal dose regimen for milrinone that increases the likelihood of achieving therapeutic aims and highlights the importance of pharmacokinetic studies in neonatal clinical pharmacology.

Cardiovascular Diseases↗
PubMed2006

Pilot study of milrinone for low systemic blood flow in very preterm infants.

OBJECTIVES: To examine the hemodynamic effects of milrinone given prophylactically to very preterm infants at high risk of low superior vena cava (SVC) flow and to investigate the preliminary efficacy and safety of an optimal dose. STUDY DESIGN: This was a prospective, open-label study in two stages. The first involved dose escalation in two cohorts. Milrinone infusions of 0.25 microg/kg per minute (n = 8) and then 0.5 microg/kg per minute (n = 11) were administered from 3 to 24 hours of age. Population pharmacokinetic modeling was used to develop an optimized dose regimen. Ten infants then were loaded with 0.75 microg/kg per minute for 3 hours, followed by 0.2 microg/kg per minute maintenance until 18 hours of age. Infants were monitored for blood pressure, serial echocardiograms, and blood milrinone levels. The primary outcome was maintenance of SVC flow greater than 45 mL/kg per minute through the first 24 hours. RESULTS: Low SVC flow developed in 36% of babies at both 0.25 microg/kg per minute and 0.5 microg/kg per minute of milrinone. Blood levels on these two regimens were slow to reach the target range and accumulated above this range by 24 hours. At 0.75 to 0.2 microg/kg per minute, no infant had SVC flow below 45 mL/kg per minute, compared with 61% in historic control subjects. Four infants needed an additional inotrope to support blood pressure. Blood levels were within the target range in 9 of 10 babies. CONCLUSIONS: We used population pharmacokinetic modeling to develop an optimal dosing regimen for milrinone. The efficacy and safety in this novel preventative approach to circulatory support is encouraging but inconclusive. We do not recommend the use of milrinone in preterm infants outside a research setting.

Cardiac Output, Low↗
PubMed2005

Spectrophotometric determination of uranium with arsenazo-III in perchloric acid.

A short, sensitive and reliable spectrophotometric method, which has advantages over all known "wet chemistry" methods for uranium determination with regard to tolerance to common interferences, has been developed for the determination of uranium. Selectivity, molar absorptivity and the determination range of uranium have been enhanced by using 0.07% arsenazo-III as a chromogenic reagent. The use of 3 mol dm(-3) perchloric acid as a medium of determination was found to be excellent in terms of good solvent compatibility on dilution, destruction of organic contamination and simplicity of operation. The uranium-arsenazo-III complex formed instantly, and was found to be stable for more than 3 weeks with constant absorbance. Beer's law was obeyed up to a uranium concentration of 16 microg g(-1), with a molar absorptivity at 651 nm of 1.45x10(5) mol(-1) dm(3) cm(-1) at 24+/-2 degrees C. Only phosphate and citrate at 70-fold excess over uranium interfere seriously, whereas other anions studied could be tolerated up to a 70-fold excess over uranium. Of the cations studied, only Mn(II), Co(II), Ni(II), Cu(II) and Cr(III) decreased the normal absorbance of the complex. Iron(III), Ce(III) and Y(III) enhanced the absorbance. Other cations studied did not affect the absorbance up to a 50-fold excess. The accuracy was checked by determining uranium from standard solutions in the range 10-50 microg g(-1). It was found to be accurate with a 96.0-98.6% recovery rate. The method has been successfully applied to standard reference materials and ore samples at microg g(-1) levels.

Absorption↗
PubMed2004

Chronic postoperative endophthalmitis caused by Actinomyces neuii.

Uneventful phacoemulsification with implantation of a foldable, acrylic posterior chamber intraocular lens was performed in the right eye of a 73-year-old white man. Postoperatively, the patient developed a chronic, low-grade intraocular inflammation. Cultures from the aqueous specimen grew Actinomyces neuii, an unusual gram-positive bacillus. The low-grade intraocular inflammation persisted with intensive topical steroid-antibiotic medication and systemic antibiotics. A diagnostic, 3-port, pars plana vitrectomy was performed, and aqueous aspirate specimens were sent for culture and sensitivity and to look for abnormal cells. Intracameral antibiotics were not injected. The specimens were sterile to culture, and chronic inflammatory cells were reported on the vitreous specimen. On examination 6 months later, inflammation had not recurred and the best corrected visual acuity was 6/18.

Actinomyces↗
PubMed2004

Low superior vena cava flow and neurodevelopment at 3 years in very preterm infants.

