Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force.

OBJECTIVES: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN: Review and task force position statements with necessary guidance. SETTING: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

Association of Active Renin Content With Mortality in Critically Ill Patients: A Post hoc Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) Trial.

OBJECTIVE: Sepsis is a leading cause of mortality. Predicting outcomes is challenging and few biomarkers perform well. Defects in the renin-angiotensin system (RAS) can predict clinical outcomes in sepsis and may outperform traditional biomarkers. We postulated that RAS dysfunction (elevated active renin, angiotensin 1-7 [Ang-(1-7)], and angiotensin-converting enzyme 2 (ACE2) activity with depressed Ang-II and ACE activity) would be associated with mortality in a cohort of septic patients. DESIGN: Post hoc analysis of patients enrolled in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized controlled trial. SETTING: Forty-three hospitals across the United States. PATIENTS: Biorepository samples of 103 patients. INTERVENTIONS: We analyzed day 0 (within 24 hr of respiratory failure, septic shock, or both) and day 3 samples ( n = 103 and 95, respectively) for assessment of the RAS. The association of RAS values with 30-day mortality was determined using Cox proportional hazards regression with multivariable adjustments for age, sex, VICTAS treatment arm, systolic blood pressure, Sequential Organ Failure Assessment Score, and vasopressor use. MEASUREMENTS AND MAIN RESULTS: High baseline active renin values were associated with higher 30-day mortality when dichotomized to the median of 188.7 pg/mL (hazard ratio [HR] = 2.84 [95% CI, 1.10-7.33], p = 0.031) or stratified into quartiles (Q1 = ref, HR Q2 = 2.01 [0.37-11.04], HR Q3 = 3.22 [0.64-16.28], HR Q4 = 5.58 [1.18-26.32], p for linear trend = 0.023). A 1- sd (593.6 pg/mL) increase in renin from day 0 to day 3 was associated with increased mortality (HR = 3.75 [95% CI, 1.94-7.22], p < 0.001), and patients whose renin decreased had improved survival compared with those whose renin increased (HR 0.22 [95% CI, 0.08-0.60], p = 0.003). Ang-(1-7), ACE2 activity, Ang-II and ACE activity did not show this association. Mortality was attenuated in patients with renin over the median on day 0 who received the VICTAS intervention, but not on day 3 ( p interaction 0.020 and 0.137, respectively). There were no additional consistent patterns of mortality on the RAS from the VICTAS intervention. CONCLUSIONS: Baseline serum active renin levels were strongly associated with mortality in critically ill patients with sepsis. Furthermore, a greater relative activation in circulating renin from day 0 to day 3 was associated with a higher risk of death.

Incidence and Risk Factors of Chronic Postoperative Pain in Same-day Surgery: A Prospective Cohort Study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: This study assessed pain 90 days after ambulatory surgery in an international, multicenter prospective cohort study of patients at least 45 yr old with comorbidities or at least 65 yr old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change of more than 1 point in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain was defined as a score greater than 4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2,054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain before surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were active smoking (odds ratio, 1.82; 95% CI, 1.20 to 2.76), orthopedic surgery (odds ratio, 4.7; 95% CI, 2.24 to 9.7), plastic surgery (odds ratio, 4.3; 95% CI, 1.97 to 9.2), breast surgery (odds ratio, 2.74; 95% CI, 1.29 to 5.8), vascular surgery (odds ratio, 2.71; 95% CI, 1.09 to 6.7), and ethnicity (i.e., for Hispanic/Latino ethnicity, odds ratio, 3.41; 95% CI, 1.68 to 6.9 and for First Nations/native persons, odds ratio, 4.0; 95% CI, 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, is usually moderate to severe in nature, and occurs mostly in patients without chronic pain before surgery.

ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. METHODS: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h. RESULTS: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients. CONCLUSIONS: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Sepsis-associated acute kidney injury: recent advances in enrichment strategies, sub-phenotyping and clinical trials.

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.

Impact of continuous and wireless monitoring of vital signs on clinical outcomes: a propensity-matched observational study of surgical ward patients.

