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Biomedical subjects

Robert H Bartlett

Publications and source records attributed to Robert H Bartlett.

At least 19 recordsLinked to original sources
PubMed2006

The Bartlett et al extracorporeal membrane oxygenation case series from 1977, with expert commentary provided by Dr P. Pearl O'Rourke.

In this Classic Papers feature, we highlight Dr. Robert H. Bartlett's ground-breaking case series from 1977 reporting 28 pediatric and adult patients supported by extracorporeal membrane oxygenation (ECMO). Dr. P. Peal O'Rourke, who conducted early, innovative clinical research on ECMO, provides her perspective on the state of critical care for children in the late 1970s, how this paper and Dr. Bartlett himself influenced it, and difficulties faced in developing ECMO programs in the 1980s. Dr. Bartlett offers answers to questions about how his work on ECMO began, the reaction of the critical care community to the use of ECMO, and how challenges in studying ECMO in clinical trials have been approached.

Critical Care↗
PubMed2006

Extracorporeal life support.

Extracorporeal life support (ECLS) denotes the use of prolonged extracorporeal cardiopulmonary bypass in patients with acute, reversible cardiac or respiratory failure. As technology has advanced, organ support functions other than gas exchange, such as liver, renal, and cardiac support, have been provided by ECLS, and others, such as immunologic support, will be developed. The future of ECLS will include improvements in devices accompanied by circuit simplification and auto-regulation. Such enhancements in technology will allow application of ECLS to populations currently excluded from such support; for example, thromboresistant circuits will eliminate the need for systemic anticoagulation and lead to the use of this technique in premature newborns. As the ECLS technique becomes safer and simpler, and as morbidity and mortality are minimized, criteria for application of ECLS will be relaxed. New approaches to ECLS, such as pumpless arteriovenous bypass, the artificial placenta, arteriovenous CO(2) removal (AVCO(2)R), and intravenous oxygenators (IVOX), will become more commonly applied. Such advances in technology will allow broader and more routine application of ECLS for lung and other organ system failure.

Ambulatory Care↗
PubMed2006

Acute lung injury and acute respiratory distress syndrome: extracorporeal life support and liquid ventilation for severe acute respiratory distress syndrome in adults.

Acute respiratory distress syndrome (ARDS) has many underlying causes and carries an overall mortality of 40 to 60%. For those patients with severe ARDS who have a predicted mortality of 80 to 100%, extracorporeal life support (ECLS) can provide an extraordinary means of support. We recently demonstrated a survival to hospital discharge of 52% in this subset of patients. ECLS is capable of providing full respiratory and cardiac support, allowing time for the patient to recover from the underlying disease process. Additionally, ventilator settings are reduced to "rest" settings, avoiding the consequences of ventilator-induced lung injury that can contribute to a worse outcome. Systemic heparinization is a mainstay of ECLS therapy because of platelet activation in the circuit. Mechanical complications and significant bleeding can occur in up to one quarter of patients, requiring close attention and prompt intervention should they occur. Although not currently in clinical practice, liquid ventilation using perfluorocarbons to provide gas exchange in the lungs is a potentially useful adjunct in the management of severe respiratory failure.

Extracorporeal Membrane Oxygenation↗
PubMed2006

Pulsatile flow and mass transport over an array of cylinders: gas transfer in a cardiac-driven artificial lung.

The pulsatile flow and gas transport of a Newtonian passive fluid across an array of cylindrical microfibers are numerically investigated. It is related to an implantable, artificial lung where the blood flow is driven by the right heart. The fibers are modeled as either squared or staggered arrays. The pulsatile flow inputs considered in this study are a steady flow with a sinusoidal perturbation and a cardiac flow. The aims of this study are twofold: identifying favorable array geometry/spacing and system conditions that enhance gas transport; and providing pressure drop data that indicate the degree of flow resistance or the demand on the right heart in driving the flow through the fiber bundle. The results show that pulsatile flow improves the gas transfer to the fluid compared to steady flow. The degree of enhancement is found to be significant when the oscillation frequency is large, when the void fraction of the fiber bundle is decreased, and when the Reynolds number is increased; the use of a cardiac flow input can also improve gas transfer. In terms of array geometry, the staggered array gives both a better gas transfer per fiber (for relatively large void fraction) and a smaller pressure drop (for all cases). For most cases shown, an increase in gas transfer is accompanied by a higher pressure drop required to power the flow through the device.

