Increased Postoperative Opioid Consumption in the Presence of Co-administration of 5-HT3 Antagonists with Acetaminophen: A Hospital Registry Study.

BACKGROUND: Acetaminophen and 5-hydroxytryptamine-type-3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies however suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting. METHODS: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts, United States of America, from 2015 to 2022. Using binary exposure variables and a comprehensive selection of pre-planned patient- and procedure-related covariates for confounder control, we investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in mg oral morphine equivalents (OME) administered in the post-anesthesia care unit (PACU). A multivariable, zero-inflated negative binomial regression model was applied. RESULTS: 3,166 (5.8%) patients received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median PACU opioid dose was 7.5 mg OME (interquartile range 7.5 to 14.3 mg OME) among 16,640/55,016 (30.3%) patients who received opioids and the average opioid dose was 3.2 mg OME across all patients (maximum cumulative dose: 20.4 mg OME). Acetaminophen administration was associated with a 5.5% (95%CI -9.6% to -1.4%;p=0.009; adjusted absolute difference -0.19 mg OME;95%CI -0.33 to -0.05;p=0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference 0.00 mg OME; 95%CI -0.06 to 0.05;p=0.93,p-for-interaction=0.012). CONCLUSION: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were co-administered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis.

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.

Intraoperative Opioid Waste and Association of Intraoperative Opioid Dose with Postoperative Adverse Outcomes: A Hospital Registry Study.

INTRODUCTION: Perioperative opioid use has been associated with adverse clinical outcomes. Additionally, opioid disposal carries significant costs, due to the waste of pharmaceutical products and the time needed by skilled labor to report the waste. In this study, we aimed to estimate costs and predict factors of opioid-associated intraoperative product waste, as well as to evaluate whether higher intraoperative opioid doses are associated with increased risk of adverse postoperative outcomes. METHODS: We included 170,607 patients undergoing general anesthesia and receiving intraoperative fentanyl, hydromorphone, or morphine at Beth Israel Deaconess Medical Center, Boston, MA, USA, between January 2010 and June 2020. We estimated product waste-associated costs based on various opioid syringe sizes and determined predictors of opioid waste. Further, we evaluated whether higher opioid doses were associated with postoperative adverse events according to the severity-indexed, incident report-based medication error-reporting program classification. The primary outcome included post-extubation desaturation, postoperative nausea or vomiting, or postoperative somnolence or sedation. RESULTS: The use of the smallest syringe sizes (50 mcg for fentanyl, 0.2 mg for hydromorphone, and 2 mg for morphine) resulted in the lowest product waste-associated costs. The main predictor of opioid waste was the administration of more than one intraoperative opioid (adjusted odds ratio [aOR] = 7.64, 95% CI 7.40-7.89, P < 0.001). Intraoperative doses of fentanyl > 50-100 mcg (aOR = 1.17 [1.10-1.25], P < 0.001, adjusted risk difference [ARD] 2%) and > 100 mcg (aOR = 1.24 [1.16-1.33], P < 0.001, ARD 3%), hydromorphone > 1 mg (aOR = 1.13 [1.06-1.20], P < 0.001, ARD 2%), and morphine > 2-4 mg (aOR = 1.26 [1.02-1.56], P = 0.04, ARD 3%) and > 4 mg (aOR = 1.45 [1.18-1.77], P < 0.001, ARD 5%) were associated with higher risk of the primary outcome. CONCLUSION: Smaller syringe sizes of intraoperative opioids may help to reduce product waste and associated costs, as well postoperative adverse events through utilization of lower intraoperative opioid doses.

Recovery and safety with prolonged high-frequency jet ventilation for catheter ablation of atrial fibrillation: A hospital registry study from a New England healthcare network.