BACKGROUND: Continuous and wireless vital sign monitoring is superior to intermittent monitoring in detecting vital sign abnormalities; however, the impact on clinical outcomes has not been established. METHODS: We performed a propensity-matched analysis of data describing patients admitted to general surgical wards between January 2018 and December 2019 at a single, tertiary medical centre in the USA. The primary outcome was a composite of in-hospital mortality or ICU transfer during hospitalisation. Secondary outcomes were the odds of individual components of the primary outcome, and heart failure, myocardial infarction, acute kidney injury, and rapid response team activations. Data are presented as odds ratios (ORs) with 95% confidence intervals (CIs) and n (%). RESULTS: We initially screened a population of 34,636 patients (mean age 58.3 (Range 18-101) yr, 16,456 (47.5%) women. After propensity matching, intermittent monitoring (n=12 345) was associated with increased risk of a composite of mortality or ICU admission (OR 3.42, 95% CI 3.19-3.67; P<0.001), and heart failure (OR 1.48, 95% CI 1.21-1.81; P<0.001), myocardial infarction (OR 3.87, 95% CI 2.71-5.71; P<0.001), and acute kidney injury (OR 1.32, 95% CI 1.09-1.57; P<0.001) compared with continuous wireless monitoring (n=7955). The odds of rapid response team intervention were similar in both groups (OR 0.86, 95% CI 0.79-1.06; P=0.726). CONCLUSIONS: Patients who received continuous ward monitoring were less likely to die or be admitted to ICU than those who received intermittent monitoring. These findings should be confirmed in prospective randomised trials.

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery.

BACKGROUND: Vasoplegia is common after cardiac surgery, is associated with hyperreninemia, and can lead to acute kidney stress. We aimed to conduct a pilot study to test the hypothesis that, in vasoplegic cardiac surgery patients, angiotensin-II (AT-II) may not increase kidney stress (measured by [TIMP-2]*[IGFBP7]). METHODS: We randomly assigned patients with vasoplegia (cardiac index [CI] > 2.1l/min, postoperative hypotension requiring vasopressors) and Δ-renin (4-hour postoperative-preoperative value) ≥3.7 µU/mL, to AT-II or placebo targeting a mean arterial pressure ≥65 mm Hg for 12 hours. The primary end point was the incidence of kidney stress defined as the difference between baseline and 12 hours [TIMP-2]*[IGFBP7] levels. Secondary end points included serious adverse events (SAEs). RESULTS: We randomized 64 patients. With 1 being excluded, 31 patients received AT-II, and 32 received placebo. No significant difference was observed between AT-II and placebo groups for kidney stress (Δ-[TIMP-2]*[IGFBP7] 0.06 [ng/mL] 2 /1000 [Q1-Q3, -0.24 to 0.28] vs -0.08 [ng/mL] 2 /1000 [Q1-Q3, -0.35 to 0.14]; P = .19; Hodges-Lehmann estimation of the location shift of 0.12 [ng/mL] 2 /1000 [95% confidence interval, CI, -0.1 to 0.36]). AT-II patients received less fluid during treatment than placebo patients (2946 vs 3341 mL, P = .03), and required lower doses of norepinephrine equivalent (0.19 mg vs 4.18mg, P < .001). SAEs were reported in 38.7% of patients in the AT-II group and in 46.9% of patients in the placebo group. CONCLUSIONS: The infusion of AT-II for 12 hours appears feasible and did not lead to an increase in kidney stress in a high-risk cohort of cardiac surgery patients. These findings support the cautious continued investigation of AT-II as a vasopressor in hyperreninemic cardiac surgery patients.

Overview and Clinical Applications of Artificial Intelligence and Machine Learning in Cardiac Anesthesiology.

