Unmatched ventilation and perfusion measured by electrical impedance tomography predicts the outcome of ARDS.

BACKGROUND: In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO2/FiO2 and compliance. METHODS: Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units. RESULTS: Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27-47]% vs. 21[17-27]%, p < 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07-1.39, p = 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79-0.97, p < 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 [27-38]% vs. 18 [13-21]%, p < 0.001), while the opposite was true for perfusion (28 [22-38]% vs. 36 [32-44]%, p < 0.001). Higher percentage of only perfused units was correlated with lower dorsal ventilation (r = - 0.486, p < 0.001) and with lower PaO2/FiO2 ratio (r = - 0.293, p = 0.039). CONCLUSIONS: EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.

Tissue temperature, flux and oxygen of sacral and trochanteric area under pressure of healthy subjects: A quasi-experimental study.

AIM: To evaluate the changes that take place in the perfusion, oxygenation and local temperature of the skin of the sacrum and trochanter when subjected to direct pressure for 2 h. METHODS: Quasi-experimental study in the preclinical phase with healthy subjects acting as their own controls (intrasubject control). The outcome variables were measured with a laser Doppler system (local temperature and oxygenation) and by near-infrared spectroscopy (perfusion). The pressure exerted was measured with a capacitive pressure sensor. No more than one week elapsed between the sacrum and trochanter measurements. RESULTS: The study sample consisted of 18 persons. The comparative analysis of the fluctuations in the parameters measured on the skin of the trochanters and sacrum, according to the time elapsed, revealed a statistically significant increase in temperature and in the pressure exerted. On the other hand, the changes in capillary blood flow and in SaO2 were not statistically significant. CONCLUSION: Our study results show that changes found in terms of temperature and pressure should be taking into account when planning personalised repositioning to patients according to biomechanical and biological situations that vary between anatomical areas. In future research, the changes reported could be evaluated in patients with risk factors for the development of pressure ulcers, thus facilitating the introduction of more personalised planning in the care and prevention of these injuries.

Delayed Implantation of Pumped Kidneys Decreases Renal Allograft Futility in Combined Liver-Kidney Transplantation.

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.

Ex vivo limb perfusion for traumatic amputation in military medicine.

BACKGROUND: Limb loss has a drastic impact on a patient's life. Severe trauma to the extremities is common in current military conflicts. Among other aspects, "life before limb" damage control surgery hinders immediate replantation within the short post-traumatic timeframe, which is limited in part by the ischemic time for successful replantation. Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation. PRESENTATION OF THE HYPOTHESIS: The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device, as there are several opportunities present with the introduction of this technique on the horizon. We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time, provide surgical opportunities such as preparation of the stump and limb, allow for spare-part surgery, enable rigorous antibiotic treatment of the limb, reduce ischemia-reperfusion injuries, enable a tissue function assessment before replantation, and enable the development of large limb transplant programs. TESTING THE HYPOTHESIS: Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h. In the military setting, notably longer perfusion times need to be realized. Therefore, future animal studies must focus especially on long-term perfusion, since this represents the military setting, considering the time for stabilization of the patient until evacuation to a tertiary treatment center. IMPLICATIONS OF THE HYPOTHESIS: The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members. Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent, life-threatening situation to a highly methodical, well-prepared starting point for optimal treatment of the wounded service member. With its introduction, the principle of "life before limb" will change to "life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".

Ex-Vivo Normothermic Limb Perfusion With a Hemoglobin-Based Oxygen Carrier Perfusate.

