[Challenge in modern intensive care: chronic critical illness - pathophysiology and therapeutic options]. / A modern intenzív terápia kihívása: az elhúzódó kritikus állapot kórélettani háttere és terápiás lehetoségei.

The recent developments in intensive care have resulted in improved survival rates of patients treated with acute organ deficiency. As a consequence, the rate of those who survive the acute phase and subsequently require protracted organ support due to persisting organ dysfunction has been growing. Several survivors display chronic health status deterioration leading to prolonged rehabilitation or nursing, and repeated hospitalizations. The condition developed following the survival of the acute phase and requiring long-lasting intensive care is frequently termed as chronic critical illness (CCI). Several definitions exist, most of these are based on the number of ventilator days, or days of stay at the intensive care unit. Nevertheless, in spite of the initially heterogenous etiology of the acute illness, the complications associated with CCI, as well as the pathophysiological processes underlying these, are relatively uniform. This causes CCI to be a unique clinical syndrome characterized by the development of secondary infections, myopathy, central and peripheral neuropathy, and typical alterations of the hormonal and immune system functions. The outcome is heavily influenced by the frailty and comorbidities of the patient, in addition to the severity of the acute illness. The treatment of CCI patients presents a complicated task requiring multidisciplinary view and individualized therapeutic measures. Since the aging of the population and the continuously improving success rates in overcoming acute conditions also facilitate the development of CCI, the systematic overview of the underlying pathophysiological processes is pivotal for the optimization of the medical, nursing, social and economical burden presented by this syndrome. Orv Hetil. 2023; 164(18): 702-712.

Endocrine Management and Hormone Replacement Therapy in Cardiac Donor Management: A Retrospective Observational Study.

BACKGROUND: Pituitary dysfunction after brainstem death can cause various hormone deficiencies in potential heart donors. The aim of this study was to evaluate the relationship between hormone replacement therapy (HRT; including antidiuretic hormone analog, thyroid hormone, and methylprednisolone) in heart donors and the recipients' outcomes after heart transplantation (HTx). METHODS: We retrospectively analyzed HTxs performed between January 2012 and October 2018. Donor and recipient characteristics were retrieved with a focus on endocrine parameters and HRT. The primary outcome was primary graft dysfunction (PGD). Secondary outcomes were the 30-day and 2-year mortality of the recipients. Univariate and multivariate Cox regression analyses were applied. RESULTS: The study included 297 HTxs. PGD occurred in 56 recipients (18.9%). In the multivariable Cox analysis, methylprednisolone and thyroxine treatment in donors were associated with a lower odds for PGD (odds ratio [OR], 0.43; 95% CI, 0.19-1.01; P = .052; and OR,: 0.34; 95% CI, 0.15-0.76; P = .009, respectively). In multivariate analysis, thyroxine treatment in donors was associated with a lower odds of PGD (OR, 0.38; 95% CI, 0.17-0.86; P = .020). Donor thyroxine supplementation also had a beneficial effect on recipients' 2-year survival (OR, 0.53; 95% CI, 0.29-0.96; P = .036). CONCLUSIONS: Combined thyroxine and methylprednisolone treatment could be a protective factor against PGD. Thyroxine administration was associated with better 2-year survival in recipients.

Preoperative nutritional state is associated with mid- and long-term mortality after cardiac surgery.

BACKGROUND: The frailty score has been developed to determine physiological functioning capacity. The aim of our research was to explore the relationship between frailty factors and mortality in cardiac surgery patients. METHODS: Our research is an observational, single-center, prospective cohort study (registered on ClinicalTrials.gov: NCT02224222), and we studied 69 patients who underwent elective cardiac surgery between 2014 and 2017. Thirty days before the surgery, they completed a questionnaire that contained questions related to social support, self-reported life quality-happiness, cognitive functions, anxiety and depression. Demographic, anthropometric and medical data were widely collected. The Geriatric Nutritional Risk Index (GNRI) and the Comprehensive Geriatric Assessment (CGA)-based frailty index were calculated as a sum and the domains, respectively. Cox regression and the Kaplan-Meier tests were applied to analyze survival and relative risk. The primary outcome was mid-term mortality. RESULTS: The patients' mean age was 65.43 years [standard deviation (SD): 9.81 years]. The median follow-up was 1,656 days of survival [interquartile range (IQR), 1,336-2,081 years], during this period 14 patients died. The median of EuroSCORE II was 1.56 (1.00-2.58) points. The median preoperative albumin level was 32.80 g/L (IQR, 29.9-35.8 g/L). Major adverse cardiovascular and cerebral events (MACCEs) occurred 7 times during follow-up. The nutrition score of the CGA was significantly associated with worse long-term survival [score; hazard ratio (HR): 5.35; 95% CI: 1.10-25.91, P=0.037]. After adjustment for EuroSCORE II and postoperative complications the noncardiovascular CGA score was associated with overall mortality [adjusted hazard ratio (AHR): 1.44, 95% CI: 1.02-2.04, P=0.036]. In the multivariable Cox regression, GNRI <91 showed an increased risk for mortality (AHR: 4.76, 95% CI: 1.52-14.92, P=0.007). CONCLUSIONS: The CGA-based noncardiovascular score and nutritional status should be assessed before cardiac surgery prehabilitation and may help decrease long-term mortality.

