Improving management of ARDS: uniting acute management and long-term recovery.

Acute Respiratory Distress Syndrome (ARDS) is an important global health issue with high in-hospital mortality. Importantly, the impact of ARDS extends beyond the acute phase, with increased mortality and disability for months to years after hospitalization. These findings underscore the importance of extended follow-up to assess and address the Post-Intensive Care Syndrome (PICS), characterized by persistent impairments in physical, cognitive, and/or mental health status that impair quality of life over the long-term. Persistent muscle weakness is a common physical problem for ARDS survivors, affecting mobility and activities of daily living. Critical illness and related interventions, including prolonged bed rest and overuse of sedatives and neuromuscular blocking agents during mechanical ventilation, are important risk factors for ICU-acquired weakness. Deep sedation also increases the risk of delirium in the ICU, and long-term cognitive impairment. Corticosteroids also may be used during management of ARDS, particularly in the setting of COVID-19. Corticosteroids can be associated with myopathy and muscle weakness, as well as prolonged delirium that increases the risk of long-term cognitive impairment. The optimal duration and dosage of corticosteroids remain uncertain, and there's limited long-term data on their effects on muscle weakness and cognition in ARDS survivors. In addition to physical and cognitive issues, mental health challenges, such as depression, anxiety, and post-traumatic stress disorder, are common in ARDS survivors. Strategies to address these complications emphasize the need for consistent implementation of the evidence-based ABCDEF bundle, which includes daily management of analgesia in concert with early cessation of sedatives, avoidance of benzodiazepines, daily delirium monitoring and management, early mobilization, and incorporation of family at the bedside. In conclusion, ARDS is a complex global health challenge with consequences extending beyond the acute phase. Understanding the links between critical care management and long-term consequences is vital for developing effective therapeutic strategies and improving the quality of life for ARDS survivors.

The effect of a bundle intervention for ambulatory otorhinolaryngology procedures on same-day case cancellation rate and associated costs.

Cancellations within 24 h of planned elective surgical procedures reduce operating theatre efficiency, add unnecessary costs and negatively affect patient experience. We implemented a bundle intervention that aimed to reduce same-day case cancellations. This consisted of communication tools to improve patient engagement and new screening instruments (automated estimation of ASA physical status and case cancellation risk score plus four screening questions) to identify patients in advance (ideally before case booking) who needed comprehensive pre-operative risk stratification. We studied patients scheduled for ambulatory surgery with the otorhinolaryngology service at a single centre from April 2021 to December 2022. Multivariable logistic regression and interrupted time-series analyses were used to analyse the effects of this intervention on case cancellations within 24 h and costs. We analysed 1548 consecutive scheduled cases. Cancellation within 24 h occurred in 114 of 929 (12.3%) cases pre-intervention and 52 of 619 (8.4%) cases post-intervention. The cancellation rate decreased by 2.7% (95%CI 1.6-3.7%, p < 0.01) during the first month, followed by a monthly decrease of 0.2% (95%CI 0.1-0.4%, p < 0.01). This resulted in an estimated $150,200 (£118,755; €138,370) or 35.3% cost saving (p < 0.01). Median (IQR [range]) number of days between case scheduling and day of surgery decreased from 34 (21-61 [0-288]) pre-intervention to 31 (20-51 [1-250]) post-intervention (p < 0.01). Patient engagement via the electronic health record patient portal or text messaging increased from 75.9% at baseline to 90.8% (p < 0.01) post-intervention. The primary reason for case cancellation was patients' missed appointment on the day of surgery, which decreased from 7.2% pre-intervention to 4.5% post-intervention (p = 0.03). An anaesthetist-driven, clinical informatics-based bundle intervention decreases same-day case cancellation rate and associated costs in patients scheduled for ambulatory otorhinolaryngology surgery.

The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

Awareness, usage and perceptions of authorship guidelines: an international survey of biomedical authors.

