Association between choice of reversal agent for neuromuscular block and postoperative pulmonary complications in patients at increased risk undergoing non-emergency surgery: STIL-STRONGER, a multicentre matched cohort study.

BACKGROUND: Postoperative pulmonary complications are a source of morbidity after major surgery. In patients at increased risk of postoperative pulmonary complications we sought to assess the association between neuromuscular blocking agent reversal agent and development of postoperative pulmonary complications. METHODS: We conducted a retrospective matched cohort study, a secondary analysis of data collected in the prior STRONGER study. Data were obtained from the Multicenter Perioperative Outcomes Group. Included patients were aged 18 yr and older undergoing non-emergency surgery under general anaesthesia with tracheal intubation with neuromuscular block and reversal, who were predicted to be at elevated risk of postoperative pulmonary complications. This risk was defined as American Society of Anesthesiologists Physical Status 3 or 4 in patients undergoing either intrathoracic or intra-abdominal surgery who were either aged >80 yr or underwent a procedure lasting >2 h. Cohorts were defined by reversal with neostigmine or sugammadex. The primary composite outcome was the occurrence of pneumonia or respiratory failure. RESULTS: After matching by institution, sex, age (within 5 yr), body mass index, anatomic region of surgery, comorbidities, and neuromuscular blocking agent, 3817 matched pairs remained. The primary postoperative pulmonary complications outcome occurred in 224 neostigmine cases vs 100 sugammadex cases (5.9% vs 2.6%, odds ratio 0.41, P<0.01). After adjustment for unbalanced covariates, the adjusted odds ratio for the association between sugammadex use and the primary outcome was 0.39 (P<0.0001). CONCLUSIONS: In a cohort of patients at increased risk for pulmonary complications compared with neostigmine, use of sugammadex was independently associated with reduced risk of subsequent development of pneumonia or respiratory failure.

Neuromuscular Blockade and Reversal Practice Variability in the Outpatient Setting: Insights From US Utilization Patterns.

BACKGROUND: Neuromuscular blockade (NMB) is a critical part of many surgical procedures. Data on practice patterns of NMB agents (NMBAs) and NMB reversal in recent years in the US ambulatory surgical care setting are limited. METHODS: This retrospective analysis of US adult outpatients was conducted using the Premier Healthcare Database. We describe anesthesia practice trends in NMB management and assess the association of patient, procedural, and site characteristics with NMB reversal approach using multivariable logistic regression. RESULTS: Approximately 5.2 million outpatient surgical encounters involving NMB and 4.6 million involving rocuronium or vecuronium between January 2014 and June 2019 were included. Following the introduction of sugammadex to US clinical practice (~2016), there was an increased use of rocuronium or vecuronium and a decrease in succinylcholine alone. Before 2016, NMB was pharmacologically reversed with neostigmine in approximately two-thirds of outpatient encounters. Over time, active reversal increased; by 2019, 42.3% and 36.0% of encounters were reversed by neostigmine and sugammadex, respectively, with 21.7% undergoing spontaneous recovery. Choice of NMBA (rocuronium or vecuronium alone), time since 2016, obesity, peripheral vascular disease, and procedures on the digestive, ocular, and female genital systems (vs musculoskeletal procedures) were independently and positively associated with pharmacologic reversal (versus spontaneous reversal). Conversely, advanced age; Western geography; and cardiovascular, endocrine, hemic/lymphatic, respiratory, and ear, nose, and throat procedures were independently and negatively associated with pharmacologic reversal of NMB.Among pharmacologic reversals, time since 2016 was positively and independently associated with sugammadex compared with neostigmine (odds ratios [ORs], ranged from 1.8 in 2017 to 3.2, P < .0001 in 2019). Those administered rocuronium or vecuronium without succinylcholine, with increased age and history of certain comorbidities, and those undergoing ocular or respiratory procedures (compared with musculoskeletal) were positively associated with reversal with sugammadex and endocrine procedure negatively and independently associated with reversal with sugammadex. There was variability in the association of several factors with NMB reversal choices by geographic region, particularly in patients' race, ethnicity, and size of affiliated hospital. CONCLUSIONS: Overall, active pharmacological reversal of NMB increased in US adult outpatients following the introduction of sugammadex, although there remains significant practice variability. The multifactorial relationship between patient-, procedural-, and environmental-level characteristics and NMB management is rapidly evolving. Additional research on how these anesthesia practice patterns may be impacted by the shift to the ambulatory care setting and how they may impact patient outcomes and health disparities is warranted.

Neuromuscular Blocking Agents and Reversal Agents Among Hospitalized Children: A Cerner Database Study.

