Coronavirus Disease 2019: Anesthesia Machine Circuit Pressure During Use as an Improvised Intensive Care Unit Ventilator.

BACKGROUND: Use of anesthesia machines as improvised intensive care unit (ICU) ventilators may occur in locations where waste anesthesia gas suction (WAGS) is unavailable. Anecdotal reports suggest as much as 18 cm H2O positive end-expiratory pressure (PEEP) being inadvertently applied under these circumstances, accompanied by inaccurate pressure readings by the anesthesia machine. We hypothesized that resistance within closed anesthesia gas scavenging systems (AGSS) disconnected from WAGS may inadvertently increase circuit pressures. METHODS: An anesthesia machine was connected to an anesthesia breathing circuit, a reference manometer, and a standard bag reservoir to simulate a lung. Ventilation was initiated as follows: volume control, tidal volume (TV) 500 mL, respiratory rate 12, ratio of inspiration to expiration times (I:E) 1:1.9, fraction of inspired oxygen (Fio2) 1.0, fresh gas flow (FGF) rate 2.0 liters per minute (LPM), and PEEP 0 cm H2O. After engaging the ventilator, PEEP and peak inspiratory pressure (PIP) were measured by the reference manometer and the anesthesia machine display simultaneously. The process was repeated using prescribed PEEP levels of 5, 10, 15, and 20 cm H2O. Measurements were repeated with the WAGS disconnected and then were performed again at FGF of 4, 6, 8, 10, and 15 LPM. This process was completed on 3 anesthesia machines: Dräger Perseus A500, Dräger Apollo, and the GE Avance CS2. Simple linear regression was used to assess differences. RESULTS: Utilizing nonparametric Bland-Altman analysis, the reference and machine manometer measurements of PIP demonstrated median differences of -0.40 cm H2O (95% limits of agreement [LOA], -1.00 to 0.55) for the Dräger Apollo, -0.40 cm H2O (95% LOA, -1.10 to 0.41) for the Dräger Perseus, and 1.70 cm H2O (95% LOA, 0.80-3.00) for the GE Avance CS2. At FGF 2 LPM and PEEP 0 cm H2O with the WAGS disconnected, the Dräger Apollo had a difference in PEEP of 0.02 cm H2O (95% confidence interval [CI], -0.04 to 0.08; P = .53); the Dräger Perseus A500, <0.0001 cm H2O (95% CI, -0.11 to 0.11; P = 1.00); and the GE Avance CS2, 8.62 cm H2O (95% CI, 8.55-8.69; P < .0001). After removing the hose connected to the AGSS and the visual indicator bag on the GE Avance CS2, the PEEP difference was 0.12 cm H2O (95% CI, 0.059-0.181; P = .0002). CONCLUSIONS: Displayed airway pressure measurements are clinically accurate in the setting of disconnected WAGS. The Dräger Perseus A500 and Apollo with open scavenging systems do not deliver inadvertent continuous positive airway pressure (CPAP) with WAGS disconnected, but the GE Avance CS2 with a closed AGSS does. This increase in airway pressure can be mitigated by the manufacturer's recommended alterations. Anesthesiologists should be aware of the potential clinically important increases in pressure that may be inadvertently delivered on some anesthesia machines, should the WAGS not be properly connected.

Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial.

PURPOSE: This randomized, placebo-controlled, double-blind, dose-escalation acute ischemic stroke trial was designed to demonstrate maximum tolerated dose, characterize adverse events (AEs), and explore clinical outcomes when intravenous dodecafluoropentane emulsion (DDFPe) was used as neuroprotection. METHODS: Acute ischemic stroke patients (n = 24) with National Institutes of Health Stroke Scale (NIHSS) score of 2-20 were randomized to either 3 doses of intravenous DDFPe or placebo, 1 every 90 minutes, starting within 12 hours of symptom onset. Doses were given without affecting standard stroke care. Each of the 3 dose cohorts included 8 patients, with 2 receiving placebo and 6 receiving DDFPe. Primary outcomes were serious adverse events (SAEs), AEs, NIHSS score, and modified Rankin Score (mRS). RESULTS: No dose-limiting toxicities were encountered, and no maximum tolerated dose was defined. One unrelated delayed death occurred in a DDFPe patient, and another occurred in the placebo group. Group SAEs and AEs were similar in incidence and severity. Early initiation of DDFPe treatment resulted in better NIHSS score response than late initiation (P = .03). Thirty- and 90-day mRS after high-dose therapy suggested clinical improvement (P = .01 and P = .03, respectively). However, the significance of differences in clinical outcomes was limited by small patient numbers and differences in stroke severity between cohorts. CONCLUSIONS: Intravenous DDFPe appears to be safe at all doses tested. Clinical improvements in NIHSS score and mRS were significant but compromised by small sample size.

