[A critical carol : Being an essay on anemia, suffocation, starvation, and other forms of intensive care, after the manner of Dickens]. / Eine kritische Weihnachtsgeschichte : Essay über Anämie, Ersticken, Verhungern und andere Behandlungsverfahren der Intensivmedizin ­ im Stil von Dickens.

Somewhere in the USA, shortly before Christmas, tipsy Charlie Cratchit intends to cross a street but is hit by an oncoming city bus und suffers severe trauma: serial rib fracture, femoral fracture, fibula fracture, splenic, pancreatic and bowel ruptures. He is operated on in a maximum care hospital and then transferred to the critical care unit. From then on, an anonymous, very experienced physician continuously takes care of him. Four nights before Christmas, the ghost of the famous British physiologist Ernest Henry Starling appears at the patient's bed. The ghost involves the anonymous physician in a dialogue and is very interested in the inserted Swan-Ganz catheter, then he disappears. He repeats his visits the next 3 nights. On the first occasion he is displeased with Cratchit's low haematocrit, the second time he dislikes the mechanical ventilator settings, and on his final visit he is concerned with Cratchit's clinical nutrition. At first, the anonymous physician is indignant with the ghost's criticism and indoctrinations, but then recognizes that ultimately they are the key to Cratchit's convalescence and acts accordingly. Successfully! Following the ghost's proposals, he changes the ventilator settings, transfuses 3 units of packed red blood cells, and starts clinical nutrition. Shortly thereafter, Cratchit's trachea is extubated, and on New Year's Day he is ready to be discharged from the critical care unit. In this essay, Robert Bartlett transposed Charles Dickens' "Christmas Carol" into the world of critical care. Its intention is to encourage the intensivist to scrutinize common therapeutic measures, such as mechanical ventilation, haemodynamic interventions and transfusion of blood products. Background information and comments on the addressed problems of modern intensive care are provided subsequent to the essay.

Enhancing analytical accuracy of intravascular electrochemical oxygen sensors via nitric oxide release using S-nitroso-N-acetyl-penicillamine (SNAP) impregnated catheter tubing.

Implantable medical devices are an integral part of primary/critical care. However, these devices carry a high risk for blood clots, caused by platelet aggregation on a foreign body surface. This study focuses on the development of a simplified approach to create nitric oxide (NO) releasing intravascular electrochemical oxygen (O2) sensors with increased biocompatibility and analytical accuracy. The implantable sensors are prepared by embedding S-nitroso-N-acetylpenacillamine (SNAP) as the NO donor molecule in the walls of the catheter type sensors. The SNAP-impregnated catheters were prepared by swelling silicone rubber tubing in a tetrahydrofuran solution containing SNAP. Control and SNAP-impregnated catheters were used to fabricate the Clark-style amperometric PO2 sensors. The SNAP-impregnated sensors release NO under physiological conditions for 18 d as measured by chemiluminescence. The analytical response of the SNAP-impregnated sensors was evaluated in vitro and in vivo. Rabbit and swine models (with sensors placed in both veins and arteries) were used to evaluate the effects on thrombus formation and analytical in vivo PO2 sensing performance. The SNAP-impregnated PO2 sensors were found to more accurately measure PO2 levels in blood continuously (over 7 and 20 h animal experiments) with significantly reduced thrombus formation (as compared to controls) on their surfaces.

Rodent Skeletal Muscle Metabolomic Changes Associated With Static Cold Storage.

OBJECTIVE: The aim of this study was to evaluate the impact of static cold storage preservation on skeletal muscle metabolism using a rodent model. METHODS: Sixteen male Lewis rats (250 ± 25 g) were distributed into 4 groups, including naive control, warm ischemia for 2 hours, static warm storage for 6 hours, and static cold storage for 6 hours. Energy status, metabolomics profiling, and histopathology of the muscle were analyzed. RESULTS: In the warm ischemia and static warm storage groups, glycolytic pathway metabolites decreased, but the Krebs cycle metabolite of succinate and the purine degradation product of hypoxanthine accumulated. Increased succinate and hypoxanthine levels were associated with increased injury severity scores. During static cold storage, the glycolytic pathway activity and the energy status were preserved. Succinate and hypoxanthine levels showed no significant difference from the naive group. CONCLUSION: Warm ischemia results in reduced glycolysis and Krebs cycle metabolites. Static cold storage preserves the glycolytic pathway and represents a favorable contribution to cellular energy demand. Succinate and hypoxanthine might be used as novel potential biomarkers for the assessment of viability and injury severity.