INTRODUCTION: Ex-vivo normothermic limb perfusion (EVNLP) has been proven to preserve limb viability better than standard cold storage. Perfusates containing packed red blood cells (pRBC) improve outcomes when compared to acellular perfusates. Limitations of pRBC-based perfusion include limited availability, need for cross match, mechanical hemolysis, and activation of pro-inflammatory proteins. Hemoglobin-based oxygen carrier (HBOC)-201 (Hemopure) is a solution of polymerized bovine hemoglobin, characterized by low immunogenicity, no risk of hemolytic reaction, and enhanced convective and diffusive oxygen delivery. This is a preliminary study on the feasibility of EVNLP using HBOC-201 as an oxygen carrier. MATERIALS AND METHODS: Three porcine forelimb perfusions were performed using an established EVNLP model and an HBOC-201-based perfusate. The perfusion circuit included a roller pump, oxygenator, heat exchanger, and reservoir. Electrolytes, limb temperature, weight, compartment pressure, nerve conduction, and perfusion indicated by indocyanine green angiography and infra-red thermography were monitored. Histological evaluation was performed with hematoxylin and eosin and electron microscopy. RESULTS: Three limbs were perfused for 21.3 ± 2.1 hours. Muscle contractility was preserved for 10.6 ± 2.4 hours. Better preservation of the mitochondrial ultrastructure was evident at 12 hours in contrast to crystallization and destruction features in the cold-storage controls. CONCLUSIONS: An HBOC-201-EVNLP produced outcomes similar to RBC-EVNLP with preservation of muscle contractility and mitochondrial structure.

The Use of the Oxygenated AirdriveTM Machine Perfusion System in Kidney Graft Preservation: A Clinical Pilot Study.

BACKGROUND: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ischemic damage. This pilot study was undertaken to assess the feasibility and patient safety of the AirdriveTM HMP system in clinical kidney transplantation. METHODS: Five deceased-donor kidneys were preserved using the oxygenated Airdrive HMP system between arrival at the recipient center (Amsterdam UMC) and implantation in the patient. The main study end-points were adverse effects due to the use of Airdrive HMP. Secondary end-points were clinical outcomes and perfusion parameters. All events occurring during the transplantation procedure or within 1 month of follow-up were monitored. RESULTS: Five patients were included in this pilot study. No technical failures were observed during the preservation period using the Airdrive HMP. Mean perfusion parameters were: duration 8.5 h (3-15 h), pressure 25 mm Hg (18-25 mm Hg), flow 49.77 mL/min (19-58 mL/min), resistance 0.57 mm Hg/min/mL (0.34-1.3 mm Hg/min/mL), and temperature 8.2 °C (2-13°C). Mean cold ischemia time (CIT) was 20.2 h (11-29.5 h). No adverse events or technical failures were observed during preservation and transplantation or during the 1-month follow-up. CONCLUSIONS: This pilot study showed the feasibility of the use of the Airdrive HMP system with no adverse events in clinical kidney transplantation.

Effect of Botulinum Toxin-A Injected to Muscle Tissue on Perfusion and Survival of Fasciocutaneous Single Perforator-pedicled Propeller Flap in Rats

Background: In plastic surgery practice, fasciocutaneous single-perforator-pedicled propeller flap is a preferred procedure; however, its survival rate is below than expected, especially in flaps with a big rotation arc. When botulinum toxin-A is injected into the muscle tissue that the perforator pedicle is arisen, the tonus of pertinent muscle can reduce and the blood flow of its perforator pedicle can increase. Therefore this procedure can improve the survival rate of single-perforator-pedicled propeller flap. Aims: To evaluate the effect of botulinum toxin-A injected with ultrasonographic guidance into the muscle tissue that the perforator pedicle is arisen from one month ago on the perfusion of flap scintigraphically and the survival rate of single-perforator-pedicled propeller flap in a rat model. Study Design: Animal experiment. Methods: Three study groups were receiving botulinum toxin-A (16 IU-0.4 mL), normal saline (0.4 mL), and no study drug one month ago before flap surgery. Injections were performed under ultrasonography guidance. Flaps were elevated fasciocutaneously over the right 2nd perforator pedicle, under the corneous, with a surgical loupe and microsurgery tool and were rotated clockwise 180°. Then the scintigraphic measurements were obtained after flap elevations in the study groups, including the whole-body and flap perfusions in the study rats. The involvement rate presents the ratio of flap perfusion to whole-body perfusion. Flaps were sutured back to the abdominal wall at the latest twisting angles. With standard photographs taken in all the groups on day 8 after the operation, whole and necrotic flap areas were calculated. Results: Scintigraphically the involvement rate (the ratio of flap perfusion to whole-body perfusion) of the flaps in the botulinum toxin-A group were found significantly higher than those in the other groups (p<0.05). The area of a flap in the botulinum toxin-A group on day 8 post flap suturing was found to be significantly higher than those in the other groups (p<0.05). The area of a necrosis and the percentage of necrosis on day 8 post flap suturing in the botulinum toxin-A group was found significantly lower than those of the sham and null groups (p<0.05). Conclusion: In a rat model, if with the ultrasonographic guidance, botulinum toxin-A is injected to the muscle which perforator of the prospective single-perforator-pedicled propeller flap originated and flap surgery is performed one month later after this injection, the perfusion of single-perforator-pedicled propeller flap increases scintigraphically and this improves flap survival and reduces its necrosis.

