Physiologic profile associated with severe multisystem inflammatory syndrome in children: a retrospective study.

OBJECTIVE: The purpose of this study was to describe the clinical presentation and physiologic profile of individuals with varying degrees of severity of multisystem inflammatory syndrome in children (MIS-C). METHODS: We performed a retrospective study of children diagnosed with MIS-C admitted to a single quaternary children's hospital from May 2020 to April 2021. We created an MIS-C severity score using the following parameters: hospital admission status (e.g., floor vs intensive care unit), need for inotropic or vasoactive medications, and need for mechanical ventilation. Univariate and multivariate analyses were performed to associate risk factors corresponding to the MIS-C severity score. RESULTS: The study included 152 children who were followed for 14 days post hospital admission. A stepwise forward selection process identified seven physiologic variables associated with "severe" MIS-C according to a logistic regression. Specifically, a combination of elevated creatinine (p = 0.013), international normalized ratio (p = 0.002), brain natriuretic peptide (p = 0.001), white blood cell count (p = 0.009), ferritin (p = 0.041), respiratory rate (p = 0.047), and decreased albumin (p = 0.047) led to an excellent discrimination between mild versus severe MIS-C (AUC = 0.915). CONCLUSION: This study derived a physiologic profile associated with the stratification of MIS-C severity. IMPACT: Based on a cohort of 152 individuals diagnosed with MIS-C, this study derived a nomenclature that stratifies the severity of MIS-C. Investigated demographic, presentational vital signs, and blood analytes associated with severity of illness. Identification of a multivariate physiologic profile that strongly associates with MIS-C severity. This model allows the care team to recognize patients likely to require a higher level of intensive care.

Descriptors of Failed Extubation in Norwood Patients Using Physiologic Data Streaming.

The objective of this study is to evaluate the utility of high-frequency physiologic data during the extubation process and other clinical variables for describing the physiologic profile of extubation failure in neonates with hypoplastic left heart syndrome (HLHS) post-Norwood procedure. This is a single-center, retrospective analysis. Extubation events were collected from January 2016 until July 2021. Extubation failure was defined as the need for re-intubation within 48 h of extubation. The data included streaming heart rate, respiratory rate, blood pressure, arterial oxygen saturation, and cerebral/renal near-infrared spectroscopy (NIRS). The most recent blood laboratory results before extubation were also included. These markers, demographics, clinical characteristics, and ventilatory settings were compared between successful and failed extubations. The analysis included 311 extubations. The extubation failure rate was 10%. According to univariable analyses, failed extubations were preceded by higher respiratory rates (p = 0.029), lower end-tidal CO2 (p = 0.009), lower pH (p = 0.043), lower serum bicarbonate (p = 0.030), and lower partial pressure of O2 (p = 0.022). In the first 10 min after extubation, the failed events were characterized by lower arterial (p = 0.028) and cerebral NIRS (p = 0.018) saturations. Failed events were associated with persistently lower values for cerebral NIRS 2 h post-extubation (p = 0.027). In multivariable analysis, vocal cord anomaly, cerebral NIRS at 10 min post-extubation, renal NIRS at pre-extubation and post-extubation, and end-tidal CO2 at pre-extubation remained as significant co-variables. Oximetric indices before, in the 10 min immediately after, and 2 h after extubation and vocal cords paralysis are associated with failed extubation events in patients with parallel circulation.

Decreased Heart Rate Variability in Children with Acute Decompensated Heart Failure is Associated with Poor Outcomes.