[The old man and the I sea U : Essay on faith, fate and evidence - after the manner of Hemingway]. / Der alte Mann und die "I sea U" : Essay über Vertrauen, Schicksal und Evidenz ­ im Stil von Hemingway.

Robert Bartlett, emeritus Professor of surgery at the University of Michigan in Ann Arbor, USA, transformed classical works of world literature (Charles Dickens: A Christmas Carol, Lewis Carroll: Alice in Wonderland) into teaching aids for advanced training in intensive care medicine. He recently turned his hand to the well-known work of Ernest Hemingway: the Nobel Prize winning novel The Old Man and the Sea. Subsequent to Robert Bartlett's essay this article provides background information and comments on the current problems in modern intensive care medicine addressed in his essay.

A simple technique to prevent limb ischemia during veno-arterial ECMO using the femoral artery: the posterior tibial approach.

Lower extremity ischemia is common when the femoral artery is used for veno-arterial extracorporeal membrane oxygenation (VA ECMO). We describe a new technique to reperfuse the extremity. The ipsilateral posterior tibial artery is exposed via a small incision behind the medial malleolus. The vessel is cannulated in a retrograde fashion and connected to the arterial limb of the ECMO circuit. Thirty-six patients received a posterior tibial reperfusion cannula: average flow was 155.8 ml/min and increased over the initial 24 hours. Fifty-eight percent received the posterior tibial cannula within 6 hours of ECMO initiation and none sustained permanent lower extremity injury. Of the remaining 42%, three required amputation or developed permanent neurologic injury. Overall survival was 41%. Cannulation of the posterior tibial artery is a simple technique to reperfuse the lower extremity during VA ECMO. The cannula should be inserted within 6 hours of ECMO initiation to avoid irreversible ischemic damage.

Current status of extracorporeal life support (ECMO) for cardiopulmonary failure.

Extracorporeal life support with artificial heart and lung for cardiopulmonary failure is commonly called extracorporeal membrane oxygenation (ECMO). ECMO can provide partial or total support, is temporary, and requires systemic anticoagulation. ECMO controls gas exchange and perfusion, stabilizes the patient physiologically, decreases the risk of ongoing iatrogenic injury, and allows ample time for diagnosis, treatment, and recovery from the primary injury or disease. ECMO is used in a variety of clinical circumstances and the results depend on the primary indication. ECMO provides life support but is not a form of treatment. Survival ranges from 30% in extracorporeal cardiopulmonary resuscitation to 95% for neonatal meconium aspiration syndrome. The major limitations to widespread applications are the need for anticoagulation and bleeding complications. However, nowadays, the new devices allow only minor bleeding that is rarely a fatal complication. Research on non-thrombogenic surfaces holds the promise of prolonged extracorporeal circulation without anticoagulation and without bleeding. The next decade may bring routine application of ECMO to all advanced Intensive Care Units where patients with profound respiratory and cardiac failure are treated.

Extracorporeal support: improves donor renal graft function after cardiac death.

Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4-6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min +/- 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min +/- 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h +/- 1.7). DCD-30 had lower CrCl (0.9 mL/min +/- 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI.

Hematological changes during short-term tidal flow extracorporeal life support.

Various methods exist in the clinical practice of long-term venovenous (VV) extracorporeal life support (ECLS). Among the clinical techniques used are single venous access with a dual-lumen catheter, and cannulation of the jugular and femoral veins. Tidal flow VV ECLS uses a single-lumen catheter to achieve both venous drainage and arterialized reinfusion through a series of tubing occluders that are automated by a pump. A single venous occluder tidal flow system with a 15 Fr single-lumen cannula (n = 6) and passive filling M pump was compared to a conventional 14 Fr dual-lumen cannula (n = 7) and roller pump for four hours of VV ECLS. The changes in platelet count and plasma-free hemoglobin (pHgb) were compared. The results showed a decline in platelet counts typical of ECLS in both groups that were not significantly different from each other. A small elevation in pHgb did not rise above normal clinical levels of 15 mg/dL in either group after four hours of ECLS. Some recirculation was observed and needs to be addressed in future studies. Single occluder tidal flow ECLS may be feasible and efficacious for long-term application once recirculation is resolved and the system evaluated for long-term support.

Assessment of liver function during extracorporeal membrane oxygenation in the non-heart beating donor swine.

