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Biomedical subjects

Vinod K Bhutani

Publications and source records attributed to Vinod K Bhutani.

At least 19 recordsLinked to original sources
PubMed2006

Early inhaled nitric oxide therapy in premature newborns with respiratory failure.

BACKGROUND: The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain. METHODS: We performed a multicenter, randomized trial involving 793 newborns who were 34 weeks of gestational age or less and had respiratory failure requiring mechanical ventilation. Newborns were randomly assigned to receive either inhaled nitric oxide (5 ppm) or placebo gas for 21 days or until extubation, with stratification according to birth weight (500 to 749 g, 750 to 999 g, or 1000 to 1250 g). The primary efficacy outcome was a composite of death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Secondary safety outcomes included severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly. RESULTS: Overall, there was no significant difference in the incidence of death or bronchopulmonary dysplasia between patients receiving inhaled nitric oxide and those receiving placebo (71.6 percent vs. 75.3 percent, P=0.24). However, for infants with a birth weight between 1000 and 1250 g, as compared with placebo, inhaled nitric oxide therapy reduced the incidence of bronchopulmonary dysplasia (29.8 percent vs. 59.6 percent); for the cohort overall, such treatment reduced the combined end point of intracranial hemorrhage, periventricular leukomalacia, or ventriculomegaly (17.5 percent vs. 23.9 percent, P=0.03) and of periventricular leukomalacia alone (5.2 percent vs. 9.0 percent, P=0.048). Inhaled nitric oxide therapy did not increase the incidence of pulmonary hemorrhage or other adverse events. CONCLUSIONS: Among premature newborns with respiratory failure, low-dose inhaled nitric oxide did not reduce the overall incidence of bronchopulmonary dysplasia, except among infants with a birth weight of at least 1000 g, but it did reduce the overall risk of brain injury. (ClinicalTrials.gov number, NCT00006401 [ClinicalTrials.gov].).

Administration, Inhalation↗
PubMed2006

Hyperbilirubinemia and kernicterus.

This article describes new findings concerning the basic science of bilirubin neurotoxicity, new considerations of the definition of clinical kernicterus, and new and useful tools to diagnose kernicterus in older children, and discusses treatments for kernicterus beyond the newborn period and why proper diagnosis is important.

Bilirubin↗
PubMed2006

Early recognition of neonatal hyperbilirubinemia and its emergent management.

Hyperbilirubinemia and kernicterus are re-emerging as prominent clinical concerns and have been hypothesized to be secondary to increased breast-feeding rates, early hospital discharges and overall lack of concern for the potential impact of severe hyperbilirubinemia on healthy term newborns. Although the clinical symptoms can be non-specific and vague, they could be early, insidious and heralding signs of acute bilirubin encephalopathy (ABE) or acute stage kernicterus. Because it is highly prevalent, evaluation of a jaundiced neonate requires detailed questions about specific signs, review of birth and postnatal histories, evaluation of predischarge data, and possibly an emergency clinical evaluation of the neurological status of the infant. Medical urgency to evaluate, investigate and monitor such a newborn ensues from the possibility of rapid progression that might lead to permanent sequelae of bilirubin-induced neurologic dysfunction (BIND). Early recognition of the urgency and rapid transition to treatment seem to be the major barriers leading to delay in therapy. However, because there is a well-established and relatively safe treatment for neonatal jaundice, there should be zero tolerance for kernicterus, and BIND prevention has become a national priority in the USA. This paper reviews the clinical signs and epidemiology of ABE and BIND and presents a system-based strategy for preventing their occurrence, focusing particularly on the transition from recognition of clinical jaundice to actual treatment. A novel emergency-room-based protocol is presented as an example of how to expedite and facilitate rapid progression to treatment.

Bilirubin↗
PubMed2006

Kernicterus in late preterm infants cared for as term healthy infants.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Birth Weight↗
PubMed2006

Toward understanding kernicterus: a challenge to improve the management of jaundiced newborns.

