A study protocol of external validation of eight COVID-19 prognostic models for predicting mortality risk in older populations in a hospital, primary care, and nursing home setting.

BACKGROUND: The COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥ 70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting. METHODS: Based on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2 + model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch older population (three hospital cohorts, two primary care cohorts, and a nursing home cohort). All prognostic models will be validated in a hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥ 70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated. DISCUSSION: Insight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older population. Such insight will be important for possible future waves of the COVID-19 pandemic or future pandemics.

How does SARS-CoV-2 targets the elderly patients? A review on potential mechanisms increasing disease severity.

IMPORTANCE: Among COVID-19 cases, especially the (frail) elderly show a high number of severe infections, hospital admissions, complications, and death. The highest mortality is found between 80 and 89 years old. Why do these patients have a higher risk of severe COVID-19? In this narrative review we address potential mechanisms regarding viral transmission, physical reserve and the immune system, increasing the severity of this infection in elderly patients. OBSERVATIONS: First, the spread of COVID-19 may be enhanced in elderly patients. Viral shedding may be increased, and early identification may be complicated due to atypical disease presentation and limited testing capacity. Applying hygiene and quarantine measures, especially in patients with cognitive disorders including dementia, can be challenging. Additionally, elderly patients have a decreased cardiorespiratory reserve and are more likely to have co-morbidity including atherosclerosis, rendering them more susceptible to complications. The aging innate and adaptive immune system is weakened, while there is a pro-inflammatory tendency. The effects of SARS-CoV-2 on the immune system on cytokine production and T-cells, further seem to aggravate this pro-inflammatory tendency, especially in patients with cardiovascular comorbidity, increasing disease severity. CONCLUSIONS AND RELEVANCE: The combination of all factors mentioned above contribute to the disease severity of COVID-19 in the older patient. While larger studies of COVID-19 in elderly patients are needed, understanding the factors increasing disease severity may improve care and preventative measures to protect the elderly patient at risk for (severe) COVID-19 in the future.

A mini-fluid challenge of 150mL predicts fluid responsiveness using ModelflowR pulse contour cardiac output directly after cardiac surgery.

STUDY OBJECTIVE: The mini-fluid challenge may predict fluid responsiveness with minimum risk of fluid overloading. However, the amount of fluid as well as the best manner to evaluate the effect is unclear. In this prospective observational pilot study, the value of changes in pulse contour cardiac output (CO) measurements during mini-fluid challenges is investigated. DESIGN: Prospective observational study. SETTING: Intensive Care Unit of a university hospital. PATIENTS: Twenty-one patients directly after elective cardiac surgery on mechanical ventilation. INTERVENTIONS: The patients were subsequently given 10 intravenous boluses of 50mL of hydroxyethyl starch with a total of 500mL per patient while measuring pulse contour CO. MEASUREMENTS: We measured CO by minimal invasive ModelflowR (COm) and PulseCOR (COli), before and one minute after each fluid bolus. We analyzed the smallest volume that was predictive of fluid responsiveness. A positive fluid response was defined as an increase in CO of >10% after 500mL fluid infusion. MAIN RESULTS: Fifteen patients (71%) were COm responders and 13 patients (62%) COli responders. An increase in COm after 150mL of fluid >5.0% yielded a positive and negative predictive value (+PV and -PV) of 100% with an area under the curve (AUC) of 1.00 (P<0.001). An increase in COli >6.3% after 200mL was able to predict a fluid response in COli after 500mL with a +PV of 100% and -PV of 73%, with an AUC of 0.88 (P<0.001). CONCLUSION: The use of minimal invasive ModelflowR pulse contour CO measurements following a mini-fluid challenge of 150mL can predict fluid responsiveness and may help to improve fluid management.

Different effects of fluid loading with saline, gelatine, hydroxyethyl starch or albumin solutions on acid-base status in the critically ill.

