Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Minimally invasive fetal therapy for hydropic lung masses: three different approaches and review of the literature.

OBJECTIVE: To report three different antenatal therapeutic approaches for fetal lung masses associated with hydrops. METHODS: Three prospectively followed cases are described, and all 30 previously published minimally invasive cases of fetal therapy for hydropic lung masses are reviewed. RESULTS: Three hydropic fetuses with large intrathoracic lung masses presented at 17, 25 and 21 weeks of gestation, respectively. An aortic feeding vessel was identified in each case and thus a bronchopulmonary sequestration (BPS) was suspected. Under ultrasound guidance, the feeding vessel was successfully occluded with interstitial laser (Case 1), radiofrequency ablation (RFA) (Case 2) and thrombogenic coil embolization (Case 3). Complete (Cases 1 and 2) or partial (Case 3) resolution of the lung mass and hydrops was observed. A healthy infant was born at term after laser therapy (Case 1), and the involved lung lobe was resected on day 2 of postnatal life. In Case 2, hydrops resolved completely following RFA, but an iatrogenic congenital diaphragmatic hernia and abdominal wall defect became apparent 4 weeks later. The neonate died from sepsis following spontaneous preterm labor at 33 weeks. In Case 3, despite technical success in complete vascular occlusion with coils, a stillbirth ensued 2 days after embolization. CONCLUSIONS: The prognosis of large microcystic or echogenic fetal chest masses associated with hydrops is dismal. This has prompted attempts at treatment by open fetal surgery, with mixed results, high risk of premature labor and consequences for future pregnancies. We have demonstrated the possibility of improved outcome following ultrasound-guided laser ablation of the systemic arterial supply. Despite technical success, RFA and coil embolization led to procedure-related complications and need further evaluation.

Growth restriction alters adult spatial memory and sensorimotor gating in a sex-specific manner.

In Western society, impaired uteroplacental blood flow is the major cause of human intrauterine growth restriction. Infants born small and who experience late childhood accelerated growth have an increased risk of developing adult diseases. Recent studies also suggest a link between birth weight and altered adult behavior, particularly relating to motor function, learning and memory, depression and schizophrenia. The aim of this study was to determine the relative influence of prenatal and postnatal growth restriction on adult behavioral outcomes in male and female rats. Uteroplacental insufficiency was induced in Wistar Kyoto rats by bilateral uterine vessel ligation on day 18 of gestation producing growth-restricted offspring (Restricted group). The Control group had sham surgery. Another group underwent sham surgery, with a reduction in litter size to five at birth equivalent to the Restricted litter size (Reduced Litter group). At 6 months of age, a series of behavioral tests were conducted in male and female offspring. Growth restriction did not impair motor function. In fact, Restricted and Reduced Litter males showed enhanced motor performance compared with Controls (P < 0.05). Spatial memory was greater in Restricted females only (P < 0.05). The Porsolts test was unremarkable, however, males exhibited more depressive-like behavior than females (P < 0.05). A reduction in sensorimotor gating function was identified in Reduced Litter males and females (P < 0.05). We have demonstrated that growth restriction and/or a poor lactational environment can affect adult rat behavior, particularly balance and coordination, memory and learning, and sensorimotor gating function, in a sex-specific manner.

Improved procedural performance following a simulation training session may not be transferable to the clinical environment.

OBJECTIVE: Neonatal intubation is a life-saving procedural skill required by pediatricians. Trainees receive insufficient clinical exposure to develop this competency. Traditional training comprises a Neonatal Resuscitation Program (NRP) complemented by clinical experience. More recently, simulation is being used in procedural skills training. The objective of this study is to examine the impact of a simulation session, which teaches the skill of neonatal intubation by comparing pre- and post-intervention performance, and examining transferability of skill acquisition to the clinical setting. STUDY DESIGN: First-year pediatric residents with NRP training, but no previous neonatal experience, attended a 2-h intubation education session conducted by two experienced respiratory therapists. Individual components of the skill were taught, followed by practice on a high-fidelity infant mannequin with concurrent feedback. Skills were assessed using a validated neonatal intubation checklist (CL) and a five-point global rating scale (GRS), pre- and immediately post-intervention, using the mannequin. Clinical intubations performed in the subsequent 8-week neonatal intensive-care unit (NICU) rotation were evaluated by documenting success rates, time taken to intubate, and CL and GRS scores. Performance was also compared with similar data collected on intubations performed by a historical cohort of first-year residents who did not receive the training intervention. Data were analyzed using descriptive statistics, Student's t-test and χ (2)-test as appropriate, and analysis of variance. RESULT: Thirteen residents participated in the educational session. Mean pre-intervention CL score was 65.4 ± 18% (s.d.) and GRS was 3 ± 0.7 (s.d.). Performance improved following the intervention with post-training CL score of 93 ± 5% (P<0.0001) and GRS of 3.92 ± 0.4 (P=0.0003). These trainees performed 40 intubations during their subsequent NICU rotation, with a success rate of 67.5% compared with 63.15% in the cohort group (NS). However, mean CL score for the study trainees during the NICU rotation was 64.6 ± 20%, significantly lower than their post-training CL score (P<0.001), and significantly lower than the historical cohort score of 82.5 ± 15.4% (P=0.001). In the intervention group, there were no significant differences between the pre-intervention and real-life CL scores of 65 ± 18% and 64.63 %, respectively, and the pre-intervention and real-life GRS of 3.0 ± 0.7 and 2.95 ± 0.86, respectively. CONCLUSION: Trainees showed significant improvement in intubation skills immediately post intervention, but this did not translate into improved-clinical performance, with performance returning to baseline. In fact, significantly higher CL scores were demonstrated by the cohort group. These data suggest that improved performance in the simulation environment may not be transferable to the clinical setting. They also support the evidence that although concurrent feedback may lead to improved performance immediately post training intervention, this does not result in improved skill retention overall.

