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Biomedical subjects

K J Barrington

Publications and source records attributed to K J Barrington.

At least 19 recordsLinked to original sources
PubMed2006

Nitric oxide for respiratory failure in infants born at or near term.

BACKGROUND: Nitric oxide is a major endogenous regulator of vascular tone. Inhaled nitric oxide gas has been investigated as a treatment for persistent pulmonary hypertension of the newborn. OBJECTIVES: To determine whether treatment of hypoxaemic term and near-term newborn infants with inhaled nitric oxide (iNO) improves oxygenation and reduces the rates of death, the requirement for extracorporeal membrane oxygenation (ECMO), or affects long term neurodevelopmental outcomes. SEARCH STRATEGY: Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information. SELECTION CRITERIA: Randomized and quasi-randomized studies of inhaled nitric oxide in term and near term infants with hypoxic respiratory failure. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation. DATA COLLECTION AND ANALYSIS: Trial reports were analysed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. Results of mortality, oxygenation, short term clinical outcomes (particularly need for ECMO), and long term developmental outcomes were tabulated. STATISTICS: For categorical outcomes, typical estimates for relative risk and risk difference were calculated. For continuous variables, typical estimates for weighted mean difference were calculated. 95% confidence intervals were used. A fixed effect model was assumed for meta-analysis. MAIN RESULTS: Fourteen eligible randomized controlled studies were found in term and near term infants with hypoxia. Seven of the trials compared iNO to control (placebo or standard care without iNO) in infants with moderate or severe severity of illness scores. Four of the trials compared iNO to control, but allowed back up treatment with iNO if the infants continued to satisfy the same criteria for severity of illness after a defined period of time. Two trials enrolled infants with moderate severity of illness score (OI or AaDO2) and randomized to immediate iNO treatment or iNO treatment only if they deteriorated to more severe criteria. One trial studied only infants with congenital diaphragmatic hernia (Ninos 1997), and one trial enrolled both preterm and term infants (Mercier 1998), but reported the majority of the results separately for the two groups. Inhaled nitric oxide appears to improve outcome in hypoxaemic term and near term infants by reducing the incidence of the combined endpoint of death or need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced. Oxygenation improves in approximately 50% of infants receiving nitric oxide. The Oxygenation Index decreases by a (weighted) mean of 15.1 within 30 to 60 minutes after commencing therapy and PaO2 increases by a mean of 53 mmHg. Whether infants have clear echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN) or not does not appear to affect outcome. The outcome of infants with diaphragmatic hernia was not improved; indeed there is a suggestion that outcome was slightly worsened. The incidence of disability, incidence of deafness and infant development scores are all similar between tested survivors who received nitric oxide or not. AUTHORS' CONCLUSIONS: On the evidence presently available, it appears reasonable to use inhaled nitric oxide in an initial concentration of 20 ppm for term and near term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.

Administration, Inhalation↗
PubMed2006

Diagnostic criteria and therapeutic interventions for the hypotensive very low birth weight infant.

INTRODUCTION: The diagnosis and management of hypotension in the very low birth weight (VLBW) is a controversial area. OBJECTIVE: To establish if there is any consensus in the diagnostic criteria and therapeutic interventions in the hypotensive VLBW among neonatologists in Canada. METHODS: A postal questionnaire was sent to neonatologists in all level II and III neonatal intensive care units throughout Canada. RESULTS: In total, 120 questionnaires were sent. Ninety-five completed questionnaires were returned. Seventy-six percent of respondents work in units where at least 50 VLBWs and 43% where at least 100 VLBWs are cared for annually. Fifty-seven percent of the respondents have at least 10 years experience as practicing neonatologists. 25.8% rely on blood pressure values alone when intervening, the most common being a blood pressure less than gestational age in weeks. Ninety-seven percent of respondents commence therapy with a fluid bolus. Normal saline is the predominant volume administered (95%). Dopamine remains the pressor of choice. Great variation exists in starting doses and total amount administered. Similar variation exists with epinephrine, with tenfold differences in starting doses (0.01-0.1 mcg/kg/min) and tenfold differences in maximum dose (0.4-4 mc/kg/min) administered. Steroid doses used ranged from 0.1 mg/kg/dose of hydrocortisone to 5 mg/kg/dose. Bicarbonate is rarely used. Three predominant therapeutic regimes exist. These include (i) volume followed by dopamine then a steroid (32%), (ii) volume, dopamine, dobutamine (29%), (iii) volume, dopamine, epinephrine (22%). CONCLUSION: This is the first large study of practices among neonatologists addressing hypotension in the VLBW infant. There is wide variation in practice, which is a reflection of the lack of good evidence currently available for this very common problem.