INTRODUCTION: Fluid administration in critically ill patients may affect acid-base balance. However, the effect of the fluid type used for resuscitation on acid-base balance remains controversial. METHODS: We studied the effect of fluid resuscitation of normal saline and the colloids gelatine 4%, hydroxyethyl starch (HES) 6%, and albumin 5% on acid-base balance in 115 clinically hypovolemic critically ill patients during a 90 minute filling pressure-guided fluid challenge by a post-hoc analysis of a prospective randomized clinical trial. RESULTS: About 1700 mL was infused per patient in the saline and 1500 mL in each of the colloid groups (P<0.001). Overall, fluid loading slightly decreased pH (P<0.001) and there was no intergroup difference. This mildly metabolic acidifying effect was caused by a small increase in chloride concentration and decrease in strong ion difference in the saline- and HES-, and an increase in (uncorrected) anion gap in gelatine- and albumin-loaded patients, independent of lactate concentrations. CONCLUSION: In clinically hypovolemic, critically ill patients, fluid resuscitation by only 1500-1700 mL of normal saline, gelatine, HES or albumin, resulted in a small decrease in pH, irrespective of the type of fluid used. Therefore, a progressive metabolic acidosis, even with increased anion gap, should not be erroneously attributed to insufficient fluid resuscitation. TRIAL REGISTRATION: ISRCTN Registry ISRCTN19023197.

Diuretic response to colloid and crystalloid fluid loading in critically ill patients.

AIMS: In the critically ill patient, fluid loading is commonly done to stabilise hemodynamics and increase diuresis, whereas the absence of diuresis may predispose to harmful overloading. The goal of the current study was to evaluate the diuretic response and determinants thereof upon crystalloid and colloid fluid loading. SUBJECTS AND METHODS: This is a substudy on 42 clinically hypovolemic, septic or non-septic patients without acute kidney injury, who were randomly assigned, after stratification for sepsis, to a 90-min fluid loading protocol with either 0.9% saline or a colloid solution (gelatin, hydroxyethyl starch 200/0.5 or albumin). Hemodynamics, biochemical parameters and diuresis were recorded. A response was defined by an increase in diuresis of >10% during fluid loading. RESULTS: Diuresis increased more during saline than colloid infusion, together with a decline in colloid osmotic pressure (COP) of plasma and less increase in plasma volume and global hemodynamics with saline, at similar fluid balance. Nine patients (82%) receiving saline had a diuretic response, compared to 13 patients (42%) receiving colloids (P = 0.04), and the response was not predicted by underlying condition, global hemodynamics, volume of fluid infused and COP. CONCLUSION: In critically ill patients with clinical hypovolemia, diuresis increases more during saline than colloid fluid loading, only partly dependent of a fall in plasma COP.

[A woman with a red demarcation of the tongue]. / Een vrouw met een rode streep over de tong.

A 68-year-old woman had a red demarcation of the tongue, without any discomfort. Because of the use of corticosteroid inhalations, it was thought that this was caused by median rhomboid glossitis, based on Candida albicans. Oral antimycotic therapy made the demarcation disappear, which confirmed the diagnosis.

[Long-term complications of bariatric surgery]. / Langetermijncomplicaties van bariatrische chirurgie: het mes snijdt aan twee kanten.

The prevalence of morbid obesity is increasing, with a corresponding increase in the demand for bariatric surgery, a proven effective treatment option. Bariatric surgery has potentially severe complications, including micro- and macronutrient deficiencies. Additionally, stenosis and ulceration of the anastomosis, reflux oesophagitis, cholelithiasis, steatohepatitis and altered pharmacokinetics and -dynamics may occur. Doctors in both the hospital setting and general practice will be increasingly confronted with the occasionally adverse long-term effects of bariatric surgery. Early detection, efficient follow-up and a multidisciplinary team approach are crucial in preventing and adequately treating the complications of bariatric surgery.

