Adjustments of Ventilator Parameters during Operating Room-to-ICU Transition and 28-Day Mortality.

Rationale: Lung-protective mechanical ventilation strategies have been proven beneficial in the operating room (OR) and the ICU. However, differential practices in ventilator management persist, often resulting in adjustments of ventilator parameters when transitioning patients from the OR to the ICU. Objectives: To characterize patterns of ventilator adjustments during the transition of mechanically ventilated surgical patients from the OR to the ICU and assess their impact on 28-day mortality. Methods: Hospital registry study including patients undergoing general anesthesia with continued, controlled mechanical ventilation in the ICU between 2008 and 2022. Ventilator parameters were assessed 1 hour before and 6 hours after the transition. Measurements and Main Results: Of 2,103 patients, 212 (10.1%) died within 28 days. Upon OR-to-ICU transition, VT and driving pressure decreased (-1.1 ml/kg predicted body weight [IQR, -2.0 to -0.2]; P < 0.001; and -4.3 cm H2O [-8.2 to -1.2]; P < 0.001). Concomitantly, respiratory rates increased (+5.0 breaths/min [2.0 to 7.5]; P < 0.001), resulting overall in slightly higher mechanical power (MP) in the ICU (+0.7 J/min [-1.9 to 3.0]; P < 0.001). In adjusted analysis, increases in MP were associated with a higher 28-day mortality rate (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.14; P < 0.001; adjusted risk difference, 0.7%; 95% confidence interval, 0.4-1.0, both per 1 J/min). Conclusion: During transition of mechanically ventilated patients from the OR to the ICU, ventilator adjustments resulting in higher MP were associated with a greater risk of 28-day mortality.

Intensity of one-lung ventilation and postoperative respiratory failure: A hospital registry study.

BACKGROUND: Studies linked a high intensity of mechanical ventilation, measured as high mechanical power (MP) to postoperative respiratory failure (PRF) in the setting of two-lung ventilation. We investigated whether a higher MP during one-lung ventilation (OLV) is associated with PRF. METHODS: In this registry-based study, adult patients who underwent general anesthesia with OLV for thoracic surgeries between 2006 and 2020 at a New England tertiary healthcare network were included. The association between MP during OLV and PRF (emergency non-invasive ventilation or reintubation within seven days) was assessed in a cohort weighted through a generalized propensity score conditional on a priori defined preoperative and intraoperative factors. Dominance of components of MP and intensity of OLV versus two-lung ventilation in predicting PRF was investigated. RESULTS: Out of 878 included patients, 106 (12.1%) developed PRF. The median (IQR) MP during OLV was 9.8 J/min (7.5-11.8) and 8.3 J/min (6.6-10.2) in patients with and without PRF respectively. A higher MP during OLV was associated with PRF (ORadj 1.22 per 1 J/min increase; 95%CI 1.13-1.31; p < 0.001) and characterized by a U-shaped dose-response curve, with the lowest probability of PRF (7.5%) at 6.4 J/min. Dominance analysis of PRF predictors showed a stronger contribution of driving pressure over respiratory rate and tidal volume, the dynamic over the static component of MP, and MP during OLV over two-lung ventilation (contribution to Pseudo-R2: 0.017, 0.021, and 0.036, respectively). CONCLUSION: A higher intensity of OLV, mainly driven by driving pressure, is dose-dependently associated with PRF and might constitute a target for mechanical ventilation.

Development and validation of a machine learning ASA-score to identify candidates for comprehensive preoperative screening and risk stratification.

OBJECTIVE: The ASA physical status (ASA-PS) is determined by an anesthesia provider or surgeon to communicate co-morbidities relevant to perioperative risk. Assigning an ASA-PS is a clinical decision and there is substantial provider-dependent variability. We developed and externally validated a machine learning-derived algorithm to determine ASA-PS (ML-PS) based on data available in the medical record. DESIGN: Retrospective multicenter hospital registry study. SETTING: University-affiliated hospital networks. PATIENTS: Patients who received anesthesia at Beth Israel Deaconess Medical Center (Boston, MA, training [n = 361,602] and internal validation cohorts [n = 90,400]) and Montefiore Medical Center (Bronx, NY, external validation cohort [n = 254,412]). MEASUREMENTS: The ML-PS was created using a supervised random forest model with 35 preoperatively available variables. Its predictive ability for 30-day mortality, postoperative ICU admission, and adverse discharge were determined by logistic regression. MAIN RESULTS: The anesthesiologist ASA-PS and ML-PS were in agreement in 57.2% of the cases (moderate inter-rater agreement). Compared with anesthesiologist rating, ML-PS assigned more patients into extreme ASA-PS (I and IV), (p < 0.01), and less patients in ASA II and III (p < 0.01). ML-PS and anesthesiologist ASA-PS had excellent predictive values for 30-day mortality, and good predictive values for postoperative ICU admission and adverse discharge. Among the 3594 patients who died within 30 days after surgery, net reclassification improvement analysis revealed that using the ML-PS, 1281 (35.6%) patients were reclassified into the higher clinical risk category compared with anesthesiologist rating. However, in a subgroup of multiple co-morbidity patients, anesthesiologist ASA-PS had a better predictive accuracy than ML-PS. CONCLUSIONS: We created and validated a machine learning physical status based on preoperatively available data. The ability to identify patients at high risk early in the preoperative process independent of the provider's decision is a part of the process we use to standardize the stratified preoperative evaluation of patients scheduled for ambulatory surgery.

