Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers.

Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high-risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia-reperfusion injury. We aimed to resuscitate and test the viability of initially-discarded, high-risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin-based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE-NMP, the first 18 procedures were performed with a HBOC-based perfusion solution and the subsequent 36 procedures were performed with an RBC-based perfusion solution for the NMP phase. All but one livers were derived from extended criteria donation after circulatory death donors, with a median donor risk index of 2.84 (IQR 2.52-3.11). After functional assessment during NMP, 34 livers (63% utilization), met the viability criteria and were transplanted. One-year graft and patient survival were 94% and 100%, respectively. Post-transplant cholangiopathy occurred in 1 patient (3%). There were no significant differences in utilization rate and post-transplant outcomes between the HBOC and RBC group. Ex situ machine perfusion using sequential DHOPE-NMP for resuscitation and viability assessment of high-risk donor livers results in excellent transplant outcomes, irrespective of the oxygen carrier used.

Long-term normothermic machine preservation of human livers: what is needed to succeed?

Although short-term machine perfusion (≤24 h) allows for resuscitation and viability assessment of high-risk donor livers, the donor organ shortage might be further remedied by long-term perfusion machines. Extended preservation of injured donor livers may allow reconditioning, repairing, and regeneration. This review summarizes the necessary requirements and challenges for long-term liver machine preservation, which requires integrating multiple core physiological functions to mimic the physiological environment inside the body. A pump simulates the heart in the perfusion system, including automatically controlled adjustment of flow and pressure settings. Oxygenation and ventilation are required to account for the absence of the lungs combined with continuous blood gas analysis. To avoid pressure necrosis and achieve heterogenic tissue perfusion during preservation, diaphragm movement should be simulated. An artificial kidney is required to remove waste products and control the perfusion solution's composition. The perfusate requires an oxygen carrier, but will also be challenged by coagulation and activation of the immune system. The role of the pancreas can be mimicked through closed-loop control of glucose concentrations by automatic injection of insulin or glucagon. Nutrients and bile salts, generally transported from the intestine to the liver, have to be supplemented when preserving livers long term. Especially for long-term perfusion, the container should allow maintenance of sterility. In summary, the main challenge to develop a long-term perfusion machine is to maintain the liver's homeostasis in a sterile, carefully controlled environment. Long-term machine preservation of human livers may allow organ regeneration and repair, thereby ultimately solving the shortage of donor livers.

Association Between an Increase in Serum Sodium and In-Hospital Mortality in Critically Ill Patients.

OBJECTIVES: In critically ill patients, dysnatremia is common, and in these patients, in-hospital mortality is higher. It remains unknown whether changes of serum sodium after ICU admission affect mortality, especially whether normalization of mild hyponatremia improves survival. DESIGN: Retrospective cohort study. SETTING: Ten Dutch ICUs between January 2011 and April 2017. PATIENTS: Adult patients were included if at least one serum sodium measurement within 24 hours of ICU admission and at least one serum sodium measurement 24-48 hours after ICU admission were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A logistic regression model adjusted for age, sex, and Acute Physiology and Chronic Health Evaluation-IV-predicted mortality was used to assess the difference between mean of sodium measurements 24-48 hours after ICU admission and first serum sodium measurement at ICU admission (Δ48 hr-[Na]) and in-hospital mortality. In total, 36,660 patients were included for analysis. An increase in serum sodium was independently associated with a higher risk of in-hospital mortality in patients admitted with normonatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.61 [1.44-1.79], Δ48 hr-[Na] > 10 mmol/L odds ratio: 4.10 [3.20-5.24]) and hypernatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.47 [1.02-2.14], Δ48 hr-[Na] > 10 mmol/L odds ratio: 8.46 [3.31-21.64]). In patients admitted with mild hyponatremia and Δ48 hr-[Na] greater than 5 mmol/L, no significant difference in hospital mortality was found (odds ratio, 1.11 [0.99-1.25]). CONCLUSIONS: An increase in serum sodium in the first 48 hours of ICU admission was associated with higher in-hospital mortality in patients admitted with normonatremia and in patients admitted with hypernatremia.

