Simultaneous Venous-Arterial Doppler Ultrasound During Early Fluid Resuscitation to Characterize a Novel Doppler Starling Curve: A Prospective Observational Pilot Study.

Background: The likelihood of a patient being preload responsive-a state where the cardiac output or stroke volume (SV) increases significantly in response to preload-depends on both cardiac filling and function. This relationship is described by the canonical Frank-Starling curve. Research Question: We hypothesize that a novel method for phenotyping hypoperfused patients (ie, the "Doppler Starling curve") using synchronously measured jugular venous Doppler as a marker of central venous pressure (CVP) and corrected flow time of the carotid artery (ccFT) as a surrogate for SV will refine the pretest probability of preload responsiveness/unresponsiveness. Study Design and Methods: We retrospectively analyzed a prospectively collected convenience sample of hypoperfused adult emergency department (ED) patients. Doppler measurements were obtained before and during a preload challenge using a wireless, wearable Doppler ultrasound system. Based on internal jugular and carotid artery Doppler surrogates of CVP and SV, respectively, we placed hemodynamic assessments into quadrants (Qx) prior to preload augmentation: low CVP with normal SV (Q1), high CVP and normal SV (Q2), low CVP and low SV (Q3) and high CVP and low SV (Q4). The proportion of preload responsive and unresponsive assessments in each quadrant was calculated based on the maximal change in ccFT (ccFTΔ) during either a passive leg raise or rapid fluid challenge. Results: We analyzed 41 patients (68 hemodynamic assessments) between February and April 2021. The prevalence of each phenotype was: 15 (22%) in Q1, 8 (12%) in Q2, 39 (57%) in Q3, and 6 (9%) in Q4. Preload unresponsiveness rates were: Q1, 20%; Q2, 50%; Q3, 33%, and Q4, 67%. Interpretation: Even fluid naïve ED patients with sonographic estimates of low CVP have high rates of fluid unresponsiveness, making dynamic testing valuable to prevent ineffective IVF administration.

The Correlation between Carotid Artery Corrected Flow Time and Velocity Time Integral during Central Blood Volume Loss and Resuscitation.

Background: Doppler ultrasound of the common carotid artery is used to infer central hemodynamics. For example, change in the common carotid artery corrected flow time (ccFT) and velocity time integral (VTI) are proposed surrogates of changing stroke volume. However, conflicting data exist which may be due to inadequate beat sample size and measurement variability - both intrinsic to handheld systems. In this brief communication, we determined the correlation between changing ccFT and carotid VTI during progressively severe central blood volume loss and resuscitation. Methods: Measurements were obtained through a novel, wireless, wearable Doppler ultrasound system. Sixteen participants (ages of 18-40 years with no previous medical history) were studied across 25 lower body-negative pressure protocols. Relationships were assessed using repeated-measures correlation regression models. Results: In total, 33,110 cardiac cycles comprise this analysis; repeated-measures correlation showed a strong, linear relationship between ccFT and VTI. The strength of the ccFT-VTI relationship was dependent on the number of consecutively averaged cardiac cycles (R1 cycle = 0.70, R2 cycles = 0.74, and R10 cycles = 0.81). Conclusions: These results positively support future clinical investigations employing common carotid artery Doppler as a surrogate for central hemodynamics.

A Retrospective Cohort Study Comparing In-Person and Telemedicine-Based Opioid Agonist Treatment in Ontario, Canada, Using Administrative Health Data.

BACKGROUND: This study evaluated how telemedicine as a modality for opioid agonist treatment compares to in-person care. METHODS: We conducted a retrospective cohort study of patients enrolled in opioid agonist treatment between January 1, 2011, and December 31, 2015, in Ontario, Canada. We compared patients who received opioid agonist treatment predominantly in person, mixed, and predominantly by telemedicine. We used a logistic regression model to evaluate mortality, a Cox proportional hazard model to assess retention, and a negative binomial regression model to evaluate emergency department visits and hospitalizations. The study was performed using administrative health data with physician billing data from the Ontario Health Insurance Plan and prescription data from the Ontario Drug Benefit databases. RESULTS: A total of 55,924 individuals were included in the study. Receiving opioid agonist treatment by predominantly telemedicine was not associated with all-cause mortality (OR = 0.9, 95% CI: 0.8-1.0), 1-year treatment retention (OR = 1.0, 95% CI: 0.9-1.1), or opioid-related emergency department visits and hospitalizations when compared to in-person care. The rate of emergency department visits (IRR = 1.4), the rate of mental health-related emergency department visits (IRR = 1.5), and the rate of mental health-related hospitalizations per year (IRR = 1.2) was higher for patients who received opioid agonist treatment predominantly by telemedicine compared to in person. CONCLUSION: Our findings support the conclusion that telemedicine is equal to in-person care regarding mortality opioid-related emergency department visits and retention, and is a viable option for those seeking opioid agonist treatment.

