Rosendo A. Rodriguez

Reliability estimates for steady ― state evoked potentials

The steady-state evoked potentials are most efficiently recorded using Fourier analysis. The reliability of this evoked potential is best estimated using either Hotellings T2 or phase coherence. Using these techniques, the response to 500 Hz tones presented at a rate of 40/sec can be reliably recognized on average down to intensities of below 15 dB SL in an awake subject. Sleep significantly decreases the amplitude of the response and significantly raises the threshold for recognizing the response by 11 dB.

Human auditory steady state responses: effects of intensity and frequency

Human auditory steady state responses were recorded in 41 normal subjects and 22 patients with hearing loss. The effect of intensity on the responses at different tonal frequencies was assessed using the sweep technique. The amplitude of the responses increases and the phase delay decreases with increasing intensity. Both the amplitude and the phase delay are smaller for high frequency tone bursts. Notched noise decreases the amplitude of the response by a factor of two but does not affect the phase of the responses. Thresholds were estimated in waking subjects using two techniques: intensity sweeps analyzed by linear regressions, and fixed intensities analyzed by Hotellings T2 test. Frequency-specific thresholds obtained with notched noise were less variable and more accurate with the fixed intensity technique. In patients with sensorineural hearing loss the amplitude increased more with increasing intensity above threshold than in patients with conductive hearing loss.

Predictors of Early Neurocognitive Deficits in Low-Risk Patients Undergoing On-Pump Coronary Artery Bypass Surgery

Background— Postoperative cognitive deficits (POCDs) are a source of morbidity and occur frequently even in low-risk patients undergoing cardiac surgery. Predictors of neurocognitive deficits can identify potentially modifiable risk factors as well as high-risk patients in whom alternate revascularization strategies may be considered. Methods and Results— 448 patients undergoing coronary surgery (coronary artery bypass graft [CABG]) underwent standardized preoperative and postoperative neurocognitive testing as part of 2 randomized trials evaluating the effects of mild hypothermia during coronary surgery. Prospectively collected data were used to identify univariate predictors of POCDs and multivariable logistic regression models were constructed. Models were bootstrapped 1000 times. POCDs occurred in 59% of patients. Significant univariate predictors included intraoperative normothermia, impaired left ventricular (LV) function, higher educational level, elevated serum creatinine and reduced creatinine clearance, prolonged intubation time, intensive care unit (ICU) stay, and hospital stay. Advanced age, presence of carotid disease, and cardiopulmonary bypass time were not associated with increased POCDs in this cohort. Multivariable modeling identified intraoperative normothermia (odds ratio [95% confidence interval] −1.15 [1.01, 1.31]), poor LV function (1.53 [1.02, 2.30]), and elevated preoperative creatinine (1.01 [1.00 to 1.03] for every 1 mmol/L increase), prolonged (>24 hours) ICU stay (1.88 [1.27 to 2.79]), and higher educational level (1.52 [1.01 to 2.28]) as independent predictors of POCD occurrence. Conclusions— Mild hypothermia, in the intraoperative and perioperative period, may be a protective strategy for the prevention of POCDs. Patients with elevated pre-operative creatinine and poor LV function carry a higher risk of POCDs and may benefit from revascularization strategies other than conventional on-pump CABG.

Effect of perfusionist technique on cerebral embolization during cardiopulmonary bypass

Objective: To determine the association between high-intensity transient signals (HITS) and perfusionist interventions, purging techniques, pump flows and venous reservoir blood volume levels during cardiopulmonary bypass. Methods: Transcranial Doppler was used to detect HITS in the middle cerebral artery during the period of aortic crossclamping in patients undergoing coronary artery bypass grafting. Perfusionist-related interventions were recorded and included blood sampling (including the number of times that the oxygenator sampling manifold was purged), drug bolus injections and infusions (vasopressors, crystalloid and mannitol). Pump flows and venous reservoir volume levels were also documented. Results: There were 534 interventions in 90 patients [median number of interventions per patient: 6 (quartiles: 4, 8)]. The median total HITS count from all interventions was 17 (5, 37). This represented 38% of the total HITS counts during aortic crossclamping. Factors contributing to differences in the HITS count included type of intervention (p<0.0001) and perfusionist (p=0.0012). Blood sampling (p<0.001) and drug bolus injections (p=0.06) had higher HITS counts per patient than infusions. Repetitive purging significantly increased HITS counts (r=0.74; p<0.001). Purging perfusionists (purging: 1 - 10 times) had higher HITS counts per patient [5 HITS (1, 15) than nonpurgers [0 HITS (0, 1) p<0.0001]. HITS counts were significantly correlated with reservoir volumes (r=-0.20, p=0.017) and pump flow rates (r=0.21, p=0.008). Reservoir volume levels ≤ 800 mL were associated with higher HITS counts per intervention [11 HITS (2, 27)] during blood sampling compared with higher volume levels [3 HITS (1, 10), p=0.001]. Conclusions: Cerebral emboli associated with perfusionist interventions can be minimized by not purging the sampling manifold, using continuous infusions rather than bolus injections, and maintaining high blood-volume levels (>800 mL) in the venous reservoir.