Blood Pressure↗
PubMed2006

Facilitation of neonatal endotracheal intubation with mivacurium and fentanyl in the neonatal intensive care unit.

BACKGROUND: Endotracheal intubation in the neonate is painful and is associated with adverse physiological effects. Some premedication regimens have been shown to reduce these effects, but the optimal regimen is not yet determined. METHOD: Data on semi-elective intubations were prospectively collected in the neonatal intensive care unit over a six month period. Patients received 20 microg/kg atropine, 200 microg/kg mivacurium (a non-depolarising muscle relaxant) followed by 5 microg/kg fentanyl. RESULTS: Thirty three patients were electively intubated during this time period. The primary reason for intubation was surfactant administration (53%). Median (range) birth weight, gestational age, and age at intubation were 1360 g (675-4200), 29 weeks (25-38), and 33 hours (1-624) respectively. Twenty two of the infants were intubated on the first attempt. Median duration from initial insertion of the laryngoscope to successful intubation was 60 seconds (15 seconds to 20 minutes). In 18 cases, the first attempt was by a trainee with no previous successful intubation experience, 10 of whom intubated within two attempts. Muscle relaxation occurred at a mean (SD) of 94 (51) seconds, and mean (range) time to return of spontaneous movements was 937 seconds (480-1800). Intubation conditions were scored as excellent using a validated intubation scale. CONCLUSION: Effective analgesia can be administered and intubation performed with some brief desaturations, even when junior personnel are being taught their first intubation. In this first report of mivacurium for intubation in the newborn, effective bag and mask ventilation was easily achieved during muscle relaxation and was associated with excellent intubation conditions, permitting a high success rate for inexperienced personnel.

Analgesics, Opioid↗
PubMed2006

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn infants (< 35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular haemorrhage, or neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2005. In addition, we searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Randomised and quasi randomised studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide compared to control with or without placebo. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular haemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Seven randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia (Subhedar 1997). One study studied routine use of inhaled NO in all ventilated preterm infants (Schreiber 2003). The remaining studies consisted of infants with high predicted mortality based on poor oxygenation (Kinsella 1999; Hascoet 2005; INNOVO 2005; Van Meurs 2005; Mercier 1999). No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. There was no evidence of effect on the risk of intraventricular haemorrhage. There may be short term improvements in oxygenation. Two studies (Schreiber 2003; INNOVO 2005) have so far presented data on long term neurodevelopmental outcome, one of which demonstrated improved outcome at two years corrected age. AUTHORS' CONCLUSIONS: The currently published evidence from randomised trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. Further studies may need to be performed to evaluate the potential benefit of routine use of this therapy in infants with milder forms of respiratory failure, and these trials will need to be designed to evaluate not only neonatal survival, and the occurrence of neonatal morbidities, but should be powered to evaluate neurodevelopmental outcome at a minimum of two years of age.

Administration, Inhalation↗
PubMed2001

The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets.

