Keywords cardiopulmonary bypass - neurology/neurological - hypothermia/circulatory arrest -
pediatric - ischemia/reperfusion
Introduction
Therapeutic hypothermia is standard practice during pediatric open-heart surgery to
reduce cerebral metabolism and oxygen consumption and thus increase tissue tolerance
of a temporarily poor oxygen supply, with the aim of neuroprotection. From animal
studies, we know that hypothermia reduces cerebral metabolism by approximately 5 to
10% per °C cooling and, therefore, decreases the oxygen demand in neurons.[1 ] Although deep hypothermic cardiac arrest (DHCA) is an older organ protection technique,
it remains indispensable in certain types of cardiac surgical procedures such as aortic
arch reconstruction. Nowadays, selective cerebral perfusion (SCP) is the most widespread
technique for neuroprotection.[2 ]
[3 ] Intraoperative hypoxia and other critical events trigger impaired outcomes.[4 ] Cerebral hypoperfusion is known to carry the highest risk during cooling and the
subsequent rewarming phase during cardiopulmonary bypass (CPB).[5 ] There are different cooling and rewarming techniques, and protocols are not uniform,
varying from center to center. Other surgical disciplines already have standardized
rewarming protocols, e.g., after asphyxia or resuscitation, with rewarming periods
extending up to 3 days.[6 ]
Relying on these guidelines, in this study, we tried to evaluate the rewarming speed's
impact on cerebral oxygenation and electrocortical activity. Our infants with congenital
heart defects were rewarmed following an in-house standard or a modified slow-rewarming
strategy after deep hypothermic CPB. Simultaneous extended neuromonitoring was performed
using near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography
(aEEG).
NIRS serves to monitor the potential imbalance of oxygen supply and consumption as
well as hypoxic events. Rising cerebral metabolic rates and decreased oxygen saturation
have been reported during cardiac bypass surgery. Findings like this during intraoperative
phases might indicate, i.e., the oxygen supply's adequacy during antegrade SCP.[7 ]
The aEEG as a diagnostic tool enables reliable interpretation of electrocortical activity.
Considering that anesthetic drugs suppress the clinical symptoms of seizures and that
neonatal seizures are usually subclinical, aEEG provides additional information.
Suppressed aEEG patterns and seizures tend to be more common in the neonatal brain.[8 ] Age-dependent electrocortical reactions are known to occur during events like hypothermia
or anesthesia.[9 ] The brain's immaturity is considered a reason for this phenomenon.[10 ] A correlation between depressed electrical brain activity and an adverse neurological
outcome has been described in children with complex congenital heart disease (CHD).[11 ]
Both methods represent easy means of continuous, noninvasive, real-time bedside neuromonitoring,
and providing attending physicians with valuable information might help to rapidly
detect situations carrying a high risk for neurological injury and low cardiac output.[12 ]
Materials and Methods
Patients
We examined a series of infants (<1 year of age) who underwent cardiac surgery for
congenital heart defects via CPB in our tertiary center between April 2014 and August
2017. Inclusion criteria were an age under 12 months and the need for CPB with intraoperative
hypothermia below 33°C. Exclusion criteria were the absence of parental consent to
participate in the study as well as any suspicion of a syndromic disease (i.e., trisomy
21, DiGeorge) or the evidence of cerebral malformations in cerebral sonography or
neonatal seizures diagnosed before surgery. Our local ethics committee approved the
study; the application number was 452/14. Children were then chronologically assigned
to either the control group undergoing the standard rewarming protocol after cooling,
or to a slow-rewarming group as described in detail below.
To facilitate analysis, we estimated the complexity of the congenital heart defect
according to the basic EACTS (European Association for Cardio-Thoracic Surgery) mortality
score, classifying diagnoses combined with performed procedures in five categories
(1 = atrial septal defect/ventricular septal defect correction, 5 = Norwood procedure).[13 ]
Anesthesia
Anesthesia was induced in all patients with midazolam, sufentanil, and pancuronium.
