Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Decompressing posthaemorrhagic ventricular dilatation significantly improves regional cerebral oxygen saturation in preterm infants F Norooz1,*, B Urlesberger2,*, V Giordano1, K Klebermasz-Schrehof1, M Weninger1, A Berger1, M Olischar ([email protected])1 1.Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria 2.Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
Keywords Amplitude-integrated electroencephalography, Hydrocephalus, Near-infrared spectroscopy, Posthaemorrhagic ventricular dilatation, Visual evoked potentials Correspondence Monika Olischar, Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Tel: +43-1-40400-3232 | Fax: +43-1-40400-6453 | Email: [email protected] Received 28 May 2014; revised 25 September 2014; accepted 14 January 2015. DOI:10.1111/apa.12942 *These authors contributed equally to this work.
ABSTRACT Aim: This study aimed to delineate the impact of posthaemorrhagic ventricular dilatation (PHVD) on regional cerebral oxygen saturation (rcSO2) in preterm infants before and after ventricular decompression using near-infrared spectroscopy (NIRS). Methods: rcSO2 values were recorded, fractional tissue oxygen extraction (FTOE) was calculated, cerebral ultrasound scans were performed, and resistive indices and ventricular width were collected before and after decompression. Where possible, amplitudeintegrated electroencephalography (aEEG) and visual evoked potentials (VEPs) were recorded before and after decompression. Results: We included nine preterm infants: nine with cranial ultrasound scan data, eight with NIRS data, seven with aEEG data and four with VEPs. The resistive index was stable and remained unchanged after decompression in all patients. Before decompression, the mean rcSO2 value was 42.6 12.9% and increased to 55 12.2% after decompression. With increasing ventricular width, FTOE showed a mean value of 0.51 0.05 and decreased to a mean of 0.39 0.12 after decompression. Amplitudeintegrated electroencephalography showed a more continuous pattern, and VEPs showed delayed latencies in all patients before intervention, improving afterwards. Conclusion: Near-infrared spectroscopy may be of additional clinical value in progressive PHVD to determine the optimal time point for ventricular decompression.
INTRODUCTION Despite advances in perinatal medicine, intraventricular haemorrhage (IVH) remains a major cause of adverse neurodevelopmental outcome in preterm infants (1). When drainage of cerebrospinal fluid is impaired due to pathophysiological processes caused by the haemorrhage, posthaemorrhagic ventricular dilatation (PHVD) subsequently develops (2). PHVD is thought to be associated with profound neurodevelopmental impairment as it leads to increasing intracerebral pressure, distortion and free radical injury with inflammation resulting in white matter injury (2–4). Due to the cartilageous structure and the still open sutures of a preterm infant´s skull, ventricular width can increase without any clinical sign of increasing intracranial pressure. Possible clinical symptoms of ventriculomegaly
Abbreviations aEEG, Amplitude-integrated electroencephalography; EVD, External ventricular drainage; FTOE, Fractional tissue oxygenation extraction; IVH, Intraventricular haemorrhage; NICU, Neonatal intensive care unit; NIRS, Near-infrared spectroscopy; PHVD, Posthaemorrhagic ventricular dilatation; rcSO2, Regional cerebral oxygen saturation; SWC, Sleep–wake cycling; VEP, Visual evoked potential.
include a bulging fontanelle, splayed cranial sutures and episodes of bradycardia. Therefore, close surveillance of the fontanelle and the occipitofrontal circumference, a structured neurological examination and neuroimaging are mandatory to avoid severe brain damage (1). A retrospective multicentre cohort trial including preterm infants with IVH within the Hydrocephalus Clinical Research Network showed that about 40% of patients with PHVD required treatment (3). However, the therapeutic management of
Key notes
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 663–669
This study aimed to delineate the impact of posthaemorrhagic ventricular dilatation (PHVD) on regional cerebral oxygen saturation (rcSO2) in nine preterm infants before and after ventricular decompression using nearinfrared spectroscopy (NIRS). After decompression, the resistive index was stable, the mean rcSO2 value increased, fractional tissue oxygen extraction decreased, and aEEG monitoring and visual evoked potentials both improved. Our findings show that NIRS may determine the optimal time point for ventricular decompression.
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PHVD is complex with regard to the optimal timing and method of ventricular decompression (5). The decision when to intervene is so far mainly based on clinical signs and on sonographic changes using cranial ultrasound scans in terms of ventricular index and resistive index (4–6). Electrophysiological methods, such as amplitude-integrated electroencephalography (aEEG) as well as visual evoked potentials (VEPs), have shown to be of additional value in narrowing the right time point for intervention (4–6). Preterm infants with PHVD show suppressed background patterns in aEEG even before clinical signs of increasing intracranial pressure or sonographic changes of cerebral perfusion can be observed (9,10). After ventricular decompression, a continuous aEEG pattern can be observed in most patients (11). Similar to these findings, studies have shown a delay in latencies of VEPs with increasing intracranial pressure and a normalisation thereof after neurosurgical intervention (4,5,11). However, little is known about changes in cerebral oxygenation in preterm infants with PHVD (6). Therefore, we aimed to investigate the impact of progressive PHVD on cerebral haemodynamics using near-infrared spectroscopy (NIRS) in preterm infants additionally to routine cranial ultrasound imaging, aEEG monitoring as well as VEPs. In doing so, we mainly focused on the additional value of NIRS when using different neurophysiological methods and we hypothesised that NIRS would detect changes in haemodynamics due to a cerebral circulatory compromise with increased intracranial pressure.
PATIENTS AND METHODS Between June 2011 and March 2013, all patients admitted to the neonatal intensive care unit (NICU) of the Medical University of Vienna presenting with severe IVH and subsequent progressive PHVD were eligible for inclusion in the present prospective observational study. Data on those patients who required ventricular decompression were used for analysis after informed parental consent had been obtained. The study was approved by the local ethics committee (EK-Nr: 369/2011). Cranial ultrasound All preterm infants admitted to our unit received a routine cranial ultrasound scan on day 1 of life and days 3, 5, 7 and 10, followed by a weekly schedule using the Acuson Sequoia C512 (Siemens AcusonTM) with a 7.5 MHz transducer. IVH was defined and classified according to the criteria of Papile (7). When IVH > II was detected, cranial ultrasound scans were performed every second day. The ventricular index as described by Levene was used to define PHVD by measuring the distance from the lateral wall of the body of the lateral ventricle to the falx in the coronal plane (8). Furthermore, blood flow velocity and resistive index were assessed in the anterior cerebral artery with every scan using Doppler sonography (20).
