Problems with the use of self-adhesive electrode pads in neonates.

The use of hands free self-adhesive electrode pads for monitoring and defibrillation, rather than using defibrillation paddles, has been widely adopted in many hospitals. This system can be used on automated external defibrillators as well as manual defibrillators. We describe two cases where we could not cardiovert neonates safely using self-adhesive electrode pads (SAEP) with a manual defibrillator and why we had to revert to using standard paediatric defibrillator paddles.

Tie2 ligands angiopoietin-1 and angiopoietin-2 are coexpressed with vascular endothelial cell growth factor in growing human bone.

Angiogenesis is essential for bone growth and repair. Recent studies have shown that the endothelial-specific mitogen vascular endothelial growth factor (VEGF) is a key regulator of vascular invasion into the growth plate in infant and adolescent animals. In order to identify mechanisms regulating VEGF-induced angiogenesis in growing bone, we have investigated the expression of the angiopoietins (Ang-1 and Ang-2) in human neonatal ribs. Ang-1 and Ang-2 exhibited similar patterns of staining in the growing rib. In the cartilage, expression of Ang-1 and Ang-2 increased with chondrocyte maturation. Ang-1, Ang-2, and VEGF were not detected in the resting zone except adjacent to vascular canals, and maximum expression was detected at the cartilage bone interface. In the cartilage, Ang-2 was more highly expressed than Ang-1 or VEGF, with staining observed in the proliferating, hypertrophic, and mineralized zones. In the bone, Ang-1, Ang-2, and VEGF were detected in modeling and remodeling sites. Ang-1 was detected in the majority of osteoblasts, osteoclasts, and in some marrow space cells. Ang-2 was expressed at variable levels by osteoblasts and osteoclasts in modeling and remodeling bone. VEGF was detected in cells at bone surfaces and in the marrow spaces. Strong staining for VEGF was observed in osteoblasts and osteoclasts in modeling and remodeling bone. In the perichondrium, Ang-1, Ang-2, and VEGF were most highly expressed adjacent to the hypertrophic zone and at sites of bone collar formation. In the periosteum, Ang-1, Ang-2, and VEGF expression colocalized with alkaline phosphatase expression. These observations provide the first evidence for the expression of the angiopoietins in growing human bone in vivo. The distribution of Ang-1, Ang-2, and VEGF indicate these factors may play key roles in the regulation of angiogenesis at sites of endochondral ossification, intramembranous ossification, and bone turnover in the growing human skeleton.

Expression and distribution of transforming growth factor-beta isoforms and their signaling receptors in growing human bone.

Transforming growth factors type beta (TGF-beta1, -beta2, and -beta3) are potent stimulators of bone formation and have been shown to regulate chondrocyte, osteoblast, and osteoclast formation and function. However, the distribution of the different isoforms and their signaling receptors in human bone in vivo has not previously been reported. Using samples of normal (neonatal rib) and pathological (osteophytic) developing human bone, we have investigated the expression of the different TGF-beta isoforms and their signaling receptors (TGF-betaRI and RII) at the messenger ribonucleic acid (mRNA) and protein levels by in situ hybridization and immunolocalization to establish the sites of TGF-beta production and their possible sites of action during human bone development in vivo. All three TGF-beta isoforms and the receptors were detected at sites of endochondral and intramembranous ossification. At sites of endochondral ossification, TGF-beta2 was detected in all zones of the cartilage, with the highest expression seen in the hypertrophic and mineralizing zones. TGF-beta3 was detected in proliferative and hypertrophic zone chondrocytes, while TGF-beta1 expression was restricted to the proliferative and upper hypertrophic zones. TGF-betaRI and RII exhibited similar distributions with maximum expression in the hypertrophic and mineralizing zones in the neonatal rib but in the resting/proliferative zone in the developing osteophyte. At sites of intramembranous ossification TGF-beta3 was the most widely distributed isoform and showed both matrix- and cell-associated staining. TGF-beta2 and -beta1 were expressed almost exclusively at sites of mineralization. These observations demonstrate that the different TGF-beta isoforms and their receptors exhibit distinct but overlapping patterns of expression, and support the hypothesis that they are involved in the regulation of endochondral and intramembranous ossification during human bone development in vivo.