Heterogeneity of Human Pancreatic Islet Isolation Around Europe: Results of a Survey Study.

BACKGROUND: Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries. METHODS: A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan. RESULTS: Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations per year over the last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions per year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation, and release criteria for transplantation (glucose-stimulated insulin secretion tests, islet numbers, and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities. CONCLUSIONS: The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria.

Feasibility of myocardial perfusion assessment with contrast echocardiography: can it improve recognition of significant coronary artery disease in the ICU?

BACKGROUND: Diagnosis of significant coronary artery disease (CAD) and acute coronary artery occlusion in ICU can be difficult, and an inappropriate intervention is potentially harmful. Myocardial contrast perfusion echo (MCPE) examines ultrasound contrast intensity replenishment curves in individual myocardial segments measuring peak contrast intensity and slope of return as an index of myocardial blood flow (units = intensity of ultrasound per second [dB/s]). MCPE could possibly serve as a triage tool to invasive angiography by estimating blood flow in the myocardium. We sought to assess feasibility in the critically ill and if MCPE could add incremental value to the clinical acumen in predicting significant CAD. METHODS: This is a single-centre, prospective, observational study. Inclusion criteria were as follows: adult ICU patients with troponin I > 50 ng/L and cardiology referral being made for consideration of inpatient angiography. Exclusion criteria were as follows: poor echo windows (2 patients), known ischaemic heart disease, and contrast contraindications. Seven cardiologists and 6 intensivists blinded to outcome assessed medical history, ECG, troponin, and 2D echo images to estimate likelihood of significant CAD needing intervention (clinical acumen). Clinical acumen, quantitative MCPE, and subjective (visual) MCPE were assessed to predict significant CAD. RESULTS: Forty patients underwent MCPE analysis, 6 (15%) had significant CAD, and median 11 of 16 segments (IQR 8-13) could be imaged (68.8% [IQR 50-81]). No adverse events occurred. A significant difference was found in overall MCPE blood flow estimation between those diagnosed with significant CAD and those without (3.3 vs 2.4 dB/s, p = 0.050). A MCPE value of 2.8 dB/s had 67% sensitivity and 88% specificity in detecting significant CAD. Clinical acumen showed no association in prediction of CAD (OR 0.6, p = 0.09); however, if quantitative or visual MCPE analysis was included, a significant association occurred (OR 17.1, p = 0.01; OR 23.0, p = 0.01 respectively). CONCLUSIONS: MCPE is feasible in the critically ill and shows better association with predicting significant CAD vs clinical acumen alone. MCPE adds incremental value to initial assessment of the presence of significant CAD which may help guide those who require urgent angiography.

The relationship of abdominal perfusion pressure with mortality in critically ill pediatric patients.