The Evolution of Echocardiographic Type and Anesthetic Technique for Transcatheter Aortic Valve Replacement at a High-Volume Transcatheter Aortic Valve Replacement Center.

OBJECTIVE: Describe the change in intraoperative transcatheter aortic valve replacement (TAVR) care by examining the utilization of transesophageal echocardiography (TEE) versus transthoracic echocardiography (TTE) and general anesthesia (GA) versus conscious sedation (CS) over time. DESIGN: Retrospective, observational. SETTING: A university, single, high-volume TAVR center. PARTICIPANTS: Patients who underwent TAVR. INTERVENTIONS: Retrospective data collection from the electronic medical records on TAVR patients at a single institution from March 1, 2014 to August 31, 2017. The intraoperative echocardiographic modality, anesthetic type, Society of Thoracic Surgeons (STS) operative mortality risk score, and date each new TAVR valve first was employed at the institution were recorded. MEASUREMENTS AND MAIN RESULTS: Data were analyzed using descriptive statistics apportioned into 6-month intervals. The Fisher exact test and chi-square test were used to test the association of anesthesia type and echocardiography over time, respectively. STS score, anesthetic type, and echocardiographic type were compared using the Wilcoxon rank sum test. Analysis showed increased use of TTE and CS, from 0% and 0% intially to 68.42% and 63.16% most recently (p < 0.0001). In the final study period (after March 1, 2017), the use of TTE and CS surpassed TEE and GA, respectively. STS scores were significantly higher among patients having TEE versus TTE (median STS 6.34 v 4.45, respectively [p = 0.0047]) and GA versus CS (median STS 6.36 v 4.37, respectively [p = 0.0090]). CONCLUSION: Although TAVR initially was conducted exclusively under GA with TEE, nearly two-thirds of TAVR procedures now are performed using CS and TTE at the authors' institution. STS scores were significantly lower in patients having CS and TTE.

Emergency transport of stroke suspects in a rural state: opportunities for improvement.

INTRODUCTION: Time delay is the key obstacle for receiving successful stroke treatment. Alteplase therapy must start within 4.5 hours from stroke occurrence. Rapid transport to a primary stroke center (PSC) or acute stroke-ready hospital (ASRH) by the emergency medical system (EMS) paramedics is vital. We determined transport time and destination data for EMS-identified and -delivered stroke suspects in Arkansas during 2013. Our objective was to analyze transport time and the hospital qualification for stroke care across the state. METHODS: The state's 75 counties were placed into 8 geographical regions (R1-R8). Transport time and hospital qualification were determined for all EMS-identified strokes. Each hospital's stroke care status was categorized as PSC, ASRH, a nonspecialty or unknown care facility (NSCF), out-of-state, or nonapplicable designation facilities. RESULTS: There were 9588 EMS stroke ground transports with median within-region transport times of 29-40 minutes. Statewide, only 65% of EMS-transported stroke patients were transported to either PSC (12%) or ASRH (53%) facilities. One-third of the patients (30.6%) were delivered to NSCFs, where acute stroke therapy may rarely be performed. Regions with the highest suspected-stroke cases per capita also had the highest percentage of transports to NSCFs. CONCLUSION: With only a few PSCs in Arkansas, EMS agencies should prioritize transporting stroke patients to ASRHs when PSCs are not regionally located.

Developing a Checklist: Consensus Via a Modified Delphi Technique.

OBJECTIVE: To create a universal checklist of key preparatory steps to aid anesthesiologists in patient separation from cardiopulmonary bypass. DESIGN: Multistep, iterative survey with statistically guided refinement of survey items using a modified Delphi technique. SETTING: Internet-based surveys. PARTICIPANTS: Ninety active members of the Society of Cardiovascular Anesthesiologists volunteered to participate, including geographically distributed private practice and academic physicians. INTERVENTIONS: A series of checklist items was created and distributed to 90 anesthesiologists, who assessed each item's importance in preparing for patient separation from cardiopulmonary bypass and added, deleted, or modified any items as they saw fit. Items meeting a threshold of greater than 90% group acceptance were carried forward to a second survey. These items then were evaluated using a 5-point Likert scale to grade relative importance and then compared with the group's responses, creating a third survey with refined checklist items. The results then were used to generate a final survey based on each item achieving certain predefined statistical criteria, which then were scored again by the participants, generating a final checklist via statistically guided consensus. MEASUREMENTS AND MAIN RESULTS: An initial checklist containing 28 possible items was proposed to the participants. After the iterative process was completed, a final checklist of 10 items deemed essential to prepare for bypass separation was created. CONCLUSIONS: A checklist to aid in bypass separation was created with key steps derived from a statistically driven Delphi process. This technique of iterative consensus building may be useful in developing additional safety checklists.

