Opioid-Sparing Cardiac Anesthesia: Secondary Analysis of an Enhanced Recovery Program for Cardiac Surgery.

BACKGROUND: Cardiac anesthetics rely heavily on opioids, with the standard patient receiving between 70 and 105 morphine sulfate equivalents (MSE; 10-15 µg/kg of fentanyl). A central tenet of Enhanced Recovery Programs (ERP) is the use of multimodal analgesia. This study was performed to assess the association between nonopioid interventions employed as part of an ERP for cardiac surgery and intraoperative opioid administration. METHODS: This study represents a post hoc secondary analysis of data obtained from an institutional ERP for cardiac surgery. Consecutive patients undergoing cardiac surgery received 5 nonopioid interventions, including preoperative gabapentin and acetaminophen, intraoperative dexmedetomidine and ketamine infusions, and regional analgesia via serratus anterior plane block. The primary objective, the association between intraoperative opioid administration and the number of interventions provided, was assessed via a linear mixed-effects regression model. To assess the association between intraoperative opioid administration and postoperative outcomes, patients were stratified into high (>50 MSE) and low (≤50 MSE) opioids, 1:1 propensity matched based on 15 patients and procedure covariables and assessed for associations with postoperative outcomes of interest. To investigate the impact of further opioid restriction, ultralow (≤25 MSE) opioid participants were then identified, 1:3 propensity matched to high opioid patients, and similarly compared. RESULTS: A total of 451 patients were included in the overall analysis. Analysis of the primary objective revealed that intraoperative opioid administration was inversely related to the number of interventions employed (estimated -7.96 MSE per intervention, 95% confidence interval [CI], -9.82 to -6.10, P < .001). No differences were detected between low (n = 136) and high (n = 136) opioid patients in postoperative complications, postoperative pain scores, time to extubation, or length of stay. No differences were found in outcomes between ultralow (n = 63) and high (n = 132) opioid participants. CONCLUSIONS: Nonopioid interventions employed as part of an ERP for cardiac surgery were associated with a reduction of intraoperative opioid administration. Low and ultralow opioid use was not associated with significant differences in postoperative outcomes. These findings are hypothesis-generating, and future prospective studies are necessary to establish the role of opioid-sparing strategies in the setting of cardiac surgery.

Results from an enhanced recovery program for cardiac surgery.

OBJECTIVE: Enhanced recovery programs are multidisciplinary perioperative bundles of evidence-based process measures. Following the design and implementation of preanesthesia and intraoperative enhanced recovery programs for cardiac surgery guidelines, we evaluated the association between compliance and key clinical outcomes. METHODS: Consecutive patients undergoing cardiac surgery at a single tertiary medical center from September 2017 to June 2018 were included. Patients were stratified into low (0-4 measures) and high (5-7 measures) compliance groups and then 1-to-3 propensity matched on the basis of 15 patient and surgical covariables. The primary outcome of interest was time to postoperative extubation. Secondary outcomes included interval time point extubation rates and intensive care unit, floor, and hospital lengths of stay. RESULTS: A total of 451 patients were included in the study. After propensity matching (n = 315), patients in the high compliance group (n = 84) had a significant reduction in time to extubation (P < .001), floor length of stay (P = .01), and hospital length of stay (P = .03) compared with patients in the low compliance group (n = 231). Patients in the high compliance group were more likely to be extubated in the operating room (odds ratio, 35.8; 95% confidence interval, 10.66-168.75; P < .001) and within 6 hours of surgery (odds ratio, 2.6; 95% confidence interval, 1.18-6.07; P < .02). High compliance was associated with a median estimated time reduction of 3.4 hours to postoperative extubation (P < .001) and 19.4 hours in hospital length of stay (P = .01) compared with low compliance counterparts. There were no reintubations reported among patients extubated in the operating room (0/62 patients). CONCLUSIONS: There is value in developing phase-specific enhanced recovery programs guidelines, which improve rates of early extubation and affect the duration of stay after cardiac surgery. These results are hypothesis generating, and further prospective study is necessary to identify clinical impact of further program expansion.

