Kraus, Molly B

Abstract Background Pharmacogenomics is an emerging and affordable tool that may improve postoperative pain control. One challenge to successful pain control is the large interindividual variability among analgesics in their efficacy and adverse drug events. Whether preoperative pharmacogenomic testing is worthwhile for patients undergoing TKA is unclear. Questions/purposes (1) Are the results of preoperative pharmacogenetic testing associated with lower postoperative pain scores as measured by the Overall Benefit of Analgesic Score (OBAS)? (2) Do the results of preoperative pharmacogenomic testing lead to less total opioids given? (3) Do the results of preoperative pharmacogenomic testing lead to changes in opioid prescribing patterns? Methods Participants of this randomized trial were enrolled from September 2018 through December 2021 if they were aged 18 to 80 years and were undergoing primary TKA under general anesthesia. Patients were excluded if they had chronic kidney disease, a history of chronic pain or narcotic use before surgery, or if they were undergoing robotic surgery. Preoperatively, patients completed pharmacogenomic testing (RightMed, OneOME) and a questionnaire and were randomly assigned to the experimental group or control group. Of 99 patients screened, 23 were excluded, one before randomization; 11 allocated patients in each group did not receive their allocated interventions for reasons such as surgery canceled, patients ultimately undergoing spinal anesthesia, and change in surgery plan. Another four patients in each group were excluded from the analysis because they were missing an OBAS report. This left 30 patients for analysis in the control group and 38 patients in the experimental group. The control and experimental groups were similar in age, gender, and race. Pharmacogenomic test results for patients in the experimental group were reviewed before surgery by a pharmacist, who recommended perioperative medications to the clinical team. A pharmacist also assessed for clinically relevant drug-gene interactions and recommended drug and dose selection according to guidelines from the Clinical Pharmacogenomics Implementation Consortium for each patient enrolled in the study. Patients were unaware of their pharmacogenomic results. Pharmacogenomic test results for patients in the control group were not reviewed before surgery; instead, standard perioperative medications were administered in adherence to our institutional care pathways. The OBAS (maximum 28 points) was the primary outcome measure, recorded 24 hours postoperatively. A two-sample t-test was used to compare the mean OBAS between groups. Secondary measures were the mean 24-hour pain score, total morphine milligram equivalent, and frequency of opioid use. Postoperatively, patients were assessed for pain with a VAS (range 0 to 10). Opioid use was recorded preoperatively, intraoperatively, in the postanesthesia care unit, and 24 hours after discharge from the postanesthesia care unit. Changes in perioperative opioid use based on pharmacogenomic testing were recorded, as were changes in prescription patterns for postoperative pain control. Preoperative characteristics were also compared between patients with and without various phenotypes ascertained from pharmacogenomic test results. Results The mean OBAS did not differ between groups (mean ± SD 4.7 ± 3.7 in the control group versus 4.2 ± 2.8 in the experimental group, mean difference 0.5 [95% CI -1.1 to 2.1]; p = 0.55). Total opioids given did not differ between groups or at any single perioperative timepoint (preoperative, intraoperative, or postoperative). We found no difference in opioid prescribing pattern. After adjusting for multiple comparisons, no difference was observed between the treatment and control groups in tramadol use (41% versus 71%, proportion difference 0.29 [95% CI 0.05 to 0.53]; nominal p = 0.02; adjusted p > 0.99). Conclusion Routine use of pharmacogenomic testing for patients undergoing TKA did not lead to better pain control or decreased opioid consumption. Future studies might focus on at-risk populations, such as patients with chronic pain or those undergoing complex, painful surgical procedures, to test whether pharmacogenomic results might be beneficial in certain circumstances. Level of Evidence Level I, therapeutic study.

