Early appearance of tuberous sclerosis complex on cerebral ultrasound in extremely preterm infant.

Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder. Diagnosis of early onset TSC in newborn infants is usually made by cardiac ultrasound because of circulatory problems due to cardiac rhabdomyoma. Early appearance of cortical tubers on cerebral ultrasound in newborn infants is very rare. Mostly TSC is diagnosed on MRI and not by cerebral ultrasound. Subependymal nodules are the usual presenting sign of TSC on cerebral ultrasound in neonates, which are often misdiagnosed as subependymal hemorrhage, calcifications or ischemic lesions after intrauterine germinal matrix hemorrhage. In this case report, multiple cortical and subcortical tubers are demonstrated in an extremely preterm infant, which were not observed on antenatal ultrasound. Together with cardial rhabdomyoma and the identification of the TSC2 pathogenic mutation in DNA from normal tissue the diagnosis of TSC has been confirmed. To our knowledge this is the first case report of early appearance of disseminated cortical tubers on cerebral ultrasound postnatal in an extremely preterm infant with TSC.

[Skin to skin contact and breast-feeding after birth: not always without risk!]. / Huid-op-huidcontact en borstvoeding na de geboorte.

Skin-to-skin contact after birth is propagated to facilitate breast-feeding and mother-child bonding. We describe two term infants with sudden unexpected postnatal collapse (SUPC) during skin-to-skin contact. The infants were found with abnormal colour, hypotonia and apnoea, in a prone position on the chest of their mothers, both of whom were primipara with a high BMI. After stimulation, both infants recovered completely. No specific potential cause, other than the position, could be found. These cases illustrate that skin-to-skin contact after birth is not without risk. In available literature, risk factors for SUPC include primiparity and infant orientation such as prone and lateral positions. These positions are also risk factors for sudden infant death syndrome (SIDS). To improve safety, a primipara should be supervised during skin-to-skin contact and not be left alone in the first hours after delivery; the infant should be guaranteed a free airway, especially when the mother has a high BMI.

Estimation of extravascular lung water using the transpulmonary ultrasound dilution (TPUD) method: a validation study in neonatal lambs.

Increased extravascular lung water (EVLW) may contribute to respiratory failure in neonates. Accurate measurement of EVLW in these patients is limited due to the lack of bedside methods. The aim of this pilot study was to investigate the reliability of the transpulmonary ultrasound dilution (TPUD) technique as a possible method for estimating EVLW in a neonatal animal model. Pulmonary edema was induced in 11 lambs by repeated surfactant lavages. In between the lavages, EVLW indexed by bodyweight was estimated by TPUD (EVLWItpud) and transpulmonary dye dilution (EVLWItpdd) (n = 22). Final EVLWItpud measurements were also compared with EVLWI estimations by gold standard post mortem gravimetry (EVLWIgrav) (n = 6). EVLWI was also measured in two additional lambs without pulmonary edema. Bland-Altman plots showed a mean bias between EVLWItpud and EVLWItpdd of -3.4 mL/kg (LOA ± 25.8 mL/kg) and between EVLWItpud and EVLWIgrav of 1.7 mL/kg (LOA ± 8.3 mL/kg). The percentage errors were 109 and 43 % respectively. The correlation between changes in EVLW measured by TPUD and TPDD was r2 = 0.22. Agreement between EVLWI measurements by TPUD and TPDD was low. Trending ability to detect changes between these two methods in EVLWI was questionable. The accuracy of EVLWItpud was good compared to the gold standard gravimetric method but the TPUD lacked precision in its current prototype. Based on these limited data, we believe that TPUD has potential for future use to estimate EVLW after adaptation of the algorithm. Larger studies are needed to support our findings.

Central line bloodstream infections can be reduced in newborn infants using the modified Seldinger technique and care bundles of preventative measures.