OBJECTIVES: To investigate authors' awareness and use of authorship guidelines, and to assess their perceptions of the fairness of authorship decisions. DESIGN: A cross-sectional online survey. SETTING AND PARTICIPANTS: Corresponding authors of research papers submitted in 2014 to 18 BMJ journals. RESULTS: 3859/12 646 (31%) researchers responded. They worked in 93 countries and varied in research experience. Of these, 1326 (34%) reported their institution had an authorship policy providing criteria for authorship; 2871 (74%) were 'very familiar' with the International Committee of Medical Journal Editors' authorship criteria and 3358 (87%) reported that guidelines were beneficial when preparing manuscripts. Furthermore, 2609 (68%) reported that their use was 'sometimes' or 'frequently' encouraged in their research setting. However, 2859 respondents (74%) reported that they had been involved in a study at least once where someone was added as an author who had not contributed substantially (honorary authorship), and 1305 (34%) where someone was not listed as an author but had contributed substantially (ghost authorship). Only 740 (19%) reported that they had never experienced either honorary or ghost authorship; 1115 (29%) reported that they had experienced both at least once. There was no clear pattern in experience of authorship misappropriation by continent. For their last coauthored article, 2187 (57%) reported that explicit authorship criteria had been used to determine eligibility, and 3088 (80%) felt that the decision made was fair. When institutions frequently encouraged use of authorship guidelines, authorship eligibility was more likely to be discussed early (817 of 1410, 58%) and perceived as fairer (1273 of 1410, 90%) compared with infrequent encouragement (974 of 2449, 40%, and 1891 of 2449, 74%). CONCLUSIONS: Despite a high level of awareness of authorship guidelines and criteria, these are not so widely used; more explicit encouragement of their use by institutions may result in more favourable use of guidelines by authors.

The development and validation of the Score for the Prediction of Postoperative Respiratory Complications (SPORC-2) to predict the requirement for early postoperative tracheal re-intubation: a hospital registry study.

Postoperative pulmonary complications are associated with an increase in mortality, morbidity and healthcare utilisation. The Agency for Healthcare Research and Quality recommends risk assessment for postoperative respiratory complications in patients undergoing surgery. In this hospital registry study of adult patients undergoing non-cardiac surgery between 2005 and 2017 at two independent healthcare networks, a prediction instrument for early postoperative tracheal re-intubation was developed and externally validated. This was based on the development of the Score for Prediction Of Postoperative Respiratory Complications. For predictor selection, stepwise backward logistic regression and bootstrap resampling were applied. Development and validation cohorts were represented by 90,893 patients at Partners Healthcare and 67,046 patients at Beth Israel Deaconess Medical Center, of whom 699 (0.8%) and 587 (0.9%) patients, respectively, had their tracheas re-intubated. In addition to five pre-operative predictors identified in the Score for Prediction Of Postoperative Respiratory Complications, the final model included seven additional intra-operative predictors: early post-tracheal intubation desaturation; prolonged duration of surgery; high fraction of inspired oxygen; high vasopressor dose; blood transfusion; the absence of volatile anaesthetic use; and the absence of lung-protective ventilation. The area under the receiver operating characteristic curve for the new score was significantly greater than that of the original Score for Prediction Of Postoperative Respiratory Complications (0.84 [95%CI 0.82-0.85] vs. 0.76 [95%CI 0.75-0.78], respectively; p < 0.001). This may allow clinicians to develop and implement strategies to decrease the risk of early postoperative tracheal re-intubation.

Effects of low-dose intraoperative fentanyl on postoperative respiratory complication rate: a pre-specified, retrospective analysis.

BACKGROUND: Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs). METHODS: We performed a pre-specified analysis of 145 735 adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used. RESULTS: PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses [median: 3.85; inter-quartile range (IQR): 3.42-4.50 µg kg-1, quartile 4 (Q4)], low intraoperative fentanyl dose [median: 0.80, IQR: 0.00-1.14 µg kg-1, quartile 1 (Q1)] was significantly associated with lower odds of PRCs [Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75-0.84; P<0.001; adjusted absolute risk difference (aARD) -1.7%]. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD -6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD -2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD -3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75-0.89, P<0.001). CONCLUSIONS: Intraoperative low-dose fentanyl (about 60-120 µg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups. CLINICAL TRIAL REGISTRATION: NCT03198208.

The association of early postoperative desaturation in the operating theatre with hospital discharge to a skilled nursing or long-term care facility.

