Ultrasound-guided vascular access in critical illness.

Over the past two decades, ultrasound (US) has become widely accepted to guide safe and accurate insertion of vascular devices in critically ill patients. We emphasize central venous catheter insertion, given its broad application in critically ill patients, but also review the use of US for accessing peripheral veins, arteries, the medullary canal, and vessels for institution of extracorporeal life support. To ensure procedural safety and high cannulation success rates we recommend using a systematic protocolized approach for US-guided vascular access in elective clinical situations. A standardized approach minimizes variability in clinical practice, provides a framework for education and training, facilitates implementation, and enables quality analysis. This review will address the state of US-guided vascular access, including current practice and future directions.

Bolus thrombolytic infusion during prolonged refractory cardiac arrest of undiagnosed cause.

Acute myocardial infarction (AMI) and pulmonary embolism (PE) account for about 70% of cardiac arrest. Although thrombolytic therapy is an effective therapy for both AMI and PE, it is not routinely recommended during cardiopulmonary resuscitation (CPR) for fear of life threatening bleeding complications. Numerous case reports and retrospective studies have suggested a beneficial effect of thrombolytics in cardiac arrest secondary to AMI and PE; however, we present a case of successful use of bolus thrombolytics during CPR in a patient with undifferentiated cardiac arrest (undiagnosed cause) after prolonged conventional resuscitation without success.

Cell column chromatography: a new research tool to quantify cerebral cell volume changes following chemically-induced anoxia/re-oxygenation.

OBJECTIVE: The roles of individual types of cerebral cells in contributing to brain edema are undefined. The objective of this study was to determine the role of cerebral cell-column chromatography in quantifying cell volumes of individual cerebral cell lines, under chemically-induced anoxia/re-oxygenation (A/R). METHODS: Cerebral endothelial cells (4 experiments) or type II astrocytes (4 experiments) were cultured to confluence on microcarrier beads. A chromatographic cell-column of 1.5 cm height was filled with non-treated cell-covered beads. The column was perfused at 1 ml/min with a balanced perfusate for one hour (Baseline). The perfusate was then switched to that containing 5 mM thioglycolic acid for one hour (Anoxia). Then the column was perfused with the normal perfusate for another two hours (Re-oxygenation). The total free space in the column, reversely reflecting cell volumes, was determined by averaged transit time (TTa) of a non-permeable flow tracer blue dextran. Decreased TTa means that cells swell, and vice versa. RESULTS: TTa in endothelial cell columns increased with a peak at 60 minutes of re-oxygenation. TTa in astrocyte columns decreased with a nadir at 30 minutes of re-oxygenation. CONCLUSION: Cell column chromatography can be used to determine the cerebral cell volume changes following chemically-induced anoxia/re-oxygenation.

Ifenprodil treatment is associated with a down-regulation of brain aquaporin 4 following cardiac arrest in rats.

OBJECTIVES: Ifenprodil, a NMDA receptor polyamine site antagonist, reduces experimental cardiac arrest (CA)-elicited brain edema, which is associated with an up-regulation of aquaporin 4 (AQP4), a brain water-selective channel. However, the interacting roles of NMDA receptors and AQP4 in CA-elicited brain edema are unknown. The objective of this study was to test our hypothesis that ifenprodil treatment is associated with a down-regulation of brain AQP4. METHODS: Twenty-five rats were assigned to normal controls (group 1, n = 6) or subjected to eight minutes of asphyxial CA treated with placebo (group 2, n = 9) or ifenprodil (group 3, n = 10). Ifenprodil at 10 mg/kg or normal saline of equal volume was given intraperitoneally, 5 minutes before CA. The density of AQP4 protein and actin bands was scanned and expressed as the ratios of the optical density of AQP4 relative to that of actin. The ANOVA analysis was used to compare the group differences. RESULTS: The ratios of the optical density of AQP4 to that of actin were 0.88 +/- 0.06 in group 1, 1.11 +/- 0.08 in group 2 (p < 0.05 vs. group 1), and 0.78 +/- 0.04 in group 3 (p < 0.01 vs. group 2; NS vs. group 1). CONCLUSION: Ifenprodil given before CA is associated with a downregulation of brain AQP4 in rats.

