Norepinephrine infusion improves haemodynamics in the preterm infants during septic shock.

AIM: This study evaluated the clinical and haemodynamic effects of norepinephrine infusion in preterm infants. METHODS: The effects of norepinephrine therapy for refractory hypotension were evaluated in preterm infants between April 2009 and April 2011 at the neonatal intensive care unit of Sainte-Justine Hospital, Montreal, Quebec. Changes in haemodynamics and clinical parameters were analysed eight hours before and eight hours after the start of norepinephrine infusion, and eight hours after its cessation. RESULTS: During the study, 30 preterm infants at a mean gestational age of 26.5 ± 2.6 weeks (median: 25.7, 23.4-34) and birthweight of 903 ± 437 g (median 827, 450-2550) received norepinephrine infusion for neonatal septic shock. After eight hours of treatment, mean blood pressure, urine output and FiO2 significantly improved. Eight hours after cessation of norepinephrine infusion, the number of patients treated with other inotropes decreased significantly, 24 patients (80%) had normal mean blood pressure and 27 patients (90%) had normal urine output. CONCLUSION: Norepinephrine therapy could be considered to improve blood pressure and urine output during neonatal septic shock in preterm infants. Further studies are needed to prove the efficacy and safety of norepinephrine infusion in neonates.

Preventing postnatal growth restriction in infants with birthweight less than 1300 g.

AIM: To examine nutritional and growth outcomes in very preterm infants with a birthweight (BW) of ≤1300 g before and after the introduction of enhanced enteral and parenteral nutrition protocols. METHODS: A comparison of two historical cohorts. RESULTS: There were 153 infants in cohort 1 and 118 in cohort 2. A total of 19% were growth restricted at birth in both cohorts. Feeds advanced more quickly in cohort 2, with decreased duration of central lines and TPN; breastmilk fortification occurred sooner. Calorie and protein intakes were increased during all of the first 14 days of life. Adverse clinical outcomes were unchanged, including NEC. The proportion of infants discharged <10th percentile of expected weight, decreased from 23% to 9%. In cohort 2, the z-score for body weight decreased by 0.39, compared to an average 1.03 in cohort 1 (p < 0.001). Head circumference and body weight were also significantly improved at discharge (p < 0.01), but length was improved to a lesser degree. CONCLUSION: Early and enhanced postnatal intravenous and enteral feeding can provide good postnatal growth among very immature infants without adverse effects. Calorie and particularly protein intake in early life could probably be further optimised.

A tiny baby intubation team improves endotracheal intubation success rate but decreases residents' training opportunities.

OBJECTIVE: To assess the educational and clinical impact of a tiny baby intubation team (TBIT). STUDY DESIGN: Retrospective study comparing endotracheal intubation (ETI) performed: pre-implementation of a TBIT (T1), 6 months post-implementation (T2), and 4 years post-implementation (T3). RESULTS: Post-implementation (T2), first-attempt success rate in tiny babies increased (44% T1; 59% T2, p = 0.04; 56% T3, p = NS) and the proportion of ETIs performed by residents decreased (53% T1; 37% T2, p = 0.001; 45% T3, p = NS). After an educational quality improvement intervention (prioritizing non-tiny baby ETIs to residents, systematic simulation training and ETI using videolaryngoscopy), in T3 residents' overall (67% T1; 60% T2, p = NS; 79% T3, p = 0.02) and non-tiny baby ETI success rate improved (72% T1; 60% T2, p = NS; 82% T3, p = 0.02). CONCLUSION: A TBIT improves success rate of ETIs in ELBW infants but decreases educational exposure of residents. Educational strategies may help maintain resident procedural competency without impacting on quality of care.

Decision-making for extremely preterm infants with severe hemorrhages on head ultrasound: Science, values, and communication skills.