Perioperative Low Tetraiodothyronine Levels and Adverse Outcomes After Heart Transplantation: A Retrospective, Observational Study.

OBJECTIVES: Thyroid dysfunction has been shown to be associated with increased all-cause mortality and severity of chronic heart failure in critical illness and severe cardiac diseases. The present study was conducted to ascertain the relationship between perioperative free triiodothyronine and free tetraiodothyronine (fT4) levels and postoperative adverse outcomes after heart transplantation (HTX). DESIGN: Retrospective, observational study. SETTING: Single-center study in a quaternary care university clinical center. PARTICIPANTS: The study comprised adult patients who underwent HTX between 2015 and 2019 and had at least 1 perioperative thyroid hormone laboratory test on the day of surgery or in the 24 hours before/after the procedure (free triiodothyronine, fT4, and thyroid-stimulating hormone). INTERVENTIONS: No interventions were applied. MEASUREMENTS AND MAIN RESULTS: The primary outcome was primary graft dysfunction (PGD), defined by the consensus conference of the International Society for Heart and Lung Transplantation. A total of 151 patients were included in the final analyses. Twenty-nine (19.2%) patients had PGD. Fourteen (9.3%) patients had low fT4 levels. An independent association was found between fT4 and PGD (odds ratio 6.49; 95% confidence interval 2.26-18.61; p = 0.001), with adjusted multivariate Cox regression models. CONCLUSION: The perioperative fT4 level could be a prognostic marker of adverse outcomes in HTX. The authors suggest appropriate perioperative monitoring of fT4 levels. Additional research is warranted to examine the optimal timing, dosage, and method of replacement.

Model for end-stage liver disease scores in veno-arterial extracorporeal membrane oxygenation.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation is a valuable therapeutic approach in patients with severe heart failure due to different etiologies. Current prognosis with veno-arterial extracorporeal membrane oxygenation is unsatisfactory, and the risk stratification is still challenging. Therefore, we aimed to evaluate the predictive value of different baseline model for end-stage liver disease scores for survival in patients with veno-arterial extracorporeal membrane oxygenation. METHODS: We conducted an observational, retrospective study of consecutive veno-arterial extracorporeal membrane oxygenation-treated patients between January 2012 and August 2018. The four types of model for end-stage liver disease scores-model for end-stage liver disease, international normalized ratio-excluded model for end-stage liver disease, modified model for end-stage liver disease, and model for end-stage liver disease with sodium-were calculated preoperatively. Veno-arterial extracorporeal membrane oxygenation was used based on the four clinical indications: primer graft failure after heart transplantation, weaning failure from cardiopulmonary bypass, acute myocardial infarction with refractory cardiogenic shock, and bridge to transplantation or bridge to candidacy. The primary endpoint of the study was overall mortality. The secondary endpoint was in-hospital mortality. We performed univariable and multivariable Cox regression analyses. RESULTS: Data from 135 patients were analyzed. The median follow-up was 952 days (interquartile range = 417-1555 days). In-hospital mortality was 62.2%, and overall mortality was 71.1%. The multivariable Cox regression analysis is adjusted for indication, and the survival after veno-arterial extracorporeal membrane oxygenation score showed that the following scores were associated with overall mortality: model for end-stage liver disease (hazard ratio = 1.04; 95% confidence interval = 1.01-1.07; p = 0.016), modified model for end-stage liver disease (hazard ratio = 1.04; 95% confidence interval = 1.01-1.06; p = 0.006), and model for end-stage liver disease with sodium (hazard ratio = 1.05; 95% confidence interval = 1.02-1.08; p = 0.001). CONCLUSION: Model for end-stage liver disease, modified model for end-stage liver disease, and model for end-stage liver disease with sodium scores could be useful in the risk stratification of veno-arterial extracorporeal membrane oxygenation treatment in varying clinical indications.

Frailty In Patients Undergoing Vascular Surgery: A Narrative Review Of Current Evidence.

