Nicole L. Werner

Ex situ perfusion of human limb allografts for 24 hours

Background Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. Methods Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL. Results Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury. Conclusions Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.

Prenatal and postnatal markers of severity in congenital diaphragmatic hernia have similar prognostic ability.

The purpose of this study was to compare prenatal versus postnatal markers of congenital diaphragmatic hernia (CDH) severity at a single fetal‐care center.

The University of Michigan Experience with Veno-venoarterial Hybrid Mode of Extracorporeal Membrane Oxygenation

The veno-venoarterial (VVA) mode of extracorporeal membrane oxygenation (ECMO) is defined by having both venous and arterial reinfusion cannulas. It is purposed to improve upper body oxygenation as the venous reinfusion cannula is typically placed in the upper body. We performed a single-center retrospective review to better characterize the patients placed on this mode. Adults (n = 23) were 40.4 ± 14.7 years old and were supported with ECMO for a median of 141 (97, 253) hours, with VVA support 110 (63, 179) hours. Ten (43%) were initially cannulated VVA; reasons for conversion included cardiac failure (46%), North-South syndrome (38%), and worsening hypoxia (15%). Survival was 39% and neurological complications 13%. Pediatrics (n = 8) were 13.0 ± 2.4 years old and were supported with ECMO for a median of 258 (168, 419) hours, with VVA support 131 (98, 161) hours. One (12.5%) was initially cannulated VVA; reasons for conversion were North-South syndrome (42%), cardiac failure (29%), and worsening hypoxia (29%). Survival was 71% and neurological complications 29%. We concluded that there was neither survival advantage nor complication reduction with the VVA mode in this cohort; however, VVA does have value for unique clinical situations when conventional ECMO modes do not meet support needs.

Critical Care: Pulmonary

Pulmonary complications [atelectasis, pneumonia, pulmonary edema, COPD exacerbation, acute respiratory failure, acute respiratory distress syndrome (ARDS)] are common in geriatric trauma and acute care surgery patients. Pneumonia and acute respiratory failure are most common. Acute respiratory failure and ARDS are life-threatening pulmonary complications that require mechanical ventilation and intensive care unit admission, and are associated with increased risk for ventilator-associated pneumonia. This chapter reviews epidemiology, risk factors, diagnosis, treatment, and prevention of pulmonary complications in geriatric patients.

Effects of an artificial placenta on brain development and injury in premature lambs

PURPOSE We evaluated whether brain development continues and brain injury is prevented during Artificial Placenta (AP) support utilizing extracorporeal life support (ECLS). METHODS Lambs at EGA 118days (term=145; n=4) were placed on AP support (venovenous ECLS with jugular drainage and umbilical vein reinfusion) for 7days and sacrificed. Early (EGA 118; n=4) and late (EGA 127; n=4) mechanical ventilation (MV) lambs underwent conventional MV for up to 48h and were sacrificed, and early (n=5) and late (n=5) tissue control (TC) lambs were sacrificed at delivery. Brains were harvested, formalin-fixed, rehydrated, and studied by magnetic resonance imaging (MRI). The gyrification index (GI), a measure of cerebral folding complexity, was calculated for each brain. Diffusion-weighted imaging was used to determine fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in multiple structures to assess white matter (WM) integrity. RESULTS No intracranial hemorrhage was observed. GI was similar between AP and TC groups. ADC and FA did not differ between AP and late TC groups in any structure. Compared to late MV brains, AP brains demonstrated significantly higher ADC (0.45±0.08 vs. 0.27±0.11, p=0.02) and FA (0.61±0.04 vs. 0.44±0.05; p=0.006) in the cerebral peduncles. CONCLUSIONS After 7days of AP support, WM integrity is preserved relative to mechanical ventilation. TYPE OF STUDY Research study.

