Systemic Inflammation Differences in Brain-vs. Circulatory-Dead Donors: Impact on Lung Transplant Recipients.

Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72 h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor's plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.

Legislation and Policy Recommendations on Organ and Tissue Donation and Transplantation From an International Consensus Forum.

There is a shared global commitment to improving baseline donation and transplantation performance metrics in a manner consistent with ethics and local cultural and social factors. The law is one tool that can help improve these metrics. Although legal systems vary across jurisdictions, our objective was to create expert, consensus guidance for law and policymakers on foundational issues underlying organ and tissue donation and transplantation (OTDT) systems around the world. Methods: Using the nominal group technique, a group composed of legal academics, a transplant coordinator/clinician, and a patient partner identified topic areas and recommendations on foundational legal issues. The recommendations were informed by narrative literature reviews conducted by group members based on their areas of expertise, which yielded a range of academic articles, policy documents, and sources of law. Best practices were identified from relevant sources in each subtopic, which formed the basis of the recommendations contained herein. Results: We reached consensus on 12 recommendations grouped into 5 subtopics: (i) legal definitions and legislative scope, (ii) consent requirements for donation' (iii) allocation of organs and tissue' (iv) operation of OTDT systems' and (v) travel for transplant and organ trafficking. We have differentiated between those foundational legal principles for which there is a firm basis of support with those requiring further consideration and resolution. Seven such areas of controversy are identified and discussed alongside relevant recommendations. Conclusions: Our recommendations encompass some principles staunchly enshrined in the OTDT landscape (eg, the dead donor rule), whereas others reflect more recent developments in practice (eg, mandatory referral). Although some principles are widely accepted, there is not always consensus as to how they ought to be implemented. As the OTDT landscape continues to evolve, recommendations must be reconsidered for the law to keep pace with developments in knowledge, technology, and practice.

Psychological symptoms in difficult-to-sedate critical care survivors.

BACKGROUND: Critical care survivors often experience symptoms of anxiety, depression, or post-traumatic stress disorder (PTSD). AIMS: To determine the prevalence and severity of psychological symptoms during the first 6 months after discharge from the intensive care unit (ICU) and to evaluate its association with patients who are difficult to sedate during admission. DESIGN: Descriptive, prospective analysis of psychological symptoms in survivors from medicosurgical ICU over a 2-year period. METHODS: All ICU survivors who required mechanical ventilation (MV) for more than 24 hours were followed for 6 months after their ICU discharge. ICU outcome and complications as well as the presence of psychological symptoms, 1 to 3 to 6 months after discharge were prospectively evaluated through phone interviews comparing the incidence and intensity of patients who were difficult to sedate during their ICU stay with those who were not. Descriptive analysis and multivariate logistic regression were performed. RESULTS: Data were obtained for 195 patients, of whom 30% experienced difficult sedation (DS). Difficult-to-sedate patients were younger (P = .001), less critically ill (APACHE II score P = .002), and more likely to engage in harmful use of alcohol (P = .001) and psychoactive/psychotropic drug abuse. They also spent longer times on MV and in the ICU (P = .001). Anxiety incidence at 1 to 3 to 6 months post-discharge was significantly higher in DS patients than in those who were not (87.7% vs 45.4%, 75.5% vs 29.0%, and 70.8% vs 23.7%; P < .01), respectively. Depression incidence was also significantly higher in the DS group (82.4% vs 43.1%, 66% vs 33.9%, and 60.4% vs 27.2%; [P = .001]) at 1 to 3 to 6 months, respectively. A higher percentage of patients in the DS group reported symptoms of PTSD at 1 month (28.1% vs 11.5%) (P = .007) when compared with non-DS group. CONCLUSIONS: Critical care survivors who are difficult to sedate during their ICU stay are more likely to present psychological sequelae. Early identification of at-risk patients is necessary to implement appropriate preventive strategies. RELEVANCE TO CLINICAL PRACTICE: Patients who are difficult to sedate in the ICU may develop psychological disorders upon discharge, which may negatively affect their recovery. The prevention of DS and the early detection of psychological disorders are essential to minimize its subsequent impact.

Impact of difficult sedation on the management and outcome of critically ill patients.

