Chronic critical illness after trauma injury: outcomes and experience in a trauma center.

OBJECTIVE: To determine the prevalence, risk factors and functional results of chronic critical illness (CCI) in polytrauma patients. DESIGN: Single-center observational retrospective study. SETTING: ICU at a tertiary hospital in Santander, Spain, between 2015 and 2019. PATIENTS: Adult trauma patients who survived beyond 48 h after injury. CCI was defined as the need for mechanical ventilation for at least 14 days or tracheostomy for difficult weaning. MEASUREMENTS AND MAIN RESULTS: About 62/575 developed CCI. These patients were characterized by higher ISS score [17 (SD 10) vs. 13.8 (SD 8.2); p < 0.001] and higher NISS (26 (SD 11) vs. 19.2 (SD 10.5); p = 0.001). CCI group had greater proportion of hospital-acquired infections (100% vs. 18.1%; p < 0.001), and acute kidney failure (33.9% vs. 22.8% p < 0.001). During the first 24 h of admission, CCI group required in a greater proportion surgical intervention (50% vs. 29%; p = 0.001), and blood products (31.3% vs. 20.5%; p < 0.047). Hospital ward stay was longer in CCI patients [9.5 days (IQR 5-16.9) vs. 43.9 (IQR 30.3-53) p < 0.001]. The CCI mortality was higher (19.5% vs. 8.1%; p = 0.004). Surgical intervention in the first 24 h (OR 2.5 95% CI 1.1-4.1), age (> 55 years) (OR 2.1 95%CI 1.1-4.2), ISS score (OR 1.1 95%CI 1.02-1.3), GCS score (OR 0.8 95%CI 0.4-23.2) and multiple organ failure (OR 9.5 95%CI 3.9-23.2) were predictors of CCI in the multivariate analysis. CONCLUSIONS: CCI after severe trauma appears in a considerable proportion of patients. Early identification and implementation of specific interventions could change the evolution of this process.

Heart transplantation from controlled donation after circulatory death using thoracoabdominal normothermic regional perfusion and cold storage.

BACKGROUND: Heart transplantation from controlled donation after the circulatory determination of death (cDCDD) may be an option to increase the pool of grafts for transplantation. MATERIALS AND METHODS: Initial experiences on cDCDD heart transplantation were based on the direct procurement of the heart followed by preservation with ex situ perfusion devices. Later, the use of thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as an option to recover hearts. We present a case of a heart transplant using a graft from controlled donation after circulatory death. Cardiac preservation was performed by postmortem TA-NRP followed by cold storage. Ex situ perfusion device was not used. DISCUSSION AND CONCLUSION: This is one of the first published cases of a controlled donation after circulatory death heart retrieved using only TA-NRP and successfully transplanted.

Strict selection criteria in uncontrolled donation after circulatory death provide excellent long-term kidney graft survival.

BACKGROUND: We aimed to report our experience in uncontrolled donation after circulatory death (uDCD) kidney transplantation applying a strict donor selection and preservation criteria. METHODS: All kidney recipients received a graft from a local uDCD. As controls, we included all renal transplants from local standard criteria donation after brain death (SDBD) donors. Normothermic regional perfusion was the preservation method in all cases. RESULTS: A total of 19 kidneys from uDCD donors were included and 67 controls. Delayed graft function (DGF) was higher in the uDCD group (42.1% vs 17.9%; P = .033), whereas no differences were observed in primary nonfunction (0% cases vs 3% controls; P = .605). The estimated glomerular filtration rate was identical in both groups. No differences were observed in graft survival censored for death between the uDCD and the SDBD groups at 1-year (100% vs 95%) or 5-year follow-up (92% vs 91%). uDCD kidney recipients did not have higher risk of graft loss in the multivariate analysis adjusted by recipient age, cold ischemic time, presence of DGF, and second kidney transplant (HR: 0.4; 95% CI 0.02-6; P = .509). CONCLUSIONS: Obtaining renal grafts from uDCD is feasible in a small city and provides similar outcomes compared to standard DBD donors.