Artificial Organs↗
PubMed2006

Hyperkalemia of the blood-primed ECLS circuit does not result in post-initiation hyperkalemia in infants < 10 kg.

OBJECTIVE: To assess the risk of hyperkalemia with blood-primed extracorporeal life support (ECLS) circuits in infants < 10 kg. DESIGN: Retrospective cohort study of all neonatal and pediatric patients < 10 kg placed on ECLS from May 1998 to April 2001. MEASUREMENTS AND MAIN RESULTS: Data collection including patient weight, patient potassium levels pre- and post-initiation of ECLS, potassium level of the primed ECLS circuit, age of the packed red blood cell (PRBC) unit, type of preservative, and preservative reduction status. Seventy-six circuits were available for the analysis. The age of the PRBC unit and preservative reduction status significantly affected the potassium level of the primed ECLS circuit. Multivariate linear regression analysis showed no significant effect on the post-ECLS initiation patient potassium level with respect to the PRBC age, the preservative reduction status, the patient potassium level prior to ECLS initiation, and the potassium level of the primed ECLS circuit. CONCLUSIONS: Initiation of ECLS in infants < 10 kg should not be delayed unnecessarily to perform preservative reduction or to utilize PRBC units of a specific age, as hyperkalemia of the primed ECLS circuit is not associated with systemic hyperkalemia in the patient post-initiation of ECLS.

Blood Preservation↗
PubMed2005

Development of an artificial placenta: CO2 elimination and hemodynamics as a function of arteriovenous blood flow.

BACKGROUND: As a first step toward the development of an artificial placenta, we investigated the relationship between blood flow rate through an arteriovenous (A-V) circuit/oxygenator and both CO2 elimination and hemodynamic stability in a small animal model. METHODS: Male New Zealand rabbits (N = 10) with an average weight of 2.7 +/- 0.2 kg were anesthetized, paralyzed, and heparinized before carotid-jugular cannulation. A tracheostomy tube, an arterial catheter, and an aortic flow probe were placed. Arteriovenous flow through a custom-made, low-resistance, 0.5 m2 hollow fiber oxygenator was initiated. Oxygen sweep flow was maintained at 300 mL/min, whereas blood flow was controlled at 10 to 40 mL/(kg min). Ventilation was discontinued during each blood flow rate trial. Hemodynamic and preoxygenator and postoxygenator blood gas data were recorded 30 minutes after initiation of each flow rate. CO2 removal was the product of the oxygen sweep gas flow rate and the sweep flow exhaust CO2 content as determined by capnometry. Data were analyzed by analysis of variance with post hoc Dunnett's t test. RESULTS: CO2 removal increased and PaCO2 decreased as a function of A-V blood flow rate. Simultaneously, systolic blood pressure did not significantly change. CO2 removal was effective at device flows greater than 20% of cardiac output. CONCLUSION: In this rabbit model, A-V blood flows at 25% to 30% of cardiac output allow full gas exchange without hemodynamic compromise. This model raises the possibility of using A-V support and an artificial placenta in newborns with respiratory failure.

Animals↗
PubMed2005

Extracorporeal life support: history and new directions.

This review recounts the development of extracorporeal life support (ECLS, ECMO) from the laboratory and early clinical trials to routine clinical application. Lessons from neonatal ECMO have led to better understanding of neonatal lung physiology, improved methods of treatment, and application of ECLS to other patient populations.

Extracorporeal Circulation↗
PubMed2005

Extracorporeal support for organ donation after cardiac death effectively expands the donor pool.

BACKGROUND: We sought to evaluate the effect on short-term outcomes of normothermic, extracorporeal perfusion (ECMO) for donation of abdominal organs for transplantation after cardiac death (DCD). Study parameters included increase in number of donors and organs, types of organs procured, and viability of kidneys transplanted. METHODS: We retrospectively reviewed medical record data for all patients enrolled in our ECMO-supported DCD donor protocol between 10/1/2000 to 2/01/2004. We also reviewed the records for all patients undergoing organ donation after brain-death (DBD) during the study period at our institution. Recipient data were obtained and analyzed for all kidneys procured from both groups. RESULTS: Twenty patients were enrolled in our DCD protocol and underwent attempted organ donation. Fifteen patients completed the protocol; 3 maintained cardiac function throughout the prescribed 60 minutes after withdrawal of life support, and two patients' organs were deemed unsuitable for transplantation. Fourteen (70%) of the DCD donor patients originated on the trauma service and six (30%) were from other clinical services. The DCD program increased the potential donor pool by 33% (61 versus 81 patients) and the number of kidneys transplanted by 24% (100 versus 124). A total of 24 kidney, 5 liver, and 1 pancreas transplants were performed with these organs. Two of 24 (8.3%) DCD kidneys had delayed graft function. There were no perioperative rejection episodes or deaths. CONCLUSION: The implementation of a DCD protocol using extracorporeal perfusion increased the potential organ donor pool at our institution by 33%. This was accomplished without short term adverse effect on organ function compared with kidneys transplanted from DBD donors.