FDG-PET/CT in intensive care patients with bloodstream infection.

BACKGROUND: 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in intensive care patients is scarce. The purpose of this study was to evaluate the diagnostic yield of FDG-PET/CT in intensive care patients with BSI. METHODS: In this retrospective cohort study, all intensive care patients from our Dutch university medical center who had culture-proven BSI between 2010 and 2020 and underwent FDG-PET/CT to find the focus of infection were included. Diagnostic performance was calculated and logistic regression analysis was performed to evaluate the association between FDG-PET/CT outcome and C-reactive protein level (CRP), leukocyte count, duration of antibiotic treatment, duration of ICU stay, quality of FDG-PET/CT, and dependency on mechanical ventilation. In addition, the impact of FDG-PET/CT on clinical treatment was evaluated. RESULTS: 30 intensive care patients with BSI were included. In 21 patients, an infection focus was found on FDG-PET/CT which led to changes in clinical management in 14 patients. FDG-PET/CT achieved a sensitivity of 90.9% and specificity of 87.5% for identifying the focus of infection. Poor quality of the FDG-PET images significantly decreased the likelihood of finding an infection focus as compared to reasonable or good image quality (OR 0.16, P = 0.034). No other variables were significantly associated with FDG-PET/CT outcome. No adverse events during the FDG-PET/CT procedure were reported. CONCLUSION: FDG-PET/CT has a high diagnostic yield for detecting the infection focus in patients with BSI admitted to intensive care. Poor PET image quality was significantly associated with a decreased likelihood of finding the infection focus in patients with BSI. This could be improved by adequate dietary preparation and cessation of intravenous glucose and glucose-regulating drugs. Recent advances in PET/CT technology enable higher image quality with shorter imaging time and may contribute to routinely performing FDG-PET/CT in intensive care patients with BSI of unknown origin.

Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers.

Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ metabolism depends on oxygen to produce adenosine triphosphate and temperatures below 37 °C reduce the metabolic rate and oxygen requirements. The transport and delivery of oxygen in machine perfusion are key determinants in preserving organ viability and cellular function. Oxygen delivery is more challenging than carbon dioxide removal, and oxygenation of the perfusion fluid is temperature dependent. The maximal oxygen content of water-based solutions is inversely related to the temperature, while cellular oxygen demand correlates positively with temperature. Machine perfusion above 20 °C will therefore require an oxygen carrier to enable sufficient oxygen delivery to the liver. Human red blood cells are the most physiological oxygen carriers. Alternative artificial oxygen transporters are hemoglobin-based oxygen carriers, perfluorocarbons, and an extracellular oxygen carrier derived from a marine invertebrate. We describe the principles of oxygen transport, delivery, and consumption in machine perfusion for donor livers using different oxygen carrier-based perfusion solutions and we discuss the properties, advantages, and disadvantages of these carriers and their use.

Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution.

Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was ≥10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation.

Transplantation of High-risk Donor Livers After Ex Situ Resuscitation and Assessment Using Combined Hypo- and Normothermic Machine Perfusion: A Prospective Clinical Trial.

OBJECTIVE: The aim of this study was to evaluate sequential hypothermic and normothermic machine perfusion (NMP) as a tool to resuscitate and assess viability of initially declined donor livers to enable safe transplantation. SUMMARY BACKGROUND DATA: Machine perfusion is increasingly used to resuscitate and test the function of donor livers. Although (dual) hypothermic oxygenated machine perfusion ([D]HOPE) resuscitates livers after cold storage, NMP enables assessment of hepatobiliary function. METHODS: In a prospective clinical trial, nationwide declined livers were subjected to ex situ NMP (viability assessment phase), preceded by 1-hour DHOPE (resuscitation phase) and 1 hour of controlled oxygenated rewarming (COR), using a perfusion fluid containing an hemoglobin-based oxygen carrier. During the first 2.5 hours of NMP, hepatobiliary viability was assessed, using predefined criteria: perfusate lactate <1.7 mmol/L, pH 7.35 to 7.45, bile production >10 mL, and bile pH >7.45. Livers meeting all criteria were accepted for transplantation. Primary endpoint was 3-month graft survival. RESULTS: Sixteen livers underwent DHOPE-COR-NMP. All livers were from donors after circulatory death, with median age of 63 (range 42-82) years and median Eurotransplant donor risk index of 2.82. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 livers bile pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, with 100% patient and graft survival at 3 and 6 months. Introduction of DHOPE-COR-NMP increased the number of deceased donor liver transplants by 20%. CONCLUSIONS: Sequential DHOPE-COR-NMP enabled resuscitation and safe selection of initially declined high-risk donor livers, thereby increasing the number of transplantable livers by 20%. TRIAL REGISTRATION: www.trialregister.nl; NTR5972.

Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: results from a randomised controlled multicentre trial in the Netherlands.

BACKGROUND: Procalcitonin (PCT) testing can help in safely reducing antibiotic treatment duration in intensive care patients with sepsis. However, the cost-effectiveness of such PCT guidance is not yet known. METHODS: A trial-based analysis was performed to estimate the cost-effectiveness of PCT guidance compared with standard of care (without PCT guidance). Patient-level data were used from the SAPS trial in which 1546 patients were randomised. This trial was performed in the Netherlands, which is a country with, on average, low antibiotic use and a short duration of hospital stay. As quality of life among sepsis survivors was not measured during the SAPS, this was derived from a Dutch follow-up study. Outcome measures were (1) incremental direct hospital cost and (2) incremental cost per quality-adjusted life year (QALY) gained from a healthcare perspective over a one-year time horizon. Uncertainty in outcomes was assessed with bootstrapping. RESULTS: Mean in-hospital costs were €46,081/patient in the PCT group compared with €46,146/patient with standard of care (i.e. - €65 (95% CI - €6314 to €6107); - 0.1%). The duration of the first course of antibiotic treatment was lower in the PCT group with 6.9 vs. 8.2 days (i.e. - 1.2 days (95% CI - 1.9 to - 0.4), - 14.8%). This was accompanied by lower in-hospital mortality of 21.8% vs. 29.8% (absolute decrease 7.9% (95% CI - 13.9% to - 1.8%), relative decrease 26.6%), resulting in an increase in mean QALYs/patient from 0.47 to 0.52 (i.e. + 0.05 (95% CI 0.00 to 0.10); + 10.1%). However, owing to high costs among sepsis survivors, healthcare costs over a one-year time horizon were €73,665/patient in the PCT group compared with €70,961/patient with standard of care (i.e. + €2704 (95% CI - €4495 to €10,005), + 3.8%), resulting in an incremental cost-effectiveness ratio of €57,402/QALY gained. Within this time frame, the probability of PCT guidance being cost-effective was 64% at a willingness-to-pay threshold of €80,000/QALY. CONCLUSIONS: Although the impact of PCT guidance on total healthcare-related costs during the initial hospitalisation episode is likely negligible, the lower in-hospital mortality may lead to a non-significant increase in costs over a one-year time horizon. However, since uncertainty remains, it is recommended to investigate the long-term cost-effectiveness of PCT guidance, from a societal perspective, in different countries and settings.

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control: a randomized controlled trial.

INTRODUCTION: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. METHODS: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol--Glucose Regulation for Intensive care Patients (GRIP)--was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC15). ICU length of stay and mortality were observed as well. RESULTS: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC15 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC15 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). CONCLUSIONS: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. TRIAL REGISTRATION: ClinicalTrials.gov NCT00293592 . Registered 16 February 2006.

Effect of Metformin on Renal Function After Primary Percutaneous Coronary Intervention in Patients Without Diabetes Presenting with ST-elevation Myocardial Infarction: Data from the GIPS-III Trial.