BACKGROUND: The term "difficult sedation" (DS) refers to situations of therapeutic failure, tolerance, or deprivation of the sedatives administered. AIMS: To characterize the profile of patients who developed DS and to assess its impact on the duration of mechanical ventilation (MV) and intensive care unit length of stay (ICU-LOS), as well as other complications related to their stay. DESIGN: A prospective descriptive analysis was conducted of the practices of analgesia/sedation in a medical-surgical intensive care unit (ICU) over a 2-year period. METHODS: All critically ill patients undergoing MV and sedation for more than 24 hours were prospectively followed until death or discharge. Demographic data, type, duration, complications of analgesia/sedation, and clinical outcome during ICU stay were recorded. Patients who developed DS were compared with those who were not difficult to sedate (not-DS). RESULTS: A total of 327 patients were included, 24.1% of whom were difficult to sedate (DS). Patients in the DS group were younger (P = .001); less severely ill (P = .003); and were more likely to have a history of smoking (P = .045), alcohol (P < .001), and psychotropic use (P = .001) than the not-DS group. Patients included in the DS group were sedated for longer periods (P < .001) and required higher doses of midazolam (P < .036), propofol (P = .023), and remifentanyl (P = .026) than those in the not-DS group. Difficult-to-sedate patients were twice as likely to require more than one sedative simultaneously (P < .001), presented more periods of over-sedation (P = .031)/under-sedation (P = .024), and suffered more pain (P < .001) than patients in the not-DS group. Patients in the DS group had prolonged MV times (P < .001), developed more pressure ulcers (P > .001) and ventilator-associated pneumonias (P = .025), and were more likely to require tracheotomy (P = .001) than those in the not-DS group. CONCLUSION: DS develops in one of four critically ill patients and has a negative impact on their outcomes. Early identification of the clinical profile of this group and active prevention and treatment are essential strategies in order to minimize its impact. RELEVANCE TO CLINICAL PRACTICE: A quarter of mechanically ventilated patients may develop situations of DS, which negatively affects their outcome. Early detection and prevention of DS are essential to minimize its impact.

Critical pathway for deceased tissue donation: a novel adaptative European systematic approach.

A 'Critical pathway for deceased tissue donation' was developed by the European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) with the aim of providing a common systematic approach to the deceased tissue donation process. Definitions of tissue donors according to the donation stage have been developed so that they can be adapted to different local scenarios. This critical pathway can be used retrospectively to evaluate the potential of tissue donation, assess performance in the tissue donation process and identify areas for improvement. It sets the basis to build indicators to compare organizations, regions and countries. The critical pathway can also be used prospectively to promote good practices in tissue donation programmes aimed at covering the tissue transplantation needs of patients.

Online education about end-of-life care and the donation process after brain death and circulatory death. Can we influence perception and attitudes in critical care doctors? A prospective study.

Impact of training on end-of-life care (EOLC) and the deceased donation process in critical care physicians' perceptions and attitudes was analysed. A survey on attitudes and perceptions of deceased donation as part of the EOLC process was delivered to 535 physicians working in critical care before and after completion of a online training programme (2015-17). After training, more participants agreed that nursing staff should be involved in the end-of-life decision process (P < 0.001) and that relatives should not be responsible for medical decisions (P < 0.001). Postcourse, more participants considered 'withdrawal/withholding' as similar actions (P < 0.001); deemed appropriate the use of pre-emptive sedation in all patients undergoing life support treatment adequacy (LSTA; P < 0.001); and were favourable to approaching family about donation upon LSTA agreement, as well as admitting them in the intensive care unit (P < 0.001) to allow the possibility of donation. Education increased the number of participants prone to initiate measures to preserve the organs for donation before the declaration of death in patients undergoing LSTA (P < 0.001). Training increased number of positive terms selected by participants to describe donation after brain and circulatory death. Training programmes may be useful to improve physicians' perception and attitude about including donation as part of the patient's EOLC.

Effects of the extracorporeal membrane oxygenation circuit on plasma levels of ceftolozane.

INTRODUCTION: New antibiotics with bactericidal activity against multi-drug-resistant bacteria are increasingly used in the intensive care units. Here, we aimed to evaluate the influence of the extracorporeal membrane oxygenation on plasma levels of ceftolozane. CASE REPORT: A 34-year-old female was admitted to the intensive care unit after bilateral lung transplantation, complicated by primary graft dysfunction and cardiogenic shock needing venoarterial extracorporeal membrane oxygenation. Ceftolozane/tazobactam was started. Plasma ceftolozane levels were monitored on the first and third days of antibiotic treatment. A non-compartment pharmacokinetic analysis was performed and the extraction rate through the oxygenator was calculated. DISCUSSION: The extracorporeal circuit of extracorporeal membrane oxygenation may alter the pharmacokinetics of antibiotics, to varying degrees due to drug sequestration and increased distribution volume. In this case, the extracorporeal membrane oxygenation circuit had little impact on the ceftolozane plasma concentration. CONCLUSION: Plasma levels of ceftolozane are stable in the extracorporeal membrane oxygenation circuit, suggesting that adjustment of standard doses of ceftolozane in patients with extracorporeal membrane oxygenation support may not be needed.

