[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.

[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.

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.

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.

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.

Neonatal vocal cord paralysis following extracorporeal membrane oxygenation.

Five cases of unilateral vocal cord paralysis/paresis were diagnosed following extracorporeal membrane oxygenation for newborn respiratory failure. All were right sided and transient in nature. None of the five patients had other findings commonly associated with vocal cord palsy. The extracorporeal membrane oxygenation procedure requires surgical dissection in the carotid sheath on the right side of the neck, an area immediately adjacent to both the vagus and recurrent laryngeal nerve. It is speculated that vocal cord paralysis in these infants was acquired as a result of the extracorporeal membrane oxygenation cannulation. Although the vocal cord paralysis resolved in all cases, two patients had difficult courses after extracorporeal membrane oxygenation. Therefore, laryngoscopic examination should be considered for patients after extracorporeal membrane oxygenation.

One- to three-year outcome for 14 neonatal survivors of extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation, using venoarterial or venovenous perfusion, is a safe and effective procedure in the term of near-term infant with life-threatening respiratory failure. Without extracorporeal membrane oxygenation, due to the severity of their disease, these children are at high risk for neurologic damage, chronic lung disease, and death. Because survival is not expected without extracorporeal membrane oxygenation therapy, there is no corresponding control group to which these survivors may be compared. In this report, we reviewed the outcome at 1 to 3 years in the first 14 survivors of extracorporeal membrane oxygenation treated at our institution. Seven of 14 neonatal extracorporeal membrane oxygenation survivors (50%) were normal or near normal at between 1 and 3 years of age. Ten (71%) had normal mental ability. We conclude that in neonates with high mortality risk from respiratory failure, near-normal growth and development can be expected in the majority who survive with extracorporeal membrane oxygenation treatment.

Follow-up of infants treated with extracorporeal membrane oxygenation for newborn respiratory failure.

Follow-up studies were conducted to assess the medical and developmental outcome of 92 infants treated with extracorporeal membrane oxygenation at the University of Michigan. Of 118 near-term (greater than 34 weeks' gestation) infants who received extracorporeal membrane oxygenation, 103 (87%) were surviving and available for follow-up at between 1 and 7 years of age. Ninety-two of these children were seen on at least one occasion. Each visit included a history and physical examination, an evaluation by a physical therapist, and developmental testing by a pediatric psychologist. Medical outcome during year 1 found 31% of the children rehospitalized, primarily with respiratory illness. Outpatient-treated lower respiratory tract illness was seen in an additional 31% of the children. New or nonstatic neurologic problems were noted in 6% of the children. Abnormal growth during year 1 occurred in 26% of the children. At last clinic visit 16% of the children exhibited moderate-to-severe neurologic abnormalities, and 8% had moderate-to-severe cognitive delay. Sensorineural hearing loss occurred in 4% of children. Nine percent of the children were receiving speech and language therapy; screening tests showed that an additional 6% had speech and language delay. Overall, at last visit 16 (20%) of the children exhibited some type of handicap. A review of the literature on follow-up studies of non-extracorporeal membrane oxygenation-treated infants with persistent pulmonary artery hypertension produced an impairment rate of 18.5%. Outcome post-extracorporeal membrane oxygenation appears similar to that seen in less ill cohorts of infants treated with more "conventional" therapy. Long-term follow-up of all such infants remains essential.

Right-sided brain lesions in infants following extracorporeal membrane oxygenation.

In retrospective review of survivors of neonatal extracorporeal membrane oxygenation, eight patients with varying degrees of right hemispheric brain injury were identified. The extent of preextracorporeal membrane oxygenation hypoxia and ischemia was documented: five of eight patients had arterial PO2 values of less than 40 mm Hg, seven of eight required dopamine for blood pressure support, and five of eight required cardiopulmonary resuscitation. Two patients had proven neurologic abnormalities before extracorporeal membrane oxygenation. Postextracorporeal membrane oxygenation CT brain scans showed right hemispheric focal abnormalities in three patients. Seven infants had neuromotor abnormalities which were lateralizing in nature; all were left sided, suggesting right-sided brain injury. EEGs showed an increased incidence of slowing and attenuation over the right hemisphere. These findings indicate that right-sided brain abnormalities exist after extracorporeal membrane oxygenation and that carotid artery ligation for extracorporeal membrane oxygenation is not without risk.

Intracranial hemorrhage during extracorporeal membrane oxygenation in neonates.

