Gajić, Ognjen

Abstract Rationale No previous studies have examined the role of prehospital vulnerability in acute respiratory distress syndrome (ARDS) development and mortality in an acutely ill adult population. Objectives To describe the association between prehospital vulnerability and 1) the development of ARDS, 2) 28-day mortality, and 3) 1-year mortality. Methods This was a longitudinal prospective cohort study nested within the multicenter LIPS-A (Lung Injury Prevention Study-Aspirin) trial. We analyzed 301 participants who completed Vulnerable Elders Survey (VES) at baseline. Multivariable logistic regression and Cox regression analyses were used to describe the association between vulnerability and short-term outcomes (ARDS and 28-day mortality) and long-term outcomes (1-year mortality), respectively. Results The VES score ranged from 0 to 10 (median [interquartile range], 2.0 [0–6]); 143 (47.5%) fit criteria for prehospital vulnerability (VES ≥ 3). Vulnerability was not significantly associated with ARDS development (10 [7.0%] vulnerable patients developed ARDS as per LIPS-A study criteria vs. 20 [12.7%] without vulnerability; P = 0.10; adjusted odds ratio [95% confidence interval (CI)], 0.54 [0.24–1.24]; P = 0.15). Nor was vulnerability associated with 28-day mortality (15 [10.5%] vulnerable patients were dead by Day 28 vs. 11 [7.0%] nonvulnerable patients; P = 0.28; adjusted odds ratio [95% CI], 0.95 [0.39–2.26]; P = 0.90). Vulnerability was significantly associated with 1-year mortality in hospital survivors (35 [26.9%] vs. 13 [9.3%]; adjusted hazard ratio [95% CI], 2.20 [1.10–4.37]; P = 0.02). Conclusions In a population of adults recruited for their high risk of ARDS, prehospital vulnerability, measured by VES, was highly prevalent and strongly associated with 1-year mortality.

Objectives: Midodrine is an α1-agonist approved for orthostatic hypotension. Recently, it has received attention as an oral vasopressor to facilitate ICU discharge. The purpose of this study was to identify the incidence of continuation of newly initiated midodrine upon ICU and hospital discharge and identify risk factors associated with its occurrence. Design: Single-center retrospective study. Setting: ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. Patients: Adult patients admitted to any ICU who received new midodrine for hypotension and survived to discharge. Interventions: None. Measurements and Main Results: During the study period, 1,010 patients were newly started on midodrine and survived to ICU discharge. Midodrine was continued in 67% (672/1,010) of patients at ICU discharge. Admission to cardiovascular surgery ICU and mixed medical/surgical ICU was a risk factor for midodrine continuation at ICU discharge (odds ratio, 3.94 [2.50–6.21] and 2.03 [1.29–3.20], respectively). At hospital discharge, 34% (311/909) of patients were continued on midodrine therapy. History of congestive heart failure predicted midodrine continuation at hospital discharge (odds ratio, 1.49 [1.05–2.12]). Hypertension and use of mechanical ventilation were associated with a decreased odds of midodrine prescription at both ICU and hospital discharge. Of those discharged from the ICU or hospital on midodrine, 50% were concomitantly prescribed antihypertensives. Discharge from the ICU on midodrine was associated with a significantly shorter ICU length of stay (7.5 ± 8.9 vs 10.6 ± 13.4 d) and reduced risk of in-hospital mortality (hazard ratio, 0.47 [95% CI, 0.32–0.70]; p < 0.001), despite no difference in baseline severity of illness scores. In contrast, patients discharged from the hospital on midodrine had a higher risk of 1-year mortality (hazard ratio, 1.60 [95% CI, 1.26–2.04]; p < 0.001). Conclusions: This study established a high prevalence of midodrine continuation in transitions of care. The risks and benefits of this practice remain unclear. Future studies should explore the impact of this practice on patient outcomes and resource utilization. These insights could be used to model interventions for proper tapering, discontinuation, or follow-up of new start midodrine.

AbstractAcute respiratory distress syndrome (ARDS) remains an important clinical entity in the intensive care unit with a significant impact on morbidity and mortality. Effective therapeutic interventions are limited; thus current research focus has shifted from treatment to the prevention of this pulmonary syndrome. In recent decades, a decrease in the incidence of ARDS has been observed and this reduction is largely due to preventive strategies including safe lung ventilation practices, avoidance of iatrogenic exposures, and improvement in care of predisposing conditions such as sepsis and pneumonia. Early identification of at-risk patients, prompt treatment of predisposing conditions, and adoption of evidence-based best practice including restrictive transfusion strategies, conservative fluid management, avoidance of large tidal volume ventilation, and aspiration precaution practices are key preventive strategies with demonstrated benefits. There are currently no effective pharmacological preventive strategies for ARDS.