Total extracorporeal arteriovenous carbon dioxide removal in acute respiratory failure: a phase I clinical study.

OBJECTIVE: To evaluate the safety and efficacy of pumpless extracorporeal arteriovenous carbon dioxide removal (AVCO2R) in subjects with acute respiratory failure and hypercapnia. DESIGN: A phase I within-group time series trial in which subjects underwent up to 72 h of support with AVCO2R in intensive care units of two university hospitals. PATIENTS: Eight patients with acute hypercapnic respiratory failure or hypoxemic respiratory failure managed with permissive hypercapnia. INTERVENTIONS: Extracorporeal CO2 removal was achieved through percutaneous cannulation of the femoral artery and vein, and a simple extracorporeal circuit using a commercially available membrane gas exchange device for carbon dioxide exchange. MEASUREMENTS AND RESULTS: Measurements of hemodynamics, blood gases, ventilatory settings, and laboratory values were made before initiation of AVCO2R, and at subsequent intervals for 72 h. PaCO2 decreased significantly from 90.8+/-7.5 mmHg to 52.3+/-4.3 and 51.8+/-3.1 mmHg at 1 and 2 h, respectively. This decrease occurred despite a decrease in minute ventilation from a baseline of 6.92+/-1.64 l/min to 4.22+/-.46 and 3.00+/-.53 l/min at 1 and 2 h. There was a normalization of pH, with an increase from 7.19+/-.06 to 7.35+/-.07 and 7.37+/-.05 at 1 and 2 h. These improvements persisted during the full period of support with AVCO2R. Four subjects underwent apnea trials in which AVCO2R provided total carbon dioxide removal during apneic oxygenation, resulting in steady-state PaCO2 values from 57 to 85 mmHg. Hemodynamics were not significantly altered with the institution of AVCO2R. There were no major complications attributed to the procedure. CONCLUSION: Pumpless extracorporeal AVCO2R is capable of providing complete extracorporeal removal of carbon dioxide during acute respiratory failure, while maintaining mild to moderate hypercapnia. Applied in conjunction with mechanical ventilation and permissive hypercapnia, AVCO2R resulted in normalization of arterial PCO2 and pH and permitted significant reductions in the level of mechanical ventilation.

The changing demographics of neonatal extracorporeal membrane oxygenation patients reported to the Extracorporeal Life Support Organization (ELSO) Registry.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an important treatment tool in the management of near-term and term neonates with severe hypoxemic respiratory failure. To better understand how health care for patients treated with ECMO has changed, we studied the demographic and treatment data reported to the Extracorporeal Life Support Organization (ELSO) registry from January 1, 1988, through January 1, 1998. METHODS: We used data stored in the ELSO registry and evaluated the changes in demographics, use of alternate therapies before ECMO, severity of illness, duration of ECMO therapy, and mortality over a 10-year period. All data on neonates reported between January 1, 1988, and January 1, 1998 were used. Verification checks were performed on all fields to eliminate nonsense outliers. We separated the neonates into 2 groups-those with and those without a congenital diaphragmatic hernia (CDH). All analyses were performed on the total group and each subgroup separately. Changes in continuous data were analyzed by year using analysis of variance. Year differences in categorical data were evaluated with chi(2) analysis. We also used the linear trend test and the Cochran-Armitage trend test to evaluate time-related changes. RESULTS: We reviewed 12 175 neonates. Over the decade, there were no changes in mean gestational age, gender, age at which ECMO was started, pH, or PaCO(2) just before ECMO. The proportion of neonates with CDH increased from 18% to 26%, while the proportion with respiratory distress syndrome decreased from 15% to 4%. Other diagnostic categories remained constant. The use of surfactant, high-frequency ventilation, and inhaled nitric oxide increased from 0% in 1988 to 36%, 46%, and 24%, respectively, in 1997. The mean peak pressure being used just before ECMO decreased (47 +/- 10 in 1988 to 39 +/- 12 in 1997), and the mean PaO(2)/FIO(2) ratio increased (38 +/- 23 in 1988 to 48 +/- 36 in 1997). The primary mode of ECMO remains venoarterial; however, the use of venovenous ECMO increased from 1% to 32% over the decade. Duration of ECMO treatment increased overall, and this trend was seen for patients with and without CDH (124 +/- 67 to 141 +/- 104 hours for the non-CDH group, 161 +/- 99 to 238 +/- 141 hours for the CDH group). The number of centers reporting neonatal data to the ELSO registry increased from 52 in 1988 to a peak of 100 in 1993. In 1997, 96 centers reported data to ELSO. The average number of neonatal patients reported from each site decreased from a peak of 18 in 1991 to 9 in 1997. Mortality increased from 18% to 22%; however, when corrected for the relative increase in neonates with CDH, this trend disappeared. Diagnoses-specific mortality rates remained constant. The occurrence of intracranial hemorrhage and/or infarct also stayed constant at 16%. CONCLUSIONS: The population of neonates treated with ECMO in 1997 was very different from patients treated in the 1980s and early 1990s. They were exposed to an ever-expanding group of new therapies, appeared to be healthier based on indices of gas exchange, and were cared for at centers that reported fewer cases per year.