Intracranial hemorrhage is a complication of extracorporeal membrane oxygenation for the treatment of neonatal respiratory failure. A retrospective review of 35 neonates treated with extracorporeal membrane oxygenation was performed; ten had intracranial hemorrhage. Infants with intracranial hemorrhage had lower birth weights and were gestationally younger than infants with intracranial hemorrhage. Eight of eight neonates of less than 35 weeks' gestational age sustained intracranial hemorrhage. Six died immediately after extracorporeal membrane oxygenation was stopped. Two lived less than 1 year. Two of 27 neonates older than 34 weeks' gestational age sustained intracranial hemorrhage. One child is normal, the other died at 18 months of age. Based on the results of this study, the risk of intracranial hemorrhage appears low in neonates of greater than 34 weeks' gestational age who undergo extracorporeal membrane oxygenation treatment for severe respiratory failure. The use of extracorporeal membrane oxygenation, as it is presently performed, is contraindicated in neonates of less than 35 weeks' gestational age because of the risk of intracranial hemorrhage.

Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study.

A prospective controlled randomized study of the use of extracorporeal membrane oxygenation to treat newborns with respiratory failure was carried out using the "randomized play-the-winner" statistical method. In this method the chance of randomly assigning an infant to one treatment or the other is influenced by the outcome of treatment of each patient in the study. If one treatment is more successful, more patients are randomly assigned to that treatment. A group of 12 infants with birth weight greater than 2 kg met objective criteria for high mortality risk. One patient was randomly assigned to conventional treatment (that patient died); 11 patients were randomly chosen for extracorporeal membrane oxygenation (all survived). Intracerebral hemorrhage occurred in one of 11 surviving children. Extracorporeal membrane oxygenation allows lung rest and improves survival compared to conventional ventilator therapy in newborn infants with severe respiratory failure.

Recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor as an anticoagulant in venovenous extracorporeal circulation in rabbits.

Investigations were performed to characterize a recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor (rKPI) as anticoagulants. After a single intravenous infusion of wild type rKPI into dogs, its elimination fit a two compartment model with a t1/2alpha and t1/2beta of 5 and 77 min, respectively. Further investigations determined if a variant form of rKPI with 178-fold more potent anti-factor Xa activity (rKPI-DD135, Ki = 0.9 nM) could serve as an anticoagulant in a rabbit model of extracorporeal circulation using a venovenous shunt. A prospective investigation was initiated to compare standard heparin (n = 8) at 400 U/kg with different infusion concentrations of rKPI-DD135. After a single intravenous infusion of 1.89 mg/kg of rKPI-DD135 followed by a constant infusion at 0.003 (n = 3), 0.03 (n = 7), or 0.3 (n = 5) mg/kg/min, the anti-factor Xa activity of the animals' plasma rapidly reaches a steady state for the two lower infusion concentrations of the agent. All infusions of rKPI-DD135 prolong the activated clotting time with less variation than that seen with heparin administration. rKPI-DD135 anticoagulation does not prevent a drop in the platelet counts. Fibrinogen levels decrease only slightly when the circuit is anticoagulated with rKPI-DD135. rKPI-DD135 markedly prolongs the APTT, has little effect on the PT, and reduces plasma prekallikrein and plasminogen activation. The 0.3 mg/kg/min infusion concentration of rKPI-DD135 results in reduced deposition of 111Indium-labeled platelets on the circuit when compared to heparin. Last, after a steady state level is achieved, 60% of the plasma anti-factor Xa activity of rKPI-DD135 is eliminated within 60 min after stopping the infusion. These data show the rKPI-DD135 can provide single agent anticoagulation in a rabbit extracorporeal circuit. Development of short acting factor Xa inhibitors may be useful anticoagulants for cardiopulmonary bypass.

A procedure for management of acquired tracheoesophageal fistula in ventilator patients.

An operative technique is presented for acquired tracheosophageal fistula including cervical esophagostomy, division and closure of the distal esophagus, and use of the cervical and thoracic esophageal segment as a patch to close the posterior trachea wall. Later coloesophagoplasty is used to establish gastrointestinal continuity. An external negative-pressure ventilator (Drinker-Collins iron lung) is used in combination with a conventional positive-pressure ventilator to diminish airway pressure after the tracheal repair.

Evaluation of a new blood autotransfusion device.

A new autotransfusion device was evaluated in dogs. The device uses citrate phosphate dextrose as the blood anticoagulant and automatically delivers the agent in a ratio approximating that found in banked blood. Bleeding, aspiration, and autotransfusion of approximately 3 estimated blood volumes produced small changes in hematologic and coagulation studies. Blood electrolytes stayed within normal ranges. Activated clotting times stayed within normal range after autotransfusion of 2 blood volumes but increased slightly after 3 blood volume transfusions. No significant histopathologic changes were found in any organ system. Rapid infusion of citrated blood causes myocardial depression, which can be reversed by giving calcium. Overall performance of the device was excellent, suggesting further documentation in a clinical setting and evaluation with human blood.

Extracorporeal life support for status asthmaticus.