Artificial intelligence- (AI) and machine learning (ML)-based applications are becoming increasingly pervasive in the healthcare setting. This has in turn challenged clinicians, hospital administrators, and health policymakers to understand such technologies and develop frameworks for safe and sustained clinical implementation. Within cardiac anesthesiology, challenges and opportunities for AI/ML to support patient care are presented by the vast amounts of electronic health data, which are collected rapidly, interpreted, and acted upon within the periprocedural area. To address such challenges and opportunities, in this article, the authors review 3 recent applications relevant to cardiac anesthesiology, including depth of anesthesia monitoring, operating room resource optimization, and transthoracic/transesophageal echocardiography, as conceptual examples to explore strengths and limitations of AI/ML within healthcare, and characterize this evolving landscape. Through reviewing such applications, the authors introduce basic AI/ML concepts and methodologies, as well as practical considerations and ethical concerns for initiating and maintaining safe clinical implementation of AI/ML-based algorithms for cardiac anesthesia patient care.

Sustainability of the Subspecialty of Anesthesiology Critical Care: An Expert Consensus and Review of the Literature.

While considerable literature exists with respect to clinical aspects of critical care anesthesiology (CCA) practice, few publications have focused on how anesthesiology-based critical care practices are organized and the challenges associated with the administration and management of anesthesiology critical care units. Currently, numerous challenges are affecting the sustainability of CCA practice, including decreased applications to fellowship positions and decreased reimbursement for critical care work. This review describes what is known about the subspecialty of CCA and leverages the experience of administrative leaders in adult critical care anesthesiologists in the United States to describe potential solutions.

Assessment of skin pigmentation-related bias in pulse oximetry readings among adults.

PURPOSE: Recent reports that pulse oximeters may overestimate oxygen saturation in individuals with darker skin pigmentation have prompted concerns from regulatory authorities regarding racial bias. We investigated the performance of TruSignal SpO2 sensors (GE Healthcare, Helsinki, Finland) in adults with varying skin pigmentation. METHODS: A retrospective study was conducted using a set of pooled assessments of SpO2/SaO2 measurements from nine studies to assess bias, accuracy (Arms), and precision of TruSignal sensors in healthy adults under induced hypoxia. Subgroup analyses were performed based on oxygen saturation levels (band 1, ≥ 70 and ≤ 80%; band 2, > 80 and ≤ 90%; band 3, > 90 and ≤ 100%). RESULTS: Of the 10,800 data points from 131 individuals, 8,202 (75.9%) and 2,598 (24.1%) were assigned to the light and dark pigment groups, respectively. Bias was 0.14% overall and less than 1% across oxygenation bands. The difference in bias between dark and light pigment groups was statistically significant at the low oxygenation band with SpO2 ≥ 70 and ≤ 80% (+ 0.58% and + 0.30% respectively; p = 0.0035). Throughout the saturation range, Arms was 1.64% in the light and 1.71% in the dark pigment group, within device specifications and regulatory requirements. Oxygenation was the dominating factor in stepwise ANOVA modeling. The mixed model also showed that bias was strongly affected by the oxygenation range. CONCLUSION: TruSignal sensors demonstrated higher bias at lower oxygen saturation, with less than 0.5% difference between pigment groups. These findings raise new questions, such as ways to improve pulse oximetry measurements during challenging clinical conditions, including low perfusion.

Agreement between cardiac output estimation with a wireless, wearable pulse decomposition analysis device and continuous thermodilution in post cardiac surgery intensive care unit patients.

