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Biomedical subjects

K J S Anand

Publications and source records attributed to K J S Anand.

At least 19 recordsLinked to original sources
PubMed2006

Effects of low-dose naloxone on opioid therapy in pediatric patients: a retrospective case-control study.

OBJECTIVE: To develop novel therapies that prevent opioid tolerance in critically ill children we examined the effects of low-dose naloxone infusions on patients' needs for analgesia or sedation. DESIGN AND SETTING: Matched case-control study in a pediatric intensive care unit at a university children's hospital. PATIENTS: We compared 14 pediatric ICU patients receiving low-dose naloxone and opioid infusions with 12 matched controls receiving opioid infusions. MEASUREMENTS AND MAIN RESULTS: Opioid analgesia and sedative requirements were assessed as morphine- and midazolam-equivalent doses, respectively. No differences were observed between groups in opioid doses at baseline or during naloxone, but in the postnaloxone period opioid doses tended to be lower in the naloxone group. Compared to baseline the naloxone group required more opioids during naloxone but fewer opioids after naloxone. Total sedative doses were comparable at baseline in both groups, with no differences in the postnaloxone period. The naloxone group required less sedation after naloxone but sedation doses were unchanged in controls. The two groups did not differ in pain scores, sedation scores, or opioid side effects. CONCLUSIONS: Naloxone did not reduce the need for opioid during the infusion period but tended to reduce opioid requirements in the postnaloxone period without additional need for sedation. Randomized clinical trials may examine the effects of low-dose naloxone on opioid tolerance and side effects in pediatric ICU patients requiring prolonged opioid analgesia.

Analgesia↗
PubMed2006

Assessment of persistent pain or distress and adequacy of analgesia in preterm ventilated infants.

Indicators of persistent pain in preterm neonates are poorly defined. In the setting of a double blind, placebo-controlled trial investigating morphine use in ventilated preterm infants (NEOPAIN Trial) we aimed to identify factors that may be useful in assessing persistent pain. Twenty-two babies (morphine 12; placebo 10) were assessed for comfort, pain or distress and clinical staff described the factors they had considered. This assessment was performed during the first period of duty with the baby. Based on this, they stated which study drug they believed the infant was receiving. Eighty-nine assessments were made in total (1-14 per baby). The drug was correctly identified on 71% of occasions. Staff considered one or more of the following factors: infant activity; response to routine care; known pain-related behaviours; posture/quality of movements; respiratory effort; synchrony with ventilator; blood pressure and heart rate. Four factors most frequently identified babies receiving placebo: facial expressions of pain, high activity levels, poor response to handling and poor synchrony with ventilation. Absence of pain-related behaviour was less discriminating. Observation of a good response to handling, good synchrony with ventilation, a "settled" baby, normal blood pressure and heart rate were poor discriminators. Hypotension and poor respiratory drive were noted exclusively in babies receiving morphine infusions. Facial expressions of pain, high activity levels, poor response to routine care, and poor ventilator synchrony were associated with placebo versus morphine therapy, and may be considered useful markers for persistent pain in preterm infants.

Age Factors↗
PubMed2006

Pain control: opioid dosing, population kinetics and side-effects.

Neonates undergoing invasive procedures, postoperative pain or ventilatory support commonly receive opioids for treating pain and stress. Randomized clinical trials have examined the benefits and adverse effects of morphine or fentanyl for ventilated neonates and other indications. This paper summarizes the current evidence for opioid dosing in newborns, reviews their side-effects and explains the use of population kinetics and non-linear mixed-effects modeling to analyze the data from clinical trials. Opioid use should be reserved for severe pain postoperatively or during intensive care in neonates, using continuous infusions rather than intermittent boluses. The safety and efficacy data from prolonged opioid use, particularly on the long-term outcomes of neonates, is still lacking. The pharmacodynamics and pharmacogenetics of opioid use in infancy needs further investigation, using non-linear mixed-effects models to drive individualized therapy. The current interest in opioid research will reap rich dividends in providing pain relief for neonates and avoiding dangerous side effects.