Status asthmaticus is a life-threatening form of reactive airway disease, refractory to initial control with ordinary medical measures, sometimes requiring mechanical ventilatory assistance. In this report, we describe a patient whose bronchospasm could not be controlled with conventional measures, with severe respiratory acidosis (PaCO2 consistently > 100 mm Hg), who was successfully supported with extracorporeal life support (ECLS). During ECLS, arterial blood gas values rapidly returned to normal, and bronchospasm resolved during the subsequent 24 h. The patient was extubated hours later, and discharged to home 4 days later, neurologically normal. We believe that this represents the first application of this technology to this disease in an adult patient.

Evaluation of the Velcom-100 pulse Doppler cardiac output computer.

The use of Doppler ultrasound as a means of obtaining cardiac output (CO) measurements quickly, easily, and noninvasively has been made possible by recent technologic developments. We evaluated a new pulse Doppler ultrasonic unit (Velcom-100, Waters Instruments, Inc) in the Surgical Intensive Care Unit at the University of Michigan Medical Center. Accuracy of this device was determined by comparison of CO results obtained from the Velcom-100 (COV) against those of conventional thermal dilution cardiac output (COT) measurements. Twenty-six postoperative patients were used for this study, ranging in age from 20 to 82 years old. Initial studies prior to in vivo standardization demonstrated a significantly lower result (p = 0.039) for the Velcom-100 with a mean difference of 0.86 L/min (COT-COV). This comparison was significantly improved in subsequent studies following in vivo standardization (COT-COV = 0.02 L/min, p = 0.646). Linear regression analysis showed a significant, positive correlation between the two results (r = 0.82, p less than 0.05) indicating an excellent trending capability for the Velcom-100. Our evaluation found the Velcom-100 to be user friendly, allowing rapid training of ICU technicians and applicability for postoperative monitoring.

A prospective study of acute hypoxic respiratory failure.

A prospective study of acute hypoxic respiratory failure was carried out by nine centers in a collaborative NIH study from 1 September 1975 to 1 March 1977. Serious hypoxic respiratory failure was defined in 713 patients by the presence of (1) endotracheal intubation and positive airway pressure for at least 24 hours, and (2) the administration of at least 50 percent oxygen. The 490 patients between 12 to 65 years of age had a mortality of 61 percent. Mortality increased with increasing organ failure: one organ system failure (lung only) 40 percent; two, 54 percent; three, 72 percent; four, 84 percent, five, 100 percent. Only 103 patients died with isolated lung failure, whereas 353 died of a combination of lung and other organ failures. Both the overall mortality (66 percent) and the mortality of those with only isolated lung failure (40 percent) were much higher than anticipated for the selection criteria.

Improvement of gas exchange, pulmonary function, and lung injury with partial liquid ventilation. A study model in a setting of severe respiratory failure.

STUDY OBJECTIVE: To evaluate gas exchange, pulmonary function, and lung histology during gas ventilation of the perfluorocarbon-filled lung compared with gas ventilation of the gas-filled lung in severe respiratory failure. STUDY DESIGN: Application of gas (GV) or partial liquid (PLV) ventilation in lung-injured sheep. SETTING: A research laboratory at a university medical center. SUBJECTS: Eleven sheep 17.1 +/- 1.8 kg in weight. INTERVENTIONS: Lung injury was induced by intravenous administration of 0.07 mL/kg oleic acid followed by saline pulmonary lavage. When alveolar-arterial oxygen pressure difference (P[A-a]O2) was 600 mm Hg or more and PaO2 was 50 mm Hg or less with fraction of inspired oxygen of 1.0, bijugular venovenous extracorporeal life support (ECLS) was instituted. For the first 30 min on ECLS, all animals were ventilated with gas. Over the ensuing 2.5 h, ventilation with 15 mL/kg gas was continued without intervention in the control group (GV, n = 6) or with the addition of 35 mL/kg of perflubron (PLV, n = 5). MEASUREMENTS AND RESULTS: At 3 h after initiation of ECLS, Qps/Qt was significantly reduced in the PLV animals when compared with the GV animals (PLV = 41 +/- 13%; GV = 93 +/- 4%; p < 0.005). At the same time point, pulmonary compliance was increased in the PLV when compared with the GV group (PLV = 0.61 +/- 0.14 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.005). The ECLS flow rate required to maintain the PaO2 in the 50 to 80 mm Hg range was substantially and significantly lower in the PLV group when compared with that of the GV group (PLV = 25 +/- 20 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p < 0.001). Light microscopy performed on lung biopsy specimens demonstrated a marked reduction in lung injury in the liquid ventilated (LV) when compared with the GV animals. CONCLUSION: In a model of severe respiratory failure, PLV improves pulmonary gas exchange and pulmonary function and is associated with a reduction in pulmonary pathology.