STUDY OBJECTIVE: To investigate post-procedural recovery as well as peri-procedural respiratory and hemodynamic safety parameters with prolonged use of high-frequency jet ventilation (HFJV) versus conventional ventilation in patients undergoing catheter ablation for atrial fibrillation. DESIGN: Hospital registry study. SETTING: Tertiary academic teaching hospital in New England. PATIENTS: 1822 patients aged 18 years and older undergoing catheter ablation between January 2013 and June 2020. INTERVENTIONS: HFJV versus conventional mechanical ventilation. MEASUREMENTS: The primary outcome was post-anesthesia care unit (PACU) length of stay. In secondary analyses we assessed the effect of HFJV on intra-procedural hypoxemia, defined as the occurrence of peripheral hemoglobin oxygen saturation (SpO2) <90%, post-procedural respiratory complications (PRC) as well as intra-procedural hypocarbia and hypotension. Multivariable negative binomial and logistic regression analyses, adjusted for patient and procedural characteristics, were applied. MAIN RESULTS: 1157 patients (63%) received HFJV for a median (interquartile range [IQR]) duration of 307 (253-360) minutes. The median (IQR) length of stay in the PACU was 244 (172-370) minutes in patients who underwent ablation with conventional mechanical ventilation and 226 (163-361) minutes in patients receiving HFJV. In adjusted analyses, patients undergoing HFJV had a longer PACU length of stay (adjusted absolute difference: 37.7 min; 95% confidence interval [CI] 9.7-65.8; p = 0.008). There was a higher risk of intra-procedural hypocarbia (adjusted odds ratio [ORadj] 5.90; 95%CI 2.63-13.23; p < 0.001) and hypotension (ORadj 1.88; 95%CI 1.31-2.72; p = 0.001) in patients undergoing HFJV. No association was found between the use of HFJV and intra-procedural hypoxemia or PRC (p = 0.51, and p = 0.97, respectively). CONCLUSION: After confounder adjustment, HFJV for catheter ablation procedures for treatment of atrial fibrillation was associated with a longer length of stay in the PACU. It was further associated with an increased risk of intra-procedural abnormalities including abnormal carbon dioxide homeostasis, as well as intra-procedural arterial hypotension.

Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Association of Obstructive Sleep Apnea With Postoperative Delirium in Procedures of Moderate-to-High Complexity: A Hospital-Registry Study.

BACKGROUND: Patients suffering from obstructive sleep apnea (OSA) experience chronic sleep disturbances and desaturation, factors that have been associated with postoperative delirium and that can be aggravated after anesthesia for complex procedures. We investigated whether OSA is associated with delirium after anesthesia, and whether this association is modified by procedural complexity. METHODS: Hospitalized patients ≥60 years who underwent general anesthesia or procedural sedation for procedures of moderate-to-high complexity between 2009 and 2020 at a tertiary health care network in Massachusetts were included. The primary exposure was OSA, defined based on International Classification of Diseases ( Ninth/Tenth Revision, Clinical Modification ) ( ICD-9 / 10-CM ) diagnostic codes, structured nursing interviews, anesthesia alert notes, and a validated risk score (BOSTN [body mass index, observed apnea, snoring, tiredness, and neck circumference]). The primary end point was delirium within 7 days after the procedure. Multivariable logistic regression and effect modification analyses adjusted for patient demographics, comorbidities, and procedural factors were applied. RESULTS: A total of 46,352 patients were included, of which 1694 patients (3.7%) developed delirium, 537 (3.2%) with OSA, and 1,157 (4.0%) without OSA. In adjusted analyses, OSA was not associated with postprocedural delirium in the overall cohort (adjusted odds ratio [OR adj ], 1.06; 95% confidence interval [CI], 0.94-1.20; P = .35). However, a high procedural complexity modified the primary association ( P value for interaction = .002). OSA patients had a higher risk of delirium after high-complexity procedures (≥40 work relative value units) such as cardiac (OR adj , 1.33; 95% CI, 1.08-1.64; P = .007, P value for interaction = .005) or thoracic surgery (OR adj , 1.89; 95% CI, 1.19-3.00; P = .007, P value for interaction = .009), but no increased risk after moderate complexity procedures, including general surgery (OR adj , 0.86; 95% CI, 0.55-1.35; P = .52). CONCLUSIONS: Compared to non-OSA patients, a history of OSA is associated with a higher risk after high-complexity procedures such as cardiac or thoracic surgery but not after procedures of moderate complexity.