Cerebral Emboli Detected by Transcranial Doppler During Cardiopulmonary Bypass Are Not Correlated With Postoperative Cognitive Deficits

Background and Purpose— High-intensity transient signals (HITS) are the transcranial Doppler representation of both air and solid cerebral emboli. We studied the frequency of HITS associated with different surgical maneuvers during cardiopulmonary bypass for coronary artery bypass graft surgery and their association with postoperative cognitive dysfunction (POCD). Methods— We combined 356 patients undergoing coronary artery bypass graft from 2 clinical trials who had both neuropsychological testing (before, 1 week and 3 months after surgery) and transcranial Doppler during cardiopulmonary bypass. HITS were grouped into periods that included: cannulation, cardiopulmonary bypass onset, aortic crossclamp-on, aortic crossclamp-off, side clamp-on, side clamp-off, and decannulation. POCD was defined by a decreased combined Z-score of at least 2.0 or reduction in Z-scores of at least 2.0 in 20% of the individual tests. Results— Incidence of POCD was 47.3% and 6.3% at 1 week and 3 months after surgery. There was no association between cardiopulmonary bypass counts of HITS and POCD at 1 week (P=0.617) and 3 months (P=0.110). No differences in HITS counts were identified at any of the surgical periods between patients with and without POCD. Factors affecting HITS counts were surgical period (P<0.0001), blood flow velocity (P=0.012), cardiopulmonary bypass duration (P=0.040), and clinical study (P=0.048). Conclusions— Although cerebral microemboli have been implicated in the pathogenesis of POCD, in this study that included low-risk patients undergoing coronary artery bypass surgery, there was no demonstrable correlation between the counts of HITS and POCD.

Evaluation of brain-stem auditory evoked potentials using dynamic time warping

Dynamic time warping is a procedure whereby portions of a temporal sequence of values are stretched or shrunk to make it similar to another sequence. This procedure can be used to align the brain-stem auditory evoked potentials recorded from different subjects prior to averaging. The resultant warp-average more closely resembles the wave form of a typical subject than the conventional average. Dynamic time warping can also be used to compare one brain-stem auditory evoked potential to another. This comparison can show the differences that result from changes in a stimulus parameter such as intensity or repetition rate. When a patients wave form is compared to a normal template, warping can identify the peaks in the patients wave form that correspond most closely to the peaks in the normal template. Compared to an experienced human interpreter, warping is very accurate in identifying the waves of normal brain-stem auditory evoked potentials (error rate between 0 and 4%) and reasonably accurate in identifying the peaks in abnormal wave forms (error rate between 3 and 18%).

Postbypass effects of delayed rewarming on cerebral blood flow velocities in infants after total circulatory arrest

Cerebral perfusion is reduced after prolonged periods of total circulatory arrest in infants. Methods of rewarming after arrest may modify the flow pattern of recovery, and a single report has suggested that using cold reperfusion to delay rewarming could mitigate abnormalities in cerebral blood flow. Cerebral perfusion was evaluated by transcranial Doppler sonography in 16 infants who required periods of total circulatory arrest of 35 minutes or more. In group A (n = 9) rewarming was begun immediately on reperfusion, whereas in group B (n = 7) a 10-minute period of cold reperfusion was instituted before rewarming was begun. The mean and end-diastolic flow velocities were measured before incision (baseline) and at 20, 45, and 90 minutes after conclusion of cardiopulmonary bypass. Mean arterial pressure, hematocrit value, and arterial carbon dioxide tension were controlled, with no significant differences between the two groups (p > 0.05). In group A, the mean cerebral blood flow velocity was below the baseline level at all three postbypass measurements (p < 0.001). In group B, however, mean velocity did not differ significantly from the baseline value (p > 0.05). Twenty minutes after bypass, 89% of the patients in group A had no diastolic Doppler signal, indicating absence of perfusion during diastole, compared with only 28% in group B (p = 0.02). These preliminary results suggest that a delay in rewarming on reperfusion may be beneficial in infants after circulatory arrest.