Severe intracranial hemorrhages are not rare in extremely preterm infants. They occur early, generally when babies require life-sustaining interventions. This may lead to ethical discussions and decision-making about levels of care. Prognosis is variable and depends on the extent, location, and laterality of the lesions, and, importantly also on the subsequent occurrence of other clinical complications or progressive ventricular dilatation. Decision-making should depend on prognosis and parental values. This article will review prognosis and the uncertainty of outcomes for different lesions and provide an outline of ways to conduct an ethically appropriate discussion on the decision of whether to continue life sustaining therapy. It is possible to communicate in a compassionate and honest way with parents and engage in decision-making, focussing on personalized information and decisions, and on function, as opposed to diagnosis.

Neonates with hypoxic-ischemic encephalopathy treated with hypothermia: Observations in a large Canadian population and determinants of death and/or brain injury.

BACKGROUND: Birth asphyxia in term neonates remains a serious condition that causes significant mortality and long-term neurodevelopmental sequelae despite hypothermia treatment. The objective of this study was to review therapeutic hypothermia practices in a large population of neonates with hypoxic-ischemic encephalopathy (HIE) across Canada and to identify determinants of adverse outcome. METHODS: Our retrospective observational cohort study examined neonates≥36 weeks, admitted to the Canadian Neonatal Network NICUs between 2010 and 2014, diagnosed with HIE, and treated with hypothermia. Adverse outcome was defined as death and/or brain injury. Maternal, birth, and postnatal characteristics were compared between neonates with adverse outcome and those without. The association between the variables which were significantly different (p < 0.05) between the two groups and adverse outcome were further tested, while adjusting for gestational age, birth weight, gender, and initial severity of encephalopathy. RESULTS: A total of 2187 neonates were admitted for HIE; 52% were treated with hypothermia and 40% developed adverse outcome. Initial severity of encephalopathy (moderate, p = 0.006; severe, p < 0.0001), hypotension treated with inotropes (p = 0.001), and renal failure (p = 0.007) were significantly associated with an increased risk of death and/or brain injury. CONCLUSIONS: In asphyxiated neonates treated with hypothermia, not only their initial severity of encephalopathy on admission, but also their cardiac and renal complications during the first days after birth were significantly associated with risk of death and/or brain injury. Careful monitoring and cautious management of these complications is warranted.

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) has been proven to be effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Therefore, analysis of the efficacy and toxicities of iNO in infants born before 35 weeks is necessary. OBJECTIVES: To determine the effect of treatment with iNO on the rates of death, bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), or neurodevelopmental disability in preterm newborn infants (< 35 weeks gestation) with respiratory disease. SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) were searched, using the following keywords: nitric oxide, clinical trial, and newborn covering the years from 1985 to 2006. In addition, the abstracts of the Pediatric Academic Societies were also searched. SELECTION CRITERIA: Randomised and quasi-randomised studies in preterm infants with respiratory disease that compared the effects of administration of iNO gas compared to control, with or without placebo are included in this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including death, BPD (defined as oxygen dependence at 36 weeks postmenstrual age), IVH, periventricular leukomalacia (PVL), long term neurodevelopmental outcome and short term effects on oxygenation were excerpted from the trial reports by the investigators. 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: Eleven randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. The trials have been grouped post hoc into three categories depending on the entry criteria; entry in the first three days of life based on oxygenation criteria (Kinsella 1999; Hascoet 2004; INNOVO 2005; Van Meurs 2004; Mercier 1999; Dani 2006), routine use in intubated preterm babies (Schreiber 2003; Kinsella 2006) and later enrolment based on an increased risk of BPD (Subhedar 1997; Ballard 2006). The usefulness of the overall analyses was considered limited by the differing characteristics of the studies, and only subgroup analyses were performed. Trials of early rescue treatment of infants based on oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD. The subgroup of studies with routine use of iNO in intubated preterm infants demonstrated a marginally significant reduction in the combined outcome of death or BPD [typical RR 0.91 (95% CI 0.84, 0.99); typical RD -0.06 (95% CI -0.12, -0.01)]. Later treatment with iNO based on the risk of BPD demonstrated no significant benefit for this outcome in our analysis. Studies of early rescue treatment with iNO demonstrated a trend toward increased risk of severe IVH, whereas the subgroup of studies with routine use in intubated preterm infants seems to show a reduction in the risk of having either a severe IVH or PVL [typical RR 0.70 (95% CI 0.53, 0.91); typical RD -0.07 (95% CI -0.12, -0.02)]. Later iNO treatment of infants at risk of BPD is given after the major risk period for IVH, and does not appear to lead to progression of old lesions. Two studies (Schreiber 2003; INNOVO 2005) presented data on long term neurodevelopmental outcome. The early routine treatment study (Schreiber 2003) showed an improved outcome at two years corrected age, while the rescue treatment study (INNOVO 2005) showed no effect of iNO. AUTHORS' CONCLUSIONS: iNO as rescue therapy for the very ill ventilated preterm infant does not appear to be effective and may increase the risk of severe IVH. Later use of iNO to prevent BPD also does not appear to be effective. Early routine use of iNO in mildly sick preterm infants may decrease serious brain injury and may improve survival without BPD. Further studies are needed to confirm these findings, to define groups most likely to benefit, and to describe long term outcomes.