Heart rate variability (HRV) is a noninvasive indicator of the health of neurocardiac interactions of the autonomic nervous system. In adults, decreased HRV correlates with increased cardiovascular mortality. However, the relationship between HRV and outcomes in children with acute decompensated heart failure (ADHF) has not been described. Patients < 21 years old hospitalized with ADHF from 2013 to 2019 were included (N = 79). Primary outcome was defined as death, heart transplant, or mechanical circulatory support (MCS). The median standard deviation of the R-to-R interval in 5-min intervals (SDNN) was calculated from telemetry data obtained across the first 24 h of admission. Patients who met the primary outcome had significantly lower median SDNN (13.8 [7.8, 29.1]) compared to those who did not (24.6 [15.3, 84.4]; p = 0.004). A median SDNN of 20 ms resulted in a sensitivity of 68% and specificity of 69%. Median SDNN < 20 ms represented decreased freedom from primary outcome (p = 0.043) and a hazard ratio of 2.2 in multivariate analysis (p = 0.016). Pediatric patients with ADHF who died, underwent heart transplant, or required MCS had significantly decreased HRV at presentation compared to those that did not. This supports HRV as a noninvasive tool to improve prognostication in children in ADHF.

Comparison of Laboratory and Hemodynamic Time Series Data Across Original, Alpha, and Delta Variants in Patients With Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: To compare the clinical, laboratory, and hemodynamic parameters during hospitalization for patients with multisystem inflammatory syndrome in children (MIS-C), across the Original/Alpha and the Delta variants of severe acute respiratory syndrome coronavirus 2 infection. DESIGN: Retrospective cohort study. SETTING: Single-center quaternary children's hospital. PATIENTS: Children with MIS-C admitted from May 2020 to February 2021(Original and Alpha variant cohort) and August 2021 to November 2021 (Delta variant cohort). MEASUREMENTS AND MAIN RESULTS: Continuous vital sign measurements, laboratory results, medications data, and hospital outcomes from all subjects were evaluated. Of the 134 patients (102 with Original/Alpha and 32 with Delta), median age was 9 years, 75 (56%) were male, and 61 (46%) were Hispanics. The cohort with Original/Alpha variant had more males (61% vs 41%; p = 0.036) and more respiratory/musculoskeletal symptoms on presentation compared with the Delta variant ( p < 0.05). More patients in the Original/Alpha variant cohort received mechanical ventilation (16 vs 0; p = 0.009). Median hospital length of stay (LOS) was 7 days, and ICU LOS was 3 days for the entire cohort. ICU LOS was shorter in cohort with the Delta variant compared with the Original/Alpha variant (4 vs 2 d; p = 0.001). Only one patient had cardiac arrest, two needed extracorporeal membrane oxygenation, and two needed left ventricular assist device (Impella, Danvers, MA), all in the Original/Alpha variant cohort; no mortality occurred in the entire cohort. MIS-C cohort associated with the Delta variant had lower INR, prothrombin time, WBCs, sodium, phosphorus, and potassium median values ( p < 0.05) during hospitalization compared with the Original/Alpha variants. Hemodynamic assessment showed significant tachycardia in the Original/Alpha variants cohort compared with the Delta variant cohort ( p < 0.05). INTERVENTIONS: None. CONCLUSIONS: Patients with MIS-C associated with the Delta variants had lower severity during hospitalization compared with the Original/Alpha variant. Analysis of distinct trends in clinical and laboratory parameters with future variants of concerns will allow for potential modification of treatment protocol.

Novel Method of Calculating Pulse Pressure Variation to Predict Fluid Responsiveness to Transfusion in Very Low Birth Weight Infants.

A novel technique was used to calculate pulse pressure variation. The algorithm reliably predicted fluid responsiveness to transfusion, with a receiver operating characteristic area under the curve of 0.89. This technique may assist clinicians in the management of fluids and vasoactive medications for premature infants.

Creatinine filtration kinetics in critically Ill neonates.

