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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.

Purpose: Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA)., Methods: An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements., Results: The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care., Conclusion: Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century. Recently, a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres, finding diverse applications in intensive care settings. In the dynamic landscape of intensive care, volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements, managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus, conditions of high sedative requirements including burns, high opioid or alcohol use and neurological conditions such as status epilepticus. Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry, providing intensivists with multiple options to tailor therapy. Furthermore, their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy, mitigating risks associated with conventional sedation modalities. Despite the amounting enthusiasm for the use of these therapies, barriers to widespread utilization include expanding equipment availability, staff familiarity and training of safe use. This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology, administration considerations in intensive care settings, complication considerations, and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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.

Competing Interests: Declaration of competing interest Nathan J. Smischney holds a patent on “KETOFOL” reformulation.

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: Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit (ICU), with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation. As clonidine is an enterally available alpha-2A adrenergic agonist, it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes. The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known. The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms., Aim: To systematically review the practice, dosing schema, and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults., Methods: This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults (≥ 18 years). Randomized controlled trials, prospective cohorts, and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included. The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal. Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use, re-initiation of dexmedetomidine, duration of mechanical ventilation, and ICU length of stay., Results: A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients. All three studies were observational, two being prospective and one retrospective. In all included studies, the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician. Weaning time ranged from 13 to 167 h on average. Enteral clonidine was started in the prospective studies in a similar protocolized method, with 0.3 mg every 6 h. After starting clonidine, patients remained on dexmedetomidine for a median of 1-28 h. Following the termination of dexmedetomidine, two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h, 12h, and 24 h, followed by clonidine discontinuation. For indicators of enteral clonidine withdrawal, the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol. The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation. The re-initiation of dexmedetomidine was not documented in any study. Only 17 (37%) patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies. ICU lengths of stay were similar., Conclusion: Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine. There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

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: Whilst intraoperative hypotension is associated with postoperative acute kidney injury (AKI), the link between intraoperative hypotension and acute kidney disease (AKD), defined as continuing renal dysfunction for up to 3 months after exposure, has not yet been studied., Methods: We conducted a retrospective multicentre cohort study using data from noncardiac, non-obstetric surgery extracted from a US electronic health records database. Primary outcome was the association between intraoperative hypotension, at three MAP thresholds (≤75, ≤65, and ≤55 mm Hg), and the following two AKD subtypes: (i) persistent (initial AKI incidence within 7 days of surgery, with continuation between 8 and 90 days post-surgery) and (ii) delayed (renal impairment without AKI within 7 days, with AKI occurring between 8 and 90 days post-surgery). Secondary outcomes included healthcare resource utilisation for patients with either AKD subtype or no AKD., Results: A total of 112 912 surgeries qualified for the study. We observed a rate of 2.2% for delayed AKD and 0.6% for persistent AKD. Intraoperative hypotension was significantly associated with persistent AKD at MAP ≤55 mm Hg (hazard ratio 1.1; 95% confidence interval: 1.38-1.22; P<0.004). However, IOH was not significantly associated with delayed AKD across any of the MAP thresholds. Patients with delayed or persistent AKD had higher healthcare resource utilisation across both hospital and intensive care admissions, compared with patients with no AKD., Conclusions: Intraoperative hypotension is associated with persistent but not delayed acute kidney disease. Both types of acute kidney disease appear to be associated with increased healthcare utilisation. Correction of intraoperative hypotension is a potential opportunity to decrease postoperative kidney injury and associated costs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To derive and validate a multivariate risk score for the prediction of respiratory failure after extubation., Patients and Methods: We performed a retrospective cohort study of adult patients admitted to the intensive care unit from January 1, 2006, to December 31, 2015, who received mechanical ventilation for ≥48 h. Extubation failure was defined as the need for reintubation within 72 h after extubation. Multivariate logistic regression model coefficient estimates generated the R e- I ntubation S ummation C alculation (RISC) score., Results: The 6,161 included patients were randomly divided into 2 sets: derivation ( n = 3,080) and validation ( n = 3,081). Predictors of extubation failure in the derivation set included body mass index <18.5 kg/m 2 [odds ratio (OR), 1.91; 95% CI, 1.12-3.26; P = 0.02], threshold of Glasgow Coma Scale of at least 10 (OR, 1.68; 95% CI, 1.31-2.16; P < 0.001), mean airway pressure at 1 min of spontaneous breathing trial <10 cmH 2 O (OR, 2.11; 95% CI, 1.68-2.66; P < 0.001), fluid balance ≥1,500 mL 24 h preceding extubation (OR, 2.36; 95% CI, 1.87-2.96; P < 0.001), and total mechanical ventilation days ≥5 (OR, 3.94; 95% CI 3.04-5.11; P < 0.001). The C-index for the derivation and validation sets were 0.72 (95% CI, 0.70-0.75) and 0.72 (95% CI, 0.69-0.75). Multivariate logistic regression demonstrated that an increase of 1 in RISC score increased odds of extubation failure 1.6-fold (OR, 1.58; 95% CI, 1.47-1.69; P < 0.001)., Conclusion: RISC predicts extubation failure in mechanically ventilated patients in the intensive care unit using several clinically relevant variables available in the electronic medical record but requires a larger validation cohort before widespread clinical implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bansal, Smischney, Kashyap, Li, Marquez, Diedrich, Siegel, Sen, Tomlinson, Venegas-Borsellino and Freeman.)