Inhaled sevoflurane and continuous infusion of midazolam and sufentanil ensured maintained
anesthesia. Midazolam and sufentanil were administered postoperatively until recovery
and weaning from ventilation. Our routine monitoring consisted of central venous and
arterial lines. Arterial blood pressure was monitored by an arterial line in the radial
or femoral artery.
Extracorporeal Circulation
CPB took place with the mast-mounted Stockert SIII heart–lung machine (Sorin Group,
Mirandola, Italy) with customized tubing set in combination with the oxygenator Dideco
D100 (Sorin Group Deutschland GmbH, München, Germany) and an arterial filter D130
(Sorin Group, Mirandola, Italy). We maintained a cardiac index of 3.0 L/min/sqm during
normothermia in all patients. Intermittent Buckberg's blood cardioplegia was infused
for myocardial protection. Hematocrit was kept over a range of 20% and pH was managed
according to the α-stat principle. Blood gas was measured at 20-minute intervals.
Continuous invasive blood gas monitoring was also established with the Terumo CDI500
(Terumo Corporation, Tokyo, Japan). Perfusion pressure was recorded continuously.
Depending on the surgery's complexity and duration, the patient's temperature was
cooled down and adjusted using the Stockert 3T Heater Cooler Device (Sorin Group,
Mirandola, Italy). The corporal core temperature was measured continuously via a rectal
sonde, providing data every 20 seconds. The surgeon performed surgery in DHCA according
to the location and complexity of the cardiac defect. For antegrade SCP, an additional
arterial cannula was introduced into either the carotid artery or to distal end of
a modified Blalock–Taussig Shunt.
Our study protocol was developed by an interdisciplinary team to determine two different
rewarming rates. The first group, our control cohort, was rewarmed at a relatively
quick rate, namely +1°C in less than 5 minutes. To prevent prolonging the duration
of CPB, slower rewarming was done according to the depth of hypothermia, meaning + 1°C
in 5 to 8 minutes. Our rewarming strategy is illustrated in [Fig. 1 ].
Fig. 1 Flowchart with intraoperative rewarming protocol: division of our study patients
into two groups, standard and slow-rewarming group. Slow-rewarming group with variable
rewarming rate depending on minimal intraoperative temperature. Illustration of rewarming
curve is shown at the bottom of the figure.
Aortic reconstruction and diagnosis of total anomalous pulmonary venous connection
were major indications for employing DHCA. If weaning from the CPB was impossible
without an excessive demand for catecholamines like adrenaline or noradrenaline (>0.3–0.5 μg/kg/min),
extracorporeal life support (ECLS) was implanted to facilitate myocardial recovery.
In case of any relevant postoperative myocardial edema, sternal closure was delayed.
Postoperative temperatures were measured with a rectal thermometer every 1 or 2 hours,
as we were trying to prevent postoperative hyperthermia (>38.5°C). In case of hypothermia,
a baby warming unit was established with an individual warming temperature to reach
physiological body core temperatures of 35 to 37°C. In case of fever, an external
cooling was set up as needed (cold infusions, cooling pillows, cooling mat). Postoperative
resuscitation temperature management was individually determined according to internal
standards entailing either moderate hypothermia 32 to 34°C or normothermia 35 to 37°C.
Accurate management was ensured by ECLS.
Neurological Monitoring
NIRS measured regional cerebral oxygenation in the frontal neocortex (CrSO2 ) of both hemispheres continuously via two self-adhesive optodes placed on the forehead
([Fig. 2 ]). The principles of NIRS were described previously. We used the (INVOS 5100c Oximeter
Somanetics, Medtronic, Minneapolis, Minnesota, United States), which measured CrSO2 at a sample rate of every 20 seconds. Cerebral desaturation was defined as a drop
in CrSO2 to values under 55% for longer than 5 minutes.
