Palliative Care Exposure Relative to Predicted Risk of Six-Month Mortality in Hospitalized Adults.

CONTEXT: The optimal strategy for implementing mortality-predicting algorithms to facilitate clinical care, prognostic discussions, and palliative care interventions remains unknown. OBJECTIVES: To develop and validate a real-time predictive model for 180 day mortality using routinely available clinical and laboratory admission data and determine if palliative care exposure varies with predicted mortality risk. METHODS: Adult admissions between October 1, 2013 and October.1, 2017 were included for the model derivation. A separate cohort was collected between January 1, 2018 and July 31, 2020 for validation. Patients were followed for 180 days from discharge, and logistic regression with selected variables was used to estimate patients' risk for mortality. RESULTS: In the model derivation cohort, 7963 events of 180 day mortality (4.5% event rate) were observed. Median age was 53.0 (IQR 24.0-66.0) with 92,734 females (52.5%). Variables with strongest association with 180 day mortality included: Braden Score (OR 0.83; 95% CI 0.82-0.84); admission Do Not Resuscitate orders (OR 2.61; 95% CI 2.43-2.79); admission service and admission status. The model yielded excellent discriminatory ability in both the derivation (c-statistic 0.873; 95% CI 0.870-0.877; Brier score 0.04) and validation cohorts (c-statistic 0.844; 95% CI 0.840-0.847; Brier score 0.072). Inpatient palliative care consultations increased from 3% of minimal-risk encounters to 41% of high-risk encounters (P < 0.01). CONCLUSION: We developed and temporally validated a predictive mortality model for adults from a large retrospective cohort, which helps quantify the potential need for palliative care referrals based on risk strata. Machine learning algorithms for mortality require clinical interpretation, and additional studies are needed to design patient-centered and risk-specific interventions.

Improving Mortality Attribution in Otolaryngology - Head and Neck Surgery.

OBJECTIVE/HYPOTHESIS: Mortality attribution can have significant implications for reimbursement, hospital/department rankings, and perceptions of safety. This work seeks to compare the accuracy of externally assigned diagnosis-related group (DRG)-based service line mortality attribution in otolaryngology to an internal review process that assigns mortality to the teams that cared for a patient during hospitalization. STUDY DESIGN: Retrospective case series. METHODS: Mortality events at Vanderbilt University Medical Center (VUMC) from 2012 to 2018 were compared. Included events were assigned to the otolaryngology service line (OSL) via the following methods: an external agency (Vizient) using DRG, utilization management assignment based on the service that provided care at admission (admission service), discharge (discharge service), or throughout hospitalization (major service line), or through the internal VUMC mortality review committee. Internal review was considered the standard for comparison. RESULTS: Of the 28 mortality events assigned to OSL by the DRG-based external method, nine (32%) were actually attributable to OSL. Of the 23 total mortality events attributable to OSL at our institution, external DRG-based review captured nine (39%). The designation of major service during hospitalization was correct 95% of the time and captured 87% of mortality events. Differences between external and internal attribution methods were statistically significant (P < .001). CONCLUSIONS: DRG-based models are frequently utilized but can be inaccurate when attributing mortality for an individual otolaryngology department. Otolaryngology mortalities appear to be captured and assigned more accurately by assigning deaths to the service that renders the majority of care during hospitalization. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1805-E1810, 2021.

Reducing intraoperative red blood cell unit wastage in a large academic medical center.