It is unclear which criteria should be used to define readiness for tracheal extubation in the operating theatre. We studied the effects of desaturation in the operating theatre immediately after tracheal extubation on long-term outcomes. Performing a pre-specified, retrospective analysis of 71,025 cases involving previously independent adults undergoing non-cardiac surgery, we evaluated the association between desaturation events (oxygen saturation < 90%) within 10 min of tracheal extubation and adverse discharge (to a skilled nursing facility or long-term care facility). A total of 404 (12.3%) cases with, and 5035 (7.4%) cases without, early postoperative desaturation had an adverse discharge. Early postoperative desaturation was associated with higher odds of being discharged to a nursing facility (adjusted odds ratio 1.36 (95%CI 1.20-1.54); p < 0.001). Increased duration of desaturation augmented the effect (p for trend < 0.001). Desaturation was associated with a higher risk of respiratory, renal and cardiovascular complications as well as increased duration of hospital stay, postoperative intensive care unit admission frequency and cost. Several modifiable factors were associated with desaturation including: high intra-operative long-acting opioid administration; high neostigmine dose; high intra-operative inspired oxygen concentration; and low oxygen delivery immediately before tracheal extubation. There was substantial provider variability between anaesthetists in the incidence of postoperative desaturation unexplained by patient- and procedure-related factors. Early postoperative desaturation is a potentially preventable complication associated with a higher risk of adverse discharge disposition. Anaesthetists may consider developing guidelines to define tracheal extubation readiness that contain postoperative desaturation as an adverse outcome after tracheal extubation.

Major Complications Independently Increase Long-Term Mortality After Pancreatoduodenectomy for Cancer.

BACKGROUND: Postoperative major morbidity has been associated with worse survival gastrointestinal tumors. This association remains controversial in pancreatic cancer (PC). We analyzed whether major complications after surgical resection affect long-term survival. METHODS: Records of all PC patients resected from 2007 to 2015 were reviewed. Major morbidity was defined as any grade-3 or higher 30-day complications, per the Clavien-Dindo Classification. Patients who died within 90 days after surgery were excluded from survival analysis. RESULTS: Of 616 patients, 81.7% underwent pancreatoduodenectomy (PD) and 18.3% distal pancreatectomy (DP). Major complications occurred in 19.1% after PD and 15.9% after DP. In patients who survived > 90 days, the likelihood of receiving adjuvant treatment was 43.9% if major complications had occurred, vs. 68.5% if not (p < 0.001), and those who received it started the treatment median 10 days later compared with uncomplicated patients (median 60 days (50-72) vs. 50 days (41-61), p = 0.001). By univariate analysis, in addition to the conventional pathology-related prognostic determinants and the receipt of adjuvant treatment, major complications worsened long-term survival after PD (median OS 26 months vs. 15, p = 0.008). A difference was also seen after DP, but it did not reach statistical significance, likely related to the small sample size (median OS 33 months vs. 18, p = 0.189). At multivariate analysis for PD, major postoperative complications remained independently associated with worse survival [HR 1.37, 95%CI (1.01-1.86)]. CONCLUSIONS: Major surgical complications after pancreaticoduodenectomy are associated with worse long-term survival in pancreatic cancer. This effect is independent of the receipt of adjuvant treatment.

Intraoperative Fluid Administration and Surgical Outcomes Following Pancreaticoduodenectomy: External Validation at a Tertiary Referral Center.

BACKGROUND: While intraoperative fluid overload is associated with higher complication rates following surgery, data for pancreaticoduodenectomy are scarce and heterogeneous. We evaluated multiple prior definitions of restrictive and liberal fluid regimens and analyzed whether these affected surgical outcomes at our tertiary referral center. METHODS: Studies evaluating different intraoperative fluid regimens on outcomes after pancreatic resections were retrieved. After application of all prior definitions of restrictive and liberal fluid regimens to our patient cohort, relative risks of each outcome were calculated using all reported infusion regimens. RESULTS: Five hundred and seven pancreaticoduodenectomies were included. Nine different fluid regimens were evaluated. Two regimens utilized absolute volume cutoffs, and the remaining evaluated various infusion rates, ranging from 5 to 15 mL/kg/h. Total volume administration of >5000 mL and >6000 mL was associated with increased complications (RR 1.25 and RR 1.17, respectively) and >6000 mL with increased sepsis (RR 2.14). Conversely, a rate of <5 mL/kg/h was associated with increased risk of postoperative pancreatic fistula (POPF, RR 3.16) and sepsis (RR 3.20), <6.8 mL/kg/h with increased major morbidity (RR 1.64) and sepsis (RR 2.27), and <8.2 mL/kg/h with increased POPF (RR 2.16). No effects were observed on pulmonary complications, surgical site infections, length of stay, or mortality. CONCLUSIONS: In an uncontrolled setting with no standard intraoperative or postoperative care map, the volume of intraoperative fluid administration appears to have limited impact on early postoperative outcomes following pancreaticoduodenectomy, with adverse outcomes only seen at extreme values.

