Smischney, Nathan J.

Background Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state; leading to multiple sequelae. We sought to detect whether thromboelastography (TEG) parameters would be able to detect thromboembolic events in patients hospitalized with COVID-19. Methods We performed a retrospective multicenter case–control study of the Collaborative Research to Understand the Sequelae of Harm in COVID (CRUSH COVID) registry of 8 tertiary care level hospitals in the United States (US). This registry contains adult patients with COVID-19 hospitalized between March 2020 and September 2020. Results A total of 277 hospitalized COVID-19 patients were analyzed to determine whether conventional coagulation TEG parameters were associated with venous thromboembolic (VTE) and thrombotic events during hospitalization. A clotting index (CI) >3 was present in 45.8% of the population, consistent with a hypercoagulable state. Eighty-three percent of the patients had clot lysis at 30 min (LY30) = 0, consistent with fibrinolysis shutdown, with a median of 0.1%. We did not find TEG parameters (LY30 area under the receiver operating characteristic [ROC] curve [AUC] = 0.55, 95% CI: 0.44-0.65, P value = .32; alpha angle [α] AUC = 0.58, 95% CI: 0.47-0.69, P value = .17; K time AUC = 0.58, 95% CI: 0.46-0.69, P value = .67; maximum amplitude (MA) AUC = 0.54, 95% CI: 0.44-0.64, P value = .47; reaction time [R time] AUC = 0.53, 95% CI: 0.42-0.65, P value = .70) to be a good discriminator for VTE. We also did not find TEG parameters (LY30 AUC = 0.51, 95% CI: 0.42-0.60, P value = .84; R time AUC = 0.57, 95%CI: 0.48-0.67, P value .07; α AUC = 0.59, 95%CI: 0.51-0.68, P value = .02; K time AUC = 0.62, 95% CI: 0.53-0.70, P value = .07; MA AUC = 0.65, 95% CI: 0.57-0.74, P value < .01) to be a good discriminator for thrombotic events. Conclusions In this retrospective multicenter cohort study, TEG in COVID-19 hospitalized patients may indicate a hypercoagulable state, however, its use in detecting VTE or thrombotic events is limited in this population.

Background Hypotension with endotracheal intubation (ETI) is common and associated with adverse outcomes. We sought to evaluate whether a previously described hypotension prediction score (HYPS) for ETI is associated with worse patient outcomes and/or clinical conditions. Methods This study is a post hoc analysis of a prospective observational multicenter study involving adult (age ≥18 years) intensive care unit (ICU) patients undergoing ETI in which the HYPS was derived and validated on the entire cohort and a stable subset (ie, patients in stable condition). We evaluated the association between increasing HYPSs in both subsets and several patient-centered outcomes and clinical conditions. Results Complete data for HYPS calculations were available for 783 of 934 patients (84%). Logistic regression analysis showed increasing odds ratios (ORs) for the highest risk category for new-onset acute kidney injury (OR, 7.37; 95% CI, 2.58-21.08); new dialysis need (OR, 8.13; 95% CI, 1.74-37.91); ICU mortality (OR, 16.39; 95% CI, 5.99-44.87); and hospital mortality (OR, 18.65; 95% CI, 6.81-51.11). Although not increasing progressively, the OR for the highest risk group was significantly associated with new-onset hypovolemic shock (OR, 6.06; 95% CI, 1.47-25.00). With increasing HYPSs, median values (interquartile ranges) decreased progressively (lowest risk vs. highest risk) for ventilator-free days (23 [18-26] vs. 1 [0-21], P < .001) and ICU-free days (20 [11-24] vs. 0 [0-13], P < .001). Of the 729 patients in the stable subset, 598 (82%) had complete data for HYPS calculations. Logistic regression analysis showed significantly increasing ORs for the highest risk category for new-onset hypovolemic shock (OR, 7.41; 95% CI, 2.06-26.62); ICU mortality (OR, 5.08; 95% CI, 1.87-13.85); and hospital mortality (OR, 7.08; 95% CI, 2.63-19.07). Conclusions As the risk for peri-intubation hypotension increases, according to a validated hypotension prediction tool, so does the risk for adverse clinical events and certain clinical conditions. Trial Registration The study was registered at ClinicalTrials.gov (NCT02508948).