Fig. 2 Example of combined neuromonitoring with noninvasive continuous measurements of cerebral
oxygenation via NIRS (two optodes on the infants' forehead) and of electrocortical
activity deduced from aEEG electrodes (one self-adhesive reference electrode, two-needle
electrodes on each hemisphere, fixed with white tape). Also, note the breathing tube
and infusion line for venous access. aEEG, amplitude-integrated electroencephalography;
NIRS, near-infrared spectroscopy.
aEEG continuously measured electrocortical activity via the Olympic Brain Monitor
BRM-3 (MedCare Visions, Unterschleißheim/München, Germany). This monitor applied a
computer-generated algorithm to filter and compress raw data for each cerebral hemisphere.
Data were considered acceptable for analysis according to the following criteria:
impedance of under 10 kΩ, absence of movement or electrocardiographic artifact on
the raw trace, and absence of interference from diathermy or other electrical devices.
With a standardized template, four-needle electrodes were positioned in the C3/P3
on the left and the C4/P4 positions on the right hemisphere of the international 10
to 20 electroencephalography (EEG) system, one self-adhesive reference electrode was
placed on the child's forehead ([Fig. 2 ]). This two-channel EEG yields separate data from each hemisphere. A pediatric neurologist
experienced in interpreting aEEGs and blinded to clinical information cross-checked
all anonymized aEEG recordings offline. The complete compressed background recording
and intraoperative raw traces were assessed. Background patterns were classified according
to the dominant pattern into five different types of activity according to Hellström-Westas:
continuous normal voltage (CNV), discontinuous normal voltage (DNV), burst suppression
(BS), continuous low voltage (CLV), and flat trace (FT). We documented the time taken
for the aEEG to return to CNV with sleep–wake cycling (SWC) for up to 72 postoperative
hours. We defined seizures as repetitive waveforms evolving over a minimum of 10 seconds
on either hemisphere. The raw EEG signal was used to confirm suspected seizures on
the amplitude-integrated component.
We documented the mean NIRS-derived CrSO2 and the aEEG trace's dominant pattern at each of the predefined phases below:
Beginning: time from start of monitoring to initiating CPB.
Cooling: start of cooling and maintenance of minimal temperature during hypothermia,
possible with either SCP or DHCA.
Rewarming: from minimal temperature to core temperature > 36.0°C.
Weaning: 36.0°C until weaning from CPB/start of ECLS.
Ending: time between disconnecting CPB and end of surgery.
6 hours postoperatively.
12 hours postoperatively.
Statistical Analysis
Hemodynamically and neuromonitoring-derived data were collected simultaneously during
each phase for each child. For statistical analysis, we used Statistical Package for
the Social Sciences (IBM Statistics 20) and Excel (version 15.38). Data were presented
with descriptive statistics using median (min–max) for not normally distributed variables.
Comparisons were performed with t -test for continuous variables, with Mann–Whitney U test for categorical variables
and with Fisher's exact test for dichotomous variables. Correlations were calculated
with the Spearman's rank correlation. For variance analysis, analysis of variance
was performed to identify dependent variables. A p -value < 0.05 was set for statistical significance.
Results
Patients' Characteristics
Thirty-two infants with a median age of 11 (4–365) days, median weight of 3.5 (2.9–8.8)
kg underwent cardiac surgery during their first year of life. Twenty-one (65%) infants
were male, 18 (56%) were neonates, 97% term infants. Leading diagnoses are listed
in [Table 1 ]. Surgical procedures included corrective surgeries (arterial switch operation, aortic
reconstruction, complex corrective surgeries with methods like Yasui, Nikaidoh, Rastelli,
Colin type 1) as well as palliative surgery (Norwood type 1).
Table 1
Patient diagnoses
Congenital heart defect
n
%
d-TGA
11
34
TOF
6
19
Complex SV
4
13
HLHS
4
13
TAPVC
3
9
TAC
2
6
PA
2
6
Note: List of underlying congenital heart defects requiring cardiac surgery.
