Systemic haemodynamics in infants with vein of Galen malformation: assessment and basis for therapy.

Systemic haemodynamics in three infants with severe cardiac failure secondary to vein of Galen malformation (VGAM) were studied using two-dimensional and Doppler echocardiography. In all cases, ventricular outputs were over two times normal and superior vena caval flows up to 10 times normal reflecting high flow through the low-resistance fistula. Severe pulmonary hypertension, right heart dilatation and retrograde flow in the descending aorta were uniformly present. Systemic blood flow below the head and neck was reduced resulting in metabolic acidosis at presentation. Two infants had patent arterial ducts, in which flow was entirely right to left and on entering the aorta passed predominantly retrogradely towards the VGAM. These findings provide a basis for understanding the pathophysiology of cardiac failure in VGAM and support treatment with pulmonary and systemic vasodilating agents.

Death in the neonatal intensive care unit: changing patterns of end of life care over two decades.

BACKGROUND: Death remains a common event in the neonatal intensive care unit, and often involves limitation or withdrawal of life sustaining treatment. OBJECTIVE: To document changes in the causes of death and its management over the last two decades. METHODS: An audit of infants dying in the neonatal intensive care unit was performed during two epochs (1985-1987 and 1999-2001). The principal diagnoses of infants who died were recorded, as well as their apparent prognoses, and any decisions to limit or withdraw medical treatment. RESULTS: In epoch 1, 132 infants died out of 1362 admissions (9.7%), and in epoch 2 there were 111 deaths out of 1776 admissions (6.2%; p<0.001). Approximately three quarters of infants died after withdrawal of life sustaining treatment in both epochs. There was a significant reduction in the proportion of deaths from chromosomal abnormalities, and from neural tube defects in epoch 2. CONCLUSIONS: There have been substantial changes in the illnesses leading to death in the neonatal intensive care unit. These may reflect the combined effects of prenatal diagnosis and changing community and medical attitudes.

Hemodynamic disturbances associated with endovascular embolization in newborn infants with vein of Galen malformation.

OBJECTIVE: To examine hemodynamic changes following endovascular embolization in newborn infants with vein of Galen malformation and severe cardiac failure in the first week of life. STUDY DESIGN: Over a recent 5-year period, nine such infants were identified. In seven of these infants, changes in arterial blood pressure were analyzed in relation to the timing of embolization procedures. RESULTS: A significant increase in arterial blood pressure was noted after most embolizations. In two infants, this systemic hypertension was severe and treated using intravenous antihypertensive drugs. Both infants subsequently developed complete infarction of both cerebral hemispheres with sparing of the brainstem and cerebellum. Mortality in the nine infants was 33%, and 83% of the survivors were neurologically normal or near normal at follow-up. CONCLUSION: The systemic hypertension observed following endovascular embolizations may provide a protective mechanism to maintain cerebral blood flow after reperfusion injury. Lowering blood pressure in this situation may therefore be detrimental.

Intracranial haemorrhage due to late onset vitamin K deficiency bleeding in Hanoi province, Vietnam.

BACKGROUND: In many developing countries vitamin K prophylaxis is not routinely administered at birth. There are insufficient data to assess the cost effectiveness of its implementation in such countries. OBJECTIVE: To estimate the burden of intracranial haemorrhage caused by late onset vitamin K deficiency bleeding in Hanoi, Vietnam. METHODS: Cases of intracranial haemorrhage in infants aged 1-13 weeks were identified in Hanoi province for 5 years (1995-1999), and evidence for vitamin K deficiency was sought. The data were compared with those on vitamin K deficiency bleeding in developed countries and used to obtain an approximation to the incidence of intracranial haemorrhage caused by vitamin K deficiency bleeding in Hanoi. RESULTS: The estimated incidence of late onset vitamin K deficiency bleeding in infants who received no prophylaxis was unexpectedly high (116 per 100,000 births) with 142 and 81 per 100,000 births in rural and urban areas respectively. Mortality was 9%. Of the surviving infants, 42% were neurologically abnormal at the time of hospital discharge. Identified associations were rural residence, male sex, and low birth weight. A significant reduction in the incidence was observed in urban Hanoi during 1998 and 1999, after vitamin K prophylaxis was introduced at one urban obstetric hospital. CONCLUSIONS: Vitamin K deficiency bleeding is a major public health problem in Hanoi. The results indicate that routine vitamin K prophylaxis would significantly reduce infant morbidity and mortality in Vietnam and, costing an estimated 87 US dollars (48 pounds, 72 Euro) per disability adjusted life year saved, is a highly cost effective intervention.