Adolescent↗
PubMed2004

Injectable microparticle-gel system for prolonged and localized lidocaine release. I. In vitro characterization.

Current treatment protocol for postoperative pain is to infuse anesthetic solution around nerves or into the epidural space. This clinical practice is beset by the short duration of the anesthetic effect unless the infusion is continuous. Continuous infusion, however, requires hospitalization of the patients, thereby increasing medical costs. In addition, it also causes systemic accumulation of the drug. We reported herein a novel treatment for the postoperative pain by applying to the surgical site a biodegradable microsphere-gel system for prolonged and localized release of encapsulated anesthetic drugs. This lidocaine-containing biodegradable poly(D,L-lactic acid) (PLA) microsphere system, although being established previously by other investigators, was hindered by a burst release and a followed rapid release of the drug within several hours in vitro. In this article, we demonstrated that by a step-by-step modification of the formulation, prolonged release of lidocaine, up to several days in vitro, could be achieved. Differential scanning calorimetry revealed a lower glass transition temperature for these lidocaine-loaded microspheres comparing to that of lidocaine-free microspheres. This decreased Tg explained for the tendency of the lidocaine-loaded microspheres to physically fuse at higher temperatures. In vitro studies showed that microspheres, when loaded with 35% lidocaine, yielded a threefold increase in the degradation rate. The molecular weight of PLA of the drug-loaded microspheres was reduced by 50% within a period of 1 month. Based on the results (of prolonged lidocaine release and rapid PLA microsphere degradation), this lidocaine-loaded PLA microsphere system could offer a simple solution to the treatment of postoperative pain.

Anesthetics, Local↗
PubMed2004

Injectable microparticle-gel system for prolonged and localized lidocaine release. II. In vivo anesthetic effects.

Current treatment protocols for postoperative pain are beset by either the short duration of the anesthetic effect or requirement of hospitalization of the patients. We reported herein a novel treatment by applying to the surgical site a biodegradable microparticle-gel system for prolonged and localized release of encapsulated anesthetic drugs. In a previous publication, lidocaine-loaded poly(D,L-lactic acid) microspheres were fabricated and their formulations were optimized. In vitro characterization of these lidocaine-loaded microspheres, however, revealed a shortcoming of this system; that is, microspheres tend to fuse physically. Fusion of the microspheres could hinder their clinical applications, as it would clog the needle. In this article, we demonstrated that fabricating microspheres with high molecular weight (approximately 60 KDa) poly(lactic-co-glycolic acid) would increase the glass transition temperature of the microspheres after lidocaine loading, thereby increasing their mechanical stability and eliminating their fusion during storage. Such microspheres containing 31% (w/w) lidocaine in the presence or absence of 25% (w/v) poloxamer 407 gel were then evaluated in vivo by monitoring the sensory and motor functions of the rats after sciatic nerve block, using the previously established hot-plate and weight-bearing testing methods. Results showed that microspheres formulated with poloxamer 407 gel yielded the longest duration of sensory and motor block for a period of approximately 8.5 h, compared to 5 h by microspheres in saline, 5 h by lidocaine in poloxamer 407 gel, and 2 h by lidocaine in saline. This study suggests that the microsphere-gel system containing lidocaine could potentially be applied clinically to the treatment of postoperative pain.

Anesthetics, Local↗
PubMed2004

Assessment of the development of choked flow during total liquid ventilation.