PURPOSE: The association between metformin use and renal function needs further to be elucidated since data are insufficient whether metformin affects renal function in higher risk populations such as after ST-elevation myocardial infarction (STEMI). METHODS: We studied 379 patients included in the GIPS-III trial in which patients without diabetes or renal dysfunction, who underwent primary percutaneous coronary interventions (PCI) for STEMI, were randomized to metformin 500 mg or placebo twice daily for four months. At baseline and at seven scheduled visits up to four months after PCI, estimated glomerular filtration rate (eGFR) was determined (2582 values). Contrast-induced acute kidney injury (CI-AKI) was defined as an increase in serum creatinine of ≥0.3 mg/dl or 25 % rise within 48 h after PCI. RESULTS: At all visits, the mean eGFR was similar in patients randomized to metformin or placebo. Over the four month period, mixed-effect repeated-measures model analysis showed a least-squares mean ± standard error change in eGFR of -5.9±0.8 ml/min/1.73 m2 in the metformin group and −7.1 ±0.8 ml/min/1.73 m2 in the control group (P=0.27 for overall interaction). The incidence of CI-AKI was 14.8 %; 29 (15.2 %) patients in the metformin group versus 27 (14.4 %) controls (P=0.89). After adjustment for covariates, metformin treatment was not associated with CI-AKI (odds ratio: 0.96, 95%CI 0.52−1.75, P=0.88). CONCLUSION: We conclude that initiation of metformin shortly after primary PCI has no adverse effect on renal function in patients without diabetes or prior renal impairment, further providing evidence of the safety of metformin use after myocardial infarction and subsequent contrast exposure.

Introducing intravascular microdialysis for continuous lactate monitoring in patients undergoing cardiac surgery: a prospective observational study.

INTRODUCTION: Lactate is a marker of hypoperfusion and may be used for risk assessment in critically ill patients. Although evidence suggests that repeated lactate measurements are of clinical interest, how and when lactate should be analyzed is controversial. Intravascular microdialysis provides a novel method for the continuous monitoring of lactate, which may be clinically beneficial in critically ill patients. METHODS: Circulating lactate levels were continuously monitored in 80 patients undergoing cardiac surgery using either a separate single-lumen microdialysis catheter or a triple-lumen central venous catheter with an integrated microdialysis function. The catheter was placed with the tip positioned in the superior vena cava. Arterial blood gas samples were taken every hour to obtain reference values, and the lactate levels were analyzed in a blood gas analyzer. RESULTS: A total of 1,601 paired microdialysis-arterial blood gas lactate samples were obtained. Bland-Altman analysis showed a bias (mean difference) ± limits of agreement (±1.96 SD) of 0.02 ± 0.42 mmol/L. The regression coefficient was 0.98 (P = 0.0001). CONCLUSIONS: Central venous microdialysis is an accurate and reliable method for continuous blood lactate monitoring in patients undergoing cardiac surgery. The system may be useful for early lactate-guided therapy in critically ill patients.

Continuous Renal Replacement Therapy During Long-term Normothermic Machine Perfusion of Human Donor Livers for up to 7 D.

Background: Normothermic machine perfusion (NMP) is used to preserve and test donor livers before transplantation. During NMP, the liver is metabolically active and produces waste products, which are released into the perfusate. In this study, we describe our simplified and inexpensive setup that integrates continuous renal replacement therapy (CRRT) with NMP for up to 7 d. We also investigated if the ultrafiltrate could be used for monitoring perfusate concentrations of small molecules such as glucose and lactate. Methods: Perfusate composition (urea, osmolarity, sodium, potassium, chloride, calcium, magnesium, phosphate, glucose, and lactate) was analyzed from 56 human NMP procedures without CRRT. Next, in 6 discarded human donor livers, CRRT was performed during NMP by integrating a small dialysis filter (0.2 m2) into the circuit to achieve continuous ultrafiltration combined with continuous fluid substitution for up to 7 d. Results: Within a few hours of NMP without CRRT, a linear increase in osmolarity and concentrations of urea and phosphate to supraphysiological levels was observed. After integration of CRRT into the NMP circuit, the composition of the perfusate was corrected to physiological values within 12 h, and this homeostasis was maintained during NMP for up to 7 d. Glucose and lactate levels, as measured in the CRRT ultrafiltrate, were strongly correlated with perfusate levels (r = 0.997, P < 0.001 and r = 0.999, P < 0.001, respectively). Conclusions: The integration of CRRT into the NMP system corrected the composition of the perfusate to near-physiological values, which could be maintained for up to 7 d. The ultrafiltrate can serve as an alternative to the perfusate to monitor concentrations of small molecules without potentially compromising sterility.