Percutaneous extracorporeal arteriovenous CO2 removal for severe respiratory failure.

BACKGROUND: In previous animal studies, arteriovenous CO2 removal (AVCO2R) achieved significant reduction in ventilator pressures and improvement in the Pao2 to fraction of inspired oxygen ratio during severe respiratory failure. For our initial clinical experience, 5 patients were approved for treatment of severe respiratory failure and CO2 retention to evaluate the feasibility and safety of percutaneous AVCO2R. METHODS: Patients were anticoagulated with heparin (activated clotting time, 260 to 300 seconds), underwent percutaneous femoral cannulation (10F to 12F arterial and 12F to 15F venous catheters), and then were connected to a low-resistance, 2.5-m2 hollow-fiber oxygenator for 72 hours. RESULTS: Mean AVCO2R flow at 24, 48, and 72 hours was 837.4+/-73.9, 873+/-83.6, and 750+/-104.5 mL/min, respectively, with no vascular complications and no significant change in heart rate or mean arterial pressure. Removal of CO2 plateaued at an AVCO2R flow of 1086 mL/min with 208 mL/min CO2 removed. Average CO2 transfer at 24 and 48 hours was 142+/-17 and 129+/-16 mL/min. Use of AVCO2R allowed a significant decrease in minute ventilation from 7.2+/-2.3 L/min at baseline to 3.4+/-0.8 L/min at 24 hours. CONCLUSIONS: All patients survived the experimental period without adverse sequelae. Percutaneous AVCO2R can achieve approximately 70% CO2 removal in adults with severe respiratory failure and CO2 retention without hemodynamic compromise or instability.

Aspiration of activated charcoal elicits an increase in lung microvascular permeability.

BACKGROUND: Gastric decontamination with orally administered activated charcoal is the recommended treatment for many poisonings. However, ingestion of central nervous system depressants resulting in loss of protective airway reflexes may result in pulmonary aspiration of activated charcoal. Although activated charcoal has been reported to be an inert substance, evidence suggests that pulmonary aspiration of charcoal is associated with lung edema formation and pulmonary compromise. This study tested the hypothesis that intratracheal instillation of activated charcoal disrupts the integrity of the lung microvascular barrier. METHODS: The capillary filtration coefficient (Kf,c), a sensitive measure of lung microvascular permeability, was determined isogravimetrically prior to and after intratracheal instillation of activated charcoal 0.04 g/kg (12% weight/vol solution, pH 7.4) or an equal volume of sterile water in isolated, perfused rat lungs. Arterial blood gas analysis was determined prior to and after tracheal instillation of activated charcoal or sterile water in a separate group of animals. RESULTS: Intratracheal instillation of activated charcoal resulted in a significant increase in pulmonary microvascular permeability compared to lungs treated with sterile water or control lungs (delta Kf,c = +0.21 +/- 0.076; -0.014 +/- 0.04; and -0.041 +/- 0.02 mL/min/cm H2O/100 g lung tissue, respectively, p < 0.05 ANOVA). There was no significant difference in baseline blood gases in the 3 experimental groups. There was a significant decrease in arterial Po2, bicarbonate, and pH in animals administered activated charcoal compared to time-matched controls and animals administered sterile water. CONCLUSIONS: Intratracheal instillation of activated charcoal is associated with a significant increase in lung microvascular permeability and arterial blood gas derangements. The effects of activated charcoal on pulmonary microvascular barrier integrity may contribute to the lung edema formation and pulmonary compromise observed following clinical aspiration of activated charcoal.