Pneumonia versus graft dysfunction as the cause of acute respiratory failure after lung transplant: a 4-year multicentre prospective study in 153 adults requiring intensive care admission.

We aimed to assess the main causes of intensive care unit (ICU) readmissions in lung transplant adults and to identify independent predictors of ICU mortality (primary end-point).This Spanish five-centre prospective cohort study enrolled all lung transplant adults with ICU readmissions after post-transplant ICU discharge between 2012 and 2016. Patients were followed until hospital discharge or death.153 lung transplant recipients presented 174 ICU readmissions at a median (interquartile range) of 6 (2-25) months post-transplant. Chronic lung allograft dysfunction was reported in 39 (25.5%) recipients, 13 of whom (all exitus) had restrictive allograft syndrome (RAS). Acute respiratory failure (ARF) (110 (71.9%)) was the main condition requiring ICU readmission. Graft rejection (six (5.4%) acute) caused only 12 (10.8%) readmissions whereas pneumonia (56 (36.6%)) was the main cause (50 admitted for ARF and six for shock), with Pseudomonas aeruginosa (50% multidrug resistant) being the predominant pathogen. 55 (35.9%) and 69 (45.1%) recipients died in the ICU and the hospital, respectively. Bronchiolitis obliterans syndrome (BOS) stage 2 (adjusted OR (aOR) 7.2 (95% CI 1.0-65.7)), BOS stage 3 (aOR 13.7 (95% CI 2.5-95.3)), RAS (aOR >50) and pneumonia at ICU readmission (aOR 2.5 (95% CI 1.0-7.1)) were identified in multivariate analyses as independent predictors of ICU mortality. Only eight (5.2%) patients had positive donor-specific antibodies prior to ICU readmission and this variable did not affect the model.ARF was the main condition requiring ICU readmission in lung transplant recipients and was associated with high mortality. Pneumonia was the main cause of death and was also an independent predictor. RAS should receive palliative care rather than ICU admission.

Super-refractory nonconvulsive status epilepticus secondary to fat embolism: A clinical, electrophysiological, and pathological study.

BACKGROUND: Fat embolism syndrome (FES) is a rare complication of long-bone fractures and joint reconstruction surgery. To the best of our knowledge, we describe the clinical, electrophysiological, neuroimaging, and neuropathological features of the first case of super-refractory nonconvulsive status epilepticus (sr-NCSE) secondary to fat embolism. CLINICAL CASE: An 82-year-old woman was transferred to our intensive care unit because of a sudden decrease of consciousness level, right hemiparesis, and acute respiratory failure in the early postoperative period of knee prosthesis surgery. Brain computed tomography (TC) including angio-CT and CT perfusion was normal. An urgent video-electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform discharges ceased after the administration of 5mg of intravenous diazepam, and background activity constituted by diffuse theta waves was observed without clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring was also started. Despite antiepileptic therapy, epileptiform activity recurred after the interruption of profound sedation, and valproate and lacosamide were added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small scattered foci of acute ischemic infarcts and diffuse petechiae involving the basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super-refractory nonconvulsive status epilepticus remained without control for 2 weeks. Finally, the patient died. The clinical autopsy revealed a bilateral lung fat embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty lesions were also seen in the intestine and pancreas. Scattered microscopic cerebral infarcts associated with fat emboli in the capillaries were noticed, affecting both supra- and infratentorial structures. In addition, occasional focal areas of ischemic injury showing filiform neurons with reactive astrocytic gliosis background consistent with acute lesions were observed in CA3. CONCLUSIONS: Fat embolism should be considered a potential cause of sr-NCSE. This article is part of a Special Issue entitled "Status Epilepticus".

Aggressive lung donor management increases graft procurement without increasing renal graft loss after transplantation.