The association of intraoperative low driving pressure ventilation and nonhome discharge: a historical cohort study.

PURPOSE: To evaluate whether intraoperative ventilation using lower driving pressure decreases the risk of nonhome discharge. METHODS: We conducted a historical cohort study of patients aged ≥ 60 yr who were living at home before undergoing elective, noncardiothoracic surgery at two tertiary healthcare networks in Massachusetts between 2007 and 2018. We assessed the association of the median driving pressure during intraoperative mechanical ventilation with nonhome discharge using multivariable logistic regression analysis, adjusted for patient and procedural factors. Contingent on the primary association, we assessed effect modification by patients' baseline risk and mediation by postoperative respiratory failure. RESULTS: Of 87,407 included patients, 12,584 (14.4%) experienced nonhome discharge. In adjusted analyses, a lower driving pressure was associated with a lower risk of nonhome discharge (adjusted odds ratio [aOR], 0.88; 95% confidence interval [CI], 0.83 to 0.93, per 10 cm H2O decrease; P < 0.001). This association was magnified in patients with a high baseline risk (aOR, 0.77; 95% CI, 0.73 to 0.81, per 10 cm H2O decrease, P-for-interaction < 0.001). The findings were confirmed in 19,518 patients matched for their baseline respiratory system compliance (aOR, 0.90; 95% CI, 0.81 to 1.00; P = 0.04 for low [< 15 cm H2O] vs high [≥ 15 cm H2O] driving pressures). A lower risk of respiratory failure mediated the association of a low driving pressure with nonhome discharge (20.8%; 95% CI, 15.0 to 56.8; P < 0.001). CONCLUSIONS: Intraoperative ventilation maintaining lower driving pressure was associated with a lower risk of nonhome discharge, which can be partially explained by lowered rates of postoperative respiratory failure. Future randomized controlled trials should target driving pressure as a potential intervention to decrease nonhome discharge.

RéSUMé: OBJECTIF: Évaluer si la ventilation peropératoire utilisant une pression motrice plus faible diminue le risque de congé hors domicile. MéTHODE: Nous avons réalisé une étude de cohorte historique de patients âgés de ≥ 60 ans vivant à la maison avant de bénéficier d'une chirurgie non cardiothoracique non urgente dans deux réseaux de soins de santé tertiaires du Massachusetts entre 2007 et 2018. Nous avons évalué l'association entre la pression motrice médiane pendant la ventilation mécanique peropératoire et le congé ailleurs qu'au domicile à l'aide d'une analyse de régression logistique multivariable, ajustée pour tenir compte des facteurs liés aux patients et à l'intervention. En fonction de l'association primaire, nous avons évalué la modification de l'effet par le risque initial des patients et la médiation par l'insuffisance respiratoire postopératoire. RéSULTATS: Sur les 87 407 patients inclus, 12 584 (14,4 %) ont reçu leur congé ailleurs qu'au domicile. Dans les analyses ajustées, une pression motrice plus faible était associée à un risque réduit de congé hors domicile (rapport de cotes ajusté [RCa], 0,88; intervalle de confiance [IC] à 95 %, 0,83 à 0,93, par diminution de 10 cm H2O; P < 0,001). Cette association a été amplifiée chez les patients présentant un risque initial élevé (RCa, 0,77; IC 95 %, 0,73 à 0,81, par diminution de 10 cm H2O, P-pour-interaction < 0,001). Les résultats ont été confirmés chez 19 518 patients appariés pour la compliance initiale de leur système respiratoire (RCa, 0,90; IC 95 %, 0,81 à 1,00; P = 0,04 pour des pressions motrices faibles [< 15 cm H2O] vs élevées [≥ 15 cm H2O]). Un risque plus faible d'insuffisance respiratoire a entraîné une association entre une faible pression motrice et un congé à l'extérieur du domicile (20,8 %; IC 95 %, 15,0 à 56,8 ; P < 0,001). CONCLUSION: La ventilation peropératoire maintenant une pression motrice plus faible a été associée à un risque plus faible de congé hors domicile, ce qui peut s'expliquer en partie par des taux réduits d'insuffisance respiratoire postopératoire. Les futures études randomisées contrôlées devraient cibler la pression motrice comme intervention potentielle pour réduire les congés hors domicile.

Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients.

BACKGROUND: Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. METHODS: In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 h each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced change in beta-gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. RESULTS: Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively (p = .013). Resistive work of breathing decreased from 0.4 (0.1-0.6) J/l at baseline to 0.2 (0.1-0.3) J/l after ketamine 10 mcg/kg/min (p = .042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline (p < .01). CONCLUSIONS: In intubated, spontaneously breathing patients receiving a constant rate of propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an "activated" electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation.

Association between intraoperative tidal volume and postoperative respiratory complications is dependent on respiratory elastance: a retrospective, multicentre cohort study.

BACKGROUND: The impact of high vs low intraoperative tidal volumes on postoperative respiratory complications remains unclear. We hypothesised that the effect of intraoperative tidal volume on postoperative respiratory complications is dependent on respiratory system elastance. METHODS: We retrospectively recorded tidal volume (Vt; ml kg-1 ideal body weight [IBW]) in patients undergoing elective, non-cardiothoracic surgery from hospital registry data. The primary outcome was respiratory failure (requiring reintubation within 7 days of surgery, desaturation after extubation, or both). The primary exposure was defined as the interaction between Vt and standardised respiratory system elastance (driving pressure divided by Vt; cm H2O/[ml kg-1]). Multivariable logistic regression models, with and without interaction terms (which categorised Vt as low [Vt ≤8 ml kg-1] or high [Vt >8 ml kg-1]), were adjusted for potential confounders. Additional analyses included path mediation analysis and fractional polynomial modelling. RESULTS: Overall, 10 821/197 474 (5.5%) patients sustained postoperative respiratory complications. Higher Vt was associated with greater risk of postoperative respiratory complications (adjusted odds ratio=1.42 per ml kg-1; 95% confidence interval [CI], 1.35-1.50]; P<0.001). This association was modified by respiratory system elastance (P<0.001); in patients with low compliance (<42.4 ml cm H2O-1), higher Vt was associated with greater risk of postoperative respiratory complications (adjusted risk difference=0.3% [95% CI, 0.0-0.5] at 41.2 ml cm H2O-1 compliance, compared with 5.8% [95% CI, 3.8-7.8] at 14 ml cm H2O-1 compliance). This association was absent when compliance exceeded 41.2 ml cm H2O-1. Adverse effects associated with high Vt were entirely mediated by driving pressures (P<0.001). CONCLUSIONS: The association of harm with higher tidal volumes during intraoperative mechanical ventilation is modified by respiratory system elastance. These data suggest that respiratory elastance should inform the design of perioperative trials testing intraoperative ventilatory strategies.

Reintubation After Lung Cancer Resection: Development and External Validation of a Predictive Score.

BACKGROUND: Reintubation after lung cancer resection is an important quality metric because of increased disability, mortality and cost. However, no validated predictive instrument is in use to reduce reintubation after lung resection. This study aimed to create and validate the PRediction Of REintubation After Lung cancer resection (PROREAL) score. METHODS: The study analyzed lung resection cases from 2 university hospitals. The primary end point was reintubation within 7 days after surgery. Predictors were selected through backward stepwise logistic regression and bootstrap resampling. The investigators used reclassification and receiver-operating characteristic (ROC) curve analyses to assess score performance and compare it with an established score for all surgical patients (Score for Prediction of Postoperative Respiratory Complications [SPORC]). RESULTS: The study included 2672 patients who underwent resection for lung cancer (1754, development cohort; 918, validation cohort) between 2008 and 2020, of whom 71 (2.7%) were reintubated within 7 days after surgery. Identified score variables were surgical extent and approach, American Society of Anesthesiologists physical status, heart failure, renal disease, and diffusing capacity of the lung for carbon monoxide. The score achieved excellent discrimination in the development cohort (ROC AUC, 0.90; 95% CI, 0.87-0.94) and good discrimination in the validation cohort (ROC AUC, 0.74, 95% CI; 0.66-0.82), thus outperforming the SPORC in both cohorts (P < .001 and P = .018, respectively; validation cohort net reclassification improvement, 0.39; 95% CI, 0.18-0.60; P = .001). The score cutoff of ≥5 yielded a sensitivity of 88% (95% CI, 72-95) and a specificity of 81% (95% CI,79-83) in the development cohort. CONCLUSIONS: A simple score (PROREAL) specific to lung cancer predicts postoperative reintubation more accurately than the nonspecific SPORC score. Operative candidates at risk may be identified for preventive intervention or alternative oncologic therapy.

Association of desphospho-uncarboxylated matrix gla protein with incident cardiovascular disease and all-cause mortality: Results from the prospective Bruneck Study.

