Impact of Oral Anticoagulation on Clinical Outcomes in Postoperative Atrial Fibrillation.

INTRODUCTION: The impact of postoperative oral anticoagulation (OAC) with warfarin on postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) was the focus of this examination of patients from the randomized endo-vein graft prospective (REGROUP) Trial. MATERIAL AND METHODS: REGROUP was a prospective randomized Veterans Affairs cooperative study comparing endoscopic versus open vein harvest in elective CABG patients (March 2014-April 2017) at 16 Veterans Affairs facilities. This study compared new-onset POAF patients who were treated with warfarin versus no-warfarin. Outcomes included stroke during active follow-up and a major adverse cardiac event composite of mortality, acute myocardial infarction, and repeat revascularization during active and passive follow-up. RESULTS: Of the 316/1103 (28.6%) of REGROUP patients who developed new-onset POAF, 45 patients were excluded - mainly for preoperative warfarin use. Of the remaining 269 patients, 85 received OAC with warfarin (OAC group); 184 did not (no-OAC group). Stroke rates during active follow-up (32 [IQR 24-38] mo) were 3.5% OAC group versus 5.4% no-OAC group (P = 0.76); major adverse cardiac eventrates were 20% OAC versus 11.4% no-OAC (P = 0.06). On longer follow-up of (median 4.61 [IQR 3.9-5.1] y), discharge OAC use was associated with all-cause mortality after adjusting for Society of Thoracic Surgeons mortality risk (20.0% versus 11.4% no-OAC use; HR = 2.00, 95% CI: 1.05-3.81, P = 0.035). CONCLUSIONS: REGROUP patients with POAF treated with OAC had similar stroke and higher mortality rates versus no-OAC patients. Further investigation of the risk-benefit ratio of OAC in post-CABG patients and which POAF patient subgroups might derive the most benefit with anticoagulation appears warranted.

Surgical strategy in lithium-associated hyperparathyroidism: A population-based study.

BACKGROUND: The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes. METHODS: A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH). RESULTS: Lithium exposure was significantly more common among PHPT (n = 202, 2.3%) than in controls (n = 416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5 years duration of lithium exposure prior to surgery. CONCLUSIONS: The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence.

Influence of Neostigmine on Early Postoperative Cognitive Dysfunction in Older Adult Patients Undergoing Noncardiac Surgery: A Double-Blind, Placebo-Controlled, Randomized Controlled Trial.

BACKGROUND: The goal of this study was to investigate the efficacy of neostigmine on postoperative cognitive dysfunction (POCD) and determine its effect on systematic markers of oxidative stress in older patients. METHODS: This double-blind placebo-controlled trial enrolled 118 elderly patients (≥65 years) undergoing noncardiac surgeries who were allocated to a neostigmine treatment group (0.04 mg/kg) or a placebo control group (normal saline) postoperatively. POCD was diagnosed if the Z -scores for the mini-mental state examination and the Montreal Cognitive Assessment were both ≤-1.96. Postoperative serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were also compared. Multivariable regression analysis with dose adjustment of atropine was used to demonstrate the influence of neostigmine on the incidence of POCD. RESULTS: Patients receiving neostigmine had a significantly reduced incidence of POCD compared to patients who were treated with placebo on the first day after surgery (-22%, 95% confidence interval [CI], -37 to -7), but not on the third (8%, 95% CI, -4 to 20) or seventh day after surgery (3%, 95% CI, -7 to 13). Postoperative plasma MDA levels were significantly lower ( P = .016), but SOD and BDNF levels were increased ( P = .036 and .013, respectively) in the neostigmine group compared to the control group on the first day after surgery. CONCLUSIONS: Neostigmine reduced POCD on the first day after noncardiac surgery in older patients. Neostigmine treatment inhibited oxidative stress and increased serum BDNF levels. There was no significant influence of neostigmine on POCD on the third or seventh day after surgery. The clinical influence of neostigmine on POCD should be further investigated.

Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Risks of serious adverse events with non-steroidal anti-inflammatory drugs in gastrointestinal surgery: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly recommended for perioperative opioid-sparing multimodal analgesic treatments. Concerns regarding the potential for serious adverse events (SAEs) associated with perioperative NSAID treatment are especially relevant following gastrointestinal surgery. We assessed the risks of SAEs with perioperative NSAID treatment in patients undergoing gastrointestinal surgery. METHODS: We conducted a systematic review of randomised clinical trials assessing the harmful effects of NSAIDs versus placebo, usual care or no intervention in patients undergoing gastrointestinal surgery. The primary outcome was an incidence of SAEs. We systematically searched for eligible trials in five major databases up to January 2024. We performed risk of bias assessments to account for systematic errors, trial sequential analysis (TSA) to account for the risks of random errors, performed meta-analyses using R and used the Grading of Recommendations Assessment, Development and Evaluation framework to describe the certainty of evidence. RESULTS: We included 22 trials enrolling 1622 patients for our primary analyses. Most trials were at high risk of bias. Meta-analyses (risk ratio 0.78; 95% confidence interval [CI] 0.51-1.19; I2 = 4%; p = .24; very low certainty of evidence) and TSA indicated a lack of information on the effects of NSAIDs compared to placebo on the risks of SAEs. Post-hoc beta-binomial regression sensitivity analyses including trials with zero events showed a reduction in SAEs with NSAIDs versus placebo (odds ratio 0.73; CI 0.54-0.99; p = .042). CONCLUSION: In adult patients undergoing gastrointestinal surgery, there was insufficient information to draw firm conclusions on the effects of NSAIDs on SAEs. The certainty of the evidence was very low.

Systemic glucocorticoid exposure and postoperative infection risk in 143,782 appendectomy patients-a Danish longitudinal nationwide study.

BACKGROUND: Glucocorticoids are conventionally associated with increased postoperative infection risk. It is necessary to clarify if preoperative glucocorticoid exposure is associated with postoperative infection in appendectomy patients and if the association is different for open and laparoscopic appendectomies. METHODS: A Danish nationwide study of appendectomy patients between 1996 and 2018. Exposures were defined as high (≥ 5 mg) versus no/low (< 5 mg) glucocorticoid exposure in milligram prednisone-equivalents/day preoperatively. The main outcome was any postoperative infection. Then, 90-day cumulative incidences (absolute risk) and adjusted hazard ratios (relative risk) of the outcome were calculated for high versus no/low glucocorticoid exposure within all appendectomies and within open and laparoscopic subgroups. Propensity-score matching was used for sensitivity analysis. RESULTS: Of 143,782 patients, median age was 29 years, 74,543 were female, and 7654 experienced at least one infection during the 90-day follow-up. The 90-day cumulative incidence for postoperative infection was 5.3% within the no/low glucocorticoid exposure group and 10.0% within the high glucocorticoid exposure group. Compared to no/low glucocorticoid exposure, adjusted hazard ratios for 90-day postoperative infection with high glucocorticoid exposure were 1.25 [95% CI 1.02-1.52; p = 0.03] for all appendectomies, 1.59 [1.16-2.18; p = 0.004] for laparoscopic appendectomies, and 1.09 [0.85-1.40; p = 0.52] for open appendectomies (pinteraction < 0.001). The results were robust to sensitivity analyses. CONCLUSION: Preoperative high (≥ 5 mg/day) glucocorticoid exposure was associated with increased absolute risk of postoperative infections in open and laparoscopic appendectomies. The relative risk increase was significant for laparoscopic but not open appendectomies, possibly due to lower absolute risk with no/low glucocorticoid exposure in the laparoscopic subgroup.

Ketofol versus Dexmedetomidine for preventing postoperative delirium in elderly patients undergoing intestinal obstruction surgeries: a randomized controlled study.

