Brain hemodynamic changes in preterm infants after maintenance dose caffeine and aminophylline treatment

OBJECTIVE: To investigate the acute effects of low-dose caffeine and aminophylline on cerebral blood flow in preterm infants, using both near-infrared spectroscopy (NIRS) and cerebral Doppler ultrasonography. METHODS: Preterm infants with a gestational age of <32 weeks and birth weight of <1,500 g were randomized to receive either caffeine or aminophylline treatment for apnea of prematurity. The study period went from 30 min before to 60 min after the administration of the maintenance dose of pure caffeine (2.5 mg/kg once a day) or aminophylline (1.25 mg/kg twice a day). NIRS was used to measure changes in oxygenated hemoglobin (O(2)Hb), deoxygenated hemoglobin (HHb), oxidized-reduced cytochrome aa3 (CtOx), and mean cerebral oxygen saturation (SmO(2) = O(2)Hb/total Hb). Changes in cerebral blood volume (DeltaCBV) after caffeine or aminophylline administration were calculated. Cerebral blood flow velocity (CBV) in the pericallosal artery was evaluated by cerebral Doppler ultrasounds. RESULTS: Data collected by NIRS and cerebral Doppler ultrasounds did not show significant differences before and after caffeine treatment. We observed a significant increase in O(2)Hb and HHb concentration and in CBV at 30 min after the infusion of aminophylline, which tended to return to baseline at the end of the study period. CONCLUSION: Caffeine does not significantly affect brain hemodynamics, while aminophylline induces a significant transient increase in O(2)Hb and HHb concentration and CBV.     

Physiologic effects of doxapram in idiopathic apnea of prematurity

Twelve premature infants with significant apnea of prematurity while receiving therapeutic doses of aminophylline were given an intravenous infusion of doxapram, 2 or 2.5 mg/kg/hr. The ventilatory effects of the medication were monitored by means of face mask spirometry and airway occlusion studies. Doxapram therapy was associated with significant increases in minute ventilation, tidal volume, mean inspiratory flow, and airway pressure 100 msec after occlusion. Respiratory frequency and the relative duration of inspiration and expiration were unchanged. Paco2 decreased significantly during the infusion. The apnea attack rate, monitored by continuous recording, was significantly reduced after the first 6 hours of therapy. Six hours after starting doxapram, mean arterial blood pressure was significantly elevated, and continued to increase during the 24 hours of therapy. Doxapram is effective in treatment of apnea of prematurity refractory to aminophylline, and appears to act by increasing respiratory center output.     

Low-dose doxapram therapy for idiopathic apnea of prematurity

BACKGROUND: Doxapram is contraindicated for newborn infants in Japan because of its serious side effects. However, because of encouraging results of recent studies regarding the efficacy and safety of therapy for apnea of prematurity (AOP) with lower doses of doxapram than those previously proposed, approximately 60% of Japanese neonatologists continue to use doxapram at small doses. Caution is warranted because the sample sizes of the former studies are inadequate to evaluate doxapram for both its beneficial and harmful effects. Therefore, we conducted the present study in order to investigate the efficacy and harmful events of low-dose doxapram therapy for idiopathic AOP in very low-birth weight (VLBW) infants in a larger population. METHODS: One hundred and six VLBW infants with idiopathic AOP were treated with doxapram at a dose of 0.2-1.0 mg/kg per h in combination with methylxanthines and the frequency of apnea and secondary outcomes were compared with a group of control infants. RESULTS: An approximate 80% reduction in the frequency of apnea was found with only minimal side effects following low-dose doxapram. Although there were no significant differences in secondary outcomes between the doxapram-treated and control groups, mortality in doxapram-treated infants was significantly lower than that in control infants. CONCLUSIONS: Patients with AOP unresponsive to treatment with methylxanthines may benefit from the addition of low-dose doxapram.     