Trends and Updates on Cardiopulmonary Bypass Setup in Pediatric Cardiac Surgery.

Perfusion strategies for cardiopulmonary bypass have direct consequences on pediatric cardiac surgery outcomes. However, inconsistent study results and a lack of uniform evidence-based guidelines for pediatric cardiopulmonary bypass management have led to considerable variability in perfusion practices among, and even within, institutions. Important aspects of cardiopulmonary bypass that can be optimized to improve clinical outcomes of pediatric patients undergoing cardiac surgery include extracorporeal circuit components, priming solutions, and additives. This review summarizes the current literature on circuit components and priming solution composition with an emphasis on crystalloid, colloid, and blood-based primes, as well as mannitol, bicarbonate, and calcium.

Initiation of a High-Frequency Jet Ventilation Strategy for Catheter Ablation for Atrial Fibrillation: Safety and Outcomes Data.

OBJECTIVES: The aim of the current investigation is to examine whether use of high-frequency jet ventilation (HFJV) during pulmonary vein isolation (PVI) performed with force-sensing catheters is associated with improved outcomes. BACKGROUND: Catheter ablation is well established as therapy for symptomatic atrial fibrillation (AF). Reconnection following PVI is commonly observed during repeat ablation procedures. Technologies that may optimize catheter stability and lesion delivery include both force-sensing ablation catheters and HFJV. METHODS: Patients undergoing PVI at Johns Hopkins Hospital were prospectively enrolled in a registry. The study compared procedural characteristics, adverse event rates, and 1-year procedural outcomes in patients undergoing PVI supported either by standard ventilation or HFJV. Patient and procedural aspects were otherwise constant. RESULTS: Eighty-four HFJV patients and 84 matched control patients with 1-year outcome data were identified. Atrial arrhythmia recurrence occurred in 26 of 84 HFJV patients (31%) and 42 of 84 control patients (50%; p = 0.019). In patients with paroxysmal AF, arrhythmia recurrence in HFJV and control patients was 27.3% and 47.3%, respectively (p = 0.045). In patients with persistent AF, arrhythmia recurrence rates were not significantly different (37.9% in HFJV patients, 55.2% in control patients; p = 0.184). On multivariate analysis, HFJV was independently associated with improved freedom from arrhythmia recurrence. Vasopressor use during HFJV cases was significantly higher than during standard ventilation (79.7% vs. 22.4%; p = 0.001). Indices of catheter stability and contact force adequacy were significantly higher in the HFJV patients than in control patients. Complication rates in the 2 groups were similarly low. CONCLUSIONS: Use of HFJV in patients undergoing PVI with radiofrequency force-sensing catheters is associated with improved outcomes, without appreciable increase in adverse procedural events.

A Review of Goal-Directed Cardiopulmonary Bypass Management in Pediatric Cardiac Surgery.

Cardiopulmonary bypass perfusion management significantly affects postoperative outcomes. In recent years, the principles of goal-directed therapy have been applied to the field of cardiothoracic surgery to improve patient outcomes. Goal-directed therapy involves continuous peri- and postoperative monitoring of vital clinical parameters to tailor perfusion to each patient's specific needs. Closely measured parameters include fibrinogen, platelet count, lactate, venous oxygen saturation, central venous oxygen saturation, mean arterial pressure, perfusion flow rate, and perfusion pulsatility. These parameters have been shown to influence postoperative fresh frozen plasma transfusion rate, coagulation state, end-organ perfusion, and mortality. In this review, we discuss the recent paradigm shift in pediatric perfusion management toward goal-directed perfusion.

Focused Review of Perioperative Care of Patients with Pulmonary Hypertension and Proposal of a Perioperative Pathway.

