Vinod (Vinny) K. Bhutani

Abstract

Background:The therapeutic phototherapy action spectrum ranges from 420 to 500nm. However, a recent report of improved efficacy offluorescent "turquoise"light (~490 nm) compared toblue light(~450 nm) underscores the need to define an optimal action spectrum for precision-targeted phototherapy using very narrow wavelength ranges.Methods:We used a current semi-empirical model of theoptical properties of skinfor robust calculations of the fraction of light absorbed by bilirubin at various wavelengths that could be confounded by hemoglobin, melanin and skin thickness. Applying assumptions regarding the wavelength dependence of bilirubin photochemistry, "action spectra"wereassembled from the calculated values.Results:All the calculated action spectra displayed a peak between 472 and 480 nm (most at 476 nm), which is a significant shift from the well-reported 460 nm absorption peak of bilirubin. Interestingly, the relative amplitudes of the action spectra showed an inverse relationship with hematocrit.Conclusion:We speculate that narrow range of light at 476 nmshould be 60% more effective than blue (broad-band) fluorescent lamps. Because hemoglobin serves as a major competitor of bilirubin for light absorption, the calculations also predict that the efficacy of phototherapy is dependent on the hematocrit.A high hematocrit could reduce therapeutic efficiency.Pediatric Research (2013); doi:10.1038/pr.2013.67.

View details for DOI 10.1038/pr.2013.67

View details for Web of Science ID 000321795300009

View details for PubMedID 23604171

View details for PubMedID 23665596

View details for PubMedID 23335271

View details for DOI 10.1007/s13312-012-0149-7

View details for Web of Science ID 000309225900004

View details for PubMedID 23024077

View details for DOI 10.1111/j.1651-2227.2012.02605.x

View details for Web of Science ID 000302349200016

View details for PubMedID 22251098

Abstract

Phototherapy is the treatment of choice to reduce the severity of neonatal unconjugated hyperbilirubinemia regardless of its etiology. Its implementation requires a technical framework that conforms to existing evidence-based guidelines that promote its safer and effective use worldwide. Optimal use of phototherapy has been defined by specific ranges of total serum bilirubin thresholds configured to an infant's postnatal age (in hours) and potential risk for bilirubin neurotoxicity. Effective phototherapy implies its use at specific blue light wavelengths (peak emission, 450 ± 20 nm) and emission spectrum (range, 400-520 nm), preferably in a narrow bandwidth that is delivered at an irradiance of ?30 ?W/cm(2)/nm to up to 80% of an infant's body surface area. However, this is often not feasible in clinical settings with limited or constrained resources. To identify and bridge implementation barriers, we propose minimum criteria for device performance for safe and practical use of phototherapy as a prophylactic intervention to prevent severe hyperbilirubinemia.

View details for DOI 10.1053/j.semperi.2011.02.015

View details for Web of Science ID 000292057900014

View details for PubMedID 21641494

Abstract

Breakdown in systems for safe newborn health-care delivery accounts for the majority of kernicterus cases encountered in the United States. Traditional epidemiologic investigations do not track the national incidence of severe hyperbilirubinemia and kernicterus or recognize its recent surge. Innovative investigative strategies are needed to seek more sensitive surrogates for kernicterus (often diagnosed late in infancy) and to overcome the limitations of retrospective continuity of adverse neonatal experiences because of severe hyperbilirubinemia. Root cause analysis of a cohort of infants who manifested kernicterus in the past two decades attests to some of the clinical and health-service barriers encountered by families as they negotiate health care from multiple providers at multiple sites during the first week after birth. Clinicians, health-care organizations, parents, and payors and purchasers of health care were often unaware of the ongoing patterns of care that may have obstructed preventive care. Now, partly based on these analyses, key recommendations have led to clinical usable guidelines for practitioners and have contributed to systems-oriented national guidelines for evidence-based safer management of newborn jaundice.(1) Clinician- and family-oriented tool kits have been made available, based on the report presented in this study, to facilitate effective implementation and thus optimize and institutionalize these guidelines (http://www.cdc.gov/jaundice). An informed partnership of parents and clinicians seems to be the most effective strategy to prevent severe neonatal hyperbilirubinemia and 'near-miss' cases of kernicterus in the United States.

View details for DOI 10.1038/jp.2008.210

View details for PubMedID 19177058

Abstract

To address systems failures and promote a safer management of newborn jaundice, we propose an 'aviation safety standard' for newborn health-care services during the first week after birth. Systems failure in newborn jaundice management has been characterized by lapses in concern, loss of continuity, and delays in care by multiple providers at multiple sites. Components for a six-step national strategy to prevent severe neonatal hyperbilirubinemia and possibly kernicterus are being implemented as delineated in the 2004 AAP guidelines. The clinical guidelines for safer and evidence-based practice have been characterized by both healthcare and societal communities. Professional and community organizations are optimizing outreach resources and facilitating institutionalization of these practices. Nationwide implementation at individual birthing hospitals concurrent with surveillance feedback needs to be initiated. Implementation of a 'six-sigma' approach, as proposed to the current Center for Disease Control and Prevention-initiated partnership (health-care providers, public health and community advocates) may be achieved through collaboration with state and national agencies.

View details for DOI 10.1038/jp.2008.213

View details for Web of Science ID 000263604400011

View details for PubMedID 19177062

Abstract

Acute kernicterus remains a clinical emergency and its delayed management represents an easily preventable neonatal brain injury. Yet, practitioners encounter recurrent questions regarding the risk and timing of bilirubin-related neurotoxicity. These include the following: does bilirubin damage the brain of healthy infants? Is there a re-emergence of kernicterus in the United States? Was kernicterus previously prevented in the United States? What was the public health impact of 1994 American Academy of Pediatrics Guidelines? What is the current incidence of kernicterus and severe neonatal hyperbilirubinemia? What is the estimated risk of kernicterus in infants with excessive hyperbilirubinemia? Is there a specific bilirubin threshold total serum bilirubin (TSB) value for neurotoxicity? Are there sequelae of severe or prolonged moderate hyperbilirubinemia in the absence of recognized acute bilirubin encephalopathy? Can we define a bilirubin level that is safe in newborns? We address these questions in the context of available data and evidence, and estimate the current risk of chronic kernicterus is about one in seven in infants with TSB >30 mg per 100 ml (513 micromol l(-1)).

View details for DOI 10.1038/jp.2008.212

View details for Web of Science ID 000263604400006

View details for PubMedID 19177056

View details for Web of Science ID 000262840800003

View details for PubMedID 19179712

Abstract

Passage of fetal bowel movement (meconium) is common (in about one out of six births), and in some the staining of the amniotic fluid is a sign of fetal distress. Inhalation of meconium (aspiration syndrome, in upto one out of five to eight such births) just before or at birth may be preventable by a coordinated approach by well-trained and informed birth attendants. Respiratory failure secondary to meconium aspiration syndrome (MAS) remains a major cause of morbidity and mortality in the neonatal population. Infants with hypoxemic respiratory failure because of MAS, persistent pulmonary hypertension of the newborn and pneumonia/sepsis have an increased survival with extracorporeal membrane oxygenation (ECMO). Other treatment options earlier limited to inotropic support, continuous airway pressure (CPAP), conventional ventilatory management, respiratory alkalosis, paralysis and intravenous vasodilators have been replaced by synchronized intermittent mandatory ventilation (SIMV), high-frequency oscillatory ventilation (HFOV), surfactant and inhaled nitric oxide (iNO). HFOV has been advocated for use to improve lung inflation while potentially decreasing lung injury through volutrauma. Other reports describe the enhanced efficacy of HFOV when combined with iNO. Subsequent to studies reporting that surfactant deficiency or inactivation may contribute to neonatal respiratory failure, exogenous surfactant therapy has been implemented with apparent success. Recent studies have shown that iNO therapy in the neonate with hypoxemic respiratory failure can result in improved oxygenation and decreased need for ECMO. However, these innovative interventions are costly, require a sophisticated infrastructure and are not universally accessible. In this paper, a context of systems-approach for prenatal, natal and postnatal management of babies delivered through meconium stained amniotic fluid (MSAF) so that adverse outcomes are minimized and the least number of babies require innovative ventilatory support is described. Previously reported data from a single urban perinatal center (Philadelphia, PA, USA), over a 6-year period (1995-2000), demonstrated that 14.5% (3370/23175 of live births babies were delivered with MSAF. These data also showed that 4.6% of babies (155/3370) with MSAF sustained MAS. Overall, 26% of babies (40/155) with MAS needed ventilatory support (or 0.17% of all live births); of these, only 20% (8/40 or 0.035% of live births) needed innovative ventilatory support. None died or needed ECMO. These data describe the components for a systems approach to prevent and manage adverse outcomes related to MSAF at the regional level II or III perinatal center. Replication of a similar strategy may be more relevant to cost containment and be a safer approach for neonates at risk for MAS-related respiratory failure. This paper assess the evidence for pivotal steps needed to prevent MAS and ensuing neonatal death and disease in the context of diverse perinatal health services.

View details for DOI 10.1038/jp.2008.159

View details for Web of Science ID 000261417200007

View details for PubMedID 19057608

Abstract

Inhibition of heme oxygenase (HO), the rate-limiting enzyme in heme catabolism, may be an ideal strategy for preventing neonatal jaundice. Although natural and synthetic heme analogs, called metalloporphyrins (Mps), have been extensively investigated for this purpose, some Mps are phototoxic, affect the activity of other enzymes, or induce HO-1 transcription-properties that may limit their clinical use. Another class of compounds, imidazole-dioxolanes, has been shown to selectively inhibit the inducible isozyme HO-1. Therefore, we investigated the efficacy of azalanstat (AZA), an imidazole-dioxolane, towards inhibiting HO activity in 7-day-old mice. We found that a single dose of AZA at 500 micromol.kg(-1) body mass (BM) administered i.p. significantly inhibited HO activity and reduced in vivo bilirubin production. In the spleen, HO inhibition (>50%) was observed within 0.25-3 h after administration. After 24 h, however, spleen HO activity, HO-1 protein, and HO-1 mRNA levels significantly increased 1.2-, 2.4-, and 4.0-fold, respectively. We conclude that AZA effectively inhibits in vivo HO activity only at a high dose and that it also induces spleen HO-1 gene transcription. Therefore, other imidazole-dioxolanes should be evaluated to determine whether they are more potent than AZA for use in treating neonatal jaundice.

View details for DOI 10.1139/Y08-069

View details for Web of Science ID 000260168100001

View details for PubMedID 18841169

Abstract

The purpose of this work was to compare the predictive accuracy of alternative risk-assessment strategies used to screen for the risk of significant neonatal hyperbilirubinemia.We conducted a prospective cohort study of 823 term and near-term newborns admitted to the well-infant nursery at the Hospital of the University of Pennsylvania. Maternal, infant, and delivery risk factors for significant hyperbilirubinemia were obtained from chart review, structured interviews with parents, and nurse assessments before discharge. Transcutaneous bilirubin measurement was performed daily until discharge and once by a visiting home nurse between 3 and 8 days of life. We used the c statistic to compare the predictive accuracy of 3 risk-assessment strategies for estimating the risk of significant neonatal hyperbilirubinemia, defined as a bilirubin level that at any time after birth exceeded or was within 1 mg/dL (17 micromol/L) of the hour-specific phototherapy treatment threshold recommended by the American Academy of Pediatrics in 2004. The compared strategies included those that use (1) a predischarge bilirubin level (obtained before 52 hours) expressed as a risk zone on an hour-specific bilirubin nomogram, (2) clinical risk factors other than the predischarge bilirubin level, and (3) a combination of the predischarge bilirubin risk zone and additional clinical risk factors.Forty-eight patients (6%) developed significant neonatal hyperbilirubinemia. The predischarge (<52 hours) bilirubin level expressed as a risk zone on the bilirubin nomogram and a prediction model that combined multiple other clinical risk factors had similar accuracy for predicting significant hyperbilirubinemia. The only clinical risk factor that could be added to the predischarge risk zone to improve overall predictive accuracy was gestational age. The predischarge bilirubin risk zone and gestational age could be used to stratify patients into a large group (n = 523 [70%]) of infants with a very low (0.2%) risk of developing significant hyperbilirubinemia, a small group of infants (n = 127 [17%]) with a low (4%) risk of developing significant hyperbilirubinemia, and an even smaller group of infants (n = 100 [13%]) with a high (42%) risk of developing significant hyperbilirubinemia.An infant's risk of developing significant hyperbilirubinemia can be simply and accurately assessed by using just the infant's predischarge bilirubin level and gestational age.