AIM: There has been no evidence to show whether care bundles of preventive measures reduce central line-associated bloodstream infection (CLABSI) in peripherally inserted central catheters using the modified Seldinger technique, which requires more specific skills than the traditional technique. The aim of this study was to address that gap in our knowledge and to determine whether other variables influenced the outcome. METHODS: This prospective observational study was conducted on a neonatal intensive care unit. We observed the incidence of CLABSI in 45 newborn infants with peripheral catheters before the introduction of bundles of preventative measures and 88 infants after the introduction. RESULTS: Laboratory-confirmed CLABSI decreased after the introduction of the bundles, from 12.9 per 1000 days to 4.7/1000 days (p = 0.09). When we combined the rates for laboratory-confirmed CLABSI and clinical CLABSI in a survival analysis, the incidence reduced significantly after introduction of the bundles (p = 0.02). There were no other variables that affected the outcome. CONCLUSION: Cost-effective care bundles reduced CLABSI in peripherally inserted central catheters using the modified Seldinger technique, despite the specific insertion skills that were required. The bundles of preventative measures may increase healthcare professionals' awareness of the need to care for central catheters and reduce CLABSI infections.

[Pertussis in young infants: a dangerous disease with non-specific signs]. / Kinkhoest bij jonge zuigelingen: een gevaarlijke ziekte met aspecifieke verschijnselen.

Pertussis, or whooping cough, caused by Bordetella pertussis, still occurs despite vaccination. Most of the cases occurring in adolescents and adults are mild or have a subclinical course, but these patients can be a source of transmission to unvaccinated or partially vaccinated infants. Symptoms of infant pertussis are often not specific, but pertussis can be fatal. In this article, we present one case of unvaccinated twins who each presented with initial signs of a viral respiratory disease. Within a few days, each developed rapidly progressive respiratory failure complicated by refractory pulmonary hypertension due to malignant pertussis. Both patients died eventually. It is important for paediatricians, general practitioners, midwives and gynaecologists to be alert to coughing in their patients. More efficient vaccination strategies should be discussed to prevent both the transmission of B. pertussis and the occurrence of severe and fatal pertussis in young infants.

Influence of lung injury on cardiac output measurement using transpulmonary ultrasound dilution: a validation study in neonatal lambs.

BACKGROUND: Transpulmonary ultrasound dilution (TPUD) is a promising method for cardiac output (CO) measurement in severely ill neonates. The incidence of lung injury in this population is high, which might influence CO measurement using TPUD because of altered lung perfusion. We evaluated the influence of lung injury on the accuracy and precision of CO measurement using TPUD in an animal model. METHODS: In nine neonatal lambs, central venous and arterial catheters were inserted and connected to the TPUD monitor. Repeated lavages with warmed isotonic saline were performed to gradually induce lung injury. CO measurements with TPUD (COtpud) were compared with those obtained by an ultrasonic transit-time flow probe around the main pulmonary artery (COufp). An increase in oxygenation index was used as an indicator of induced lung injury during the experiment. Post-mortem lung injury was confirmed by histopathological examination. RESULTS: Fifty-five sessions of three paired CO measurements were analysed. The mean COufp was 1.53 litre min(-1) (range 0.66-2.35 litre min(-1)), and the mean COtpud was 1.65 litre min(-1) (range 0.78-2.91 litre min(-1)). The mean bias (standard deviation) between the two methods was 0.13 (0.15) litre min(-1) with limits of agreement of ±0.29 litre min(-1). The overall percentage error was 19.1%. The accuracy and precision did not change significantly during progressive lung injury. Histopathological severity scores were consistent with heterogeneous lung injury. The capability to track changes in CO using TPUD was moderate to good. CONCLUSIONS: The accuracy and precision of CO measurement using TPUD is not influenced in the presence of heterogeneous lung injury in an animal model.

Cardiac output measurement with transpulmonary ultrasound dilution is feasible in the presence of a left-to-right shunt: a validation study in lambs.