Operating room fire prevention: creating an electrosurgical unit fire safety device.

OBJECTIVE: To reduce the incidence of surgical fires. BACKGROUND: Operating room fires represent a potentially life-threatening hazard and are triggered by the electrosurgical unit (ESU) pencil. Carbon dioxide is a fire suppressant and is a routinely used medical gas. We hypothesize that a shroud of protective carbon dioxide covering the tip of the ESU pencil displaces oxygen, thereby preventing fire ignition. METHODS: Using 3-dimensional modeling techniques, a polymer sleeve was created and attached to an ESU pencil. This sleeve was connected to a carbon dioxide source and directed the gas through multiple precisely angled ports, generating a cone of fire-suppressive carbon dioxide surrounding the active pencil tip. This device was evaluated in a flammability test chamber containing 21%, 50%, and 100% oxygen with sustained ESU activation. The sleeve was tested with and without carbon dioxide (control) until a fuel was ignited or 30 seconds elapsed. Time to ignition was measured by high-speed videography. RESULTS: Fires were ignited with each control trial (15/15 trials). The control group median ± SD ignition time in 21% oxygen was 3.0 ± 2.4 seconds, in 50% oxygen was 0.1 ± 1.8 seconds, and in 100% oxygen was 0.03 ± 0.1 seconds. No fire was observed when the fire safety device was used in all concentrations of oxygen (0/15 trials; P < 0.0001). The exact 95% confidence interval for absolute risk reduction of fire ignition was 76% to 100%. CONCLUSIONS: A sleeve creating a cone of protective carbon dioxide gas enshrouding the sparks from an ESU pencil effectively prevents fire in a high-flammability model. Clinical application of this device may reduce the incidence of operating room fires.

Mitigating operating room fires: development of a carbon dioxide fire prevention device.

Operating room fires are sentinel events that present a real danger to surgical patients and occur at least as frequently as wrong-sided surgery. For fire to occur, the 3 points of the fire triad must be present: an oxidizer, an ignition source, and fuel source. The electrosurgical unit (ESU) pencil triggers most operating room fires. Carbon dioxide (CO2) is a gas that prevents ignition and suppresses fire by displacing oxygen. We hypothesize that a device can be created to reduce operating room fires by generating a cone of CO2 around the ESU pencil tip. One such device was created by fabricating a divergent nozzle and connecting it to a CO2 source. This device was then placed over the ESU pencil, allowing the tip to be encased in a cone of CO2 gas. The device was then tested in 21%, 50%, and 100% oxygen environments. The ESU was activated at 50 W cut mode while placing the ESU pencil tip on a laparotomy sponge resting on an aluminum test plate for up to 30 seconds or until the sponge ignited. High-speed videography was used to identify time of ignition. Each test was performed in each oxygen environment 5 times with the device activated (CO2 flow 8 L/min) and with the device deactivated (no CO2 flow-control). In addition, 3-dimensional spatial mapping of CO2 concentrations was performed with a CO2 sampling device. The median ± SD [range] ignition time of the control group in 21% oxygen was 2.9 s ± 0.44 [2.3-3.0], in 50% oxygen 0.58 s ± 0.12 [0.47-0.73], and in 100% oxygen 0.48 s ± 0.50 [0.03-1.27]. Fires were ignited with each control trial (15/15); no fires ignited when the device was used (0/15, P < 0.0001). The CO2 concentration at the end of the ESU pencil tip was 95%, while the average CO2 concentration 1 to 1.4 cm away from the pencil tip on the bottom plane was 64%. In conclusion, an operating room fire prevention device can be created by using a divergent nozzle design through which CO2 passes, creating a cone of fire suppressant. This device as demonstrated in a flammability model effectively reduced the risk of fire. CO2 3-dimensional spatial mapping suggests effective fire reduction at least 1 cm away from the tip of the ESU pencil at 8 L/min CO2 flow. Future testing should determine optimum CO2 flow rates and ideal nozzle shapes. Use of this device may substantially reduce the risk of patient injury due to operating room fires.