BACKGROUND: The wastage of red blood cell (RBC) units within the operative setting results in significant direct costs to health care organizations. Previous education-based efforts to reduce wastage were unsuccessful at our institution. We hypothesized that a quality and process improvement approach would result in sustained reductions in intraoperative RBC wastage in a large academic medical center. STUDY DESIGN AND METHODS: Utilizing a failure mode and effects analysis supplemented with time and temperature data, key drivers of perioperative RBC wastage were identified and targeted for process improvement. RESULTS: Multiple contributing factors, including improper storage and transport and lack of accurate, locally relevant RBC wastage event data were identified as significant contributors to ongoing intraoperative RBC unit wastage. Testing and implementation of improvements to the process of transport and storage of RBC units occurred in liver transplant and adult cardiac surgical areas due to their history of disproportionately high RBC wastage rates. Process interventions targeting local drivers of RBC wastage resulted in a significant reduction in RBC wastage (p < 0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15-0.39), despite an increase in operative case volume over the period of the study. Studied process interventions were then introduced incrementally in the remainder of the perioperative areas. CONCLUSIONS: These results show that a multidisciplinary team focused on the process of blood product ordering, transport, and storage was able to significantly reduce operative RBC wastage and its associated costs using quality and process improvement methods.

Diastolic field stimulation: the role of shock duration in epicardial activation and propagation.

Detailed knowledge of tissue response to both systolic and diastolic shock is critical for understanding defibrillation. Diastolic field stimulation has been much less studied than systolic stimulation, particularly regarding transient virtual anodes. Here we investigated high-voltage-induced polarization and activation patterns in response to strong diastolic shocks of various durations and of both polarities, and tested the hypothesis that the activation versus shock duration curve contains a local minimum for moderate shock durations, and it grows for short and long durations. We found that 0.1-0.2-ms shocks produced slow and heterogeneous activation. During 0.8-1 ms shocks, the activation was very fast and homogeneous. Further shock extension to 8 ms delayed activation from 1.55 ± 0.27 ms and 1.63 ± 0.21 ms at 0.8 ms shock to 2.32 ± 0.41 ms and 2.37 ± 0.3 ms (N = 7) for normal and opposite polarities, respectively. The traces from hyperpolarized regions during 3-8 ms shocks exhibited four different phases: beginning negative polarization, fast depolarization, slow depolarization, and after-shock increase in upstroke velocity. Thus, the shocks of >3 ms in duration created strong hyperpolarization associated with significant delay (P < 0.05) in activation compared with moderate shocks of 0.8 and 1 ms. This effect appears as a dip in the activation-versus-shock-duration curve.

The potential of dual camera systems for multimodal imaging of cardiac electrophysiology and metabolism.

Fluorescence imaging has become a common modality in cardiac electrodynamics. A single fluorescent parameter is typically measured. Given the growing emphasis on simultaneous imaging of more than one cardiac variable, we present an analysis of the potential of dual camera imaging, using as an example our straightforward dual camera system that allows simultaneous measurement of two dynamic quantities from the same region of the heart. The advantages of our system over others include an optional software camera calibration routine that eliminates the need for precise camera alignment. The system allows for rapid setup, dichroic image separation, dual-rate imaging, and high spatial resolution, and it is generally applicable to any two-camera measurement. This type of imaging system offers the potential for recording simultaneously not only transmembrane potential and intracellular calcium, two frequently measured quantities, but also other signals more directly related to myocardial metabolism, such as [K(+)](e), NADH, and reactive oxygen species, leading to the possibility of correlative multimodal cardiac imaging. We provide a compilation of dye and camera information critical to the design of dual camera systems and experiments.

Effects of unipolar stimulation on voltage and calcium distributions in the isolated rabbit heart.