Background: Sugammadex (Bridion) was approved by the US Food and Drug Administration (FDA) in December 2015 for the reversal of neuromuscular block (NMB) induced by rocuronium and vecuronium bromide in adults undergoing surgery and approved for use in both adults and children in the European Union in 2008. Sugammadex use in children has been reported in the United States, but to what extent is not clear. Aims: The aim was to describe the utilization pattern of NMB agents and factors associated with the use of reversal agents (neostigmine and sugammadex) in US children. Methods: Cross-sectional study of children with exposure to NMB agents between 2015 and 2017 in the Cerner Health Facts® database, which is an electronic health record (EHR) database across 600 facilities in the United States. Logistic regression estimated factors associated with the use of sugammadex vs neostigmine. Results: A total of 27 094 pediatric clinical encounters were exposed to neuromuscular blocking agents (NMBAs), in which 21 845 were exposed to rocuronium (76%), vecuronium (18%), or both (6%). Among children with exposure to rocuronium and vecuronium, the use of sugammadex was 1.7% in 2016 and 7.6% in 2017. The multivariable logistic model suggested that children who were older (age 12-17 years vs 0-1 year; odds ratio [OR] 1.96; 95% confidence interval [CI], 1.36-2.83), Hispanic or Latino ethnicity and other ethnicities (vs non-Hispanic or Latino; OR 2.03 and 1.56; 95% CI, 1.55-2.67 and 1.15-2.13, respectively), in teaching facilities (OR 1.26; 95% CI, 1.00-1.59), or admitted through emergency departments (OR 1.65; 95% CI, 1.06-2.58) were independently more likely to receive sugammadex than neostigmine after controlling for other covariates. Conclusions: In Cerner Health Facts database 2015 to 2017, among children, rocuronium was more commonly used than vecuronium, and sugammadex use was observed since 2016. Sugammadex and neostigmine users varied by demographic, clinical, and site-level characteristics.

Sugammadex versus Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER): A Multicenter Matched Cohort Analysis.

BACKGROUND: Five percent of adult patients undergoing noncardiac inpatient surgery experience a major pulmonary complication. The authors hypothesized that the choice of neuromuscular blockade reversal (neostigmine vs. sugammadex) may be associated with a lower incidence of major pulmonary complications. METHODS: Twelve U.S. Multicenter Perioperative Outcomes Group hospitals were included in a multicenter observational matched-cohort study of surgical cases between January 2014 and August 2018. Adult patients undergoing elective inpatient noncardiac surgical procedures with general anesthesia and endotracheal intubation receiving a nondepolarizing neuromuscular blockade agent and reversal were included. Exact matching criteria included institution, sex, age, comorbidities, obesity, surgical procedure type, and neuromuscular blockade agent (rocuronium vs. vecuronium). Other preoperative and intraoperative factors were compared and adjusted in the case of residual imbalance. The composite primary outcome was major postoperative pulmonary complications, defined as pneumonia, respiratory failure, or other pulmonary complications (including pneumonitis; pulmonary congestion; iatrogenic pulmonary embolism, infarction, or pneumothorax). Secondary outcomes focused on the components of pneumonia and respiratory failure. RESULTS: Of 30,026 patients receiving sugammadex, 22,856 were matched to 22,856 patients receiving neostigmine. Out of 45,712 patients studied, 1,892 (4.1%) were diagnosed with the composite primary outcome (3.5% sugammadex vs. 4.8% neostigmine). A total of 796 (1.7%) patients had pneumonia (1.3% vs. 2.2%), and 582 (1.3%) respiratory failure (0.8% vs. 1.7%). In multivariable analysis, sugammadex administration was associated with a 30% reduced risk of pulmonary complications (adjusted odds ratio, 0.70; 95% CI, 0.63 to 0.77), 47% reduced risk of pneumonia (adjusted odds ratio, 0.53; 95% CI, 0.44 to 0.62), and 55% reduced risk of respiratory failure (adjusted odds ratio, 0.45; 95% CI, 0.37 to 0.56), compared to neostigmine. CONCLUSIONS: Among a generalizable cohort of adult patients undergoing inpatient surgery at U.S. hospitals, the use of sugammadex was associated with a clinically and statistically significant lower incidence of major pulmonary complications.