PURPOSE: To the best of our knowledge, in the literature, there is no data regarding clinical utility of the abdominal perfusion pressure (APP) in critically ill children. Thus, in the present study, we aimed to investigate the clinical utility of APP in predicting of survival in critically ill children with IAH. DESIGN: A prospective cohort study of patients between 1 month to 18 years who had risk for intra-abdominal hypertension from June 2013 to January 2014. SETTING: Pediatric intensive care unit (PICU) at a tertiary university hospital. PATIENTS: Thirty-five (16 female) PICU patients who had risk for the development of IAH were included. Serial intraabdominal pressure (IAP) and mean arterial pressure (MAP) measurements were performed. Abdominal perfusion pressure was calculated using the formula (MAP-IAP). MEASUREMENTS AND MAIN RESULTS: Overall mortality rate was 49% (n = 17). The mortality rate in patients with IAP mean ≥10 mmHg (n = 27, 77%) was 55% (n = 15), while 53% (n = 16) in patients with IAP max ≥10 mmHg (n = 30, 86%) and 47% (n = 7) in patients with IAP min ≥ 10 mmHg (n = 15, 43%). Overall mean APP was 58 ±â€¯20 mmHg. Logistic regression analysis revealed that decrease in minAPP was associated with increased risk for mortality (Odds ratio for each 1 mmHg decrease in APP was 1.052 [CI 95%, 1.006-1.100], p < 0.05). ROC curve analysis revealed that, in predicting mortality, area under curve for minAPP was 0.765. The optimal cut-off point for APP was obtained as 53 mmHg with the 77.8% sensitivity and 70.6% specificity using the IU method. CONCLUSIONS: Our findings showed that APP seems to be a useful tool in predicting mortality. Interventions to improve APP may be associated with better outcomes in critically ill PICU patients. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Diagnostic.

Kidney transplantation from donors after uncontrolled circulatory death: the Spanish experience.

Donation after uncontrolled circulatory death (uDCD) refers to donation from persons who have died following cardiac arrest and unsuccessful attempt at resuscitation. We report the Spanish experience of uDCD kidney transplantation, and identify factors related to short-term post-transplant outcomes. The Spanish CORE system compiles data on all donation and transplant procedures in the country. Between 2012-2015, 517 kidney transplants from 288 uDCD donors were performed. The incidence of primary non-function was 10%, and the incidence of delayed graft function was 76%. One-year death-censored graft survival was 87%. In a Cox-Model, donor age ≥ 60 years (odds ratio [OR] 2.7; 95% confidence interval [CI] 1.2-6.1), in situ cooling of kidneys versus normothermic regional perfusion (OR 5.6; 95% CI 2.7-11.5) or hypothermic regional perfusion based on the use of extracorporeal membrane oxygenation devices (OR 4.3; 95% CI 2.1-8.6), and a recipient history of prior kidney transplant (OR 3.5; 95% CI 1.5-8.3) all significantly increased the risk of graft loss during the first year after transplantation. Kidney transplantation from uDCD donors provides acceptable 1-year outcomes, although there is room for improvement. Hypothermic and normothermic regional perfusion strategies are preferable to in situ cooling of kidneys from uDCD donors.

Resuscitation of Hypotensive Traumatic Brain Injured Animals With Spray-Dried Plasma Does Not Adversely Alter Physiology and Improves Blood-Brain Barrier Function.

