Intraoperative Hypotension and Acute Kidney Injury in Non-Cardiac Surgery at Providence Sacred Heart Medical Center

Background Acute kidney injury (AKI) is a serious postoperative complication that increases a patient’s risk for both long and short-term morbidity and mortality.1 Intraoperative hypotension (IOH) is an independent risk factor for AKI,2-5 which can be readily modified by anesthesia providers. This project aims to describe the risk factors and rates of AKI following IOH at various absolute mean arterial blood pressure (MAP) thresholds for specified durations of time among adults undergoing non-cardiac surgery at Providence Sacred Heart Medical Center (PSHMC). Methods PSHMC approved this retrospective, observational evidence-based project and deemed the project exempt by the Institutional Review Board from human subjects testing. Project inclusion criteria consisted of adults undergoing general anesthesia for non-cardiac surgery at PSHMC from 2015-2019 with pre- and postoperative serum creatinine lab results to evaluate for AKI via the KDIGO Criteria. Obstetrics, urology, dialysis history and records with missing serum creatinine values were excluded. The study group was further stratified by recorded MAP measurement intervals of ≤ 5 minutes to capture IOH. An a-priori power analysis revealed 2,181 records would power results (1-β=0.80, α=0.05, Df=1, W=0.06). PSHMC sponsor extracted, deidentified, encrypted and stored data in a HIPAA compliant REDCap database. Project team members performed univariate, bivariate and multivariable analyses using Microsoft Excel, MedCalc and G*Power platforms on PSHMC designated computers. Discussion Project findings revealed that 8.3% of patients had both pre- and postoperative serum creatinine results to evaluate for AKI. Of this study population (n=4,603), 8.9% experienced postoperative AKI. The literature reports rates of AKI to be 5- 7.5%. 5 Risk for AKI increased from 7.7% to 11.3% among patients exposed to MAPs less than 60mmHg for at least 10 minutes (RR 1.48, 95% CI [1.19-1.84], p\u3c0.001). According to the literature, AKI risk increases with the duration and severity of IOH exposure. 5 In a fully adjusted model, IOH, ASA 4 or greater, history of chronic kidney disease, baseline eGFR less than 60 ml/min/1.73m2 , and vascular surgery were identified as independent risk factors for AKI at PSHMC. Exploring AKI rates and risk factors at PSHMC helps identify potential areas of anesthesia practice improvement and informs further research surrounding AKI. As blood pressure is a modifiable risk factor for AKI, limiting IOH exposure may mitigate end organ damage and improve patient outcomes.https://digitalcommons.psjhealth.org/other_pubs/1103/thumbnail.jp

Postoperative Length of Stay Following Enhanced Recovery After Surgery Protocol Implementation for Scheduled Cesarean Deliveries

Background Cesarean delivery is the most common major surgery worldwide. 1 In 2018, 1.2 million cesarean deliveries occurred in the United States, accounting for nearly 32% of all deliveries.2 Research has shown ERAS benefits include decreased length of stay, improved pain control, and improved patient satisfaction.2,3 Despite its use in numerous surgical specialties, ERAS implementation within obstetrics has been slow.2 The ERAS Society released a three-part guideline specific to cesarean deliveries in 2018 and 2019,4,5,6 yet few studies have assessed the impact of ERAS on cesarean postoperative outcomes.2 An improved perioperative course would be particularly beneficial for mothers undergoing cesarean delivery as they require a quick recovery in order to care for their newborn. The purpose of this retrospective, observational study was to determine how the recovery process following cesarean delivery may be improved by standardizing the perioperative care pathway, with the primary outcome of interest being postoperative length of stay. Methods • Design: Retrospective, observational cohort study at Providence Sacred Heart Medical Center (PSHMC) • This project was approved by the PSHMC Clinical Innovation and Research Council and deemed exempt from human subjects research by Providence Health Care Institutional Review Board. • Human subjects protection: Patient demographic and surgical data from electronic medical records were extracted, deidentified, and encrypted using a REDCap data collection tool • Inclusion Criteria: parturients 18 years of age or older who underwent scheduled cesarean delivery between June 1, 2017 to May 31, 2018 for pre-intervention group and June 1, 2019 to February 29, 2019 for postintervention group. • Exclusion Criteria: urgent or emergent cesarean deliveries, cesarean deliveries occurring in the run-in time period of June 1, 2018 through May 31, 2019, and mothers under the age of 18 years. • Outcome measurement: postoperative length of stay, defined as time of end of surgery to time of discharge • Exposure measurement: defined as post-ERAS protocol implementation following April 1, 2019. • Other variables considered included: age, weeks gestation, BMI, ASA, primary vs repeat cesarean, weeks gestation, and multiparty births. • Statistical analysis: a-prior power analysis, univariate analysis, bivariate analysis, and multivariate analysis Discussion In this retrospective observational study, this facility’s postoperative LOS following cesarean delivery was found to be low, with a median of 52.4 hours. Following ERAS implementation, the median postoperative LOS decreased to 51.2 hours but was not found to be statistically significant in an adjusted model. Cesarean deliveries comprised nearly 29% of all births at this facility, 58.5% of which were scheduled or elective cesarean deliveries. Characteristics of parturients were very similar among the pre- and post-ERAS patient groups; most patients were classified as ASA 2 and a mean age of 31 years. Repeated multivariate analysis using run-in periods of varying lengths and controlling for time consistently showed no significant difference in postoperative LOS between the pre-ERAS and post-ERAS groups. With the postoperative LOS at PSHMC being low prior to protocol implementation, it is likely that other facilities with longer postoperative LOS may see a greater benefit of ERAS implementation. Additional work is still required to further the understanding of ERAS for cesarean deliveries and its impact on postoperative recovery. Future studies of interest includes determining 30-day readmission rates and emergency room visits following discharge. In order to determine the true effect ERAS may have on postoperative length of stay and the recovery process following cesarean delivery, large prospective control trials are needed.https://digitalcommons.psjhealth.org/other_pubs/1110/thumbnail.jp