BACKGROUND: The effect of electric stimulation on the polarization of cardiac tissue (virtual electrode effect) is well known; the corresponding response of intracellular calcium concentration ([Ca(2+)](i)) and its dependence on coupling interval between conditioning stimulus (S1) and test stimulus (S2) has yet to be elucidated. OBJECTIVE: Because uncovering the transmembrane potential (V(m))-[Ca(2+)](i) relationship during an electric shock is imperative for understanding arrhythmia induction and defibrillation, we aimed to study simultaneous V(m) and [Ca(2+)](i) responses to strong unipolar stimulation. METHODS: We used a dual-camera optical system to image concurrently V (m) and [Ca(2+)](i) responses to unipolar stimulation (20 ms +/- 20 mA) in Langendorff-perfused rabbit hearts. RH-237 and Rhod-2 fluorescent dyes were used to measure V(m) and [Ca(2+)](i), respectively. The S1-S2 interval ranged from 10 to 170 ms to examine stimulation during the action potential. RESULTS: The [Ca(2+)](i) deflections were less pronounced than changes in V(m) for all S1-S2 intervals. For cathodal stimulation, [Ca(2+)](i) at the central virtual cathode region increased with prolongation of S1-S2 interval. For anodal stimulation, [Ca(2+)](i) at the central virtual anode area decreased with shortening of the S1-S2 interval. At very short S1-S2 intervals (10-20 ms), when S2 polarization was superimposed on the S1 action potential upstroke, the [Ca(2+)](i) distribution did not follow V(m) and produced a more complex pattern. After S2 termination [Ca(2+)](i) exhibited three outcomes in a manner similar to V(m): non-propagating response, break stimulation, and make stimulation. CONCLUSIONS: Changes in the [Ca(2+)](i) distribution correlate with the behavior of the V (m) distribution for S1-S2 coupling intervals longer than 20 ms; at shorter intervals S2 creates more heterogeneous [Ca(2+)](i) distribution in comparison with V(m). Stimulation in diastole and at very short coupling intervals caused V(m)-[Ca(2+)](i) uncoupling at the regions of positive polarization (virtual cathode).

High-resolution high-speed panoramic cardiac imaging system.

A panoramic cardiac imaging system consisting of three high-speed CCD cameras has been developed to image the surface electrophysiology of a rabbit heart via fluorescence imaging using a voltage-sensitive fluorescent dye. A robust, unique mechanical system was designed to accommodate the three cameras and to adapt to the requirements of future experiments. A unified computer interface was created for this application - a single workstation controls all three CCD cameras, illumination, stimulation, and a stepping motor that rotates the heart. The geometric reconstruction algorithms were adapted from a previous cardiac imaging system. We demonstrate the system by imaging a polymorphic cardiac tachycardia.

A high-voltage cardiac stimulator for field shocks of a whole heart in a bath.

Defibrillators are a critical tool for treating heart disease; however, the mechanisms by which they halt fibrillation are still not fully understood and are the subject of ongoing research. Clinical defibrillators do not provide the precise control of shock timing, duration, and voltage or other features needed for detailed scientific inquiry, and there are few, if any, commercially available units designed for research applications. For this reason, we have developed a high-voltage, programmable, capacitive-discharge stimulator optimized to deliver defibrillation shocks with precise timing and voltage control to an isolated animal heart, either in air or in a bath. This stimulator is capable of delivering voltages of up to 500 V and energies of nearly 100 J with timing accuracy of a few microseconds and with rise and fall times of 5 micros or less and is controlled only by two external timing pulses and a control computer that sets the stimulation parameters via a LABVIEW interface. Most importantly, the stimulator has circuits to protect the high-voltage circuitry and the operator from programming and input-output errors. This device has been tested and used successfully in field shock experiments on rabbit hearts as well as other protocols requiring high voltage.

Cathodal stimulation in the recovery phase of a propagating planar wave in the rabbit heart reveals four stimulation mechanisms.