High Mechanical Power and Driving Pressures are Associated With Postoperative Respiratory Failure Independent From Patients' Respiratory System Mechanics.

OBJECTIVES: High mechanical power and driving pressure (ΔP) have been associated with postoperative respiratory failure (PRF) and may be important parameters guiding mechanical ventilation. However, it remains unclear whether high mechanical power and ΔP merely reflect patients with poor respiratory system mechanics at risk of PRF. We investigated the effect of mechanical power and ΔP on PRF in cohorts after exact matching by patients' baseline respiratory system compliance. DESIGN: Hospital registry study. SETTING: Academic hospital in New England. PATIENTS: Adult patients undergoing general anesthesia between 2008 and 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was high (≥ 6.7 J/min, cohort median) versus low mechanical power and the key-secondary exposure was high (≥ 15.0 cm H 2 O) versus low ΔP. The primary endpoint was PRF (reintubation or unplanned noninvasive ventilation within seven days). Among 97,555 included patients, 4,030 (4.1%) developed PRF. In adjusted analyses, high intraoperative mechanical power and ΔP were associated with higher odds of PRF (adjusted odds ratio [aOR] 1.37 [95% CI, 1.25-1.50]; p < 0.001 and aOR 1.45 [95% CI, 1.31-1.60]; p < 0.001, respectively). There was large variability in applied ventilatory parameters, dependent on the anesthesia provider. This facilitated matching of 63,612 (mechanical power cohort) and 53,260 (ΔP cohort) patients, yielding identical baseline standardized respiratory system compliance (standardized difference [SDiff] = 0.00) with distinctly different mechanical power (9.4 [2.4] vs 4.9 [1.3] J/min; SDiff = -2.33) and ΔP (19.3 [4.1] vs 11.9 [2.1] cm H 2 O; SDiff = -2.27). After matching, high mechanical power and ΔP remained associated with higher risk of PRF (aOR 1.30 [95% CI, 1.17-1.45]; p < 0.001 and aOR 1.28 [95% CI, 1.12-1.46]; p < 0.001, respectively). CONCLUSIONS: High mechanical power and ΔP are associated with PRF independent of patient's baseline respiratory system compliance. Our findings support utilization of these parameters for titrating mechanical ventilation in the operating room and ICU.

Inflammatory subphenotypes in patients at risk of ARDS: evidence from the LIPS-A trial.

PURPOSE: Latent class analysis (LCA) has identified hyper- and non-hyper-inflammatory subphenotypes in patients with acute respiratory distress syndrome (ARDS). It is unknown how early inflammatory subphenotypes can be identified in patients at risk of ARDS. We aimed to test for inflammatory subphenotypes upon presentation to the emergency department. METHODS: LIPS-A was a trial of aspirin to prevent ARDS in at-risk patients presenting to the emergency department. In this secondary analysis, we performed LCA using clinical, blood test, and biomarker variables. RESULTS: Among 376 (96.4%) patients from the LIPS-A trial, two classes were identified upon presentation to the emergency department (day 0): 72 (19.1%) patients demonstrated characteristics of a hyper-inflammatory and 304 (80.9%) of a non-hyper-inflammatory subphenotype. 15.3% of patients in the hyper- and 8.2% in the non-hyper-inflammatory class developed ARDS (p = 0.07). Patients in the hyper-inflammatory class had fewer ventilator-free days (median [interquartile range, IQR] 28[23-28] versus 28[27-28]; p = 0.010), longer intensive care unit (3[2-6] versus 0[0-3] days; p < 0.001) and hospital (9[6-18] versus 5[3-9] days; p < 0.001) length of stay, and higher 1-year mortality (34.7% versus 20%; p = 0.008). Subphenotypes were identified on day 1 and 4 in a subgroup with available data (n = 244). 77.9% of patients remained in their baseline class throughout day 4. Patients with a hyper-inflammatory subphenotype throughout the study period (n = 22) were at higher risk of ARDS (36.4% versus 10.4%; p = 0.003). CONCLUSION: Hyper- and non-hyper-inflammatory subphenotypes may precede ARDS development, remain identifiable over time, and can be identified upon presentation to the emergency department. A hyper-inflammatory subphenotype predicts worse outcomes.