Acute exacerbations of interstitial lung disease (AE-ILD) represent an acute, frequent and often highly morbid event in the disease course of ILD patients. Admission in the intensive care unit (ICU) is very common and the need for mechanical ventilation arises early. While non-invasive ventilation has shown promise in staving off intubation in selected patients, it is unclear whether mechanical ventilation can alter the exacerbation course unless it is a bridge to lung transplantation. Risk stratification using clinical and radiographic findings, and early palliative care involvement, are important in ICU care. In this review, we discuss many of the pathophysiological aspects of AE-ILD and raise the hypothesis that ventilation strategies used in acute respiratory distress syndrome might be implemented in AE-ILD. We present possible decision-making and management algorithms that can be used by the intensivist when caring for these patients., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Endotracheal intubation is one of the most common, yet most dangerous procedure performed in the intensive care unit (ICU). Complications of ICU intubations include severe hypotension, hypoxemia, and cardiac arrest. Multiple observational studies have evaluated risk factors associated with these complications. Among the risk factors identified, the choice of sedative agents administered, a modifiable risk factor, has been reported to affect these complications (hypotension). Propofol, etomidate, and ketamine or in combination with benzodiazepines and opioids are commonly used sedative agents administered for endotracheal intubation. Propofol demonstrates rapid onset and offset, however, has drawbacks of profound vasodilation and associated cardiac depression. Etomidate is commonly used in the critically ill population. However, it is known to cause reversible inhibition of 11 β-hydroxylase which suppresses the adrenal production of cortisol for at least 24 h. This added organ impairment with the use of etomidate has been a potential contributing factor for the associated increased morbidity and mortality observed with its use. Ketamine is known to provide analgesia with sedation and has minimal respiratory and cardiovascular effects. However, its use can lead to tachycardia and hypertension which may be deleterious in a patient with heart disease or cause unpleasant hallucinations. Moreover, unlike propofol or etomidate, ketamine requires organ dependent elimination by the liver and kidney which may be problematic in the critically ill. Lately, a combination of ketamine and propofol, "Ketofol", has been increasingly used as it provides a balancing effect on hemodynamics without any of the side effects known to be associated with the parent drugs. Furthermore, the doses of both drugs are reduced. In situations where a difficult airway is anticipated, awake intubation with the help of a fiberoptic scope or video laryngoscope is considered. Dexmedetomidine is a commonly used sedative agent for these procedures., Competing Interests: Conflict-of-interest statement: Nathan Smischney has a patent application titled Ketamine and Propofol Admixture: #16/606,056, pending., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Study Objective: Determine if perioperative hypotension, a modifiable risk factor, is associated with increased postoperative healthcare resource utilization (HRU)., Design: Retrospective cohort study., Setting: Multicenter using the Optum® electronic health record database., Patients: Patients discharged to the ward after non-cardiac, non-obstetric surgeries between January 1, 2008 and December 31, 2017 with six months of data, before and after the surgical visit., Interventions/exposure: Perioperative hypotension, a binary variable (presence/absence) at an absolute MAP of ≤65-mmHg, measured during surgery and within 48-h after, to dichotomize patients with greater versus lesser hypotensive exposures., Measurements: Short-term HRU defined by postoperative length-of-stay (LOS), discharge to a care facility, and 30-day readmission following surgery discharge. Mid-term HRU (within 6 months post-discharge) quantified via number of outpatient and emergency department (ED) visits, and readmission LOS., Main Results: 42,800 distinct patients met study criteria and 37.5% experienced perioperative hypotension. After adjusting for study covariates including patient demographics and comorbidities, patients with perioperative hypotension had: longer LOS (4.01 vs. 3.83 days; LOS ratio, 1.05; 95% CI, 1.04-1.06), higher odds of discharge to a care facility (OR, 1.18; 95% CI, 1.12-1.24; observed rate 22.1% vs. 18.1%) and of 30-day readmission (OR, 1.22; 95% CI, 1.11-1.33; observed rate 6.2% vs. 5.0%) as compared to the non-hypotensive population (all outcomes, p < 0.001). During 6-month follow-up, patients with perioperative hypotension showed significantly greater HRU regarding number of ED visits (0.34 vs. 0.31 visits; visit ratio, 1.10; 95% CI, 1.05-1.15) and readmission LOS (1.06 vs. 0.92 days; LOS ratio, 1.15; 95% CI, 1.07-1.24) but not outpatient visits (10.47 vs. 10.82; visit ratio, 0.97; 95% CI, 0.95-0.99) compared to those without hypotension. There was no difference in HRU during the 6-month period before qualifying surgery., Conclusions: We report a significant association of perioperative hypotension with an increase in HRU, including additional LOS and readmissions, both important contributors to overall medical costs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

