Biomedical subjects

Mona C Toet

Publications and source records attributed to Mona C Toet.

9 recordsLinked to original sources

PubMed2006

Development of an optimal lidocaine infusion strategy for neonatal seizures.

INTRODUCTION: Lidocaine is an effective drug for the treatment of neonatal convulsions not responding to traditional anticonvulsant therapy. However, one of the side-effects is a risk of cardiac arrhythmias. The aim of this study was to develop an optimal dosing strategy with minimal risk of cardiac arrhythmias. MATERIALS AND METHODS: As a first step, we studied 20 neonates during routine treatment of neonatal seizures with lidocaine. All were given a loading dose of 2 mg/kg in 10 min, followed by the continuous infusion of 6 mg/kg per hour for 12 h, 4 mg/kg per hour for 12 h and finally 2 mg/kg per hour for 12 h. Effectiveness, cardiac toxicity and lidocaine plasma concentrations were then determined. RESULTS: No cardiac arrhythmias were observed, and lidocaine was effective in 76% of the treatments. In most of the treatments (13 out of 20) maximal lidocaine plasma concentrations were >9 mg/L. Plasma levels >9 mg/L have been related to cardiac toxicity when used as an anti-arrhythmic drug in adults. It was of interest that all preterm infants showed high lidocaine plasma levels. Secondly, we developed the optimal dosing regimen, which was defined as an infusion regimen at which maximal lidocaine plasma concentrations are <9 mg/L. Simulations with the developed pharmacokinetic model indicated a reduction in the infusion duration of lidocaine at 6 mg/kg per hour from 12 to 6 h. Thirdly, the new lidocaine dosing regimen was evaluated. Fifteen neonates (16 treatments) were studied. No cardiac arrhythmias were observed, and lidocaine was effective in 78% of the treatments. In most of the treatments (11 out of 16) maximal lidocaine plasma concentrations were <9 mg/L. Again preterm infants showed relatively high lidocaine plasma levels. CONCLUSION: A new lidocaine dosing schedule was developed. This new regimen should have a lower risk of cardiac arrhythmias and appears to be as effective in term infants. For preterm infants the optimal regimen needs to be determined.

Anti-Arrhythmia Agents↗

PubMed2006

Amplitude integrated electroencephalography in the full-term newborn.

Amplitude-integrated electroencephalography (aEEG) is beginning to play an important role in the care of full-term infants who have neonatal encephalopathy. The three main features an aEEG provides include (1) the background pattern, showing the activity at admission to the neonatal intensive care unit and the rate of recovery during the first 24 to 48 hours after birth; (2) the presence or absence of sleep-wake cycling; and (3) the presence of most electrographic discharges.

Brain↗

PubMed2006

Cerebral oxygenation and electrical activity after birth asphyxia: their relation to outcome.

OBJECTIVE: To determine the value of regional cerebral oxygen saturation (rSo2), fractional cerebral tissue oxygen extraction (FTOE) measured by near-infrared spectroscopy (NIRS), and amplitude integrated electroencephalogram (aEEG) after birth asphyxia in relation to neurodevelopmental outcome. METHODS: NIRS measured rSo2, FTOE, and aEEG were monitored simultaneously, together with arterial oxygen saturation (Sao2) and blood pressure during the first 48 hours after severe birth asphyxia in 18 term infants. FTOE was calculated as [Sao2-rSo2]/Sao2. Neurodevelopmental outcome was assessed at 3, 9, and 18 months and 3 and 5 years of age. At the time points 6, 12, 18, 24, 30, 36, 42, and 48 hours after birth, the mean values of Sao2, rSo2, FTOE, and mean arterial blood pressure were calculated over a 1-hour period. A stepwise-regression model was used to investigate the relative contribution of rSo2, FTOE, or aEEG to developmental outcome. RESULTS: Nine Infants died during the neonatal period as a result of neurologic deterioration, and 8 infants had a normal outcome at 5 years of age. One child developed learning disabilities and a mild diplegia. The rSo2 and FTOE remained stable in infants with a normal outcome. The rSo2 increased and the FTOE decreased after 24 hours in the infants with an adverse outcome. (rSo2: 65% vs 84% at 12 and 48 hours, respectively; FTOE: 0.32 vs 0.12 at 12 and 48 hours, respectively). aEEG showed the closest relationship with outcome, but also rSo2 showed a significant correlation 24 hours after birth. CONCLUSIONS: rSo2 and FTOE seem to reflect secondary energy failure. aEEG showed the closest relationship with outcome after severe birth asphyxia.

Asphyxia Neonatorum↗

PubMed2005

Cerebral oxygen saturation and electrical brain activity before, during, and up to 36 hours after arterial switch procedure in neonates without pre-existing brain damage: its relationship to neurodevelopmental outcome.