BACKGROUND: The most appropriate inotropic agent for use in the newborn is uncertain. Dopamine and epinephrine are commonly used, but have unknown effects during hypoxia and pulmonary hypertension; the effects on the splanchnic circulation, in particular, are unclear. METHODS: The effects on the systemic, pulmonary, hepatic, and mesenteric circulations of infusions of dopamine and epinephrine (adrenaline) were compared in 17 newborn piglets. Three groups [control (n = 5), dopamine (n = 6) and epinephrine (n = 6)] of fentanyl anesthetized newborn piglets were instrumented to measure cardiac index (CI), hepatic arterial and portal venous blood flow, mean systemic arterial pressure (SAP), mean pulmonary arterial pressure (PAP), and arterial, portal and mixed venous oxygen saturations. Systemic, pulmonary, and mesenteric vascular resistance indices [systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), mesenteric vascular resistance index (MVRI)], and systemic and splanchnic oxygen extraction and consumption were calculated. Alveolar hypoxia was induced, with arterial oxygen saturation being maintained at 55-65%. After 1 h of stabilization during hypoxia, each animal received either dopamine or epinephrine; randomly administered doses of 2, 10, and 32 microg kg-1 min-1 and 0.2, 1.0, and 3.2 microg kg-1 min-1 respectively were infused for 1 h at each dose. Results were compared with the 1 h hypoxia values by two-way analysis of variance. RESULTS: Epinephrine increased CI at all doses, with no significant effects on SAP and SVRI. Although epinephrine increased PAP at 3.2 microg kg-1min-1, it had no effect on PVRI. Dopamine had no effect on CI, SAP, and SVRI, but increased PAP at all doses and PVRI at 32 microg kg-1min-1. The SAP/PAP ratio was decreased with 32 microg kg-1min-1 dopamine, whereas epinephrine did not affect the ratio. In the mesenteric circulation, dopamine at 32 microg kg-1 min-1 increased portal venous flow and total hepatic blood flow and oxygen delivery, and decreased MVRI; epinephrine had no effect on these variables. Epinephrine increased hepatic arterial flow at 0.2 microg kg-1 min-1; dopamine had no effect on hepatic arterial flow at any dose. Despite these hemodynamic changes, there were no differences in systemic or splanchnic oxygen extraction or consumption at any dose of dopamine or epinephrine. CONCLUSIONS: Epinephrine is more effective than dopamine at increasing cardiac output during hypoxia in this model. Although epinephrine preserves the SAP/PAP ratio, dopamine shows preferential pulmonary vasoconstriction, which might be detrimental if it also occurs during the management of infants with persistent fetal circulation. Dopamine, but not epinephrine, increases portal flow and total hepatic flow during hypoxia.

Animals↗
PubMed2001

The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs.

BACKGROUND: Recent reports have raised concerns that postnatal steroids may cause neuro-developmental impairment in preterm infants. This systematic review was performed with the objective of determining whether glucocorticoid therapy, to prevent or treat bronchopulmonary dysplasia, impairs neuro-developmental outcomes in preterm infants. METHOD: A systematic review of the literature was performed. Medline was searched and articles retrieved using predefined criteria. Data from randomized controlled trials with adequate neuro-developmental follow up (to at least one year) were entered into a meta-analysis to determine the effects of postnatal treatment of preterm infants with glucocorticoids. Cerebral palsy rates, and neuro-developmental impairment (developmental score more than 2SD below the mean, or cerebral palsy or blindness) were analyzed. The studies were divided into 2 groups according to the extent of contamination of the results by treatment of controls with steroids after the initial study period, those with less than 30% contamination, and those with more than 30% contamination or size of contamination not reported. RESULTS: Postnatal steroid therapy is associated with an increase in cerebral palsy and neuro-developmental impairment. The studies with less contamination show a greater effect of the steroids, consistent with a real direct toxic effect of steroids on the developing central nervous system. The typical relative risk for the development of cerebral palsy derived from studies with less than 30% contamination is 2.86 (95% CI 1.95, 4.19). The typical relative risk for the development of neuro-developmental disability among followed up infants from studies with less than 30% contamination is 1.66 (95% CI 1.26, 2.19). From this subgroup of studies, the number of premature infants who need to be treated to have one more infant with cerebral palsy (number needed to harm, NNH) is 7; to have one more infant with neuro-developmental impairment the NNH is 11. CONCLUSIONS: Postnatal pharmacologic steroid treatment for prevention or treatment of bronchopulmonary dysplasia is associated with dramatic increases in neuro-developmental impairment. As there is no clear evidence in the literature of long term benefit, their use for this indication should be abandoned.

Adrenal Cortex Hormones↗
PubMed2001

Sequential analysis for quality control in the neonatal intensive care unit.