PURPOSE: Postoperative delirium (POD) is considered the most common postoperative neurological complication in elderly patients. The aim of this study was to evaluate the efficacy of the administration of ketofol versus dexmedetomidine (DEX) for minimizing POD in elderly patients undergoing urgent exploration for intestinal obstruction. METHODS: This prospective double-blinded randomized clinical trial was conducted on 120 elderly patients undergoing urgent exploration for intestinal obstruction. Patients were randomly allocated to one of the three groups: Group C (control group) patients received normal saline 0.9%, group D received dexmedetomidine, and group K received ketofol (ketamine: propofol was 1:4). The primary outcome was the incidence of POD. Secondary outcomes were incidence of emergence agitation, postoperative pain, consumption of rescue opioids, hemodynamics, and any side effects. RESULTS: The incidence of POD was statistically significantly lower in ketofol and DEX groups than in the control group at all postoperative time recordings. Additionally, VAS scores were statistically significantly decreased in the ketofol and DEX groups compared to the control group at all time recordings except at 48 and 72 h postoperatively, where the values of the three studied groups were comparable. The occurrence of emergence agitation and high-dose opioid consumption postoperatively were found to be significant predictors for the occurrence of POD at 2 h and on the evening of the 1st postoperative day. CONCLUSION: The administration of ketofol provides a promising alternative option that is as effective as DEX in reducing the incidence of POD in elderly patients undergoing urgent exploration for intestinal obstruction. TRIAL REGISTRATION: This clinical trial was approved by the Institutional Review Board (IRB) at Zagazig University (ZU-IRB# 6704// 3/03/2021) and ClinicalTrials.gov (NCT04816162, registration date 22/03/ 2021). The first research participant was enrolled on 25/03/2021).

Association between postoperative ibuprofen exposure and acute kidney injury after pediatric cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery and is associated with worse outcomes. Ibuprofen is widely used in the perioperative period and can affect kidney function in children. However, the association between ibuprofen exposure and AKI after pediatric cardiac surgery has not been determined yet. METHODS: In this retrospective cohort study, children undergoing cardiac surgery with cardiopulmonary bypass were studied. Exposure was defined as given ibuprofen in the first 7 days after surgery. Postoperative AKI was diagnosed using the KDIGO criteria. A multivariable Cox regression model was used to assess the association between ibuprofen exposure and postoperative AKI by taking ibuprofen as a time-varying covariate. RESULTS: Among 1,112 included children, 198 of them (17.8%) experienced AKI. In total, 396 children (35.6%) were exposed to ibuprofen. AKI occurred less frequently among children who were administered ibuprofen than among those who were not (46 of 396 [11.6%] vs. 152 of 716 [21.2%], p < 0.001). Using the Cox regression model accounting for time-varying exposures, ibuprofen treatment was not associated with AKI (adjusted HR, 0.99; 95% CI 0.70-1.39, p = 0.932). This insignificant association was consistent across the sensitivity and subgroup analyses. CONCLUSIONS: Postoperative ibuprofen exposure in pediatric patients undergoing cardiac surgery was not associated with an increased risk of AKI.

Spinal infection after vertebral augmentation: a covert complication with serious havoc.

INTRODUCTION: Vertebral augmentation, including percutaneous vertebroplasty (PVP) or kyphoplasty (PKP), is the current least invasive surgical option and has been widely used to treat the painful osteoporotic vertebral compression fractures (OVCF). However, the postoperative infections could be life-threatening, even though they rarely occur. Our studies aim to clarify the causation and outcomes of spinal infections following augmentation and meanwhile to identify the risk factors. METHODS: A retrospective study was conducted on patients with OVCF who underwent PVP or PKP, and were subsequently admitted to our institution with postoperative spinal infection between January 2010 and December 2022. A total of 33 patients were finally included. RESULTS: The rate of spinal infection after augmentation in our single institute was 0.05% (2/3893). In addition to these 2 patients, the remaining 31 were referred from other hospitals. All 33 patients exhibited elevated inflammatory parameters, 14 patients presented with fever, and 9 patients experienced neurological deficits. Additionally, 29 patients had comorbidity and risk factors. Pathogens were identified in 26 patients, while only 7 patients were examined as culture negative. 27 patients underwent revision surgery and 6 patients only received conservative therapy. Anterior surgery was performed in 2 patients, while posterior surgery was performed in 20 patients. A combined anterior-posterior surgery was performed in 5 patients. At the final follow-up, 18 patients had unrestricted mobility, 10 patients required assistance from crutches or a walker for ambulation, 4 patients needed a wheelchair, and 1 patients died after revision surgery. CONCLUSIONS: Spinal infection after vertebral augmentation is rare, but it cannot be ignored. Surgeons should make every effort to detect the potential preoperative spondylitis or discitis. Once postoperative spinal infection is confirmed, a prompt intravenous antibiotic therapy is warranted. If medication therapy fails, revision surgery involving debridement and spinal reconstruction should be considered.

