A quality improvement strategy to reduce unintended extubation in the very low birth weight infant: A case report.

BACKGROUND: Unintended extubations remain a common complication across neonatal intensive care units, with very low birthweight infants being the most vulnerable of them all. Ongoing efforts across different institutions exist with the goal of reducing the rate of unintended extubations to keep a median rate of <2 events per 100 ventilator days as defined by the Vermont Oxford Network. Our objective was to reduce unintended extubations in the very low birthweight infant in a large delivery hospital to ≤2/100 ventilator days. METHODS: A collaborative group was formed between two academic health institutions targeting training and implementation of the Children's National unintended extubation system, focusing on endotracheal tube securement methods and surveillance protocols. RESULTS: The unintended extubation rate decreased from 3.23 to 0.64 per 100 ventilator days. Changes were implemented from 2018-2020 with a sustained reduction in the unintended extubation rate of 1.54 per 100 ventilator days. Most events occurred between 12 : 00 pm -4 : 00 pm and the commonest cause was spontaneous (25%) followed by dislodgment during repositioning (19%). CONCLUSION: Very low birth weight infants present a challenge to endotracheal tube maintenance due to their developmental and anatomical changes during their neonatal intensive care unit stay. Successful reduction of unintended extubations in the very low birthweight infant can be achieved by adaptation of successful protocols for older infants.

Non-anaemic iron deficiency in pregnancy: the views of health service users and health care professionals.

BACKGROUND: The prevalence of anaemia in pregnancy in Europe is 25% and that resulting from iron deficiency is estimated at 40%. The maternal and fetal morbidity of non-anaemic iron deficiency (NAID) in pregnancy is likely to be significant. OBJECTIVES: To determine the views and opinions of health service users and clinicians concerning NAID in pregnancy in order to inform future research. METHODS: Two semi-structured focus groups were carried out to determine health service users' views on anaemia and NAID in pregnancy. A questionnaire was administered to obstetricians, haematologists, midwives and anaesthetists to elucidate their views on NAID in pregnancy. RESULTS: The study indicated that health service users and clinicians were interested in implementing testing for NAID in pregnancy with serum ferritin, if proven to be effective at reducing the effects of anaemia and improving maternal and neonatal outcomes. Clinicians had reservations in the use of intravenous iron supplementation for NAID in pregnancy. CONCLUSION: NAID is now accepted as a target condition for research by health service users and clinicians. The focus of future research should be on screening for NAID and its treatment.

Brain excitatory amino acid concentrations are lower in the neonatal pig: a buffer against excitotoxicity?

Hypoglycemic brain damage has been associated with high levels of the excitatory amino acids (EAA) aspartate and glutamate in the newborn and adult. We hypothesized that newborn piglet EAA would be different from those of older pigs when stressed with severe insulin-induced hypoglycemia (<30 mg/dl). Brain EAA were measured in piglets and adolescent pigs via microdialysis. Eleven of 12 newborn normoglycemic piglets had no detectable baseline levels (<0.5 microM) of EAA, while pigs had aspartate and glutamate concentrations of 1.78 +/- 0.44 and 3.43 +/- 1.14 microM (mean +/- SEM), respectively. Piglet aspartate and glutamate concentrations reached but did not significantly exceed normoglycemic pig levels after 2 h with plasma glucose values < or =20 mg/ml. Elevations in EAA were only detected in piglets whose EEG activity ceased. Aspartate and glutamate concentrations did not increase in insulin-treated pigs nor in control animals. We speculate that newborns with blood glucose less than clinically acceptable values (35 mg/dl) may be protected from EAA-associated neuronal damage during acute hypoglycemia. Lower normoglycemic and hypoglycemic levels of EAA in newborns when compared to older pigs provide this protection.

Ontogeny of serine hydroxymethyltransferase isoenzymes in fetal sheep liver, kidney, and placenta.

