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Biomedical subjects

Steven M Donn

Publications and source records attributed to Steven M Donn.

At least 19 recordsLinked to original sources

Fetal-to-neonatal maladaptation.

Although the majority of newly born babies will establish normal respiratory and circulatory function without help, 1-2% might run into difficulties because of a disturbance in the normal adaptive processes required for a smooth transition from intrauterine to extrauterine life. An understanding of the normal and abnormal perinatal physiology is important to appreciate the practical differences in the approach to caring for such babies, and also for avoiding actions that might be detrimental in the longer term.

Adaptation, Biological↗

Mechanical ventilation of very low birth weight infants: is volume or pressure a better target variable?

OBJECTIVE: To compare the efficacy and safety of volume-controlled (VC) ventilation to time-cycled pressure-limited (TCPL) ventilation in very low birth weight infants with respiratory distress syndrome (RDS). STUDY DESIGN: Newborns weighing between 600 and 1500 g and with a gestational age of 24 to 31 weeks who had RDS were randomized to receive either VC or TCPL ventilation and treated with a standardized protocol. The 2 modalities were compared by determining the time required to achieve a predetermined success criterion, on the basis of either the alveolar-arterial oxygen gradient <100 mm Hg or the mean airway pressure <8 cm H(2)O. Secondary outcomes included mortality, duration of mechanical ventilation, and complications commonly associated with ventilation. RESULTS: The mean time to reach the success criterion was 23 hours in the VC group versus 33 hours in the TCPL group (P = .15). This difference was more striking in babies weighing <1000g (21 versus 58 hours; P = .03). Mean duration of ventilation with VC was 255 hours versus 327 hours with TCPL (P = .60). There were 5 deaths in the VC group and 10 deaths in the TCPL group (P = .10). The incidence of other complications was similar. CONCLUSION: VC ventilation is safe and efficacious in very low birth weight infants and may have advantages when compared with TCPL, especially in smaller infants.

Female↗

Risk management of severe neonatal hyperbilirubinemia to prevent kernicterus.

Our approach for risk management of severe neonatal hyperbilirubinemia to prevent kernicterus--one of the most easily preventable causes of neonatal brain damage--includes management of certain high-risk clinical situations, identification of systems failure, and suggestions for implementation strategies to enhance patient safety.

Humans↗

Medical liability, risk management, and the quality of health care.

The medical malpractice situation in many countries is reaching epidemic proportions. This paper examines the concepts of medical liability and professional risk management, as well as the relationship they play in determining the quality of healthcare services. The role of documentation and accurate record keeping is also stressed. High-risk clinical situations and medication errors are also addressed.

Documentation↗

Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy and the postpartum period. These drugs are capable of crossing the placenta and being transferred to the newborn during lactation. This report reviews the available information regarding the effects of SSRIs on the fetus and newborn; including long-term neurodevelopmental outcomes.

Child Development↗

A crossover analysis of mandatory minute ventilation compared to synchronized intermittent mandatory ventilation in neonates.

BACKGROUND: Mandatory minute ventilation (MMV) is a novel ventilator mode that combines synchronized intermittent mandatory ventilation (SIMV) breaths with pressure-supported spontaneous breaths to maintain a desired minute volume. The SIMV rate is automatically adjusted to maintain minute ventilation. OBJECTIVE: To evaluate MMV in a cohort of infants without parenchymal lung disease alternately ventilated by MMV and SIMV. DESIGN/METHODS: Neonates >33 weeks' gestational age and electively intubated for medical or surgical procedures were enrolled. Exclusionary criteria included: nonintact respiratory drive or active pulmonary disease. Infants were randomized to receive 2 hours of either SIMV or MMV and then crossed over to the other mode for 2 hours. Ventilator parameters and end-tidal CO(2) (etCO(2)) were measured via inline, mainstream monitoring and recorded every minute. RESULTS: In total, 20 infants were evaluated. No statistically significant differences were found for overall means between etCO(2), minute volumes, peak inspiratory pressure (PIP), or positive end expiratory pressure (PEEP). However, there was a significant difference in the type of ventilator breaths given and in the mean airway pressure. Additionally, there was a statistically significant negative trend in MMV over time compared to SIMV, although this was subtle and could have been due to extreme cases. CONCLUSIONS: Neonates with an intact respiratory drive can be successfully managed with MMV without an increase in etCO(2). While this mode generates similar PIP and PEEP, the decrease in mechanical breaths and the mean airway pressure generated with MMV may reduce the risk of some of the long-term complications associated with mechanical ventilation.