Treating hypotension in the preterm infant: when and with what: a critical and systematic review.

UNLABELLED: A very large proportion of extremely preterm infants receive treatments for hypotension. There are, however, marked variations in indications for treatment, and in the interventions used, between neonatal intensive care units and between neonatologists. METHODS: We performed systematic reviews of the literature in order to determine which preterm infants may benefit from treatment with interventions to elevate blood pressure (BP), and which interventions improve clinically important outcomes. RESULTS: Our review was not able to define a threshold BP that was significantly predictive of a poor outcome, nor whether any interventions for hypotensive infants improved outcomes, nor which interventions were more likely to be beneficial. CONCLUSIONS: There is a distinct lack of prospective research of this issue, which prevents good clinical care. It is possible that a simple BP threshold that indicates the need for therapy does not exist, and other factors, such as the clinical status or systemic blood flow measurements, may be much more informative. Such a paradigm shift will also require careful prospective study.

Moral distress in the neonatal intensive care unit: caregiver's experience.

BACKGROUND: The Neonatal Intensive Care Unit (NICU) can be ethically charged, which can create challenges for health-care workers. OBJECTIVE: To determine the frequency with which nurses and residents have experienced ethical confrontations and what factors are associated with increased frequency. DESIGN/METHODS: An anonymous questionnaire was distributed to nurses in a university center, a high-risk obstetric service, a maternity hospital NICU with 85% in-born patients and an outborn NICU, most of whose preterm admissions are those with surgical complications. Obstetric and pediatric residents in the four universities of the province also received the questionnaire, which included demographics, opinions regarding the gestational age threshold at which resuscitation of a premature infant with bradycardia was appropriate, knowledge of cerebral palsy (CP) outcomes (as an indicator of knowledge about long-term sequelae of prematurity) and questions about ethical confrontation in the NICU. RESULTS: Two hundred and seventy-nine caregivers participated (115 full time nurses and 164 residents). All the distributed questionnaires were completed. Frequent ethical confrontation was reported by 35% of the nurses and 19% of the residents. Among the nurses, moral distress differed significantly between work environments. Nurses working in an out-born NICU and obstetric nurses were more likely to overestimate CP prevalence (P<0.05). Nurses who overestimated CP rates had higher thresholds for resuscitation and were more likely to experience ethical confrontations. Of the residents, 60% were pediatric and 40% obstetric. All groups of residents frequently overestimated the prevalence of CP, and knowledge differed significantly by residency program (P<0.05). The residents who overestimated CP rates had higher thresholds for resuscitation, had more incorrect answers regarding prematurity outcomes and were less likely to have ethical confrontations. CONCLUSIONS: A large proportion of nurses and residents report frequent ethical confrontations. Many residents and nurses have limited knowledge of outcomes and high threshold for resuscitation. Ethical confrontation is more common among nurses with poor knowledge about outcomes, and less common in residents with poor knowledge about outcomes.