Extracorporeal life support 1997.

Data from the annual international Extracorporeal Life Support Organization (ELSO) Registry Report for 1997 are presented. Over 17,000 patients treated with extracorporeal life support as submitted to the ELSO Registry are reported. Seventy-five percent (over 13,000) patients were cases of neonatal respiratory failure, with an 80% overall survival. The number of neonatal respiratory cases reported to the Registry has been decreasing for 5 years, whereas the number of pediatric respiratory, cardiac, and adult respiratory cases has been increasing. Cumulative survival in these categories is 53%, 42%, and 47% respectively. Survival in pediatric and adult respiratory failure cases supported with extracorporeal life support continues to improve. A description of the re-engineering of the ELSO registry, to include redesigning of the database structure and elements, electronic submission and validation of data, and Internet based submission and retrieval of data, is also provided.

Arteriovenous extracorporeal carbon dioxide removal: a mathematical model and experimental evaluation.

To explore the feasibility and operating limits of arteriovenous extracorporeal CO2 removal (AVCO2R) for support of acute respiratory failure, the authors developed a mathematical model to simulate (AVCO2R), evaluate the effects of several parameters used in its application, and predict the feasibility and necessary conditions for total CO2 removal. The mathematical model incorporated compartments representing blood, pulmonary alveoli, pulmonary capillaries, peripheral tissues and capillaries, and an extracorporeal gas exchange device. The model was validated against an animal model of extracorporeal CO2 removal. This model consisted of anesthetized and mechanically ventilated piglets. An extracorporeal CO2 removal device was placed by cannulation of a femoral artery and vein. Dynamic and steady state measurements of CO2 transfer were made and compared with simulations using the mathematical model. There was good agreement between experimental and simulated data, validating the mathematical model under a variety of conditions. The mathematical model was used to determine operating parameters for total CO2 removal. Relationships between extracorporeal blood flow, device diffusing capacity, and device gas sweep flow were established for CO2 removal at various levels of CO2 production. These simulations indicate that it is possible to achieve total CO2 removal using an extracorporeal shunt fraction of 10%-15% of cardiac output, a device diffusing capacity of 0.5 ml x min(-1) x torr(-1) (kg body weight)(-1), and a gas:blood flow of 5 or greater.

Using Intranet Technology in the ICU.

Current information management tends to focus on patient information, although non-patient-derived information is equally important in the delivery of health care. Intranets, based on technologies derived from the global Internet and the World Wide Web, are a viable means to strategically bring nonclinical information to the point of care.

Advances in the management of respiratory failure. Advanced strategies for mechanical ventilation in severe acute respiratory failure.

A number of strategies exist to improve gas exchange during mechanical ventilation. Any strategy used, however, should have as a basic tenet of its use the principles of lung rest, the reduction of the risk of ventilator associated lung injury, and avoidance of hemodynamic compromise. The techniques presented above are intended to meet these goals and represent measures that can be applied without significant additional resources.

Tracking nutrition trends, 1989-1994: an update on Canadians' attitudes, knowledge and reported actions.

The National Institute of Nutrition tracks changes in Canadians' attitudes, understanding and reported actions related to nutrition issues--particularly fat cholesterol and fibre. Personal interviews were conducted in 1994 with a national sample of 1,953 adults, and the results were compared with data obtained in 1989. The number of people claiming that nutrition is of considerable importance in choosing their food has increased from 59% to 66%. More Canadians are now concerned about fat (82% vs 71%) and "chemicals" in foods (76% vs 68%) and more are planning to further reduce fat or increase fibre intake. Forty-three percent report having excellent or very good eating habits. The apparent use of food labels, lower fat/low--cholesterol products, and bran/high-fibre foods has grown in five years. Although awareness of nutrition terms has increased, understanding has changed little. The challenge is to build on consumer interest to reduce barriers to healthy eating through education and a supportive marketplace.

Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of liposomal prostaglandin E1 (TLC C-53) in the treatment of patients with the acute respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial. SETTING: Eight community and university-affiliated hospitals in the United States. PATIENTS: Twenty-five patients with ARDS. INTERVENTIONS: Patients were prospectively randomized in an unbalanced ratio within each site to receive either TLC C-53 (n = 17) or placebo (n = 8). Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period, starting at a dose of 0.15 micrograms/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 micrograms/kg/hr) was attained, intolerance to further increases developed, or invasive monitoring was discontinued. Patients received standard, aggressive, medical/surgical care throughout the trial. MEASUREMENTS AND MAIN RESULTS: Outcome measurements were Pao2/FI0(2), dynamic pulmonary compliance, ventilator dependence on day 8, and 28-day all-cause mortality rate. At baseline, the distribution of variables describing Lung Injury Scores, Acute Physiology and Chronic Health Evaluation II scores, Pao2/FI0(2), pulmonary compliance, and time from onset of ARDS to first dose of study drug was similar between patients in the TLC C-53 and placebo treatment groups. On day 8, all eight patients given placebo required mechanical ventilation, while eight of 17 patients given TLC C-53 were healthy enough to be removed from the ventilator (p = .03). Improvement in PaO2/FIO2 during the initial 8-day study period was greater in patients receiving TLC C-53. This trend achieved statistical significance on day 3, when the increase in PaO2/FIO2 from baseline was 82.5 +/- 14.6 in the TLC C-53 group compared with 28.3 +/- 22.1 in the placebo group (p = .05). By day 8, lung compliance also increased from baseline significantly more in TLC C-53 patients than in placebo patients (5.7 +/- 1.7 vs -1.5 +/- 1.8 mL/cm H2O; p = .01). The 28-day mortality rate was 6% (1/17 patients) in the TLC C-53 group and 25% (2/8 patients) in the placebo group (p = .23). Drug-related adverse events were reported in 82% of the patients receiving TLC C-53 compared with 38% of the placebo group, with half of the adverse events in the TLC C-53 group being localized infusion site irritation. TLC C-53 was hemodynamically well tolerated, with transient hypotension occurring in three patients. CONCLUSIONS: In patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency.

Intravenacaval membrane oxygenation and carbon dioxide removal in severe acute respiratory failure.

STUDY OBJECTIVE: To characterize the physiologic response to, and safety of, intravenacaval membrane oxygenation and carbon dioxide removal. DESIGN: Interventional before-after study. SETTING: University teaching hospital ICU. PATIENTS: Twenty-two patients with severe acute respiratory distress syndrome (ARDS). INTERVENTIONS: Implantation of a hollow-fiber membrane oxygenator (IVOX; CardioPulmonics; Salt Lake City, Utah) into the superior and inferior venae cavae by venotomy of the right femoral or right internal jugular vein for a duration of up to 20 days. MEASUREMENTS: Hemodynamic measurements using pulmonary artery and systemic artery catheters, ventilator settings (FIO2, minute ventilation, peak inspiratory pressure, and positive end-expiratory pressure), arterial and mixed venous blood gases (pH, PCO2, PO2, and measured saturation), and clinical laboratory determinations (CBC, fibrinogen, plasma hemoglobin, complement C3 and C5) were obtained. Calculations of PaO2/FIO2 ratio and PaCO2-VE product were used to assess gas exchange efficacy. Microbiologic cultures were obtained from the device and wound following explantation. Survival to ICU discharge and hospital discharge were recorded. RESULTS: Implantation was successful in 20 of 22 patients. Gas exchange rates averaged 50.4 +/- 15.8 mL.min-1 for carbon dioxide and 71.1 +/- 20.2 mL.min-1 for oxygen. A reduction in FIO2 from 0.78 +/- 0.16 to 0.63 +/- 0.21 and in VE from 177 +/- 94 mL.kg-1.min-1 to 127 +/- 58 mL.kg-1.min-1 was possible within 4 h post-implantation. By 12 h, FIO2 was reduced to 0.57 +/- 0.18. Indices of gas exchange improved significantly after implantation, with PaO2/FIO2 ratio increasing from 79 +/- 20 to 112 +/- 47 and PaCO2-VE product decreasing from 7.6 +/- 4.2 to 4.9 +/- 2.5 within 4 h. A significant reduction in peak inspiratory pressure was achieved (45 +/- 10 to 38 +/- 9 cm H2O). Major complications were blood loss during implantation requiring transfusion in 11 patients, a retroperitoneal bleed in 1 patient, and femoral deep venous thrombosis in 4 patients, but there were no long-term sequelae or IVOX-related deaths. The ICU and hospital survival were 10/20 (50%) and 8/20 (40%), respectively. CONCLUSIONS: Intravenacaval membrane oxygen and carbon dioxide removal can provide partial respiratory support during severe respiratory failure and permit reductions in the level of mechanical ventilator support, with an acceptable safety profile.

