[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Improving the Outcomes of Organs Obtained From Controlled Donation After Circulatory Death Donors Using Abdominal Normothermic Regional Perfusion.

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients' outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty-seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty-seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1-year death-censored kidney survival was 91%, and delayed graft function rate was 27%. The 1-year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.

Experience of a Maastrich type II non heart beating donor program in a small city: preliminary results.

OBJECTIVE: To study the results of a non-controlled cardiac death (Maastricht type II) donor program in a city of 200,000 inhabitants. The study was initially focused on lung donation and was extended to kidney donation after 9 months. DESIGN: A prospective observational study was conducted between October 2012 and December 2013. SETTING: The Intensive Care Unit of Marqués de Valdecilla University Hospital in Santander (Spain), and surrounding areas. POPULATIONS: Patients (< 55 years) who died of out-of-hospital cardiac arrest. INTERVENTIONS: All out-of-hospital cardiac arrests were treated with mechanical cardiac compression (LUCAS II). The diagnosis of death and organ preservation were performed in the ICU. RESULTS: A total of 14 calls were received, of which three were discarded. Of the 11 potential donors, 7 were effective donors with a median age of 39.5 years (range: 32-48). A total of 5 single lung transplants and four kidney transplants were performed. In addition, corneas and tissues were harvested. The non-valid donors were rejected mainly due to technical problems. There were no donation refusals on the part of the patient relatives. The lung transplant patient survival rate was 100% after one month and 80% after one year. One month after transplantation, the kidney recipients had a serum creatinine concentration of<2mg/dl. The interval from cardiac arrest to renal preservation was 80minutes (range: 71-89), and the interval from cardiac arrest to lung preservation was 84minutes (range: 77-94). CONCLUSIONS: A Maastricht type II donation program in a small city is viable for both abdominal and thoracic organs. The program was initially very cautious, but its potential is easily improvable by increasing donor and by equipping mobile ICU ambulances with mechanical cardiac compression systems. Full management of the donor in the ICU, avoiding the emergency department or operating rooms, reduces the warm ischemia time, thereby improving transplant outcomes.

Effects of antibiotic administration delay and inadequacy upon the survival of septic shock patients.

OBJECTIVE: To assess how antibiotic administration delay and inadequacy influence survival in septic shock patients. DESIGN: A prospective, observational cohort study was carried out between September 2005 and September 2010. SCOPE: Patients admitted to the ICU of a third level hospital. PATIENTS: A total of 342 septic shock patients INTERVENTIONS: None VARIABLES OF INTEREST: The time to antibiotic administration (difference between septic shock presentation and first administered dose of antibiotic) and its adequacy (in vitro susceptibility testing of isolated pathogens) were determined. RESULTS: ICU and hospital mortality were 26.4% and 33.5%, respectively. The median delay to administration of the first antibiotic dose was 1.7h. Deceased patients received antibiotics significantly later than survivors (1.3±14.5h vs. 5.8±18.02h; P=.001). Percentage drug inadequacy was 12%. Those patients who received inadequate antibiotics had significantly higher mortality rates (33.8% vs. 51.2%; P=.03). The coexistence of treatment delay and inadequacy was associated to lower survival rates. CONCLUSIONS: Both antibiotic administration delay and inadequacy exert deleterious effects upon the survival of septic shock patients, independently of their characteristics or severity.

[Antifungal prophylaxis in the postoperative period of lung transplant surgery in Spain]. / Profilaxis antifúngica en el postoperatorio de trasplante de pulmón en España.

OBJECTIVES: To examine the type and duration of antifungal prophylaxis provided during the postoperative period of lung transplant recipients, together with the most frequent complications during admission to Intensive Care Units in Spain. PATIENTS AND METHODS: A questionnaire was developed including demographic data on each transplant center, the type of antifungal prophylaxis used, its duration, and the most frequent complications. The questionnaire was distributed among the 7 Spanish national lung transplant centers, followed by analysis of the results obtained. RESULTS: All 7 centers completed the questionnaire. All of them provided universal prophylaxis in lung transplant patients. Monotherapy was the most widely used protocol (5/7; 71.4%), with amphotericin B in liposomal or conventional form being the most frequent drug, administered via the inhalatory route. In the case of combination therapy, a great diversity of drugs was observed. The most frequently administered second choice drug was anidulafungin (3/7; 43%), followed by voriconazole (2/7; 28.5%). Antifungal therapy was maintained on an indefinite basis by 43% of the centers. Invasive fungal infection (IFI) in the postoperative period of transplantation during admission to the Intensive Care Unit was suspected in 5-10% of the cases but was confirmed in less than 5%. Among other complications registered in these patients in the Intensive Care Unit, the most frequent problems were respiratory infections (5/7; 71.5%). CONCLUSIONS: Antifungal prophylaxis during the postoperative period of lung transplantation is provided on a universal basis, though consensus is lacking as to the drug of choice, the administration route and the duration of such treatment.