OBJECTIVE: The flow rate of a liquid drainage from the lungs is limited because of the elastic nature of the airways. This study was designed to clarify the relationship between intrapulmonary liquid volume and the development of the flow limitation or choked flow phenomenon as a function of expiratory flow rate during total liquid ventilation with perflubron. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Rabbits with a weight of 3.2 +/- 0.3 kg. INTERVENTIONS: After the rabbits were killed, the lungs were filled to functional residual capacity with perflubron, followed by administration of an additional volume of 30, 45, or 60 mL of perflubron (initial volume = functional residual capacity + additional volume). MEASUREMENTS AND RESULTS: In one set of five animals, the intratracheal pressure at the occurrence of choked flow was established at -20 mm Hg. In another set of six animals, we demonstrated that the volume remaining in the lung at the point of development of choked flow (Vch) was stable for the first 40 mins after the animals were killed. Flow rates of 1.25, 2.5, 3.75, 5.0, 7.5, 10.0, and 12.5 mL/sec were then applied at an additional volume of 30, 45, or 60 mL to 34 animals. Vch approximately doubled as the flow rate increased from 1.25 mL/sec to 12.5 mL/sec (p <.001). At the same flow, Vch was higher for an additional volume of 60 mL than 30 mL when the flow was > or =2.5 mL/sec. CONCLUSIONS: From these data, we conclude that choked flow occurs at intratracheal pressure of less than -20 mm Hg, that Vch is stable for the first 40 mins after the animals are killed, and that Vch is a function of flow rate and initial volume.

Airway Obstruction↗
PubMed2004

A prototype of a liquid ventilator using a novel hollow-fiber oxygenator in a rabbit model.

OBJECTIVE: A functional total liquid ventilator should be simple in design to minimize operating errors and have a low priming volume to minimize the amount of perfluorocarbon needed. Closed system circuits using a membrane oxygenator have partially met these requirements but have high resistance to perfluorocarbon flow and high priming volume. To further this goal, a single piston prototype ventilator with a low priming volume and a new high-efficiency hollow-fiber oxygenator in a circuit with a check valve flow control system was developed. DESIGN: Prospective, controlled animal laboratory study. SETTING: Research facility at a university medical center. SUBJECTS: Seven anesthetized, paralyzed, normal New Zealand rabbits INTERVENTIONS: The prototype oxygenator, consisting of cross-wound silicone hollow fibers with a surface area of 1.5 m2 with a priming volume of 190 mL, was tested in a bench-top model followed by an in vivo rabbit model. Total liquid ventilation was performed for 3 hrs with 20 mL.kg(-1) initial fill volume, 17.5-20 mL.kg(-1) tidal volume, respiratory rate of 5 breaths/min, inspiratory/expiratory ratio 1:2, and countercurrent sweep gas of 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Bench top experiments demonstrated 66-81% elimination of CO2 and 0.64-0.76 mL.min(-1) loss of perfluorocarbon across the fibers. No significant changes in PaCO2 and PaO2 were observed. Dynamic airway pressures were in a safe range in which ventilator lung injury or airway closure was unlikely (3.6 +/- 0.5 and -7.8 +/- 0.3 cm H2O, respectively, for mean peak inspiratory pressure and mean end expiratory pressure). No leakage of perfluorocarbon was noted in the new silicone fiber gas exchange device. Estimated in vivo perfluorocarbon loss from the device was 1.2 mL.min(-1). CONCLUSIONS: These data demonstrate the ability of this novel single-piston, nonporous hollow silicone fiber oxygenator to adequately support gas exchange, allowing successful performance of total liquid ventilation.

Animals↗
PubMed2004

Extracorporeal life support for severe acute respiratory distress syndrome in adults.

OBJECTIVE: Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. METHODS: We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio < or =100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung "rest" at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. RESULTS: During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH < or =7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. CONCLUSION: Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not respond to conventional mechanical ventilator strategies.

Adolescent↗
PubMed2004

Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.