Identifying the need for infection-related consultations in intensive care patients using machine learning models.

Infection-related consultations on intensive care units (ICU) have a positive impact on quality of care and clinical outcome. However, timing of these consultations is essential and to date they are typically event-triggered and reactive. Here, we investigate a proactive approach to identify patients in need for infection-related consultations by machine learning models using routine electronic health records. Data was retrieved from a mixed ICU at a large academic tertiary care hospital including 9684 admissions. Infection-related consultations were predicted using logistic regression, random forest, gradient boosting machines, and long short-term memory neural networks (LSTM). Overall, 7.8% of admitted patients received an infection-related consultation. Time-sensitive modelling approaches performed better than static approaches. Using LSTM resulted in the prediction of infection-related consultations in the next clinical shift (up to eight hours in advance) with an area under the receiver operating curve (AUROC) of 0.921 and an area under the precision recall curve (AUPRC) of 0.541. The successful prediction of infection-related consultations for ICU patients was done without the use of classical triggers, such as (interim) microbiology reports. Predicting this key event can potentially streamline ICU and consultant workflows and improve care as well as outcome for critically ill patients with (suspected) infections.

Multiple biomarkers for the prediction of short and long-term mortality after ST-segment elevation myocardial infarction: the Amsterdam Groningen collaboration.

Multiple biomarkers improve prognostication for long-term mortality in ST-segment elevation myocardial infarction (STEMI). However, one-third of mortality after STEMI occurs within initial discharge. Our objective was to determine whether multiple biomarkers (glucose, N-terminal pro-brain natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR)) predict both short-term as long-term mortality in STEMI. We used a patient-pooled dataset of consecutive STEMI patients, with complete biomarkers, who underwent primary percutaneous coronary intervention (PCI) in two single centers (Amsterdam and Groningen). With a previously developed multimarker risk score, based on three biomarkers, patients were indicated as low-, intermediate- or high risk. Cumulative 4-year mortality was estimated with the Kaplan-Meier method and compared with a log-rank test. We compared short-term and long-term mortality with a landmark set at 30 days because previous studies have shown that mortality largely occurs within 30 days. A total of 2,355 STEMI-patients were treated with primary PCI. The mortality rates in the low- (n = 1,531), intermediate- (n = 403) and high-risk (n = 421) groups were 4.8, 16.1, and 43.9 %, respectively. The differences were observed at a follow-up up to 30 days (log-rank p < 0.001) as well as after 30 days (log-rank p < 0.001). A multimarker risk score, based on admission levels of glucose, NT-proBNP, and eGFR identifies STEMI patients at low-, intermediate-, and high-risk for short-term and long-term mortality.

Practice of 18F-FDG-PET/CT in ICU Patients: A Systematic Review.

18F-FDG-PET/CT imaging has become a key tool to evaluate infectious and inflammatory diseases. However, application of 18F-FDG-PET/CT in patients in the intensive care unit (ICU) is limited, which is remarkable since the development of critical illness is closely linked to infection and inflammation. This limited use is caused by perceived complexity and risk of planning and executing 18F-FDG-PET/CT in such patients. The aim of this systematic review was to investigate the feasibility of 18F-FDG-PET/CT in ICU patients with special emphasis on patient preparation, transport logistics and safety. Therefore, a systematic search was performed in PubMed, Embase, and Web of Science using the search terms: intensive care, critically ill, positron emission tomography and 18F-FDG or derivates. A total of 1183 articles were found of which 10 were included. Three studies evaluated the pathophysiology of acute respiratory distress syndrome, acute lung injury and acute chest syndrome. Three other studies applied 18F-FDG-PET/CT to increase understanding of pathophysiology after traumatic brain injury. The remaining four studies evaluated infection of unknown origin. These four studies showed a sensitivity and specificity between 85%-100% and 57%-88%, respectively. A remarkable low adverse event rate of 2% was found during the entire 18F-FDG-PET/CT procedure, including desaturation and hypotension. In all studies, a team consisting of an intensive care physician and nurse was present during transport to ensure continuation of necessary critical care. Full monitoring during transport was used in patients requiring mechanical ventilation or vasopressor support. None of the studies used specific patient preparation for ICU patients. However, one article described specific recommendations in their discussion. In conclusion, 18F-FDG-PET/CT has been shown to be feasible and safe in ICU patients, even when ventilated or requiring vasopressors. Specific recommendations regarding patient preparation, logistics and scanning are needed. Including 18F-FDG-PET/CT in routine workup of infection of unknown origin in ICU patients showed potential to identify source of infection and might improve outcome.

