Inhaled volatile anesthetics in the intensive care unit.

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.

Association of Shock Indices with Peri-Intubation Hypotension and Other Outcomes: A Sub-Study of the KEEP PACE Trial.

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.

Noninvasive Cardiac Output Monitoring (NICOM) in the Critically Ill Patient Undergoing Endotracheal Intubation: A Prospective Observational Study.

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/m2]: -2.7 ± 778.2) but stabilization in cardiac index (delta change (L/min/m2]: 0.1 ± 1.5) while etomidate and ketamine demonstrated increases in total peripheral resistance index (etomidate delta change [dynes × s/cm-5/m2]: 302.1 ± 414.3; ketamine delta change [dynes × s/cm-5/m2]: 278.7 ± 418.9) but only etomidate resulted in a decrease in cardiac index (delta change [L/min/m2]: -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.

Trajectory of PaO2/FiO2 Ratio in Shock After Angiotensin II.

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 PaO2/FiO2 and SpO2/FiO2 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. PaO2, SpO2, and FiO2 were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO2/FiO2 and SpO2/FiO2 were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO2/FiO2 ≤ 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 PaO2/FiO2 change -4.7 mm Hg/hr, 95% CI - 6.0 to -3.5, p < .001; hourly SpO2/FiO2 change -3.1/hr, 95% CI-3.7 to -2.4, p < .001). Ang-2 treatment was associated with significant improvements in PaO2/FiO2 and SpO2/FiO2 in the 48-h after initiation (hourly PaO2/FiO2 change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p = .003; hourly SpO2/FiO2 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 (pinteraction < 0.001 for both PaO2/FiO2 and SpO2/FiO2). This improvement was associated with significantly fewer patients having a PaO2/FiO2 ≤ 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 PaO2/FiO2 ≤ 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 PaO2/FiO2 and SpO2/FiO2. 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.

Clonidine use during dexmedetomidine weaning: A systematic review.

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.

Thromboelastography Parameters do not Discriminate for Thrombotic Events in Hospitalized Patients With COVID-19.

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.

Intraoperative hypotension is associated with persistent acute kidney disease after noncardiac surgery: a multicentre cohort study.

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.

Acute exacerbation of interstitial lung disease in the intensive care unit.

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.

Endotracheal intubation sedation in the intensive care unit.

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 ß-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.

Hypotension Prediction Score for Endotracheal Intubation in Critically Ill Patients: A Post Hoc Analysis of the HEMAIR Study.

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).

Intensive Care Unit Sedation Practices at a Large, Tertiary Academic Center.

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.

Association of perioperative hypotension with subsequent greater healthcare resource utilization.

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.

Postoperative Hypotension and Adverse Clinical Outcomes in Patients Without Intraoperative Hypotension, After Noncardiac Surgery.

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.

Intraoperative Hypotension Is Associated With Adverse Clinical Outcomes After Noncardiac Surgery.

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.

Reintubation Summation Calculation: A Predictive Score for Extubation Failure in Critically Ill Patients.

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 Re-Intubation Summation Calculation (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/m2 [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 cmH2O (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.

Risk Factors for and Outcomes Associated With Peri-Intubation Hypoxemia: A Multicenter Prospective Cohort Study.

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 SpO2 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 SPO2. 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.

Description of Pharmacogenomic Testing Among Patients Admitted to the Intensive Care Unit After Cardiovascular Surgery.

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.

Postoperative hypotension in patients discharged to the intensive care unit after non-cardiac surgery is associated with adverse clinical outcomes.

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.

Risk factors for and prediction of post-intubation hypotension in critically ill adults: A multicenter prospective cohort study.

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.