OBJECTIVE: This article describes a novel application of a statistical technique for continuous quality assurance in the NICU. METHODS: We used prospective analysis of rates of survival to 28 days of life, without major IVH in ELBW infants in a single tertiary NICU, before and after the introduction of an evidence-based treatment protocol. By using the CUSUM function, each infant's results were sequentially plotted, and significant changes in outcomes were noted when the plot crossed predetermined boundary lines. RESULTS: Significant changes in outcomes were evident with this method sooner than traditional analyses on the basis of year-end or other arbitrary intervals. The introduction of the ELBW protocol was temporally associated with significant improvement in intact short-term survival. CONCLUSION: Sequential analysis techniques are useful tools for ongoing quality assurance; deviations in outcomes may be detected more quickly, which should assist in the identification of improvements or decrements in performance of the NICU.

Data Interpretation, Statistical↗
PubMed2001

TBC3711, an ET(A) receptor antagonist, reduces neonatal hypoxia-induced pulmonary hypertension in piglets.

The pulmonary vasculature of newborns with persistent pulmonary hypertension is characterized by active vasoconstriction and vascular remodeling. It has been suggested that endothelin-1 (ET-1), a potent vasoconstrictor and growth promoter, may be involved in the pathogenesis of persistent pulmonary hypertension of the newborn. To determine whether treatment with an ET(A) receptor antagonist can reverse pulmonary hypertension in the neonate, 1-d-old piglets were exposed to hypoxia for 3 d to induce pulmonary hypertension and then treated for the remainder of the 14 d with an orally active, nonpeptidic ET(A) antagonist (TBC3711, 22 mg x kg(-1) x d(-1)). At the end of the exposure, Hb, pulmonary artery pressure, right ventricle to left ventricle plus septum weight ratio, percentage wall thickness, ET-1 circulating levels, perfusion pressure, and dilator response to the nitric oxide (NO) donor, SIN-1 (3-morpholinosydnonimine-N-ethylcarbamide) in isolated perfused lungs were determined. Exhaled NO and hemodynamic variables were also examined in an intact anesthetized animal preparation that had undergone the same treatment. By 3 d of exposure to hypoxia, piglets had already developed significant pulmonary hypertension as estimated by their pulmonary artery pressure (24.0 +/- 1.3 mm Hg versus 14.2 +/- 3.4 mm Hg) and percentage wall thickness (26.6 +/- 5.9% versus 18.7 +/- 2.4% for vessels 0-30 microm). Whereas further exposure to hypoxia for 14 d did not enhance the increase in pulmonary artery pressure and percentage wall thickness, it did augment the right ventricle to left ventricle plus septum weight ratio (0.71 +/- 0.09 versus 0.35 +/- 0.01). ET-1 circulating levels were increased only when exposure to hypoxia was prolonged to 14 d (5.1 +/- 2.4 pg/mL versus 1.0 +/- 0.4 pg/mL). Treatment with TBC3711 from d 3 to d 14, once pulmonary hypertensive changes were established and while hypoxic exposure persisted, caused significant reduction in the right ventricle to left ventricle plus septum weight ratio (0.60 +/- 0.06), pulmonary artery pressure (20.0 +/- 4.8 mm Hg), and percentage wall thickness (18.5 +/- 3.3%) and restored the dilator response to the NO donor SIN-1. Prolonged hypoxia markedly reduced exhaled NO concentrations (0.3 +/- 0.6 ppb), although treatment of hypoxic animals with TBC3711 restored the concentration of exhaled NO (4.4 +/- 2.8 ppb) to the level of normoxic controls (4.9 +/- 3.0 ppb). Lastly, treatment with TBC3711 increased ET-1 circulating levels in both the normoxic (5.4 +/- 2.8 pg/mL) and hypoxic (13.0 +/- 6.3 pg/mL) groups. In conclusion, the specific ET(A) receptor antagonist, TBC3711, can significantly ameliorate the morphologic changes encountered in hypoxia-induced pulmonary hypertension in the newborn piglet and may improve the dilator response to NO.

Animals↗
PubMed2001

Randomized trial of nasal synchronized intermittent mandatory ventilation compared with continuous positive airway pressure after extubation of very low birth weight infants.

