Neonatal Hypotension Research Articles

A survey on management practices of hypotension in preterm neonates: an Indian perspective.

Hypotension is a common entity in the neonatal intensive care unit (NICU) and is reported in 24%-50% of preterm infants with birth weight less than 1,500 g. Rapid diagnosis and aggressive management is crucial to reduce its detrimental effects on end-organs especially the brain. Physicians often rely on blood pressure alone as a reliable indicator of tissue perfusion, but variations exist in the definition of this crucial parameter. There are also practice variations in the use of diagnostic tools and management modalities among physicians. A physician-based cross-sectional survey of management practices of hypotension in preterm neonates in Indian NICUs was conducted using an online survey tool. The questionnaire addressed diagnostic criteria used, utility of echocardiography for the assessment of hypotension, and management strategies used, such as volume expansion, inotropes and steroids. Three hundred and twenty physicians, working predominantly in Level III NICUs, responded to the survey. The practice of delayed cord clamping was followed in the units of 78% respondents. Only 44% respondents had an institutional written protocol for the management of hypotension. The criteria for the diagnosis of hypotension varied, with 52% using mean blood pressure (BP) less than gestational age as the criteria. Capillary refill time, blood pressure and heart rate were the most common clinical criteria used. 85% respondents used echocardiography in the NICU, but only 73% utilised it for assessment of a hypotensive neonate. Physicians preferred a 'volume-inotrope-echo-steroid' strategy, with 85% respondents using volume expansion. Dopamine was the preferred first line inotrope, followed by norepinephrine and low-dose epinephrine. This survey reflects significant variations in practice amongst neonatal physicians in India. Bedside targeted echocardiography needs to be better utilised as a vital tool to determine the pathophysiology of disease and hemodynamic monitoring in the management of hypotension in neonates. While further research is needed on outcome-oriented objectives, awareness and dissemination of already existing guidelines would be useful to standardize clinical practice.

Inotrope therapy for neonatal hypotension: answers

Inotrope therapy for neonatal hypotension: answers

Questions and controversies in the management of hypotension in preterm infants

Hypotension is a frequent condition that affects preterm infants during the first days of life, within the transition period to an extra uterine environment, or associated with neonatal pathology. Persistent hypotension in the neonatal period is associated with increased neonatal morbidity and mortality. Understanding neonatal hemodynamics is the first step in approaching hypotensive neonatal patients. Treating hypotension should be to restore impaired blood flow and maintain cellular metabolism. Neonatologists should look beyond values of blood pressure and check for markers of low systemic blood flow and inadequate organ perfusion. There are many anti-hypotensive agents, but choosing the most appropriate intervention should take into consideration the underlying pathophysiologic process, the effectiveness versus side effects of the drug, and medium and long-term developmental outcomes. This article intends to review the therapeutic options for neonatal hypotension to offer the clinicians support for an evidence-based choice.

An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication.

Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment. In this review, after a short review of AH definitions used in neonates and existing data on pathophysiology of AH, we discuss currently available data on pharmacokinetic and hemodynamic effects, as well as the effectiveness and safety of anti-hypotensive medications in neonates. In addition, data on the comparisons between anti-hypotensive medications and current suggestions for the main indications of each medication are discussed.

Corticosteroid use in neonatal hypotension: A survey of Canadian neonatologists

ObjectiveTo assess prescribing practices and perspectives regarding the use of corticosteroids in the management of neonatal hypotension. MethodsCross-sectional questionnaire-based electronic survey of neonatologists (n = 206) practicing at tertiary neonatal intensive care units across 30 academic centres in Canada. ResultsThe overall response rate was 33% (72/206), with a completion rate was 94%. Most (48/72, 64%) worked in a unit that covered both inborn and outborn infants, and 53% (37/70) worked in units with >100 very low birth weight infants admitted annually. Among the 72 respondents, 39% use a loading dose, of whom most (57%) use 2 mg/kg. Dosing ranges were variable, most using either 0.5 mg/kg or 1 mg/kg, q6h. Among the 56% (40/72) of neonatologists who reported measuring cortisol before initiation of hydrocortisone, cut-offs for initiation of hydrocortisone varied from <100 to <500 nmol/L, most of whom (48%) used <100 nmol/L. Of 71 respondents, 92% (65) indicated that a randomized control trial examining the use of corticosteroids in neonatal hypotension is needed, of whom 52% (37) indicated that the intervention group should receiving hydrocortisone after one vasopressor/inotrope. ConclusionsThis survey provides insight into the prescribing practices of tertiary neonatologists with regards to the use of corticosteroids in neonatal hypotension. While corticosteroids are frequently prescribed, there is variability in the indication, dosing, and duration of corticosteroid use. The findings from this survey can be used to inform further research, including a clinical trial, regarding the practice in the management of neonatal hypotension.