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., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Background: Vasoplegic shock is a challenging complication of cardiac surgery and is often resistant to conventional therapies for shock. Norepinephrine and epinephrine are standards of care for vasoplegic shock, but vasopressin has increasingly been used as a primary pressor in vasoplegic shock because of its unique pharmacology and lack of inotropic activity. It remains unclear whether vasopressin has distinct benefits over standard of care for patients with vasoplegic shock., Aim: To summarize the available literature evaluating vasopressin vs non-vasopressin alternatives on the clinical and patient-centered outcomes of vasoplegic shock in adult intensive care unit (ICU) patients., Methods: This was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegic shock after cardiac surgery. Randomized controlled trials, prospective cohorts, and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine, methylene blue, hydroxocobalamin, or other pressors were included. The primary outcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke, ICU length of stay, duration of vasopressor therapy, incidence of acute kidney injury stage II-III, and mechanical ventilation for greater than 48 h., Results: A total of 1161 studies were screened for inclusion with 3 meeting inclusion criteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality, stroke, ventricular arrhythmias, and duration of mechanical ventilation were similar between groups. Conflicting results were observed for acute kidney injury stage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of stay with higher certainty of evidence in favor of vasopressin serving a protective role for these outcomes., Conclusion: Vasopressin was not found to be superior to alternative pressor therapy for any of the included outcomes. Results are limited by mixed methodologies, small overall sample size, and heterogenous populations., Competing Interests: Conflict-of-interest statement: The authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The postoperative period is critical for a patient's recovery, and postoperative hypotension, specifically, is associated with adverse clinical outcomes and significant harm to the patient. However, little is known about the association between postoperative hypotension in patients in the intensive care unit (ICU) after non-cardiac surgery, and morbidity and mortality, specifically among patients who did not experience intraoperative hypotension. The goal of this study was to assess the impact of postoperative hypotension at various absolute hemodynamic thresholds (≤ 75, ≤ 65 and ≤ 55 mmHg), in the absence of intraoperative hypotension (≤ 65 mmHg), on outcomes among patients in the ICU following non-cardiac surgery., Methods: This multi-center retrospective cohort study included specific patient procedures from Optum® healthcare database for patients without intraoperative hypotension (MAP ≤ 65 mmHg) discharged to the ICU for ≥ 48 h after non-cardiac surgery with valid mean arterial pressure (MAP) readings. A total of 3185 procedures were included in the final cohort, and the association between postoperative hypotension and the primary outcome, 30-day major adverse cardiac or cerebrovascular events, was assessed. Secondary outcomes examined included all-cause 30- and 90-day mortality, 30-day acute myocardial infarction, 30-day acute ischemic stroke, 7-day acute kidney injury stage II/III and 7-day continuous renal replacement therapy/dialysis., Results: Postoperative hypotension in the ICU was associated with an increased risk of 30-day major adverse cardiac or cerebrovascular events at MAP ≤ 65 mmHg (hazard ratio [HR] 1.52; 98.4% confidence interval [CI] 1.17-1.96) and ≤ 55 mmHg (HR 2.02, 98.4% CI 1.50-2.72). Mean arterial pressures of ≤ 65 mmHg and ≤ 55 mmHg were also associated with higher 30-day mortality (MAP ≤ 65 mmHg, [HR 1.56, 98.4% CI 1.22-2.00]; MAP ≤ 55 mmHg, [HR 1.97, 98.4% CI 1.48-2.60]) and 90-day mortality (MAP ≤ 65 mmHg, [HR 1.49, 98.4% CI 1.20-1.87]; MAP ≤ 55 mmHg, [HR 1.78, 98.4% CI 1.38-2.31]). Furthermore, we found an association between postoperative hypotension with MAP ≤ 55 mmHg and acute kidney injury stage II/III (HR 1.68, 98.4% CI 1.02-2.77). No associations were seen between postoperative hypotension and 30-day readmissions, 30-day acute myocardial infarction, 30-day acute ischemic stroke and 7-day continuous renal replacement therapy/dialysis for any MAP threshold., Conclusions: Postoperative hypotension in critical care patients with MAP ≤ 65 mmHg is associated with adverse events even without experiencing intraoperative hypotension.

Objective: Hypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation., Methods: A multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure <65 mmHg; 2) systolic blood pressure <80 mmHg and/or decrease in systolic blood pressure of 40% from baseline; 3) or the initiation or increase in any vasopressor in the 30 minutes following endotracheal intubation., Results: Post-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotension: increasing illness severity; increasing age; sepsis diagnosis; endotracheal intubation in the setting of cardiac arrest, mean arterial pressure <65 mmHg, and acute respiratory failure; diuretic use 24 hours preceding endotracheal intubation; decreasing systolic blood pressure from 130 mmHg; catecholamine and phenylephrine use immediately prior to endotracheal intubation; and use of etomidate during endotracheal intubation. A model excluding unstable patients' pre-intubation (those receiving catecholamine vasopressors and/or who were intubated in the setting of cardiac arrest) was also developed and included the above variables with the exception of sepsis and etomidate. In the full cohort, the 11 variable model had a C-statistic of 0.75 (95% CI 0.72, 0.78). In the stable cohort, the 7 variable model C-statistic was 0.71 (95% CI 0.67, 0.75). In both cohorts, a clinical risk score was developed stratifying patients' risk of hypotension., Conclusions: A novel multivariable risk score predicted post-intubation hypotension with accuracy in both unstable and stable critically ill patients., Study Registration: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101., Competing Interests: The authors have declared that no competing interests exist.

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), I 2  = 88.6%), a statistically significant increase in systolic blood pressure (weighted mean difference, 9.67 mmHg (95% CI, 1.48, 17.86), I 2  = 87.2%), a nonsignificant increase in diastolic blood pressure (weighted mean difference, 2.18 mmHg (95% CI, -2.82, 7.19), I 2  = 73.1%), and a nonsignificant increase in mean arterial pressure (weighted mean difference, 3.28 mmHg (95% CI, -0.94, 7.49), I 2  = 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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Nathan J. Smischney et al.)

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.

