Chronic dysglycemia and risk of SARS-CoV-2 associated respiratory failure in hospitalized patients.

BACKGROUND: Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS-CoV-2 positive patients. METHODS: In this retrospective observational study, we included 385 hospitalized SARS-CoV-2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS-CoV-2-induced respiratory failure. RESULTS: Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS-CoV-2-induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27-39.43), unknown diabetes (OR 15.86, 95% CI 4.55-55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77-53.74) was independently associated with increased risk of SARS-CoV-2-induced respiratory failure. CONCLUSION: In our cohort of hospitalized SARS-CoV-2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS-CoV-2-associated respiratory failure.

Opioid use following cardio-thoracic intensive care: risk factors and outcomes: a cohort study.

Opioid misuse has become a serious public health problem. Patients admitted to cardio-thoracic critical care are usually exposed to opioids, but the incidence and effects of chronic opioid use are not known. The primary objective was to describe opioid use after admission to a cardio-thoracic intensive care unit. Secondary objectives were to identify factors associated with chronic opioid usage and analyze risk of death. This cohort study included all cardio-thoracic ICU care episodes in Sweden between 2010 and 2018. Among the 34,200 patients included in the final study cohort, 4050 developed persistent opioid use after ICU care. Younger age, preadmission opioid use, female sex, presence of comorbidities and earlier year of ICU admission were all found to be associated with persistent opioid use. The adjusted hazard ratio for mortality between 6 and 18 months after admission among individuals with persistent opioid use was 2.2 (95% CI 1.8-2.6; P < 0.001). For opioid-naïve patients before ICU admission, new onset of chronic opioid usage was significant during the follow-up period of 24 months. Despite the absence of conclusive evidence supporting extended opioid treatment, the average opioid consumption remains notably elevated twelve months subsequent to cardio-thoracic ICU care.

Benzodiazepine Dependence After Cardiothoracic Intensive Care: A Nationwide Cohort Study.

BACKGROUND: This study aimed to describe benzodiazepine use after cardiothoracic intensive care unit (ICU) care, including factors associated with new long-term high-potency benzodiazepine use after critical care, and to determine whether benzodiazepine use is associated with an increased risk of death. METHODS: A nationwide retrospective cohort study was conducted of all cardiothoracic ICU patients in Sweden between 2010 and 2018. All patients older than 18 years who survived the first 3 months after admission to a cardiothoracic ICU were eligible for inclusion. A total of 36,135 patients were screened, and 4163 were ineligible. RESULTS: In the final study cohort of 31,972 benzodiazepine-naive patients admitted to critical care, 578 patients had persistent high-potency benzodiazepine use. The proportion of new persistent benzodiazepine users was 5% in the first 3 months after ICU care, followed by a decline to a consistent level of 2% at 2 years of follow-up. Factors associated with persistent benzodiazepine use included higher age, female sex, psychiatric and somatic comorbidities, substance abuse, and preadmission opioid and low-potency benzodiazepine use. Adjusted hazard ratio for death 6 to 18 months after admission for new persistent benzodiazepine users was 2.2 (95% CI, 1.5-3.1; P < .001). CONCLUSIONS: High-potency benzodiazepine consumption is increased 2 years after admission to cardiothoracic ICU care despite lack of support for long-term use of benzodiazepines. Being older and female, prior opioid use, and comorbid conditions were among risk factors for persistent benzodiazepine use. Persistent benzodiazepine users had an increased risk of death.

Prevalence and impact of chronic dysglycaemia among patients with COVID-19 in Swedish intensive care units: a multicentre, retrospective cohort study.

