Characterizing the Stability of Angiotensin II in 0.9% Sodium Chloride Using High Performance Liquid Chromatography and Liquid Chromatography Tandem Mass Spectrometry.

Purpose: The purpose of this study was to evaluate the stability of angiotensin II in 0.9% sodium chloride for up to 5 days. Methods: We prepared angiotensin II dilutions, by aseptically diluting 2.5 mg (1 mL) in 249 mL 0.9% sodium chloride creating a solution of 10 000 ng/mL. Admixtures were stored under refrigeration (5 ± 3°C). Stability of the dilution was assessed by: preservation of clarity, consistency of pH, and retention of concentration. Solutions were sampled at times 0, 24, 48, 72, 96, 120 hours. Solutions were analyzed via High-Performance Liquid Chromatography (HPLC-UV) and Liquid Chromatography Mass Spectrometry (LC-MS/MS). Retention of concentration was set a priori at > 90% of initial concentration. Results: Clarity, color, and pH at all sample time points remained constant. Both methods of analysis confirmed similar results. When stored under refrigeration, the concentration of angiotensin II solution remained above 90% of initial concentration throughout the entire sampling period. Conclusions: Angiotensin II in 0.9% sodium chloride stored in infusion bags under refrigeration (5 ± 3°C) maintained at least 90% of their original concentrations for up to 5 days. Stability was also demonstrated based on turbidity, color, and pH assessment.

Retrospective evaluation of LCP-tacrolimus (Envarsus XR) dosing in de novo kidney transplant.

INTRODUCTION: Tacrolimus is known to exhibit significant inter- and intra-patient pharmacokinetic (PK) and pharmacodynamic (PD) variability regarding therapeutic response. LCP-tacrolimus (LCPT-Envarsus XR) was approved in 2018 for use as a de novo immunosuppressive agent in kidney transplants, but there is limited evidence to guide de novo dosing of LCPT in patients with obesity. The primary objective of this study was to evaluate the impact of different calculated weight-based de novo LCPT dosing on early transplant outcomes. METHODS: This was a retrospective study of patients with obesity (BMI ≥ 30 kg/m2 ) who received a kidney transplant at the University of Illinois Hospital and Health System (UIH), between March 2019 and March 2021. Subjects were included if were age 18 years or older and received de novo LCPT throughout index hospitalization. The primary endpoint of this study was to compare correlations between the first tacrolimus trough level and dosing weight strategy (e.g., TBW, AdjBW, IBW). RESULTS: There was a statistically significant, though modest, correlation between all three dosing strategies and the first tacrolimus trough level (TBW correlation coefficient = .431, p < .001; AdjBW correlation coefficient = .455, p < .001; IBW correlation coefficient = .465; p < .001). In regression modeling for supratherapeutic levels each additional .01 mg/kg increase in dose by TBW, AdjBW, and IBW increased the odds of a supratherapeutic level by 1.46, 1.34, and 1.24, respectively (p < .001). CONCLUSIONS: The use of LCPT in kidney transplant recipients with obesity dosed using TBW demonstrated the strongest correlation with initial supratherapeutic tacrolimus levels. Larger prospective studies are needed to investigate the further impact of body weight on dosing regimens in the obese population.

Effects of angiotensin II in the management of perioperative hypotension in kidney transplant recipients.

BACKGROUND: Due to the mechanisms of action of conventional catecholamine vasopressors, there is increased risk of renal allograft injury and adverse events in transplant recipients with fluid-refractory distributive shock during the perioperative period. As such, mechanistically alternative vasopressors like angiotensin II (ATII) may avoid these complications, but there is an absence of data supporting use in this population. METHODS: This was a single-center, single-arm, open-label, phase 4 study conducted as a 1-year pilot of 20 adult renal transplant recipients receiving ATII as their first continuous infusion vasopressor in the perioperative period. The study aim was to systematically assess the safety and hemodynamic effects of ATII. Safety was assessed based on the incidence of adverse events. Hemodynamic effect was assessed by the achievement of per protocol hemodynamic goals (i.e., SBP ≥120 mmHg) and the need for adjunct vasopressors. RESULTS: Most cases involved deceased donors (70%), with a corresponding mean (SD) cold ischemia time of 14.7 (8.6) h. Over a surgery duration of 5.3 (1.2) h, subjects received 3.2 (2.0) L of total volume resuscitation prior to ATII initiation. No adverse events were directly related to ATII administration. Throughout this period, ATII was utilized for a median of 1.0 (IQR, 1.5) h intraoperatively (N = 7), 26.5 (IQR, 84.8) h postoperatively (N = 4), and 63.8 (IQR, 57.8) h in subjects who required ATII both intra- and postoperatively (N = 9). Only one of the 20 patients needed adjunct continuous infusion vasopressors in addition to ATII. CONCLUSIONS: Based on the observations of this pilot study, ATII is a safe and effective vasopressor option for renal transplant recipients requiring perioperative hypotension reversal.

