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Background: The TREX (Trial Remifentanil DEXmedetomidine) trial aimed to determine if, in children < 2 years old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia (LD-SEVO) is superior to standard dose sevoflurane (STD-SEVO) anesthesia in terms of global cognitive function at 3 years of age. The aim of the present secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms., Methods: This Phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. Four hundred and fifty-five infants <2 years of age expected to undergo general anesthesia for at least 2 hours were enrolled. They were randomized between LD-SEVO and STD-SEVO. The short-term perioperative outcomes noted above were compared between these two groups., Results: There was less hypotension (risk difference -11.6%, 95% confidence interval (CI) -18.9% to -4.3%) and more bradycardia (risk difference 18.2%, 95% CI 8.8% to 27.7%) in the LD-SEVO compared to the STD-SEVO arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the LD-SEVO arm. Time from eye-opening to Post Anesthesia Care Unit (PACU) discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event but neither suffered long-term sequelae., Conclusions: These early postoperative results suggest that in children less than 2 years of age receiving greater than 2 hours of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other., Competing Interests: Conflicts of Interest: Dean B. Andropoulos, MD has been Medical Officer of SmartTots; he was not involved in funding decisions for the TREX Trial from the SmartTots organization., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design : Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

The critical closing pressure (CrCP) of the cerebral vasculature is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. Because the ABP of preterm infants is low and close to the CrCP, there is often no CBF during diastole. Thus, estimation of CrCP may become clinically relevant in preterm neonates. Transcranial Doppler (TCD) ultrasound has been used to estimate CrCP in preterm infants. Diffuse correlation spectroscopy (DCS) is a continuous, noninvasive optical technique that measures microvascular CBF. Our objective was to compare and validate CrCP measured by DCS versus TCD ultrasound. Hemorrhagic shock was induced in 13 neonatal piglets, and CBF was measured continuously by both modalities. CrCP was calculated using a model of cerebrovascular impedance, and CrCP determined by the two modalities showed good correlation by linear regression, median r 2 = 0.8 (interquartile range (IQR) 0.71-0.87), and Bland-Altman analysis showed a median bias of -3.5 (IQR -4.6 to -0.28). This is the first comparison of CrCP determined by DCS versus TCD ultrasound in a neonatal piglet model of hemorrhagic shock. The difference in CrCP between the two modalities may be due to differences in vasomotor tone within the microvasculature of the cerebral arterioles versus the macrovasculature of a major cerebral artery.

Background: Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours., Methods: Sixty infants (age 1-12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used., Results: One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40-50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg)., Conclusion: A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants., (© 2018 John Wiley & Sons Ltd.)

Background: Clinical studies measuring cerebral blood flow in infants during deep hypothermia have demonstrated diminished cerebrovascular pressure autoregulation. The coexistence of hypotension in these cohorts confounds the conclusion that deep hypothermia impairs cerebrovascular pressure autoregulation., Aim: We sought to compare the lower limit of autoregulation and the static rate of autoregulation between normothermic and hypothermic piglets., Methods: Twenty anesthetized neonatal piglets (5-7 days old; 10 normothermic and 10 hypothermic to 20°C) had continuous measurements of cortical red cell flux using laser Doppler flowmetry, while hemorrhagic hypotension was induced without cardiopulmonary bypass. Lower limit of autoregulation was determined for each subject using piecewise regression and SRoR was determined above and below each lower limit of autoregulation as (%change cerebrovascular resistance/%change cerebral perfusion pressure)., Results: The estimated difference in lower limit of autoregulation was 1.4 mm Hg (lower in the hypothermic piglets; 95% C.I. -10 to 14 mm Hg; P=0.6). The median lower limit of autoregulation in the normothermic group was 39 mm Hg [IQR 38-51] vs 35 mm Hg [31-50] in the hypothermic group. Intact steady-state pressure autoregulation was defined as static rate of autoregulation >0.5 and was demonstrated in all normothermic subjects (static rate of autoregulation=0.72 [0.65-0.87]) and in 9/10 of the hypothermic subjects (static rate of autoregulation=0.65 [0.52-0.87]). This difference in static rate of autoregulation of 0.06 (95% C.I. -0.3 to 0.1) was not significant (P=0.4)., Conclusion: Intact steady-state cerebrovascular pressure autoregulation is demonstrated in a swine model of profound hypothermia. Lower limit of autoregulation and static rate of autoregulation were similar in hypothermic and normothermic subjects., (© 2017 John Wiley & Sons Ltd.)