AbstractDiabetes insipidus is characterized by polyuria due to an inability to auto‐regulate water balance resulting in dangerous metabolic derangements. Intraoperative anesthetics have been increasingly identified as a cause of diabetes insipidus in adult patients; however, it is rare in pediatrics. We present a case of a 16‐year‐old male undergoing resection of a recurrent left juvenile nasopharyngeal angiofibroma who experienced intraoperative polyuria concerning diabetes insipidus. Urine output drastically decreased following discontinuation of dexmedetomidine with complete resolution within 24 h. We conclude that this case of transient diabetes insipidus was associated with dexmedetomidine administration.

AbstractExtended‐release liposomal bupivacaine is frequently used in surgical infiltration for postoperative pain control. The manufacturer recommends against subsequent local anesthetics within 96 hours. We administered epidural bupivacaine one day after local liposomal bupivacaine infiltration for staged hemipelvectomy without symptoms of LAST. Further pharmacokinetic and clinical safety studies are needed.

AbstractBackgroundPatients undergoing kidney transplantation traditionally receive liberal amounts of fluid during surgery. However, excessive fluids can lead to fluid overload and ileus. In this retrospective cohort study, we compared the effect of restrictive versus liberal fluid therapy on kidney transplantation outcomes.MethodsPatients who underwent deceased‐donor kidney transplantation at Mayo Clinic from January 2014 to March 2019 were included. Those who received <3 L of intravenous fluids intraoperatively were categorized as “restrictive;” those who received ≥3 L were categorized as “liberal.” The primary outcome was incidence of delayed graft function (DGF). Secondary outcomes included length of stay, readmission within 30 days, time to return of bowel function, and incidence of postoperative complications.ResultsOf the 1171 patients included, 557 were in the restrictive group and 614 in the liberal group. The mean (SD) fluid intake was 2.17 (.54) L in the restrictive group and 3.67 (.68) L in the liberal group (P<.001). There was no difference in DGF (relative risk, 1.03; P = .56), length of stay (P = .34), readmission (P = .80), return of bowel function (P = .71), or other postoperative complications.ConclusionsIntraoperative restrictive fluid therapy during kidney transplantation was not associated with DGF or worse outcomes when compared with liberal fluid therapy.

BACKGROUND: A gender-based compensation gap among physicians is well documented. Even after adjusting for age, experience, work hours, productivity, and academic rank, the gender gap remained and widened over the course of a physician’s career. This study aimed to examine if a significant gender pay gap still existed for anesthesiologists in the United States. METHODS: In 2018, we surveyed 28,812 physician members of the American Society of Anesthesiologists to assess the association of compensation with gender and to identify possible causes of wage disparities. Gender was the primary variable examined in the model, and compensation by gender was the primary outcome. Compensation was defined as the amount reported as direct compensation on a W-2, 1099, or K-1, plus all voluntary salary reductions (eg, 401[k], health insurance). The survey directed respondents to include salary, bonuses, incentive payments, research stipends, honoraria, and distribution of profits to employees. Respondents had the option of providing a point estimate of their compensation or selecting a range in $50,000 increments. Potential confounding variables that could affect compensation were identified based on a scoping literature review and the consensus expertise of the authors. We fitted a generalized ordinal logistic regression with 7 ranges of compensation. For the sensitivity analyses, we used linear regressions of log-transformed compensation based on respondent point estimates and imputed values. RESULTS: The final analytic sample consisted of 2081 observations (response rate, 7.2%). This sample represented a higher percentage of women and younger physicians compared to the demographic makeup of anesthesiologists in the United States. The adjusted odds ratio associated with gender equal to woman was an estimated 0.44 (95% confidence interval, 0.37–0.53), indicating that for a given compensation range, women had a 56% lower odds than men of being in a higher compensation range. Sensitivity analyses found the relative percentage difference in compensation for women compared to men ranged from −8.3 to −8.9. In the sensitivity analysis based on the subset of respondents (n = 1036) who provided a point estimate of compensation, the relative percentage difference (−8.3%; 95% confidence interval, −4.7 to −11.7) reflected a $32,617 lower compensation for women than men, holding other covariates at their means. CONCLUSIONS: Compensation for anesthesiologists showed a significant pay gap that was associated with gender even after adjusting for potential confounding factors, including age, hours worked, geographic practice region, practice type, position, and job selection criteria.