Norepinephrine versus phenylephrine for managing maternal hypotension during cesarean delivery under spinal anesthesia: a meta-analysis of maternal and neonatal outcomes

Norepinephrine or phenylephrine administration to prevent and treat hypotension during spinal anesthesia for cesarean section has been a significant topic of discussion. This meta-analysis aimed to update existing evidence and provide further insights into neonatal and maternal outcomes associated with norepinephrine and phenylephrine. Review of randomized controlled trials (RCTs) was performed to assess the effectiveness of norepinephrine and phenylephrine in managing maternal hypotension during cesarean delivery under spinal anesthesia. Neonatal umbilical cord blood pH and maternal hypotension were the primary outcomes. Based on the analysis of 26 RCTs with 2984 participants, we found no significant difference between the norepinephrine and phenylephrine groups in umbilical artery pH in neonates (mean difference (MD) 0.00; 95% confidence interval (CI) −0.00 to 0.01, p = 0.20). Neonates Apgar scores did not differ between both groups. Norepinephrine was associated with lower incidences of bradycardia (risk ratio (RR) 0.44; 95% CI 0.37 to 0.51, p &lt; 0.001) and reactive hypertension (RR 0.53; 95% CI 0.39 to 0.72, p &lt; 0.001) in parturient women than phenylephrine. In neither group did umbilical cord blood levels of partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and base excess (BE) levels of neonates differ significantly, nor did maternal hypotension, nausea or vomiting incidence during delivery. For maternal hypotension after spinal anesthesia, norepinephrine and phenylephrine did not significantly differ in neonatal acidemia. Despite similarities to phenylephrine in managing hypotension and maintaining maternal hemodynamic stability, norepinephrine is a promising alternative.

Hypotension in Preterm Newborns and Its Short-Term Outcome: Experience of a Tertiary Care Hospital in Bangladesh

Background: Blood pressure values of too low or too high can be related with serious morbidity and mortality. Neonatal hypotension has been found to be related with serious short term as well as significant long-term health complications. Thus, identifying this low blood pressure in preterm neonates with its impacts on neonatal health is crucial. Objectives: To evaluate blood pressure values in preterm newborn and short-term impacts of hypotension on neonatal health. Methods: This prospective observational study was conducted in Neonatal Intensive Care Unit (NICU) of Bangabandhu Sheikh Mujib Medical University a tertiary care hospital of Dhaka city after approval from Institutional Review Board for a period of one years. Neonates having gestation&lt; 37 completed weeks admitted in NICU of BSMMU were enrolled in the study after getting informed consent from the parents. Proper antenatal and postnatal history were recorded in data collection form. Blood pressure was measured by non-invasive oscillometric method in all neonates within 24 hours after birth by ideal procedure. Blood pressure was monitored at an interval of 12 hours or more frequently when required till discharge or death. Information on neonatal mortality and morbidity were recorded in data collection form. Results: A total of 114 preterm neonates were studied during the study period, among them 61 (53.5%) had normal blood pressure and 53 (46.5%) had hypotension. Among the enrolled patients, 15 (13.2%) patients died, 3 (2.6%) left against medical advice, 11 (9.6%) 96 (84.2%) were discharged with advice. Short time outcomes like culture proven sepsis, use of ionotrops, need for oxygen support and assisted ventilation, feeding intolerance, Necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity and duration of hospital stay were significantly higher in hypotensive group. Mortality was also higher in hypotensive group than normotensive group (26.4% vs 3.3%, p &lt;0.001). Conclusion: Hypotension in preterm neonates was associated with significant mortality and morbidity in early post-natal period.

