Toxicology Screening Testing in Patients Undergoing Spine Surgery: A Prospective Observational Pilot Study.

BACKGROUND: Chronic opioid use and polypharmacy are commonly seen in chronic pain patients presenting for spine procedures. Substance abuse and misuse have also been reported in this patient population. Negative perioperative effects have been found in patients exposed to chronic opioid, alcohol, and recreational substances. Toxicology screening testing (TST) in the perioperative period provides useful information for adequate preoperative optimization and perioperative planning. METHODS: We designed a pilot study to understand this population's preoperative habits including accuracy of self-report and TST-detected prescribed and unprescribed medications and recreational substances. We compared the results of the TST to the self-reported medications using Spearman correlations. RESULTS: Inconsistencies between TST and self-report were found in 88% of patients. Spearman correlation was 0.509 between polypharmacy and intraoperative propofol use, suggesting that propofol requirement increased as the number of substances used increased. CONCLUSIONS: TST in patients presenting for spine surgery is a useful tool to detect substances taken by patients because self-report is often inaccurate. Discrepancies decrease the opportunity for preoperative optimization and adequate perioperative preparation.

Hypoxemia Within the First 3 Postoperative Days Is Associated With Increased 1-Year Postoperative Mortality After Adjusting for Perioperative Opioids and Other Confounders.

BACKGROUND: Postoperative hypoxemia (POH) is common and primarily treated with temporary oxygen supplementation. Because the clinical impact of POH is sometimes presumed as minor, efforts to better understand and minimize it have been limited. Here, we hypothesized that, after adjusting for opioids received perioperatively and other confounders, the frequency of POH events (POH%) reported within the first 3 postoperative days (PODs) is associated with increased postoperative 1-year mortality. METHODS: With prior institutional review board (IRB) approval, the Epic Clarity database was queried for all adult inpatient anesthesia encounters performed at our health system (1 academic and 2 community hospitals) from January 1, 2012 to March 31, 2016. Patients with multiple hospitalizations or subsequent surgeries within the same hospitalization were excluded. We classified patients based on the presence (POH) or not (No-POH) of ≥1 documented peripheral saturation of oxyhemoglobin (SpO2) ≤85% event of any duration occurring between the discharge from the postanesthesia care unit (PACU) until POD 3. Demographics, comorbidities, surgery duration, morphine milligram equivalents (OMME) administered perioperatively, respiratory therapies, intensive care unit (ICU) admission, and hospital length of stay (LOS) were also collected. Logistic regression was used to characterize the association between POH and 1-year postoperative mortality after adjusting for perioperatively administered opioids and other confounding factors. RESULTS: A total of 43,011 patients met study criteria. At least 1 POH event was reported in 10,727 (24.9%) patients. Of these, 7179 (66.9%) had ≥1 hypoxemic event on POD 1, 5340 (49.8%) on POD 2, and 3455 (32.3%) on POD 3. Patients with ≥1 POH event, compared to No-POH patients, were older, had more respiratory and other comorbidities, underwent longer surgeries, received greater opioid doses on the day of surgery and POD 1, and received more continuous pulse oximetry monitoring. POH patients required more frequent postoperative oxygen therapy, noninvasive ventilation (NIV), intubation, and ICU admission. One-year postoperative mortality occurred in 4.4% of patients with ≥1 POH and 3.0% of No-POH patients (P < .001). After adjusting for confounding factors, for every 10% increase in the frequency of SpO2 ≤85% readings, the odds of postoperative 1-year mortality were 1.20 (95% confidence interval [CI], 1.11-1.29; P < .001). Perioperative opioids were not independently associated with increased 1-year mortality. CONCLUSIONS: After adjusting for perioperative opioids and other confounders, moderate/severe POH within the first 3 PODs was independently associated with increased 1-year postoperative mortality. Increased efforts should be directed to understand if efforts to detect and reduce POH lead to improved patient outcomes.

Evaluation of a Formal Wellness Curriculum to Reduce Burnout in Anesthesia Residents: A Pilot Study.