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.

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.

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.

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.

The Lacuna Trial: a double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant.

OBJECTIVE: To determine tolerability of bovine lactoferrin (bLF) in very preterm infants, and whether the intervention can be adequately masked. STUDY DESIGN: In a single-center masked pilot trial infants under 31 weeks gestation were randomized before 48 h of age to receive milk with 100 mg per day of bLF or control. The primary outcome was feeding tolerance, defined as time to achieve full feeds (140 ml kg(-1) per day). Parents answered a short questionnaire regarding acceptability of the intervention. RESULTS: Seventy-nine infants were enrolled and analyzed according to intention to treat. There was no effect of bLF on the primary outcome. In addition, mortality, late onset sepsis and other complications of prematurity were no different. Equal numbers of parents in both groups believed their infant received bLF. CONCLUSION: We demonstrated that bLF is well tolerated, easy to administer and its presence in prepared milk is not evident. Trial registration number ISRCTN66482337.

Renal dopamine receptors: mechanisms of action and developmental aspects.

Dopamine is important for renal perfusion, natriuresis, and the control of blood pressure. Modulation of the activities of adenylyl cyclase, phospholipase C and protein kinases is involved in the signal transduction pathway of dopamine. Peripheral dopamine receptors are classified as the DA1 and DA2 subtypes on the basis of synaptic localization and their pharmacological profiles. In the kidney, DA1 receptors are localized in the medial layer of the renal vasculature and along the nephron; DA2 receptors are found in the glomerulus and the nerves surrounding renal blood vessels. While DA1 receptor stimulation results in renal vasodilatation and natriuresis, DA2 receptors may play a synergistic role in the DA1 modulated natriuresis. There is increasing evidence that these effects of dopamine are attenuated in younger than in older animals. Future studies should be directed to identify the ontogenic differences in vascular and tubular dopamine receptors (density and affinity) and their coupling mechanisms, in order to evaluate the role of dopamine which is frequently used in the management of shock in newborns.

Temporal effects of prolonged hypoxaemia and reoxygenation on systemic, pulmonary and mesenteric perfusions in newborn piglets.

OBJECTIVE: Temporal effects of prolonged hypoxaemia and reoxygenation, on the systemic pulmonary and mesenteric circulations in newborn piglets, were investigated. METHODS: Two groups [control (n = 5), hypoxaemic (n = 7)] of 1-3 day old anaesthetised piglets were instrumented with ultrasound flow probes placed to measure cardiac, hepatic arterial flow and portal venous flow indices, and catheters inserted for measurements of systemic and pulmonary arterial pressures. Hypoxaemia with arterial oxygen saturation 40-50% was maintained for 3 h, followed by reoxygenation with 100% inspired oxygen. RESULTS: Cardiac index was transiently elevated at 30-60 min of hypoxaemia (23% increase from baseline 158 +/- 39 ml/kg/min), along with increases in stroke volume but not heart rate. A significant decrease in systemic vascular resistance after 30 min of hypoxaemia was followed by hypotension at 180 min of hypoxaemia. Progressive pulmonary hypertension with significant vasoconstriction was found after 30 min of hypoxaemia. The hypoxaemic mesenteric vasoconstriction was transient with a 37% decrease in portal venous flow index at 15 min of hypoxaemia (29 +/- 12 vs. 46 +/- 18 ml/kg/min of baseline, p < 0.05). The hepatic arterial to total hepatic oxygen delivery ratio increased significantly during hypoxaemia. In contrast to the significant increase in systemic oxygen extraction throughout hypoxaemia, elevation in mesenteric oxygen extraction decreased after 30 min of hypoxaemia associated with modest decreases in oxygen consumption. Following reoxygenation, the pulmonary hypertension was partially reversed. Cardiac index decreased further (130 +/- 39 ml/kg/min) with reduced stroke volume, persistent systemic hypotension and decreased systemic oxygen delivery. CONCLUSIONS: We demonstrated differential temporal changes in systemic, pulmonary and mesenteric circulatory responses during prolonged hypoxaemia. Cautions need to be taken upon reoxygenation because the neonates are at risk of developing myocardial stunning, persistent pulmonary hypertension and necrotising enterocolitis.