Dose regimen for vancomycin not needing serum peak levels?

AIM: To determine the safety, efficacy, and need to measure peak serum vancomycin concentrations in a neonatal population using a standard vancomycin dosage regimen. METHOD: A total of 101 infants who were admitted to a regional neonatal intensive care unit and received vancomycin (15 mg/kg every 12 or 18 hours depending on postnatal age) were studied retrospectively. Infants who had been started on vancomycin before they were transferred to the unit were excluded. The proportion of infants was measured whose serum vancomycin concentrations were within a conservative therapeutic range of trough 5-10 mg/l, peak 20-40 mg/l, and a less conservative, but still safe, range of trough 5-12 mg/l, peak 15-60 mg/l. RESULTS: Trough concentrations of 5-10 mg/l were achieved by 46.5% of infants, and 5-12 mg/l by 55.4%. Peak concentrations of 20-40 mg/l were found in 83.2% of infants, and 15-60 mg/l in 99.0%. Highest peak concentration was 47.2 mg/l. Some 89.4% of infants with trough concentrations of 5-10 mg/l had a peak concentration of 20-40 mg/l. CONCLUSIONS: The vancomycin dosage regimen used in this study produces acceptable therapeutic serum vancomycin concentrations. Peak serum vancomycin concentrations do not need to be measured in neonates using this dosage regimen.

Percutaneous femoral arterial and venous catheterisation during neonatal intensive care.

BACKGROUND: Femoral vessel catheterisation is generally avoided in the neonatal period because of technical difficulties and the fear of complications. AIM: To review the use of femoral arterial and venous catheters inserted percutaneously on the neonatal intensive care unit. METHODS: Infants admitted to one of two regional neonatal intensive care units who underwent femoral vessel catheterisation were identified. Information collected included basic details, indication for insertion of catheter, type of catheter and insertion technique, duration of use, and any catheter related complications. RESULTS: Sixty five femoral catheters were inserted into 53 infants. The median gestational age was 29 weeks (range 23-40). Twenty three femoral arterial catheters (FACs) were inserted into 21 infants and remained in situ for a median of three days (range one to eight). Twelve (52%) FACs remained in place until no longer required, and four (17%) infants developed transient ischaemia of the distal limb. Forty two femoral venous catheters (FVCs) were inserted into 40 infants and remained in situ for a median of seven days (range 1-29). Twenty seven (64%) FVCs remained in place until no longer required, and eight (19%) catheters were removed because of catheter related bloodstream infection. CONCLUSIONS: FACs and FVCs are useful routes of vascular access in neonates when other sites are unavailable. Complications from femoral vessel catheterisation include transient lower limb ischaemia with FACs and catheter related bloodstream infection.

Pericardial effusion and cardiac tamponade as complications of neonatal long lines: are they really a problem?

AIM: To estimate the frequency of pericardial effusion/cardiac tamponade associated with the use of neonatal percutaneous long lines (PLLs) over the past five years. METHOD: A retrospective nationwide postal survey, of all neonatal and special care units in the United Kingdom. RESULTS: Eighty two cases of pericardial effusion/cardiac tamponade were reported from the five year period, during which we estimate that 46 000 PLLs were inserted. The calculated frequency of pericardial effusion/cardiac tamponade occurring with PLLs was 1.8/1000 lines. There were 30 deaths, giving a fatality rate after pericardial effusion of 0.7/1000 lines. CONCLUSIONS: Pericardial effusion/cardiac tamponade is a serious but infrequent complication of PLL use.

Analysis of cerebral blood flow autoregulation in neonates.