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Near-infrared spectroscopy For the purpose of this study, we monitored our patients using NIRS (INVOS System by Covidien©). The neonatal cerebral sensor was applied on the right frontoparietal side of the patient´s head. Changes in regional cerebral oxygen saturation (rcSO2) were measured continuously for at least 2 h before and after ventricular decompression. rcSO2 values were recorded in an 8-sec interval. Mean values were calculated for each patient using all values obtained during the entire measurement period. Additionally, pulseoximetric peripheral oxygen saturation and heart rate were measured continuously. Fractional tissue oxygen extraction (FTOE) was calculated for the entire duration of the measurement before and after decompression to investigate the balance between oxygen delivery and oxygen supply. For calculation, the equation FTOE = (peripheral oxygen saturation-rcSO2)/peripheral oxygen saturation was used. An increased oxygen extraction is reflected by an increased FTOE, whereas a decrease in FTOE describes a decreased oxygen utilisation in the tissue (9). Amplitude-integrated electroencephalography As soon as a patient met the inclusion criteria, we measured brain function using aEEG (Olympic Cerebral Function Monitor 6000). The method is described elsewhere (10). aEEG monitoring was performed until normalisation of the pattern – continuous background pattern and presence of sleep–wake cycling (SWC) – occurred. aEEG tracings were classified according to five background patterns (18): continuous, discontinuous, burst suppression, low voltage pattern and flat trace. In addition, the appearance of SWC and the presence of seizure activity were described. SWC was described as cyclical sinusoidal variations of amplitude and continuity with a minimum duration of 20 min and classified in mature and immature SWC (11,18). Seizure activity was described as single seizures, repetitive seizures or status epilepticus (18). The aEEG pattern was then scored according to the following: 1. Background activity (age-adequate distribution of pattern according to reference values previously published) (19) 2. Appearance of SWC 3. Occurence of seizure activity: a normal aEEG pattern (score = 0) was defined when all three categories were classified as normal; a moderately abnormal aEEG pattern (score = 1) was defined when one-third of the categories were classified as abnormal; and a severely abnormal aEEG pattern (score = 2) was defined when two to three of three categories were classified as abnormal Visual evoked potentials Furthermore, we aimed to perform VEPs before drainage of cerebrospinal fluid and thereafter using a Nihon Kohden Neuropack S1 MEB9400 Ver. 08-16. We performed VEPs as soon as the ventricular index reached the 97th percentile and after insertion of an external ventricular drainage
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(EVD) as soon as technically possible, meaning as soon as the post-operative bandage after placement of the EVD on the infant’s scalp was removed. Those patients who received VEPs before and after intervention were included in the analysis. The VEPs were carried out in a semi-dark environment. An emitting diode of the VEPs’ red light was held approximately 5 cm from the patient´s eyes. The evoked potentials were recorded by three electrodes placed on the patient´s scalp. For stimulation, a frequency of 0.5 Hz is used, for the emitting light energy was 0.4 Lux with an electrical impedance below 5 kOhm. Two courses aiming for 30–50 responses were averaged using band pass filter of 1–100 Hz and a sweep time of 1-sec. Trials were performed binocularly. Waveforms and latencies were analysed off-line for every measurement. According to the reference values of Pike et al. (21), reproducible positive and negative waves were named in the order of their appearance N0, N1, P1, N2, P2 and N3. Neurosurgical intervention A ventricular decompression was performed when the patient presented with clinical signs of increased intracranial pressure, such as increasing frequency of apnoeas, bradycardia, drowsiness, vomiting, increasing head circumference or a bulging fontanelle and/or the ventricular index in cranial ultrasound scans crossing the 97th percentile plus 4 mm. The intervention of choice for ventricular decompression at our institution is the insertion of an EVD. The procedure is performed at the bedside by the neurosurgical team under general anaesthesia including intubation and mechanical ventilation for very small or haemodynamically unstable patients. We administer 5 µg/kg fentanyl and, where necessary, an additional dosage of 0.1 mg/kg vecuronium bromide. The correct placement of the EVD in the ventricle is verified using ultrasound right after the insertion. Furthermore, every patient receives perioperative antibiotic prophylaxis with cefuroxime for a total duration of 3 days. Patients are extubated the same day, as soon as the procedure is over. Postinterventional follow-up at our unit includes a close clinical monitoring, daily cerebral ultra-
sound scans including VI and Doppler measurements with the calculation of RI, aEEG monitoring and VEPs where possible. Every second day, cerebrospinal fluid samples are collected for microbiological investigations. The drained amount of cerebrospinal fluid per day was 0.5–1 mL/kg/h. Statistical analysis The SAS (SAS/STAT User’s Guide version 9.3 2002-2010 by SAS Institute Inc, Cary, NC, USA) was used for statistical analysis. Considering the small sample size, nonparametric tests were used for the detection of differences between means before and after the Intervention.
RESULTS Patients During the study period, 10 patients acquired an IVH with consecutive PHVD and the need for ventricular decompression: two with IVH grade II, six with IVH grade III and two with IVH grade IV. Patient number eight was born at 23 + 4 weeks’ gestational age with a birthweight of 380 g suffering from necrotising enterocolitis. He died of septicaemia within 3 h of EVD placement. Because of his very early death, immediately after EVD placement, we thought this infant might not be representative, and we excluded him from the analysis. We had cranial ultrasound scan data for nine, NIRS data for eight, aEEG data for seven and VEPs for four patients. All patients received sedative and analgesic drugs before and after the intervention. None of them required anticonvulsive treatment and six required more than one EVD. However, in this study, we only collected data about changes and fluctuations before and after the first ventricular decompression. The patients´ characteristics are summarised in Table 1. NIRS results Near-infrared spectroscopy measurements of eight of the nine patients were of high quality and could therefore be included into analysis. The median total duration was 4 h (Q1–Q3: 2.75–6.62) before and 12.75 h (Q1–Q3: 4.12–25) after EVD placement. The last NIRS measurement before
Table 1 Clinical characteristics of study cohort Variable PID
GA (weeks + days)
1 2 3 4 5 6 7 9 10
26 27 35 26 29 26 25 27 27
+ + + + + + + + +
8 3 4 6 4 2 4 2 6
BW (g)
Apgar (1/5/10 min)
IVH (grade)
EVD (day of life)
Shunt
Survival
840 1060 1970 1043 955 1000 900 1200 826
2/3/intubation 7/8/8 1/intubation 2/6/6 8/8/9 4/6/8 6/7/8 5/7/7 6/8/9
IV lll ll lll ll lll ll, lll ll, lll lll
11 12 23 16 17 35 18 17 13
Yes No Yes No No Yes Yes No No
Yes Yes No Yes Yes Yes Yes Yes Yes
PID, Patient identification number; GA, Gestational age; BW, Birthweight; IVH, Intraventricular haemorrhage; EVD, External ventricular drainage.
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decompression was performed within a median of 5.8 h (Q1–Q3: 1–18.6), and the first NIRS after decompression was performed within a median of 24.62 h (Q1–Q3: 7.4– 46). In eight of the nine infants, we observed an increase of rcSO2 levels after ventricular decompression, and in seven of the infants, we observed a consecutive decrease in FTOE values after the intervention. rcSO2 increased by a mean of 12.38%, whereas the FTOE values decreased by a mean of 0.115 after the intervention (Figs 1 and 2, Table 2). The mean increase in rcSO2 showed a trend towards significance, and the mean decrease in FTOE was significant (p = 0.065 and 0.015, respectively). Cranial ultrasound results In five patients, ventricular index exceeded the 97th percentile plus 4 mm according to Levene when the EVD was inserted, and in four patients, EVD was placed earlier because of clinical deterioration (ventricular index > 97th
rcSO2% before and after EVD insertion 80
rcSO2%
40
*
1
2
3
4
5
6
7
Patients 1 rcSO2% before EVD insertion 54 rcSO2% after EVD insertion 67
2 50 59
3 48 60
4 44 49
5 35 51
10 6 15 32
Mean 7 54 71
10 Mean 41 42.6 51 55
Figure 1 rcSO2% before and after external ventricular drainage (EVD) insertion.
FTOE before and after EVD insertion 0.7 0.6 FTOE
0.5 0.4
*
0.3 0.2 0.1 1
2
3
4
5
Patients
6
7
10
Mean
4 7 1 2 3 5 6 10 Mean FTOE before EVD insertion 0.44 0.45 0.51 0.5 0.62 0.55 0.52 0.52 0.51 FTOE after EVD insertion 0.27 0.37 0.37 0.43 0.45 0.64 0.23 0.43 0.39
Figure 2 Fractional tissue oxygen extraction (FTOE) before and after external ventricular drainage (EVD) insertion.
