Chloe Joynt

Intestinal hemodynamic effects of milrinone in asphyxiated newborn pigs after reoxygenation with 100% oxygen: a dose-response study.

Neonatal asphyxia can result in poor perfusion, vasoconstriction, and decreased oxygen delivery in the intestine. Milrinone increases myocardial contractility and causes peripheral vasodilatation. We examined the dose-response of milrinone on the intestinal circulation, oxygen metabolism, and injury in a newborn piglet model of asphyxia-reoxygenation. Piglets (aged 1 - 3 days, weighing 1.5 - 2.3 kg) were acutely instrumented to measure superior mesenteric artery (SMA) flow and oxygen delivery. After stabilization, hypoxia (inspired oxygen concentration, 0.08 - 0.15) was induced for 2 h followed by reoxygenation with 100% O2 for 1 h then 21% O2 for 3 h. At 2 h of reoxygenation, saline or milrinone infusion at doses of 0.25, 0.5, or 0.75 &mgr;g/kg per min was given for 2 h in a blinded randomized fashion (n = 7 per group). Hemodynamic and oxygen transport parameters were analyzed at predefined time points. Intestinal tissue lactate concentrations, plasma milrinone levels, and intestinal glutathione redox status were determined at the end of the experiment. In the intestinal tract, milrinone significantly increased SMA flow and oxygen delivery while decreasing vascular resistance at a dose of 0.75 &mgr;g/kg per min (P < 0.05, ANOVA). A modest increase in SMA flow and oxygen delivery was found with milrinone at 0.5 &mgr;g/kg per min. Plasma milrinone levels correlated with SMA flow and vascular resistance (r = 0.5 and r = −0.6, respectively, P < 0.05). Intestinal lactate concentrations and histopathology were not significantly different among groups. Oxidized glutathione correlated with SMA vascular resistance and negatively with milrinone levels (r = 0.6 and r = −0.5, P < 0.05). When used to treat shock in a newborn model of asphyxia-reoxygenation, milrinone dose-dependently increases SMA flow and oxygen delivery with a significantly decreased SMA vascular resistance at higher doses.

Does teaching crisis resource management skills improve resuscitation performance in pediatric residents

Objective: The effect of teaching crisis resource management skills on the resuscitation performance of pediatric residents is unknown. The primary objective of this pilot study was to determine if teaching crisis resource management to residents leads to improved clinical and crisis resource management performance in simulated pediatric resuscitation scenarios. Design: A prospective, randomized control pilot study. Setting: Simulation facility at tertiary pediatric hospital. Subjects: Junior pediatric residents. Interventions: Junior pediatric residents were randomized to 1 hour of crisis resource management instruction or no additional training. Measurements and Main Results: Time to predetermined resuscitation tasks was noted in simulated resuscitation scenarios immediately after intervention and again 3 months post intervention. Crisis resource management skills were evaluated using the Ottawa Global Rating Scale. Fifteen junior residents participated in the study, of which seven in the intervention group. The intervention crisis resource management group placed monitor leads 24.6 seconds earlier (p = 0.02), placed an IV 47.1 seconds sooner (p = 0.04), called for help 50.4 seconds faster (p = 0.03), and checked for a pulse after noticing a rhythm change 84.9 seconds quicker (p = 0.01). There was no statistically significant difference in time to initiation of cardiopulmonary resuscitation (p = 0.264). The intervention group had overall crisis resource management performance scores 1.15 points higher (Ottawa Global Rating Scale [out of 7]) (p = 0.02). Three months later, these differences between the groups persisted. Conclusions: A 1-hour crisis resource management teaching session improved time to critical initial steps of pediatric resuscitation and crisis resource management performance as measured by the Ottawa Global Rating Scale. The control group did not develop these crisis resource management skills over 3 months of standard training indicating that obtaining these skills requires specific education. Larger studies of crisis resource education are required.

Two-year neurodevelopmental outcomes of infants undergoing neonatal cardiac surgery for interrupted aortic arch: A descriptive analysis