In vivo gas transfer performance of the intravascular oxygenator in acute respiratory failure.

The intravascular oxygenator (IVOX) has undergone both animal and clinical trials. Data from the animal studies have demonstrated that the device is capable of transferring up to approximately 100 ml/min of oxygen and carbon dioxide. Initial data from the human trials suggest that gas transfer, although approaching these levels, varied widely in patients with respiratory failure. We studied the factors affecting gas exchange in 26 patients with severe acute respiratory failure who underwent intravenacaval support of gas exchange with IVOX. The patients underwent monitoring of IVOX gas transfer rates, hemodynamics, blood gases, and ventilation parameters at scheduled intervals following device insertion. All devices functioned following implantation. The mean value for O2 transfer was 64 +/- 21 SD ml/min (range 15-114 ml/min) and for CO2 transfer was 48 +/- 17 ml.min-1 (range 14-112 ml/min). CO2 transfer correlated positively with device surface area, cardiac output, and mixed venous Pco2 and negatively with duration of implantation. O2 transfer did not correlate with any patient factors probably due to error inherent in the measurement of this variable. Independent measurements of IVOX gas transfer by respiratory gas exchange in a subset of patients with normal values of mixed venous Pco2 were in good agreement with the routine measurements and indicated that the device provided up to 26% of gas exchange requirements in this subset. We conclude that IVOX transfers clinically useful amounts of oxygen and carbon dioxide in vivo. Factors that influence gas transfer include device surface area, PvCO2, cardiac output, and duration of implantation. Optimization of these factors (such as with permissive hypercapnea) could result in enhanced performance in vivo.

Major findings from the clinical trials of the intravascular oxygenator.

Major clinically relevant findings have been extracted and summarized from the database developed from the international multicenter clinical trials of the intravascular oxygenator (IVOX) as a means for augmenting the deficient blood gas transfer of patients in advanced acute respiratory failure (ARF). Between February 1990 and May 1993, a total of 164 IVOX devices were utilized in 160 clinical trial patients who were hypoxemic and/or hypercarbic while receiving closed system positive pressure mechanical ventilator support at or exceeding generally accepted minimum safe levels of intensity. The average rates of oxygen and carbon dioxide transfer into and out of circulating venous blood by means of the IVOX device varied from 40-70 ml/min. Evidence of patient benefit during IVOX utilization includes improvement in blood gas partial pressures associated with decreased intensity of mechanical ventilation, improved hemodynamics in patients with mechanical ventilator depressed cardiovascular function, and decreased indices of lung dysfunction. Clinically recognized IVOX-related complications or adverse events were reported in 24.5% of the clinical trials patients. At necropsy examination of 68 clinical trials patients who died during or after IVOX utilization, forensic pathologists reported 4 cases in which IVOX utilization could have been a primary or contributing cause of death. Significant IVOX device mechanical and/or performance malfunction problems were recognized in 29 (17.7%) of the IVOX devices utilized in clinical trials. IVOX clinical trials data collected and analyzed to date indicate IVOX utilization has a favorable risk/benefit ratio in patients in severe, acute, potentially reversible ARF.