Therapeutic doses of neostigmine, depolarising neuromuscular blockade and muscle weakness in awake volunteers: a double-blind, placebo-controlled, randomised volunteer study.

Neostigmine reverses non-depolarising neuromuscular blockade, but may cause muscle weakness when administered after full recovery of neuromuscular function. We hypothesised that neostigmine in therapeutic doses impairs muscle strength and respiratory function in awake healthy volunteers. Twenty-one volunteers were randomised to receive two doses of either intravenous (i.v.) neostigmine 2.5 mg with glycopyrrolate 450 µg (neostigmine group, n = 14) or normal saline 0.9% (placebo group, n = 7). The first dose was administered immediately after obtaining baseline measurements, and the second dose was administered 15 min later. All 14 volunteers in the neostigmine group received the first dose, mean (SD) 35 (5.8) µg.kg-1 , but only nine of these volunteers agreed to receive the second dose, 34 (3.5) ?g.kg-1 . The primary outcome was hand grip strength. Secondary outcomes were train-of-four ratio, single twitch height, forced expiratory volume in 1 s, forced vital capacity, forced expiratory volume in 1 s/forced vital capacity ratio, oxygen saturation, heart rate and mean arterial pressure. The first dose of intravenous neostigmine with glycopyrrolate resulted in reduced grip strength compared with placebo, -20 (20) % vs. +4.3 (9.9) %, p = 0.0016; depolarising neuromuscular blockade with decreased single twitch height, -14 (11) % vs. -3.8 (5.6) %, p = 0.0077; a restrictive spirometry pattern with decreased predicted forced expiratory volume in 1 s, -15 (12) % vs. -0.47 (3.4) %, p = 0.0011; and predicted forced vital capacity, -20 (12) % vs. -0.59 (3.2) %, p < 0.0001 at 5 min after administration. The second dose of neostigmine with glycopyrrolate further decreased grip strength mean (SD) -41 (23) % vs. +1.0 (15) %, p = 0.0004; single twitch height -25 (15) % vs. -2.5 (6.6) %, p = 0.0030; predicted forced expiratory volume in 1 s -23 (24) % vs. -0.7 (4.4) %, p = 0.0063; and predicted forced vital capacity, -27.1 (22.0) % vs. -0.66 (3.9) %, p = 0.0010. Train-of-four ratio remained unchanged (p = 0.22). In healthy volunteers, therapeutic doses of neostigmine induced significant and dose-dependent muscle weakness, demonstrated by a decrease in maximum voluntary hand grip strength and a restrictive spirometry pattern secondary to depolarising neuromuscular blockade.

Implementation of a new strategy to improve the peri-operative management of neuromuscular blockade and its effects on postoperative pulmonary complications.

Inappropriate dosing of neostigmine for antagonism of neuromuscular blockade has been associated with postoperative pulmonary complications. We evaluated the effects of a quality improvement initiative tailored to optimise the use of neostigmine in antagonising neuromuscular blockade on postoperative pulmonary complications, costs and duration of hospital stay. The quality improvement initiative consisted of: a reduction in available neostigmine aliquot sizes; a cognitive aid; an educational component; and a financial incentive for the intra-operative documentation of train-of-four measurement before administration of neostigmine. We conducted a pre-specified analysis of data obtained in our quality improvement study. Additional analyses were conducted in a propensity-matched cohort. An interrupted time series design was used to discriminate between the intervention and a counterfactual scenario. We analysed 12,025 consecutive surgical cases performed in 2015. Postoperative pulmonary complications occurred in 220 (7.5%) of 2937 cases pre-intervention and 568 (6.3%) of 9088 cases post-intervention. Adjusted regression analyses showed significantly a lower risk of postoperative pulmonary complications (OR 0.73 (95%CI 0.61-0.88); p = 0.001), lower costs (incidence rate ratio 0.95 (95%CI 0.93-0.97); p < 0.001) and shorter duration of hospital stay (incidence rate ratio 0.91 (95%CI 0.87-0.94); p < 0.001) after implementation of the quality improvement initiative. Analyses in a propensity-matched sample (n = 2936 per group) and interrupted time series analysis (n = 27,202 cases) confirmed the findings. Our data show that a local, multifaceted quality improvement initiative can enhance the quality of intra-operative neuromuscular blocking agent utilisation, thereby reducing the incidence of postoperative pulmonary complications.

Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

BACKGROUND: The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. METHODS: We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. RESULTS: Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. CONCLUSIONS: High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.