General anesthesia with remimazolam for emergency cesarean section in a patient with acute infective endocarditis: a case report

BackgroundThe anesthetic management of pregnant women with acute heart failure remains challenging with regard to maintaining the hemodynamic status of the mother and baby. The likelihood of decreased blood pressure is lower with remimazolam than with propofol. However, there is no report of general anesthesia with remimazolam for cesarean section.Case presentationThe patient was a 34-year-old pregnant woman who was diagnosed with acute heart failure associated with infective endocarditis. We performed cesarean section under general anesthesia using remimazolam, with percutaneous cardiopulmonary support on standby. The mother’s mean blood pressure was maintained above 65 mmHg during the surgery, without catecholamines or vasopressors. The infant’s Apgar scores were 4 at 1 min and 7 at 5 min.ConclusionCesarean section was successfully performed under general anesthesia with remimazolam in a pregnant patient with acute heart failure. Further studies are needed to clarify the association between remimazolam and neonatal hypotension.

A case of PURA syndrome in a newborn child (neurodevelopmental disorder syndrome with neonatal respiratory failure, hypotension and feeding difficulties; nEDRIHf(OMIM 616158))

A case of PURA syndrome in a newborn child (neurodevelopmental disorder syndrome with neonatal respiratory failure, hypotension and feeding difficulties; nEDRIHf(OMIM 616158))

The role of human milk feeds on inotrope use in newborn infants with sepsis.

Regarding neonatal hypotension, there is no certainty as to whether inotrope properties are beneficial or whether they may be harmful. However, given that the antioxidant content of human milk plays a compensatory role in neonatal sepsis and that human milk feeding has direct effects in modulating the cardiovascular function of sick neonates, this research hypothesized that human milk feeds might predict lower requirements of vasopressors in the management of neonatal septic shock. Between January 2002 and December 2017, all late preterm and full-term infants attending a neonatal intensive care unit, with clinical and laboratory findings of bacterial or viral sepsis, were identified in a retrospective study. During their first month of life, data on feeding type and early clinical characteristics were collected. A multivariable logistic regression model was constructed to determine the impact of human milk on the use of vasoactive drugs in septic newborns. 322 newborn infants were eligible to participate in this analysis. Exclusively formula-fed infants were more likely to be delivered via C-section, to have a lower birth weight and a lower 1-minute Apgar score than their counterparts. Human milk-fed newborns had 77% (adjusted OR = 0.231; 95% CI: 0.07-0.75) lower odds of receiving vasopressors than exclusively formula-fed newborns. We report that any human milk feeding is associated with a decrease in the need for vasoactive medications in sepsis-affected newborns. This observation encourages us to undertake further research to determine whether human milk feeds mitigate the use of vasopressors in neonates with sepsis.

Use of Vasopressin as Rescue Therapy in Refractory Hypoxia and Refractory Systemic Hypotension in Term Neonates with Severe Persistent Pulmonary Hypertension-A Prospective Observational Study.

Persistent pulmonary hypertension of the newborn (PPHN) is a serious cardiorespiratory problem. PPHN is frequently associated with refractory hypoxia and hypotension, and optimal management has the potential to improve important clinical outcomes including mortality. The primary objective is to evaluate the efficacy and safety of rescue vasopressin (VP) therapy in the management of severe (refractory) hypoxia and refractory systemic hypotension in term neonates with severe PPHN. Neonates with refractory hypoxia and refractory hypotension due to severe PPHN needing VP were prospectively enrolled in the study. Refractory hypoxia was defined as oxygenation index (OI) ≥ 25 for at least 4 hours after the commencement of high-frequency oscillatory ventilation and nitric oxide at 20 ppm. Refractory hypotension was defined as mean blood pressure lesser than mean gestational age lasting for more than 15 minutes in spite of dopamine infusion at 10 µg/kg/min, adrenaline infusion at 0.3 µg/kg/min, and noradrenaline infusion at 0.1 µg/kg/min. Thirty-two neonates with PPHN were recruited. The baseline OI (mean ± standard deviation [SD]) before starting VP was 33.43 ± 16.54 which started decreasing significantly between 1 and 6 hours after the commencement of VP (p < 0.05). The mean blood pressure also increased concomitantly with a significant effect seen by 1 hour (p < 0.05). The vasoactive infusion score before the commencement of VP was mean 46.07 (SD = 25.72) and started decreasing after 12 to 24 hours of commencement of VP (p < 0.05). Lactate levels (mean ± SD) before starting VP were 7.8 ± 8.6 mmol/L and started decreasing between 6 and 12 hours (p < 0.05). Two neonates died due to refractory hypoxia and refractory hypotension (overall mortality 6.2%) CONCLUSION: Rescue VP therapy is a useful adjunct in the management of neonates with severe PPHN with refractory hypoxia and/or refractory hypotension. Improvement in oxygenation and hemodynamics with the use of VP results in reduced mortality. · Rescue vasopressin is a useful adjunct in the management of neonates with severe PPHN.. · Vasopressin helps reduce OI.. · Vasopressin reduces the vasoactive inotrope score..