Low-dose doxapram therapy in premature infants and its CSF and serum concentrations

The efficacy of low-dose doxapram therapy (0.2 mg/kg/h) in combination with methylxanthines was evaluated in 20 premature infants with idiopathic apnea unresponsive to methylxanthines alone, and in 13 premature infants with secondary apnea. The serum concentrations of doxapram and, in some infants, the simultaneous cerebrospinal fluid and serum concentrations were measured, and the correlation between cerebrospinal fluid and serum concentrations in the postnatal period was determined. The following results were obtained: 1) In idiopathic apnea of prematurity, low-dose doxapram therapy was as effective as a dose of 1.0-2.5 mg/kg/h and the side effects were few, mild, and reversible. 2) In premature infants over seven days of age, serum concentrations of doxapram were almost stable but were significantly lower than in infants within the first six days of life. 3) The ratio of the cerebrospinal fluid to serum doxapram concentration was 0.48 +/- 0.13 (mean +/- SD). There was a good correlation between cerebrospinal fluid and serum concentrations (r = 0.933, p less than 0.001). The initial doxapram dose can be set as low as 0.2 mg/kg/h in very young premature infants with idiopathic apnea of prematurity unresponsive to methylxanthines.     

Effect of blood transfusions on cerebral haemodynamics in preterm infants

Aim: To assess the possible cerebral haemodynamic changes occurring in preterm infants after blood transfusions. Methods: Preterm infants who had undergone blood transfusions were prospectively studied using both near infrared spectroscopy and cerebral Doppler ultrasonography. Results: Fourteen infants (mean gestational age 29.6 wk, SD 2.6; mean birthweight 1430 g, SD 332) were studied at the mean age of 29 (SD 14) d. A significant increase in oxygenated haemoglobin (O 2 Hb), deoxygenated haemoglobin (HHb), mixed cerebral oxygen saturation (SmO 2 ) and change in cerebral blood volume occurred after transfusion. Between ultrasound parameters, we found a decrease in diastolic velocity and an increase in resistance index.

Conclusion: Blood transfusions improve cerebral oxygen supply and induce a decrease in cerebral blood volume, probably due to an increase in cerebral vessel resistance.     

Monitoring of cerebral oxygenation during hypoxic gas management in congenital heart disease with increased pulmonary blood flow

In the preoperative management of congenital heart disease (CHD) with increased pulmonary blood flow, hypoxic gas management to control pulmonary blood flow is useful. However, the cerebral oxygenation state has rarely been studied, and there is concern about neurologic development. In eight infants with CHD accompanied by increased pulmonary blood flow, hypoxia was induced after a 1-h baseline period in room air (FiO2, 0.21). The infants were simultaneously monitored in both the front-temporal region and the right-brachial region for 90 min using near-infrared spectroscopy (NIRS). The minimum SaO2 (pulse oximetry) after hypoxic gas administration was 80.8 +/- 2.9% when the minimum FiO2 was 16.2 +/- 1.1%. With a decrease in SaO2, oxy-Hb (O2Hb) decreased and total Hb [cHb: O2Hb + deoxy-Hb (HHb)] increased in both regions in the majority of infants. HHb increased in both regions with a decrease in SaO2. The maximum change in the tissue oxygenation index (TOI: O2Hb/cHb x 100) was -8.3 +/- 2.6% in the front-temporal region and -3.6 +/- 2.3% in the right-brachial region. Cerebral oxygenation decreased despite an increase in cerebral blood flow during hypoxic gas management. The change in TOI was < or =10% when the SaO2 was > or =80%. Safer control of SaO2 should be maintained over 80% for hypoxia management in CHD based on the results of the present study.     