BACKGROUND AND AIMS: Matrix Gla protein (MGP), a vitamin K-dependent protein, is a potent inhibitor of vascular calcification. Desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K insufficiency, has been shown to predict cardiovascular disease (CVD) and all-cause mortality in high-risk populations. Whether the increased risk associated with dp-ucMGP also applies to the general, and especially, the elderly population has not yet been fully elucidated. METHODS AND RESULTS: Plasma dp-ucMGP was measured in 684 individuals aged 50-89 years of the prospective population-based Bruneck Study (baseline evaluation in 2000). Baseline median dp-ucMGP was 478.4 (IQR 335.0-635.2) pmol/L. Over a median follow-up of 15.5 years, 163 CVD events occurred and 235 participants died. Age-/sex-adjusted hazard ratios (HRs) per 1-SD higher level of loge transformed dp-ucMGP were 1.30 (95%CI: 1.09-1.55; p=0.004) for incident CVD and 1.36 (95%CI: 1.17-1.57; p<0.001) for all-cause mortality. After multivariable adjustment, the associations remained significant with HRs of 1.23 (95%CI: 1.02-1.47, p=0.029) for CVD and 1.40 (95%CI: 1.20-1.64; p<0.001) for all-cause mortality. The associations remained virtually unchanged after additional adjustment for dietary quality as measured with the Alternative Healthy Eating Index. We found no association of dp-ucMGP with myocardial infarction and sudden cardiac deaths, but a strong association with other vascular deaths and non-vascular/non-cancer deaths. CONCLUSIONS: This study shows a significant association of plasma dp-ucMGP with incident CVD and a significant and even stronger association with all-cause mortality. Clinical trials are needed to investigate whether vitamin K substitution results in improved health outcomes.

Mechanical Power during General Anesthesia and Postoperative Respiratory Failure: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mechanical power during ventilation estimates the energy delivered to the respiratory system through integrating inspiratory pressures, tidal volume, and respiratory rate into a single value. It has been linked to lung injury and mortality in the acute respiratory distress syndrome, but little evidence exists regarding whether the concept relates to lung injury in patients with healthy lungs. This study hypothesized that higher mechanical power is associated with greater postoperative respiratory failure requiring reintubation in patients undergoing general anesthesia. METHODS: In this multicenter, retrospective study, 230,767 elective, noncardiac adult surgical out- and inpatients undergoing general anesthesia between 2008 and 2018 at two academic hospital networks in Boston, Massachusetts, were included. The risk-adjusted association between the median intraoperative mechanical power, calculated from median values of tidal volume (Vt), respiratory rate (RR), positive end-expiratory pressure (PEEP), plateau pressure (Pplat), and peak inspiratory pressure (Ppeak), using the following formula: mechanical power (J/min) = 0.098 × RR × Vt × (PEEP + ½[Pplat - PEEP] + [Ppeak - Pplat]), and postoperative respiratory failure requiring reintubation within 7 days, was assessed. RESULTS: The median intraoperative mechanical power was 6.63 (interquartile range, 4.62 to 9.11) J/min. Postoperative respiratory failure occurred in 2,024 (0.9%) patients. The median (interquartile range) intraoperative mechanical power was higher in patients with postoperative respiratory failure than in patients without (7.67 [5.64 to 10.11] vs. 6.62 [4.62 to 9.10] J/min; P < 0.001). In adjusted analyses, a higher mechanical power was associated with greater odds of postoperative respiratory failure (adjusted odds ratio, 1.31 per 5 J/min increase; 95% CI, 1.21 to 1.42; P < 0.001). The association between mechanical power and postoperative respiratory failure was robust to additional adjustment for known drivers of ventilator-induced lung injury, including tidal volume, driving pressure, and respiratory rate, and driven by the dynamic elastic component (adjusted odds ratio, 1.35 per 5 J/min; 95% CI, 1.05 to 1.73; P = 0.02). CONCLUSIONS: Higher mechanical power during ventilation is statistically associated with a greater risk of postoperative respiratory failure requiring reintubation.

Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study From a New England Health Care Network.

OBJECTIVES: To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to -3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients who received a high proportion of deep sedation using benzodiazepine compared with propofol-based sedation (adjusted absolute difference, -1.17 d; 95% CI, -0.64 to -1.69; p < 0.001). This differential effect was magnified in elderly patients (age > 65) and in patients with liver or kidney failure (p-for-interaction < 0.001) but not observed in patients who received a low proportion of deep sedation (p = 0.95). GABAergic-induced deep sedation days during mechanical ventilation was a better predictor of post-extubation delirium than the GABAergic daily average effective dose (area under the curve 0.76 vs 0.69; p < 0.001). CONCLUSIONS: Deep sedation during mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.