Rupture of membranes before the age of viability and birth after the age of viability: comparison of outcomes in a matched cohort study.

OBJECTIVE: To compare composite adverse outcome rate of infants <32 weeks gestational age (GA) who were born after preterm premature rupture of membranes (PPROM) at previable gestation to those born without PPROM. STUDY DESIGN: Retrospective review of prospective collected data for infants discharged between 2004 and 2007 was conducted. Cases were infants with >7 days of PPROM that occurred before 24 weeks. Matched cohort consisted of infants born without PPROM (matched for GA, sex and admission date). Composite adverse outcome was assessed considering death or any of the following three severe morbidities (severe neurological injury, severe retinopathy of prematurity or chronic lung disease). RESULT: The 29 cases had higher mean severity of illness score compared with 74 matched infants. Mean duration of ROM was 45 vs 2 days and mean GA at the ROM was 21 vs 27 weeks, respectively. Logistic regression confirmed significantly higher risk of composite adverse outcome rates for cases (69 vs 47%; P=0.02, adjusted odds ratio 4.0, 95% CI 1.2, 13.6). CONCLUSION: The survival rate for infants born at <32 weeks following PPROM at previable age has improved significantly; however, these infants had a higher rate of adverse composite neonatal outcome.

Failure of pediatric and neonatal trainees to meet Canadian Neonatal Resuscitation Program standards for neonatal intubation.

OBJECTIVE: Neonatal intubation skills are initially taught through the Neonatal Resuscitation Program (NRP) and thereafter complemented by further practical clinical training. The aim of this study is to compare the ability of NRP trained individuals to successfully complete a neonatal intubation. STUDY DESIGN: A prospective observational study was performed at an inborn high-risk level 3 perinatal center. Participants were postgraduate years 1 and 3 pediatric residents, neonatal-perinatal medicine subspecialty residents and fellows, and neonatal intensive care unit (NICU) respiratory therapists (RTs) with earlier NRP training. Intubations were scored on a checklist as well as a global assessment scale. Characteristics of the intubation attempt were recorded for each patient. RESULT: Fifty neonatal intubations were assessed, of which 73% of the attempts were deemed successful. A higher proportion of endotracheal tubes were successfully placed by RTs (100%, P<0.05), compared with both NICU fellows (69%) and pediatric residents (63%). The overall mean time for successful neonatal intubation was 51+/-28 s, which is greater than twice the time currently recommended by the NRP and American Heart Association guidelines. Attempts by pediatric residents and NICU fellows were longer (P<0.05, analysis of variance) and received lower global assessment scale (P<0.05, analysis of variance) and checklist (P<0.05, analysis of variance) scores, when compared with RTs. CONCLUSION: The success rate and overall quality of neonatal intubations performed by neonatal and pediatric trainees in Canada did not meet NRP standards; in particular, the time taken to intubate by pediatric residents and neonatal fellows is concerning. Re-evaluation of training methods and the volume of formalized exposure to neonatal intubation in Canadian residency programs are required.

Maternal exposure to dexamethasone or cortisol in early pregnancy differentially alters insulin secretion and glucose homeostasis in adult male sheep offspring.