Background: Autoregulation monitoring has been proposed as a means to identify optimal arterial blood pressure goals during cardiopulmonary bypass, but it has been observed that cerebral blood flow is pressure passive during hypothermic bypass. When neonates cooled during cardiopulmonary bypass are managed with vasodilators and controlled hypotension, it is not clear whether hypothermia or hypotension were the cause of impaired autoregulation., Aim: We sought to measure the effect of both arterial blood pressure and hypothermia on autoregulation in a cohort of infants cooled for bypass, hypothesizing a collinear relationship between hypothermia, hypotension, and dysautoregulation., Methods: Cardiopulmonary bypass was performed on 72 infants at Texas Children's Hospital during 2015 and 2016 with automated physiologic data capture, including arterial blood pressure, nasopharyngeal temperature, cerebral oximetry, and a cerebral blood volume index derived from near infrared spectroscopy. Cooling to 18°C, 24°C, and 30°C was performed on 33, 12, and 22 subjects, respectively. The hemoglobin volume index was calculated as a moving correlation coefficient between mean arterial blood pressure and the cerebral blood volume index. Positive values of the hemoglobin volume index indicate impaired autoregulation. Relationships between variables were assessed utilizing a generalized estimating equation approach., Results: Hypothermia was associated with hypotension, dysautoregulation, and increased cerebral oximetry. Comparing the baseline temperature of 36°C with 18°C, arterial blood pressure was 44 mm Hg (39-52) vs 25 mm Hg (21-31); the hemoglobin volume index was 0.0 (-0.02 to 0.004) vs 0.5 (0.4-0.7) and cerebral oximetry was 59% (57-61) vs 88% (80-92) (Median, 95% CI of median; P<.0001 for all three associations by linear regression with generalized estimation of equations with data from all temperatures measured)., Conclusions: Arterial blood pressure, temperature, and cerebral autoregulation were collinear in this cohort. The conclusion that hypothermia causes impaired autoregulation is thus confounded. The effect of temperature on autoregulation should be delineated before clinical deployment of autoregulation monitors to prevent erroneous determination of optimal arterial blood pressure. Showing the effect of temperature on autoregulation will require a normotensive hypothermic model., (© 2017 John Wiley & Sons Ltd.)

Objective: We evaluated ST-segment monitoring to detect clinical decompensation in infants with single ventricle anatomy. We proposed a signal processing algorithm for ST-segment instability and hypothesized that instability is associated with cardiopulmonary arrests., Design: Retrospective, observational study., Setting: Tertiary children's hospital 21-bed cardiovascular ICU and 36-bed step-down unit., Patients: Twenty single ventricle infants who received stage 1 palliation surgery between January 2013 and January 2014. Twenty rapid response events resulting in cardiopulmonary arrests (arrest group) were recorded in 13 subjects, and nine subjects had no interstage cardiopulmonary arrest (control group)., Interventions: None., Measurements and Main Results: Arrest data were collected over the 4-hour time window prior to cardiopulmonary arrest. Control data were collected from subjects with no interstage arrest using the 4-hour time window prior to cardiovascular ICU discharge. A paired subgroup analysis was performed comparing subject 4-hour windows prior to arrest (prearrest group) with 4-hour windows prior to discharge (postarrest group). Raw values of ST segments were compared between groups. A 3D ST-segment vector was created using three quasi-orthogonal leads (II, aVL, and V5). Magnitude and instability of this continuous vector were compared between groups. There was no significant difference in mean unprocessed ST-segment values in the arrest and control groups. Utilizing signal processing, there was an increase in the ST-vector magnitude (p = 0.02) and instability (p = 0.008) in the arrest group. In the paired subgroup analysis, there was an increase in the ST-vector magnitude (p = 0.05) and instability (p = 0.05) in the prearrest state compared with the postarrest state prior to discharge., Conclusions: In single ventricle patients, increased ST instability and magnitude were associated with rapid response events that required intervention for cardiopulmonary arrest, whereas conventional ST-segment monitoring did not differentiate an arrest from control state.