Low-Dose Doxapram Therapy in Premature Infants and Its CSF and Serum Concentrations

ABSTRACT. The efficacy of low-dose doxapram therapy (0.2 mg/kg/h) in combination with methylxanthines was evaluated in 20 premature infants with idiopathic apnea unresponsive to methylxanthines alone, and in 13 premature infants with secondary apnea. The serum concentrations of doxapram and, in some infants, the simultaneous cerebrospinal fluid and serum concentrations were measured, and the correlation between cerebrospinal fluid and serum concentrations in the postnatal period was determined. The following results were obtained: 1) In idiopathic apnea of prematurity, low-dose doxapram therapy was as effective as a dose of 1.0-2.5 mg/kg/h and the side effects were few, mild, and reversible. 2) In premature infants over seven days of age, serum concentrations of doxapram were almost stable but were significantly lower than in infants within the first six days of life. 3) The ratio of the cerebrospinal fluid to serum doxapram concentration was 0.48 ± 0.13 (mean ± SD). There was a good correlation between cerebrospinal fluid and serum concentrations ( r = 0.933, p < 0.001). The initial doxapram dose can be set as low as 0.2 mg/kg/h in very young premature infants with idiopathic apnea of prematurity unresponsive to methylxanthines.     

Determinants of doxapram utilization: a survey of practice in the French Neonatal and Intensive Care Units.]

Methylxanthines and doxapram have been used to stimulate breathing and to prevent apnea in preterm infants. The use of doxapram is controversial because the therapeutic index seems to be narrow and short-term adverse effects have been described. OBJECTIVE: To determine the use of doxapram in the French neonatal and intensive care units. METHODS: A structured postal questionnaire was sent to all the 236 neonatology and neonatal intensive care units of level IIa, IIb and III in France. The questionnaires were analysed after four months. RESULTS: Answers were obtained from 159 chiefs of department (67.4%), 102 used doxapram (64.1%). Doxapram was mainly used as a second step, if methylxanthines failed to reduce the frequency of apneic spells (102/159 units, 64.1%). Doxapram was usually administered intravenously (91/102 units, 89.2%). Only 57 respondents (35.8%) did not use doxapram, because they were aware of the potential adverse effects or they did not know the drug. Monitoring of drug plasma concentrations was rarely performed (11/102 services, 10.8%). Nevertheless, there was a significant interest in this monitoring. CONCLUSION: Doxapram is frequently used in France to reduce apnea of prematurity if methylxanthine therapy fails. Further studies are needed to determine safety of doxapram at short and long-term. A multicenter, randomised, double-blinded clinical trial would be interesting to perform, similar to the ongoing caffeine for Apnoea of Prematurity trial (CAP) . The French setting seems appropriate for this kind of study.     

Brain haemodynamic effects of nasal continuous airway pressure in preterm infants of less than 30 weeks' gestation

AIM: To evaluate the hypothesis that increasing levels of nasal continuous positive airway pressure (NCPAP) may decrease cerebral blood volume (CBV) and cerebral oxygenation in infants with gestational age (GA) less than 30 weeks. METHODS: We prospectively studied a cohort of preterm infants treated with NCPAP using near-infrared spectroscopy (NIRS). The pressure limit of NCPAP was set at 2, 4, 6 and again 2 cm H(2)O for 30 min. RESULTS: Changes of pressure levels were not followed by significant changes of oxygenated haemoglobin (O(2)Hb), deoxygenated haemoglobin (HHb), cerebral intravascular oxygenation (HbD), oxidized-reduced cytochrome aa3 (CtOx), tissue oxygenation index (TOI), tissue haemoglobin index (THI) and cerebral blood volume (DeltaCBV). CONCLUSION: NCPAP at 2-6 cm H(2)O pressure levels did not affect cerebral oxygenation and CBV. These findings are reassuring and confirm the safety of NCPAP in preterm infants with GA less than 30 weeks.     