BACKGROUND Serotonin syndrome is a life-threatening condition that can lead to neurologic complications and is associated with the use of serotonergic medications. As the use of antidepressant medications has increased, the incidence of perioperative serotonin syndrome has transitioned from a rare diagnosis to one that should be considered as a differential diagnosis for any patient displaying signs of neuroexcitation. CASE REPORT A 70-year-old man (ASA 2) with a history of vestibular migraines (treated with venlafaxine), gastroesophageal reflux disease, and benign prostatic hyperplasia presented to our institution for photoselective vaporization of the prostate. Upon review of prior anesthetic records, his medical chart was found to list a propofol allergy. In discussion with the patient, he stated the reaction was rigidity. The anesthesiologist and patient agreed this was not an allergy. Thus, the patient was induced with propofol and given ketamine and fentanyl boluses throughout the procedure. During emergence, the patient exhibited myoclonic jerks in the upper and lower extremities. He was given intravenous meperidine for postoperative shivering; minutes after administration, the myoclonic jerks and rigidity worsened. The anesthesia team raised concern about serotonin syndrome. Intravenous midazolam improved the patient's myoclonic jerks and rigidity. CONCLUSIONS Patients with a history of rigidity/movement disorders during the perioperative period may have experienced serotonin toxicity. It is possible, as in our case, for this history to have been labelled as an allergy to a perioperative medication. Clinicians should remain vigilant for patients at risk of developing serotonin syndrome, such as those taking outpatient medications that increase neuronal serotonin.

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.

Background: Emergent use research-research involving human subjects that have a life-threatening medical condition and who are unlikely to provide informed consent-in critical illness is fraught with challenges related to obtaining informed consent. Per federal regulations, to meet criteria to conduct such trials, the investigators have to seek community consultations. Effective ways of obtaining this consultation remains ill-defined., Objective: We sought to describe methods, interpretations, and our experiences of conducting community consultation in a planned emergent use randomized controlled trial., Methods: As part of a planned emergent use clinical trial in our study, community consultation consisted of four focus groups sessions with members from the community in which the clinical trial was conducted. Three focus group sessions were conducted with members who had an affiliation to Mayo Clinic, and the other focus group session was conducted with non-Mayo affiliation members. The feedback from the focus group sessions led to the creation of the public notification plan. The public was notified of the trial through community meetings as well as social media., Results: As compared to community meetings, focus group sessions resulted in greater attendance with more interactive discussions. Moreover, focus group sessions resulted in greater in-depth conversations leading to institutional acceptance of the clinical trial under study., Conclusions: Exception from informed consent can be acceptable to the community. Focus groups provided better participation and valuable interactive insight as compared to community meetings in our study. This could serve as a valuable guide for investigators pursuing exception from informed consent in their research studies., (©Nathan J Smischney, Jasleen Pannu, Richard F Hinds, Jennifer B McCormick. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 02.05.2018.)

Background/aims: To evaluate and compare the performance of ocular ultrasonography (US) and magnetic resonance imaging (MRI) for detecting increased intracranial pressure (ICP) in patients with idiopathic intracranial hypertension (IIH)., Methods: Twenty-two patients with papilledema from IIH and 22 with pseudopapilledema were prospectively recruited based on funduscopic and clinical findings. Measurements of optic nerve sheath diameters (ONSDs) 3 mm behind the inner sclera were performed on B-scan US and axial T2-weighted MRI examinations. Pituitary-to-sella height ratio (pit/sella) was also calculated from sagittal T1-weighted MRI images. Lumbar puncture was performed in all patients with IIH and in five patients with pseudopapilledema., Results: Average US and MRI ONSD were 4.4 (SD ± 0.7) and 5.2 ± 1.4 mm for the pseudopapilledema group and 5.2 ± 0.6 and 7.2 ± 1.6 mm for the papilledema group ( p  < 0.001). Average MRI pit/sella ratio was 0.7 ± 0.3 for the pseudopapilledema group and 0.3 ± 0.2 for the papilledema group ( p  < 0.001). Based on receiver-operator curve analysis, the optimal thresholds for detecting papilledema are US ONSD > 4.8 mm, MRI ONSD > 6.0 mm, and MRI pit/sella < 0.5. Combining a dilated US ONSD or MRI ONSD with a below-threshold MRI pit/sella ratio yielded a sensitivity of 73% and specificity of 96% for detecting IIH. Adding the US ONSD to the MRI ONSD and pit/sella ratio only increased the sensitivity by 5% and did not change specificity., Conclusion: US and MRI provide measurements of ONSD that are well-correlated and sensitive markers for increased ICP. The combination of the ONSD and the pit/sella ratio can increase specificity for the diagnosis of IIH.