Serine is an amino acid that is not transported from the placenta to the ovine fetus. Thus, fetal plasma serine levels may be controlled by flux through their relevant biosynthetic pathways. This study was designed to determine, in fetal sheep tissues, the ontogeny of the three key enzymes in the biosynthetic pathway for serine, the cytosolic (c) and mitochondrial (m) isoforms of serine hydroxymethyltransferase (SHMT), phosphoglycerate dehydrogenase (PGD), and phosphoserine aminotransferase (PSAT). PGD and PSAT activity did not vary during gestation in either liver (PSAT, 9.4 +/- 1.3 nmol/min/mg cytosolic protein; and PGD, 76 +/- 10 mU/mg protein) or placenta (PGD, 8.0 +/- 3.6 mU/mg protein). In the liver, cSHMT activity was low early in gestation (0.6 +/- 0.5 nmol/min/mg protein at 45 days), rose in the last one-third of gestation, and peaked in the newborn period (25 +/- 3 nmol/min/mg protein at 1 week of age). Hepatic cSHMT RNA levels parallel the activity pattern. Mitochondrial SHMT was stable throughout gestation and with low constant mSHMT RNA levels. In contrast, the kidney and placenta had high mSHMT and steady low cSHMT activity throughout gestation. These data support the possible role of SHMT in the fetal control of plasma serine levels. While cSHMT may contribute to fetal hepatic serine production, its activity pattern does not support a primary role in the control of fetal hepatic serine biosynthesis. In the placenta, mSHMT may be important for glycine production from serine.

L-2-chloropropionic acid-induced cerebellar granule cell necrosis is potentiated by L-type calcium channel antagonists.

We have used the model of L-2-chloropropionic acid (L-CPA)-induced selective cerebellar granule necrosis to study excitatory amino acid-induced necrotic cell death in vivo produced by the activation of N-methyl-D-aspartate (NMDA) receptors. However, the mechanism for the NMDA receptor activation and the biochemical events which dictate the anatomical selectivity for the L-CPA-induced lesion are as yet unknown. We examined whether blockade of sodium and calcium channels may reduce the neurotoxicity through a reduction of glutamate release from granule cells. None of the sodium channel antagonists examined, i.e. phenytoin, lamotrigine or rilazole nor the mixed sodium/calcium channel blocker, lifarazine, altered the L-CPA neurotoxicity. However, L-type calcium channel blockers, verapamil and nifedipine enhanced the L-CPA-induced granule cell necrosis, assessed by measuring the degree of L-CPA-induced reductions in cerebellar aspartate concentration, increases in cerebellar glycine concentrations and the development of cerebellar oedema. In addition, the locomotor activity of rats receiving both L-CPA and either verapamil or nifedipine was significantly lower than when rats received L-CPA alone, suggesting an enhancement of the neurotoxicity of L-CPA by L-type calcium channel blockade. The data suggest that L-CPA may interfere with non-L-type calcium channels located on granule cell bodies and nerve terminals leading to reduction of the calcium entry into the cells. We suggest that a combination of L-type channel blockade and non-L-type channels which are sensitive to L-CPA produces reductions in intracellular calcium concentrations below that required for neuronal survival.

Comparison of leucine, serine and glycine transport across the ovine placenta.

To estimate the transport rate of maternal glycine across the placenta [1-13C]glycine and L-[1-13]serine were infused intravenously in pregnant sheep using both continuous and bolus infusions. Each tracer was infused together with L-[1-13C]leucine, to enable a comparison with the placental transport of an essential amino acid. At steady state, fetal plasma leucine enrichment was 40 per cent of maternal enrichment, indicating that approximately 60 per cent of the entry rate of leucine into fetal plasma is derived from protein breakdown in the placenta and fetus. Fetal plasma glycine enrichment was 11 per cent of maternal and there was no detectable fetal serine enrichment. The direct flux of maternal leucine into the fetal circulation was approximately 3.0 (bolus experiments) to 3.6 (continuous infusion experiments) mumol/min (kg fetus) and greater than the estimated 1.4 mumol/min (kg fetus) direct flux of maternal glycine, despite the fact that the net umbilical uptake of glycine exceeds that of leucine. This supports the conclusion that placental glycine production is a quantitatively important contribution to fetal glycine uptake via the umbilical circulation. The fetal glycine supply from the placenta is provided by a relatively small direct maternal glycine transplacental flux and a larger contribution derived from serine utilization within the placenta for glycine production.

Main routes of plasma lactate carbon disposal in the midgestation fetal lamb.