BACKGROUND: Cardiac output (CO) monitoring remains complex in newborns as most of the current technologies fail to accurately measure systemic blood flow in the presence of shunts. We validated CO measurements using transpulmonary ultrasound dilution (TPUD) in a neonatal lamb model with a left-to-right shunt. METHODS: Regular arterial and central venous catheters were inserted into seven lambs (3.5-8.3 kg). A surgically constructed left-to-right aorto-pulmonary Gore-Tex(®) shunt was intermittently opened and closed, while CO was manipulated by creating haemorrhagic hypotension. CO measurements with TPUD (COtpud) were compared with those obtained by an ultrasonic transit-time flow probe positioned around the main pulmonary artery (COufp). RESULTS: We performed 72 sessions of three paired CO measurements. The mean COufp was 1.00 litre min(-1) (range 0.47-1.75 litre min(-1)) and mean COtpud 1.05 litre min(-1) (range 0.54-1.87 litre min(-1)). With an open shunt, the mean Qp/Qs ratio was 1.8 (range 1.3-2.6). A comparison between COufp and COtpud showed a mean bias (sd) of 0.03 (0.09) and 0.07 (0.10) litre min(-1), respectively, for measurements with a closed and an open shunt. The percentage error was 18% and 20% for measurements with a closed and an open shunt. Polar plot analysis showed good trending ability for both closed and open shunt groups. CONCLUSIONS: TPUD is a reliable technology to measure CO in the presence of a left-to-right shunt.

[A right-sided congenital diaphragmatic hernia masked by pneumonia]. / Een rechtszijdige congenitale hernia diaphragmatica gemaskeerd door een pneumonie.

A 1-day-old premature newborn (34 weeks and 6 days) presented with respiratory insufficiency due to a group B haemolytic streptococcal (GBS) pneumonia. She recovered after temporary treatment with mechanical ventilation and antibiotics. At the time of discharge there was a slight increased fogging on the right side of the chest X-ray, interpreted as residual pleural effusion. Three days later the patient was readmitted with respiratory failure and a need for respiratory support. A chest CT scan revealed a right-sided congenital diaphragmatic hernia (CDH) with a large part of the liver and intestine in the chest. The diaphragmatic defect was closed during a surgical procedure. After an uneventful recovery the patient was discharged in good clinical condition. The combination of delayed presentation of right-sided CDH and neonatal GBS infection occurs rarely but has been described. Its pathogenesis is still unclear.

Disturbed cerebral circulation during opening of the venoarterial bypass bridge in extracorporeal membrane oxygenation.

PURPOSE: To describe the effects on cerebral blood flow velocity (CBFV) of intermittent opening of the venoarterial bridge (VA bridge) during venoarterial extracorporeal membrane oxygenation (VA-ECMO). STUDY DESIGN: Prospective study in 22 newborns during VA ECMO. CBFV was measured in the pericallosal artery by Doppler ultrasound. Changes in peak systolic flow velocity (PSV), end diastolic flow velocity (EDV) and time-averaged mean flow velocity (TAM) on day 1, 2, 3, and 5 and at low ECMO flow (50- 150 ml/min) were analyzed (mean percentage+/-standard deviation (t-tests, p<0.05)). Changes >25% were considered relevant. The relationship between changes in CBFV and ECMO flow rate (Pearson correlation, p<0.01) was studied. RESULTS: Opening of the VA bridge resulted in statistically significant and relevant decreases in PSV (35 +/- 18%), EDV (93 +/- 15%) and TAM (68 +/- 13%), persisting during the consecutive days of treatment. Smaller changes in CBFV at low ECMO flow were statistically significant and mostly relevant: PSV (15 +/- 7%), EDV (76 +/- 21%) and TAM (40 +/- 12%). Changes in CBFV were positively correlated to the ECMO flow. CONCLUSION: Use of the VA bridge results in significant and relevant ECMO flow-dependent changes in CBFV, persisting during the treatment. The VA bridge should be used in such a way as to allow regular unclamping to be omitted.

Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants.