Purpose: Our primary aim was to identify predictors of immediate hemodynamic decompensation during the peri-intubation period., Methods: We conducted a nested case-control study of a previously identified cohort of adult patients needing intubation admitted to a medical-surgical ICU during 2013-2014. Hemodynamic derangement was defined as cardiac arrest and/or the development of systolic blood pressure <90mmHg and/or mean arterial pressure <65mmHg 30min following intubation. Data during the peri-intubation period was analyzed., Results: The final cohort included 420 patients. Immediate hemodynamic derangement occurred in 170 (40%) patients. On multivariate modeling, age/10year increase (OR 1.20, 95% CI 1.03-1.39, p=0.02), pre-intubation non-invasive ventilation (OR 1.71, 95% CI 1.04-2.80, p=0.03), pre-intubation shock index/1 unit (OR 5.37 95% CI 2.31-12.46, p≤0.01), and pre-intubation modified shock index/1 unit (OR 2.73 95% CI 1.48-5.06, p≤0.01) were significantly associated with hemodynamic derangement. Those experiencing hemodynamic derangement had higher ICU [47 (28%) vs. 33 (13%); p≤0.001] and hospital [69 (41%) vs. 51 (20%); p≤0.001] mortality., Conclusions: Hemodynamic derangement occurred at a rate of 40% and was associated with increased mortality. Increasing age, use of non-invasive ventilation before intubation, and increased pre-intubation shock and modified shock index values were significantly associated with hemodynamic derangement post-intubation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Arterial desaturations experienced during endotracheal intubation (ETI) may lead to poor outcomes. Thus, our primary aim was to identify predictors of arterial desaturation (pulse oximetry <90%) during the peri-intubation period and to assess outcomes of those who developed arterial hypoxemia., Methods: Adult patients admitted to a medical and/or surgical intensive care unit (ICU) over the time period of January 1st 2013 through December 31st 2014 who required ETI were included. Only the first intubation was captured. Arterial desaturation was defined as pulse oximetry readings of <90% (hypoxemia) in the immediate peri-intubation period. Patients were then grouped in cases (those who developed desaturation) and controls (those who did not develop this complication)., Results: The final cohort included 420 patients. Arterial desaturations occurred in 74 (18%) patients. When adjusting for significant predictors on univariate analysis and known predictors of a difficult airway, only acute respiratory failure (OR 2.38; 95% CI: 1.15-4.93; P=0.02) and provider training level (OR 7.12; 95% CI: 1.65-30.67; P=0.016) remained significant. Higher pulse oximetry readings prior to intubation was found to be protective on multivariate analysis (OR 0.92; 95% CI: 0.89-0.96; P<0.01; per one percent increase)., Conclusions: Patients who were intubated for acute respiratory failure and those who were intubated by junior level trainees had increased odds of experiencing arterial desaturation in the peri-intubation period. Patients experiencing arterial desaturation had lower pulse oximetry readings prior to intubation suggesting a possible delay at intubation., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

With the ever-increasing adoption of shift models for intensive care unit (ICU) staffing, improving shift-to-shift handoffs represents an important step in reducing medical errors. The authors developed an electronic handoff tool integrated within the existing electronic medical record to improve handoffs in an adult ICU. First, stakeholder (staff intensivists, fellows, and nurse practitioners/physician assistants) input was sought to define what elements they perceived as being essential to a quality handoff. The principal outcome measure of handoff accuracy was the concordance between data transmitted by the outgoing team and data received by the incoming team (termed as agreement). Based on stakeholder input, the authors developed the handoff tool and provided regular education on its use. Handoffs were observed before and after implementation of the tool. There was an increase in the level of agreement for tasks and other important data points handed off without an increase in the time required to complete the handoff.

Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on sepsis, we conducted a systematic review of all randomized controlled EGDT trials. Focus was laid on the setting (emergency department versus ICU) where EGDT was carried out. Early recognition of sepsis, through clinical or automated systems for early alert, together with well-timed initiation of the recommended therapy bundles may improve patients' outcome. However, the original "EGDT" protocol by Rivers and coworkers has been largely modified in subsequent trials. Currently, many investigators opt for an "expanded" EGDT (as suggested by the Surviving Sepsis Campaign). Evidence is also presented on the effectiveness of automated systems for early sepsis alert. Early recognition of sepsis and well-timed initiation of the SSC bundle may improve patient outcome., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: To describe the practice of intubation of the critically ill at a single academic institution, Mayo Clinic's campus in Rochester, Minnesota, and to report the incidence of immediate postintubation complications., Patients and Methods: Critically ill adult (≥18 years) patients admitted to a medical-surgical intensive care unit from January 1, 2013, to December 31, 2014, who required endotracheal intubation included., Results: The final cohort included 420 patients. The mean age at intubation was 62.9 ± 16.3 years, with 58% (244) of the cohort as male. The most common reason for intubation was respiratory failure (282 [67%]). The most common airway device used was video laryngoscopy (204 [49%]). Paralysis was used in 264 (63%) patients, with ketamine as the most common sedative (194 [46%]). The most common complication was hypotension (170 [41%]; 95% confidence interval [CI]: 35.7-45.3) followed by hypoxemia (74 [17.6%]; 95% CI: 14.1-21.6), with difficult intubation occurring in 20 (5%; 95% CI: 2.9-7.3)., Conclusion: We found a high success rate of first-pass intubation in critically ill patients (89.8%), despite the procedure being done primarily by trainees 92.6% of the time; video was the preferred method of laryngoscopy (48.6%). Although our difficult intubation (4.8%) and complication rates typically associated with the act of intubation such as aspiration (1.2%; 95% CI: 0.4-2.8) and esophageal intubation (0.2%; 95% CI: 0.01-1.3) are very low compared to other published rates (8.09%), postintubation hypotension (40.5%) and hypoxemia (17.6%) higher.

Sepsis is a heterogeneous disease caused by an infection stimulus that triggers several complex local and systemic immuno-inflammatory reactions, which results in multiple organ dysfunction and significant morbidity and mortality. The diagnosis of sepsis is challenging because there is no gold standard for diagnosis. As a result, the clinical diagnosis of sepsis is ever changing to meet the clinical and research requirements. Moreover, although there are many novel biomarkers and screening tools for predicting the risk of sepsis, the diagnostic performance and effectiveness of these measures are less than satisfactory, and there is insufficient evidence to recommend clinical use of these new techniques. As a consequence, diagnostic criteria for sepsis need regular revision to cope with emerging evidence. This review aims to present the most updated information on diagnosis and early recognition of sepsis. Recommendations for clinical use of different diagnostic tools rely on the Grades of Recommendation Assessment, Development and Evaluation (GRADE) framework. Because most of the studies were observational and did not allow a reliable assessment of these tools, a two-step inference approach was employed. Future trials need to confirm or refute a particular index test and should directly explore relevant patient outcome parameters., Competing Interests: The authors have no conflicts of interest to declare.