Early Postoperative Acetaminophen Administration and Severe Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Oxidative stress may contribute to the development of acute kidney injury (AKI) after cardiac surgery. Acetaminophen can be considered an antioxidant because it inhibits hemoprotein-catalyzed lipid peroxidation. We hypothesized that perioperative acetaminophen administration is associated with reduced AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who had cardiac surgery were identified from 2 publicly available clinical registries: the Medical Information Mart for Intensive Care III (MIMIC-III) and the eICU Collaborative Research Database (eICU). EXPOSURE: Administration of acetaminophen in the first 48 hours after surgery. OUTCOME: Severe AKI in the first 7 days after surgery, defined as stage 2 or stage 3 AKI according to KDIGO criteria. ANALYTICAL APPROACH: Multivariable cause-specific hazards regression analysis. RESULTS: We identified 5,791 patients from the MIMIC-III and 3,840 patients from the eICU registries. The overall incidence of severe AKI was 58% (3,390 patients) in the MIMIC-III cohort and 37% (1,431 patients) in the eICU cohort. Acetaminophen was administered in the early postoperative period to 4,185 patients (72%) and 2,737 patients (71%) in these 2 cohorts, respectively. In multivariable regression models, early postoperative use of acetaminophen was associated with a lower risk of severe AKI in both the MIMIC-III (adjusted hazard ratio [AHR], 0.86 [95% CI, 0.79-0.94]) and eICU (AHR, 0.84 [95% CI, 0.72-0.97]) cohorts. The benefit was consistent across sensitivity and subgroup analyses. LIMITATIONS: No data on acetaminophen dose. CONCLUSIONS: Early postoperative acetaminophen administration was independently associated with a lower risk of severe AKI in adults recovering from cardiac surgery. Prospective trials are warranted to assess the extent to which the observed association is causal and estimate the extent to which acetaminophen administration might prevent or reduce the severity of AKI. PLAIN-LANGUAGE SUMMARY: There is uncertainty about whether antioxidant medications such as acetaminophen may protect against kidney injury. Therefore, we evaluated the associations between acetaminophen use and kidney outcomes in adults recovering from cardiac surgery in 2 large clinical registries. Acetaminophen treatment was significantly associated with a 14%-16% lower risk of severe and any-stage acute kidney injury but similar risks of kidney replacement therapy and in-hospital mortality. Our findings suggest that acetaminophen use may protect against kidney injury in adult patients recovering from cardiac surgery.

Preoperative ß-Blocker Therapy and Stroke or Major Adverse Cardiac Events in Major Abdominal Surgery: A Retrospective Cohort Study.

BACKGROUND: Perioperative ß-blocker therapy has been associated with increased risk of stroke. However, the association between ß-blocker initiation before the day of surgery and the risk of stroke is unknown. The authors hypothesized there would be no association between preoperative ß-blocker initiation within 60 days of surgery or chronic ß-blockade (more than 60 days) and the risk of stroke in patients undergoing major abdominal surgery. METHODS: Data on elective major abdominal surgery were obtained from the IBM (USA) Truven Health MarketScan 2005 to 2015 Commercial and Medicare Supplemental Databases. Patients were stratified by ß-blocker dispensing exposure: (1) ß-blocker-naïve, (2) preoperative ß-blocker initiation within 60 days of surgery, and (3) chronic ß-blocker dispensing (more than 60 days). The authors compared in-hospital stroke and major adverse cardiac events between the different ß-blocker therapy exposures. RESULTS: There were 204,981 patients who underwent major abdominal surgery. ß-Blocker exposure was as follows: perioperative initiation within 60 days of surgery for 4,026 (2.0%) patients, chronic ß-blocker therapy for 45,424 (22.2%) patients, and ß-blocker-naïve for 155,531 (75.9%) patients. The unadjusted frequency of stroke for patients with ß-blocker initiation (0.4%, 17 of 4,026) and chronic ß-blocker therapy (0.4%, 171 of 45,424) was greater than in ß-blocker-naïve patients (0.2%, 235 of 155,531; P < 0.001). After propensity score weighting, patients initiated on a ß-blocker within 60 days of surgery (odds ratio, 0.90; 95% CI, 0.31 to 2.04; P = 0.757) or on chronic ß-blocker therapy (odds ratio, 0.86; 95% CI, 0.65 to 1.15; P = 0.901) demonstrated similar stroke risk compared to ß-blocker-naïve patients. Patients on chronic ß-blocker therapy demonstrated lower adjusted risk of major adverse cardiac events compared to ß-blocker-naïve patients (odds ratio, 0.81; 95% CI, 0.72 to 0.91; P = 0.007), despite higher unadjusted absolute event rate (2.6% [1,173 of 45,424] vs. 0.6% [872 of 155,531]). CONCLUSIONS: Among patients undergoing elective major abdominal surgery, the authors observed no association between preoperative ß-blocker initiation within 60 days of surgery or chronic ß-blocker therapy and stroke.