Prolonged periodic breathing: significance in sleep studies.

Periodic breathing (PB) is a pattern of breathing that is frequently recognized in infants being studied for possible sleep apnea. Infants presenting to a sleep laboratory over a 3 1/2-year period who had evidence on their initial study of prolonged (greater than 15% of total sleep time) PB were prospectively studied in an effort to determine the significance of this pattern of breathing. Of the 331 infants studied, 40 demonstrated prolonged PB. Sixteen of these infants, who were of 37 weeks' gestation or greater at birth and did not receive pharmacologic therapy, were studied on at least two occasions (group 1). Of the remaining 24 infants, 11 were treated with methylxanthines by their attending physician (group 2), and 13 did not return for sequential studies (group 3). All infants who were of less than 37 weeks' gestation at birth were separately evaluated (group 4). For group 1, who were studied at a mean age of 15 postnatal weeks, there was a mean of 36.4% periodicity which decreased on the second study to 18.0%. By the fourth study, this had decreased to 9.2%. In group 2, there was a mean of 41.3% periodicity during the first study which decreased to 6.4% on the second study. Infants of group 3 had a mean of 31.4% PB on their initial study and the premature infants, group 4, had 30.1% PB. All infants showed a decrease in PB with sequential studies and no infant was known to have died of sudden infant death syndrome or any other disorder in the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Contralateral pneumothoraces in the newborn: incidence and predisposing factors.

A prospective study was performed to ascertain the incidence of, and risk factors for, the development of a contralateral pneumothorax in 32 neonates with respiratory distress, without evidence of pulmonary hypoplasia, who had an initial unilateral air leak requiring pleural drainage. The mean postnatal age of occurrence of the first pneumothorax was 31.04 hours (range 0.1 to 92 hours); a subsequent contralateral pneumothorax developed in 14 infants (44%) at a mean postnatal age of 61.5 hours (range 8 to 106 hours). Thirteen of the 14 infants with a subsequent contralateral pneumothorax had pulmonary interstitial emphysema visible on the chest radiograph taken immediately after drainage of the first pneumothorax, compared with eight of the 18 infants without a contralateral pneumothorax (P less than .005). Other factors significantly associated with a contralateral pneumothorax were alveolar-arterial oxygen gradient (P less than .01) and FiO2 (P less than .005), both measured one hour after the pneumothorax, and gestational age (P less than .05). Multivariate discriminant function analysis did not usefully add to the predictive power of pulmonary interstitial emphysema alone. Infants with pulmonary interstitial emphysema at the time of an initial unilateral pneumothorax are at significant risk for the development of a contralateral pneumothorax.

Dose-response relationship of doxapram in the therapy for refractory idiopathic apnea of prematurity.

