Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

The influence of low-, normal-, and high-carbohydrate meals on blood pressure in elderly patients with postprandial hypotension.

BACKGROUND: Postprandial hypotension (PPH) is a common and serious disorder of blood pressure (BP) regulation in elderly people. It has been suggested that primarily the carbohydrate (CH) content of a meal induces the BP decrease. Therefore, we examined the relationship between the CH content of meals and postprandial BP responses in elderly patients diagnosed with PPH. METHODS: Twelve geriatric patients (aged 75 to 91 years; 6 men) who were previously diagnosed with PPH received standardized liquid meals with low- (25 g), normal- (65 g), and high- (125 g) CH content in random order on three separate days. Systolic BP (SBP), diastolic BP, and heart rate were measured every 5 minutes from 20 minutes before until 75 minutes after each meal. Postprandial symptoms were recorded every 15 minutes. RESULTS: The maximum decrease in SBP was significantly smaller after the low-CH meal (-28 +/- 5 mm Hg) than after the normal- (-39 +/- 7 mm Hg) and high-CH meals (-40 +/- 5 mm Hg) (p <.050 between groups). In addition, the duration of PPH was significantly shorter (p <.010), and postprandial symptoms were less frequent and less severe after the low-CH meal. CONCLUSIONS: Reducing the CH amount in meals induces significantly smaller decreases in SBP, shorter duration of PPH, and reduction of PPH-related symptoms. Therefore, limiting the CH content of an elderly patient's meal can be a clinically effective nonpharmacological treatment for PPH in elderly patients and can reduce the risk of developing symptomatic PPH.

Effect of levodopa on orthostatic and postprandial hypotension in elderly Parkinsonian patients.

BACKGROUND: This study describes orthostatic and postprandial hypotension in elderly Parkinsonian patients and evaluates the effect of levodopa therapy on orthostatic and postprandial hypotension in these patients. METHODS: Seventeen elderly patients with a clinical diagnosis of Parkinson's disease or Parkinsonism based on the U.K. Parkinson's Disease Society Brain Bank criteria (age range, 66-84 years) participated in the study. Blood pressure was continuously monitored during standardized standing and meal tests, after starting 125-mg b.i.d. doses of levodopa/benserazide (Madopar) or placebo, in a double-blind, randomized, cross-over design. Seventeen age- and sex-matched healthy subjects served as controls. RESULTS: Orthostatic hypotension was infrequently found in Parkinsonian patients (13%) and healthy subjects (6%; p =.58, between groups), whereas postprandial hypotension was more frequent in Parkinsonian patients (82%) than in healthy subjects (41%; p <.05, between groups). Doses of levodopa/benserazide, administered 2 times per day, did not result in significantly larger blood pressure decreases after standing or eating, or in higher frequencies of orthostatic or postprandial hypotension in the Parkinsonian group. Postprandial hypotension was related to disease severity (r = -.56, p <.05). CONCLUSIONS: Postprandial hypotension, but not orthostatic hypotension, was more common in elderly Parkinsonian patients than in healthy subjects. Therapy with 125-mg b.i.d. doses of levodopa/benserazide did not significantly aggravate orthostatic or postprandial hypotension.

Achieving haemodynamic baseline values with Finapres in elderly subjects during supine rest.

BACKGROUND: Clear guidelines for the resting time necessary to achieve stable blood pressure (BP) levels are scant in gerontology research. Therefore, we aimed to determine the minimum period required for obtaining haemodynamic baseline values in elderly subjects during supine rest. In addition, we evaluated the effect of cardiovascular morbidity, such as diastolic heart failure, and the effect of complex comorbidity of geriatric patients, on haemodynamic changes during supine rest. METHODS: A total of 17 healthy subjects, 18 heart failure patients with normal systolic function and 24 geriatric patients, aged 70 years and more, participated. After an overnight fast, changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR), and stroke volume (SV) were determined by Finapres beat-to-beat non-invasive BP monitoring during a 20-min supine rest. The procedure was repeated in the healthy subjects and geriatric patients on a second day. RESULTS: Complete BP stabilization was reached in each group within 5 min of supine rest, as SBP remained essentially unchanged and DBP did not change significantly anymore after the fourth minute. In the heart failure patients, HR decreased and SV increased until the twelfth minute of rest. The SBP, DBP, HR, and SV changes during supine rest showed good reproducibility. CONCLUSIONS: A span of 5 min of supine rest ensured achievement of reliable and reproducible baseline BP values by Finapres in elderly subjects. However, we recommend at least 12 min of rest to obtain full haemodynamic stability in elderly patients with diminished cardiac compliance and diastolic function.

Sympathoadrenal activation and the dumping syndrome after gastric surgery.

