Corrigendum: The functional trajectory in frail compared with non-frail critically ill patients during the hospital stay.

[This corrects the article DOI: 10.3389/fmed.2021.748812.].

Risk factors for Herpes simplex virus (HSV) and Cytomegalovirus (CMV) infections in critically-ill COVID-19 patients.

Background: To assess the prevalence of Herpes simplex and Cytomegalovirus infection in respiratory samples of critically-ill COVID-19 patients, its role in outcome and mortality and the influence of dexamethasone treatment in the early stage of SARS-CoV-2 infection. Methods: All mechanically ventilated COVID-19 patients treated on ICU between March 2020 and January 2021 were included. Respiratory specimens were tested for Herpes simplex virus (HSV) type 1, 2 and Cytomegalovirus (CMV) by quantitative real-time PCR. Clinical parameters were compared in the cohorts with and without HSV-1- infection. Results: 134 patients with a median age of 72.5 years (73.0% male, n=98) were included. HSV-1 reactivation occurred in 61 patients (45.5%), after median 9 (7-13) days of mechanical ventilation. The main factor for reactivation was length of stay on ICU (24 days vs 13 days, p<0.001) and duration of mechanical ventilation (417 vs 214 hours, p<0.001). Treatment with dexamethasone and a history of immunosuppression did not associate with HSV-infection in the univariate analysis (39 vs 41, p=0.462 and 27.9% vs 23.3%, p=0.561, respectively). Both ICU and hospital mortality were not significantly different in the cohorts with and without HSV-infection (57.4% vs 45.2%, p=0.219). Conclusions: Our study shows a high prevalence of HSV-infection in critically-ill COVID-19 patients which was unexpectedly higher than the prevalence of CMV-infections and unrelated to dexamethasone treatment. The main risk factors for HSV and CMV in the studied cohorts were the length of ICU stay and duration of mechanical ventilation. Therefore, we recommend routine monitoring of critically ill COVID-19 patients for these viral co-infections and consider treatment in those patients.

The Functional Trajectory in Frail Compared With Non-frail Critically Ill Patients During the Hospital Stay.

Background: Long-term outcome is determined not only by the acute critical illness but increasingly by the reduced functional reserve of pre-existing frailty. The patients with frailty currently account for one-third of the critically ill, resulting in higher mortality. There is evidence of how frailty affects the intrahospital functional trajectory of critically ill patients since prehospital status is often missing. Methods: In this prospective single-center cohort study at two interdisciplinary intensive care units (ICUs) at a university hospital in Germany, the frailty was assessed using the Clinical Frailty Scale (CFS) in the adult patients with critical illness with an ICU stay >24 h. The functional status was assessed using the sum of the subdomains "Mobility" and "Transfer" of the Barthel Index (MTB) at three time points (pre-hospital, ICU discharge, and hospital discharge). Results: We included 1,172 patients with a median age of 75 years, of which 290 patients (25%) were frail. In a propensity score-matched cohort, the probability of MTB deterioration till hospital discharge did not differ in the patients with frailty (odds ratio (OR) 1.3 [95% CI 0.8-1.9], p = 0.301), confirmed in several sensitivity analyses in all the patients and survivors only. Conclusion: The patients with frailty have a reduced functional status. Their intrahospital functional trajectory, however, was not worse than those in non-frail patients, suggesting a rehabilitation potential of function in critically ill patients with frailty.

Rapid clinical evolution for COVID-19 translates into early hospital admission and unfavourable outcome: a preliminary report.

BACKGROUND: A wide range of mortality rates has been reported in COVID-19 patients on the intensive care unit. We wanted to describe the clinical course and determine the mortality rate in our institution's intensive care units. METHODS: To this end, we performed a retrospective cohort study of 50 COVID-19 patients admitted to the ICU at a large German tertiary university hospital. Clinical features are reported with a focus on ICU interventions, such as mechanical ventilation, prone positioning and extracorporeal organ support. Outcome is presented using a 7-point ordinal scale on day 28 and 60 following ICU admission. RESULTS: The median age was 64 years, 78% were male. LDH and D-Dimers were elevated, and patients were low on Vitamin D. ARDS incidence was 75%, and 43/50 patients needed invasive ventilation. 22/50 patients intermittently needed prone positioning, and 7/50 required ECMO. The interval from onset of the first symptoms to admission to the hospital and to the ICU was shorter in non-survivors than in survivors. By day 60 after ICU admission, 52% of the patients had been discharged. 60-day mortality rate was 32%; 37% for ventilated patients, and 42% for those requiring both: ventilation and renal replacement therapy. CONCLUSIONS: Early deterioration might be seen as a warning signal for unfavourable outcome. Lung-protective ventilation including prone positioning remain the mainstay of the treatment.

Randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS): protocol for a randomized controlled trial.

BACKGROUND: Albumin is a key regulator of fluid distribution within the extracellular space and has several properties beyond its oncotic activity. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock. METHODS/DESIGN: The randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS) investigates whether the replacement with albumin and the maintenance of its serum levels of at least 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. Adult patients (≥ 18 years) with septic shock are randomly assigned within a maximum of 24 h after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group receive a 60-g loading dose of human albumin 20% over 2-3 h. Serum albumin levels are maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. The control group is treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary endpoint is 90 days mortality and secondary endpoints include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, total amount of fluid administration and total fluid balance in the ICU, and lengths of ICU and hospital stay. In total, 1412 patients need to be analysed, 706 per group. For the sample size estimation, a 15% reduction in 90-day mortality is assumed, i.e. an absolute reduction of 7.5% points to 42.5% (relative risk 1.18). Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated. DISCUSSION: The results of the clinical trial may influence the treatment of patients with septic shock. The expected improvement in patient survival may result in a reduction in the resources currently used in the treatment of these patients and in the socioeconomic burden of this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03869385 . Registration on 18 July 2019. Protocol version: Final 3.0.

Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.

BACKGROUND: Acute kidney injury is a common complication after major surgery. In this study, we investigated whether an algorithm-guided goal-directed haemodynamic therapy (GDT) can improve renal outcome compared to good standard clinical care. METHODS: A total of 180 patients undergoing major abdominal surgery were prospectively and randomly assigned to one of two groups: in the GDT group, patients were treated with a GDT algorithm using transpulmonary thermodilution while standard care was applied to the control patients. Change in creatinine was studied as the primary end point, postoperative complications as well as 1-year mortality as secondary outcomes. Haemodynamics in GDT and control patients were compared calculating goal-achievement rates. RESULTS: Postoperative change in creatinine (18 ± 39 µmol/l (control) vs. 16 ± 42 µmol/l (GDT); mean difference (95 % confidence interval) 1.6 µmol/l (-10 to 13 µmol/l)) was comparable between the GDT and the control group. Postoperative complications and mortality during hospital stay and after 1 year were not influenced by the use of a GDT algorithm. Achievement rates of haemodynamic goals were not higher in the GDT group compared to the already high (>80 %) rates in the control group. Multivariate regression analysis revealed intraoperative hypotension (MAP < 70 mmHg) and postoperative hypovolaemia (GEDI < 640 ml/m(2)) as risk factors for postoperative renal impairment. CONCLUSIONS: In this study, GDT was not superior to standard clinical care in order to avoid renal failure after major abdominal surgery. The reason for this finding is most likely the high achievement rate of haemodynamic goals in the control group, which cannot be improved by the GDT algorithm. TRIAL REGISTRATION: Clinicaltrials.gov; NCT01035541; registered 17 December 2009.

Nefopam and ketamine comparably enhance postoperative analgesia.

Opioids alone sometimes provide insufficient postoperative analgesia. Coadministration of drugs may reduce opioid use and improve opioid efficacy. We therefore tested the hypothesis that the administration of ketamine or nefopam to postoperative patients with pain only partly alleviated by morphine reduces the amount of subsequent opioid necessary to produce adequate analgesia. Patients (n=77) recovering from major surgery were given up to 9 mg of IV morphine. Those who still had pain were randomly assigned to blinded administration of 1) isotonic saline (control group; n=21), 2) ketamine 10 mg (ketamine group; n=22), or 3) nefopam 20 mg (nefopam group; n=22). Three-milligram morphine boluses were subsequently given at 5-min intervals until adequate analgesia was obtained, until 60 min elapsed after the beginning of study drug administration, or until ventilation became insufficient (respiratory rate <10 breaths/min or saturation by pulse oximetry <95%). Supplemental morphine (i.e., after test drug administration) requirements were significantly more in the control group (mean +/- sd; 17 +/- 10 mg) than in the nefopam (10 +/- 5 mg; P <0.005) or ketamine (9 +/- 5 mg; P <0.001) groups. Morphine titration was successful in all ketamine and nefopam patients but failed in four control patients (two because of respiratory toxicity and two because of persistent pain). Tachycardia and profuse sweating were more frequent in patients given nefopam, and sedation was more intense with ketamine; however, the incidence of other potential complications did not differ among groups.

Endoscopic ultrasonography for upper gastrointestinal submucosal lesions: a cost minimization analysis with an international perspective.

OBJECTIVES: Our prospective clinical study of prospectively compared physicians' management of submucosal tumors (SMTs) with and without endoscopic ultrasound (EUS). It showed that EUS reduced further tests by more than 50%, but it is unclear whether it reduced the overall costs. The aim of this study was to determine whether EUS would reduce costs. METHODS: Based on the data from the clinical study, a decision analysis was created to compare the direct hospital costs for diagnosing SMTs with and without EUS. Cost data from Germany, Canada, Japan, France, and the United States were used. Costs were expressed as a ratio of the cost of esophagogastroduodenoscopy (EGD). Average cost ratios for each procedure were as follows (sensitivity analysis ranges are 95% CIs): EGD = 1; large particle biopsy (LPB) 0.75 (0.22-1.24); endoscopic ultrasound (EUS) 2.0 (1.22-2.79); abdominal ultrasound (US) 0.77 (0.31-1.24); computed tomography (CT) 1.79 (0.64-2.95); magnetic resonance imaging (MRI) 3.54 (1.28-5.79); and ERCP 3.45 (0.82-6.07). RESULTS: Initial inputs show the "no EUS" strategy is less costly when cost data for all countries are averaged (expected cost 2.13 vs 2.71, expressed as a ratio of the cost of EGD]) and for all countries individually except Germany. In descending order, overall management costs were most sensitive to the relative costs of CT and EUS, the cost of LPB, and to the probability of no further testing when the "no EUS" strategy is used. However, threshold analysis showed that changes in only one variable, the ratio of the cost of EUS compared to CT (the "EUS/CT ratio"), were able to shift the optimal strategy from "no EUS" to "EUS." "EUS" becomes less costly only if the EUS/CT cost ratio is <0.85 (i.e., if the cost of EUS is <85% that of CT). If the potential for EUS to reduce severe complications caused by LPB of high risk lesions is incorporated, "EUS" is less costly if this risk is >2% (range 1-5%). CONCLUSIONS: When used to diagnose SMTs, EUS may reduce the need for further tests but not necessarily costs. For this indication, the relative cost of EUS compared with CT is what most limits its potential value as a cost-minimizing test. The costs, economic impact, and hence the relative appropriateness of EUS and other procedures may vary in different health care systems.