Background Sedatives are frequently administered in an ICU and are often dependent on patient population and ICU type. These differences may affect patient-centered outcomes. Objective Our primary objective was to identify differences in sedation practice among three different ICU types at an academic medical center. Methods This was a retrospective cross-sectional study of adult patients (≥18 years) requiring a continuous sedative for ≥6 h and admitted to a medical ICU, surgical ICU, and medical/surgical ICU at a single academic medical center in Rochester Minnesota from June 1, 2018 to May 31, 2020. We extracted baseline characteristics; sedative type, dose, and duration; concomitant therapies; and patient outcomes. Summary statistics are presented. Results A total of 2154 patients met our study criteria (1010 from medical ICU, 539 from surgical ICU, 605 from medical/surgical ICU). Propofol was the most frequently used sedative in all ICU settings (74.1% in medical ICU, 53.8% in surgical ICU, 68.9% in medical/surgical ICU, and 67.5% in all ICUs). The mortality rate was highest in the medical/surgical ICU (40.2% in medical ICU, 26.0% in surgical ICU, 40.7% in medical/surgical ICU, and 36.8% in all ICUs). 90.7% of all patients required mechanical ventilation (92.9% in medical ICU, 88.5% in surgical ICU, and 89.1% in medical/surgical ICU). Overall, patients spent more time in light sedation than deep sedation, 75% versus 10.3%, during their ICU admission. Patients in the medical ICU spent a greater proportion of time positive for delirium than the other ICU settings (35.7% in medical ICU, 9.8% in surgical ICU, and 20% in medical/surgical ICU). Similar amounts of opioids (morphine milligram equivalents) were used during the continuous sedative infusion between the three settings. Conclusions We observed that patients in the medical ICU spent more time deeply sedated with multiple agents which was associated with a higher proportion of delirium.

BACKGROUND: Postoperative hypotension (POH) is associated with major adverse events. However, little is known about the association of blood pressure thresholds and outcomes in postoperative patients without intraoperative hypotension (IOH) on the general-care ward. We evaluated the association of POH with major adverse cardiac or cerebrovascular events (MACCE) in patients without IOH. METHODS: This retrospective analysis included 67,968 noncardiac patient-procedures (2008–2017) for patients discharged to the ward with postoperative mean arterial pressure (MAP) readings, managed for ≥48 hours postsurgery, with no evidence of IOH. The primary outcome was 30-day MACCE evaluated by postoperative MAP thresholds: ≤75, ≤65, and ≤55 mm Hg (POH defined as a single measurement below threshold). Secondary outcomes included all-cause mortality (30-/90-day), 30-day acute myocardial infarction, 30-day acute ischemic stroke, 30-day readmission, 7-day acute kidney injury, and 30-day readmission. Associations between POH and adverse events were also evaluated in a cohort (#2) of 16,034 patient-procedures with IOH (intraoperative MAP ≤65 mm Hg). RESULTS: In patients without IOH, exposure to POH was not associated with MACCE at any investigated MAP threshold ( P < .016 was considered significant: ≤75 mm Hg, hazard ratio [HR] 1.18 [98.4% confidence interval {CI} 0.99-1.39], P = .023; ≤65 mm Hg, HR 1.18 [0.99–1.41], P = .028; ≤55 mm Hg, HR 1.23 [0.90–1.71], P = .121); however, associations were observed at all MAP thresholds for secondary outcomes of acute kidney injury and 30-day readmission, for 30-/90-day mortality for MAP ≤65 mm Hg, and 90-day mortality for MAP ≤55 mm Hg, compared to those without POH. No associations were detected between POH and secondary outcomes of acute ischemic stroke or acute myocardial infarction at any MAP threshold. No interaction between POH and IOH was found when we evaluated the association of POH on outcomes in the data set including all patients, regardless of IOH status ( P values for interaction terms nonsignificant). When the interaction term was utilized, the association between POH without IOH and MACCE was significant for MAP ≤75 mm Hg (HR 1.20 [1.01–1.41]) and MAP ≤65 mm Hg (HR 1.21 [1.02-1.45]), but not MAP ≤55 mm Hg. Cohort #2 (POH with IOH) showed largely similar results for MACCE: not significant for MAP ≤75 and ≤65 mm Hg, but significant for MAP ≤55 mm Hg (HR 1.53 [1.05–2.22], P = .006). CONCLUSIONS: POH in patients without IOH was not associated with MACCE at any MAP investigated. No interaction was identified between POH and IOH. Large prospective randomized trials are necessary to develop better evidence and inform clinicians the value of postoperative blood pressure management.