BACKGROUND: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. OBJECTIVES: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. METHODS: 11 patients (GA 26.6-33.0 weeks, BW 780-2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4-33.3 weeks, BW 842-1,955 g) were sedated with morphine (loading dose 0.05 mg/kg, maintenance 0.01 mg/kg/h). Changes in oxyhemoglobin (Delta cO2Hb) and deoxyhemoglobin (Delta cHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= Delta cO(2)Hb - Delta cHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (Delta ctHb = Delta cO2Hb + Delta cHHb) represent changes in cerebral blood volume (DeltaCBV). Changes in cerebral blood flow velocity (DeltaCBFV) were intermittently measured using Doppler ultrasound. Heart rate (HR), mean arterial blood pressure (MABP), arterial oxygen saturation (saO2) and transcutaneous measured pO2 (tcpO2) and pCO2 (tcpCO2) were continuously registered. Statistical analyses were carried out using linear mixed models to account for the longitudinal character study design. RESULTS: Within 15 min after the loading dose of midazolam, a decrease in saO2, tcpO2 and cHbD was observed in 5/11 infants. In addition, a fall in MABP and CBFV was observed 15 min after midazolam administration. Immediately after morphine infusion a decrease in saO2, tcpO2 and cHbD was observed in 6/10 infants. Furthermore, morphine infusion resulted in a persistent increase in CBV. CONCLUSIONS: Administration of midazolam and morphine in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful.

Effects of rapid versus slow infusion of sodium bicarbonate on cerebral hemodynamics and oxygenation in preterm infants.

BACKGROUND: Sodium bicarbonate (NaHCO3) is often used for correction of metabolic acidosis in preterm infants. The effects of NaHCO3 administration on cerebral hemodynamics and oxygenation are not well known. Furthermore, there is no consensus on infusion rate of NaHCO3. OBJECTIVES: To evaluate the effects of rapid versus slow infusion of NaHCO3 on cerebral hemodynamics and oxygenation in preterm infants. METHODS: Twenty-nine preterm infants with metabolic acidosis were randomized into two groups (values are mean +/-SD): In group A (GA 30.5 +/- 1.7 weeks, b.w. 1,254 +/- 425 g) NaHCO3 4.2% was injected as a bolus. In group B (GA 30.3 +/- 1.8 weeks, b.w. 1,179 +/- 318 g) NaHCO3 4.2% was administered over a 30-min period. Concentration changes of oxyhemoglobin (cO2Hb) and deoxyhemoglobin (cHHb) were assessed using near infrared spectrophotometry. Changes in HbD (= cO2Hb - cHHb) represent changes in cerebral blood oxygenation and changes in ctHb (= cO2Hb + cHHb) reflect changes in cerebral blood volume. Cerebral blood flow velocity was intermittently measured using Doppler ultrasound. Longitudinal data analysis was performed using linear mixed models (SAS procedure MIXED), to account for the fact that the repeated observations in each individual were correlated. RESULTS: Administration of NaHCO3 resulted in an increase of cerebral blood volume which was more evident if NaHCO3 was injected rapidly than when infused slowly. HbD and cerebral blood flow velocity did not show significant changes in either group. CONCLUSION: To minimize fluctuations in cerebral hemodynamics, slow infusion of sodium bicarbonate is preferable to rapid injection.

Monitoring cerebral perfusion using near-infrared spectroscopy and laser Doppler flowmetry.

This paper describes the simultaneous use of two, noninvasive, near-infrared techniques near-infrared spectroscopy (NIRS) and a continuous wave NIR laser Doppler flow system (LDF) to measure changes in the blood oxygenation, blood concentration and blood flow velocity in the brain. A piglet was used as animal model. A controlled change in the arterial CO2 pressure (PaCO2) was applied for achieving changes in the listed cerebrovascular parameters. The time courses of blood concentration parameters (NIRS) and RMS blood flow velocity (LDF) were found to correspond closely with those of carotid blood flow and arterial carbon dioxide pressure (PaCO2). This result shows the additional value of LDF when combined with NIRS, preferably in one instrument. Development of pulsed LDF for regional blood flow measurement is indicated.

Assessment of local changes of cerebral perfusion and blood concentration by ultrasound harmonic B-mode contrast measurement in piglet.