Morbidity and mortality risk increase considerably for patients with pulmonary hypertension (PH) undergoing non-cardiac surgery. Unfortunately, there are no comprehensive, evidence-based guidelines for perioperative evaluation and management of these patients. We present a brief review of the literature on perioperative outcomes for patients with PH and describe the implementation of a collaborative perioperative management program for these high-risk patients at a tertiary academic center.

Relationship Between the Ambulatory Arterial Stiffness Index and the Lower Limit of Cerebral Autoregulation During Cardiac Surgery.

BACKGROUND: Pulse pressure, the ambulatory arterial stiffness index (AASI), and the symmetric AASI are established predictors of adverse cardiovascular outcomes. However, little is known about their relationship to cerebral autoregulation. This study evaluated whether these markers of vascular properties relate to the lower limit of cerebral autoregulation (LLA). METHODS AND RESULTS: The LLA was determined during cardiac surgery with transcranial Doppler ultrasonography in 181 patients. All other variables were calculated from continuous intraoperative readings obtained before cardiopulmonary bypass. The LLA varied directly with the AASI (ß=3.12 per 0.1 change in AASI, P<0.001) and to a lesser extent the symmetric AASI (ß=2.02 per 0.1 change in symmetric AASI, P≤0.022), while peripheral pulse pressure was not significantly related (ß=0.0, P>0.99). Logistic regression revealed that the likelihood of LLA being >65 mm Hg increased by 50% (95% confidence interval, 11%-102%, P=0.008) for every 0.1 increase in the AASI. The AASI was able to predict a LLA above certain thresholds (area under the curve receiver operating characteristic for AASI predicting an LLA >65 mm Hg: 0.60; 95% confidence interval, 0.51%-0.68%, P=0.043). Incorporating additional variables improved the model's predictive ability (area under the curve for AASI predicting a LLA >65 mm Hg: 0.75; 95% confidence interval, 0.68-0.82, P=0.036). CONCLUSIONS: These data indicate that the LLA is related to the mechanical properties of the vasculature as represented by the AASI. The AASI can be used to predict LLA threshold levels during cardiac surgery. It is now possible to link elevations in the LLA with an increased AASI as determined from readily accessible intraoperative variables.

Pulse wave travel distance as a novel marker of ventricular-arterial coupling.

Each stroke volume ejected by the heart is distributed along the arterial system as a pressure waveform. How far the front of the pressure waveform travels within the arterial system depends both on the pulse wave velocity (PWV) and the ejection time (ET). We tested the hypothesis that ET and PWV are coupled together, in order to produce a pulse wave travel distance (PWTD = PWV × ET) which would match the distance from the heart to the most distant site in the arterial system. The study was conducted in 11 healthy volunteers. We recorded lead II of the ECG along with pulse plethysmography at ear, finger and toe. The ET at the ear and pulse arrival time to each peripheral site were extracted. We then calculated PWV followed by PWTD for each location. Taken into account the individual subject variability PWTDToe in the supine position was 153 cm (95% CI 146-160 cm). It was not different from arterial pathway distance from the heart to the toe (D Toe 153 cm). The PWTDFinger and PWTDEar were longer than the distance from the heart to the finger and ear irrespective of body position. ETEar and PWVToe appear to be coupled in healthy subjects to produce a PWTD that is roughly equivalent to the arterial pathway distance to the toe. We propose that PWTD should be evaluated further to test its potential as a noninvasive parameter of ventricular-arterial coupling in subjects with cardiovascular diseases.

Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition.