[A teenager with Prader-Willi syndrome with loss of appetite]. / Een tiener met Prader-Willi-syndroom zonder eetlust.

BACKGROUND: Prader-Willi syndrome is characterised by hyperphagia and binge eating, without regurgitation. CASE DESCRIPTION: We present a 16-year-old girl with Prader-Willi syndrome exhibiting loss of appetite, stomach ache and regurgitation. Gastro-enteritis was suspected. However, she rapidly developed severe septic shock. During emergency surgery, a fully necrotic and ruptured stomach was seen. Despite respiratory, haemodynamic and surgical efforts, the patient died of necrotic intestinal bleeding. CONCLUSION: Binge eating or deviant gastric homeostasis could account for the relatively high incidence of gastric necrosis in patients with Prader-Willi syndrome. Loss of appetite and regurgitation in patients with this syndrome should be considered as warning signs of a possible life-threatening disorder.

Dose and type of crystalloid fluid therapy in adult hospitalized patients.

OBJECTIVE: In this narrative review, an overview is given of the pros and cons of various crystalloid fluids used for infusion during initial resuscitation or maintenance phases in adult hospitalized patients. Special emphasis is given on dose, composition of fluids, presence of buffers (in balanced solutions) and electrolytes, according to recent literature. We also review the use of hypertonic solutions. METHODS: We extracted relevant clinical literature in English specifically examining patient-oriented outcomes related to fluid volume and type. RESULTS: A restrictive fluid therapy prevents complications seen with liberal, large-volume therapy, even though restrictive fluid loading with crystalloids may not demonstrate large hemodynamic effects in surgical or septic patients. Hypertonic solutions may serve the purpose of small volume resuscitation but carry the disadvantage of hypernatremia. Hypotonic solutions are contraindicated in (impending) cerebral edema, whereas hypertonic solutions are probably more helpful in ameliorating than in preventing this condition and improving outcome. Balanced solutions offer a better approach for plasma composition than unbalanced ones, and the evidence for benefits in patient morbidity and mortality is increasing, particularly by helping to prevent acute kidney injury. CONCLUSIONS: Isotonic and hypertonic crystalloid fluids are the fluids of choice for resuscitation from hypovolemia and shock. The evidence that balanced solutions are superior to unbalanced ones is increasing. Hypertonic saline is effective in mannitol-refractory intracranial hypertension, whereas hypotonic solutions are contraindicated in this condition.

Systolic time intervals vs invasive predictors of fluid responsiveness after coronary artery bypass surgery.

OBJECTIVES: Haemodynamic parameters for predicting fluid responsiveness in intensive care patients are invasive, technically challenging or not universally applicable. We compared the initial systolic time interval (ISTI), a non-invasive measure of the time interval between the electrical and mechanical activities of the heart measured by impedance cardiography, with invasively measured haemodynamic parameters in predicting fluid responsiveness after cardiac surgery. METHODS: Thirty-two clinically hypovolemic patients admitted to the intensive care unit after coronary artery bypass surgery received 500 ml of gelatine solution in two volume loading steps of 250 ml at an infusion rate of 1000 ml/h. Haemodynamic and biochemical measurements were done at baseline and 15 min after each volume loading step with continuous recording of the impedance cardiogram and electrocardiogram. RESULTS: Forty-four percentage (n = 14) of patients showed a stroke volume (SV) index increase >10%. ISTI predicted fluid responsiveness with an optimum threshold of >153 ms (P = 0.023) and a sensitivity of 71% and specificity of 78%. The predictive values of ISTI did not differ from those of arterial pressure or SV at baseline. A decrease of ISTI of ≥8.3 ms predicted fluid responsiveness with the highest positive predictive value (88%, P = 0.004) among the variables, and absence thereof virtually excluded fluid responsiveness (specificity 94%). CONCLUSIONS: Non-invasively measured ISTI is able to predict and monitor fluid responsiveness after cardiac surgery non-inferiorly to invasively measured haemodynamic indices.