[18F]FDG-PET/CT in mechanically ventilated critically ill patients with COVID-19 ARDS and persistent inflammation.

Purpose: We report the findings of four critically ill patients who underwent an [18F]FDG-PET/CT because of persistent inflammation during the late phase of their COVID-19. Methods: Four mechanically ventilated patients with COVID-19 were retrospectively discussed in a research group to evaluate the added value of [18F]FDG-PET/CT. Results: Although pulmonary PET/CT findings differed, bilateral lung anomalies could explain the increased CRP and leukocytes in all patients. This underscores the limited ability of the routine laboratory to discriminate inflammation from secondary infections. Based on PET/CT findings, a secondary infection/inflammatory focus was suspected in two patients (pancreatitis and gastritis). Lymphadenopathy was present in patients with a detectable SARS-CoV-2 viral load. Muscle uptake around the hips or shoulders was observed in all patients, possibly due to the process of heterotopic ossification. Conclusion: This case series illustrates the diagnostic potential of [18F]FDG-PET/CT imaging in critically ill patients with persistent COVID-19 for the identification of other causes of inflammation and demonstrates that this technique can be performed safely in mechanically ventilated critically ill patients.

Prognostic value of admission glycosylated hemoglobin and glucose in nondiabetic patients with ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention.

BACKGROUND: In nondiabetic patients with ST-segment-elevation myocardial infarction, acute hyperglycemia is associated with adverse outcome. Whether this association is due merely to hyperglycemia as an acute stress response or whether longer-term glycometabolic derangements are also involved is uncertain. It was our aim to determine the association between both acute and chronic hyperglycemia (hemoglobin A(1c) [HbA(1c)]) and outcome in nondiabetic patients with ST-segment-elevation myocardial infarction. METHODS AND RESULTS: This observational study included consecutive patients (n=4176) without known diabetes mellitus admitted with ST-segment-elevation myocardial infarction. All patients were treated with primary percutaneous intervention. Both glucose and HbA(1c) were measured on admission. Main outcome measure was total long-term mortality; secondary outcome measures were 1-year mortality and enzymatic infarct size. One-year mortality was 4.7%, and mortality after total follow-up (3.3 ± 1.5 years) was 10%. Both elevated HbA(1c) levels (P<0.001) and elevated admission glucose (P<0.001) were associated with 1-year and long-term mortality. After exclusion of early mortality (within 30 days), HbA(1c) remained associated with long-term mortality (P<0.001), whereas glucose lost significance (P=0.09). Elevated glucose, but not elevated HbA(1c), was associated with larger infarct size. After multivariate analysis, HbA(1c) (hazard ratio, 1.2 per interquartile range; P<0.01), but not glucose, was independently associated with long-term mortality. CONCLUSIONS: In nondiabetic patients with ST-segment-elevation myocardial infarction, both elevated admission glucose and HbA(1c) levels were associated with adverse outcome. Both of these parameters reflect different patient populations, and their association with outcome is probably due to different mechanisms. Measurement of both parameters enables identification of these high-risk groups for aggressive secondary risk prevention.

Determinants of renal potassium excretion in critically ill patients: the role of insulin therapy.