BACKGROUND: To determine the impact of an aggressive protocol on the rate of lung grafts available for transplant. We analyzed the impact of this management on kidney graft survival after kidney transplantation. METHODS: A cohort study. Lung donors and kidney recipients from 2009 and 2010 were considered the prospective cohort with 2003-2008 as the historical control period. The number of lungs available for transplantation was the main outcome measures. For recipients, kidney graft survival was the main outcome measure. RESULTS: We quadrupled the number of lung donors in the period 2009-2010 compared with the historical control. Management in the prospective cohort included higher use of positive end-expiratory pressure (PEEP) (p < 0.0001), increased use of hormonal resuscitation therapy (HRT) (p < 0.0001), and lower level of central venous pressure (p < 0.05) than historical control. The probability of renal graft survival at one yr after transplant was 88.6% (CI 95%: 74.8-95.1) in historical control and 94.7% (CI 95%: 81-98.7%) in the prospective cohort (p = 0.226). CONCLUSIONS: Aggressive management strategy in potential lung donors, which includes ventilator recruitment maneuvers, PEEP ≥ 8 cm H(2)O, the use of HRT, and restrictive fluid balance increases the rate of lung grafts available for transplantation without adverse effect on kidney graft survival.

Effect of neuroprotective therapies (hypothermia and cyclosporine a) on dopamine-induced apoptosis in human neuronal SH-SY5Y cells.

INTRODUCTION: This study aimed to evaluate the effect of hypothermia and CyA on neuronal survival after induced injury in a neuronal model. METHODS: Human neuroblastoma SH-SY5Y cells were seeded and allowed to grow. To determine whether lower temperatures protect from dopamine-induced apoptosis, cells were treated with dopamine at 100 µM, at 300 µM or without dopamine and incubated at 32 °C or 37 °C for 24 hours. To assess the effect of CyA, cells were pre-incubated with CyA at 37 °C and after dopamine was added. RESULTS: After 24 hours of incubation at 37 °C, 100 µM and 300 µM dopamine induced 42% (SD = 21) and 58% (SD = 7.9) apoptotic SH-SY5 cells, respectively. In cultures at 32 °C dopamine-induced apoptosis could be reversed by hypothermia [7% (SD = 1.4) and 3.45% (SD = 1.1) for 100 µM and 300 µM, respectively], similar to levels obtained in non-treated cells [2.4% (SD = 1.5)]. Cyclosporine A treatment did not render the expected result, since CyA-pre-treated cells and SH-SY5Y cells showed higher levels of apoptosis than those observed with dopamine alone CONCLUSIONS: Hypothermia has a marked protective effect against apoptotic cell death induced by dopamine in a human neuroblastic cell line. The neuroprotective effect of CyA described with other apoptotic cell death stimuli was not demonstrated with our experimental conditions.

Controlled Donation After Circulatory Death Program: Analysis and Results at a Tertiary Care Hospital.

BACKGROUND: The objective of the study was to evaluate the impact in organs obtained and transplanted from controlled donation after circulatory death (cDCD). METHODS: Transplants from cDCD donors performed at the Hospital Universitario Marqués de Valdecilla from the beginning of the program (December 2013) to December 2020 were evaluated. All procedures were performed with normothermic regional perfusion. Donors after brain death (DBDs) during the same period were used as a control group. RESULTS: A total of 95 donors after cardiac death and 152 DBDs were included. Age was similar in both groups (60 years [IQR, 53-68 years vs 62 years {IQR, 51-79 years]; P = .390). The number of organs recovered per donor was higher in the DBD group (4 [IQR, 3-5] vs 3 [IQR, 2-4], P < .001], as well as the number of transplanted organs (4 [IQR, 2-4] vs 2 [IQR, 2-4]; P = .002]. However, the number of noneffective donors was similar. DBDs presented a higher rate of liver donation (30.5% vs 46.7%; P = .012), lung donation (25.3% vs 38.2%; P = .036), and cardiac donation (1.1% vs 21.7%; P < .001) with respect to the donors after cardiac death group, but kidney and pancreatic donation were similar. CONCLUSIONS: The cDCD with normothermic regional perfusion program is fully established in our center. The age of the cDCD donor has increased with experience and it is currently identical to the control group (DBD). After overcoming the learning curve, cDCD is a multiorgan donation that presents an excellent profitability in the number of organs extracted and transplanted.