An adverse intrauterine environment increases the risk of developing various adult-onset diseases, whose nature varies with the timing of exposure. Maternal undernutrition in humans can increase adiposity, and the risk of coronary heart disease and impaired glucose tolerance in adult life, which may be partly mediated by maternal or fetal endocrine stress responses. In sheep, dexamethasone in early pregnancy impairs cardiovascular function, but not glucose homeostasis in adult female offspring. However, male offspring are often more susceptible to early life "programming". Pregnant sheep were infused intravenously with saline (0.19 ml/h), dexamethasone (0.48 mg/h), or cortisol (5 mg/h), for 2 days from 26 to 28 days of gestation. In male offspring, size at birth and postnatal growth were measured, and glucose tolerance [intravenous glucose tolerance test (IVGTT)], insulin secretion, and insulin sensitivity of glucose, alpha-amino nitrogen, and free fatty acid metabolism were assessed at 4 yr of age. We show that cortisol, but not dexamethasone, treatment of mothers causes fasting hyperglycemia in adult male offspring. Maternal cortisol induced a second-phase hyperinsulinemia during IVGTT, whereas maternal dexamethasone induced a first-phase hyperinsulinemia. Dexamethasone improved glucose tolerance, while cortisol had no impact, and neither affected insulin sensitivity. This suggests that maternal glucocorticoid exposure in early pregnancy alters glucose homeostasis and induces hyperinsulinemia in adult male offspring, but in a glucocorticoid-specific manner. These consequences of glucocorticoid exposure in early pregnancy may lead to pancreatic exhaustion and diabetes longer term and are consistent with stress during early pregnancy contributing to such outcomes in humans.

Differential effects of prenatal exposure to dexamethasone or cortisol on circulatory control mechanisms mediated by angiotensin II in the central nervous system of adult sheep.

Prenatal exposure to elevated maternal glucocorticoids (dexamethasone (DEX) or cortisol (CORT)) for 2 days early in pregnancy can 'programme' alterations in adult offspring of sheep, including elevated arterial pressure. DEX treatment also results in greater angiotensin II type 1 (AT1) receptor expression in the medulla oblongata in late gestation fetuses than in saline (SAL)- or CORT-exposed animals. We hypothesized that this would result in functional changes in brainstem angiotensinergic control of cardiovascular function in DEX- but not CORT-exposed animals. To test this hypothesis, cardiovascular responses to intracerebroventricular (I.C.V.) angiotensin II were examined in adult male offspring exposed to DEX (0.48 mg h(-1); n = 7), CORT (5 mg h(-1), n = 6) or SAL (n = 9) from 26 to 28 days of gestation. Increases in mean arterial pressure during i.c.v. infusion of angiotensin II (1 or 10 microg h(-1)) were significantly greater in the DEX group (10 +/- 1 mmHg at 1 microg h(-1)) compared with SAL (6 +/- 1 mmHg) or CORT (6 +/- 1 mmHg) animals (P < 0.05). I.C.V. infusion of the AT1 antagonist losartan significantly decreased cardiac output and heart rate in DEX animals, but not in SAL or CORT animals. Thus, increased expression of brainstem AT1 receptor mRNA after prenatal DEX is associated with increased responsiveness of cardiovascular control to activation of brain AT receptors by exogenous and endogenous angiotensin II. The altered role of the brain RAS in sheep exposed prenatally to DEX was not observed in sheep exposed prenatally to cortisol, suggesting these two glucocorticoids have distinct programming actions.

Prolonged low-dose dexamethasone treatment, in early gestation, does not alter blood pressure or renal function in adult sheep.

Low-dose dexamethasone treatment is used in pregnancies where the fetus is suspected to be at risk of congenital adrenal hyperplasia (CAH). In order to see if such treatment had long-term effects, pregnant ewes were treated with dexamethasone (20 micro g/kg maternal body weight) or saline from 25 to 45 days of gestation and blood pressure and renal function studied in offspring at 2 Years of age. There were 11 animals from dexamethasone treatment (six females and five males) and nine lambs from saline treatment (five females and four males). We aimed to study blood pressure and heart rate in the adult animals of both genders, and renal function only in the adult female animals. In both females and males, blood pressure and heart rate were similar between the two groups of animals. The excretion rates of sodium and potassium were similar between the two groups of animals. In addition, glomerular filtration rate was not different between the two groups of animals (112+/-11 ml/kg per h (S.E.M.) in saline-treated females vs 112+/-10 ml/kg per h in dexamethasone-treated females). There were no differences in body weight or weights of the kidney and heart between the treatments in both females and males. In conclusion, these results are reassuring for patients similarly exposed to prenatal dexamethasone treatment for CAH, as in our animal model no evidence of altered renal function or predisposition to adult hypertension was found.

The management and outcome of higher order multifetal pregnancies: obstetric, neonatal and follow-up data.

The objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (> or = 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (> or = 3 viable fetuses > or = 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990-December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the percent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.

The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial.

OBJECTIVE: To determine whether indomethacin tocolysis in preterm labour is associated with a better perinatal outcome than placebo. DESIGN: A randomised placebo-controlled trial. SETTING: Two university teaching hospitals with level three neonatal intensive care units. POPULATION: Women in preterm labour with intact membranes between 23 and 30 weeks of gestation. METHODS: Random allocation to tocolysis with indomethacin (50 mg followed by 25 mg 6 hourly for 48 hours) or placebo in a double-blind fashion. MAIN OUTCOME MEASURES: The primary outcome, perinatal mortality or severe neonatal morbidity, was defined as perinatal death, necrotising enterocolitis, bronchopulmonary dysplasia, intraventricular haemorrhage or peri-ventricular leucomalacia. Data were analysed using odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Between March 1995 and February 1996, 34 women (39 babies) were recruited. The baseline characteristics of the two groups were similar. No patient was lost to follow up. In the indomethacin group, gestation was prolonged by > 48 hours in 13/16 (81%) of women vs 10/18 (56%) in the placebo group. The incidence of perinatal mortality or severe neonatal morbidity was not significantly different between the groups, but occurred in twice as many babies in the indomethacin group as in the placebo group--6/19 (32%) vs 3/20 (15%) OR (95% CI) 2.62 (0.44-18.8). There was one perinatal death, of a baby delivered at 24 weeks of gestation. This occurred in the indomethacin group. CONCLUSION: There is no evidence that indomethacin tocolysis is beneficial, and further trials are needed to assess the impact of indomethacin tocolysis in preterm labour.

A comparison of a peripheral DXA system with conventional densitometry of the spine and femur.

Because of the perceived high cost of dual-energy X-ray absorptiometry (DXA) studies of the spine and femur, there is renewed interest in small, low-cost X-ray devices for scanning the peripheral skeleton. We have compared forearm bone mineral density (BMD) measurements (distal and ultradistal sites) performed on a DTX-200 (Osteometer MediTech, Hoersholm, Denmark) with spine (L1-L4) and femur (femoral neck and total hip sites) scans performed on a QDR-4500 (Hologic, Waltham, MA) in 172 white UK women aged 22-84 yr with a view to establishing differences caused by inconsistent reference ranges and different age-related changes in BMD. All BMDs were expressed as T-scores using the manufacturers' reference ranges for the forearm and spine, and the National Health and Nutrition Examination Survey (NHANES) ranges for the femur. Linear regression between peripheral and axial sites gave correlation coefficients r = 0.71-0.74 and roof mean standard errors (RMSE) 0.88-1.14 in T-score units. Subjects were divided into the following five age groups: <40 yr; 40-49 yr; 50-59 yr; 60-69 yr and >/=70 yr. A large systematic difference between distal and ultradistal T-scores (mean DeltaT = 0.59, SEM = 0.05) was found affecting all age groups. When the mean difference in T-score between each forearm site (distal, ultradistal) and each axial site (spine, femoral neck, total hip) was examined for premenopausal subjects (n = 58) the mean difference between forearm and axial T-score showed a consistent negative offset (DeltaT = -0.41 to -0.48) for the distal forearm site and a consistent positive offset (DeltaT = +0.30 to +0.37) for the ultradistal site. When interpreting results in postmenopausal women, age-related T-score changes in the forearm were in close agreement with the femoral neck region of exterest (ROI), but systematic differences were found between the forearm and the spine and total hip sites. The two forearm and three axial sites were compared to evaluate the number of postmenopausal subjects identified as osteoporotic on the basis of the World Health Organization (WHO) Study Group criteria (T-score <-2.5). Although forearm and spine T-scores identified approximately equal numbers of subjects as osteoporotic (distal 38/114; ultradistal 31/114; spine 30/114), the two femur sites identified fewer subjects as osteoporotic (femoral neck 25/114; total hip 16/114). The number for the total hip site was statistically significantly smaller than the spine and forearm sites.

Concordance and precision of dual X-ray absorptiometry with a 10 s scan.