This study tested the hypothesis that changes in the blood concentration, and possibly in the perfusion, of different areas in the brain can be assessed by the use of ultrasound contrast agent (CA) and (linear) echo densitometry. The experiments were performed with piglets (n=3) under general anesthesia and artificial ventilation. Ultrasound CA was administered through a femoral vein as a short bolus. First passage wash-in curve was measured from image gray level during continuous low level (mechanical index<0.2) ultrasound imaging. This curve was obtained from 1-cm2 areas of the cortex (surface), the brain stem (inner) and the left carotid artery (vessel). Cerebral hemoglobin concentration changes were measured with near-infrared spectroscopy (NIRS). This approach enabled a cross-validation of these techniques. The measurements were repeated under conditions of normocapnia, mild hypercapnia and deep hypercapnia. Several physiologic signals, as well as the carotid blood flow, were measured simultaneously and related to gray level by linear regression analysis. The most significant results found were a high R2-statistic of the regression of the percentage change of the peak of the surface and inner wash-in curves with the arterial carbon dioxide pressure (R2=0.63 and R2=0.70, respectively), the blood pH (R2=0.79 and R2=0.81), the carotid flow (R2=0.75 and R2=0.72) and the partial arterial oxygen pressure (R2=0.47 and R2=0.55). Finally, a high correlation of peak gray level with total hemoglobin concentration change, independently measured by NIRS, was found (R2=0.69). In conclusion, these experiments show a reasonable intersubject variability of various relative measures derived from gray level ultrasound wash-in curves. High sensitivity to physiologic changes related to hypercapnia was observed for the peak contrast of wash-in curves. For up-slope and area-under-the-curve (first passage) this was lower but still highly significant. The gray-level ultrasound measures are highly correlated to changes in regional hemoglobin concentration in brain tissue assessed by NIRS.

Experimental verification of conditions for near infrared spectroscopy (NIRS).

OBJECTIVES: in vitro assessment of the reproducibility and the optimal separation and position of the optodes in continuous wave (CW-) NIRS measurement of local inhomogeneities in absorption and/or scattering. METHODS: a CW- NIRS system (OXYMON) was used with laser diodes at wavelengths of 767 nm, 845 nm, 905 nm, 945 nm and 975 nm. For practical considerations (dimensions of neonatal head) the measurements were performed on a cylindrical tissue-equivalent phantom (70 mm diameter of base material with mua = 0.01 mm(-1) (800 nm) and mu's = 1.00 mm(-1) (800 nm)), containing rods with 10 x absorption, or 10 x scattering, and 5 x both Monte Carlo simulations were carried out of a cylinder with transport scattering coefficient mu's = 0.525 mm(-1) and absorption coefficient mua = 0.075 mm(-1) and two optode positions. RESULTS: reproducibility of repeated measurements (n = 10) was +/- 0.005 OD. Maximum OD in case of absorbing rod, and of absorbing + scattering rod was measured with optodes separated by 90 degrees and rod position angle symmetrically (45 degrees ) in between. Minimum OD for these rods was obtained with optodes at 150 degrees angle and rod position at 240 degrees (i.e. relative to transmitting optode position at 0 degrees ). A second maximum OD was obtained at an optode angle 180 degrees and rod position at 180 degrees. Maximum OD (i.e. attenuation) for the scattering rod was at optode separation angle of 90 degrees and rod at 0 degrees. Minimum OD for this case was obtained with optode angle of 180 degrees and rod positions around 80 degrees and 280 degrees. Maximum OD changes by absorbing rod were in the order of +0.12 OD and -0.04 OD, respectively. Simulations at an optode separation angle of 90 degrees showed a spatial sensitivity path enclosing the rod position at maximum absorption found experimentally. CONCLUSIONS: when considering the phantom as a realistic geometrical model for the neonatal head, it can be concluded that the optode position at 90 degrees angle would be optimal for detecting an inhomogeneity at 15 mm depth, i.e. the location of the periventricular white matter. Since the rods are relatively strongly different from the base material the question remains to be answered whether local ischemia, which might lead to irreversible brain damage, can be detected by CW-NIRS

Changes in cerebral, renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin.