Long-term life history predicts current gut microbiome in a population-based cohort study.

Extensive scientific and clinical microbiome studies have explored contemporary variation and dynamics of the gut microbiome in human health and disease1-3, yet the role of long-term life history effects has been underinvestigated. Here, we analyzed the current, quantitative microbiome composition in the older adult Bruneck Study cohort (Italians, Bruneck, n = 304 (male, 154; female, 150); age 65-98 years) with extensive clinical, demographic, lifestyle and nutritional data collected over the past 26 years4. Multivariate analysis of historical variables indicated that medication history, historical physical activity, past dietary habits and specific past laboratory blood parameters explain a significant fraction of current quantitative microbiome variation in older adults, enlarging the explanatory power of contemporary covariates by 33.4%. Prediction of current enterotype by a combination of past and contemporary host variables revealed good levels of predictability (area under the curve (AUC), 0.78-0.83), with Prevotella and dysbiotic Bacteroides 2 being the best predicted enterotypes. These findings demonstrate long-term life history effects on the microbiota and provide insights into lifestyle variables and their role in maintaining a healthy gut microbiota in later life.

Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

BACKGROUND: It is unclear whether intraoperative arterial hypotension is associated with postoperative delirium. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with increased odds of delirium after surgery. METHODS: Adult noncardiac surgical patients undergoing general anesthesia at 2 academic medical centers between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as the cumulative duration of an intraoperative mean arterial pressure (MAP) <55 mm Hg, categorized into and short (<15 minutes; median [interquartile range {IQR}], 2 [1-4] minutes) and prolonged (≥15 minutes; median [IQR], 21 [17-31] minutes) durations of intraoperative hypotension. The primary outcome was a new diagnosis of delirium within 30 days after surgery. In secondary analyses, we assessed the association between a MAP decrease of >30% from baseline and postoperative delirium. Multivariable logistic regression adjusted for patient- and procedure-related factors, including demographics, comorbidities, and markers of procedural severity, was used. RESULTS: Among 316,717 included surgical patients, 2183 (0.7%) were diagnosed with delirium within 30 days after surgery; 41.7% and 2.6% of patients had a MAP <55 mm Hg for a short and a prolonged duration, respectively. A MAP <55 mm Hg was associated with postoperative delirium compared to no hypotension (short duration of MAP <55 mm Hg: adjusted odds ratio [ORadj], 1.22; 95% confidence interval [CI], 1.11-1.33; P < .001 and prolonged duration of MAP <55 mm Hg: ORadj, 1.57; 95% CI, 1.27-1.94; P < .001). Compared to a short duration of a MAP <55 mm Hg, a prolonged duration of a MAP <55 mm Hg was associated with greater odds of postoperative delirium (ORadj, 1.29; 95% CI, 1.05-1.58; P = .016). The association between intraoperative hypotension and postoperative delirium was duration-dependent (ORadj for every 10 cumulative minutes of MAP <55 mm Hg: 1.06; 95% CI, 1.02-1.09; P =.001) and magnified in patients who underwent surgeries of longer duration (P for interaction = .046; MAP <55 mm Hg versus no MAP <55 mm Hg in patients undergoing surgery of >3 hours: ORadj, 1.40; 95% CI, 1.23-1.61; P < .001). A MAP decrease of >30% from baseline was not associated with postoperative delirium compared to no hypotension, also when additionally adjusted for the cumulative duration of a MAP <55 mm Hg (short duration of MAP decrease >30%: ORadj, 1.13; 95% CI, 0.91-1.40; P = .262 and prolonged duration of MAP decrease >30%: ORadj, 1.19; 95% CI, 0.95-1.49; P = .141). CONCLUSIONS: In patients undergoing noncardiac surgery, a MAP <55 mm Hg was associated with a duration-dependent increase in odds of postoperative delirium. This association was magnified in patients who underwent surgery of long duration.

Neutrophil-Derived Protein S100A8/A9 Alters the Platelet Proteome in Acute Myocardial Infarction and Is Associated With Changes in Platelet Reactivity.

OBJECTIVE: Platelets are central to acute myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome during MI and identify corresponding functional consequences. Approach and Results: Platelets from patients experiencing ST-segment-elevation MI (STEMI) before and 3 days after treatment (n=30) and matched patients with severe stable coronary artery disease before and 3 days after coronary artery bypass grafting (n=25) underwent quantitative proteomic analysis. Elevations in the proteins S100A8 and S100A9 were detected at the time of STEMI compared with stable coronary artery disease (S100A8: FC, 2.00; false discovery rate, 0.05; S100A9: FC, 2.28; false discovery rate, 0.005). During STEMI, only S100A8 mRNA and protein levels were correlated in platelets (R=0.46, P=0.012). To determine whether de novo protein synthesis occurs, activated platelets were incubated with 13C-labeled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was confidently detected. Platelet S100A8 and S100A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were coincubated under quiescent and activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Neutrophils released S100A8/A9 as free heterodimer, rather than in vesicles or extracellular traps. In the community-based Bruneck study (n=338), plasma S100A8/A9 was inversely associated with platelet reactivity-an effect abrogated by aspirin. CONCLUSIONS: Leukocyte-to-platelet protein transfer may occur in a thromboinflammatory environment such as STEMI. Plasma S100A8/A9 was negatively associated with platelet reactivity. These findings highlight neutrophils as potential modifiers for thrombotic therapies in coronary artery disease.

