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Background: Based on current evidence, there appears to be an association between peri-intubation hypotension and patient morbidity and mortality. Studies have identified shock indices as possible pre-intubation risk factors for peri-intubation hypotension. Thus, we sought to evaluate the association between shock index (SI), modified shock index (MSI), and diastolic shock index (DSI) and peri-intubation hypotension along with other outcomes., Methods: The present study is a sub-study of a randomized controlled trial involving critically ill patients undergoing intubation. We defined peri-intubation hypotension as a decrease in mean arterial pressure <65 mm Hg and/or a reduction of 40% from baseline; or the initiation of, or increase in infusion dosage of, any vasopressor medication (bolus or infusion) during the 30-min period following intubation. SI, MSI, and DSI were analyzed as continuous variables and categorically using pre-established cut-offs. We also explored the effect of age on shock indices., Results: A total of 151 patients were included in the analysis. Mean pre-intubation SI was 1.0  ±  0.3, MSI 1.5  ±  0.5, and DSI 1.9  ±  0.7. Increasing SI, MSI, and DSI were significantly associated with peri-intubation hypotension (OR [95% CI] per 0.1 increase  =  1.16 [1.04, 1.30], P   =  .009 for SI; 1.14 [1.05, 1.24], P   =  .003 for MSI; and 1.11 [1.04, 1.19], P   =  .003 for DSI). The area under the ROC curves did not differ across shock indices (0.66 vs 0.67 vs 0.69 for SI, MSI, and DSI respectively; P   =  .586). Increasing SI, MSI, and DSI were significantly associated with worse sequential organ failure assessment (SOFA) score (spearman rank correlation: r  =  0.30, r  =  0.40, and r  =  0.45 for SI, MSI, and DSI, respectively, all P  < .001) but not with other outcomes. There was no significant impact when incorporating age., Conclusions: Increasing SI, MSI, and DSI were all significantly associated with peri-intubation hypotension and worse SOFA scores but not with other outcomes. Shock indices remain a useful bedside tool to assess the potential likelihood of peri-intubation hypotension., Trial Registration: ClinicalTrials.gov identifier - NCT02105415., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cardiovascular instability occurring during endotracheal intubation (ETI) in the critically ill is a commonly recognized phenomenon. However, this complication has not been evaluated in terms of the physiological cause (ie, decreased preload, contractility, or afterload) leading to the instability. Thus, the aim of the current investigation was to describe the hemodynamics occurring during ETI with noninvasive physiologic monitoring and to collect preliminary data on the hemodynamic effects of induction agents and positive pressure ventilation. Methods: A multicenter prospective study enrolling adult (≥18 years) critically ill patients undergoing ETI with noninvasive cardiac output monitoring in a medical/surgical intensive care unit from June 2018 to May 2019 was conducted. This study used the Cheetah Medical noninvasive cardiac output monitor to collect hemodynamic data during the peri-intubation period. Additional data collected included baseline characteristics such as illness severity, peri-intubation pharmacologic administration, and mechanical ventilation settings. Results: From the original 27 patients, only 19 (70%) patients had complete data and were included in the final analysis. Propofol was the most common sedative 8 (42%) followed by ketamine 6 (32%) and etomidate 5 (26%). Patients given propofol demonstrated a decrease in total peripheral resistance index (delta change [dynes × s/cm -5 /m 2 ]: -2.7 ± 778.2) but stabilization in cardiac index (delta change (L/min/m 2 ]: 0.1 ± 1.5) while etomidate and ketamine demonstrated increases in total peripheral resistance index (etomidate delta change [dynes × s/cm -5 /m 2 ]: 302.1 ± 414.3; ketamine delta change [dynes × s/cm -5 /m 2 ]: 278.7 ± 418.9) but only etomidate resulted in a decrease in cardiac index (delta change [L/min/m 2 ]: -0.3 ± 0.5). Positive pressure ventilation resulted in minimal changes to hemodynamics during ETI. Conclusions: The current study demonstrates that although propofol administration leads to a decrease in total peripheral resistance index, cardiac index is maintained while etomidate leads to a decrease in cardiac index with both etomidate and ketamine increasing total peripheral resistance index. These hemodynamic profiles are minimally affected by positive pressure ventilation. Study registration: ClinicalTrials.gov ID, NCT03525743., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NJS is a consultant for Edwards Lifesciences.