The impact of intra-abdominal pressure on perioperative outcomes in laparoscopic cholecystectomy: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic cholecystectomy involves using intra-abdominal pressure (IAP) to facilitate adequate surgical conditions. However, there is no consensus on optimal IAP levels to improve surgical outcomes. Therefore, we conducted a systematic literature review (SLR) to examine outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. METHODS: An electronic database search was performed to identify randomized controlled trials (RCTs) that compared outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. A Bayesian network meta-analysis (NMA) was used to conduct pairwise meta-analyses and indirect treatment comparisons of the levels of IAP assessed across trials. RESULTS: The SLR and NMA included 22 studies. Compared with standard IAP, on a scale of 0 (no pain at all) to 10 (worst imaginable pain), low IAP was associated with significantly lower overall pain scores at 24 h (mean difference [MD]: - 0.70; 95% credible interval [CrI]: - 1.26, - 0.13) and reduced risk of shoulder pain 24 h (odds ratio [OR] 0.24; 95% CrI 0.12, 0.48) and 72 h post-surgery (OR 0.22; 95% CrI 0.07, 0.65). Hospital stay was shorter with low IAP (MD: - 0.14 days; 95% CrI - 0.30, - 0.01). High IAP was not associated with a significant difference for these outcomes when compared with standard or low IAP. No significant differences were found between the IAP levels regarding need for conversion to open surgery; post-operative acute bleeding, pain at 72 h, nausea, and vomiting; and duration of surgery. CONCLUSIONS: Our study of published trials indicates that using low, as opposed to standard, IAP during laparoscopic cholecystectomy may reduce patients' post-operative pain, including shoulder pain, and length of hospital stay. Heterogeneity in the pooled estimates and high risk of bias of the included trials suggest the need for high-quality, adequately powered RCTs to confirm these findings.

Post-operative urinary retention is impacted by neuromuscular block reversal agent choice: A retrospective cohort study in US hospital setting.

STUDY OBJECTIVE: Perioperative neuromuscular blocking agents are pharmacologically reversed to minimize complications associated with residual neuromuscular block. Neuromuscular block reversal with anticholinesterases (e.g., neostigmine) require coadministration of an anticholinergic agent (e.g., glycopyrrolate) to mitigate muscarinic activity; however, sugammadex, devoid of cholinergic activity, does not require anticholinergic coadministration. Single-institution studies have found decreased incidence of post-operative urinary retention associated with sugammadex reversal. This study used a multicenter database to better understand the association between neuromuscular block reversal technique and post-operative urinary retention. DESIGN: Retrospective cohort study utilizing large healthcare database. SETTING: Non-profit, non-governmental and community and teaching hospitals and health systems from rural and urban areas. PATIENTS: 61,898 matched adult inpatients and 95,500 matched adult outpatients. INTERVENTIONS: Neuromuscular block reversal with sugammadex or neostigmine plus glycopyrrolate. MEASUREMENTS: Incidence of post-operative urinary retention by neuromuscular block reversal agent and the independent association of neuromuscular block reversal technique and risk of post-operative urinary retention. MAIN RESULTS: The incidence of post-operative urinary retention was 2-fold greater among neostigmine with glycopyrrolate compared to sugammadex patients (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients; both p < 0.0001). Multivariable logistic regression identified reversal with neostigmine to be independently associated with greater risk of post-operative urinary retention (inpatients: odds ratio, 2.20; 95% confidence interval, 2.00 to 2.41; p < 0.001; outpatients: odds ratio, 2.57; 95% confidence interval, 2.13 to 3.10; p < 0.001). Post-operative urinary retention-related visits within 2 days following discharge were five-fold higher among those reversed with neostigmine than sugammadex among inpatients (0.05% vs. 0.01%, respectively; p = 0.018) and outpatients (0.5% vs. 0.1%; p < 0.0001). CONCLUSION: Though this study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk, additional studies are needed to fully understand the association.

Trends in the use of neuromuscular blocking agents, reversal agents and neuromuscular transmission monitoring: a single-centre retrospective cohort study.

BACKGROUND: Residual neuromuscular blockade (rNMB) remains a persistent and preventable problem, with serious risks. METHODS: Our objective was to describe and assess patterns in the use of neuromuscular blocking agents (NMBAs), neuromuscular transmission (NMT) monitoring, and factors associated with the use of sugammadex. We performed a retrospective, observational cohort study based on electronic medical records in a large teaching hospital in the Netherlands that introduced an integrated NMT monitoring module with automatic recording in 2017. A total of 22,000 cases were randomly selected from all surgeries between January 2015 and December 2019 that required endotracheal intubation with the use of an NMBA. A total of 14,592 cases fulfilled all the inclusion criteria for complete analyses. RESULTS: Relative NMBA usage remained the same over time. For rocuronium, spontaneous reversal decreased from 86 to 81%, sugammadex reversal increased from 12 to 18%. There was a decline in patients extubated in the operating room (OR) with neither documented NMT monitoring nor sugammadex-mediated reversal from 46 to 31%. The percentage of patients extubated in the OR without a documented train-of-four ratio ≥ 0.9, decreased from 77 to 56%. Several factors were independently associated with the use of sugammadex, including BMI > 30 kg/m2 (odds ratio: 1.41; 95% CI: 1.24-1.60), ASA class 3 or 4 (1.20; 1.07-1.34), age > 60 years (1.37; 1.23-1.53), duration of surgery < 120 min (3.01; 2.68-3.38), emergency surgery (1.83; 1.60-2.09), laparoscopic surgery (2.01; 1.71-2.36), open abdominal/thoracic surgery (1.56; 1.38-1.78), NMT monitoring used (5.31; 4.63-6.08), total dose of rocuronium (1.99; 1.76-2.25), and (inversely) use of inhalational anaesthetics (0.88; 0.79-0.99). CONCLUSION: Our data demonstrate that the implementation of NMT monitoring with automatic recording coincides with a gradual increase in the (documented) use of NMT monitoring and an increased use of sugammadex with a more precise dose. Factors associated with sugammadex use include higher age, ASA score, BMI, abdominal and thoracic surgery, higher rocuronium doses, emergency surgery and the use of NMT monitoring. Trial registration N/A. KEY POINTS: • Introduction of NMT monitoring with automatic recording coincides with an increase in (documented) use of NMT monitoring. • Sugammadex is more frequently used in patients with a presumed higher a priori risk of pulmonary complications. • Despite increased NMT monitoring and use of sugammadex a significant percentage of patients remain at potential risk of rNMB.