We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the nonvisual G protein-coupled receptor melanopsin (Opsin 4; Opn4). Here we tested the hypothesis that nonvisual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G protein-coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2, as demonstrated with a proximity ligation assay. Light elicited an intensity-dependent relaxation of PAs preconstricted with phenylephrine (PE), with a maximum response between 400 and 460 nm (blue light). Wavelength-specific photorelaxation was attenuated in PAs from Opn4-/- mice and further reduced following shRNA-mediated knockdown of Opn3. Inhibition of GRK2 amplified the response and prevented physiological desensitization to repeated light exposure. Blue light also prevented PE-induced constriction in isolated PAs, decreased basal tone, ablated PE-induced single-cell contraction of PASMCs, and reversed PE-induced depolarization in PASMCs when GRK2 was inhibited. The photorelaxation response was modulated by soluble guanylyl cyclase but not by protein kinase G or nitric oxide. Most importantly, blue light induced significant vasorelaxation of PAs from rats with chronic pulmonary hypertension and effectively lowered pulmonary arterial pressure in isolated intact perfused rat lungs subjected to acute hypoxia. These findings show that functional Opn3 and Opn4 in PAs represent an endogenous "optogenetic system" that mediates photorelaxation in the pulmonary vasculature. Phototherapy in conjunction with GRK2 inhibition could therefore provide an alternative treatment strategy for pulmonary vasoconstrictive disorders.

Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery.

Acute kidney injury after cardiac surgery is associated with increased morbidity and mortality. Methods for measuring urine output in real time may better ensure renal perfusion perioperatively in contrast to the current standard of care where urine output is visually estimated after empiric epochs of time. In this study, we describe an accurate method for monitoring urine output continuously during cardiopulmonary bypass. This may provide a means for setting patient-specific targets for blood pressure and cardiopulmonary bypass flow as a potential strategy to reduce the risk for acute kidney injury.

A Pulse Wave Velocity Based Method to Assess the Mean Arterial Blood Pressure Limits of Autoregulation in Peripheral Arteries.

Background: Constant blood flow despite changes in blood pressure, a phenomenon called autoregulation, has been demonstrated for various organ systems. We hypothesized that by changing hydrostatic pressures in peripheral arteries, we can establish these limits of autoregulation in peripheral arteries based on local pulse wave velocity (PWV). Methods: Electrocardiogram and plethysmograph waveforms were recorded at the left and right index fingers in 18 healthy volunteers. Each subject changed their left arm position, keeping the right arm stationary. Pulse arrival times (PAT) at both fingers were measured and used to calculate PWV. We calculated ΔPAT (ΔPWV), the differences between the left and right PATs (PWVs), and compared them to the respective calculated blood pressure at the left index fingertip to derive the limits of autoregulation. Results: ΔPAT decreased and ΔPWV increased exponentially at low blood pressures in the fingertip up to a blood pressure of 70 mmHg, after which changes in ΔPAT and ΔPWV were minimal. The empirically chosen 20 mmHg window (75-95 mmHg) was confirmed to be within the autoregulatory limit (slope = 0.097, p = 0.56). ΔPAT and ΔPWV within a 20 mmHg moving window were not significantly different from the respective data points within the control 75-95 mmHg window when the pressure at the fingertip was between 56 and 110 mmHg for ΔPAT and between 57 and 112 mmHg for ΔPWV. Conclusions: Changes in hydrostatic pressure due to changes in arm position significantly affect peripheral arterial stiffness as assessed by ΔPAT and ΔPWV, allowing us to estimate peripheral autoregulation limits based on PWV.

Difference between ejection times measured at two different peripheral locations as a novel marker of vascular stiffness.

Pulse wave velocity (PWV) has been recommended as an arterial damage assessment tool and a surrogate of arterial stiffness. However, the current technology does not allow to measure PWV both continuously and in real-time. We reported previously that peripherally measured ejection time (ET) overestimates ET measured centrally. This difference in ET is associated with the inherent vascular properties of the vessel. In the current study we examined ETs derived from plethysmography simultaneously at different peripheral locations and examined the influence of the underlying arterial properties on ET prolongation by changing the subject's position. We calculated the ET difference between two peripheral locations (ΔET) and its corresponding PWV for the same heartbeat. The ΔET increased with a corresponding decrease in PWV. The difference between ΔET in the supine and standing (which we call ET index) was higher in young subjects with low mean arterial pressure and low PWV. These results suggest that the difference in ET between two peripheral locations in the supine vs standing positions represents the underlying vascular properties. We propose ΔET in the supine position as a potential novel real-time continuous and non-invasive parameter of vascular properties, and the ET index as a potential non-invasive parameter of vascular reactivity.