INTRODUCTION: Although the use of non-heart beating donors (NHBD) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to warm ischemia (WI), biliary tree injury, and inadequate organ assessment. Warm blood reperfusion using extracorporeal membrane oxygenation (ECMO) can be a suitable option to reduce WI in organs from NHBD, allowing one to determine hepatic flow characteristics and bile production and facilitating assessment of organ viability. METHODS: This work evaluates the use of warm blood veno-arterial ECMO reperfusion in NHBD swine. Systemic and hepatic hemodynamics, bile, urine, and mixed venous blood were measured. After baseline data collection, 10 kU heparin was given intravenously followed by 1 g KCl to elicit cardiac arrest (CA). ECMO was started after 30 or 60 minutes of CA and kept running for 120 minutes. RESULTS: One-way repeated measures analysis of variance (ANOVA) with Tukey test analysis was used within a group. Two-way ANOVA was used between groups. ECMO can restore venous SO2 and pH in both groups; the values were close to baseline in the 30-minute CA group. Also, in this group, bile production was > 65% from baseline early during reperfusion and its value was lower in the longer CA group < 55% (P < .001). Aspartate aminotransferase (AST) was doubled at the end of ECMO support in the 60-minute CA group (P < .05). CONCLUSION: In this preheparinized NHBD swine model, ECMO support restores liver perfusion, oxygenation, and bile production after 60 minutes of CA. Quantification and analysis of bile production could be a determinant of liver function during ECMO resuscitation, and it may be a predictor of graft viability before transplantation.

An artificial lung reduces pulmonary impedance and improves right ventricular efficiency in pulmonary hypertension.

OBJECTIVE: Artificial lungs may have a role in supporting patients with end-stage lung disease as a bridge or alternative to lung transplantation. This investigation was performed to determine the effect of an artificial lung, perfused by the right ventricle in parallel with the pulmonary circulation, on indices of right ventricular load in a model of pulmonary hypertension. METHODS: Seven adult male sheep were connected to a low-resistance membrane oxygenator through conduits anastomosed end to side to the pulmonary artery and left atrium. Banding of the distal pulmonary artery generated acute pulmonary hypertension. Data were obtained with and without flow through the device conduits. Outcome measures of right ventricular load included hemodynamic parameters, as well as analysis of impedance, power consumption, wave reflections, cardiac efficiency, and the tension-time index. RESULTS: The model of pulmonary hypertension increased all indices of right ventricular load and decreased ventricular efficiency. Allowing flow through the artificial lung significantly reduced mean pulmonary artery pressure, zero harmonic impedance, right ventricular power consumption, amplitude of reflected waves, and the tension-time index. Cardiac efficiency was significantly increased. CONCLUSIONS: An artificial lung perfused by the right ventricle and applied in parallel with the pulmonary circulation reduces ventricular load and improves cardiac efficiency in the setting of pulmonary hypertension. These data suggest that an artificial lung in this configuration may benefit patients with end-stage lung disease and pulmonary hypertension with right ventricular strain.

Results of a phase I trial evaluating a liver support device utilizing albumin dialysis.

BACKGROUND: We have previously reported the clearance of protein-bound and water-soluble hepatic toxins, in vitro and in an animal model, using albumin dialysis as an extracorporeal hepatic support (ECHS) device. OBJECTIVE: The objective of this study was to evaluate albumin dialysis through a phase I clinical trial. We hypothesized that albumin dialysis would (1) decrease elevated levels of hepatic toxins, (2) increase the Fischer ratio, and (3) decrease hepatic encephalopathy (HES) and intracranial pressure (ICP), while (4) maintaining stable hemodynamics. METHODS: Patients with acute liver failure were treated with an ECHS device utilizing continuous hemodiafiltration with continuous albumin dialysis. Mean arterial blood pressure (MAP), heart rate (HR), systemic venous oxygen saturation (Svo(2)), ICP, and HES were recorded. Blood samples were evaluated for hepatic toxins and factor VII levels. RESULTS: Nine patients were enrolled (status I, n = 5; status IIA, n = 4). There was no significant change in MAP, HR, or Svo(2) (MAP: Pre = 81 +/- 5.6 mm Hg, Post = 79 +/- 5.9 mm Hg, P =.70; HR: Pre = 104 +/- 5.2 bpm, Post = 107 +/- 6.2 bpm, P =.62; Svo(2): Pre = 72 +/- 3.5, Post = 71 +/- 1.7, P =.77). There was a decrease in the ammonia and total bilirubin levels (NH(3): Pre = 129.8 +/- 23.8 mg/dL, Post = 63.9 +/- 16.1 mg/dL, P =.01; total bilirubin: Pre = 20.3 +/- 2.5 mg/dL, Post = 17.6 +/- 2.7 mg/dL, P =.4). There was a significant increase of the Fischer ratio and factor VII levels (Fischer ratio: Pre = 0.98 +/- 0.2, Post = 2.17 +/- 0.5, P =.038; factor VII: Pre = 13.9 +/- 4.9, Post = 23.2 +/- 4.8, P =.015). There was a significant decrease in the HES and ICP (HES: Pre = 3.8 +/- 0.1, Post = 2 +/- 0.7, P =.02; ICP: Pre = 37 +/- 3.9, Post = 13.3 +/- 2.8, P =.048). Of 5 status I patients, 1 recovered native hepatic function and 3 were bridged to transplantation. CONCLUSIONS: This phase I study suggests that albumin dialysis as a liver support device is safe and effective in clearing hepatic toxins, with an associated decrease in the HES and ICP. This encouraging efficacy data warrant further investigation with a phase II/III trial.