INTRODUCTION: According to the Defense and Veterans Brain Injury Center and the Armed Forces Health Surveillance Center, the number of soldiers who have sustained a traumatic brain injury (TBI) has risen dramatically over the past decade. Studies have shown that brain damage can be exacerbated if blood loss occurs (often occurring in polytrauma). As blood supply is critical for brain function and survival, TBI patients must be properly resuscitated to maintain blood volume, blood pressure, and cerebral perfusion. Recent studies have suggested that blood loss can damage the vascular endothelium and enhance blood-brain barrier (BBB) permeability. Brain endothelial cells and the tight junctions between them are key structural components of the BBB. As the BBB is critical for isolating the brain from potential pathogens and for regulating the influx of molecules into the brain, evaluation of resuscitation fluids for their efficacy to improve BBB function has clinical relevance. Although whole blood and fresh frozen plasma (FFP) contain the essential coagulation factors, ions, and other factors, the transport and storage of these products in remote, austere environments can be challenging. The use of spray-dried plasma (SDP) has several advantages including storage at ambient temperature, can be readily reconstituted before use, and infectious materials can be inactivated during the drying process. In this study, we compared FFP and SDP for their effects on blood pressure, cerebral blood flow, BBB integrity, and markers of endothelial cells and tight junction proteins, in TBI animals with blood loss. MATERIALS AND METHODS: All procedures were reviewed and approved by the UTHealth animal welfare committee. Sprague Dawley rats received controlled cortical impact brain injury followed by removal of 25% blood volume. Animals were resuscitated 40 minutes later with either FFP or concentrated SDP (Resusix) Heart rate and blood pressure were monitored continuously using catheters implanted into the femoral artery. Cerebral perfusion was assessed using a scanning laser Doppler device. Twenty-four hours after the injury and resuscitation with either FFP or SDP, BBB integrity were monitored by measuring the amount of Evans Blue dye in the injured brain following its intravenous administration. As this dye is excluded from the uninjured brain, its presence in the injured brain is an indicator of BBB breakdown. In addition, von Willebrand Factor immunohistochemistry was used to examine endothelial cell loss, whereas claudin-5 immunohistochemistry was used to assess the loss of tight junctions, in FFP- and SDP-resuscitated TBI animals. RESULTS: Our results show that post-TBI resuscitation with FFP and SDP had similar influences on cardiovascular physiology and cerebral perfusion. Resuscitation with SDP after TBI was found to decrease BBB permeability as indicated by reduced Evans Blue dye extravasation, and increased levels of von Willebrand Factor and claudin-5, as compared to resuscitation with FFP. CONCLUSIONS: These preclinical results show that resuscitation with SDP may be superior to FFP, and support the further evaluation of this product as a resuscitation fluid for polytrauma patients with TBI.

Non-Heart-Beating Donor Program: Results After 3 Years of Experience.

BACKGROUND: Non-heart-beating donation (NHBD) is a useful way to obtain organs and tissues. Therefore, since 2012 we have had an NHBD protocol in the metropolitan area of Seville. The aim of this work was to present the results obtained after 3 years of program. METHODS: Prospective observational study carried out from 2012 to 2014. We included all patients with an extrahospitalary sudden death who did not survive despite cardiopulmonary resuscitation, becoming a potential donors (PD). Variables included number of consultations, PD, allowed donor (AD), real donor (RD), and family or legal refusals; minutes of out-hospital care, in-hospital care, cannulation, and perfusion of the RD; and number of organs and tissues removed and viable proportion. Nonallowed donors were grouped according to the discarding cause. RESULTS: We received 97 consultations, of which 40 were performed as PD. Of these, 24 were AD (60%) and 22 RD (55%). There were only 2 family refusals. In 2012, 10 patients were donors, 5 in 2013, and 7 in 2014. The out-hospital median time was 71 (interquartile range [IQR] 60-76) minutes, in-hospital 29 (26-34) minutes, cannulation 28 (24-33) minutes, and perfusion 135 (105-177) minutes. Eighteen tissues and 43 organs were extracted, of which 32 were implanted (75%), with kidneys (96%) being more frequent. Nonallowed donors numbered 12 in 2012, 4 in 2013, and 1 in 2014, and out-hospital causes were the most frequent discard reason. CONCLUSIONS: NHBD is a useful program in our city with a low refusal rate (8%), an average of 1.45 organs per donor, and kidney the most frequent organ.

Machine perfusion: not just for marginal kidney donors.

Interest in machine perfusion (MP) for donated kidneys has markedly increased in the past decade as a means to improve graft function, although the donor populations in which it should be applied have not yet been resolved. All adults undergoing de-novo isolated kidney transplantation from standard-criteria donors in the UNOS database 2005 to 2011 were reviewed with the primary endpoint of delayed graft function (DGF), defined as dialysis within seven days of transplantation, in those who received kidneys that underwent MP versus cold storage (CS) alone. Three methods were used to control for differences between groups. Multivariable logistic regression was performed, adjusting for donor and recipient characteristics significantly associated with DGF. Rates were also compared in a cohort of propensity-matched MP vs CS recipients. Finally, a paired-kidney study was performed, where one kidney underwent MP and the contralateral underwent CS. There were 36,323 patients, with unadjusted DGF rates of 18.6 per cent (n = 1830/9882) and 22.4 per cent (n = 5931/26,441; P < 0.001) in the MP vs CS groups, respectively. After multivariable analysis, the odds ratio for DGF in the MP group was 0.59 (P < 0.001) versus CS. In the propensity-matched cohort, there were 8929 patients each in the MP and CS groups. DGF occurred in 16.8 per cent of the MP group vs 25.3 per cent with CS (P < 0.001, OR 0.59). In the paired-kidney study, rates of DGF were 16.7 per cent vs 24.3 per cent (P < 0.001) in the 1665 recipients each in the MP versus CS groups (OR 0.6). In conclusion, machine perfusion is beneficial in reducing DGF even when standard donors are utilized, and thus should not be limited to marginal kidneys.