Treatment patterns of patients with worsening heart failure with reduced ejection fraction.

AIMS: Patients with HFrEF and worsening HF events (WHFE) are at particularly high risk and urgently need disease-modifying therapy. CHART-HF assessed treatment patterns and reasons for medication decisions among HFrEF patients with and without WHFE. METHODS AND RESULTS: CHART-HF collected retrospective electronic medical records of outpatients with HF and EF < 45% between 2017-2019 from a nationwide panel of 238 cardiologists (458 patients) and the Geisinger Health System (GHS) medical record (1000 patients). The index visit in the WHFE cohort was the first outpatient cardiologist visit ≤6 months following the WHFE, and in the reference cohort was the last visit in a calendar year without WHFE. Demographic characteristics were similar between patients with and without WHFE in both the nationwide panel and GHS. In the nationwide panel, the proportion of patients with versus without WHFE receiving ≥50% of guideline-recommended dose on index visit was 35% versus 40% for beta blocker, 74% versus 83% for ACEI/ARB/ARNI, and 48% versus 49% for MRA. The proportion of patients receiving ≥50% of guideline-recommended dose was lower in the GHS: 29% versus 34% for beta-blocker, 16% versus 31% for ACEI/ARB/ARNI, and 18% versus 22% for MRA. For patients with and without WHFE, triple therapy on index date was 42% and 44% of patients from the nationwide panel, and 14% and 17% in the GHS. Comparing end of index clinic visit with 12-month follow-up in the GHS, the proportion of patients on no GDMT increased from 14% to 28% in the WHFE cohort and from 14 to 21% in the non-WHFE group. CONCLUSIONS: Major gaps in use of GDMT, particularly combination therapy, remain among US HFrEF patients. These gaps persist during longitudinal follow-up and are particularly large among patients with recent WHFE.

Contemporary outpatient management of patients with worsening heart failure with reduced ejection fraction: Clinical outcome results from the CHART-HF study.

Background: Based on available data from randomized clinical trials, patients with heart failure with reduced ejection fraction (HFrEF) and worsening HF events (WHFE) have substantial disease burden and poor outcomes. WHFE clinical outcome data in non-clinical trial patients, more representative of the US clinical practice, has not been demonstrated. Methods and results: CHART-HF collected data from two complementary, non-clinical trial cohort with HFrEF (LVEF <45 %): 1) 1,000 patients from an integrated delivery network and 2) 458 patients from a nationwide physician panel. CHART-HF included patients with WHFE between 2017 and 2019 followed by an index outpatient cardiology visit ≤6 months, and patients without WHFE in a given year between 2017 and 2019, with the last outpatient cardiology visit in the same year as the index visit. Compared to patients without WHFE (after covariate adjustment, all p < 0.05), patients with WHFE had a greater risk of HF-related hospitalization (hazard ratio [HR]: 1.53-2.40) and next WHFE event (HR: 1.67-2.41) following index visits in both cohorts. Conclusion: HFrEF patients with recent WHFE consistently had worse clinical outcomes in these non-clinical trial cohorts. Despite advances in therapies, unmet need to improve clinical outcomes in HFrEF patients with WHFE remains.

REVersal of nEuromusculAr bLocking Agents in Patients Undergoing General Anaesthesia (REVEAL Study).