BACKGROUND: Long-term exhaustion and chronic occupational stress often result in physician burnout, which can have adverse consequences for patients, physicians, their families, and society. We hypothesized that increased engagement with a wellness curriculum would reduce the level of burnout, as measured by the Maslach Burnout Inventory Human Services Survey (MBI-HSS). METHODS: We created a yearlong multifaceted pilot wellness curriculum for anesthesia residents at our institution. All residents could experience the wellness curriculum regardless of enrollment in the study. Residents completed the MBI-HSS three times during the year and indicated the number of wellness events attended via web survey. We assessed the influence of different curriculum components and time on the trajectory of three MBI-HSS subscales: emotional exhaustion, depersonalization, and personal accomplishment. RESULTS: Thirty-nine of 43 residents consented to participate in the study and completed at least one survey. Residents showed high levels of emotional exhaustion (mean 29.6; SD 11.14), depersonalization (12.8; 4.49), and personal accomplishment (45.0; 6.50) at baseline. Only personal accomplishment showed a significant increase over time (P < .036). Off-campus, wellness group sessions significantly decreased depersonalization (P = .001) and showed no difference in emotional exhaustion (P = .090). However, didactic workshops and wellness-related grand rounds failed to improve our measure of physician burnout, underscoring the need for alternative interventions to reduce this problem. CONCLUSIONS: A formal wellness curriculum that used classic didactic teaching methods was ineffective at decreasing resident burnout scores. Only wellness group meetings significantly reduced burnout measures. Our findings have important implications for planning future resident wellness interventions.

Obstetric Anesthesia Workforce Survey: A 30-Year Update.

BACKGROUND: Obstetric Anesthesia Workforce Surveys were conducted in 1981, 1992, and 2001, and the 10-year update was conducted in 2012. Anesthesia providers from US hospitals were surveyed to identify the methods used to provide obstetric anesthesia. Our primary hypothesis was that the provision of obstetric anesthesia services has changed in the past 10 years. METHODS: A sample of hospitals was generated based on the number of births per year and US census region. Strata were defined as follows: I ≥ 1500 annual births (n = 341), II ≥ 500 to 1499 annual births (n = 438), and III < 500 annual births (n = 414). Contact email information for the anesthesia provider in charge of obstetric services was obtained by phone call. Electronic questionnaires were sent through email. RESULTS: Administration of neuraxial (referred to as "regional" in previous surveys) labor analgesia was available 24 hours per day in all stratum I hospitals responding to the survey. Respondents across all strata reported high rates of in-house coverage, with 86.3% (95% confidence interval [CI] = 82.7%-90%) of stratum I providers reporting that they provided in-house anesthesiology services for obstetrics. The use of patient-controlled epidural analgesia in stratum I hospitals was reported to be 35% in 2001 and 77.6% (95% CI = 73.2%-82.1%) in this survey. Independent Certified Registered Nurse Anesthetists were reported to provide obstetric anesthesia services in 68% (95% CI = 57.9%-77.0%) of stratum III hospitals. Although 76% (95% CI = 71.2%-80.3%) of responding stratum I hospitals allow postpartum tubal ligations, 14% report inadequate staffing to provide anesthesia either always or at off-hours. CONCLUSIONS: Since 2001, there have been significant changes in how responding hospitals provide obstetric anesthesia care and staff the labor and delivery ward. Obstetric anesthesia surveys, updated every 10 years, continue to provide information about changes in obstetric anesthesia practice.

Opioid Use and Storage Patterns by Patients after Hospital Discharge following Surgery.