Association of reintubation and hospital costs and its modification by postoperative surveillance: A multicenter retrospective cohort study.

OBJECTIVE: We estimated hospital costs associated with postoperative reintubation and tested the hypothesis that prolonged surveillance in the post-anesthesia care unit (PACU) modifies the hospital costs of reintubation. DESIGN: Retrospective observational research study. SETTING: Two tertiary care academic healthcare networks in the Bronx, New York and Boston, Massachusetts, USA. PATIENTS: 68,125 adult non-cardiac surgical patients undergoing general anesthesia between 2016 and 2021. INTERVENTIONS: The exposure variable was unplanned reintubation within 7 days of surgery. MEASUREMENTS: The primary outcome was direct hospital costs associated with patient care related activities. We used a multivariable generalized linear model based on log-transformed costs data, adjusting for pre- and intraoperative confounders. We matched our data with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP-NIS). In the key secondary analysis, we examined if prolonged postoperative surveillance, defined as PACU utilization (≥4 h) modifies the association between reintubation and costs of care. MAIN RESULTS: 1759 (2.6%) of patients were re-intubated within 7 days after surgery. Reintubation was associated with higher direct hospital costs (adjusted model estimate 2.05; 95% CI: 2.00-2.10) relative to no reintubation. In the HCUP-NIS matched cohort, the adjusted absolute difference (ADadj) in costs amounted to US$ 18,837 (95% CI: 17,921-19,777). The association was modified by the duration of PACU surveillance (p-for-interaction <0.001). In patients with a shorter PACU length of stay, reintubation occurred later (median of 2 days; IQR 1, 5) versus 1 days (IQR 0, 2; p < .001), and was associated with magnified effects on hospital costs compared to patients who stayed in the PACU longer (ADadj of US$ 23,444, 95% CI: 21,217-25,799 versus ADadj of US$ 17,615, 95% CI: 16,350-18,926; p < .001). CONCLUSION: Postoperative reintubation is associated with 2-fold higher hospital costs. Prolonged surveillance in the recovery room mitigated this effect. The cost-saving effect of longer PACU length of stay was likely driven by earlier reintubation in patients who needed this intervention.

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.

Mechanical power and 30-day mortality in mechanically ventilated, critically ill patients with and without Coronavirus Disease-2019: a hospital registry study.