View details for DOI 10.1542/peds.2006-3499

View details for Web of Science ID 000252096300061

View details for PubMedID 18166536

Abstract

Kernicterus is still occurring but should be largely preventable if health care personnel follow the recommendations listed in this guideline. These recommendations emphasize the importance of universal, systematic assessment of the risk of severe hyperbilirubinemia, lactation support, close follow-up, and prompt intervention when necessary. A systems-based approach to prevent severe neonatal hyperbilirubinemia should be implemented at all birthing facilities and coordinated with continuing ambulatory care. Translational research is needed to better understand the mechanisms of bilirubin neurotoxicity and potential therapeutic interventions.

View details for DOI 10.1159/000113463

View details for Web of Science ID 000256573000011

View details for PubMedID 18204221

Abstract

To propose and implement a family-centered systems approach to manage newborn jaundice for safer outcomes.Observational study for known adverse outcomes.Semiprivate urban birthing hospital.31,059 well babies discharged as healthy from a cohort of 41,961 live births (1990-2000).Incremental implementation of a systems approach that incorporated a hospital policy to (a) authorize nurses to obtain a bilirubin (total serum/transcutaneous) measurement for clinical jaundice, (b) universal predischarge total serum bilirubin (at routine metabolic screening), and (c) targeted follow-up, using the bilirubin nomogram (hour-specific, percentile-based total serum bilirubin/transcutaneous bilirubin).Known adverse outcomes assessed for early- and late-onset severe hyperbilirubinemia before, during, and after systems approach implementation.Adverse outcomes decreased for well babies: exchange transfusion, intensive phototherapy, and readmission. During the study period, there were no "never events" (total serum bilirubin greater than or equal to 30 mg/dl), while "close calls" (total serum bilirubin greater than or equal to 25 mg/dl) were 1 in 15,000 as compared to a reported incidence of 1 in 625.Reduced adverse events, significant reduction in close calls, and no never events met family expectations for safer experiences with this approach.

View details for DOI 10.1111/J.1552-6909.2006.00044.x

View details for Web of Science ID 000239009100002

View details for PubMedID 16881988

Abstract

To compare the clinical profile and health care experiences related to management of newborn jaundice and hyperbilirubinemia in preterm infants (<37(0/7) weeks gestation) who are cared for as term infants (> or =37(0/7) weeks) and develop acute and/or chronic posticteric sequelae.Retrospective study of a convenient sample of term and near term infants voluntarily reported to the Pilot Kernicterus Registry (1992-2003). Study infants were required to meet the clinical definitions for acute bilirubin encephalopathy (moderate or advanced severity) and/or the classical signs of kernicterus. Main outcome measures were the comparison of etiology, severity and duration of extreme hyperbilirubinemia (TSB levels >20 mg/dL), response to interventions of intensive phototherapy and exchange transfusion, and health care delivery experiences in preterm as compared with term infants.No targeted attention was accorded to preterm infants during their neonatal health care experiences as related to predischarge risk assessment, feeding, discharge follow-up instructions, or breastfeeding, regardless of the known vulnerability of preterm infants to safely transition during the first week after birth. The TSB levels, age at re-hospitalization, and birth weight distribution were similar for late preterm and term infants. Large for gestational age and late preterm infants disproportionately developed kernicterus as compared with those who were appropriate for gestational age and term. Clinical management of extreme of hyperbilirubinemia, by the attending clinical providers, was not impacted or influenced by the gestational age, clinical signs, or risk assessment. This resulted in severe posticteric sequelae which was more severe and frequent in late preterm infants.Late prematurity (34(0/7) to 36(6/7) weeks) of healthy infants was not recognized as a risk factor for hazardous hyperbilirubinemia by clinical practitioners. Unsuccessful lactation experience was the most frequent experience; being large for gestational age as well as the other known biologic risk factors for hyperbilirubinemia and bilirubin neurotoxicity were not identified by the clinical care providers either before discharge or at immediate postdischarge follow up.

View details for DOI 10.1053/j.semperi.2006.04.001

View details for Web of Science ID 000238327000008

View details for PubMedID 16731283

View details for PubMedID 16027713

Abstract

To compare the predictive performance of clinical risk factor assessment and pre-discharge bilirubin measurement as screening tools for identifying infants at risk of developing significant neonatal hyperbilirubinaemia (post-discharge total serum bilirubin (TSB) >95th centile).Retrospective cohort study of term and near term infants born in an urban community teaching hospital in Pennsylvania (1993-97). A clinical risk factor scoring system was developed and its predictive performance compared to a pre-discharge TSB expressed as a risk zone on a bilirubin nomogram. Main outcome measures were prediction model discrimination, range of predicted probabilities, and sensitivity, specificity, positive and negative predictive values, and likelihood ratios for various positivity criteria.The clinical risk factor scoring system developed included birth weight, gestational age <38 weeks, oxytocin use during delivery, vacuum extraction, breast feeding, and combination breast and bottle feeding. The pre-discharge bilirubin risk zone had better discrimination (c = 0.83; 95% CI 0.80 to 0.86) than the clinical risk factor score (c = 0.71; 95% CI 0.66 to 0.76) and predicted risk of significant hyperbilirubinaemia as high as 59% compared with a maximum of 44% for the clinical risk factor score. Neither the risk score nor the pre-discharge TSB risk zone predicted the outcome with > or =0.98 sensitivity without significantly compromising specificity (0.13 and 0.21, respectively). Multi-level clinical risk factor scores and TSB risk zones produced likelihood ratios of 0.15-3.25 and 0.05-9.43, respectively.The pre-discharge bilirubin expressed as a risk zone on an hour specific bilirubin nomogram is more accurate and generates wider risk stratification than a clinical risk factor score.

View details for DOI 10.1136/adc.2004.060079

View details for Web of Science ID 000227805500026

View details for PubMedID 15781937

Abstract

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.

View details for DOI 10.1016/j.clp.2004.11.002

View details for Web of Science ID 000227662400009

View details for PubMedID 15777825

Abstract

Kernicterus, preventable in most cases but with untreatable and tragic sequelae, is a matter of public health concern that requires implementation of safer community healthcare standards to prevent its occurrence.

View details for PubMedID 15684449

Abstract

Kernicterus in sick and preterm infants is a rarity. Universal availability of phototherapy and concerted clinical efforts to identify, effectively manage and establish clinical guidelines have been instrumental in preventing kernicterus in US intensive care nurseries. However, in sick and preterm infants the absence of precise data on prevalence of bilirubin induced neurologic injury, the lack of proven predictive indices and the absence of evidence-based studies that clearly demonstrate the actual risk of kernicterus. These leave questions regarding the basis for clinical strategies and recommendations for the management of neonatal jaundice in this select population. This article reviews 6 preterm infants selected from the Pilot Kernicterus Registry who had recovered from life-threatening neonatal illnesses, briefly discusses current indices used to ascertain risk, and offers an initial bilirubin level based identification of infants while future directions and studies are conducted to supplement our presently incomplete knowledge for safer clinical practice.

View details for DOI 10.1053/j.demperi.2004.09.006

View details for Web of Science ID 000226212000002

View details for PubMedID 15686262

Abstract

Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders. At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.

View details for PubMedID 15254556

Abstract

New data support restructuring the approach toward diagnosis and management of hyperbilirubenia in the term neonate to make it more physician-friendly and gain wider implementation. The authors advocate clear criteria for patient safety, preventive approaches, and timely interventions. Structural changes to facilitate a system-based approach should include predischarge bilirubin management; follow-up bilirubin management; and lactational support and nutritional management. The authors advocate total serum bilirubin screening and a scoring system based on clinical risk factors as predischarge screening strategies; we should screen all babies for hyperbilirubinemia and for targeted follow-up based on an hour-specific total serum bilirubin measured for risk assessment. We should also provide focused universal education emphasizing adequate lactational nutrition, to decrease severe hyperbilirubinemia and thus prevent kernicterus.

View details for DOI 10.1016/j.pcl.2004.03.011

View details for Web of Science ID 000223511000002

View details for PubMedID 15275978

Abstract

Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates.Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat.Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024).Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

View details for Web of Science ID 000221546300007

View details for PubMedID 15158628

View details for PubMedID 15123860

View details for DOI 10.1373/clinchem.2003.024489

View details for Web of Science ID 000189287500006

View details for PubMedID 14726464

Abstract

Respiratory failure remains a major cause of morbidity and mortality in the neonatal population. Infants with hypoxemic respiratory failure because of meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN), and pneumonia/sepsis have a potential for increased survival with extracorporeal membrane oxygenation (ECMO). Other treatment options previously limited to inotropic support, conventional ventilatory management, respiratory alkalosis, paralysis and intravenousvasodilators have been replaced by high-frequency oscillatory ventilation (HFOV), surfactant, and inhaled nitric oxide (iNO). HFOV has been advocated for use to improve lung inflation while potentially decreasing lung injury through volutrauma. Other reports describe enhanced efficacy of HFOV when combined with iNO. Subsequent to studies reporting surfactant deficiency or inactivation may contribute to neonatal respiratory failure exogenous surfactant therapy has been implemented with apparent success. Recent studies have shown that iNO therapy in the neonate with hypoxemic respiratory failure can result in improved oxygenation and decreased need for ECMO. In this article, the authors place in context of a system-based strategy the prenatal, natal and postnatal management of babies delivered through meconium stained amniotic fluid (MSAF) so that adverse outcomes are minimized, and the least number of babies require innovative ventilatory support. At Pennsylvania Hospital, over a six-year period (1995 to 2000), 14.5% (3370/23,175 of live births babies were delivered with MSAF. These data show that 4.6% (155/3370) of babies with MSAF sustained MAS. Overall, 26% (40/155) of babies with MAS needed ventilatory support (or 0.17% of all live-births); of these only 20% (8/40 or 0.035% of live births) needed innovative ventilatory support. None died or needed ECMO. These data describe the impact of a system-based approach to prevent and manage adverse outcomes related to MSAF at regional Level III perinatal center.