Transcranial Doppler characteristics of different embolic materials during in vivo testing.

Purpose. The authors investigated whether ultrasonic characteristics of embolic signals could be used to differentiate embolic composition. Materials and Methods. The authors analyzed high‐intensity transient signals (HITS) from 3 patients with patent foramen ovale during the bubble contrast test and during total joint replacement surgery. In 3 anesthetized dogs, latex microspheres, fat particles, and air bubbles were injected into the internal carotid artery and HITS were identified in the cerebral circulation. The area under the receiver operating characteristic curve quantified the usefulness of each measure to distinguish embolic composition. Results. In humans, HITS intensity (area: 0.80) and frequency (area: 0.73) but not duration (area: 0.32) were useful to distinguish air bubbles from presumed solid emboli. In animals, intensity distinguished micro‐spheres from air (area: 0.94) and microspheres from fat (area: 0.94) but was less useful for fat and air (area: 0.64). The duration (area: 0.54–0.76) and frequency (area: 0.54–0.63) were poor discriminators. Conclusion. The HITS intensity best distinguished embolic composition. Particle size should be taken into account in future research.

Sources of Variability in the Detection of Cerebral Emboli with Transcranial Doppler During Cardiac Surgery

Objective. The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high‐intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB). Methods. Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods. Results. Reviewers achieved agreement in 96% of 2190 Doppler signals (κ= 0.90). Relative intensities calculated with the TCD‐software method were 3 dB (95% CI: 3.0‐3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively. Conclusions. Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.

A method to distinguish between gaseous and solid cerebral emboli in patients with prosthetic heart valves

BACKGROUND The difficulty of distinguishing solid from air emboli using transcranial Doppler has limited its use in situations where both types of emboli can occur, such as in mechanical heart valve patients. To make transcranial Doppler clinically useful, a method must be found to distinguish benign air bubbles from the more damaging solid particulates. Since inhalation of 100% oxygen reduces the amount of air bubbles in mechanical heart valve patients, the ultrasonic features of the remaining emboli would be characteristic of solid particulates. OBJECTIVE We determined the accuracy of the signal relative intensity measured with transcranial Doppler to distinguish between gaseous and non-gaseous emboli in mechanical heart valve patients examined during room air and 100% oxygen. Embolic signals detected in patients with bioprosthetic valves examined during 100% oxygen comprised the source of solid particulates. METHODS Embolic signals were detected during room air (n=141) and 100% oxygen (n=45) from 17 mechanical valve patients at two Doppler examinations (4h and 4 days after surgery). Solid embolic signals (n=31) from seven patients with bioprosthetic valves were identified with 100% oxygen within the first 4h after surgery. Frequency plots and receiver operating characteristic curves assessed signal intensity differences between mechanical and bioprosthetic valve groups during 100% oxygen and the efficacy of the relative intensity for differentiating gaseous from solid emboli. RESULTS Administration of 100% oxygen during transcranial Doppler examination in mechanical heart valve patients decreased the count of embolic signals compared with room air (p=0.006). The embolic signals of mechanical heart valve patients breathing 100% oxygen showed lower relative intensities compared with those during room air. The distribution of the signal relative intensity between mechanical and bioprosthetic valve groups during 100% oxygen was similar. A 16dB cut-off threshold achieved the best accuracy for differentiating non-gaseous from gaseous emboli (sensitivity: 60%; specificity: 82%; area: 0.721; p<0.0001). CONCLUSIONS The use of a signal intensity cut-off offers adequate discrimination of the embolic composition in mechanical heart valve patients. Future studies evaluating prophylactic treatments of thrombosis in these patients should assess the predictive value of this intensity threshold and their potential association with outcome indicators and procoagulant markers.