R. Blaine Easley

Real-Time Continuous Monitoring of Cerebral Blood Flow Autoregulation Using Near-Infrared Spectroscopy in Patients Undergoing Cardiopulmonary Bypass

Background and Purpose— Individualizing mean arterial blood pressure targets to a patients cerebral blood flow autoregulatory range might prevent brain ischemia for patients undergoing cardiopulmonary bypass (CPB). This study compares the accuracy of real-time cerebral blood flow autoregulation monitoring using near-infrared spectroscopy with that of transcranial Doppler. Methods— Sixty adult patients undergoing CPB had transcranial Doppler monitoring of middle cerebral artery blood flow velocity and near-infrared spectroscopy monitoring. The mean velocity index (Mx) was calculated as a moving, linear correlation coefficient between slow waves of middle cerebral artery blood flow velocity and mean arterial blood pressure. The cerebral oximetry index was calculated as a similar coefficient between slow waves of cerebral oximetry and mean arterial blood pressure. When cerebral blood flow is autoregulated, Mx and cerebral oximetry index vary around zero. Loss of autoregulation results in progressively more positive Mx and cerebral oximetry index. Results— Mx and cerebral oximetry index showed significant correlation (r=0.55, P<0.0001) and good agreement (bias, 0.08±0.18, 95% limits of agreement: −0.27 to 0.43) during CPB. Autoregulation was disturbed in this cohort during CPB (average Mx 0.38, 95% CI 0.34 to 0.43). The lower cerebral blood flow autoregulatory threshold (defined as incremental increase in Mx >0.45) during CPB ranged from 45 to 80 mm Hg. Conclusions— Cerebral blood flow autoregulation can be monitored continuously with near-infrared spectroscopy in adult patients undergoing CPB. Real-time autoregulation monitoring may have a role in preventing injurious hypotension during CPB. Clinical Trials Registration— at www.clinicaltrials.gov (NCT00769691).

Continuous Time-Domain Analysis of Cerebrovascular Autoregulation Using Near-Infrared Spectroscopy

Background and Purpose— Assessment of autoregulation in the time domain is a promising monitoring method for actively optimizating cerebral perfusion pressure (CPP) in critically ill patients. The ability to detect loss of autoregulatory vasoreactivity to spontaneous fluctuations in CPP was tested with a new time-domain method that used near-infrared spectroscopic measurements of tissue oxyhemoglobin saturation in an infant animal model. Methods— Piglets were made progressively hypotensive over 4 to 5 hours by inflation of a balloon catheter in the inferior vena cava, and the breakpoint of autoregulation was determined using laser-Doppler flowmetry. The cerebral oximetry index (COx) was determined as a moving linear correlation coefficient between CPP and INVOS cerebral oximeter waveforms during 300-second periods. A laser-Doppler derived time-domain analysis of spontaneous autoregulation with the same parameters (LDx) was also determined. Results— An increase in the correlation coefficient between cerebral oximetry values and dynamic CPP fluctuations, indicative of a pressure-passive relationship, occurred when CPP was below the steady state autoregulatory breakpoint. This COx had 92% sensitivity (73% to 99%) and 63% specificity (48% to 76%) for detecting loss of autoregulation attributable to hypotension when COx was above a threshold of 0.36. The area under the receiver-operator characteristics curve for the COx was 0.89. COx correlated with LDx when values were sorted and averaged according to the CPP at which they were obtained (r=0.67). Conclusions— The COx is sensitive for loss of autoregulation attributable to hypotension and is a promising monitoring tool for determining optimal CPP for patients with acute brain injury.

Blood Pressure Excursions Below the Cerebral Autoregulation Threshold During Cardiac Surgery Are Associated With Acute Kidney Injury

Objectives:To determine whether mean arterial blood pressure excursions below the lower limit of cerebral blood flow autoregulation during cardiopulmonary bypass are associated with acute kidney injury after surgery. Setting:Tertiary care medical center. Patients:Four hundred ten patients undergoing cardiac surgery with cardiopulmonary bypass. Design:Prospective observational study. Interventions:None. Measurements and Main Results:Autoregulation was monitored during cardiopulmonary bypass by calculating a continuous, moving Pearson’s correlation coefficient between mean arterial blood pressure and processed near-infrared spectroscopy signals to generate the variable cerebral oximetry index. When mean arterial blood pressure is below the lower limit of autoregulation, cerebral oximetry index approaches 1, because cerebral blood flow is pressure passive. An identifiable lower limit of autoregulation was ascertained in 348 patients. Based on the RIFLE criteria (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease), acute kidney injury developed within 7 days of surgery in 121 (34.8%) of these patients. Although the average mean arterial blood pressure during cardiopulmonary bypass did not differ, the mean arterial blood pressure at the limit of autoregulation and the duration and degree to which mean arterial blood pressure was below the autoregulation threshold (mm Hg × min/hr of cardiopulmonary bypass) were both higher in patients with acute kidney injury than in those without acute kidney injury. Excursions of mean arterial blood pressure below the lower limit of autoregulation (relative risk 1.02; 95% confidence interval 1.01 to 1.03; p < 0.0001) and diabetes (relative risk 1.78; 95% confidence interval 1.27 to 2.50; p = 0.001) were independently associated with for acute kidney injury. Conclusions:Excursions of mean arterial blood pressure below the limit of autoregulation and not absolute mean arterial blood pressure are independently associated with for acute kidney injury. Monitoring cerebral oximetry index may provide a novel method for precisely guiding mean arterial blood pressure targets during cardiopulmonary bypass.