View details for PubMedID 12841404

Abstract

Kernicterus, a preventable injury to the brain from severe neonatal jaundice, has re-emerged in the United States as a public and societal health concern. Kernicterus, in its usually recognized form, causes devastating disabilities, including athetoid cerebral palsy and speech and hearing impairment. This condition not only ranks amongst the highest cost per new case (per CDCs Financial Burden of Disability study, 1992), but also results in profound and uncompromising grief for the family and loss to siblings of healthy, talkative playmates. And for the child with kernicterus (usually remarkably intelligent, but trapped in an uncontrollable body), grief and frustration are enormous. In 2001 national healthcare organizations, including Centers for Disease Control (CDC), the Joint Commission for the Accreditation of Healthcare Organizations (JACHO) and the American Academy of Pediatrics (AAP) issued alerts to all accredited hospitals and public health professionals in the United States that all healthy infants are at potential risk of kernicterus if their newborn jaundice is unmonitored and inadequately treated. The re-emergence of kernicterus in the United States is the result of interacting phenomena including (a) Early hospital discharge (before extent of jaundice is known and signs of impending brain damage have appeared); (b) Lack of adequate concern for the risks of severe jaundice in healthy term and near newborns; (c) An increase in breast feeding; (d) Medical care cost constraints; (e) Paucity of educational materials to enable parents to participate in safeguarding their newborns; and (f) Limitations within in healthcare systems to monitor the outpatient progression of jaundice. A multidisciplinary approach that encompasses both healthcare and societal needs should be evaluated at a national level for practical and easy to implement strategies. An approach that is based on principles of evidence-based medicine, patient-safety and family centeredness is presented in this article. These strategies should also be based on public awareness campaign such that the healthcare providers can attempt to achieve a "Zero Tolerance of Kernicterus" and thereby decrease both childhood disabilities and infant mortality within the community.

View details for PubMedID 12841402

View details for Web of Science ID 000181960600037

View details for PubMedID 12671137

Abstract

Pulmonary function and mechanics testing are emerging as a valuable tool to aid clinical decision making in the management of ventilated infants. Although there are as yet no published randomized controlled trials to suggest that pulmonary mechanics testing reduces mortality or morbidity, it has--in conjunction with clinical, radiological, and blood gas monitoring--changed neonatal ventilation from "good judgement" to "informed judgement". It is not surprising that pulmonary graphics are increasingly being used as a tool for assessment of patient status, therapeutic evaluation, and management guidance of infants who become dependent on ventilator. A working knowledge of pulmonary graphics also improves understanding of pulmonary physiology and pathophysiology, and their responses to mechanical ventilatory support. Recent advances in microprocessor technology for on-line analysis of pulmonary mechanics have made such evaluations easily available for bedside clinical application.

View details for PubMedID 12464501

View details for DOI 10.1067/mpd.2002.123098

View details for Web of Science ID 000175524400007

View details for PubMedID 12006952

View details for PubMedID 11803423

View details for Web of Science ID 000172398500006

View details for PubMedID 11726722

Abstract

The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life.From nine multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998 through February 22, 1999. Measurements of both ETCOc and STB were performed at 30+/-6 hours of life; STB also was measured at 96+/-12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study.A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breast-fed infants was 8.92+/-4.37 mg/dl at 96 hours versus 7.63+/-3.58 mg/dl in those fed formula only. The mean ETCOc at 30+/-6 hours for the total population was 1.48+/-0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45+/-0.47 and 1.81+/-0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30+/-6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB > or =95th percentile. When infants with STB > or =95th percentile at <36 hours of age were excluded, the STB at 30+/-6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these two measurements at 30+/-6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV.This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30+/-6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

View details for PubMedID 11803421

Abstract

Decades of research have led to the understanding of neonatal pulmonary physiology and have influenced the clinical care that neonatologists provide to the sick newborn. Advances in microprocessor technology have allowed for clinical access of the research-based measurements of neonatal pulmonary functions. These evaluations are not only the integrated evaluation of the three primary vectors of respiration (driving pressure, air flow, and volume measured over time) but also values calculated by known physiologic equations. Clinical use of these data may not only be relevant and helpful in the bedside management, but also provides a uniquely objective and research-oriented data collection for individual newborns.

View details for Web of Science ID 000171029800002

View details for PubMedID 11570150

Abstract

The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life.From 9 multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998, through February 22, 1999. Measurements of both ETCOc and STB were performed at 30 +/- 6 hours of life; STB also was measured at 96 +/- 12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study.A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breastfed infants was 8.92 +/- 4.37 mg/dL at 96 hours versus 7.63 +/- 3.58 mg/dL in those fed formula only. The mean ETCOc at 30 +/- 6 hours for the total population was 1.48 +/- 0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45 +/- 0.47 ppm and 1.81 +/- 0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30 +/- 6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB >/=95th percentile. When infants with STB >95th percentile at <36 hours of age were excluded, the STB at 30 +/- 6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these 2 measurements at 30 +/- 6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV. Conclusions. This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30 +/- 6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

View details for Web of Science ID 000169571400025

View details for PubMedID 11433051

Abstract

In view of the limitations in the accurate visual assessment of jaundice and its potential role as a predictive vector for serious neurologic sequelae, we propose that a universal screening of bilirubin be considered concurrent to the routine pre-discharge metabolic screening. Universal bilirubin screening in the term and near-term newborns when plotted on "Hour-specific Bilirubin Nomogram" in lieu of the usual "day-specific" value will predict the high-risk and the low-risk groups and facilitate cost-effective and individualized follow-up of those babies at risk. A percentile based bilirubin nomogram for the first week of age was constructed from hour-specific pre- and post-discharge bilirubin values of 2840 healthy term and near-term babies. The accuracy of the pre-discharge bilirubin values was determined as a predictive vector. Pre-discharge (18-72 hours age), 6.1% of the study population had bilirubin values in the high-risk zone (> 95th percentile). Of these, 39.5% remained in that zone (likelihood ratio ¿LR¿ = 14.08). Pre-discharge, 32.1% of the study population had bilirubin values in the intermediate risk zone (40-75th percentiles). In a clinically significant minority of these babies (6.4%), the post-discharge values moved to the high-risk zone (L-R = 3.2 for the move from the upper-intermediate zone and 0.48 from the lower-intermediate zone). In the remainder 61.8% of the population who were identified to be at low risk, there was no measurable risk for significant hyperbilirubinemia (L-R = 0). The bilirubin nomogram can predict which infant is at high, intermediate, and low risk for subsequent excessive hyperbilirubinemia and allows for the individualized follow-up of these high-risk babies with particular attention to those who may need evaluation and intervention. Whereas, identification of the low risk group allows for a less intense bilirubin follow-up and in whom a visual check by an experienced care-provider may suffice.

View details for PubMedID 11105424

Abstract

Jaundice in near-term and term newborns is a frequent diagnosis that may prompt hospital readmission in the first postnatal week. Hyperbilirubinemia, when excessive, can lead to potentially irreversible bilirubin-induced neurotoxicity. Predischarge risk assessment (at 24-72 hours of age) for subsequent excessive hyperbilirubinemia is feasible by a laboratory-based assay of total serum bilirubin (TSB). Hypothesis. Noninvasive, transcutaneous, point-of-care measurement of transcutaneous bilirubin (TcB) predischarge by multiwavelength spectral analysis, using a portable BiliCheck device (SpectRx Inc, Norcross, GA), is clinically equivalent to measurement of TSB in a diverse, multiracial term and near-term newborn population and predictive of subsequent hyperbilirubinemia.We evaluated a hand-held device that uses multiwavelength spectral reflectance analysis to measure TcB (BiliCheck). The study population (490 term and near-term newborns) was racially diverse (59.1% white, 29.5% black, 3.46% Hispanic, 4.48% Asian, and 3.46% other) and was evaluated at 2 separate institutions using multiple (11) devices. The postnatal age ranged from 12 to 98 hours and the ranges of birth weights and gestational ages were 2000 to 5665 g and 35 to 42 weeks, respectively. All transcutaneous evaluations were performed contemporaneously and paired with a heelstick TSB measurement. All TSB assays were performed by high performance liquid chromatography, as well as by diazo dichlorophenyldiazonium tetrafluoroborate techniques.TSB values ranged from .2 to 18.2 mg/dL (mean +/- standard deviation: 7.65 +/- 3.35 mg/dL). The overall correlation of TSB (by high performance liquid chromatography technique) to TcB (by BiliCheck devices) was linear and statistically significant (r =.91; r(2) =.83; TcB =.84; TSB = +.75; standard error of regression line = 1.38; P <.001; n = 490 infants; 1788 samples). Similar regression statistics were evident in subset populations categorized by race (white: r =.91 [n = 289 infants]; black: r =.91 [n = 145 infants]) as well as by gestation (term: r =. 91 [n = 1625 samples]; near-term: r =.89 [n = 163 samples]). Intradevice precision was determined to be.59 mg/dL (2-3 measurements per infant with 1 device; n = 210 infants; 510 samples in a separate subset). Interdevice evaluation of 11 devices determined the precision to be.68 mg/dL (2-4 devices used for measurements per patient). In 23 of 419 of the study population infants who were in the 24- to 72-hour age range, the predischarge TSB values designated them to be at high risk for subsequent excessive hyperbilirubinemia (above the 95th percentile track on the hour-specific bilirubin nomogram). For these infants, the paired BiliCheck TcB values were all above the 75th percentile track (negative predictive value = 100%; positive predictive value = 32. 86%; sensitivity = 100%; specificity = 88.1%; likelihood ratio = 8. 43).Our data demonstrate the accuracy and reproducibility of the predischarge BiliCheck measurements in term and near-term newborn infants of diverse races and ethnicities. Infants with predischarge BiliCheck values above the 75th percentile of hour-specific TSB values on the bilirubin nomogram may be considered to be at high risk for subsequent excessive hyperbilirubinemia. Further studies are needed to assess the efficacy of this technique in preterm infants, those undergoing phototherapy, and those with TSB values of >/=15 mg/dL (>/=256 micromol/L).

View details for Web of Science ID 000088538100003

View details for PubMedID 10920173

Abstract

Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease.We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age.The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%).Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.

View details for Web of Science ID 000082777500010

View details for PubMedID 10509496

Abstract

This article reviews the current trends in the evaluation and management of bacterial infection involving the uterus, placenta, membranes, amniotic fluid, and fetus occurring near the time of birth. The discussion includes information regarding risk, incidence, pathophysiology, bedside diagnosis, interventional options including antibiotics, corticosteroids, fetal monitoring, and delivery, and possible preventive measures which affect the outcome. The adequate evaluation and management of perinatal infection requires a team approach with obstetricians and pediatricians. Clinical screening is useful in developing the diagnosis, but amniotic fluid evaluation remains the proposed gold standard. The role of cytokines is becoming increasingly important, as is seen in the association of IL-6 with positive amniotic fluid cultures and periventricular leukomalacia. Prompt recognition and management of the pregnancy affected by infection can improve perinatal outcomes. A management protocol is presented to help structure the approach to suspected infection. Premature delivery due to perinatal infection may be preventable.

View details for PubMedID 10773948

Abstract

Factors believed to have contributed to the reemergence of kernicterus in the United States during the 1990's are discussed: these include decreased concern about toxicity of bilirubin in term and near-term infants, increased prevalence of breastfeeding, and increasingly shortened postnatal hospital stays. The rationale for a universal predischarge bilirubin measurement at the time of the routine predischarge metabolic screen is presented: the hour-specific level of bilirubin at discharge, plotted on an Hour-Specific Bilirubin Nomogram, improves prediction of risk of excessive jaundice postdischarge and facilitates safe, cost-effective follow-up. This minimizes repeat bilirubin measurements and maximizes recognition of confounding variables and risk of hyperbilirubinemia so that timely, minimally invasive, preventive therapy can be instituted if needed.