OBJECTIVE: To determine whether noninvasive, nasal synchronized intermittent mandatory ventilation (nSIMV) improves the likelihood that very low birth weight infants will be successfully extubated. METHODS: Infants of <1251-g birth weight who were due to be extubated before 6 weeks of age were eligible once they were receiving <35% oxygen and were on a ventilator rate of <18 breaths per minute (bpm). Extubation was performed following intravenous loading with aminophylline, after a successful trial of 12 hours of endotracheal synchronized intermittent mandatory ventilation at a rate of 8. Infants were randomized to either nasal continuous positive airway pressure (nCPAP) at 6 cm H(2)O or nSIMV after extubation. nSIMV was commenced at a rate of 12 bpm with pressure on the ventilator set to achieve a delivered pressure of at least 12 cm H(2)O and a peak end expiratory pressure of 6 cm H(2)O. Continuous recording for diagnosis of apnea was performed for 72 hours after extubation. Objective criteria for failure of extubation were as follows: a PaCO(2) >70; FIO(2) >0.7; or severe recurrent apnea (>2 apneas requiring intermittent positive-pressure ventilation in 24 hours or >6 apneas >20 seconds per day). The study ended after 72 hours postextubation or when infants satisfied failure criteria. A sample size of 54 was determined by power analysis. RESULTS: Mean birth weight (831 standard deviation [SD]: 193 g) and gestation (26.3 SD: 1.8 weeks) did not differ between groups. Mean age at extubation was 7.6 (SD: 9.7) days, range 1 to 40 days. The nSIMV group had a lower incidence of failed extubation 4/27 compared with the continuous positive airway pressure group, 12/27. This was attributable to both a decreased incidence of apnea and a decreased incidence of hypercarbia. There was no increase in the incidence of abdominal distension or feeding intolerance. DISCUSSION: nSIMV is effective in preventing extubation failure in very low birth weight infants in the first 72 hours after extubation. Noninvasive ventilation may have other roles in the care of the very low birth weight infant.

Aminophylline↗
PubMed2001

Randomized, prospective study of low-dose versus high-dose inhaled nitric oxide in the neonate with hypoxic respiratory failure.

OBJECTIVE: There is little information on the response to very low doses of inhaled nitric oxide (iNO) in hypoxic near-term infants. The potential toxicities of iNO are dose related; thus, the ability to use lower doses safely and effectively may be advantageous. We hypothesized that there is no difference in the acute improvement in oxygenation between treatment with inhaled nitric oxide at 1 to 2 parts per million (ppm) or 10 to 20 ppm. METHODS: We randomized near-term and term infants with hypoxic respiratory failure with oxygenation indices (OIs) of >/=10 and PaO(2) <100 on 2 separate blood gases taken at least 30 minutes apart. Infants with congenital diaphragmatic hernia were excluded. After parental consent was obtained, patients were randomized to receive a starting nitric oxide (iNO) dose of either 1 to 2 ppm (low-dose group, n = 15) or 10 to 20 ppm (high-dose group, n = 21). The response to iNO was assessed according to the increase in arterial PaO(2) and decrease in OI 30 to 60 minutes after exposure to the initial starting concentration. A response of <10% increase on PaO(2) and a <10% decrease in OI resulted in a doubling of iNO within the dose range protocol (1, 2, 4, and 8 ppm for the low-dose group; 10, 20, 40, and 80 ppm for the high-dose group). RESULTS: Thirty minutes after the study gas was initiated, PaO(2) increased significantly overall in the low-dose (90.7 +/- 41 torr to 166.8 +/- 95.6 torr) and high-dose (76.2 +/- 32.7 torr to 198.7 +/- 142.8 torr) groups; the maximal increase was seen in the infants who initially were treated with 10 ppm. The OI also decreased significantly overall and also was significant in the high-dose group (21.0 +/- 13.7 to 11.4 +/- 10.4; low-dose: 18.3 +/- 7.1 to 13.2 +/- 12.3). There was a nonsignificant fall of PaCO(2) with iNO treatment (low dose 35 +/- 7.3 to 30 +/- 8.5 torr vs high dose 35.2 +/- 9.9 to 32.4 +/- 10.7 torr). A sustained response (ie, maintaining a PaO(2) and OI gain greater than 20% for the duration of the study gas administration) was greater in the high-dose group (53.3% vs 30.0%). In addition, dose increases were required more often in the low-dose group than in the high-dose group (80.0% vs 57.1%). Among patients who did not respond to the initial iNO dose, 100.0% and 83.3% responded at higher doses of iNO for the low- and high-dose groups, respectively. There were no differences for death, need for extracorporeal membrane oxygenation, or other outcomes between the groups. CONCLUSIONS: We did not find any significant difference in response to low- versus high-dose iNO. An initial exposure to low-dose iNO does not compromise the response to higher doses if required and may result in less toxicity.