Dose-response relationship of doxapram in the therapy for refractory idiopathic apnea of prematurity

Eighteen infants with idiopathic apnea of prematurity refractory to therapeutic levels of aminophylline were treated with incremental doses of doxapram beginning at 0.5 mg/kg/h. Continuous recording of heart rate, thoracic impedance, and transcutaneous PO2 demonstrated that 47% of the infants satisfied objective response criteria at the lowest dose, 53% responded at 1.0 mg/kg/h, 65% at 1.5 mg/kg/h, 82% at 2.0 mg/kg/h, and 89% at the highest allowed dose of 2.5 mg/kg/h. The mean serum doxapram concentration at the response dose was 2.9 +/- 1.3 micrograms/mL, and all infants who responded had levels greater than 1.5 micrograms/mL. BP was significantly elevated at doses higher than 1.5 mg/kg/h (P less than .05). Minute ventilation significantly increased and PCO2 significantly decreased as the doxapram dosage was increased (P = .02). Terminal elimination half-life was 9.9 +/- 2.9 hours. When doxapram is used for treatment of refractory neonatal apnea the starting dosage should be no more than 0.5 mg/kg/h.     

The effect of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in newborn infants investigated by near infrared spectrophotometry

The objective of this study was to investigate the influence of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables in newborn infants. Thirteen preterm infants with anaemia (haematocrit < 0.33) and ten infants with polycythaemia (haematocrit > 0.65) were studied during blood transfusion and haemodilution respectively using adult red blood cells and partial plasma exchange transfusion. Changes in cerebral concentrations of oxyhaemoglobin (cO₂Hb), deoxyhaemoglobin (cHHb), total haemoglobin (ctHb), (oxidized - reduced) cytochrome aa₃ (cCyt.- aa₃) were continuously measured using near infrared spectrophotometry throughout the whole procedure. Simultaneously, changes of mean CBFV in the internal carotid artery were continuously measured using pulsed Doppler ultrasound. Heart rate, transcutaneous partial pressure of oxygen and carbon dioxide, and arterial O₂ saturation were continuously and simultaneously measured. Blood transfusion resulted in increase of cO₂Hb, cHHb, ctHb and red cell transport (product of CBFV and haematocrit), whereas CBFV decreased. The increase of cO₂Hb exceeded that of cHHb, reflecting improvement of cerebral O₂ supply. Haemodilution resulted in a decrease of cO₂Hb, cHHb and ctHb, whereas CBFV increased. Red cell transport was unchanged. The decrease of cO₂Hb exceeded that of cHHb, reflecting decreased cerebral O₂ supply. cCyt.aa₃ decreased after blood transfusion and remained unchanged after haemodilution, but the reliability of these results is uncertain. With the exception of a small, but significant increase in transcutaneous partial pressure of oxygen after blood transfusion, the other variables showed no changes. Each blood withdrawal during exchange transfusion resulted in only a significant increase in heart rate without changes in the other variables measured, suggesting unchanged cerebral perfusion. Conclusion In newborn infants blood transfusion in anaemia results in improvement of cerebral oxygenation, but haemodilution in polycythaemia does not improve cerebral oxygenation despite possible improvement of cerebral perfusion. Received: 21 December 1995 and in revised form: 29 August 1996 / Accepted: 4 September 1996     

Clinical and physiological responses to prolonged nasogastric administration of doxapram for apnea of prematurity

We hypothesized that enteral doxapram would effectively treat apnea of prematurity without the appearance of major side effects. Of 16 infants, 10 (BW 1,520 +/- 102 g) received doxapram alone and 6 (BW 1,020 +/- 35 g) received doxapram plus theophylline. Apneas decreased from 16.7 +/- 1.9 to 2.1 +/- 0.6 in infants receiving doxapram alone, and from 38.2 +/- 4.4 to 7.9 +/- 2.2 apneas/24 h in those receiving doxapram plus theophylline. This was associated with an increase in alveolar ventilation, a shift of the ventilatory response to CO2 to the left, and no change in the immediate ventilatory response to 100% oxygen. Side effects included premature teeth buds corresponding to the lower central incisors, prevalence of occult blood in stool and necrotizing enterocolitis. The findings suggest that doxapram effectively controls apnea when given enterally, but should be used cautiously because of potentially harmful side effects.     

Isolated mental developmental delay in very low birth weight infants: association with prolonged doxapram therapy for apnea.