Effect of increasing heart rate and tidal volume on stroke volume variability in vascular surgery patients.

OBJECTIVE: Because heart rate affects ventricular filling, the aim of the present study was to assess the effects of increasing heart rate and tidal volume on stroke volume variability to determine whether this dynamic index is heart-rate dependent. DESIGN: Prospective, randomized study. SETTING: Single university hospital. PARTICIPANTS: Eighteen vascular surgery patients having general anesthesia and endotracheal intubation with an arterial catheter connected to the Vigileo FloTrac system (Edwards Lifesciences, Irvine, CA) and a transesophageal atrial pacemaker (CardioComman Inc, Tampa, FL). INTERVENTION: A 2 × 2 factorial study of changes in heart rate (80 bpm and 110 bpm) and tidal volume (6 mL/kg and 10 mL/kg). MEASUREMENTS AND MAIN RESULTS: With tidal volume at 6 mL/kg, increasing heart rate from 80 mL/kg to 110 bpm caused stroke volume variability to increase from 12.2% ± 5.7% to 13.2% ± 5.3% (p<0.05), and with tidal volume at 10 mL/kg, increasing heart rate from 80 mL/kg to 110 bpm caused stroke volume variability to increase from 19.7% ± 7.9% to 22.0% ± 8.6% (p<0.05). In comparison, increasing tidal volume from 6 mL/kg to 10 mL/kg produced a significantly greater effect on stroke volume variability than increasing heart rate. CONCLUSIONS: Stroke volume variability is sensitive to increases in heart rate in addition to tidal volume. Increasing heart rate caused stroke volume variability to increase significantly, although not to the same magnitude as increasing tidal volume. When using dynamic volume indices, clinicians should be aware of increases in heart rate, although its clinical impact may be relatively minor compared with changes in tidal volume.

Checklist usage decreases critical task omissions when training residents to separate from simulated cardiopulmonary bypass.

OBJECTIVE: Separation from cardiopulmonary bypass (CPB) requires multiple preparatory steps, during which mistakes, omissions, and human errors may occur. Checklists have been used extensively in aviation to improve performance of complex, multistep tasks. The aim of this study was to (1) develop a checklist using a modified Delphi process to identify essential steps necessary to prepare for separation from CPB, and (2) compare the frequency of completed items with and without the use of a checklist in simulation. It was hypothesized that the use of a checklist would reduce the number of omissions. DESIGN: High-fidelity simulation study. SETTING: University-affiliated tertiary care facility. PARTICIPANTS: Seven cardiac anesthesiologists created a checklist using a modified Delphi process. Ten residents participated in 4 scenarios separating from CPB in simulation. INTERVENTIONS: Each scenario was performed first without a checklist and then again with a checklist. An observer graded participants' performance. MEASUREMENTS AND MAIN RESULTS: A pre-separation checklist containing 9 tasks was created using the Delphi process. Without using this checklist, 4 tasks were completed in at least 75% of scenarios, and 8 tasks were completed at least 75% of the time when using the checklist. There was a significant improvement in completion of 5 of the 9 items (p< 0.01). CONCLUSIONS: A modified Delphi process can be used to create a checklist of steps in preparing to separate from CPB. Using this checklist during simulation resulted in increased frequency of completing designated tasks in comparison to relying on memory alone. Checklists may reduce omission errors during complex periods of anesthesiologists' perioperative workflow.

Changing the Culture: Increasing and Sustaining Anesthesiology Resident Physician Publication Rates.

Background: Academic inquiry is foundational to the advancement of medicine and resident training and must be demonstrated to the Accreditation Council for Graduate Medical Education. Past attempts at increasing publication rates have failed to identify educational best practice models. Our aim was to increase resident publication rates via culture and value changes that are universally implementable, affordable, effective, and sustainable. Methods: In 2018, a multifaceted initiative was implemented to shift departmental values and foster a culture of academic productivity. This culture change stressed the value of scientific publication through frequent, consistent messaging from department leaders. In addition, residents were provided the freedom to choose their scholarly activities. In this retrospective cohort innovation, resident authors were identified for 4 academic years before and after the intervention and publication rates were determined (2014-2018 vs 2018-2022). Resident authors and publications per resident per year were compared using descriptive statistics and Student t test. Results: The pre- and postintervention groups included 38 and 37 residents, respectively. Resident-authored publications increased from 7 preintervention to 24 postintervention, representing 343% of baseline. Mean ± SD publications per resident per year similarly increased 357% from 0.183 ± 0.16 to 0.654 ± 0.11 postintervention. Unpaired t test analysis demonstrated a significant difference in total publications per year (P = .002) and authorship rate (P = .003). Conclusions: A multifaceted academic initiative resulted in a threefold increase in resident publication rates. This initiative demonstrates that local advocacy by leaders, freedom of choice for authors, and supportive departmental culture are driving factors in publication rates.