The association of nitrous oxide on length of stay in the postanesthesia care unit: a retrospective observational study.

PURPOSE: To assess whether intraoperative use of nitrous oxide (N2O) as an adjunct to general anesthesia is associated with a shorter length of stay in the postanesthesia care unit (PACU). METHODS: We analyzed data from adult patients who underwent non-cardiothoracic surgery under general anesthesia between May 2008 and December 2018. We assessed the association between intraoperative low- and high-dose N2O and PACU length of stay. RESULTS: A total of 148,284 patients were included in the primary analysis. After adjusting for a priori defined confounders, a high dose of N2O significantly decreased PACU length of stay, with a calculated difference of -9.1 min (95% confidence interval [CI], -10.5 to -7.7; P < 0.001). Patients who received high-dose N2O had a lower incidence of both short- and prolonged-duration of intraoperative hypotension (adjusted odds ratio [aOR], 0.85; 95% CI, 0.83 to 0.88; P < 0.001 and aOR, 0.76; 95% CI, 0.73 to 0.80; P < 0.001, respectively) and received a lower total intraoperative vasopressor dose (-0.04 mg of norepinephrine equivalents; 95% CI, -0.06 to -0.01; P = 0.01). The effect of high-dose N2O on PACU length of stay was modified by surgical complexity (adjusted absolute difference: -26.1 min; 95% CI, -29.2 to -23.1; P < 0.001; P for interaction < 0.001), and most pronounced in patients who underwent complex surgery and received intraoperative antiemetic therapy (adjusted absolute difference: -38.9 min; 95% CI, -43.1 to -34.6; P < 0.001; P for interaction < 0.001). CONCLUSIONS: Nitrous oxide was dose-dependently associated with a decreased PACU length of stay. The effect was clinically relevant (> 30 min difference) in patients who underwent complex surgical procedures and received intraoperative antiemetic therapy.

RéSUMé: OBJECTIF: L'objectif de cette étude était de déterminer si l'utilisation peropératoire de protoxyde d'azote (N2O) en complément à l'anesthésie générale était associée à une durée de séjour écourtée en salle de réveil (SDR). MéTHODE: Nous avons analysé les données de patients adultes qui ont subi une chirurgie non cardiothoracique sous anesthésie générale entre mai 2008 et décembre 2018. Nous avons évalué l'association entre une faible dose et une dose élevée de N2O peropératoire et la durée du séjour en SDR. RéSULTATS: Au total, 148 284 patients ont été inclus dans notre analyse primaire. Après ajustement tenant compte des facteurs de confusion définis a priori, une dose élevée de N2O a considérablement écourté la durée du séjour en salle de réveil, avec une différence calculée de −9,1 min (intervalle de confiance [IC] à 95 %, −10,5 à −7,7 ; P < 0,001). Chez les patients ayant reçu une dose élevée de N2O, l'incidence d'hypotension peropératoire de courte ou plus longue durée était plus faible (rapport de cotes ajusté [RCA], 0,85; IC 95 %, 0,83 à 0,88; P < 0,001 et RCA, 0,76; IC 95 %, 0,73 à 0,80; P < 0,001, respectivement); en outre, ces patients ont reçu une dose totale de vasopresseurs peropératoires inférieure (−0,04 mg d'équivalents de norépinéphrine; IC 95 %, −0,06 à −0,01; P = 0,01). L'effet d'une dose élevée de N2O sur la durée du séjour en SDR a été modifié par la complexité de la chirurgie (différence absolue ajustée : −26,1 min; IC 95 %, −29,2 à −23,1; P < 0,001; P pour l'interaction < 0,001), et était le plus prononcé chez les patients ayant subi une chirurgie complexe et reçu un traitement antiémétique peropératoire (différence absolue ajustée : −38,9 min; IC 95 %, −43,1 à −34,6; P < 0,001; P pour l'interaction < 0,001). CONCLUSION: Le protoxyde d'azote a été associé de façon dose-dépendante à une réduction de la durée du séjour en SDR. L'effet était cliniquement pertinent (différence > 30 minutes) chez les patients qui subissaient des interventions chirurgicales complexes et recevaient un traitement antiémétique peropératoire.