BACKGROUND: Creatinine values are unreliable within the first weeks of life; however, creatinine is used most commonly to assess kidney function. Controversy remains surrounding the time required for neonates to clear maternal creatinine. METHODS: Eligible infants had multiple creatinine lab values and were admitted to the neonatal intensive care unit (NICU). A mathematical model was fit to the lab data to estimate the filtration onset delay, creatinine filtration half-life, and steady-state creatinine concentration for each subject. Infants were grouped by gestational age (GA) [(1) 22-27, (2) >27-32, (3) >32-37, and (4) >37-42 weeks]. RESULTS: A total of 4808 neonates with a mean GA of 34.4 ± 5 weeks and birth weight of 2.34 ± 1.1 kg were enrolled. Median (95% confidence interval) filtration onset delay for Group 1 was 4.3 (3.71, 4.89) days and was significantly different than all other groups (p < 0.001). Creatinine filtration half-life of Groups 1, 2, and 3 were significantly different from each other (p < 0.001). There was no difference in steady-state creatinine concentration among the groups. CONCLUSIONS: We quantified the observed kidney behavior in a large NICU population as a function of day of life and GA using creatinine lab results. These results can be used to interpret individual creatinine labs for infants to detect those most at risk for acute kidney injury. IMPACT: One of the largest cohorts of premature infants to describe the evolution of kidney development and function over their entire hospitalization. New concept introduced of the kidney filtration onset delay, the time needed for the kidney to begin clearance of creatinine, and that it can be used as an early indicator of kidney function. The smallest premature infants from 22 to 27 weeks gestation took the longest time to begin and complete maternal creatinine clearance. Clinicians can easily compare the creatinine level of their patient to the normative curves to improve understanding of kidney function at the bedside.

Critical Closing Pressure by Diffuse Correlation Spectroscopy in a Neonatal Piglet Model.

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.

Observed and calculated cerebral critical closing pressure are highly correlated in preterm infants.

BACKGROUND: Cerebrovascular critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow ceases. Preterm ABP is low and close to CrCP. The diastolic closing margin (diastolic ABP minus CrCP) has been associated with intraventricular hemorrhage in preterm infants. CrCP is estimated from middle cerebral artery cerebral blood flow velocity (CBFV) and ABP waveforms. However, these estimations have not been validated due to a lack of gold standard. Direct observation of the CrCP in preterm infants with hypotension is an opportunity to validate synchronously estimated CrCP. METHODS: ABP and CBFV tracings were obtained from 24 extremely low birth weight infants. Recordings where diastolic CBFV was zero were identified. The gold standard CrCP was delineated using piecewise regression of ABP and CBFV values paired by rank ordering and then estimated using a published formula. The measured and estimated values were compared using linear regression and Bland-Altman analysis. RESULTS: Linear regression showed a high degree of correlation between measured and calculated CrCP (r2 = 0.93). CONCLUSIONS: This is the first study to validate a calculated CrCP by comparing it to direct measurements of CrCP from preterm infants when ABP is lower than CrCP.

Hypotensive Response to IV Acetaminophen in Pediatric Cardiac Patients.

OBJECTIVES: Acetaminophen is ubiquitously used as antipyretic/analgesic administered IV to patients undergoing surgery and to critically ill patients when enteral routes are not possible. Widely believed to be safe and free of adverse side effects, concerns have developed in adult literature regarding the association of IV acetaminophen and transient hypotension. We hypothesize that there are hemodynamic effects after IV acetaminophen in the PICU and assess the prevalence of such in a large pediatric cardiovascular ICU population using high-fidelity data. DESIGN: Observational study analyzing an enormous set of continuous physiologic data including millions of beat to beat blood pressures surrounding medication administration. SETTING: Quaternary pediatric cardiovascular ICU between January 1, 2013, and November 13, 2017. PATIENTS: All patients less than or equal to 18 years old who received IV acetaminophen. Mechanical support devices excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic vital sign data were analyzed in 5-minute intervals starting 60 minutes before through 180 minutes after completion. Hypotension defined as mean arterial pressure -15% from baseline and relative hypotension defined -10%. Only doses where patients received no other medications, including vasopressors, within the previous hour were included. t test and a correlation matrix were used to eliminate correlated factors before a logistic regression analysis was performed. Six-hundred eight patients received 777 IV acetaminophen doses. Median age was 8.8 months (interquartile range, 2-62 mo) with a dose of 12.5 mg/kg (interquartile range, 10-15 mg/kg). Data were normalized for age and reference values. One in 20 doses (5%) were associated with hypotension, and one in five (20%) associated with relative hypotension. Univariate analysis revealed hypotension associated with age, baseline mean arterial pressure, and skin temperature (p = 0.05, 0.01, and 0.09). Logistic regression revealed mean arterial pressure (p = 0.01) and age (p = 0.05) remained predictive for hypotension. CONCLUSIONS: In isolation of other medication, a hemodynamic response to IV acetaminophen has a higher prevalence in critically ill children with cardiac disease than previously thought and justifies controlled studies in the perioperative and critical care setting. The added impact on individual patient hemodynamics and physiologic instability will require further study.