PURPOSE: Pulse Decomposition Analysis (PDA) uses integration of the systolic area of a distally transmitted aortic pulse as well as arterial stiffness estimates to compute cardiac output. We sought to assess agreement of cardiac output (CO) estimation between continuous pulmonary artery catheter (PAC) guided thermodilution (CO-CCO) and a wireless, wearable noninvasive device, (Vitalstream, Caretaker Medical, Charlottesville, VA), that utilizes the Pulse Decomposition Analysis (CO-PDA) method in postoperative cardiac surgery patients in the intensive care unit. METHODS: CO-CCO measurements were compared with post processed CO-PDA measurements in prospectively enrolled adult cardiac surgical intensive care unit patients. Uncalibrated CO-PDA values were compared for accuracy with CO-CCO via a Bland-Altman analysis considering repeated measurements and a concordance analysis with a 10% exclusion zone. RESULTS: 259.7 h of monitoring data from 41 patients matching 15,583 data points were analyzed. Mean CO-CCO was 5.55 L/min, while mean values for the CO-PDA were 5.73 L/min (mean of differences +- SD 0.79 ± 1.11 L/min; limits of agreement - 1.43 to 3.01 L/min), with a percentage error of 37.5%. CO-CCO correlation with CO-PDA was moderate (0.54) and concordance was 0.83. CONCLUSION: Compared with the CO-CCO Swan-Ganz, cardiac output measurements obtained using the CO-PDA were not interchangeable when using a 30% threshold. These preliminary results were within the 45% limits for minimally invasive devices, and pending further robust trials, the CO-PDA offers a noninvasive, wireless solution to complement and extend hemodynamic monitoring within and outside the ICU.

An updated "norepinephrine equivalent" score in intensive care as a marker of shock severity.

Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.

Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial.

BACKGROUND: High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II). METHODS: Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation. RESULTS: Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups. CONCLUSIONS: This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial. TRIAL REGISTRATION: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.

Intraoperative arterial pressure management: knowns and unknowns.

Preventing postoperative organ dysfunction is integral to the practice of anaesthesia. Although intraoperative hypotension is associated with postoperative end organ dysfunction, there remains ambiguity with regards to its definition, targets, thresholds for initiating treatment, and ideal treatment modalities.

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.

Angiotensin II for Vasodilatory Hypotension in Patients Requiring Mechanical Circulatory Support.

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min (P = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Artificial Intelligence for Perioperative Medicine: Perioperative Intelligence.

The anesthesiologist's role has expanded beyond the operating room, and anesthesiologist-led care teams can deliver coordinated care that spans the entire surgical experience, from preoperative optimization to long-term recovery of surgical patients. This expanded role can help reduce postoperative morbidity and mortality, which are regrettably common, unlike rare intraoperative mortality. Postoperative mortality, if considered a disease category, will be the third leading cause of death just after heart disease and cancer. Rapid advances in technologies like artificial intelligence provide an opportunity to build safe perioperative practices. Artificial intelligence helps by analyzing complex data across disparate systems and producing actionable information. Using artificial intelligence technologies, we can critically examine every aspect of perioperative medicine and devise innovative value-based solutions that can potentially improve patient safety and care delivery, while optimizing cost of care. In this narrative review, we discuss specific applications of artificial intelligence that may help advance all aspects of perioperative medicine, including clinical care, education, quality improvement, and research. We also discuss potential limitations of technology and provide our recommendations for successful adoption.

Level of Evidence of Guidelines for Perioperative Management of Patients With Obstructive Sleep Apnea: An Evaluation Using the Appraisal of Guidelines for Research and Evaluation II Tool.

Currently, the quality of guidelines for the perioperative management of patients with obstructive sleep apnea (OSA) is unknown, leaving anesthesiologists to make perioperative management decisions with some degree of uncertainty. This study evaluated the quality of clinical practice guidelines regarding the perioperative management of patients with OSA. This study was reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the MedlineALL (Ovid) database was conducted from inception to February 26, 2021, for clinical practice guidelines in the English language. Quality appraisal of guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework. Descriptive statistical analysis of each of the 6 domains was expressed as a percentage using the formula: (obtained score - minimum possible score)/(maximum possible score - minimum possible score). Of 192 articles identified in the search, 41 full texts were assessed for eligibility, and 10 articles were included in this review. Intraclass correlation coefficients of the AGREE II scores across the 7 evaluators for each guideline were each >0.9, suggesting that the consistency of the scores among evaluators was high. Sixty percent of recommendations were based on evidence using validated methods to grade medical literature, while the remainder were consensus based. The median and range scores of each domain were: (1) scope and purpose, 88% (60%-95%); (2) stakeholder involvement, 52% (30%-82%); (3) rigor of development, 67% (40%-90%); (4) clarity of presentation, 74% (57%-88%); (5) applicability, 46% (20%-73%); and (6) editorial independence, 67% (19%-83%). Only 4 guidelines achieved an overall score of >70%. This critical appraisal showed that many clinical practice guidelines for perioperative management of patients with OSA used validated methods to grade medical literature, such as Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and Oxford classification, with lower scores for stakeholder involvement due to lack of engagement of patient partners and applicability domain due to lack of focus on the complete perioperative period such as postdischarge counseling. Future efforts should be directed toward establishing higher focus on the quality of evidence, stakeholder involvement, and applicability to the wider perioperative patient experience.