INTRODUCTION: Opioid-based analgesic therapy represents a cornerstone of pain management after surgery. The recent rise in opioid sales and opioid overdoses suggests it is important to maximize the safety of opioid prescribing after surgery. Given that patients may live with other family members in the home, safe storage and appropriate disposal of excess opioids after hospital discharge are necessary to prevent unintended secondary exposures. Identifying characteristics of patients who are likely to be prescribed excess opioids after surgery may enable more targeted prescription practices and safety interventions. Our study aimed to elucidate patient-reported opioid use patterns and modes of home storage of opioids among patients discharged home after Cesarean section (C-section) and thoracic surgery. Specifically, we sought to identify characteristics of patients who reported using about half or more versus less of the opioids prescribed to them for use after hospital discharge. METHODS: For this cohort study, we developed a survey on quality of analgesia following hospital discharge, amounts of opioids taken relative to the amount prescribed, reasons for not taking all prescribed medications, and storage and disposal methods for leftover opioids. Adult patients, who had C-section or thoracic surgery at a tertiary academic medical center, were given a web-based self-administered survey after discharge. Descriptive statistics (means and standard deviations, proportions) were used to describe the study sample and survey results. Comparisons between patients who reported taking about half or more versus less of the opioids prescribed to them for use after hospital discharge were made using unpaired t-tests, Mann-Whitney tests, and Chi-square tests as appropriate. RESULTS: The majority (53%) of respondents after C-section (N = 30) reported taking either no or very few (less than 5) prescribed opioid pills; 83% reported taking half or less; and 17% of women, reported taking all or nearly all (5 or fewer pills left over) of their opioid prescription. In a cohort of patients after thoracic surgery (n = 31) 45% reported taking either no or very few (5 or less) prescribed opioid pills; 71% reported taking half or less; and 29% of patients reported taking all or nearly all (5 or fewer pills left over) of their opioid prescription. In both cohorts, use of opioids while hospitalized was higher in the group reporting using about half or more of prescribed opioids after discharge. Leftover opioids were stored in an unlocked location in 77% and 73% of cases following C-section and thoracic surgery, respectively. CONCLUSION: Our findings from surveys in two distinct patient populations at a single academic medical center suggest that current opioid prescribing practices for pain management at hospital discharge following Cesarean section and thoracic surgery may not account for individual patients' analgesic requirements. Excess opioid pills are commonly stored in unsecured locations and represent a potential source for non-medical opioid use and associated morbidity and mortality in patients and their families. Research to develop goal-directed and patient-centered post-discharge opioid prescription practices and encourage opioid safety practices after surgery is needed.

Randomized, double-blind, placebo-controlled, single intravenous dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of the novel coronary smooth muscle cell proliferation inhibitor Biolimus A9 in healthy individuals.

Biolimus A9 (BA9) is a novel proliferation inhibitor of coronary smooth muscle cells that has been specifically designed for coating drug-eluting stents. The goals of this study were to identify the highest safe intravenous dose of BA9, to evaluate the dose-dependent pharmacokinetics of BA9 after intravenous administration in humans, and to characterize early clinical symptoms of BA9 toxicity in healthy subjects. This phase 1 trial in healthy subjects was designed as a double-blind, placebo-controlled, randomized, ascending single-dose study. After screening and randomization, 28 volunteers received either placebo (n = 7) or BA9 (n = 21) in a double-blinded fashion. Doses from 0.0075 mg/kg were escalated to 0.25 mg/kg in 4 cohorts. BA9 concentrations were measured using liquid chromatography-tandem mass spectrometry. BA9 doses up to 0.075 mg/kg were well tolerated. Only the highest BA9 dose of 0.25 mg/kg produced reversible drug-related adverse events. The most frequent adverse events were headache, nausea, and mouth ulcers, most likely due to immunosuppression. Exposure to BA9 did not result in electrocardiographic or clinical laboratory changes. BA9 had a terminal half-life of 90.0 ± 40.0 hours (all n = 21, mean ± standard deviation), an apparent clearance from blood of 0.96 ± 1.07 L/kg/h, and a volume of distribution of 96.5 ± 72.6 L/kg.

Toxicodynamic effects of ciclosporin are reflected by metabolite profiles in the urine of healthy individuals after a single dose.