Background: We aim to report the incidence of post-intubation hypotension in the critically ill, to report in-hospital mortality and length of stay in those who developed post-intubation hypotension, and to explore possible risk factors associated with post-intubation hypotension., Material/methods: Adult (≥18 years) ICU patients who received emergent endotracheal intubation were included. We excluded patients if they were hemodynamically unstable 60 minutes pre-intubation. Post-intubation hypotension was defined as the administration of any vasopressor within 60 minutes following intubation., Results: Twenty-nine patients developed post-intubation hypotension (29/147, 20%). Post-intubation hypotension was associated with increased in-hospital mortality (11/29, 38% vs. 19/118, 16%) and length of stay (21 [10-37] vs. 12 [7-21] days) on multivariate analysis. Three risk factors for post-intubation hypotension were identified on multivariate analysis: 1) decreasing mean arterial pressure pre-intubation (per 5 mmHg decrease) (p-value=0.04; 95% CI 1.01-1.55); 2) administration of neuromuscular blockers (p-value=0.03; 95% CI 1.12-6.53); and 3) intubation complication (p-value=0.03; 95% CI 1.16-15.57)., Conclusions: Post-intubation hypotension was common in the ICU and was associated with increased in-hospital mortality and length of stay. These patients were more likely to have had lower mean arterial pressure prior to intubation, received neuromuscular blockers, or suffered a complication during intubation.

In this paper we present the viewpoints of three members of a research team, on the approach to teamwork in the development of an emergent use clinical trial when dealing with diversity of opinions, in order to facilitate stakeholder buy-in. We also discuss a specific approach to the coordination of the team members, which in our opinion had a positive impact on the implementation of the project. We also comment on the influence of the team organization in the timeline and completion of a clinical trial. We hope to start a conversation on team dynamics in the design of clinical trials, especially in the context of emergent use research.

Background: Evidence is lacking for what defines post-intubation hypotension in the intensive care unit (ICU). If a valid definition could be used, the potential exists to evaluate possible risk factors and thereby improve post-intubation. Thus, our objectives were to arrive at the best surrogate for post-intubation hypotension that accurately predicts both in-hospital and 90-day mortality in a population of ICU patients and to report mortality rates between the exposed and unexposed cohorts., Methods: We conducted a retrospective cohort study of emergent endotracheal intubations in a medical-surgical ICU from January 1, 2010 to December 31, 2011 to evaluate surrogates for post-intubation hypotension that would predict in-hospital and 90-day mortality followed by an analysis of exposed versus unexposed using our best surrogate. Patients were ≥18 years of age, underwent emergent intubation during their first ICU admission, and did not meet any of the surrogates 60 min pre-intubation., Results: The six surrogates evaluated 60 min post-intubation were those with any systolic blood pressures ≤90 mmHg, any mean arterial pressures ≤65 mmHg, reduction in median systolic blood pressures of ≥20%, any vasopressor administration, any non-sinus rhythm and, fluid administration of ≥30 ml/kg. A total of 147 patients were included. Of the six surrogates, only the administration of any vasopressor 60 min post-intubation remained significant for mortality. Twenty-nine patients were then labeled as hemodynamically unstable and compared to the 118 patients labeled as hemodynamically stable. After adjusting for confounders, the hemodynamically unstable group had a significantly higher in-hospital and 90-day mortality [OR (95% CI); 3.84 (1.31-11.57) (p value = 0.01) and 2.37 (1.18-4.61) (p-value = 0.02)]., Conclusions: Emergently intubated patients manifesting hemodynamic instability after but not before intubation, as measured by vasoactive administration 60 min post-intubation, have a higher association with in-hospital and 90-day mortality.

Endotracheal intubation is frequently performed in the intensive care unit (ICU). It can be life-saving for many patients who present with acute respiratory distress. However, it is equally associated with complications that may lead to unwanted effects in this patient population. According to the literature, the rate of complications associated with endotracheal intubation is much higher in an environment such as the ICU as compared to other, more controlled environments (i.e., operating room). Thus, the conduct of performing such a procedure needs to be accomplished with the utmost care. To facilitate establishment of the breathing tube, sedation is routinely administered. Given the tenuous hemodynamic status of the critically ill, etomidate was frequently chosen to blunt further decreases in blood pressure and/or heart rate. Recently however, reports have demonstrated a possible association with the use of etomidate for endotracheal intubation and mortality in the critically ill. In addition, this association seems to be predominantly in patients diagnosed with sepsis. As a result, some have advocated against the use of this medication in septic patients. Due to the negative associations identified with etomidate and mortality, several investigators have evaluated potential alternatives to this solution (e.g., ketamine and ketamine-propofol admixture). These studies have shown promise. However, despite the evidence against using etomidate for endotracheal intubation, other studies have demonstrated no such association. This leaves the critical care clinician with uncertainty regarding the best sedative to administer in this patient population. The following editorial discusses current evidence regarding etomidate use for endotracheal intubation and mortality. In particular, we highlight a recent article with the largest population to date that found no association between etomidate and mortality in the critically ill and illustrate important findings that the reader should be aware of regarding this article.