Early identification of infectious complications in lung transplant recipients using procalcitonin.

OBJECTIVES: The purpose of this study was to determine how sequential measurements of procalcitonin (PCT) could improve the diagnosis of early infectious complications after lung transplantation, and to compare this molecule with other commonly used markers (serum C-reactive protein [CRP] and leukocyte count). METHODS: Prospective observational study in a 34-bed university hospital intensive care unit (ICU). All lung transplant (LT) recipients between January and November 2010 were included. Biomarkers were measured just before surgery, on ICU admission, and daily on postoperative days 2, 3, 4, and 7. RESULTS: A total of 25 patients were included. Those patients with infectious complications presented with significantly higher levels of PCT as early as the first day after transplantation and during subsequent days. The area under receiver operating characteristic curve for PCT as a predictor of infection ranged between 0.83 and 0.97. PCT cutoff of 8.18 ng/mL on day 2 had a sensitivity of 80% and specificity of 100% for prediction of infection development. Neither CRP levels nor leukocyte count could discriminate between the patients with and without infections at any time. CONCLUSIONS: In contrast with CRP levels and leukocyte counts, measurement of PCT appears to be a useful diagnostic tool in detecting early infectious complications in LT patients.

[Primary graft dysfunction after lung transplantation]. / Disfunción primaria del injerto tras el trasplante pulmonar.

Lung transplantation is a therapeutic option for pulmonary diseases in which the other treatment options have failed or in cases of rapid disease progression. However, transplantation is not free from complications, and primary graft dysfunction is one of them. Primary graft dysfunction is a form of acute lung injury. It characteristically develops during the immediate postoperative period, being associated to high morbidity and mortality, and increased risk of bronchiolitis obliterans. Different terms have been used in reference to primary graft dysfunction, leading to a consensus document to clarify the definition in 2005. This consensus document regards primary graft dysfunction as non-cardiogenic pulmonary edema developing within 72 hours of reperfusion and intrinsically attributable to alteration of the lung parenchyma. A number of studies have attempted to identify risk factors and to establish the underlying physiopathology, with a view to developing potential therapeutic options. Such options include nitric oxide and pulmonary surfactant together with supportive measures such as mechanical ventilation or oxygenation bypass.

Solid organ transplant training objectives for residents.

With the aim of analyzing the current state of the educational objectives in the training of medical residents in solid organ transplantation (SOT), we conducted a review of the status of the official programs of the specialities involved in SOT, focusing particularly on lung transplantation. A survey of medical residents was also conducted to allow reflexion about the topic. We obtained 44 surveys from 4 University Hospitals with active programs in SOT, mainly from intensive care medicine and anesthesiology residents. We detected an important number of courses oriented to organ donation but very limited in terms of basic training in the management of the immediate postoperative period, principles of immunosuppression and updates on immunosuppressive therapy and complications (particularly rejection and infection). We also identified that these educational aspects should be directed not only to medical residents from specialities with a close retation to SOT, but also to all who may at some time have a relation to such patients. The use of information and communication techniques (ICTs), on-line courses and also simulations should be instruments to take into account in the biomedical training of medical residents. We conclude that we need a specific training program in complications of SOT, as well as fundamental principles in immunology and immunosuppressor pharmacology.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

[Lung transplantation using donors 55 years and older]. / Trasplante pulmonar con donantes de edad marginal (≥ 55 años).

OBJECTIVE: We analyzed short, medium and long-term mortality in transplant recipients who received lungs from donors aged 55 years or more. PATIENTS AND METHODS: All patients who underwent lung transplantation from donors aged 55 years or more were included. The association between the different study variables and early death and death at 1 year and 5 years was studied. A logistic regression model was used to study the association between early death and variables with a trend towards significance (P<.2) in the bivariate analysis. The risk factors for mortality at 1 year and 5 years were analyzed with a Cox regression model. The Kaplan-Meier method was used to analyze survival. RESULTS: A total of 33 patients were included. The probability of survival was 90.9%, 78.5% and 44.8% at 1 month, 1 year, and 5 years after lung transplantation, respectively. The elevated age of the recipient (P=.16) and single-lung transplantation (P=.09) were the variables associated to or with a trend towards significant associations with mortality. CONCLUSIONS: The final decision to accept a lung graft should be based on individual evaluation of each donor and recipient. However, given the lack of lung donors, donors aged 55 years or more should be considered for lung transplantation.

Prognostic factors and outcome after drowning in an adult population.