Administration, Inhalation↗
PubMed2001

Intravenous lipid composition affects hypoxic pulmonary vasoconstriction in the newborn piglet.

To examine the effects of altering the fatty acid (FA) composition of intravenous (IV) lipid emulsions on pulmonary vascular resistance (PVR) and thromboxane production, we studied three groups of newborn piglets after three days of either sow's milk (milk), or total parenteral nutrition (TPN) with either iv soy bean oil (SBO, 52% n-6 and 8% n-3 FA) or fish oil (FO, 5% n-6 and 51% n-3 FA) emulsions. At baseline, and during hypoxia at 20 min and 2 h, cardiac output (Q) was measured, PVR calculated and plasma levels of a prostacyclin metabolite (6-keto-PgF1alpha) and thromboxane B2 (TxB2) were measured. Fatty acid composition of the lung phospholipids was analyzed. There was an exaggerated increase in PVR and decrease in Q during prolonged hypoxia in the TPN-SBO group as compared with the other two groups. There was no difference in PVR and Q between the milk and TPN-FO groups. FA of lung phospholipids reflected the high dietary level of long chain n-3 FA in the TPN-FO group. However, no differences in plasma levels of 6-keto-PgF1alpha or TxB2 were found. Intravenous emulsions made from SBO reduced cardiac output and increased pulmonary vascular resistance in the hypoxic newborn piglet, whereas iv FO emulsions did not. When subjects with pulmonary hypertension are receiving TPN iv SBO may be detrimental; iv FO may be beneficial, giving similar responses as in a milk-fed subject.

Animals↗
PubMed2000

Nitric oxide for respiratory failure in infants born at or near term.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To determine whether treatment of hypoxemic newborn infants with inhaled nitric oxide (INO) improves oxygenation and reduces the rates of death, or the requirement for ECMO. SEARCH STRATEGY: Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information. SELECTION CRITERIA: Randomized and quasi randomized studies in term and near term infants. Administration of inhaled nitric oxide. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation. DATA COLLECTION AND ANALYSIS: Eight randomized controlled studies were found in term and near term infants with hypoxia. Entry criteria were reasonably consistent except for the one trial that studied only infants with congenital diaphragmatic hernia (Ninos 1997). MAIN RESULTS: Inhaled nitric oxide appears to improve outcome in hypoxemic term and near term infants by reducing the incidence of the combined endpoint of death or need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced. Oxygenation improves in approximately 50% of infants receiving nitric oxide. The Oxygenation Index decreases by a (weighted) mean of 15.1 within 30 to 60 minutes after commencing therapy and PaO2 increases by a mean of 53 mmHg. It does not appear to affect outcome whether infants have clear echocardiographic evidence of PPHN or not. The outcome of infants with diaphragmatic hernia was not improved; indeed there is a suggestion that outcome was slightly worsened. REVIEWER'S CONCLUSIONS: On the evidence presently available, it appears reasonable to use inhaled nitric oxide in a concentration of 20 ppm for term and near term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia. Longterm neurodevelopmental and pulmonary followup of surviving infants enrolled in randomized trials of INO are required to establish more firmly the role of INO in the treatment of neonatal respiratory failure.

Fetal Hypoxia↗
PubMed2000

Umbilical artery catheters in the newborn: effects of position of the catheter tip.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To determine whether the position of the tip of an umbilical arterial catheter influences the frequency of ischemic events, aortic thrombosis, intraventricular hemorrhage, mortality or necrotising enterocolitis in newborn infants. SEARCH STRATEGY: Randomized and quasi randomized controlled trials of umbilical catheterization use were obtained from the following sources: 1. Effective Care of the Newborn Infant, edited by JC Sinclair and MB Bracken. 2. Medline Search using Melvyl Medline Plus and the keyword headings 'Umbilic#', 'Catheter#' and subject heading 'Infant, Newborn' 3. Search of personal data files SELECTION CRITERIA: Randomized trials in newborn infants of any birthweight or gestation. Comparison of high catheter placement with the tip above the diaphragm to a lower position just above the aortic bifurcation. Clinically important end points such as ischemic events or aortic thrombosis. DATA COLLECTION AND ANALYSIS: Five randomized controlled trials and one alternate assignment study had sufficiently detailed data to allow interpretation. MAIN RESULTS: High placed umbilical artery catheters are associated with a lower incidence of clinical vascular complications, without an increase in any adverse sequelae. Intraventricular hemorrhage rates, death and necrotising enterocolitis are not more frequent with high compared to low catheters. REVIEWER'S CONCLUSIONS: There appears to be no evidence to support the use of low placed umbilical artery catheters. High catheters should be used exclusively.