Eighteen infants with idiopathic apnea of prematurity refractory to therapeutic levels of aminophylline were treated with incremental doses of doxapram beginning at 0.5 mg/kg/h. Continuous recording of heart rate, thoracic impedance, and transcutaneous PO2 demonstrated that 47% of the infants satisfied objective response criteria at the lowest dose, 53% responded at 1.0 mg/kg/h, 65% at 1.5 mg/kg/h, 82% at 2.0 mg/kg/h, and 89% at the highest allowed dose of 2.5 mg/kg/h. The mean serum doxapram concentration at the response dose was 2.9 +/- 1.3 micrograms/mL, and all infants who responded had levels greater than 1.5 micrograms/mL. BP was significantly elevated at doses higher than 1.5 mg/kg/h (P less than .05). Minute ventilation significantly increased and PCO2 significantly decreased as the doxapram dosage was increased (P = .02). Terminal elimination half-life was 9.9 +/- 2.9 hours. When doxapram is used for treatment of refractory neonatal apnea the starting dosage should be no more than 0.5 mg/kg/h.

Limitations of self-inflating resuscitators.

In an effort to characterize the performance of self-inflating resuscitators, three examples of three models were subjected to laboratory testing: the Ohio Hope II resuscitator (Ohio Medical Products, Madison, WI), the PMR-2 resuscitator (Puritan Medical Products, Lenexa, KS), and the Laerdal resuscitator (AS Laerdal, Stavanger, Norway). The devices were connected to a test lung and compressed at frequencies of from 10 to 60 and at greater than 60 breaths per minute at 5, 10, and 15 L/min of flow. These devices were used with and without a reservoir and were compressed at less than and more than the pop-off valve pressures. The results revealed that all devices equipped with reservoirs delivered a significantly higher oxygen concentration than those without (P less than .001), and that activation of the pop-off valve significantly reduced Fio2 under all conditions (P less than .005). The pop-off valves for each device were activated throughout a wide range of pressures, the Laerdal 41 to 72 cm H2O, PMR-2 51 to 97 cm H2O, and the Ohio Hope II 38 to 106 cm H2O, well in excess of the manufacturer's specifications. Only the Laerdal with reservoir was able to deliver an Fio2 of greater than 0.9 when compressed at more than the pop-off valve pressure at rates of up to 30 breaths per minute using flows of 10 L/min, and it was the only device to produce Fio2 values of greater than 0.9 at all rates to 60 breaths per minute when compressed at less than the pop-off valve pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

The hemodynamic effects of prolonged respiratory alkalosis in anesthetized newborn piglets.

OBJECTIVE: To test the hypothesis that prolonged alkalosis decreases cardiac output and, furthermore, exacerbates hypoxic pulmonary vasoconstriction, as respiratory alkalosis is frequently induced as a therapy for persistent pulmonary hypertension of the newborn despite a lack of controlled evidence of improved outcomes. Potential adverse effects of prolonged alkalosis have been demonstrated. METHOD: Two groups (control, n = 6, and hypocapnic alkalosis, n = 6) of 1-3 day old fentanyl-anesthetized, vecuronium-paralyzed piglets were instrumented to measure cardiac index (CI) and mean systemic (MAP) and pulmonary (PAP) arterial pressures. Baseline values were recorded. Alveolar hypoxia was then induced to achieve an arterial oxygen saturation of between 50 and 60% for 15 min. Respiratory alkalosis was then induced, by increasing ventilation to achieve a pH between 7.55-7.60, and was continued for 240 min. Inspired carbon dioxide was used with hyperventilation in the control group to maintain pressure of arterial carbon dioxide (PaCO2) at 35-45 mmHg and pH of 7.35-7.45. Hypoxia was induced again at 15 and 240 min. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated. RESULTS: Prolonged alkalosis led to a significant and progressive fall in mean MAP from 61 (SD 7) mmHg at the start of the study falling to 50 (SD 6.9, p = 0.043), with no effect on CI. Calculated SVR decreased (0.45 SD 0.03 vs 0.36 SD 0.05). There were no statistically significant changes in any of the variables in the control group. Neither acute nor prolonged respiratory alkalosis had a significant effect on hypoxic pulmonary vasoconstriction. CONCLUSIONS: Prolonged hyperventilation leads to systemic hypotension, however it does not exacerbate hypoxic pulmonary vasoconstriction.