An effective model of cerebrovascular pressure reactivity and blood flow autoregulation.

Understanding cerebral blood flow dynamics is crucial for the care of patients at risk of poor cerebral perfusion. We describe an effective model of cerebral hemodynamics designed to reveal important macroscopic features of cerebral blood flow without having to resolve the detailed microvasculature of the brain. Based on principles of fluid and elastic dynamics and vascular pressure-reactivity, the model quantifies the physical means by which the vasculature executes autoregulatory reflexes. We demonstrate that the frequency response of the proposed model matches experimental measurements and explains the influence of mechanical factors on the autoregulatory performance. Analysis of the model indicates the existence of an optimal mean arterial pressure which minimizes the sensitivity of the flow to changes in perfusion pressure across the frequency spectrum of physiological oscillations. We highlight the simplicity of the model and its potential to improve monitoring of brain perfusion via real-time computational simulations of cerebro- and cardio-vascular interventions.

Finding representative electrocardiogram beat morphologies with CUR.

In this paper, we use the CUR matrix factorization as a means of dimension reduction to identify important subsequences in electrocardiogram (ECG) time series. As opposed to other factorizations typically used in dimension reduction that characterize data in terms of abstract representatives (for example, an orthogonal basis), the CUR factorization describes the data in terms of actual instances within the original data set. Therefore, the CUR characterization can be directly related back to the clinical setting. We apply CUR to a synthetic ECG data set as well as to data from the MIT-BIH Arrhythmia, MGH-MF, and Incart databases using the discrete empirical interpolation method (DEIM) and an incremental QR factorization. In doing so, we demonstrate that CUR is able to identify beat morphologies that are representative of the data set, including rare-occurring beat events, providing a robust summarization of the ECG data. We also see that using CUR-selected beats to label the remaining unselected beats via 1-nearest neighbor classification produces results comparable to those presented in other works. While the electrocardiogram is of particular interest here, this work demonstrates the utility of CUR in detecting representative subsequences in quasiperiodic physiological time series.

Epinephrine syringe exchange events in a paediatric cardiovascular ICU: analysing the storm.

Introduction Haemodynamically unstable patients can experience potentially hazardous changes in vital signs related to the exchange of depleted syringes of epinephrine to full syringes. The purpose was to determine the measured effects of epinephrine syringe exchanges on the magnitude, duration, and frequency of haemodynamic disturbances in the hour after an exchange event (study) relative to the hours before (control). Materials and methods Beat-to-beat vital signs recorded every 2 seconds from bedside monitors for patients admitted to the paediatric cardiovascular ICU of Texas Children's Hospital were collected between 1 January, 2013 and 30 June, 2015. Epinephrine syringe exchanges without dose/flow change were obtained from electronic records. Time, magnitude, and duration of changes in systolic blood pressure and heart rate were characterised using Matlab. Significant haemodynamic events were identified and compared with control data. RESULTS: In all, 1042 syringe exchange events were found and 850 (81.6%) had uncorrupted data for analysis. A total of 744 (87.5%) exchanges had at least 1 associated haemodynamic perturbation including 2958 systolic blood pressure and 1747 heart-rate changes. Heart-rate perturbations occurred 37% before exchange and 63% after exchange, and 37% of systolic blood pressure perturbations happened before syringe exchange, whereas 63% occurred after syringe exchange with significant differences found in systolic blood pressure frequency (p<0.001), duration (p<0.001), and amplitude (p<0.001) compared with control data. CONCLUSIONS: This novel data collection and signal processing analysis showed a significant increase in frequency, duration, and magnitude of systolic blood pressure perturbations surrounding epinephrine syringe exchange events.