OBJECTIVE: Using glycated haemoglobin A1c (HbA1c) screening, we aimed to determine the prevalence of chronic dysglycaemia among patients with COVID-19 admitted to the intensive care unit (ICU). Additionally, we aimed to explore the association between chronic dysglycaemia and clinical outcomes related to ICU stay. DESIGN: Multicentre retrospective observational study. SETTING: ICUs in three hospitals in Stockholm, Sweden. PARTICIPANTS: COVID-19 patients admitted to the ICU between 5 March 2020 and 13 August 2020 with available HbA1c at admission. Chronic dysglycaemia was determined based on previous diabetes history and HbA1c. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was the actual prevalence of chronic dysglycaemia (pre-diabetes, unknown diabetes or known diabetes) among COVID-19 patients. Secondary outcome was the association of chronic dysglycaemia with 90-day mortality, ICU length of stay, duration of invasive mechanical ventilation (IMV) and renal replacement therapy (RRT), accounting for treatment selection bias. RESULTS: A total of 308 patients with available admission HbA1c were included. Chronic dysglycaemia prevalence assessment was restricted to 206 patients admitted ICUs in which HbA1c was measured on all admitted patients. Chronic dysglycaemia was present in 82.0% (95% CI 76.1% to 87.0%) of patients, with pre-diabetes present in 40.2% (95% CI 33.5% to 47.3%), unknown diabetes in 20.9% (95% CI 15.5% to 27.1%), well-controlled diabetes in 7.8% (95% CI 4.5% to 12.3%) and uncontrolled diabetes in 13.1% (95% CI 8.8% to 18.5%). All patients with available HbA1c were included for the analysis of the relationship between chronic dysglycaemia and secondary outcomes. We found no independent association between chronic dysglycaemia and 90-day mortality, ICU length of stay or duration of IMV. After excluding patients with specific treatment limitations, no association between chronic dysglycaemia and RRT use was observed. CONCLUSIONS: In our cohort of critically ill COVID-19 patients, the prevalence of chronic dysglycaemia was 82%. We found no robust associations between chronic dysglycaemia and clinical outcomes when accounting for treatment limitations.

The Use of Levosimendan after Out-of-Hospital Cardiac Arrest and Its Association with Outcome-An Observational Study.

Background: Levosimendan improves resuscitation rates and cardiac performance in animal cardiac arrest models. The aim of this study was to describe the use of levosimendan in out-of-hospital cardiac arrest (OHCA) patients and its association with outcome. Methods: A retrospective observational study of OHCA patients admitted to six intensive care units in Stockholm, Sweden, between 2010 and 2016. Patients treated with levosimendan within 24 h from admission were compared with those not treated with levosimendan. Propensity score matching and multivariable logistic regression analysis were used to assess the association between levosimendan treatment and 30-day mortality Results: Levosimendan treatment was initiated in 94/940 (10%) patients within 24 h. The proportion of men (81%, vs. 67%, p = 0.007), initial shockable rhythm (66% vs. 37%, p < 0.001), acute myocardial infarction, AMI (47% vs. 24%, p < 0.001) and need for vasoactive support (98% vs. 61%, p < 0.001) were higher among patients treated with levosimendan. After adjustment for age, sex, bystander cardiopulmonary resuscitation, witnessed status, initial rhythm and AMI, the odds ratio (OR) for 30-day mortality in the levosimendan group compared to the no-levosimendan group was 0.94 (95% Confidence interval [CI], 0.56−1.57, p = 0.82). Similar results were seen when using a propensity score analysis comparing patients with circulatory shock. Conclusions: In this observational study of OHCA patients, levosimendan was used in a limited patient group, most often in those with initial shockable rhythms, acute myocardial infarction and with a high need for vasopressors. In this limited patient cohort, levosimendan treatment was not associated with 30-day mortality. However, a better matching of patient factors and indications for use is required to derive conclusions on associations with outcome.

Electrolyte and acid-base imbalance in severe COVID-19.