19 Quality Improvement bundled approach reduces the use of inotropes in extremely premature babies

Abstract Background Consensus on definition and management of hypotension in preterm neonates is lacking. Owing to this, there are wide variations in the reported incidence of hypotension in premature infants, especially during first week of life. Inotropes can often cause vasoconstriction, which may alter brain perfusion especially in the absence of established cerebral autoregulation. Use of these drugs is associated with multiple short- and long-term morbidities. Objectives To evaluate the effect of quality improvement (QI) bundle on rate of inotrope use and associated morbidities. Design/Methods Inborn preterm neonates born at &amp;lt;29weeks gestational age (GA) and admitted to level III NICU were included. Neonates with major congenital malformations, congenital heart diseases, antenatal diagnosed genetic defects, and neonates admitted after 72 hours of age were excluded from the study. We implemented a QI bundle (Figure 1) focussing on first 72hours from birth which included delayed cord clamping, avoidance of routine echocardiography, addition of clinical criteria to define hypotension, factoring iatrogenic causes of hypotension (ruling out lung hyperinflation), and standardization of respiratory management. Rate of use of inotropes in the first 72hours of life along with acute brain injury and mortality before and after implementation of the QI bundle were compared. The balancing measure was the rate of ischemic lesions in the form of cPVL. Cranial ultrasound was performed to screen for brain injury. Study was approved by the local research ethics board (REB14-1466). Results We included 671 neonates (301 before and 364 after the implementation of the bundle) among which 6 neonates were excluded based on the criteria. QI bundle implementation was associated with significant reduction in overall use of inotropes (24% vs 7%, p&amp;lt;0.001), dopamine (18% vs 5%, p&amp;lt;0.001), and dobutamine (17% vs 4%, p&amp;lt;0.001). Rate of acute brain injury decreased significantly: Acute brain injury of any grade (34% vs 20%, p&amp;lt;0.001) and severe brain injury (15% vs 6%, p&amp;lt;0.001). There was no difference in incidence of cPVL (1% vs 1.4%, p=0.66). Associations remained significant after adjusting for confounding factors. The QI bundle implementation was associated with a significant reduction in the use of inotropes when analyzed based on the 6 monthly time intervals (p = 0.006) (Figure 2) Conclusion Our QI bundled approach resulted in reduction in inotrope use and associated brain morbidities in premature babies. Follow-up studies evaluating the impact of this initiative on long-term outcomes in survivors are required to complement findings of improved short-term outcomes seen in this study.

Systematic Review and Meta-Analysis of Cardiovascular Medications in Neonatal Hypotension

Background: Comparative studies among the various cardiovascular medications used for the treatment of neonatal hypotension are lacking. Methods: This systematic review and pairwise meta-analysis of the anti-hypotensive treatments in preterm and term infants was conducted to evaluate efficacy and impact on outcome. Electronic databases were searched up to February 2021 for relevant articles. As an extension of the current approach for study selection, a machine learning technique was used. Only randomized controlled trials (RCTs) of inotropes, pressors, volume therapy, and corticosteroids were included. Response to treatment was the primary outcome while secondary outcomes included mortality and common morbidities. Results: Nineteen RCTs involving 758 preterm and term neonates were found, and 8 treatments were evaluated. Most studies involved subjects with early hypotension associated with prematurity. Pairwise meta-analysis among treatments showed that dopamine was more effective than dobutamine regarding the response to treatment (restoration of normotension or normalization of blood pressure) (7 trials, 286 neonates, odds ratio, 3.06 [95% CI = 1.06–8.87]; I² = 49%, very low quality of the evidence per GRADE). Comparisons of other treatments were not significant. No differences were found among regimens regarding survival and other secondary outcomes. Conclusion: In this systematic review and pairwise meta-analysis, only the comparison of dopamine versus dobutamine provided evidence for efficacy of treatment and favored dopamine. No safe conclusions could be reached in regard to other treatments. Data regarding the management of arterial hypotension in conditions other than transition after birth in preterm newborns are sparse both in preterm and term infants.