BACKGROUND: Intraoperative hypotension (IOH) occurs frequently during surgery and may be associated with organ ischemia; however, few multicenter studies report data regarding its associations with adverse postoperative outcomes across varying hemodynamic thresholds. Additionally, no study has evaluated the association between IOH exposure and adverse outcomes among patients by various age groups. METHODS: A multicenter retrospective cohort study was conducted between 2008 and 2017 using intraoperative blood pressure data from the US electronic health records database to examine postoperative outcomes. IOH was assessed in 368,222 noncardiac surgical procedures using 5 methods: (a) absolute maximum decrease in mean arterial pressure (MAP) during surgery, (b) time under each absolute threshold, (c) total area under each threshold, (d) time-weighted average MAP under each threshold, and (e) cumulative time under the prespecified relative MAP thresholds. MAP thresholds were defined by absolute limits (≤75, ≤65, ≤55 mm Hg) and by relative limits (20% and 40% lower than baseline). The primary outcome was major adverse cardiac or cerebrovascular events; secondary outcomes were all-cause 30- and 90-day mortality, 30-day acute myocardial injury, and 30-day acute ischemic stroke. Residual confounding was minimized by controlling for observable patient and surgical factors. In addition, we stratified patients into age subgroups (18–40, 41–50, 51–60, 61–70, 71–80, >80) to investigate how the association between hypotension and the likelihood of major adverse cardiac or cerebrovascular events and acute kidney injury differs in these age subgroups. RESULTS: IOH was common with at least 1 reading of MAP ≤75 mm Hg occurring in 39.5% (145,743) of cases; ≤65 mm Hg in 19.3% (70,938) of cases, and ≤55 mm Hg in 7.5% (27,473) of cases. IOH was significantly associated with the primary outcome for all age groups. For an absolute maximum decrease, the estimated odds of a major adverse cardiac or cerebrovascular events in the 30-day postsurgery was increased by 12% (95% confidence interval [CI], 11-14) for ≤75 mm Hg; 17.0% (95% CI, 15-19) for ≤65 mm Hg; and by 26.0% (95% CI, 22-29) for ≤55 mm Hg. CONCLUSIONS: IOH during noncardiac surgery is common and associated with increased 30-day major adverse cardiac or cerebrovascular events. This observation is magnified with increasing hypotension severity. The potentially avoidable nature of the hazard, and the extent of the exposed population, makes hypotension in the operating room a serious public health issue that should not be ignored for any age group.

Background: Little is known about hypoxemia surrounding endotracheal intubation in the critically ill. Thus, we sought to identify risk factors associated with peri-intubation hypoxemia and its effects’ on the critically ill. Methods: Data from a multicenter, prospective, cohort study enrolling 1,033 critically ill adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 were used to identify risk factors associated with peri-intubation hypoxemia and its effects on patient outcomes. We defined hypoxemia as any pulse oximetry ≤ 88% during and up to 30 minutes following endotracheal intubation. Results: In the full analysis (n = 1,033), 123 (11.9%) patients experienced the primary outcome. Five risk factors independently associated with our outcome were identified on multiple logistic regression: cardiac related reason for endotracheal intubation (OR 1.67, [95% CI 1.04, 2.69]); pre-intubation noninvasive ventilation (OR 1.66, [95% CI 1.09, 2.54]); emergency intubation (OR 1.65, [95% CI 1.06, 2.55]); moderate-severe difficult bag-mask ventilation (OR 2.68, [95% CI 1.72, 4.19]); and crystalloid administration within the preceding 24 hours (OR 1.24, [95% CI 1.07, 1.45]; per liter up to 4 liters). Higher baseline S p O 2 was found to be protective (OR 0.93, [95% CI 0.91, 0.96]; per percent up to 97%). Consistent results were seen in a separate analysis on only stable patients (n = 921, 93 [10.1%]) (those without baseline hypoxemia ≤ 88%). Peri-intubation hypoxemia was associated with in-hospital mortality (OR 2.40, [95% CI 1.33, 4.31]; stable patients: OR 2.67, [95% CI 1.38, 5.17]) but not ICU length of stay (point estimate 0.9 days, [95% CI −1.0, 2.8 days]; stable patients: point estimate 1.5 days, [95% CI −0.4, 3.4 days]) after adjusting for age, body mass index, illness severity, airway related reason for intubation (i.e., acute respiratory failure), and baseline S P O 2 . Conclusions: Patients with pre-existing noninvasive ventilation and volume loading who were intubated emergently in the setting of hemodynamic compromise with bag-mask ventilation described as moderate-severe were at increased risk for peri-intubation hypoxemia. Higher baseline oxygenation was found to be protective against peri-intubation hypoxemia. Peri-intubation hypoxemia was associated with in-hospital mortality but not ICU length of stay. Trial registration: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