Analgesics, Opioid↗
PubMed2006

Pain activates cortical areas in the preterm newborn brain.

To study the patterns of supraspinal pain processing in neonates, we hypothesized that acute pain causes haemodynamic changes associated with activation of the primary somatosensory cortex. Forty preterm neonates at 28-36 weeks of gestation (mean=32.0) and at 25-42 h (mean=30.7) of age were studied following standardized tactile (skin disinfection) and painful (venipuncture) stimuli. Changes in regional cerebral haemodynamics were monitored by near infrared spectroscopy (NIRS) over both somatosensory cortices in 29 newborns, and over the contralateral somatosensory and occipital areas in 11 newborns. Heart rate (HR) and peripheral oxygen saturation (SaO2) were recorded simultaneously with NIRS parameters: oxygenated [HbO2], deoxygenated, and total hemoglobin. Tactile stimulation produced no changes in HR or SaO2. HR increased in the first 20s (p<0.001), while SaO2 decreased during the 40s after venipuncture (p<0.0001). Following tactile or painful stimulation, [HbO2] increased bilaterally regardless of which hand was stimulated (p<0.0001). Pain-induced [HbO2] increases in the contralateral somatosensory cortex (p<0.05) were not mirrored in the occipital cortex (p>0.1). Pain-related [HbO2] increases were more pronounced in male neonates (p<0.05 on left, p<0.001 on right), inversely correlated with gestational age (r=-0.53 on left, p<0.01; r=-0.42 on right, p<0.05) and directly correlated with postnatal age (r=0.75 on left, p<0.0001; r=0.67 on right, p<0.0001). Painful and tactile stimuli elicit specific haemodynamic responses in the somatosensory cortex, implying conscious sensory perception in preterm neonates. Somatosensory cortical activation occurs bilaterally following unilateral stimulation and these changes are more pronounced in male neonates or preterm neonates at lower gestational ages.

Brain Mapping↗
PubMed2006

Variation in pediatric intensive care therapies and outcomes by race, gender, and insurance status.

CONTEXT: The differential allocation of medical resources to adult patients according to characteristics such as race, gender, and insurance status raises the serious concern that such issues apply to critically ill children as well. OBJECTIVE: This study examined whether medical resources and outcomes for children admitted to pediatric intensive care units differed according to race, gender, or insurance status. DESIGN: An observational analysis was conducted with use of prospectively collected data from a multicenter cohort. Data were collected on 5,749 consecutive admissions for children from three pediatric intensive care units located in large urban children's hospitals. PARTICIPANTS: Children aged </=18 years admitted over an 18-month period beginning in June 1996 formed the study sample. MAIN OUTCOME MEASURES: Hospital mortality, length of hospital stay, and overall resource use were examined in relation to severity of illness. Standardized ratios were formed with generalized regression analyses that included the Pediatric Index of Mortality for risk adjustment. RESULTS: After adjustment for differences in illness severity, standardized mortality ratios and overall resource use were similar with regard to race, gender, and insurance status, but uninsured children had significantly shorter lengths of stay in the pediatric intensive care unit. Uninsured children also had significantly greater physiologic derangement on admission (mortality probability, 8.1%; 95% confidence interval [CI], 6.2-10.0) than did publicly insured (3.6%; 95% CI, 3.2-4.0) and commercially insured patients (3.7%; 95% CI, 3.3-4.1). Consistent with greater physiologic derangement, hospital mortality was higher among uninsured children than insured children. CONCLUSIONS: Risk-adjusted mortality and resource use for critically ill children did not differ according to race, gender, or insurance status. Policies to expand health insurance to children appear more likely to affect physiologic derangement on admission rather than technical quality of care in the pediatric intensive care unit setting.