A Novel Electrocardiogram Algorithm Utilizing ST-Segment Instability for Detection of Cardiopulmonary Arrest in Single Ventricle Physiology: A Retrospective Study.

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.

Does hypothermia impair cerebrovascular autoregulation in neonates during cardiopulmonary bypass?

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.

Comparison of reduced models for blood flow using Runge-Kutta discontinuous Galerkin methods.

One-dimensional blood flow models take the general form of nonlinear hyperbolic systems but differ in their formulation. One class of models considers the physically conserved quantities of mass and momentum, while another class describes mass and velocity. Further, the averaging process employed in the model derivation requires the specification of the axial velocity profile; this choice differentiates models within each class. Discrepancies among differing models have yet to be investigated. In this paper, we comment on some theoretical differences among models and systematically compare them for physiologically relevant vessel parameters, network topology, and boundary data. In particular, the effect of the velocity profile is investigated in the cases of both smooth and discontinuous solutions, and a recommendation for a physiological model is provided. The models are discretized by a class of Runge-Kutta discontinuous Galerkin methods.

Predicting Intracranial Pressure and Brain Tissue Oxygen Crises in Patients With Severe Traumatic Brain Injury.

OBJECTIVES: To develop computer algorithms that can recognize physiologic patterns in traumatic brain injury patients that occur in advance of intracranial pressure and partial brain tissue oxygenation crises. The automated early detection of crisis precursors can provide clinicians with time to intervene in order to prevent or mitigate secondary brain injury. DESIGN: A retrospective study was conducted from prospectively collected physiologic data. intracranial pressure, and partial brain tissue oxygenation crisis events were defined as intracranial pressure of greater than or equal to 20 mm Hg lasting at least 15 minutes and partial brain tissue oxygenation value of less than 10 mm Hg for at least 10 minutes, respectively. The physiologic data preceding each crisis event were used to identify precursors associated with crisis onset. Multivariate classification models were applied to recorded data in 30-minute epochs of time to predict crises between 15 and 360 minutes in the future. SETTING: The neurosurgical unit of Ben Taub Hospital (Houston, TX). SUBJECTS: Our cohort consisted of 817 subjects with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Our algorithm can predict the onset of intracranial pressure crises with 30-minute advance warning with an area under the receiver operating characteristic curve of 0.86 using only intracranial pressure measurements and time since last crisis. An analogous algorithm can predict the start of partial brain tissue oxygenation crises with 30-minute advanced warning with an area under the receiver operating characteristic curve of 0.91. CONCLUSIONS: Our algorithms provide accurate and timely predictions of intracranial hypertension and tissue hypoxia crises in patients with severe traumatic brain injury. Almost all of the information needed to predict the onset of these events is contained within the signal of interest and the time since last crisis.

Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants.

OBJECTIVE: To determine whether the diastolic closing margin (DCM), defined as diastolic blood pressure minus critical closing pressure, is associated with the development of early severe intraventricular hemorrhage (IVH). STUDY DESIGN: A reanalysis of prospectively collected data was conducted. Premature infants (gestational age 23-31 weeks) receiving mechanical ventilation (n = 185) had ∼1-hour continuous recordings of umbilical arterial blood pressure, middle cerebral artery cerebral blood flow velocity, and PaCO2 during the first week of life. Models using multivariate generalized linear regression and purposeful selection were used to determine associations with severe IVH. RESULTS: Severe IVH (grades 3-4) was observed in 14.6% of the infants. Irrespective of the model used, Apgar score at 5 minutes and DCM were significantly associated with severe IVH. A clinically relevant 5-mm Hg increase in DCM was associated with a 1.83- to 1.89-fold increased odds of developing severe IVH. CONCLUSION: Elevated DCM was associated with severe IVH, consistent with previous animal data showing that IVH is associated with hyperperfusion. Measurement of DCM may be more useful than blood pressure in defining cerebral perfusion in premature infants.