The effect of norepinephrine on clinical and hemodynamic parameters in neonates with shock: a retrospective cohort study.

changes in mean blood pressure (MBP) at 6, 12, and 24h post-initiation of NE. Changes in (i) diastolic BP, systolic BP, and vasoactive inotrope score (VIS) at 6, 12, and 24h, (ii) urine output after initiation of NE ii) pH, lactate, fraction of inspired oxygen (FiO2) after initiation of NE, and (iv) adverse outcomes. Fifty infants received NE with mean (SD) gestational age of 34.3 (4.3) weeks and a mean birth weight of 2215 (911) g. Treatment began at a median age of 36 (IQR: 15.2, 67.2) hours of life and lasted 30.5 (IQR: 12.7, 58) hours. MBP improved from 34.4mm Hg (SD: 6.6) at baseline to 39.4mm Hg (SD: 10.5, p < 0.001) at 6h, to 39.6mm Hg (SD: 12.1, p = 0.002) at 12h and to 40.4mm Hg (SD: 15.5, p = 0.004) at 24h after NE initiation. Vasoactive inotrope score declined from 30 (20, 32) to 10 (4, 30; p < 0.001) at 24h. Urine output improved within 24h [1.5ml/kg/h (0.5, 2.3) at baseline to 3 (1.9, 4.3) at 24h; p = 0.04]. Oxygen requirement decreased after NE initiation. The use of NE appears to be effective and safe for treating systemic hypotension in neonates. Being a retrospective study, trial registration was not considered. •Dopamine has traditionally been used as the initial agent for treatment of neonatal hypotension. •Norepinephrine has recently been recommended as the first-choice vasopressor agent to correct hypotension in adults and pediatric patients, with insufficient data on the cardiovascular effects of NE in neonates What is new: •Mean blood pressure improved significantly at 6, 12, and 24h with reduction in vasoactive infusion score at 12 and 24h after norepinephrine infusion. •No significant change in heart rate or abnormal abdominal adverse effects noted in this study.

Blood Pressure Goals: Is Cerebral Saturation the New Mean Arterial Pressure?

The objective of this article was to correlate hypotension and cerebral saturation from near-infrared spectroscopy (cNIRS) in neonates on dopamine. Retrospective review of neonates receiving dopamine between August 2018 and 2019 was performed. Hypotension thresholds included mean arterial pressure (MAP) of postmenstrual age (PMA) ± 5 and 30 mm Hg and gestational age (GA) ± 5 mm Hg. Time below threshold MAP was compared with time with cerebral hypoxia (cNIRS <55%). Hypotension occurred 6 to 33% of the time on dopamine in 59 cases. Hypotension did not correlate with abnormal cNIRS overall, within PMA subgroups or by outcomes. Hypotensive periods with MAP < GA had fewer corresponding percent time with abnormal cNIRS events (3.7 ± 1.3%) compared with MAP < PMA (11.9 ± 4.9%, p < 0.003) or 30 mm Hg thresholds (12.2 ± 4.7%, p < 0.0001). In most premature infants, mean cNIRS values during hypotension were still within normal range (57 ± 6%). cNIRS may be a more clinically relevant measure than MAP for the assessment of neonatal hypotension. · Hypotension occurred 6 to 33% of the time on dopamine in 59 cases.. · Hypotension did not correlate with abnormal cNIRS overall, within PMA subgroups or by outcomes.. · MAP. · We found no cNIRS difference between IVH grades, mortality, average Hct, lactates, or urine output.. · cNIRS may be a more clinically relevant measure than MAP for the assessment of neonatal hypotension..

Comparison of Invasive Arterial Blood Pressure Monitoring vs. Non-Invasive Blood Pressure Monitoring in Preterm Infants < 37 Weeks in the Neonatal Intensive Care Unit- A Prospective Observational Study.