Adolescent↗
PubMed2006

Collaborative Pediatric Critical Care Research Network (CPCCRN).

Pediatric critical care was formally recognized as a separate subspecialty in pediatrics in 1987. Since that time the numbers of pediatric intensivists, pediatric intensive care units, and pediatric intensive care beds in the United States have increased dramatically. Research efforts have lagged behind, however, as this new discipline has struggled to identify the necessary time, funding, and other resources to pursue clinical and laboratory investigation. In April 2004, the National Center for Medical Rehabilitation Research of the National Institute for Child Health and Human Development issued a request for applications to establish the Collaborative Pediatric Critical Care Research Network (CPCCRN). The CPCCRN provides an infrastructure to pursue collaborative clinical trials and descriptive studies in pediatric critical care medicine. Six pediatric centers involving seven intensive care units and a data-coordinating center were identified through a competitive application process. Network goals include the support of collaborative clinical trials otherwise impracticable in single institutions and the establishment of a framework for developing the scientific basis for pediatric critical care practice. This article describes how the CPCCRN was established, its organization, and its goals and future plans.

Child↗
PubMed2006

Pharmacological therapy for analgesia and sedation in the newborn.

Rapid advances have been made in the use of pharmacological analgesia and sedation for newborns requiring neonatal intensive care. Practical considerations for the use of systemic analgesics (opioids, non-steroidal anti-inflammatory agents, other drugs), local and topical anaesthetics, and sedative or anaesthetic agents (benzodiazepines, barbiturates, other drugs) are summarised using an evidence-based medicine approach, while avoiding mention of the underlying basic physiology or pharmacology. These developments have inspired more humane approaches to neonatal intensive care. Despite these advances, little is known about the clinical effectiveness, immediate toxicity, effects on special patient populations, or long-term effects after neonatal exposure to analgesics or sedatives. The desired or adverse effects of drug combinations, interactions with non-pharmacological interventions or use for specific conditions also remain unknown. Despite the huge gaps in our knowledge, preliminary evidence for the use of neonatal analgesia and sedation is available, but must be combined with a clear definition of clinical goals, continuous physiological monitoring, evaluation of side effects or tolerance, and consideration of long-term clinical outcomes.

Analgesia↗
PubMed2006

Assessing postoperative pain in neonates: a multicenter observational study.

OBJECTIVE: A multicenter observational study was conducted to evaluate the practices of postoperative pain assessment and management in neonates to identify specific targets for improvement in clinical practice. METHODS: Ten participating NICUs collected data for the 72 hours after a surgical operation on 25 consecutive neonates (N = 250), including demographics, principal diagnoses, operative procedure, other painful procedures, pain assessments, interventions (pharmacologic and nonpharmacologic), and adverse events in neonates who underwent minor and major surgery. Descriptive and logistic-regression analyses were performed by using SPSS and Stata. RESULTS: The neonates studied had a birth weight of 2.4 +/- 1.0 kg (mean +/- SD) and gestational age of 36 +/- 4.3 weeks; 57% were male, and length of hospital stay was 23.5 +/- 30.0 days. Participating hospitals used 7 different numeric pain scales, with nursing pain assessments documented for 88% (n = 220) of the patients and physician pain assessments documented for 9% (n = 23) of the patients. Opioids (84% vs 60%) and benzodiazepines (24% vs 11%) were used more commonly after major surgery than minor surgery, and a small proportion (7% major surgery, 12% minor surgery) received no analgesia. Logistic-regression analyses showed that physician pain assessment was the only significant predictor of postsurgical analgesic use, whereas major surgery and postnatal age in days did not seem to contribute. Physician pain assessment was documented for 23 patients; 22 of these received postoperative analgesia. CONCLUSIONS: Documentation of postoperative pain assessment and management in neonates was extremely variable among the participating hospitals. Pain assessment by physicians must be emphasized, in addition to developing evidence-based guidelines for postoperative care and educating professional staff to improve postoperative pain control in neonates.