Association between preoperative administration of gabapentinoids and 30-day hospital readmission: A retrospective hospital registry study.

STUDY OBJECTIVE: To evaluate the effectiveness of preoperative gabapentinoid administration. DESIGN: Retrospective hospital registry study. SETTING: Tertiary referral center (Boston, MA). PATIENTS: 111,008 adult non-emergency, non-cardiac surgical patients between 2014 and 2018. INTERVENTIONS: Preoperative administration of gabapentinoids (gabapentin or pregabalin). MEASUREMENTS: We tested the primary hypothesis that preoperative gabapentinoid use was associated with lower odds of hospital readmission within 30 days. Contingent on this hypothesis, we examined whether lower intraoperative opioid utilization mediated this effect. Secondary outcome was postoperative respiratory complications. MAIN RESULTS: Gabapentinoid administration was associated with lower odds of readmission (adjusted odds ratio [ORadj] 0.80 [95% CI, 0.75-0.85]; p < 0.001). This effect was in part mediated by lower intraoperative opioid utilization in patients receiving gabapentinoids (8.2% [2.4-11.5%]; p = 0.012). Readmissions for gastrointestinal disorders (ORadj 0.74 [0.60-0.90]; p = 0.003), neuro-psychiatric complications (ORadj 0.66 [0.49-0.87]; p = 0.004), non-surgical site infections (ORadj 0.68 [0.52-0.88; p = 0.004) and trauma or poisoning (ORadj 0.25 [0.16-0.41]; p < 0.001) occurred less frequently in patients receiving gabapentinoids. The risk of postoperative respiratory complications was lower in patients receiving gabapentinoids (ORadj 0.77 [0.70-0.85]; p < 0.001). Lower doses of pregabalin (< 75 mg) and gabapentin (< 300 mg) compared to both, no and high-dose administration of gabapentinoids, were associated with a lower risk of postoperative respiratory complications (ORadj 0.61 [0.50-0.75]; p < 0.001 and ORadj 0.70 [0.53-0.92]; p = 0.012, respectively). These lower gabapentinoid doses prevented 30-day readmission (ORadj 0.74 [0.65-0.85]; p < 0.001). The results were robust in several sensitivity analyses including surgical procedure defined subgroups and patients undergoing ambulatory surgery. CONCLUSIONS: The preoperative use of pregabalin and gabapentin, up to doses of 75 and 300 mg respectively, mitigates the risks of hospital readmission and postoperative respiratory complications which can in part be explained by lower intraoperative opioid use. Further research is warranted to elucidate mechanisms of the preventive action.

Evaluation of early postoperative intravenous opioid rescue as a novel quality measure in patients who receive thoracic epidural analgesia: a retrospective cohort analysis and prospective performance improvement intervention.

BACKGROUND: In this study, we explored the utility of intravenous opioid rescue analgesia in the post anesthesia care unit (PACU-OpResc) as a single marker of thoracic epidural analgesia (TEA) failure and evaluated the resource implications and quality improvement applications of this measure. METHODS: We performed a retrospective analysis of all TEA placements over a three-year period at a single academic medical center in Boston, Massachusetts. The study exposure was PACU-OpResc. Primary outcome was PACU length of stay (LOS). Secondary outcomes included reasons for delayed PACU discharge and intraoperative hypotension. The analyses were adjusted for confounding variables including patient comorbidities, surgical complexity, intraoperative intravenous opioids, chronic opioid use and local anesthetic bolus through TEA catheter. Post analysis chart review was conducted to determine the positive predictive value (PPV) of PACU-OpResc for inadequate TEA. As a first Plan-Do-Study-Act cycle, we then introduced a checkbox for documentation of a sensory level check after TEA placement. Post implementation data was collected for 7 months. RESULTS: PACU-OpResc was required by 211 (22.1%) patients who received preoperative TEA, was associated with longer PACU LOS (incidence rate ratio 1.20, 95% CI:1.07-1.34, p = 0.001) and delayed discharge due to inadequate pain control (odds ratio 5.15, 95% CI 3.51-7.57, p <  0.001). PACU-OpResc had a PPV of 76.3 and 60.4% for re-evaluation and manipulation of the TEA catheter in PACU, respectively. Following implementation of a checkbox, average monthly compliance with documented sensory level check after TEA placement was noted to be 39.7%. During this time, a reduction of 8.2% in the rate of PACU-OpResc was observed. CONCLUSIONS: This study demonstrates that PACU-OpResc can be used as a quality assurance measure or surrogate for TEA efficacy, to track performance and monitor innovation efforts aimed at improving analgesia, such as our intervention to facilitate sensory level checks and reduced PACU-OpResc. TRIAL REGISTRATION: not applicable.