Purpose Parental leave for new parents is essential as they adjust to the physical and psychological changes that accompany childbirth and caring for a newborn. This study sought to determine the current state of parental leave policies for medical students at medical schools in the United States. Method From November to December 2019, 2 researchers independently reviewed the websites of 199 U.S. MD-granting and DO-granting medical schools (including in U.S. territories). Online student handbooks and school webpages were searched for the following keywords: “pregnant” OR “pregnancy” OR “maternity” OR “parent” OR “family” OR “child” OR “birth.” Data were analyzed using descriptive statistics. Fisher’s exact tests evaluated differences in proportion by group. Results Of 199 schools, 65 (32.66%) had parental leave policies available online or in the handbook: 39 of 155 (25.16%) MD-granting and 26 of 44 (59.09%) DO-granting schools. Of those policies, 59 (90.77%) were included in the student handbook. Most policies (28, 43.08%) were included as an option within the school’s general leave of absence policy. Both parents were included in 38 (58.46%) policies; 23 (35.38%) policies mentioned only mothers; and 4 (6.15%) were unknown. An option to maintain original graduation date was offered in 21 (32.1%) schools’ policies. Three schools (4.62%) included adoption as qualifying for parental leave. When comparing MD and DO programs, DO programs were statistically more likely to have a parental leave policy: 39 (25.16%) vs 26 (59.09%); P < .001. Conclusions Balancing medical school with pregnancy and childbirth necessitates administrative support to address the inherent scheduling challenges. Currently, many schools lack parental leave policies for medical students that are easily accessible, are separate from formal leaves of absence, allow for at least 12 weeks, and are tailored to the student academic year to ensure on-time completion of medical education.

Diabetes insipidus (DI) is an uncommon perioperative complication that can occur secondary to medications or surgical manipulation and can cause significant hypovolemia and electrolyte abnormalities. We reviewed and evaluated the current literature and identified 29 cases of DI related to medications commonly used in anesthesia such as propofol, dexmedetomidine, sevoflurane, ketamine, and opioids. This review summarizes the case reports and frequency of DI with each medication and presents possible pathophysiology. Medication-induced DI should be included in the differential diagnosis when intraoperative polyuria is identified. Early identification, removal of the agent, and treatment of intraoperative DI are critical to minimize complications.

Background and objectives The costoclavicular brachial plexus block is performed deep and posterior to the midpoint of the clavicle. There are limited data evaluating the spread of the costoclavicular brachial plexus block. We performed a cadaveric study to evaluate the spread of injectate after a costoclavicular brachial plexus block. Methods Five ultrasound-guided costoclavicular block injections were performed with 20 mL of 0.1% methylene blue. The brachial plexus and its branches were dissected from the level of C4 to the lower axilla. The extent of dye spread was recorded including spread to the phrenic nerve, suprascapular nerve, roots, trunks, divisions, cords and terminal branches of the brachial plexus. Results The dye extended cephalad to the level of the cricoid cartilage in two of the five injections; three injections had dye extending 0.75 cm, 1.5 cm and 2 cm caudad to the level of the cricoid cartilage, respectively. The C7, C8 and T1 nerve roots were stained in all injections. The dye did not extend cephalad to the C5 and C6 nerve roots. All trunks, cords and divisions of the brachial plexus were stained, as was the suprascapular nerve. There was no spread of dye to the phrenic nerve in any of the specimens. Conclusions This cadaveric study demonstrates that ultrasound-guided injection in the costoclavicular space spreads cephalad to the brachial plexus in the supraclavicular space, consistently reaching the suprascapular nerve and all trunks and cords of the brachial plexus, while sparing the phrenic nerve.