OBJECTIVE This study determined neurodevelopmental outcomes of survivors of neonatal cardiac surgery for interrupted aortic arch through an interprovincial program and explored preoperative, intraoperative, and postoperative outcome predictors. METHODS Children who underwent neonatal cardiac surgery for interrupted aortic arch at 6 weeks old or younger between 1996 and 2006 had a multidisciplinary neurodevelopmental assessment at 18 to 24 months old (mental and psychomotor developmental indices as mean +/- SD and delay [score <70]). Survivor outcomes were compared by univariate and multivariate analyses and compared between children with and without chromosomal abnormality. RESULTS Outcomes were available for all 26 survivors (mortality, 3.7%). Mental and psychomotor developmental indices were 75.8 +/- 17.1 and 72.3 +/- 16.9, respectively, with significantly lower scores for children with chromosomal abnormalities, which accounted for 29% of the variance in developmental indices. For the remaining 17 children without chromosomal abnormalities, mental and psychomotor developmental indices were 82.7 +/- 14.5 and 79.1 +/- 14.3, respectively, with deep hypothermic circulatory arrest time and Apgar score at 5 minutes contributing 46% of the variance in mental developmental index. CONCLUSIONS The neurodevelopmental indices of children who have undergone neonatal cardiac surgery for interrupted aortic arch are below normative values; those of children with chromosomal abnormalities are even lower. For children without a chromosomal abnormality, longer deep hypothermic circulatory arrest times and low Apgar scores predict lower mental developmental indices at 18 to 24 months of age.

A descriptive report of end-of-life care practices occurring in two neonatal intensive care units

Background: In Canada and other developed countries, the majority of neonatal deaths occur in tertiary neonatal intensive care units. Most deaths occur following the withdrawal of life-sustaining treatments. Aim: To explore neonatal death events and end-of-life care practices in two tertiary neonatal intensive care settings. Design: A structured, retrospective, cohort study. Setting/participants: All infants who died under tertiary neonatal intensive care from January 2009 to December 2013 in a regional Canadian neonatal program. Deaths occurring outside the neonatal intensive care unit in delivery rooms, hospital wards, or family homes were not included. Overall, 227 infant deaths were identified. Results: The most common reasons for admission included prematurity (53.7%), prematurity with congenital anomaly/syndrome (20.3%), term congenital anomaly (11.5%), and hypoxic ischemic encephalopathy (12.3%). The median age at death was 7 days. Death tended to follow a decision to withdraw life-sustaining treatment with anticipated poor developmental outcome or perceived quality of life, or in the context of a moribund dying infant. Time to death after withdrawal of life-sustaining treatment was uncommonly a protracted event but did vary widely. Most dying infants were held by family members in the neonatal intensive care unit or in a parent room off cardiorespiratory monitors. Analgesic and sedative medications were variably given and not associated with a hastening of death. Conclusion: Variability exists in end-of-life care practices such as provision of analgesic and sedative medications. Other practices such as discontinuation of cardiorespiratory monitors and use of parent rooms are more uniform. More research is needed to understand variation in neonatal end-of-life care.

The Effect of Milrinone on Splanchnic and Cerebral Perfusion in Infants With Congenital Heart Disease Prior to Surgery: An Observational Study.

ABSTRACT Despite the advancement in the postoperative care of neonates with congenital heart disease (CHD), there is little information on preoperative management of systemic and regional hemodynamics, which may be related to outcomes. We aimed to determine the preoperative effect of milrinone, a phosphodiesterase III inhibitor, on cardiac output and splanchnic and cerebral perfusion in neonates with CHD. Neonates with CHD requiring cardiac surgery were enrolled in a prospective, single-blinded study once a clinical decision of starting milrinone (0.75 &mgr;g/kg per minute intravenously) using institutional criteria was made. Demographic and clinical variables and outcomes were recorded. Combined cardiac output and measures of splanchnic (superior mesenteric and celiac arteries) and cerebral (anterior and middle cerebral arteries) perfusion were determined by Doppler studies at 0, 6, 24, and 48 h after milrinone infusion. Investigators were unaware of intervention time points and patients in analyzing blood flow measurements. Seventeen term (39.2 ± 1.3 weeks) neonates were included with hypoplastic left-sided heart syndrome (78.5%) as the most common diagnosis. Combined cardiac output increased by 28% within 48 h (613 ± 154 vs. 479 ± 147 mL/kg per minute at baseline, P < 0.05). Superior mesenteric artery mean velocity increased at 6 h and throughout 48 h of milrinone infusion (P < 0.05). Peak and mean velocities at cerebral arteries increased with milrinone infusion (P < 0.05∼0.08), and the corresponding changes at celiac artery were modest. There were no significant changes in splanchnic and cerebral resistive and pulsatility indices during milrinone infusion. Milrinone increases cardiac output with concurrent effects on splanchnic and cerebral blood flows during the short-term preoperative use in neonates with CHD.

Differential Hemodynamic Effects of Levosimendan in a Porcine Model of Neonatal Hypoxia-Reoxygenation

Background: Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates. Methods: Mixed breed piglets (1–4 days old, weight 1.6–2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10–15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer’s lactate 10 ml/kg), either levosimendan (0.1 or 0.2 µg/kg/min) or D5W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7–8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared. Results: At 0.1 and 0.2 µg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 µg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 µg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels. Conclusions: In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates.