Breath Tests↗

Lucinactant: a novel synthetic surfactant for the treatment of respiratory distress syndrome.

Lucinactant (Surfaxin, Discovery Laboratories) is a synthetic surfactant, which contains the novel peptide, sinapultide, a surfactant-associated protein B mimic. Randomised clinical trials suggest that this compound is a safe and effective treatment for respiratory distress syndrome in preterm infants. It is also being actively investigated for other indications, including meconium aspiration syndrome, treatment of bronchopulmonary dysplasia in neonates, acute respiratory distress syndrome and asthma. A novel aerosol formulation administered with nasal continuous positive airway pressure is also under development for treatment of respiratory insufficiency in neonates. Its non-animal origin may make it an attractive alternative to present animal-derived surfactants by eliminating the risks of infection and immunogenicity related to the latter.

Animals↗

Immediate changes in lung compliance following natural surfactant administration in premature infants with respiratory distress syndrome: a controlled trial.

OBJECTIVE: To compare immediate changes in lung compliance following the administration of two commercially available natural surfactants. METHOD: We conducted a prospective, randomized study of 40 preterm infants with respiratory distress syndrome requiring surfactant. Infants received either Infasurf or Survanta. The primary outcome measure was the change in compliance assessed by bedside pulmonary monitoring. RESULTS: There were no significant changes in dynamic lung compliance within or between the two groups 1 hour after surfactant administration. However, infants given Survanta required more doses per patient (4 vs 2, p=0.05) and were more likely to require >2 doses (57 vs 26%, p=0.05). Infants requiring >1 dose of surfactant had a greater change in airway pressure and improved oxygenation just before the second dose when treated with Infasurf. CONCLUSIONS: We found no significant difference in acute changes in lung compliance. However, treatment with Infasurf seems to be more long lasting than Survanta.

Biological Products↗

Can mechanical ventilation strategies reduce chronic lung disease?

Chronic lung disease (CLD) continues to be a significant complication in newborn infants undergoing mechanical ventilation for respiratory failure. Although the aetiology of CLD is multifactorial, specific factors related to mechanical ventilation, including barotrauma, volutrauma and atelectrauma, have been implicated as important aetiologic mechanisms. This article discusses the ways in which these factors might be manipulated by various mechanical ventilatory strategies to reduce ventilator-induced lung injury. These include continuous positive airway pressure, permissive hypercapnia, patient-triggered ventilation, volume-targeted ventilation, proportional assist ventilation, high-frequency ventilation and real-time monitoring.

Bronchopulmonary Dysplasia↗

Randomized trial of normal saline versus 5% albumin for the treatment of neonatal hypotension.

OBJECTIVES: This study was designed to assess the comparative efficacy of normal saline (NS) and 5% albumin (ALB) for treatment of hypotension in the acutely ill newborn. STUDY DESIGN: Newborn infants who were < 24 hours old and were admitted to the Holden Neonatal Intensive Care Unit at the University of Michigan were randomized to receive one of the two solutions for volume expansion. Hypotension was defined as a sustained (> or =30 minutes) mean arterial pressure (MAP) of < 30 mmHg for infants weighing < or =2500 g, or a MAP of < 40 mmHg for those weighing > 2500 g. The short-term outcome measure was the resolution of hypotension defined as a MAP over the minimum limits set for birthweight sustained for > or =30 minutes. RESULTS: In total 41 infants met criteria and were entered. Of these, 21 infants received ALB and 20 received NS. Successful treatment was seen in 17/21 (81%) of infants in the ALB group and 17/20 (85%) of infants in the NS group. There was no statistically significant difference in response to treatment (p=0.30). In addition, there was no statistically significant difference in the magnitude of change in MAP between the two (p=0.41). CONCLUSIONS: NS was shown to be as effective as ALB for the correction of acute hypotension in the newborn infant. Given comparable efficacy of NS, along with its relatively low cost and availability, it should be considered the initial treatment of choice in this setting.