Efficacy and safety of angiotensin II in cardiogenic shock: A systematic review.

BACKGROUND: Cardiogenic shock (CS) is associated with high morbidity and mortality. In recent times, there is increasing interest in the role of angiotensin II in CS. We sought to systematically review the current literature on the use of angiotensin II in CS. METHODS: PubMed, EMBASE, Medline, Web of Science, PubMed Central, and CINAHL databases were systematically searched for studies that evaluated the efficacy of angiotensin II in patients with CS during 01/01/2010-07/07/2022. Outcomes of interest included change in mean arterial pressure (MAP), vasoactive medication requirements (percent change in norepinephrine equivalent [NEE] dose), all-cause mortality, and adverse events. RESULTS: Of the total 2,402 search results, 15 studies comprising 195 patients were included of which 156 (80%) received angiotensin II. Eleven patients (84.6%) in case reports and case series with reported MAP data at hour 12 noted an increase in MAP. Two studies noted a positive hemodynamic response (defined a priori) in eight (88.9%) and five (35.7%) patients. Eight studies reported a reduction in NEE dose at hour 12 after angiotensin II administration and one study noted a 100% reduction in NEE dose. Out of 47 patients with documented information, 13 patients had adverse outcomes which included hepatic injury (2), digital ischemia (1), ischemic optic neuropathy (1), ischemic colitis (2), agitated delirium (1), and thrombotic events (2). CONCLUSIONS: In this first systematic review of angiotensin II in CS, we note the early clinical experience. Angiotensin II was associated with improvements in MAP, decrease in vasopressor requirements, and minimal reported adverse events.

Incidence of postoperative opioid-induced respiratory depression episodes in patients on room air or supplemental oxygen: a post-hoc analysis of the PRODIGY trial.

BACKGROUND: Supplemental oxygen (SO) potentiates opioid-induced respiratory depression (OIRD) in experiments on healthy volunteers. Our objective was to examine the relationship between SO and OIRD in patients on surgical units. METHODS: This post-hoc analysis utilized a portion of the observational PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial dataset (202 patients, two trial sites), which involved blinded continuous pulse oximetry and capnography monitoring of postsurgical patients on surgical units. OIRD incidence was determined for patients receiving room air (RA), intermittent SO, or continuous SO. Generalized estimating equation (GEE) models, with a Poisson distribution, a log-link function and time of exposure as offset, were used to compare the incidence of OIRD when patients were receiving SO vs RA. RESULTS: Within the analysis cohort, 74 patients were always on RA, 88 on intermittent and 40 on continuous SO. Compared with when on RA, when receiving SO patients had a higher risk for all OIRD episodes (incidence rate ratio [IRR] 2.7, 95% confidence interval [CI] 1.4-5.1), apnea episodes (IRR 2.8, 95% CI 1.5-5.2), and bradypnea episodes (IRR 3.0, 95% CI 1.2-7.9). Patients with high or intermediate PRODIGY scores had higher IRRs of OIRD episodes when receiving SO, compared with RA (IRR 4.5, 95% CI 2.2-9.6 and IRR 2.3, 95% CI 1.1-4.9, for high and intermediate scores, respectively). CONCLUSIONS: Despite oxygen desaturation events not differing between SO and RA, SO may clinically promote OIRD. Clinicians should be aware that postoperative patients receiving SO therapy remain at increased risk for apnea and bradypnea. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02811302, registered June 23, 2016.