Benzodiazepines and postoperative delirium: should we be as cautious as we are?

A recent systematic review and meta-analysis by Wang and colleagues in the British Journal of Anaesthesia calls into question the concept that perioperative benzodiazepine administration is associated with development of postoperative delirium in older individuals after anaesthesia and surgery. This editorial focuses on potential bias within the systematic review and addresses major concerns surrounding benzodiazepine use in the older perioperative population.

How robust are the STRONGER and STIL-STRONGER studies?

In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first time that use of sugammadex is associated with fewer postoperative pulmonary complications than use of neostigmine. In a recent publication in the British Journal of Anaesthesia, a secondary analysis of the same data, the Association Between Neuromuscular Blockade Reversal Agent Choice and Postoperative Pulmonary Complications (STIL-STRONGER) study, has produced similar evidence of the advantages of sugammadex over neostigmine in high-risk and older patients undergoing prolonged, elective surgery. Here we consider the implications of the detailed statistical analysis used in these two studies and how its limitations could possibly have enhanced the statistical differences between the two drugs with respect to postoperative pulmonary complications.

Emergency colectomies in the NOAC era: a nationwide analysis demonstrating increased complications.

BACKGROUND: The use of Non-vitamin K antagonist oral anticoagulants (NOAC) has increased substantially since their introduction in 2010. The lack of readily available reversal agents poses a challenge in perioperative management. The aim of this study was to evaluate the impact of NOACs on the outcomes of emergency colectomies. METHODS: All adult patients on long-term anticoagulation who underwent emergency colectomies were identified from the Nationwide Inpatient Sample (NIS) database from 2002 to 2018. Long-term anticoagulation was defined using ICD-9/10 codes. Two cohorts were compared: anticoagulated patients in the pre-NOAC era (2002-2010) and anticoagulated patients in the NOAC era (2010-2018). Outcomes of interest were postoperative surgical complications, mortality and need for transfusion. RESULTS: Of 13,218 patients on long-term anticoagulation, 3,264 patients were treated in the pre-NOAC era and 9,954 in the NOAC era. Over the study period, there was a significant increase in the proportion of anticoagulated patients undergoing emergency colectomies (R2 = 0.91). On univariate analysis, anticoagulated patients in the NOAC era were medically more comorbid and had higher rates of postoperative surgical complications (73.3% vs 60.3%, p < 0.001) and mortality (8.2% vs. 6.7%, p = 0.006), but had lower rates of postoperative bleeding (3.5% vs. 4.4%, p = 0.002) and transfusions (38.1% vs. 45.4%, p < 0.001). On multivariable regression, after accounting for clinically significant covariates, anticoagulation in the NOAC era was associated with decreased rates of postoperative bleeding (OR 0.70, 95%CI 0.57-0.88) and transfusions (OR 0.71 95%CI 0.64-0.77) but remained an independent predictor of increased overall postoperative complications (OR 1.26, 95%CI 1.14-1.39). CONCLUSION: Prevalence of long-term anticoagulation in patients undergoing emergency colectomies is increasing. Although associated with lower rates of postoperative bleeding and transfusions, anticoagulation in the NOAC era is associated with higher rates of overall postoperative complications. Evidence-based guidelines for perioperative management of patients on NOACs in the emergency colorectal surgery setting are needed.