Background: Neuromuscular blocking agent (NMBA) monitoring and reversals are key to avoiding residual curarization and improving patient outcomes. Sugammadex is a NMBA reversal with favorable pharmacological properties. There is a lack of real-world data detailing how the diffusion of sugammadex affects anesthetic monitoring and practice. Methods: We conducted an electronic health record analysis study, including all adult surgical patients undergoing general anesthesia with orotracheal intubation, from January 2016 to December 2019, to describe changes and temporal trends of NMBAs and NMBA reversals administration. Results: From an initial population of 115,046 surgeries, we included 37,882 procedures, with 24,583 (64.9%) treated with spontaneous recovery from neuromuscular block and 13,299 (35.1%) with NMBA reversals. NMBA reversals use doubled over 4 years from 25.5% to 42.5%, mainly driven by sugammadex use, which increased from 17.8% to 38.3%. Rocuronium increased from 58.6% (2016) to 94.5% (2019). Factors associated with NMBA reversal use in the multivariable analysis were severe obesity (OR 3.33 for class II and OR 11.4 for class III obesity, p-value < 0.001), and high ASA score (OR 1.47 for ASA III). Among comorbidities, OSAS, asthma, and other respiratory diseases showed the strongest association with NMBA reversal administration. Conclusions: Unrestricted availability of sugammadex led to a considerable increase in pharmacological NMBA reversal, with rocuronium use also rising. More research is needed to determine how unrestricted and safer NMBA reversal affects anesthesia intraoperative monitoring and practice.

Systematic review and meta-analysis of the efficacy of cardioversion by vernakalant and comparators in patients with atrial fibrillation.

PURPOSE: Rate and rhythm control are two well established treatment objectives for atrial fibrillation (AF) patients. While symptom reduction is a primary treatment goal, therapeutic practice related to cardioversion varies by region and patient, with several precautions associated with the use of current therapies. No comprehensive literature review on the relative efficacy of existing cardioversion approaches compared to newly available therapies has been conducted. METHODS AND RESULTS: A systematic literature review and meta-analysis were undertaken to evaluate the efficacy of pharmacologic therapies in eliciting cardioversion within 2 and 8-24 h among patients with recent-onset, short duration AF. Eligible studies included randomized controlled trials in which cardioversion rates were evaluated in at least 2 treatment groups. Bayesian mixed-treatment comparisons estimated odds ratios (95% credible intervals) for successful cardioversion. Results within 2 h showed vernakalant IV, propafenone IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24 h. Few adverse events were reported, with the most common being bradycardia and hypotension. CONCLUSIONS: In pair-wise comparisons of active treatment arms to one another, results suggest vernakalant IV, propafenone IV and flecainide appear to be effective in achieving rapid cardioversion in patients with short duration AF compared to other agents. Application of these findings to clinical practice need to account for the variable comorbidity profiles of patients, important determinants in the selection of appropriate therapy for individual patients. Though best practice methods were used, further research comparing treatments through direct head-to-head comparisons may be warranted to confirm these findings and further inform clinical practice.

RHYTHM-AF: design of an international registry on cardioversion of atrial fibrillation and characteristics of participating centers.

BACKGROUND: Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. METHODS/DESIGN: RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (±10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. DISCUSSION: A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve cardiovascular outcomes in patients with atrial fibrillation. TRIAL REGISTRATION: Clinical trials NCT01119716.

The Use of Muscle Relaxants and Reversal Agents in a Setting Without Cost Restrictions: Experience from a Tertiary Academic Hospital in the Netherlands.

Introduction: Muscle relaxants are often given during general anesthesia to facilitate endotracheal intubation. However lingering effects after anesthesia-end may lead to respiratory compromise in the PACU. Strategies to reduce these adverse events include monitoring neuromuscular block, the use of short-acting agents and active pharmacological reversal before extubation. At Leiden University Medical Center (LUMC), a tertiary care academic hospital in the Netherlands, various muscle relaxants and reversal agents are freely available to all clinicians without restrictions. In this setting, we intended to evaluate how patient and surgical characteristics impacted the use of these agents for a variety of non-cardiac surgeries. Material and Methods: This is a retrospective database study of adult patients that had received elective, non-cardiac surgery and general anesthesia with endotracheal intubation between 2016 and 2020 at LUMC in the Netherlands. Exclusion criteria consisted of patients pharmacologically reversed with both sugammadex and neostigmine during the same procedure, diagnosed with myasthenia gravis, receiving pyridostigmine therapy, or with renal failure (eGFR <30 mL.min.1.73m2). Results: We retrieved 23,373 patient records of which 9742 were excluded because one or more exclusion criteria were met. The final cohort consisted of 13,631 cases. Rocuronium was the most commonly used muscle relaxant (88.5%); sugammadex was the most commonly used reversal agent (99.9% of those pharmacologically reversed). Of all cases that received rocuronium as muscle relaxant, 76.9% of patients were not reversed, while 23.1% were reversed with sugammadex. The odds of reversal increased with age, BMI, ASA class (1-3) and shorter duration of surgery. Conclusion: In an unrestricted clinical environment, rocuronium and sugammadex are the preferred agents for muscle relaxation and reversal. Pharmacologic reversal of neuromuscular block was uncommon overall, but more likely in older and obese patients, higher ASA classification and shorter lasting procedures. Sugammadex has largely replaced neostigmine for this purpose.