Background: The upper limit of cerebrovascular pressure autoregulation (ULA) is inadequately characterized., Objective: To delineate the ULA in an infant swine model., Methods: Neonatal piglets with sham surgery (n = 9), interventricular fluid infusion (INF) (n = 10), controlled cortical impact (CCI) (n = 10), or CCI + INF (n = 11) had intracranial pressure monitoring and bilateral cortical laser-Doppler flowmetry recordings during arterial hypertension to lethality using an aortic balloon catheter. An increase of red cell flux as a function of cerebral perfusion pressure was determined by piecewise linear regression, and static rates of autoregulation were determined above and below this inflection. The ULA was rendered as the first instance of an upward deflection of Doppler flux causing a static rate of autoregulation decrease greater than 0.5., Results: ULA was identified in 55% of piglets after sham surgery, 70% after INF, 70% after CCI, and 91% after CCI with INF (P = .36). When identified, the median (interquartile range) ULA was as follows: sham group, 102 mm Hg (97-109 mm Hg); INF group, 75 mm Hg (52-84 mm Hg); CCI group, 81 mm Hg (69-101 mm Hg); and CCI + INF group, 61 mm Hg (52-57 mm Hg) (P = .01). In post hoc analysis, both groups with interventricular INF had significantly lower ULA than that observed in the sham group., Conclusion: Neonatal piglets without intracranial pathology tolerated acute hypertension with minimal perturbation of cerebral blood flow. Piglets with acutely increased intracranial pressure with or without trauma demonstrated loss of autoregulation when subjected to arterial hypertension.

The pressure reactivity index (PRx) identifies optimal cerebral perfusion pressure after traumatic brain injury. We describe a method to improve PRx precision by induced variations in arterial blood pressure (ABP) using positive end-expiratory pressure (PEEP) modulation (iPRx). Neonatal swine (n = 10) were ventilated with static PEEP and then with PEEP oscillated between 5 and 10 cmH(2)O at a frequency of 1/min. PRx was recorded as a moving correlation coefficient between ABP and intracranial pressure (ICP) from spontaneous ABP activity (0.05-0.003 Hz) during static PEEP. iPRx was similarly recorded with PEEP oscillation-induced ABP waves. The lower limit of autoregulation (LLA) was delineated with continuous cortical laser Doppler flux monitoring. PEEP oscillation increased autoregulation-monitoring precision. The ratios of median absolute deviations to range of possible values for the PRx and iPRx were 9.5% (8.3-13.7%) and 6.2% (4.2-8.7%), respectively (P = 0.006; median, interquartile range). The phase-angle difference between ABP and ICP above LLA was 161° (150°-166°) and below LLA, -31° (-42° to 12°, P < 0.0001). iPRx above LLA was -0.42 (-0.67 to -0.29) and below LLA, 0.32 (0.22-0.43, P = 0.0004). A positive iPRx was 97% specific and 91% sensitive for perfusion pressure below LLA. PEEP oscillation caused stable, low-frequency ABP oscillations that reduced noise in the PRx. Safe translation of these findings to clinical settings is expected to yield more accurate and rapid delineation of individualized optimal perfusion-pressure goals for patients.

Prevention of brain injury during congenital heart surgery has focused on intraoperative and perioperative neuroprotection and neuromonitoring. Many strategies have been adopted as "standard of care." However, the strength of evidence for these practices and the relationship to long-term outcomes are unknown. We performed a systematic review (January 1, 1990 to July 30, 2010) of neuromonitoring and neuroprotection strategies during cardiopulmonary bypass (CPB) in infants of age 1 year or less. Papers were graded individually and as thematic groups, assigning evidence-based medicine and American College of Cardiology/American Heart Association (ACC/AHA) level of evidence grades. Consensus scores were determined by adjudication. Literature search identified 527 manuscripts; 162 met inclusion criteria. Study designs were prospective observational cohort (53.7%), case-control (21.6%), randomized clinical trial (13%), and retrospective observational cohort (9.9%). Median sample size was 43 (range 3 to 2,481). Primary outcome was evidence of structural brain injury or functional disability (neuroimaging, electroencephalogram, formal neurologic examination, or neurodevelopmental testing) in 43%. Follow-up information was reported in only 29%. The most frequent level of evidence was evidence-based medicine level 4 (33.3%) or ACC/AHA class IIB: level B (42%). The only intervention with sufficient evidence to recommend "the procedure or treatment should be performed" was avoidance of extreme hemodilution during CPB. Data supporting use of current neuromonitoring and neuroprotective techniques are limited. The level of evidence is insufficient to support effectiveness of most of these strategies. Well-designed studies with correlation to clinical outcomes and long-term follow-up are needed to develop guidelines for neuromonitoring and neuroprotection during CPB in infants., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Operative repair of an atrioventricular septal defect is not without risk. The purpose of this review is to highlight various key topics in the perioperative treatment of patients with atrioventricular septal defects, including challenges related to Down syndrome, postoperative arrhythmias, pulmonary hypertension, hypothyroidism, postoperative residual and recurrent lesions, including systemic atrioventricular valvar regurgitation and left ventricular outflow tract obstruction, sedation and analgesia, and vascular access.