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.

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

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

Impact of total intravenous anesthesia and total inhalation anesthesia as the anesthesia maintenance approaches on blood glucose level and postoperative complications in patients with type 2 diabetes mellitus: a double-blind, randomized controlled trial.

BACKGROUND: Diabetes mellitus is a prevalent metabolic disease in the world. Previous studies have shown that anesthetics can affect perioperative blood glucose levels which related to adverse clinical outcomes. Few studies have explored the choice of general anesthetic protocol on perioperative glucose metabolism in diabetes patients. We aimed to compare total intravenous anesthesia (TIVA) with total inhalation anesthesia (TIHA) on blood glucose level and complications in type 2 diabetic patients undergoing general surgery. METHODS: In this double-blind controlled trial, 116 type 2 diabetic patients scheduled for general surgery were randomly assigned to either the TIVA group or TIHA group (n = 56 and n = 60, respectively). The blood glucose level at different time points were measured and analyzed by the repeated-measures analysis of variance. The serum insulin and cortisol levels were measured and analyzed with t-test. The incidence of complications was followed up and analyzed with chi-square test or Fisher's exact test as appropriate. The risk factors for complications were analyzed using the logistic stepwise regression. RESULTS: The blood glucose levels were higher in TIHA group than that in TIVA group at the time points of extubation, 1 and 2 h after the operation, 1 and 2 days after the operation, and were significantly higher at 1 day after the operation (10.4 ± 2.8 vs. 8.1 ± 2.1 mmol/L; P < 0.01). The postoperative insulin level was higher in TIVA group than that in TIHA group (8.9 ± 2.9 vs. 7.6 ± 2.4 IU/mL; P = 0.011). The postoperative cortisol level was higher in TIHA group than that in TIVA group (15.3 ± 4.8 vs. 12.2 ± 8.9 ug/dL ; P = 0.031). No significant difference regarding the incidence of complications between the two groups was found based on the current samples. Blood glucose level on postoperative day 1 was a risk factor for postoperative complications (OR: 1.779, 95%CI: 1.009 ~ 3.138). CONCLUSIONS: TIVA has less impact on perioperative blood glucose level and a better inhibition of cortisol release in type 2 diabetic patients compared to TIHA. A future large trial may be conducted to find the difference of complications between the two groups. TRIAL REGISTRATION: The protocol registered on the Chinese Clinical Trials Registry on 20/01/2020 (ChiCTR2000029247).

Association Between the Use of Midazolam During Cardiac Anesthesia and the Incidence of Postoperative Delirium: A Retrospective Cohort Study Using a Nationwide Database.

OBJECTIVE: To evaluate the association between the intraoperative administration of midazolam and the incidence of postoperative delirium in patients undergoing cardiac surgery. DESIGN: Retrospective observational cohort study. SETTING: The Japanese Diagnosis Procedure Combination database. PARTICIPANTS: Patients aged 65 years and older who underwent cardiovascular surgery (excluding transcatheter surgeries, multiple surgeries per admission, and preoperative delirium) between April 1, 2015, and October 31, 2019. MEASUREMENTS AND MAIN RESULTS: Patients who received midazolam (midazolam group) were compared with those who did not receive midazolam (no midazolam group). The primary outcome was the incidence of postoperative delirium. The secondary outcomes were the incidence of postoperative nausea and vomiting, mortality, and duration of intensive care unit stay and hospitalization. Propensity scores were estimated using logistic regression based on the covariates. The outcomes were compared using stabilized inverse probability of treatment-weighting analyses. Among the 16,185 patients analyzed, 10,633 (65.7%) received midazolam. No significant differences were observed in the incidences of postoperative delirium (odds ratio [OR] 0.95; 95% CI 0.87-1.03; p = 0.21) and hospital mortality (OR 0.92; 95% CI 0.76-1.11; p = 0.39) between the groups; however, the midazolam group had slightly longer durations of intensive care unit stay (3.5 [3.5-3.6] v 3.3 [3.3-3.4] days, p < 0.001) and hospitalization (31.5 [31.1-31.9] v 29.4 [28.8-29.9] days, p < 0.001), and slightly lower incidences of postoperative nausea and vomiting (OR 0.92; 95% CI 0.85-0.99; p = 0.03). The sensitivity analyses supported these results. CONCLUSIONS: Intraoperative administration of midazolam may not induce postoperative delirium in patients undergoing cardiac surgery.