Albumins↗

Gentamicin pharmacokinetics in term newborn infants receiving high-frequency oscillatory ventilation or conventional mechanical ventilation: a case-controlled study.

OBJECTIVE: To compare the pharmacokinetics of gentamicin in infants receiving high-frequency oscillatory ventilation (HFOV) with infants receiving conventional mechanical ventilation. DESIGN: A case-controlled study design was used to compare the pharmacokinetics of gentamicin in critically ill infants receiving HFOV and conventional mechanical ventilation. Medical records of all full-term newborn infants (> or =37 weeks gestational age) who received either high-frequency mechanical ventilation or conventional mechanical ventilation between 1991 and 2001 were reviewed and relevant patient demographics, renal function tests and gentamicin administration and plasma concentration data collected. Elimination rate constant, half-life, volume of distribution and clearance for both groups were calculated using standard kinetics equations. SETTING: A tertiary care children's hospital. PATIENTS: Newborn infants, > or =37 weeks gestational age, receiving gentamicin and high-frequency mechanical ventilation or conventional mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: In total, 18 patients were included in the conventional mechanical ventilation group and 15 in the HFOV group. The mean gentamicin dose for conventional mechanical ventilation and HFOV groups infants were 2.52+/-0.07 and 2.5+/-0.07 mg/kg/dose, respectively. Initial dosing interval was 12 hours in all of the conventional mechanical ventilation infants and 13 of the 15 HFOV infants. The dosing interval for the remaining two HFOV infants was 18 hours. No patient in either group demonstrated oliguria. Statistical analysis using the Student t-test for unequal variances yielded significant differences between the two groups with regard to elimination rate constant, half-life, volume of distribution and clearance, with a p value of <0.05 for all the observations. The mean of the highest P(aw) received by each patient in the HFOV group (19.2+/-4.05) was considerably higher than in the conventional mechanical ventilation group (13.4+2.23) (p>0.05). CONCLUSION: Infants receiving HFOV had reduced gentamicin clearance. Full-term infants receiving HFOV should be initiated at gentamicin dosing intervals of 18 hours rather than the traditional 12 hours recommended for this age group.

Anti-Bacterial Agents↗

Severe neutrophilia in an infant with persistent pulmonary hypertension of the newborn.

We report the case of a term male infant with severe persistent pulmonary hypertension of the newborn, who developed massive neutrophilia of unknown etiology. An extensive evaluation failed to disclose an obvious cause for his neutrophilia. A bone marrow aspirate was performed and was consistent with a leukemoid reaction. This paper reviews the neonatal leukemoid reaction and its significance.

Humans↗

Invasive and noninvasive neonatal mechanical ventilation.

Neonatal respiratory failure consists of several different disease entities, with different pathophysiologies. During the past 30 years technological advances have drastically altered both the diagnostic and therapeutic approaches to newborns requiring mechanical assistance. Treatments have become both patient- and disease-specific. The clinician has numerous choices among the noninvasive and invasive ventilatory treatments that are currently in use. This article reviews the pathophysiology of respiratory failure in the newborn and the available methods to treat it, including continuous positive airway pressure, conventional and high-frequency mechanical ventilation, extracorporeal membrane oxygenation, and styles of ventilation and monitoring.

Extracorporeal Membrane Oxygenation↗

Mechanisms of ventilator-induced lung injury in premature infants.

Mechanical ventilation in premature infants may injure the lungs or exacerbate the pre-existing condition that led to the need for mechanical ventilation. Ventilator-induced lung injury (VILI) may be associated with alveolar structural damage, pulmonary oedema, inflammation, and fibrosis. This injury is not uniform and is associated with surfactant dysfunction. Recovery from VILI includes clearance of pulmonary oedema and alveolar structural repair. Mechanisms of VILI include high airway pressure (barotrauma), large gas volumes (volutrauma), alveolar collapse and re-expansion (atelectotrauma), and increased inflammation (biotrauma). Injury to the lung may lead to other organ dysfunction. The premature lung is more susceptible to VILI, and lung injury may exacerbate the disturbance of lung development that occurs after birth. Therapies targeting specific processes in lung injury, and which complement the protective ventilator management strategies to avoid atelectotrauma and lung overdistension are an area of active research.

Bronchopulmonary Dysplasia↗

Newer techniques of mechanical ventilation: an overview.