Analgesics↗
PubMed2005

The pharmacological treatment of neonatal pain.

Optimal analgesia remains a major challenge for all involved in the care of (critically) ill newborns. The rapid changes in liver metabolism involving maturation of liver enzymes and renal clearance of drugs render (extreme) very low birth weight infants different from newborns of later postconceptional age with regards to the use of opioids such as morphine and fentanyl. Acute and/or procedural pain has been investigated fairly recently in randomized controlled trials and there are now guidelines. The long-term effects of opioid use in this particular age group of vulnerable babies await further evaluation.

Analgesics, Opioid↗
PubMed2005

Analgesia and local anesthesia during invasive procedures in the neonate.

BACKGROUND: Preterm and full-term neonates admitted to the neonatal intensive care unit or elsewhere in the hospital are routinely subjected to invasive procedures that can cause acute pain. Despite published data on the complex behavioral, physiologic, and biochemical responses of these neonates and the detrimental short- and long-term clinical outcomes of exposure to repetitive pain, clinical use of pain-control measures in neonates undergoing invasive procedures remains sporadic and suboptimal. As part of the Newborn Drug Development Initiative, the US Food and Drug Administration and the National Institute of Child Health and Human Development invited a group of international experts to form the Neonatal Pain Control Group to review the therapeutic options for pain management associated with the most commonly performed invasive procedures in neonates and to identify research priorities in this area. OBJECTIVE: The goal of this article was to review and synthesize the published clinical evidence for the management of pain caused by invasive procedures in preterm and full-term neonates. METHODS: Clinical studies examining various therapies for procedural pain in neonates were identified by searches of MEDLINE (1980-2004), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2004), the reference lists of review articles, and personal files. The search terms included specific drug names, infant-newborn, infant-preterm, and pain, using the explode function for each key word. The English-language literature was reviewed, and case reports and small case series were discarded. RESULTS: The most commonly performed invasive procedures in neonates included heel lancing, venipuncture, IV or arterial cannulation, chest tube placement, tracheal intubation or suctioning, lumbar puncture, circumcision, and SC or IM injection. Various drug classes were examined critically, including opioid analgesics, sedative/hypnotic drugs, nonsteroidal anti-inflammatory drugs and acetaminophen, injectable and topical local anesthetics, and sucrose. Research considerations related to each drug category were identified, potential obstacles to the systematic study of these drugs were discussed, and current gaps in knowledge were enumerated to define future research needs. Discussions relating to the optimal design for and ethical constraints on the study of neonatal pain will be published separately. Well-designed clinical trials investigating currently available and new therapies for acute pain in neonates will provide the scientific framework for effective pain management in neonates undergoing invasive procedures.

Analgesia↗
PubMed2005

Analgesia and sedation during mechanical ventilation in neonates.

BACKGROUND: Endotracheal intubation and mechanical ventilation are major components of routine intensive care for very low birth weight newborns and sick full-term newborns. These procedures are associated with physiologic, biochemical, and clinical responses indicating pain and stress in the newborn. Most neonates receive some form of analgesia and sedation during mechanical ventilation, although there are marked variations in clinical practice. Clinical guidelines for pharmacologic analgesia and sedation in newborns based on robust scientific data are lacking, as are measures of clinical efficacy. OBJECTIVE: This article represents a preliminary attempt to develop a scientific rationale for analgesia sedation in mechanically ventilated newborns based on a systematic analysis of published clinical trials. METHODS: The current literature was reviewed with regard to the use of opioids (fentanyl, morphine, diamorphine), sedative-hypnotics (midazolam), nonsteroidal anti-inflammatory drugs (ibuprofen, indomethacin), and acetaminophen in ventilated neonates. Original meta-analyses were conducted that collated the data from randomized clinical comparisons of morphine or fentanyl with placebo, or morphine with fentanyl. RESULTS: The results of randomized trials comparing fentanyl, morphine, or midazolam with placebo, and fentanyl with morphine were inconclusive because of small sample sizes. Meta-analyses of the randomized controlled trials indicated that morphine and fentanyl can reduce behavioral and physiologic measures of pain and stress in mechanically ventilated preterm neonates but may prolong the duration of ventilation or produce other adverse effects. Randomized trials of midazolam compared with placebo reported significant adverse effects (P < 0.05) and no apparent clinical benefit; the findings of a meta-analysis suggest that there are insufficient data to justify use of IV midazolam for sedation in ventilated neonates. CONCLUSIONS: Despite ongoing research in this area, huge gaps in our knowledge remain. Well-designed and adequately powered clinical trials are needed to establish the safety, efficacy, and short- and long-term outcomes of analgesia and sedation in the mechanically ventilated newborn.