PURPOSE: We sought to evaluate the sensitivity and specificity of total serum bilirubin concentration (TSB) and free (unbound) bilirubin concentration (Bf) as predictors of risk for bilirubin toxicity and kernicterus and to examine consistency between these findings and proposed mechanisms of bilirubin transport and brain uptake. METHODS: A review of literature was undertaken to define basic principles of bilirubin transport and brain uptake leading to neurotoxicity. We then reviewed experimental and clinical evidence that relate TSB or Bf to risk for bilirubin toxicity and kernicterus. RESULTS: There are insufficient published data to precisely define sensitivity and specificity of either TSB or Bf in determining risk for acute bilirubin neurotoxicity or chronic sequelae (kernicterus). However, available laboratory and clinical evidence indicate that Bf is better than TSB in discriminating risk for bilirubin toxicity in patients with severe hyperbilirubinemia. These findings are consistent with basic pharmacokinetic principles involved in bilirubin transport and tissue uptake. CONCLUSIONS: Experimental and clinical data strongly suggest that measurement of Bf in newborns with hyperbilirubinemia will improve risk assessment for neurotoxicity, which emphasizes the need for additional clinical evaluation relating Bf and TSB to acute bilirubin toxicity and long-term outcome. We speculate that establishing risk thresholds for neurotoxicity by using newer methods for measuring Bf in minimally diluted serum samples will improve the sensitivity and specificity of serum indicators for treating hyperbilirubinemia, thus reducing unnecessary aggressive intervention and associated cost and morbidity.

Bilirubin↗
PubMed2005

Postnatal changes in pulmonary mechanics and energetics of infants with respiratory distress syndrome following surfactant treatment.

BACKGROUND: Postnatal alterations in pulmonary mechanics, energetics and functional residual capacity (FRC) describe the structural maturation of the preterm respiratory system. OBJECTIVE: To evaluate longitudinal changes in pulmonary function in infants with respiratory distress syndrome (RDS) treated with oxygen, positive pressure ventilation and synthetic surfactant (Exosurf). METHODS: Serial pulmonary function tests were performed in surfactant-treated infants [mean +/- SD birth weight (BW) = 1,112 +/- 276 g, gestational age (GA) = 29 +/- 3 weeks] at postnatal ages: <3 days, 1, 2, 3, 4 and 6-8 weeks until term postmenstrual age (PMA). Tidal volume, pulmonary compliance (C(L)), pulmonary resistance (R(T)) and flow-resistive work were analyzed following simultaneous measurements of airflow and transpulmonary pressure signals. Serial FRC measurements were made in a randomly selected group. RESULTS: Prior to 28 weeks' PMA, C(L) was unchanged irrespective of GA. At age 1 week the likelihood ratio (LR) for bronchopulmonary dysplasia (BPD) based on C(L), R(T) and GA was predicted to be >90% for those with BW <750 g (LR >100) as compared to <10% probability (LR = 0.3) for infants >1,500 g. Significant linear increase in C(L) to PMA was evident >28 weeks' PMA (r = 0.86, p < 0.01) at 0.17 ml/cm H2O/kg/week. By term PMA, mean C(L) was 2.60 +/- 0.07 ml/cm H2O. Improvements in FRC of preterm infants with RDS who recovered occur at a more rapid rate ( approximately 25 ml/kg) compared to those who developed BPD ( approximately 20 ml/kg). CONCLUSIONS: Slow but incremental postnatal pulmonary improvement, minimal <28 weeks' PMA, were comparable for all infants. Along with diminished FRC, these changes reflect persistent deleterious effects of positive pressure ventilation, alveolar hyperoxia and unrecognized pulmonary overdistension.

Continuous Positive Airway Pressure↗
PubMed2005

Risk management of severe neonatal hyperbilirubinemia to prevent kernicterus.

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

Humans↗
PubMed2004

Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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.

Analgesics, Opioid↗
PubMed2004

Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week.

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.

Exchange Transfusion, Whole Blood↗
PubMed2004

Kernicterus: epidemiological strategies for its prevention through systems-based approaches.

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.

Female↗
PubMed2004

Kernicterus in sick and preterm infants (1999-2002): a need for an effective preventive approach.

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.

Bilirubin↗
PubMed2003

Newborn jaundice and kernicterus--health and societal perspectives.

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.

Cost of Illness↗