Pharyngeal oxygen delivery device sustains manikin lung oxygenation longer than high-flow nasal cannula.

Purpose: Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates. Methods: We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, and a control arm with no oxygen flow after initial preoxygenation. Five randomized 20-minute trials were performed for each arm (20 trials total). Descriptive statistics and analysis of variance were used with statistical significance of P < 0.05. Results: Mean oxygen concentrations were statistically different and decreased from 97% as follows: 41 ± 0% for the control, 90 ± 1% for HFNC at 20 LPM, 88 ± 2% for HFNC at 60 LPM, and 97 ± 1% (no change) for the PODD at 10 LPM. Conclusion: Oxygen delivery with the PODD maintained oxygen concentration longer than HFNC in this manikin model at lower flow rates than HFNC.

Flammability of surgical drapes and materials in varying concentrations of oxygen.

BACKGROUND: Over 600 operating room fires occur annually although many cases go unreported. Over 81% of operating room fires involve surgical drapes, yet limited data exist on the differing degrees of flammability of drapes and other surgical fuel sources in varying oxygen concentrations. The purpose of this study is to assess the flammability characteristics of fuels in the operating room under varying oxygen concentrations. METHODS: Five fuel sources were analyzed in three levels of oxygen: 21%, 50%, and 100%. Three test samples of each material were burned in a manner similar to that established by the Consumer Product Safety Commission. Time to sample ignition and time to complete burn were measured with video analysis. RESULTS: The median [minimum, maximum] ignition time in 21% oxygen was 0.9 s [0.3, 1.9], in 50% oxygen 0.4 s [0.1, 1.2], and in 100% oxygen 0.2 s [0.0, 0.4]. The median burn time in 21% oxygen was 20.4 s [7.8, 33.5], in 50% oxygen 3.1 s [1.4, 8.1], and in 100% oxygen 1.7 s [0.6, 2.7]. Time to ignite and total burn times decreased as oxygen concentration increased (P < 0.001). Flammability characteristics differed by material and oxygen concentration. Utility drapes and surgical gowns did not support combustion in room air, whereas other materials quickly ignited. Flash fires were detected on woven cotton materials in oxygen-enriched environments. CONCLUSIONS: Operating room personnel should be aware that common materials in the operating room support rapid combustion in oxygen-enriched environments. The risk of ignition and speed of fire propagation increase as oxygen exposure increases. Advances in material science may reduce perioperative fire risk.

Accuracy of noninvasive estimated continuous cardiac output (esCCO) compared to thermodilution cardiac output: a pilot study in cardiac patients.

OBJECTIVE: To compare the noninvasive estimated continuous cardiac output (esCCO), device-derived cardiac output (CO) to simultaneous pulmonary artery catheter (PAC) thermodilution (TD) CO. DESIGN: A prospective study comparing pulse wave transit time (estimated continuous cardiac output, esCCO; Nihon Kohden, Tokyo, Japan) to intermittent TD CO. SETTING: One academic hospital. PARTICIPANTS: Patients presenting for cardiac surgery. INTERVENTIONS: Intraoperative CO measurements at 4 distinct time points (after induction, after sternotomy, after cardiopulmonary bypass, and after chest closure). MEASUREMENTS AND MAIN RESULTS: The study population consisted of American Society of Anesthesiologists (ASA) IV subjects, 27 (77%) males and 8 (23%) females, with a mean age of 64.6 ± 12.2 years. Data points from esCCO and TD were collected simultaneously and means per time point compared using Bland-Altman, Pearson R coefficient, and percent error. Mean TD CO for the study was 5.4 L/min. The Pearson R coefficient, percent error, and bias in L/min were: 0.57, 44%, 0.66 (after induction); 0.54, 51%, 0.88 (after sternotomy); 0.60, 60%, 0.95 (after cardiopulmonary bypass); and 0.57, 60%, 0.75 (after chest closure) respectively. CONCLUSIONS: esCCO is easy to use and provides continuous CO measurements, but has wide limits of agreement and large percentage errors with a consistently positive bias in comparison to TD.