A cohort study evaluating the association between concurrent mental disorders, mortality, morbidity, and continuous treatment retention for patients in opioid agonist treatment (OAT) across Ontario, Canada, using administrative health data.

BACKGROUND: Due to the high prevalence of mental disorders among people with opioid use disorder, the objective of this study was to determine the association between concurrent mental disorders, mortality, morbidity, and continuous treatment retention for patients in opioid agonist treatment in Ontario, Canada. METHODS: We conducted a retrospective cohort study of patients enrolled in opioid agonist treatment between January 1, 2011, and December 31, 2015. Patients were stratified into two groups: those diagnosed with concurrent mental disorders and opioid use disorder and those with opioid use disorder only, using data from the Ontario Health Insurance Plan Database, Ontario Drug Benefit Plan Database. The primary outcome studied was all-cause mortality using data from the Registered Persons Database. Emergency department visits from the National Ambulatory Care Database, hospitalizations Discharge Abstract Database, and continuous retention in treatment, defined as 1 year of uninterrupted opioid agonist treatment using data from the Ontario Drug Benefit Plan Database were measured as secondary outcomes. Encrypted patient identifiers were used to link information across databases. RESULTS: We identified 55,924 individuals enrolled in opioid agonist treatment, and 87% had a concurrent mental disorder diagnosis during this period. We observed that having a mental disorder was associated with an increased likelihood of all-cause mortality (odds ratio (OR) 1.4; 95% confidence interval (CI) 1.2-1.5). For patients diagnosed with mental disorders, the estimated rate of ED visits per year was 2.25 times higher and estimated rate of hospitalization per year was 1.67 times higher than for patients with no mental disorders. However, there was no association between having a diagnosis of a mental disorder and 1-year treatment retention in OAT-adjusted hazard ratio (HR) = 1.0; 95% CI 0.9 to 1.1. CONCLUSION: Our findings highlight the consequences of the high prevalence of mental disorders for individuals with opioid use disorder in Ontario, Canada.

The State of Opioid Agonist Therapy in Canada 20 Years after Federal Oversight.

Opioid agonist therapy was introduced in Canada in 1959 with the use of methadone for the treatment of opioid dependence. The regulation of methadone was the responsibility of Health Canada until 1995, when oversight was transferred to the provincial health systems. During the more than 20 years since the federal health authority transferred oversight of methadone to the provincial level, methadone programming has evolved differently in every province. The landscape of opioid dependence treatment is varied across the country, with generally increasing treatment capacity in all provinces and dramatic increases in some. Each province has an independent methadone program with differing policies, contingency management strategies, laboratory monitoring policies, and delivery methods. Treatment options have increased, with buprenorphine- and heroin-assisted treatment becoming available to limited degrees. Despite this, access remains a challenge in many parts of the country (particularly rural and remote areas) because the demand for treatment has increased even more rapidly than the capacity. Although treatment access remains a priority in many jurisdictions, there is also a need to attend to treatment quality as treatment access expands, including integration with addiction counselling, primary care, and mental health care. As well, coordinated monitoring and reporting of treatment need, quality, and delivery are required; implementing a national policy to promote planning would have tremendous value.

The impact of benzodiazepine use in patients enrolled in opioid agonist therapy in Northern and rural Ontario.

BACKGROUND: Benzodiazepine use is common among patients in opioid agonist therapy; this puts patients at an increased risk of overdose and death. In this study, we examine the impact of baseline and ongoing benzodiazepine use, and whether patients are more likely to terminate treatment with increasing proportion of benzodiazepine positive urine samples. We also study whether benzodiazepine use differs by geographic location. METHODS: We conducted a retrospective cohort study using anonymized electronic medical records from 58 clinics offering opioid agonist therapy in Ontario. One-year treatment retention was the primary outcome of interest and was measured for patients who did and did not have a benzodiazepine positive urine sample in their first month of treatment, and as a function of the proportion of benzodiazepine-positive urine samples throughout treatment. Cox proportional hazard model was used to characterize one-year retention. RESULTS: Our cohort consisted of 3850 patients, with the average retention rate of 43.4%. Baseline benzodiazepine users had a retention rate of 39.9% and non-users had a retention rate of 44%. Patients who were benzodiazepine negative on admission benefited from an increased median days retained of 265 vs. 215 days. Patients with more than 75% of urines positive for benzodiazepines were 175% more likely to drop out of treatment than those patients with little or no benzodiazepine use. CONCLUSIONS: Baseline benzodiazepine use is predictive of decreased retention. Patients who have a higher proportion of benzodiazepine-positive urine samples are more likely to drop out of treatment compared to those who have little or no benzodiazepine detection in their urine.