The stimulation of cardiac tissue in the recovery phase has significant importance in relation to reentry induction. In the theoretical experiment proposed by Winfree, termed the 'pinwheel' experiment, a point stimulus (S2) is applied in the wake of a freely propagating planar wave (S1). Reentry induced from this S1-S2 pinwheel protocol has been observed experimentally in heart preparations. However, in these experiments, which focused on activation outcomes, only mapping of extracellular voltages has been conducted. The lack of transmembrane potential (Vm) distribution data makes it impossible to analyse the underlying stimulation mechanisms which precede the reentry induction. In this work we sought to elucidate the stimulation mechanisms throughout the heart cycle using the pinwheel protocol. We examined the cardiac tissue responses during and immediately after cathodal stimulation in the refractory wake of a propagating planar wave. The voltage-sensitive dye di-4-ANEPPS was utilized to measure Vm directly from quasi two-dimensional preparations of cryoablated Langendorff-perfused rabbit hearts. Four stimulation mechanisms were observed that depended on the Vm magnitude during S2 cathodal stimulation. Make stimulation always occurred during diastolic stimulation. When stimulation was at the beginning of the relative refractory period (RRP), transitional make-break stimulation was detected. During the RRP the excitation was due to the break mechanism. While approaching the effective refractory period (ERP), the tissue response is characterized by a damped wave mediated response. These four stimulation mechanisms were observed in all hearts whether the S1 planar wave propagation was parallel or perpendicular to the fibre direction. This study is the first examination of Vm and the stimulation mechanisms throughout the cardiac cycle using the pinwheel protocol, and the results have implications in the development and improvement of pacing protocols for artificial cardiostimulators.

Examination of stimulation mechanism and strength-interval curve in cardiac tissue.

Understanding the basic mechanisms of excitability through the cardiac cycle is critical to both the development of new implantable cardiac stimulators and improvement of the pacing protocol. Although numerous works have examined excitability in different phases of the cardiac cycle, no systematic experimental research has been conducted to elucidate the correlation among the virtual electrode polarization pattern, stimulation mechanism, and excitability under unipolar cathodal and anodal stimulation. We used a high-resolution imaging system to study the spatial and temporal stimulation patterns in 20 Langendorff-perfused rabbit hearts. The potential-sensitive dye di-4-ANEPPS was utilized to record the electrical activity using epifluorescence. We delivered S1-S2 unipolar point stimuli with durations of 2-20 ms. The anodal S-I curves displayed a more complex shape in comparison with the cathodal curves. The descent from refractoriness for anodal stimulation was extremely steep, and a local minimum was clearly observed. The subsequent ascending limb had either a dome-shaped maximum or was flattened, appearing as a plateau. The cathodal S-I curves were smoother, closer to a hyperbolic shape. The transition of the stimulation mechanism from break to make always coincided with the final descending phase of both anodal and cathodal S-I curves. The transition is attributed to the bidomain properties of cardiac tissue. The effective refractory period was longer when negative stimuli were delivered than for positive stimulation. Our spatial and temporal analyses of the stimulation patterns near refractoriness show always an excitation mechanism mediated by damped wave propagation after S2 termination.

Spatiotemporal dynamics of damped propagation in excitable cardiac tissue.

Compared to steadily propagating waves (SPW), damped waves (DW), another solution to the nonlinear wave equation, are seldom studied. In cardiac tissue after electrical stimulation in an SPW wake, we observe DW with diminished amplitude and velocity that either gradually decrease as the DW dies, or exhibit a sharp amplitude increase after a delay to become an SPW. The cardiac DW-SPW transition is a key link in understanding defibrillation and stimulation close to the refractory period, and is ideal for a general study of DW dynamics.

Effects of elevated extracellular potassium on the stimulation mechanism of diastolic cardiac tissue.

During cardiac disturbances such as ischemia and hyperkalemia, the extracellular potassium ion concentration is elevated. This in turn changes the resting transmembrane potential and affects the excitability of cardiac tissue. To test the hypothesis that extracellular potassium elevation also alters the stimulation mechanism, we used optical fluorescence imaging to examine the mechanism of diastolic anodal unipolar stimulation of cardiac tissue under 4 mM (normal) and 8 mM (elevated) extracellular potassium. We present several visualization methods that are useful for distinguishing between anodal-make and anodal-break excitation. In the 4-mM situation, stimulation occurred by the make, or stimulus-onset, mechanism that involved propagation out of the virtual cathodes. For 8-mM extracellular potassium, the break or stimulus termination mechanism occurred with propagation out of the virtual anode. We conclude that elevated potassium, as might occur in myocardial ischemia, alters not only stimulation threshold but also the excitation mechanism for anodal stimulation.