OBJECTIVES: Low superior vena cava (SVC) flow is common in the first hours after very preterm birth and has a strong association with subsequent periventricular/intraventricular hemorrhage. We report the neurodevelopmental outcome at 3 years of age of very preterm babies who had serial echocardiographic studies, including measures of SVC flow, during the first 48 hours after birth. STUDY DESIGN: A prospective observational study was performed on a cohort of 126 babies (<30 weeks), 103 of whom survived to discharge. Neurodevelopmental follow-up data, which included abnormal developmental quotient, abnormal motor score, and cerebral palsy, were available for 93% of this cohort at 3 years of age. Relations between 3-year outcome and early hemodynamic measures and clinical parameters were explored. RESULTS: After controlling for confounding variables, average SVC flow over the first 24 hours of life was significantly associated with the primary outcome of death or survival with any disability (P=.004) and with the secondary outcome of abnormal developmental quotient (P = .006). A greater number of low SVC flow readings during the first 24 hours was significantly related to death and adverse developmental outcome, but the individual lowest SVC flow was not, suggesting the importance of duration of low SVC flow. After adjustment, there was no significant association between average mean blood pressure over the first 24 hours and abnormal developmental outcome, whereas the proportion of mean blood pressure readings less than the gestational age showed a trend toward an association with death and any disability. CONCLUSIONS: Low early postnatal blood flow to the upper body and brain may be one factor in the causal pathway of impaired preterm neurodevelopmental outcome.

Blood Pressure↗
PubMed2004

Severe neonatal toxoplasmosis after third trimester maternal infection.

We report an unusual case of neonatal toxoplasmosis. After a late third trimester maternal infection, the infant developed severe disseminated intravascular coagulopathy with thrombocytopenia, hepatitis, jaundice and severe pneumonitis. Clinicians that manage infants with severe unexplained systemic disease should consider the possibility of congenital toxoplasmosis.

Adult↗
PubMed2003

Do we practice evidence-based care in our neonatal intensive care units?

The RPA NICU has attempted to work as a team to provide consistent family centered care based on the best available evidence. This has been facilitated by a number of factors. The RPA NICU is in an academic institution with most staff involved in teaching and research and clinical care. All of the consultant neonatologists have research degrees, a factor associated with the use of evidence in practice. A key factor is the collaborative effort among consultant neonatologists with an agreement that consistent care is important. Staff buy-in is important for consistent approaches to care 24 hours a day at every bedside when there are rotating house staff and nurses. A team effort involving both physicians and nurses is particularly important in this regard. Difficulties do arise when there is insufficient evidence to inform practice in acute care settings. When treating seriously ill newborns, pressure from anxious staff and parents to "do something" is great. It is tempting to introduce new high-technology treatments, such as high-frequency oscillatory ventilation or extracorporeal membrane oxygenation, before their usefulness has been established. In these situations, a clear distinction is required between practice and research. Where possible, new treatments should be evaluated within a scientific framework so as to add new knowledge about the clinical intervention. It is difficult (although not necessarily impossible) to discontinue a practice that has been in routine use despite a lack of evidence. Management of hyperbilirubinemia in term and preterm infants is a good example. Replacing competition with collaboration and consensus among staff and agreeing to a broad framework for systematic evaluation, implementation, and evaluation of evidence in patient-centered care should allow the authors' center and others to improve patient outcomes in the short term and promote better clinical research to improve outcomes in the future.

Biomedical Research↗
PubMed2003

Volume expansion during neonatal intensive care: do we know what we are doing?

Although volume expansion is liberally used in newborn intensive care, we know little about its effects on hemodynamics or outcomes. Given appropriately to a truly hypovolemic baby, it can be life-saving, but the clinical diagnosis of hypovolemia is probably very inaccurate. We know that volume expansion has less effect on blood pressure than dopamine, and although it seems to produce immediate increases in systemic blood flow, we do not know for how long these increases are sustained. There is evidence to show that the routine use of volume expansion in preterm babies has no effect on outcome, and there is little evidence to support its routine use during resuscitation or the treatment of metabolic acidosis. Whether crystalloids or colloids are preferable is also unclear in newborns. In situations of concern related to circulatory compromise, if possible, define the hemodynamics echocardiographically. Otherwise, if in doubt, some volume should be given, although it is probably unwise to keep expanding the volume if this is not improving physiologic (blood pressure and heart rate) or echocardiographic systemic blood flow parameters.

Blood Pressure↗
PubMed2003

Current controversies in the diagnosis and treatment of patent ductus arteriosus in preterm infants.

This article presents common misconceptions about the physiologic significance of early ductal shunting and reviews the evidence regarding the preferential use of echocardiography rather than reliance on clinical signs to diagnose patent ductus arteriosus. The rationale for the treatment of symptomatic versus presymptomatic versus prophylactic is compared and contrasted. Finally, a novel but untested treatment approach, using early echocardiographic findings to direct treatment decisions, is proposed as a direction for future research.

Atrial Function, Left↗
PubMed2003

Randomized trial of high-frequency oscillatory ventilation versus conventional ventilation: effect on systemic blood flow in very preterm infants.