Malignancies in Deceased Organ Donors: The Spanish Experience.

BACKGROUND: To better define the risk of malignancy transmission through organ transplantation, we review the Spanish experience on donor malignancies. METHODS: We analyzed the outcomes of recipients of organs obtained from deceased donors diagnosed with a malignancy during 2013-2018. The risk of malignancy transmission was classified as proposed by the Council of Europe. RESULTS: Of 10 076 utilized deceased donors, 349 (3.5%) were diagnosed with a malignancy. Of those, 275 had a past (n = 168) or current (n = 107) history of malignancy known before the transplantation of organs into 651 recipients. Ten malignancies met high-risk criteria. No donor-transmitted cancer (DTC) was reported after a median follow-up of 24 (interquartile range [IQR]: 19-25) mo. The other 74 donors were diagnosed with a malignancy after transplantation. Within this group, 64 donors (22 with malignancies of high or unacceptable risk) whose organs were transplanted into 126 recipients did not result in a DTC after a median follow-up of 26 (IQR: 22-37) mo, though a prophylactic transplantectomy was performed in 5 patients. The remaining 10 donors transmitted an occult malignancy to 16 of 25 recipients, consisting of lung cancer (n = 9), duodenal adenocarcinoma (n = 2), renal cell carcinoma (n = 2), extrahepatic cholangiocarcinoma (n = 1), prostate cancer (n = 1), and undifferentiated cancer (n = 1). After a median follow-up of 14 (IQR: 11-24) mo following diagnosis, the evolution was fatal in 9 recipients. In total, of 802 recipients at risk, 16 (2%) developed a DTC, which corresponds to 6 cases per 10 000 organ transplants. CONCLUSIONS: Current standards may overestimate the risk of malignancy transmission. DTC is an infrequent but difficult to eliminate complication.

Thyroid panel reference intervals in healthy children and adolescents: A Spanish cohort.

OBJECTIVES: In children, thyroid hormones are essential for correct physical and neurological development. The recommended process for defining reference intervals (RIs) is the direct approach; however, indirect methods are an effective alternative. This study aimed to explore age- and sex-dependent relationships between serum concentrations of thyroid hormones in a large population-based cohort of healthy Spanish Caucasian children and calculate RIs. MATERIAL AND METHODS: Results of serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were collected from laboratory data of N (TSH = 23201; fT4 = 20728) patients aged 1 month - 15 years. These results were validated with a prospective study. Analyses of serum concentrations of TSH and fT4 were performed on ARCHITECT i2000 (Abbott Diagnostics, US). Percentiles (2.5th to 97.5th) were determined for each variable and taken as the RI. RESULTS: No difference was found between serum TSH concentrations in male and female children of all age groups. A difference between serum fT4 concentrations in males and females and an age-dependent correlation for both sexes were found. CONCLUSION: There is very little consensus on RIs in children. Our data confirm it is possible to use data mining techniques to calculate reliable and clinically useful RIs.

Serum levels of S100B from jugular bulb as a biomarker of poor prognosis in patients with severe acute brain injury.