Sepsis in patients with cirrhosis is associated with high mortality. An impaired immune response accounts for the increased infection risk observed in these patients. Hemodynamic and systemic changes suggestive of sepsis may be observed in patients with cirrhosis in the absence of infection; therefore, diagnosis and treatment of sepsis may be delayed. The optimal management of the critically ill patient with sepsis and cirrhosis has not been well established and is generally extrapolated from consensus guidelines and expert recommendations made for management of patients without cirrhosis with sepsis. Despite the lack of strong evidence, we propose a contemporary pragmatic approach to sepsis management in patients with cirrhosis, including the choice of fluids, vasopressors, and antibiotics.

Objectives: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment. Design: An observational case-control study. Settings: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015. Patients: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge. Interventions: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization. Measurements and Main Results: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and persistent cognitive dysfunction was associated with higher frequency of acute brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia, hyperthermia, fluctuations in serum glucose, and treatment with quinolones or vancomycin. Association with sepsis observed in univariate analysis did not persist after adjustment. Conclusions: Cognitive dysfunction is highly prevalent in ICU patients. Incident new and persistent cognitive impairment is less common but important, potentially preventable problem after critical illness. Chronic comorbidities and number of ICU stays increase the risk of post-ICU cognitive dysfunction irrespective of age. Modifiable ICU exposures were identified as potential targets for future prevention trials.

Purpose of review In this review, we will discuss efforts and challenges in understanding and developing meaningful outcomes of critical care research, quality improvement and policy, which are patient-centered and goal concordant, rather than mortality alone. We shall discuss different aspects of what could constitute outcomes of critical illness as meaningful to the patients and other stakeholders, including families and providers. Recent findings Different outcome pathways after critical illness impact the patients, families and providers in multiple ways. For patients who die, it is important to consider the experience of dying. For the increasing number of survivors of critical illness, challenges of survival have surfaced. The physical, mental and social debility that survivors experience has evolved into the entity called post-ICU syndrome. The importance of prehospital health state trajectory and the need for the outcome of critical care to be aligned with the patients’ goals and preferences have been increasingly recognized. Summary A theoretical framework is outlined to help understand the impact of critical care interventions on outcomes that are meaningful to patients, families and healthcare providers.

Objectives: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. Design: Retrospective case series. Setting: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. Patients: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. Interventions: None. Measurements and Main Results: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50–74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58–87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass six (3.6%), total parenteral nutrition four (2.4%); exposure to valproic acid 17 (10%); status epilepticus 11 (6.6%), high tumour burden 19 (11.3%), and renal failure 82 (49.1%). Urea cycle defects were diagnosed in seven patients (4.1%). Hospital mortality was high (30%), and median ammonia level was higher among the nonsurvivors (74 vs 67 µg/dL; p = 0.05). Deaths were more likely in hyperammonemic patients who were older (p = 0.016), had greater illness severity (higher Acute Physiology and Chronic Health Evaluation III score, p < 0.01), malignancy (p < 0.01), and solid organ transplantation (p = 0.04), whereas seizure disorder was more common in survivors (p = 0.02). After adjustment, serum ammonia level was not associated with increased mortality. Conclusions: Hyperammonemia occurs in a substantial minority of critically ill patients without liver failure. These patients have a poor prognosis, although ammonia level per se is not independently associated with mortality. Serum ammonia should be measured when risk factors are present, such as nutritional deficiencies and protein refeeding, treatment with valproic acid, high tumour burden, and known or suspected urea cycle abnormalities.

Objectives: Midodrine is an oral alpha-agonist approved for orthostatic hypotension. The use of midodrine as a vasopressor sparing agent has steadily increased in the ICU despite limited evidence for its safety in that setting. We describe the trends in use and reported side effects and complications of midodrine in multidisciplinary ICUs of a tertiary care institution. Design: Single-center retrospective case series. Setting: Medical and surgical ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. Patients: Adult patients admitted to any ICU who received midodrine for hypotension were eligible. Interventions: None. Measurements and Main Results: We reviewed the mean arterial pressures and cumulative vasopressor dose before and after midodrine administration and assessed for reported complications. During the study period, a total of 1,119 patients were initiated on midodrine, 56% in surgical ICUs, 42% in medical ICUs, and 2% in a mixed medical and surgical neurology ICU. There was a significant decrease in the number of patients on vasopressors 24 hours after initiation of midodrine (663 to 344; p < 0.001); among the patients that remained on vasopressors, there was a significant decrease in the median cumulative vasopressor dose (p = 0.002). There was a significant increase in median mean arterial pressure 24 hours after initiation of midodrine among patients who were not on vasopressors (65–68; p < 0.01). Asymptomatic bradycardia (heart rate < 50 beats/min) was the most common side effect (n = 172 patients, median 39 beats/min). Two patients developed bowel ischemia after initiation of midodrine that prompted discontinuation of midodrine in one case. Evaluating trends of utilization, the off-label use of midodrine has increased steadily over the years across ICUs. Conclusions: Our results suggest that midodrine is being increasingly used as an adjunct to increase mean arterial pressure and facilitate weaning of vasopressors in the ICU. Prospective trials are required to further establish the appropriate timing, efficacy, safety, and cost-effectiveness of midodrine use in ICU patients.