OBJECTIVE: To monitor the pattern of cerebral oxygen saturation (rSat), by use of NIRS, in term infants before, during and after the arterial switch operation and to evaluate its relation to neurodevelopmental outcome. METHODS: In 20 neonates without pre-existing brain damage hemodynamics and arterial oxygen saturation (AO2-Sat) were monitored simultaneously with rSat and amplitude-integrated EEG (aEEG) from 4 h to 12 h before up to 36 h after cardiopulmonary bypass (CPB) and short duration of cardiac arrest during deep hypothermia (DHCA). The Bayleys developmental scale was performed at 30 months. RESULTS: Before surgery rSat was <50% in 16 patients. During CPB rSat increased to normal values, with a sharp decrease during brief CA (median 6.5 min). Post-CPB rSat showed a transient decrease (30-45%) despite normal PaO2 with sustained normalization after 6-26 h. Recovery time of the rSat seemed longer when pre-operative rSat was below 35%, and for lower minimum nasopharyngeal temperature and longer duration of CPB and of DHCA. Recovery time of the aEEG varied and did not correlate with normalization of rSat. Neurodevelopmental outcome was normal in all but two patients. Patients with lower pre-operative rSat (<35%) tended to have lower DQ (developmental quotient) scores at 30-36 months. (median: mental 102 and motor 101 (range 58-125) compared with mental 100 and motor 110 (range 83-125)) CONCLUSION: Despite prompt normalization of circulation and oxygenation after surgery, recovery of rSat of the brain took 6-26 h, probably because of higher energy demand after CPB. Pre-operative cerebral oxygenation may be underestimated as a possible cause of adverse post-operative outcome.

Brain↗

PubMed2005

Postneonatal epilepsy following amplitude-integrated EEG-detected neonatal seizures.

To assess the incidence of postneonatal epilepsy in term infants treated with antiepileptic drugs for neonatal seizure discharges that were detected with amplitude-integrated electroencephalography (aEEG), 206 term infants were monitored using this modality. They received antiepileptic drugs for clinical as well as subclinical neonatal seizures. Follow-up data were analyzed for the development of postneonatal epilepsy and for their neurodevelopmental outcome, assessed at 3, 9, 18 months, and 3 and 5 years of age. A total of 169 (82%) neonates received two or more antiepileptic drugs. Overall mortality was 39% (n = 80). Forty-one of the 126 survivors (33%) were abnormal at follow-up, and 12 of them developed postneonatal epilepsy (9.4%). Eighty-four children survived after hypoxic-ischemic encephalopathy grade II (n = 92), and 6 (7%) developed postneonatal epilepsy. In this subgroup, no postneonatal epilepsy was observed if seizures were controlled within 48 hours after birth and when not more than two antiepileptic drugs were required. Twenty-four children survived after an intracranial hemorrhage (n = 28), and only 1 (4%) developed postneonatal epilepsy. Eleven children survived after perinatal arterial stroke (n = 13), and 2 (18%) developed postneonatal epilepsy. In conclusion, the incidence of postneonatal epilepsy after treatment of clinical and subclinical neonatal seizures detected with continuous amplitude-integrated electroencephalography was 9.4%; This figure is lower than previously reported in children who only received treatment for clinical seizures.

Anticonvulsants↗

PubMed2005

Treatment of symptomatic congenital cytomegalovirus infection with valganciclovir.

Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. Some congenitally infected infants will develop sequelae later in life, especially sensorineural hearing loss (SNHL) and mental retardation. There is no generally accepted antiviral therapy for the treatment of symptomatic congenital CMV infections yet. We present a neonate with symptomatic congenital CMV infection, who was treated with intravenous (iv) ganciclovir (GCV) during 18 days and subsequently with oral valganciclovir (VGCV) for 5.5 months, in an attempt to prevent development of SNHL. GCV was given intravenously 10 mg/kg/day in two doses and VGCV doses ranged from 280-850 mg/m2 bidaily (bid). Our experience shows that it is not possible to give a fixed dosing regime for VGCV in neonates and that continuous adaptation of dose is necessary to achieve stable target levels of GCV and to keep the viral load in urine at undetectable level. At 18 months of age no hearing deterioration has occurred. While the current findings are encouraging, the limitations of a single case report with a relatively short follow-up emphasizes the need for further prospective randomized studies to evaluate pharmacokinetics, efficacy and safety of VGCV therapy in neonates with congenital CMV infection.

Antiviral Agents↗

PubMed2005

Sleep-wake cycling on amplitude-integrated electroencephalography in term newborns with hypoxic-ischemic encephalopathy.