Congenital heart defects are the most common cause of death in infants and young children in the developed world. As the mortality in this population has declined to less than 5%, more attention is being focused now on reducing post-procedural morbidities that may seriously impact the patient and their families. Because of multiple reasons, paediatric cardiac surgery and anaesthesia is a perfect model for studying human errors and their impact on patient safety. Congenital cardiac disease is a common lesion causing much morbidity, pain, and loss of life. Over 44,000 surgical procedures are performed yearly to repair congenital cardiac problems in the United States alone. The reduction or elimination of iatrogenic adverse outcomes, given the current mortality rates of 4.2%-4.5%, might lead to as many as 500 children achieving better outcomes or shorter hospitalizations.Efforts to quantify the frequency of complications related to anaesthesia in patients undergoing congenital cardiac surgery have been difficult to date because of the low occurrence of this surgery compared to other surgeries on children and the relatively rare incidence of complications related to anaesthesia in this population. Anaesthesiologists play a crucial role in the reduction, recognition, and timely treatment of medical errors that impact this morbidity. Paediatric cardiac surgery encompasses many complex procedures that are highly dependent upon a sophisticated organizational structure, effective communication, coordinated efforts of multiple individuals working as a team, and high levels of cognitive and technical performance. Human factor error analysis in this patient population has shown how frequently both minor and major errors occur. The goal of this paper is to outline the frequency and sources of these errors and to suggest treatment strategies which may minimize their occurrence.

The Congenital Cardiac Anesthesia Society was formed in 2005 by representatives from many of the busiest congenital cardiac surgical programs in North America and is now in the process of partnering with The Society of Thoracic Surgeons to create a joint congenital cardiac surgery and congenital cardiac anaesthesia database. Even the busiest of congenital cardiac programs have a low frequency of anaesthesia-related cardiac complications and deaths. One of the only mechanisms for accurately determining the incidence and outcomes of low frequency events is to aggregate large amounts of data from multiple sources. To that end, the Congenital Cardiac Anesthesia Society has joined with the Society of Thoracic Surgeons Congenital Database Task Force to incorporate anaesthesia-specific data points into their surgical registry, which is now the largest single reporting site for children and adults undergoing surgical repair of congenital cardiac malformations in North America. The Joint Congenital Cardiac Anesthesia Society--Society of Thoracic Surgeons Database will therefore become an optional module of The Society of Thoracic Surgeons Congenital Heart Surgery Database. Initial data fields have been selected and are presented in this article. Efforts are ongoing to make this initiative a global project. Initial collaborative discussions have taken place about the possibility of linking this initiative with the European Association of Cardiothoracic Anesthesiologists. It is certainly possible and desirable that the planned anaesthesia module of The Society of Thoracic Surgeons Congenital Heart Database has an identical module in the congenital heart database of The European Association for Cardio-Thoracic Surgery and The European Congenital Heart Surgeons Association. This project should also ideally spread beyond North America and Europe. Efforts to involve Africa, Asia, Australia, and South America are necessary and already underway. The creation of a joint cardiac surgery and anaesthesia database is another step towards the ultimate goal of creating a database for congenital heart disease that spans both geographical and subspecialty boundaries.

Neonates with congenital cardiac disease are a special population. They are often critically ill, and need prolonged intravenous access. To date, no study has evaluated the efficacy and safety of peripherally inserted central venous catheters placed in this unique population. Our goal was to evaluate the use of such catheters in neonates with critical congenital cardiac disease, and to study features such as duration of use, reasons for removal of catheters, and complications. We inserted a total of 124 catheters in 115 neonates with critical congenital cardiac disease who were admitted to the Intensive Care Unit at Texas Children's Hospital from August 2002 to August 2004. The patients had a mean age of 10 days, and a mean weight of 3.1 kilograms. The peripherally inserted catheters were in place for a mean of 22.3 days. Therapy was completed in 76.6% patients at the time of removal of the catheter. The incidence of occlusion, dislodgement, and thrombus was 4.0%, 2.4%, and 1.6%, respectively. The infection rate was 3.6 per 1000 catheter-days, with a median onset on 37 days after placement. We conclude that central venous catheters, when inserted peripherally, provide reliable and safe access for prolonged intravenous therapy in neonates with critical congenital cardiac disease.