Intensive Care to Facilitate Organ Donation: A Report on the 4-Year Experience of a Spanish Center With a Multidisciplinary Model to Promote Referrals Out of the Intensive Care Unit.

BACKGROUND: Intensive care to facilitate organ donation (ICOD) has been defined as the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom treatment for curative purposes is deemed futile, and who are considered possible organ donors, with the aim of offering donation after brain death (DBD) inside their end-of-life care plans. We describe the effect on the donation and transplantation activity of the implementation of ICOD protocol at a university hospital. METHODS: Retrospective analysis (2015-2018) of demographics and outcomes of all patients with a DBI, in whom ICOD was considered as part of their end-of-life care in Vall d'Hebron University Hospital, Barcelona. RESULTS: Of the 983 possible donors evaluated, ICOD was considered in 206 (21%), of whom 115 (55.8%) were medically unsuitable for donation. Family consent was obtained for 69 (76%) of the remaining patients. Refusal rate was twice as high when nontherapeutic ventilation was required for organ donation (34%) vs patients previously ventilated (13.6%) (P = .02). Patients subject to ICOD died in a median of 2 days (1-3 d) and 88.4% became actual donors (39 after brain death; 22 after circulatory death). Nine (17.6%) donors were finally not utilized. ICOD contributed to 29% (ranging from 27.7% in 2015 to 31.6% in 2018) of the 208 actual donors and 26% of the 603 organs transplanted. CONCLUSIONS: ICOD is well-accepted by families and offers the donation option to an increasing number of patients at our hospital. It provides an important and sustained increment of the organ pool for transplantation.

Management of donation after brain death (DBD) in the ICU: the potential donor is identified, what's next?

The success of any donation process requires that potential brain-dead donors (PBDD) are detected and referred early to professionals responsible for their evaluation and conversion to actual donors. The intensivist plays a crucial role in organ donation. However, identification and referral of PBDDs may be suboptimal in the critical care environment. Factors influencing lower rates of detection and referral include the lack of specific training and the need to provide concomitant urgent care to other critically ill patients. Excellent communication between the ICU staff and the procurement organization is necessary to ensure the optimization of both the number and quality of organs transplanted. The organ donation process has been improved over the last two decades with the involvement and commitment of many healthcare professionals. Clinical protocols have been developed and implemented to better organize the multidisciplinary approach to organ donation. In this manuscript, we aim to highlight the main steps of organ donation, taking into account the following: early identification and evaluation of the PBDD with the use of checklists; donor management, including clinical maintenance of the PBDD with high-quality intensive care to prevent graft failure in recipients and strategies for optimizing donated organs by simplified care standards, clinical guidelines and alert tools; the key role of the intensivist in the donation process with the interaction between ICU professionals and transplant coordinators, nurse protocol managers, and communication skills training; and a final remark on the importance of the development of research with further insight into brain death pathophysiology and reversible organ damage.

Impact of training on intensive care providers' attitudes and knowledge regarding limitation of life-support treatment and organ donation after circulatory death.

The limitation of life-sustaining treatment is common practice in critical care units, and organ donation after circulatory death has come to be included as an option within this care plan. Lack of knowledge and misunderstandings can raise barriers between health-care providers (e.g., confusion about professional roles, lack of collaboration, doubts about the legality of the process, and not respecting patients' wishes in the decision-making process). The aim of the present study was to determine the knowledge and attitudes of intensive care physicians and nurses before and after a multidisciplinary online training program. A cross-sectional study was performed, and comparisons between the two groups were made using a χ2 -test for categorical data and unpaired t-test or Mann-Whitney rank sum test for continuous data according to its distribution. Training benefited both professional categories, helping nurses to be more open-minded and willing to collaborate, while physicians became more aware of nurses' presence and the need to collaborate with them.

Procalcitonin accurately predicts lung transplant adults with low risk of pulmonary graft dysfunction and intensive care mortality.