Development of dual energy X-ray absorptiometry (DXA) scanners with multidetector array technology has resulted in greatly shortened scanning times. The Hologic QDR-4500 includes an ultrafast (10 s) "turbo" scan mode recommended by the manufacturer for fast screening studies or as an aid to positioning the patient prior to scanning using the normal fast (30 s), medium (1 min) or high definition (2 min) modes. The suitability of the turbo mode for use in routine clinical studies was assessed by examining the concordance of bone mineral density (BMD) measurements obtained in this mode with measurements obtained using the three normal scanning modes. Studies in 151 female patients showed statistically significant discrepancies in four out of the six scan sites studied with systematic differences of 2.9% and 3.1% being observed for the posteroanterior (PA) spine and intertrochanteric region of the hip, respectively. In vivo precision for the 10 s scan found by performing duplicate measurements on 37 patients had a coefficient of variation of 1.3% for PA spine and 2.5% for femoral neck BMD. An investigation of the dependence of precision on body mass index (BMI) shows that the precision of spine and hip BMD was adversely affected with increasing BMI but the trend was statistically significant only in the spine. It was concluded that turbo mode scans are acceptable for routine clinical studies of the spine and hip but should not be used for longitudinal studies or patients with BMI greater than 30 kg m-2.

Sequential changes in pulmonary epithelial permeability after birth in term and preterm rabbits.

We assessed sequential changes in the permeability properties of the pulmonary epithelium in spontaneously breathing, newborn term (30 days of gestation) and preterm (28 days) rabbit pups, using the rate of pulmonary clearance of 99mTc-DTPA (MW = 492) as an index of permeability. In term rabbits, clearance was faster at 1 h of age than at hourly timepoints thereafter (p < 0.05). In preterm rabbits, clearance rates measured from 1 to 5 h after birth were not quite significantly different (p = 0.0519) although the trend to slower clearance with increasing time after birth was significant. When term and preterm rabbits were compared, clearance was similar at 1 h after birth but was faster at both 2 and 3 h in the preterm rabbits (p < 0.05). Pulmonary epithelial permeability appears to be increased in the immediate postnatal period and the duration of increased permeability is longer in preterm rabbits. Because lung water content at birth is greater in the preterm rabbits, we speculate that the permeability changes may be associated with clearance of fetal lung liquid.

Tibial hemimelia and tetralogy of Fallot associated with first trimester exposure to amantadine.

Although amantadine hydrochloride has been extensively used for the prevention of influenza A2, few data exist regarding its safety in pregnancy. We report the outcome of a pregnancy during which the mother was treated with amantadine in the first trimester. The infant, born at 29 weeks gestation, has tetralogy of Fallot and tibial hemimelia. Follow-up of the four prospective cases known to date to the Motherisk Program in Toronto did not identify any abnormalities.

99mTc-DTPA clearance in preterm lambs. Effect of surfactant therapy and ventilation.

Surfactant therapy and high-frequency oscillatory ventilation (HFO) may minimize damage to the pulmonary epithelium of surfactant-deficient newborns. Using pulmonary clearance of insufflated, aerosolized 99mTc-DTPA (molecular weight 492) as an index of lung epithelial permeability, we examined the effects of 300 mg bovine lipid extract surfactant (S) administered at birth to preterm lambs ventilated by either HFO or conventional mechanical ventilation (CMV). Four groups of lambs, delivered by cesarean section at 129 to 133 days of gestation, were studied: (1) HFO + S, (2) CMV + S, (3) HFO, and (4) CMV. 99mTc-DTPA clearance was assessed at 2, 4, and 5.5 h after birth. Surfactant treatment improved oxygenation and lung pressure-volume relationships, with oxygenation best maintained by the combination of HFO + S. All groups had similar biexponential clearance curves at the three time points, however, and there was no significant difference in the mean rates of clearance (k) between the four groups at 2 h (k = 6.03 +/- 0.60 [SEM], 7.04 +/- 1.46, 5.67 +/- 0.91, and 7.23 +/- 0.97 %/min for Groups 1, 2, 3, and 4, respectively), 4 h (k = 6.95 +/- 0.77, 5.60 +/- 0.51, 6.39 +/- 0.64, and 6.78 +/- 1.71 %/min), and 5.5 h (k = 7.43 +/- 0.78, 6.08 +/- 0.80, 7.86 +/- 0.90, and 7.95 +/- 0.66 %/min). These data suggest that neither surfactant nor HFO significantly alters pulmonary epithelial permeability to a small radiolabeled molecule in preterm lambs.

A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants.

A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were randomly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates (10 ml/kg). The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions. In 22 (28%) of the 78 treated infants and 19 (26%) of the 74 control infants, either a new intracranial hemorrhage developed or an already-present one became more extensive (p = 0.73). Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography. Similar numbers of infants received fresh frozen plasma and packed red blood cells, but treated infants received less of both. The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened (mean difference, 79.0; 95% confidence interval, 73.1 to 84.9). Subanalysis of the control group showed that infants with platelet counts < 60 x 10(9)/L (n = 21) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)