Cerebrovascular Reactivity Measured by Near-Infrared Spectroscopy

BACKGROUND AND PURPOSE The pressure reactivity index (PRx) describes cerebral vessel reactivity by correlation of slow waves of intracranial pressure (ICP) and arterial blood pressure. In theory, slow changes in the relative total hemoglobin (rTHb) measured by near-infrared spectroscopy are caused by the same blood volume changes that cause slow waves of ICP. Our objective was to develop a new index of vascular reactivity, the hemoglobin volume index (HVx), which is a low-frequency correlation of arterial blood pressure and rTHb measured with near-infrared spectroscopy. METHODS Gradual hypotension was induced in piglets while cortical laser-Doppler flux was monitored. ICP was monitored, and rTHb was measured continuously using reflectance near-infrared spectroscopy. The HVx was recorded as a moving linear correlation between slow waves (20 to 300 seconds) of arterial blood pressure and rTHb. Autoregulation curves were constructed by averaging values of the PRx or HVx in 5-mm Hg bins of cerebral perfusion pressure. RESULTS The laser-Doppler flux-determined lower limit of autoregulation was 29.4+/-6.7 mm Hg (+/-SD). Coherence between rTHb and ICP was high at low frequencies. HVx was linearly correlated with PRx. The PRx and HVx both showed higher values below the lower limit of autoregulation and lower values above the lower limit of autoregulation. Areas under the receiver operator characteristic curves were 0.88 and 0.85 for the PRx and HVx, respectively. CONCLUSIONS Coherence between the rTHb and ICP waveforms at the frequency of slow waves suggests that slow waves of ICP are related to blood volume changes. The HVx has potential for further development as a noninvasive alternative to the PRx.

Monitoring Cerebral Blood Flow Pressure Autoregulation in Pediatric Patients During Cardiac Surgery

Background and Purpose— The limits of cerebral blood flow-pressure autoregulation have not been adequately defined for pediatric patients. Mean arterial blood pressure below these limits might contribute to brain injury during cardiac surgery. The purpose of this pilot study was to assess a novel method of determining the lower limits of pressure autoregulation in pediatric patients supported with cardiopulmonary bypass. Methods— A prospective, observational pilot study was conducted in children (n=54) undergoing cardiac surgery with cardiopulmonary bypass for correction of congenital heart defects. Cerebral oximetry index (COx) was calculated as a moving, linear correlation coefficient between slow waves of arterial blood pressure and cerebral oximetry measured with near-infrared spectroscopy. An autoregulation curve was constructed for each patient with averaged COx values sorted by arterial blood pressure. Results— Hypotension was associated with increased values of COx (P<0.0001). For 77% of patients, an individual estimate of lower limits of pressure autoregulation could be determined using a threshold COx value of 0.4. The mean lower limits of pressure autoregulation for the cohort using this method was 42±7 mm Hg. Conclusions— This pilot study of COx monitoring in pediatric patients demonstrates an association between hypotension during cardiopulmonary bypass and impairment of autoregulation. The COx may be useful to identify arterial blood pressure-dependent limits of cerebral autoregulation during cardiopulmonary bypass. Larger trials with neurological outcomes are indicated.

CT-measured regional specific volume change reflects regional ventilation in supine sheep

Computer tomography (CT) imaging techniques permit the noninvasive measurement of regional lung function. Regional specific volume change (sVol), determined from the change in lung density over a tidal breath, should correlate with regional ventilation and regional lung expansion measured with other techniques. sVol was validated against xenon (Xe)-CT-specific ventilation (sV) in four anesthetized, intubated, mechanically ventilated sheep. Xe-CT used expiratory gated axial scanning during the washin and washout of 55% Xe. sVol was measured from the tidal changes in tissue density (H, houndsfield units) of lung regions using the relationship sVol = [1,000(Hi - He)]/[He(1,000 + Hi)], where He and Hi are expiratory and inspiratory regional density. Distinct anatomical markings were used to define corresponding lung regions of interest between inspiratory, expiratory, and Xe-CT images, with an average region of interest size of 1.6 +/- 0.7 ml. In addition, sVol was compared with regional volume changes measured directly from the positions of implanted metal markers in an additional animal. A linear relationship between sVol and sV was demonstrated over a wide range of regional sV found in the normal supine lung, with an overall correlation coefficient (R(2)) of 0.66. There was a tight correlation (R(2) = 0.97) between marker-measured volume changes and sVol. Regional sVol, which involves significantly reduced exposure to radiation and Xe gas compared with the Xe-CT method, represents a safe and efficient surrogate for measuring regional ventilation in experimental studies and patients.