OBJECTIVES: Insulin administration lowers plasma potassium concentration by augmenting intracellular uptake of potassium. The effect of insulin administration on renal potassium excretion is unclear. Some studies suggest that insulin has an antikaliuretic effect although plasma potassium levels were poorly controlled. Since the introduction of glycemic control in the intensive care unit, insulin use has increased. We examined the relation between administered insulin and renal potassium excretion in critically ill patients under computer-assisted glucose and potassium regulation. DESIGN: Prospective observational study. SETTING: Twelve-bed surgical intensive care unit of a university teaching hospital. PATIENTS: Consecutive intensive care unit patients. INTERVENTIONS: Potassium and glucose levels were regulated by a computer-assisted decision support system. Both potassium and insulin were continuously administered by syringe pump. MEASUREMENTS AND MAIN RESULTS: Renal potassium excretion was measured daily in the 24-hr urine collections. The 24-hr urinary samples of patients with kidney failure or on renal replacement therapy were excluded. Multivariate analysis with potassium excretion as the dependent variable was performed. In 178 consecutive patients, 1,456 24-hr urinary samples, were analyzed. Mean ± SD plasma potassium was 4.2 ± 0.3 mmol/L, with 79 ± 46 mmol/d of potassium administered and a mean insulin dose of 53 ± 38 U/day. Renal potassium excretion was 126 ± 51 mmol/day. After multivariate analysis correcting for relevant variables (including diuretics, pH, potassium levels and renal sodium excretion), insulin administration was independently and positively associated with renal potassium excretion. Other significant variables were potassium levels, potassium administration, renal sodium and chloride excretion, creatinine clearance, diuretic therapy, pH, known diabetes and intensive care unit admission day (R = .52; p <. 001). CONCLUSION: Insulin administration is associated with an increase in the renal potassium excretion in critically ill patients.

Comparison of Machine Learning Models Including Preoperative, Intraoperative, and Postoperative Data and Mortality After Cardiac Surgery.

Importance: A variety of perioperative risk factors are associated with postoperative mortality risk. However, the relative contribution of routinely collected intraoperative clinical parameters to short-term and long-term mortality remains understudied. Objective: To examine the performance of multiple machine learning models with data from different perioperative periods to predict 30-day, 1-year, and 5-year mortality and investigate factors that contribute to these predictions. Design, Setting, and Participants: In this prognostic study using prospectively collected data, risk prediction models were developed for short-term and long-term mortality after cardiac surgery. Included participants were adult patients undergoing a first-time valve operation, coronary artery bypass grafting, or a combination of both between 1997 and 2017 in a single center, the University Medical Centre Groningen in the Netherlands. Mortality data were obtained in November 2017. Data analysis took place between February 2020 and August 2021. Exposure: Cardiac surgery. Main Outcomes and Measures: Postoperative mortality rates at 30 days, 1 year, and 5 years were the primary outcomes. The area under the receiver operating characteristic curve (AUROC) was used to assess discrimination. The contribution of all preoperative, intraoperative hemodynamic and temperature, and postoperative factors to mortality was investigated using Shapley additive explanations (SHAP) values. Results: Data from 9415 patients who underwent cardiac surgery (median [IQR] age, 68 [60-74] years; 2554 [27.1%] women) were included. Overall mortality rates at 30 days, 1 year, and 5 years were 268 patients (2.8%), 420 patients (4.5%), and 612 patients (6.5%), respectively. Models including preoperative, intraoperative, and postoperative data achieved AUROC values of 0.82 (95% CI, 0.78-0.86), 0.81 (95% CI, 0.77-0.85), and 0.80 (95% CI, 0.75-0.84) for 30-day, 1-year, and 5-year mortality, respectively. Models including only postoperative data performed similarly (30 days: 0.78 [95% CI, 0.73-0.82]; 1 year: 0.79 [95% CI, 0.74-0.83]; 5 years: 0.77 [95% CI, 0.73-0.82]). However, models based on all perioperative data provided less clinically usable predictions, with lower detection rates; for example, postoperative models identified a high-risk group with a 2.8-fold increase in risk for 5-year mortality (4.1 [95% CI, 3.3-5.1]) vs an increase of 11.3 (95% CI, 6.8-18.7) for the high-risk group identified by the full perioperative model. Postoperative markers associated with metabolic dysfunction and decreased kidney function were the main factors contributing to mortality risk. Conclusions and Relevance: This study found that the addition of continuous intraoperative hemodynamic and temperature data to postoperative data was not associated with improved machine learning-based identification of patients at increased risk of short-term and long-term mortality after cardiac operations.