UNLABELLED: Vasoconstriction induced by bolus injection of indomethacin reduces organ perfusion and has been related to the well-known side effects of indomethacin given for closure of the patent ductus arteriosus (PDA). The aim of the study was to compare the changes in cerebral, renal and mesenteric blood flow velocities after continuous infusion versus bolus injection of indomethacin for closure of the PDA. Thirty-two preterm infants (range 26-35 wk gestational age) with PDA were randomly assigned to receive the same amount of indomethacin either as three bolus injections (n = 14) or as a continuous infusion (n = 18) over 36 h. Blood flow velocities were measured in the internal carotid, right renal and superior mesenteric arteries at baseline and serially at 10, 30, 60 and 120 min and 12, 24, 36 and 48 h after the start of indomethacin treatment. There were no differences in blood flow velocities between both groups at baseline. During continuous infusion of indomethacin there was no significant change in the cerebral, renal and mesenteric blood flow velocities, whereas the flow velocities in the infants receiving bolus injections decreased significantly during the first 2 h after indomethacin administration in all arteries measured. There was a transient, but significant reduction in urine output after bolus injection of indomethacin. CONCLUSION: In contrast to bolus injections, decrease of organ blood flow and impairment of urine output do not accompany continuous infusion of indomethacin over 36 h.

Early versus late treatment of posthaemorrhagic ventricular dilatation: results of a retrospective study from five neonatal intensive care units in The Netherlands.

UNLABELLED: Posthaemorrhagic ventricular dilatation (PHVD) in very preterm infants carries a poor prognosis. As earlier studies have failed to show a benefit of early intervention, it is recommended that PHVD be first treated when head circumference is rapidly increasing and/or when symptoms of raised intracranial pressure develop. Infants with PHVD, admitted to 5 of the 10 Dutch neonatal intensive care units were studied retrospectively, to investigate whether there was a difference in the time of onset of treatment of PHVD and, if so, whether this was associated with a difference in the requirement of a ventriculo-peritoneal (VP) shunt and/or neurodevelopmental outcome. The surviving infants with a gestational age <34 wk, born between 1992 and 1996, diagnosed as having a grade III haemorrhage according to Papile on cranial ultrasound and who developed PHVD were included in the study. PHVD was defined as a ventricular index (VI) exceeding the 97th percentile according to Levene (1981), and severe PHVD as a VI crossing the p 97 + 4 mm line. Ninety-five infants met the entry criteria. Intervention was not deemed necessary in 22 infants, because of lack of progression. In 31 infants lumbar punctures (LP) were done before the p 97 + 4 mm line was crossed (early intervention). In 20/31 infants, stabilization occurred. In 9 a subcutaneous reservoir was placed, with subsequent stabilization in 6. In 5/31 infants a VP shunt was eventually inserted. In 42 infants treatment was started once the p 97 + 4 mm line was crossed (late intervention). In 30 infants LPs were performed and in 17 of these a VP shunt was eventually inserted. In 11 infants a subcutaneous reservoir was immediately inserted and in 8 of these infants a VP shunt was needed. In one infant a VP shunt was immediately inserted, without any other form of treatment. Infants with late intervention crossed the p 97 + 4 mm earlier (p 0.03) and needed a shunt (26/42; 62%) more often than those with early intervention (5/31; 16%). Early LP was associated with a strongly reduced risk of VP-shunting (odds ratio = 0.22, 95% confidence interval: 0.08-0.62). The number of infants who developed a moderate or severe handicap was also higher (11/42; 26%) in the late intervention group, compared with those not requiring any intervention (3/22; 14%) or treated early (5/31; 16%). CONCLUSION: In this retrospective study, infants receiving late intervention required shunt insertion significantly more often than those treated early. A randomized prospective intervention study, comparing early and late drainage, is required to further assess the role of earlier intervention.

Recirculation in double lumen catheter veno-venous extracorporeal membrane oxygenation measured by an ultrasound dilution technique.