View details for Web of Science ID 000076016000005

View details for PubMedID 9779334

Abstract

Short-term inhaled dexamethasone therapy was evaluated in a double blind placebo controlled trial in 36 ventilator dependent preterm neonates (BW < 1500 gm, postnatal age > 7 days) who were at risk for bronchopulmonary dysplasia. Pulmonary and systemic effects were compared at early (day 3), late (7-10 days) and post (14 days after initiation) phases of therapy. Airflow mechanics improved as demonstrated by a net 101% improvement in pulmonary resistance (a decrease from 139 to 101 cm H2O/L/s in the dexamethasone treated infants as compared to an increase from 153 to 267 cmH2O/L/s in the placebo treated infants during the early phase of therapy); this was associated with a 45% increase in inspiratory airflow (1.29 +/- 0.43 to 1.87 +/- 0.978 L/min; p < 0.01), and 37% increase in expiratory airflow. These changes resulted in a significant reduction in the work of breathing such that the mean tidal driving pressure significantly decreased from 13.6 cmH2O to 9.4 cm H2O with inhaled steroid administration. Though the brief duration of therapy did not result in cessation of ventilatory support, the level of support was significantly reduced (decreased values of oxygen supplementation, mean airway pressure and oxygenation index and increased ventilatory efficiency index). The inhaled dexamethasone therapy was also associated with systemic absorption of the drug as evidenced by transient but apparently reversible reduction in serum cortisol levels. No systemic side effects of hypertension, hyperglycemia or nosocomial sepsis were observed. These data demonstrate beneficial effects of short-term inhaled dexamethasone on the resistive airflow properties of preterm infants at risk for BPD and may provide adjunctive means to facilitate weaning in the ventilator dependent neonates.

View details for PubMedID 10771973

View details for Web of Science ID A1996VF50600020

View details for PubMedID 8784375

Abstract

Pulsed Doppler ultrasound blood flow profiles were studied, before the initiation of enteral feedings, in 23 neonates with birth asphyxia. We observed a significant direct correlation between the reduction of peak velocity and increased resistance in the renal and superior mesenteric arteries to the severity of asphyxia (r = 0.8; p < 0.05); the changes often persisted up to 3 days of age. Longitudinal evaluation of flow in these vessels might help to time the initiation of enteral nutrition in neonates with asphyxia.

View details for Web of Science ID A1994PK52900023

View details for PubMedID 7931888

Abstract

Both surfactant replacement and positive end-expiratory pressure (PEEP) increase lung volume in infants with respiratory distress syndrome (RDS). We measured pulmonary mechanics and functional residual capacity (FRC) in 21 preterm infants with RDS, > 48 hr post-surfactant therapy (BW, 1,168 +/- 441 g; GA, 28.3 +/- 2.8 weeks; postnatal age, 3-7 days). A non-linear but significant increase in mean FRC was noted as PEEP increased from 2 to 5 cmH2O: 18.4 +/- 4.7 mL/kg at 2 cmH2O; 19.7 +/- 4.3 mL at 3 cmH2O; 22.6 +/- 5.5 ml/kg at 4 cmH2O; and 26.2 +/- 6.2 mL/kg at 5 cmH2O (P < 0.01). Because of the synergistic combined effect on lung volume, surfactant treated neonates should be weaned cautiously from PEEP during ventilatory management. Our study also suggests that the occurrence of inadvertent end-distending pressure during FRC measurement in the ventilated neonate lead to erroneous results.

View details for Web of Science ID A1994PD75200005

View details for PubMedID 7970924

Abstract

The influence of head-neck posture (neutral, 15 degrees, 30 degrees, and 45 degrees extension and flexion) on airflow and pulmonary mechanics was evaluated in 10 spontaneously breathing healthy preterm neonates (mean +/- SD; birth weight, 1.32 +/- 0.23 kg; gestational age, 29.4 +/- 2.4 weeks; study age, 36.6 +/- 1.6 weeks) who had had respiratory distress syndrome. Head-neck postures were quantified using specially constructed wooden wedges. Airflow was measured by a pneumotachometer via face mask. Lung compliance (CL) and resistance (RL) were measured using an esophageal balloon. Airflow interruption was designated as mild (10-40%), moderate (40-80%), and severe (> 80-100%) decrease of airflow. At neutral head-neck posture, 42.8 +/- 7.5% SEM of breaths had airflow interruption (71.4% mild, 19.9% moderate, 8.7% severe). There was no significant change with 15 degrees and 30 degrees head-neck flexion and extension. However, at 45 degrees flexion the overall incidence of airflow interruption (77.3 +/- 4.8%, P < 0.05) and RL (86.6 +/- 6.7 vs. 64.2 +/- 3.9 cmH2O/L/s, mean +/- SEM; P < 0.05) significantly increased. Extension to 45 degrees caused severe airflow interruption and increased RL in some infants, but no statistically significant change for the whole group. The incidence of severe airflow interruption significantly increased (P < 0.05) from 8.7% at neutral head-neck posture to 26.3% at hyperflexion (45 degrees). No changes in CL were observed. We conclude that minor (15-30 degrees) deviations from neutral neck posture are insignificant, whereas hyperflexion, and in some infants, hyperextension, can significantly affect airflow and pulmonary mechanics.

View details for Web of Science ID A1994MY96300002

View details for PubMedID 8196994

Abstract

To compare the effects of intermittent and continuous feedings on pulmonary function, we studied 24 very low birth weight neonates (mean +/- SD: birth weight, 1.2 +/- 0.3 kg; gestational age, 30.5 +/- 1.1 weeks) at 2 to 4 weeks of age. All infants had a previous diagnosis of respiratory distress syndrome but no subsequent diagnosis of bronchopulmonary dysplasia. Pulmonary mechanics were measured before the beginning of intermittent or continuous feedings and 10 minutes after each meal was completed. Twelve infants were randomly assigned to intermittent and 12 to continuous feedings. These infants had similar birth weight, gestational age, study age, and baseline lung function. After intermittent feedings, there was a significant decrease in tidal volume (38%), minute ventilation (44%), and dynamic compliance (28%), whereas pulmonary resistance increased significantly (100%). In comparison, the pulmonary function data remained unchanged after continuous feedings. These data demonstrate that intermittent feeding of very low birth weight infants can lead to airflow and respiratory instability. These adverse effects appear to be dependent on the rate that feedings are administered. A slower pace of feeding may be more advantageous for infants prone to respiratory instability.

View details for Web of Science ID A1993LC74500018

View details for PubMedID 8496756

Abstract

The pulmonary outcome for preterm infants 1 year after synthetic surfactant replacement for respiratory distress syndrome was assessed by examining their pulmonary status and the results of pulmonary function tests. A total of 47 infants were followed: 13 infants mean +/- SD: birth weight, 1960 +/- 616 gm; gestation, 32 +/- 1.1 weeks) had been assigned to the placebo group and 34 (birth weight = 1890 +/- 530 gm; gestation = 32 +/- 2.5 weeks) to surfactant treatment. The infants were examined at 3 to 6 months of age (n = 45) and at 9 to 12 months of age (n = 36). There were no significant differences between the two groups in predisposing clinical conditions that would lead to chronic lung disease. The infants had similar patterns of growth, respiratory-related illness, and need for theophylline therapy, diuretic therapy, or both. None had hypoxemia by pulse oximetry. Mean (+/- SEM) values for pulmonary mechanics and energetics in surfactant-treated infants were significantly (p < 0.01) lower for total pulmonary resistance in late infancy (57.7 +/- 11.7 vs 35.3 +/- 4.6 cm H2O/L per second). Lower values (mean +/- SEM) of resistive work of breathing were also measured in the surfactant-treated group (60.7 +/- 12.0 vs 38.2 +/- 3.6 gm-cm/kg per breath). The dynamic pulmonary compliance values were in the low-normal range for both groups, and the mean (+/- SEM) peak-to-peak esophageal pressure values were elevated (11.47 +/- 2.26 cm H2O in the placebo group; 9.24 +/- 0.69 cm H2O in the surfactant group). Forced expiratory flow measurements in late infancy demonstrated significant (p < 0.01) improvement in expiratory reserves and reduced evidence of airflow obstruction in the surfactant-treated infants (peak flow (mean +/- SEM): 287.1 +/- 69 vs 396.9 +/- 27 ml/sec; forced expiratory flow (mean +/- SEM) at functional residual capacity: 56.3 +/- 7.5 vs 83.4 +/- 19.5 ml/sec). No significant differences in pulmonary functions were noted in early infancy. These data suggest that surfactant replacement for respiratory distress syndrome may be associated with beneficial long-term effects on the resistive airflow properties of larger preterm infants.

View details for Web of Science ID A1993KQ59200023

View details for PubMedID 8441104

Abstract

Manual ventilation (MAV) or handbagging is a frequent and often life-saving procedure for neonates; however, few studies allow for an objective evaluation of techniques or possible risks. We compared parameters of ventilation and pulmonary mechanics obtained during routine pressure-limited MAV to those obtained during spontaneous breathing (SPB) in the same infant at approximately the same time. We selected 20 preterm neonates in the recovery phase of respiratory distress syndrome who received periodic MAV and were capable of optimum spontaneous minute ventilation (> 300 mL/kg/min). During MAV compared to SPB we measured higher tidal volume (8.1 +/- 0.5 SE vs. 5.4 +/- 0.4 SE mL/kg, P < 0.001), lower total pulmonary compliance (0.65 +/- 0.05 vs. 1.16 +/- 0.11 SE mL/cmH2O, P < 0.001), end-inspiratory compliance, higher pulmonary resistance (121 +/- 11 vs. 61 +/- 7 SE cmH2O/L/s, P < 0.001) and higher peak inspiratory airflow (2.8 +/- 0.2 vs. 1.6 +/- 0.1 L/s, P < 0.001). Inspiratory time (Ti) was consistently longer during MAV (0.49 +/- 0.02 vs. 0.36 +/- 0.02 SE, P < 0.001) such that during MAV the difference between actual Ti and minimal effective Ti (fivefold inspiratory time constant) was larger (0.29 +/- 0.03 vs. 0.13 +/- 0.03 s, P < 0.05). Our study suggests that operator-dependent ventilatory variables such as tidal volume, inspiratory time, frequency, and airflow need to be further evaluated in order to develop standardized guidelines for the safe administration of MAV. Until then the ventilator used for brief or augmented ventilatory support is a reasonable alternative to administering MAV by inconsistent standards.

View details for Web of Science ID A1993KN86900008

View details for PubMedID 8474783

Abstract

Ophthalmic administration of phenylephrine caused decreased pulmonary compliance, tidal volume, and peak airflow values in infants with bronchopulmonary dysplasia but not in control infants. The alpha-adrenergic effects of phenylephrine may aggravate the bronchospastic component of bronchopulmonary dysplasia.

View details for Web of Science ID A1992JR92000024

View details for PubMedID 1328578

Abstract

Adaptive adjustment of inspired oxygen (FIO2), based on a desired percent arterial hemoglobin saturation (SO2) was achieved by on-line bedside control of the oxygen concentration delivered to the neonate. Fourteen infants with bronchopulmonary dysplasia (BW, 860 +/- 80 g; GA, 26 +/- 1 weeks; study age, 41 +/- 8 days) receiving oxygen-air mixtures by hood were studied. The desired range of SO2 from 92 to 96% with a target value of 95% was determined by pulse oximetry and maintained with adjustment of FIO2 using three modes: 1) standard neonatal intensive care protocol with oxygen delivery evaluated at 20 minutes intervals; 2) bedside manual control with FIO2 manipulation every 2 to 5 minutes; and 3) adaptive control with on-line adjustment of FIO2 according to a specifically designed adaptive program. Each study period was of 40 minute duration. SO2 values within a steady 94 to 96% range was achieved for 54% of the time with standard protocol, compared to 69% (P less than 0.01) with bedside manual control and 81% (P less than 0.01) with adaptive control. In addition, fluctuations in SO2 values and overshoots were less apparent with adaptive control of oxygen delivery. These data describe adaptive FIO2 control as an efficient alternative technique for achieving a stable desired range of oxygenation in neonates.

