Kashyap, Rahul

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.

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.

Treatment options may be limited for infants with obstructive sleep apnea when there is no surgically correctable upper airway lesion. We therefore evaluated, retrospectively, the efficacy of low-flow oxygen as a therapeutic option for infant obstructive sleep apnea. We reviewed the medical charts of 23 infants who had undergone a therapeutic trial of low-flow oxygen during polysomnography. Split-night polysomnography was used in 21/23 subjects while 2/23 had undergone two separate, full-night polysomnography sleep architecture and respiratory findings on the baseline polysomnogram segment that was obtained in room air were compared with the segment on low-flow oxygen (0.25–1 L/min). Wilcoxon signed rank or McNemar’s test were used as indicated for comparing apnea hypopnea index and measures of sleep architecture at baseline and with oxygen therapy. The mean (±SD) age of subjects was 4.8 (±2.7) months, with 52% being males. The median apnea hypopnea index fell from a baseline of 18 (range 7–43) to 3 (range 1–19; p = 0.001) on oxygen. The baseline median obstructive/mixed apnea index decreased from 2 (range 1–16) to 1 during oxygen therapy (range 0–1; p = 0.003). Additionally, a significant decrease in central apnea index (median interquartile range (IQR) 1 (0–2) vs. 0 (0–1), p = 0.002) was noted. Sleep efficiency remained unaffected, while O2 saturation (SaO2) average and SaO2 nadir improved on oxygen. We were able to confirm the utility of low-flow oxygen in reducing central, obstructive, and mixed apneas and improving average oxygen saturation in infants with obstructive sleep apnea (OSA).

Background Troponin‐T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin‐T testing in the prognostication of these patients. Methods and Results This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin‐T and significant delta troponin‐T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in‐hospital mortality. Secondary outcomes included 1‐year mortality and lengths of stay. During this 8‐year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin‐T ≥0.01 ng/mL. Serial troponin‐T values were available in 732 (78%) patients. Elevated admission troponin‐T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin‐T was associated with higher severity of illness. Admission log 10 troponin‐T was associated with unadjusted in‐hospital (odds ratio 1.6; P =0.003) and 1‐year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin‐T and log 10 delta troponin‐T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin‐T remained an independent predictor of in‐hospital mortality (odds ratio 1.4; P =0.04) and 1‐year survival (hazard ratio 1.3; P =0.008). Conclusions In patients with sepsis and septic shock, elevated admission troponin‐T was associated with higher short‐ and long‐term mortality. Routine serial troponin‐T testing did not add incremental prognostic value in these patients.

Abstract Background: The association between new-onset left ventricular (LV) dysfunction during sepsis with long-term heart failure outcomes is lesser understood. Methods: Retrospective cohort study of all adult patients with severe sepsis and septic shock between 2007 and 2014 who underwent echocardiography within 72 h of admission to the intensive care unit. Patients with prior heart failure, LV dysfunction, and structural heart disease were excluded. LV systolic dysfunction was defined as LV ejection fraction <50% and LV diastolic dysfunction as ≥grade II. Primary composite outcome included new hospitalization for acute decompensated heart failure and all-cause mortality at 2-year follow-up. Secondary outcomes included persistent LV dysfunction, and hospital mortality and length of stay. Results: During this 8-year period, 434 patients with 206 (48%) patients having LV dysfunction were included. The two groups had similar baseline characteristics, but those with LV dysfunction had worse function as demonstrated by worse LV ejection fraction, cardiac index, and LV diastolic dysfunction. In the 331 hospital survivors, new-onset acute decompensated heart failure hospitalization did not differ between the two cohorts (15% vs. 11%). The primary composite outcome was comparable at 2-year follow-up between the groups with and without LV dysfunction (P = 0.24). Persistent LV dysfunction was noted in 28% hospital survivors on follow-up echocardiography. Other secondary outcomes were similar between the two groups. Conclusions: In patients with severe sepsis and septic shock, the presence of new-onset LV dysfunction did not increase the risk of long-term adverse heart failure outcomes.