The correlation between carotid artery Doppler and stroke volume during central blood volume loss and resuscitation.

BACKGROUND: Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. METHODS: Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. RESULTS: In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm ]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. CONCLUSIONS: There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.

The effect of gravity-induced preload change on the venous excess ultrasound (VExUS) score and internal jugular vein Doppler in healthy volunteers.

BACKGROUND: The venous excess ultrasound (VExUS) score is a multi-organ Doppler approach to assess venous congestion. Despite growing use of VExUS in research and clinical practice, other veins can be visualized to assess for venous hypertension, which may overcome acquisition barriers of the VExUS exam. In this pilot, observational study, we used a wearable Doppler ultrasound to assess the relationship between jugular venous Doppler and the VExUS score under different preload conditions. We hypothesized that jugular Doppler morphology would accurately distinguish preload conditions, that it would most closely relate to the hepatic venous Doppler morphology in the fully supine position and that the VExUS score would be influenced by preload condition. RESULTS: We recruited 15 healthy volunteers with no cardiovascular history. Preload change was achieved using a tilt-table with three positions: supine, fully upright, and 30-degree head-down tilt. In each position, a VExUS score was performed; furthermore, inferior vena collapsibility and sphericity index were calculated. At the same time, jugular venous Doppler was captured by a novel, wireless, wearable ultrasound system. A continuous jugular venous Doppler morphology was 96% accurate for detecting the low preload condition. The jugular venous Doppler morphology was highly correlated with the hepatic vein, but only in the supine position. Gravitational position did not significantly affect the sphericity index or the VExUS score. CONCLUSIONS: The jugular vein Doppler morphology was able to accurately distinguish low from high preload conditions in healthy volunteers. Comparisons between VExUS Doppler morphologies and other veins should occur in the supine position when gravitational pressure gradients are minimized; finally, different preload conditions in healthy subjects did not affect the VExUS score.

Carotid Artery Corrected Flow Time Measured by Wearable Doppler Ultrasound Accurately Detects Changing Stroke Volume During the Passive Leg Raise in Ambulatory Volunteers.

BACKGROUND: The change in the corrected flow time of the common carotid artery (ccFTΔ) has been used as a surrogate of changing stroke volume (SVΔ) in the critically-ill. Thus, this relatively easy-to-obtain Doppler measure may help clinicians better define the intended effect of intravenous fluids. Yet the temporal evolution of SVΔ and ccFTΔ has not been reported in volunteers undergoing a passive leg raise (PLR). METHODS: We recruited clinically-euvolemic, non-fasted, adult, volunteers in a local physiology lab to perform 2 PLR maneuvers, each separated by a 5 minute 'wash-out'. During each PLR, SV was measured by a non-invasive pulse contour analysis device. SV was temporally-synchronized with a wireless, wearable Doppler ultrasound worn over the common carotid artery that continuously measured ccFT. RESULTS: 36 PLR maneuvers were obtained across 19 ambulatory volunteers. 8856 carotid Doppler cardiac cycles were analyzed. The ccFT increased nearly ubiquitously during the PLR and within 40-60 seconds of PLR onset; the rise in SV from the pulse contour device was more gradual. SVΔ by +5% and +10% were both detected by a +7% ccFTΔ with sensitivities, specificities and areas under the receiver operator curve of 59%, 95% and 0.77 (p < 0.001) and 66%, 76% and 0.73 (p < 0.001), respectively. CONCLUSIONS: The ccFTΔ during the PLR in ambulatory volunteers was rapid and sustained. Within the limits of precision for detecting a clinically-significant rise in SV by a non-invasive pulse contour analysis device, simultaneously-acquired ccFT from a wireless, wearable ultrasound system was accurate at detecting 'preload responsiveness'.

Continuous Venous-Arterial Doppler Ultrasound During a Preload Challenge.