Development of an implantable artificial lung: challenges and progress.

Unlike dialysis, which functions as a bridge to renal transplantation, or a ventricular assist device, which serves as a bridge to cardiac transplantation, no suitable bridge to lung transplantation exists. Our goal is to design and build an ambulatory artificial lung that can be perfused entirely by the right ventricle and completely support the metabolic O2 and CO2 requirements of an adult. Such a device could realize a substantial clinical impact as a bridge to lung transplantation, as a support device immediately post-lung transplant, and as a rescue and/or supplement to mechanical ventilation during the treatment of severe respiratory failure. Research on the artificial lung has focused on the design, mode of attachment to the pulmonary circulation, and intracorporeal versus paracorporeal placement of the device.

The use of extracorporeal life support in adult patients with primary cardiac failure as a bridge to implantable left ventricular assist device.

BACKGROUND: Extracorporeal life support (ECLS) is an effective technique for providing emergent circulatory assistance, and may represent a life-saving option in patients who might not initially be considered a candidate for other forms of circulatory support (extracorporeal or implantable left ventricular assist device [LVAD]). In the setting of cardiac arrest, ECLS represents the only viable method of initiating circulatory support. However, ECLS has a number of disadvantages that include high complication rates (eg, stroke, bleeding) and a limited duration of potential support, which have prevented its widespread acceptance, particularly in the adult population. With the increased successful application of long-term implantable LVADs as a bridge to transplant, the major limitation of ECLS could be overcome by bridging patients to a long-term implantable LVAD ("bridge to bridge"), thereby reducing the reluctance to utilize ECLS when indicated. After acquisition of the HeartMate LVAD (Thermo Cardiosystems, Inc, Woburn, MA) we investigated the use of ECLS as a bridge to an implantable LVAD and subsequent transplantation in selected high-risk patients. METHODS AND RESULTS: From Oct 1, 1996 to Sept 30, 2000, 33 adult patients presenting with cardiac arrest or severe hemodynamic instability were placed on ECLS for the bridge to bridge indication. Of the 33 patients, 10 patients survived to LVAD implant, 1 was bridged directly to transplant, 5 weaned from ECLS, and 16 died on ECLS. Overall, 12 patients survived to discharge. One-year actuarial survival from the initiation of ECLS was 36%. One-year actuarial survival from the time of LVAD implant, conditional on surviving ECLS, was 80%. CONCLUSIONS: The 1-year survival of adult patients placed on ECLS and who subsequently survived to an implantable LVAD was favorable. These data support a strategy of ECLS to implantable LVAD bridge to heart transplant in adult patients who are in need of circulatory support and who are not initially candidates for other forms of mechanical support. The favorable results of this strategy support utilization of ECLS even in situations where myocardial recovery is thought to be unlikely.

A novel stable reproducible model of hepatic failure in canines.

BACKGROUND: Stable and reproducible large animal models of hepatic failure, which allow the assessment of liver-assist devices, are not available. Our objective was to develop a physiologically stable animal model of hepatic failure on which the safety and efficacy of an extracorporeal liver-assist device can be tested. We hypothesized that a surgical model which consists of an end-to-side portocaval shunt combined with common bile duct ligation and transection would create hepatic failure with: (1) elevations in amino transferases, total bilirubin, and ammonia; (2) a decrease in the ratio of branched chain to aromatic amino acids; and (3) histologic evidence of hepatic injury. METHODS: Eleven mongrel dogs underwent common bile duct transection and an end-to-side portocaval shunt. Aminotransferases (AST, ALT), total bilirubin, ammonia, and branched chain and aromatic amino acids were measured prior to operation (baseline) and after 9 days. A necropsy was performed on Postoperative Day 9 and liver biopsies were obtained for histology. RESULTS: By Postoperative Day 9, AST, ALT, total bilirubin, and ammonia values were significantly elevated compared to baseline (P < 0.02). The ratio of branched chain to aromatic amino acids was significantly reduced compared to baseline (P < 0.003). There was histologic evidence of cholestasis and inflammation. CONCLUSION: Portocaval shunt with common bile duct transection produces liver failure with elevations in aminotransferases, total bilirubin, and ammonia, a decreased branched chain to aromatic amino acid ratio, and histologic inflammation. Unlike ischemic or chemically induced models of liver failure, the dogs were hemodynamically and neurologically stable. This model can be used to test the safety and efficacy of liver-assist devices aimed at temporizing the detoxification functions of the failing liver.