Purpose: Preintubation shock index (SI) and modified shock index (MSI) have demonstrated predictive capability for postintubation hypotension in emergency department. The primary aim was to explore this relationship in the critical care environment. The secondary aims were to evaluate the relationship of shock indices with other short-term outcomes like mortality and length of stay in intensive care unit., Materials and Methods: This is a nonconcurrent cohort study, conducted in eligible 140 adult intensive care unit (ICU) patients of a tertiary care medical center. Eligibility criterion was emergent endotracheal intubation in apparently hemodynamically stable patients., Results: Preintubation SI ≥ 0.90 had a significant association with postintubation hypotension as defined by systolic blood pressure < 90 mm Hg in the univariate (P = .03; odds ratio [OR], 2.13; 95% confidence interval [CI], 1.07-4.35) and multivariate analyses (P = .01; OR, 3.17; 95% CI, 1.36-7.73) after adjusting for confounders. It was also associated with higher ICU mortality in both the univariate (P = .01; OR, 4.00; 95% CI, 1.26-12.67) and multivariate analyses (P = .01; OR, 5.75; 95% CI, 1.58-26.48). There was no association of preintubation MSI with postintubation hemodynamic instability and ICU mortality. No association was found between preintubation SI and MSI, with ICU length of stay and 30-day mortality., Conclusions: Our findings indicate that preintubation SI greater than or equal to 0.90 is a predictor of postintubation hypotension (systolic blood pressure <90 mm Hg) and ICU mortality in emergently intubated adult patients in intensive care units., (Published by Elsevier Inc.)

Background: The primary aim of this study was to determine the period prevalence of the single-syringe ketamine-propofol admixture used for sedation and induction among anesthesia providers during a 5-year period before and after educational sessions addressing barriers to its use. Secondary aims were to determine barriers to its use and address the most prevalent concerns through educational sessions., Material and Methods: Surveys were administered to certified and student registered nurse anesthetists, anesthesia residents, and anesthesiologists at Mayo Clinic Rochester, MN before and after educational sessions addressing common barriers. Identified barriers were addressed by oral and/or electronic presentations with identical content., Results: Pre-education period prevalence for sedation was 110 (43%) and 64 (25%) for induction. Identified barriers were uncertainty of benefit in 62 respondents (23%), mixed controlled substance disposal in 48 (18%), regulatory/institutional policies in 20 (7%), and compatibility in 9 (3%). Post-education period prevalence for sedation was 102 (44%), and induction 63 (27%). No concerns were noted in 72% of the post-education group verses 42% in the pre-education group (p<0.01). No concerns were reported in 51% of the electronic only education group verses 64% in the oral education group (p<0.01)., Conclusions: The period prevalence of "ketofol" was greater for sedation than induction. The period prevalence following education showed a slight increase in both sedation and induction use. There was a significant reduction in barriers following education, with oral presentations being more effective than electronic only. Period prevalence was increasing following education; however, allowing more time may have shown a significant practice change.

Background: Endotracheal intubation (ETI) is commonly performed as a life-saving procedure in the intensive care unit (ICU). It is often associated with significant hemodynamic perturbations and can severely impact the outcome of ICU patients. Etomidate is often chosen by many critical care providers for the patients who are hypotensive because of its superior hemodynamic profile compared to other induction medications. However, recent evidence has raised concerns about the increased incidence of adrenal insufficiency and mortality associated with etomidate use. A combination of ketamine and propofol (known as ketofol) has been studied in various settings as an alternative induction agent. In recent years, studies have shown that this combination may provide adequate sedation while maintaining hemodynamic stability, based on the balancing of the hemodynamic effects of these two individual agents. We hypothesized that ketofol may offer a valuable alternative to etomidate in critically ill patients with or without hemodynamic instability., Methods/design: A randomized controlled parallel-group clinical trial of adult critically ill patients admitted to either a medical or surgical ICU at Mayo Clinic in Rochester, MN will be conducted. As part of planned emergency research, informed consent will be waived after appropriate community consultation and notification. Patients undergoing urgent or emergent ETI will receive either etomidate or a 1:1 admixture of ketamine and propofol (ketofol). The primary outcome will be hemodynamic instability during the first 15 minutes following drug administration. Secondary outcomes will include ICU length of stay, mortality, adrenal function, ventilator-free days and vasoactive medication use, among others. The planned sample size is 160 total patients., Discussion: The overall goal of this trial is to assess the hemodynamic consequences of a ketamine-propofol combination used in critically ill patients undergoing urgent or emergent ETI compared to etomidate, a medication with an established hemodynamic profile. The trial will address a crucial gap in the literature regarding the optimal induction agent for ETI in patients that may have potential or established hemodynamic instability. Greater experience with planned emergency research will, hopefully, pave the way for future prospective randomized clinical trials in the critically ill population., Trial Registration: Clinicaltrials.gov: NCT02105415. 31 March 2014.