Acute systemic diseases, such as severe infections, can lead to electrolyte and acid-base alterations. To study the presence of electrolyte imbalance in severe COVID-19, we investigated the frequency and consequences of changes in electrolyte and acid-base patterns over time. We performed a retrospective cohort study including 406 patients with severe COVID-19. Levels of electrolytes, base excess, pH, serum osmolality, and hematocrit, the first 2 weeks of hospitalization, were collected daily from the laboratory database and clinical data from patients' medical records. We found that hyponatremia was present in 57% of the patients at admission and 2% in hypernatremia. However, within 2 weeks of hospitalization 42% of the patients developed hypernatremia, more frequently in critically ill patients. Lower levels of sodium and potassium during admission were associated with the need for mechanical ventilation. Decreased pH at admission was associated with both death and the need for mechanical ventilation. Hypernatremia in the ICU was combined with rising base excess and a higher pH. In the group without intensive care, potassium levels were significantly lower in the patients with severe hypernatremia. Presence of hypernatremia during the first 2 weeks of hospitalization was associated with 3.942 (95% CI 2.269-6.851) times higher odds of death. In summary, hypernatremia was common and associated with longer hospital stay and a higher risk of death, suggesting that the dynamics of sodium are an important indicator of severity in COVID-19.

Continuous renal replacement therapy in intensive care patients with COVID-19; survival and renal recovery.

BACKGROUND: Outcome for critically ill patients with COVID-19 treated with continuous renal replacement therapy (CRRT) is largely unknown. We describe mortality and renal outcome in this group. METHODS: This observational study was conducted at a university hospital in Sweden. We studied critically ill adult COVID-19 patients with Acute Kidney injury (AKI) who received CRRT. RESULTS: In 451 patients, AKI incidence was 43.7%. 18.2% received CRRT. Median age of CRRT patients was 60 years (IQR 54-65), 90% were male, median BMI was 29 (IQR 25-32), 23.2% had Diabetes, 37.8% hypertension and 6.1% chronic kidney disease prior to admission. 100% required mechanical ventilation. 8.5% received Extra Corporeal Membrane Oxygenation. Median length of stay was 23 days (IQR 15-26). ICU mortality was 39% and 90-day mortality was 45.1%. Age, baseline creatinine values and body weight change were associated with 60 days mortality. Of the survivors, no patients required dialysis at hospital discharge, 73.8% recovered renal function and a median 10.5% of body weight was lost during admission. CONCLUSIONS: Critically ill COVID-19 patients with AKI who received CRRT had a 90-day mortality of 45.1%. At follow-up, three quarters of survivors had recovered renal function. This information is important in the clinical management of COVID-19.

COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.

SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.

Thromboembolism, Hypercoagulopathy, and Antiphospholipid Antibodies in Critically Ill Coronavirus Disease 2019 Patients: A Before and After Study of Enhanced Anticoagulation.

To determine the prevalence of thrombotic events, functional coagulation tests, inflammatory biomarkers, and antiphospholipid antibodies before and after enhanced anticoagulation in critically ill coronavirus disease 2019 patients. DESIGN: Retrospective. SETTING: Tertiary intensive care unit. PATIENTS: Two cross-sectional cohorts of ICU-treated coronavirus disease 2019 patients were included before (cohort 1, n = 12) and after (cohort 2, n = 14) enhanced prophylactic anticoagulation strategy. INTERVENTIONS: Before and after study of enhanced anticoagulation. MEASUREMENTS AND MAIN RESULTS: Thromboelastometry point-of-care coagulation tests were performed by thromboelastography (Tem International GmbH, Munich, Germany), standard blood tests were extracted from patient charts, and presence of antiphospholipid antibodies in plasma was measured. All patients were males on mechanical ventilation. In cohort 1 (low-molecular-weight heparin dose: 129 ± 53 U/kg/24 hr), 50% had pulmonary embolism, and thromboelastography analysis revealed hypercoagulation in a majority of patients and greater than 80% had detectable antiphospholipid antibodies. In the second cohort (enhanced low-molecular-weight heparin dose: 200 ± 82 U/kg/24 hr; p = 0.04 vs cohort 1), we found a nonsignificantly lower prevalence of pulmonary embolism (21%; p = 0.22), lower fibrinogen (6.3 ± 2.5 vs 8.7 ± 2.0; p = 0.02), reduced fibrinogen-dependent thromboelastography (p < 0.001), and lower inflammatory markers. CONCLUSIONS: In these two cross-sectional cohorts of ICU-treated coronavirus disease 2019 patients, thromboembolic complications, hypercoagulation, and antiphospholipid antibodies were common. A more aggressive anticoagulation regime was associated with a reduction in inflammatory biomarkers including plasma fibrinogen and a reduction in fibrinogen-dependent hypercoagulation, as indicated by thromboelastography analyses.