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After intervention
p-Value
229 15.5
201 28
0.400
370 19.7
322 17
0.029*
517 39
420 45.8
0.029*
1.14 0.69 14.3 57.1
0.6 0.78 57.1 28.6
0.174
28.6 57.2 42.9 0 0.51 0.05 42.6 12.9
14.3 42.9 57.1 14.3 0.39 0.12 55 12.2
0.015* 0.065
percentile). All patients showed normal resistive index values in the arterial cerebral artery before ventricular decompression. Before EVD insertion, the median resistive index was 0.76 (range: 0.68–0.8) and remained unchanged after decompression showing a median of 0.76 (range: 0.74– 0.77).
20
0
VEP data P1 latency in ms (mean SD) N2 latency in ms (mean SD) P2 Latency in ms (mean SD) aEEG data aEEG score (mean SD) aEEG normal (%) aEEG moderately abnormal (%) aEEG severely abnormal (%) SWC no or immature (%) SWC present (%) Seizures (%) NIRS FTOE (mean SD) rcSO2% (mean SD)
Before intervention
*Statistically significant.
60
0
Table 2 Results of fVEPS, amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) prior to and after neurosurgical intervention
aEEG results Electrocortical activity was measured for a median total duration of 10 h (Q1–Q3: 3.5–20.2) before and a mean total of 14.5 h (Q1–Q3: 12–18) after ventricular decompression. aEEG measurements of seven of the nine patients were of high quality and could therefore be included in the analysis. In these seven patients, aEEG was performed at a median of 7.2 h (Q1–Q3: 1–44) before EVD insertion and within a median of 33 h (Q1–Q3: 3–110) afterwards. In all patients, aEEG showed a discontinuous pattern before intervention normalising to a more continuous pattern after decompression (Fig. 3). SWC significantly improved in two patients, three patients showed immature SWC before and after intervention, and two patients showed mature SWC already before intervention. aEEG patterns improved at a mean of 12.5 days (range: 0.5–77 days) after intervention. An example is shown in Figure 4. aEEG scores before and after intervention are summarised in Table 2. VEP results Visual evoked potentials measurements were available in four of nine patients. They were performed at a mean of 7 days (1–19 days) before and 18 days (2–46 days) after decompression. The results are summarised in Table 2.
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ventricular index, whereas deteriorations in aEEG background pattern, increases in VEP latencies and deterioration of rcSO2 and FTOE could be detected with progressive ventricular dilatation.
Figure 3 Percentage of amplitude-integrated electroencephalography (aEEG) patterns before and after external ventricular drainage (EVD) insertion.
A
B
Figure 4 Example of a preterm baby boy born 25 + 4 weeks’ gestational age, intraventricular haemorrhage (IVH) III both sides on day of life 2; amplitudeintegrated electroencephalography (aEEG) before external ventricular drainage (EVD) insertion on the day of surgery shows a suppressed background pattern (burst suppression/flat trace) and no sleep–wake cycling (SWC); aEEG after EVD insertion 1.5 days after surgery shows a discontinuous/continuous background pattern with the re-emergence of immature SWC.
Correlation of cranial ultrasound, NIRS, aEEG and VEP results The analysis of all data obtained from cranial ultrasound, NIRS, aEEG and VEP showed that cranial ultrasound did not reveal signs of an impaired cerebral haemodynamic before ventricular decompression. Cranial ultrasound did not show abnormal resistive index values with increasing
DISCUSSION The present study demonstrates the effect of progressive PHVD and subsequent cerebrospinal fluid drainage on cerebral oxygen saturation and oxygen extraction measured by NIRS and its effects on cranial ultrasound, aEEG and VEPs. We found that NIRS was another sensitive tool and of additional help for the decision of when to intervene in the course of PHVD. In all patients, the aEEG pattern normalised from a primarily discontinuous or suppressed pattern to a more continuous pattern with the presence of SWC. We could reproduce our findings, published earlier, where we demonstrated that aEEG indicated an impaired cerebral function before clinical or sonographic signs of an increased cerebral pressure occurred (11). Interestingly, these findings were not reproduced by de Vries et al. They studied 11 preterm infants with progressive ventricular dilatation requiring reservoir insertion, and their patients did not show any signs of aEEG deterioration before intervention (23). One possible reason for this might be a difference in gestational age, as the de Vries study consisted of preterm infants with a postmenstrual age of >30 weeks, whereas our study patients had a mean gestational age of 27.5 weeks. We hypothesise that the pathology of the IVH itself and/or the ventricular dilatation potentially increased the impact on brain function of the most immature preterm infants compared to the less immature. Also, the degree of IVH itself could present another explanation for the differences in our observations, as it is known that IVH grade IV has a greater impact on aEEG background patterns than lowgrade IVH (24). Additionally, all of our patients were treated by inserting an EVD instead of a cerebral spinal fluid reservoir, allowing a continuous decompression of the ventricular system, whereas the daily punctures of a reservoir system may result in rather rapid changes of ventricular size and pressure directly after the procedure. In the present study, VEP measurements could only be performed in four patients. Also, measurements were only performed irregularly with a great time lag to and from the time of ventricular decompression. Nevertheless, the results show an increase in latencies, especially in N1 and P2 before ventricular decompression improving after decompression. The present results confirm our previous findings, showing the relevance of VEPs as an additional tool for monitoring patients with increasing ventricular width (11). Both NIRS parameters, rcSO2 and FTOE, were impaired with increasing ventricular size in all patients. Any increase in cerebral FTOE may be due to either a compensation of decreased oxygen delivery or an increased oxygen extraction of the tissue, due to increased activity. Taking into account the reduced aEEG activity with increasing ventricular width, we hypothesise that within the present study an
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 663–669
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impairment of oxygen delivery was present during the increase of intracranial pressure. Right after ventricular decompression, an increase of rcSO2 could be observed, and in correlation with this, the FTOE decreased. These observations are supported by the findings of Soul et al., who demonstrated that removal of cerebrospinal fluid in infants with PHVD had an important and potentially beneficial effect on cerebral haemodynamics (12). The SafeBoosC trial, which used NIRS as an early tool in intensive care in very preterm infants, was conducted in Europe (25). The protocol included a clinical intervention algorithm based on the main determinants of cerebral perfusion–oxygenation changes during the first hours after birth. The authors proposed a threshold of 55% rcSO2 for initiation of a clinical intervention algorithm. Interestingly, our patients showed a mean rcSO2 of 42.6% before intervention. After ventricular decompression, rcSO2 increased to a mean of 55%. We hypothesise that this threshold value could be of use in the decision when to intervene in patients with progressive PHVD. The strength and novelty of the present study was the utilisation of all previously presented methods together. Cranial ultrasound scans, aEEG, VEPs and finally NIRS may represent pieces of a puzzle, and all together have their value in the management of patients with PHVD. We were able to show that resistive index was the weakest parameter for the decision when to intervene. aEEG and VEPs were very helpful tools though not necessarily the most sensitive parameters. When interpreting our NIRS results, we conclude that the changes we observed before and after decompression were not only sensitive and accurate, but also potentially important indicators of the instantaneous condition of the patient. According to the protocol limits of the SafeBoosC trial (25), we propose that the threshold of rcSO2 of 55% could also be of use in the difficult discussion with regard to when to intervene in patients suffering from PHVD. Larger prospective trials will be needed to verify this hypothesis. Limitations Although cranial ultrasound scans were obtained in all patients, we know that measuring the ventricular index only is one pitfall of the present study. As many ventricles do not enlarge laterally but occipitally, the additional information of the thalamo-occipital distance as well as the anterior horn width might has been of additional value. Also, the timing of our aEEG, NIRS and VEP measurements is not optimal. It would have been ideal to have continuous aEEG and NIRS monitoring until 1 h before EVD insertion and to continue the monitoring the same day shortly after surgery. Unfortunately, this tight schedule was complicated by the preparation for surgery, and furthermore, by extubation immediately after the intervention. Only the VEP data of four patients could be included in the analysis, because VEP measurements had often been collected very early before or very late after decompression. The problem with our way of dealing with PHVD is that the freshly sutured canula of the EVD needs to be protected by
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a bandage during the first week and sometimes longer. This impedes the performance of VEPs and explains the long delays in the present study. Therefore, we are aware that our results have to be interpreted as preliminary results and that the following study protocol needs to include closer monitoring intervals, simultaneous aEEG and NIRS measurements, consistent VEP measurements in all patients and a greater number of patients through a multicentre study design. Simultaneity of measurements using different tools is also important to define which tool is most sensitive in revealing signs of deterioration.