BACKGROUND: Drowning remains an actual problem. Although medical assistance has improved, it still has high rates of morbidity and mortality. We set out to explore the clinical characteristics and outcome of drowning patients admitted to the intensive care unit (ICU) of tertiary-care university hospital. METHODS: We designed a retrospective observational study to analyse all drowning patients admitted to our ICU after successful cardiopulmonary resuscitation. The study was conducted during 1 January 1992-31 December 2005. There was no exclusion. We used a univariate analysis to evaluate the effect on patient and management characteristics on survival. RESULTS: There were 43 patients (five children and 38 adults), with male predominance. Fifteen patients, all adults (34.9%), died. Submersion time, age, Glasgow Coma Score (GCS), pupillary reactivity and acute physiology and chronic health evaluation (APACHE II) at ICU admission were related to mortality. Non-survivors presented a higher glycaemia level at ICU admission than survivors (P=0.005). CONCLUSIONS: The outcome is closely related to the patient's clinical status on arrival to the hospital. We have found that submersion time, age, GCS, pupillary reactivity and APACHE II at ICU admission were related to mortality. Further research in prospective studies is needed.

[Brain abscess in a third-level hospital: epidemiology and prognostic factors related to mortality]. / Abscesos cerebrales en un hospital de tercer nivel: epidemiología y factores que influyen en la mortalidad.

OBJECTIVE: To document the epidemiology, causes, treatment and prognostic factors associated with mortality of patients with brain abscess in a tertiary medical center. METHODS: Observational retrospective cohort study of patients with cerebral abscess admitted at a tertiary hospital during 13 years. RESULTS: The case records of 71 patients admitted to a tertiary hospital between January 1992 and December 2005 and diagnosed of brain abscess were review. Brain abscess occurred at all ages, more frequently in men than in women. Fever, headache and altered mental status were common presenting symptoms. The most common site of infection was the frontal lobe (28 patients). Seventeen patients had multiple abscesses. Staphylococcal infection was seen most commonly. Computed tomography provided sufficient diagnostic information in all cases. Twenty six patients had early surgical drainage. Thirty four patients were admitted to the intensive care Unit (ICU). The overall mortality was 21% (15 patients), all of that related to the infection. Six patients died in ICU. More than 65 years of age (OR, 1.0; CI 95%, 1.0-1.1), medical treatment without surgery (OR, 8.9; CI 95%, 1.1-73.8), presence of multiple abscesses, (OR, 6.0; CI 95%, 1.0-34.9), immunosuppression (OR, 21.5; CI 95%, 2.9-157.2) and delay in starting antibiotherapy (OR, 1.5 per day of delay; CI 95%, 1.0-2.1) were independent predictors of in-hospital death. CONCLUSIONS: In spite of improvement in diagnosis and treatment of patients with cerebral abscess, mortality is still high. Factors related to patient underlying diseases and the delay in the start an antibiotic treatment were associated with increased mortality (50% increase of mortality risk per day in the delay of starting antibiotherapy).

Static Cold Storage vs Ex Vivo Machine Perfusion: Results From a Comparative Study on Renal Transplant Outcome in a Controlled Donation After Circulatory Death Program.

INTRODUCTION: We aimed to evaluate if ex vivo machine perfusion could minimize the negative impact of cold ischemia on those renal grafts obtained from controlled donation after circulatory death (cDCD). MATERIAL AND METHODS: Prospective observational paired study of kidney transplants from cDCD performed in our center. The kidney from each pair preserved on ice was transplanted first within the first few hours following procurement, while the contralateral kidney was machine-perfused with a LifePort device (Organ Recovery Systems, Brussels, Belgium) and transplanted the following day. RESULTS: A total of 12 cDCDs were included. No differences were observed in delayed graft dysfunction or graft survival between the 2 groups. CONCLUSION: The use of ex vivo perfusion devices is simple and they do not require any large infrastructural or high economic investments, considering the fact that it allows a better selection of recipients and viable organs no longer need to be discarded because of prolonged warm ischemia times.

Results After Implementing a Program of Intensive Care to Facilitate Organ Donation.

A program of intensive care to facilitate organ donation (ICOD) represents one of the ways to increase donation rate following brain death (BD). OBJECTIVES: To analyze the impact and cost-effectiveness of setting up an ICOD strategy. METHOD: Retrospective cases of BD donors from the Spanish region La Rioja were included, after implementation of an ICOD program (2011-2016). This was activated in cases of devastating neurologic injury where treatment had been rejected following therapeutic futility criteria. Follow-up of kidney and liver transplant patients with the obtained grafts was carried out. RESULTS: A total of 134 potential donors were admitted to intensive care unit (ICU), of whom 106 were selected under the ICOD strategy. BD was diagnosed in 108 cases (25 conventional donors, 83 ICOD donors). A total of 21.6% of potential ICOD donors did not evolve to BD, subsequently dying in the ICU. ICOD cases accounted for more than 50% of donors each year. This cohort had an average stay of 2.4 days in the ICU and accounted for a small proportion of total ICU admissions. A total of 68 (81.9%) ICOD donors were finally effective and 146 grafts were extracted, the majority being abdominal organs (liver and kidney). Probability of survival 1 year after liver transplant (ICOD donor) was 90.9%, with 1 case of primary graft failure. Survival 1 year after kidney transplant (ICOD donor) was 92.7%. No differences were detected in survival rates of kidney and liver transplant patients regarding donor type (ICOD vs conventional). CONCLUSIONS: Implementation of an ICOD program allows an increase in the pool of valid and quality grafts for transplant as well as implying a minimum consumption of intensive medicine resources. The results in transplant patients support this strategy.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