Dumping symptoms suggest concomitant sympathoadrenal activation. To evaluate the relation between dumping symptoms and postprandial plasma catecholamine changes, standardized dumping-provocation tests with use of oral glucose were performed for 16 gastric surgery patients with dumping, for 14 gastric surgery patients without dumping, and for 14 healthy control patients. Early dumping symptoms were present for all patients with dumping, and late symptoms developed in three patients with dumping after glucose ingestion. Patients without dumping and healthy control patients had slight complaints or no complaints. Systolic and diastolic blood pressure remained unaffected for the three groups. Positive breath-hydrogen tests, heart rate increments, and reactive plasma glucose decrements were present for patients with dumping and for patients without dumping, but not for control patients. Plasma noradrenaline and adrenaline increased for patients with dumping and for patients without dumping, but not for control patients. The noradrenaline increment was higher for patients with dumping (98%) than for patients without dumping (78%; p <0.05). The noradrenaline increment was related to the dumping score and to the heart rate increment for the first hour after glucose ingestion, whereas the adrenaline increment was related to the plasma glucose decrement for the third hour. Therefore, dumping symptoms clearly are accompanied by postprandial sympathoadrenal activation, but sympathoadrenal activation cannot account completely for development of dumping symptoms.

Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years or older.

In the elderly, standing can frequently be accompanied by blood pressure (BP) changes and cerebral symptoms such as dizziness, fall, or even syncope, but this may vary from day-to-day. Therefore, we aimed to investigate the reproducibility of orthostatic responses of cerebral cortical oxygenation and systemic haemodynamics in elderly subjects. In 27 healthy elderly subjects (age 70-84 years), changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR) and stroke volume (SV) were continuously monitored by Finapres (Finger Arterial Pressure), and changes in oxyhaemoglobin ([O2Hb]) and deoxyhaemoglobin ([HHb]) concentrations were continuously measured over the right frontal cortex by near infrared spectroscopy (NIRS) during supine rest and 10 min of active standing on two separate occasions. SBP and DBP increased by 6.7 +/- 15.4 mmHg (P<0.05, mean +/- SD) and 8.2 +/- 6.4 mmHg (P<0.01), respectively, whereas HR increased by 9.5 +/- 5.0 bpm (P<0.01) and SV decreased by -8.3 +/- 7.4 ml (P<0.01) during standing on the first occasion. [O2Hb] decreased by -3.9 +/- 2.9 micromol l-1 (P<0.01), while [HHb] increased by 1.8 +/- 2.2 micromol l-1 (P<0.01). Group-averaged orthostatic changes in cortical oxygenation and systemic haemodynamics were very similar on the two occasions, although an intraindividual variation was found. Cortical oxygenation changes were not accompanied by severe cerebral symptoms. Active standing induced reproducible group-averaged frontal cortical oxygenation declines in healthy elderly subjects, although an intraindividual day-to-day variability was present, possibly related to the variability of orthostatic BP responses. These findings indicate that cerebral autoregulation fails to compensate completely for postural changes in elderly subjects, which might predispose elderly subjects to ischaemic cerebral symptoms.

Cerebral oxygenation declines in healthy elderly subjects in response to assuming the upright position.

BACKGROUND AND PURPOSE: With increasing age, assuming the upright position is more often accompanied by symptoms such as dizziness and lightheadedness, possibly as a result of a diminished oxygen supply to the brain due to impaired cerebral autoregulation. We aimed to quantify postural changes in cerebral oxygenation and systemic hemodynamics in healthy elderly and young subjects. METHODS: In 18 healthy elderly subjects (aged 70 to 83 years) and 10 healthy young subjects (aged 22 to 45 years), frontal cortical oxygenation and hemodynamic responses were continuously monitored by near infrared spectroscopy and Finapres, respectively, before and during 10 minutes of active standing. RESULTS: -Cortical oxyhemoglobin concentration [O(2)Hb] decreased by -4.6+/-2.2 micromol/L (P<0.001) and cortical deoxyhemoglobin concentration increased by 1.5+/-2.4 micromol/L (P<0.05) in the elderly subjects after posture change, whereas these variables did not change significantly in the young subjects. The postural hemodynamic changes tended to be attenuated in the elderly subjects, except for the increases in systolic blood pressure (BP). Smaller postural increases in diastolic BP were related to larger [O(2)Hb] decreases (r=0.53, P<0.01, corrected for the age effect). CONCLUSIONS: Assuming the upright position evokes an asymptomatic decrease in frontal cortical oxygenation in healthy elderly subjects but not in healthy young subjects. Cortical [O(2)Hb] changes are affected by diastolic BP changes. These findings may indicate that regulation of cerebral oxygenation alters with increasing age.