Introduction: High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO 2 /FiO 2 and SpO 2 /FiO 2 in patients in shock., Methods: Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study. PaO 2 , SpO 2 , and FiO 2 were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO 2 /FiO 2 and SpO 2 /FiO 2 were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO 2 /FiO 2  ≤ 300 mm Hg at the time of Ang-2 initiation and 48 h after was also examined., Results: The study included 254 patients. In the 48 h prior to Ang-2 initiation, oxygenation was significantly declining (hourly PaO 2 /FiO 2 change -4.7 mm Hg/hr, 95% CI - 6.0 to -3.5, p  < .001; hourly SpO 2 /FiO 2 change -3.1/hr, 95% CI-3.7 to -2.4, p  < .001). Ang-2 treatment was associated with significant improvements in PaO 2 /FiO 2 and SpO 2 /FiO 2 in the 48-h after initiation (hourly PaO 2 /FiO 2 change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p   =  .003; hourly SpO 2 /FiO 2 change +0.9/hr, 95% CI 0.5-1.2, p  < .001). The difference in the hourly change in oxygenation before and after Ang-2 initiation was also significant ( p interaction  < 0.001 for both PaO 2 /FiO 2 and SpO 2 /FiO 2 ). This improvement was associated with significantly fewer patients having a PaO 2 /FiO 2  ≤ 300 mm Hg at 48 h compared to baseline (mean difference -14.9%, 95% CI -25.3% to -4.6%, p   =  .011). Subgroup analysis found that patients with either a baseline PaO 2 /FiO 2  ≤ 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 µg/kg/min had the greatest associations with oxygenation improvement., Conclusions: Ang-2 is associated with improved PaO 2 /FiO 2 and SpO 2 /FiO 2 . The mechanisms for this improvement are not entirely clear but may be due to catecholamine-sparing effect or may also be related to improved ventilation-perfusion matching, intrapulmonary shunt, or oxygen delivery.

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: 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: 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.

Objectives: Our primary aim was to ascertain the frequency of postintubation hypotension in immunocompromised critically ill adults with secondary aims of arriving at potential risk factors for the development of postintubation hypotension and its impact on patient-related outcomes., Methods: Critically ill adult patients (≥18 years) were included from January 1, 2010, to December 31, 2014. We defined immunocompromised as patients with any solid organ or nonsolid organ malignancy or transplant, whether solid organ or not, requiring current chemotherapy. Postintubation hypotension was defined as a decrease in systolic blood pressure to less than 90 mm Hg or a decrease in mean arterial pressure to less than 65 mm Hg or the initiation of any vasopressor medication. Patients were then stratified based on development of postintubation hypotension. Potential risk factors and intensive care unit (ICU) outcome metrics were electronically captured by a validated data mart system., Results: The final cohort included 269 patients. Postintubation hypotension occurred in 141 (52%; 95% confidence interval: 46-58) patients. Several risk factors predicted postintubation hypotension on univariate analysis; however, only Acute Physiology and Chronic Health Evaluation III score in the first 24 hours, preintubation shock status, and preintubation hemodynamic instability remained significant on all 4 multivariate analyses. Patients developing postintubation hypotension had higher ICU and hospital mortality (54 [38%] vs 31 [24%], P = .01; 69 [49%] vs 47 [37%], P = .04)., Conclusion: Based on previous literature, we found a higher frequency of postintubation hypotension in the immunocompromised than in the nonimmunocompromised critically ill adult patients. Acute Physiology and Chronic Health Evaluation III score in the first 24 hours, preintubation shock status, and preintubation hemodynamic instability were significant predictors on multivariate analyses. Postintubation hypotension led to higher ICU and hospital mortality in those experiencing this complication.

Purpose: Data regarding best practices for ventilator management strategies that improve outcomes in acute respiratory distress syndrome (ARDS) are readily available. However, little is known regarding processes to ensure compliance with these strategies. We developed a goal-directed mechanical ventilation order set that included physician-specified lung-protective ventilation and oxygenation goals to be implemented by respiratory therapists (RTs). We sought as a primary outcome to determine whether an RT-driven order set with predefined oxygenation and ventilation goals could be implemented and associated with improved adherence with best practice., Methods: We evaluated 1302 patients undergoing invasive mechanical ventilation (1693 separate episodes of invasive mechanical ventilation) prior to and after institution of a standardized, goal-directed mechanical ventilation order set using a controlled before-and-after study design. Patient-specific goals for oxygenation partial pressure of oxygen in arterial blood (Pao 2 ), ARDS Network [Net] positive end-expiratory pressure [PEEP]/fraction of inspired oxygen [Fio 2 ] table use) and ventilation (pH, partial pressure of carbon dioxide) were selected by prescribers and implemented by RTs., Results: Compliance with the new mechanical ventilation order set was high: 88.2% compliance versus 3.8% before implementation of the order set ( P < .001). Adherence to the PEEP/Fio 2 table after implementation of the order set was significantly greater (86.0% after vs 82.9% before, P = .02). There was no difference in duration of mechanical ventilation, intensive care unit (ICU) length of stay, and in-hospital or ICU mortality., Conclusions: A standardized best practice mechanical ventilation order set can be implemented by a multidisciplinary team and is associated with improved compliance to written orders and adherence to the ARDSNet PEEP/Fio 2 table.