The turnover rates of plasma lactate, normalized for O2 consumption rate, are higher in the fetus than in the adult. This occurs despite very low rates of fetal gluconeogenesis which preclude the recycling of lactate carbon into glucose. In an effort to establish the main routes of disposal of fetal plasma lactate, 12 midgestation ovine fetuses (age 74 +/- 1 days) were infused intravenously at constant rate with L-[U-14C]lactate for a 4-hour period. At the end of the infusion, the amounts of 14C retained by the fetus and by the placenta, and the distribution of the retained 14C in free and protein-bound amino acids and in lipids were measured. Of the total 14C infused, 17.0 +/- 1.4% was recovered in the placenta, 4.0 +/- 0.3% in the fetal liver, and 15.0 +/- 0.8% in the extrahepatic fetal tissues. Of the retained radioactive carbon, 45-57% was recovered in the free and protein-bound amino acid fractions and 11-17% in the lipid fractions. Approximately 90% of the 14C in the free amino acid fractions was present as glutamate/glutamine, serine, glycine, and alanine carbon. In conjunction with data on fetal CO2 production from lactate carbon, these results demonstrate that the main routes of fetal lactate disposal are oxidation and synthesis of nonessential amino acids and lipids.

Placental and fetal serine fluxes at midgestation in the fetal lamb.

Plasma serine disposal rate (DR), decarboxylation, and conversion to fetal plasma glycine by the placenta were measured in six fetal lambs at 72 +/- 1 days gestation. L-[1-13C]serine, L-[U-14C]serine, and 3H2O were infused over 3 h into the fetal circulation, the latter for measurement of uterine and umbilical blood flow. The fetal plasma serine DR was 8.7 +/- 1.0 mumol/min or 61.8 +/- 4 mumol.min-1.kg fetus-1. Approximately 90% of the DR represented placental uptake of fetal serine. There was no detectable release of fetal serine into the maternal circulation. The fetal arterial plasma glycine-to-serine enrichment ratio was approximately 0.30. The conversion rate of fetal serine to fetal plasma glycine by the placenta was 5.8 +/- 0.7% of the serine DR. Fetal and placental CO2 production from fetal plasma serine carbon was 1.9 +/- 0.4 and 1.2 +/- 0.4 mumol/min, respectively. Thus, at midgestation, there is a rapid fetoplacental serine exchange that constitutes most of the fetal plasma serine turnover. Placental conversion of serine to fetal glycine and serine oxidation together account for only 10% of the placental uptake of fetal serine.

Glutamate metabolism in fetus and placenta of late-gestation sheep.

Glutamate is produced by the fetal liver and taken up by the placenta. To explore the functional meaning of this exchange, the disposal rate (DR), clearance, conversion to glutamine, and decarboxylation rate of fetal plasma glutamate were studied at 129 +/- 2 days of gestation in seven fetal lambs infused via a systemic vein with L-[2,3,3,4,4-2H5]glutamate and L-[1-14C]glutamate. In two experiments, L-[1-13C]glutamate was also infused. The mean glutamate DR and clearance were 11.9 +/- 1.3 mumol.min-1.kg-1 and 200 +/- 8 ml.min-1.kg-1, respectively. The placenta extracted 88.5 +/- 0.8% of the tracer glutamate carried by the umbilical circulation and contributed to 61.3 +/- 3.2% of the glutamate DR. Most of the 14C infused as L-[1-14C]glutamate was converted to 14CO2: 37 +/- 4% by the fetus and 41 +/- 6% by the placenta. Of the labeled glutamate taken up by the placenta, 6.2 +/- 1.5% was returned to the fetus as glutamine. The glutamine-to-glutamate enrichment ratio in fetal arterial plasma was 0.066 +/- 0.008. We conclude that fetal plasma glutamate has an exceptionally high clearance because the flux of glutamate into the placenta is virtually equal to umbilical glutamate delivery rate. The main pathway of fetal plasma glutamate disposal is oxidation by placental and fetal tissues. Placental conversion of glutamate to fetal glutamine is a relatively small component of the placental metabolism of fetal glutamate.

Metabolism and transport of maternal serine by the ovine placenta: glycine production and absence of serine transport into the fetus.

The present study compares the transplacental transport of L-[l-13C]serine and L-[l-13C]leucine in sheep. An in vivo preparation using twin gestations was set up such that the arterial circulation to one uterine horn, including its placenta and fetus, was infused with tracer serine and leucine while the umbilical circulations of both fetuses were sampled. Uterine and umbilical blood flows were measured in each horn. Plasma serine enrichments were 14.6 +/- 2.7% and 4.3 +/- 1.6% in the uterine veins draining the experimental and control horns, respectively. Fetal plasma leucine enrichments in the umbilical veins were 50 and 55% of the uterine venous enrichments in the control and experimental fetuses, respectively. By contrast, during 280 min of infusion, there was no detectable serine enrichment in either fetal circulation. However, significant plasma glycine enrichment was present in the fetal circulation of the experimental horn and venous glycine enrichments in the experimental horn were significantly greater than arterial glycine enrichments for both the umbilical (p < 0.02) and uterine (p < 0.001) circulations. We conclude that under conditions in which leucine transport is easily demonstrable there is no significant transplacental transport of maternal serine and that maternal plasma serine is used within the uteroplacental tissues for producing glycine, some of which is delivered into the fetal circulation.