PURPOSE: We evaluated the association of procalcitonin (PCT), IL-6-8-10 plasma levels during the first 72h after lung transplantation (LT) with ICU-mortality, oxygenation, primary graft dysfunction (PGD), and one-year graft function after LT. MATERIAL AND METHODS: Prospective, observational study. PCT and IL-6-8-10 plasma levels were measured at 24h, 48h and 72h after LT from 100 lung transplant recipients (LTr). Patients were followed until one year after LT. End-points were ICU survival, grade 3 PGD at 72h and one-year graft function. RESULTS: Higher PCT at 24h was associated with lower PaO2/FIO2 ratio and Grade 3 PGD over the first 72h after LT (p<0.05). PCT at 24h was higher in the 9 patients who died (2.90 vs 1.47ng/mL, p<0.05), with AUC=0.74 for predicting ICU-mortality. All patients with PCT<2ng/mL at 24h following LT, survived in the ICU (p<0.05). PCT and IL-10 at 48h were correlated with FEV1 (rho=-0.35) and FVC (rho=-0.29) one year after LT. (p<0.05). CONCLUSIONS: A breakpoint of PCT<2ng/mL within 24h has a high predictive value to exclude grade 3 PGD at 72h and for ICU survival. Moreover, both PCT and IL-10 within 48h were associated with significantly better graft function one year after surgery.

Successful liver transplantation despite donor-transmitted ESBL-producing Klebsiella pneumoniae infection: Case report and review of the literature.

Donor-derived bacterial infection is a recognized complication of solid organ transplantation. Patients admitted to the intensive care unit are increasingly exposed to infection with multidrug-resistant microorganisms. However, no specific recommendations are available about their suitability as donors. We report a case of donor-transmitted extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infection in a liver recipient, and review the related literature.

Nurses' attitudes and knowledge regarding organ and tissue donation and transplantation in a provincial hospital: A descriptive and multivariate analysis.

The attitudes and knowledge of nursing personnel regarding organ and tissue donation can influence the decision to donate. This study aimed to determine these two factors among nurses at a district hospital in Barcelona, Spain. A survey was carried out using a 35 item questionnaire. Results were subjected to descriptive and comparative statistical analyses using bivariate and multivariate analyses to examine the relation between demographic data and attitudes toward donation. The completion rate was 68.2%, with 98.6% of those responding stating that they were in favor of organ donation. The respondents were unsure as to whether the criteria for inclusion in transplant waiting lists were appropriate (57.5%), whereas 72.2% agreed that brain death is equivalent to death. The bivariate analysis revealed a significant association between a positive attitude toward donation and working on permanent night shift no religious beliefs. Attitudes toward donation among nurses were generally positive; a negative attitude, although attitudes towards donation among the nurses participating in the study were generally positive, it should be pointed out that when a negative attitude does exist this affects significant aspects such as belief in the diagnosis of brain death or the criteria for inclusion on the waiting list, amongst others, which reflects that specific training in donation focused on nurses continues to be needed.

Successful multiple organ donation after donor brain death due to Actinomyces israelii meningitis.

The increasing gap between availability of solid organs for transplantation and the demand has led to the inclusion of donor organs that, according to current guidelines, may be discarded, some of them because of the possibility for transmission of infection to the recipients. We present the first report, to the best of our knowledge, of a case of a brain-dead donor with a localized and treated Actinomyces israelii central nervous system infection who, after a thorough evaluation, provided organs for successful transplant procedures in four recipients. There was no evidence of transmission of infection within a 6-month follow-up. Relative contraindications must be individualized in order to expand the number of real organ donors, emphasizing caution in rare causes for brain death in which patients should be thoroughly evaluated for possible donation.

Related factors to semi-recumbent position compliance and pressure ulcers in patients with invasive mechanical ventilation: An observational study (CAPCRI study).