View details for Web of Science ID A1992JP73000008

View details for PubMedID 1437348

Abstract

The clinical and pulmonary function test evidence of abnormal airway function in infants with BPD is now well established. Studies have shown persistence of airway obstruction into childhood and evidence of residual dysfunction into adulthood. Furthermore, preterm neonates who have been mechanically ventilated but do not meet any of the BPD definitions also have residual pulmonary dysfunction during infancy. As an increasing number of very low birth weight infants survive in the surfactant era, care must be taken to note that their airways are likely to be extremely compliant and thereby exceedingly susceptible to airway barotrauma in the neonatal period. The long-term consequences of airway injury could lead to residual abnormal airway function during infancy. It is hoped that barotrauma can be minimized substantially with a reduction in both the magnitude and duration of ventilatory support following surfactant therapy. With the advent of user-friendly commercial pulmonary function testing equipment, most neonatal follow-up services should include a comprehensive pulmonary follow-up ancillary to the existing neurodevelopmental follow-up services and may thereby reduce the severity of respiratory morbidities and the need for hospital readmissions.

View details for Web of Science ID A1992LA27000010

View details for PubMedID 1526076

Abstract

Pulmonary mechanics were measured in 43 preterm neonates (mean +/- SD values of birth weight 1.2 +/- 0.3 kg, gestational age 30 +/- 2 weeks) with respiratory failure who were concurrently randomly assigned to receive conventional mechanical ventilation (n = 22) or high-frequency ventilation (n = 21). The incidence of bronchopulmonary dysplasia was comparable in the two groups (high-frequency ventilation 57%, conventional ventilation 50%). Pulmonary functions were determined at 0.5, 1.0, 2.0, and 4.0 weeks postnatal ages. Data were collected while subjects were in a nonsedated state during spontaneous breathing. These sequential data show similar patterns of change in pulmonary mechanics during high-frequency ventilation and conventional mechanical ventilation irrespective of gestational age, birth weight stratification, or bronchopulmonary dysplasia. There was no significant difference in the pulmonary functions with either mode of ventilation during the acute phase (less than or equal to 4 weeks) of respiratory disease. When evaluated by the clinical diagnosis of bronchopulmonary dysplasia, the pulmonary data suggested a less severe dysfunction in the high-frequency oscillatory ventilation-treated bronchopulmonary dysplasia group compared with the conventional mechanical ventilation-treated group. These results indicate that high-frequency oscillatory ventilation in preterm neonates does not reduce the risk of acute lung injury; however, the magnitude of the pulmonary dysfunction in the first 2 weeks of life merits a reevaluation.

View details for Web of Science ID A1991FF72700010

View details for PubMedID 2011425

Abstract

The reported effects of indomethacin on pulmonary compliance are variable depending upon the patient population and on the degree to which indomethacin resulted in successful ductal closure. Eleven fluid-restricted, furosemide-treated premature infants being mechanically ventilated for respiratory distress syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had pulmonary function testing performed before and after successful closure of the PDA. The diagnosis of a significant PDA was made by clinical and echocardiographic criteria. Indomethacin was administered at a dosage of 0.2 mg/kg/dose every 12 to 18 h for 1 to 3 doses. To control for the 48-h time interval to achieve ductal closure, nine premature infants being ventilated for RDS but who did not have a significant PDA also had pulmonary function evaluations performed before and after the 48 h. Also, to control for the independent effect of fluid restriction and diuretic therapy on pulmonary compliance, eight such premature infants with a PDA had pulmonary function evaluations performed at a 48-h interval. Successful closure of the ductus with indomethacin was associated with an improvement in compliance and ventilation parameters in all infants in the indomethacin-treated infants. In the indomethacin-treated group, the mean percent improvements were noted in the following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%. There were no significant changes in the pulmonary functions in the 48-h RDS or the 48-h PDA fluid-restricted, furosemide-treated control groups. In conclusion, successful closure of the ductus with indomethacin causes a significant improvement in compliance and ventilation parameters in infants being mechanically ventilated for RDS.

View details for Web of Science ID A1991EX24500006

View details for PubMedID 1990934

Abstract

Albuterol is a specific beta-2 agonist that has been reported to be effective in treating infants and children with bronchospastic pulmonary disease. The use of oral albuterol has not been investigated in patients with bronchopulmonary dysplasia (BPD). Thirty premature infants were randomized to receive oral albuterol (0.15 mg/kg/dose q8h) or a volume- and color-matched placebo (D5/W). Pulmonary functions were evaluated at baseline and at 48 and 96 hours after entry to the study. The study was also designed for crossover from placebo to albuterol or albuterol to caffeine in the event that the infant's total pulmonary resistance did not improve at the time of the 48 hour pulmonary function evaluation. Heart rate and respiratory rate showed a statistically significant but clinically unimportant increase in the albuterol-treated infants. There were no significant differences noted in systolic or diastolic blood pressure. Percent improvement in the pulmonary function indices were calculated from baseline to 48 hours and from baseline to 96 hours for the placebo and albuterol-treated groups. The results indicate that at 48 hours there were statistically significant improvements in total resistance (14.5%), inspiratory resistance (10.8%), and expiratory resistance (12.9%) in the albuterol-treated infants as compared to the spontaneous deterioration of the same values by 25%, 81%, and 11%, respectively, in the placebo-treated infants. In conclusion, oral albuterol therapy of 48 hours duration improved pulmonary resistance without major cardiovascular side effects in ventilator-dependent premature infants.

View details for Web of Science ID A1991FL38700006

View details for PubMedID 1852516

View details for Web of Science ID A1990EM11600027

View details for PubMedID 2246701

Abstract

Placental transfer of vitamin E was investigated from 19 to 35 weeks of gestation by analysis of fetal and maternal blood samples for total tocopherol, total lipids, and fetal red blood cell antioxidant reserves. Fifty-two fetal blood samples were obtained under ultrasonographic guide by percutaneous umbilical blood sampling. Thirteen were from fetuses with gestational age less than or equal to 22 weeks (x serum vitamin E = 0.4 +/- 0.14 mg/dl), 12 were from fetuses at 23-27 weeks gestation (x serum vitamin E = 0.4 +/- 0.21 mg/dl), and 27 were from fetuses with gestational age 28-38 weeks (x serum level = 0.37 +/- 0.18). Total lipid levels ranged from 140 to 216 mg/dl. Maternal plasma vitamin E concentrations correlated significantly with concurrent values in the fetus. There were no significant differences in serum vitamin E levels or vitamin E to total lipid ratio in samples from early, mid, or late gestation in either the mother or fetus. Red blood cell antioxidant reserve on samples from 18 fetuses were grossly abnormal by three different functional assays. On the basis of these data, placental transfer of vitamin E appears to be relatively constant through advancing gestation. Red blood cell antioxidant reserve is uniformly low.

View details for Web of Science ID A1990DQ46000006

View details for PubMedID 2212388

Abstract

Sequential changes in pulmonary mechanics in response to single dose exogenous surfactant instillation were studied in 15 preterm neonates who had hyaline membrane disease (HMD). The infants were part of a larger double-blind national study. Birth weight ranged from 0.88 to 1.55 kg, and gestational age was between 27 to 32 wk. There were six infants in the surfactant group and nine in the placebo group. Pulmonary mechanics were studied before and at 2, 24, 60, and 96 h after surfactant or sham instillation using a pneumotachometer and an esophageal balloon catheter. The variables studied were dynamic compliance (Cdyn), pulmonary resistance, work of breathing, tidal volume, and minute ventilation. Infants in the surfactant group showed an immediate and significant (p less than .05) improvement in gas exchange ratio, decreased mean airway pressure (9.7 +/- 0.9 to 7.9 +/- 0.4 cm H2O) and airway resistance (133 +/- 6.3 to 92 +/- 14.9 cm H2O/L.sec) (p less than .05). Changes in Cdyn were noted only at 24 h after surfactant instillation. In the control group, gradual improvement occurred after the initial deterioration. The findings suggest that the immediate improvement in oxygenation after surfactant instillation is the result of factors other than changes in lung compliance, such as improved ventilation/perfusion and better capillary stability with decreased leakage of fluid into alveoli.

View details for Web of Science ID A1990DH23600002

View details for PubMedID 2111754

Abstract

Brain-stem auditory evoked potentials (BAEPs) were elicited by bone conducted stimuli in the very immature lamb following delivery, wherein liquid ventilation techniques were utilized to control cardiopulmonary and acid-base conditions, independent of umbilical-placenta support. Unlike previous studies of the in utero fetal lamb in which the BAEP could not be elicited by earphone delivered stimuli until 117 days gestation, our results demonstrate that the BAEP emerges at least as early as 106 days gestation in the lamb and consists of a full complement of readily discernible and reproducible wave forms. In addition, the results demonstrate substantial maturation of the BAEP from 106 to 122 days gestation during which time there is a significant decrease in absolute and interpeak latencies with an increase in developmental age. It is concluded that the ability to elicit the BAEP utilizing bone conduction at this early stage of gestation is related to improved stimuli delivery. Furthermore, this study demonstrates the feasibility and flexibility afforded by liquid ventilation and bone conduction BAEP techniques to study brain-stem function at particularly vulnerable stages of development.

View details for Web of Science ID A1990CT88700013

View details for PubMedID 1689647

Abstract

Pulmonary mechanics and energetics were determined in 33 healthy low birthweight infants (less than 1,500 g, 28-34 weeks gestation) who had never received ventilatory support. Tidal volume, dynamic pulmonary compliance, pulmonary resistance, pressure-volume relationships, and tidal flow-volume measurements were obtained by pneumotachography and the esophageal balloon technique. Standardized data collection and software data analysis by least mean squares technique yielded data at 0.5, 1, 2, and 4 weeks postnatally, as a function of gestational age (less than 30, 30-32, and greater than 32 weeks gestation). Relatively stable values were obtained for tidal volume and minute ventilation (normalized for body weight); these were associated with values of peak-to-peak esophageal pressure significantly (P less than 0.001) increasing from 4.4 +/- 0.3 SEM cmH2O at 0.5 weeks to 8.1 +/- 0.8 SEM cmH2O at 4 weeks of age. Dynamic pulmonary compliance ranged from 2.0 to 2.4 mL/cmH2O in the first 4 weeks of life. When normalized for weight, compliance decreased with age, which may suggest a slower pulmonary maturation as compared to increase of body weight. Mean pulmonary resistance decreased from 62.9 cmH2O/L/s at less than 30 weeks gestation to 32.5 cmH2O/L/s at greater than 32 weeks gestation, 0.5 weeks postnatally. Pulmonary resistance peaked at 2 weeks postnatally (P less than 0.05), at all gestational ages, then decreased. Changes in pulmonary mechanics resulted in increasing resistive work of breathing. Our findings suggest a postnatal retardation of pulmonary and airway growth, relative to gestation maturation. These data can provide an objective base of comparison for data in sick, low birthweight neonates.

View details for Web of Science ID A1990CR92000004

View details for PubMedID 2352789

View details for Web of Science ID A1989CV07100031

View details for PubMedID 2629603

Abstract

Compliant immature airways sustain significant deformation following positive pressure ventilation. To evaluate the structural changes induced by in vivo positive pressure ventilation, tracheae of preterm lambs (107-116 d gestational age) were studied histologically. Nonventilated (group I: n = 7) and ventilated (group II: n = 7) tracheal segments were excised and studied by histologic and morphometric techniques. Computerized image analysis was used to measure dimensions of tracheal wall components and of the tracheal section. The circumference, diameter, and cross-sectional area of the section as well as the length of the trachealis muscle were significantly greater; although the thickness of the muscle and cartilage were seen to be significantly lower in group II sections compared to group I sections. Also, in comparison to group I, in group II sections there was lesser overlap of the posterior free ends of tracheal cartilage and the epithelial layer was flattened and focally abraded. Our findings demonstrate structural changes in the airway of preterm animals and characterize alterations in the geometric arrangement of muscle and cartilage after PPV. These results suggest possible structural mechanisms for the functional changes seen during and subsequent to mechanical ventilation.