CONCLUSION All patients with PHVD showed a compromised rcSO2 before intervention, improving after EVD placement in all but one. Corresponding to that, FTOE values were elevated before the intervention and decreased afterwards. The optimal time point of when to intervene in patients presenting with progressive PHVD is still uncertain. aEEG recordings and VEP measurements have already been proven to be of great importance. As mentioned by de Vries et al. (23), the lack of clinical signs or an absence of abnormal aEEG background pattern should not reassure clinicians that a deterioration of cerebral haemodynamics is not taking place. Additionally, NIRS provides further information on cerebral oxygen delivery and extraction. Low rcSO2 values and/or increased FTOE values may be indicative of the necessity to perform ventricular decompression.
References 1. Whitelaw A, Aquilina K. Management of posthaemorrhagic ventricular dilatation. Arch Dis Child Fetal Neonatal Ed 2012; 97: F229–3. 2. Murphy BP, Inder TE, Rooks V, Taylor GA, Anderson NJ, Mogridge N, et al. Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. Arch Dis Child Fetal Neonatal Ed 2002; 87: F37–41. 3. Volpe JJ. Neurology of the newborn, 5th ed. Philadelphia: Saunders Elsevier, 2008. 4. Amato M, Howald H, von Muralt G. Neurological prognosis of high-risk preterm infants with peri-intraventricular hemorrhage and ventricular dilatation. Eur Neurol 1986; 25: 241–7. 5. Wellons JC, Shannon CN, Kulkarni AV, Simon TD, RivaCambrin J, Whitehead WE, et al. A multicenter retrospective comparison of conversion from temporary to permanent cerebrospinal fluid diversion in very low birth weight infants with posthemorrhagic hydrocephalus. J Neurosurg Pediatr 2009; 4: 50–5. 6. Hill A, Volpe JJ. Decrease in pulsatile flow in the anterior cerebral arteries in infantile hydrocephalus. Pediatrics 1982; 69: 4–7. 7. Nishimaki S, Iwasaki Y, Akamatsu H. Cerebral blood flow velocity before and after cerebrospinal fluid drainage in infants with posthemorrhagic hydrocephalus. J Ultrasound Med 2004; 23: 1315–9. 8. Taylor GA. Sonographic assessment of posthemorrhagic ventricular dilatation. Radiol Clin North Am 2001; 39: 541–51.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 663–669
Norooz et al.
9. Olischar M, Klebermass K, Hengl B, Hunt RW, Waldhoer T, Pollak A, et al. Cerebrospinal fluid drainage in posthaemorrhagic ventricular dilatation leads to improvement in amplitude-integrated electroencephalographic activity. Acta Paediatr 2009; 98: 1002–9. 10. Olischar M, Klebermass K, Kuhle S, Hulek M, Messerschmidt A, Weninger M. Progressive posthemorrhagic hydrocephalus leads to changes of amplitude-integrated EEG activity in preterm infants. Childs Nerv Syst 2004; 20: 41–5. € r T, Czaba C, Beke A, 11. Klebermass-Schrehof K, Rona Z, Waldho Weninger M, et al. Can neurophysiological assessment improve timing of intervention in posthaemorrhagic ventricular dilatation? Arch Dis Child Fetal Neonatal Ed 2013; 98: F291–7. 12. Kato T, Okumura A, Hayakawa F, Kuno K, Watanabe K. The evolutionary change of flash visual evoked potentials in preterm infants with periventricular leukomalacia. Clin Neurophysiol 2005; 116: 690–5. 13. Ehle A, Sklar F. Visual evoked potentials in infants with hydrocephalus. Neurology 1979; 29: 1541–4. 14. Alderliesten T, Lemmers PM, Smarius JJ, van de Vosse RE, Baerts W, van Bel F. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatr 2013; 162: 698–704.e2. 15. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92: 529–34. 16. Levene MI. Measurement of the growth of the lateral ventricles in preterm infants with real-time ultrasound. Arch Dis Child 1981; 56: 900–4. 17. Lemmers PM, Toet MC, van Bel F. Impact of patent ductus arteriosus and subsequent therapy with indomethacin on
Decompressing dilated ventricles improves cerebral oxygenation
18.
19.
20.
21.
22.
23.
24.
25.
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cerebral oxygenation in preterm infants. Pediatrics 2008; 121: 142–7. € m-Westas L, Rosen I. Continuous brain-function Hellstro monitoring: state of the art in clinical practice. Semin Fetal Neonatal Med 2006; 11: 503–11. Olischar M, Klebermass K, Kuhle S, Hulek M, Kohlhauser C, € cklinger E, et al. Reference values for amplitude-integrated Ru electroencephalographic activity in preterm infants younger than 30 weeks’ gestational age. Pediatrics 2004; 113: e61–6. Deeg KH, Wolf A. Doppler ultrasound diagnosis of increased intracranial pressure by comparison of 2 blood flow velocities in the extra- and intracranial segment of the internal carotid artery. 2: findings in children with increased intracranial pressure. Ultraschall Med 2001; 22: 66–74. Pike AA, Marlow N, Reber C. Maturation of the flash visual evoked potential in preterm infants. Early Hum Dev 1999; 54: 215–22. Soul JS, Eichenwald E, Walter G, Volpe JJ, du Plessis AJ. CSF removal in infantile posthemorrhagic hydrocephalus results in significant improvement in cerebral hemodynamics. Pediatr Res 2004; 55: 872–6. de Vries LS, Brouwer AJ, Groenendaal F. Posthaemorrhagic ventricular dilatation: when should we intervene? Arch Dis Child Fetal Neonatal Ed 2013; 98: F284–5. Olischar M, Klebermass K, Waldhoer T, Pollak A, Weninger M. Background patterns and sleep-wake cycles on amplitudeintegrated electroencephalography in preterms younger than 30 weeks gestational age with peri-/intraventricular haemorrhage. Acta Paediatr 2007; 96: 1743–50. Pellicer A, Greisen G, Benders M, Claris O, Dempsey E, Fumagalli M, et al. The SafeBoosC phase II randomised clinical trial: a treatment guideline for targeted near-infraredderived cerebral tissue oxygenation versus standard treatment in extremely preterm infants. Neonatology 2013; 104: 171–8.