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT * Ciclosporin's nephrotoxicity initially targets the proximal tubule and is, at least in part, driven by increased formation of oxygen radicals. * (1)H-nuclear magnetic resonance spectroscopy (NMR)- and mass spectrometry (MS)-based biochemical profiling (metabolomics) allows for the sensitive detection of metabolite pattern changes in urine. * In systematic studies in rats we showed that ciclosporin caused urine metabolite pattern changes typical for proximal tubule damage and that these pattern changes seemed to be more sensitive than established clinical kidney function markers such as serum creatinine concentrations. WHAT THIS PAPER ADDS * This study showed that urine metabolite pattern changes as assessed by (1)H-NMR and HPLC-MS are sensitive enough to detect the effect of ciclosporin as early as 4 h after a single oral dose. * In our previous rat studies, changes in urine metabolite pattern in response to ciclosporin translated into healthy humans, indicating the involvement of the same toxicodynamic mechanisms. * The results provide proof of concept for further development of this combination molecular marker strategy into diagnostic tools for the detection and monitoring of drug nephrotoxicity. AIMS The immunosuppressant ciclosporin is an efficient prophylaxis against transplant organ rejection but its clinical use is limited by its nephrotoxicity. Our previous systematic studies in the rat indicated urine metabolite pattern changes to be sensitive indicators of the negative effects of ciclosporin on the kidney. To translate these results, we conducted an open label, placebo-controlled, crossover study assessing the time-dependent toxicodynamic effects of a single oral ciclosporin dose (5 mg kg(-1)) on the kidney in 13 healthy individuals. METHODS In plasma and urine samples, ciclosporin and 15-F(2t)-isoprostane concentrations were assessed using HPLC-MS and metabolite profiles using (1)H-NMR spectroscopy. RESULTS The maximum ciclosporin concentrations were 1489 +/- 425 ng ml(-1) (blood) and 2629 +/- 1308 ng ml(-1) (urine). The increase in urinary 15-F(2t)-isoprostane observed 4 h after administration of ciclosporin indicated an increase in oxidative stress. 15-F(2t)-isoprostane concentrations were on average 2.9-fold higher after ciclosporin than after placebo (59.8 +/- 31.2 vs. 20.9 +/- 19.9 pg mg(-1) creatinine, P < 0.02). While there were no conclusive changes in plasma 15-F(2t)-isoprostane concentrations or metabolite patterns, non-targeted metabolome analysis using principal components analysis and partial least square fit analysis revealed significant changes in urine metabolites typically associated with negative effects on proximal tubule cells. The major metabolites that differed between the 4 h urine samples after ciclosporin and placebo were citrate, hippurate, lactate, TMAO, creatinine and phenylalanine. CONCLUSION Changes in urine metabolite patterns as a molecular marker are sufficiently sensitive for the detection of the negative effects of ciclosporin on the kidney after a single oral dose.

A survey of propofol abuse in academic anesthesia programs.

BACKGROUND: Although propofol has not traditionally been considered a drug of abuse, subanesthetic doses may have an abuse potential. We used this survey to assess prevalence and outcome of propofol abuse in academic anesthesiology programs. METHODS: E-mail surveys were sent to the 126 academic anesthesiology training programs in the United States. RESULTS: The survey response rate was 100%. One or more incidents of propofol abuse or diversion in the past 10 yr were reported by 18% of departments. The observed incidence of propofol abuse was 10 per 10,000 anesthesia providers per decade, a fivefold increase from previous surveys of propofol abuse (P = 0.005). Of the 25 reported individuals abusing propofol, 7 died as a result of the propofol abuse (28%), 6 of whom were residents. There was no established system to control or monitor propofol as is done with opioids at 71% of programs. There was an association between lack of control of propofol (e.g., pharmacy accounting) at the time of abuse and incidence of abuse at the program (P = 0.048). CONCLUSIONS: Propofol abuse in academic anesthesiology likely has increased over the last 10 yr. Much of the mortality is in residents. Most programs have no pharmacy accounting or control of propofol stocks. This may be of concern, given that all programs reporting deaths from propofol abuse were centers in which there was no pharmacy accounting for the drug.

Risk of impaired coagulation in warfarin patients ascending to altitude (>2400 m).

Approximately 476,000 people on warfarin therapy visit a resort at altitude (>2400 m) annually in Colorado. Clinicians practicing at altitude have expressed concern that ascent to altitude adversely affects coagulation in patients taking warfarin in both high altitude residents and visitors. We sought to determine the effect of ascent to and descent from altitude on coagulation in warfarin patients, as assessed by the international normalized ratio (INR). A retrospective medical chart review was conducted on all warfarin patients treated between August 1998 and October 2003 at a cardiology clinic in which travel to and from altitude was documented in association with each INR measurement in high altitude residents. Of the 1139 INR measurements in 49 patients, 143 were associated with changes in altitude (in 32 of 49 patients). The odds of an INR measurement being below the prescribed range were 2.7 times (95% CI: 1.2-5.8) higher among warfarin patients with recent ascent to altitude, 2.1 times (95% CI: 1.4-3.2) higher among warfarin patients with atrial fibrillation, and 5.6 (95% CI: 2.3-13.7) times higher among warfarin patients with both atrial fibrillation and recent ascent to altitude. Increasing altitude is a risk factor for subtherapeutic INR in warfarin patients and this risk is doubled in atrial fibrillation patients.