Analgesia↗
PubMed2005

Analgesia and anesthesia for neonates: study design and ethical issues.

OBJECTIVE: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. METHODS: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. RESULTS: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters. CONCLUSIONS: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field.

Analgesia↗
PubMed2005

Does neonatal surgery lead to increased pain sensitivity in later childhood?

Does pain or tissue damage in early life lead to hyperalgesia persisting into childhood? We performed a cross-sectional study in 164 infants to investigate whether major surgery within the first 3 months of life increases pain sensitivity to subsequent surgery and to elucidate whether subsequent surgery in the same dermatome or in a different dermatome leads to differences in pain sensitivity. All infants received standard intraoperative and postoperative pain management, with rescue analgesia guided by a treatment algorithm. Differences in pain sensitivity during surgery were assessed by the intraoperative fentanyl intake and by (nor)epinephrine plasma concentrations. Differences in postoperative pain sensitivity were assessed by the observational pain measures COMFORT and VAS, and by morphine intake and (nor)epinephrine plasma concentrations. Infants previously operated upon in the same dermatome needed more intraoperative fentanyl, had higher COMFORT and VAS scores, had greater (nor)epinephrine plasma concentrations, and needed also more morphine than did infants with no prior surgery. In contrast, infants who previously underwent surgery in another dermatome had only significant higher postoperative analgesic requirements and norepinephrine plasma concentrations in comparison with infants with no prior surgery. These preliminary differences may indicate the occurrence of spinal and supraspinal changes following neonatal surgery. We conclude that the long-term consequences of surgery in early infancy are greater in areas of prior tissue damage and that these effects may portend limited clinical but important neurobiological differences.

Analgesics, Opioid↗
PubMed2005

Effect of inborn versus outborn delivery on clinical outcomes in ventilated preterm neonates: secondary results from the NEOPAIN trial.

OBJECTIVE: The objective of this study was to evaluate the effect of birth center (inborn versus outborn) on morbidity and mortality for preterm neonates (23 to 32 weeks) using data collected prospectively within a uniform protocol. STUDY DESIGN: Secondary analyses of data from the NEurologic Outcomes and Pre-emptive Analgesia In Neonates (NEOPAIN) trial (n=898) were performed to evaluate the effect of inborn versus outborn delivery on neonatal outcomes, including the occurrence of severe intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), chronic lung disease (CLD), and mortality. RESULTS: Outborn babies were more likely to have severe IVH (p=0.0005); this increased risk persisted after controlling for severity of illness. When adjustments for antenatal steroids were added, the effect of birth center was no longer significant. Neither the occurrences of PVL or CLD nor mortality were significantly different between the inborn and outborn infants. CONCLUSION: Outborn babies are more likely to have severe IVH than inborn babies, perhaps because their mothers are less likely to receive antenatal steroids. Improvements in antenatal steroid administration to high-risk women may substantially reduce neonatal morbidity.

Adult↗
PubMed2005

Hospitalizations for critically ill children with traumatic brain injuries: a longitudinal analysis.