2497: Near normothermic ex-situ perfusion extends human limb allograft survival up to 24 hours

2497: Near normothermic ex-situ perfusion extends human limb allograft survival up to 24 hours Kagan Ozer, MD, Nicole Werner, MD, Fares Alghanem, BS, Stephanie L. Rakestraw, BS, Dylan Sarver, BS, Bruce Nicely, RN, MSN, Richard Pietroski, MS, Paul Lange, MD, Steve M. Rudich, MD, PhD, Chris L. Mendias, PhD, Alvaro Rojas-Pena, MD, John C. Magee, MD, and Robert H. Bartlett, MD University of Michigan, Ann Arbor, MI, USA; Gift of Life, Ann Arbor, MI, USA Background Currently vascularized composite allografts (VCA) are cold preserved (4 C) until transplantation. This process is time limited, as the tissue has to be revascularized within 4–6 hours to minimize ischemia reperfusion (IR) injury. Normothermic perfusion was proposed as an alternative method of preservation in solid organ transplantation Method helps to avoid complications associated with cold preservation and maintains tissue viability without inducing IR injury Using this method, previous investigators demonstrated its potential to prolong swine forelimb allograft survival up to 24 hours (4,5) In this study, we aimed to test this system on human forearm allografts Methods Five human forearms were procured from braindead adult donors under tourniquet control. Following elbow disarticulation, the brachial artery was cannulated. The limb was flushed with heparinized saline and connected to a temperature controlled (30–33 C) ex situ perfusion system (Figure) for 24 hours. The perfusate consisted of plasma and red blood cells with a target hemoglobin (Hb) concentration of 4–6 g/dL. Muscle biopsies (flexor carpi radialis) were obtained at 0, 12, and 24 hours Results Average warm ischemia time was 76 minutes Average arterial systolic pressure was 93§2 mmHg, perfusion flow 310 § 20 mL/min (»6–8% of the donor’s estimated cardiac output), and vascular resistance 153 § 16 mmHg/mL/min. Perfusate had an average pH of 743 § 004 , pCO2 32 § 1 mmHg, pO2 317 § 18 mmHg, and Hb 48 § 04 g/dL Electrolytes (sodium, potassium, chloride) remained within a physiologic range Lactate started to increase steadily throughout the experiment; however, neuromuscular electrical stimulation revealed ongoing contraction throughout the experiment H&E staining showed mild fatty infiltration on some myocytes at 24 hours There was minimal change in fiber size, likely due to variation in age and gender between donors Muscle architecture was preserved at the end of 24 hours perfusion Conclusions All limbs remained viable after 24 hours of nearnormothermic ex situ perfusion as evidenced by ongoing neuromuscular stimulation While no assumptions can be drawn about the long-term function of the extremity, this approach could help extend VCA transplantation to a wider geographic area It also has the potential to circumvent complications associated with cold preservation. CONTACT Kagan Ozer, MD kozer@umich.edu

Extracorporeal Membrane Oxygenation (ECMO)/Extracorporeal Carbon Dioxide Removal (ECCO 2 R)

Extracorporeal membrane oxygenation (ECMO) is a means of supporting severe pulmonary and cardiac dysfunction. It stabilizes critical derangements of oxygenation and ventilation, allowing time to diagnose, treat, and recover from the underlying cause of organ failure. The extracorporeal circuit has three main components: large-bore cannulae and circuit tubing to provide access to the native circulation, an artificial membrane lung to provide gas exchange, and an active pump to facilitate perfusion. Multiple clinical studies have evaluated this technology, the strongest evidence to date supporting its use being the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial, which showed survival advantage when patients were treated with a protocol that included ECMO. Extracorporeal carbon dioxide removal (ECCO2R) is similar in concept to ECMO, but has a lower flow rate and does not significantly oxygenate the patient. It is a primary treatment for hypercarbic respiratory failure or is an adjunct to reduce potentially injurious levels of mechanical ventilator support in hypoxemic respiratory failure. Complications are common occurrences on both types of therapy. Strong institutional commitment and a team approach are critical to successful implementation. Additional randomized trials are needed to clarify the appropriate indications and best practices for these lifesaving therapies.