Race differences in access to health care and disparities in incident chronic kidney disease in the US.

BACKGROUND: The contribution of race differences in access to health care to disparities in chronic kidney disease (CKD) incidence in the United States is unknown. METHODS: We examined race differences in usual source of health care, health insurance and CKD incidence among 3883 Whites and 1607 Blacks with hypertension or diabetes enrolled in the Atherosclerosis Risk in Communities Study. In multivariable analyses, we explored the incremental contribution of access to health care in explaining Blacks' excess CKD incidence above and beyond other socioeconomic, lifestyle and clinical factors. RESULTS: Compared with Whites, Blacks had poorer access to health care (3 vs 0.3% with no usual source of health care or health insurance, P < 0.001) and experienced greater CKD incidence (14.7 vs 12.0 cases per 1000 person-years, P < 0.001). Blacks' excess risk of CKD persisted after adjusting for demographic, socioeconomic, lifestyle and clinical factors [hazard ratio (HR) (95% confidence interval (95% CI)) = 1.21 (1.01-1.47)]. Adjustment for these factors explained 64% of the excess risk among Blacks. The increased risk for CKD among Blacks was attenuated after additional adjustment for race differences in access to health care [HR (95% CI) = 1.19 (0.99-1.45)], which explained an additional 10% of the disparity. Conclusions. In this population at risk for developing CKD, we found that poorer access to health care among Blacks explained some of Blacks' excess risk of CKD, beyond the excess risk explained by demographic, socioeconomic, lifestyle and clinical factors. Improved access to health care for high-risk individuals could narrow disparities in CKD incidence.

Albuminuria and estimated glomerular filtration rate independently associate with acute kidney injury.

Acute kidney injury (AKI) is increasingly common and a significant contributor to excess death in hospitalized patients. CKD is an established risk factor for AKI; however, the independent graded association of urine albumin excretion with AKI is unknown. We analyzed a prospective cohort of 11,200 participants in the Atherosclerosis Risk in Communities (ARIC) study for the association between baseline urine albumin-to-creatinine ratio and estimated GFR (eGFR) with hospitalizations or death with AKI. The incidence of AKI events was 4.0 per 1000 person-years of follow-up. Using participants with urine albumin-to-creatinine ratios <10 mg/g as a reference, the relative hazards of AKI, adjusted for age, gender, race, cardiovascular risk factors, and categories of eGFR were 1.9 (95% CI, 1.4 to 2.6), 2.2 (95% CI, 1.6 to 3.0), and 4.8 (95% CI, 3.2 to 7.2) for urine albumin-to-creatinine ratio groups of 11 to 29 mg/g, 30 to 299 mg/g, and ≥300 mg/g, respectively. Similarly, the overall adjusted relative hazard of AKI increased with decreasing eGFR. Patterns persisted within subgroups of age, race, and gender. In summary, albuminuria and eGFR have strong, independent associations with incident AKI.

Heart rate variability predicts ESRD and CKD-related hospitalization.

Autonomic imbalance, a feature of both diabetes and hypertension, may contribute to adverse cardiovascular outcomes. In animal models, sympathetic nerve activity contributes to renal damage but the extent to which autonomic dysfunction precedes the development of CKD and ESRD in humans is unknown. We measured resting heart rate and heart rate variability in 13,241 adults (45- to 64-years old) followed for a median of 16 years in the Atherosclerosis Risk in Communities (ARIC) Study. We examined heart rate parameters by quartiles, defining those in the lowest quartile (by time and frequency domain measures separately) as the risk group of interest. We identified 199 cases of incident ESRD and 541 patients with CKD-related hospitalizations; higher resting heart rate and lower heart rate variability associated with both outcomes. The fully adjusted hazard ratios for ESRD were 1.98 (95% confidence interval [CI] 1.45 to 2.70) among those in the highest heart rate quartile and 1.56 (95% CI 1.14 to 2.14) for high-frequency power. Other time and frequency domain measures were similarly and significantly associated with ESRD and CKD-related hospitalizations. These results suggest that autonomic dysfunction may be an important risk factor for ESRD and CKD-related hospitalizations and call for further studies to define the mechanisms that underlie these associations.

A Clinical and Budgetary Impact Analysis of Introducing Sugammadex for Routine Reversal of Neuromuscular Blockade in a Hypothetical Cohort in the US.