OBJECTIVE: This study examines the incidence, utilization of procedures, and outcomes for critically ill children hospitalized with traumatic brain injury over the period 1988-1999 to describe the benefits of improved treatment. DESIGN: Retrospective analysis of hospital discharges was conducted using data from the Health Care Cost and Utilization Project Nationwide Inpatient Sample that approximates a 20% sample of U.S. acute care hospitals. SETTING: Hospital inpatient stays from all types of U.S. community hospitals. PARTICIPANTS: The study sample included all children aged 0-21 with a primary or secondary ICD-9-CM diagnosis code for traumatic brain injury and a procedure code for either endotracheal intubation or mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deaths occurring during hospitalization were used to calculate mortality rates. Use of intracranial pressure monitoring and surgical openings of the skull were investigated as markers for the aggressiveness of treatment. Patients were further classified by insurance status, household income, and hospital characteristics. Over the 12-yr study period, mortality rates decreased 8 percentage points whereas utilization of intracranial pressure monitoring increased by 11 percentage points. The trend toward more aggressive management of traumatic brain injury corresponded with improved hospital outcomes over time. Lack of insurance was associated with vastly worse outcomes. An estimated 6,437 children survived their traumatic brain injury hospitalization because of improved treatment, and 1,418 children died because of increased mortality risk associated with being uninsured. Improved treatment was valued at approximately dollar 17 billion, whereas acute care hospitalization costs increased by dollar 1.5 billion (in constant 2000 dollars). Increased mortality in uninsured children was associated with a dollar 3.76 billion loss in economic benefits. CONCLUSIONS: More aggressive management of pediatric traumatic brain injury appears to have contributed to reduced mortality rates over time and saved thousands of lives. Additional lives could be saved if mortality rates could be equalized between insured and uninsured children.

Adolescent↗
PubMed2005

Morphine, hypotension, and adverse outcomes among preterm neonates: who's to blame? Secondary results from the NEOPAIN trial.

OBJECTIVES: Hypotension occurs commonly among preterm neonates, but its cause and consequences remain unclear. Secondary data analyses from the NEOPAIN trial identified the clinical factors associated with hypotension and examined the contributions of morphine treatment or hypotension to severe intraventricular hemorrhage (IVH) (grades 3 and 4), any IVH (grades 1-4), or death. METHODS: In the NEOPAIN trial, 898 ventilated neonates between 23 and 32 weeks of gestation were enrolled, with equal numbers randomized to receive masked morphine or placebo infusions. Additional doses of open-label morphine were administered as necessary by medical staff members. IVH was diagnosed with centralized readings of early and late cranial ultrasonograms. Hypotension was assessed before study drug infusion, during the loading dose, and at 24 and 72 hours during study drug infusion. Logistic regression analyses with stepdown elimination identified the predictor factors associated with the hypotension, severe IVH, any IVH, or death outcomes at each time point. RESULTS: Hypotension was associated with 23 to 26 weeks of gestation, morphine infusions, severity of illness, additional morphine doses, and prior hypotension. Severe IVH was associated with shorter gestation, higher Clinical Risk Index for Babies scores, no prenatal steroids, pulmonary hemorrhage, hypotension before the loading dose, and morphine doses before intubation and at 25 to 72 hours. Neonatal deaths were associated with 23 to 26 weeks of gestation, higher Clinical Risk Index for Babies scores, pulmonary hemorrhage, patent ductus arteriosus, thrombocytopenia, and hypotension before the loading dose. Morphine infusions were not a significant factor in logistic models for severe IVH, any IVH, or death. CONCLUSIONS: Preemptive morphine infusions, additional morphine, and lower gestational age were associated with hypotension among preterm neonates. Severe IVH, any IVH, and death were associated with preexisting hypotension, but morphine therapy did not contribute to these outcomes. Morphine infusions, although they cause hypotension, can be used safely for most preterm neonates but should be used cautiously for 23- to 26-week neonates and those with preexisting hypotension.

Age Factors↗