Ejection time: influence of hemodynamics and site of measurement in the arterial tree.

The left ventricular ejection time is routinely measured from a peripheral arterial waveform. However, the arterial waveform undergoes constant transformation as the pulse wave propagates along the arterial tree. Our goal was to determine if the left ventricular ejection time measured peripherally in the arterial tree accurately reflected the ejection time measured through the aortic valve. Moreover, we examined/accessed the modulating influence of hemodynamics on ejection time measurements. Continuous wave Doppler waveform images through the aortic valve and the simultaneously obtained radial artery pressure waveforms were analyzed to determine central and peripheral ejection times, respectively. The peripheral ejection time was significantly longer than the simultaneously measured central ejection time (174.5±25.2 ms vs. 120.7±14.4 ms; P<0.0001; 17.4±8.7% increase). Moreover, the ejection time prolongation was accentuated at lower blood pressures, lower heart rate and lower pulse wave velocity. The time difference between centrally and peripherally measured ejection times likely reflects intrinsic vascular characteristics. Moreover, given that the ejection time also depends on blood pressure, heart rate and pulse wave velocity, peripherally measured ejection times might need to be adjusted to account for changes in these variables.

The impact of posture on the cardiac depolarization and repolarization phases of the QT interval in healthy subjects.

BACKGROUND: Postural changes affect both heart rate and the QT interval. OBJECTIVE: To investigate the effects of postural changes on the depolarization and repolarization phases of the QT interval. METHODS: A three lead ECG from 12 healthy young volunteers was recorded in the standing, sitting and in the supine positions. For the purpose of this study, we defined the depolarization phase as the QRS complex plus the ST segment and the repolarization phase as the duration of the T wave. RESULTS: QTc did not change with changes in position. The ratio of the duration of the depolarization phase to the repolarization phase was higher in the supine position (0.98±0.13) compared to the standing position (0.83±0.17). CONCLUSIONS: The origin of the T wave moves closer to the QRS complex during standing compared to the supine position. The observed changes are mainly due to shortening of the ST segment during standing compared to supine position.

Noninvasive Assessment of the Effect of Position and Exercise on Pulse Arrival to Peripheral Vascular Beds in Healthy Volunteers.

Background: The effects of position and exercise on pulse wave distribution across a healthy, compliant arterial tree are not fully understood. We studied the effects of exercise and position on the pattern of pulse arrival times (PATs) in healthy volunteers. Moreover, we compared the pulse arrival time ratios to the respective distance ratios between different locations. Methods: Thirteen young healthy volunteers were studied, using an electrocardiogram and plethysmograph to simultaneously record pulse wave arrival at the ear lobe, index finger and big toe. We compared the differences in PAT between each location at rest and post-exercise in the supine, sitting, and standing position. We also compared the PAT ratio (toe/ear, toe/finger, and finger/ear) to the corresponding pulse path distance ratios. Results: PAT was shortest at the ear then finger and longest at the toe regardless of position or exercise status. PATs were shorter post-exercise compared to rest. When transitioning from a standing to sitting or supine position, PAT to the ear decreased, while the PAT to the toe increased, and PAT to the finger didn't significantly change. PAT ratios were significantly smaller than predicted by the path distance ratios regardless of position or exercise status. Conclusions: Exercise makes PATs shorter. Standing position decrease PAT to the toe and increase to the ear. We conclude that PAT and PAT ratio represent the arterial vascular tree properties as surely as pulse transit time and pulse wave velocity.