Joseph B. Clark

Morbidity with contemporary prostate biopsy

To determine the incidence of complications associated with contemporary prostate biopsy, a review of 670 men undergoing transrectal prostate biopsy using 18 gauge biopsy needles was conducted. Of the men 580 received 1 to 3 days of ciprofloxacin antibiotic prophylaxis. A total of 16 patients (2.1%) suffered complications of whom 4 (0.6%) required hospitalization. These data demonstrate the low morbidity associated with contemporary transrectal prostate biopsy.

Mechanical circulatory support for end-stage heart failure in repaired and palliated congenital heart disease.

Approximately one in one hundred children is born with congenital heart disease. Most can be managed with corrective or palliative surgery but a small group will develop severe heart failure, leaving cardiac transplantation as the ultimate treatment option. Unfortunately, due to the inadequate number of available donor organs, only a small number of patients can benefit from this therapy, and mortality remains high for pediatric patients awaiting heart transplantation, especially compared to adults. The purpose of this review is to describe the potential role of mechanical circulatory support in this context and to review current experience. For patients with congenital heart disease, ventricular assist devices are most commonly used as a bridge to cardiac transplantation, an application which has been shown to have several important advantages over medical therapy alone or support with extracorporeal membrane oxygenation, including improved survival to transplant, less exposure to blood products with less immune sensitization, and improved organ function. While these devices may improve wait list mortality, the chronic shortage of donor organs for children is likely to remain a problem into the foreseeable future. Therefore, there is great interest in the development of mechanical ventricular assist devices as potential destination therapy for congenital heart disease patients with end-stage heart failure. This review first discusses the experience with the currently available ventricular assist devices in children with congenital heart disease, and then follows to discuss what devices are under development and may reach the bedside soon.

In Vivo Hemodynamic Performance Evaluation of Novel Electrocardiogram-Synchronized Pulsatile and Nonpulsatile Extracorporeal Life Support Systems in an Adult Swine Model

The primary objective of this study was to evaluate a novel electrocardiogram (ECG)-synchronized pulsatile extracorporeal life support (ECLS) system for adult partial mechanical circulatory support for adequate quality of pulsatility and enhanced hemodynamic energy generation in an in vivo animal model. The secondary aim was to assess end-organ protection during nonpulsatile versus synchronized pulsatile flow mode. Ten adult swine were randomly divided into a nonpulsatile group (NP, n = 5) and pulsatile group (P, n = 5), and placed on ECLS for 24 h using an i-cor system consisting of an i-cor diagonal pump, an iLA membrane ventilator, an 18 Fr femoral arterial cannula and a 23/25 Fr femoral venous cannula. Trials were conducted at a flow rate of 2.5 L/min using nonpulsatile or pulsatile mode (with assist ratio 1:1). Real-time pressure and flow data were recorded using a custom-based data acquisition system. To the best of our knowledge, the oxygenator and circuit pressure drops were the lowest for any available system in both groups. The ECG-synchronized i-cor ECLS system was able to trigger pulsatile flow in the porcine model. After 24-h ECLS, energy equivalent pressure, surplus hemodynamic energy, and total hemodynamic energy at preoxygenator and prearterial cannula sites were significantly higher in the P group than those in the NP group (P < 0.05). Urine output was higher in P versus NP (3379 ± 443 mL vs. NP, 2598 ± 1012 mL), and the P group seemed to require less inotropic support, but both did not reach statistical significances (P > 0.05). The novel i-cor system performed well in the nonpulsatile and ECG-synchronized pulsatile mode in an adult animal ECLS model. The iLA membrane oxygenator had an extremely lower transmembrane pressure gradient and excellent gas exchange capability. Our findings suggest that ECG-triggered pulsatile ECLS provides superior end-organ protection with improved renal function and systemic vascular tone.

Evaluation of a Novel Pulsatile Extracorporeal Life Support System Synchronized to the Cardiac Cycle: Effect of Rhythm Changes on Hemodynamic Performance