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REGULAR ARTICLE
Decompressing posthaemorrhagic ventricular dilatation significantly improves regional cerebral oxygen saturation in preterm infants F Norooz1,*, B Urlesberger2,*, V Giordano1, K Klebermasz-Schrehof1, M Weninger1, A Berger1, M Olischar ([email protected])1 1.Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria 2.Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
Keywords Amplitude-integrated electroencephalography, Hydrocephalus, Near-infrared spectroscopy, Posthaemorrhagic ventricular dilatation, Visual evoked potentials Correspondence Monika Olischar, Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Tel: +43-1-40400-3232 | Fax: +43-1-40400-6453 | Email: [email protected] Received 28 May 2014; revised 25 September 2014; accepted 14 January 2015. DOI:10.1111/apa.12942 *These authors contributed equally to this work.
ABSTRACT Aim: This study aimed to delineate the impact of posthaemorrhagic ventricular dilatation (PHVD) on regional cerebral oxygen saturation (rcSO2) in preterm infants before and after ventricular decompression using near-infrared spectroscopy (NIRS). Methods: rcSO2 values were recorded, fractional tissue oxygen extraction (FTOE) was calculated, cerebral ultrasound scans were performed, and resistive indices and ventricular width were collected before and after decompression. Where possible, amplitudeintegrated electroencephalography (aEEG) and visual evoked potentials (VEPs) were recorded before and after decompression. Results: We included nine preterm infants: nine with cranial ultrasound scan data, eight with NIRS data, seven with aEEG data and four with VEPs. The resistive index was stable and remained unchanged after decompression in all patients. Before decompression, the mean rcSO2 value was 42.6 12.9% and increased to 55 12.2% after decompression. With increasing ventricular width, FTOE showed a mean value of 0.51 0.05 and decreased to a mean of 0.39 0.12 after decompression. Amplitudeintegrated electroencephalography showed a more continuous pattern, and VEPs showed delayed latencies in all patients before intervention, improving afterwards. Conclusion: Near-infrared spectroscopy may be of additional clinical value in progressive PHVD to determine the optimal time point for ventricular decompression.
INTRODUCTION Despite advances in perinatal medicine, intraventricular haemorrhage (IVH) remains a major cause of adverse neurodevelopmental outcome in preterm infants (1). When drainage of cerebrospinal fluid is impaired due to pathophysiological processes caused by the haemorrhage, posthaemorrhagic ventricular dilatation (PHVD) subsequently develops (2). PHVD is thought to be associated with profound neurodevelopmental impairment as it leads to increasing intracerebral pressure, distortion and free radical injury with inflammation resulting in white matter injury (2–4). Due to the cartilageous structure and the still open sutures of a preterm infant´s skull, ventricular width can increase without any clinical sign of increasing intracranial pressure. Possible clinical symptoms of ventriculomegaly
Abbreviations aEEG, Amplitude-integrated electroencephalography; EVD, External ventricular drainage; FTOE, Fractional tissue oxygenation extraction; IVH, Intraventricular haemorrhage; NICU, Neonatal intensive care unit; NIRS, Near-infrared spectroscopy; PHVD, Posthaemorrhagic ventricular dilatation; rcSO2, Regional cerebral oxygen saturation; SWC, Sleep–wake cycling; VEP, Visual evoked potential.
include a bulging fontanelle, splayed cranial sutures and episodes of bradycardia. Therefore, close surveillance of the fontanelle and the occipitofrontal circumference, a structured neurological examination and neuroimaging are mandatory to avoid severe brain damage (1). A retrospective multicentre cohort trial including preterm infants with IVH within the Hydrocephalus Clinical Research Network showed that about 40% of patients with PHVD required treatment (3). However, the therapeutic management of
Key notes
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 663–669
This study aimed to delineate the impact of posthaemorrhagic ventricular dilatation (PHVD) on regional cerebral oxygen saturation (rcSO2) in nine preterm infants before and after ventricular decompression using nearinfrared spectroscopy (NIRS). After decompression, the resistive index was stable, the mean rcSO2 value increased, fractional tissue oxygen extraction decreased, and aEEG monitoring and visual evoked potentials both improved. Our findings show that NIRS may determine the optimal time point for ventricular decompression.
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PHVD is complex with regard to the optimal timing and method of ventricular decompression (5). The decision when to intervene is so far mainly based on clinical signs and on sonographic changes using cranial ultrasound scans in terms of ventricular index and resistive index (4–6). Electrophysiological methods, such as amplitude-integrated electroencephalography (aEEG) as well as visual evoked potentials (VEPs), have shown to be of additional value in narrowing the right time point for intervention (4–6). Preterm infants with PHVD show suppressed background patterns in aEEG even before clinical signs of increasing intracranial pressure or sonographic changes of cerebral perfusion can be observed (9,10). After ventricular decompression, a continuous aEEG pattern can be observed in most patients (11). Similar to these findings, studies have shown a delay in latencies of VEPs with increasing intracranial pressure and a normalisation thereof after neurosurgical intervention (4,5,11). However, little is known about changes in cerebral oxygenation in preterm infants with PHVD (6). Therefore, we aimed to investigate the impact of progressive PHVD on cerebral haemodynamics using near-infrared spectroscopy (NIRS) in preterm infants additionally to routine cranial ultrasound imaging, aEEG monitoring as well as VEPs. In doing so, we mainly focused on the additional value of NIRS when using different neurophysiological methods and we hypothesised that NIRS would detect changes in haemodynamics due to a cerebral circulatory compromise with increased intracranial pressure.
PATIENTS AND METHODS Between June 2011 and March 2013, all patients admitted to the neonatal intensive care unit (NICU) of the Medical University of Vienna presenting with severe IVH and subsequent progressive PHVD were eligible for inclusion in the present prospective observational study. Data on those patients who required ventricular decompression were used for analysis after informed parental consent had been obtained. The study was approved by the local ethics committee (EK-Nr: 369/2011). Cranial ultrasound All preterm infants admitted to our unit received a routine cranial ultrasound scan on day 1 of life and days 3, 5, 7 and 10, followed by a weekly schedule using the Acuson Sequoia C512 (Siemens AcusonTM) with a 7.5 MHz transducer. IVH was defined and classified according to the criteria of Papile (7). When IVH > II was detected, cranial ultrasound scans were performed every second day. The ventricular index as described by Levene was used to define PHVD by measuring the distance from the lateral wall of the body of the lateral ventricle to the falx in the coronal plane (8). Furthermore, blood flow velocity and resistive index were assessed in the anterior cerebral artery with every scan using Doppler sonography (20).