Objectives: To study the effects of tele-ICU monitoring on interhospital transfers from community-based ICUs to the quaternary care hospital at Mayo Clinic, Rochester, MN. Design: This is a retrospective review of data on interhospital transfers comparing trends prior to tele-ICU implementation to those following implementation. Setting: Tele-ICU programs are increasingly utilized to fill resource gaps in caring for critically ill patients. How such programs impact population and bed management within a healthcare system are not known. Mayo Clinic serves as quaternary referral care center for hospitals in the region within the Mayo Clinic Health System. In August 2013, we implemented tele-ICU monitoring at six Mayo Clinic Health System hospital ICUs. Subjects: All adult ICU admissions during the study period (preimplementation phase: January 1, 2012, to December 31, 2012; and postimplementation phase: January 1, 2014, to December 31, 2014) in any of the six specified community ICUs were included in the study. Measurements and Main Results: Interhospital transfers significantly increased post institution of tele-ICU (p = 0.040) and was attributed primarily to transfer from less specialized ICUs (p = 0.037) as compared with more resource-intensive ICUs (p = 0.88). However, for such patient transfers, there were no significant differences before and after severity of illness scores, ICU mortality, or inhospital mortality. Conclusion: In a regional healthcare system, implementation of a tele-ICU program is associated with an increase in interhospital transfers from less resourced ICUs to the referral center, a trend that is not readily explained by increased severity of illness.

Objectives: Sarcopenia is associated with a poor prognosis in the ICU. The purpose of this study was to describe a simple sarcopenia index using routinely available renal biomarkers and evaluate its association with muscle mass and patient outcomes. Design: A retrospective cohort study. Setting: A tertiary-care medical center. Patients: High-risk adult ICU patients from October 2008 to December 2010. Interventions: The gold standard for muscle mass was quantified with the paraspinal muscle surface area at the L4 vertebrae in the subset of individuals with an abdominal CT scan. Using Pearson’s correlation coefficient, serum creatinine-to-serum cystatin C ratio was found to be the best performer in the estimation of muscle mass. The relationship between sarcopenia index and hospital and 90-day mortality, and the length of mechanical ventilation was evaluated. Measurements and Main Results: Out of 226 enrolled patients, 123 (54%) were female, and 198 (87%) were white. Median (interquartile range) age, body mass index, and body surface area were 68 (57–77) years, 28 (24–34) kg/m2, and 1.9 (1.7–2.2) m2, respectively. The mean (± sd) Acute Physiology and Chronic Health Evaluation III was 70 (± 22). ICU, hospital, and 90-day mortality rates were 5%, 12%, and 20%, respectively. The correlation (r) between sarcopenia index and muscle mass was 0.62 and coefficient of determination (r 2) was 0.27 (p < 0.0001). After adjustment for Acute Physiology and Chronic Health Evaluation III, body surface area, and age, sarcopenia index was independently predictive of both hospital (p = 0.001) and 90-day mortality (p < 0.0001). Among the 131 patients on mechanical ventilator, the duration of mechanical ventilation was significantly lower on those with higher sarcopenia index (–1 d for each 10 unit of sarcopenia index [95% CI, –1.4 to –0.2; p = 0.006]). Conclusions: The sarcopenia index is a fair measure for muscle mass estimation among ICU patients and can modestly predict hospital and 90-day mortality among patients who do not have acute kidney injury at the time of measurement.

Objectives: Approximately half of ICU admissions are comprised of patients older than 65 years old. Mild cognitive impairment is a common disorder affecting 10–20% of patients in the same age group. A need exists for exploring mild cognitive impairment and risk of critical illness. As mild cognitive impairment may be a contributor to poorer overall health or be a result of it, we sought to determine whether the presence of mild cognitive impairment independently increases the risk of critical illness admissions. Design: Data from the Mayo Clinic Study of Aging were analyzed. All study participants underwent prospective comprehensive cognitive testing and expert panel consensus diagnosis of both cognitive function and clinical state at baseline and subsequent visits. Comparisons were made between those with normal cognitive function and mild cognitive impairment regarding baseline health and frequency of critical illness. Setting: Single-center population-based cohort out of Olmsted County, MN. Participants: All individuals 70–89 years old were screened for prospective enrollment in the Mayo Clinic Study of Aging. Patients with preexisting dementia and ICU admission within 3 years of entry to the study were excluded from this analysis. Interventions: None. Measurements and Main Results: Of 2,425 patients analyzed from the Mayo Clinic Study of Aging, 1,734 patients (71%) were included in the current study. Clinical factors associated with baseline mild cognitive impairment included age, male gender, stroke, and poorer health self-rating. Using a Cox regression model adjusting for these and a priori variables of baseline health, the presence of mild cognitive impairment remained a significant predictor of ICU admission (hazard ratio, 1.50 [1.15–1.96]; p = 0.003). Conclusions and Relevance: The presence of mild cognitive impairment is independently associated with increased critical illness admission. Further prospective studies are needed to analyze the impact of critical illness on cognitive function.