The dynamic response of cerebral autoregulation to spontaneous changes in arterial blood pressure (ABP) is described by the relationship between cerebral blood flow velocity (CBFV) and resistance-area product (RAP). CBFV was measured with Doppler ultrasound in the middle cerebral artery and ABP with an intra-arterial catheter in 66 neonates. Spontaneous changes in mean ABP were automatically detected and the maximum derivative was used to synchronize the coherent averaging of corresponding CBFV and RAP transients. These were classified into two groups corresponding to intact (group A) or impaired (group B) autoregulation. The cross correlation between RAP and CBFV indicates a significant relationship with a time delay of 5 s for group A. The frequency response of RAP was estimated by the cross spectra with CBFV. Groups A and B present a similar amplitude spectra but the phase spectra of group A lags that of group B. The impulse responses of the two groups are also markedly different and were used to simulate the velocity response to a 5% step change in ABP. Impulse responses were also obtained for four different levels of pCO2 showing that hypercapnia leads to an impulse response similar to that of group B (impaired autoregulation). This method can be used to extend the usual dichotomic classification adopted in clinical studies of autoregulation.

Frequency-domain analysis of cerebral autoregulation from spontaneous fluctuations in arterial blood pressure.

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in cerebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n = 23) or impaired (group B, n = 21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables is demonstrated by mean values of squared coherence > 0.50 for both groups in the frequency range 0.02-0.50 Hz. However, group A has significantly smaller coherences than group B in the frequency ranges 0.02-0.10 Hz and 0.33-0.49 Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.3 +/- 1.05, and 1.80 +/- 1.2 rad Hz-1, respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25-0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.

Accurately administering oral medication to children isn't child's play.

OBJECTIVE: Parents administer oral medications with various measuring devices including metal teaspoons, calibrated spoons and oral syringes. We aimed to determine which was the most accurate. DESIGN: Self-controlled, non-randomised, experimental study. SETTING: Caregivers attending paediatric outpatient clinics. METHODOLOGY: Caregivers measured 5 ml of 120 mg/5 ml paracetamol suspension using a 5.0 ml metal teaspoon, 5.0 ml calibrated spoon and 5.0 ml oral syringe. Samples were weighed and converted to mls. MAIN OUTCOME MEASURES: The mean volume and variance of volumes were measured for each device. RESULTS: We recruited 277 caregivers (98% parents). Volumes measured ranged from 0.83-6.52 ml. Accuracy did not vary with caregivers' age, gender, instrument preference, number and age of children. The mean volumes measured with the oral syringe (95% CI 5.09 to 5.17 ml) and metal spoon (95% CI 3.90 to 4.08 ml) were significantly different to the desired 5 ml volume (p<0.0001), dissimilar to the mean volume measured using the calibrated spoon (95% CI 4.91 to 5.09 ml, p=0.99). The variance of volumes measured with the oral syringe (SD 0.348 ml) was significantly smaller (p<0.0001) than that measured using a calibrated spoon (SD 0.762 ml) or metal spoon (SD 0.749 ml). CONCLUSIONS: The calibrated spoon was the most accurate producing a mean volume of 5 ml, while the oral syringe had the smallest variance. The increased variability of calibrated or metal spoons may result in under or overdosing especially when administering drugs with a narrow therapeutic window. Health care professionals must make a case-by-case decision regarding which device is preferable depending on the medication in question. Parental education could improve measuring accuracy.

Reversible neurologic dysfunction following isoflurane sedation in pediatric intensive care.

OBJECTIVE: To examine the relationship between prolonged isoflurane sedation and reversible neurologic dysfunction in children requiring intensive care. DESIGN: Retrospective, case note review from January 1987 to August 1993. SETTING: Pediatric intensive care unit. PATIENTS: Twenty-nine children, aged 6 months to 10 yrs, requiring endotracheal intubation and mechanical ventilation for upper airway infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fourteen patients with laryngotracheobronchitis (croup) and 15 patients with epiglottitis required endotracheal intubation and ventilation. These children were treated with different sedative and muscle relaxant drugs, including opiates, benzodiazepines and chloral hydrate. Twelve (41%) of 29 children were sedated with isoflurane (0.25% to 1.5%) for > 24 hrs. All patients subsequently developed reversible ataxia, agitation, hallucinations, and confusion lasting < or = 72 hrs postextubation. Neurologic dysfunction was not observed in 12 patients who did not receive isoflurane nor in five patients who received isoflurane for between 1 and 15 hrs. Neurologic signs resolved in all patients before hospital discharge, and all children had normal neurologic examinations 4 to 6 wks later as outpatients. CONCLUSIONS: A high occurrence rate of reversible neurologic dysfunction occurs when isoflurane is used as a sedative for > 24 hrs in pediatric patients.

