Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a ...major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient's severity and outcome.
We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as well as microbiological samples, whenever present.
Of a total of 65 patients with COVID-19 admitted to our ICU we included 41 patients with repeated measure of IL-6. There was a significant difference in IL-6 levels between survivors and non-survivors over time (p = 0.001); moreover, non survivors had a significantly higher IL-6 maximal value when compared to survivors (720 349-2116 vs. 336 195-646 pg/mL, p = 0.01). The IL-6 maximal value had a significant predictive value of ICU mortality (AUROC 0.73 95% CI 0.57-0.89; p = 0.01).
Repeated measurements of IL-6 can help clinicians in identifying critically ill COVID-19 patients with the highest risk of poor prognosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Brain hypoxia can occur after non-traumatic subarachnoid hemorrhage (SAH), even when levels of intracranial pressure (ICP) remain normal. Brain tissue oxygenation (PbtO
2
) can be measured ...as a part of a neurological multimodal neuromonitoring. Low PbtO
2
has been associated with poor neurologic recovery. There is scarce data on the impact of PbtO
2
guided-therapy on patients’ outcome. This single-center cohort study (June 2014–March 2020) included all patients admitted to the ICU after SAH who required multimodal monitoring. Patients with imminent brain death were excluded. Our primary goal was to assess the impact of PbtO
2
-guided therapy on neurological outcome. Secondary outcome included the association of brain hypoxia with outcome. Of the 163 patients that underwent ICP monitoring, 62 were monitored with PbtO
2
and 54 (87%) had at least one episode of brain hypoxia. In patients that required treatment based on neuromonitoring strategies, PbtO
2
-guided therapy (OR 0.33 CI 95% 0.12–0.89) compared to ICP-guided therapy had a protective effect on neurological outcome at 6 months. In this cohort of SAH patients, PbtO
2
-guided therapy might be associated with improved long-term neurological outcome, only when compared to ICP-guided therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the ...association between CAPA development and the incidence and prognosis of
(CMV) reactivation in critically ill COVID-19 patients. We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from 25 February 2020 to 8 May 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. CAPA occurred in 96 patients (16.6%) of the 579 patients analyzed. Among the CAPA population, 40 (41.7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7-27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (
= 0.166). The CAPA+CMV group had a longer ICU stay, fewer ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21-4.48,
= 0.011). In critically ill COVID-19 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality.
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Electroencephalography (EEG) is widely used to monitor critically ill patients. However, EEG interpretation requires the presence of an experienced neurophysiologist and is time-consuming. Aim of ...this study was to evaluate whether parameters derived from an automated pupillometer (AP) might help to assess the degree of cerebral dysfunction in critically ill patients.
Prospective study conducted in the Department of Intensive Care of Erasme University Hospital in Brussels, Belgium. Pupillary assessments were performed using the AP in three subgroups of patients, concomitantly monitored with continuous EEG: "anoxic brain injury", "Non-anoxic brain injury" and "other diseases". An independent neurologist blinded to patient's history and AP results scored the degree of encephalopathy and reactivity on EEG using a standardized scale. The mean value of Neurologic Pupil Index (NPi), pupillary size, constriction rate, constriction and dilation velocity (CV and DV) and latency for both eyes, obtained using the NPi®-200 (Neuroptics, Laguna Hills, CA, USA), were reported.
We included 214 patients (mean age 60 years, 55% male). EEG tracings were categorized as: mild (
= 111, 52%), moderate (
= 65, 30%) or severe (
= 16, 8%) encephalopathy; burst-suppression (
= 19, 9%) or suppression background (
= 3, 1%); a total of 38 (18%) EEG were classified as "unreactive". We found a significant difference in all pupillometry variables among different EEG categories. Moreover, an unreactive EEG was associated with lower NPi, pupil size, pupillary reactivity, CV and DV and a higher latency than reactive recordings. Low DV (Odds ratio 0.020 95% confidence intervals 0.002-0.163;
< 0.01) was independently associated with an unreactive EEG, together with the use of analgesic/sedative drugs and high lactate concentrations. In particular, DV values had an area under the curve (AUC) of 0.86 0.79-0.92;
< 0.01 to predict the presence of unreactive EEG. In subgroups analyses, AUC of DV to predict unreactive EEG was lower (0.72 0.56-0.87;
< 0.01) in anoxic brain injury than Non-anoxic brain injury (0.92 0.85-1.00;
< 0.01) and other diseases (0.96 0.90-1.00;
< 0.01).
This study suggests that low DV measured by the AP might effectively identify an unreactive EEG background, in particular in critically ill patients without anoxic brain injury.
The aim of our study was to evaluate whether the introduction of SDD in a structured protocol for VAP prevention was effective in reducing the occurrence of ventilator-associated pneumonia (VAP) in ...COVID-19 patients without changes in the microbiological pattern of antibiotic resistance. This observational pre-post study included adult patients requiring invasive mechanical ventilation (IMV) for severe respiratory failure related to SARS-CoV-2 admitted in three COVID-19 intensive care units (ICUs) in an Italian hospital from 22 February 2020 to 8 March 2022. Selective digestive decontamination (SDD) was introduced from the end of April 2021 in the structured protocol for VAP prevention. The SDD consisted of a tobramycin sulfate, colistin sulfate, and amphotericin B suspension applied in the patient's oropharynx and the stomach via a nasogastric tube. Three-hundred-and-forty-eight patients were included in the study. In the 86 patients (32.9%) who received SDD, the occurrence of VAP decreased by 7.7% (
= 0.192) compared to the patients who did not receive SDD. The onset time of VAP, the occurrence of multidrug-resistant microorganisms AP, the length of invasive mechanical ventilation, and hospital mortality were similar in the patients who received and who did not receive SDD. The multivariate analysis adjusted for confounders showed that the use of SDD reduces the occurrence of VAP (HR 0.536, CI 0.338-0.851;
= 0.017). Our pre-post observational study indicates that the use of SDD in a structured protocol for VAP prevention seems to reduce the occurrence of VAP without changes in the incidence of multidrug-resistant bacteria in COVID-19 patients.