Arterial Cannulation Near-Miss During Jugular Venous Catheterization With Carotid Artery Aneurysm: A Case Report.

Central venous catheterization is a common procedure that may lead to inadvertent arterial cannulation, potentially causing bleeding, hematoma, stroke or rarely, death. In this near-miss case presentation, an aneurysmal carotid artery was misidentified with ultrasound by a junior resident, nearly leading to placement of a sheath into the artery. This case highlights arterial punctures that still occur even with ultrasound guidance. Further, training inadequacies as well as anatomic, cultural, and production pressure factors led to this potentially highly morbid near-miss. Physician teachers should critically evaluate teaching methods to confirm that trainees are learning skills as intended. (A&A Practice. 2023;17:e01661.).

Dodecafluoropentane emulsion decreases infarct volume in a rabbit ischemic stroke model.

PURPOSE: To assess the efficacy of dodecafluoropentane emulsion (DDFPe), a nanodroplet emulsion with significant oxygen transport potential, in decreasing infarct volume in an insoluble-emboli rabbit stroke model. MATERIALS AND METHODS: New Zealand White rabbits (N = 64; weight, 5.1 ± 0.50 kg) underwent angiography and received embolic spheres in occluded internal carotid artery branches. Rabbits were randomly assigned to groups in 4-hour and 7-hour studies. Four-hour groups included control (n = 7, embolized without treatment) and DDFPe treatment 30 minutes before stroke (n = 7), at stroke onset (n = 8), and 30 minutes (n = 5), 1 hour (n = 7), 2 hours (n = 5), or 3 hours after stroke (n = 6). Seven-hour groups included control (n = 6) and DDFPe at 1 hour (n = 8) and 6 hours after stroke (n = 5). DDFPe dose was a 2% weight/volume intravenous injection (0.6 mL/kg) repeated every 90 minutes as time allowed. After euthanasia, infarct volume was determined by vital stains on brain sections. RESULTS: At 4 hours, median infarct volume decreased for all DDFPe treatment times (pretreatment, 0.30% [P = .004]; onset, 0.20% [P = .004]; 30 min, 0.35% [P = .009]; 1 h, 0.30% [P = .01]; 2 h, 0.40% [P = .009]; and 3 h, 0.25% [P = .003]) compared with controls (3.20%). At 7 hours, median infarct volume decreased with treatment at 1 hour (0.25%; P = .007) but not at 6 hours (1.4%; P = .49) compared with controls (2.2%). CONCLUSIONS: Intravenous DDFPe in an animal model decreases infarct volumes and protects brain tissue from ischemia, justifying further investigation.

Influences of microbubble diameter and ultrasonic parameters on in vitro sonothrombolysis efficacy.

PURPOSE: To quantify the effects of microbubble (MB) size, elasticity, and pulsed ultrasonic parameters on in vitro sonothrombolysis (ultrasound [US]-mediated thrombolysis) efficacy. MATERIALS AND METHODS: Monodispersive MBs with diameters of 1 µm or 3 µm were exposed to pulsed US (1 MHz or 3 MHz) to lyse rabbit blood clots. Sonothrombolysis efficacy (clot mass loss) was measured as functions of MB size and concentration, ultrasonic frequency and intensity, pulse duration (PD), pulse repeat frequency (PRF), and duty factor. RESULTS: Sonothrombolysis at 1 MHz was more effective using 3-µm MBs and at 3 MHz using 1-µm MBs. Sonothrombolysis was more effective at 1 MHz when≥75% of MBs remained intact, especially for 3-µm MBs; improving sonothrombolysis by increasing PRF from 100 Hz to 400 Hz at 3 MHz was associated with increasing 3-µm MB survival. However, 60% of 1-µm MBs were destroyed during maximal sonothrombolysis at 3 MHz, indicating that considerable MB collapse may be required for sonothrombolysis under these conditions. CONCLUSIONS: The ability to control MB size and elasticity permits using a wide range of US parameters (eg, frequency, intensity) to produce desired levels of sonothrombolysis. Comparable, maximal sonothrombolysis efficacy was achieved at 20-fold lower intensity with 3-µm MBs (0.1W/cm(2)) than with 1-µm MBs (2.0W/cm(2)), a potential safety issue for in vivo sonothrombolysis. US parameters that maximized MB survival yielded maximal sonothrombolysis efficacy except with 1-µm MBs at 3MHz where most MBs were destroyed.