Perfusion computed tomography for detection of hepatocellular carcinoma in patients with liver cirrhosis.

PURPOSE: To evaluate the diagnostic performance of dynamic perfusion CT (P-CT) for detection of hepatocellular carcinoma (HCC) in the cirrhotic liver. MATERIALS AND METHODS: Twenty-six cirrhotic patients (19 men, aged 69 ± 10 years) with suspicion of HCC prospectively underwent P-CT of the liver using the 4D spiral-mode (100/80 kV; 150/175mAs/rot) of a dual-source system. Two readers assessed: (1) arterial liver-perfusion (ALP), portal-venous liver-perfusion (PLP) and hepatic perfusion-index (HPI) maps alone; and (2) side-by-side with maximum-intensity-projections of arterial time-points (art-MIP) for detection of HCC using histopathology and imaging follow-up as standard of reference. Another reader quantitatively assessed perfusion maps of detected lesions. RESULTS: A total of 48 HCCs in 21/26 (81%) patients with a mean size of 20 ± 10 mm were detected by histopathology (9/48, 19%) or imaging follow-up (39/48, 81%). Detection rates (Reader1/Reader2) of HPI maps and side-by-side analysis of HPI combined with arterial MIP were 92/88% and 98/96%, respectively. Positive-predictive values were 63/63% and 68/71%, respectively. A cut-off value of ≥85% HPI and ≥99% HPI yielded a sensitivity and specificity of 100%, respectively, for detection of HCC. CONCLUSION: P-CT shows a high sensitivity for detection of HCC in the cirrhotic liver. Quantitative assessment has the potential to reduce false-positive findings improving the specificity of HCC diagnosis. KEY POINTS: • Visual analysis of perfusion maps shows good sensitivity for detection of HCC. • Additional assessment of anatomical arterial MIPs further improves detection rates of HCC. • Quantitative perfusion analysis has the potential to reduce false-positive findings. • In cirrhotic livers, a hepatic-perfusion-index ≥ 9 9% might be specific for HCC.

Lung transplantation from donors after circulatory death using portable ex vivo lung perfusion.

BACKGROUND: Donation after circulatory death is a novel method of increasing the number of donor lungs available for transplantation. Using organs from donors after circulatory death has the potential to increase the number of transplants performed. METHODS: Three bilateral lung transplants from donors after circulatory death were performed over a six-month period. Following organ retrieval, all sets of lungs were placed on a portable ex vivo lung perfusion device for evaluation and preservation. RESULTS: Lung function remained stable during portable ex vivo perfusion, with improvement in partial pressure of oxygen/fraction of inspired oxygen ratios. Mechanical ventilation was discontinued within 48 h for each recipient and no patient stayed in the intensive care unit longer than eight days. There was no postgraft dysfunction at 72 h in two of the three recipients. Ninety-day mortality for all recipients was 0% and all maintain excellent forced expiratory volume in 1 s and forced vital capacity values post-transplantation. CONCLUSION: The authors report excellent results with their initial experience using donors after circulatory death after portable ex vivo lung perfusion. It is hoped this will allow for the most efficient use of available donor lungs, leading to more transplants and fewer deaths for potential recipients on wait lists.

Detailed statistical analysis plan for the pulmonary protection trial.