Ovine fetal placental lactate exchange and decarboxylation at midgestation.

In a study of the metabolic implications of the large placental-to-fetal mass ratio that characterizes early fetal development, fetal plasma lactate disposal rate and CO2 production from fetal plasma lactate by fetus and placenta were measured in six midgestation (71-80 days) pregnant sheep. A constant fetal intravenous infusion of L-[U-14C]lactate and 3H2O was given to establish fetal steady-state lactate specific activity and to measure uterine and umbilical blood flows. Fetal and placental weights were 158.6 +/- 19.7 and 441.9 +/- 32.7 g, respectively. There was a significant net lactate flux into the uterine circulation (31 +/- 4.3 mumol/min, P < 0.01) but no measurable umbilical uptake. Fetal plasma lactate disposal rate was 21.2 +/- 2.7 mumol/min, approximately one-half of which represented fetal lactate flux into the placenta (9.9 +/- 1.9 mumol/min). The oxidation rate of tracer lactate carbon to 14CO2 by placenta plus fetus was 72.6 +/- 4.7% of the infused tracer and was fairly evenly distributed between the placenta and the fetus (42.4 +/- 3.9 vs. 30.3 +/- 2.2%). The midgestation placenta metabolizes and produces fetal plasma lactate at rapid and nearly equal rates. This contrasts with the late-gestation placenta, which makes a small contribution to fetal lactate disposal and is a major net source of fetal lactate.

Inhibition of Friend virus (FVP)-induced murine erythropoiesis with prostaglandin (PGF2 alpha): potentiation and inhibition of erythropoietin and prevention of both with PGD2.

An erythropoietin-independent virus-induced murine erythroleukemia (FVP) is used to compare the effects of an erythropoiesis inhibitory factor (EIF) isolated from human urine with the effects of prostaglandin F2 alpha. The consequent inhibition of FVP-induced erythropoiesis suggests that EIF and PGF2 alpha have similar effects on the FVP-induced erythropoiesis in mice, and the effect of PGF2 alpha is indirect. The similarity of the actions of EIF and PGF2 alpha may indicate a potential role for prostaglandins in the physiological control of some types of erythrocytosis.

Inhibition of erythropoiesis by plasma component(s) from sheep, goats, and rabbits.

Plasma from hypertransfused and normal sheep and experimentally induced anemic and normal goats was fractionated by ultrafiltration. Fractions obtained were assayed for erythropoiesis stimulatory factor (ESF) or erythropoiesis inhibitory factor (EIF) activity (or both) in the posthypoxic polycythemic mouse assay. The most potent sheep plasma-inhibitor fraction was found in the retentate on a membrane with a cutoff at mol wt 50,000. The most potent EIF fraction from anemic goats passed into the ultrafiltrate, but the comparable EIF from normal goats remained in the retentate on a membrane with a cutoff at mol wt 500. The yield of the most potent EIF fraction was higher from anemic goats than was the yield from normal goats. During thin-layer chromatography, EIF extracted from goat plasma fractions had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction IV-4 had an inhibitory factor, and a benzene extract of the fraction contained a component that had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction V contained a component that potentiated an erythropoietin-generating factor.

A comparison of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) vs. nitrogen mustard in advanced Hodgkin's disease.

A randomized study of patients with advanced Hodgkin's disease was designed to determine whether the improved therapeutic effectiveness of combination chemotherapy was due to the use of a combination of drugs or might be achieved with a single agent if given as intensively and for as long a period. A combination of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) was compared with nitrogen mustard (HN2) alone. Treatment with both regimens was given to tolerance on cylic basis and was continued for six cycles of treatment. Sixty-one evaluable patients were treated with MOPP and 47 with HN2. The complete remission rate of 47.5% with MOPP was significantly better than the 12.8% with HN2 (p less than .05). Complete remission lasted a median of 15 months after MOPP and 12 months after HN2. The survival of patients initially treated with MOPP was significantly better than that of those initially treated with HN2.