Objectives: Our primary aim was to determine the factors leading to prophylactic endotracheal intubation in intensive care unit (ICU) patients undergoing gastrointestinal endoscopy. Secondary aims were to determine the rate of unplanned endotracheal intubations during endoscopy and to determine the rate of aspiration following endoscopy for patients admitted to the ICU., Methods: Critically ill adult (≥18 years) patients who underwent upper and lower endoscopic procedures from January 2012 to July 2016 in a medical/surgical ICU were included. Determinants of prophylactic endotracheal intubation prior to endoscopy as well as other postprocedure outcomes were electronically captured by a validated data mart system. Given our focus on aspiration in those who were not endotracheally intubated prior to endoscopy, we used a validated definition a priori., Results: A total of 320 patients were included in the final analysis: 76(24%) were intubated prior to endoscopy and 244 (76%) were not. The endotracheally intubated group had a significantly higher Acute Physiologic and Chronic Health Evaluation III (44.5 [16.2] vs 39.5 [15.5]; P = .02) and Sequential Organ Failure Assessment (6.9 [4.4] vs 3.8 [3]; P ≤ .01) scores, higher rate of hematemesis within 24 hours of endoscopy (28 [37%] vs 45 [18%]; P ≤ .01), and higher rate of upper endoscopy (72 [96%] vs 181 [74%]; P ≤ .01). We composed a composite outcome for multivariable analyses, which demonstrated the rate of any complication was significantly higher among those who were intubated prior to the procedure versus those who were not intubated previously (odds ratio: 2.80, 95% confidence interval (CI): 1.16-6.72, P = .02)., Conclusion: Endoscopy performed in the ICU without endotracheal intubation is safe. However, patient selection for prophylactic intubation prior to endoscopy is of critical importance as illustrated in this study with higher illness severity, planned upper endoscopy, and hematemesis 24 hours prior being key factors on deciding to perform endotracheal intubation. Prophylactic intubation for endoscopy and preexisting cardiac disease were associated with a higher rate of adverse outcomes.

Purpose: To assess whether exposure to modified shock index (MSI) in the first 24 hours of intensive care unit (ICU) admission is associated with increased in-hospital mortality., Methods: Adult critically ill patients were included in a case-control design with 1:2 matching. Cases (death) and controls (alive) were abstracted by a reviewer blinded to exposure status (MSI). Cases were matched to controls on 3 factors-age, end-stage renal disease, and ICU admission diagnosis., Results: Eighty-three cases and 159 controls were included. On univariate analysis, lorazepam administration (odds ratio [OR]: 5.75, confidence interval [CI] = 2.28-14.47; P ≤ .01), shock requiring vasopressors (OR: 3.62, CI = 1.77-7.40; P ≤ .01), maximum MSI (OR: 2.77 per unit, CI = 1.63-4.71; P ≤ .001), and elevated acute physiologic and chronic health evaluation (APACHE) III score at 1 hour (OR: 1.41 per 10 units, CI = 1.19-1.66; P ≤ .001) were associated with mortality. Maximum MSI (OR: 1.93 per unit, CI = 1.07-3.48, P = .03) and APACHE III score at 1 hour (OR: 1.29 per 10 units, CI = 1.09-1.53; P = .003) remained significant with mortality in the multivariate analysis. The optimal cutoff point for high MSI and mortality was 1.8., Conclusion: Critically ill patients who demonstrate an elevated MSI within the first 24 hours of ICU admission have a significant mortality risk. Given that MSI is easily calculated at the bedside, clinicians may institute interventions earlier which could improve survival.

Objectives: In the last decade, the practice of intubation in the intensive care unit (ICU) has evolved. To further examine the current intubation practice in the ICU, we administered a survey to critical care physicians., Design: Cross-sectional survey study design., Setting: Thirty-two academic/nonacademic centers nationally and internationally., Measurements and Main Results: The survey was developed among a core group of physicians with the assistance of the Survey Research Center at Mayo Clinic, Rochester, Minnesota. The survey was pilot tested for functionality and reliability. The response rate was 82 (51%) of 160 among the 32 centers. Although propofol was the induction drug of choice, there was a significant difference with actual ketamine use and those who indicated a preference for it (ketamine: 52% vs 61%; P < .001). The most common airway device used for intubation was direct laryngoscopy (Miller laryngoscope blade) at 56 (68%) followed by video laryngoscopy at 26 (32%). Most (>90%) indicated that they have a difficult airway cart, but only 55 (67%) indicated they have a documented plan to handle a difficult airway with even lower results for documented review of adverse events (49%)., Conclusion: Although propofol was the induction drug of choice, ketamine was a medication that many preferred to use, possibly relating to the fact that the most common complication postintubation is hypotension. Direct laryngoscopy remains the primary airway device for endotracheal intubation. Finally, although the majority stated they had a difficult airway cart available, most did not have a documented plan in place when encountering a difficult airway or a documented process to review adverse events surrounding intubation.