Opioid Consumption After Scheduled Cesarean Delivery Following Implementation of Enhanced Recovery After Surgery

Background With 47,600 opioid overdose related deaths in the U.S. in 2017, the opioid crisis is of national concern.1 Cesarean delivery is the most common surgery worldwide, with over 1.2 million in the U.S. in 2018 alone.2,3 As cesarean delivery is a highly prevalent surgery it has a large capacity to influence the opioid epidemic. Literature is showing that Enhanced Recovery after Surgery (ERAS) and multimodal analgesia are effective means of managing postoperative pain while minimizing opioid use.4,5,6,7,8 This project aims to help discover if introduction of ERAS, and more specifically it’s multimodal analgesia aspect, has helped decrease oral morphine milligram equivalent (MME) consumption of opioids following cesarean delivery. Methods • Design: Retrospective Observational Cohort Study • Human Subjects Protection: Data fully de-identified and stored only in a secure REDCap database; patient care was not altered • Inclusion Criteria: Adult women undergoing scheduled cesarean delivery at Providence Sacred Heart Medical Center, Spokane, WA • Exclusion Criteria: Urgent/emergent cesarean delivery, use of an intravenous opioid patient-controlled analgesia (PCA) device • Measured Outcome: Cumulative 72-hr oral MME consumption following cesarean delivery • Baseline Comparability Demographics: Age, ASA, BMI, gravida/parity, weeks gestation, prior cesarean delivery, multiple birth, estimated blood loss, etc. (table 1) • Statistical Analysis: • A Priori Power Analysis: n=670 (n=335 per group) participants for adequate power (α=0.5, β=0.2) • Bivariate Analysis: Independent Samples T-Test (symmetrical data) and Mann Whitney U Test (skewed data) • Multivariate Analysis: An interrupted time series was conducted for comparison of oral median MME over time • Split File Analysis conduced to confirm accuracy of findings Discussion The implementation of ERAS and use of multimodal analgesia led to a sustained MME decrease among women utilizing opioids post scheduled cesarean delivery. The pre-implementation group (n=464) utilized a median of 90 [IQR 37.5-165] oral MME while the post-implementation group (n=514) used 71.3 [IQR 30-127.5] median oral MME (p\u3c0.01). This was a difference of 18.7 oral MME, or a 21% reduction. The use of multimodal analgesia following scheduled cesarean delivery is an effective means of managing postoperative pain while also reducing the need for opioids.https://digitalcommons.psjhealth.org/other_pubs/1109/thumbnail.jp

Rate of Unscheduled Administration of an Epidural Bolus Among Pregnant Women Receiving Labor Epidurals