Arrhythmias are a frequent complication during extracorporeal life support (ECLS). A new ECLS system can provide pulsatile flow synchronized to the patients intrinsic cardiac cycle based upon the R wave of the electrocardiogram (ECG). It is unclear how the occurrence of arrhythmias may alter the hemodynamic performance of the system. This in vitro study evaluated the effect of simulated arrhythmias on hemodynamics during R wave-triggered pulsatile ECLS. The ECLS circuit with an i-cor diagonal pump and iLA membrane ventilator was primed with whole blood at room temperature. Flow and pressure data were collected at 2.5 and 4 L/min for each condition using a customized data acquisition system. Pulsatile ECLS flow was R wave synchronized to an ECG simulator using 1:1, 1:2, and 1:3 assist ratios. Conditions tested included sinus rhythm at 45 and 90 bpm, supraventricular tachycardia (SVT), ventricular tachycardia (VT), and irregular rhythms such as ventricular fibrillation. Pulsatile mode was successfully triggered by ECG signals of normal sinus rhythm, SVT, VT, atrial fibrillation, atrial flutter, and ventricular bigeminy with assist ratios 1:1, 1:2, and 1:3. Regular rhythm at 90 bpm generated the best surplus hemodynamic energy (SHE). For SVT and VT, an assist ratio of 1:2 resulted in maximum pulsatile flow waveforms with optimal SHE at 2.5 L/min flow rate. At 4 L/min, SHE declined and the pressure drop increased independent of arrhythmia condition. Irregular rhythms still produced adequate pulsatile wave forms at lower pulsatile frequency. This study demonstrated the feasibility of generating pulsatile ECLS flow with the novel ECG-synchronized i-cor system during various simulated rhythms. The optimal rate for pulsatile flow was 90 bpm. During irregular rhythms, the lower pulsatile frequency was the more reliable synchronization mode for generating pulsatile flow.

Current Techniques and Outcomes in Extracorporeal Life Support

For patients with catastrophic cardiac or pulmonary failure, extracorporeal life support (ECLS) often represents the last line of defense against impending and near-certain demise. Recent increases in the application of this technology for adult support have contributed to the continued growth of ECLS utilization in the USA and around the world. With widened application, there is increased clinical demand for this expensive yet potentially life-saving technology. For scientists and clinicians working in the field, there is an obligation to pursue the continued refinement of ECLS technology, all with the goal of improving patient survival and subsequent quality of life. As ECLS becomes more common, providers will be challenged to be judicious in the selection of both the most appropriate patients for ECLS as well as the most appropriate equipment. In this report, we aim to review current ECLS use and outcomes, both nationally and at our center, and to describe our recent and future translational research projects intended to elevate ECLS circuitry.

Hemodynamic evaluation of arterial and venous cannulae performance in a simulated neonatal extracorporeal life support circuit.

Objective: To construct an ideal extracorporeal life support (ECLS) circuit in terms of hemodynamic performance, each component of the circuit should be evaluated. Most cannulae manufacturers evaluate their products using water as the priming solution. We conducted this study to evaluate the different sizes of arterial and venous cannulae in a simulated neonatal ECLS circuit primed with human blood. Methods: The simulated neonatal ECLS circuit was composed of a Capiox Baby RX05 oxygenator, a Rotaflow centrifugal pump and a heater & cooler unit. Three Medtronic Bio-Medicus arterial cannulae (8Fr, 10Fr, 12Fr) and three venous cannulae (10Fr, 12Fr, 14Fr) were tested in seven combinations (8A-10V, 8A-12V, 10A-10V, 10A-12V, 10A-14V, 12A-12V, 12A-14V). All the experiments were conducted using human blood at a hematocrit of 40% and at a constant temperature of 37°C. The “tip to tip” priming volume of the entire circuit was 135ml. The blood volume of the pseudo patient was 500ml. Results: Flow rates increased linearly with increasing size in both venous and arterial cannulae at the same pump speeds. The increase in flow rate was greater when changing the arterial cannulae (next size larger) compared to changing the venous cannulae (next size larger). The pressure drops of the arterial cannula were correlated with the flow rates, regardless of the pseudo patient pressure and the venous cannula used simultaneously. Conclusions: The results show the difference in flow ranges and pressure drops of seven combinations of arterial and venous cannulae. It also suggests that the arterial cannula, not the venous cannula, has greater impact on the flow rate when a centrifugal pump is used in a neonatal ECLS circuit. The results of this study have been translated to further advancing the clinical practice in our institution.

An investigational study of minimum rotational pump speed to avoid retrograde flow in three centrifugal blood pumps in a pediatric extracorporeal life support model.

During extracorporeal life support with centrifugal blood pumps, retrograde pump flow may occur when the pump revolutions decrease below a critical value determined by the circuit resistance and the characteristics of the pump. We created a laboratory model to evaluate the occurrence of retrograde flow in each of three centrifugal blood pumps: the Rotaflow, the CentriMag, and the Bio-Medicus BP-50. At simulated patient pressures of 60, 80, and 100 mmHg, each pump was evaluated at speeds from 1000 to 2200 rpm and flow rates were measured. Retrograde flow occurred at low revolution speeds in all three centrifugal pumps. The Bio-Medicus pump was the least likely to demonstrate retrograde flow at low speeds, followed by the Rotaflow pump. The CentriMag pump showed the earliest transition to retrograde flow, as well as the highest degree of retrograde flow. At every pump speed evaluated, the Bio-Medicus pump delivered the highest antegrade flow and the CentriMag pump delivered the least.