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Near-infrared spectroscopy For the purpose of this study, we monitored our patients using NIRS (INVOS System by Covidien©). The neonatal cerebral sensor was applied on the right frontoparietal side of the patient´s head. Changes in regional cerebral oxygen saturation (rcSO2) were measured continuously for at least 2 h before and after ventricular decompression. rcSO2 values were recorded in an 8-sec interval. Mean values were calculated for each patient using all values obtained during the entire measurement period. Additionally, pulseoximetric peripheral oxygen saturation and heart rate were measured continuously. Fractional tissue oxygen extraction (FTOE) was calculated for the entire duration of the measurement before and after decompression to investigate the balance between oxygen delivery and oxygen supply. For calculation, the equation FTOE = (peripheral oxygen saturation-rcSO2)/peripheral oxygen saturation was used. An increased oxygen extraction is reflected by an increased FTOE, whereas a decrease in FTOE describes a decreased oxygen utilisation in the tissue (9). Amplitude-integrated electroencephalography As soon as a patient met the inclusion criteria, we measured brain function using aEEG (Olympic Cerebral Function Monitor 6000). The method is described elsewhere (10). aEEG monitoring was performed until normalisation of the pattern – continuous background pattern and presence of sleep–wake cycling (SWC) – occurred. aEEG tracings were classified according to five background patterns (18): continuous, discontinuous, burst suppression, low voltage pattern and flat trace. In addition, the appearance of SWC and the presence of seizure activity were described. SWC was described as cyclical sinusoidal variations of amplitude and continuity with a minimum duration of 20 min and classified in mature and immature SWC (11,18). Seizure activity was described as single seizures, repetitive seizures or status epilepticus (18). The aEEG pattern was then scored according to the following: 1. Background activity (age-adequate distribution of pattern according to reference values previously published) (19) 2. Appearance of SWC 3. Occurence of seizure activity: a normal aEEG pattern (score = 0) was defined when all three categories were classified as normal; a moderately abnormal aEEG pattern (score = 1) was defined when one-third of the categories were classified as abnormal; and a severely abnormal aEEG pattern (score = 2) was defined when two to three of three categories were classified as abnormal Visual evoked potentials Furthermore, we aimed to perform VEPs before drainage of cerebrospinal fluid and thereafter using a Nihon Kohden Neuropack S1 MEB9400 Ver. 08-16. We performed VEPs as soon as the ventricular index reached the 97th percentile and after insertion of an external ventricular drainage
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(EVD) as soon as technically possible, meaning as soon as the post-operative bandage after placement of the EVD on the infant’s scalp was removed. Those patients who received VEPs before and after intervention were included in the analysis. The VEPs were carried out in a semi-dark environment. An emitting diode of the VEPs’ red light was held approximately 5 cm from the patient´s eyes. The evoked potentials were recorded by three electrodes placed on the patient´s scalp. For stimulation, a frequency of 0.5 Hz is used, for the emitting light energy was 0.4 Lux with an electrical impedance below 5 kOhm. Two courses aiming for 30–50 responses were averaged using band pass filter of 1–100 Hz and a sweep time of 1-sec. Trials were performed binocularly. Waveforms and latencies were analysed off-line for every measurement. According to the reference values of Pike et al. (21), reproducible positive and negative waves were named in the order of their appearance N0, N1, P1, N2, P2 and N3. Neurosurgical intervention A ventricular decompression was performed when the patient presented with clinical signs of increased intracranial pressure, such as increasing frequency of apnoeas, bradycardia, drowsiness, vomiting, increasing head circumference or a bulging fontanelle and/or the ventricular index in cranial ultrasound scans crossing the 97th percentile plus 4 mm. The intervention of choice for ventricular decompression at our institution is the insertion of an EVD. The procedure is performed at the bedside by the neurosurgical team under general anaesthesia including intubation and mechanical ventilation for very small or haemodynamically unstable patients. We administer 5 µg/kg fentanyl and, where necessary, an additional dosage of 0.1 mg/kg vecuronium bromide. The correct placement of the EVD in the ventricle is verified using ultrasound right after the insertion. Furthermore, every patient receives perioperative antibiotic prophylaxis with cefuroxime for a total duration of 3 days. Patients are extubated the same day, as soon as the procedure is over. Postinterventional follow-up at our unit includes a close clinical monitoring, daily cerebral ultra-
sound scans including VI and Doppler measurements with the calculation of RI, aEEG monitoring and VEPs where possible. Every second day, cerebrospinal fluid samples are collected for microbiological investigations. The drained amount of cerebrospinal fluid per day was 0.5–1 mL/kg/h. Statistical analysis The SAS (SAS/STAT User’s Guide version 9.3 2002-2010 by SAS Institute Inc, Cary, NC, USA) was used for statistical analysis. Considering the small sample size, nonparametric tests were used for the detection of differences between means before and after the Intervention.
RESULTS Patients During the study period, 10 patients acquired an IVH with consecutive PHVD and the need for ventricular decompression: two with IVH grade II, six with IVH grade III and two with IVH grade IV. Patient number eight was born at 23 + 4 weeks’ gestational age with a birthweight of 380 g suffering from necrotising enterocolitis. He died of septicaemia within 3 h of EVD placement. Because of his very early death, immediately after EVD placement, we thought this infant might not be representative, and we excluded him from the analysis. We had cranial ultrasound scan data for nine, NIRS data for eight, aEEG data for seven and VEPs for four patients. All patients received sedative and analgesic drugs before and after the intervention. None of them required anticonvulsive treatment and six required more than one EVD. However, in this study, we only collected data about changes and fluctuations before and after the first ventricular decompression. The patients´ characteristics are summarised in Table 1. NIRS results Near-infrared spectroscopy measurements of eight of the nine patients were of high quality and could therefore be included into analysis. The median total duration was 4 h (Q1–Q3: 2.75–6.62) before and 12.75 h (Q1–Q3: 4.12–25) after EVD placement. The last NIRS measurement before
Table 1 Clinical characteristics of study cohort Variable PID
GA (weeks + days)
1 2 3 4 5 6 7 9 10
26 27 35 26 29 26 25 27 27
+ + + + + + + + +
8 3 4 6 4 2 4 2 6
BW (g)
Apgar (1/5/10 min)
IVH (grade)
EVD (day of life)
Shunt
Survival
840 1060 1970 1043 955 1000 900 1200 826
2/3/intubation 7/8/8 1/intubation 2/6/6 8/8/9 4/6/8 6/7/8 5/7/7 6/8/9
IV lll ll lll ll lll ll, lll ll, lll lll
11 12 23 16 17 35 18 17 13
Yes No Yes No No Yes Yes No No
Yes Yes No Yes Yes Yes Yes Yes Yes
PID, Patient identification number; GA, Gestational age; BW, Birthweight; IVH, Intraventricular haemorrhage; EVD, External ventricular drainage.
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decompression was performed within a median of 5.8 h (Q1–Q3: 1–18.6), and the first NIRS after decompression was performed within a median of 24.62 h (Q1–Q3: 7.4– 46). In eight of the nine infants, we observed an increase of rcSO2 levels after ventricular decompression, and in seven of the infants, we observed a consecutive decrease in FTOE values after the intervention. rcSO2 increased by a mean of 12.38%, whereas the FTOE values decreased by a mean of 0.115 after the intervention (Figs 1 and 2, Table 2). The mean increase in rcSO2 showed a trend towards significance, and the mean decrease in FTOE was significant (p = 0.065 and 0.015, respectively). Cranial ultrasound results In five patients, ventricular index exceeded the 97th percentile plus 4 mm according to Levene when the EVD was inserted, and in four patients, EVD was placed earlier because of clinical deterioration (ventricular index > 97th
rcSO2% before and after EVD insertion 80
rcSO2%
40
*
1
2
3
4
5
6
7
Patients 1 rcSO2% before EVD insertion 54 rcSO2% after EVD insertion 67
2 50 59
3 48 60
4 44 49
5 35 51
10 6 15 32
Mean 7 54 71
10 Mean 41 42.6 51 55
Figure 1 rcSO2% before and after external ventricular drainage (EVD) insertion.
FTOE before and after EVD insertion 0.7 0.6 FTOE
0.5 0.4
*
0.3 0.2 0.1 1
2
3
4
5
Patients
6
7
10
Mean
4 7 1 2 3 5 6 10 Mean FTOE before EVD insertion 0.44 0.45 0.51 0.5 0.62 0.55 0.52 0.52 0.51 FTOE after EVD insertion 0.27 0.37 0.37 0.43 0.45 0.64 0.23 0.43 0.39
Figure 2 Fractional tissue oxygen extraction (FTOE) before and after external ventricular drainage (EVD) insertion.