Catecholamine Vasopressor Exposure Is Associated With Early Poor Allograft Function and Adverse Events in Living Donor Kidney Transplant Recipients.

BACKGROUND: Hypoperfusion leads to allograft injury during kidney transplantation. Catecholamine vasopressors are used to maintain blood pressure in the perioperative period but have demonstrated negative outcomes in the deceased-donor kidney transplant population. Little is known regarding living donor kidney transplants (LDKTs) and vasopressor use. The aim of this study is to describe the incidence of vasopressor use in LDKT and characterize its effects on allograft function and patient outcomes. METHODS: This retrospective, observational cohort study included adult patients who underwent an isolated LDKT between August 1, 2017, and September 1, 2018. Patients were divided into those who received perioperative vasopressors and those who did not. The primary objective was to compare allograft function between LDKT recipients that received vasopressors and those who did not. Secondary outcomes included safety endpoints and the identification of clinical variables associated with vasopressor use. RESULTS: A total of 67 patients received an LDKT during the study period. Of those, 25 (37%) received perioperative vasopressors, and 42 (62%) did not. Poor graft function, as defined by the development of slow or delayed graft function, occurred more frequently in patients receiving perioperative vasopressors compared with those who did not (6 [24%] vs 1 [2.4%], P = .016). In multivariable regression modeling, only perioperative vasopressors were statistically significantly associated with poor graft function. In addition, patients exposed to vasopressors experienced more postoperative arrhythmias (8 [32%] vs 1 [4.8%], P = .0025). CONCLUSION: Using perioperative vasopressors was independently associated with worsened early renal allograft function, including delayed graft function and adverse events in the LDKT population.

Surgical opioid-avoidance protocol: a postoperative pharmacological multimodal analgesic intervention in diverse patient populations.

INTRODUCTION: This study evaluated the effect of a surgical opioid-avoidance protocol (SOAP) on postoperative pain scores. The primary goal was to demonstrate that the SOAP was as effective as the pre-existing non-SOAP (without opioid restriction) protocol by measuring postoperative pain in a diverse, opioid-naive patient population undergoing inpatient surgery across multiple surgical services. METHODS: This prospective cohort study was divided into SOAP and non-SOAP groups based on surgery date. The non-SOAP group had no opioid restrictions (n=382), while the SOAP group (n=449) used a rigorous, opioid-avoidance order set with patient and staff education regarding multimodal analgesia. A non-inferiority analysis assessed the SOAP impact on postoperative pain scores. RESULTS: Postoperative pain scores in the SOAP group compared with the non-SOAP group were non-inferior (95% CI: -0.58, 0.10; non-inferiority margin=-1). The SOAP group consumed fewer postoperative opioids (median=0.67 (IQR=15) vs 8.17 morphine milliequivalents (MMEs) (IQR=40.33); p<0.01) and had fewer discharge prescription opioids (median=0 (IQR=60) vs 86.4 MMEs (IQR=140.4); p<0.01). DISCUSSION: The SOAP was as effective as the non-SOAP group in postoperative pain scores across a diverse patient population and associated with lower postoperative opioid consumption and discharge prescription opioids.

Perioperative Vasopressors are Associated with Delayed Graft Function in Kidney Transplant Recipients in a Primarily Black and Hispanic Cohort.

Introduction: Negative outcome studies of vasopressors in kidney transplant have not focused on patient populations that are predominantly Black or Hispanic. Project Aims: The evaluation sought to investigate the independent impact of perioperative vasopressors on postoperative renal allograft function in a sample drawn from a primarily Black and Hispanic population. Design: Retrospective, observational, single-center evaluation of patients > 18 years old who underwent kidney transplantation comparing outcomes based on vasopressor exposure. Results: The study included 150 patients of which 60 received vasopressors. The primary outcome differed between groups with delayed graft function occurring in 17(28%) versus 11(12.2%) occurring more often in those that received perioperative vasopressors (P = 0.02). The serum creatinine at postoperative day 7 was higher (2.69 vs1.52 mg/dL, P = 0.004), postoperative day 7 eGFR was worse (27.3 vs 52.9 mL/min/1.73m2, P = 0.002) in patients who received vasopressors. Patients who received perioperative vasopressors experienced more postoperative arrhythmias (15% vs 8%, P = 0.007), insulin infusion therapy (26.7% vs 13.3%, P = 0.04), and increased hospital length of stay (6 days vs 5 days, P = 0.006). Using IPWRA, patients receiving vasopressors were more likely to experience delayed function, relative risk difference of 22% (95% CI:0.08-0.35;P = 0.002) and in multivariate logistic regression modeling, an increased odds ratio of 3.2 (95% CI:1.1-8.62;P = 0.022). Conclusions: The use of perioperative vasopressors was independently associated with worsened early renal allograft function including delayed graft function, increased adverse events such as postoperative arrhythmias, and longer ICU length of stay. Further investigation is needed surrounding vasopressor use in this population.