BACKGROUND: Pulmonary dysfunction complicates cardiac surgery that includes cardiopulmonary bypass. The pulmonary protection trial evaluates effect of pulmonary perfusion on pulmonary function in patients suffering from chronic obstructive pulmonary disease. This paper presents the statistical plan for the main publication to avoid risk of outcome reporting bias, selective reporting, and data-driven results as an update to the published design and method for the trial. RESULTS: The pulmonary protection trial is a randomized, parallel group clinical trial that assesses the effect of pulmonary perfusion with oxygenated blood or Custodiol™ HTK (histidine-tryptophan-ketoglutarate) solution versus no pulmonary perfusion in 90 chronic obstructive pulmonary disease patients. Patients, the statistician, and the conclusion drawers are blinded to intervention allocation. The primary outcome is the oxygenation index from 10 to 15 minutes after the end of cardiopulmonary bypass until 24 hours thereafter. Secondary outcome measures are oral tracheal intubation time, days alive outside the intensive care unit, days alive outside the hospital, and 30- and 90-day mortality, and one or more of the following selected serious adverse events: pneumothorax or pleural effusion requiring drainage, major bleeding, reoperation, severe infection, cerebral event, hyperkaliemia, acute myocardial infarction, cardiac arrhythmia, renal replacement therapy, and readmission for a respiratory-related problem. CONCLUSIONS: The pulmonary protection trial investigates the effect of pulmonary perfusion during cardiopulmonary bypass in chronic obstructive pulmonary disease patients. A preserved oxygenation index following pulmonary perfusion may indicate an effect and inspire to a multicenter confirmatory trial to assess a more clinically relevant outcome. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01614951, registered on 6 June 2012.

Normothermic ex vivo allograft blood perfusion in clinical heart transplantation.

BACKGROUND: Cold ischemia associated with cold static storage is an independent risk factor for primary allograft failure and survival of patients after orthotopic heart transplantation. The effects of normothermic ex vivo allograft blood perfusion on outcomes after orthotopic heart transplantation compared to cold static storage have been studied. METHODS: In this prospective, nonrandomized, single-institutional clinical study, normothermic ex vivo allograft blood perfusion has been performed using an organ care system (OCS) (TransMedics, Andover, MA, USA). Included were consecutive adult transplantation patients who received an orthotopic heart transplantation (oHTx) without a history of any organ transplantation, in the absence of a congenital heart disorder as an underlying disease and not being in need of a combined heart-lung transplantation. Furthermore, patients with fixed pulmonary hypertension, ventilator dependency, chronic renal failure, or panel reactive antibodies >20% and positive T-cell cross-matching were excluded. Inclusion criteria for donor hearts was age of <55 years, systolic blood pressure >85 mmHg at the time of final heart assessment under moderate inotropic support, heart rate of <120 bpm at the time of explantation, and left ventricular ejection fraction >40% assessed by an transcutaneous echo/Doppler study with the absence of gross wall motion abnormalities, absence of left ventricular hypertrophy, and absence of valve abnormalities. Donor hearts which were conventionally cold stored with histidine-tryptophan-ketoglutarate solution (Custodiol; Koehler Chemie, Ansbach, Germany) constituted the control group. The primary end point was the recipients' survival at 30 days and 1 and 2 years after their heart transplantation. Secondary end points were primary and chronic allograft failure, noncardiac complications, and length of hospital stay. RESULTS: Over a 2-year period (January 2006 to July 2008), 159 adult cardiac allografts were transplanted. Twenty-nine were assigned for normothermic ex vivo allograft blood perfusion and 130 for cold static storage with HTK solution. Cumulative survival rates at 30 days and 1 and 2 years were 96%, 89%, and 89%, respectively, whereas in the cold static storage group survival after oHTx was 95%, 81%, and 79%. Primary graft failure was less frequent in the recipients of an oHTx who received a donor heart which had been preserved with normothermic ex vivo allograft blood perfusion using an OCS (6.89% versus 15.3%; P = .20). Episodes of severe acute rejection (23% versus 17.2%; P = .73), as well as, cases of acute renal failure requiring haemodialysis (25.3% versus 10%; P = .05) were more frequent diagnosed among recipients of a donor heart which had been preserved using the cold static storage. The length of hospital stay did not differ (26 days versus 28 days; P = .80) in both groups. CONCLUSIONS: Normothermic ex vivo allograft blood perfusion in adult clinical orthotopic heart transplantation contributes to better outcomes after transplantation in regard to recipient survival, incidence of primary graft dysfunction, and incidence of acute rejection.