Abbreviations: d-TGA, d-transposition of the great arteries; HLHS, hypoplastic left
heart syndrome; PA, pulmonary atresia; TAC, truncus arteriosus communis; TAPVC, total
anomalous pulmonary venous connection; TOF, tetralogy of Fallot; SV, single ventricle
(Shone's complex with ALCAPA [anomalous left coronary artery from the pulmonary artery],
DORV [double outlet right ventricle] with TAPVC).
Fifteen children were enrolled in the standard rewarming group and 17 in the slow-rewarming
group. Demographic data are presented in [Table 2 ]. There was no significant difference in age at surgery, gestational age, or weight
between these two cohorts (p > 0.49).
Table 2
Demographic data on patients
Patients
Standard rewarming
n = 15
Slow rewarming
n = 17
Age (d)
13 (5–251)
9 (4–365)
Body weight (kg)
3.5 (2.9–7.0)
3.7 (2.9–8.8)
Body length (cm)
51 (46–66)
55 (47–75)
Note: Data are displayed as median (minimum–maximum).
As a matter of fact, rewarming lasted significantly longer in the slow-rewarming group
(p < 0.05). However, none of the other intra- and postoperative parameters revealed
any significant differences, especially total duration of CPB was similar in both
cohorts. We detected no significant difference in terms of delayed chest closure,
complexity of heart failure, ECLS implantation, or mortality between the control and
intervention groups ([Table 3 ]). Postoperative hyperthermia (rectal temperature > 38.5°C) occurred in four patients
(12.5%) during the first 48 hours after surgery. Intensive care unit (ICU) interventions
were external cooling with a mat, administration of paracetamol (PCM), ibuprofen,
and metamizole. Four infants underwent resuscitation; two of them had an ECLS implanted.
One of them was kept hypothermic for 48 hours, three were kept in normothermia.
Table 3
Perioperative data on both groups
Perioperative data
Standard rewarming
n = 15
Slow rewarming
n = 17
Time on CPB (min)
174 (120–354)
197 (87–341)
Minimum temperature (°C)
26.6 (17.2–29.8)
25.7 (20.1–31.4)
Duration of rewarming (min)[a ]
33 (21–78)
66 (34–122)
Aortic cross-clamp time (min)
107 (6–241)
108 (56–183)
DHCA (min) [n = number of patients]
15.5 (2–81) [6]
11.5 (2–56) [6]
SCP (min) [n = number of patients]
68 (22–81) [5]
54 (36–56) [3]
Highest lactate intraoperative (mmol/L)
3 (1–9.5)
3.5 (1.5–9.9)
Duration of stay in PCICU (h)
228 (44–480)
183 (21–663)
Time on mechanical ventilation (h)
55 (9–443)
98 (8–444)
Highest lactate postop (mmol/L)
4.8 (2–18)
4.1 (1.3–25)
Delayed closure of chest [n = no. of patients]
6 (2–12) [8]
4 (3–9) [9]
ECLS [n = number of patients]
4 (3–7) [3]
2 (2–2) [1]
Death [n = number of patients]
3
2
Abbreviations: CPB, cardiopulmonary bypass; DHCA, deep hypothermic cardiac arrest;
ECLS, extracorporeal life support; PCICU, pediatric cardiac intensive care unit; postop,
postoperative; SCP, selective cerebral perfusion.
Note: Data are displayed as median (minimum–maximum).
a Difference was statistically significant at p < 0.05. [n = number of patients]: as not all patients underwent DHCA or SCP, the actual numbers
are displayed in square brackets.
The aEEG background pattern was suppressed during extracorporeal perfusion to CLV
or FT in more than 60% of all children. During optional phases of CPB, namely SCP
and DHCA, suppression was detected in 100%. Median CrSO2 values were stable (60–68.5% with the highest median saturation during SCP.
General Observations
All our 19 newborn patients (≤28 days of age) displayed a suppressed aEEG pattern
during cooling compared with only 50% of the infants (n = 7; p = 0.02). Moreover, suppression of aEEG tracing continued in all 19 newborns during
rewarming compared with only 28% of the infants (n = 4; p < 0.05; [Fig. 3 ]). Perioperative seizures occurred in 19% of our patients, all of whom were newborns;
seizures were subclinical and thus detected in aEEG; they occurred only during the
cooling phase or postoperatively.