BACKGROUND: Semi-recumbent position is recommended to prevent ventilator-associated pneumonia. Its implementation, however, is below optimal. OBJECTIVES: We aimed to assess real semi-recumbent position compliance and the degree of head-of-bed elevation in Spanish intensive care units, along with factors determining compliance and head-of-bed elevation and their relationship with the development of pressure ulcers. Finally, we investigated the impact that might have the diagnosis of pressure ulcers in the attitude toward head-of-bed elevation. METHODS: We performed a prospective, multicenter, observational study in 6 intensive care units. Inclusion criteria were patients ≥18 years old and expected to remain under mechanical ventilator for ≥48h. Exclusion criteria were patients with contraindications for semi-recumbent position from admission, mechanical ventilation during the previous 7 days and prehospital intubation. Head-of-bed elevation was measured 3 times/day for a maximum of 28 days using the BOSCH GLM80(®) device. The variables collected related to patient admission, risk of pressure ulcers and the measurements themselves. Bivariate and multivariate analyses were carried out using multiple binary logistic regression and linear regression as appropriate. Statistical significance was set at p<0.05. All analyses were performed with IBM SPSS for Windows Version 20.0. RESULTS: 276 patients were included (6894 measurements). 45.9% of the measurements were <30.0°. The mean head-of-bed elevation was 30.1 (SD 6.7)° and mean patient compliance was 53.6 (SD 26.1)%. The main reasons for non-compliance according to the staff nurses were those related to the patient's care followed by clinical reasons. The factors independently related to semi-recumbent position compliance were intensive care unit, ventilation mode, nurse belonging to the research team, intracranial pressure catheter, beds with head-of-bed elevation device, type of pathology, lateral position, renal replacement therapy, nursing shift, open abdomen, abdominal vacuum therapy and agitation. Twenty-five patients (9.1%) developed a total of 34 pressure ulcers. The diagnosis of pressure ulcers did not affect the head-of-bed elevation. In the multivariate analysis, head-of-bed elevation was not identified as an independent risk factor for pressure ulcers. CONCLUSIONS: Semi-recumbent position compliance is below optimal despite the fact that it seems achievable most of the time. Factors that affect semi-recumbent position include the particular intensive care unit, abdominal conditions, renal replacement therapy, agitation and bed type. Head-of-bed elevation was not related to the risk of pressure ulcers. Efforts should be made to clarify semi-recumbent position contraindications and further analysis of its safety profile should be carried out.

Ventilator-associated pneumonia caused by ESKAPE organisms: cause, clinical features, and management.

PURPOSE OF REVIEW: Despite important geographical variations, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (ESKAPE) pathogens constitute more than 80% of ventilator-associated pneumonia (VAP) episodes. Their clinical importance relies on their virulence and ability in developing mechanisms to decrease susceptibility to antimicrobials, increasing inappropriate therapy and affecting negatively on ICU patients' outcome. This review updates information on VAP due to ESKAPE pathogens. RECENT FINDINGS: Although methicillin-resistant Staphylococcus aureus VAP may be clinically similar to that caused by susceptible strains, it is associated with poorer outcomes despite adequate treatment. Local colonization determines treatment options. The contribution of tracheobronchitis is an important issue. Minimum inhibitory concentration should be considered for nonfermentative Gram-negative bacteria VAP to prescribe extended infusion ß-lactam treatment due to an increase of resistant strains. Strategies promoting antimicrobial diversity may protect against emergence and spread of resistance by ESKAPE pathogens. SUMMARY: VAP due to ESKAPE pathogens represents a global challenge that can be prevented using stewardship programmes promoting diversity.

Effect of antibiotic diversity on ventilator-associated pneumonia caused by ESKAPE Organisms.

BACKGROUND: The aim of this study was to test in the clinic whether antimicrobial diversity affects resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens in ventilator-associated pneumonia (VAP). METHODS: Three different strategies of empirical antimicrobial prescription for VAP were consecutively implemented in an ICU: patient specific (10 months); scheduling, including sequential quarterly prioritization (12 months) and restriction (12 months) of antimicrobials; and mixing (10 months). Periods were compared, measuring the antimicrobial heterogeneity index (AHI). Incidence and resistance patterns of VAP caused by ESKAPE were compared. RESULTS: Overall, 127 microbiologic VAP episodes were documented. ESKAPE VAP increased significantly during scheduling (AHI, 0.65) compared with patient-specific (AHI, 0.88) and mixing (AHI, 0.87) periods (relative risk, 2.67 and 3.84, respectively). This finding was associated with a significant (P < .05) increase of carbapenem-resistant A baumannii during the scheduling period (15.0%) compared with the patient-specific (2.4%) and mixing (0%) periods. ICU mortality of resistant patients with ESKAPE VAP was doubled that of patients without ESKAPE VAP (relative risk, 2.25; 95% CI, 1.67-9.48). Thirty-day mechanical ventilation-free days was significantly increased (5 days) in patients with resistant ESKAPE VAP. CONCLUSIONS: Antibiotic strategies promoting diversity may prevent the emergence of resistance of ESKAPE organisms, improving use of health-care resources.