Antegrade and retrograde arterial perfusion strategy in minimally invasive mitral-valve surgery: a propensity score analysis on 1280 patients.

OBJECTIVES: Recent studies have suggested an increased risk of stroke in patients undergoing minimally invasive mitral-valve surgery with retrograde perfusion when compared with antegrade perfusion. The aim of the present study was therefore to evaluate the impact on early outcome of retrograde arterial perfusion (RAP) strategy vs antegrade arterial perfusion strategy in a consecutive large cohort of patients who underwent minimally invasive mitral-valve surgery through a right minithoracotomy. METHODS: Between 2003 and 2012, 1280 consecutive patients underwent first-time minimally invasive mitral-valve surgery at our institution. A total of 167 (13%) of these patients received a retrograde perfusion, while 1113 (87%) received antegrade perfusion. Logistic analysis was used to evaluate outcomes and risk factors for stroke. Treatment selection bias was controlled by constructing a propensity score from core patient characteristics. The propensity score was the probability of receiving retrograde perfusion and was included along with the comparison variable in the multivariable analyses of outcome. RESULTS: The overall frequency of in-hospital mortality was 1.1% (14/1280) and postoperative stroke was 1.6% (21/1280). After adjusting for the propensity score, RAP was associated with a higher incidence of stroke (5 vs 1%; P = 0.002), postoperative delirium (14 vs 5%, P = 0.001) and aortic dissection (1.7 vs 0%; P = 0.01). Multivariable regression analysis revealed that the use of retrograde perfusion was an independent risk factor for stroke [odds ratio (OR) 4.28; P = 0.02] and postoperative delirium (OR 3.51; P = 0.001). CONCLUSIONS: Minimally invasive mitral valve procedure can be performed with low morbidity and mortality. The use of retrograde perfusion is associated with a higher incidence of neurological complications and aortic dissection when compared with antegrade perfusion. Central aortic cannulation allows the avoidance of complications associated with retrograde perfusion while extending the suitability of minimally invasive mitral procedures also to those patients who have an absolute contraindication to femoral artery cannulation.

Cold reperfusion before rewarming reduces neurological events after deep hypothermic circulatory arrest.

OBJECTIVES: To identify a safety threshold of deep hypothermic circulatory arrest (DHCA) duration; to determine which protection offers the best outcome and whether a 10-min period of cold perfusion (20°C) preceding rewarming can reduce neurological events (NE). METHODS: From January 1988 to April 2009, 456 patients underwent aortic surgery using DHCA: for chronic disease in 239 and acute in 217. Cerebral protection was obtained by straight DHCA (sDHCA) in 69 cases, retrograde perfusion (RCP) in 198 and antegrade perfusion (ACP) in 189. In 247 subjects, a 10-min period of cold perfusion (20°C) preceded rewarming; in 209 rewarming was restarted without this preliminary. RESULTS: Fifty-eight patients (13%) experienced NE. Twenty-two (5%) suffered temporary neurological dysfunction (TND) and 36 (8%) suffered stroke. DHCA duration >30 min was predictive for higher rate of NE (25.2% vs. 2.0%, P 0.001); after this value, only ACP was able to reduce incidence of NE (16.5% vs. 30.5%, P = 0.035). Cold reperfusion before rewarming significantly reduced incidence of NE (7.7% vs. 18.7%, P < 0.001) and extended the safe period to 40 min. Thirty-day mortality was 16.0%. Predictors of higher early mortality were acute aortic disease, longer DHCA, lack of ACP or prompt rewarming when DHCA >30 min and postoperative stroke. CONCLUSIONS: sDHCA remains a safe and easy tool for cerebral protection when DHCA duration is expected to be less than 30 min. When aortic surgery requires a longer period, ACP should be instituted. Before rewarming, a 10-min period of cold perfusion significantly reduces incidence of NE.