View details for Web of Science ID A1989AX12100009

View details for PubMedID 2682500

View details for Web of Science ID A1989T561100022

View details for PubMedID 2921689

Abstract

This article reviews historical developments and ethical problems, including quality of life determinations, surrogate decision making, informed consent, and medical uncertainty. Procedural aspects of ethical decision making and a framework for resolving ethical dilemmas are described, and case examples are provided.

View details for Web of Science ID A1989T887700019

View details for PubMedID 2656064

Abstract

The inherent mechanical characteristics of the airways are determined in part by their elastic and viscoelastic properties. As compliant structures during early development, the airways are susceptible to significant distention and collapse, depending on the proportionality between airway volume and transmural pressure. To characterize the age-related changes in airway mechanical properties, the elastic and viscoelastic behavior of in vivo tracheal segments were evaluated in preterm and newborn lambs over a wide range of developmental age (108 to 154 days postconceptional age). Tracheal pressure-vol relationships and concomitant airway compliance measurements were used to determine elastic behavior. Calculations of the tracheal relaxation time constant on the same tracheal segments were used to evaluate airway viscoelastic behavior. Data demonstrated a significant (p less than 0.01) correlation with developmental age. With increasing age, the airways were found to be less compliant, and the tracheal relaxation time constant was observed to decrease. The difference in elastic properties of the trachea, in vivo compared to in vitro, suggest that neural-humoral and surrounding connective tissue factors may affect the elasticity of the developing airway. Although the modulating effects of smooth muscle tone and supporting connective tissue assist in the control of airway dimension and resistance to airflow in the intact airway, the age-related differences in the elastic properties may be a factor that predisposes the more immature airway to positive pressure-induced damage.

View details for Web of Science ID A1989R964600007

View details for PubMedID 2919128

Abstract

The effects of caffeine upon pulmonary mechanics were measured in 16 infants with bronchopulmonary dysplasia (BPD). Pulmonary function tests were performed immediately prior to and 1 hour following a dose of 10 mg/kg of caffeine. A 37% increase in minute ventilation (mean +/- SEM; 436.6 +/- 26.3 to 580.8 +/- 30.7 ml/min/kg) was seen with caffeine administration (P less than 0.001), primarily from a 42% increase in tidal volume (6.2 +/- 0.4 to 8.5 +/- 0.4 ml/kg) (P less than 0.001). Total lung resistance decreased by 20% (134.6 + 24.2 to 105.3 +/- 20.1 cmH2O/L/sec) (P = 0.01), and total pulmonary compliance improved by 47% (0.642 +/- 0.104 to 0.908 +/- 0.190 ml/cmH2O/kg) (P less than 0.01). In five matched control infants with BPD, no effects of placebo upon pulmonary mechanics were detected. Since caffeine has a wide therapeutic index with few side effects, it may be an effective adjunct in the treatment of infants with BPD.

View details for Web of Science ID A1989R964400009

View details for PubMedID 2704583

Abstract

Pulmonary function tests were performed on 36 very low birth weight neonates (birth weight less than or equal to 1000 gm, gestational age less than or equal to 30 weeks, appropriate size for gestational age) from birth until 8 weeks of age. Tidal airflow was measured by means of a pneumotachygraph, and the transpulmonary pressure changes were determined by the esophageal balloon technique. Pulmonary mechanics and energetics were calculated by the least mean square analysis technique at 1/2, 1, 2, 4, 6, and 8 weeks of age. Compliance was lowest at 2 weeks and subsequently increased linearly (at approximately 0.1 ml/cm H2O/wk). When compliance was based on body weight, however, no change was noted with advancing age. Resistance was greatest at 2 weeks and subsequently decreased. The infants maintained a normal minute ventilation with a slightly increased resistive work of breathing. Despite our ability to wean 53% of the infants to room air by 8 weeks, none of them had pulmonary mechanics considered normal for term infants. Infants with and without bronchopulmonary dysplasia (BPD) had similar patterns of pulmonary development. At 8 weeks of age, the pulmonary mechanics in infants with BPD who had been weaned to room air were comparable to those in infants without BPD, an observation that calls into question the rationale for defining BPD at 4 weeks in this population. These data suggest that such pulmonary function profiles provide evidence of persistent lung parenchymal abnormalities.

View details for Web of Science ID A1988Q533800022

View details for PubMedID 3171798

Abstract

In this report, an experimental approach and newly designed apparatus for liquid ventilation of preterm animals are described. Findings of age-related changes in cardiopulmonary function of this animal preparation are presented. Thirty-one lambs, 102-137 days gestation (term 147 +/- 3 days), were studied. The carotid artery, jugular vein, and trachea of the exteriorized fetus were cannulated under local anesthesia. Immediately after cesarean section delivery, ventilation commenced; warmed (39 degrees C) and oxygenated (PIO2 greater than 500 Torr) liquid fluorocarbon (RIMAR 101) was delivered to the lung by a mechanically assisted liquid ventilation system. Skeletal muscle paralysis, low-dose exogenous buffering, and thermal support were maintained during the 3-h experiment. Pulmonary gas exchange, acid-base status, and cardiopulmonary and metabolic function were assessed. By utilizing these techniques, effective arterial oxygenation, CO2 elimination, acid-base status, and cardiovascular stability were supported independent of gestational age. The results demonstrate a developmental increase in specific lung compliance and mean arterial pressure and decrease in heart rate and systemic O2 consumption per kilogram with advancing gestational age. These findings demonstrate that liquid ventilation negates the dependency of effective pulmonary gas exchange on surfactant development, thereby extending the limits of viability of the immature extrauterine lamb. As such this new experimental approach is useful for the study of physiological development over an age range previously limited to fetal animal preparations and, therefore, may provide insight regarding adaptation of the premature to the extrauterine environment.

View details for Web of Science ID A1988Q092100062

View details for PubMedID 3182511

Abstract

We assessed pulmonary mechanics in 35 premature infants with respiratory distress syndrome just before and one hour after the administration of 90 mg of surfactant to each infant. Transpulmonary pressure was measured between the airway opening and an esophageal balloon with use of a differential transducer, and flow rates were measured by a pneumotachometer. Values for pulmonary mechanics were then calculated by microcomputer processing. The administration of surfactant produced a large decrease (56 percent) in the mean (+/- SEM) ratio of alveolar to arterial oxygen, from 7.1 +/- 0.5 to 3.1 +/- 0.2 (P less than 0.0001)--a change that indicates improvement in gas exchange. Associated changes in pulmonary mechanics were not demonstrable when 10 of the infants were studied during continuous mechanical ventilation. However, in the 25 infants examined during spontaneous breathing with continuous positive airway pressures (identical airway pressures before and after treatment), large and consistent improvements in pulmonary mechanics were found after the administration of surfactant. Tidal volume increased by 32 percent (P less than 0.03), minute ventilation by 38 percent (P less than 0.02), dynamic compliance by 29 percent (P less than 0.004), and inspiratory flow rates by 54 percent (P less than 0.01). We conclude that significant improvement in pulmonary mechanics results from surfactant-replacement therapy for respiratory distress syndrome, but that these mechanical changes are apparent only during spontaneous respiration and can be masked if measurements are made during mechanical ventilation.

View details for Web of Science ID A1988P821000004

View details for PubMedID 3405254

View details for Web of Science ID A1988N308700039

View details for PubMedID 3361400

Abstract

Pancuronium bromide (Pavulon) is used to induce skeletal muscle paralysis in preterm infants, presumably for effective ventilatory support during acute respiratory failure. Twelve infants with respiratory failure were evaluated for sequential changes in pulmonary mechanics during continuous pancuronium administration (0.1 mg/kg every two to three hours) for more than 48 hours. The study weight of the neonates ranged from 980 to 2,950 g, and the postconceptional age ranged from 27 to 41 weeks. Pulmonary compliance, resistance, and resistive work of breathing were determined, using least mean square analysis technique, daily for three days and after discontinuation of pancuronium (even though there was no clinical improvement in ventilatory management). The dynamic pulmonary compliance decreased from 0.38 +/- 0.05 to 0.30 +/- 0.04 mL/cm H2O/kg (mean +/- SE) (P less than .05) and the total pulmonary resistance increased 51% from 115.6 +/- 21.3 to 174.9 +/- 27.3 cm H2O/L/s (P less than .005) during prolonged skeletal muscle paralysis. Upon discontinuation of pancuronium, the dynamic pulmonary compliance increased 43% to 0.43 +/- 0.4 mL/cm H2O/kg (P less than .05) and the total pulmonary resistance decreased by 41% (P less than .005). These data question the advisability of prolonged skeletal muscle paralysis in neonates and suggest the need for further detailed evaluation of the effects of prolonged paralysis on neonatal pulmonary mechanics.

View details for Web of Science ID A1988M438800015

View details for PubMedID 3344185

Abstract

Pulmonary mechanics, using a two factor least mean square analysis technique, were determined in 22 preterm neonates with respiratory failure. The respiratory system is modelled as a linear mechanical system. Concurrent signals of airflow and transpulmonary pressure were utilized to calculate values of dynamic lung compliance and pulmonary resistances; these determinations were made over the entire tidal volume range. In addition, values of resistive work of breathing, pulmonary time constants, scalar records of sequential breaths, pressure-volume and flow-volume relationships were available for data review and interpretation. The mean +/- SEM value of tidal volume was 7.4 +/- 0.6 ml/kg; dynamic lung compliance was 0.44 +/- 0.04 ml/cmH2O/kg; and the pulmonary resistance of the whole breath was 106 +/- 9.1 cmH2O/liter/s. The resistive work of breathing (hysteresis) was 41.8 +/- 5.9 gm.cm/kg. In correlating the measured values of pressure and flow to those predicted by the model, the mean value of the correlation coefficient for the least mean square analysis for all 22 studies was 0.995 +/- 0.001; the standard error of estimate of the predicted pressure was less than 4.4% of the range of pressures measured. Thereby, the model was considered to be appropriate for the neonatal respiratory system. In addition to the traditional procedures of evaluating the respiratory status of a sick neonate, bedside analysis of pulmonary mechanics provide graphical information, and quantitative data which should be useful in day-to-day pulmonary management.

View details for Web of Science ID A1988N147300004

View details for PubMedID 3374983

Abstract

Energetics and mechanics of sucking in preterm and term neonates were determined by simultaneous records of intraoral pressure, flow, volume, and work of individual sucks. Nine term infants (mean postconceptional age: 38.6 +/- 0.7 SD weeks; mean postnatal age: 18.4 +/- 6.1 SD days) and nine preterm infants (mean postconceptional age: 35.2 +/- 0.7 SD weeks; mean postnatal age: 21.9 +/- 5.4 SD days) were studied under identical feeding conditions. Preterm infants generated significantly lower peak pressure (mean values of 48.5 cm H2O compared with 65.5 cm H2O in term infants; P less than 0.01), and the volume ingested per such was generally less than or equal to 0.5 mL. Term infants demonstrated a higher frequency of sucking, a well-defined suck-pause pattern, and a higher minute consumption of formula. Energy and caloric expenditure estimations revealed significantly lower work performed by preterm infants for isovolumic feeds (1190 g/cm/dL in preterm infants compared with 2030 g.cm/dL formula ingested in term infants; P less than 0.01). Furthermore, work performed by term infants was disproportionately higher for volumes greater than or equal to 0.5 mL ingested. This study indicates that preterm infants expend less energy than term infants to suck the same volume of feed and also describes an objective technique to evaluate nutritive sucking during growth and development.