Catheterization↗
PubMed2000

Umbilical artery catheters in the newborn: effects of heparin.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To determine whether the use of heparin in fluids infused through an umbilical arterial catheter in newborn infants influences the frequency of clinical ischemic events, catheter occlusion, aortic thrombosis, intraventricular hemorrhage, hypertension, death, or the duration of catheter usability. SEARCH STRATEGY: Randomized and quasi randomized controlled trials of umbilical catheterization use were obtained from the following sources: 1. Effective Care of the Newborn Infant, edited by JC Sinclair and MB Bracken. 2. Medline Search using Melvyl Medline Plus and the keyword headings 'Umbilic#', 'Catheter#' and subject heading 'Infant, Newborn' 3. Search of personal data files SELECTION CRITERIA: Randomized trials in newborn infants of any birthweight or gestation. Comparison of heparinised to non heparinised infusion fluids, including comparison of heparin in the infusate to heparin just in the flush solution. Clinically important end points such as catheter occlusion or aortic thrombosis. DATA COLLECTION AND ANALYSIS: There were five randomized controlled trials retrieved. All gave details of the incidence of catheter occlusion. Two also reported the incidence of aortic thrombosis. The intervention was reasonably consistent: heparin in the infusate at a concentration of 1 unit/mL was investigated in all trials except one which used a concentration of 0.25 units/mL. Studies generally included both term and preterm infants. MAIN RESULTS: Heparinization of the infusate decreases the incidence of catheter occlusion but does not affect the frequency of aortic thrombosis. Heparinization of the flush solution is not an adequate alternative. There does not appear to be an effect on frequency of intraventricular hemorrhage, death or clinical ischemic phenomena. REVIEWER'S CONCLUSIONS: Heparinization of the fluid infused through an umbilical arterial catheter decreases the likelihood of umbilical arterial catheters occluding. The lowest concentration tested so far (0.25 units/mL) has been shown to be effective. Heparinization of flushes without heparinizing the infusate is ineffective. The frequency of aortic thrombosis has not been shown to be affected; however, the confidence intervals for this effect are very wide. The frequency of intraventricular hemorrhage has not been shown to be affected by heparinization of the infusate, but again the confidence intervals are very wide and even a major increase in the incidence of grade 3 and 4 intraventricular hemorrhage would not have been detected.

Anticoagulants↗
PubMed2000

Umbilical artery catheters in the newborn: effects of catheter design (end vs side hole).

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To determine whether the design of an umbilical arterial catheter influences the frequency of ischemic events, aortic thrombosis, intraventricular hemorrhage, mortality or necrotising enterocolitis in newborn infants. SEARCH STRATEGY: Randomized and quasi randomized controlled trials of umbilical catheterization use were obtained from the following sources: 1. Effective Care of the Newborn Infant, edited by JC Sinclair and MB Bracken. 2. Medline Search using Melvyl Medline Plus and the keyword headings 'Umbilic#', 'Catheter#' and subject heading 'Infant, Newborn' 3. Search of personal data files SELECTION CRITERIA: Randomized trials in newborn infants of any birthweight or gestation. Comparison of end hole catheters with side hole catheters. Clinically important end points such as ischemic events or aortic thrombosis. DATA COLLECTION AND ANALYSIS: There appears to be only a single trial which has addressed this issue (Wesstrom 1979). MAIN RESULTS: End hole catheters are associated with a much decreased risk of aortic thrombosis compared to side hole catheters. RR = 0.27 (95% CI 0.11, 0.67) REVIEWER'S CONCLUSIONS: Side hole catheters should be avoided for umbilical arterial catheterisation in the newborn.

Catheterization↗