The Effect of Preoperative Bisphosphonate Use on Total Hip Arthroplasty Outcomes.

BACKGROUND: Patients undergoing total hip arthroplasty (THA) commonly have osteoporosis for which bisphosphonates (BPs) are Food and Drug Administration (FDA)-approved for treatment. Bisphosphonate use post-THA is associated with decreased periprosthetic bone loss or revisions, and increased longevity of implants. However, evidence is lacking for preoperative bisphosphonate use in THA recipients. This study investigated the association between bisphosphonate use pre-THA and outcomes. METHODS: A retrospective review of a national administrative claims database was conducted. Among THA recipients who had a prior diagnosis of hip osteoarthritis and osteoporosis/osteopenia, the treatment group (BP-exposed) consisted of patients who had a history of bisphosphonate use at least 1 year before THA; controls (BP-naive) comprised patients who did not have preoperative bisphosphonate use. The BP-exposed were matched to BP-naive in a 1:4 ratio by age, sex, and comorbidities. Logistic regressions were used to calculate the odds ratio for intraoperative and 1-year postoperative complications. RESULTS: The BP-exposed group had significantly higher rates of intraoperative and 1-year postoperative periprosthetic fractures (odds ratio (OR): 1.39, 95% confidence interval (CI): 1.23, 1.57) and revisions (OR: 1.14, 95% CI: 1.04, 1.25) compared with the BP-naive controls. BP-exposed also experienced higher rates of aseptic loosening, dislocation, periprosthetic osteolysis, and stress fracture of the femur or hip/pelvis compared to the BP-naive controls, but these values were not statistically significant. CONCLUSION: The use of bisphosphonates in THA patients preoperatively is associated with higher rates of intraoperative and 1-year postoperative complications. These findings may impact the management of patients undergoing THA who have a prior diagnosis of osteoporosis/osteopenia and use of bisphosphonates. LEVEL OF EVIDENCE: Retrospective Cohort Study (Level 3).

Safe perioperative tamoxifen use in autologous breast free flap reconstruction: systematic review and meta-analysis.

BACKGROUND: Perioperative tamoxifen remains a valuable therapeutic modality for breast cancer patients. Studies in the existing literature have suggested a potential increased risk of thrombotic complications in autologous breast free flap reconstruction patients exposed to tamoxifen perioperatively. However, several recent publications have questioned the validity of these associations. Therefore, we aim to perform a systematic appraisal of the existing literature to determine if perioperative tamoxifen exposure increases the risk of flap complications in autologous breast-free flap reconstruction patients. METHODS: A systematic literature search was performed using: PubMed, EMBASE, Cochrane Central, Web of Science, EBSCOHost, ClinicalTrials.gov, and TRIP databases from their inception up to April 2021. Articles analyzing the impact of perioperative tamoxifen in autologous breast free flap patients were included. The outcomes assessed were total flap loss, overall flap complications, thrombotic flap complications, which was defined as the sum of arterial and venous flap thrombi, and systemic venous thromboembolism (VTE). Pooled estimates and relative risk were calculated using a random effects model. RESULTS: 9294 Articles were screened and 7 were selected for analysis, which included 3669 flaps in 2759 patients. Compared to patients who did not receive tamoxifen perioperatively, those who received tamoxifen did not have an increased risk of thrombotic flap complications (pooled RR 1.06; 95% CI 0.61-1.84), total flap loss (pooled RR 2.17; 95% CI 0.79-5.95), overall flap complications (pooled RR 1.04; 95% CI 0.76-1.41), or systemic VTE (pooled RR 1.93; 95% CI 0.72-5.13). The heterogeneity of the studies was not significant for any of the outcomes. CONCLUSIONS: The purpose of this study was to update the current understanding of the impact of perioperative tamoxifen on autologous breast free flap reconstruction outcomes. The existing literature supports that the perioperative continuation of tamoxifen in breast free flap patients is not associated with an increased risk of thrombotic flap complications, total flap loss, overall flap complications, or systemic VTE.