Frailty is presumably associated with an elevated risk of postoperative mortality and adverse outcome in vascular surgery patients. The aim of our review was to identify possible methods for risk assessment and prehabilitation in order to improve recovery and postoperative outcome. The literature search was performed via PubMed, Embase, OvidSP, and the Cochrane Library. We collected papers published in peer-reviewed journals between 2001 and 2018. The selection criterion was the relationship between vascular surgery, frailty and postoperative outcome or mortality. A total number of 52 publications were included. Frailty increases the risk of non-home discharge independently of presence or absence of postoperative complications and it is related to a higher 30-day mortality and major morbidity. The modified Frailty Index showed significant association with elevated risk for post-interventional stroke, myocardial infarction, prolonged in-hospital stays and higher readmission rates. When adjusted for comorbidity and surgery type, frailty seems to impact medium-term survival (within 2 years). Preoperative physical exercising, avoidance of hypalbuminemia, psychological and cognitive training, maintenance of muscle strength, adequate perioperative nutrition, and management of smoking behaviours are leading to a reduced length of stay and a decreased incidence of readmission rate, thus improving the effectiveness of early rehabilitation. Pre-frailty is a dynamically changing state of the patient, capable of deteriorating or improving over time. With goal-directed preoperative interventions, the decline can be prevented.

The Impact of l-Thyroxine Treatment of Donors and Recipients on Postoperative Outcomes After Heart Transplantation.

OBJECTIVE: The effect of thyroid dysfunction on adverse outcomes has been studied in many different patient populations. The objective of this study was to investigate the effect of thyroid hormone supplementation of donors and recipients on postoperative outcomes after orthotopic heart transplantation. DESIGN: Retrospective. SETTING: Single center, university hospital. PARTICIPANTS: Two-hundred and sixty-six consecutive patients undergoing heart transplantation. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, and clinical characteristics; donor and recipient United Network for Organ Sharing scores; and information on thyroid hormone support of donors and recipients were recorded. During the median follow-up of 4.59 years (interquartile range 4.26-4.92 y), 70 patients (26.3%) died. After adjustments were made for the United Network for Organ Sharing score, recipients who were treated preoperatively with l-thyroxine had a lower risk for all-cause mortality (adjusted hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.06-0.98; p = 0.047) compared with recipients who were not treated with l-thyroxine. In addition, l-thyroxine treatment of donors was associated with a better recipient survival (HR 0.31, 95% CI 0.11-0.87; p = 0.025). CONCLUSIONS: Pretransplantation thyroid hormone supplementation of donors and recipients was associated with improved long-term survival after heart transplantation.

Higher Transaminase Levels in the Postoperative Period After Orthotopic Heart Transplantation Are Associated With Worse Survival.

OBJECTIVE: Preoperative liver function in heart failure patients is associated with extensive functional, structural, and hemodynamic abnormalities. The authors hypothesized that perioperative liver dysfunction is associated with worse 2-year survival after orthotopic heart transplantation. DESIGN: Retrospective study. SETTING: Single-center, university hospital. PARTICIPANTS: The study comprised 209 consecutive patients undergoing heart transplantation. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Hepatobiliary markers, hemodynamic parameters, echocardiographic parameters, the need for mechanical cardiac support, demographic parameters, and United Network for Organ Sharing and Model for End-Stage Liver Disease (MELD) scores were investigated. Fifty-five patients (26.3%) died, and the mean survival time was 3.61 years after transplantation. In multivariate Cox regression analysis, in addition to the preoperative modified MELD score, the 4th quartiles of the maximum aspartate transaminase (AST) and alanine transaminase levels on the 4th through 7th postoperative days were independently associated with mortality (odds ratio [OR] 2.46, 95% confidence interval [CI] 1.09-5.55; p = 0.031 and OR 2.41, 95% CI 1.13-5.18; p = 0.024, respectively). By expressing the transaminase values as the multiplier of the sex-specific top normal value, the maximum AST and alanine transaminase levels (OR 1.02, 95% CI 1.01-1.02; p < 0.001 and OR 1.02, 95% CI 1.01-1.03; p = 0.001, respectively) were linked to worse survival. Among the postdischarge parameters, the modified MELD score (OR 1.17, 95% CI 1.09-1.27; p < 0.001) and the AST level were associated with postdischarge mortality (OR 1.002, 95% CI 1.001-1.003; p < 0.001 as a continuous variable; OR 1.07, 95% CI 1.05-1.10; p < 0.001, expressed as the multiplier of the sex-specific normal value, respectively). CONCLUSIONS: The severity of postoperative liver dysfunction negatively influences survival after heart transplantation, and liver function should be closely assessed in these patients.