OBJECTIVE: We investigated factors associated with isolated mental delay in infants weighing < 1250 g at birth. STUDY DESIGN: With a case-control design, matching variables for 40 cases included gestation, birth weight, sex, grade of intraventricular hemorrhage, and socioeconomic status. Case subjects had a mental developmental index < 70, and controls had a mental developmental index > or = 85, according to the Bayley Scales of Infant Development II at 18 months' corrected age. RESULTS: There were no differences between the case and control subjects for neonatal complications and antenatal or postnatal steroid use. There was a marked difference in the cumulative dosage and duration of doxapram therapy used for apnea of prematurity (total dose 2233 +/- 1927 mg vs 615 +/- 767 mg, P < .001; duration 45.2 +/- 32.5 days vs 19.4 +/- 23.4 days, P < .001 for case subjects and control subjects, respectively). Multivariate analysis did not identify additive predictive variables. CONCLUSION: Isolated mental delay in infants weighing < 1250 g at birth was associated with the total dosage and duration of doxapram therapy for severe apnea. Although this may be a marker for cerebral dysfunction manifesting as apnea of prematurity, possible adverse effects of doxapram or its preservative, benzyl alcohol, on the developing brain deserve further study.     

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.     

Doxapram for the initial treatment of idiopathic apnea of prematurity.

The ventilatory effects of doxapram in the initial pharmacotherapy for apnea in the newborn were evaluated in 8 premature infants with idiopathic apnea. All received doxapram for 48 h at 0.25 mg/kg/h on the first day and 1 mg/kg/h on the second day. The ventilatory effects and the airway occlusion pressure (p0.1) were measured by means of a face mask, and a pneumotachograph. Compared to the pretreatment period, the mean of the frequency of central apnea greater than or equal to 15 s decreased significantly (p less than 0.01) by 48 and 75% during the first and second day, respectively. Both doses significantly increased inspiratory drive measured by airway occlusion pressure by 20% (p less than 0.05) and 32% (p less than 0.01) on the first and second day of drug treatment, respectively. Minute ventilation, tidal volume and mean respiratory flow significantly increased only with 1 mg/kg/h of doxapram, accompanied by a significant decrease in transcutaneous PCO2. No side effects were noted. Data suggested that doxapram alone at a dose of 1 mg/kg/h is effective for the treatment of neonatal apnea.     

Cerebral vascular responses to changes in carbon dioxide tension in term and preterm infants with apnea

Carbon dioxide (CO(2)) plays important roles in regulating both respiratory drive and cerebral blood flow. These effects are mediated, in part, by activity of the sympathetic nervous system. We hypothesized that the presence of acute life-threatening events or apnea in term or preterm infants, respectively, would serve as a marker for immaturity of cerebral autonomic innervation and that such infants would display a reduced cerebral vascular response to elevated pCO(2). Therefore, we evaluated the cerebral vascular response during CO(2) challenge tests in groups of term and preterm infants with primary apnea. In term infants (39 +/- 2 weeks gestation) with acute life-threatening events, elevated pCO(2) was accompanied by decreasing pulsatility index and increasing mean anterior cerebral blood flow velocity. However, in preterm infants (29 +/- 2 weeks' gestation) with apnea, pulsatility index and anterior cerebral artery flow velocity did not significantly change in response to CO(2) supplementation. We conclude that preterm, but not term, infants with apnea exhibit impaired vascular responses to hypercarbia.     

Obstructive, mixed, and central apnea in the neonate: physiologic correlates.