INTRODUCTION: Sugammadex rapidly reverses the effects of rocuronium- and vecuronium-induced neuromuscular blockade (NMB), offering a more complete and predictable NMB recovery than cholinesterase inhibitors. Despite clinical benefits, cost pressures on hospital budgets influence the choice of the NMB reversal method. This study evaluated clinical and healthcare system payer's budget impacts associated with sugammadex in the US for routine reversal of moderate or deep rocuronium- or vecuronium-induced NMB in adults undergoing surgery. METHODS: A 1-year decision analytic model was constructed reflecting a set of procedures using rocuronium or vecuronium that resulted in moderate or deep NMB at the end of surgery. Two scenarios were considered for a hypothetical cohort of 100,000 patients: without sugammadex versus with sugammadex. Comparators included neostigmine (+glycopyrrolate) and no neuromuscular blocking agents (NMBAs). Total costs (in 2019 US dollars) to a healthcare system [net of costs of reversal agents and overall cost offsets via reduction in postoperative pulmonary complications (PPC)] were compared. RESULTS: A total of 9971 surgical procedures utilized rocuronium or vecuronium, resulting in moderate (91.0% of cases) or deep (9.0%) blockade at the end of surgeries. In the with sugammadex scenario, sugammadex replaced neostigmine in 4156 of 9585 procedures versus the without sugammadex scenario that used only neostigmine for NMB reversal. Introducing sugammadex reduced PPC events by 12% (58 cases) among the modeled procedures, leading to a budget impact of -$3,079,703 (-$309 per modeled procedure, or a 10.9% reduction in total costs). The results did not vary qualitatively in one-way sensitivity analyses. CONCLUSIONS: The additional costs of sugammadex for the reversal of rocuronium- or vecuronium-induced NMB could be offset by improved outcomes (i.e., reduced PPC events), and potentially lead to overall healthcare budgetary savings versus reversal with neostigmine or spontaneous recovery. This study provides insights into savings that can be obtained beyond the anesthesia budget, reducing the broader clinical and budgetary burden on the hospital.

Neuromuscular Blockade and Reversal Agent Practice Variability in the US Inpatient Surgical Settings.

INTRODUCTION: The management of neuromuscular blockade (NMB) has evolved over time and remains a critical component of general anesthesia. However, NMB use varies by patient and procedural characteristics, clinical practices, protocols, and drug access. National utilization patterns are unknown. We describe changes in NMB and NMB reversal agent administration in surgical inpatients since the US introduction of sugammadex in December 2015. METHODS: In a retrospective observational study of inpatients involving NMB with rocuronium or vecuronium in the Premier Healthcare Database, we estimate associations between factors related to choice of (1) active NMB reversal versus spontaneous recovery and (2) sugammadex versus neostigmine as the reversal agent. RESULTS: Among 4.3 million adult inpatient encounters involving rocuronium or vecuronium, the most widely administered NMB agent was rocuronium alone (86%). Over time, gradual declines in both neostigmine use and spontaneous reversal were observed (64% and 36% in 2014 to 38% and 28%, respectively in the first half of 2019). Several factors were independently associated with use of active versus spontaneous NMB recovery including years since 2016, patient (age, race, comorbidities), and procedure (admission and surgery type) characteristics. Among those actively reversed, these and other factors were independently associated with choice of reversal agent administered, including size and teaching affiliation of hospital. While both impacted choices in treatment, the direction and magnitude of effect of patient comorbidities and procedure type varied in their impact on choice of mode (pharmacologic vs. spontaneous) and agent (neostigmine vs. sugammadex) of NMB reversal independent of other factors and each other. Sites which adopted sugammadex earlier were more likely to choose sugammadex over neostigmine compared with later adopters independent of other factors. CONCLUSIONS: Among US adult inpatients administered NMBs, we observed complex relationships between patient, site, procedural characteristics, and NMB management choices as NMBA choice and active reversal options among inpatient cases changed over time.

Neuromuscular blocking agents, medications that temporarily paralyze muscles, are used frequently during surgical procedures to facilitate intubation and patient immobility. Over time, muscle function can return spontaneously or through pharmacological reversal agents. This study looked at how the use of reversal agents in inpatients undergoing surgical procedures changed after a new reversal agent, sugammadex, became available for use in the USA in December 2015.Medical records of 4.3 million adult patients treated with neuromuscular blocking agents (rocuronium or vecuronium) in the USA were studied. In 2014 (before sugammadex was available), one-third of patients (36%) recovered spontaneously from a neuromuscular blocking agent and two-thirds (64%) were treated with the reversal agent neostigmine. The use of both neostigmine and spontaneous recovery reduced gradually after sugammadex became available, so that by the first half of 2019, 38% of patients were treated with neostigmine and 28% of patients recovered spontaneously.Whether or not a patient was treated with a reversal agent and what type of agent was chosen were affected by the length of time since 2016, patient characteristics, the type of surgical procedure that was performed as well as local hospital characteristics and practice differences.