View details for Web of Science ID A1987L199300023

View details for PubMedID 3681557

Abstract

Abdominal pregnancy is a rare condition that is associated with a high infant mortality, as well as orthopedic and pulmonary deformations. This article describes the clinical and radiological courses of two infants born after abdominal pregnancies. Evidence of pulmonary hypoplasia secondary to fetal compression was present. The morbidity and mortality for infants born of abdominal pregnancies may depend on the extent of pulmonary involvement, which may relate to the length of fetal compression.

View details for Web of Science ID A1987K198800031

View details for PubMedID 3630998

Abstract

Real time ultrasound was used in pregnant women who were considered to be at risk for development of pulmonary hypoplasia (n = 26). The population consisted of women who had either premature rupture of membranes (n = 16) or oligohydramnios (n = 10). The ratio calculated by comparing the fetal thoracic circumference to abdominal circumference was obtained in all cases within 10 days of delivery. This ratio correlated strongly with neonatal outcome. Multivariate regression models of neonatal outcome were developed to analyze the relationship of gestational age at which premature membrane rupture occurred, the duration of premature rupture, date of birth, and prenatal diagnosis. The addition of the thoracic circumference to the abdominal circumference ratio increased significantly the proportion of explained variability. Application of this ratio should be considered in evaluating fetal status in oligohydramnios and in the expectant management of premature rupture of membranes.

View details for Web of Science ID A1987K198900046

View details for PubMedID 3307430

Abstract

The ability of tracheal smooth muscle tone to modulate the mechanical properties of neonatal airways was evaluated in six newborn lambs. Tracheal pressure-volume relationships, isovolumic compliance, hysteresis, and the relaxation time constant of the smooth muscle were evaluated as a function of incremental cholinergic stimulation. Tracheal active tensions were also determined at the graded levels of cholinergic stimulation. Data show that a maximal cholinergic stimulation resulted in a mean developed active tension value of 14.3 +/- 2.13 SEM X 10(3) dynes/cm. The resultant 55% decrease in tracheal compliance was linearly correlated to the increase in active tension (r = 0.90, p less than 0.01). Cholinergic stimulation also resulted in a 18.4% decrease (p less than 0.02) in the relaxation time constant of the smooth muscle, and in a 82% increase (p less than 0.01) in tracheal hysteresis. This study demonstrates that both elastic and viscoelastic properties of the neonatal lamb trachea are effected by tracheal smooth muscle contraction. Since neonatal airways are more compliant than adult airways, cholinergic stimulation could conceivably enhance airway rigidity and may provide a protective mechanism against pressure-induced deformation.

View details for Web of Science ID A1986F145800002

View details for PubMedID 3797112

View details for Web of Science ID A1986E633300038

View details for PubMedID 3763314

Abstract

The effect of high-frequency jet ventilation (HFJV) on both tracheal dimensions and mechanics was evaluated in preterm and term rabbit airways. Seven tracheal segments were studied at 27 days (group I) and 31 days (group II) of gestation, respectively. Tracheal dimensions and segmental pressure-volume relationships were determined before and after 60 minutes of HFJV (peak pressure 20 cm H2O; mean airway pressure 6.7 to 6.8 cm H2O at 10 Hz). Both tracheal lengths and diameters increased significantly (p less than 0.01) in each group and resulted in increased tracheal volumes: 109% in group I (p less than 0.01) and 60% in group II (p less than 0.01). The mean specific tracheal compliance decreased in group I, from 0.036 cm H2O-1 to 0.015 cm H2O-1 (p less than 0.01), and in group II from 0.029 cm H2O-1 to 0.021 cm H2O-1 (p less than 0.01). Furthermore, the collapsing transmural pressure (the pressure required for total collapse of tracheal segments) decreased significantly (p less than 0.01) in both groups. These data demonstrate significant dimensional and mechanical deformation of tracheal segments after HFJV. An increased propensity toward collapsibility is also observed following HFJV. These changes are similar to those with tracheomalacia. The influence of such deformation on tracheal gas flow during HFJV needs to be further investigated.

View details for Web of Science ID A1986F158100002

View details for PubMedID 3808774

Abstract

This study defines the physiologic changes in pulmonary mechanics induced by subcutaneous terbutaline administration in ventilator-dependent infants with severe bronchopulmonary dysplasia (BPD). Eight such infants (mean +/- SEM weight = 2.56 +/- 0.32 kg, postnatal age = 13.0 +/- 3.2 weeks) were chosen for the study. Pulmonary mechanics and arterial blood gases were measured in the control state and at 30 and 60 minutes following the subcutaneous injection of 5 micrograms/kg terbutaline. There was a significant (p less than 0.001) improvement in lung compliance from baseline values at 30 minutes and at 60 minutes (38%). A significant (p less than 0.05) decrease of 23% in the average pulmonary resistance at 30 minutes and a 26% decrease at 60 minutes from control values were observed. An increase in the I/E ratio occurred in all patients at 60 minutes (p less than 0.01). In addition, clinical improvement was noted in six of eight infants. Administration of terbutaline demonstrated a significant improvement in the pulmonary mechanics of infants with severe BPD.

View details for Web of Science ID A1986E394600002

View details for PubMedID 3774383

Abstract

Survival and significant chronic morbidity were determined by retrospective chart review for 107 inborn "micropremies." "Micropremies" are defined as appropriate-for-gestational age neonates of less than 1,001 grams and less than or equal to 28 weeks gestation. The overall survival rate for "micropremies" was 64 percent, ranging from 20 percent at 24 weeks to 83 percent at 27 weeks gestation. Race and sex are important determinants of survival in these infants. The incidence of severe, chronic morbidity in "micropremies" is relatively low. The acceptable outcome for "micropremies" supports aggressive perinatal management for fetuses as low as 24 to 25 weeks gestation. However, it is important for physicians to use current statistics from their own institutions when counseling parents and making management decisions.

View details for Web of Science ID A1986D516900001

View details for PubMedID 3731666

Abstract

Neonatal pulmonary manifestations of prolonged (2-8 weeks) amniotic fluid leak (PAL) were evaluated in 22 neonates. The severity of respiratory insufficiency was evaluated by a profile scoring system based on arterial blood gases, ventilatory support, and evidence of "fetal compression". The spectrum included acute respiratory failure with pulmonary hypoplasia (3), pulmonary hemorrhage (2), severe bronchopulmonary dysplasia (3), subacute lung disease (5), and transient respiratory disease (2). Seven neonates were completely asymptomatic. Clinical manifestations were correlated to age of onset and duration of PAL. The onset of PAL in the asymptomatic babies had occurred after 32 weeks gestation (mean +/- SEM, 33.5 +/- 1.1 wk; duration was 4.4 +/- 1.1 wk). In symptomatic neonates the onset of PAL was 24.0 +/- 1.0 weeks; duration being 6.0 +/- 0.6 weeks. When PAL occurred before 22 weeks and the duration of leak was longer than 6 weeks, the pulmonary profile score was less than 3 and associated with severe respiratory sequelae. These manifestations culminated in neonatal demise despite aggressive conventional ventilatory techniques. Onset of PAL between 23 and 28 weeks gestation and continuing longer than 8 weeks also was associated with a similar outcome. Duration of PAL between 2 and 7 weeks in this group was associated with less severe pulmonary manifestations and higher scores. Pulmonary morbidity was significantly correlated to the initial profile score (P less than .05) and was influenced by the prenatal reduction in thoracic volume.

View details for Web of Science ID A1986D108300015

View details for PubMedID 3718644

Abstract

The effect of smooth muscle tone on the functional characteristics of neonatal airways was studied in six newborn lambs. Tracheal mechanics, resistance, and collapsibility were determined in tracheal segments of uniform length which were surgically isolated just caudal to the cricoid cartilage. Resistance to airflow through uncompressed (zero transmural pressure) and compressed (increased transmural pressure) trachea was evaluated over a range of physiological flows both before and after induced contraction of airway smooth muscle. Results demonstrate that neonatal tracheal smooth muscle does respond to cholinergic stimulation and that there was a significant decrease in airway compliance. Furthermore, the consequent increase in airway rigidity may play a role in resisting collapse or compression of the intrathoracic airway during expiration.

View details for Web of Science ID A1986C430200002

View details for PubMedID 2872649

Abstract

Proximal airways are compliant structures at early gestational ages and may be susceptible to pressure-induced deformation following prolonged ventilatory support. Sixteen neonates (mean +/- SD gestational age, 27.0 +/- 0.6 weeks; mean +/- SD birth weight, 847 +/- 68 g) were studied to assess tracheal volume deformation. The neonates received ventilatory support for a mean +/- SD duration of 25.4 +/- 4.9 days. During this period the maximum peak inspiratory pressures ranged from 15 to 25 cm H2O, and respirations ranged from 20/min to 60/min. These neonates were studied at seven days postextubation and were individually matched for body weight with 16 nonventilated neonates. The width of the tracheal air column was measured at the lower border of the first thoracic (T-1) and third thoracic (T-3) vertebrae. The average tracheal width (average of T-1 and T-3) was significantly (38%) wider in the ventilated group, and the mean +/- SD tracheal width values were 3.79 +/- 0.29 mm, as compared with the control values of 2.74 +/- 0.31 mm. Based on these data it was estimated that the tracheal volume was 91% greater in the ventilated group. These observations demonstrate tracheal volume deformation and acquired tracheomegaly in neonates who have received mechanical ventilatory support. In addition to increased dead space ventilation, these findings also indicate underlying mechanical deformation of the tracheal wall.

View details for Web of Science ID A1986C085200024

View details for PubMedID 3962939

Abstract

A variety of methods have been employed for the induction of hypothermia; however, there are still some inherent problems that remain with current techniques. Liquid ventilation, a process used in several other environmental and clinical research areas, may be a feasible method since it takes advantage of the effectiveness of the pulmonary architecture as a heat exchanger. Hypothermia induced by liquid ventilation was studied in 8 newborn lambs, mean age = 10 +/- 8 SEM days. Each lamb was anesthetized with sodium pentobarbitol (20 mg/kg) and intubated. Cardiopulmonary measurements were taken during a control period prior to induced hypothermia. Liquid temperatures of 20 and 30 degrees C were used in cooling the animal while monitoring rectal and surface temperatures. Temperatures decreased producing rectal cooling rates of 8.4 and 4.8 degrees C/hr, respectively. Blood gas analysis showed adequate physiological gas exchange for all lambs during the liquid ventilation period. Based on the data, the process of liquid ventilation offers a unique potential both in experimental and clinical areas as a new approach to the technique of induced hypothermia.

View details for Web of Science ID A1986AXQ1100006

View details for PubMedID 3941549

Abstract

The mechanics and energetics of breathing were studied in preterm infants with bronchopulmonary dysplasia while spontaneously breathing control gas and helium-oxygen (Heliox) gas mixtures. During Heliox breathing, there was a significant decrease in pulmonary resistance, resistive work of breathing, and mechanical power of breathing, whereas ventilation remained unchanged. Breathing a lower density gas mixture (Heliox) may have therapeutic value by decreasing the demands on the respiratory muscles and the caloric requirements for breathing. Therefore, this modality may reduce potential respiratory muscle fatigue and avail additional calories for growth and recovery in the preterm infant with bronchopulmonary dysplasia.