A preload challenge (PC) is a clinical maneuver that, first, increases the cardiac filling (i.e., preload) and, second, calculates the change in cardiac output. Fundamentally, a PC is a bedside approach for testing the Frank-Starling-Sarnoff (i.e., "cardiac function") curve. Normally, this curve has a steep slope such that a small change in the cardiac preload generates a large change in the stroke volume (SV) or cardiac output. However, in various disease states, the slope of this relationship flattens such that increasing the volume into the heart leads to little rise in the SV. In this pathological scenario, additional cardiac preload (e.g., intravenous fluid) is unlikely to be physiologically effective and could lead to harm if organ congestion evolves. Therefore, inferring both the cardiac preload and output is clinically useful as it may guide intravenous (IV) fluid resuscitation. Accordingly, the goal of this protocol is to describe a method for contemporaneously tracking the surrogates of cardiac preload and output using a novel, wireless, wearable ultrasound during a well-validated preload challenge.

Inferior Vena Caval Measures Do Not Correlate with Carotid Artery Corrected Flow Time Change Measured Using a Wireless Doppler Patch in Healthy Volunteers.

(1) Background: The inspiratory collapse of the inferior vena cava (IVC), a non-invasive surrogate for right atrial pressure, is often used to predict whether a patient will augment stroke volume (SV) in response to a preload challenge. There is a correlation between changing stroke volume (SV∆) and corrected flow time of the common carotid artery (ccFT∆). (2) Objective: We studied the relationship between IVC collapsibility and ccFT∆ in healthy volunteers during preload challenges. (3) Methods: A prospective, observational, pilot study in euvolemic, healthy volunteers with no cardiovascular history was undertaken in a local physiology lab. Using a tilt-table, we studied two degrees of preload augmentation from (a) supine to 30-degrees head-down and (b) fully-upright to 30-degrees head down. In the supine position, % of IVC collapse with respiration, sphericity index and portal vein pulsatility was calculated. The common carotid artery Doppler pulse was continuously captured using a wireless, wearable ultrasound system. (4) Results: Fourteen subjects were included. IVC % collapse with respiration ranged between 10% and 84% across all subjects. Preload responsiveness was defined as an increase in ccFT∆ of at least 7 milliseconds. A total of 79% (supine baseline) and 100% (head-up baseline) of subjects were preload-responsive. No supine venous measures (including IVC % collapse) were significantly related to ccFT∆. (5) Conclusions: From head-up baseline, 100% of healthy subjects were 'preload-responsive' as per the ccFT∆. Based on the 42% and 25% IVC collapse thresholds in the supine position, only 50% and 71% would have been labeled 'preload-responsive'.

Detecting the Change in Total Circulatory Flow with a Wireless, Wearable Doppler Ultrasound Patch: A Pilot Study.

Measuring fluid responsiveness is important in the management of critically ill patients, with a 10-15% change in cardiac output typically being used to indicate "fluid responsiveness." Ideally, these changes would be measured noninvasively and peripherally. The aim of this study was to determine how the common carotid artery (CCA) maximum velocity changes with total circulatory flow when confounding factors are mitigated and determine a value for CCA maximum velocity corresponding to a 10% change in total circulatory flow. DESIGN: Prospective observational pilot study. SETTING: Patients undergoing elective, on-pump coronary artery bypass grafting (CABG) surgery. PATIENTS: Fourteen patients were referred for elective coronary artery bypass grafting surgery. INTERVENTIONS: Cardiopulmonary bypass (CPB) pump flow changes during surgery, as chosen by the perfusionist. MEASUREMENTS: A hands-free, wearable Doppler patch was used for CCA velocity measurements with the aim of preventing user errors in ultrasound measurements. Maximum CCA velocity was determined from the spectrogram acquired by the Doppler patch. CPB flow rates were recorded as displayed on the CPB console, and further measured from the peristaltic pulsation frequency visible on the recorded Doppler spectrograms. MAIN RESULTS: Changes in CCA maximum velocity tracked well with changes in CPB flow. On average, a 13.6% change in CCA maximum velocity was found to correspond to a 10% change in CPB flow rate. CONCLUSIONS: Changes in CCA velocity may be a useful surrogate for determining fluid responsiveness when user error can be mitigated.

Simultaneous venous-arterial Doppler during preload augmentation: illustrating the Doppler Starling curve.

Providing intravenous (IV) fluids to a patient with signs or symptoms of hypoperfusion is common. However, evaluating the IV fluid 'dose-response' curve of the heart is elusive. Two patients were studied in the emergency department with a wireless, wearable Doppler ultrasound system. Change in the common carotid arterial and internal jugular Doppler spectrograms were simultaneously obtained as surrogates of left ventricular stroke volume (SV) and central venous pressure (CVP), respectively. Both patients initially had low CVP jugular venous Doppler spectrograms. With preload augmentation, only one patient had arterial Doppler measures indicative of significant SV augmentation (i.e., 'fluid responsive'). The other patient manifested diminishing arterial response, suggesting depressed SV (i.e., 'fluid unresponsive') with evidence of ventricular asynchrony. In this short communication, we describe how a wireless, wearable Doppler ultrasound simultaneously tracks surrogates of cardiac preload and output within a 'Doppler Starling curve' framework; implications for IV fluid dosing are discussed.