The introduction of newer, state-of-the-art, microprocessor controlled ventilator systems provides clinicians with opportunities to apply a number of advanced ventilatory modalities which were not previously available for treating newborns. Some of these techniques will need further scientific evaluation in controlled trials, but this should not preclude their use in clinical settings, as their safety has already been proved by "standard setters" for use in neonates. There is a firm physiological rationale for their use, and individual centres have already acquired substantial experience in the application of these modalities. The trend towards increasing sophistication and greater versatility is likely to continue, and clinicians involved in the care of sick newborn infants must keep abreast of these developments.

Equipment Design↗

Weaning newborns from mechanical ventilation.

While there is a relative consensus as to whether mechanical ventilation should be initiated, the management of babies during recovery from respiratory failure remains largely subjective and is predominantly determined by institutional or individual practices or preferences. This can lead to babies either being left on the ventilator too long, or extubated too hastily, thus requiring repeated re-intubation. The current scientific literature fails to provide a uniform view of the most appropriate way to wean babies from mechanical ventilation. This might stem from a lack of understanding of the relative merits of the different techniques of discontinuing mechanical ventilation, given the availability of a variety of primary ventilatory modes which were not available to a neonatal population before, and limited research into the pathophysiological mechanisms responsible for an unsuccessful extubation. The purpose of this paper is to review the physiological, mechanical, and clinical principles of weaning, and to highlight areas still in need of investigation.

Clinical Competence↗

A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.

OBJECTIVE: Infants with meconium aspiration syndrome (MAS) have marked surfactant dysfunction. Airways and alveoli of affected neonates contain meconium, inflammatory cells, inflammatory mediators, edema fluid, protein, and other debris. The objective of this study was to compare treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS. METHODS: Inclusion criteria were 1) gestational age > or =35 weeks, 2) enrollment within 72 hours of birth, 3) diagnosis of MAS, 4) need for mechanical ventilation, and 5) an oxygenation index > or =8 and < or =25. Subjects were randomized to either lavage with Surfaxin or standard care (2:1 proportion). In lavaged infants, a volume of 8 mL/kg dilute Surfaxin (2.5 mg/mL) was instilled into each lung over approximately 20 seconds followed by suctioning after 5 ventilator breaths. The procedure was repeated twice. The third and final lavage was with a more concentrated solution (10 mg/mL) of Surfaxin. RESULTS: Twenty-two infants were enrolled (15 Surfaxin and 7 control). Demographic characteristics were similar. There were trends (not significant) for Surfaxin-lavaged infants to be weaned from mechanical ventilation earlier (mean of 6.3 vs 9.9 days, respectively), as well as to have a more rapid decline in their oxygenation indexes compared with control infants, the latter difference persisting for the 96-hour-long study period. The therapy was safe and generally well tolerated by the infants. CONCLUSIONS: Dilute Surfaxin lavage seems to be a safe and potentially effective therapy in the treatment of MAS. Data from this investigation support future prospective, controlled clinical trials of bronchoalveolar lavage with Surfaxin in neonates with MAS.

Bronchoalveolar Lavage↗

Relationship of neonatal endotracheal tube size and airway resistance.

BACKGROUND: Infants receiving mechanical ventilation require narrow-lumen, small-diameter endotracheal tubes. OBJECTIVE: Compare the resistances of endotracheal tubes used in the neonatal intensive care unit. METHODS: Endotracheal tubes of internal diameter 2.5, 3.0, 3.5, and 4.0 mm were tested with a standard neonatal ventilator and a test lung. An endotracheal tube of each diameter was cut to 12 cm and connected to a flow transducer at one end and the test lung at the other. Serial measurements of resistance were made at various flows (6, 8, 10, and 12 L/min) and ventilator rates (30-90 breaths/min) encompassing the ranges of clinical practice. Analysis of variance was performed for each tube size, comparing resistance to flows and ventilator rates. RESULTS: Resistance was significantly higher with the 2.5 mm tube than with the others. There was also a consistent trend, in all the tube sizes, towards higher resistance as flow was increased. CONCLUSIONS: The higher resistance of the 2.5 mm tube may be detrimental to extremely low birthweight infants kept on mechanical support merely "to grow." The higher resistance may increase the work of breathing and thus increase caloric expenditure and impede growth.

Airway Resistance↗