BACKGROUND: Previous studies linked a high intensity of ventilation, measured as mechanical power, to mortality in patients suffering from "classic" ARDS. By contrast, mechanically ventilated patients with a diagnosis of COVID-19 may present with intact pulmonary mechanics while undergoing mechanical ventilation for longer periods of time. We investigated whether an association between higher mechanical power and mortality is modified by a diagnosis of COVID-19. METHODS: This retrospective study included critically ill, adult patients who were mechanically ventilated for at least 24 h between March 2020 and December 2021 at a tertiary healthcare facility in Boston, Massachusetts. The primary exposure was median mechanical power during the first 24 h of mechanical ventilation, calculated using a previously validated formula. The primary outcome was 30-day mortality. As co-primary analysis, we investigated whether a diagnosis of COVID-19 modified the primary association. We further investigated the association between mechanical power and days being alive and ventilator free and effect modification of this by a diagnosis of COVID-19. Multivariable logistic regression, effect modification and negative binomial regression analyses adjusted for baseline patient characteristics, severity of disease and in-hospital factors, were applied. RESULTS: 1,737 mechanically ventilated patients were included, 411 (23.7%) suffered from COVID-19. 509 (29.3%) died within 30 days. The median mechanical power during the first 24 h of ventilation was 19.3 [14.6-24.0] J/min in patients with and 13.2 [10.2-18.0] J/min in patients without COVID-19. A higher mechanical power was associated with 30-day mortality (ORadj 1.26 per 1-SD, 7.1J/min increase; 95% CI 1.09-1.46; p = 0.002). Effect modification and interaction analysis did not support that this association was modified by a diagnosis of COVID-19 (95% CI, 0.81-1.38; p-for-interaction = 0.68). A higher mechanical power was associated with a lower number of days alive and ventilator free until day 28 (IRRadj 0.83 per 7.1 J/min increase; 95% CI 0.75-0.91; p < 0.001, adjusted risk difference - 2.7 days per 7.1J/min increase; 95% CI - 4.1 to - 1.3). CONCLUSION: A higher mechanical power is associated with elevated 30-day mortality. While patients with COVID-19 received mechanical ventilation with higher mechanical power, this association was independent of a concomitant diagnosis of COVID-19.

Prevalence and association of non-medical cannabis use with post-procedural healthcare utilisation in patients undergoing surgery or interventional procedures: a retrospective cohort study.

Background: There is paucity of data regarding prevalence and key harms of non-medical cannabis use in surgical patients. We investigated whether cannabis use in patients undergoing surgery or interventional procedures patients was associated with a higher degree of post-procedural healthcare utilisation. Methods: 210,639 adults undergoing non-cardiac surgery between January 2008 and June 2020 at an academic healthcare network in Massachusetts, USA, were included. The primary exposure was use of cannabis, differentiated by reported ongoing non-medical use, self-identified during structured, preoperative nursing/physician interviews, or diagnosis of cannabis use disorder based on International Classification of Diseases, 9th/10th Revision, diagnostic codes. The main outcome measure was the requirement of advanced post-procedural healthcare utilisation (unplanned intensive care unit admission, hospital re-admission or non-home discharge). Findings: 16,211 patients (7.7%) were identified as cannabis users. The prevalence of cannabis use increased from 4.9% in 2008 to 14.3% by 2020 (p < 0.001). Patients who consumed cannabis had higher rates of psychiatric comorbidities (25.3 versus 16.8%; p < 0.001) and concomitant non-tobacco substance abuse (30.2 versus 7.0%; p < 0.001). Compared to non-users, patients with a diagnosis of cannabis use disorder had higher odds of requiring advanced post-procedural healthcare utilisation after adjusting for patient characteristics, concomitant substance use and socioeconomic factors (aOR [adjusted odds ratio] 1.16; 95% CI 1.02-1.32). By contrast, patients with ongoing non-medical cannabis use had lower odds of advanced post-procedural healthcare utilisation (aOR 0.87; 95% CI 0.81-0.92, compared to non-users). Interpretation: One in seven patients undergoing surgery or interventional procedures in 2020 reported cannabis consumption. Differential effects on post-procedural healthcare utilisation were observed between patients with non-medical cannabis use and cannabis use disorder. Funding: This work was supported by an unrestricted philantropic grant from Jeff and Judy Buzen to Maximilian S. Schaefer.

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.

Association of sugammadex reversal of neuromuscular block and postoperative length of stay in the ambulatory care facility: a multicentre hospital registry study.