Extracorporeal life support in the management of severe respiratory failure.

ECLS is a safe and effective means to keep patients alive during severe respiratory failure that would otherwise be fatal. In addition to direct and indirect treatment of the lungs during ECLS, the technique allows days of time for study and treatment of other conditions and other organ failure. The technique has been refined in newborn infants and children, in whom survival rates are high and the technology is proven by prospective randomized trials. ECLS is usually applied to adults with respiratory failure when the mortality risk is over 80%. With these indications, the survival rate in experienced centers is 50% to 60%. A new prospective, randomized trial of ECLS in adult patients is underway in the United Kingdom. In the meantime, intensivists who are charged with the management of moribund ARDS patients who fail to respond to other methods of therapy should consider the risks versus the benefits of transferring such patients to an ECLS center.

Hemolytic potential of hydrodynamic cavitation.

The purpose of this study was to determine the hemolytic potentials of discrete bubble cavitation and attached cavitation. To generate controlled cavitation events, a venturigeometry hydrodynamic device, called a Cavitation Susceptibility Meter (CSM), was constructed. A comparison between the hemolytic potential of discrete bubble cavitation and attached cavitation was investigated with a single-pass flow apparatus and a recirculating flow apparatus, both utilizing the CSM. An analytical model, based on spherical bubble dynamics, was developed for predicting the hemolysis caused by discrete bubble cavitation. Experimentally, discrete bubble cavitation did not correlate with a measurable increase in plasma-free hemoglobin (PFHb), as predicted by the analytical model. However, attached cavitation did result in significant PFHb generation. The rate of PFHb generation scaled inversely with the Cavitation number at a constant flow rate, suggesting that the size of the attached cavity was the dominant hemolytic factor.

Respiratory failure. Conventional and high-tech support.

Although significant progress has been made in the treatment of patients with acute lung failure in the critical care setting, the mortality rate from acute lung injury and ARDS is unacceptably high, given the numbers of patients treated for these syndromes each year. The improved understanding of the pathophysiology of respiratory failure from basic science and clinical research is reflected in improved survival rates over the years. Advances in the mechanical ventilator (through microprocessor technology); biosurface technology; liquid ventilation; and, in some cases, returning to so-called "antiquated" practices of patient care (e.g., prone positioning) seem to have had an impact nonetheless. As refinement continues to occur in these areas, morbidity and mortality from lung failure will have a lesser impact on patients as physicians treat the consequences of organ failure in the ICU.

Percutaneous cannulation for pediatric venovenous extracorporeal life support.

BACKGROUND/PURPOSE: The objective of this study was to show the safety and efficacy of a method of percutaneous cannulation for venovenous extracorporeal life support (ECLS) access in nonneonatal (>10 kg) pediatric patients. METHODS: Between June 1992 and October 1998, 26 pediatric patients (age range, 3 to 17 years; weight range, 19 to 100 kg) underwent attempted percutaneous cannulation for venovenous ECLS at our institution. Venous drainage access was attempted using a modified Seldinger technique via the right internal jugular vein (RIJ, n = 22) or right femoral vein (RFV, n = 4). Reinfusion access was attempted via the RFV (n = 19), RIJ (n = 4), or left femoral vein (n = 3). RESULTS: The percutaneous technique was successful in 24 of 26 patients (92.3%). Maximum blood flow during ECLS was 80.1 +/- 30.0 mL/kg/min, generating a postmembrane lung outlet pressure of 138 +/- 54.8 mm Hg. Adequate gas exchange was achieved in all patients, and survival to discharge was 79.2%. There was no procedure-related mortality. Complications potentially related to the percutaneous technique included RIJ thrombosis (n = 1) detected after decannulation and cannula site bleeding (n = 3). CONCLUSION: Percutaneous access may be used safely and effectively for venovenous ECLS in pediatric patients.