Recirculation is a limiting factor for oxygen delivery in double lumen catheter veno-venous extracorporeal membrane oxygenation (DLVV-ECMO). This study compares three different methods for the determination of the recirculation fraction during double lumen catheter veno-venous ECMO at ECMO flow rates of 150, 125, 100, 75, and 50 ml/kg.min in nine lambs: (1) an ultrasound dilution method, in which the change in ultrasound velocity in blood after injection of a saline bolus as a marker is used for determination of recirculation; (2) an SvO2 method using real mixed venous blood oxygen saturation, the gold standard, for determination of recirculation fraction; and (3) the CVL method, in which oxygen saturation of a blood sample of the inferior vena cava is considered to represent mixed venous oxygen saturation. In all methods, the recirculation fraction increased with increasing ECMO flow rate. The correlation coefficient between the ultrasound dilution method and the SvO2 method was 0.68 (p < 0.01); mean difference was -2.4% (p = 0.6). Correlation coefficient between the ultrasound dilution method and the CVL method was 0.48 (p < 0.01); mean difference was -18.1% (p < 0.01). The correlation coefficient between the SvO2 method and the CVL method was 0.51 (p < 0.01); mean difference was -15.7% (p < 0.01). The ultrasound dilution method is a useful method for measurement of the recirculation fraction in DLVV-ECMO and is easier to use than the other methods.

Congenital absence of the trachea.

UNLABELLED: Congenital absence of the trachea is a rare cause of severe neonatal respiratory distress. Experimental studies show that it is probably caused by disorders in a system of folds in the tracheo-oesophageal space rather than abnormalities of a tracheo-oesophageal septum. A literature review disclosed 82 cases of tracheal agenesis, which showed male predominance and an association with prematurity and polyhydramnios. In 90% of cases associated congenital malformations were present, most frequently affecting the cardiovascular or gastro-intestinal systems and the genito-urinary tract. Clinical signs of tracheal agenesis or atresia are respiratory insufficiency, often with severe respiratory distress, absence of audible crying and difficult or impossible endotracheal intubation. At present, curative repair and survival are impossible unless there is enough proximal or distal trachea to create a tracheostoma. Important ongoing research is aimed at tissue-engineered cartilage for surgical repair of tracheal defects. CONCLUSION: Tracheal agenesis, although very rare, can be recognised from a characteristic clinical pattern. Mostly associated congenital malformations are present. Research into tissue-engineering might lead to possibilities for definitive surgical repair of tracheal agenesis or atresia; however, until curative repair becomes possible, prolonged ventilation via the oesophageal tube does not seem to be worthwhile.

Topical use of local anesthetics in neonates.

INTRODUCTION: Various local anesthetics as in lidocaine ointment, amethocaine cream and EMLA cream are used topically for minor invasive interventions, such as venipuncture, both in children and adults. Since neonates have a nervous system that, albeit immature, enables them to feel pain, analgesia for these procedures is also indicated. Several studies in neonates have been carried out to establish effectiveness and safety of topically applied local anesthetics. These studies are reviewed in order to assess effectiveness and safety. METHODS: A Medline search was made in order to review all studies on effectiveness and safety of topical use of local anesthetics in neonates. Effectivity or safety studies using local anesthetics for circumcision were rejected. RESULTS: Seven studies on effectiveness were found: Three studies examined lidocaine ointment and four examined EMLA cream. Effectiveness of lidocaine ointment was questionable in two studies and negative in one. Effectiveness of EMLA cream was positive in two studies and negative in the other two. Four studies were found on safety of EMLA cream. All studies indicated that use of EMLA cream was safe. DISCUSSION: The poor effectiveness found in the reviewed studies is possibly due to too long an application time, a lipophilic carrier used and difficulties in assessing pain. The time of application is often based upon studies in children. Since the skin of neonates acts more as a mucosa than as mature skin the local anesthetics are able to cross this barrier more rapidly. Also a high bloodflow in the heel enhances the uptake of the drug. The application time in neonates should therefore be reduced compared to children. The use of a lipophilic carrier should be avoided since a lipophilic carrier impedes the local anesthetic to be absorbed, leading to reduced effect. Various methods of pain assessment were being used. Since not all methods used are validated it is difficult to obtain an objective end point. CONCLUSION AND RECOMMENDATION: The articles reviewed are non conclusive in their results of effective analgesia. Due to a lipophilic base form and a hydrophilic matrix EMLA cream is most effective. An application time of 30 minutes is recommended. In spite of the present precautions due to fear of methemoglobinemia, use of EMLA cream proved to be safe when used once a day. Since the clinical situation often requires more than one application a day, more research is needed to establish a safe and effective local anesthetic which can be applied topically several times a day in the neonate.