Sequential Changes of Hemodynamics and Blood Gases in Newborn Piglets With Developing Pneumothorax

Little information is available regarding the temporal changes in hemodynamics and blood gases during the development of a moderate pneumothorax in a neonate. In this study, we aim to investigate the temporal changes of hemodynamics and arterial blood gases in a neonatal swine model of unilateral pneumothorax.

A comparison of combination dopamine and epinephrine treatment with high-dose dopamine alone in asphyxiated newborn piglets after resuscitation

Background:When asphyxiated neonates require additional cardiovascular support to moderate doses of dopamine infusion, controversy exists on the differential hemodynamic effects of two approaches (adding a second inotrope vs. increasing dopamine dosage). We hypothesized that high-dose dopamine (HD) would be detrimental to systemic and regional perfusion as compared with dopamine and epinephrine (D + E) combination therapy using a swine model of neonatal hypoxia–reoxygenation (H-R).Methods:Twenty-seven piglets (1–4 d, 1.5–2.5 kg) were used for continuous monitoring of systemic arterial pressure (mean arterial pressure, MAP) and pulmonary arterial pressure (PAP), cardiac output (cardiac index, CI), and carotid (carotid artery flow index, CAFI), superior mesenteric (superior mesenteric artery flow index), and renal arterial flows. H-R piglets underwent 2 h of hypoxia followed by 2 h of reoxygenation before drug infusion (2 h).Results:The hemodynamics of H-R piglets deteriorated gradually after reoxygenation. HD and D + E infusions improved CI similarly (both groups vs. control; P < 0.05). Both regimens increased MAP (P < 0.05) but not PAP, with decreased PAP/MAP ratio in D + E piglets. Both regimens improved CAFI and superior mesenteric artery flow index, with decreased mesenteric vascular resistance in HD-treated piglets. No significant effect on renal perfusion was observed.Conclusion:In H-R newborn piglets treated with a moderate dose of dopamine, adding epinephrine or further increasing dopamine improved systemic hemodynamics similarly; these treatments have differential effects on the pulmonary and mesenteric circulations.

Milrinone is preferred to levosimendan for mesenteric perfusion in hypoxia-reoxygenated newborn piglets treated with dopamine

Introduction:There is little information regarding the comparative hemodynamic effects of adding milrinone or levosimendan to dopamine infusion in hypoxia-reoxygenated (H-R) newborns.Results:Severely hypoxic piglets had cardiogenic shock with depressed cardiac index (CI) and mean arterial pressure (MAP). The hemodynamics deteriorated gradually after initial recovery upon reoxygenation. Heart rate and CI improved with milrinone (D+M) and levosimendan (D+L) administration (P < 0.05 vs. control). Both regimens improved carotid arterial flow and carotid vascular resistance; D+M additionally improved superior mesentric arterial flow (all P < 0.05 vs. control). No effect was found on renal arterial flow or elevated lactate state with either regimen. D+M piglets also had a lower myocardial oxidized/reduced glutathione ratio (P < 0.05 vs. control).Discussion:In conclusion, adding milrinone or levosimendan to dopamine similarly improved systemic hemodynamics in H-R newborn piglets. Milrinone also improved mesenteric perfusion and attenuated myocardial oxidative stress.Methods:Twenty-eight piglets (1–4 d, 1.5–2.5 kg) were instrumented for continuous monitoring of systemic MAP and pulmonary arterial pressure (PAP), CI, and carotid, superior mesenteric, and renal arterial flows. Piglets were randomized with blinding to sham-operated, H-R control (saline), and H-R dopamine (10 μg/kg/min) with D+M or D+L groups. H-R piglets underwent H-R followed by 2 h of drug infusion after reoxygenation. Tissue was collected for biochemical/oxidative stress testing and histological analysis.

Treating Hypotension in Preterm Neonates With Vasoactive Medications

Preterm neonates often have hypotension which may be due to various etiologies. While it is controversial to define hypotension in preterm neonates, various vasoactive medications are commonly used to provide the cardiovascular support to improve the blood pressure, cardiac output, or to treat shock. However, the literature on the systemic and regional hemodynamic effects of these antihypotensive medications in neonates is deficient and incomplete, and cautious translation of findings from other clinical populations and animal studies is required. Based on a literature search on published reports, meta-analytic reviews, and selected abstracts, this review discusses the current available information on pharmacologic actions, clinical effects, and side effects of commonly used antihypotensive medications including dopamine, dobutamine, epinephrine, norepinephrine, vasopressin, and milrinone in preterm neonates.