Accurate measurement of blood pressure (BP) is extremely important in the management of sick preterm newborns. The primary objective of this study was to compare non-invasive blood pressure measurement (NIBP) with invasive blood pressure measurement (IBP) using peripheral arterial cannulation (PAC) in preterm neonates < 37 weeks in the neonatal intensive care unit. Preterm neonates needing PAC were prospectively enrolled in the study. NIBP measurements were taken in the same limb as that of peripheral arterial line. Initially IBP was recorded followed by NIBP within 1 min using the same monitor. These were called as paired measurements since they are taken within 1 min of each other. Seventy-three preterm infants with 1703 paired measurements were included in the final analysis (median gestational age 32 weeks, IQR 30-34 weeks, median birth weight 1540 g, IQR 1160-2100 g). In preterm infants not receiving vasoactive agents (n = 51, 1428 paired measurements, Bland-Altman analysis for agreement between invasive mean blood pressure (MBP) and non-invasive mean BP revealed a bias of -2.9123 mmHg (SD 7.8074). The 95% limits of agreement were from -18.2157 to 12.3893 mmHg. In preterm infants with hypotension, we detected a bias of -3.9176 mmHg (SD 5.1135) between invasive MBP and non-invasive MBP. The 95% limits of agreement were from -13.9401 to 6.1048 mmHg. In normotensive preterm infants receiving vasoactive agents, we detected a bias of -0.7629 mmHg (SD 8.0539) between invasive MBP and non-invasive MBP. The 95% limits of agreement were from -16.5485 to 15.02274 mmHg. There is poor level of agreement between IBP and NIBP measurements in sick preterm neonates, leading to overestimation or underestimation of blood pressure. The bias was less for mean BP measurements as compared with systolic BP measurements and also for normotensive neonates as compared with hypotensive neonates. Hence, NIBP may be used as a screening method in haemodynamically stable preterm infants, but infants who are haemodynamically unstable and need to be commenced on vasoactive agents should have IBP monitoring.

Efficacy of Antenatal Magnesium Sulfate for Neuroprotection in Extreme Prematurity: A Comparative Observational Study.

BackgroundSurvival of preterm infants has improved drastically. In addition to significant contribution to neonatal mortality, impact of prematurity among survivors may continue through life impairing long-term physical life through neuro-disability and increased risk of cerebral palsy. Maternal administration of magnesium sulfate prior to impending preterm birth is an effective strategy to reduce neuromorbidity.AimTo investigate the effectiveness of antenatal magnesium sulfate for neuroprotection in preterm infants between 26 and 34 weeks in preventing early neonatal morbidity and mortality. Secondary objective was to assess any adverse events with the use of magnesium sulfate on the mother and neonate.MethodThis was a prospective observational comparative study for 2 years at our tertiary care hospital of 100 pregnant women who gave preterm births. Fifty infants each were born to mothers who were either not given MgSO4 (Group 1) or given 4gm intravenous loading dose MgSO4 (Group 2), preferably 4 h prior to preterm birth.ResultsAmong all the preterm in our study, 81% delivered between 30 and 34 weeks. There was no significant difference in terms of maternal mortality or serious morbidity including postpartum hemorrhage, caesarian section rates or length of hospital stay among women receiving MgSO4 versus no MgSO4. Mild maternal side effects secondary to magnesium sulfate were experienced in 8% cases. There were no significant differences between both groups for low 5 min APGAR, need for NICU admission, neonatal convulsions, hyperbilirubinemia, necrotizing enterocolitis, periventricular leukomalacia and septicemia. There was a trend toward reduced risk in the magnesium sulfate group for need for mechanical ventilation and ongoing respiratory support, intraventricular hemorrhage, neonatal hypotension, hypothermia, length of NICU stay. IVH was less frequent and less severe in babies exposed to antenatal MgSO4 (8%) as compared to non-MgSO4 group (16%). Neonatal morbidities were more when antenatal MgSO4 was given less than 4 h from delivery.ConclusionMgSO4 is a safe drug to use in antenatal women at risk for impending preterm. Antenatal magnesium sulfate given to women in established preterm labor conferred significant neuroprotective advantage to the neonate. MgSO4 also has protective effect on the need of invasive ventilatory support in preterm infants. Given the breadth of evidence in its favor, it is time for us to start using MgSO4 in clinical practice for neuroprotective intent in all our extreme preterm births.

Determination of the optimal dose of ephedrine in the treatment of arterial hypotension due to general anesthesia in neonates and infants below 6\u2009months old: the ephedrine study protocol for a randomized, open-label, controlled, dose escalation trial