In COVID-19 patients, procalcitonin (PCT) and C-reactive protein (CRP) performance in identifying bacterial infections remains unclear. Our study aimed to evaluate the association of PCT and CRP with ...secondary infections acquired during ICU stay in critically ill COVID-19 patients. This observational study included adult patients admitted to three COVID-19 intensive care units (ICUs) from February 2020 to May 2022 with respiratory failure caused by SARS-CoV-2 infection and ICU stay ≥ 11 days. The values of PCT and CRP collected on the day of infection diagnosis were compared to those collected on day 11 after ICU admission, the median time for infection occurrence, in patients without secondary infection. The receiver operating characteristic curve (ROC) and multivariate logistic model were used to assess PCT and CRP association with secondary infections. Two hundred and seventy-nine patients were included, of whom 169 (60.6%) developed secondary infection after ICU admission. The PCT and CRP values observed on the day of the infection diagnosis were larger (p < 0.001) than those observed on day 11 after ICU admission in patients without secondary infections. The ROC analysis calculated an AUC of 0.744 (95%CI 0.685–0.803) and 0.754 (95%CI 0.695–0.812) for PCT and CRP, respectively. Multivariate logistic models showed that PCT ≥ 0.16 ng/mL and CRP ≥ 1.35 mg/dL were associated (p < 0.001) with infections acquired during ICU stay. Our results indicated that in COVID-19 patients, PCT and CRP values were associated with infections acquired during the ICU stay and can be used to support, together with clinical signs, rather than predict or rule out, the diagnosis of these infections.
: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients.
: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. ...Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm
. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia.
: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic-ROC curve, 0.84 (95% CIs 0.78-0.90) and 0.84 (95% CIs 0.77-0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings.
: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available.
Pain assessment is a challenge in critically ill patients, in particular those who are unable to express movements in reaction to noxious stimuli. The purpose of the study was to compare the ...pupillary response and skin conductance to pain stimulation in critically ill unconscious patients.
This observational study included adult patients admitted to the intensive care unit (ICU) with acute brain injury (Glasgow Coma Scale < 9 with a motor response < 5) and/or requirements for deep level of sedation. Automated pupillometry (Algiscan, ID-MED, Marseille, France) was used to determine pupillary reflex dilation during tetanic stimulation. The maximum intensity of the stimulation value allowed the determination of a pupillary pain index score ranging from 1 (no nociception) to 9 (high nociception): a pupillary pain index (PPI) score of ≤4 was used to reflect adequate pain control. For skin conductance (SC), the number of SC peaks per second (NSCF) was collected concomitantly to tetanic stimulation. An NSCF of ≤0.07 peak/second was used to reflect adequate pain control.
Of the 51 included patients, there were 32 with brain injury and 19 receiving deep sedation. Mean PPI score was 5 (Interquartile Range= 2-7); a total of 28 (55%) patients showed inadequate control of the nociceptive stimulation according to the PPI assessment. Only 15 (29%) patients showed a detectable skin conductance, with NSCF values from 0.07 to 0.47/s. No correlation was found between skin conductance algesimeter (SCA)-derived variables and PPI score or pupillary dilation to pain.
Detection of inadequate pain control might vary according to the method used to assess nociception in ICU patients. A poor agreement between quantitative pupillometry and skin conductance was observed.
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Blood lactate concentrations are often used to assess global tissue perfusion in critically ill patients; however, there are scarce data on lactate concentrations after subarachnoid hemorrhage (SAH). ...We aimed to assess the prognostic role of serial blood lactate measurements on hospital mortality and neurological outcomes at 3 months after SAH. We reviewed all SAH patients admitted to the intensive care unit from 2007 to 2019 and recorded the highest daily arterial lactate concentration for the first 6 days. Patients with no lactate concentration were excluded. Hyperlactatemia was defined as a blood lactate concentration >2.0 mmol/L. A total of 456 patients were included: 158 (35%) patients died in hospital and 209 (46%) had an unfavorable outcome (UO) at 3 months. The median highest lactate concentration was 2.7 (1.8-3.9) mmol/L. Non-survivors and patients with UO had significantly higher lactate concentrations compared to other patients. Hyperlactatemia increased the chance of dying (OR 4.19 (95% CI 2.38-7.39)) and of having UO in 3 months (OR 4.16 (95% CI 2.52-6.88)) after adjusting for confounding factors. Therefore, initial blood lactate concentrations have prognostic implications in patients with SAH; their role in conjunction with other prognostic indicators should be evaluated in prospective studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
OBJECTIVES:To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients.
DESIGN:Retrospective analysis of prospectively collected ...data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020.
SETTING:ICU of an University Hospital in Belgium.
PATIENTS AND INTERVENTIONS:Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin).
MEASUREMENTS AND MAIN RESULTS:Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4–8 d) since ICU admission and 12 days (9–16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs0.78–1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%—odds ratio 0.13 0.02–0.69; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 0.24–3.26; p = 0.99).
CONCLUSIONS:In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.
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