The time cost of physiologically ineffective intravenous fluids in the emergency department: an observational pilot study employing wearable Doppler ultrasound.

BACKGROUND: Little data exist on the time spent by emergency department (ED) personnel providing intravenous (IV) fluid to 'responsive' versus 'unresponsive' patients. METHODS: A prospective, convenience sample of adult ED patients was studied; patients were enrolled if preload expansion was indicated for any reason. Using a novel, wireless, wearable ultrasound, carotid artery Doppler was obtained before and throughout a preload challenge (PC) prior to each bag of ordered IV fluid. The treating clinician was blinded to the results of the ultrasound. IV fluid was deemed 'effective' or 'ineffective' based on the greatest change in carotid artery corrected flow time (ccFT∆) during the PC. The duration, in minutes, of each bag of IV fluid administered was recorded. RESULTS: 53 patients were recruited and 2 excluded for Doppler artifact. There were 86 total PCs included in the investigation comprising 81.7 L of administered IV fluid. 19,667 carotid Doppler cardiac cycles were analyzed. Using ccFT∆ ≥ + 7 ms to discriminate 'physiologically effective' from 'ineffective' IV fluid, we observed that 54 PCs (63%) were 'effective', comprising 51.7 L of IV fluid, whereas, 32 (37%) were 'ineffective' comprising 30 L of IV fluid. 29.75 total hours across all 51 patients were spent in the ED providing IV fluids categorized as 'ineffective.' CONCLUSIONS: We report the largest-known carotid artery Doppler analysis (i.e., roughly 20,000 cardiac cycles) in ED patients requiring IV fluid expansion. A clinically significant amount of time was spent providing physiologically ineffective IV fluid. This may represent an avenue to improve ED care efficiency.

Building an inpatient addiction medicine consult service in Sudbury, Canada: preliminary data and lessons learned in the era of COVID-19.

OBJECTIVE: The goal of this study was to (1) Describe the patient population of a newly implemented addiction medicine consult service (AMCS); (2) Evaluate referrals to community-based addiction support services and acute health service use, over time; (3) Provide lessons learned. METHODS: A retrospective observational analysis was conducted at Health Sciences North in Sudbury, Ontario, Canada, with a newly implemented AMCS from November 2018 and July 2021. Data were collected using the hospital's electronic medical records. The outcomes measured included the number of emergency department visits, inpatient admissions, and re-visits over time. An interrupted time-series analysis was performed to measure the effect of AMCS implementation on acute health service use at Health Sciences North. RESULTS: A total of 833 unique patients were assessed through the AMCS. A total of 1,294 referrals were made to community-based addiction support services, with the highest proportion of referrals between August and October 2020. The post-intervention trend for ED visits, ED re-visits, ED length of stay, inpatient visits, re-visits, and inpatient length of stay did not significantly differ from the pre-intervention period. CONCLUSION: Implementation of an AMCS provides a focused service for patients using with substance use disorders. The service resulted in a high referral rate to community-based addiction support services and limited changes in health service usage.

A Novel Spectral Index for Tracking Preload Change from a Wireless, Wearable Doppler Ultrasound.

A wireless, wearable Doppler ultrasound offers a new paradigm for linking physiology to resuscitation medicine. To this end, the image analysis of simultaneously-acquired venous and arterial Doppler spectrograms attained by wearable ultrasound represents a new source of hemodynamic data. Previous investigators have reported a direct relationship between the central venous pressure (CVP) and the ratio of the internal jugular-to-common carotid artery diameters. Because Doppler power is directly related to the number of red cell scatterers within a vessel, we hypothesized that (1) the ratio of internal jugular-to-carotid artery Doppler power (V/APOWER) would be a surrogate for the ratio of the vascular areas of these two vessels and (2) the V/APOWER would track the anticipated CVP change during simulated hemorrhage and resuscitation. To illustrate this proof-of-principle, we compared the change in V/APOWER obtained via a wireless, wearable Doppler ultrasound to B-mode ultrasound images during a head-down tilt. Additionally, we elucidated the change in the V/APOWER during simulated hemorrhage and transfusion via lower body negative pressure (LBNP) and release. With these Interesting Images, we show that the Doppler V/APOWER ratio qualitatively tracks anticipated changes in CVP (e.g., cardiac preload) which is promising for both diagnosis and management of hemodynamic unrest.