Influence of donor-recipient gender mismatch in early outcome after lung transplantation.

OBJECTIVE: Donor and recipient genders are not considered in lung transplantation (LT) programs. However, recent data have suggested a possible biologic effect of gender combination on the outcome of LT. We ought to evaluate the effect of gender combinations on early survival in a single-institution experience in transplant recipients. METHODS: We analyzed the potential effect of donor-recipient gender combinations (male [M] or female [F]) on early survival of all patients whose LTs were performed between January 1999 and December 2006. Patients were distributed into 4 groups: M donor to M recipient (M-M group); M donor to F recipient (M-F group); F donor to F recipient (F-F group); and F donor to M recipient (F-M group). The comparison between groups was performed using two-tailed Fisher exact test and analysis of variance (ANOVA). RESULTS: During the study period, 152 LTs were performed in 149 patients, including 99 male donors and 53 female donors. The mean age of the recipients was 54 +/- 10 years (range, 14-70). The 30-day survival rate was 86% (95% confidence interval [CI], 77%- 92%) for the M-M group, 67% (95% CI, 41%-87%) for the F-M group, 89% (95% CI, 52%-100%) for the M-F group, and 83% (95% CI, 66%-93%) for the F-F group. No differences were observed between group survivals according to the Fisher test (P = .27). CONCLUSIONS: We found no association between donor-recipient gender mismatch and improved survival in lung transplant recipients. Further investigation is needed to finally understand the possible role of gender combinations in LT.

Conditioned blocking is re-established by neurotransplantation in mature rats.

Aging has been associated with a decay of hippocampal function that may begin well before senescence. Conditioned blocking is a complex learning phenomenon that requires an intact hippocampus in young-adult rats and is absent in middle-aged rats. The aim of the present study was to test the possibility of re-establishing conditioned blocking in 17-month-old Wistar rats by neurotransplantation. Solid embryonic hippocampal or nigral tissue was bilaterally transplanted in the proximity of the dorsal hippocampus (lateral ventricle and alveus). Conditioned blocking of an aversion to a cider vinegar (3%) solution presented in compound with a previously conditioned saccharin solution (0.1%) appeared 14 days after transplantation and persisted 3 months later only in the hippocampal grafted group, showing the possibility of restoring age-related cognitive deficits.

Differential effects of bicuculline and muscimol microinjections into the nucleus basalis magnocellularis in taste and place aversive memory formation.

The role of the nucleus basalis magnocellularis (NBM) in learning and memory has been demonstrated in different learning paradigms such as conditioned taste aversion (CTA) and inhibitory avoidance (IA). This participation has been related to the cholinergic system, but recent studies have reported the potential role of other neurotransmitters such as GABA. The effects of acute intracerebral administration of the GABAergic antagonist bicuculline (0.05 microg) and the GABAergic agonist muscimol (0.05 microg) into the NBM of male Wistar rats were assessed in CTA and IA learning. In both learning tasks, the drug administration was performed before the acquisition. Taste aversion learning was not affected by the infusion of any of the drugs administered. IA acquisition was not affected by the administration of bicuculline or muscimol, requiring similar number of trials to reach the learning criterion. However, when the rats were tested 24 h later, those injected with bicuculline or muscimol showed an impairment of the IA learning. The present results support a role of the GABAergic system in the consolidation process of IA learning.

Development of a simple and sensitive technique for detection of point mutations in the K-ras oncogene.

We sought to develop a simple and sensitive method based on mutant allele-specific amplification (MASA) for the detection of point mutations in the k-ras oncogene in blood samples. We used MASA and three nested MASA methods to detect a point mutation (GGT-->GAT) in rat DHD cells at codon 12 of exon 1 of the k-ras gene. MASA allowed us to detect one k-ras mutated cell on a background of 10(7) normal cells. The third nested-MASA (nested-MASA.c) method that we developed allowed us to detect one mutated cell among 10(10) normal cells. Our methods should allow the detection of small amounts of mutant k-ras DNA in tissue, serum, and plasma, combining speed with efficiency and specificity.