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After intervention
p-Value
229 15.5
201 28
0.400
370 19.7
322 17
0.029*
517 39
420 45.8
0.029*
1.14 0.69 14.3 57.1
0.6 0.78 57.1 28.6
0.174
28.6 57.2 42.9 0 0.51 0.05 42.6 12.9
14.3 42.9 57.1 14.3 0.39 0.12 55 12.2
0.015* 0.065
percentile). All patients showed normal resistive index values in the arterial cerebral artery before ventricular decompression. Before EVD insertion, the median resistive index was 0.76 (range: 0.68–0.8) and remained unchanged after decompression showing a median of 0.76 (range: 0.74– 0.77).
20
0
VEP data P1 latency in ms (mean SD) N2 latency in ms (mean SD) P2 Latency in ms (mean SD) aEEG data aEEG score (mean SD) aEEG normal (%) aEEG moderately abnormal (%) aEEG severely abnormal (%) SWC no or immature (%) SWC present (%) Seizures (%) NIRS FTOE (mean SD) rcSO2% (mean SD)
Before intervention
*Statistically significant.
60
0
Table 2 Results of fVEPS, amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) prior to and after neurosurgical intervention
aEEG results Electrocortical activity was measured for a median total duration of 10 h (Q1–Q3: 3.5–20.2) before and a mean total of 14.5 h (Q1–Q3: 12–18) after ventricular decompression. aEEG measurements of seven of the nine patients were of high quality and could therefore be included in the analysis. In these seven patients, aEEG was performed at a median of 7.2 h (Q1–Q3: 1–44) before EVD insertion and within a median of 33 h (Q1–Q3: 3–110) afterwards. In all patients, aEEG showed a discontinuous pattern before intervention normalising to a more continuous pattern after decompression (Fig. 3). SWC significantly improved in two patients, three patients showed immature SWC before and after intervention, and two patients showed mature SWC already before intervention. aEEG patterns improved at a mean of 12.5 days (range: 0.5–77 days) after intervention. An example is shown in Figure 4. aEEG scores before and after intervention are summarised in Table 2. VEP results Visual evoked potentials measurements were available in four of nine patients. They were performed at a mean of 7 days (1–19 days) before and 18 days (2–46 days) after decompression. The results are summarised in Table 2.
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ventricular index, whereas deteriorations in aEEG background pattern, increases in VEP latencies and deterioration of rcSO2 and FTOE could be detected with progressive ventricular dilatation.
Figure 3 Percentage of amplitude-integrated electroencephalography (aEEG) patterns before and after external ventricular drainage (EVD) insertion.
A
B
Figure 4 Example of a preterm baby boy born 25 + 4 weeks’ gestational age, intraventricular haemorrhage (IVH) III both sides on day of life 2; amplitudeintegrated electroencephalography (aEEG) before external ventricular drainage (EVD) insertion on the day of surgery shows a suppressed background pattern (burst suppression/flat trace) and no sleep–wake cycling (SWC); aEEG after EVD insertion 1.5 days after surgery shows a discontinuous/continuous background pattern with the re-emergence of immature SWC.
Correlation of cranial ultrasound, NIRS, aEEG and VEP results The analysis of all data obtained from cranial ultrasound, NIRS, aEEG and VEP showed that cranial ultrasound did not reveal signs of an impaired cerebral haemodynamic before ventricular decompression. Cranial ultrasound did not show abnormal resistive index values with increasing
DISCUSSION The present study demonstrates the effect of progressive PHVD and subsequent cerebrospinal fluid drainage on cerebral oxygen saturation and oxygen extraction measured by NIRS and its effects on cranial ultrasound, aEEG and VEPs. We found that NIRS was another sensitive tool and of additional help for the decision of when to intervene in the course of PHVD. In all patients, the aEEG pattern normalised from a primarily discontinuous or suppressed pattern to a more continuous pattern with the presence of SWC. We could reproduce our findings, published earlier, where we demonstrated that aEEG indicated an impaired cerebral function before clinical or sonographic signs of an increased cerebral pressure occurred (11). Interestingly, these findings were not reproduced by de Vries et al. They studied 11 preterm infants with progressive ventricular dilatation requiring reservoir insertion, and their patients did not show any signs of aEEG deterioration before intervention (23). One possible reason for this might be a difference in gestational age, as the de Vries study consisted of preterm infants with a postmenstrual age of >30 weeks, whereas our study patients had a mean gestational age of 27.5 weeks. We hypothesise that the pathology of the IVH itself and/or the ventricular dilatation potentially increased the impact on brain function of the most immature preterm infants compared to the less immature. Also, the degree of IVH itself could present another explanation for the differences in our observations, as it is known that IVH grade IV has a greater impact on aEEG background patterns than lowgrade IVH (24). Additionally, all of our patients were treated by inserting an EVD instead of a cerebral spinal fluid reservoir, allowing a continuous decompression of the ventricular system, whereas the daily punctures of a reservoir system may result in rather rapid changes of ventricular size and pressure directly after the procedure. In the present study, VEP measurements could only be performed in four patients. Also, measurements were only performed irregularly with a great time lag to and from the time of ventricular decompression. Nevertheless, the results show an increase in latencies, especially in N1 and P2 before ventricular decompression improving after decompression. The present results confirm our previous findings, showing the relevance of VEPs as an additional tool for monitoring patients with increasing ventricular width (11). Both NIRS parameters, rcSO2 and FTOE, were impaired with increasing ventricular size in all patients. Any increase in cerebral FTOE may be due to either a compensation of decreased oxygen delivery or an increased oxygen extraction of the tissue, due to increased activity. Taking into account the reduced aEEG activity with increasing ventricular width, we hypothesise that within the present study an
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 663–669
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impairment of oxygen delivery was present during the increase of intracranial pressure. Right after ventricular decompression, an increase of rcSO2 could be observed, and in correlation with this, the FTOE decreased. These observations are supported by the findings of Soul et al., who demonstrated that removal of cerebrospinal fluid in infants with PHVD had an important and potentially beneficial effect on cerebral haemodynamics (12). The SafeBoosC trial, which used NIRS as an early tool in intensive care in very preterm infants, was conducted in Europe (25). The protocol included a clinical intervention algorithm based on the main determinants of cerebral perfusion–oxygenation changes during the first hours after birth. The authors proposed a threshold of 55% rcSO2 for initiation of a clinical intervention algorithm. Interestingly, our patients showed a mean rcSO2 of 42.6% before intervention. After ventricular decompression, rcSO2 increased to a mean of 55%. We hypothesise that this threshold value could be of use in the decision when to intervene in patients with progressive PHVD. The strength and novelty of the present study was the utilisation of all previously presented methods together. Cranial ultrasound scans, aEEG, VEPs and finally NIRS may represent pieces of a puzzle, and all together have their value in the management of patients with PHVD. We were able to show that resistive index was the weakest parameter for the decision when to intervene. aEEG and VEPs were very helpful tools though not necessarily the most sensitive parameters. When interpreting our NIRS results, we conclude that the changes we observed before and after decompression were not only sensitive and accurate, but also potentially important indicators of the instantaneous condition of the patient. According to the protocol limits of the SafeBoosC trial (25), we propose that the threshold of rcSO2 of 55% could also be of use in the difficult discussion with regard to when to intervene in patients suffering from PHVD. Larger prospective trials will be needed to verify this hypothesis. Limitations Although cranial ultrasound scans were obtained in all patients, we know that measuring the ventricular index only is one pitfall of the present study. As many ventricles do not enlarge laterally but occipitally, the additional information of the thalamo-occipital distance as well as the anterior horn width might has been of additional value. Also, the timing of our aEEG, NIRS and VEP measurements is not optimal. It would have been ideal to have continuous aEEG and NIRS monitoring until 1 h before EVD insertion and to continue the monitoring the same day shortly after surgery. Unfortunately, this tight schedule was complicated by the preparation for surgery, and furthermore, by extubation immediately after the intervention. Only the VEP data of four patients could be included in the analysis, because VEP measurements had often been collected very early before or very late after decompression. The problem with our way of dealing with PHVD is that the freshly sutured canula of the EVD needs to be protected by
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a bandage during the first week and sometimes longer. This impedes the performance of VEPs and explains the long delays in the present study. Therefore, we are aware that our results have to be interpreted as preliminary results and that the following study protocol needs to include closer monitoring intervals, simultaneous aEEG and NIRS measurements, consistent VEP measurements in all patients and a greater number of patients through a multicentre study design. Simultaneity of measurements using different tools is also important to define which tool is most sensitive in revealing signs of deterioration.