Oral sucrose for procedural pain in sick hospitalized infants: a randomized-controlled trial.

OBJECTIVE: To determine the efficacy of 25% oral sucrose in the reduction of pain during a heel lance procedure in sick hospitalized infants. METHODOLOGY: In a blinded randomized- controlled trial, hospitalized infants were given either 1 mL 25% sucrose or 1 mL water 2 min prior to a heel lance procedure. Pain assessment comprised a four-point facial expression score, incidence and duration of crying, heart rate and oxygen saturation changes. RESULTS: A total of 128 infants were included. Facial scores immediately upon heel lance, and at 1 and 2 min in the recovery period were reduced in the treatment (sucrose) group compared to the placebo (water) group (P < 0.05). At other observation points, the differences in facial scores between the two groups of infants did not reach statistical significance. Neither incidence nor duration of crying whilst the blood collection was in progress was significantly reduced by sucrose. In the 3-min recovery period following completion of the blood collection, incidence and duration of crying were significantly less in the treatment group of infants (P < 0.05). Physiological responses of heart rate and oxygen saturation were not attenuated by sucrose at any time point during or following the blood collection. CONCLUSION: Oral sucrose was effective in reducing behavioural responses to pain upon heel lance and in the period following completion of a heel lance procedure in this group of sick hospitalized infants. This simple strategy can be promoted in institutions caring for sick babies, as a method of reducing behavioural responses to procedural pain.

Clinical course and medical management of neonates with severe cardiac failure related to vein of Galen malformation.

BACKGROUND: Neonatal presentation of vein of Galen aneurysmal malformations (VGAMs) with intractable cardiac failure is considered a poor prognostic sign. Interventional neuroradiology with embolisation has been shown to control cardiac failure, but there is a perception that neurological outcome in survivors is poor. OBJECTIVE: To determine if aggressive intensive care and anaesthetic management of cardiac failure before urgent embolisation can influence morbidity and mortality. PATIENTS: Nine newborns (four boys, five girls) were diagnosed with symptomatic vein of Galen malformations in the neonatal period during the period 1996-2001. Eight developed intractable high output cardiac failure requiring initial endovascular treatment in the first week of life. RESULTS: The immediate outcome after a series of endovascular procedures was control of cardiac failure and normal neurological function in six (66%) patients, one death from intractable cardiac failure in the neonatal period, and two late deaths with severe hypoxic-ischaemic neurological injury (33% mortality). Clinical review at 6 months to 4 years of age showed five infants with no evidence of neurological abnormality or cardiac failure and one child with mild developmental delay (11%). CONCLUSIONS: Aggressive medical treatment of cardiac failure and early neurointervention combined with modern neuroanaesthetic care results in good survival rates with low morbidity even in cases of high risk VGAM presenting in the immediate perinatal period with cardiac failure. Systemic arterial vasodilators improve outcome in neonates with cardiac failure secondary to VGAM. Excessive beta adrenergic stimulation induced by conventional inotropic agents may exacerbate systemic hypoperfusion.

Endovascular management of vein of Galen aneurysmal malformations presenting in the neonatal period.