Risk of incident ESRD: a comprehensive look at cardiovascular risk factors and 17 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Diabetes and hypertension are potent risk factors for end-stage renal disease (ESRD). Previous studies suggest that other cardiovascular risk factors also may increase the risk of ESRD; however, risk associated with a comprehensive cardiovascular risk-factor assessment has not been quantified in a population-based sample. STUDY DESIGN: The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort. SETTING & PARTICIPANTS: 15,324 white and African American participants aged 45-64 years from 4 US communities were followed up after a baseline visit that occurred in 1987-1989. PREDICTOR: A comprehensive collection of cardiovascular risk factors were examined. OUTCOMES & MEASUREMENTS: Incidence of ESRD (transplant, dialysis, catheter placement or kidney failure, and death) exclusive of acute kidney failure was ascertained through active surveillance of hospitalizations through 2004. RESULTS: During a median 16-year follow-up, 241 cases of ESRD developed (incidence rate, 1.04 cases/1,000 person-years). Male sex, African American race, diabetes, hypertension, history of coronary heart disease, smoking, older age, body mass index, and triglyceride concentration were associated with increased risk of ESRD after adjustment for baseline estimated glomerular filtration rate (eGFR) and each other. There was a graded curvilinear association between risk of ESRD and lower baseline eGFR at levels < 90 mL/min/1.73 m(2) and moderately increased levels > 120 mL/min/1.73 m(2). The relative risk of eGFR on ESRD risk generally was greater in women and individuals with diabetes than in their counterparts. LIMITATIONS: Only events occurring in acute-care hospitals were investigated (but there was long-term continuous active surveillance of events). CONCLUSIONS: We quantify the relative risk of ESRD in a community-based African American and white population associated with established cardiovascular risk factors (diabetes, hypertension, male sex, and African American race) and report prospective data identifying greater risk of ESRD associated with other cardiovascular risk factors: moderately decreased eGFR, increased eGFR, higher body mass index, smoking, and increased triglyceride level.

Risk implications of the new CKD Epidemiology Collaboration (CKD-EPI) equation compared with the MDRD Study equation for estimated GFR: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently published an equation for estimated glomerular filtration rate (eGFR) using the same variables (serum creatinine level, age, sex, and race) as the Modification of Diet in Renal Disease (MDRD) Study equation. Although the CKD-EPI equation estimates GFR more precisely compared with the MDRD Study equation, whether this equation improves risk prediction is unknown. STUDY DESIGN: Prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study. SETTING & PARTICIPANTS: 13,905 middle-aged participants without a history of cardiovascular disease with median follow-up of 16.9 years. PREDICTOR: eGFR. OUTCOMES & MEASUREMENTS: We compared the association of eGFR in categories (>or=120, 90-119, 60-89, 30-59, and <30 mL/min/1.73 m(2)) using the CKD-EPI and MDRD Study equations with risk of incident end-stage renal disease, all-cause mortality, coronary heart disease, and stroke. RESULTS: The median value for eGFR(CKD-EPI) was higher than that for eGFR(MDRD) (97.6 vs 88.8 mL/min/1.73 m(2); P < 0.001). The CKD-EPI equation reclassified 44.9% (n = 3,079) and 43.5% (n = 151) of participants with eGFR(MDRD) of 60-89 and 30-59 mL/min/1.73 m(2), respectively, upward to a higher eGFR category, but reclassified no one with eGFR(MDRD) of 90-119 or <30 mL/min/1.73 m(2), decreasing the prevalence of CKD stages 3-5 from 2.7% to 1.6%. Participants with eGFR(MDRD) of 30-59 mL/min/1.73 m(2) who were reclassified upward had lower risk compared with those who were not reclassified (end-stage renal disease incidence rate ratio, 0.10 [95% CI, 0.03-0.33]; all-cause mortality, 0.30 [95% CI, 0.19-0.48]; coronary heart disease, 0.36 [95% CI, 0.21-0.61]; and stroke, 0.50 [95% CI, 0.24-1.02]). Similar results were observed for participants with eGFR(MDRD) of 60-89 mL/min/1.73 m(2). More frequent reclassification of younger, female, and white participants explained some of these trends. Net reclassification improvement in participants with eGFR < 120 mL/min/1.73 m(2) was positive for all outcomes (P < 0.001). LIMITATIONS: Limited number of cases with eGFR < 60 mL/min/1.73 m(2) and no measurement of albuminuria. CONCLUSIONS: The CKD-EPI equation more appropriately categorized individuals with respect to long-term clinical risk compared with the MDRD Study equation, suggesting improved clinical usefulness in this middle-aged population.