Fig. 3 Bar graph presenting age-dependent aEEG-data during two phases of CPB: aEEG background
pattern with suppressed aEEG (CLV, FT) in different shades of gray BS +/− striped,
DNV in white, and CNV dotted. On the left, aEEG background pattern during the cooling
phase in newborns (<28 days) versus older infants (>28 days). On the right, same bars
for rewarming phase. Significant differences in background patterns due to age are
labeled with *. aEEG, amplitude-integrated electroencephalography; BS, burst suppression;
CLV, continuous low voltage; CNV, continuous normal voltage; CPB, cardiopulmonary
bypass; DNV, discontinuous normal voltage; FT, flat trace.
We performed cooling to a body temperature of less than 25°C in 12 children. We observed
suppressed electrocortical activity at the end of cooling in all of those children
(100%), compared with 60% of the 20 children who were cooled down to a body temperature
exceeding 25°C (p < 0.01). Variance analysis revealed no significant difference between newborns and
infants concerning the core temperature (p = 0.3). FT was significantly more common in children with higher EACTS Score (p = 0.001); CrSO2 revealed no significant change. There was a negative correlation between complexity
of heart failure (EACTS Score), minimal core temperature or age (p < 0.05), but a positive correlation to duration of CPB (r = 0.6, p = 0.001).
We measured electrocortical activity during cerebral desaturation (CrSO2 < 45% for more than 5 minutes) in 30 patients (93%). Depths of desaturation in combination
with aEEG depression varied, but there was no significant correlation. Eight of these
patients with a median minimum of 36% (23–51) showed unchanged electrocortical activity;
15 patients with a median minimum CrSO2 of 32% (15–43) revealed a consecutively suppressed aEEG signal ([Fig. 4 ]) and seven patients with a median minimum CrSO2 of 37% (18–55) revealed a suppressed aEEG pattern before and during desaturation.
Minimal cerebral oxygenation did not differ significantly between those children experiencing
contemporaneous electrocortical depression and those who did not (p = 0.3). Subgroup analysis between the two cohorts such as DHCA versus no DHCA or
ECLS versus no ECLS showed no significant difference in the aEEG pattern, occurrence
of seizures, or in cerebral oxygen supply (p = 0,3).
Fig. 4 Cerebral oxygenation (%) is traced above with the left hemisphere displayed by the
upper line and the right hemisphere by the bottom line. Simultaneous tracing of electrocortical
activity is displayed below with initial discontinuous normal voltage (DNV) tracing
after anaesthetization, which was suppressed further to a burst suppression (BS) during
cooling down to 25°C. During rewarming, a slow return to DNV was observed, but with
a decrease in cerebral oxygenation, which fell below 50% after the attempt to wean
from cardiopulmonary bypass in unstable hemodynamic conditions. At 5:00 p.m., cerebral
desaturation resulted in a short-term BS. An extracorporeal life support system was
implanted followed by immediately improved cerebral oxygenation and a return to DNV.
Rewarming Strategy
Electrocortical activity was less suppressed during the rewarming phase in the slowly
rewarmed cohort; however, the aEEG signal suppression was not statistically significant
([Table 4 ]).
Table 4
Each group's dominant amplitude-integrated electroencephalography patterns during
rewarming are displayed
aEEG pattern during rewarming
Standard rewarming (%)
Slow rewarming (%)
p -Value
Normal patterns (CNV/DNV)
26.6
41.2
0.3
Suppressed patterns (FT/BS/CLV)
73.4
58.8
0.3
Abbreviations: aEEG, amplitude-integrated electroencephalography; BS, burst suppression;
CLV continuous low voltage; CNV, continuous normal voltage; DNV, discontinuous normal
voltage; FT, flat trace.