Background The labor and delivery process is a painful experience that pregnant women undergo and while various medical options are available for managing labor pain, labor epidurals are the most common.1,3 Breakthrough pain, or inadequate analgesia, is a significant complication of labor epidurals that is typically managed with the administration of an unscheduled epidural bolus. The purpose of this evidence-based practice (EBP) project is to describe the rate of unscheduled epidural bolus administration in pregnant women receiving continuous labor epidurals (CLE) at Providence Sacred Heart Medical Center (PSHMC) and Providence Holy Family Hospital (PHFH). Methods • Design: Retrospective, observational, EBP project • Human subjects protection: De-identified data was extracted into a HIPPA compliant REDCap database after facility approval and IRB exemption • Inclusion Criteria: Parturient women age ≥18 with labor epidurals at PSHMC and PHFH from January 2015 to December 2019 (Table 1) • Outcome Measurement: Unscheduled provider administered epidural bolus after epidural initialization (Figure 1) • Bivariate: T-tests (symmetrical continuous data), Mann Whitney U (skewed continuous data), Chi-Test (categorical data) • Multivariate: Kaplan Meier analysis performed on epidural bolus timing (Figure 2) • Multivariate multivariable: Proportional hazards model was used to identify independent risk factors associated with time to first unscheduled provider administered epidural bolus (Table 2) Discussion We found that approximately 36.7% of parturient women with a CLE required at least one unscheduled provider administered epidural bolus. Gravida 1, elective case type, increased BMI and CLE duration were identified as independent risk factors associated with receiving a provider bolus. Of the identified risk factors, gravida 1 was the most significant with women having a 1.22 increase in risk of requiring an unscheduled provider administered epidural bolus (hazard risk 1.22; 95% CI 1.14 – 1.31; p \u3c0.001). The rate of 36.7% is higher compared to literature reported rates of 30.7% and 14.4% from RCTs and observational studies that had comparable epidural regimens and techniques to our facilities. 2,4,5 Further in-depth investigation is warranted in describing with more detail the patient characteristics and anesthesia provider practices as they relate to unscheduled epidural bolus administration.https://digitalcommons.psjhealth.org/other_pubs/1104/thumbnail.jp

Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents

Proteins of the CLCA gene family including the human ClCa1 (hClCa1) have been suggested to constitute a new family of chloride channels mediating Ca2+-dependent Cl− currents. The present study examines the relationship between the hClCa1 protein and Ca2+-dependent Cl− currents using heterologous expression of hClCa1 in HEK293 and NCIH522 cell lines and whole cell recordings. By contrast to previous reports claiming the absence of Cl− currents in HEK293 cells, we find that HEK293 and NCIH522 cell lines express constitutive Ca2+-dependent Cl− currents and show that hClCa1 increases the amplitude of Ca2+-dependent Cl− currents in those cells. We further show that hClCa1 does not modify the permeability sequence but increases the Cl− conductance while decreasing the GSCN−/GCl− conductance ratio from ∼2–3 to ∼1. We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers. We conclude that hClCa1 does not form Ca2+-dependent Cl− channels per se or enhance the trafficking/insertion of constitutive channels in the HEK293 and NCIH522 expression systems. Rather, hClCa1 elevates the single channel conductance of endogenous Ca2+-dependent Cl− channels by lowering the energy barriers for ion translocation through the pore

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Intraoperative Hypotension and Acute Kidney Injury in Non-cardiac Surgery at a Large Tertiary Care Medical Center.

Acute kidney injury (AKI) is a serious postoperative complication that increases patients\u27 risk for long- and shortterm morbidity and mortality. Risk for developing AKI increases following intraoperative hypotension (IOH). This project aimed to describe the rate of and establish IOH as an independent risk factor for AKI among adults undergoing non-cardiac surgery at a large tertiary care medical center. An observational, retrospective, evidence-based practice project was conducted. Records were extracted for adults undergoing general anesthesia for non-cardiac surgery from 2015 to 2019 with available serum creatinine laboratory results. The primary project outcome was postoperative AKI. Among 4,603 cases, 8.9% experienced postoperative AKI. Cases with IOH (MAPs less than 60 mmHg for at least 10 minutes) compared to cases without IOH had increased risks for AKI (RR 1.48, 95% CI [1.19-1.84], P\u3c.001). In a fully adjusted model, IOH was an independent risk factor for AKI (OR 1.50, 95% CI [1.18-1.92], P=.001). Among cases with serum creatinine laboratory results, the rate of AKI was higher than reported literature rates. IOH was confirmed as an independent risk factor. Quantifying the rate of and risk factors for AKI may precipitate heightened attention to prevention strategies and encourage quality improvement initiatives