Molecular Cloning and Characterization of Canine Pre-B-Cell Colony-Enhancing Factor

During our previous attempt to search for the candidate genes to acute lung injury (ALI), we unexpectedly identified PBEF as the most highly upregulated gene in a canine model of ALI by crosshybridizing canine lung cRNA to the Affymetrix human gene chip HG-U133A. The result suggested that PBEF may be a potential biomarker in ALI. To extend and translate that finding, we have performed the molecular cloning and characterization of canine PBEF cDNA in this study. Deduced amino acid sequence alignment revealed that the PBEF gene is evolutionarily highly conserved, with the canine PBEF protein sequence 96% identical to human PBEF and 94% identical to both murine and rat PBEF counterparts. Canine PBEF protein was successfully expressed both by in vitro transcription coupled with translation in a cell-free system and by transfection of canine PBEF cDNA into the human lung type II alveolar adenocarcinoma cell line A549. The expressed canine PBEF protein was visualized by either an anti-V5 tag peptide polyclonal antibody or an anti-canine PBEF peptide polyclonal antibody. RT-PCR assay indicates that canine PBEF is expressed in canine lung, brain, heart, liver, spleen, kidney, pancreas, and muscle, with liver showing the highest expression, followed by muscle. Isolation of the canine PBEF cDNA and expression of its recombinant protein may provide molecular tools to study the molecular mechanism of ALI in the canine model and to elucidate the potential role of PBEF as an ALI biomarker.

Monitored Anesthesia Care With a Combination of Ketamine and Dexmedetomidine During Cardiac Catheterization

No specific regimen has been universally accepted as ideal for sedation during cardiac catheterization in infants and children. We evaluated a combination of ketamine and dexmedetomidine for sedation during cardiac catheterization in children with congenital heart disease. The study design included a retrospective analysis of data sheets and hospital records. The protocol for sedation was standardized and data collected prospectively for an ongoing quality assurance project. Heart rate, blood pressure, and oxygen saturation were recorded every 1 minute for the first 5 minutes and then at 5-minute intervals. The efficacy of sedation was judged by the need for supplemental ketamine doses. The study cohort included 16 infants and children undergoing either diagnostic or therapeutic cardiac catheterization. Sedation was initiated with a bolus dose of ketamine (2 mg/kg) and dexmedetomidine (1 μg/kg) administered over 3 minutes followed by a continuous infusion of dexmedetomidine (2 μg/kg per hour for the initial 30 minutes followed by 1 μg/kg per hour for the duration of the case). Supplemental analgesia/sedation was provided by ketamine (1 mg/kg) as needed. The baseline heart rate was 103 ± 21 beats/minute. After the bolus dose of ketamine and dexmedetomidine, the heart rate increased by 7 ± 5 beats/minute. The greatest increase was 15 beats/minute. The low heart rate after the bolus dose of ketamine/dexmedetomidine or during the subsequent dexmedetomidine infusion was 91 ± 20 beats/minute (P < 0.001 compared with baseline) and the high heart rate was 110 ± 25 beats/minute (P < 0.01 compared with baseline). In two patients, the dexmedetomidine infusion was decreased from 2 to 1 μg/kg per hour at 12 to 15 minutes instead of 30 minutes as a result of a decreased heart rate. No clinically significant changes in blood pressure or respiratory rate were noted. Two patients developed upper airway obstruction, which responded to repositioning of the airway. No apnea was noted. During the procedure, the PaCO2 varied from 37.5 to 48 mm Hg and was ≥45 mm Hg in seven patients. No patient responded to local infiltration of the groin and placement of the arterial and venous cannulae. Three patients required a supplemental dose of ketamine (1 mg/kg) during the procedure. In two of these patients, this was required before changing the cannulae. Our preliminary data suggest that a combination of ketamine and dexmedetomidine provides effective sedation for cardiac catheterization in infants and children without significant effects on cardiovascular or ventilatory function.

The association between brain injury, perioperative anesthetic exposure, and 12‐month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study

Adverse neurodevelopmental outcomes are observed in up to 50% of infants after complex cardiac surgery. We sought to determine the association of perioperative anesthetic exposure with neurodevelopmental outcomes at age 12 months in neonates undergoing complex cardiac surgery and to determine the effect of brain injury determined by magnetic resonance imaging (MRI).

Dexmedetomidine for the treatment of postanesthesia shivering in children

Background:  Shivering is a common postanesthesia adverse event with multiple etiologies and multiple suggested prophylactic and abortive treatment regimens. Dexmedetomidine, a centrally acting α2‐adrenergic agonist, has been used as a sedative agent and is known to reduce the shivering threshold. We hypothesized that children with postanesthesia shivering would reduce shivering behavior following a single bolus dose of dexmedetomidine.