OBJECTIVE: Low superior vena cava (SVC) flow is common in very preterm infants in the first day and strongly associated with periventricular hemorrhage and disability. We examined the effect of high-frequency oscillatory ventilation (HFOV) compared with conventional ventilation (CV) on SVC flow and right ventricular output. METHODS: Forty-five infants <29 weeks were randomized before 1 hour of age to HFOV or CV. Echocardiography was performed on 43 infants at 3, 10, and 24 hours of age. Infants with low SVC flow (<50 mL/kg/min) or hypotension (mean blood pressure < or =20) were treated with volume and inotrope. RESULTS: Infants allocated to HFOV (n=23) and to CV (n=20) were well matched. There was a nonsignificant trend toward more infants on HFOV having SVC flow <50 mL/kg/min (48% vs 20%) and receiving volume and inotropes (61% vs 40%). There were no significant differences in mean SVC flow or right ventricular output at 3, 10, or 24 hours. Infants on HFOV had a significantly higher calculated upper body vascular resistance at 10 hours and mean blood pressure at 24 hours. CONCLUSIONS: There were no significant adverse effects of HFOV on systemic blood flow in very preterm infants during the first 24 hours of life.

Blood Circulation↗
PubMed2003

Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants.

OBJECTIVES: To determine hemodynamic and antecedent risk factors for early and late periventricular/intraventricular hemorrhage (P/IVH) in premature infants. METHODS: Two prospective cohort studies of 126 (1995-1996) and 128 (1998-1999) infants born <30 weeks' gestation. Head ultrasounds were performed at <6 hours of age, and at 7 and 28 days of age. P/IVH was classified as early (present on initial scan) and late (developed subsequently). Echocardiographic measurement of the superior vena cava (SVC) flow was performed at <6, 10, and 24 hours of age. RESULTS: Infants with early P/IVH were significantly more likely to be born by vaginal delivery in both cohorts (1995-1996 adjusted odds ratios [OR]: 13.29; 1998-1999 adjusted OR: 18.15). An association with a 1-minute Apgar < or =4 was only significant in the 1998-1999 cohort (adjusted OR: 9.14). Low SVC flow was the only independent risk factor for late P/IVH in both cohorts (1995-1996 adjusted OR: 20.39; 1998-1999 adjusted OR: 5.16). Adjusted for perinatal risk factors, low SVC flow was associated with lower gestation and higher average mean airway pressure in both cohorts, and with a large diameter ductus diameter only in the 1995-1996 cohort. CONCLUSIONS: Early and late P/IVH have distinct and different risk factors. Early P/IVH is associated with vaginal delivery and possibly low Apgar scores. Late P/IVH is associated with antecedent low SVC flow in the first day.

Age of Onset↗
PubMed2002

Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow.

OBJECTIVE: Our purpose was to determine if dobutamine or dopamine results in greater improvements in systemic blood flow in very preterm infants with low flow during the first 24 hours of life. STUDY DESIGN: A 2-center, randomized, double-blind study. Infants (n = 42) with low superior vena cava (SVC) flow (<41 mL/kg/min) in the first 12 hours were randomly assigned to receive 10 mL/kg normal saline solution, followed by 10 microg/kg/minute of dobutamine or dopamine. If low flow persisted or recurred, the inotrope was increased to 20 microg/kg/minute, with crossover to the other inotrope if treatment failed to maintain flow. RESULTS: Volume produced a more significant increase in SVC flow than dopamine (+43%). At the highest dose, dobutamine resulted in a significantly greater increase in SVC flow than dopamine (mean, +9.9 vs -3.2 mL/kg/min, P =.02). Dopamine resulted in a significantly greater increase in blood pressure. Infants receiving dobutamine only at 24 hours had a greater right ventricular output than infants receiving dopamine (mean, 295 vs 167 mL/kg/min, P <.001). Forty percent failed to increase or maintain SVC flow in response to either inotrope. No significant differences in mortality or morbidity were found. CONCLUSIONS: Dobutamine produced a greater increase in blood flow than dopamine.

Blood Circulation↗
PubMedDate not supplied

Aortic wall thickness in newborns with intrauterine growth restriction.

Much epidemiological evidence has linked low birthweight with late cardiovascular risk. We measured aortic wall thickness (a marker of early atherosclerosis) by ultrasonography in 25 newborn babies with intrauterine growth restriction and 25 with normal birthweight. Maximum aortic thicknesses were significantly higher in the babies with intrauterine growth restriction (810 microm [SD 113]) than in those without (743 microm [76], p=0.02), more so after adjustment for birthweight (300 microm/kg [45] vs 199 microm/kg [29], p<0.0001). Newborn babies with growth restriction have significant aortic thickening, suggesting that prenatal events might predispose to later cardiovascular risk.

Aorta, Abdominal↗