The effect of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model - A blinded randomized placebo-controlled study in swine.

BACKGROUND: Survival after out-of-hospital cardiac arrest remains poor. Levosimendan could be a new intervention in this setting. Therefore, we conducted a blinded, placebo controlled randomized study investigating the effects of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model in swine. METHODS: Twenty-four anesthetised swines underwent experimentally-induced acute myocardial infarction and ventricular fibrillation. At the start of CPR, a bolus dose of levosimendan (12 µg kg-1) or placebo was given followed by a 24-h infusion (0.2 µg kg-1 min-1) after return of spontaneously circulation. Animals were evaluated by risk of death, post-resuscitation hemodynamics and infarction size by magnetic resonance imaging (MRI) up to 32 h post arrest. RESULTS: Spontaneous circulation was restored in all (12/12) animals in the levosimendan group compared to two thirds (8/12) in the placebo group (P = 0.09). Protocol survival was higher for the levosimendan group (P = 0.02) with an estimated 88% lower risk of death compared to placebo (hazard ratio [95% confidence interval] 0.12 [0.01-0.96], P = 0.046). Cardiac output (CO) recovered 40% faster during the first hour of the intensive care period for the levosimendan group (difference 0.13 [0.01-0.26] L min-1P = 0.04). The placebo group required higher inotropic support during the intensive care period which masked an even bigger recovery in CO in the levosimendan group (58%). The MRI showed no difference in myocardial scar size or in myocardial area at risk. CONCLUSIONS: Levosimendan given intra-arrest and during the first 24-h of post-resuscitation care improved survival and cardiac performance in this ischemic cardiac arrest model. Institutional Protocol Number; KERIC 5.2.18-14933.

Drug therapy in cardiac arrest: a review of the literature.

The aim of this study was to review the literature on human studies of drug therapy in cardiac arrest during the last 25 years. In May 2015, a systematic literature search was performed in PubMed, Embase, the Cochrane Library, and CRD databases. Prospective interventional and observational studies evaluating a specified drug therapy in human cardiac arrest reporting a clinical endpoint [i.e. return of spontaneous circulation (ROSC) or survival] and published in English 1990 or later were included, whereas animal studies, case series and reports, studies of drug administration, drug pharmacology, non-specified drug therapies, preventive drug therapy, drug administration after ROSC, studies with primarily physiological endpoints, and studies of traumatic cardiac arrest were excluded. The literature search identified a total of 8936 articles. Eighty-eight articles met our inclusion criteria and were included in the review. We identified no human study in which drug therapy, compared with placebo, improved long-term survival. Regarding adrenaline and amiodarone, the drugs currently recommended in cardiac arrest, two prospective randomized placebo-controlled trials, were identified for adrenaline, and one for amiodarone, but they were all underpowered to detect differences in survival to hospital discharge. Of all reviewed studies, only one recent prospective study demonstrated improved neurological outcome with one therapy over another using a combination of vasopressin, steroids, and adrenaline as the intervention compared with standard adrenaline administration. The evidence base for drug therapy in cardiac arrest is scarce. However, many human studies on drug therapy in cardiac arrest have not been powered to identify differences in important clinical outcomes such as survival to hospital discharge and favourable neurological outcome. Efforts are needed to initiate large multicentre prospective randomized clinical trials to evaluate both currently recommended and future drug therapies.