BACKGROUND: Acute renal failure (ARF) in intensive care unit patients continues to have mortality rates exceeding 70%, despite hemodialysis or continuous renal replacement therapy (CRRT). The delivery of cellular metabolic function to CRRT may provide more complete renal replacement therapy, thereby changing the natural history of this disease process. An FDA-approved Phase I/II clinical trial on 10 patients has been completed, and demonstrated that this experimental treatment can be delivered safely for up to 24 hours. METHODS: The bioartificial kidney is a synthetic hemofilter connected in series with a bioreactor cartridge containing approximately 10(9) human proximal tubule cells, as a renal tubule assist device (RAD), within an extracorporeal perfusion circuit utilizing standard hemofiltration pump systems. All 10 patients had ARF and multiorgan failure (MOF), with predicted hospital mortality rates averaging above 85%. RESULTS: Data indicate that the RAD maintains viability, durability, and functionality in this ex vivo clinical setting. The device also demonstrated differentiated metabolic and endocrinologic activity, with glutathione degradation and endocrinologic conversion of 25-OH-D(3) to 1,25-(OH)(2)-D(3). All but one treated patient with more than a 3-day follow-up in the intensive care unit showed improvement as assessed by acute physiologic scores 1 to 7 days following therapy. Six of the 10 treated patients survived past 30 days. One patient expired within 12 hours after RAD treatment due to his family's request to withdraw ventilatory life support. Three other patients died due to complications from acute or chronic comorbidities unrelated to ARF or RAD therapy. Plasma cytokine levels suggest that RAD therapy produced dynamic and individualized responses in patients. For the subset of patients who had excessive proinflammatory levels, RAD treatment resulted in significant declines in granulocyte colony stimulating factor (G-CSF), interleukin (IL)-6, IL-10, and IL-6/IL-10 ratios. CONCLUSION: The addition of human renal tubule cell therapy to CRRT has been accomplished and demonstrates metabolic activity with systemic effects in patients with ARF and MOF. These initial clinical results are encouraging, so that a randomized, controlled Phase II clinical trial is underway to further assess the clinical safety and efficacy of this new therapeutic approach.

Acute Kidney Injury↗
PubMed2003

Nitric oxide-releasing fumed silica particles: synthesis, characterization, and biomedical application.

The preparation, characterization, and preliminary biomedical application of various nitric oxide (NO)-releasing fumed silica particles (0.2-0.3 microm) are reported. The tiny NO-releasing particles are synthesized by first tethering alkylamines onto the surface of the silica using amine-containing silylation reagents. These amine groups are then converted to corresponding N-diazeniumdiolate groups via reaction with NO(g) at high pressure in the presence of methoxide bases (e.g., NaOMe). N-Diazeniumdiolate groups were found to form more readily with secondary amino nitrogens than primary amino nitrogens tethered to the silica. Different alkali metal cations of the methoxide bases, however, have little effect on the degree of N-diazeniumdiolate formation. The N-diazeniumdiolate moieties attached on the silica surface undergo a primarily proton-driven dissociation to NO under physiological conditions, with an "apparent" reaction order somewhat greater than 1 owing to local increases in pH at the surface of the particles as free amine groups are generated. The rates of N-diazeniumdiolate dissociation are further related to the parent amine structures and the pH of the soaking buffer. The N-diazeniumdiolate groups also undergo slow thermal dissociation to NO, with zero-order dissociation observed at both -15 and 23 degrees C. It is further shown that the resulting NO-releasing fumed silica particles can be embedded into polymer films to create coatings that are thromboresistant, via the release of NO at fluxes that mimic healthy endothelial cells (EC). For example a polyurethane coating containing 20 wt % of NO-releasing particles prepared with pendant hexane diamine structure (i.e., Sil-2N[6]-N(2)O(2)Na) is shown to exhibit improved surface thromboresistivity (compared to controls) when used to coat the inner walls of extracorporeal circuits (ECC) employed in a rabbit model for extracorporeal blood circulation.

Amines↗
PubMed2003

Outcome of pediatric patients treated with extracorporeal life support after cardiac surgery.

BACKGROUND: Extracorporeal life support (ECLS) has been used for over two decades in select patients after cardiac surgery. We previously described factors associated with death in this population. We now review our recent experience to reassess factors related to mortality. METHODS: All pediatric patients who received ECLS support within 7 days after surgery between July 1995 and June 2001 were examined to describe clinical features associated with survival. We compared the results with our prior report to assess changes in practice and outcome. RESULTS: Seventy-four patients were followed. Fifty percent survived to discharge. Hospital survival was not significantly related to patient age, cannulation site, or indication. Thirty-five percent of patients required hemofiltration while on ECLS and were significantly less likely to survive (23% vs 65%). A multivariate analysis combining all children from our prior report with the present cohort revealed that patients who received hemofiltration were five times more likely to die (odds ratio 5.01, 95% confidence interval 2.11-11.88). Children with an adequate two-ventricular repair had lower risk of death (odds ratio 0.42, 95% confidence interval 0.19-0.91) after adjusting for patient age, study period, and hours elapsed before initiation of ECLS after surgery. CONCLUSIONS: Patients with an adequate two-ventricle repair have significantly higher hospital survival, whereas those with single ventricle physiology or need for dialysis have decreased survival.

Cardiac Surgical Procedures↗