BACKGROUND AND PURPOSE: Neonates with vein of Galen aneurysmal malformations (VGAMs) presenting with cardiac failure have high morbidity and mortality, and outcomes are significantly better in those presenting in later childhood. Neurologic outcomes in survivors are perceived to be uniformly poor, which may lead to the neonate being denied treatment. We assessed outcomes of modern neonatal intensive care and endovascular embolization in a consecutive series of such neonates presenting with cardiac failure. METHODS: Between 1996 and 1998, five infants (three male, two female) were diagnosed with symptomatic VGAMs in the first week of life, four of whom had intractable, high-output cardiac failure and underwent initial endovascular treatment. There were 15 endovascular procedures and one neurosurgical clipping in these five patients. Transarterial and transvenous routes were required, using multiple embolic agents. We emphasized the use of sonographically guided, percutaneous transtorcular-venous-access, moveable-core guidewire as an embolic agent; routine MR imaging; and MR angiography. RESULTS: Immediate outcomes included control of cardiac failure with normal neurologic function in four (80%) patients and one (20%) death from intractable cardiac failure. On follow-up examination, three (60%) infants showed no evidence of neurologic abnormality or cardiac failure; one (20%) infant showed moderate developmental delay. Two have had no further shunting on angiography, one has minimal flow, and one is awaiting follow-up imaging. CONCLUSION: Endovascular therapy with modern neuroanesthetic and neurointensive care can provide good outcomes even in the highest-risk neonates with VGAMs and cardiac failure. If medical management of cardiac failure fails, and there is no evidence of gross cerebral parenchymal damage on imaging, urgent endovascular treatment is feasible and can reduce the almost-100% mortality otherwise expected, without invariably severe morbidity. Use of multiple embolization strategies in multiple stages usually is necessary in these patients, and novel approaches and embolic agents may be necessary.

Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K.

UNLABELLED: There is consensus that late vitamin K deficiency bleeding (VKDB) should be prevented by vitamin K prophylaxis. One single dose of 1 mg vitamin K1 is effective if given i.m. or s.c., but not if given orally. Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established. Different oral dose schedules are presently used in different countries. In Australia, Germany, The Netherlands and Switzerland active surveillance data on late VKDB were collected in a similar manner and failure rates compared. Identical case definitions were used. There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries: (1) daily supplementation of low dose vitamin K (25 micrograms) for breast-fed infants (The Netherlands); (2) 3 x 1 mg orally [Australia (January 1993-March 1994) and Germany (December 1992-December 1994)]; (3) 1 mg vitamin K i.m. (Australia since March 1994); and (4) 2 x 2 mg vitamin K (new mixed micellar preparation) (Switzerland). The respective failure rates per 100,000 live births (including cases given all recommended doses and those given incomplete prophylaxis) were for strategy: (1) 0.2 (0-1.3) in The Netherlands; (2) 2.3 (95% CI 1.6-3.4) in Germany and 2.5 (1.1-4.8) in Australia (oral prophylaxis); (3) Australia (i.m. prophylaxis) 0 (0-0.9); and (4) 3.6 (0.7-10.6) in Switzerland. The failure rates for complete prophylaxis only were: strategy (1) 0 (0-0.7) in The Netherlands; (2) 1.8 (1.1-2.8) in Germany and 1.5 (0.5-3.6) in Australia; (3) Australia (i.m.) 0 (0-0.9); and (4) 1.2 (0-6.5) in Switzerland. CONCLUSIONS: The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m. vitamin K prophylaxis. A daily low oral dose of 25 micrograms vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis. The effectiveness of the "mixed-micellar" preparation of vitamin K1 needs further study.

Does intramuscular vitamin K1 act as an unintended depot preparation?

OBJECTIVE: To propose a hypothesis that the long duration of effect of intramuscular (i.m.) vitamin K1 in preventing late onset haemorrhagic disease results from a depot effect after i.m. injection. METHODOLOGY: Review of scientific literature relating to the pharmacology of vitamin K, and the aetiology of late onset haemorrhagic disease. RESULTS: A single i.m. dose of vitamin K1 is effective for at least 2 months, whereas the duration of effect of a single oral dose is about 3-4 weeks. The known pharmacological properties of vitamin K1 are seemingly at variance with the long duration of effect of an i.m. dose. Menaquinones (vitamins K2) are absent in the newborn liver, but gradually accumulate after birth. This, together with the low concentrations of vitamin K1 in human breast milk, may explain the peak frequency of late onset haemorrhagic disease at 4-8 weeks. We hypothesize that after i.m. injection, vitamin K1 acts as a depot preparation by forming a viscous mass in muscle tissue which is slowly absorbed over many weeks. This hypothesis is supported by reports indicating significantly higher plasma vitamin K1 levels several weeks after i.m., as compared to oral vitamin K1. CONCLUSIONS: The prolonged efficacy of i.m. vitamin K1, compared to oral preparations may be due to a depot effect. New oral preparations of vitamin K1, despite greatly improved bioavailability, may have a shorter duration of effect than i.m. vitamin K1, and therefore be less effective for long-term prophylaxis.

Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1.

The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K1 prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K1, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K1. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K1 were to have a longer duration of effect than intravenous vitamin K1. This may be because intramuscular vitamin K1 acts as a depot preparation. The findings suggest that intravenous vitamin K1 is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K1 should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.

Accuracy of pulse oximetry in hypothermic neonates and infants undergoing cardiac surgery.

OBJECTIVES: To assess the accuracy of pulse oximetry under hypothermic conditions in neonates and infants undergoing cardiac surgery, and to assess the effect of probe site as well as probe site skin temperature on the reliability of pulse oximetry. DESIGN: Prospective Study. SETTING: Cardiac operating room and intensive care unit of children's hospital. PATIENTS: Twenty-five infants <3 months of age undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Pulse oximeter readings (Sp O2) from probes placed on the hand and foot were recorded at various skin temperatures and compared with hemoximeter oxygen saturations (Sa O2) obtained on simultaneously drawn arterial blood samples. Core temperature, arterial pressure and vasodilator use were recorded simultaneously. MEASUREMENTS AND MAIN RESULTS: Pulse oximetry bias (Sp O2 - Sa O2) increased to an unacceptable range (>+3% or <-3%) in 45.5% of the readings at foot probe site temperatures of <27 degrees. Pulse oximetry bias was within an acceptable range in 94.7% of the readings at temperatures >29 degrees. There was no significant difference between oximeter readings obtained from two probe sites (hand and foot). Administration of phenoxybenzamine improved the accuracy of pulse oximetry in ten infants at skin temperature of <27 degrees. CONCLUSIONS: Pulse oximetry readings in small infants are likely to be unreliable at skin temperatures of <27 degrees, irrespective of probe site. Intravenous phenoxybenzamine appeared to improve the accuracy of pulse oximetry at low temperatures.

High frequency oscillation in newborn infants with respiratory failure.

OBJECTIVE: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV). METHODOLOGY: Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation. RESULTS: Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights < 1500 g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight > 1500 g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing < 1500 g who received HFOV in the first week of life developed periventricular haemorrhage. CONCLUSION: The initial results of HFOV for severe failure were encouraging although a learning curve was encountered with its introduction.

Neurogenic pulmonary oedema in man: aetiology and management with vasodilators based on haemodynamic studies.

Acute pulmonary oedema is a rare complication of head injury. A case is reported in which the pulmonary oedema was treated initially by tracheal intubation, constant positive airway pressure, ventilation and isoprenaline. Subsequent treatment was by vasodilation with sodium nitroprusside and phenoxybenzamine and the patient made a good recovery. The findings are discussed in relation to reported experimental work. The aetiology appears to be related to a massive sympathetic discharge leading to systemic vasoconstriction, shift of blood to the pulmonary circulation with left ventricular failure and pulmonary oedema.

Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol.

The antinausea and antivomiting effects of delta-9-tetrahydrocannabinol (THC) in children receiving cancer chemotherapy were compared with those of metoclopramide syrup and prochlorperazine tablets in two double-blind studies. THC was found to be a significantly better antinausea and antivomiting agent, but not all patients obtained relief of nausea and vomiting with THC. In some patients, THC enhanced appetite during a course of chemotherapy. In two patients, a "high" associated with THC administrationwas reported. Drowsiness was reported significantly more frequently with THC.

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.

Paroxysmal supraventricular tachycardia during theophylline therapy in a premature infant.

An episode of supraventricular tachycardia occurred in an infant born at 31 weeks' gestation after three days of therapy with theophylline 3.5 mg/kg every six hours. The infant had a plasma theophylline half-life of 24.7 hours and a low plasma theophylline clearance of 12.7 ml/kg/hour. The plasma theophylline concentration at the time of the arrhythmia was about 42 mg/l. The extent of drug accumulation with these kinetic characteristics is emphasized. Serious adverse effects due to theophylline may occur with few signs of symptoms of impending toxicity. Plasma theophylline concentration measurements are valuable in avoiding such toxicity.