View details for Web of Science ID A1984SR58100025

View details for PubMedID 6546945

Abstract

Alterations in tracheal volume were evaluated in a developmental in vivo rabbit model during and following the application of continuous positive pressure (CPP). Sequential volume changes were recorded during 60 min of CPP to a bypassed tracheal segment. The distal trachea was utilized for spontaneous ventilation. CPP of 10 cm H2O was applied to three developmental groups: group I, 5 term newborn pups; group II, 5, 7-day-old pups, and group III, 5 adult female rabbits of 18 +/- 6 months old. Changes in tracheal volume were measured by a micropipette system. Following 60 min of CPP, tracheal volumes increased (p less than 0.01) by 39.8% in group I; 36.1% in group II and 5.1% in group III. During a recovery period (60 min), return towards initial resting volume was observed in all groups, though maximal persistent volume deformation was observed in groups I and II. Thus, these data indicate tracheal barotrauma in the form of persistent dimensional deformation at early stages of development in an in vivo rabbit model.

View details for Web of Science ID A1984TK78000006

View details for PubMedID 6386060

Abstract

Seven lambs (0.93 term gestation) were delivered by cesarean section with evidence of meconium in the amniotic fluid, meconium staining, and respiratory distress. The initial arterial blood gas and acid-base status indicated severe hypoxemia and acidosis. Three of these lambs developed pneumothoraces and died on control gas ventilation with positive end expiratory pressure. During the control period (90 min) with ventilatory support, there were no significant alterations in mean arterial oxygen tension (PaO2) and alveolar-arterial oxygen gradient (A-aDO2). The initial hypercarbia and acidosis were effectively controlled and corrected using mechanical ventilation and bicarbonate infusion. Fifteen min after the onset of fluorocarbon ventilation mean PaO2 significantly increased and A-aDo2 decreased. After 90 min of fluorocarbon ventilation, lambs were returned to gas ventilation. During this recovery period, PaO2 and A-aDo2 remained significantly improved compared with control gas values. Dynamic lung compliance increased, alveolar and peak tracheal pressure decreased and inspiratory elastic work of breathing decreased during liquid ventilation.

View details for Web of Science ID A1984RX66100009

View details for PubMedID 6422432

Abstract

The mechanical properties of the newborn piglet gallbladder were evaluated in both the stimulated and unstimulated states. The pressure-volume relationships, compliance, and the estimated active tension of the gallbladder were determined in 10 newborn piglets (2-7 days of age). Agonist stimulation was achieved by administration of histamine (25 micrograms/kg/h) and cholecystokinin (CCK) (60 ng/kg/h). Both histamine and CCK increased the intracholecystic pressure at the 50% resting volume from 12.4 cm H2O to 18.9 and 15.5 cm H2O, respectively. This resulted in a significant (p less than 0.05) increase in the active tension. However, no significant changes were observed in the gallbladder compliance after stimulation. These findings characterize the mechanical properties of the normal neonatal gallbladder. The low magnitude of intracholecystic pressure response to agonist stimulation, when compared to adult data, may explain the occurrence of decreased neonatal choledochal bile flow.

View details for Web of Science ID A1984TQ20200026

View details for PubMedID 6514445

View details for Web of Science ID A1983RL51300033

View details for PubMedID 6620027

Abstract

The effects of fluorocarbon ventilation on cardiopulmonary function were studied in 8 preterm lambs, 132-136 days gestation. After mechanical ventilation with 100% oxygen (control period), the lambs were ventilated with fluorocarbon (PIO2 = 622 torr). The liquid was then removed from their lungs and gas ventilation resumed (recovery period). During normothermic liquid breathing the alveolar-arterial O2 gradient (A-a DO2) decreased (P less than 0.01) from control by 154 torr and remained decreased (P less than 0.05) by 85 torr during recovery. Dynamic lung compliance (CL) increased 50% (P less than 0.05); PaO2 increased 50% (P less than 0.05); and PaCO2 decreased 29% (P less than 0.01) as compared to control values. The change in A-a DO2 and PaO2 before and after liquid ventilation was correlated (r = 0.79 and P less than 0.01) with control CL. There was a gradual decrease (P less than 0.01) in mean arterial pressure from 62 +/- 5.4 torr (control) to 53,1 +/- 9,3 torr (recovery); however, there were no significant alterations in mean central venous pressure, heart rate, or mean electrical axis.

View details for Web of Science ID A1983QJ21600017

View details for PubMedID 6856391

Abstract

Cardiopulmonary function was evaluated in very preterm lambs (106 +/- 0.7 S.E. days gestation, 1.66 +/- 0.12 S.E. kg birth weight) during fluorocarbon ventilation. Lambs were delivered by cesarean section after epidural anesthesia. Indwelling arterial, venous, and tracheal cannulae were placed before clamping the cord. Lambs were then mechanically ventilated with oxygenated fluorocarbon for approximately 2 h. During this period it was possible to maintain adequate gas exchange and stable cardiac function. Transpulmonary pressure, liquid flow, and tidal volume tracings enabled determination of lung compliance, CL = 0.58 +/- 0.12 S.E. ml X cmH2O-1 X kg-1, inspiratory resistance, RI = 3600 +/- 604 S.E. cmH2O X liter-1 X sec-1, and expiratory resistance, RE = 4034 +/- 2183 S.E. cmH2O/liter/sec. Lung compliance of the 106-day-old fluorocarbon-filled lung is similar to the more mature 138-143-day-old air-filled lung in preterm lambs. Based on the data presented herein we have extended the viability of the preterm lamb to the limit of pulmonary capillary development rather than that of the pulmonary surfactant system.

View details for Web of Science ID A1983QZ96100016

View details for PubMedID 6889011

Abstract

Liquid ventilation with fluorocarbon has been demonstrated as a viable mode of ventilatory support to preterm or distressed lambs. The effect of liquid ventilation and its high inflation pressures in proximal airways was evaluated on the mechanical behavior of the preterm trachea. 7 preterm lambs (134 +/- 1.5 SE days of gestation; 90% term) were ventilated with fluorocarbon (Rimar) for 58.6 +/- 8 min. The tracheae were dissected and the ventilated, distal segments were compared to nonventilated proximal segments. Pressure-volume curves were determined by plethysmography and specific tracheal compliance was computed. Tracheal dimensions increased 13.6 and 25.6% in diameter and volume (p less than 0.05), respectively, and the compliance decreased 29.9% (p less than 0.05). The magnitude of these changes is comparable to that observed during gaseous ventilation of term animals.

View details for Web of Science ID A1983RM75200001

View details for PubMedID 6639995

Abstract

Sequential magnitude and the rate of change in tracheal mechanics after application of intermittent positive pressure (IPP), and the time constant, tau, of this deformation were determined in fetal (21 and 27 days gestation), neonatal (term, 31 days gestation) and adult rabbits. In vitro tracheal mechanics were determined by liquid plethysmography before and after IPP, (25 cm H2O at 30 cycles/min) of 20, 40, 60, and 120 min duration. A sequential decrease in tracheal compliance was documented at all ages. This was associated with increased values of tau as the maturational age advanced. Further, the rate of tracheal deformation was 0.008 cm H2O min-1 at 21 days gestation compared to 0.00025 cm H2O min-1 at adulthood. The decrease in rate of deformation was related to the gestational maturity and duration of IPP. The rate of deformation, as predicted by calculated deformation time constants, appears to be a function of structural elastic and viscoelastic properties of the trachea as well as the duration and magnitude of applied pressure. The deformation time constant may be defined as a useful index to predict the rate of airway deformation. Utilizing the rabbit model, this provides a measure of comparing barotrauma with different modes of ventilation in preterms.

View details for Web of Science ID A1982PJ85500006

View details for PubMedID 6755370

Abstract

The effect of positive pressure ventilation on the highly compliant fetal airways was evaluated utilizing fetal rabbit tracheal segments. The degree of mechanical and dimensional deformation was quantified to the pressure applied intermittently (IPP) or continuously (CPAP) for 60 min. Excised tracheal segments were obtained at 21, 27, and 31 days fetal rabbit gestation (term = 31 days) and from 18 +/- 6-month-old adults. Internal diameter, resting length, and volume of the tracheal segments were measured, and their pressure-volume relationships were determined by plethysmography. Tracheal specific compliance at deflation pressure of 0 to 10 cm H2O was calculated from these data. In all fetal groups, the application of positive pressure resulted in a decrease of both tracheal distensibility and the slope of the pressure-volume curves; in addition, a highly significant decrease in tracheal specific compliance was documented. At 21 days gestation, the tracheal specific compliance decreased from 0.089 to 0.034 cm H20-1 (P less than 0.001) after CPAP and to 0.025 cm H2O (P less than 0.001) after IPP. For the same group, the resting tracheal volume increased by a dramatic 89% (P less than 0.001) after CPAP and by 124% (P less than 0.001) after IPP. The magnitude of these alterations decreased as gestational age advanced; the changes were not significant by adulthood. These data indicate that significant pressure-induced deformation (barotrauma) is sustained by susceptible immature airways.

View details for Web of Science ID A1981LM90000009

View details for PubMedID 7017562

Abstract

The physical properties of the trachea in fetal, newborn, and adult rabbits change with age. Tracheal dimensions and pressure--volume relationships were determined in excised tracheae at a wide developmental age range (from early gestational age to infancy and adulthood). At intraluminal pressures of 0 to 10 cm H2O, the tracheal specific compliance was 0.089 (cm H2O)(-1) for a 21 day old fetus. By adulthood, the tracheal specific compliance decreased five fold to 0.017 (cm H2O)(-1); a dramatic proportion of this reduction occurred during fetal life itself, followed by a steady, progressive decline to adult age. The volume of the tracheal segment, at intraluminal pressure of 20 cm H2O, increased by 29% (adult), 41.5% (31 day fetus) and 113% (21 day fetus). Developmental alterations in the specific airway compliance suggest significant changes in anatomical dead space would occur as a function of maturation and airway transmural pressure.

View details for Web of Science ID A1981LK88600005

View details for PubMedID 7280379

Abstract

This article presents a brief overview of respiratory muscle mechanics and the effects of lung disease and neuromuscular disease on pulmonary function. A variety of current specific and general muscle training techniques are described and discussed. Also presented is a current review of training studies and the effects of muscle training on cardiopulmonary function, muscle strength, endurance and fatigue, and exercise tolerance.

View details for Web of Science ID A1981MU67800002

View details for PubMedID 7312944

Abstract

Tracheal dimension, pressure-volume relationships and bulk modulus (K) were determined in excised fetal and adult rabbit tracheal segments before and after application of intermittent positive pressure (IPP) which was 0--25 cm H2O pressure, at 30 cycles/min, and for a duration of 60 min. Both tracheal elastic behavior and dimensions underwent dramatic changes following IPP. At 21, 27, 31 days gestation age, the bulk modulus, K, of the rabbit trachea approximated those of the adult control values. However, the adult values of K did not vary significantly after IPP. The associated increase in tracheal dimensions were also related to the maturity of the animal. Significant structural and functional barotrauma is thus sustained by immature airways, and may account for the tracheal deformation frequently observed as a result of IPP.

View details for Web of Science ID A1981MC19300007

View details for PubMedID 7025137

Abstract

Tracheal dimensions, pressure-volume relationships, and bulk moduli, K, were determined in excised tracheae at different developmental ages: 21-, 27-1, and 31-day rabbit fetuses; 7-day pups; and adult rabbits 18 +/- 6 months of age. Alterations in tracheal dimensions paralleled the growth of the animal. At low segmental pressures such as 10 cm H2O, the tracheal segments became stiffer with age (K = 20.4 cm H2O for the 21-day fetus to K = 58.0 cm H2O for the adult). However, at segmental pressures greater than 15 cm H2O, the overdistended immature trachea became stiffer than even those of the adults. Developmental alterations in bulk modulus suggest significant changes in the material and mechanical properties of the wirways as a function of both pressure and developmental age.

View details for Web of Science ID A1980KK22100006

View details for PubMedID 7423068