We detected postoperative seizures in three children (20%) in the standard rewarming
group, whereas no seizure (0%) was detected during the postoperative phase in the
slowly rewarmed group (p = 0.057). All children revealing seizures in aEEG tracing were newborns.
The median duration to return to CNV with SWC traced in the aEEG was 24 (6–138) hours
in children in the standard rewarming group compared with 26 (6–140) hours in those
in the slowly rewarmed group (p = 0.9).
Cerebral oxygenation reflected by the measured median CrSO2 showed a slightly higher increase by +3,5% during rewarming in the slowly rewarmed
group versus + 1.5% in the standard group, but this difference was not statistically
significant (p < 0.939).
Discussion
In our study involving 32 infants and newborns with complex congenital heart defects,
we performed continuous noninvasive neuromonitoring during surgical repair via CPB
and intraoperative hypothermia. Simultaneous use of NIRS and aEEG was feasible and
might provide important information on cerebral oxygenation and electrocortical activity
while facilitating the detection of subclinical seizures.
Our findings in aEEG background patterns are consistent with the literature. There
is ample evidence that electrocortical activity is reduced after the administration
of anaesthetics[14 ] and that it is even more significantly depressed during hypothermia,[15 ] certainly one of the neuroprotective mechanisms to reduce the metabolic demand during
phases of reduced or interrupted perfusion and oxygen supply. We administered sufentanil,
midazolam, and inhaled sevoflurane in our study. These anesthetics trigger suppressed
cerebral activity.[16 ] In addition, anesthesia influences autoregulatory mechanisms of the brain, thus
affecting cerebral oxygenation. The complex interaction of blood pressure, neurovascular
coupling, and vasomotor reactivity to maintain cerebral blood flow is affected.[17 ] Other factors influencing cerebral oxygenation are the hemodynamic status, hemoglobin
concentration, and body temperature, all controlled by CPB.[18 ] Procedure-induced changes in cerebral blood supply must be considered as well. For
example, the pulmonary blood steel effect after shunt operations as well as the lower
systemic oxygen saturation in these children do certainly have an impact on the cerebral
oxygenation and in a situation with an impaired cerebral autoregulation may be also
on electrocortical activity. However, in our study, the performed shunt operations
were equally distributed between the two cohorts, and therefore, an impact on the
general results should not be expected.
aEEG tracing was depressed to flat trace during cooling, especially in neonates. The
fact that seizures occurred only in our study group's neonates together with our observation
that their electrocortical activity was significantly more depressed supports the
research evidence indicating that the neonatal brain seems to be more vulnerable during
CPB and hypothermia.[19 ] The cerebral reaction to anesthetic drugs also seems to differ depending on gestational
age.[9 ]
Furthermore, we observed significantly lower electrocortical activity in infants cooled
to body temperatures beneath 25°C, while median cerebral saturation appeared to be
slightly higher. There are similar aEEG findings in the literature consistent with
ours regarding hypothermia.[8 ] A correlation between the depth of hypothermia and oxygen consumption has been well
investigated, with hypothermia providing a longer duration of tissue tolerance to
less or even no perfusion.[1 ] One could assume that these results reveal success in meeting the metabolic demands
of reduced cerebral metabolism. It might also be reflected by the preserved cerebral
oxygenation measured during SCP or hypothermic cardiac arrest, as described in another
study.[20 ] Such simultaneous monitoring revealed the highest levels of median cerebral oxygenation
combined with suppressed cerebral activity occurring during SCP, striking why this
method has become the preferred approach nowadays.[21 ]
Children who were slowly rewarmed exhibited a tendency toward less suppressed electrocortical
activity during rewarming. At the same time, their cerebral oxygenation rose more
than in the standard rewarming group, but neither effect reached statistical significance.