OBJECTIVE: The objective of this amplitude-integrated electroencephalography (aEEG) study was to evaluate the influence of perinatal hypoxia-ischemia on sleep-wake cycling (SWC) in term newborns and assess whether characteristics of SWC are of predictive value for neurodevelopmental outcome. METHODS: From a consecutive series of newborns born during a 10-year period, the aEEG tracings of 171 term newborns with hypoxic-ischemic encephalopathy were assessed for the presence, time of onset, and quality of SWC. SWC patterns were categorized with regard to the background pattern on which they presented, as normal or abnormal SWC. RESULTS: SWC was seen in 95.4% of the surviving newborns and in 8.1% of those who died. The median time intervals from birth to onset of SWC were significantly different in newborns with hypoxic-ischemic encephalopathy grades I, II, and III (7, 33, and 62 hours, respectively). Newborns with seizure discharges developed SWC with a delay of 30.5 hours. Good outcome was associated with earlier onset of SWC and normal SWC pattern. The difference in the median Griffiths' developmental quotients in newborns who started SWC before/after 36 hours was 8.5 points. The good/poor neurodevelopmental outcome was predicted correctly by the onset of SWC before/after 36 hours in 82% of newborns. CONCLUSIONS: The presence, time of onset, and quality of SWC reflected the severity of the hypoxic-ischemic insult to which newborns were exposed. The time of onset of SWC has a predictive value for neurodevelopmental outcome.

Activity Cycles↗

PubMed2004

Cardiac arrhythmias in neonates receiving lidocaine as anticonvulsive treatment.

UNLABELLED: Lidocaine has been used in neonates as an effective drug in controlling neonatal seizures not responding to traditional anticonvulsant therapy. Little is known about the effect of lidocaine on heart rate or occurrence of cardiac arrhythmias in neonates. The purpose of the present study was to assess the incidence of cardiac arrhythmias associated with lidocaine use for neonatal seizures. A retrospective review was performed in 207 neonates who received lidocaine for treatment of neonatal seizures. All were given a loading dose of 2 mg/kg in 10 min followed by a continuous infusion of 6 mg/kg per h, tailed off over the next 48 h. A total of ten (4,8%) infants developed cardiac arrhythmias during lidocaine infusion. In five infants a bradycardia developed, associated with a prolonged QRS complex in one. In one infant a tachycardia was seen following the bolus administration. In the other four an irregular heart rate was noted. In eight infants the arrhythmias disappeared immediately following discontinuation of lidocaine. In two infants, with severe encephalopathy, who died, the association was not so clear. CONCLUSION: The present study demonstrates that continuous cardiac monitoring of neonates who receive lidocaine for neonatal seizures is indicated, as there is a risk to develop cardiac arrhythmias. Lidocaine should be discontinued immediately when a cardiac arrhythmia occurs. Lidocaine should not be given to patients with a congenital heart disease and to infants who have already been treated with diphantoine.

Anticonvulsants↗

PubMed2002

Comparison between simultaneously recorded amplitude integrated electroencephalogram (cerebral function monitor) and standard electroencephalogram in neonates.

OBJECTIVE: To assess the value and the limitations of amplitude integrated electroencephalogram (EEG) using the cerebral function monitor (CFM) in comparison with standard EEG in neonates who have hypoxic ischemic encephalopathy or were suspected of having convulsions. METHODS: In 36 neonates with a gestational age > or =36 weeks, CFM and simultaneously recorded EEG traces were analyzed off-line and independently classified. CFM background activity: continuous normal voltage; continuous normal voltage, slightly discontinuous (DNV); burst-suppression (BS); continuous extremely low voltage; flat tracing. CFM epileptiform activity: suspected epileptic activity, single seizure (SS), repetitive seizures (RS), status epilepticus (SE). EEG background activity: normal, depressed, low voltage undifferentiated, excessive discontinuity, BS, no activity. Epileptiform activity: interictal unifocal, interictal multifocal, ictal unifocal, ictal multifocal, SE. RESULTS: A total of 33 traces were suitable for analysis. Interobserver agreement on background activity was reached in 31 cases (kappa = 0.92) for CFM and in 27 cases (kappa = 0.74) for EEG. There was full agreement on CFM ictal activity (RS, SS, or SE) and EEG ictal activity. A normal CFM (continuous normal voltage) corresponded with a normal or a depressed EEG in 90% of the cases. The positive predictive value for a severely abnormal CFM (BS, continuous extremely low voltage, flat tracing) to correspond with a severely abnormal EEG (excessive discontinuity, BS, low voltage undifferentiated, no activity) was 100% (negative predictive value, 80%; sensitivity, 76%; specificity, 100%). DNV (10) on CFM corresponded either with depressed (6) or excessive discontinuity (4) on EEG. Ictal activity on EEG corresponded with SS, RS, or SE on CFM in 8 cases (sensitivity, 80%; specificity, 100%; positive predictive value, 100%; negative predictive value, 92%). CONCLUSION: CFM is a reliable tool for monitoring both background patterns (especially normal and severely abnormal) and ictal activity. Certain focal, low amplitude, and very short periods of seizure discharges can be missed. We recommend using CFM as a monitoring device and performing intermittent standard EEG whenever there is any doubt about the classification of the CFM (ie, DNV pattern or suspected epileptiform activity).

Child, Preschool↗