BackgroundArterial hypotension induced by general anesthesia is commonly identified as a risk factor of morbidity, especially neurological, after cardiac or noncardiac surgery in adults and children. Intraoperative hypotension is observed with sevoflurane anesthesia in children, in particular in neonates, infants younger than 6 months, and preterm babies. Ephedrine is commonly used to treat intraoperative hypotension. It is an attractive therapeutic, due to its dual action on receptors alpha and beta and its possible peripheral intravenous infusion. There are few data in the literature on the use of ephedrine in the context of pediatric anesthesia. The actual recommended dose of ephedrine (0.1 to 0.2 mg/Kg) frequently leads to a therapeutic failure in neonates and infants up to 6 months of age. The use of higher doses would probably lead to a better correction of hypotension in this population.The objective of our project is to determine the optimal dose of ephedrine for the treatment of hypotension after induction of general anesthesia with sevoflurane, in neonates and infants up to 6 months of age.MethodsThe ephedrine study is a prospective, randomized, open-label, controlled, dose-escalation trial. The dose escalation consists of 6 successive cohorts of 20 subjects. The doses studied are 0.6, 0.8, 1, 1.2, and 1.4 mg/kg. The dose chosen as the reference is 0.1 mg/kg, the actual recommended dose. Neonates and infants younger than 6 months, males and females, including preterm babies who undergo a surgery with general anesthesia inducted with sevoflurane were eligible. Parents of the subject were informed. Then, the subjects were randomized if presenting a decrease in mean blood pressure superior to 20% of their initial mean blood pressure (before induction of anesthesia), despite a vascular filling with sodium chloride 0.9%. The primary outcome is the success of the therapy defined as an mBP superior to 80% of the baseline mBP (prior to anesthesia) within 10 min post ephedrine administration. The subjects were followed-up for 3 days postanesthesia.DiscussionThis study is the first randomized, controlled trial intending to determine the optimal dose of ephedrine to treat hypotension in neonates and infants below 6 months old.Trial registrationClinicalTrials.gov NCT02384876. Registered on March 2015.

Genetic characterization and assessment of demographic bottleneck in Caspian horse population.

The aim of this study was to evaluate genetic characterization of the Caspian horse population using microsatellite markers. This study determined the efficiency of microsatellite markers for conservation plans and breeding strategies in Caspian horse population. For this purpose, 120 Caspian horse samples including 95 adults and 25 foals were genotyped by using seventeen microsatellite markers recommended by ISAG. The number of allele per locus varied from 5 (HMS01 and HTG07) to 9 (HTG10) with an average value of 7.41. The observed heterozygosity and the expected heterozygosity ranged 0.505-0.831 (mean 0.684), from 0.615-0.835 (mean 0.748) respectively. PIC value ranged from 0.716 (HMS01) to 0.834 (AHT04) with average 0.787. The total exclusion probability of the 17 microsatellite loci was 0.9999. Low values of Wright's fixation index, Fis (0.084) indicated low levels of inbreeding. A significant heterozygote excess on the basis of different models suggested that Caspian horse population has decreased to low numbers in the past, but a bottleneck event is still scrutable, and its number has recently increased is not in mutation drift equilibrium. The present study contributes to our knowledge of the genetic diversity of the Caspian horse population and helps to define its genetic conservation strategies.

Cerebral and peripheral muscle oxygenation and perfusion: Course in moderate and late preterm neonates during the first day after birth.

To investigate the ratio of cerebral tissue oxygenation index (cTOI) to peripheral muscle tissue oxygenation index (pTOI) measured by near-infrared spectroscopy (NIRS) in cardio-circulatory stable preterm neonates without signs of inflammation/infection on the first day after birth. Observational study analysing secondary outcome parameters of the 'Avoiding Hypotension in Preterm Neonates (AHIP)' trial (ClinicalTrials.gov identifier: NCT01910467). Preterm neonates, who had cTOI and pTOI measurements during 24 h after birth, were included. In each neonate the mean of the cTOI/pTOI-ratio, cTOI, pTOI and routine monitoring parameters were calculated for each hour and for the 24-h measuring period. Courses of all measured parameters were analysed. Eighty-seven stable preterm neonates (33.1 [32.1-34.1] weeks of gestation) were included. The mean value over the 24-h measuring period for the cTOI/pTOI-ratio was 0.96 ± 0.02, for cTOI 70.1 ± 1.4 and for pTOI 73.4 ± 0.9. Routine monitoring parameters were in the normal ranges over 24 h. The courses of the cTOI/pTOI-ratio and cTOI showed significantly lower values from hour 5 to 15 compared to the first hours after birth. Heart rate decreased significantly over time, whereas mean arterial blood pressure increased significantly. pTOI, arterial oxygen saturation and body temperature showed no significant change over time. We are the first to report on cTOI/pTOI-ratios for cardio-circulatory stable preterm neonates over a 24-h period after birth, showing significantly lower values from hour 5 to 15 compared to the first hours after birth.