Background: Pharmacogenomic (PGx) testing has the potential to provide information on specific drug-metabolizing enzymes that may lead to an absence, reduction, or increase in medication effect in patients. There is a paucity of prospective studies examining PGx testing in the intensive care unit (ICU) setting. Research Aims: To (1) obtain a PGx panel in a sample of cardiovascular (CV) surgical patients with a planned ICU stay and identify phenotypes, and (2) identify PGx variants that may inform treatment regimens and may warrant prescribing adjustments. Design and Methods: Descriptive, single cohort cross-sectional design. Adult (≥18 years) CV patients with an anticipated postoperative ICU stay were enrolled from a large Midwestern tertiary academic medical center. Eligible patients provided informed consent at the time of their CV clinic appointment; PGx testing was then ordered. Pharmacogenomic testing consisted of the Focused Pharmacogenomics panel which included 10 genes and 55 medications. Results: Of the 272 patients screened, 100 (68% male) patients completed PGx testing (mean age 66.2 ± 9.6 years, mean Acute Physiology, Age and Chronic Health Evaluation III score 76.1 ± standard deviation). Pharmacogenomic results were available in the medical record within a median of 52.4 hours (interquartile range: 33.4-80.3). Pharmacogenomic testing results identified 5 CYP2C19 poor metabolizers, 26 CYP2C19 rapid metabolizers, 5 CYP2C19 ultrarapid metabolizers, 6 CYP2D6 poor metabolizers, 5 CYP2D6 poor to intermediate metabolizers, and 2 CYP2D6 rapid metabolizers identified. Overall, 98% of patients had actionable or potentially actionable PGx results, including 82% for warfarin, 65% for propafenone, 65% for tramadol, 46% for oxycodone, 45% for metoprolol, 33% for clopidogrel, 32% for proton pump inhibitors, 25% for statins, and 12% for haloperidol. Conclusions: A significant portion of patients had identified genetic variants that may warrant changes in medication management during and after CV-ICU stay. It remains to be seen if PGx testing leads to improvements in ICU patient outcomes.

To evaluate the effectiveness of an admixture of ketamine and propofol on peri-induction hemodynamics during airway manipulation, we searched electronic databases of randomized controlled trials from January 1, 2000, to October 17, 2018. Trial screening, selection, and data extraction were done independently by two reviewers with outcomes pooled across included trials using the random-effects model. We included 10 randomized trials (722 patients, mean age of 53.99 years, 39.96% female). American Society of Anesthesiologists physical status was reported in 9 trials with classes I and II representing the majority. Ketamine/propofol admixture was associated with a nonsignificant increase in heart rate (weighted mean difference, 3.36 beats per minute (95% CI, −0.88, 7.60), I2 = 88.6%), a statistically significant increase in systolic blood pressure (weighted mean difference, 9.67 mmHg (95% CI, 1.48, 17.86), I2 = 87.2%), a nonsignificant increase in diastolic blood pressure (weighted mean difference, 2.18 mmHg (95% CI, −2.82, 7.19), I2 = 73.1%), and a nonsignificant increase in mean arterial pressure (weighted mean difference, 3.28 mmHg (95% CI, −0.94, 7.49), I2 = 69.9%) compared to other agents. The risk of bias was high and the certainty of evidence was low. In conclusion, among patients undergoing airway manipulation and needing sedation, the use of a ketamine/propofol admixture may be associated with better hemodynamics compared to nonketamine/propofol sedation. This trial is registered with CRD42019125725.