In Vitro Hemodynamic Evaluation of a Novel Pulsatile Extracorporeal Life Support System: Impact of Perfusion Modes and Circuit Components on Energy Loss

The objective of this study is to investigate the impact of every component of extracorporeal life support (ECLS) circuit on hemodynamic energy transmission in terms of energy equivalent pressure (EEP), total hemodynamic energy (THE), and surplus hemodynamic energy (SHE) under nonpulsatile and pulsatile modes in a novel ECLS system. The ECLS circuit consisted of i-cor diagonal pump and console (Xenios AG, Heilbronn, Germany), an iLA membrane ventilator (Xenios AG), an 18 Fr femoral arterial cannula, a 23/25 Fr femoral venous cannula, and 3/8-in ID arterial and venous tubing. The circuit was primed with lactated Ringers solution and human whole blood (hematocrit 33%). All trials were conducted under room temperature at the flow rates of 1-4 L/min (1 L/min increments). The pulsatile flow settings were set at pulsatile frequency of 75 beats per minute and differential speed values of 1000-4000 rpm (1000 rpm increments). Flow and pressure data were collected using a custom-based data acquisition system. EEP was significantly higher than mean arterial pressure in all experimental conditions under pulsatile flow (P < 0.01). THE was also increased under pulsatile flow compared with the nonpulsatile flow (P < 0.01). Under pulsatile flow conditions, SHE was significantly higher and increased differential rpm resulted in significantly higher SHE (P < 0.01). There was no SHE generated under nonpulsatile flow. Energy loss depending on the circuit components was almost similar in both perfusion modes at all different flow rates. The pressure drops across the oxygenator were 3.8-24.9 mm Hg, and the pressure drops across the arterial cannula were 19.3-172.6 mm Hg at the flow rates of 1-4 L/min. Depending on the pulsatility setting, i-cor ECLS system generates physiological quality pulsatile flow without increasing the mean circuit pressure. The iLA membrane ventilator is a low-resistance oxygenator, and allows more hemodynamic energy to be delivered to the patient under pulsatile mode. The 18 Fr femoral arterial cannula has acceptable pressure drops under nonpulsatile and pulsatile modes. Further in vivo studies are warranted to confirm these results.

Comparative effects of pulsatile and nonpulsatile flow on plasma fibrinolytic balance in pediatric patients undergoing cardiopulmonary bypass.

In the brain, the components of the fibrinolytic system, tissue plasminogen activator (tPA) and its endogenous inhibitor plasminogen activator inhibitor-1 (PAI-1), regulate various neurophysiological and pathological responses. Fibrinolytic balance depends on PAI-1 and tPA concentrations. The objective of this study is to compare the effects of pulsatile and nonpulsatile perfusion on fibrinolytic balance in children undergoing pediatric cardiopulmonary bypass (CPB). Plasma PAI-1 antigen and tPA antigen were measured in 40 children (n = 20 pulsatile and n = 20 nonpulsatile group). Plasma samples (1.5 mL) were collected (i) prior to incision, (ii) 1 h after CPB, and (iii) 24 h after CPB. PAI-1 and tPA levels were measured at each time point. PAI-1 and tPA levels were significantly increased at 1 h after CPB, followed by a decrease at 24 h. Nonpulsatile but not pulsatile CPB lowered PAI-1 : tPA ratio significantly at 24 h (median PAI-1 : tPA ratio 4.63 ± 0.83:1.98 ± 0.48, P = 0.03, for the nonpulsatile group and 4.50 ± 0.92:3.56 ± 1.28, P = 0.2, for the pulsatile group). These results suggest that pulsatile flow maintains endogenous fibrinolytic balance after pediatric cardiopulmonary bypass. Further studies are needed to define the clinical significance of these differences.

Microemboli detection and classification during pediatric cardiopulmonary bypass.

Microemboli may be a cause of postoperative neurological morbidity. Improved detection of microemboli may lead to better strategies to minimize embolization and improve neurological outcomes. Transcranial Doppler may have limited sensitivity for very small microemboli. The Emboli Detection and Classification (EDAC) Quantifier offers increased sensitivity (10 μm) and potentially improved capability for microemboli monitoring. EDAC was used to measure microemboli in the cardiopulmonary bypass circuit during 33 pediatric heart operations. More microemboli were detected in the venous than the arterial line (median, 11,830 vs 1298). Venous microemboli tended to be larger in size than arterial microemboli (>40 μm; 59% vs 7%). Increased venous and arterial microemboli were seen at the onset of bypass; increased venous microemboli were also seen with clamp removal. Thousands of microemboli <40 μm are transmitted to pediatric patients during heart surgery. Initiation of bypass may be a key offender and may result from air in the venous line. Although the significance of microemboli remains unknown, increased awareness may lead to improved techniques to minimize microemboli, with improvement in neurological outcomes.