AIMS/BACKGROUND: To evaluate the correlation between protein S100B concentrations measured in the jugular bulb as well as at peripheral level and the prognostic usefulness of this marker. METHODS: A prospective study of all patients admitted to the intensive care unit with acute brain damage was carried out. Peripheral and jugular bulb blood samples were collected upon admission and every 24h for three days. The endpoints were brain death diagnosis and the Glasgow Outcome Scale score after 6months. RESULTS: A total of 83 patients were included. Jugular protein S100B levels were greater than systemic levels upon admission and also after 24 and 72h (mean difference>0). Jugular protein S100B levels showed acceptable precision in predicting brain death both upon admission [AUC 0.67 (95% CI 0.53-0.80)] and after 48h [AUC 0.73 (95% CI 0.57-0.89)]. Similar results were obtained regarding the capacity of jugular protein S100B levels upon admission to predict an unfavourable outcome (AUC 0.69 (95% CI 0.56-0.79)). The gradient upon admission (jugular-peripheral levels) showed its capacity to predict the development of brain death [AUC 0.74 (95% CI 0.62-0.86)] and together with the Glasgow Coma Scale constituted the independent factors associated with the development of brain death. CONCLUSION: Regional protein S100B determinations are higher than systemic determinations, thus confirming the cerebral origin of protein S100B. The transcranial protein S100B gradient is correlated to the development of brain death.

Influence of specific thoracic donor therapy on kidney donation and long-term kidney graft survival.

OBJECTIVE: To analyze the impact of a specific thoracic donor-treatment protocol (including restrictive fluid balance) on kidney donation and on kidney graft survival. METHODS: A cohort study. Lung Donors and kidney recipients from 2003 to 2008 were the pre-protocol cohort, and those from 2009 to 2013 were the protocol cohort. The main outcome variables were graft survival and rate of kidney donation. RESULTS: Kidney donation rates were similar in both periods (86.2 vs. 86.2 %; p > 0.05). Both donors and kidney recipients were older and with more comorbidities in the protocol group and this is the reason there were more cases of delayed graft function (differences not statistically significant) and with higher sequential creatinine levels of kidney recipients during the protocol period. However, graft survival was similar in both groups. The probability of graft survival 5 years after transplantation was 0.75 (95 % confidence interval 0.65-0.85) in the pre-protocol cohort and 0.81 (0.70-0.92) in the protocol cohort. CONCLUSIONS: Specific treatment for multi-organ donors including restrictive fluid balance does not affect kidney donation or kidney graft loss, and has no impact on long-term viability. Hemodynamics must be closely monitored by medical personnel with specific training.

Apoptosis of Jurkat cells induced by serum of patients with acute severe brain injury.

OBJECTIVE: To investigate the capacity of serum samples draining from the neuronal lesions to induce apoptosis of the lymphoid Jurkat cells in vitro and to analyze whether this effect is related to patient outcome. DESIGN AND SETTING: Prospective clinical investigation in a 21-bed intensive care unit (ICU) in a university hospital. PATIENTS: Forty-two patients who had suffered from acute brain injury (traumatic brain injury or spontaneous intracranial hemorrhage) requiring intensive care. INTERVENTIONS: Blood samples were obtained simultaneously from jugular bulb vein (regional) and from central venous catheter (systemic) on admission to the ICU and after 24, 48, and 72 h. Jurkat cells were incubated in the presence of 10% of heat-inactivated patients sera. The percentages of apoptotic cultured cells was measured by staining with annexin V and propidium iodide. MEASUREMENTS AND RESULTS: Regional serum draining from the lesions induced higher percentages of early and late apoptotic cells than systemic serum. The apoptotic effect was clearer with the sera from the patients who developed brain death. The apoptotic effect maintained a relationship with the mortality and the functional outcome at 6 months after the injury. CONCLUSIONS: Despite being performed on lymphoid cells because of the easier technical handling, our data help to elucidate the role of apoptosis for brain damage in acute brain injury. This and other undergoing studies on neuronal cells will enhance the understanding and management of apoptotic cell death in patients with acute brain injury admitted to the ICU.

Un caso particular de broncoaspiración de cuerpo extraño en el paciente politraumatizado / An unusual case of bronchoaspiration of a foreign body in a polytraumatized patient

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Hemoptisis como manifestación de la ectopia torácica de cálculos biliares / Hemoptysis as a Manifestation of Gallstone Ectopia in the Lungs

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