Successful treatment of aortic thrombosis after umbilical catheterization with tissue plasminogen activator.

An infant presented 10 days after removal of a high umbilical arterial catheter with total occlusion of the distal abdominal aorta. Complete dissolution was achieved with a combination of i.v. tissue plasminogen activator and heparin. Ultrasound examination confirmed the diagnosis and subsequent resolution of the thrombus.

Cerebral autoregulation dynamics in premature newborns.

BACKGROUND AND PURPOSE: Autoregulation of cerebral blood flow is easily disrupted, and loss of this normal physiological reflex may worsen the neurological outcome for patients undergoing intensive care. We studied the response of cerebral blood flow velocity to changes in mean arterial blood pressure. METHODS: Cerebral blood flow velocity was measured with Doppler ultrasonography in one middle cerebral artery for 5-minute periods in 33 babies of gestational age < 33 weeks admitted to a neonatal intensive care unit. Two methods of evaluating autoregulation were developed. The first used linear regression analysis of blood flow velocity on blood pressure. Records were classified as showing loss of autoregulation if the regression slope was greater than a critical value. A minimum change in mean arterial blood pressure of 5 mm Hg and a critical slope of 1.5%/mm Hg were found to be adequate criteria for the classification of records by the regression method. The second method used coherent averaging, a technique similar to that used in recording evoked potentials. Spontaneous transient increases in blood pressure were automatically detected, and the instant corresponding to its maximum rate of rise was used to synchronize averages of the blood pressure and blood velocity transients. The resulting coherent averages were classified into two groups based on the morphology of the cerebral blood flow velocity average. RESULTS: Whereas the regression method allowed the classification of only 51 of 106 records, the coherent average method classified 101 of 106 (95.3%) of the records available. For 51 records that were classified by both methods, there was agreement in 42 cases (82.3%). The coherent average of all records classified as having an active autoregulation showed cerebral blood flow velocity returning to baseline much earlier than blood pressure, suggesting that autoregulation was taking place within 1 to 2 seconds. This pattern was absent in records in which autoregulation was classified as absent. CONCLUSIONS: Computerized coherent averaging of the cerebral blood flow velocity response to spontaneous blood pressure transients offers a promising new method for noninvasive bedside assessment of autoregulation in patients undergoing intensive care. The time course for autoregulation, when present, is in agreement with that reported in adults.

Estimation of critical closing pressure in the cerebral circulation of newborns.

We have developed a method to estimate the critical closing pressure (CrCP) of the cerebral circulation based on the intrinsic variability of arterial blood pressure (BP) around stable values of mean arterial pressure (MAP). A consecutive cohort of 33 premature newborns was studied at 6, 12, 24, 48 and 72 hours of age. Cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery and BP was recorded in the abdominal aorta or in a peripheral artery. Continuous measurements lasting five minutes were recorded on digital magnetic tape and signals were digitized at a rate of 200 samples/seconds for processing on a digital computer. Mean values of BP (mBP) and CBFV (mBV) were computed for each cardiac cycle and CrCP was determined as the pressure axis intercept of the regression line of mBV as a function of mBP using 100 sequential heart beats. The resistance-area product (RAP) was obtained from the slope of the regression line. For 57 records (30 patients) the mean +/- SD values of CrCP and RAP were 23.9 +/- 11.6 mmHg and 4.07 +/- 1.83 x 10(4) kg.m-2.s-1, respectively. CrCP has a highly significant correlation with mean arterial pressure (p < 0.001) but RAP has not. Neither CrCP nor RAP are significantly correlated (p > 0.05) with PO2, PCO2, pH, haematocrit, gestational age, birthweight, postnatal age, heart rate on Pourcelot's resistance index. Our results suggest that cerebral perfusion pressure should be defined as MAP-CrCP for normal values of intracranial pressure.