CONCLUSION All patients with PHVD showed a compromised rcSO2 before intervention, improving after EVD placement in all but one. Corresponding to that, FTOE values were elevated before the intervention and decreased afterwards. The optimal time point of when to intervene in patients presenting with progressive PHVD is still uncertain. aEEG recordings and VEP measurements have already been proven to be of great importance. As mentioned by de Vries et al. (23), the lack of clinical signs or an absence of abnormal aEEG background pattern should not reassure clinicians that a deterioration of cerebral haemodynamics is not taking place. Additionally, NIRS provides further information on cerebral oxygen delivery and extraction. Low rcSO2 values and/or increased FTOE values may be indicative of the necessity to perform ventricular decompression.
References 1. Whitelaw A, Aquilina K. Management of posthaemorrhagic ventricular dilatation. Arch Dis Child Fetal Neonatal Ed 2012; 97: F229–3. 2. Murphy BP, Inder TE, Rooks V, Taylor GA, Anderson NJ, Mogridge N, et al. Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. Arch Dis Child Fetal Neonatal Ed 2002; 87: F37–41. 3. Volpe JJ. Neurology of the newborn, 5th ed. Philadelphia: Saunders Elsevier, 2008. 4. Amato M, Howald H, von Muralt G. Neurological prognosis of high-risk preterm infants with peri-intraventricular hemorrhage and ventricular dilatation. Eur Neurol 1986; 25: 241–7. 5. Wellons JC, Shannon CN, Kulkarni AV, Simon TD, RivaCambrin J, Whitehead WE, et al. A multicenter retrospective comparison of conversion from temporary to permanent cerebrospinal fluid diversion in very low birth weight infants with posthemorrhagic hydrocephalus. J Neurosurg Pediatr 2009; 4: 50–5. 6. Hill A, Volpe JJ. Decrease in pulsatile flow in the anterior cerebral arteries in infantile hydrocephalus. Pediatrics 1982; 69: 4–7. 7. Nishimaki S, Iwasaki Y, Akamatsu H. Cerebral blood flow velocity before and after cerebrospinal fluid drainage in infants with posthemorrhagic hydrocephalus. J Ultrasound Med 2004; 23: 1315–9. 8. Taylor GA. Sonographic assessment of posthemorrhagic ventricular dilatation. Radiol Clin North Am 2001; 39: 541–51.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 663–669
Norooz et al.
9. Olischar M, Klebermass K, Hengl B, Hunt RW, Waldhoer T, Pollak A, et al. Cerebrospinal fluid drainage in posthaemorrhagic ventricular dilatation leads to improvement in amplitude-integrated electroencephalographic activity. Acta Paediatr 2009; 98: 1002–9. 10. Olischar M, Klebermass K, Kuhle S, Hulek M, Messerschmidt A, Weninger M. Progressive posthemorrhagic hydrocephalus leads to changes of amplitude-integrated EEG activity in preterm infants. Childs Nerv Syst 2004; 20: 41–5. € r T, Czaba C, Beke A, 11. Klebermass-Schrehof K, Rona Z, Waldho Weninger M, et al. Can neurophysiological assessment improve timing of intervention in posthaemorrhagic ventricular dilatation? Arch Dis Child Fetal Neonatal Ed 2013; 98: F291–7. 12. Kato T, Okumura A, Hayakawa F, Kuno K, Watanabe K. The evolutionary change of flash visual evoked potentials in preterm infants with periventricular leukomalacia. Clin Neurophysiol 2005; 116: 690–5. 13. Ehle A, Sklar F. Visual evoked potentials in infants with hydrocephalus. Neurology 1979; 29: 1541–4. 14. Alderliesten T, Lemmers PM, Smarius JJ, van de Vosse RE, Baerts W, van Bel F. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatr 2013; 162: 698–704.e2. 15. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92: 529–34. 16. Levene MI. Measurement of the growth of the lateral ventricles in preterm infants with real-time ultrasound. Arch Dis Child 1981; 56: 900–4. 17. Lemmers PM, Toet MC, van Bel F. Impact of patent ductus arteriosus and subsequent therapy with indomethacin on
Decompressing dilated ventricles improves cerebral oxygenation
18.
19.
20.
21.
22.
23.
24.
25.
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cerebral oxygenation in preterm infants. Pediatrics 2008; 121: 142–7. € m-Westas L, Rosen I. Continuous brain-function Hellstro monitoring: state of the art in clinical practice. Semin Fetal Neonatal Med 2006; 11: 503–11. Olischar M, Klebermass K, Kuhle S, Hulek M, Kohlhauser C, € cklinger E, et al. Reference values for amplitude-integrated Ru electroencephalographic activity in preterm infants younger than 30 weeks’ gestational age. Pediatrics 2004; 113: e61–6. Deeg KH, Wolf A. Doppler ultrasound diagnosis of increased intracranial pressure by comparison of 2 blood flow velocities in the extra- and intracranial segment of the internal carotid artery. 2: findings in children with increased intracranial pressure. Ultraschall Med 2001; 22: 66–74. Pike AA, Marlow N, Reber C. Maturation of the flash visual evoked potential in preterm infants. Early Hum Dev 1999; 54: 215–22. Soul JS, Eichenwald E, Walter G, Volpe JJ, du Plessis AJ. CSF removal in infantile posthemorrhagic hydrocephalus results in significant improvement in cerebral hemodynamics. Pediatr Res 2004; 55: 872–6. de Vries LS, Brouwer AJ, Groenendaal F. Posthaemorrhagic ventricular dilatation: when should we intervene? Arch Dis Child Fetal Neonatal Ed 2013; 98: F284–5. Olischar M, Klebermass K, Waldhoer T, Pollak A, Weninger M. Background patterns and sleep-wake cycles on amplitudeintegrated electroencephalography in preterms younger than 30 weeks gestational age with peri-/intraventricular haemorrhage. Acta Paediatr 2007; 96: 1743–50. Pellicer A, Greisen G, Benders M, Claris O, Dempsey E, Fumagalli M, et al. The SafeBoosC phase II randomised clinical trial: a treatment guideline for targeted near-infraredderived cerebral tissue oxygenation versus standard treatment in extremely preterm infants. Neonatology 2013; 104: 171–8.
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