In an attempt to determine physiologic responses to neonatal apnea, we evaluated changes in heart rate and oxygen saturation as measured by pulse oximetry during 2082 episodes of apnea lasting 15 seconds or more in 47 infants less than 34 weeks of gestational age with idiopathic apnea of prematurity. Of these episodes, 832 (39.9%) were central, 1032 (49.6%) were mixed, and 218 (10.5%) were obstructive. Oxygen saturation decreased with increasing duration of apnea regardless of type or treatment, and the decrease in saturation was correlated with preapnea saturation. The baseline heart rate was similar for all apnea types. Infants receiving doxapram had a lower baseline heart rate (137.8 +/- 10.5 beats/min) than did infants receiving no therapy (142.8 +/- 16.6 beats/min) and infants receiving theophylline (149.7 +/- 15.0 beats/min) (p = < 0.001). A heart rate fall to less than 100 beats/min was seen more frequently with central apnea than with mixed or obstructive events, and in infants who were not receiving therapy. Falls in heart rate were significantly less in infants receiving doxapram (27.8% +/- 18.0%) than in infants receiving theophylline (44.5% +/- 19.0%) or no therapy (48.4% +/- 18.3%) (p = < 0.001). The most common heart rate pattern overall was a gradual decrease interrupted by accelerations, whereas an initial heart rate acceleration was the most common pattern in obstructive apnea. We conclude that heart rate response to neonatal apnea is a complex and is dependent on therapy and on type and duration of apnea.     

Cerebral blood flow and left ventricular output in spontaneously breathing, newborn preterm infants treated with caffeine or aminophylline

Aminophylline and caffeine are commonly used for prophylaxis of apnea in premature infants. Previous studies have indicated different effects of the drugs on cerebral circulation. Therefore, we have compared the acute effects of bolus administration of caffeine citrate or aminophylline on left ventricular output, heart rate, blood pressure and global cerebral blood flow. The study group consisted of 33 newborn, spontaneously breathing, preterm infants randomly assigned to receive either aminophylline 5mg/kg (n = 19) or caffeine citrate 20mg/kg ( n = 14). Two hours after iv drug administration, global cerebral blood flow measured by the Xe-clearance technique was significantly lower after aminophylline than after caffeine (mean(SD)): 13.2 (+2.9/ - 2.3) versus 17.2 (+7.1/ - 5.1) ml/100 g/min) (p = 0.01). There were no other statistically significant differences in circulatory or ventilatory parameters between the groups. Further studies are needed to clarify the clinical relevance of these results.     

Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus

A prospective randomized controlled trial was performed to compare the effects of ibuprofen with indomethacin on cerebral hemodynamics measured using near infrared spectroscopy in preterm infants during treatment for patent ductus arteriosus. Infants were randomly assigned to three intravenous doses of either indomethacin (0.20-0.25 mg/kg, 12 hourly) or ibuprofen (5-10 mg/kg, 24 hourly) and also received a dose of saline. The primary end points of the study were the effects of the first dose on cerebral blood flow (CBF) and cerebral blood volume. Fifteen infants received indomethacin and 18 received ibuprofen. The group mean (SD) values for CBF (mL x 100 g(-1) x min(-1)) before and after the first dose of indomethacin were 13.6 (4.1) and 8.3 (3.1), respectively, the change being significant (p<0.001). In contrast, no significant changes in CBF were observed with the first dose of ibuprofen, the respective before and after values being 13.3 (3.2) and 14.9 (4.7) mL x 100 g(-1) x min(-1). The median (interquartile range) value for change in cerebral blood volume (mL/100 g) after the first dose in the indomethacin group was -0.4 (-0.3 to -0.6) and in the ibuprofen group was 0.0 (0.1 to -0.1), the difference between the two groups being significant (p<0.001). Cerebral oxygen delivery changed significantly after the first dose in the indomethacin group but not in the ibuprofen group. Significant reductions in CBF, cerebral blood volume, and cerebral oxygen delivery also occurred after the 24-h dose of indomethacin, but there were no significant changes after the 48-h dose of saline in the indomethacin group or after the 24- and 48-h doses of ibuprofen. The patent ductus arteriosus closure rates after indomethacin and ibuprofen were 93 and 78%, respectively. We conclude that ibuprofen, unlike indomethacin, has no adverse effects on cerebral hemodynamics and appears to mediate patent ductus arteriosus closure.     

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.