Background: U.S. federal regulations require that certain ethical elements be followed to protect human research subjects. The location and clinical circumstances of a proposed research study can differ substantially and can have significant implications for these ethical considerations. Both the location and clinical circumstances are particularly relevant for research in intensive care units (ICUs), where patients are often unable to provide informed consent to participate in a proposed research intervention., Purpose: Our goal is to elaborate on the updated 2013 U.S. Food and Drug Administration (FDA) guidance document regarding an exemption from the requirement of obtaining informed consent from patients or their surrogates and to address certain elements within that document, thereby assisting clinicians in developing a framework for emergency research in accordance with the regulatory bodies at their own institutions and in the United States., Methods: Review of the 2011 and updated FDA guidance document on exemption from informed consent., Results: The current process of obtaining informed consent within ICUs needs to be revisited, especially for research in which timely informed consent is not likely. In particular, the process of obtaining informed consent may not be appropriate or even ethical for critically ill patients in extremis who require an intervention for which there is no current acceptable standard of care and clinical equipoise exists. We provide clinicians with a viewpoint that further elaborates on the FDA guidance document., Limitations: The viewpoints provided herein are those of the authors and are therefore inherently limited by the personal views of a selected few. Other clinicians or researchers may not interpret the FDA guidelines in a similar manner. Moreover, the discussion of a guideline document is a limitation in and of itself. The guidelines set forth by the FDA are precisely that-guidelines. Therefore, they may not be followed as outlined in the guidance document within one's own institution. Our goal is that, by elaborating on the guidelines for planned research involving human subjects in the ICU, institutional regulatory bodies may gain a better understanding in drafting their own document when faced with a clinician or a researcher who wishes to conduct planned research in an ICU., Conclusions: We believe that the interpretations provided will allow clinicians to safely undertake planned research in ICUs without endangering the main tenets of ethical research involving human participants. This research is needed for the advancement of care in the critically ill., (Copyright 2015 The Journal of Clinical Ethics. All rights reserved.)

Background: Endotracheal intubation is a common procedure performed for critically ill patients that can have immediate life-threatening complications. Induction medications are routinely given to facilitate the procedure, but most of these medications are associated with hypotension. While etomidate is known for its neutral hemodynamic profile, it has been linked with increased mortality in septic patients and increased morbidity in trauma patients. Ketamine and propofol are effective anesthetics with counteracting cardiovascular profiles. No data are available about the use of this combination in critically ill patients undergoing endotracheal intubation., Case Report: We describe 6 cases in which the combination of ketamine and propofol ("ketofol") was used as an induction agent for endotracheal intubation in critically ill patients with a focus on hemodynamic outcomes. All patients received a neuromuscular blocker and fentanyl, while 5 patients received midazolam. We recorded mean arterial pressure (MAP) 1 minute before induction and 15 minutes after intubation with the combination. Of the 6 patients, 5 maintained a MAP ≥ 65 mmHg 15 minutes after intubation. One patient was on norepinephrine infusion with a MAP of 64 mmHg, and did not require an increase in the dose of the vasopressor 15 minutes after intubation. No hemodynamic complications were reported after any of the intubations., Conclusions: This case series describes the use of the "ketofol" combination as an induction agent for intubation in critically ill patients when hemodynamic stability is desired. Further research is needed to establish the safety of this combination and how it compares to other induction medications.

Rationale, Aims and Objectives: Checklists have been adopted by various institutions to improve patient outcomes. In particular, readmission prevention checklists may be of potential value to improve patient care and reduce medical costs. As a result, a prior quality improvement study was conducted to create an intensive care unit readmission prevention checklist. The previous pilot demonstrated zero readmissions when the readmission prevention checklist was utilized but yielded low compliance (30%). Thus, a subsequent quality initiative was undertaken to refine the readmission prevention checklist with the primary aim of improved compliance while maintaining a reduced readmission rate that was observed with the original quality improvement study., Method: A single-centre, cross-sectional study for assessing baseline data and a prospective observational study to assess the effectiveness of a refined readmission prevention checklist tool in a 20-bed tertiary medical-surgical intensive care unit at an academic medical centre in Rochester, MN was conducted. Medical patients admitted through the emergency department, upon direct transfer from outside facility, and post-operative surgical patients at our institution were included. A refined readmission prevention checklist tool was administered during an 8-week pilot period for medical and post-operative surgical patients., Results: The refined readmission prevention checklist resulted in an even lower compliance (10.5%) from the initial phase likely resulting from utilization of a paper readmission prevention checklist in an electronic medical environment. Moreover, the refined readmission prevention checklist demonstrated a 22% unplanned readmission rate for patients in which the tool was utilized., Conclusions: In conclusion, the findings of the current quality improvement study may serve to rethink the process of health care delivery that applies paper tools in an electronic medical environment., (© 2014 John Wiley & Sons, Ltd.)

Background: The development and validation of automated electronic medical record (EMR) search strategies are important for establishing the timing of mechanical ventilation initiation in the intensive care unit (ICU).Thus, we sought to develop and validate an automated EMR search algorithm (strategy) for time zero, the moment of mechanical ventilation initiation in the critically ill patient., Methods: The EMR search algorithm was developed on the basis of several mechanical ventilation parameters, with the final parameter being positive end-expiratory pressure (PEEP), and was applied to a comprehensive institutional EMR database. The search algorithm was derived from a secondary retrospective analysis of a subset of 450 patients from a cohort of 2,684 patients admitted to a medical ICU and a surgical ICU from January 1, 2010, through December 31, 2011. It was then validated in an independent subset of 450 patients from the same period. The overall percent of agreement between our search algorithm and a comprehensive manual medical record review in the derivation and validation subsets, using peak inspiratory pressure (PIP) as the reference standard, was compared to assess timing of mechanical ventilation initiation., Results: In the derivation subset, the automated electronic search strategy achieved an 87% (κ = 0.87) perfect agreement, with 94% agreement to within one minute. In validating this search algorithm, perfect agreement was found in 92% (κ = 0.92) of patients, with 99% agreement occurring within one minute., Conclusions: The use of an electronic search strategy resulted in highly accurate extraction of mechanical ventilation initiation in the ICU. The search algorithm of mechanical ventilation initiation is highly efficient and reliable and can facilitate both clinical research and patient care management in a timely manner.