The relationship between cerebral blood flow velocity fluctuations and sleep state in normal newborns.

Cerebral blood flow velocity was recorded for an average of 23 4-min epochs during natural sleep in 11 normal full-term newborn babies. Intracranial pressure, core temperature, and respiration were simultaneously and non-invasively monitored. Sleep state was classified using information from EEG, pattern of respiration, and eye and body movements by a trained observer. From a total of 238 epochs, 66 were considered to occur in quiet sleep, 101 in active sleep, and in 77 the baby was awake, in a transitional state or moving excessively. Slow cyclical variations in cerebral blood flow velocity were observed with a frequency of between 2 and 6 cycles/min, and these were of significantly greater amplitude during quiet sleep (24%) compared to active sleep (16%; p < 0.0001, Mann Whitney U test). There was no difference in median cerebral blood flow velocity (7.5 cm/s). The cyclical variation observed in normal babies were similar to those described in preterm babies and adults, at a similar frequency to B waves in intracranial pressure. They may represent vasomotor waves in the small autoregulatory arteries of the brain. Reduction in sensitivity of the receptors initiating the waves may occur in active sleep or there may be competition from other oscillatory mechanisms.

Vincristine as a treatment for a large haemangioma threatening vital functions.

We report the use of vincristine to treat a large steroid resistant haemangioma of the lower face and neck. At the time of treatment the lesion had shown no signs of involution. The haemangioma was not life threatening but extension within the mouth was associated with bleeding and ulceration, which was impairing feeding and speech development. A significant improvement was seen with vincristine treatment.

Spectral pattern of neonatal cerebral blood flow velocity: comparison with spectra from blood pressure and heart rate.

The cerebral blood flow velocity (CBFV) frequency spectra were studied in 106 premature and term newborns (gestational age range. 24-42 wk) and compared with the heart rate (HR) and mean arterial blood pressure (BP) spectra over the 0.005-0.5 Hz range. CBFV, BP, and HR were shown to have similar but not identical spectral patterns. Adjustment of a l/f model to these spectra produced highly significant fittings, but the residuals were not independent. This condition was met only by the CBFV and BP spectra over a limited frequency range (0.005-0.06 Hz). These results provide a characterization of the CBFV spectra for a much larger population of newborns than hitherto available, indicating that under certain conditions CBFV and BP might show the properties of chaotic systems. In infants without major complications, gestational age (GA) did not have a significant influence on the CBFV spectrum, whereas the spectral power to 0.5 Hz of both BP and HR was found to increase with GA. The spectral power increased over the first 24 h of postnatal life for all three variables: only CBFV showed a significant spectral change in the low frequency (LF, 0.02-0.08 Hz) range. A matched group comparison, adjusted for GA and postnatal age, indicated a reduction in CBFV LF power for term infants with birth asphyxia when compared with normal infants, which was not reproduced in the HR spectra.

Immunolocalisation of vascular endothelial growth factor (VEGF) in human neonatal growth plate cartilage.

Angiogenesis is essential for the replacement of cartilage by bone during growth and repair. In order to obtain a better understanding of the mechanisms regulating vascular invasion at sites of endochondral ossification we have investigated the expression of the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), by chondrocytes in human neonatal growth plates. VEGF was absent from chondrocytes in the resting zone and only weakly expressed by occasional chondrocytes in the proliferating region. In the hypertrophic zone the number of chondrocytes stained and the intensity of staining for VEGF increased with chondrocyte hypertrophy, maximum expression of VEGF being observed in chondrocytes in the lower hypertrophic and mineralised regions of the cartilage. These observations provide the first demonstration of the presence of VEGF in situ in developing human bone and are consistent with in vitro observations demonstrating the upregulation of proangiogenic growth factor production with increasing chondrocyte hypertrophy. The presence of numerous small blood vessels and vascular structures in the subchondral region where VEGF expression was maximal indicates that VEGF produced by hypertrophic chondrocytes may play a key role in the regulation of vascular invasion of the growth plate.