Interestingly, we observed no postoperative seizure in the slowly rewarmed group,
a finding that not only stands in contrast with our control group (20%) but also with
the incidence reported in the literature.[22 ] A return to a normal pattern together with SWC traced in the aEEG did not differ
between our slowly and rapidly rewarmed groups of children. Gunn et al reported that
perioperative seizures were common in their infant cohort, but they did not affect
2-year neurodevelopmental outcomes.[11 ] As we are all aware, neurological abnormalities can develop and even first appear
after 2 years of age or even later.[23 ] A 4-year neurodevelopmental outcome study in children suffering from complex CHD
reported that an abnormal postoperative background pattern and lack of return to SWC
are markers for subsequent impaired cognitive development.[24 ] Postoperatively, hyperthermia should be avoided since it also seems to raise the
risk of neurodevelopmental impairment and mortality.[6 ] Except for this matter, the literature is quite inconsistent concerning temperature
management after cardiac surgery or cardiac arrest in children. Retrospective studies
as well as randomized controlled trials analyzing hypothermia versus normothermia
revealed no difference in mortality or functional outcome.[25 ]
[26 ]
The intraoperative duration of DHCA is an important risk factor for an impaired developmental
outcome at 8 years of age.[4 ] The protective effects of hypothermia during CPB have been questioned since the
publication of contradictory evidence.[27 ] Targeted temperature management favoring normothermia during CPB is accompanied
by improved tissue perfusion and briefer intubation, shorter ICU stays, and less need
for catecholamines.[28 ] Despite this evidence, DHCA is reserved for complex surgeries; durations of 30 to
40 minutes are considered to be safe. As longer durations can damage the central nervous
system, durations should be minimized. This technique is still being developed and
improved by additional methods like SCP.[2 ] There is unfortunately no consistent intraoperative temperature management guideline
for cardiac surgeons correcting CHDs.
Complex diagnoses, age at surgery, and postoperative complications are perioperative
variables. New data suggest intellectual impairment and significantly lower IQs, especially
in children with more severe cardiac diseases. The same risk constellation has been
described regarding the psychological well-being of infants with CHD, as they experience
emotional maladjustment and an impaired quality of life.[29 ]
As our study patients' neurological development has not yet been assessed, we cannot
say whether our slower rewarming strategy after hypothermic CPB actually enhances
neuroprotection and thus enables a better neurological outcome. We intend to conduct
a neurodevelopmental follow-up study in all of this study's surviving patients.
Simultaneous monitoring of electrocortical activity and cerebral oxygenation in our
study, especially during desaturation, revealed no clear desaturation threshold at
which cerebral activity was suppressed due to a low oxygen supply. Whether temporarily
depressed electrocortical activity after desaturation occurred or not did not retrospectively
indicate a certain depth of minimal cerebral oxygenation. A Dutch study investigating
simultaneous neuromonitoring of pediatric cardiac patients described critical oxygenation
as CrSO2 of 30 to 50%.[12 ] An animal study described cerebral hypoxia–ischemia NIRS thresholds for functional
impairment between 33 and 44%, suggesting a buffer between normal and dysfunction.[30 ] In our study (reassuringly), we probably remained within this buffer zone in most
of our children. Cerebral oxygenation is also a product of both the oxygen supply
(perfusion and oxygenation) and cerebral oxygen consumption determined by brain metabolism.
These factors can be kept in balance by targeted reduction of brain metabolism, together
with an adequate oxygen supply. The increased cerebral activity, together with a higher
increase in cerebral oxygenation we observed, might indicate the adequacy of this
balance in our slow-rewarming strategy group children. This is supported by the fact
that we detected no seizures, especially among the neonates who were rewarmed slowly.
Study Limitations
Our interventional cohort study has several limitations that may affect its results.
For one, our study cohort (containing 32 infants) is relatively small and heterogeneous
because of the broad range of various CHDs included. This limits the validity, especially
in subgroup analysis. Second, as prolonging the duration of CPB in total should be
avoided, we achieved no consistent rewarming rate. We had to adjust the rewarming
rate depending on the intraoperative depth of hypothermia.
Finally, our study patients have not yet undergone neurological reassessment.
We are planning a study providing neurological follow-up data on all surviving patients
to actually deliver evidence on possible neuroprotective effects.