The effect of intraoperative dexmedetomidine administration on length of stay in the post-anesthesia care unit in ambulatory surgery: A hospital registry study.

STUDY OBJECTIVE: Dexmedetomidine, which is commonly used for procedural sedation and as adjunct to general anesthesia for ambulatory procedures, may affect patient discharge from the post-anesthesia care unit (PACU). We hypothesized that intraoperative dexmedetomidine use in ambulatory surgery is associated with delayed discharge from the PACU and that this is modified by surgical duration and anesthesia type. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: 130,854 adult patients undergoing ambulatory surgery between 2008 and 2018. INTERVENTIONS: Intraoperative administration of dexmedetomidine. MEASUREMENTS: The primary outcome was PACU length of stay. In secondary and exploratory analyses, we examined dose-dependency, effect modification by duration of surgery and anesthesia type, effects of timing of dexmedetomidine administration, and PACU discharge delays. MAIN RESULTS: Dexmedetomidine was associated with a prolonged PACU length of stay (adjusted absolute difference [ADadj] 15.0 min; 95%CI 12.7-17.3; p < 0.001). This effect was dose-dependent (p-for-trend < 0.001), magnified in surgeries of less than one hour (ADadj 20.7 min; 95%CI 16.7-24.7; p < 0.001) and in patients undergoing monitored anesthesia care compared to general anesthesia (ADadj 16.8 min; 95%CI 14.1-19.6; p < 0.001). The effect was more pronounced if dexmedetomidine was administered within the last 60 min of surgery (ADadj 18.7 min; 95%CI 15.7-21.7; p < 0.001). Dexmedetomidine was associated with discharge delays due to cardiovascular complications (ORadj 2.27; 95%CI 1.59-3.24; p < 0.001) and over-sedation (ORadj 1.28; 95%CI 1.11-1.48; p < 0.001). In patients who received dexmedetomidine (n = 2901), the use of bolus doses only versus the combination of bolus and infusions, magnified the effects on PACU length of stay (ADadj 29.5 min per µg/kg; 95%CI 17.3-41.8 versus 18.1 min per µg/kg; 95%CI 11.4-24.8; p < 0.001). CONCLUSIONS: The intraoperative administration of dexmedetomidine was dose-dependently associated with a prolonged PACU length of stay. Clinicians should judiciously titrate dexmedetomidine, especially when using this long-acting drug for monitored anesthesia care for shorter procedures.

Association of Sedation, Coma, and In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Acute Respiratory Distress Syndrome: A Retrospective Cohort Study.

OBJECTIVES: In patients with coronavirus disease 2019-associated acute respiratory distress syndrome, sedatives and opioids are commonly administered which may lead to increased vulnerability to neurologic dysfunction. We tested the hypothesis that patients with coronavirus disease 2019-associated acute respiratory distress syndrome are at higher risk of in-hospital mortality due to prolonged coma compared with other patients with acute respiratory distress syndrome matched for disease severity. DESIGN: Propensity-matched cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: All mechanically ventilated coronavirus disease 2019 patients between March and May 2020 were identified and matched with patients with acute respiratory distress syndrome of other etiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using clinical data obtained from a hospital registry, we matched 114 coronavirus disease 2019 patients to 228 noncoronavirus disease 2019-related acute respiratory distress syndrome patients based on baseline disease severity. Coma was identified using the Richmond Agitation Sedation Scale less than or equal to -3. Multivariable logistic regression and mediation analyses were used to assess the percentage of comatose days, sedative medications used, and the association between coronavirus disease 2019 and in-hospital mortality. In-hospital mortality (48.3% vs 31.6%, adjusted odds ratio, 2.15; 95% CI, 1.34-3.44; p = 0.002), the percentage of comatose days (66.0% ± 31.3% vs 36.0% ± 36.9%, adjusted difference, 29.35; 95% CI, 21.45-37.24; p < 0.001), and the hypnotic agent dose (51.3% vs 17.1% of maximum hypnotic agent dose given in the cohort; p < 0.001) were higher among patients with coronavirus disease 2019. Brain imaging did not show a higher frequency of structural brain lesions in patients with coronavirus disease 2019 (6.1% vs 7.0%; p = 0.76). Hypnotic agent dose was associated with coma (adjusted coefficient, 0.61; 95% CI, 0.45-0.78; p < 0.001) and mediated (p = 0.001) coma. Coma was associated with in-hospital mortality (adjusted odds ratio, 5.84; 95% CI, 3.58-9.58; p < 0.001) and mediated 59% of in-hospital mortality (p < 0.001). CONCLUSIONS: Compared with matched patients with acute respiratory distress syndrome of other etiology, patients with coronavirus disease 2019 received higher doses of hypnotics, which was associated with prolonged coma and higher mortality.