BACKGROUND: Encapsulation of rocuronium or vecuronium with sugammadex can reverse neuromuscular block faster than neostigmine reversal. This pharmacodynamic profile might facilitate patient discharge after ambulatory surgery. METHODS: We included patients who underwent ambulatory surgery with general anaesthesia and neuromuscular block between 2016 and 2021 from hospital registries at two large academic healthcare networks in the USA. The primary outcome was postoperative length of stay in the ambulatory care facility (PLOS-ACF). We examined post hoc whether the type of reversal affects postoperative nausea and vomiting and direct hospital costs. RESULTS: Among the 29 316 patients included, 8945 (30.5%) received sugammadex and 20 371 (69.5%) received neostigmine for reversal. PLOS-ACF and costs were lower in patients who received sugammadex vs neostigmine (adjusted difference in PLOS-ACF: -9.5 min; 95% confidence interval [95% CI], -10.5 to -8.5 min; adjusted difference in direct hospital costs: -US$77; 95% CI, -$88 to -$66; respectively; P<0.001). The association was magnified in patients over age 65 yr, with ASA physical status >2 undergoing short procedures (<2 h) (adjusted difference in PLOS-ACF: -18.2 min; 95% CI, -23.8 to -12.4 min; adjusted difference in direct hospital costs: -$176; 95% CI, -$220 to -$128; P<0.001). Sugammadex use was associated with reduced postoperative nausea and vomiting (17.2% vs 19.6%, P<0.001), which mediated its effects on length of stay. CONCLUSIONS: Reversal with sugammadex compared with neostigmine was associated with a small decrease in postoperative length of stay in the ambulatory care unit. The effect was magnified in older and high-risk patients, and can be explained by reduced postoperative nausea and vomiting. Sugammadex reversal in ambulatory surgery may also help reduce cost of care.

Comparison of the effects of sugammadex versus neostigmine for reversal of neuromuscular block on hospital costs of care.

BACKGROUND: Sugammadex reversal of neuromuscular block facilitates recovery of neuromuscular function after surgery, but the drug is expensive. We evaluated the effects of sugammadex on hospital costs of care. METHODS: We analysed 79 474 adult surgical patients who received neuromuscular blocking agents and reversal from two academic healthcare networks between 2016 and 2021 to calculate differences in direct costs. We matched our data with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP-NIS) to calculate differences in total costs in US dollars. Perioperative risk profiles were defined based on ASA physical status and admission status (ambulatory surgery vs hospitalisation). RESULTS: Based on our registry data analysis, administration of sugammadex vs neostigmine was associated with lower direct costs (-1.3% lower costs; 95% confidence interval [CI], -0.5 to -2.2%; P=0.002). In the HCUP-NIS matched cohort, sugammadex use was associated with US$232 lower total costs (95% CI, -US$376 to -US$88; P=0.002). Subgroup analysis revealed that sugammadex was associated with US$1042 lower total costs (95% CI, -US$1198 to -US$884; P<0.001) in patients with lower risk. In contrast, sugammadex was associated with US$620 higher total costs (95% CI, US$377 to US$865; P<0.001) in patients with a higher risk (American Society of Anesthesiologists physical status ≥3 and preoperative hospitalisation). CONCLUSIONS: The effects of using sugammadex on costs of care depend on patient risk, defined based on comorbidities and admission status. We observed lower costs of care in patients with lower risk and higher costs of care in hospitalised surgical patients with severe comorbidities.

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.

Dose-dependent relationship between intra-procedural hypoxaemia or hypocapnia and postoperative delirium in older patients.

BACKGROUND: Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are associated with delirium after surgery. METHODS: Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation <90% for >2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for >5 cohering min. The primary outcome was delirium within 7 days after surgery. RESULTS: Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio [ORadj]=1.71; 95% confidence interval [CI], 1.40-2.07; P<0.001) or hypocapnia (ORadj=1.77; 95% CI, 1.30-2.41; P<0.001) was associated with a higher risk of delirium within 7 days. Both associations were dependent on the magnitude, and increased with event duration (ORadj=1.03; 95% CI, 1.02-1.04; P<0.001 and ORadj=1.01; 95% CI, 1.00-1.01; P=0.005, for each minute increase in the longest continuous episode, respectively). There was no association between occurrence of hypercapnia and postoperative delirium (ORadj=1.24; 95% CI, 0.90-1.71; P=0.181). CONCLUSIONS: Intra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.

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.