The Ontogeny of Cerebrovascular Pressure Autoregulation in Premature Infants.

Our objective was to quantify cerebrovascular autoregulation as a function of gestational age (GA) and across the phases of the cardiac cycle. One hundred eighty-six premature infants, with a GA range of 23-33 weeks, were monitored using umbilical artery catheters and transcranial Doppler insonation of middle cerebral artery flow velocity (FV) for 1-h sessions over the first week of life. Autoregulation was quantified as a moving correlation coefficient between systolic arterial blood pressure (ABP) and systolic FV (Sx); mean ABP and mean FV (Mx); diastolic ABP and diastolic FV (Dx). Autoregulation was compared across GAs for each aspect of the cardiac cycle. Systolic FV was pressure-passive in infants with the lowest GA, and Sx decreased with increased GA (r = -0.3; p < 0.001). By contrast, Dx was elevated in all subjects, and showed minimal change with increased GA (r = -0.06; p = 0.05). Multivariate analysis confirmed that GA (p < 0.001) and the "closing margin" (p < 0.01) were associated with Sx. Premature infants have low and almost always pressure-passive diastolic cerebral blood FV. Conversely, the regulation of systolic cerebral blood FV by autoregulation was manifested in this cohort at a GA of between 23 and 33 weeks.

The Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants.

Premature infants are at an increased risk of intraventricular hemorrhage (IVH). The roles of hypotension and hyperemia are still debated. Critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. When diastolic ABP is equal to CrCP, CBF occurs only during systole. The difference between diastolic ABP and CrCP is the diastolic closing margin (DCM). We hypothesized that a low DCM was associated with IVH. One hundred eighty-six premature infants, with a gestational age (GA) range of 23-33 weeks, were monitored with umbilical artery catheters and transcranial Doppler insonation of middle cerebral artery flow velocity for 1-h sessions over the first week of life. CrCP was calculated linearly and using an impedance model. A multivariate generalized linear regression model was used to determine associations with severe IVH (grades 3-4). An elevated DCM by either method was associated with IVH (p < 0.0001 for the linear method; p < 0.001 for the impedance model). Lower 5-min Apgar scores, elevated mean CBF velocity, and lower mean ABP were also associated with IVH (p < 0.0001). Elevated DCM, not low DCM, was associated with severe IVH in this cohort.

The Ontogeny of Cerebrovascular Critical Closing Pressure.

Premature infants are at risk of vascular neurological insults. Hypotension and hypertension are considered injurious, but neither condition is defined with consensus. Critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow ceases. CrCP may serve to define subject-specific low or high ABP. Our objective was to quantify CrCP as a function of gestational age (GA). One hundred eighty-six premature infants with a GA range of 23-33 weeks, were monitored with umbilical artery catheters and transcranial Doppler insonation of middle cerebral artery flow velocity (FV) for 1-h sessions over the first week of life. CrCP was calculated using an impedance model derivation with Doppler-based estimations of cerebrovascular resistance and compliance. CrCP increased significantly with GA (r = 0.47; slope = 1.4 mmHg/week gestation), an association that persisted with multivariate analysis (p < 0.001). Higher diastolic ABP and higher GA were associated with increased CrCP (p <0.001 for both). CrCP increases significantly at the end of the second and beginning of the third trimester. The low CrCP observed in premature infants may explain their ability to tolerate low ABP without global cerebral infarct or hemorrhage.